FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Phan, J Tropea, JE Waugh, DS AF Phan, J Tropea, JE Waugh, DS TI Structure of the Yersinia pestis type III secretion chaperone SycH in complex with a stable fragment of YscM2 SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID YOP VIRULON; ENTEROCOLITICA; PROTEIN; BACTERIAL; SYSTEM; IDENTIFICATION; RECOGNITION; MACROPHAGES; EXPRESSION; APPARATUS AB Pathogenic Yersinia species use a type III secretion system to inject cytotoxic effector proteins directly into the cytosol of mammalian cells, where they neutralize the innate immune response by interfering with the signal-transduction pathways that control phagocytosis and inflammation. To be exported efficiently some effectors must transiently associate with cognate cytoplasmic secretion chaperones. SycH is the. chaperone for YopH, a potent eukaryotic-like protein tyrosine phosphatase that is essential for virulence. SycH also binds two negative regulators of type III secretion, YscM1 and YscM2, both of which share significant sequence homology with the chaperone-binding domain of YopH. Here, the structure of a complex between SycH and a stable fragment of YscM2 that was designed on the basis of limited proteolysis experiments is presented. The overall fold of SycH is very similar to the structures of other homodimeric secretion chaperones that have been determined to date. YscM2 wraps around SycH in an extended fashion, with some secondary but no tertiary structure, assuming a conformation distinct from the globular fold that it is predicted to adopt in the absence of SycH. C1 NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov NR 41 TC 39 Z9 40 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD SEP PY 2004 VL 60 BP 1591 EP 1599 DI 10.1107/S907444904017597 PN 9 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 849GD UT WOS:000223525800012 PM 15333930 ER PT J AU Peculis, BA Scarsdale, JN Wright, HT AF Peculis, BA Scarsdale, JN Wright, HT TI Crystals of X29, a Xenopus laevis U8 snoRNA-binding protein with nuclear decapping activity SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID RAY-DIFFRACTION DATA; RIBOSOMAL-RNA; SNRNA AB Eukaryotic ribosome biosynthesis requires modification (methylation, pseudouridylation) and nucleolytic processing of precursor ribosomal RNAs in the nucleolus. The RNA components of the small nucleolar RNPs (snoRNAs) are essential for many of these events. One snoRNP, called U8, is necessary for maturation of 5.8S and 28S rRNA in vertebrates. In Xenopus laevis, U8 snoRNA was found to bind specifically and with high affinity to a protein called X29. X29 is a Nudix hydrolase, a nucleotide diphosphatase that removes the m 7 G and M227G caps from U8 and other RNAs. X29 requires an RNA as substrate and cap analogues are not substrates or inhibitors of cleavage. To study the determinants of X29 activity and its specificity for U8 RNA substrate, X29 was crystallized in an orthorhombic crystal form that diffracts to 2.1 Angstrom resolution. C1 Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23219 USA. Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Richmond, VA 23219 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Wright, HT (reprint author), Virginia Commonwealth Univ, Dept Biochem, 800 E Leigh St,Suite 212, Richmond, VA 23219 USA. EM xrdproc@hsc.vcu.edu NR 11 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD SEP PY 2004 VL 60 BP 1668 EP 1669 DI 10.1107/S0907444904016051 PN 9 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 849GD UT WOS:000223525800032 PM 15333950 ER PT J AU Calvo, KR Traverse-Glehen, A Pittaluga, S Jaffe, ES AF Calvo, KR Traverse-Glehen, A Pittaluga, S Jaffe, ES TI Molecular profiling provides evidence of primary mediastinal large B-cell lymphoma as a distinct entity related to classic Hodgkin lymphoma SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Article DE primary mediastinal large B-cell lymphoma; thymic B-cell lymphoma; classic Hodgkin lymphoma; nodular sclerosis; Hodgkin disease; gray zone lymphoma; gene profiling; immunohistochemistry ID CLASSIFICATION; EXPRESSION; DISEASE; GENE; RECEPTOR; SUBCLASSIFICATION; CHEMOTHERAPY; ACTIVATION; SCLEROSIS; THERAPY AB Expanding on prior studies that have used molecular profiling to elucidate the heterogeneity of diffuse large B-cell lymphomas (DLBCLs), two recent studies (Rosenwald et al and Savage et al) have characterized a third molecularly distinct subtype of DLBCL, primary mediastinal (thymic) large B-cell lymphoma (PMLBCL). Both groups found distinct gene expression patterns that were able to reliably diagnose PMLBCL and distinguish it from other DLBCLs. Notably, the signature gene expression profile of PMLBCL was more closely related to classic Hodgkin lymphoma (CHL) than other DLBCL subtypes. These studies provide further evidence that PMLBCL and nodular sclerosis CHL may represent related tumors on either ends of a continuum, whose interface includes an intermediate form of disease, mediastinal gray zone (MGZL) lymphoma. MGZLs are tumors that have a transitional morphology and phenotype, combining features of both PMLBCL and nodular sclerosis CHL, and provide a diagnostic challenge to pathologists. These studies provide insights into the biology of PMLBCL and CHL and demonstrate the utility of genomic technologies in defining and diagnosing hematopoietic tumors. The ability to map specific pathologic signal transduction pathways regulating hematopoietic differentiation, proliferation, and apoptosis through genomic or proteomic technologies promises to provide the basis for the development of individualized molecularly targeted therapies for specific tumors. C1 NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2N202,10 Ctr Dr,MSC-1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov RI Calvo, Katherine/A-8109-2009 NR 39 TC 41 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD SEP PY 2004 VL 11 IS 5 BP 227 EP 238 DI 10.1097/01.pap.0000138144.11635.f8 PG 12 WC Pathology SC Pathology GA 849SE UT WOS:000223560200001 PM 15322489 ER PT J AU Stevens, AB Coon, D Wisniewski, S Vance, D Arguelles, S Belle, S Mendelsohn, A Ory, M Haley, W AF Stevens, AB Coon, D Wisniewski, S Vance, D Arguelles, S Belle, S Mendelsohn, A Ory, M Haley, W TI Measurement of leisure time satisfaction in family caregivers SO AGING & MENTAL HEALTH LA English DT Article ID SOCIAL SUPPORT; ACTIVITY RESTRICTION; SPOUSAL CAREGIVERS; OLDER-ADULTS; DEPRESSION; PREDICTORS; DEMENTIA; HEALTH; APPRAISAL; IMPACT AB Caregiving is known to limit participation in a variety of roles. Leisure roles are increasingly recognized as important for the well-being of older adults. Little is known, however, about the impact of caregiving on leisure activities, and existing measures are of limited utility in caregiving research. We developed the Leisure Time Satisfaction (LTS) measure to allow further study of the impact of caregiving on caregivers' leisure time satisfaction, the role of leisure in understanding the caregiving process, and whether caregiving interventions improve leisure time satisfaction. The six-item LTS measure shows excellent psychometric properties, including internal consistency, a single factor structure, and convergent validity. Psychometric features are robust across diverse groups of caregivers, including subgroups varying by race/ethnicity and relationship to the care recipient. The LTS measure appears to be a promising tool for inclusion in caregiving research. C1 Univ Alabama, Dementia Care Res Program, Div Gerontol & Geriatr Med, Birmingham, AL 35294 USA. Goldman Inst Aging, San Francisco, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Ctr Adult Dev & Aging, Miami, FL USA. Texas A&M Univ Syst, NIA, College Stn, TX USA. Univ S Florida, Tampa, FL USA. RP Stevens, AB (reprint author), Univ Alabama, Dementia Care Res Program, Div Gerontol & Geriatr Med, 1530 3rd Ave S,CH19,Suite 218, Birmingham, AL 35294 USA. EM AStevens@uab.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Vance, David/0000-0002-0498-6263 FU NIA NIH HHS [AG13265, AG13255, AG13289, AG13297, AG13305, AG13313, K01AG00722]; NINR NIH HHS [NR13269] NR 38 TC 28 Z9 28 U1 0 U2 5 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD SEP PY 2004 VL 8 IS 5 BP 450 EP 459 DI 10.1080/13607860410001709737 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 857CS UT WOS:000224094400008 PM 15511743 ER PT J AU Dwyer, J AF Dwyer, J TI Nutrition and cardiovascular disease prevention in children and adolescents - Part 1: diet related cardiovascular disease risk factors SO AGRO FOOD INDUSTRY HI-TECH LA English DT Article AB Nutrition is important in cardiovascular disease prevention in children and adolescents. Part 1 briefly reviews diet related cardiovascular disease (CVD) risk factors that are often present in childhood and adolescence. These include high levels of low density lipoprotein cholesterol (LDL) and low levels of high density lipoprotein cholesterol (HDL)s in blood, hypertension, a family history of premature heart disease, and cigarette smoking. Serum lipid levels, blood pressure and body weight can be altered by dietary means. Standards for screening and assessment are now available from expert groups, and these are discussed. Part 2 discusses nutritional measures that are recommended by expert groups to reduce diet-related CVD risks in children and adolescents. C1 NIH, Office Dietary Supplements, Bethesda, MD 20892 USA. Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Dwyer, J (reprint author), NIH, Office Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 9 TC 0 Z9 0 U1 0 U2 2 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 1722-6996 J9 AGRO FOOD IND HI TEC JI Agro Food Ind. Hi-Tech PD SEP-OCT PY 2004 VL 15 IS 5 BP 47 EP 48 PG 2 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 880IK UT WOS:000225782000013 ER PT J AU Wiener, L Riekert, K Ryder, C Wood, LV AF Wiener, L Riekert, K Ryder, C Wood, LV TI Assessing medication adherence in adolescents with HIV when electronic monitoring is not feasible SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; QUALITY-OF-LIFE; REPORTED ADHERENCE; DRUG-RESISTANCE; CHILDREN; INFECTION; INTERVIEW; TYPE-1; PREDICTORS AB The purpose of this study was to compare and contrast three different methods for measuring self-reported antiretroviral medication adherence, correlate individual reports of adherence with measures of viral load, and identify the degree of concordance among self-reported medication adherence tools. Thirty-five adolescents between the ages of 11 and 21 years (mean age, 15.4) enrolled in National Cancer Institute (NCI) HIV primary treatment protocols participated in the study. Adherence approaches consisted of a clinical nurse rating (CNR), a Retrospective Self-Report Interview (RSI; using two different scoring criteria), and a 24-hour recall phone interview (Daily Phone Diary [DPD]). These were chosen because of their potential to be integrated within a clinical setting. Reported perfect adherence to protease inhibitors ranged from 31% to 54% depending on the measure used. There was little agreement between measures. Teenagers who reported perfect protease inhibitor adherence on both RSI-doses taken and DPD were approximately 5 times more likely to have a viral load less than 10,000 copies per milliliter. Advantages and disadvantages of each adherence method and clinical and research recommendations are discussed. C1 NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. RP Wiener, L (reprint author), NCI, HIV & AIDS Malignancy Branch, NIH, 9000 Rockville Pike,Bldg 10-10S255, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov NR 53 TC 32 Z9 34 U1 0 U2 3 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 2004 VL 18 IS 9 BP 527 EP 538 DI 10.1089/apc.2004.18.527 PG 12 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 860ZQ UT WOS:000224386300005 PM 15630773 ER PT J AU Frank, I Bosch, RJ Fiscus, S Valentine, F Flexner, C Segal, Y Ruan, P Gulick, R Wood, K Estep, S Fox, L Nevin, T Stevens, M Eron, JJ AF Frank, I Bosch, RJ Fiscus, S Valentine, F Flexner, C Segal, Y Ruan, P Gulick, R Wood, K Estep, S Fox, L Nevin, T Stevens, M Eron, JJ CA ACTG 307 Protocol Team TI Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: A randomized, placebo-controlled trial, ACTG 307 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTED PATIENTS; PROTEASE INHIBITOR; COMBINATION THERAPY; CUBIC MILLIMETER; PLUS DIDANOSINE; STAVUDINE; REPLICATION; MONOTHERAPY; ZIDOVUDINE AB We performed a 24-week, placebo-controlled, comparative trial of hydroxyurea (HU) monotherapy, didanosine (ddI) monotherapy, and the combination of ddI plus HU administered as 1000 mg qd or 1500 mg qd in antiretroviral-naive and experienced subjects with CD4(+) lymphocyte counts of 200 - 700 cells/mm(3). Enrollment included 134 subjects. HU enhanced the antiviral activity of ddI by 1.0 log(10) copies/ml after 8 weeks of therapy, with sustained responses over 24 weeks. HU alone over 4 weeks had no effect. Lamivudine resistance had little impact on antiretroviral activity when examined across treatment arms. Increases in absolute CD4(+) T cell counts, but not CD4(+) T cell percentages, were less in subjects who received HU compared to ddI monotherapy, and lymphoproliferative responses to antigenic and mitogenic stimuli were not altered. Subjects who received HU 1500 mg were more likely to experience dose-limiting hematological toxicities compared to those who received 1000 mg, without any additional antiviral benefit. HU may continue to have a role as a component of HIV therapy. C1 Univ Penn, Philadelphia, PA 19102 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC 27514 USA. NYU, Med Ctr, New York, NY 10016 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21205 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, MA USA. NIAID, Bethesda, MD 20814 USA. Social & Sci Syst, Silver Spring, MD 20910 USA. Bristol Myers Squibb Co, Princeton, NJ 08540 USA. RP Frank, I (reprint author), Univ Penn, 502 Johnson Pavil,36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM franki@mail.med.upenn.edu FU NCRR NIH HHS [RR00040, RR-00052, RR00046]; NIAID NIH HHS [AI25868, AI27665, AI27668, AI27742, AI32775, AI32783, AI38855, AI38858, AI46386, AI9P30-AI50410] NR 48 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2004 VL 20 IS 9 BP 916 EP 926 DI 10.1089/aid.2004.20.916 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 863FO UT WOS:000224546600002 PM 15597521 ER PT J AU Dawson, DA Grant, BF Stinson, FS Chou, PS AF Dawson, DA Grant, BF Stinson, FS Chou, PS TI Toward the attainment of low-risk drinking goals: A 10-year progress report SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID GENERAL-POPULATION SAMPLE; ALCOHOL-USE DISORDER; BINGE DRINKING; PREVENTIVE PARADOX; MORTALITY; CONSUMPTION; CONSEQUENCES; RELIABILITY; PATTERNS; AUDADIS AB Background: The Healthy People 2010 goals include reducing the proportion of U.S. adults whose alcohol consumption exceeds recommended daily and weekly limits, relative to baseline levels observed in 1991-1992. To date, there has been no assessment of initial progress toward attaining these goals. Methods: Consumption data from the 1991-1992 National Longitudinal Alcohol Epidemiology Survey (n = 42,862) and the 2001-2003 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093) were used to evaluate the trend in the proportion of U.S. adults adhering to and exceeding recommended drinking limits. These included weekly limits of no more than 14 standard drinks for men and no more than 7 standard drinks for women and daily limits of no more than 4 standard drinks for men and 3 standard drinks for women. The percentages exceeding the limits are compared for the two time periods, for the total adult population and sociodemographic subgroups, and the association between risk drinking and sociodemographic characteristics is disaggregated into a series of conditional odds ratios. Results: The proportion of U.S. adults classified as regular drinkers whose intake exceeded recommended daily or weekly limits declined from 32.1% to 29.3% in the 10-year period. The reduction in risk drinking occurred solely among persons who exceeded the daily drinking limits less than once a week but did not exceed the weekly limits. There was a very small but significant increase in the proportion of adults exceeding the weekly limits, from 9.4% to 10.3%. Reduction of sociodemographic disparities in adherence to drinking limits was limited. Conclusions: Progress to date is limited and may reflect changes in population composition rather than changes in drinking habits. Attainment of Healthy People goals and reduction of disparities in risk drinking will require sustained effort and more targeted prevention programs. C1 NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@willco.niaaa.nih.gov NR 49 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2004 VL 28 IS 9 BP 1371 EP 1378 DI 10.1097/01.ALC.0000139811.24455.3E PG 8 WC Substance Abuse SC Substance Abuse GA 856VV UT WOS:000224074300013 PM 15365308 ER PT J AU Faden, VB Fay, MP AF Faden, VB Fay, MP TI Trends in drinking among Americans age 18 and younger: 1975-2002 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ILLICIT DRUG-USE; ALCOHOL-USE; ETHNIC-DIFFERENCES; UNDERAGE DRINKERS; SUBSTANCE USE; ADOLESCENTS; YOUTH; TOBACCO AB Background: Although changes over time in the prevalence of drinking by youth under 18 have been previously reported, we present results based on data from multiple surveys, using recently developed software for trend analyses. In this study, we applied joinpoint statistical methodology to three national data sets to analyze trends in drinking by youth, age 18 and under, for the period 1975 to 2002. Methods: Information was obtained from three national data sets, Monitoring the Future for the years 1975 to 2002, the Youth Risk Behavior Survey for the years 1991 to 2001, and the National Household Survey on Drug Abuse for 1979, 1985, and 1991 to 2001. Approximately 80,000 persons between 12 and 18 were included in the most recent survey years. The alcohol consumption measures examined over time were any use of alcohol, consumption of five or more drinks on one occasion, and daily consumption. Results: Alcohol consumption by 8th, 10th and 12th graders decreased substantially since the 1970s according to joinpoint trend analyses. It remains disturbingly high, however, according to data from three national surveys (e.g., 12.4% of 8(th) and 28.6% of 12th graders drinking five or more drinks in a row in the past 2 weeks), although prevalence rates have been relatively stable for the last 5 to 10 years. Conclusions: Since the early 1990s, rates of drinking by youth under 18 remained relatively stable according to the Youth Risk Behavior Survey and National Household Survey on Drug Abuse and moved up and then down according to Monitoring the Future, underscoring the need for continued surveillance and enhanced understanding of this long-standing problem. C1 NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD 20892 USA. NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Faden, VB (reprint author), NIAAA, Div Epidemiol & Prevent Res, NIH, 5635 Fishers Lane,Room 2085,MSC 9304, Bethesda, MD 20892 USA. EM vfaden@mail.nih.gov RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 25 TC 22 Z9 22 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2004 VL 28 IS 9 BP 1388 EP 1395 DI 10.1097/01.ALC.0000139820.04539.BD PG 8 WC Substance Abuse SC Substance Abuse GA 856VV UT WOS:000224074300015 PM 15365310 ER PT J AU Braun, LR Flynn, D Ko, CW Yoder, B Greenwald, JR Curley, BB Williams, R Thompson, MW AF Braun, LR Flynn, D Ko, CW Yoder, B Greenwald, JR Curley, BB Williams, R Thompson, MW TI Gestational age-specific growth parameters for infants born at US military hospitals SO AMBULATORY PEDIATRICS LA English DT Article DE gestational age; growth; head circumference; length; military; weight ID BIRTH-WEIGHT; INTRAUTERINE GROWTH; LABORATORY OBSERVATIONS; FETAL GROWTH; CIRCUMFERENCE; HYPOGLYCEMIA; CALIFORNIA; PREGNANCY; DIAGNOSES; PATTERNS AB Background.-Military hospitals currently use gestational age-specific growth curves based on data collected in Denver, Colo, from 1948 to 1961. A number of population and environmental factors and medical practice changes may make these curves nonrepresentative. Objective. -Determine if presently used growth curves represent norms for infants born in military hospitals and create new curves for use in military hospitals. Methods.-Data were collected from medical records of tertiary- and primary-care military hospitals. We created growth curves created for birth weight, length, and head circumference and compared these curves at gestational ages 23-42 weeks to previously published norms and to 1998 national vital statistics. Racial and ethnic differences between aroups were compared. A retrospective analysis of blood-glucose measurements for healthy term infants was performed to identify potential safety issues. Results.-Significant increases in growth parameters were noted for infants born in military hospitals. Specific racial and ethnic groups within the military also had an increase when compared with these groups in the United States as a whole. Less than I% of infants classified as large for gestational age (LGA) according by old standards but average for gestational age (AGA) according to new curves experienced hypoglycernia. Conclusion.-Published growth curves may not represent infants born in military hospitals. Term infants born in military hospitals as a group and in racial and ethnic subgroups are larger than term infants born in US civilian hospitals. Prospective use of curves will help to validate their long-term applicability in military and civilian nurseries. C1 Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA. Natl Naval Med Res Inst, Dept Pediat & Clin Informat Serv, Bethesda, MD USA. Natl Inst Deafness & Other Commun Disorders, Esex Fells, NJ USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. RP Thompson, MW (reprint author), Tripler Army Med Ctr, Dept Pediat, 1 Jarrett White Rd, Honolulu, HI 96859 USA. EM mark.thompson@haw.tamc.amedd.army.mil NR 27 TC 3 Z9 3 U1 0 U2 2 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD SEP-OCT PY 2004 VL 4 IS 5 BP 461 EP 467 DI 10.1367/A03-022R.1 PG 7 WC Pediatrics SC Pediatrics GA 856HI UT WOS:000224035900012 PM 15369405 ER PT J AU Ulrich, C Grady, C AF Ulrich, C Grady, C TI Beneficent deception: Whose best interests are we serving? SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID MANAGED CARE C1 Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NIH, Dept Clin Bioeth, Sect Human Subjects Res, Bethesda, MD 20892 USA. RP Ulrich, C (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD FAL PY 2004 VL 4 IS 4 BP 76 EP 77 DI 10.1080/15265160490906772 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 893BF UT WOS:000226693600033 PM 16192217 ER PT J AU Ruhl, CE Everhart, JE Ding, JZ Goodpaster, BH Kanaya, AM Simonsick, EM Tylavsky, FA Harris, TB AF Ruhl, CE Everhart, JE Ding, JZ Goodpaster, BH Kanaya, AM Simonsick, EM Tylavsky, FA Harris, TB CA Health Aging Body Composition Stud TI Serum leptin concentrations and body adipose measures in older black and white adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE leptin; body composition; anthropometry; dual-energy X-ray absorptiometry; computed tomography; race; epidemiology; Health, Aging, and Body Composition Study; health ABC study ID PLASMA LEPTIN; POSTMENOPAUSAL WOMEN; INSULIN SENSITIVITY; RACIAL-DIFFERENCES; GENDER DIFFERENCES; MEXICAN-AMERICANS; CIGARETTE-SMOKING; AFRICAN-AMERICAN; FAT DISTRIBUTION; CAUCASIAN WOMEN AB Background: Among US adults, serum leptin concentrations are higher in women than in men and are higher in blacks than in whites independent of anthropometric measures of body fatness. Objective: Using radiographic measures of body fat, we determined the best correlates of leptin and whether adiposity can explain sex and race differences in leptin concentrations in older adults. Design: This was a cross-sectional analysis of fasting serum leptin concentrations and body fat measured by dual-energy X-ray absorptiometry (DXA), abdominal computed tomography, and standard anthropometry in 3026 well-functioning 70-79-y-old participants (42% black, 51% women) of the Health, Aging, and Body Composition Study. Results: Geometric mean (+/-SE) leptin concentrations (ng/mL) were higher in the women than in the men (16.5 +/- 0.3 and 5.7 +/- 0.1, respectively) and in the black women than in the white women (20.2 +/- 0.6 and 13.9 +/- 0.4, respectively), but did not differ significantly between the white and black men (5.8 +/- 0.2 and 5.5 +/- 0.2, respectively). Percentage fat estimated from DXA showed the highest correlation with leptin (R-2 = 0.56 for both sexes). Addition of abdominal visceral fat minimally increased the correlation. In the multivariate analysis, the association with sex was eliminated after adjustment for percentage fat and visceral fat in both whites (P = 0.051) and blacks (P = 0.34). Among women, higher leptin concentrations in blacks remained after adjustment for percentage fat and visceral fat (mean race difference = 4.95 ng/mL; P < 0.001). Among men, an association with black race emerged after adjustment for these factors (mean race difference = 1.42 ng/mL; P < 0.001). Conclusions: Among older adults, higher serum leptin concentrations in women are explained by a greater percentage of body fat. Higher leptin concentrations in blacks are not explained by percentage of body fat. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIDDKD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NIA, Lab Epidemiol & Demog & Biometry, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Univ Pittsburgh, Div Endocrinol & Metab, Dept Med, Montefiore Hosp, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU NIA NIH HHS [N01 AG 62101, N01 AG 62103, N01 AG 62106]; NIDDK NIH HHS [N01 DK 12478] NR 45 TC 46 Z9 47 U1 0 U2 0 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 SEP PY 2004 VL 80 IS 3 BP 576 EP 583 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 849SR UT WOS:000223561500007 PM 15321795 ER PT J AU Ekelund, U Sardinha, LB Anderssen, SA Harro, M Franks, PW Brage, S Cooper, AR Andersen, LB Riddoch, C Froberg, K AF Ekelund, U Sardinha, LB Anderssen, SA Harro, M Franks, PW Brage, S Cooper, AR Andersen, LB Riddoch, C Froberg, K TI Associations between objectively assessed physical activity and indicators of body fatness in 9- to 10-y-old European children: a population-based study from 4 distinct regions in Europe (the European Youth Heart Study) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE accelerometry; adiposity; children; energy expenditure; physical activity; skinfold thickness; European Youth Heart Study ID ENERGY-EXPENDITURE; CHILDHOOD OBESITY; MASS INDEX; ADOLESCENTS; ADIPOSITY; WEIGHT; OVERWEIGHT; ACCELEROMETER; CONSUMPTION; PREVALENCE AB Background: The rising prevalence of obesity in children may be due to a reduction in physical activity (PA). Objective: Our aim was to study the associations of objectively measured PA volume and its subcomponents with indicators of body fatness. Design: A cross-sectional study of 1292 children aged 9-10 y from 4 distinct regions in Europe (Odense, Denmark; the island of Madeira, Portugal; Oslo; and Tartu, Estonia) was conducted. PA was measured by accelerometry, and indicators of body fatness were the sum of 5 skinfold thicknesses and body mass index (BMI; in kg/m(2)). We examined the associations between PA and body fatness by using general linear models adjusted for potential confounding variables. Results: After adjustment for sex, study location, sexual maturity, birth weight, and parental BMI, time (min/d) spent at moderate and vigorous PA (P = 0.032) and time (min/d) spent at vigorous PA were significantly (P = 0.015) and independently associated with body fatness. Sex, study location, sexual maturity, birth weight, and parental BMI explained 29% (adjusted R-2 = 0.29) of the variation in body fatness. Time spent at vigorous PA explained an additional 0.5%. Children who accumulated <1 h of moderate PAM were significantly fatter than were those who accumulated >2 h/d. Conclusions: The accumulated amount of time spent at moderate and vigorous PA is related to body fatness in children, but this relation is weak; the explained variance was <1%. C1 MRC, Epidemiol Unit, Strangeways Res Labs, Cambridge CB1 8RN, England. Univ Orebro, Dept Phys Educ & Hlth, S-70130 Orebro, Sweden. Univ Tecn Lisboa, Fac Human Movement, Lisbon, Portugal. Univ Tartu, Dept Publ Hlth, EE-50090 Tartu, Estonia. NIDDKD, Diabet & Arthritis Epidemiol Sect, NIH, Phoenix, AZ 85016 USA. Univ Bristol, Dept Exercise & Hlth Sci, Bristol, Avon, England. Middlesex Univ, London Sport Inst, London N17 8HR, England. Univ So Denmark, Inst Sport Sci & Clin Biomech, Odense, Denmark. RP Ekelund, U (reprint author), MRC, Epidemiol Unit, Strangeways Res Labs, Worts Causeway, Cambridge CB1 8RN, England. EM ue202@medschl.cam.ac.uk RI Ekelund, Ulf/A-1046-2008; Brage, Soren/C-6415-2013; Sardinha, Luis/F-2641-2013; Cooper, Ashley/D-9956-2014; Loureiro, Nuno/I-6400-2012 OI Brage, Soren/0000-0002-1265-7355; Sardinha, Luis/0000-0002-6230-6027; Cooper, Ashley/0000-0001-8644-3870; Loureiro, Nuno/0000-0002-1166-3219 NR 44 TC 239 Z9 244 U1 3 U2 30 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2004 VL 80 IS 3 BP 584 EP 590 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 849SR UT WOS:000223561500008 PM 15321796 ER PT J AU Newby, PK Muller, D Tucker, KL AF Newby, PK Muller, D Tucker, KL TI Associations of empirically derived eating patterns with plasma lipid biomarkers: a comparison of factor and cluster analysis methods SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dietary patterns; food patterns; cluster analysis; factor analysis; dietary assessment; cholesterol; triacylglycerols; HDL; LDL ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; DIETARY PATTERNS; RISK-FACTORS; CARDIOVASCULAR-DISEASE; WAIST CIRCUMFERENCE; METABOLIC SYNDROME; FOOD PATTERNS; MEN; WOMEN AB Background: Despite the growing use of patterning methods in nutritional epidemiology, a direct comparison of factor and cluster analysis methods has not been performed. Objective: Our main objective was to compare patterns derived from the cluster and factor analysis procedures with measures of plasma lipids. Design: This cross-sectional study included 459 healthy subjects who participated in the Baltimore Longitudinal Study of Aging and had measures of diet and plasma lipids. Eating patterns were derived by using both factor and cluster analysis methods. Results: In separate multivariate-adjusted regression models, subjects in the healthy cluster had lower plasma triacylglycerols than did those not in the healthy cluster (beta = -15.97; 95% CI: -29.51, -2.43; P < 0.05), and factor 1 (reduced-fat dairy products, fruit, and fiber) was inversely related to plasma triacylglycerols (beta = -7.02 mg/dL for a one-unit increase in z score; 95% CI: -12.92, -1.12; P < 0.05). Those in the alcohol cluster had higher total cholesterol concentrations than did those not in the alcohol cluster (beta = 12.81; 95% CI: 2.74, 22.88; P < 0.05), and factor 2 (protein and alcohol) was also directly associated with total cholesterol (beta = 1.59 for a one-unit increase in z score; 95% CI: 0.55, 2.63; P < 0.05). The multivariate model containing all of the clusters was not significantly different from the model containing all of the factors in predicting each lipid outcome. Conclusion: Our study provides evidence of comparability between cluster and factor analysis methods in relation to plasma lipid biomarkers. C1 Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Newby, PK (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, 711 Washington St,9th Floor, Boston, MA 02111 USA. EM pknewby@post.harvard.edu RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X NR 40 TC 78 Z9 79 U1 1 U2 10 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 SEP PY 2004 VL 80 IS 3 BP 759 EP 767 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 849SR UT WOS:000223561500031 PM 15321819 ER PT J AU Reichert, TA Simonsen, L Sharma, A Pardo, SA Fedson, DS Miller, MA AF Reichert, TA Simonsen, L Sharma, A Pardo, SA Fedson, DS Miller, MA TI Influenza and the winter increase in mortality in the United States, 1959-1999 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE age distribution; cause of death; influenza; models, statistical; mortality; respiratory tract infections; seasons ID RESPIRATORY SYNCYTIAL VIRUS; ACUTE MYOCARDIAL-INFARCTION; CORONARY HEART-DISEASE; SEASONAL-VARIATION; REDUCED RISK; TIME-SERIES; VACCINATION; ASSOCIATION; PNEUMONIA; DEATHS AB In economically developed countries, mortality increases distinctly during winter. Many causes have been suggested, including light-dark cycles, temperature/weather, and infectious agents. The authors analyzed monthly mortality in the United States during the period 1959-1999 for four major disease classes. The authors isolated the seasonal component of mortality by removing trends and standardizing the time series. They evaluated four properties: coincidence in mortality peaks, autocorrelation structure and autoregressive integrated moving average (ARIMA) models, magnitude, and age distribution. Peak months of mortality for ischemic heart disease, cerebrovascular disease, and diabetes mellitus coincided appropriately with peaks in pneumonia and influenza, and coefficients of autocorrelation and ARIMA models were essentially indistinguishable. The magnitude of the seasonal component was highly correlated with traditional measures of excess mortality and was significantly larger in seasons dominated by influenza A(H2N2) and A(H3N2) viruses than in seasons dominated by A(H1N1) or B viruses. There was an age shift in mortality during and after the 1968/69 pandemic in each disease class, with features specific to influenza A(H3N2). These findings suggest that the cause of the winter increase in US mortality is singular and probably influenza. Weather and other factors may determine the timing and modulate the magnitude of the winter-season increase in mortality, but the primary determinant appears to be the influenza virus. C1 Entropy Res Inst, Upper Saddle River, NJ 07458 USA. NIAID, Bethesda, MD 20892 USA. Vyteris Inc, Fair Lawn, NJ USA. Becton Dickinson & Co Inc, Franklin Lakes, NJ USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Reichert, TA (reprint author), Entropy Res Inst, 262 W Saddle River Rd, Upper Saddle River, NJ 07458 USA. EM treichert@entropylimited.com OI Simonsen, Lone/0000-0003-1535-8526 NR 47 TC 222 Z9 229 U1 2 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2004 VL 160 IS 5 BP 492 EP 502 DI 10.1093/aje/kwh227 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 852YE UT WOS:000223791900011 PM 15321847 ER PT J AU Lebowitz, BD Evans, JD AF Lebowitz, BD Evans, JD TI Is Alzheimer disease a mental disorder? SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID DIAGNOSTIC-CRITERIA C1 NIMH, Geriatr Treatment & Prevent Intervent Res Branch, Bethesda, MD 20892 USA. RP Lebowitz, BD (reprint author), NIMH, Geriatr Treatment & Prevent Intervent Res Branch, 6001 Execut Blvd,Room 7160,MSC 9630, Bethesda, MD 20892 USA. EM blebowit@mail.nih.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SEP-OCT PY 2004 VL 12 IS 5 BP 443 EP 445 DI 10.1176/appi.ajgp.12.5.443 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 851LD UT WOS:000223685700001 PM 15353381 ER PT J AU Talbot, NL Duberstein, PR Cox, C Denning, D Conwell, Y AF Talbot, NL Duberstein, PR Cox, C Denning, D Conwell, Y TI Preliminary report on childhood sexual abuse, suicidal ideation, and suicide attempts among middle-aged and older depressed women SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article AB Objective: Authors examined the relationship between childhood sexual abuse histories and suicidal ideation and behavior among depressed women age 50 years and older Methods: After admission to a psychiatric unit, participants were administered the Structured Clinical Interview for DSM-III-R and measures of suicidal ideation and behavior. Results: Women who reported abuse histories were more likely to report suicidal ideation at the time of hospitalization and a history of multiple suicide attempts. Conclusions: These preliminary findings underscore the need for more study of how childhood abuse amplifies risk for suicidal ideation and behavior among women across the life course. C1 Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. NICHHD, Bethesda, MD 20892 USA. RP Talbot, NL (reprint author), Univ Rochester, Sch Med & Dent, 300 Crittenden Blvd, Rochester, NY 14642 USA. EM Nancy_Talbot@URMC.Rochester.edu FU NIMH NIH HHS [K23-MH064528, R01-MH51201, T32-MH18911] NR 9 TC 11 Z9 12 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SEP-OCT PY 2004 VL 12 IS 5 BP 536 EP 538 DI 10.1176/appi.ajgp.12.5.536 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 851LD UT WOS:000223685700014 PM 15353394 ER PT J AU Abroms, LC Fagan, P Eisenberg, ME Lee, HSH Remba, N Sorensen, G AF Abroms, LC Fagan, P Eisenberg, ME Lee, HSH Remba, N Sorensen, G TI The STRENGTH Ezine: An application of e-mail for health promotion in adolescent girls SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE e-mail; Internet; health promotion; adolescents; cancer prevention ID INTERNET; QUESTIONNAIRE; COMMUNICATION; PROGRAM; YOUTH AB Purpose. Few studies have investigated the efficacy of e-mail for promoting behavior change. This study evaluates the participation in and outcomes associated with an e-mail-based health promotion program. Methods. Adolescent girls aged 15 to 17 years were recruited at a shopping mall. Participants with an e-mail address were assigned to the interactive e-mail magazine (Ezine) group (n = 37), whereas those not reporting an e-mail address were assigned to the non-Ezine group (n = 33). Participants in the Ezine group received the health Ezine, which included a quiz and an advice column, on a weekly basis. Results. Results indicate that among the Ezine group, there was a high recall of the Ezine (81.1%), and more than one third of the participants replied to Ezine volumes with quiz answers or an advice question (36.6%). Differences in health behavior change between the Ezine and non-Ezine groups were not significant. Conclusions. E-mails on health-related matters can generate moderate levels of involvement in adolescent girls. Given the widespread use of e-mail, more studies are needed on the effective application of e-mail for health behavior change. C1 George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, Washington, DC 20037 USA. NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Minnesota, Div Gen Pediat & Adolescent Med, Natl Teen Pregnancy Prevent Res Ctr, Minneapolis, MN USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Abroms, LC (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, 2175 K St NW,Room 7015, Washington, DC 20037 USA. EM sphlca@gwumc.edu NR 14 TC 9 Z9 9 U1 1 U2 4 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 2004 VL 19 IS 1 BP 28 EP 32 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 853OR UT WOS:000223837400005 PM 15460098 ER PT J AU Nola, M Pavietic, SZ Weisenburger, DD Smith, LM Bast, MA Vose, JM Armitage, JO AF Nola, M Pavietic, SZ Weisenburger, DD Smith, LM Bast, MA Vose, JM Armitage, JO TI Prognostic factors influencing survival in patients with B-cell small lymphocytic lymphoma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE small lymphocytic lymphoma prognosis; B-cell small lymphocytic lymphoma; B-SLL; prognosis; B-cell chronic lymphocytic leukemia; B-CLL ID NON-HODGKINS-LYMPHOMA; LEUKEMIA AB The term "B-cell small lymphocytic lymphoma" (B-SLL) is generally reserved for patients with lymph node masses that show the histology and immunophenotype of B-cell chronic lymphocytic leukemia (B-CLL) but who are not leukemic. The aim of our study was to define clinical factors that predict for survival in B-SLL. Thirty-nine patients with B-SILL and with less than 5,000 mature-appearing lymphocytes/muL in the peripheral blood were studied. The median follow-up of survivors was 6.6 years (range, 1.6-12.3 years). The estimated 5-year overall survival (OS) and failure-free survival (FFS) were 66% and 23%, respectively. In the univariate analysis, significant adverse predictors for OS were age :60 years, B symptoms, elevated serum LDH, low hemoglobin (<11 g/dL), and high International Prognostic Index (IPI) score (3-5). In multivariate analysis, the IPI score was the only significant predictor of OS. Anemia and B symptoms were additionally predictive of poor OS in patients with low IPI scores. (C) 2004 Wiley-Liss, Inc. C1 Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68182 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Hematol Oncol Sect, Omaha, NE 68182 USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68182 USA. RP Pavietic, SZ (reprint author), NCI, Bldg 10,Room 12S241,10 Ctr Dr, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU NCI NIH HHS [CA36727] NR 15 TC 5 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2004 VL 77 IS 1 BP 31 EP 35 DI 10.1002/ajh.20137 PG 5 WC Hematology SC Hematology GA 848PL UT WOS:000223479500006 PM 15307103 ER PT J AU Stambolian, D Ibay, G Reider, L Dana, D Moy, C Schlifka, M Holmes, T Ciner, E Bailey-Wilson, JE AF Stambolian, D Ibay, G Reider, L Dana, D Moy, C Schlifka, M Holmes, T Ciner, E Bailey-Wilson, JE TI Genomewide linkage scan for myopia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 22q12 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FULL-LENGTH HUMAN; SIB-PAIR LINKAGE; GENETIC-HETEROGENEITY; REFRACTIVE STATUS; OCULAR REFRACTION; HEME OXYGENASE-1; RISK-FACTORS; ADULT-ONSET; LOD SCORES; I ERROR AB Mild/moderate (common) myopia is a very common disorder, with both genetic and environmental influences. The environmental factors are related to near work and can be measured. There are no known genetic loci for common myopia. Our goal is to find evidence for a myopia susceptibility gene causing common myopia. Cycloplegic and manifest refraction were performed on 44 large American families of Ashkenazi Jewish descent, each with at least two affected siblings. Individuals with at least -1.00 diopter or lower in each meridian of both eyes were classified as myopic. Microsatellite genotyping with 387 markers was performed by the Center for Inherited Disease Research. Linkage analyses were conducted with parametric and nonparametric methods by use of 12 different penetrance models. The family-based association test was used for an association scan. A maximum multipoint parametric heterogeneity LOD (HLOD) score of 3.54 was observed at marker D22S685, and nonparametric linkage analyses gave consistent results, with a P value of .0002 at this marker. The parametric multipoint HLOD scores exceeded 3.0 for a 4-cM interval, and significant evidence of genetic heterogeneity was observed. This genomewide scan is the first step toward identifying a gene on chromosome 22 with an influence on common myopia. At present, we are following up our linkage results on chromosome 22 with a dense map of >1,500 single-nucleotide-polymorphism markers for fine mapping and association analyses. Identification of a susceptibility locus in this region may eventually lead to a better understanding of gene-environment interactions in the causation of this complex trait. C1 Univ Penn, Stellar Chance Labs, Dept Ophthalmol, Philadelphia, PA 19104 USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Stambolian, D (reprint author), Univ Penn, Stellar Chance Labs, Dept Ophthalmol, Room 313,422 Curie Blvd, Philadelphia, PA 19104 USA. EM stamboli@mail.med.upenn.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NEI NIH HHS [EY12226, R01 EY012226, U10 EY012226]; NHGRI NIH HHS [N01HG65403] NR 75 TC 90 Z9 94 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2004 VL 75 IS 3 BP 448 EP 459 DI 10.1086/423789 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 845VA UT WOS:000223272200009 PM 15273935 ER PT J AU Bailey-Wilson, JE Amos, CI Pinney, SM Petersen, GM de Andrade, M Wiest, JS Fain, P Schwartz, AG You, M Franklin, W Klein, C Gazdar, A Rothschild, H Mandal, D Coons, T Slusser, J Lee, J Gaba, C Kupert, E Perez, A Zhou, X Zeng, D Liu, Q Zhang, Q Seminara, D Minna, J Anderson, MW AF Bailey-Wilson, JE Amos, CI Pinney, SM Petersen, GM de Andrade, M Wiest, JS Fain, P Schwartz, AG You, M Franklin, W Klein, C Gazdar, A Rothschild, H Mandal, D Coons, T Slusser, J Lee, J Gaba, C Kupert, E Perez, A Zhou, X Zeng, D Liu, Q Zhang, Q Seminara, D Minna, J Anderson, MW TI A major lung cancer susceptibility locus maps to chromosome 6q23-25 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MULTIPOINT LINKAGE ANALYSIS; IN-SITU HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; PROSTATE-CANCER; ALLELIC LOSS; LOD SCORES; MENDELIAN INHERITANCE; SEGREGATION ANALYSIS; BREAST-CANCER; LONG ARM AB Lung cancer is a major cause of death in the United States and other countries. The risk of lung cancer is greatly increased by cigarette smoking and by certain occupational exposures, but familial factors also clearly play a major role. To identify susceptibility genes for familial lung cancer, we conducted a genomewide linkage analysis of 52 extended pedigrees ascertained through probands with lung cancer who had several first-degree relatives with the same disease. Multipoint linkage analysis, under a simple autosomal dominant model, of all 52 families with three or more individuals affected by lung, throat, or laryngeal cancer, yielded a maximum heterogeneity LOD score (HLOD) of 2.79 at 155 cM on chromosome 6q (marker D6S2436). A subset of 38 pedigrees with four or more affected individuals yielded a multipoint HLOD of 3.47 at 155 cM. Analysis of a further subset of 23 multigenerational pedigrees with five or more affected individuals yielded a multipoint HLOD score of 4.26 at the same position. The 14 families with only three affected relatives yielded negative LOD scores in this region. A predivided samples test for heterogeneity comparing the LOD scores from the 23 multigenerational families with those from the remaining families was significant (P=.007). The 1-HLOD multipoint support interval from the multigenerational families extends from C6S1848 at 146 cM to 164 cM near D6S1035, overlapping a genomic region that is deleted in sporadic lung cancers as well as numerous other cancer types. Parametric linkage and variance-components analysis that incorporated effects of age and personal smoking also supported linkage in this region, but with somewhat diminished support. These results localize a major susceptibility locus influencing lung cancer risk to 6q23-25. C1 Univ Cincinnati, Med Ctr, Dept Environm Hlth, Kettering Lab, Cincinnati, OH 45267 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Colorado, Denver, CO 80202 USA. Karmanos Canc Inst, Detroit, MI USA. Washington Univ, St Louis, MO USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Saccomanno Res Inst, Grand Junction, CO USA. Med Coll Ohio, Toledo, OH 43699 USA. RP Anderson, MW (reprint author), Univ Cincinnati, Med Ctr, Dept Environm Hlth, Kettering Lab, ML-56,3223 Eden Ave, Cincinnati, OH 45267 USA. EM andermw@ucmail.uc.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCI NIH HHS [N01 CN065064, P50 CA058184, P50 CA070907, R01 CA060691, R01 CA087895, R01 CA60691, R01 CA637000, R01 CA87895, U01 CA076293, U01 CA76293]; NCRR NIH HHS [P41 RR003655, RR03655]; NHGRI NIH HHS [N01HG65403]; NHLBI NIH HHS [R01 HL 71197]; NIEHS NIH HHS [P30 ES006096, P30-ES06096]; PHS HHS [P50 058187] NR 88 TC 150 Z9 157 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 2004 VL 75 IS 3 BP 460 EP 474 DI 10.1086/423857 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 845VA UT WOS:000223272200010 PM 15272417 ER PT J AU Horner, RD Salazar, W Geiger, HJ Bullock, K Corbie-Smith, G Cornog, M Flores, G AF Horner, RD Salazar, W Geiger, HJ Bullock, K Corbie-Smith, G Cornog, M Flores, G CA Working Grp Changing Hlth Care Pr TI Changing healthcare professionals' behaviors to eliminate disparities in healthcare: What do we know? How might we proceed? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-VETERANS-AFFAIRS; RACIAL-DIFFERENCES; MEDICAL-SCHOOLS; REVASCULARIZATION PROCEDURES; CAROTID-ENDARTERECTOMY; RENAL-TRANSPLANTATION; EDUCATIONAL OUTREACH; CULTURAL COMPETENCE; PRACTICE GUIDELINES AB The patient-healthcare provider communication process-particularly the provider's cultural competency-is increasingly recognized as a key to reducing racial/ethnic disparities in health and healthcare utilization. A working group was formed by the Office of Minority Health, Department of Health and Human Services to identify strategies for improving healthcare providers' cultural competency. This expert panel, one of several working groups called together to explore methods of reducing healthcare disparities, was comprised of individuals from academic medical centers and health professional organizations who were nationally recognized as having expertise in healthcare communication as it relates to diverse populations. During the 2-day conference, the panel identified, from personal experience and knowledge of the literature, key points of intervention and interventions most likely to improve the cross-cultural competency of healthcare providers. Proposed interventions included introduction of cultural competence education before, during, and after clinical training; implementation of certification and accreditation requirements in cross-cultural competence for practicing healthcare providers; use of culturally diverse governing boards for clinical practices; and active promotion of workforce cross-cultural diversity by healthcare organization administrators. For each intervention, methods for implementation were specified. On-going monitoring and evaluation of processes of care using race/ethnicity data were recommended to ensure the programs were functioning. C1 Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Duke Univ, Med Ctr, Durham, NC USA. Med Coll Georgia, Augusta, GA 30912 USA. CUNY, New York, NY 10021 USA. Amer Acad FAmily Phys, Washington, DC USA. Emory Univ, Sch Med, Atlanta, GA USA. Amer Coll Physicians, Philadelphia, PA USA. Boston Univ, Boston, MA 02215 USA. RP Horner, RD (reprint author), Univ Cincinnati, Med Ctr, POB 670840, Cincinnati, OH 45267 USA. EM ronnie.horner@uc.edu NR 64 TC 24 Z9 24 U1 1 U2 7 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2004 VL 10 SI SI BP SP12 EP SP19 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 853DF UT WOS:000223805900004 PM 15481432 ER PT J AU Fiscella, K Klebanoff, MA AF Fiscella, K Klebanoff, MA TI Are racial differences in vaginal pH explained by vaginal flora? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE bacterial vaginosis; African Americans; vaginal pH ID BACTERIAL VAGINOSIS; RISK-FACTORS; GRAM STAIN; PRETERM DELIVERY; PREGNANT-WOMEN; ACQUISITION; ASSOCIATION; BIRTH; ENDOMETRITIS; LACTOBACILLI AB Objectives: The study assessed racial differences in vaginal pH among women without bacterial vaginosis. Study design: Data from the Vaginal Infections and Prematurity (VIP) Study were analyzed. From 1984 to 1989, 13,917 largely low-income women were enrolled during routine prenatal visits from 23 to 26 weeks' gestation. Vaginal Cultures, Gram stains, and pH levels were collected. Comparisons of pH by race were made among women with Gram stain scores < 7 and without trichomoniasis before and after adjustment for actual Gram stain score. Results: Among women with Grain stain scores < 7, there was a modest but statistically significant racial difference in vaginal pH level. However, after controlling for difference in Gram stain score, age, and study site, there was no longer a significant difference in vaginal pH. Conclusion: There is no significant difference in vaginal pH level between black and white women after controlling for differences in confounding factors, particularly vaginal flora. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Rochester, Sch Med & Dent, Dept Family Med & Community & Prevent Med, Rochester, NY 14627 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fiscella, K (reprint author), Univ Rochester, Sch Med & Dent, Dept Family Med & Community & Prevent Med, Rochester, NY 14627 USA. EM Kevin_Fiscella@urmc.rochester.edu FU NIAID NIH HHS [AI-4-2532]; NICHD NIH HHS [HD-3-2833, HD-3-2835, HD-3-2834, HD-3-2836, HD-3-32832] NR 31 TC 15 Z9 18 U1 1 U2 4 PU MOSBY, 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 SEP PY 2004 VL 191 IS 3 BP 747 EP 750 DI 10.1016/j.ajog.2004.03.032 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 860EZ UT WOS:000224326600010 PM 15467534 ER PT J AU Watts, DH Covington, DL Beckerman, K Garcia, P Scheuerle, A Dominguez, K Ross, B Sacks, S Chavers, S Tilson, H AF Watts, DH Covington, DL Beckerman, K Garcia, P Scheuerle, A Dominguez, K Ross, B Sacks, S Chavers, S Tilson, H TI Assessing the risk of birth defects associated with antiretroviral exposure during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LA SP Soc Maternal Fetal Med DE anti-retroviral therapy; preartancy; birth defects; HIV ID THERAPY; TRANSMISSION; COMBINATION; PREVENTION; WOMEN AB Objective: The purpose of this study was to examine teratogenic risk of anti retroviral (A RV) drugs. Study design: The Antiretroviral Pregnancy Registry (APR) monitors prenatal exposures to ARV drugs and pregnancy Outcome through a prospective exposure-registration cohort. Statistical inference uses exact methods for binomial proportions. Results: Through July 2003, APR has monitored 3583 live births exposed to ARK Among 1391 first trimester exposures, there were 38 birth defects, prevalence of 2.7% (95% CI 1.9-3.7), not significantly higher than the CDC's population surveillance rate, 3.1 per 100 live births (95% CI 3.1-3.2). For lamivudine, nelfinavir, nevirapine, stavudinc, and zidovudine, sufficient numbers of live births (>200) following first-trimester exposures have been monitored to allow detection of a 2-fold increase in risk of birth defects overall; no increases have been detected. Conclusion: APR data demonstrate no increase in prevalence of birth defects overall or among women exposed to lamivudine, nelfinavir, nevirapine, stavudine, and zidovudine. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHHD, Bethesda, MD 20892 USA. Inveresk, Wilmington, NC USA. Newark Beth Israel Med Ctr, Newark, NJ 07112 USA. Northwestern Univ, Chicago, IL 60611 USA. Genet Teratol Eth Consulting, Dallas, TX USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. F Hoffmann La Roche Ltd, Nutley, NJ USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ N Carolina, Chapel Hill, NC USA. RP Watts, DH (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH,DHHS, 6100 Execut Blvd,Room 4B11,MSC 7510, Bethesda, MD 20892 USA. EM hw59i@nih.gov NR 16 TC 34 Z9 37 U1 1 U2 4 PU MOSBY, 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 SEP PY 2004 VL 191 IS 3 BP 985 EP 992 DI 10.1016/j.ajog.2004.05.06 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 860EZ UT WOS:000224326600053 PM 15467577 ER PT J AU Lim, WK Chee, SP Sng, I Nussenblatt, RB Chan, CC AF Lim, WK Chee, SP Sng, I Nussenblatt, RB Chan, CC TI Immunopathology of progressive subretinal fibrosis: A variant of sympathetic ophthalmia. SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MULTIFOCAL GRANULOMATOUS CHORIORETINITIS; BLINDNESS AB PURPOSE: We report the immunopathology of progressive subretinal fibrosis, a variant of sympathetic ophthalmia. DESIGN: Brief case report. METHOD: Review of medical record and immunopathology of a chorioretinal biopsy of a 40,year,old man who presented with left total retinal detachment (RD) following multiple vitrectomies in the right eye for RD. Small peripherally retinal holes, snow banks, and inflammatory nodules along the ora serrata were observed during left vitrectomy. Both eyes deteriorated rapidly to blindness with progressive subretinal fibrosis and inflammation over 3 months, and the patient was unresponsive to systemic prednisolone and azathioprine. RESULT: Immunopathology of the chorioretinal biopsy of the right eye revealed aggregates of CD20+ B cells, surrounded by CD3+ T cells. CD68+ macrophages were scattered throughout. CONCLUSION: The rapid clinical course described in this case may be related to the unique immunopathology of rapidly forming peudogerminal centers in the choroids and retina. (C) 2004 by Elsevier Inc. All rights reserved. C1 Singapore Gen Hosp, Singapore Natl Eye Ctr, Dept Pathol, Singapore 0316, Singapore. Natl Univ Singapore, Singapore 117548, Singapore. NEI, NIH, Bethesda, MD 20892 USA. RP Chee, SP (reprint author), 11 3rd Hosp Ave, Singapore 168751, Singapore. EM chee_soon_phaik@snec.com.sg NR 5 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2004 VL 138 IS 3 BP 475 EP 477 DI 10.1016/j.ajo.2004.04.013 PG 3 WC Ophthalmology SC Ophthalmology GA 856SR UT WOS:000224065700023 PM 15364234 ER PT J AU Baumgarth, N Szubin, R Dolganov, GM Watnik, MR Greenspan, D Da Costa, M Palefsky, JM Jordan, R Roederer, M Greenspan, JS AF Baumgarth, N Szubin, R Dolganov, GM Watnik, MR Greenspan, D Da Costa, M Palefsky, JM Jordan, R Roederer, M Greenspan, JS TI Highly tissue substructure-specific effects of human papilloma virus in mucosa of HIV-Infected patients revealed by laser-dissection microscopy-assisted gene expression profiling SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CERVICAL EPITHELIAL-CELLS; NF-KAPPA-B; MICROARRAY ANALYSIS; RISK-FACTORS; ORAL WARTS; KERATINOCYTES; PROLIFERATION; INTERLEUKIN-1-ALPHA AB Human papilloma virus (HPV) causes focal infections of epithelial layers in skin and mucosa. HIV-infected patients on highly active antiretroviral therapy (HAART) appear to be at increased risk of developing HPV-induced oral warts. To identify the mechanisms that allow long-term infection of oral epithelial cells in these patients, we used a combination of laser-dissection microscopy (IDM) and highly sensitive and quantitative, non-biased, two-step multiplex realtime RT-PCR to study pathogen-induced alterations of specific tissue subcompartments. Expression of 166 genes was compared in three distinct epithelial and subepithelial compartments isolated from biopsies of normal mucosa from HIV-infected and non-infected patients and of HPV32-induced oral warts from HIV-infected patients. In contrast to the underlying HIV infection and/or HAART, which did not significantly elaborate tissue substructure-specific effects, changes in oral warts were strongly tissue substructure-specific. HPV 32 seems to establish infection by selectively enhancing epithelial cell growth and differentiation in the stratum spinosum and to evade the immune system by actively suppressing inflammatory responses in adjacent underlying tissues. With this highly sensitive and quantitative method tissue-specific expression of hundreds of genes can be studied simultaneously in a few cells. Because of its large dynamic measurement range it could also become a method of choice to confirm and better quantify results obtained by microarray analysis. C1 Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Stat, Davis, CA 95616 USA. Univ Calif San Francisco, Dept Stomatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, Dept Med, San Francisco, CA 94143 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Baumgarth, N (reprint author), Univ Calif Davis, Ctr Comparat Med, 1 Shields Ave, Davis, CA 95616 USA. EM nbaumgarth@ucdavis.edu RI Roederer, Mario/G-1887-2011; OI Watnik, Mitchell/0000-0002-0487-8430 FU NCI NIH HHS [P01 CA095616]; NHLBI NIH HHS [R01 HL066564, 5 P50 HL66564]; NIAID NIH HHS [1 P01 AI-00-012]; NIDCR NIH HHS [DE-P01 07496, P01 DE016839] NR 33 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2004 VL 165 IS 3 BP 707 EP 718 DI 10.1016/S0002-9440(10)63334-2 PG 12 WC Pathology SC Pathology GA 852CE UT WOS:000223732000001 PM 15331396 ER PT J AU Veeranna Kaji, T Boland, B Odrljin, T Mohan, P Basavarajappa, BS Peterhoff, C Cataldo, A Rudnicki, A Amin, N Li, BS Pant, HC Hungund, BL Arancio, O Nixon, RA AF Veeranna Kaji, T Boland, B Odrljin, T Mohan, P Basavarajappa, BS Peterhoff, C Cataldo, A Rudnicki, A Amin, N Li, BS Pant, HC Hungund, BL Arancio, O Nixon, RA TI Calpain mediates calcium-induced activation of the Erk1,2 MAPK pathway and cytoskeletal phosphorylation in neurons - Relevance to Alzheimer's disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NEUTRAL PROTEINASE CALPAIN; HIPPOCAMPAL-NEURONS; CELL-DEATH; NEUROFILAMENT PROTEINS; CORTICAL-NEURONS; MONOCLONAL-ANTIBODY; PYRAMIDAL NEURONS; NEURITE OUTGROWTH; NERVOUS-SYSTEM; ACTIVE-SITE AB Aberrant phosphorylation of the neuronal cytoskeleton is an early pathological event in Alzheimer's disease (AD), but the underlying mechanisms are unclear. Here, we demonstrate in the brains of AD patients that neurofilament hyperphosphorylation in neocortical pyramidal neurons is accompanied by activation of both Erk1,2 and calpain. Using immunochemistry, Western blot analysis, and kinase activity measurements, we show in primary hippocampal and cerebellar granule (CG) neurons that calcium influx activates calpain and Erk1,2 and increases neurofilament phosphorylation on carboxy terminal polypeptide sites known to be modulated by Erk1,2 and to be altered in AD. Blocking Erk1,2 activity either with antisense oligonucleotides to Erk1,2 mRNA sequences or by specifically inhibiting its upstream activating kinase MEK1,2 markedly reduced neurofilament phosphorylation. Calpeptin, a cell-permeable calpain inhibitor, blocked both Erk1,2 activation and neurofilament hyperphosphorylation at concentrations that inhibit calpain-mediated cleavage of brain spectrin. By contrast, inhibiting Erk1,2 with U-0126, a specific inhibitor of Mek1,2, had no appreciable effect on ionomycin-induced calpain activation. These findings demonstrate that, under conditions of calcium injury in neurons, calpains are upstream activators of Erk1,2 signaling and are likely to mediate in part the hyperphosphorylation of neurofillaments and tau seen at early stages of AD as well as the neuron survival-related functions of the MAP kinasepathway. C1 NYU, Nathan S Kline Inst Psychiat Res, Sch Med, Ctr Dementia Res, Orangeburg, NY 10962 USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. New York State Psychiat Inst & Hosp, Div Analyt Psychopharmacol, Orangeburg, NY USA. Mitsubishi Tokyo Pharmaceut Inc, Yokohama, Kanagawa, Japan. McLean Hosp, Belmont, MA 02178 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Nixon, RA (reprint author), NYU, Nathan S Kline Inst Psychiat Res, Sch Med, Ctr Dementia Res, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA. EM Nixon@nki.rfmh.org RI Boland, Barry/D-1235-2010 FU NIA NIH HHS [R37 AG005604, AG05604, R01 AG005604]; PHS HHS [P01A02219] NR 74 TC 25 Z9 25 U1 1 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2004 VL 165 IS 3 BP 795 EP 805 DI 10.1016/S0002-9440(10)63342-1 PG 11 WC Pathology SC Pathology GA 852CE UT WOS:000223732000009 PM 15331404 ER PT J AU Ivanov, SV Ward, JM Tessarollo, L McAreavey, D Sachdev, V Fananapazir, L Banks, MK Morris, N Djurickovic, D Devor-Henneman, DE Wei, MH Alvord, GW Gao, BN Richardson, JA Minna, JD Rogawski, MA Lerman, MI AF Ivanov, SV Ward, JM Tessarollo, L McAreavey, D Sachdev, V Fananapazir, L Banks, MK Morris, N Djurickovic, D Devor-Henneman, DE Wei, MH Alvord, GW Gao, BN Richardson, JA Minna, JD Rogawski, MA Lerman, MI TI Animal model - Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in mice with targeted disruption of the Cacna2d2 gene SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHANNEL ALPHA(2)DELTA SUBUNIT; GATED CA2+ CHANNELS; CALCIUM-CHANNEL; GABAPENTIN-BINDING; RELAY NEURONS; MOUSE; MUTATIONS; EPILEPSY; EXPRESSION; DIVERSITY AB CACNA2D2 is a putative tumor suppressor gene located in the human chromosome 3p21.3 region that shows frequent allelic imbalances in lung, breast, and other cancers. The alpha2delta-2 protein encoded by the gene is a regulatory subunit of voltage-dependent calcium channels and is expressed in brain, heart, and other tissues. Here we report that mice homozygous for targeted disruption of the Cacna2d2 gene exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities. The Cacna2d2(tm1NCIF) null phenotype has much in common with that of Cacna1a mutants, such as cerebellar neuro-degeneration associated with ataxia, seizures, and premature death. A tendency to bradycardia and limited response of null mutants to isoflurane implicate alpha2delta-2 in sympathetic regulation of cardiac function. in summary, our findings provide genetic evidence that the alpha2delta-2 subunit serves in vivo as a component of P/Q-type calcium channels, is indispensable for the central nervous system function, and may be involved in hereditary cerebellar ataxias and epileptic disorders in humans. C1 NCI, Basic Res Program, Frederick, MD 21702 USA. NCI, Lab Anim Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. NCI, Immunobiol Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Neural Dev Sect, Comp & Stat Serv, Ctr Canc Res, Frederick, MD 21702 USA. NHLBI, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHLBI, Clin Electrophysiol & Inherited Heart Dis Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. RP Ivanov, SV (reprint author), NCI, Basic Res Program, Bldg 560,POB B, Frederick, MD 21702 USA. EM ivanov@mail.ncifcrf.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 50 TC 35 Z9 39 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2004 VL 165 IS 3 BP 1007 EP 1018 DI 10.1016/S0002-9440(10)63362-7 PG 12 WC Pathology SC Pathology GA 852CE UT WOS:000223732000029 PM 15331424 ER PT J AU Decking, UKM Pai, VM Bennett, E Taylor, JL Fingas, CD Zanger, K Wen, H Balaban, RS AF Decking, UKM Pai, VM Bennett, E Taylor, JL Fingas, CD Zanger, K Wen, H Balaban, RS TI High-resolution imaging reveals a limit in spatial resolution of blood flow measurements by microspheres SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial perfusion; microscopy; fluorescence; magnetic resonance; iron oxide particle ID REGIONAL MYOCARDIAL FLOWS; RADIOACTIVE MICROSPHERES; HETEROGENEITY; HEART; DEPOSITIONS; ADENOSINE AB Density of 15-mum microspheres after left atrial application is the standard measure of regional perfusion. In the heart, substantial differences in microsphere density are seen at spatial resolutions <5 ml, implying perfusion heterogeneity. Microsphere deposition imaging permits a superior evaluation of the distribution pattern. Therefore, fluorescent microspheres (FMS) were applied, FMS deposition in the canine heart was imaged by epifluorescence microscopy in vitro, and the patterns were observed compared with MR images of iron oxide microspheres (IMS) obtained in vivo and in vitro. FMS deposition in myocardial slices revealed the following: 1) a nonrandom distribution, with sequentially applied FMS of different color stacked within the same vessel, 2) general FMS clustering, and 3) rather large areas devoid of FMS (n = 3). This pattern was also seen in reconstructed three-dimensional images (<1 nl resolution) of FMS distribution ( n = 4). Surprisingly, the deposition pattern of sequentially applied FMS remained virtually identical over 3 days. Augmenting flow by intracoronary adenosine ( >2 muM) enhanced local microsphere density, but did not alter the deposition pattern ( n = 3). The nonrandom, temporally stable pattern was quantitatively confirmed by a three-dimensional intermicrosphere distance analysis of sequentially applied FMS. T-2-weighted short-axis MR images (2-mul resolution) of IMS revealed similar patterns in vivo and in vitro ( n = 6), as seen with FMS. The observed temporally stable microsphere patterns are not consistent with the notion that microsphere deposition is solely governed by blood flow. We propose that at high spatial resolution (<2 μl) structural aspects of the vascular network dominate microsphere distribution, resulting in the organized patterns observed. C1 Univ Dusseldorf, Dept Cardiovasc Physiol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Inst Anat 2, D-40225 Dusseldorf, Germany. NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA. RP Decking, UKM (reprint author), Univ Dusseldorf, Dept Cardiovasc Physiol, Univ Str,Bldg 22-03, D-40225 Dusseldorf, Germany. EM decking@uni-duesseldorf.de RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 NR 28 TC 24 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2004 VL 287 IS 3 BP H1132 EP H1140 DI 10.1152/ajpheart.00119.2004 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 847MZ UT WOS:000223398600018 PM 15117718 ER PT J AU Wan, RQ Camandola, S Mattson, MP AF Wan, RQ Camandola, S Mattson, MP TI Dietary supplementation with 2-deoxy-D-glucose improves cardiovascular and neuroendocrine stress adaptation in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE blood pressure; diabetes; glucocorticoids; heart rate; insulin resistance; preconditioning ID INSULIN-RESISTANCE SYNDROME; CALORIC RESTRICTION; GLUCOSE-METABOLISM; NEUROTROPHIC FACTOR; EXERCISE; MICE; DISEASE; HYPERTENSION; SENSITIVITY; MECHANISMS AB Dietary restriction and physical exercise can enhance stress resistance and reduce the risk of cardiovascular disease. We investigated the effects of dietary supplementation with 2-deoxy-D-glucose (2-DG), a glucose analog that limits glucose availability at the cellular level, on cardiovascular and neuroendocrine responses to stress in rats. Young adult male Sprague-Dawley rats were implanted with telemetry probes to monitor blood pressure ( BP), heart rate, body temperature, and body movements. These variables were measured at designated times during a 6-mo period in rats fed control and 2-DG-supplemented (0.4% 2-DG, fed ad libitum on a schedule of 2 days on the diet and 1 day off the diet) diets during unperturbed conditions and during and after immobilization stress or cold-water swim stress. Rats fed the 2-DG diet exhibited significant reductions in resting BP, attenuated BP responses during stress, and accelerated recovery to baseline after stress. Plasma concentrations of ACTH and corticosterone were elevated under nonstress conditions in rats fed the 2-DG diet and exhibited differential responses to single ( enhanced response) and multiple ( reduced response) stress sessions compared with rats fed control rat chow ad libitum. The 2-DG diet improved glucose metabolism, as indicated by decreased concentrations of blood glucose and insulin under nonstress conditions, but glucose and insulin responses to stress were maintained. We conclude that improvements in some cardiovascular risk factors and stress adaptation in rats maintained on a 2-DG-supplemented diet are associated with reduced neuroendocrine responses to the stressors. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, GRC 4F01,5600 Nathan Schock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 35 TC 23 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2004 VL 287 IS 3 BP H1186 EP H1193 DI 10.1152/ajpheart.00932.2003 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 847MZ UT WOS:000223398600025 PM 15317676 ER PT J AU Breen, CM Sykes, DB Baehr, C Fricker, G Miller, DS AF Breen, CM Sykes, DB Baehr, C Fricker, G Miller, DS TI Fluorescein-methotrexate transport in rat choroid plexus analyzed using confocal microscopy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE image analysis; xenobiotic transport ID ORGANIC ANION TRANSPORT; CEREBROSPINAL-FLUID; ACTIVE-TRANSPORT; EXPRESSION; BRAIN; EPITHELIUM; MEMBRANE; SLC22A8; BARRIER; EFFLUX AB One function of the vertebrate choroid plexus (CP) is removal of potentially toxic metabolites and xenobiotics from cerebrospinal fluid (CSF) to blood for subsequent excretion in urine and bile. We have used confocal microscopy and quantitative image analysis to follow transport of the large organic anion fluorescein-methotrexate (FL-MTX) from bath ( CSF side) to blood vessels in intact rat CP and found concentrative transport from CSF to blood. With 2 muM FL-MTX in the bath, steady-state fluorescence in the subepithelium and vascular spaces exceeded bath levels by 5- to 10-fold, but fluorescence in epithelial cells was below bath levels. FL-MTX accumulation in subepithelium and vascular spaces was reduced by NaCN, Na removal, and by other organic anions, e. g., MTX, probenecid, and estrone sulfate. Increasing medium K 10-fold had no effect. None of these treatments affected cellular accumulation. However, two observations indicated that apical FL-MTX uptake was indeed mediated: first, cellular accumulation was a saturable function of medium substrate concentration; and second, digoxin and MK-571 reduced FL-MTX accumulation in the subepithelial/vascular spaces but also increased cellular accumulation severalfold. In the presence of digoxin and MK-571, cellular accumulation was concentrative, specific, and Na dependent. Thus transepithelial FL-MTX transport involved the following two mediated steps: Na-dependent uptake at the apical membrane and electroneutral efflux at the basolateral membrane, possibly on Oatp2 and Mrp1. C1 NIEHS, LPC, NIH, Res Triangle Pk, NC 27709 USA. Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany. RP Miller, DS (reprint author), NIEHS, LPC, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov NR 24 TC 13 Z9 13 U1 1 U2 2 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 SEP PY 2004 VL 287 IS 3 BP F562 EP F569 DI 10.1152/ajprenal.00045.2003 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 844RT UT WOS:000223178000026 PM 15126245 ER PT J AU Lovegrove, AS Sun, JH Gould, KA Lubahn, DB Korach, KS Lane, PH AF Lovegrove, AS Sun, JH Gould, KA Lubahn, DB Korach, KS Lane, PH TI Estrogen receptor alpha-mediated events promote sex-specific diabetic glomerular hypertrophy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CA SP Amer Soc Nephrol DE transforming growth factor-beta; streptozotocin; mouse; genetically altered ID RENAL TRANSFORMING GROWTH-FACTOR-BETA-1; ER-ALPHA; TISSUE DISTRIBUTION; GENE-EXPRESSION; KIDNEY-DISEASE; NULL MICE; TGF-BETA; GROWTH; VOLUME; GENDER AB Sex differences in the incidence and progression of renal diseases suggest a protective role for estrogen. This study examined the role of estrogen receptor alpha (ERalpha)-mediated events in normal and diabetic renal and glomerular growth. Wild-type and ERalpha-null mice (ERKO) were observed over 2 wk of streptozocin-induced diabetes. Blood glucose was monitored, and insulin was given daily to maintain levels of 250 - 350 mg/dl. Body weight, kidney weight, glucose, insulin, renal transforming growth factor-beta(1), and glomerular area were examined for effects of sex, genotype, and diabetes. Genotype had no effect on glomerular or renal size in male mice regardless of metabolic state. Nondiabetic female ERKO mice had kidney weights approaching those of wild-type males and much greater than those of wild-type females (0.15 +/- 0.04 vs. 0.11 +/- 0.04 g; P < 0.001). When only diabetic mice were studied, sex and/or genotype showed no effect on renal weight. Diabetic female ERKO mice had smaller glomerular areas than wild types ( 2,799 +/- 159 vs. 3,409 +/- 187 mu m(2); P = 0.01). Glomerular areas were similar in diabetic wild-type and ERKO males (3,020 +/- 199 vs. 3,406 +/- 176 mu m(2)). Transforming growth factor-beta(1) levels, expressed as picograms per milligram total protein, were similar in diabetic wild-type and ERKO males (1.0 +/- 0.6 vs. 0.9 +/- 0.6). In diabetic females, wild types had significantly higher levels of this growth factor than ERKO mice ( 3.8 +/- 0.7 vs. 1.1 +/- 0.6; P = 0.005). ER alpha-mediated processes influence normal and diabetic renal and glomerular size, but only in female mice. These data do not support a protective role for ER alpha-mediated events in diabetic nephropathy. C1 Univ Nebraska, Med Ctr, Dept Pediat, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Eppley Res Inst, Omaha, NE 68198 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65211 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Lane, PH (reprint author), Univ Nebraska, Med Ctr, Dept Pediat, 982169 Nebraska Med Ctr, Omaha, NE 68198 USA. EM phlane@unmc.edu NR 38 TC 21 Z9 21 U1 0 U2 2 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 SEP PY 2004 VL 287 IS 3 BP F586 EP F591 DI 10.1152/ajprenal.00414.2003. PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 844RT UT WOS:000223178000029 PM 15149972 ER PT J AU Woodard, GE Li, XH Rosado, JA AF Woodard, GE Li, XH Rosado, JA TI Water deprivation enhances the inhibitory effect of natriuretic peptides on cAMP synthesis in rat renal glomeruli SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE C-type natriuretic peptide; C-atrial natriuretic factor; natriuretic peptide receptor-C ID ADENYLATE-CYCLASE; MOLECULAR-BIOLOGY; FACTOR RECEPTORS; ATRIAL; KIDNEY; PROTEINS; SYSTEM; BIOCHEMISTRY; EXPRESSION; SEQUENCE AB This study investigates the effect of water deprivation on the expression of atrial natiruretic peptide (ANP)(1-28) binding sites in rat kidney. Water deprivation increased the B(max) of glomerular binding sites for ANP(1-28) and C-type natriuretic peptide (CNP)(1-22) without modifying their affinity, an effect that was prevented in the presence of C-atrial natriuretic factor (C-ANF), suggesting that natriuretic peptide receptor-C (NPR-C) binding sites might be enhanced. Our results indicate that ANP(1-28), CNP(1-22), and C-ANF inhibit cAMP synthesis directly stimulated by forskolin or by the physiological agonists histamine and 5-hydroxytryptamine. The inhibitory effect was found to be significantly greater in water-deprived rats than in controls. Our observations suggest that this effect must be attributed to the 67-kDa NPR-C-like protein, because the 67- and 77-kDa NPR-C-like proteins show high and low affinities for CNP(1-22), respectively, and the enhanced inhibitory effect of CNP on cAMP generation in water-deprived rats was detected at subnanomolar concentrations. In addition, using affinity cross-linking studies we have observed that water deprivation increases the expression of the 67-kDa NPR-C-like protein, and HS-142, which binds to NPR-A and the 77-kDa NPR-C-like but not the 67-kDa protein, reduced ligand internalization without affecting cAMP inhibition by ANP(1-28). Finally, we have found that ligand binding to the 67- kDa NPR-C-like protein is reduced by GTPgammaS, suggesting that this receptor is associated with a G protein in renal glomeruli. The enhanced inhibitory role of natriuretic peptides on cAMP synthesis induced by water deprivation may influence glomerular function in the rat kidney. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Univ Extremadura, Dept Physiol, Caceres 10071, Spain. RP Woodard, GE (reprint author), NIDDKD, NIH, Bldg 10,Rm 8C-208,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. EM GeoffreyW@intra.niddk.nih.gov RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 37 TC 5 Z9 6 U1 2 U2 2 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 SEP PY 2004 VL 287 IS 3 BP F418 EP F426 DI 10.1152/ajprenal.00069.2004 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 844RT UT WOS:000223178000009 PM 15126246 ER PT J AU Martin, WJ Iannuzzi, MC Gail, DB Peavy, HH AF Martin, WJ Iannuzzi, MC Gail, DB Peavy, HH TI Future directions in sarcoidosis research - Summary of an NHLBI working group SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE environmental; genetics; granuloma; lung disease; National Institutes of Health (United States) ID INTERSTITIAL LUNG-DISEASE; CORTICOSTEROID-THERAPY; PULMONARY SARCOIDOSIS; AFRICAN-AMERICANS; STAGE-II; SUSCEPTIBILITY; TUBERCULOSIS; INFECTIONS; DEPRESSION; BRITISH AB Sarcoidosis is a systemic granulomatous disease of unknown etiology that primarily affects the lungs. The etiology remains unclear; however, environmental, genetic, ethnic, and familial factors probably modify expression of the disease. As an example, African Americans are at greater risk of mortality and morbidity than are white Americans, and more often have a family history of sarcoidosis. Most patients with sarcoidosis recover spontaneously, but some develop chronic, debilitating disease. Corticosteroids and other drugs, although effective at controlling disease activity, may not influence the overall course of disease. Because of the many uncertainties about the pathogenesis, course, and management of sarcoidosis, the National Heart, Lung, and Blood Institute convened a working group to identify future research directions and opportunities for sarcoidosis. These include developing a tissue bank, using novel methods to identify genetic factors, studying the immunopathogenesis with human tissue and animal models, exploring new approaches to diagnose and manage disease, and, finally, conducting randomized controlled trials to assess new therapies. C1 NHLBI, Div Lung Dis, Rockledge Ctr 2, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Peavy, HH (reprint author), NHLBI, Div Lung Dis, Rockledge Ctr 2, NIH, Suite 10018,6701 Rockledge Dr,MSC 7952, Bethesda, MD 20892 USA. EM peavyh@nih.gov NR 43 TC 38 Z9 39 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2004 VL 170 IS 5 BP 567 EP 571 DI 10.1164/rccm.200308-1073WS PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 850IR UT WOS:000223605000018 PM 15142870 ER PT J AU Hornick, JL Jaffe, ES Fletcher, CDM AF Hornick, JL Jaffe, ES Fletcher, CDM TI Extranodal histiocytic sarcoma - Clinicopathologic analysis of 14 cases of a rare epithelioid malignancy SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE histiocytic sarcoma; true histiocytic lymphoma; anaplastic large cell lymphoma; malignant histiocytosis; soft tissue; gastrointestinal ID LARGE-CELL LYMPHOMAS; GENOTYPIC ANALYSIS; SMALL-INTESTINE; EXPRESSION; NEOPLASMS; ORIGIN; ENTITY; TUMORS; TISSUE; SKIN AB Histiocytic sarcoma is a rare malignant neoplasm that occurs in lymph nodes, skin, and the gastrointestinal tract. Many previously published cases were likely misdiagnosed examples of non-Hodgkin lymphoma. Only small numbers of bona fide examples exist in the world literature; cases arising primarily at extranodal sites are not well described and often seem to go unrecognized. To characterize these tumors further, 14 extranodal histiocytic sarcomas were analyzed. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring hospitals. Eight patients were female and 6 male (median age, 55 years; range, 15-89 years). All patients presented with a solitary mass, ranging in size from 1.8 to 12 cm (median 6.8 cm). Seven tumors arose in soft tissue (6 lower limb; 1 upper limb), 5 in the gastrointestinal tract (1 involving both stomach and colon, 1 ileum, 2 rectum, 1 anus), 1 in the nasal cavity, and 1 in the lung. Three gastrointestinal tract tumors also involved regional lymph nodes, and I involved the liver. Most cases had infiltrative margins. The tumors were generally composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin, and large nucleoli. Binucleated cells were common, and 6 cases contained tumor giant cells. Mitoses ranged from 1 to 64 per 10 HPF (median 11 per 10 HPF). Necrosis was present in 8 cases. Nearly all tumors showed a striking inflammatory infiltrate, most often of neutrophils or lymphocytes. All cases were reactive for LCA, CD45RO, and CD68 (KP1 and PG-M1); 13 of 14 (93%) expressed CD4,12 of 14 (86%) lysozyme, 8 of 10 (80%) CD31, 7 of 14 (50%) S-100 protein, and 5 of 14 (36%) focal CD1a. Two tumors showed weak, focal cytoplasmic positivity for CD30, and 1 for epithelial membrane antigen. The tumors were negative for ALK-1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB-45, and keratins. Gastrointestinal tract cases were negative for c-kit and desmin. Six patients were treated with postoperative radiation and 7 with chemotherapy (CHOP or ProMACE-MOPP). Follow-up was available for 10 patients (median, 24 months; range, 4 months to 11 years). Two tumors recurred locally, and 5 patients developed distant spread: 3 to lymph nodes, 1 to lung, and 1 to bone. At the last follow-up, 2 patients have died of disseminated disease, 4 and 5 months following initial diagnosis. The patients who died thus far had the largest primary tumors. Histiocytic sarcoma may arise primarily in soft tissue and shows reproducible histologic features, including abundant eosinophilic cytoplasm and a prominent inflammatory infiltrate. Metastatic carcinoma, metastatic melanoma, and large cell non-Hodgkin lymphomas should be excluded by immunohistochemistry. Histiocytic sarcoma has the potential for an aggressive clinical course, most often with lymph node involvement. However, a subset of cases presenting with clinically localized disease have a favorable long-term outcome. Tumor size may be a prognostic factor. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Fletcher, CDM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM cfletcher@partners.org NR 38 TC 112 Z9 124 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2004 VL 28 IS 9 BP 1133 EP 1144 DI 10.1097/01.pas.0000131541.95394.23 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 849RT UT WOS:000223559000002 PM 15316312 ER PT J AU Klote, MM Agodoa, LY Abbott, K AF Klote, MM Agodoa, LY Abbott, K TI Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998-2000 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Anergy; infection incidence; Mycobacterium tuberculosis; PPD; renal transplant; systemic lupus erythematosus ID HEMODIALYSIS-PATIENTS; RECIPIENTS; RIFAMPIN; CYCLOSPORINE; PREVALENCE; MORTALITY; ANERGY AB The incidence, risk factors, and prognosis for Mycobacterium tuberculosis (MTB) infection have not been reported in a national population of renal transplant recipients. We performed a retrospective cohort study of 15 870 Medicare patients who received renal transplants from January 1 1998 to July 31 2000. Cox regression analysis derived adjusted hazard ratios (AHR) for factors associated with a diagnosis of MTB infection (by Medicare Institutional Claims) and the association of MTB infection with survival. There were 66 renal transplant recipients diagnosed with tuberculosis infection after transplant (2.5 cases per 1000 person years at risk, with some falling off of cases over time). The most common diagnosis was pulmonary TB (41 cases). In Cox regression analysis, only systemic lupus erythematosus (SLE) was independently associated with TB. Mortality after TB was diagnosed was 23% at 1 year, which was significantly higher than in renal transplant recipients without TB (AHR, 4.13, 95% CI, 2.21, 7.71, p < 0.001). Although uncommon, MTB infection is associated with a substantially increased risk of mortality after renal transplantation. High-risk groups, particularly those with SLE prior to transplant, might benefit from intensified screening. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Med, Washington, DC 20307 USA. NIDDK, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. RP Abbott, K (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 29 TC 30 Z9 33 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2004 VL 4 IS 9 BP 1523 EP 1528 DI 10.1111/j.1600-6143.2004.00545.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 845ZJ UT WOS:000223283900017 PM 15307841 ER PT J AU Molina-Cruz, A De Merida, AMP Mills, K Rodriguez, F Schoua, C Yurrita, MM Molina, E Palmieri, M Black, WC AF Molina-Cruz, A De Merida, AMP Mills, K Rodriguez, F Schoua, C Yurrita, MM Molina, E Palmieri, M Black, WC TI Gene flow among Anopheles albimanus populations in Central America, South America, and the Caribbean assessed by microsatellites and mitochondrial DNA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MALARIA VECTORS; NATURAL-POPULATIONS; AFRICA; DIFFERENTIATION; DISTANCE; GAMBIAE; NUMBER; LOCI AB Gene flow was examined among Anopheles albimanus populations from Cuba, Mexico, Guatemala, El Salvador, Nicaragua, Costa Rica, Panama, Colombia, and Venezuela by examining variation at four microsatellite (MS) loci and a mitochondrial DNA (mtDNA) marker. There was little variation among Central American populations and weak isolation by distance was only observed with the MS loci. There was moderate to large variation between Central and South American populations, suggesting a barrier to gene flow between Central and South America. However, Panamanian and Pacific Costa Rican populations differed with respect to western Central America, suggesting that there may be another barrier within Central America. There was small to moderate variation among Caribbean and continental populations. Phylogenctic and diversity analyses of mtDNA indicate that more ancestral and diverse haplotypes were present in the Caribbean population, suggesting that current continental An. albimanus populations may have originated from the Caribbean. C1 NIAID, Lab Malaria & Vectoe Res, NIH, Rockville, MD 20852 USA. Univ Valle Guatemale, Med Entomol Res & Training Unit, Guatemala City 01901, Guatemala. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Molina-Cruz, A (reprint author), NIAID, Lab Malaria & Vectoe Res, NIH, Twinbrook 3,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM amolina-cruz@niaid.nih.gov; amolinac@uvg.edu.gt; web4@cvmbs.colostate.edu NR 33 TC 34 Z9 36 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2004 VL 71 IS 3 BP 350 EP 359 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 854KM UT WOS:000223901600017 PM 15381818 ER PT J AU Abu-Elyazeed, RR Wierzba, TF Frenck, RW Putnam, SD Rao, MR Savarino, SJ Kamal, KA Peruski, LF Messih, IAAE El-Alkamy, SA Naficy, AB Clemens, JD AF Abu-Elyazeed, RR Wierzba, TF Frenck, RW Putnam, SD Rao, MR Savarino, SJ Kamal, KA Peruski, LF Messih, IAAE El-Alkamy, SA Naficy, AB Clemens, JD TI Epidemiology of Shigella-associated diarrhea in rural Egyptian children SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID DAY-CARE-CENTERS; BLOODY DIARRHEA; ANTIBIOTIC-RESISTANCE; RISK-FACTOR; ENTEROPATHOGENS; SUSCEPTIBILITY; INFECTIONS; PERSISTENT; POPULATION; COMMUNITY AB During the period from February 1995 to February 1998, the epidemiology of Shigella diarrhea was studied among children less than three years of age residing in Egypt's Nile Delta. Children were visited twice a week and a stool sample was collected from any of them with diarrhea. The incidence of Shigella -associated diarrhea was 0.2 episodes/ child-year, with S. flexneri being the most common serogroup isolated (55% of Shigella episodes). Younger age and the warm months increased the risk of developing Shigella- associated diarrhea, while breastfeeding was protective. Children with Shigella were ill for a mean of four days and passed a mean of six stools per day. Common symptoms included fever (35 %), vomiting (19 %), and dehydration (16 %). Dysentery, however, was unusual, occurring in only 11 % of the cases. In conclusion, Shigella- associated diarrhea remains relatively common in Egyptian children and supports the need for additional control measures including vaccine development. C1 USN, Med Res Unit 3, Cairo, Egypt. USN, Med Res Unit 2, Jakarta, Indonesia. NICHHD, NIH, Bethesda, MD 20892 USA. USN, Med Res Ctr, Silver Spring, MD 20910 USA. Indiana Univ, Sch Med, Gary, IN 46408 USA. Egyptian Minist Hlth & Populat, Abu Homos Field Res & Training Ctr, Beheira, Egypt. Int Vaccine Inst, Seoul, South Korea. RP Abu-Elyazeed, RR (reprint author), USN, Med Res Unit 3, Cairo, Egypt. EM frenckr@namru3.org NR 47 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2004 VL 71 IS 3 BP 367 EP 372 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 854KM UT WOS:000223901600020 PM 15381821 ER PT J AU Zanuy, D Gunasekaran, K Ma, BY Tsai, HH Tsai, CJ Nussinov, R AF Zanuy, D Gunasekaran, K Ma, BY Tsai, HH Tsai, CJ Nussinov, R TI Insights into amyloid structural formation and assembly through computational approaches SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE amyloid conformations; prediction of amyloid conformations; bioinformatics; peptide simulations; beta-structures amyloidogenic proteins; Alzheimer's A beta; IAPP; gelsolin ID MOLECULAR-DYNAMICS SIMULATIONS; BETA-SHEET PROTEINS; FIBRIL FORMATION; POLYPEPTIDE IAPP; PRION PROTEIN; SPIDER SILK; PEPTIDE; SEQUENCE; FRAGMENT; BETA(2)-MICROGLOBULIN AB Amyloids are long, insoluble ordered fibers. Due to their insolubility, to date the determination of an amyloid structure with an atomic scale resolution has proven to be a difficult task. Under such circumstances, computational approaches are a preferred option, providing the means to build likely models, test their stabilities and figure out the chemistry of their prevailing interactions. Computational models can be validated by targeted experiments, such as introducing mutations and testing for amyloid formation. Computations further provide vehicles for the comprehension of the mechanisms of amyloid seed formation and oligomer toxicity. Nevertheless, computations face an immense hurdle, the outcome of the time scales involved in amyloid formation and the immense sizes of the systems. In an attempt to overcome these, we adopt a strategy that encompasses (1) bioinformatics studies of native proteins containing beta-sheet structures; (2) simulations of shorter peptides; and finally (3) construction of potential oligomeric models and tests of their stabilities. The results are correlated with experimental data where available. Here, we describe the computational methods in simple terms and present an overview of the results. The systems derive from amyloidogenic, disease-related proteins, including gelsolin, beta(2)-microglobulin, and peptides derived from the prion, Alzheimer's Abeta, IAPP and human calcitonin. Ultimately, obtaining molecular structures should facilitate efforts to therapy and drug design. C1 SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI, Bldg 469,Rm 151, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011; Zanuy, David/G-3930-2014 OI Ma, Buyong/0000-0002-7383-719X; Zanuy, David/0000-0001-7704-2178 FU NCI NIH HHS [N01-CO-12400] NR 63 TC 18 Z9 19 U1 6 U2 10 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD SEP PY 2004 VL 11 IS 3 BP 143 EP 161 DI 10.1080/13506120400000798 PG 19 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 861MP UT WOS:000224421100001 PM 15523917 ER PT J AU Heemskerk, J AF Heemskerk, J TI High throughput drug screening SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article; Proceedings Paper CT Conference on Amyotrophic Lateral Sclerosis Clinical Trials CY JUN 13-15, 2003 CL Westchester, NY SP Muscular Dystrophy Assoc ID DISCOVERY C1 NINDS, Bethesda, MD 20892 USA. RP Heemskerk, J (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 7 TC 9 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD SEP PY 2004 VL 5 SU 1 BP 19 EP 21 DI 10.1080/17434470410019735 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 865VG UT WOS:000224731500005 PM 15512863 ER PT J AU Marler, J AF Marler, J TI Randomized controlled trials SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article; Proceedings Paper CT Conference on Amyotrophic Lateral Sclerosis Clinical Trials CY JUN 13-15, 2003 CL Westchester, NY SP Muscular Dystrophy Assoc C1 NINDS, Bethesda, MD 20892 USA. RP Marler, J (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD SEP PY 2004 VL 5 SU 1 BP 42 EP 42 DI 10.1080/17434470410019933 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 865VG UT WOS:000224731500011 PM 15512869 ER PT J AU Bringans, SD O'Keefe, BR Bray, M Whitehouse, CA Boyd, MR AF Bringans, SD O'Keefe, BR Bray, M Whitehouse, CA Boyd, MR TI Development of a fluorescent microplate assay for determining cyanovirin-N levels in plasma SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE cyanovirin-N (CV-N); HIV; plasma; analysis ID VIRUS-INACTIVATING PROTEIN; GP120; BINDS; CYANOBACTERIUM; GLYCOPROTEINS; TRANSMISSION; INFECTIVITY; CD4 AB A sensitive immunosorbent competition assay was developed for quantitation of the anti-HIV protein cyanovirin-N (CV-N) in plasma using a 96-well plate format and a fluorescent endpoint. The assay is based on the binding of CV-N in plasma to plate-bound anti-CVN antibodies, followed by removal of the plasma and addition of europium-labeled CV-N (Eu3+-CV-N) to compete for the remaining antibody sites. Detection by addition of a dissociative fluorescence enhancement solution and time-resolved fluorescence measurements allowed correlation to the concentration of the native CV-N in plasma. A linear detection range of 1-100 nM (r(2)>0.99) was obtained for CV-N in mouse plasma. This assay was then utilized for analysis of plasma levels of CV-N samples following subcutaneous injection of CV-N into mice. The results of these studies confirmed the reliability and sensitivity of this assay and the feasibility of its use for pharmacokinetic studies in a variety of species. C1 NCI, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21702 USA. USA, Med Res Inst Infect Dis, Div Virol, Frederick, MD 21702 USA. Univ S Alabama, Coll Med, USA Canc Res Inst, Mobile, AL 36688 USA. RP O'Keefe, BR (reprint author), NCI, Mol Targets Dev Program, Ctr Canc Res, Bldg 562,Room 201, Frederick, MD 21702 USA. EM okeefe@dtpax2.ncifcrf.gov NR 16 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2004 VL 380 IS 2 BP 269 EP 274 DI 10.1007/s00216-004-2786-8 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 862ZB UT WOS:000224528900013 PM 15338095 ER PT J AU Salo, PM Jiang, X Johnson, CA Yan, L Avol, EL Gong, J London, SJ AF Salo, PM Jiang, X Johnson, CA Yan, L Avol, EL Gong, J London, SJ TI Indoor allergens, asthma, and asthma-related symptoms among adolescents in Wuhan, China SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE asthma; allergens; children; China; indoor ID RESPIRATORY SYMPTOMS; HAY-FEVER; ENDOTOXIN LEVELS; SCHOOL STUDENTS; CAT ALLERGEN; CHILDREN; EXPOSURE; RISK; HOME; ATOPY AB PURPOSE: Information on indoor allergen exposures among non-Western populations, which have lower prevalence of atopic illness, is scant. We examined whether exposures to common indoor allergens were associated with doctor-diagnosed asthma and asthma-related symptoms among Chinese adolescents. METHODS: A cross-sectional study of 4185 ninth grade students was conducted at 22 randomly selected schools in Wuhan, China. Information on respiratory health and exposures to indoor allergens was obtained by a self-administered questionnaire completed in class. RESULTS: Having animals currently was associated with persistent cough [prevalence odds ratio (POR) = 1.54, 95% confidence interval (CI): 1.21-2.11] and wheeze (POR = 1.41, 95% CI: 1.03-1.94). Early-life exposure to animals was also associated with doctor-diagnosed asthma (POR = 1.95, 95% CI: 1.35-2.82). Associations with respiratory symptoms strengthened with higher levels of exposure and for exposure in both early childhood and in adolescence. Exposure to cockroaches and having mold/water damage in the home contributed especially to wheezing (POR = 2.03, 95% CI: 1.41-2.90 for cockroaches; POR = 2.49, 95% CI: 1.82-3.40 for mold/water damage). CONCLUSIONS: Indoor allergen exposures were positively associated with asthma diagnosis and persistent respiratory symptoms among Chinese adolescents. Neither early-life nor current exposure to animals was protective for asthma or asthma-related symptoms. (C) 2004 Elsevier Inc. All rights reserved. C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Wuhan Publ Hlth & Antiepidem Stn, Wuhan, Hubei Province, Peoples R China. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Wuhan Bur, Wuhan, Hubei Province, Peoples R China. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [P50 CA084735, 1 P50 CA94735-02]; NIEHS NIH HHS [Z01 ES 49019, Z01 ES049019] NR 66 TC 29 Z9 34 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 2004 VL 14 IS 8 BP 543 EP 550 DI 10.1016/j.annepidem.2003.09.015 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 855PT UT WOS:000223986900005 PM 15350953 ER PT J AU Pfeiffer, RM Goldin, LR Chatterjee, N Daugherty, S Hemminki, K Pee, D X, LI Gail, MH AF Pfeiffer, RM Goldin, LR Chatterjee, N Daugherty, S Hemminki, K Pee, D X, LI Gail, MH TI Methods for testing familial aggregation of diseases in population-based samples: Application to Hodgkin lymphoma in Swedish registry data SO ANNALS OF HUMAN GENETICS LA English DT Article DE familial correlation; cluster data; marginal model; bootstrap; non-Hodgkin lymphoma; matched design ID FAILURE TIME DATA; CANCER RISK; PROBANDS; MODELS AB We use data on lymphoma in families of Hodgkin lymphoma (HL) cases from the Swedish Family Cancer Database (Hemminki et al. 2001) to illustrate survival methods for detecting familial aggregation in first degree relatives of case probands compared to first degree relatives of control probands, from registries that permit sampling of all cases. Because more than one case may occur in a given family, the first degree relatives of case probands are not necessarily independent, and we present procedures that allow for such dependence. A bootstrap procedure also accommodates matching of case and control probands by resampling the matching clusters, defined as the combined set of all first degree relatives of the matched case and control probands. Regarding families as independent sampling units leads to inferences based on "sandwich variance estimators" and accounts for dependencies from having more than one proband in a family, but not for matching. We compare these methods in analysis of familial aggregation of HL and also present simulations to compare survival analyses with analyses of binary outcome data. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21205 USA. German Canc Res Ctr, Div Mol Genet Epidemiol, D-69120 Heidelberg, Germany. Informat Management Serv Inc, Rockville, MD 20852 USA. Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden. RP Pfeiffer, RM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8030, Bethesda, MD 20892 USA. EM pfeiffer@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 13 TC 24 Z9 24 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD SEP PY 2004 VL 68 BP 498 EP 508 DI 10.1046/j.1529-8817.2003.00111.x PN 5 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 865EV UT WOS:000224686200009 PM 15469426 ER PT J AU Cookson, MR AF Cookson, MR TI Roles of the proteasome in neurodegenerative disease: Refining the hypothesis SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID MUTANT ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; INHIBITION; AGGREGATION; IMPAIRMENT; EXPRESSION; MECHANISM; DISORDERS; PROTEINS C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2004 VL 56 IS 3 BP 315 EP 316 DI 10.1002/ans.20258 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 851LU UT WOS:000223687400001 PM 15349856 ER PT J AU Hardy, J Langston, JW AF Hardy, J Langston, JW TI How many pathways are there to nigral death? SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ONSET PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; GENE; MUTATIONS; DJ-1; ASSOCIATION; DEMENTIA; DISORDER; FAMILIES C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Parkinsons Inst, Sunnyvale, CA USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RI Hardy, John/C-2451-2009 NR 25 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2004 VL 56 IS 3 BP 316 EP 318 DI 10.1002/ana.20257 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 851LU UT WOS:000223687400002 PM 15349857 ER PT J AU Saif, MW Leitman, SF Cusack, G Horne, M Freifeld, A Venzon, D PremKumar, A Cowan, KH Gress, RE Zujewski, J Kasten-Sportes, C AF Saif, MW Leitman, SF Cusack, G Horne, M Freifeld, A Venzon, D PremKumar, A Cowan, KH Gress, RE Zujewski, J Kasten-Sportes, C TI Thromboembolism following removal of femoral venous apheresis catheters in patients with breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE apheresis; breast cancer; femoral apheresis catheters; malignancy; peripheral blood stem cell transplantation; thromboembolism ID STEM-CELL TRANSPLANTATION; BLOOD PROGENITOR CELLS; VENA-CAVA CATHETERS; ADJUVANT TAMOXIFEN THERAPY; PROTEIN-C; COLLECTION; THROMBOSIS; CHEMOTHERAPY; COMPLICATIONS; EXPERIENCE AB Background: Apheresis catheters have simplified collection of peripheral blood stem cells (PBSC), but may be associated with thrombosis of the instrumented vessels. We performed a retrospective analysis to study the prevalence of thromboembolism associated with the use of femoral apheresis catheters in patients with breast cancer. Patients and methods: Patients were participants in clinical trials of high-dose chemotherapy with autologous PBSC rescue. They underwent mobilization with either high-dose cyclophosphamide (n=21) or cyclophosphamide/paclitaxel (n=64), followed by filgrastim. Double lumen catheters (12 or 13 Fr) were placed in the femoral vein and removed within 12h of the last apheresis procedure. Apheresis was performed using a continuous flow cell separator and ACD-A anticoagulant. Thromboembolism was diagnosed by either venous ultrasonography or ventilation-perfusion scan. Results: Nine of 85 patients (10.6%) undergoing large volume apheresis with use of a femoral catheter developed thromboembolic complications. Pulmonary embolus (PE) was diagnosed in five and femoral vein thrombosis in four patients. Four of the five patients who developed PE were symptomatic; one asymptomatic patient had a pleural-based, wedge-shaped lesion detected on a staging computed tomography scan. The mean number of apheresis procedures was 2.4 (range one to four) and the mean interval between removal of the apheresis catheter and diagnosis of thrombosis was 17.6 days. In contrast, none of 18 patients undergoing apheresis using jugular venous access and none of 54 healthy allogeneic donors undergoing concurrent filgrastim-mobilized PBSC donation (mean 1.7 procedures/donor) using femoral access experienced thromboembolic complications. Conclusions: Thromboembolism following femoral venous catheter placement for PBSC collection in patients with breast cancer may be more common than previously recognized. Healthy PBSC donors are not at the same risk. Onset of symptoms related to thrombosis tended to occur several weeks after catheter removal. This suggests that the physicians not only need to be vigilant during the period of apheresis, but also need to observe patients for thromboembolic complications after the catheter is removed. The long interval between the removal of apheresis catheter and the development of thromboembolism may have a potential impact on prophylactic strategies developed in future, such as the duration of prophylactic anticoagulation. Avoidance of the femoral site in breast cancer patients, and close prospective monitoring after catheter removal, are indicated. C1 NCI, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Saif, MW (reprint author), Univ Alabama, 263 Wallace Tumor Inst,1530 3rd Ave S, Birmingham, AL 35294 USA. EM wasif.saif@ccc.uab.edu RI Venzon, David/B-3078-2008 NR 32 TC 4 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2004 VL 15 IS 9 BP 1366 EP 1372 DI 10.1093/annonc/mdh347 PG 7 WC Oncology SC Oncology GA 853ZD UT WOS:000223868600010 PM 15319243 ER PT J AU Affara, NI Schanbacher, BL Mihm, MJ Cook, AC Pei, P Mallery, SR Trempus, CS Bauer, JA Robertson, FM AF Affara, NI Schanbacher, BL Mihm, MJ Cook, AC Pei, P Mallery, SR Trempus, CS Bauer, JA Robertson, FM TI Activated akt-1 in specific cell populations during multi-stage skin carcinogenesis SO ANTICANCER RESEARCH LA English DT Article DE Akt-1; protein kinase B; inositidylphosphate-3-kinase; IP3-K; multi-stage skin carcinogenesis; epidermal keratinocytes; cell survival; mast cells; papilloma; image analysis ID MYOFIBRILLAR CREATINE-KINASE; PERIPHERAL-BLOOD LEUKOCYTES; KERATINOCYTE STEM-CELLS; TUMOR PROMOTION; GENE-EXPRESSION; MOUSE SKIN; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; HAIR-FOLLICLES; MAST-CELLS AB The goal of the present study was to identify specific populations of cells that contain activated Akt-1, as determined by the presence of phosphorylated Akt at serine 473 (p Akt), during development of skin tumors using a marine multi-stage carcinogenesis model. Nucleated papillomas cells as well as both epidermal and follicular keratinocytes in hyperplastic skin contained increased pAkt compared to skin treated only with acetone or 7, 12 dimethylbenz[a]anthracene (DMBA). Although the numbers of both mast cells and neutrophils were significantly increased in the stroma of papillomas (p<0.0005; p<0.0001, respectively), only mast cells contained pAkt. The amount of total Akt protein was similar regardless of time or treatment group examined. The present results suggest that activation of Akt-1 may provide specific populations of epidermal keratinocytes that develop into skin tumors with the ability to resist terminal differentiation and have enhanced proliferation during multi-stage skin carcinogenesis. In addition, mast cells which contain activated Akt-1 may persist within the stroma of papillomas during skin tumor development and progression through this signaling pathway, thereby contributing to a pro-oxidant and pro-angiogenic microenvironment. C1 Ohio State Univ, Coll Med, Dept Mol Virol, Columbus, OH 43210 USA. Columbus Childrens Res Inst, Ctr Cardiovasc Pharmacol, Columbus, OH 43205 USA. Ohio State Univ, Coll Dent, Dept Oral Maxillofacial Surg Oral Pathol & Period, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NIEHS, Canc Biol Grp, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. RP Robertson, FM (reprint author), Ohio State Univ, Coll Med, Dept Mol Virol, 2184 Graves Hall,333 W 10th Ave, Columbus, OH 43210 USA. EM robertson.48@osu.edu NR 37 TC 7 Z9 7 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5A BP 2773 EP 2781 PG 9 WC Oncology SC Oncology GA 864JL UT WOS:000224629700024 PM 15517884 ER PT J AU Perabo, FGE Wirger, A Kamp, S Lindner, H Schmidt, DH Muller, SC Kohn, EC AF Perabo, FGE Wirger, A Kamp, S Lindner, H Schmidt, DH Muller, SC Kohn, EC TI Carboxyamido-triazole (CAI), a signal transduction inhibitor induces growth inhibition and apoptosis in bladder cancer cells by modulation of bcl-2 SO ANTICANCER RESEARCH LA English DT Article DE bladder cancer; carboxyamido-triazole (CAI); signal transduction inhibition; apoptosis; bcl-2; calcium ID FAS-MEDIATED CYTOTOXICITY; CALCIUM INFLUX INHIBITOR; ENDOPLASMIC-RETICULUM; PROSTATE-CANCER; CA2+ POOL; ANTI-FAS; PHASE-II; THAPSIGARGIN; HOMEOSTASIS; COMBINATION AB Pro- and anti-apoptotic factors and intracellular signaling pathways are targets for therapeutic development of anticancer agents. Carboxyamido-triazole (CAI) is an inhibitor of transmembrane calcium influx and intracellular calcium-requiring signal transduction pathways. The present study investigates the effects of CAI on human transitional cancer cell (TCC) viability and apoptosis, and evaluates whether apoptotic resistance may be overcome pharmacologically. Both well-differentiated (RT4, RT112/grade 1) and poorly-differentiated (T24/grade 3; SUP/grade 4) human TCC lines were shown to express Fas. Upon exposure to agonistic monoclonal Fas antibody, only well-differentiated TCC lines underwent apoptotic cell death. CAI exposure reduced cell viability and caused an at least additive anti-apoptotic effect in combination with the Fas antibody in the Fas-insensitive TCC lines. Under the same conditions under which CAI treatment augmented Fas-mediated apoptosis, it was shown to reduce intracellular bcl-2 quantity. This response to CAI indicates that apoptotic cell death is enhanced by the reduction of bcl-2 protein expression. We suggest that the antitumor effect of CAI is at least partially based on restoring a pathway of apoptosis. It may cause transformation of cell homeostasis that leads to the alteration of apoptotic mechanisms, thus allowing highly malignant tumor cells to re-enter the physiological course of cell elimination. C1 Univ Bonn, Univ Hosp, Dept Urol, D-53105 Bonn, Germany. Med Univ, Dept Urol, D-25362 Lubeck, Germany. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Perabo, FGE (reprint author), POB 1906, D-82309 Starnberg, Germany. EM perabo@lycos.com NR 34 TC 15 Z9 17 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5A BP 2869 EP 2877 PG 9 WC Oncology SC Oncology GA 864JL UT WOS:000224629700030 PM 15517890 ER PT J AU Ratnasinghe, LD Graubard, BI Kahle, L Tangrea, JA Taylor, PR Hawk, E AF Ratnasinghe, LD Graubard, BI Kahle, L Tangrea, JA Taylor, PR Hawk, E TI Aspirin use and mortality from cancer in a prospective cohort study SO ANTICANCER RESEARCH LA English DT Article DE aspirin; NSAIDs; cancer; cardiovascular disease; NHANES; cohort study ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLORECTAL-CANCER; BREAST-CANCER; GASTRIC-CANCER; URINARY-TRACT; NUDE-MICE; RISK; SULINDAC; CHEMOPREVENTION; PREVENTION AB There is evidence that use of aspirin offers several potential health benefits including cancer prevention and cardiovascular disease prevention. The purpose of this study was to assess the association between aspirin use and death from cancer and cardiovascular diseases with a special emphasis on cancer mortality. Materials and Methods: The baseline data for this prospective cohort study were collected in 1971-1975 for the first National Health and Nutrition Examination Study (NHANES I) and 1976-1980 as part of the second NHANES (NHANES II) with mortality follow-up using the National Death Index (NDI) through December 31, 1992. The main analyses were the relative risks of total mortality and cause-specific mortality for persons who used aspirin compared to persons who did not use aspirin adjusted for confounding using Cox proportional hazards. Results: The proportion of aspirin users was lower among cancer cases than non-cases (58% versus 66%) and use of aspirin decreased with age. Consequently, age was a negative confounder attenuating the protective association between aspirin use and cancer and cardiovascular mortality. After adjusting for age, BMI, sex, race, poverty index, education and smoking, we observed a significant association of reduced all cause mortality among all aspirin users (relative risk [RR] = 0.88; 95% confidence interval [CI] 0.85-0.99) and lung cancer mortality among male aspirin users (RR = 0.69; CI 0.49-0.96). However, for women we observed adverse associations between aspirin use and bladder (PR=12.31; CI 2.98-50.80) and brain cancer mortality (RR=3.13; CI 1.09-9.00), although case numbers were small. Conclusion: Aspirin use appears to offer protection from all causes of mortality and lung cancer among men. In women aspirin use is associated with increased risk of bladder and brain cancer. Because of the small number of female bladder (n = 15) and brain (n = 20) cancer cases in this cohort the findings require confirmation. C1 US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. UAMS, Arkansas Canc Res Ctr, Little Rock, AR USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. NCI, Div Canc Prevent, GOCRG, Bethesda, MD USA. NCI, Canc Res Ctr, Bethesda, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Ratnasinghe, LD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM LRatnasinghe@NCTR.FDA.gov NR 43 TC 85 Z9 86 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5B BP 3177 EP 3184 PG 8 WC Oncology SC Oncology GA 864JN UT WOS:000224629900014 PM 15510608 ER PT J AU Chen, W Abnet, CC Wei, WQ Roth, MJ Lu, N Taylor, PR Pan, OJ Luo, XM Dawsey, SM Qiao, YL AF Chen, W Abnet, CC Wei, WQ Roth, MJ Lu, N Taylor, PR Pan, OJ Luo, XM Dawsey, SM Qiao, YL TI Serum markers as predictors of esophageal squamous dysplasia and early cancer SO ANTICANCER RESEARCH LA English DT Article DE esophagus; dysplasia; MMP-9 ID SOLUBLE INTERLEUKIN-2 RECEPTOR; CELL CARCINOMA; GASTRIC-CANCER; P53 ANTIBODIES; TUMOR-MARKER; LUNG-CANCER; LINXIAN; CHINA; RISK AB Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma (ESCC). A primary screening test for ESCC which identified this lesion could lead to a reduction in disease-specific mortality. Materials and Methods: We conducted a population-based screening study in Linzhou, China. All subjects provided blood samples and underwent endoscopy with Lugol's iodine staining and biopsy. We selected a subset of 84 subjects stratified on worst squamous histologic diagnosis in six categories and measured the serum concentrations of potential markers using commercially available ELISA tests for matrix metalloprotease-9, tissue inhibitor of matrix metalloprotease-1, copper/zinc superoxide dismutase, anti-p53 auto-antibodies, and soluble serum interleukin-2 receptor. Results: Serum matrix metalloprotease-9 concentration was significantly different by esophageal squamous dysplasia status with a median (interquartile range) for subjects without dysplasia of 150 ng/ml (80-225) and subjects with dysplasia/early cancer of 97 ng/ml (58-155), p = 0.033), but the maximum sensitivity and specificity were low. The serum concentrations of the other markers tested showed no significant differences by category of worst histologic diagnosis. Conclusion: Serum matrix metalloprotease-9 concentration could contribute to a primary screening test for an ESCC, but is insufficient alone. C1 NCI, Ctr Canc Res, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100037, Peoples R China. RP Abnet, CC (reprint author), NCI, Ctr Canc Res, Canc Prevent Studies Branch, 6116 Execut Blvd, Rm 705, Bethesda, MD 20892 USA. EM qiaoy@public.bta.net.cn RI Qiao, You-Lin/B-4139-2012; OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 18 TC 12 Z9 12 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5B BP 3245 EP 3249 PG 5 WC Oncology SC Oncology GA 864JN UT WOS:000224629900024 PM 15510618 ER PT J AU Aszalos, A AF Aszalos, Adorjan TI ABC TRANSPORTERS: THEIR RELATIONSHIP TO ILLNESSES AND DRUG-DRUG INTERACTIONS SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Aszalos, Adorjan] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5D MA 20 BP 3425 EP 3425 PG 1 WC Oncology SC Oncology GA V80CV UT WOS:000205415300021 ER PT J AU Lennartsson, J Linnekin, D AF Lennartsson, Johan Linnekin, Diana TI SYNERGISTIC GROWTH OF SCF AND GM-CSF INVOLVES KINASE-DEPENDENT AND INDEPENDENT CONTRIBUTIONS FROM C-KIT SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Lennartsson, Johan; Linnekin, Diana] NCI, Basic Res Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. [Lennartsson, Johan] Ludwig Inst Canc Res, Ctr Biomed, S-75124 Uppsala, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5D MA 287 BP 3548 EP 3549 PG 2 WC Oncology SC Oncology GA V80CV UT WOS:000205415300287 ER PT J AU Papadopoulou, MY Bloomer, WD Hollingshead, MG AF Papadopoulou, M. Y. Bloomer, W. D. Hollingshead, Melinda G. TI NLCQ-1 (NSC 709257) IN COMBINATION WITH RADIATION AGAINST HUMAN GLIOMA U251 XENOGRAFTS SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Papadopoulou, M. Y.; Bloomer, W. D.] Evanston NW Healthcare, Dept Radiat Med, Evanston, IL 60201 USA. [Hollingshead, Melinda G.] NCI, Biol Testing Branch, DTP, DCTD,Fairview Ctr, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5D MA 384 BP 3592 EP 3593 PG 2 WC Oncology SC Oncology GA V80CV UT WOS:000205415300384 ER PT J AU Ried, T Ghadimi, BM Grade, M Sommerfeld, K Steinberg, W Habermann, J Auer, G Heselmeyer-Haddad, K AF Ried, Thomas Ghadimi, B. Michael Grade, Marian Sommerfeld, Kathrin Steinberg, Winfried Habermann, Jens Auer, Gert Heselmeyer-Haddad, Kerstin TI GENOMICS IN MOLECULAR PATHOLOGY SO ANTICANCER RESEARCH LA English DT Meeting Abstract C1 [Ried, Thomas; Ghadimi, B. Michael; Grade, Marian; Sommerfeld, Kathrin; Steinberg, Winfried; Habermann, Jens; Auer, Gert; Heselmeyer-Haddad, Kerstin] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2004 VL 24 IS 5D MA 423 BP 3611 EP 3611 PG 1 WC Oncology SC Oncology GA V80CV UT WOS:000205415300423 ER PT J AU Steinbach, WJ Perfect, JR Schell, WA Walsh, TJ Benjamin, DK AF Steinbach, WJ Perfect, JR Schell, WA Walsh, TJ Benjamin, DK TI In vitro analyses, animal models, and 60 clinical cases of invasive Aspergillus terreus infection SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Review ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; REFERENCE MICRODILUTION METHODS; ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; AMPHOTERICIN-B RESISTANCE; STEM-CELL TRANSPLANTS; OF-THE-LITERATURE; PULMONARY ASPERGILLOSIS; IMMUNOCOMPROMISED PATIENTS; FILAMENTOUS FUNGI C1 Duke Univ, Ctr Med, Div Pediat Infect Dis, Durham, NC 27710 USA. Duke Univ, Ctr Med, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Ctr Med, Dept Internal Med, Durham, NC 27710 USA. Duke Clin Res Inst, Durham, NC USA. Pediat Oncol Branch, Immunocompromised Host Sect, NCI, Bethesda, MD USA. RP Steinbach, WJ (reprint author), Duke Univ, Ctr Med, Div Pediat Infect Dis, Box 3499, Durham, NC 27710 USA. EM stein022@mc.duke.edu NR 103 TC 53 Z9 55 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2004 VL 48 IS 9 BP 3217 EP 3225 DI 10.1128/AAC.48.9.3217-3225.2004 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 850PV UT WOS:000223625800001 PM 15328076 ER PT J AU Pies, T Schaper, KJ Leost, M Zaharevitz, DW Gussio, R Meijer, L Kunick, C AF Pies, T Schaper, KJ Leost, M Zaharevitz, DW Gussio, R Meijer, L Kunick, C TI CDK1-inhibitory activity of paullones depends on electronic properties of 9-substituents SO ARCHIV DER PHARMAZIE LA English DT Article DE benzazepinones; cyclin-dependent kinases; inhibitors; quantitative structure-activity relationships; paullones ID ANTICANCER DRUG SCREEN; TUMOR-CELL-LINES; INHIBITORS; KINASES; CANCER; POTENT AB Multiple linear regression analysis was employed in an effort to establish a quantitative structure-activity relationship model for the CDK1-inhibitory activity of a series of 9-substituted paullones. While the electronic properties of the 9-substituents proved to be of high relevance for CDK1 inhibition, both lipophilic and steric parameters could not be included in a meaningful equation for the calculation of biological properties. The equation solely based on the electronic parameter was successfully used for the prediction of the CDK1-inhibitory activity of a small test set comprising novel paullones with sulfur-containing 9-substituents. Among these new derivatives, 2-methoxy-9-methylsulfonylpaullone proved to be superior to the standard alsterpaullone with respect to CDK1 inhibition. C1 Tech Univ Carolo Wilhelmina Braunschweig, Inst Pharmazeut Chem, D-38106 Braunschweig, Germany. Univ Hamburg, Inst Pharm, Hamburg, Germany. Res Ctr Borstel, Borstel, Germany. CNRS, Biol Stn, Cell Cycle Grp, Roscoff, France. NCI, Rockville, MD USA. RP Kunick, C (reprint author), Tech Univ Carolo Wilhelmina Braunschweig, Inst Pharmazeut Chem, Beethovenstr 55, D-38106 Braunschweig, Germany. EM c.kunick@tu-bs.de NR 24 TC 27 Z9 28 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0365-6233 J9 ARCH PHARM JI Arch. Pharm. PD SEP PY 2004 VL 337 IS 9 BP 486 EP 492 DI 10.1002/ardp.200300870 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 857TA UT WOS:000224140000003 PM 15362121 ER PT J AU Yin, JH Haney, L Walk, S Zhou, S Ravichandran, KS Wang, WD AF Yin, JH Haney, L Walk, S Zhou, S Ravichandran, KS Wang, WD TI Nuclear localization of the DOCK180/ELMO complex SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE DOCK180; ELMO; guanine nucleotide exchange factor; molecular complex; nuclear localization ID CHROMATIN-REMODELING COMPLEX; CELL-MIGRATION; CRKII/DOCK180/RAC PATHWAY; CAENORHABDITIS-ELEGANS; SIGNALING PATHWAY; MYOBLAST CITY; PROTEIN; PHAGOCYTOSIS; TRANSLOCATION; ACTIVATION AB DOCK180 protein plays a key role during development, cell motility, and phagocytosis. It forms a complex with another protein ELMO, and this complex acts as a guanine nucleotide exchange factor (GEF) for Rac. However, DOCK180-containing complexes have not been purified by unbiased biochemical approaches, and the nature and subcellular localization of these complexes remain unclear. Here, we show that a large fraction of endogenous DOCK180 is present as a 700kDa nuclear complex with ELMO proteins. In addition, this nuclear DOCK180/ELMO complex has functional Rac-GEF activity. Furthermore, endogenous DOCK180 could be found in complexes with different ELMO isoforms (ELMO1, 2 or 3) in different cell lines, depending on the ELMO isoforms expressed. These studies suggest that DOCK180 may associate with different ELMO proteins to form cell-type specific complexes and may have functions in both the nucleus and the cytoplasm. (C) 2004 Elsevier Inc. All rights reserved. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Univ Virginia, Beirne Carter Ctr Immunol Res, Charlottesville, VA 22908 USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM WangW@grc.nia.nih.gov NR 29 TC 12 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 2004 VL 429 IS 1 BP 23 EP 29 DI 10.1016/j.abb.2004.05.014 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 845XX UT WOS:000223279800003 PM 15288806 ER PT J AU Eberting, CLD Davis, J Puck, JM Holland, SM Turner, ML AF Eberting, CLD Davis, J Puck, JM Holland, SM Turner, ML TI Dermatitis and the newborn rash of hyper-IgE syndrome SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Pediatric-Dermatology CY FEB 05, 2004 CL Washington, DC SP Soc Pediat Dermatol ID PARTY DIAGNOSTIC-CRITERIA; ATOPIC-DERMATITIS; HYPERIMMUNOGLOBULINEMIA-E; RECURRENT-INFECTION; JOBS SYNDROME; SUPERANTIGENS; VALIDATION; PUSTULOSIS; CHILDREN; DISEASE AB Objective: To characterize the dermatitis, the newborn rash, and cutaneous findings in hyper-IgE syndrome, also known as Job's syndrome. Design: Prospective and retrospective evaluation and treatment of cutaneous manifestations in patients with a clinical diagnosis of hyper-IgE syndrome (HIES). Analysis of the newborn rash encountered in this population. Setting: Dermatology clinic at the National Institutes of Health, Bethesda, Md. Patients: Forty-three patients seen in our clinic between January 1998 and August 2003 who had a clinical diagnosis of HIES. Interventions: The UK Working Party's Diagnostic Criteria for Atopic Dermatitis were used to assess for atopic dermatitis in this population. To assess the newborn rash, we performed a retrospective chart review and an inperson or telephone interview of the parent or caregiver of each patient. Results: Twenty-eight (65%) of 43 patients fulfilled the criteria for atopic dermatitis. Thirty-five (8 1%) of 43 patients reported a newborn rash. Eight (19%) of 43 were born with the rash; 23 (53%) of 43 had acquired the rash within 7 days; 32 (74%) of 43 within 14 days; 34 (79%) of 43 within 30 days; and 35 (81%) of 43 had the rash within 35 days of birth. Conclusions: The dermatitis in HIES resembles classic atopic dermatitis but may have distinctive features. A newborn rash is almost always a presenting sign of HIES. After the newborn period, skin findings include retroauricular fissures, external otitis, infected dermatitis of the axillae and groin, folliculitis of the upper back and shoulders, cutaneous abscesses, mucocutaneous candidiasis, and in some patients pitted scarring of the face. C1 NCI, Canc Res Ctr, Dermatol Branch, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. RP Eberting, CLD (reprint author), NCI, Canc Res Ctr, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr,Mail Stop 1908, Bethesda, MD 20892 USA. EM eberting@mail.nih.gov NR 29 TC 40 Z9 46 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 2004 VL 140 IS 9 BP 1119 EP 1125 DI 10.1001/archderm.140.9.1119 PG 7 WC Dermatology SC Dermatology GA 853NT UT WOS:000223835000011 PM 15381553 ER PT J AU Hasin, DS Grant, BF AF Hasin, DS Grant, BF TI The co-occurrence of DSM-IV alcohol abuse in DSM-IV alcohol dependence - Results of the national epidemiologic survey on alcohol and related conditions on heterogeneity that differ by population subgroup SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; SUBSTANCE USE DISORDERS; 5-YEAR CLINICAL COURSE; SAMPLE HEAVY DRINKERS; GENERAL-POPULATION; DRUG MODULES; ICD-10 ALCOHOL; UNITED-STATES; PRIMARY-CARE; PRIME-MD AB Background: In DSM-IV, an alcohol abuse diagnosis is preempted by dependence, although the symptoms of each disorder are different. Consequently, little is known about the extent to which dependence occurs with or without abuse. The distinction is important because of potential heterogeneity in dependence as a phenotype in genetic research, as well as potential underestimation of alcohol dependence when surveys cover dependence symptoms only among those who screen positive for alcohol abuse. Objective: To present the prevalence of DSM-IV alcohol dependence with and without alcohol abuse in national and population subgroups. Design: Face-to-face inter-views. Setting: The United States, including Alaska, Hawaii, and the District of Columbia. Participants: Household and group-quarters residents, 18 years and older, in the National Epidemiologic Survey on Alcohol and Related Conditions (N=42392). Main Outcome Measures: DSM-IV alcohol dependence with and without DSM-IV alcohol abuse, assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule. Results: Among respondents with current alcohol dependence, 33.7% did not additionally meet criteria for abuse (29.0% among men and 46.1% among women). Current dependence without abuse was especially common among minority women (48.5% among African Americans, 55.2% among Hispanics). Among respondents with lifetime diagnoses of dependence, 13.9% did not additionally meet criteria for abuse (10.1% among men, 22.1% among women): proportions were highest among minorities, eg, 29.1% among Hispanic women and 19.2% among Hispanic men. Conclusions: Alcohol abuse does not always accompany alcohol dependence in the general population, especially among women and minorities. Dependence with and without abuse may represent heterogeneous phenotypes for genetic research. Use of alcohol abuse as a screening method for alcohol dependence in large epidermologic studies will differentially underestimate the prevalence of dependence by subgroup, affecting time trend and comorbidity research. Such underestimation may also perpetuate a lack of services for traditionally underserved groups. C1 Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Div Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Bethesda, MD USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,Mail Stop 9304,5635 Fishers Ln, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov FU NIAAA NIH HHS [K05AA00161, R01AA08159] NR 48 TC 136 Z9 137 U1 4 U2 7 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 SEP PY 2004 VL 61 IS 9 BP 891 EP 896 DI 10.1001/archpsyc.61.9.891 PG 6 WC Psychiatry SC Psychiatry GA 851ZY UT WOS:000223726200004 PM 15351767 ER PT J AU Smith, JA Casey, CG Tierney, BC AF Smith, JA Casey, CG Tierney, BC TI The ocular complications of small pox and smallpox immunization SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter C1 NEI, NIH, Bethesda, MD 20892 USA. RP Smith, JA (reprint author), NEI, NIH, 10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. EM smithj@nei.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2004 VL 122 IS 9 BP 1407 EP 1407 DI 10.1001/archopht.122.9.1407-a PG 1 WC Ophthalmology SC Ophthalmology GA 852AB UT WOS:000223726500027 PM 15364730 ER PT J AU Berman, JJ AF Berman, JJ TI Zero-Check: A zero-knowledge protocol for reconciling patient identities across institutions - Reply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter ID CONFIDENTIALITY C1 NIH, Canc Diagnosis Program, DCTD, NCI, Bethesda, MD 20892 USA. RP Berman, JJ (reprint author), NIH, Canc Diagnosis Program, DCTD, NCI, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2004 VL 128 IS 9 BP 954 EP + PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 852AG UT WOS:000223727000002 ER PT J AU Perrin, EM Murphy, ML Casey, JR Pichichero, ME Runyan, DK Miller, WC Swedo, SE AF Perrin, EM Murphy, ML Casey, JR Pichichero, ME Runyan, DK Miller, WC Swedo, SE TI Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children? SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ ID OBSESSIVE-COMPULSIVE DISORDER; RHEUMATIC-FEVER; TOURETTES-SYNDROME; TIC DISORDERS; PANDAS; CHILDHOOD; IDENTIFICATION; HYPOTHESIS; PARENT AB Objective: To determine whether group A beta-hemolytic streptococcal infections increase the risk of developing symptoms characteristic of the diagnosis pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Design: Prospective cohort study. Methods: Children (N = 814) aged 4 to 11 years seen for sore throat or well-child care in a large pediatric practice in Rochester, NY, were enrolled from October 2001 to June 2002 (group A beta-hemolytic streptococcal [GAS] infected, n = 411; GAS uninfected, n = 403, of whom 207 had a sore throat of presumed viral etiology and 196 were well children). Symptomatic children with GAS infection (n = 399) were treated with antibiotics. At baseline and 2 and 12 weeks following baseline, all parents completed a 20-item questionnaire about the presence/ absence of recent PANDAS symptoms in their children, and capable children answered 10 items about worries, obsessions, and compulsions. The relative risk of developing a "mild PANDAS variant" (greater than or equal to 2 new PANDAS symptoms) by illness type (GAS positive, presumed viral, or well child) and by parent and child report was determined and adjusted for potential covariates. Results: By parent report, ill children more frequently manifested several PANDAS symptoms at baseline than well children. However, neither new symptoms nor the risk of developing a mild PANDAS variant developed during the subsequent 12 weeks more commonly in children with GAS infection than in those with presumed viral illness or in well children by parent or child report. Conclusions: Ill children with GAS infection, treated for their GAS infection, were not at increased risk for developing PANDAS symptoms or a mild PANDAS variant compared with children with presumed viral illness or well children. The role of antibiotics in the prevention or treatment of PANDAS as well as the investigation of PANDAS in the asymptomatic, infectious host deserves future research. C1 Univ N Carolina, Div Gen Pediat & Adolescent Med, Dept Pediat, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Social Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Med, Div Infect Dis, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Elmwood Pediat Grp, Rochester, NY USA. Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14627 USA. NIMH, Pediat & Dev Neuropsychiat Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Perrin, EM (reprint author), Univ N Carolina, Div Gen Pediat & Adolescent Med, Dept Pediat, CB 7220,200 Mason Farm Rd,5th Floor, Chapel Hill, NC 27599 USA. EM eliana_perrin@med.unc.edu RI Miller, William/H-4800-2014 OI Miller, William/0000-0002-1934-7827 FU NICHD NIH HHS [K12 HD 01441] NR 31 TC 51 Z9 53 U1 4 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2004 VL 158 IS 9 BP 848 EP 856 DI 10.1001/archpedi.158.9.848 PG 9 WC Pediatrics SC Pediatrics GA 852IW UT WOS:000223750000001 PM 15351749 ER PT J AU Bachrach, CA King, RB AF Bachrach, CA King, RB TI Data sharing and duplication - Is there a problem? SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 NICHHD, Demog & Behav Sci Branch, Bethesda, MD 20892 USA. RP Bachrach, CA (reprint author), NICHHD, Demog & Behav Sci Branch, 6100 Execut Blvd,Rm 8B07,MSC 7510, Bethesda, MD 20892 USA. EM cbachrach@nih.gov NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2004 VL 158 IS 9 BP 931 EP 932 DI 10.1001/archpedi.158.9.931 PG 2 WC Pediatrics SC Pediatrics GA 852IW UT WOS:000223750000015 PM 15351763 ER PT J AU Jeong, JM Lee, J Paik, CH Kim, DK Lee, DS Chung, JK Lee, MC AF Jeong, JM Lee, J Paik, CH Kim, DK Lee, DS Chung, JK Lee, MC TI Site-specific Tc-99m-labeling of antibody using dihydrazinophthalazine (DHZ) conjugation to Fc region of heavy chain SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Article DE Tc-99m; site-specific labeling; radiopharmaceutical; dihydralazine; dihydrazinophthalazine; antibody; bifunctional chelating agent ID IMAGING FOCAL SITES; MONOCLONAL-ANTIBODIES; PEPTIDES; TC-99M; INFECTION; REDUCTION; INVITRO AB The development of an antibody labeling method with Tc-99m is important for cancer imaging. Most bifunctional chelate methods for Tc-99m labeling of antibody incorporate a Tc-99m chelator through a linkage to lysine residue. In the present study, a novel site-specific Tc-99m labeling method at carbohydrate side chain in the Fc region of 2 antibodies (T101 and rabbit antihuman serum albumin antibody (RPAb)) using dihydrazinophthalazine (DHZ) which has 2 hydrazino groups was developed. The antibodies were oxidized with sodium periodate to produce aldehyde on the Fc region. Then, one hydrazine group of DHZ was conjugated with an aldehyde group of antibody through the formation of a hydrazone. The other hydrazine group was used for labeling with Tc-99m. The number of conjugated DHZ was 1.7 per antibody. Tc-99m labeling efficiency was 46-85% for T101 and 67-87% for RPAb. Indirect labeling with DHZ conjugated antibodies showed higher stability than direct labeling with reduced antibodies. High immunoreactivities were conserved for both indirectly and directly labeled antibodies. A biodistribution study found high blood activity related to directly labeled T101 at early time point as well as low liver activity due to indirectly labeled T101 at later time point. However, these findings do not affect practical use. No significantly different biodistribution was observed in the other organs. The research concluded that DHZ can be used as a site-specific bifunctional chelating agent for labeling antibody with Tc-99m. Moreover, Tc-99m labeled antibody via DHZ was found to have excellent chemical and biological properties for nuclear medicine imaging. C1 Seoul Natl Univ, Coll Med, Dept Nucl Med, Seoul 110744, South Korea. Seoul Natl Univ, Coll Med, Inst Canc Res, Seoul 110744, South Korea. Kyungpook Natl Univ, Sch Med, Dept Nucl Med, Taegu 700721, South Korea. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. Ewha Womans Univ, Dept Pharm, Seoul 120750, South Korea. RP Jeong, JM (reprint author), Seoul Natl Univ Hosp, Dept Nucl Med, Seoul 110744, South Korea. EM jmjng@snu.ac.kr RI Jeong, Jae Min/E-2102-2012; Lee, Dong Soo/J-2778-2012 OI Jeong, Jae Min/0000-0003-2611-6020; NR 22 TC 8 Z9 8 U1 2 U2 8 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD SEP PY 2004 VL 27 IS 9 BP 961 EP 967 DI 10.1007/BF02975851 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 857HJ UT WOS:000224106700014 PM 15473668 ER PT J AU Manolio, TA Boerwinkle, E O'Donnell, CJ Wilson, AF AF Manolio, TA Boerwinkle, E O'Donnell, CJ Wilson, AF TI Genetics of ultrasonographic carotid atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE atherosclerosis; genes; human; carotid artery; cardiovascular disease ID INTIMA-MEDIA THICKNESS; ANGIOTENSIN-CONVERTING-ENZYME; APOLIPOPROTEIN-E POLYMORPHISM; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; ARTERIAL-WALL THICKNESS; CORONARY-HEART-DISEASE; NITRIC-OXIDE SYNTHASE; AUSTRIAN STROKE PREVENTION; INDEPENDENT RISK-FACTOR; PREMATURE MYOCARDIAL-INFARCTION AB The search for genes related to the cause of common complex disorders such as cardiovascular disease has been frustrating, partly because of the many factors known to contribute to cardiovascular disease and the potential "distance" of cardiovascular disease as a phenotype from genes and gene products. Linkage and association studies for phenotypes more proximal in the pathway from DNA sequence variation to overt clinical disease, such as ultrasound-defined carotid atherosclerosis, may potentially be more enlightening. Only one genetic variant previously reported to be associated with atherosclerosis or clinically evident cardiovascular disease, matrix metalloproteinase (MMP) 3, has shown consistently positive associations with carotid disease, although it has not been studied widely. Another, PON1 L55M, is weakly associated in subgroups only, and 2, ApoE and MTHFR, are equivocal. Genetic variants reported to be associated with clinical cardiovascular disease show weak or no relationship to carotid atherosclerosis. This may reflect the known inconsistency in associations of genetic variants with clinical cardiovascular disease itself. Alternatively, genetic determinants of ultrasound-defined carotid atherosclerosis may differ from those of clinically manifest cardiovascular disease and may require pursuit through large-scale genomic studies of carotid atherosclerosis as a distinct phenotype. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NHGRI, Inherited Dis Res Branch, Baltimore, MD USA. RP Manolio, TA (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,MSC 7934, Bethesda, MD 20892 USA. EM manolio@nih.gov RI Wilson, Alexander/C-2320-2009 NR 180 TC 49 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2004 VL 24 IS 9 BP 1567 EP 1577 DI 10.1161/01.ATV.0000138789.11433.c1 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 851CW UT WOS:000223664000007 PM 15256397 ER PT J AU Shevach, EM AF Shevach, EM TI Regulatory/suppressor T cells in health and disease SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID INDUCTION; RECEPTOR; FOXP3 C1 NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM EShevach@niaid.nih.gov NR 13 TC 81 Z9 90 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 BP 2721 EP 2724 DI 10.1002/art.20500 PG 4 WC Rheumatology SC Rheumatology GA 853AU UT WOS:000223799200001 PM 15457438 ER PT J AU Wang, B Ma, L Tao, X Lipsky, PE AF Wang, B Ma, L Tao, X Lipsky, PE TI Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NF-KAPPA-B; ETHYL-ACETATE EXTRACT; DNA-BINDING ACTIVITY; SMOOTH-MUSCLE-CELLS; RHEUMATOID-ARTHRITIS; INOS GENE; INTERFERON-GAMMA; EXPRESSION; INDUCTION; PROMOTER AB Objective. The ethyl acetate (EA) extract of Tripterygium wilfiordii Hook F (TWHF) and its major active component, triptolide, have been reported to be effective in the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases. Nitric oxide (NO) has been recognized as an important mediator of inflammation. This study was therefore undertaken to examine the effects of the EA extract and triptolide on the production of NO and inducible NO synthase (iNOS) gene expression and transcription in vivo and in vitro. Methods. Peritoneal macrophages from C57BL/6J mice treated orally with the EA extract of TWHF were assayed for NO production and iNOS messenger RNA (mRNA) expression by reverse transcriptase-polymerase chain reaction. The murine fibroblast cell line NIH3T3 was also assessed for NO production and iNOS mRNA expression, as well as for iNOS promoter activation, Oct-1 nuclear binding capacity, and Oct-1 protein content by transient transfection, electrophoretic mobility shift assay, and immunoblotting, respectively. Results. NO production and iNOS mRNA expression by macrophages from C57BL/6J mice immunized with trinitrophenyl-bovine serum albumin in Freund's complete adjuvant were significantly inhibited by oral administration of the EA extract (52.3% and 59.8% of control, respectively, at one-eighth of the dose that is lethal for 50% of the animals [LD50] and 21.0% and 38.1% of control, respectively, at one-fourth the LD50). Moreover, the EA extract and triptolide significantly inhibited NO production in vitro in activated peritoneal macrophages, which reflected a decreased level of iNOS mRNA. Finally, triptolide inhibited promoter activity of the iNOS gene and induction of the activity of the regulator of iNOS transcription, Oct-1. Conclusion. The EA extract of TWHF and triptolide inhibit transcription of the iNOS gene. This may contribute to the antiinflammatory effects of this traditional herbal remedy. C1 NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Autoimmun Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 9N228, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov OI Wang, Bin/0000-0002-5396-6111 NR 43 TC 52 Z9 62 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 BP 2995 EP 3003 DI 10.1002/art.20459 PG 9 WC Rheumatology SC Rheumatology GA 853AU UT WOS:000223799200033 PM 15457469 ER PT J AU Becker, ML Athreya, BH Rose, CD Brescia, AM Aksentijevich, I Kastner, DL AF Becker, ML Athreya, BH Rose, CD Brescia, AM Aksentijevich, I Kastner, DL TI P46L mutation in tumor necrosis factor receptor-associated periodic syndrome: A clinical description of three African-American patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 duPont Hosp Children, Wilmington, DE USA. NIAMSD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S362 EP S362 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000948 ER PT J AU Bouali, H Cooper, GS Dooley, MA Nietert, PJ Gilkeson, G AF Bouali, H Cooper, GS Dooley, MA Nietert, PJ Gilkeson, G TI -463 myeloperoxidase promoter polymorphism and systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Med Univ S Carolina, Charleston, SC 29425 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S204 EP S204 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000486 ER PT J AU Brenner, M Meng, HC Yarlett, N Remmers, EF Wilder, RL Gulko, PS AF Brenner, M Meng, HC Yarlett, N Remmers, EF Wilder, RL Gulko, PS TI Rats congenic for the chromosome 2 locus Cia10 are significantly protected in pristane-induced arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 N Shore Long Island Jewish Res Inst, Manhasset, NY USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S546 EP S547 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001496 ER PT J AU Brenner, M Remmers, EF Joe, B Meng, HC Yarlett, N Wilder, RL Gulko, PS AF Brenner, M Remmers, EF Joe, B Meng, HC Yarlett, N Wilder, RL Gulko, PS TI Cia5 on rat chromosome 10 contains two pristane-induced arthritis severity regulatory genes. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 N Shore Long Island Jewish Res Inst, Manhasset, NY USA. NIAMS, NIH, Bethesda, MD USA. Med Coll Ohio, Toledo, OH 43699 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S547 EP S547 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001497 ER PT J AU Cannon, GW Remmers, EF Corsi, T Wilder, RL Griffiths, MM AF Cannon, GW Remmers, EF Corsi, T Wilder, RL Griffiths, MM TI Control of arthritis severity during adjuvant-induced arthitis by Aia5 on rat chromosome 10. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. NIAMS, NIH, Bethesda, MD USA. NIAMS, NIH, Gaithersburg, MD USA. Medimmune Inc, Gaithersburg, MD 20878 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S546 EP S546 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001495 ER PT J AU Carlton, VEH Schrodi, SJ Hu, XL Garcia, VE Alexander, HC Chokkalingam, A Huang, QQ Brandon, RC Chang, M Ardlie, KG Catanese, JJ Leong, DU Criswell, LA Seldin, MF Kastner, DL Gregersen, PK Beasley, EM Sninsky, JJ Amos, CI Begovich, AB AF Carlton, VEH Schrodi, SJ Hu, XL Garcia, VE Alexander, HC Chokkalingam, A Huang, QQ Brandon, RC Chang, M Ardlie, KG Catanese, JJ Leong, DU Criswell, LA Seldin, MF Kastner, DL Gregersen, PK Beasley, EM Sninsky, JJ Amos, CI Begovich, AB TI Protein tyrosine phosphatase PTPN22 and rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Celera Diagnost, Alameda, CA USA. Univ Texas, Houston, TX USA. Celera Genom, Rockville, MD USA. Genom Collaborat Inc, Cambridge, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Davis, Davis, CA 95616 USA. NIH, Bethesda, MD 20892 USA. N Shore LIJ Res Inst, Manhasset, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S672 EP S672 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001864 ER PT J AU Casciola-Rosen, L Nagaraju, K Plotz, P Levine, S Caorse, A Rosen, A AF Casciola-Rosen, L Nagaraju, K Plotz, P Levine, S Caorse, A Rosen, A TI Enhanced autoantigen expression in regenerating muscle cells in myositis: A key component underlying the self-sustaining nature of systemic autoimmune disease. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S439 EP S439 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001171 ER PT J AU Colburn, NT Wang, F Tuan, R AF Colburn, NT Wang, F Tuan, R TI An innate response to fracture injury by gamma delta T-cells. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIST, Gaithersburg, MD 20899 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S61 EP S61 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000066 ER PT J AU Cooper, GS Schur, PH Fraser, PA AF Cooper, GS Schur, PH Fraser, PA TI Frequencies of anti-nuclear antibodies (ANA) in a population-based sample of healthy individuals: Possible associations of high titer ANA with occupational exposures. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Inst Environm Sci, Res Triangle Pk, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. CBR, Biomed Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S485 EP S485 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001306 ER PT J AU Dailey, NK Aksentijevich, I Chae, JJ Wesley, R Snyder, C Magalnick, M Watford, WT Gelabert, A Jones, J Pham, TH Hawkins, PN Adams, BS Moore, TL Fuhlbrigge, RC Shaham, B Lovell, DK Jarvis, J Stein, LD Vehe, RK Gardner, G Hannan, W Warren, RW O'Shea, JJ Kastner, DL Goldbach-Mansky, R AF Dailey, NK Aksentijevich, I Chae, JJ Wesley, R Snyder, C Magalnick, M Watford, WT Gelabert, A Jones, J Pham, TH Hawkins, PN Adams, BS Moore, TL Fuhlbrigge, RC Shaham, B Lovell, DK Jarvis, J Stein, LD Vehe, RK Gardner, G Hannan, W Warren, RW O'Shea, JJ Kastner, DL Goldbach-Mansky, R TI Interleukin-1 receptor antagonist anakinra in the treatment of neonatal onset multisystem inflammatory disease. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. RI Hawkins, Philip/C-5573-2008 NR 0 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S440 EP S440 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001175 ER PT J AU Gaffney, PM Grammer, AC He, LS Plenge, RM Graham, RR Nagahawatte, A Ottman, WO Gregersen, PK Altshuler, DM Lipsky, PE Behrens, TW AF Gaffney, PM Grammer, AC He, LS Plenge, RM Graham, RR Nagahawatte, A Ottman, WO Gregersen, PK Altshuler, DM Lipsky, PE Behrens, TW TI Genetic identification and characterization of the CD40 P227A polvmorphism: A gain-of-function polymorphism associated with human SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Minnesota, Minneapolis, MN USA. NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. Whitehead Inst Biomed Res, MIT, Broad Inst, Boston, MA USA. N Shore Long Isl Jewish Res Inst, New York, NY USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S601 EP S602 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001659 ER PT J AU Grammer, AC He, LS Zhang, W Fischer, R Gaffney, P Behrens, T Lipsky, P AF Grammer, AC He, LS Zhang, W Fischer, R Gaffney, P Behrens, T Lipsky, P TI A naturally occurring mutant of CD40 (P227A) in families of patients with systemic lupus erythematosus mediates spontaneous TRAF2 association and activation of NF kappa B and AP1. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Cell Biol Grp B, Autoimmun Branch, NIH, Bethesda, MD USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S258 EP S258 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000644 ER PT J AU Griffiths, MM Cannon, GW Remmers, EF Wilder, RL AF Griffiths, MM Cannon, GW Remmers, EF Wilder, RL TI Mapping candidate genes for autoimmune arthritis using nine new DA-BN QTL-congenic and chromosome substitution rat lines. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 VA, Salt Lake City, UT USA. NIAMS, NIH, Bethesda, MD USA. NIAMS, NIH, Gaithersburg, MD USA. Medimmune Inc, Gaithersburg, MD 20878 USA. Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S546 EP S546 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001494 ER PT J AU Husa, M Watford, W Li, D Muul, L Pesa, M Kanno, Y O'Shea, J AF Husa, M Watford, W Li, D Muul, L Pesa, M Kanno, Y O'Shea, J TI Induction and expression of GRSP1 and cybr proteins in IL-12 stimulated human T-cells SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, Res Scholars Program, HHMI, NIH, Bethesda, MD USA. RI Husa, Matthew/G-4850-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S111 EP S111 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000211 ER PT J AU Kok, MR Lodde, BM van Mello, NM Wang, JH Goldsmith, C Chiorini, JA Baum, BJ Tak, PP AF Kok, MR Lodde, BM van Mello, NM Wang, JH Goldsmith, C Chiorini, JA Baum, BJ Tak, PP TI Disease modifying effects of local tumor necrosis factor alpha receptor gene transfer in a murine model of Sjogren's syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Amsterdam, Dept CIR Ctr, NL-1105 AZ Amsterdam, Netherlands. US Dept HHS, NIDCR, GTTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S445 EP S445 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001189 ER PT J AU Langford, CA Talar-Williams, C McCabe, KE Barron, KS Sneller, MC AF Langford, CA Talar-Williams, C McCabe, KE Barron, KS Sneller, MC TI Disease and treatment related morbidity since the introduction of cyclophosphamide (CYC)-sparing regimens in Wegener's granulomatosis (WG). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S231 EP S231 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000570 ER PT J AU Mamyrova, G O'Hanlon, T Reed, A James-Newton, L Sherry, D Wallace, C Lindsley, C Perez, M Henrickson, M Rivas-Chacon, R Higgins, G Katona, I Olson, J Miller, FW Rider, LG AF Mamyrova, G O'Hanlon, T Reed, A James-Newton, L Sherry, D Wallace, C Lindsley, C Perez, M Henrickson, M Rivas-Chacon, R Higgins, G Katona, I Olson, J Miller, FW Rider, LG TI HLA DRB1*0301 and DQA1*0301 are independent and synergistic genetic risk factors for juvenile dermatomyositis (JDM) in Caucasians SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, NIH, DHHS, Bethesda, MD USA. Mayo Clin, Rochester, MN USA. Childrens Hosp, Philadelphia, PA 19104 USA. Childrens Hosp, Seattle, WA USA. Univ Kansas, Med Ctr, Lawrence, KS 66045 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Valley Childrens Hosp, Madera, CA USA. Miami Childrens Hosp, Miami, FL USA. Ohio State Univ, Childrens Hosp, Columbus, OH USA. USUHS, Columbus, OH USA. Ped MACC Fund Res Ctr, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S668 EP S668 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001854 ER PT J AU Mamyrova, G Haagenson, L Wong, S Perez, M Sherry, D Imundo, L Wallace, C Miller, FW Rider, LG Brown, KE AF Mamyrova, G Haagenson, L Wong, S Perez, M Sherry, D Imundo, L Wallace, C Miller, FW Rider, LG Brown, KE TI Parvovirus B19 is not associated with the onset of juvenile dermatomyositis (JDM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIEHS, DHHS, NIH, Bethesda, MD USA. NHLBI, DHHS, NIH, Bethesda, MD USA. Texas Childrens Hosp, Houston, TX 77030 USA. Childrens Hosp, Philadelphia, PA 19104 USA. PPD, Babies Hosp, New York, NY USA. Childrens Hosp, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S103 EP S103 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000187 ER PT J AU Neogi, T Zhang, YQ Hanchate, A Kiel, DP O'Donnell, CJ Terkeltaub, R Felson, D AF Neogi, T Zhang, YQ Hanchate, A Kiel, DP O'Donnell, CJ Terkeltaub, R Felson, D TI Is there an association between osteophytes and vascular calcification?. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. UCSD, VAMC, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S305 EP S305 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000777 ER PT J AU Nguyen, J Zhou, XD Weisman, MH Ward, MM Davis, JC Reveille, JD AF Nguyen, J Zhou, XD Weisman, MH Ward, MM Davis, JC Reveille, JD TI A single nucleotide polymorphism of connective tissue growth factor (CTGF) gene associated with ankylosing spondylitis in Caucasian and Hispanic populations. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Sch Med, Houston, TX USA. Cedar Sinai Hosp, Los Angeles, CA USA. NIMS, NIH, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S449 EP S449 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001202 ER PT J AU Nikolov, NP Ward, JM Tschetter, JR Kopp, JB Gonzalez, FJ Kimura, S Siegel, RM AF Nikolov, NP Ward, JM Tschetter, JR Kopp, JB Gonzalez, FJ Kimura, S Siegel, RM TI Cytochrome P4501B1 enzyme deficiency and autoimmunity in mice SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. NIAID, NIH, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S683 EP S684 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001896 ER PT J AU Niu, JB Zhang, YQ Nevitt, M Carbone, L Harris, T Kwoh, K Satterfield, S Xu, L Felson, D AF Niu, JB Zhang, YQ Nevitt, M Carbone, L Harris, T Kwoh, K Satterfield, S Xu, L Felson, D TI Chinese in Beijing have a higher prevalence of patellofemoral osteoarthritis than Americans. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 BUMC, Boston, MA USA. UCSF, San Francisco, CA USA. Univ Tennessee, Memphis, TN 38163 USA. NIA, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Peking Union Med Coll, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S483 EP S483 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001302 ER PT J AU Ochi, K Tuan, RS AF Ochi, K Tuan, RS TI An articular cartilage specific gene, SCRG1, is induced by glucocorticoid and accelerates chondrogenesis in vitro SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S649 EP S649 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001801 ER PT J AU Reveille, JD Ward, MM Davis, JC Jin, L Weisman, MH AF Reveille, JD Ward, MM Davis, JC Jin, L Weisman, MH TI Functional impairment over time in patients with ankylosing spondylitis (AS). No evidence for a role for HLA-B, DRB1, DQA1, DQB1, DPB1, IL-1RN or MMP3 genes. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Texas, Houston Hlth Sci Ctr, Houston, TX USA. NIAMS, NIH, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Cedars Sinai Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S213 EP S213 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000514 ER PT J AU Siebert, S Amos, N Fielding, CA Wang, ECY Aksentijevich, I Williams, BD Brennan, P AF Siebert, S Amos, N Fielding, CA Wang, ECY Aksentijevich, I Williams, BD Brennan, P TI Reduced tumour necrosis factor signaling in fibroblasts containing a novel tumour necrosis factor receptor superfamily 1A (TNFRSF1A) mutant SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Wales Coll Cardiff, Coll Med, Cardiff CF1 3NS, S Glam, Wales. NIAMSD, Bethesda, MD 20892 USA. RI Fielding, Ceri/F-5638-2014 OI Fielding, Ceri/0000-0002-5817-3153 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S114 EP S114 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000220 ER PT J AU Skapenko, A Leipe, J Niesner, U Devriendt, K Beetz, R Radbruch, A Kalden, JR Lipsky, PE Schulze-Koops, H AF Skapenko, A Leipe, J Niesner, U Devriendt, K Beetz, R Radbruch, A Kalden, JR Lipsky, PE Schulze-Koops, H TI GATA-3 in human T helper cell type 2 development SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Erlangen Nurnberg, D-8520 Erlangen, Germany. Deutsch Rheumaforschszentrum, Berlin, Germany. Univ Louvain, Louvain, Belgium. Univ Mainz, D-6500 Mainz, Germany. NIAMS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S MA 1858 BP S694 EP S694 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001925 ER PT J AU Stone, JH Rajapakse, VN Hoffman, GS Specks, U Merkel, PA Spiera, R Davis, JC Clair, EWS Veenstra, TD Conrads, TP Liotta, LA Petricoin, EF AF Stone, JH Rajapakse, VN Hoffman, GS Specks, U Merkel, PA Spiera, R Davis, JC Clair, EWS Veenstra, TD Conrads, TP Liotta, LA Petricoin, EF TI A serum proteomic approach to gauging the state of remission in Wegener's granulomatosis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Mayo Clin, Rochester, MN USA. Boston Univ, Boston, MA 02215 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Durham, NC USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S118 EP S118 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000232 ER PT J AU Stummvoll, GH Fritsch, RD Meyer, B Aringer, M Smolen, JS Steiner, G AF Stummvoll, GH Fritsch, RD Meyer, B Aringer, M Smolen, JS Steiner, G TI Autoreactive T cells to histone H1 in SLE patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Med Univ Vienna, Vienna, Austria. NIAMS, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S220 EP S220 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000534 ER PT J AU Valencia, X Olson, D Simone, J Goldbach-Mansky, R Lipsky, P AF Valencia, X Olson, D Simone, J Goldbach-Mansky, R Lipsky, P TI CD4+CD25+T regulatory cell function in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, OCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S526 EP S526 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001431 ER PT J AU Ward, MM Weisman, MH Davis, JC Reville, JD AF Ward, MM Weisman, MH Davis, JC Reville, JD TI Risk factors for functional limitations in ankylosing spondylitis: The PSOAS study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMS, NIH, DHHS, Bethesda, MD USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S618 EP S619 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001709 ER PT J AU Ward, MM AF Ward, MM TI Outcomes of hospitalizations for myocardial infarctions and cerebrovascular accidents in patients with systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S193 EP S194 PG 2 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000455 ER PT J AU Ward, MT Guthrie, LC AF Ward, MT Guthrie, LC TI Patients' ratings of clinically important changes in rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 NIAMSD, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S BP S317 EP S317 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799000814 ER PT J AU Whalen, G Patrick, BEJ Chriscinske, SJ Ambrose, KR Lyden, AK Elenkov, IJ Groner, K Chrousos, GP Clauw, DJ AF Whalen, G Patrick, BEJ Chriscinske, SJ Ambrose, KR Lyden, AK Elenkov, IJ Groner, K Chrousos, GP Clauw, DJ TI Increased IL-8 and catecholamine levels in fibromyalgia and related conditions SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Georgetown Univ, Washington, DC 20057 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2004 VL 50 IS 9 SU S MA 1869 BP S698 EP S698 PG 1 WC Rheumatology SC Rheumatology GA 853AS UT WOS:000223799001936 ER PT J AU Nathanson, N Mathieson, BJ AF Nathanson, N Mathieson, BJ TI AIDS vaccine: Can the scientific community outwit 10,000 nucleotides? SO ASM NEWS LA English DT Article ID NEUTRALIZING ANTIBODIES; VIRUS; MACAQUES; TRANSMISSION; PROTECTION; INFECTION; EVOLUTION C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIH, HIV AIDS Vaccine Res Coordinating Comm, Off AIDS Res, Bethesda, MD 20892 USA. RP Nathanson, N (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD SEP PY 2004 VL 70 IS 9 BP 406 EP + PG 6 WC Microbiology SC Microbiology GA 853VC UT WOS:000223856000014 ER PT J AU De Fruyt, F McCrae, RR Szirmak, A Nagy, J AF De Fruyt, F McCrae, RR Szirmak, A Nagy, J TI The Five-Factor Personality Inventory as a measure of the five-factor model - Belgian, American, and Hungarian comparisons with the NEO-PI-R SO ASSESSMENT LA English DT Article DE big five; five-factor model; Five-Factor Personality Inventory ID BIG-5; CIRCUMPLEX; VALIDITY; FACETS; FFPI AB The lexically based Five-Factor Personality Inventory (FFPI) was correlated with the factors and facets of the Revised NEO Personality Inventory (NEO-PI-R) in Belgian (N = 265), American (N = 116), and Hungarian (N = 320) samples. Results were similar across the three cultures. Analysis of orthogonalized FFPI factors showed that three of them - emotional stability, extraversion, and agreeableness-showed a direct correspondence to their NEO-PI-R counterparts. Autonomy, however, was not clearly related to openness, and facet analysis suggested that it might be interpreted as a dominance factor Better matches to NEO-PI-R conscientiousness and openness could be obtained by using vectors rotated 30degrees from the FFPI positions. Raw scale scores showed similar results. Researchers should not assume that all measures of the Five-Factor Model are qualitatively similar. C1 Univ Ghent, Dept Psychol, B-9000 Ghent, Belgium. NIA, US Dept HHS, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Dept Personal Psychol, D-1000 Berlin, Germany. Eotvos Lorand Univ, Dept Personal & Hlth Psychol, H-1364 Budapest, Hungary. RP De Fruyt, F (reprint author), Univ Ghent, Dept Psychol, H Dunantlaan 2, B-9000 Ghent, Belgium. EM Filip.DeFruyt@ugent.be RI De Fruyt, Filip/A-3083-2009 NR 39 TC 31 Z9 31 U1 4 U2 36 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD SEP PY 2004 VL 11 IS 3 BP 207 EP 215 DI 10.1177/1073191104265800 PG 9 WC Psychology, Clinical SC Psychology GA 843NV UT WOS:000223091500002 PM 15358876 ER PT J AU Prigge, JT Majerciak, V Hunt, HD Dienglewicz, RL Parcells, MS AF Prigge, JT Majerciak, V Hunt, HD Dienglewicz, RL Parcells, MS TI Construction and characterization of Marek's disease viruses having green fluorescent protein expression tied directly or indirectly to phosphoprotein 38 expression SO AVIAN DISEASES LA English DT Article DE Marek's disease virus; MDV; recombinant; pp38; GFP; cytolytic infection ID LYMPHOBLASTOID CELL-LINES; SERIAL INVITRO PASSAGE; UNIQUE SHORT REGION; MONOCLONAL-ANTIBODY; INFECTED-CELLS; PHOSPHORYLATED POLYPEPTIDES; SURFACE-ANTIGENS; MUTANT MDV; HERPESVIRUS; GENE AB Marek's disease (MD) is Caused by Marek's disease Virus (MDV), a highly cell-associated alphaherpesvirus. MD is primarily characterized by lymphocyte infiltration of the nerves and the development of lymphomas in visceral organs, muscle, and skin. MDV encodes two phosphoproteins, pp24 and pp38, that are highly expressed during lyric infection. These proteins were initially identified in MDV-induced Minors but are now known to be linked primarily to MDV lyric infection. Despite the recent characterization of a pp38 deletion Mutant MDV, the functions of these phosphoproteins remain Unknown. The goal of this work was to construct recombinant MDVs having direct fusions of a marker gene, the green fluorescent protein (GFP), to pp38 in order to Study the expression patterns and localization of this protein during stages of MDV infection. We report the construction of two recombinant viruses, one having the enhanced green fluorescent protein (eGFP) fused in-frame to the pp38 open reading frame (ORF) (RB1Bpp38/eGFP) and the other having soluble-modified GFP (smGFP) downstream but out-of-frame with pp38 (RB1Bpp38/smGFP). During construction of RB1Bpp38/eGFP, an ORF located downstream of pp38 (LORF 12) was partially deleted. In RB1Bpp38/smGFP, however, LORF12 and its immediate 5' Upstream sequence was left intact. This report describes the construction, cell Culture, and in vivo characterization of RB1Bpp38/eGFP and RB1Bpp38/smGFP. Structural analysis showed that the virus stocks of RB1Bpp38/eGFP and RB1Bpp38/smGFP had incorporated the GFP cassette and were free of contaminating parent virus (RB1B). Moreover, RB1Bpp38/eGFP and RB1Bpp38/smGFP contained two and three and four and five copies of the 132-bp repeats, respectively. Expression analysis showed that the transcription of genes in RB1Bpp38/eGFP-and RB1Bpp38/smGFP-infected chicken embryo fibroblasts (CEFs) were similar to RB1B-infected CEFs, with the notable exception of deletion of a LORF12-specific transcript in RB1Bpp38/eGFP-infected cells. In CEFs, RB1Bpp38/eGFP and RB1Bpp38/smGFP showed comparable one-step growth kinetics to parental virus (RB1B). RB1Bpp38/eGFP and RB1Bpp38/smGFP, however, showed quite distinct growth characteristics in vivo. Two independent: clones of RB1Bpp38/eGFP were highly attenuated, whereas RB1Bpp38/smGFP exhibited pathogenesis similar to parent Virus and retained oncogenicity. Our results Suggest that the RB1Bpp38/eGFP phenotype Could be due to an interference with an in vivo-specific pp38 function via GFP direct fusion, to the deletion of LORF12, or to a targeting of the immune response to eGFP. Because deletion of pp38 was recently found not to fully attenuate very virulent MDV strain MD-5, it is possible that deletion of LORF12 may be at least partially responsible for the attenuation of RB1Bpp38/eGFP. The construction of these viruses and the establishment of cell lines from RB1Bpp38/smGFP provide useful tools for the study of MDV lytic infection in cell Culture and in vivo, in studies of the reactivation of MDV from latency, and in the functional analysis of LORF12. C1 Univ Arkansas, Ctr Excellence Poultry Sci, Dept Poultry Sci, Fayetteville, AR 72701 USA. NIH, Bethesda, MD 20892 USA. USDA ARS, Avian Dis & Oncol Lab, E Lansing, MI 48823 USA. RP Parcells, MS (reprint author), Univ Arkansas, Ctr Excellence Poultry Sci, Dept Poultry Sci, Fayetteville, AR 72701 USA. NR 47 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC AVIAN PATHOLOGISTS PI ATHENS PA 953 COLLEGE STATION RD, ATHENS, GA 30602-4875 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD SEP PY 2004 VL 48 IS 3 BP 471 EP 487 DI 10.1637/7110 PG 17 WC Veterinary Sciences SC Veterinary Sciences GA 937IG UT WOS:000229917200004 PM 15529969 ER PT J AU Bossert, JM Liu, SY Lu, L Shaham, Y AF Bossert, JM Liu, SY Lu, L Shaham, Y TI A novel role of group II metabotropic glutamate receptors in the ventral tegmental area in contextual cue-induced reinstatement of heroin seeking in a rat relapse model SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT Workshop on Neurobehavioural Plasticity CY SEP 04-05, 2004 CL Rome, ITALY SP European Behavioural Pharmacol Soc C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2004 VL 15 IS 5-6 MA P6 BP A9 EP A9 DI 10.1097/00008877-200409000-00046 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 855IC UT WOS:000223965700046 ER PT J AU Shaham, Y AF Shaham, Y TI Role of growth factors in the time-dependent increases in cocaine seeking after withdrawal SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT Workshop on Neurobehavioural Plasticity CY SEP 04-05, 2004 CL Rome, ITALY SP European Behavioural Pharmacol Soc C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2004 VL 15 IS 5-6 MA S9 BP A4 EP A4 DI 10.1097/00008877-200409000-00029 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 855IC UT WOS:000223965700029 ER PT J AU Alqawi, O Bates, S Georges, E AF Alqawi, O Bates, S Georges, E TI Arginine(482) to threonine mutation in the breast cancer resistance protein ABCG2 inhibits rhodamine 123 transport while increasing binding SO BIOCHEMICAL JOURNAL LA English DT Article DE breast cancer resistance protein (BCRP); drug interactions; multidrug resistance; photoaffinity labelling; rhodamine 123 ID MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; CELL-LINES; OVEREXPRESSION; GENE; TOPOTECAN; MEMBRANE; LOCALIZATION; MITOXANTRONE; DOXORUBICIN AB ABCG2 [also known as BCRP (breast cancer resistance protein) or MXR] is an ABC (ATP-binding cassette) protein shown to confer multidrug resistance. ABCG2 was initially identified in resistant breast carcinoma cells (MCF-7/AdrVp1000) selected with doxorubicin and verapamil. Later studies demonstrated the presence of a point mutation (Arg(482) to Thr) in ABCG2 in MCF-7/AdrVp1000 cells. This mutation was shown to modulate the transport of Rh123 (rhodamine 123). In the present study, we have used a previously characterized photoreactive drug analogue of Rh123, IAARh123 (iodoaryl-azido-Rh123), to examine the effects of the Arg(482) --> Thr mutation on Rh123 binding and transport by ABCG2. Our results show that both wild-type (ABCG2(R482)) and mutant (ABCG2(T482)) ABCG2 bound directly to IAARh123. Surprisingly, however, wild-type ABCG2(R482), which does not transport Rh123, was more intensely photolabelled than mutant ABCG2(T482). In addition, inhibition of IAARh123 photolabelling using various drug substrates of ABCG2 revealed some differences between wild-type and mutant ABCG2. For example, a molar excess of mitoxantrone was more effective at inhibiting IAARh123 labelling of wild-type than of mutant ABCG2, while excess cisplatin, taxol and methotrexate showed significant inhibition of IAARh123 binding to both wild-type and mutant ABCG2. Taken together, the results of this study provide the first demonstration of the direct binding of drugs to ABCG2. C1 McGill Univ, Inst Parasitol, Ste Anne De Bellevue, PQ H9X 3V9, Canada. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Georges, E (reprint author), McGill Univ, Inst Parasitol, Macdonald Campus, Ste Anne De Bellevue, PQ H9X 3V9, Canada. EM elias.georges@McGill.ca NR 24 TC 40 Z9 44 U1 0 U2 5 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 2004 VL 382 BP 711 EP 716 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 855PP UT WOS:000223986500035 PM 15139851 ER PT J AU Farrell, N Povirk, LF Dange, Y DeMasters, G Gupta, MS Kohlhagen, G Khan, QA Pommier, Y Gewirtz, DA AF Farrell, N Povirk, LF Dange, Y DeMasters, G Gupta, MS Kohlhagen, G Khan, QA Pommier, Y Gewirtz, DA TI Cytotoxicity, DNA strand breakage and DNA-protein crosslinking by a novel transplatinum compound in human A2780 ovarian and MCF-7 breast carcinoma cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE DNA strand breakage; DNA-protein crosslinking; novel transplatinum compound; apoptosis; MCF-7; A2780 ID PLATINUM ANTITUMOR COMPLEXES; TUMOR-CELLS; PLANAR LIGANDS; CANCER-CELLS; BIOLOGICAL-ACTIVITY; INDUCED SENESCENCE; TOPOISOMERASE-II; TRANS-GEOMETRY; LEUKEMIA-CELLS; IN-VITRO AB Cisplatin, cis-[PtCl2(NH3)(2)], is commonly utilized in various combination chemotherapy protocols for the treatment of both ovarian and breast cancer while the corresponding trans isomer is therapeutically inactive. This work describes efforts to elucidate the cellular mechanism of action of a novel trans-platinum compound, trans-(dichloroamminethiazole)platinum(H) (ATZ), which demonstrates antiproliferative and cytotoxic effects against both MCF-7 human breast and A2780 human ovarian carcinoma cells in culture. A2780 cells were approximately twofold more sensitive to ATZ than MCF-7 cells in both cell growth and clonogenic survival assays. Dye exclusion studies revealed a 50-70% loss in cell viability within the first 12 h of drug treatment in both cell lines. This initial wave of cell death was succeeded by a prolonged interval of growth arrest during which a small fraction of apoptotic cells was detected. Binding of ATZ to DNA, as estimated by atomic absorption spectroscopy, was similar for the two cell lines and was almost completely reversed 24 h after drug removal. ATZ also induced DNA strand breakage as well as DNA-protein crosslinking during the initial 12 h period when the bulk of cell death was evident. However, neither the extent of DNA strand breakage nor that of DNA protein crosslinking was sufficient to explain the different drug sensitivity in the two cell lines. At 24 and 48 h after exposure of MCF-7 cells to high concentrations of ATZ, the formation of DNA-topoisomerase I complexes is detected, coincident with a high degree of apoptosis. These studies suggest that ATZ has the capacity to interfere with topoisomerase I in the tumor cell, a function not evident in cis-platinum-based drugs. (C) 2004 Elsevier Inc. All rights reserved. C1 Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gewirtz, DA (reprint author), Virginia Commonwealth Univ, Dept Med, POB 980230,1101 E Marshall St, Richmond, VA 23298 USA. EM gewirtz@mail2.vcu.edu FU NCI NIH HHS [CA40615] NR 44 TC 44 Z9 45 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 2004 VL 68 IS 5 BP 857 EP 866 DI 10.1016/j.bcp.2004.05.023 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 849DD UT WOS:000223518000007 PM 15294448 ER PT J AU Greenwald, RB Zhao, H Xia, J Wu, DC Nervi, S Stinson, SF Majerova, E Bramhall, C Zaharevitz, DW AF Greenwald, RB Zhao, H Xia, J Wu, DC Nervi, S Stinson, SF Majerova, E Bramhall, C Zaharevitz, DW TI Poly(ethylene glycol) prodrugs of the CDK inhibitor, alsterpaullone (NSC 705701): Synthesis and pharmacokinetic studies SO BIOCONJUGATE CHEMISTRY LA English DT Article ID DRUG-DELIVERY AB Two methods were devised to conjugate PEG to alsterpaullone (NSC 705701) via the N of the indole ring portion of the molecule. In the first approach, activation of the indole was accomplished by reaction with p-nitrophenyl chloroformate to produce a reactive carbamate that was then condensed with a mono blocked diamine to form a urea bond followed by deblocking and conjugation to PEG. The second route used the anion of the indole and produced a carbamate bond. Both compounds were highly water soluble, were stable in buffer, and released alsterpaullone in vitro and in vivo. Studies were conducted in mice to investigate the influence of PEGylation on the plasma pharmacokinetics of alsterpaullone. The total plasma clearance rate was decreased up to 32-fold, and the biological halflife lengthened up to 8-fold when alsterpaullone was injected i.v. as a PEG-conjugate and compared to injection of the unconjugated compound. The most pronounced effect on the pharmacokinetics of alsterpaullone was produced by a 40-kDa PEG urea-linked conjugate. When the 40- and 20-kDa urea-linked conjugates were administered by i.p. injection, high relative bioavailability (46% and 99%, respectively) of alsterpaullone was observed. C1 Enzon Pharmaceut Inc, Div Res & Dev, Piscataway, NJ 08854 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Stinson, SF (reprint author), Enzon Pharmaceut Inc, Div Res & Dev, 20 Kingsbridge Rd, Piscataway, NJ 08854 USA. EM stinson@dtpax2.ncifcrf.gov NR 11 TC 12 Z9 13 U1 0 U2 5 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 SEP-OCT PY 2004 VL 15 IS 5 BP 1076 EP 1083 DI 10.1021/bc049906a PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 854WL UT WOS:000223934300017 PM 15366962 ER PT J AU Xirasagar, S Gustafson, S Merrick, BA Tomer, KB Stasiewicz, S Chan, DD Yost, KJ Yates, JR Sumner, S Xiao, NQ Waters, MD AF Xirasagar, S Gustafson, S Merrick, BA Tomer, KB Stasiewicz, S Chan, DD Yost, KJ Yates, JR Sumner, S Xiao, NQ Waters, MD TI CEBS object model for systems biology data, SysBio-OM SO BIOINFORMATICS LA English DT Article ID QUANTITATIVE PROTEOMIC ANALYSIS; AMINO-ACID-SEQUENCES; CODED AFFINITY TAGS; MASS-SPECTROMETRY; PROTEIN IDENTIFICATION; GENE-EXPRESSION; GEL-ELECTROPHORESIS; DRUG DEVELOPMENT; MICROARRAY; METABONOMICS AB Motivation: To promote a systems biology approach to understanding the biological effects of environmental stressors, the Chemical Effects in Biological Systems (CEBS) knowledge base is being developed to house data from multiple complex data streams in a systems friendly manner that will accommodate extensive querying from users. Unified data representation via a single object model will greatly aid in integrating data storage and management, and facilitate reuse of software to analyze and display data resulting from diverse differential expression or differential profile technologies. Data streams include, but are not limited to, gene expression analysis (transcriptomics), protein expression and protein-protein interaction analysis (proteomics) and changes in low molecular weight metabolite levels (metabolomics). Results: To enable the integration of microarray gene expression, proteomics and metabolomics data in the CEBS system, we designed an object model, Systems Biology Object Model (SysBio-OM). The model is comprehensive and leverages other open source efforts, namely the Micro-Array Gene Expression Object Model (MAGE-OM) and the Proteomics Experiment Data Repository (PEDRo) object model. SysBio-OM is designed by extending MAGE-OM to represent protein expression data elements (including those from PEDRo), protein-protein interaction and metabolomics data. SysBio-OM promotes the standardization of data representation and data quality by facilitating the capture of the minimum annotation required for an experiment. Such standardization refines the accuracy of data mining and interpretation. The open source SysBio-OM model, which can be implemented on varied computing platforms is presented here. C1 Sci Applicat Int Corp, Germantown, MD 20874 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Paradigm Genet Inc, Res Triangle Pk, NC 27709 USA. RP Xirasagar, S (reprint author), Sci Applicat Int Corp, 20201 century Bldg,3rd Floor, Germantown, MD 20874 USA. EM xirasagars@saic.com RI Tomer, Kenneth/E-8018-2013 FU NIEHS NIH HHS [N01-ES-25495] NR 44 TC 36 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP 1 PY 2004 VL 20 IS 13 BP 2004 EP 2015 DI 10.1093/bioinformatics/bth189 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 853KR UT WOS:000223827000002 PM 15044233 ER PT J AU Yamaguchi, N Driscoll, CA Kitchener, AC Ward, JM Macdonald, DW AF Yamaguchi, N Driscoll, CA Kitchener, AC Ward, JM Macdonald, DW TI Craniological differentiation between European wildcats (Felis silvestris silvestris), African wildcats (F-s. lybica) and Asian wildcats (F-s. ornata): implications for their evolution and conservation SO BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY LA English DT Article DE Felidae; Felis lunensis; F. lybica; F. ornata; F. silvestris; forest cat; hybridization; morphology; Pleistocene; steppe cat ID DOMESTIC CATS; LIVING CATS; POPULATIONS; SCOTLAND; SYSTEMATICS; HYBRIDS AB Intraspecific diversification of the wildcat (Felis silvestris), including the European wildcat (F s. silvestris), the Asian wildcat (F s. ornata) and the African wildcat (F s. lybica), was examined based on 39 cranial morphology variables. The samples of free-ranging cats originated from Britain, Europe, Central Asia and southern Africa, consisting of both nominal wildcat specimens (referred to henceforth as 'wildcats') and nominal non-wildcat specimens ('non-wildcats') based on museum labels. The skull morphology of 'wildcats' from Britain and Europe is clearly different from that of 'wildcats' of Central Asia and southern Africa. The latter are characterized especially by their proportionately larger cheek teeth. On the basis of principal component, discriminant function and canonical variate analyses, the skull morphology of British 'non-wildcats' is less distinct than is that of British 'wildcats' from the skull morphologies of 'wildcats' of Central Asia and southern Africa. On the other hand, the skull morphology of southern African 'non-wildcats' is as distinct from those of 'wildcats' of Britain and Europe as is that of southern African 'wildcats'. We suggest that the evolution of the modern wildcat probably consisted of at least three different distribution expansions punctuated by two differentiation events: the exodus from Europe during the late Pleistocene, coinciding with the emergence of the steppe wildcat lineage (phenotype of Asian-African wildcat), followed by its rapid range expansion in the Old World. The second differentiation event was the emergence of the domestic cat followed by its subsequent colonization of the entire world with human assistance. Considering the recent evolutionary history of, and morphological divergence in, the wildcat, preventing hybridization between the European wildcat and the domestic cat is a high conservation priority. (C) 2004 The Linnean Society of London. C1 Dept Zool, Wildlife Conservat Res Unit, Oxford OX1 3PS, England. Natl Museum Scotland, Edinburgh EH1 1JF, Midlothian, Scotland. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Yamaguchi, N (reprint author), Dept Zool, Wildlife Conservat Res Unit, S Parks Rd, Oxford OX1 3PS, England. EM nobuyuki.yamaguchi@zoo.ox.ac.uk OI Driscoll, Carlos/0000-0003-2392-505X NR 40 TC 25 Z9 29 U1 5 U2 23 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0024-4066 J9 BIOL J LINN SOC JI Biol. J. Linnean Soc. PD SEP PY 2004 VL 83 IS 1 BP 47 EP 63 DI 10.1111/j.1095-8312.2004.00372.x PG 17 WC Evolutionary Biology SC Evolutionary Biology GA 856GB UT WOS:000224032600004 ER PT J AU Green, MF Nuechterlein, KH Gold, JM Barch, DM Cohen, J Essock, S Fenton, WS Frese, F Goldberg, TE Heaton, RK Keefe, RSE Kern, RS Kraemer, H Stover, E Weinberger, DR Zalcman, S Marder, SR AF Green, MF Nuechterlein, KH Gold, JM Barch, DM Cohen, J Essock, S Fenton, WS Frese, F Goldberg, TE Heaton, RK Keefe, RSE Kern, RS Kraemer, H Stover, E Weinberger, DR Zalcman, S Marder, SR TI Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria SO BIOLOGICAL PSYCHIATRY LA English DT Review DE cognition; cognitive assessment; cognitive enhancement; neurocognition; psychopharmacology; schizophrenia ID NEUROPSYCHOLOGICAL FUNCTION; NEUROCOGNITIVE DEFICITS; NEUROLEPTIC-NAIVE; THOUGHT-DISORDER; NEURAL BASIS; MEMORY; IMPAIRMENT; SIBLINGS; RISPERIDONE; PERFORMANCE AB To stimulate the development of new drugs for the cognitive deficits of schizophrenia, the National Institute of Mental Health (NIMH) establisbed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. This article presents an overview of decisions from the first MATRICS consensus conference . The goals of the meeting were to 1) the cognitive domains that should be represented in a consensus cognitive battery and 2) prioritize key criteria, for selection of tests for the battery. Seven cognitive domains were selected based on a review of the literatum and input from experts: working memory, attention/vigilance, verbal learning and memory, visual learning and memory. Reasoning and problem solving, speed of processing, and social cognition. Based on discussions at this meeting, five criteria were considered essential for test selection: good test-retest reliability high utility as a repeated measure, relationship to functional outcome, potential response to pharmacologic agents, and practicality/tolerability. The results from this meeting constitute the initial steps for reaching a consensus cognitive battery for clinical trials in schizopbrenia. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. NE Ohio Univ, Coll Med, Dept Psychiat, Rootstown, OH 44272 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. Duke Univ, Dept Behav Sci, Durham, NC USA. Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Geffen Sch Med, 300 Med Plaza,Room 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu RI Barch, Deanna/G-8638-2013 FU NIMH NIH HHS [MH22006] NR 59 TC 465 Z9 480 U1 4 U2 46 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2004 VL 56 IS 5 BP 301 EP 307 DI 10.1016/j.biopsych.2004.06.023 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 849ZJ UT WOS:000223580100001 PM 15336511 ER PT J AU Erdmann, AA Jung, U Foley, JE Toda, Y Fowler, DH AF Erdmann, AA Jung, U Foley, JE Toda, Y Fowler, DH TI Co-stimulated/Tc2 cells abrogate murine marrow graft rejection SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Th2; Tc2; graft rejection; GvHD; veto cells; cytotoxic T cells ID VERSUS-HOST-DISEASE; CD4(+) T-CELLS; ADOPTIVE TRANSFER; VETO CELLS; DONOR; LYMPHOMA; LEUKEMIA; TRANSPLANTATION; ENGRAFTMENT; CTLS AB CD3/CD28 co-stimulation activates T-cell cytokine and cytolytic effector function and therefore represents an approach to modulate donor T cells before allogeneic bone marrow transplantation (BMT). We hypothesized that co-stimulation of donor T cells under T2 conditions would generate CD4(+) T-helper type 2 (Th2) and CD8(+) Tc2 cells capable of abrogating marrow graft rejection with reduced graft-versus-host disease (GVHD). Relative to control co-stimulated Th1/Tc1 (T1) cells, co-stimulated T2 cells secreted reduced interleukin (IL)-2 and interferon-gamma and increased IL-4 and IL-10, expressed reduced fas ligand, and had similar total cytolytic capacity. In an F1-into-parent sublethal irradiation model, T2 cells potently abrogated rejection; this veto effect was partially attenuated if T2 cell infusion was delayed for 24 hours after BMT. Cell-tracking studies determined that T2 cells were quantitatively reduced after BMT when administered to hosts capable of mounting a host-versus-graft rejection response; both donor and host cytotoxic T lymphocytes may therefore have been deleted during Th2/Tc2 cell facilitation of engraftment. Donor T2 cells also abrogated rejection in an F1-into-parent model that used lethal host irradiation and subsequent host T-cell addback. Further experiments in a P1-into-P2 transplantation model demonstrated that donor T2 cells abrogated rejection with reduced GVHD in a transplant setting involving full major histocompatibility complex disparity in both the host-versus-graft and graft-versus-host directions. The capacity of T2 cells to abrogate rejection with reduced GVHD was a function of both the number of T2 cells infused and the number of T cells present after host preparation. Co-stimulation under T2 polarizing conditions therefore rapidly generates donor Th2/Tc2 cells that potently abrogate murine marrow rejection with reduced GVHD. (C) 2004 American Society for Blood and Marrow Transplantation. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov NR 25 TC 19 Z9 19 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2004 VL 10 IS 9 BP 604 EP 613 DI 10.1016/j.bbmt.2004.06.006 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 851HX UT WOS:000223677300003 PM 15319772 ER PT J AU Cosson, B Braun, F Paillard, L Blackshear, P Osborne, HB AF Cosson, B Braun, F Paillard, L Blackshear, P Osborne, HB TI Identification of a novel Xenopus laevis poly (A) binding protein SO BIOLOGY OF THE CELL LA English DT Article DE ePABP2; cytoplasmic protein; oocytes; embryos ID MESSENGER-RNA POLYADENYLATION; TAIL LENGTH CONTROL; POLY(A)-BINDING PROTEIN; CYTOPLASMIC POLYADENYLATION; OOCYTE MATURATION; SPECIFICITY FACTOR; FROG OOCYTES; IN-VITRO; TRANSLATION; DEADENYLATION AB Poly (A) binding proteins are intimately implicated in controlling a number of events in mRNA metabolism from nuclear polyadenylation to cytoplasmic translation and stability. The known poly(A) binding proteins can be divided into three distinct structural groups (prototypes PABP1, PABPN1/PABP2 and Nab2p) and two functional families, showing that similar functions can be accomplished by differing structural units. This has prompted us to perform a screen for novel poly(A) binding proteins using Xenopus laevis. A novel poly(A) binding protein of 32 kDa (p32) was identified. Sequence analysis showed that p32 has about 50% identity to the known nuclear poly(A) binding proteins (PABPN1) but is more closely related to a group of mammalian proteins of unknown function. The expression of Xenopus laevis ePABP2 is restricted to early embryos. Accordingly, we propose that p32 is the founder member of a novel class of poly(A) binding proteins named ePABP2. (C) 2004 Elsevier SAS. All rights reserved. C1 Univ Rennes 1, CNRS, UMR 6061, Fac Med, F-35043 Rennes, France. NIEHS, Lab Signal Transduct, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Cosson, B (reprint author), Univ Rennes 1, CNRS, UMR 6061, Fac Med, 2 Ave Prof Leon Bernard,CS 34317, F-35043 Rennes, France. EM bertrand.cosson@univ-rennes1.fr OI BRAUN, Frederique/0000-0001-5871-6042; Paillard, Luc/0000-0002-9290-7616 NR 43 TC 17 Z9 18 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD SEP PY 2004 VL 96 IS 7 BP 519 EP 527 DI 10.1016/j.biolcel.2004.04.006 PG 9 WC Cell Biology SC Cell Biology GA 859BJ UT WOS:000224236700005 PM 15380618 ER PT J AU Geho, DH Lahar, N Ferrari, M Petricoin, EF Liotta, LA AF Geho, DH Lahar, N Ferrari, M Petricoin, EF Liotta, LA TI Opportunities for nanotechnology-based innovation in tissue proteomics SO BIOMEDICAL MICRODEVICES LA English DT Article DE tissue proteomics; nanotechnology; protein microarrays; mass spectrometry ID CATALYZED REPORTER DEPOSITION; PHASE PROTEIN MICROARRAYS; MASS-SPECTROMETRY; SIGNAL AMPLIFICATION; PROSTATE-CANCER; CLINICAL PROTEOMICS; SILICON SURFACES; OVARIAN-CANCER; SERUM; EXPRESSION AB Within this review we discuss two methodologies used in tissue proteomics, namely mass-spectrometry (MS)-based protein pattern diagnostics and protein microarrays. Further, we describe current goals within the field of tissue proteomics and suggest points of departure for designing nanotechnology-based tools that will enhance the role of molecularly based diagnostics and therapeutics development in clinical medicine. C1 NCI, US FDA, NCI,Clin Proteom Program, Lab Pathol,Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, NCI, Clin Proteom Program, Ctr Biol Evaluat & Res, Bethesda, MD USA. Ohio State Univ, Dept Internal Med, Div Haematol & Oncol, Columbus, OH 43210 USA. Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. RP Geho, DH (reprint author), NCI, US FDA, NCI,Clin Proteom Program, Lab Pathol,Ctr Canc Res, Room 2N212,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM gehod@mail.nih.gov NR 59 TC 22 Z9 24 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD SEP PY 2004 VL 6 IS 3 BP 231 EP 239 DI 10.1023/B:BMMD.0000042053.51016.b4 PG 9 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 854OX UT WOS:000223914300008 PM 15377833 ER PT J AU Rao, RS Glickman, ME Glynn, RJ AF Rao, RS Glickman, ME Glynn, RJ TI Use of covariates and survey wave to adjust for nonresponse SO BIOMETRICAL JOURNAL LA English DT Article DE drug compliance; nonresponse adjustment; reluctant respondents; multiple imputation ID IMPUTED SURVEY DATA; MULTIPLE IMPUTATION; VARIANCE-ESTIMATION; NONIGNORABLE NONRESPONSE; FOLLOW-UPS AB Using covariates available on all sampled individuals along with an intensive follow-up of nonrespondents is a useful approach to reduce the impact of nonresponse. We examined the performance of several different nonresponse models to account for such covariates and multiple survey waves to estimate the prevalence of birth control use in 106463 women taking the teratogenic drug Accutane. Nonrespondents to a first mailing were followed with two more mailings and then a telephone call. The first mailing had a response rate of 59.7 percent; the overall nonresponse rate was 15.2 percent. Age was available on all women and was strongly associated with both response and birth control use. We considered both multiple imputation and weighting strategies using information on age and time to response assuming that nonrespondents were: (i) like all respondents conditional on age, (ii) like reluctant respondents conditional on age, and (iii) projected from a model which includes trend. Simulation studies were used to examine the potential bias in this setting and we compared models under different assumptions about the missing data mechanism. Results describe the extent to which availability of covariate information and use of multiple waves improves estimation. C1 Slone Epidemiol Ctr, Boston, MA 02215 USA. NCI, DHHS, Biostat Branch, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Edith Nourse Rogers Mem Hosp 152, Bedford, MA 01730 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Rao, RS (reprint author), Slone Epidemiol Ctr, Boston, MA 02215 USA. EM raos@mail.nih.gov NR 35 TC 3 Z9 5 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD SEP PY 2004 VL 46 IS 5 BP 579 EP 588 DI 10.1002/bimj.200310049 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 866TC UT WOS:000224795100010 ER PT J AU Berger, VW AF Berger, VW TI Valid adjustment of randomized comparisons for binary covariates SO BIOMETRICAL JOURNAL LA English DT Article DE principal stratification; Simpson's paradox; time-varying covariate ID CLINICAL-TRIALS; SELECTION BIAS; INFERENCE; DEMENTIA; SURVIVAL AB In randomized trials, the treatment influences not only endpoints but also other variables measured after randomization which, when used as covariates to adjust for the observed imbalance, become pseudo-covariates. There is a logical circularity in adjusting for a pseudo-covariate because the variability in the endpoint that is attributed not to the treatment but rather to the pseudo-covariate may actually represent an effect of the treatment modulated by the pseudo-covariate. This potential bias is well known, but we offer new insight into how it can lead to reversals in the direction of the apparent treatment effect by way of stage migration. We then discuss a related problem that is not generally appreciated, specifically how the absence of allocation concealment can lead to this reversal of the direction of the apparent treatment effect even when adjustment is for a true covariate measured prior to randomization. C1 Univ Maryland Baltimore Cty, NCI, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), Univ Maryland Baltimore Cty, NCI, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 20 TC 9 Z9 9 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD SEP PY 2004 VL 46 IS 5 BP 589 EP 594 DI 10.1002/bimj.200410055 PG 6 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 866TC UT WOS:000224795100011 ER PT J AU Zheng, G Chen, ZH AF Zheng, G Chen, ZH TI Robust tests for candidate-gene association using case-parents trios with a multi-allelic marker SO BIOMETRICAL JOURNAL LA English DT Article DE genetic models; maximum tests; multiple alleles; power; robustness ID LINKAGE TESTS; AFFECTED SIBS; DESIGN; SURVIVAL; POWER; TDT AB In case-parents trios design, the association between a multi-allelic candidate-gene and a disease can be detected by using maximum of score tests (max-score) when the mode of inheritance is known. We apply the maximum of the max-score statistics and the maximum of likelihood ratio statistics when the genetic model is unknown and examine their robust properties compared to max-score statistics. The simulation results demonstrate that the two maximum robust tests are more efficacious and robust across all genetic models compared with the three max-score tests. Moreover, in most situations, the maximum of the max-score tests seems to be more powerful than the maximum of the likelihood ratio tests. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD SEP PY 2004 VL 46 IS 5 BP 606 EP 611 DI 10.1002/bimj.200410057 PG 6 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 866TC UT WOS:000224795100013 ER PT J AU Xu, JL Fagerstrom, RM Prorok, PC Kramer, BS AF Xu, JL Fagerstrom, RM Prorok, PC Kramer, BS TI Estimating the cumulative risk of a false-positive test in a repeated screening program SO BIOMETRICS LA English DT Article DE cumulative risk; false-positive screens; maximum likelihood estimation; repeated screening program ID BREAST-CANCER; MAMMOGRAPHY; IMPACT AB The goal of screening tests for a chronic disease such as cancer is early detection and treatment with a consequent reduction in mortality from the disease. Screening tests, however, might produce false positive and false-negative results. With an increasing number of screening tests, it is clear that the risk of a false-positive screen, a finding with potentially significant emotional, financial, and health costs, also increases. Elmore et al. (1998, New England Journal of Medicine 338, 1089-1096), Christiansen et al. (2000, Journal of the National Cancer Institute 92, 1657-1666), and Gelfand and Wang (2000, Statistics in Medicine 19, 1865-1879) investigated this problem under the somewhat unrealistic assumption that the choice of making the decision to drop out at the kth screen does not depend upon the results of the earlier k-1 screens. In this article we obtain sufficient and necessary conditions for their assumption to hold and use one of them to provide a method for testing the validity of the assumption. A new model which does not depend on their assumption is introduced. The maximum likelihood estimator of the cumulative risk of receiving a false-positive screen under the new model is derived and its asymptotic normality is proved. The extension of the new model by incorporating covariate information is also considered. We apply our testing method and the new model to data from the breast cancer screening trial of the Health Insurance Plan of Greater New York. C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Xu, JL (reprint author), NCI, Biometry Res Grp, EPN-3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM jx2b@nih.gov NR 17 TC 18 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2004 VL 60 IS 3 BP 651 EP 660 DI 10.1111/j.0006-341X.2004.00214.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 853HP UT WOS:000223818200014 PM 15339287 ER PT J AU Conaway, MR Dunbar, S Peddada, SD AF Conaway, MR Dunbar, S Peddada, SD TI Designs for single- or multiple-agent phase I trials SO BIOMETRICS LA English DT Article DE dose escalation; order-restricted inference; partial order ID CONTINUAL REASSESSMENT METHOD; CLINICAL-TRIALS; CANCER AB Phase I trials of cytotoxic agents in oncology are usually dose-finding studies that involve a single cytotoxic agent. Many statistical methods have been proposed for these trials, all of which are based on the assumption of a monotonic dose-toxicity curve. For single-agent trials, this is a valid assumption. In many trials, however, investigators are interested in finding the maximally tolerated dose based on escalating multiple cytotoxic agents. When there are multiple agents, monotonicity of the dose-toxicity curve is not clearly defined. In this article we present a design for phase I trials in which the toxicity probabilities follow a partial order, meaning that there are pairs of treatments for which the ordering of the toxicity probabilities is not known at the start of the trial. We compare the new design to existing methods for simple orders and investigate the properties of the design for two partial orders. C1 Univ Virginia, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. CPSP GlaxoSmithKline, Philadelphia, PA USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Conaway, MR (reprint author), Univ Virginia, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. EM mconaway@virginia.edu RI Peddada, Shyamal/D-1278-2012 NR 22 TC 51 Z9 51 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2004 VL 60 IS 3 BP 661 EP 669 DI 10.1111/j.0006-341X.2004.00215.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 853HP UT WOS:000223818200015 PM 15339288 ER PT J AU Dunson, DB Holloman, C Calder, C Gunn, LH AF Dunson, DB Holloman, C Calder, C Gunn, LH TI Bayesian modeling of multiple lesion onset and growth from interval-censored data SO BIOMETRICS LA English DT Article DE interval-censored; interval counts; multiple event times; panel counts; Poisson process; recurrent events; screening data; tumor multiplicity ID PANEL COUNT DATA; REGRESSION-ANALYSIS; DISEASE; TIME AB In studying rates of occurrence and progression of lesions (or tumors), it is typically not possible to obtain exact onset times for each lesion. Instead. data consist of the number of lesions that reach a detectable size between screening examinations, along with measures of the size/severity of individual lesions at each exam time. This interval-censored data structure makes it difficult to properly adjust for the onset time distribution in assessing covariate effects on rates of lesion progression. This article proposes a joint model for the multiple lesion onset and progression process, motivated by cross-sectional data from a study of uterine leiomyoma tumors. By using a joint model, one can potentially obtain more precise inferences on rates of onset, while also performing onset time-adjusted inferences on lesion severity. Following a Bayesian approach, we propose a data augmentation Markov chain Monte Carlo algorithm for posterior computation. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Battelle Mem Inst, Stat & Data Anal Grp, Columbus, OH 43201 USA. Ohio State Univ, Dept Stat, Columbus, OH 43210 USA. Georgia So Univ, Sch Publ Hlth, Statesboro, GA 30460 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 19 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2004 VL 60 IS 3 BP 676 EP 683 DI 10.1111/j.0006-341X.2004.00217.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 853HP UT WOS:000223818200017 PM 15339290 ER PT J AU O'Brien, SM Dunson, DB AF O'Brien, SM Dunson, DB TI Bayesian multivariate logistic regression SO BIOMETRICS LA English DT Article DE block updating; categorical data; data augmentation; latent variables; MCMC algorithm; multiple binary outcomes; proportional odds ID RANDOM-EFFECTS MODELS; LINEAR MIXED MODELS; BINARY DATA; DISTRIBUTIONS; PROPRIETY; RESPONSES; EXISTENCE; OUTCOMES; PRIORS AB Bayesian analyses of multivariate binary or categorical outcomes typically rely on probit or mixed effects logistic regression models that do not have a marginal logistic structure for the individual outcomes. In addition, difficulties arise when simple noninformative priors are chosen for the covariance parameters. Motivated by these problems, we propose a new type of multivariate logistic distribution that can be used to construct a likelihood for multivariate logistic regression analysis of binary and categorical data. The model for individual outcomes has a marginal logistic structure, simplifying interpretation. We follow a Bayesian approach to estimation and inference, developing an efficient data augmentation algorithm for posterior computation. The method is illustrated with application to a neurotoxicology study. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP O'Brien, SM (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM obrien4@niehs.nih.gov RI O'Brien, Sean/H-6268-2013 NR 25 TC 53 Z9 53 U1 1 U2 15 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2004 VL 60 IS 3 BP 739 EP 746 DI 10.1111/j.0006-341X.2004.00224.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 853HP UT WOS:000223818200024 PM 15339297 ER PT J AU Polozov, IV Gawrisch, K AF Polozov, IV Gawrisch, K TI Domains in binary SOPC/POPE lipid mixtures studied by pulsed field gradient H-1 MAS NMR SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; HIGH-RESOLUTION PROTON; PHOSPHOLIPID-BILAYERS; PHASE-BEHAVIOR; FLUORESCENCE MICROSCOPY; DIFFUSION MEASUREMENTS; LATERAL DIFFUSION; MODEL MEMBRANES; CELL-MEMBRANES; CHAIN ORDER AB We studied domain formation in mixtures of the monounsaturated lipids SOPC and POPE as a function of temperature and composition by NMR. Magic angle spinning at kHz frequencies restored resolution of H-1 NMR lipid resonances in the fluid phase, whereas the linewidth of gel-phase lipids remained rather broad and spinning frequency dependent. In regions of fluid- and gel-phase coexistence, spectra are a superposition of resonances from fluid and gel domains, as indicated by the existence of isosbestic points. Quantitative determination of the amount of lipid in the coexisting phases is straightforward and permitted construction of a binary phase diagram. Lateral rates of lipid diffusion were determined by H-1 MAS NMR with pulsed field gradients. At the onset of the phase transition near 25 degreesC apparent diffusion rates became diffusion time dependent, indicating that lipid movement is obstructed by the formation of gel-phase domains. A percolation threshold at which diffusion of fluid- phase lipid becomes confined to micrometer-size domains was observed when similar to 40% of total lipid had entered the gel phase. The results indicate that common phosphatidylethanolamines may trigger domain formation in membranes within a physiologically relevant temperature range. This novel NMR approach may aid the study of lipid rafts. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 12420 Parklawn Dr,Rm 150, Rockville, MD 20852 USA. EM gawrisch@helix.nih.gov NR 47 TC 24 Z9 27 U1 2 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2004 VL 87 IS 3 BP 1741 EP 1751 DI 10.1529/biophysj.104.040725 PG 11 WC Biophysics SC Biophysics GA 851EN UT WOS:000223668500032 PM 15345553 ER PT J AU Snyder, GE Sakamoto, T Hammer, JA Sellers, JR Selvin, PR AF Snyder, GE Sakamoto, T Hammer, JA Sellers, JR Selvin, PR TI Nanometer localization of single green fluorescent proteins: Evidence that myosin V walks hand-over-hand via telemark configuration SO BIOPHYSICAL JOURNAL LA English DT Article ID MOTOR; MOLECULES; ACTIN; PROCESSIVITY; ORIENTATIONS; DIFFUSION; MOVEMENT; DYNAMICS; MODEL AB Myosin V is a homodimeric motor protein involved in trafficking of vesicles in the cell. It walks bipedally along actin. laments, moving cargo similar to37 nm per step. We have measured the step size of individual myosin heads by fusing an enhanced green fluorescent protein (eGFP) to the N-terminus of one head of the myosin dimer and following the motion with nanometer precision and subsecond resolution. We find the average step size to be 74.1 nm with 9.4 nm (SD) and 0.3 nm ( SE). Our measurements demonstrate nanometer localization of single eGFPs, confirm the hand-over-hand model of myosin V procession, and when combined with previous data, suggest that there is a kink in the leading lever arm in the waiting state of myosin V. This kink, or "telemark skier'' configuration, may cause strain, which, when released, leads to the powerstroke of myosin, throwing the rear head forward and leading to unidirectional motion. C1 Univ Illinois, Loomis Lab Phys, Dept Phys, Urbana, IL 61801 USA. Univ Illinois, Ctr Biophys & Computat Biol, Urbana, IL 61801 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Selvin, PR (reprint author), Univ Illinois, Loomis Lab Phys, Dept Phys, 1110 W Green St, Urbana, IL 61801 USA. EM selvin@uiuc.edu FU NIAMS NIH HHS [R01 AR044420, R29 AR044420, AR44420] NR 30 TC 60 Z9 61 U1 1 U2 9 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2004 VL 87 IS 3 BP 1776 EP 1783 DI 10.1529/biophysj.103.036897 PG 8 WC Biophysics SC Biophysics GA 851EN UT WOS:000223668500035 PM 15345556 ER PT J AU Gafurov, B Chen, YD Chalovich, JM AF Gafurov, B Chen, YD Chalovich, JM TI Ca2+ and ionic strength dependencies of S1-ADP binding to actin-tropomyosin-troponin: Regulatory implications SO BIOPHYSICAL JOURNAL LA English DT Article ID ACTOMYOSIN ATPASE ACTIVITY; MUSCLE THIN-FILAMENTS; ADENOSINE-TRIPHOSPHATASE ACTIVITY; X-RAY-DIFFRACTION; MYOSIN SUBFRAGMENT-1; SKELETAL-MUSCLE; COOPERATIVE BINDING; HEAVY-MEROMYOSIN; CALCIUM-BINDING; 3 STATES AB Skeletal and cardiac muscle contraction are inhibited by the actin-associated complex of tropomyosin-troponin. Binding of Ca2+ to troponin or binding of ATP-free myosin to actin reverses this inhibition. Ca2+ and ATP-free myosin stabilize different tropomyosin-actin structural arrangements. The position of tropomyosin on actin affects the binding of ATP-free myosin to actin but does not greatly affect myosin-ATP binding. Ca2+ and ATP-free myosin alter both the affinity of ATP-free myosin for actin and the kinetics of that binding. A parallel pathway model of regulation simulated the effects of Ca2+ and ATP-free myosin binding on both equilibrium binding of myosin-nucleotide complexes to actin and the general features of ATPase activity. That model was recently shown to simulate the kinetics of myosin-S1 binding but the analysis was limited to a single condition because of the limited data available. We have now measured equilibrium binding and binding kinetics of myosin-S1-ADP to actin at a series of ionic strengths and free Ca2+ concentrations. The parallel pathway model of regulation is consistent with those data. In that model the interaction between adjacent regulatory complexes fully saturated with Ca2+ was destabilized and the inactive state of actin was stabilized at high ionic strength. These changes explain the previously observed change in binding kinetics with increasing ionic strength. C1 E Carolina Univ, Brody Sch Med, Dept Biochem & Mol Biol, Greenville, NC 27834 USA. NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Chalovich, JM (reprint author), E Carolina Univ, Brody Sch Med, Dept Biochem & Mol Biol, 600 Moye Blvd, Greenville, NC 27834 USA. EM chalovichj@mail.ecu.edu OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR40540, R01 AR035216] NR 55 TC 14 Z9 15 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2004 VL 87 IS 3 BP 1825 EP 1835 DI 10.1529/biophysj.104.043364 PG 11 WC Biophysics SC Biophysics GA 851EN UT WOS:000223668500040 PM 15345561 ER PT J AU Wang, H Bash, R Yodh, JG Hager, G Lindsay, SM Lohr, D AF Wang, H Bash, R Yodh, JG Hager, G Lindsay, SM Lohr, D TI Using atomic force microscopy to study nucleosome remodeling on individual nucleosomal arrays in situ SO BIOPHYSICAL JOURNAL LA English DT Article ID HUMAN SWI/SNF; GLUCOCORTICOID-RECEPTOR; CHROMATIN; COMPLEX; HISTONE; DNA; TRANSCRIPTION; DISRUPTION; REQUIRES; ROLES AB In eukaryotes, genomic processes like transcription, replication, repair, and recombination typically require alterations in nucleosome structure on specific DNA regions to operate. ATP-dependent nucleosome remodeling complexes provide a major mechanism for carrying out such alterations in vivo. To learn more about the action of these important complexes, we have utilized an atomic force microscopy in situ technique that permits comparison of the same individual molecules before and after activation of a particular process, in this case nucleosome remodeling. This direct approach was used to look for changes induced by the action of the human Swi-Snf remodeling complex on individual, single-copy mouse mammary tumor virus promoter nucleosomal arrays. Using this technique, we detect a variety of changes on remodeling. Many of these changes are larger in scale than suggested from previous studies and involve a number of DNA-mediated events, including a preference for the removal of a complete turn (80 basepairs) of nucleosomal DNA. The latter result raises the possibility of an unanticipated mode of human Swi-Snf interaction with the nucleosome, namely via the 11-nm histone surface. C1 Arizona State Univ, Dept Phys & Astron, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. Midwestern Univ, Arizona Coll Osteopath Med, Div Basic Sci, Glendale, AZ USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. RP Lindsay, SM (reprint author), Arizona State Univ, Dept Phys, Tempe, AZ 85287 USA. EM stuart.lindsay@asu.edu FU NCI NIH HHS [R01 CA085990, CA 85990] NR 28 TC 22 Z9 24 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2004 VL 87 IS 3 BP 1964 EP 1971 DI 10.1529/biophysj.104.042606 PG 8 WC Biophysics SC Biophysics GA 851EN UT WOS:000223668500051 PM 15345572 ER PT J AU Stroh, CM Ebner, A Geretschlager, M Freudenthaler, G Kienberger, F Kamruzzahan, ASM Smith-Gil, SJ Gruber, HJ Hinterdorfer, P AF Stroh, CM Ebner, A Geretschlager, M Freudenthaler, G Kienberger, F Kamruzzahan, ASM Smith-Gil, SJ Gruber, HJ Hinterdorfer, P TI Simultaneous topography and recognition Imaging using force microscopy SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR RECOGNITION; ADHESION; SPECTROSCOPY; IMMUNOGLOBULIN; ELASTICITY; BINDING; BONDS; AFM; DNA AB We present a method for simultaneously recording topography images and localizing specific binding sites with nm positional accuracy by combining dynamic force microscopy with single molecule recognition force spectroscopy. For this we used lysozyme adsorbed to mica, the functionality of which was characterized by enzyme immunoassays. The topography and recognition images were acquired using tips that were magnetically oscillated during scanning and contained antibodies directed against lysozyme. For cantilevers with low Q-factor (similar to1 in liquid) driven at frequencies below resonance, the surface contact only affected the downward deflections (minima) of the oscillations, whereas binding of the antibody on the tip to lysozyme on the surface only affected the upwards deflections (maxima) of the oscillations. The recognition signals were therefore well separated from the topographic signals, both in space (Deltazsimilar to5 nm) and time (similar to0.1 ms). Topography and recognition images were simultaneously recorded using a specially designed electronic circuit with which the maxima (U-up) and the minima (U-down) of each sinusoidal cantilever deflection period were depicted. U-down was used for driving the feedback loop to record the height (topography) image, and U-up provided the data for the recognition image. C1 Johannes Kepler Univ, Inst Biophys, A-4040 Linz, Austria. Johannes Kepler Univ, Inst Expt Phys Atom Phys & Surface Sci, A-4040 Linz, Austria. NCI, Basic Res Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Frederick, MD 21702 USA. RP Hinterdorfer, P (reprint author), Univ Linz, Inst Biophys, Altenbergerstr 69, A-4040 Linz, Austria. EM peter.hinterdorfer@jku.at RI Hinterdorfer, Peter/C-4235-2013; Ebner, Andreas/C-4233-2013; Gruber, Hermann/C-4234-2013 OI Ebner, Andreas/0000-0001-5615-7590; NR 44 TC 101 Z9 105 U1 2 U2 31 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2004 VL 87 IS 3 BP 1981 EP 1990 DI 10.1529/biophysj.104.043331 PG 10 WC Biophysics SC Biophysics GA 851EN UT WOS:000223668500053 PM 15345574 ER PT J AU Noguchi, CT AF Noguchi, CT TI Is there something fishy about EPO? SO BLOOD LA English DT Editorial Material AB The erythropoietin gene from Fugu rubripes (pufferfish) is homologous to the human protein but lacks a flanking hypoxia-responsive element that is critical for erythropoietin induction by hypoxia in mammals. C1 NIH, Bethesda, MD 20892 USA. RP Noguchi, CT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1238 EP 1238 DI 10.1182/blood-2004-06-2092 PG 1 WC Hematology SC Hematology GA 849MX UT WOS:000223544000008 ER PT J AU Wada, T Schurman, SH Jagadeesh, GJ Garabedian, EK Nelson, DL Candotti, F AF Wada, T Schurman, SH Jagadeesh, GJ Garabedian, EK Nelson, DL Candotti, F TI Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family SO BLOOD LA English DT Article ID IN-VIVO REVERSION; FLOW-CYTOMETRIC ANALYSIS; WASP GENE-MUTATIONS; INHERITED MUTATION; LINKED THROMBOCYTOPENIA; PROTEIN EXPRESSION; SOMATIC MOSAICISM; LYMPHOCYTES; DEFICIENCY; PHENOTYPE AB We previously reported on a 43-year-old patient with Wiskott-Aldrich syndrome (WAS) who experienced progressive clinical improvement and revertant T-cell mosaicism. Deletion of the disease-causing 6-bp insertion was hypothesized to have occurred by DNA polymerase slippage. We now describe 2 additional patients from the same family who also had revertant T lymphocytes that showed selective in vivo advantage. Somatic mosaicism was demonstrated on leukocytes cryopreserved in the first patient when he was 22 years old, 11 years before his death from kidney failure. The second patient is now 16 years old, has a moderate clinical phenotype, and developed revertant cells after the age of 14 years. These results support DNA polymerase slippage as a common underlying mechanism, and they indicate that T-cell mosaicism may have different clinical effects in WAS. (C) 2004 by The American Society of Hematology. C1 NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Rm 3A20,MSC 4442,49 Convent Dr, Bethesda, MD 20892 USA. EM fabio@nhgri.nih.gov OI Schurman, Shepherd/0000-0002-9133-7906 NR 21 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1270 EP 1272 DI 10.1182/blood-2004-03-0846 PG 3 WC Hematology SC Hematology GA 849MX UT WOS:000223544000016 PM 15142877 ER PT J AU Kuramoto, K Follman, D Hematti, P Sellers, S Laukkanen, MO Seggewiss, R Metzger, ME Krouse, A Donahue, RE von Kalle, C Dunbar, CE AF Kuramoto, K Follman, D Hematti, P Sellers, S Laukkanen, MO Seggewiss, R Metzger, ME Krouse, A Donahue, RE von Kalle, C Dunbar, CE TI The impact of low-dose busulfan on clonal dynamics in nonhuman primates SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELL; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; PERIPHERAL-BLOOD; MYELODYSPLASTIC SYNDROME; CYTOTOXIC AGENTS; IN-VIVO; ENGRAFTMENT; THERAPY; PROLIFERATION AB An understanding of the number and contribution of individual pluripotent hematopoietic stem cells (HSCs) to the formation of blood lineages has important clinical implications for gene therapy and stem cell transplantation. We have been able to efficiently mark rhesus macaque long-term repopulating stem and progenitor cells with retroviral vectors, and track their in vivo contributions to hematopoiesis using the linear amplification mediated-polymerase chain reaction (LAM-PCR) technique of insertion site analysis. We assessed the impact of busulfan on contributions of individual retrovirally marked clones to hematopoiesis. There were 2 macaques that received transplants of retrovirally transduced CD34(+) cells 2 years previously that were then treated with 4 mg/kg busulfan. Despite only transient and mild suppression of peripheral blood counts, the numbers of individual stem/progenitor clones contributing to granulocyte production decreased dramatically, by 80% in the first monkey and by 60% in the second monkey. A similar impact was seen on clones contributing to T cells. The clone numbers recovered gradually back toward baseline by 5 months following busulfan in the first monkey and by 3 months in the second monkey, and have remained stable for more than one year in both animals. Tracking of individual clones with insertion-site-specific primers suggested that clones contributing to hematopoiesis prior to busulfan accounted for the majority of this recovery, but that some previously undetected clones began to contribute during this recovery phase. These results indicate that even low-dose busulfan significantly affects stem and progenitor cell dynamics. The clonal diversity of hematopoiesis was significantly decreased after even a single, clinically well-tolerated close of busulfan, with slow but almost complete recovery over the next several months, suggesting that true long-term repopulating stem cells were not permanently deleted. However, the prolonged period of suppression of many clones suggests that transplanted HSCs may have a marked competitive advantage if they can engraft and proliferate during this time period, and supports the use of this agent in nonmyeloablative regimens (C) 2004 by The American Society of Hematology. C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Cincinnati Childrens Hosp, Med Ctr, Childrens Res Fdn, Div Expt Hematol, Cincinnati, OH USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 39 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1273 EP 1280 DI 10.1182/blood-2003-08-2935 PG 8 WC Hematology SC Hematology GA 849MX UT WOS:000223544000017 PM 15126320 ER PT J AU El Kassar, N Lucas, PJ Klug, DB Zamisch, M Merchant, M Bare, CV Choudhury, B Sharrow, SO Richie, E Mackall, CL Gress, RE AF El Kassar, N Lucas, PJ Klug, DB Zamisch, M Merchant, M Bare, CV Choudhury, B Sharrow, SO Richie, E Mackall, CL Gress, RE TI A dose effect of IL-7 on thymocyte development SO BLOOD LA English DT Article ID T-CELL-RECEPTOR; DEFECTIVE LYMPHOID DEVELOPMENT; LCK PROXIMAL PROMOTER; MICE LACKING JAK3; ALPHA-BETA CELLS; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; POSITIVE SELECTION; GAMMA CHAIN; DIFFERENTIATION PATHWAY AB To study interleukin-7 (IL-7) in early thymocyte development, we generated mice transgenic (Tg) for the IL-7 gene under control of the Ick proximal promoter. Founder line TgA, with the lowest level of IL-7 overexpression, showed enhanced alphabeta T-cell development. In contrast, in the highest overexpressing founder line, TgB, alphabeta T-cell development was disturbed with a block at the earliest intrathymic precursor stage. This was due to decreased progenitor proliferation as assessed by Ki-67 staining and in vivo bromodeoxyuridine (BrdU incorporation. Bcl-2 was upregulated in T-cell-committed progenitors in all Tg lines, and accounted for greater numbers of double positive (DP), CD4 single positive (SP), and CD8SP thymocytes in TgA mice where, in contrast to TgB mice, thymocyte progenitor proliferation was normal. Mixed marrow chimeras using TgB(+) and congenic mice as donors, and experiments using anti-IL-7 monoclonal antibody (MAb) in vivo, confirmed the role of IL-7 protein in the observed TgB phenotype. In conclusion, at low Tg overexpression, IL-7 enhanced alphabeta T-cell development by increasing thymocyte progenitor survival, while at high overexpression IL-7 reduces their proliferation, inducing a dramatic block in DP production. These results show for the first time in vivo a dose effect of IL-7 on alphabeta T-cell development and have implications for IL-7 in the clinical setting. (C) 2004 by The American Society of Hematology. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. RP Gress, RE (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr,Bldg 10 Rm 4B36, Bethesda, MD 20892 USA. EM cb49m@nih.gov NR 55 TC 48 Z9 48 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1419 EP 1427 DI 10.1182/blood-2004-01-0201 PG 9 WC Hematology SC Hematology GA 849MX UT WOS:000223544000037 PM 15155461 ER PT J AU Rosenwald, A Chuang, EY Davis, RE Wiestner, A Alizadeh, AA Arthur, DC Mitchell, JB Marti, GE Fowler, DH Wilson, WH Staudt, LM AF Rosenwald, A Chuang, EY Davis, RE Wiestner, A Alizadeh, AA Arthur, DC Mitchell, JB Marti, GE Fowler, DH Wilson, WH Staudt, LM TI Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response SO BLOOD LA English DT Article ID PURINE ANALOGS; ZAP-70 EXPRESSION; DRUG-RESISTANCE; CELL-DEATH; P53; MUTATION; CHEMOTHERAPY; SURVIVAL; CYCLOPHOSPHAMIDE; APOPTOSIS AB Fludarabine, the current standard treatment for B-cell chronic lymphocytic leukemia (CLL), can induce apoptosis in CLL cells in vitro, and a number of molecular mechanisms contribute to its cytotoxicity. Using gene expression profiling, we investigated the molecular consequences of fludarabine treatment of patients with CLL in vivo. In 7 patients with CLL, a consistent gene expression signature of in vivo fludarabine exposure was identified. Many of the fludarabine signature genes were known p53 target genes and genes involved in DNA repair. In vitro treatment of CLL cells with fludarabine induced the same set of genes as observed in vivo, and many of these genes were also induced by in vitro exposure of CLL cells to ionizing radiation. Using isogenic p53 wild-type and null lymphoblastoid cell lines, we confirmed that many of the fludarabine signature genes were also p53 target genes. Because in vivo treatment with fludarabine induces a p53-dependent gene expression response, fludarabine treatment has the potential to select p53-mutant CLL cells, which are more drug resistant and associated with an aggressive clinical course. These considerations suggest that fludarabine treatment should be given in strict accordance to the current National Cancer Institute (NCI) guidelines that have established criteria of disease activity that warrant treatment. (C) 2004 by The American Society of Hematology. C1 NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol & Transplantat Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Gene & Cell Therapy, NIH, Bethesda, MD 20014 USA. Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, CCR, NIH, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Alizadeh, Arash Ash/0000-0002-5153-5625 NR 34 TC 99 Z9 105 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1428 EP 1434 DI 10.1182/blood-2003-09-3236 PG 7 WC Hematology SC Hematology GA 849MX UT WOS:000223544000038 PM 15138159 ER PT J AU Jeong, SJ Radonovich, M Brady, JN Pise-Masison, CA AF Jeong, SJ Radonovich, M Brady, JN Pise-Masison, CA TI HTLV-I tax induces a novel interaction between p65/RelA and p53 that results in inhibition of p53 transcriptional activity SO BLOOD LA English DT Article ID NF-KAPPA-B; T-CELL LEUKEMIA; VIRUS TYPE-1 TAX; TUMOR-SUPPRESSOR PROTEIN; PROSTATE-CANCER CELLS; TRANSACTIVATION FUNCTION; CONSTITUTIVE ACTIVATION; ADENOCARCINOMA CELLS; IMMUNE-RESPONSES; BREAST-CANCER AB Nuclear factor kappaB (NF-kappaB) activation plays a critical role in oncogenesis by human T-cell lymphotrophic virus type I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL), and is indispensable for maintenance of the malignant phenotype. In T lymphocytes, Tax-mediated p53 inhibition is dependent on Tax activation of the NF-kappaB pathway and is linked to p53 phosphorylation. We now report that blocking NF-kappaB transcriptional activation in HTLV-I-transformed cells restores p53 activity. Further, using mouse embryo fibroblast (MEF) null cells and antisense oligonucle-otides to inhibit expression of NF-kappaB family members, we demonstrate that the p65 subunit of NF-kappaB is uniquely involved in p53 inhibition. Coimmunoprecipitation assays demonstrate an interaction between p65 and p53 in HTLV-I-transformed cells. In transient transfection assays, we demonstrate that Tax induces the p53-p65 interaction. Phosphorylation of p53 at serines 15 and 392 is critical for complex formation. Importantly, Tax-mediated p53 inhibition correlates with p65 and p53 interaction. By using chromatin immunoprecipitation (ChIP) assays, we find that in HTLV-I-transformed cells p53 and p65 form a complex on the inactive, p53-responsive murine double minute 2 (MDM2) Promoter. Consistent with reduced transcriptional activity, transcription factor IID (TRID) binding is not observed. These studies identify a unique mechanism for p53 regulation by the p65/ReIA subunit of NF-kappaB. C1 NCI, Virus Tumor Biol Sect, Basic Res Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Pise-Masison, CA (reprint author), NCI, Virus Tumor Biol Sect, Basic Res Lab, Canc Res Ctr,NIH, Bldg 41-B303,41 Lib Dr, Bethesda, MD 20892 USA. EM masisonc@mail.nih.gov NR 70 TC 68 Z9 70 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1490 EP 1497 DI 10.1182/blood-2003-12-4174 PG 8 WC Hematology SC Hematology GA 849MX UT WOS:000223544000046 PM 15155458 ER PT J AU Donahue, RE Chen, ISY AF Donahue, RE Chen, ISY TI Transgene-specific tolerance versus immune response SO BLOOD LA English DT Letter ID CD34(+) PROGENITOR CELLS; LENTIVIRUS VECTOR; GENE-TRANSFER; INDUCTION C1 NHLBI, Hematol Branch, Rockville, MD 20850 USA. RP Donahue, RE (reprint author), NHLBI, Hematol Branch, 5 Res Ct, Rockville, MD 20850 USA. EM donahuer@nhlbi.nih.gov NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2004 VL 104 IS 5 BP 1578 EP 1579 DI 10.1182/blood-2004-02-0726 PG 2 WC Hematology SC Hematology GA 849MX UT WOS:000223544000058 PM 15317730 ER PT J AU Schaefer, M Noennig, N Karl, A Heinze, HJ Rotte, M AF Schaefer, M Noennig, N Karl, A Heinze, HJ Rotte, M TI Reproducibility and stability of neuromagnetic source imaging in primary somatosensory cortex SO BRAIN TOPOGRAPHY LA English DT Article DE somatosensory evoked fields; magnetoencephalography; dipole source localization; somatosensory cortex; reproducibility ID ELECTRIC SOURCE LOCALIZATION; LARGE-ARRAY BIOMAGNETOMETER; MAGNETOENCEPHALOGRAPHY; NEURONAVIGATION; STIMULATION; VALIDITY; HUMANS AB The present study investigated the test-retest reliability of magnetoencephalography (MEG) source localization of somatosensory evoked fields (SEFs) over an extended time period. Five healthy subjects were stimulated pneumatically at the first and fifth digit in two sessions spaced several months apart. At each location 400 stimuli were presented. The validation of the results was performed by overlay of the dipole localizations into the individual anatomic structure of the subjects' cortex by the use of magnetic resonance images (MRIs). The source localizations of the SEF component were found to be highly reproducible. The mean standard deviation of the dipole locations of the first digit was 1.55 mm in the x-, 1.55 mm in the y- and 3.49 mm in the z-direction. The mean standard deviation of the fifth digit was 3.69 mm in the x-, 4.27 mm in the y- and 6.60 mm in the z-direction. These results support the use of MEG recordings combined with MRI as an adequate method to define the organization of the human primary somatosensory cortex and provide a useful approach to the rapid detection of neuroplasticity. C1 NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. Univ Magdeburg, Dept Neurol 2, D-39106 Magdeburg, Germany. Dresden Univ Technol, Biopsychol Unit, D-8027 Dresden, Germany. RP Schaefer, M (reprint author), NINDS, NIH, Human Cort Physiol Sect, Bldg 10,Room 5S-208, Bethesda, MD 20892 USA. EM schaefem@ninds.nih.gov OI Karl, Anke/0000-0002-6472-2876 NR 18 TC 17 Z9 17 U1 0 U2 1 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0896-0267 J9 BRAIN TOPOGR JI Brain Topogr. PD FAL PY 2004 VL 17 IS 1 BP 47 EP 53 DI 10.1023/B:BRAT.0000047336.15770.86 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 878VD UT WOS:000225674300005 PM 15669755 ER PT J AU Oh, S Heflin, L Meyerowitz, BE Desmond, KA Rowland, JH Ganz, PA AF Oh, S Heflin, L Meyerowitz, BE Desmond, KA Rowland, JH Ganz, PA TI Quality of life of breast cancer survivors after a recurrence: a follow-up study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; cancer survivors; psychosocial adjustment; quality of life; recurrence ID DYADIC ADJUSTMENT; COMMUNITY SAMPLE; ADJUVANT THERAPY; WOMEN; SCALES; DEPRESSION; INVENTORY; DISEASE; IMPACT; SF-36 AB Previous studies on breast cancer recurrence provide a mixed picture of the quality of life of women following a recurrence. To clarify the picture, the present study addresses some previous methodological concerns by offering a multidimensional assessment with follow-up, a matched comparison group of disease-free survivors, and a closer look at the nature of recurrence (local versus metastatic). Fifty-Four of 817 women who participated in an earlier study experienced a recurrence at follow-up, and are compared to a matched sample of 54 women who remained disease-free. Analyses indicate that women who had a recurrence report significantly poorer functioning on various health-related quality of life (HRQOL) domains compared to women who remained disease-free. However, the differences appear to be largely due to the poorer HRQOL of women with metastatic disease. Although women who had a recurrence report good mood, low stress, and good quality of interpersonal relationships, they report significantly higher cancer-specific stress compared to disease-free women at follow-up. Women who had a recurrence also report experiencing both more meaning and vulnerability as a result of breast cancer than disease-free women, but report similar levels of spirituality and benefit-finding at follow-up as disease-free women. These results suggest that although women report relatively good psychosocial adjustment following a recurrence, cancer-specific domains of quality of life are most likely to be negatively affected. These results may be useful in identifying individuals with breast cancer recurrences who are most in need of psychosocial services. C1 Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Meyerowitz, BE (reprint author), Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. EM meyerow@usc.edu FU NCI NIH HHS [R01 CA63028] NR 35 TC 50 Z9 50 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2004 VL 87 IS 1 BP 45 EP 57 DI 10.1023/B:BREA.0000041580.55817.5a PG 13 WC Oncology SC Oncology GA 854PA UT WOS:000223914600006 PM 15377850 ER PT J AU Fichtner, I Monks, A Hose, C Stevens, MFG Bradshaw, TD AF Fichtner, I Monks, A Hose, C Stevens, MFG Bradshaw, TD TI The experimental antitumor agents Phortress and Doxorubicin are equiactive against human-derived breast carcinoma xenograft models SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast carcinoma model; cytochrome P450 1A1; doxorubicin; estrogen receptor; Phortress ID AMINO-ACID PRODRUGS; IN-VITRO; NUDE-MICE; CANCER CELLS; TUMOR-CELLS; 2-(4-AMINOPHENYL)BENZOTHIAZOLES; ESTABLISHMENT; LINES; BENZOTHIAZOLES; VIVO AB Phortress (the dihydrochloride salt of the lysylamide prodrug of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203)) is an experimental antitumor agent with potent and selective activity against human-derived carcinomas of breast, ovarian and renal origin. UK clinical trials of Phortress are scheduled to begin in 2004. The mechanism of action of Phortress is distinct from all classes of chemotherapeutic agents currently in the clinic, and involves metabolic activation by cytochrome P450 (CYP) 1A1 to electrophilic species, which generate DNA adducts in sensitive tumors only. In the present study, the antitumor efficacy of Phortress has been compared with that of doxorubicin (Dox) in nine human-derived mammary carcinoma xenograft models, cultivated subcutaneously in the flanks of nude mice. In addition, cyp1a1 mRNA expression was measured in tumors of control and treated animals. Phortress compared favorably with Dox: significant activity, independent of estrogen receptor (ER) status, was established in 7/9 xenografts; in one xenograft model, Phortress elicited superior antitumor activity; no model demonstrated complete resistance to Phortress. In accordance with this observation, all xenografts available for examination (8) displayed clear induction of cyp1a1 expression upon treatment of mice with Phortress whereas Dox failed to induce cyp1a1 expression in all models. Prolonged viability of tumor fragments, recovered for treatment ex vivo could not be sustained; thus correlations between tumor cells' response to Phortress and cyp1a1 or cyp1b1 inducibility following 5F 203 treatment could not be determined with confidence. C1 Univ Nottingham, Ctr Biomol Sci, Nottingham NG7 2RD, England. Max Delbruck Ctr Mol Med, Berlin, Germany. NCI, SAIC Frederick Inc, Screening Technol Branch, Lab Funct Genom, Frederick, MD 21701 USA. RP Bradshaw, TD (reprint author), Univ Nottingham, Ctr Biomol Sci, Univ Blvd, Nottingham NG7 2RD, England. EM tracey.brad-shaw@nottingham.uk NR 24 TC 28 Z9 29 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2004 VL 87 IS 1 BP 97 EP 107 DI 10.1023/B:BREA.0000041586.64371.88 PG 11 WC Oncology SC Oncology GA 854PA UT WOS:000223914600011 PM 15377855 ER PT J AU Viboud, C Boelle, PY Cauchemez, S Lavenu, A Valleron, AJ Flahault, A Carrat, F AF Viboud, C Boelle, PY Cauchemez, S Lavenu, A Valleron, AJ Flahault, A Carrat, F TI Risk factors of influenza transmission in households SO BRITISH JOURNAL OF GENERAL PRACTICE LA English DT Article DE antivirals; children; epidemiology; influenza; prospective studies; risk factors; vaccination ID ACUTE RESPIRATORY ILLNESS; COMMUNICABLE DISEASES; CONTROLLED TRIAL; SURVEILLANCE; PREVENTION; INFECTION; ZANAMIVIR; CONTACTS; OSELTAMIVIR; PARAMETERS AB Background: Influenza transmission in households is a subject of renewed interest, as the vaccination of children is currently under debate and antiviral treatments have been approved for prophylactic use. Aims: To quantify the risk factors of influenza transmission in households. Design of study: A prospective study conducted during the 1999 to 2000 winter season in Ranee Setting: Nine hundred and forty-six households where a member, the index patient, had visited their general practitioner (GP) because of an influenza-like illness were enrolled in the study. Five hundred and ten of the index patients tested positive for influenza A (subtype H3N2). A standardised daily questionnaire allowed for identification of secondary cases of influenza among their household contacts, who were followed-up for 15 days. Of the 395 (77%) households that completed the questionnaire, we selected 279 where no additional cases had occurred on the day of the index patient's visit to the GP. Methods: Secondary cases of influenza were those household contacts who had developed clinical influenza within 5 days of the disease onset in the index patient. Hazard ratios for individual clinical and demographic characteristics of the contact and their index patient were derived, from a Cox regression model. Results: Overall in the 279 households, 131 (24.1%) secondary cases occurred among the 543 household contacts. There was an increased risk of influenza transmission in preschool contacts (hazard ratio [HR] = 1.85, 95%; confidence interval [CI] = 1.09 to 3.26) as compared with school-age and adult contacts. There was also an increased risk in contacts exposed to preschool index patents (HR = 1.93, 95% CI = 1.09 to 3.42) and school-age index patients (HR = 1.68, 95% CI = 1.07 to 2.65), compared with those exposed to adult index cases. No other factor was associated with transmission of the disease. Conclusion: Our results support the major role of children in the dissemination of influenza in households. vaccination of children or prophylaxis with neuraminidase inhibitors would prevent, respectively, 32-38% and 21-41% of secondary cases caused by exposure to a sick child in the household. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. WHO, CCEDS, Paris, France. Univ Paris 06, Paris, France. Assistance Publ Hop Paris, Paris, France. RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov NR 24 TC 172 Z9 174 U1 0 U2 2 PU ROYAL COLL GENERAL PRACTITIONERS PI LONDON PA 14 PRINCES GATE, HYDE PARK, LONDON SW7 1PU, ENGLAND SN 0960-1643 J9 BRIT J GEN PRACT JI Br. J. Gen. Pract. PD SEP PY 2004 VL 54 IS 506 BP 684 EP 689 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 866YH UT WOS:000224808800010 PM 15353055 ER PT J AU Bishop, MR Steinberg, SA Gress, RE Hardy, NM Marchigiani, D Kasten-Sportes, C Dean, R Pavletic, SZ Gea-Banadoche, J Castro, K Hakim, F Krumlauf, M Read, EJ Carter, C Leitman, SF Fowler, DH AF Bishop, MR Steinberg, SA Gress, RE Hardy, NM Marchigiani, D Kasten-Sportes, C Dean, R Pavletic, SZ Gea-Banadoche, J Castro, K Hakim, F Krumlauf, M Read, EJ Carter, C Leitman, SF Fowler, DH TI Targeted pretransplant host lymphocyte depletion prior to T-cell depleted reduced-intensity allogeneic stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE allogeneic; T-cell depletion; reduced-intensity; graft rejection ID BONE-MARROW-TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; CONDITIONING REGIMEN; DONOR ENGRAFTMENT; MIXED CHIMERISM; THERAPY; CHEMOTHERAPY; FLUDARABINE; RESPONSES; DISEASE AB Mixed chimaerism and graft rejection are higher after reduced-intensity allogeneic stem cell transplantation (RIST) with T-cell depleted (TCD) allografts. As host immune status before RIST affects engraftment, we hypothesized that targeted depletion of host lymphocytes prior to RIST would abrogate graft rejection and promote donor chimaerism. Lymphocyte-depleting chemotherapy was administered at conventional doses to subjects prior to RIST with the intent of decreasing CD4(+) counts to <0.05 x 10(9) cells/l. Subjects (n = 18) then received reduced-intensity conditioning followed by ex vivo TCD human leucocyte antigen-matched sibling allografts. All evaluable patients (n = 17) were engrafted; there were no late graft failures. At day +28 post-RIST, 12 patients showed complete donor chimaerism. Mixed chimaerism in the remaining five patients was associated with higher numbers of circulating host CD3(+) cells (P = 0.0032) after lymphocyte-depleting chemotherapy and was preferentially observed in T lymphoid rather than myeloid cells. Full donor chimaerism was achieved in all patients after planned donor lymphocyte infusions. These data reflect the importance of host immune status prior to RIST and suggest that targeted host lymphocyte depletion facilitates the engraftment of TCD allografts. Targeted lymphocyte depletion may permit an individualized approach to conditioning based on host immune status prior to RIST. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov NR 21 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2004 VL 126 IS 6 BP 837 EP 843 DI 10.1111/j.1365-2141.2004.05133.x PG 7 WC Hematology SC Hematology GA 854IA UT WOS:000223895100010 PM 15352988 ER PT J AU Lupica, CR Riegel, AC Hoffman, AF AF Lupica, CR Riegel, AC Hoffman, AF TI Marijuana and cannabinoid regulation of brain reward circuits SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE drug abuse; nucleus accumbens; ventral tegmental area; dopamine; plasticity; long-term depression; tolerance; self-administration; conditioned place preference; intracranial self-stimulation ID VENTRAL TEGMENTAL AREA; LONG-TERM DEPRESSION; NUCLEUS-ACCUMBENS SHELL; EXCITE DOPAMINE NEURONS; GABA-CONTAINING NEURONS; RECEPTOR MESSENGER-RNA; FREELY-MOVING RATS; SYNAPTIC-TRANSMISSION; ENDOGENOUS CANNABINOIDS; CB1 RECEPTORS AB The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA. C1 NIDA, Neurophysiol Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH,US Dept Hlth & Human S, Baltimore, MD 21224 USA. RP Lupica, CR (reprint author), NIDA, Neurophysiol Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH,US Dept Hlth & Human S, Baltimore, MD 21224 USA. EM clupica@intra.nida.nih.gov RI Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 NR 82 TC 120 Z9 126 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 2004 VL 143 IS 2 BP 227 EP 234 DI 10.1038/sj.bjp.0705931 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 855HX UT WOS:000223965200001 PM 15313883 ER PT J AU Bertram, R Sherman, A AF Bertram, R Sherman, A TI A calcium-based phantom bursting model for pancreatic islets SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID OSCILLATORY INSULIN-SECRETION; INDUCED ELECTRICAL-ACTIVITY; CYTOPLASMIC FREE CA2+; MOUSE BETA-CELLS; METABOLIC OSCILLATIONS; PULSATILE INSULIN; B-CELLS; (I) OSCILLATIONS; MINIMAL MODEL; ATP/ADP RATIO AB Insulin-secreting beta-cells, located within the pancreatic islets of Langerhan,are escitable cells that produce regular bursts of action potentials when stimulated by glucose. This system has been the focus of mathematical investigation for two decades, spawning an array of mathematical models. Recectly, a new class of models has been introduced called 'phantom bursters' [Bertram et al. (2000) Biophys. J. 79.2880-2892], which acounts for the wide range of burst frequencies exhibited by islets via interaction of more than one slow process. Here, we describe one implementation of the phantom bursting mechanism in which intracellular Ca2+ controls the oscillations through both direct and indirect negative feedback pathways. We show how the model dynamics can be understood through an extension of the fast/slow analysis that is typically employed for bursting oscillations. From this perspective, the model makes use of multiple degrees of freedom to generate the full range of bursting oscillations exhibited by beta-cells. The model also accounts for a wide range of experimental phenomena, including the ubiquitous triphasic response to the step elevation of glucose and responses to perturbations of internal Ca2+ stores. Although it is not presently a complete model of all beta-cell properties it demonstrates the design principles that we anticipate will underlie future progress in beta-cell modeling. C1 Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Kasha Lab Biophys, Tallahassee, FL 32306 USA. NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu NR 67 TC 60 Z9 60 U1 1 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD SEP PY 2004 VL 66 IS 5 BP 1313 EP 1344 DI 10.1016/j.bulm.2003.12.005 PG 32 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 856PX UT WOS:000224058200015 PM 15294427 ER PT J AU Musgrove, P AF Musgrove, P TI Earmarking could be beneficial: cost-effectiveness is not the only criterion SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material ID HEALTH C1 NIH, Dis Control Priorities Project, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Musgrove, P (reprint author), NIH, Dis Control Priorities Project, Fogarty Int Ctr, 16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA. EM musgrovp@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD SEP PY 2004 VL 82 IS 9 BP 706 EP 707 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 854YW UT WOS:000223940900013 ER PT J AU Kawakami, M Kawakami, K Takahashi, S Abe, M Puri, RK AF Kawakami, M Kawakami, K Takahashi, S Abe, M Puri, RK TI Analysis of interleukin-13 receptor alpha 2 expression in human pediatric brain tumors SO CANCER LA English DT Article DE interleukin-13 receptor; receptor subunits; pediatric brain tumor; in situ expression ID PLASMINOGEN-ACTIVATOR RECEPTOR; IN-SITU HYBRIDIZATION; HUMAN GLIOMA-CELLS; SIGNAL-TRANSDUCTION; ALPHA-2 CHAIN; PSEUDOMONAS EXOTOXIN; PANCREATIC TUMORS; CHIMERIC PROTEIN; CANCER-THERAPY; IL-4 RECEPTORS AB BACKGROUND. Compared with normal brain tissue cells, human malignant glioma cells express higher levels of interleukin-13 receptor (IL-13R). However, whether this receptor is expressed in situ has not been carefully examined. With IL-13R-targeted cytotoxin (IL13-PE38QQR, comprising IL-13 and a mutated form of Pseudomonas exotoxin [PE]) being tested in three Phase I/II clinical trials for the treatment of adult human glioma, and with pediatric studies being planned, the authors set out to analyze pediatric brain tumor tissue specimens for the expression of IL-13R. METHODS. Using in situ hybridization and immunohistochemical staining, the authors examined 58 pediatric brain tumor specimens for expression of the predominant IL-13 binding and internalizing protein (IL-13Ralpha2) chain at the mRNA and protein levels. RESULTS. overall, approximately 83% of pediatric brain tumor samples expressed IL-13Ralpha2. One hundred percent (11 of 11) high-grade astrocytoma, 79% (26 of 33) low-grade astrocytoma, 67% (4 of 6) medulloblastoma, and 67% (2 of 3) ependymoma samples were positive for IL-13Ralpha2. Among IL-13Ralpha2-positive samples, 88% (42 of 48 samples) had positive expression in greater than or equal to 50% of all tumor fields. The results obtained using both assays were consistent with each other. CONCLUSIONS. The current study established that pediatric brain tumor specimens expressed the IL-13Ralpha2 chain. Because the IL-13Ralpha2 chain is a major binding component of the IL-13R complex, these results suggest that the targeting of IL-13R may represent a useful approach for the treatment of pediatric brain tumors. Published 2004 by the American Cancer Society.* C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. Nagoya City Univ, Grad Sch Med Sci, Dept Expt Pathol & Tumor Biol, Aichi, Japan. Fujita Hlth Univ, Sch Med, Dept Surg Pathol, Aichi, Japan. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,HFM-735, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 31 TC 44 Z9 49 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 BP 1036 EP 1042 DI 10.1002/cncr.20470 PG 7 WC Oncology SC Oncology GA 848HQ UT WOS:000223458600021 PM 15329913 ER PT J AU Singh, GK Miller, BA Hankey, BF Edwards, BK AF Singh, GK Miller, BA Hankey, BF Edwards, BK TI Persistent area socioeconomic disparities in US incidence of cervical cancer, mortality, stage, and survival, 1975-2000 SO CANCER LA English DT Article DE surveillance; Epidemiology and End Results program; cervical cancer; incidence; mortality; stage; survival; poverty; deprivation; socioeconomic status; race/ethnicity ID UNITED-STATES; SOCIAL-CLASS; BREAST; BLACK; DIAGNOSIS; WHITES AB BACKGROUND. Temporal cervical cancer incidence and mortality patterns and ethnic disparities in patient survival and stage at diagnosis in relation to socioeconomic deprivation measures have not been well studied in the United States. The current article analyzed temporal area socioeconomic inequalities in U.S. cervical cancer incidence, mortality, stage, and survival. METHODS. County and census tract poverty and education variables from the 1990 census were linked to U.S. mortality and Surveillance, Epidemiology, and End Results cancer incidence data from 1975 to 2000. Age-adjusted incidence and mortality rates and 5-year cause-specific survival rates were calculated for each socioeconomic group and differences in rates were tested for statistical significance at the 0.05 level. RESULTS. Substantial area socioeconomic gradients in both incidence and mortality were observed, with inequalities in cervical cancer persisting against a backdrop of declining rates. Cervical cancer incidence and mortality rates increased with increasing poverty and decreasing education levels for the total population as well as for non-Hispanic white, black, American Indian, Asian/Pacific Islander, and Hispanic women. Patients in lower socioeconomic census tracts had significantly higher rates of late-stage cancer diagnosis and lower rates of cancer survival. Even after controlling for stage, significant differences in survival remained. The 5-year survival rate among women diagnosed with distant-stage cervical cancer was approximately 30% lower in low than in high socioeconomic census tracts. CONCLUSIONS. Census-based socioeconomic measures such as area poverty and education levels could serve as important surveillance tools for monitoring temporal trends in cancer-related health inequalities and targeting interventions. Published 2004 by the American Cancer Society.* C1 NCI, Div Canc Control & Populat Sci, Surveillance Res Program, NIH, Bethesda, MD 20892 USA. RP Singh, GK (reprint author), NCI, Div Canc Control & Populat Sci, Surveillance Res Program, NIH, 6116 Execut Blvd,Suite 504,MSC8316, Bethesda, MD 20892 USA. EM gopal_singh@nih.gov NR 29 TC 154 Z9 159 U1 2 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 BP 1051 EP 1057 DI 10.1002/cncr.20467 PG 7 WC Oncology SC Oncology GA 848HQ UT WOS:000223458600023 PM 15329915 ER PT J AU Taplin, S AF Taplin, S TI Foreword: Promoting cancer screening: Lessons learned and future directions for research and practice SO CANCER LA English DT Editorial Material ID MAMMOGRAPHY C1 NCI, Off Director, Appl Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20852 USA. RP Taplin, S (reprint author), NCI, Off Director, Appl Res Program, Div Canc Control & Populat Sci,NIH, 6130 Execut Blvd,Suite 4094, Rockville, MD 20852 USA. EM taplins@mail.nih.gov NR 14 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 SU S BP 1105 EP 1106 DI 10.1002/cncr.20514 PG 2 WC Oncology SC Oncology GA 850LN UT WOS:000223613000001 ER PT J AU Meissner, HI Smith, RA Rimer, BK Wilson, KM Rakowski, W Vernon, SW Briss, PA AF Meissner, HI Smith, RA Rimer, BK Wilson, KM Rakowski, W Vernon, SW Briss, PA TI Promoting cancer screening: Learning from experience SO CANCER LA English DT Article; Proceedings Paper CT Worksdhop on Promoting Cancer Screening Lessons Learned and Future Directions for Research and Practice CY JUN 09-10, 2003 CL Washington, DC DE cancer screening; behavioral intervention; screening test efficacy; mammography; trends ID INCREASE MAMMOGRAPHY USE; HEALTH INTERVIEW SURVEY; AGED 40-49 YEARS; BREAST-CANCER; CERVICAL-CANCER; UNITED-STATES; PAP SMEAR; OLDER WOMEN; INTERVENTIONS; METAANALYSIS AB This article provides an overview of behavioral and social science cancer screening intervention research and introduces the scope of topics addressed in this supplement to Cancer. The authors identify and address issues to consider before conducting interventions to promote the uptake of screening tests, such as the benefits and harms associated with screening. Trends in the use of cancer screening tests are discussed in the context of their efficacy and adoption over time. Both the development and breadth of social and behavioral intervention research intended to increase the use of effective tests are reviewed as background for the articles that follow. The application of the lessons from this extensive knowledge base not only should accelerate the uptake of the effective cancer screening tests currently available, but also can guide future directions for research. Published 2004 by the American Cancer Society. C1 NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20852 USA. Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. Univ N Carolina, Sch Publ Hlth, Lineberger Comprehens Canc Ctr, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Brown Univ, Ctr Gerontol & Hlth Care Res, Providence, RI 02912 USA. Univ Texas, Sch Publ Hlth, Dept Epidemiol & Behav Sci, Ctr Hlth Promot & Prevent Res, Houston, TX USA. Ctr Dis Control & Prevent, Systemat Reviews Sect, Community Guide Branch, Atlanta, GA USA. RP Meissner, HI (reprint author), NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 6130 Execut Blvd,Suite 4102, Rockville, MD 20852 USA. EM hm36d@nih.gov NR 79 TC 59 Z9 60 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 SU S BP 1107 EP 1117 DI 10.1002/cncr.20507 PG 11 WC Oncology SC Oncology GA 850LN UT WOS:000223613000002 PM 15316913 ER PT J AU Rakowski, W Breslau, ES AF Rakowski, W Breslau, ES TI Perspectives on Behavioral and social science research on cancer screening SO CANCER LA English DT Article; Proceedings Paper CT Worksdhop on Promoting Cancer Screening Lessons Learned and Future Directions for Research and Practice CY JUN 09-10, 2003 CL Washington, DC DE cancer screening; behavioral and social science; epidemiologic surveillance; sociodemographics ID HEALTH INTERVIEW SURVEY; BREAST-CANCER; COLORECTAL-CANCER; CERVICAL-CANCER; MAMMOGRAPHY USE; OLDER WOMEN; TRANSTHEORETICAL MODEL; RANDOMIZED TRIALS; MORTALITY-RATES; AMERICAN WOMEN AB The first section in the current article offered several themes that characterize behavioral and social science cancer screening research to date and are likely to be relevant for studying the adoption and utilization of future screening technologies. The themes discussed included the link between epidemiologic surveillance and the priorities of intervention, the "at-risk" perspective that often guides research on screening and initiatives to redress disparities, the need to monitor the diversification of personal screening histories, the range of intervention groups and study designs that can be tested, the importance of including key questions in population-level surveys and national health objectives, and the desirability of clarifying the characteristics of cancer screening that make it an attractive field of study in its own right. The second section commented on emerging areas in which more research will allow additional lessons to be learned. The other articles in the current supplement presented many more lessons in a variety of areas, and other authors are encouraged to write similar articles that help to identify general themes characterizing cancer screening research. Published 2004 by the American Cancer Society. C1 Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Brown Univ, Ctr Gerontol & Hlth Care Res, Providence, RI 02912 USA. NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. RP Rakowski, W (reprint author), Brown Univ, Dept Community Hlth, POB G-H1, Providence, RI 02912 USA. EM william_rakowski@brown.edu NR 110 TC 22 Z9 22 U1 3 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 SU S BP 1118 EP 1130 DI 10.1002/cncr.20503 PG 13 WC Oncology SC Oncology GA 850LN UT WOS:000223613000003 PM 15329891 ER PT J AU Bastani, R Yabroff, KR Myers, RE Glenn, B AF Bastani, R Yabroff, KR Myers, RE Glenn, B TI Interventions to improve follow-up of abnormal findings in cancer screening SO CANCER LA English DT Article; Proceedings Paper CT Worksdhop on Promoting Cancer Screening Lessons Learned and Future Directions for Research and Practice CY JUN 09-10, 2003 CL Washington, DC DE abnormal findings; cancer screening; interventions; evaluation; methodologic issues ID COMPLETE DIAGNOSTIC EVALUATION; INCOME MINORITY WOMEN; COLORECTAL-CANCER; BREAST-CANCER; PAP-SMEAR; CERVICAL-CANCER; PAPANICOLAOU SMEARS; CONTROLLED-TRIAL; PSYCHOLOGICAL CONSEQUENCES; RANDOMIZED-TRIAL AB The potential reduction in morbidity and mortality through cancer cannot be realized without receipt of appropriate follow-up care for abnormalities identified via screening. In this paper, the authors critically examine the literature on correlates of receipt of appropriate follow-up care for abnormalities, as well as the literature on interventions designed to increase rates of receipt of follow-up care. Lessons learned describe what is known and not known about factors that are related to or predict receipt of follow-up care. Similarly, effective interventions to increase follow-up are described and gaps identified. A conceptual model is developed that categorizes the health care system in the United States as comprising four levels: policy, practice, provider, and patient. Some patient-level factors that influence follow-up receipt are identified, but the lack of data severely limit the understanding of provider, practice, and policy-level correlates. The majority of intervention studies to increase follow-up receipt have focused on patient-level factors and have targeted follow-up of abnormal Papanicolaou smears. Insufficient information is available regarding the effectiveness of provider, practice, or policy-level interventions. Standard definitions of what constitutes appropriate follow-up are lacking, which severely limit comparability of findings across studies. The validity of various methods of obtaining outcome data has not been clearly established. More research is needed on interventions targeting provider, system, and policy-level factors, particularly interventions focusing on follow-up of colorectal and breast abnormalities. Standardization of definitions and measures is needed to facilitate comparisons across studies. Published 2004 by the American Cancer Society. C1 Univ Calif Los Angeles, Sch Publ Hlth, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res,Dept Hlth Serv, Los Angeles, CA 90095 USA. NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. RP Bastani, R (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res,Dept Hlth Serv, 650 Charles Young Dr S,Room A2-125,CHS, Los Angeles, CA 90095 USA. EM bastani@ucla.edu OI Yabroff, K. Robin/0000-0003-0644-5572; Myers, Ronald E./0000-0002-8059-7390 FU NCI NIH HHS [U01 CA086322] NR 92 TC 56 Z9 58 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 SU S BP 1188 EP 1200 DI 10.1002/cncr.20506 PG 13 WC Oncology SC Oncology GA 850LN UT WOS:000223613000007 PM 15316914 ER PT J AU Meissner, HI Vernon, SW Rimer, BK Wilson, KM Rakowski, W Briss, PA Smith, RA AF Meissner, HI Vernon, SW Rimer, BK Wilson, KM Rakowski, W Briss, PA Smith, RA TI The future of research that promotes cancer screening SO CANCER LA English DT Article; Proceedings Paper CT Worksdhop on Promoting Cancer Screening Lessons Learned and Future Directions for Research and Practice CY JUN 09-10, 2003 CL Washington, DC DE behavioral intervention; cancer screening; standardized measures; research design; external validity ID HEALTH INTERVIEW SURVEY; REPEAT MAMMOGRAPHY; WOMEN; INTERVENTIONS; ENVIRONMENTS; PERSPECTIVE; PREVALENCE; SERVICES; PROGRAMS; BREAST AB The authors draw on the lessons highlighted in preceding articles in the current supplement to provide recommendations for cancer screening intervention research and to highlight some of the many questions that will require further investigation. Published 2004 by the American Cancer Society. C1 NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Univ Texas, Sch Publ Hlth, Dept Epidemiol & Behav Sci, Ctr Hlth Promot & Prevent Res, Houston, TX USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Brown Univ, Ctr Gerontol & Hlth Care Res, Providence, RI 02912 USA. Ctr Dis Control & Prevent, Systemat Reviews Sect, Community Guide Branch, Atlanta, GA USA. Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. RP Meissner, HI (reprint author), NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Suite 4102, Rockville, MD 20852 USA. EM hm36d@nih.gov NR 49 TC 19 Z9 20 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2004 VL 101 IS 5 SU S BP 1251 EP 1259 DI 10.1002/cncr.20510 PG 9 WC Oncology SC Oncology GA 850LN UT WOS:000223613000012 PM 15316910 ER PT J AU Linehan, WM Zbar, B AF Linehan, WM Zbar, B TI Focus on kidney cancer SO CANCER CELL LA English DT Review ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; HOGG-DUBE-SYNDROME; HYPOXIA-INDUCIBLE FACTOR; HIPPEL-LINDAU DISEASE; MET PROTOONCOGENE; CHROMOSOME-TRANSLOCATION; FAMILIAL RISKS; SPONTANEOUS PNEUMOTHORAX; NORTH-AMERICA C1 NCI, Canc Res Ctr, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Immunobiol Lab, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Canc Res Ctr, Urol Oncol Branch, Bethesda, MD 20892 USA. EM uob@mail.nih.gov NR 68 TC 85 Z9 92 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD SEP PY 2004 VL 6 IS 3 BP 223 EP 228 DI 10.1016/j.ccr.2004.09.006 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 859CM UT WOS:000224239900006 PM 15380513 ER PT J AU Warren, K Gervais, A Aikin, A Egorin, M Balis, FM AF Warren, K Gervais, A Aikin, A Egorin, M Balis, FM TI Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE carboplatin; pharmacokinetics; pediatric; brain; lobradimil ID IMPAIRED RENAL-FUNCTION; INTRACAROTID INFUSION; BRADYKININ ANALOG; PHASE-I; RMP-7; CHILDREN; BARRIER; FORMULA; DOSAGE; TRIAL AB Purpose. To determine the pharmacokinetics of adaptively dosed carboplatin when administered in combination with the bradykinin agonist, lobradimil (RMP-7, Cereport), to pediatric patients with brain tumors. Methods. Carboplatin pharmacokinetic studies were performed on 21 of 25 children with primary brain tumors who received carboplatin and lobradimil on two consecutive days every 28 days in a phase I dose-escalation trial of lobradimil. Carboplatin was adaptively dosed, based on the radioisotopic glomerular filtration rate (GFR) to achieve a target plasma area under the concentration vs time curve (AUC) of 3.5 mg.min/ml per dose x2 (2.5 mg.min/ml per dose x2 in patients with prior craniospinal radiation or myeloablative chemotherapy). The adaptive dosing formula was: carboplatin dose (mg/m(2))=target AUC (mg.min/ml) x [0.93 x GFR (ml/min/m(2))+15]. Carboplatin was infused over 60 min (n=15) or 15 min (n=6). The 10-min lobradimil infusion (100-600 ng/kg ideal body weight) began 5 min before the end of the carboplatin infusion. Frequent blood samples were drawn over 24 h after the first dose of carboplatin/lobradimil. Ultrafilterable platinum was measured by atomic absorption spectroscopy, and the AUC of ultrafilterable platinum was derived using the linear trapezoidal rule and extrapolated to infinity. Results. The median GFR was 65 ml/min/m(2) (range 38-95 ml/min/m(2)) and the median carboplatin doses for the 2.5 and 3.5 mg min/ml target AUCs were 154 and 276 mg/m(2)/day (124-235 and 179-360 mg/m(2)/day), respectively. The measured carboplatin AUC exceeded the target AUC in all 21 patients by a median of 35% (range 0.2-131%). The median carboplatin AUCs at the 2.5 and 3.5 mg.min/ml target AUCs were 3.4 and 4.8 mg.min/ml (2.51-5.8 and 3.9-7.7 mg.min/ml), respectively. Carboplatin clearance was lower than values previously reported in children and correlated poorly with GFR (r(2)=0.14). Conclusions. Adaptive dosing of carboplatin based on GFR overestimated the dose required to achieve the target carboplatin AUC in pediatric patients with brain tumors treated with concurrent lobradimil. The degree to which the measured carboplatin AUC exceeded the target AUC appeared to be greater at higher doses of lobradimil, suggesting that the failure of the adaptive dosing method was related to an unexpected pharmacokinetic drug interaction. C1 NCI, Neuroooncol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. RP Warren, K (reprint author), NCI, Neuroooncol Branch, Block Bldg,82,9030 Old Georgetown Rd, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov NR 24 TC 9 Z9 11 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 2004 VL 54 IS 3 BP 206 EP 212 DI 10.1007/s00280-004-0791-4 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 842MX UT WOS:000223009600002 PM 15156345 ER PT J AU Chatterjee, N Hartge, P Cerhan, JR Cozen, W Davis, S Ishibe, N Colt, J Goldin, L Severson, RK AF Chatterjee, N Hartge, P Cerhan, JR Cozen, W Davis, S Ishibe, N Colt, J Goldin, L Severson, RK TI Risk of non-Hodgkin's lymphoma and family history of lymphatic, hematologic, and other cancers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID UNITED-STATES; RELATIVES; DISEASE; WOMEN AB Background: An elevated risk of developing non-Hodgkin's lymphoma WHO has been associated with a family history of NHL and several other malignancies, but the magnitude of risks and mechanisms are uncertain. Methods: We used self-reported family history data from a recent multicenter. U.S.-based case-control studies of NHL to evaluate familial aggregation of NHL with various hematolymphoproliferative and other cancers. Estimates of familial aggregation were obtained as hazard ratios (HR) that compare incidence of different cancers in first-degree relatives of NHL cases with that in the first-degree relatives of NHL controls. Limitations of the study included low participation rates (76% for cases and 52% for controls) and potential differential accuracy of recall. Results: Risk of NHL was elevated in relatives of NHL cases [HR, 2.9; 95% confidence interval (95% CI), 0.95-8.53]; the aggregation seems to be stronger for siblings (HR, 7.6; 95% CI, 0.98-58.8) and for male relatives (HR, 6.2; 95% CI, 0.77-50.0). Risk of Hodgkin's lymphoma seems to be also elevated among relatives of early-onset (<50 years) NHL cases (HR, 3.2; 95% CI, 0.88-11.6). Evaluation of family history of other cancers provided modest evidence for an increased risk of melanoma of the skin (HR, 2.9; 95% CI, 1.08-7.75), pancreatic cancer (HR, 2.1; 95% CI, 0.96-4.43), stomach cancer (HR, 1.8; 95% CI, 0.91-3.63), and prostate cancer (HR, 1.3; 95% CI, 0.87-1.99). Conclusions: These results are consistent with previous findings of familial aggregation of NHL, Hodgkin's lymphoma, and a few other cancers. The pattern of male-specific and sibling-specific familial aggregation of NHL we observed, if confirmed, may shed new light on the possible mechanisms that underlie familial aggregation of the disease. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ So Calif, Sch Med, Norris Comprehens Canc Ctr, Dept Preventat Med, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8038, 6120 Execut Blvd, Rockville, MD 20852 USA. EM chattern@mail.nih.gov FU NCI NIH HHS [N01-PC-67009, N01-PC-67010, N01-PC-65064, N01-PC-67008, N02-PC-71105] NR 28 TC 99 Z9 102 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2004 VL 13 IS 9 BP 1415 EP 1421 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 851SF UT WOS:000223704900001 PM 15342441 ER PT J AU Deitz, AC Rothman, N Rebbeck, TR Hayes, RB Chow, WH Zheng, W Hein, DW Garcia-Closas, M AF Deitz, AC Rothman, N Rebbeck, TR Hayes, RB Chow, WH Zheng, W Hein, DW Garcia-Closas, M TI Impact of misclassification in genotype-exposure interaction studies: Example of N-acetyltransferase 2 (NAT2), smoking, and bladder cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK; N-ACETYLTRANSFERASE-2; POLYMORPHISMS; POPULATION; PHENOTYPE; MEAT AB Errors in genotype determination can lead to bias in the estimation of genotype effects and gene-environment interactions and increases in the sample size required for molecular epidemiologic studies. We evaluated the effect of genotype misclassification on odds ratio estimates and sample size requirements for a study of NAT2 acetylation status, smoking, and bladder cancer risk. Errors in the assignment of NAT2 acetylation status by a commonly used 3-single nucleotide polymorphism (SNP) genotyping assay, compared with an 11-SNP assay, were relatively small (sensitivity of 94% and specificity of 100%) and resulted in only slight biases of the interaction parameters. However, use of the 11-SNP assay resulted in a substantial decrease in sample size needs to detect a previously reported NAT2-smoking interaction for bladder cancer: 1,121 cases instead of 1,444 cases, assuming a 1:1 case-control ratio. This example illustrates how reducing genotype misclassification can result in substantial decreases in sample size requirements and possibly substantial decreases in the cost of studies to evaluate interactions. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Vanderbilt Univ, Nashville, TN USA. Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. RP Garcia-Closas, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM garciacm@exchange.nih.gov RI Hein, David/A-9707-2008; Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU NCI NIH HHS [CA34627, R01 CA034627, R01 CA034627-19] NR 13 TC 39 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2004 VL 13 IS 9 BP 1543 EP 1546 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 851SF UT WOS:000223704900019 PM 15342459 ER PT J AU Savage, SA Abnet, CC Haque, K Mark, SD Qiao, YL Dong, ZW Dawsey, SM Taylor, PR Chanock, SJ AF Savage, SA Abnet, CC Haque, K Mark, SD Qiao, YL Dong, ZW Dawsey, SM Taylor, PR Chanock, SJ TI Polymorphisms in interleukin-2,-6, and-10 are not associated with gastric cardia or esophageal cancer in a high-risk Chinese population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID INCIDENT ESOPHAGEAL; GENE; LINXIAN C1 NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Sci Applicat Int Corp, Frederick Inc, Gaithersburg, MD USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP Savage, SA (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol, 8717 Grovement Circle, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015; Savage, Sharon/B-9747-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843; Savage, Sharon/0000-0001-6006-0740 NR 17 TC 46 Z9 54 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2004 VL 13 IS 9 BP 1547 EP 1549 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 851SF UT WOS:000223704900020 PM 15342460 ER PT J AU Nagorsen, D Servis, C Levy, N Provenzano, M Dudley, ME Marincola, FM Levy, F AF Nagorsen, D Servis, C Levy, N Provenzano, M Dudley, ME Marincola, FM Levy, F TI Proteasomal cleavage does not determine immunogenicity of gp100-derived peptides gp100(209-217) and gp100(209-217T210M) SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE antigen; cleavage; CTL; gp100; HLA ID MELANOMA ANTIGEN GP100; I-PRESENTED PEPTIDES; DENDRITIC CELLS; T-LYMPHOCYTES; REACTIVE CTL; GENERATION; RESPONSES; EPITOPES; ANALOGS; DEGRADATION AB Immune responses against tumor-associated antigens rely on efficient epitope presentation. The melanoma-associated antigen (Ag) gp100 contains HLA-A*0201 ligands that are characterized by low to medium binding affinity, among which gp100(209-217) is the most prominent (Kawakami et al., J Immunol 154:3961-3968, 1995). While this epitope is a natural T-cell target, it primes with low-efficiency T-cell responses during immunization. A modified gp100 epitope, gp100(209-217T210M), that contains a Thr to Met substitution at position 2 of the antigenic nonamer is characterized by high binding affinity for HLA-A*0201 and elicits strong and clinically effective T-cell responses. This higher affinity is believed to represent the sole reason for enhanced immunogenicity. Contrasting with this observation is the unpredictable relationship between affinity and immunogenicity observed in other antigen systems. In addition, we noted a striking difference between the capability of endogenously processed gp100(209-217) and gp100(209-217T210M) to induce T-cell responses in an in vitro model. Therefore, we questioned whether factors other than HLA-affinity might play a role in determining the immunogenicity of these epitopes. In the present study, we evaluated the in vitro proteasomal cleavages of 23meric precursor peptides encompassing the native sequence (gp100(201-223)) or the modified sequence (gp100(201-223T210M)). Here we show that the standard proteasome liberates the C-termini of both antigenic peptides but not the N-termini. Quantitative analysis of the digestion products revealed that more of the fragments displaying the final C-termini were produced from the wild-type precursor. However, a stronger TCR engagement was observed when fractions of digested gp100(201-223T210M) were used to activate an HLA-A*0201-expressing target T-cell clone. This difference was also found using separately produced, synthetic nonamers. In conclusion, the high binding affinity of gp100(209-217T210M) seems to compensate for possible differences in proteasomal cleavage at the biological level. Since the final antigenic nonamer is not directly produced by the proteasome, additional further factors may influence the antigenic peptide availability, such as post-proteasomal processing and intracellular peptide transport. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Med Berlin, Charite, Med Klin 3, Berlin, Germany. Univ Lausanne, Lausanne Branch, Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland. NCCR Mol Oncol, Epalinges, Switzerland. Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 2004 VL 53 IS 9 BP 817 EP 824 DI 10.1007/s00262-004-0532-x PG 8 WC Oncology; Immunology SC Oncology; Immunology GA 843YK UT WOS:000223123200008 PM 15133631 ER PT J AU Pingpank, JF AF Pingpank, JF TI Therapy for unresectable hepatocellular carcinoma: Time for XRT? SO CANCER JOURNAL LA English DT Editorial Material ID TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; PERCUTANEOUS ETHANOL INJECTION; LOCAL RADIOTHERAPY; LIPIODOL CHEMOEMBOLIZATION; RADIOFREQUENCY ABLATION; LIVER-TRANSPLANTATION; RADIATION HEPATITIS; PORTAL-VEIN; TUMOR SIZE C1 NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pingpank, JF (reprint author), NCI, Surg Branch, Canc Res Ctr, NIH, Room 4-5932,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2004 VL 10 IS 5 BP 291 EP 293 DI 10.1097/00130404-200409000-00005 PG 3 WC Oncology SC Oncology GA 868IF UT WOS:000224906600005 PM 15530257 ER PT J AU Enokida, H Shiina, H Igawa, M Ogishima, T Kawakami, T Bassett, WW Anast, JW Li, LC Urakami, S Terashima, M Verma, M Kawahara, M Nakagawa, M Kane, CJ Carroll, PR Dahiya, R AF Enokida, H Shiina, H Igawa, M Ogishima, T Kawakami, T Bassett, WW Anast, JW Li, LC Urakami, S Terashima, M Verma, M Kawahara, M Nakagawa, M Kane, CJ Carroll, PR Dahiya, R TI CpG hypermethylation of MDR1 gene contributes to the pathogenesis and progression of human prostate cancer SO CANCER RESEARCH LA English DT Article ID P-GLYCOPROTEIN; RADICAL PROSTATECTOMY; BREAST-CANCER; PROLIFERATIVE ACTIVITY; OSTEOSARCOMA CELLS; PROMOTER REGION; EXPRESSION; METHYLATION; APOPTOSIS; CARCINOMA AB Multidrug resistance 1 (MDR1) gene encodes for P-glycoprotein (P-gp), a Mr 170,000 transmembrane calcium-dependent efflux pump that is inactivated in prostate cancer. We hypothesize that inactivation of the MDR1 gene through CpG methylation contributes to the pathogenesis and progression of prostate cancer. To test this hypothesis, CpG methylation status of the MDR1 promoter and its correlation with clinicopathological findings were evaluated in 177 prostate cancer samples and 69 benign prostate hypertrophy (BPH) samples. Cellular proliferation index and apoptotic index were determined by proliferating cell nuclear antigen (PCNA) and single-strand DNA immunostaining, respectively. After 5-aza-2'-deoxycytidine treatment, increased expression of MDR1 mRNA transcript was found in prostate cancer cell lines (DU145, DuPro, and ND1). MDR1 methylation frequency was significantly higher in prostate cancer samples compared with BPH samples (54.8 versus 11.6%, respectively, P < 0.001). Logistic regression analysis revealed that PC patients are 11.5 times more likely to have MDR1 methylation than BPH patients (95% confidence interval 4.87-27.0) and that MDR1 methylation is independent of the age. Significant correlation of MDR1 methylation was observed with high pT category (P < 0.001), high Gleason sum (P = 0.008), high preoperative prostate-specific antigen (P = 0.01), and advancing pathological features. In addition, PCNA-labeling index were significantly higher in methylation-specific PCR (MSP)-positive than in MSP-negative prostate cancer samples (P = 0.048). In contrast, no significant difference in apoptotic index was found between MSP-positive and -negative prostate cancer samples. These findings suggest that CpG hypermethylation of MDR1 promoter is a frequent event in prostate cancer and is related to disease progression via increased cell proliferation in prostate cancer cells. C1 Univ Calif San Francisco, Urol Res Ctr 112F, Dept Urol, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Shimane Univ, Dept Urol & Biochem, Izumo, Shimane, Japan. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Dept Urol, Kagoshima 890, Japan. RP Dahiya, R (reprint author), Univ Calif San Francisco, Urol Res Ctr 112F, Dept Urol, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urol.ucsf.edu FU NCI NIH HHS [R01CA101844]; NIA NIH HHS [R01AG21418]; NIDDK NIH HHS [T32DK07790] NR 37 TC 62 Z9 70 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2004 VL 64 IS 17 BP 5956 EP 5962 DI 10.1158/0008-5472.CAN-04-0081 PG 7 WC Oncology SC Oncology GA 850IA UT WOS:000223603200009 PM 15342374 ER PT J AU Qiu, TH Chandramouli, GVR Hunter, KW Alkharouf, NW Green, JE Liu, ET AF Qiu, TH Chandramouli, GVR Hunter, KW Alkharouf, NW Green, JE Liu, ET TI Global expression profiling identifies signatures of tumor virulence in MMTV-PyMT-transgenic mice: Correlation to human disease SO CANCER RESEARCH LA English DT Article ID MIDDLE-T-ANTIGEN; HUMAN BREAST-CANCER; MAMMARY-TUMOR; CELL-CYCLE; PHOSPHATIDYLINOSITOL KINASE; TYROSINE PHOSPHORYLATION; GENE-EXPRESSION; GELSOLIN; PROTEIN; POLYOMAVIRUS AB FVB/N-Tg (MMTV-PyMT) (634Mul)-transgenic mice develop multifocal mammary tumors with a high incidence of pulmonary metastasis. We have demonstrated previously that mammary tumors derived from transgene-positive F1 progeny in particular inbred strains display altered latency, tumor growth rates, and metastatic rates when compared with the FVB/NJ homozygous parent. To identify genes with expression that might be critical in modifying the biological behavior of MMTV-PyMT tumors, we performed a detailed comparative analysis of expression profiles from mammary tumors arising in the parental FVB/NJ background and F1 progeny from crosses with I/Lni, LP/J, MOLF/Ei, and NZB/B1NJ mice. Compared with normal mammary glands, gene expression profiles of tumors from all five strains exhibited up-regulation of genes involved in cell growth (e.g., Cks1 and CDC25C) and down-regulation of cell adhesion molecules, with many genes associated previously with human breast cancer such as STAT2, CD24 antigen, gelsolin, and lipocalin2. To identify genes with significant variation in expression between the five different genotypes, significance analysis of microarrays (SAM) and one-way ANOVA were used. Three definable groupings of tumors were identified: (a) tumors derived in the LP/J F1 and MOLF/Ei F1 strains in which tumor growth and dissemination are suppressed and latency prolonged; (b) the most aggressive tumors from the FVB/NJ parental strain and I/LnJ F1 genomic backgrounds; and (c) an intermediate virulence phenotype with tumors from NZB/B1NJ-F1 crosses. These array based assessments correlated well with a composite phenotype ranking using a "virulence" index. The gene expression signature that is associated with a high metastatic rate in the mouse contains the same 17 genes described recently as the signature gene set predictive of metastasis in human tumors (1) with 16 of the 17 genes exhibiting the same directional change in expression associated with human metastases. These results demonstrate that the genetic analysis of mouse models of tumorigenesis may be highly relevant to human cancer and that the metastatic phenotype of a tumor may be affected by the germline genetic configuration of the host. C1 NCI, Lab Cell Regulat & Carcinogenesis, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Dept Canc & Cell Biol, Mol Signalling & Oncogenesis Sect, Bethesda, MD 20892 USA. NCI, Lab Syst Biol, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, Canc Res Ctr, Bethesda, MD 20892 USA. Genome Inst Singapore, Singapore, Singapore. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Canc Res Ctr, Bethesda, MD 20892 USA. EM JEGreen@nih.gov RI Liu, Edison/C-4141-2008 NR 38 TC 75 Z9 77 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2004 VL 64 IS 17 BP 5973 EP 5981 DI 10.1158/0008-5472.CAN-04-0242 PG 9 WC Oncology SC Oncology GA 850IA UT WOS:000223603200011 PM 15342376 ER PT J AU Adams, GP Shaller, CC Dadachova, E Simmons, HH Horak, EM Tesfaye, A Klein-Szanto, AJP Marks, JD Brechbiel, MW Weiner, LM AF Adams, GP Shaller, CC Dadachova, E Simmons, HH Horak, EM Tesfaye, A Klein-Szanto, AJP Marks, JD Brechbiel, MW Weiner, LM TI A single treatment of yttrium-90-labeled CHX-A ''-C6.5 diabody inhibits the growth of established human tumor xenografts in immunodeficient mice SO CANCER RESEARCH LA English DT Article ID HUMAN-BREAST-CANCER; B-CELL LYMPHOMA; IN-VIVO; MONOCLONAL-ANTIBODY; CHAIN FV; NUDE-MICE; HER-2 NEU; BIODISTRIBUTION; DTPA; RADIOIMMUNOTHERAPY AB Antitumor diabody molecules are noncovalent single-chain Fv dimers that recapitulate the divalent binding properties of native IgG antibodies. Diabodies are capable of substantial accumulation in tumor xenografts expressing relevant antigens in immunodeficient mouse models. With a M-r of approximately 55,000, diabodies are rapidly cleared from the circulation, resulting in tumor-to-blood ratios that significantly exceed those achieved early after the administration of monoclonal antibodies. We have evaluated the therapeutic potential of the beta-emitting isotope yttrium-90 (t(1/2), 64 hours) conjugated to the C6.5K-A diabody that specifically targets the HER2/neu human tumor-associated antigen. We have found that a single intravenous dose of 150 muCi (200 mug) Y-90-CHX-A"-C6.5K-A diabody substantially inhibits the growth rates of established MDA-361/DYT2 human breast tumor xenografts in athymic nude mice. In contrast, 300 muCi (300 mug) Y-90-CHX-A"-C6.5K-A diabody resulted in only a minor delay in the growth of SK-OV-3 human ovarian cancer xenografts. The maximum tolerated dose was also dependent on the tumor xenograft model used. These studies indicate that genetically engineered antitumor diabody molecules can be used as effective vehicles for radioimmunotherapy. C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Anesthesiol & Pharmaceut Chem, San Francisco, CA 94143 USA. RP Adams, GP (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, Div Med Sci, 7701 Burholme Ave, Philadelphia, PA 19111 USA. EM gp_adams@fccc.edu RI Dadachova, Ekaterina/I-7838-2013 FU NCI NIH HHS [CA65559] NR 30 TC 63 Z9 67 U1 2 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2004 VL 64 IS 17 BP 6200 EP 6206 DI 10.1158/0008-5472.CAN-03-2382 PG 7 WC Oncology SC Oncology GA 850IA UT WOS:000223603200040 PM 15342405 ER PT J AU Ajona, D Castano, Z Garayoa, M Zudaire, E Pajares, MJ Martinez, A Cuttitta, F Montuenga, LM Pio, R AF Ajona, D Castano, Z Garayoa, M Zudaire, E Pajares, MJ Martinez, A Cuttitta, F Montuenga, LM Pio, R TI Expression of complement factor H by lung cancer cells: Effects on the activation of the alternative pathway of complement SO CANCER RESEARCH LA English DT Article ID PROTEIN FACTOR-H; MEMBRANE COFACTOR PROTEIN; DECAY-ACCELERATING FACTOR; MEDIATED LYSIS; TUMOR-CELLS; IN-VITRO; RESPIRATORY EPITHELIUM; MONOCLONAL-ANTIBODIES; NEISSERIA-GONORRHOEAE; INHIBITORY PROTEINS AB The complement system is important in immunosurveillance against tumors. However, malignant cells are usually resistant to complement-mediated lysis. In this study, we examine the expression of factor H, an inhibitor of complement activation, and factor H-like protein 1 (FHL-1), its alternatively spliced form, in lung cancer. We also evaluate the potential effect of factor H/FHL-1 in the protection of lung cancer cells against the activation of the complement cascade. By Northern blot analysis we demonstrate a high expression of factor H and FHL-1 in most non-small cell lung cancer cell lines, although neuroendocrine pulmonary tumors (small cell lung carcinoma and carcinoid cell lines) had undetectable levels. Western blot analysis of conditioned medium showed the active secretion of factor H and FHL-1 by cells that were positive by Northern blot. Expression of factor H/FHL-1 mRNA was also shown in a series of non-small cell lung cancer biopsies by in situ hybridization. Interestingly, many cultured lung cancer cells were able to bind fluorescence-labeled factor H to their surfaces. Deposition of C3 fragments from normal human serum on H1264, a lung adenocarcinoma cell line, was more efficient when factor H/FHL-1 activity was blocked by specific antibodies. Blocking factor H/FHL-1 activity also enhanced the release of anaphylatoxin C5a and moderately increased the susceptibility of these cells to complement-mediated cytotoxicity. In summary, we demonstrate the expression of factor H and FHL-1 by some lung cancer cells and analyze the contribution of these proteins to the protection against complement activation. C1 Univ Navarra, Sch Med, Dept Biochem, E-31080 Pamplona, Spain. Univ Navarra, Sch Med, Dept Histol & Pathol, E-31080 Pamplona, Spain. Ctr Appl Med Res, Div Oncol, Pamplona, Spain. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Pio, R (reprint author), Univ Navarra, Sch Med, Dept Biochem, Irunlarrea 1, E-31080 Pamplona, Spain. EM rpio@unav.es RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 NR 57 TC 46 Z9 47 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2004 VL 64 IS 17 BP 6310 EP 6318 DI 10.1158/0008-5472.CAN-03-2328 PG 9 WC Oncology SC Oncology GA 850IA UT WOS:000223603200055 PM 15342420 ER PT J AU Yamazaki, M Akahane, T Buck, T Yoshiji, H Gomez, DE Schoeffner, DJ Okajima, E Harris, SR Bunce, OR Thorgeirsson, SS Thorgeirsson, UP AF Yamazaki, M Akahane, T Buck, T Yoshiji, H Gomez, DE Schoeffner, DJ Okajima, E Harris, SR Bunce, OR Thorgeirsson, SS Thorgeirsson, UP TI Long-term exposure to elevated levels of circulating TIMP-1 but not mammary TIMP-1 suppresses growth of mammary carcinomas in transgenic mice SO CARCINOGENESIS LA English DT Article ID MATRIX-METALLOPROTEINASE INHIBITORS; BREAST EPITHELIAL-CELLS; B16-F10 MELANOMA-CELLS; HUMAN TISSUE INHIBITOR; TUMOR PROGRESSION; MESSENGER-RNAS; DISTANT METASTASES; ADVERSE PROGNOSIS; PROSTATE-CANCER; GASTRIC-CANCER AB Tissue inhibitor of metalloproteinases-1 (TIMP-1) regulates matrix metalloproteinase activity, acts as a growth stimulator and inhibits apoptosis. We developed transgenic mice to evaluate the relevance of circulating versus mammary TIMP-1 in mammary carcinogenesis. The transgene was placed under the control of the albumin (Alb) promoter for the production of large amounts of TIMP-1 in the liver and release into the systemic circulation to achieve chronically elevated blood levels. The initial 7,12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis study showed greatly decreased tumor incidence in heterozygous Alb-TIMP-1 mice (25%), compared with their wild-type (wt) littermates (83.3%). Metastatic mammary carcinomas were induced in the Alb-TIMP-1 mice through breeding with mice expressing the polyomavirus Middle T antigen (MT) under the control of the mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Both the mammary tumor burden and the incidence of lung metastases were lower in the Alb-TIMP-1/MMTV-MT mice than their MMTV-MT littermates. Analysis of the Alb-TIMP-1/MMTV-MT tumors showed evidence of decreased proliferative activity and inhibition of apoptosis, whereas microvascular density was not affected. Transgenic expression of TIMP-1 in mammary epithelial cells was accomplished by using MMTV-LTR. In contrast to the Alb-TIMP-1 mice, there was insignificant difference in the growth of both DMBA- and MT-induced mammary tumors between heterozygous MMTV-TIMP-1 mice and their wt littermates. The MT-induced mammary tumors of the MMTV-TIMP-1 mice were separated into 'low' and 'high' TIMP-1 expressing groups. The 'high' TIMP-1 expressing tumors exhibited significantly higher proliferative activity than the tumors of the MMTV-MT only mice, whereas the number of apoptotic cells and microvascular density were not different. The findings of this study show that circulating TIMP-1, but not mammary-derived TIMP-1, has growth suppressive effects on DMBA and MT-induced mammary carcinomas. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, UP (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM thorgeiu@mail.nih.gov OI Gomez, Daniel E/0000-0002-8629-0787 NR 75 TC 12 Z9 14 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 SEP PY 2004 VL 25 IS 9 BP 1735 EP 1746 DI 10.1093/carcin/bgh181 PG 12 WC Oncology SC Oncology GA 850CM UT WOS:000223588800022 PM 15166086 ER PT J AU Nicol, CJ Yoon, M Ward, JM Yamashita, M Fukamachi, K Peters, JM Gonzalez, FJ AF Nicol, CJ Yoon, M Ward, JM Yamashita, M Fukamachi, K Peters, JM Gonzalez, FJ TI PPAR gamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis SO CARCINOGENESIS LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; HUMAN BREAST-CANCER; NECROSIS-FACTOR-ALPHA; NUCLEAR HORMONE-RECEPTORS; ESTROGEN-RECEPTOR; GENE-EXPRESSION; CYCLIN D1; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); DIFFERENTIAL EXPRESSION; COLON CARCINOGENESIS AB Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis. C1 NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Ctr Canc Res, Frederick, MD 21702 USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol, University Pk, PA 16802 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Peters, Jeffrey/D-8847-2011; Yamashita, Masamichi/B-9948-2013 NR 72 TC 79 Z9 80 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2004 VL 25 IS 9 BP 1747 EP 1755 DI 10.1093/carcin/bgh160 PG 9 WC Oncology SC Oncology GA 850CM UT WOS:000223588800023 PM 15073042 ER PT J AU Woodworth, CD Michael, E Smith, L Vijayachandra, K Glick, A Hennings, H Yuspa, SH AF Woodworth, CD Michael, E Smith, L Vijayachandra, K Glick, A Hennings, H Yuspa, SH TI Strain-dependent differences in malignant conversion of mouse skin tumors is an inherent property of the epidermal keratinocyte SO CARCINOGENESIS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; P53 GENE DOSAGE; TRANSGENIC MICE; TERMINAL DIFFERENTIATION; CHEMICAL CARCINOGENESIS; CANCER RESISTANCE; MODIFIER LOCI; HIGH-RISK; SUSCEPTIBILITY; PROGRESSION AB The multistage evolution of squamous skin tumors induced by chemical or viral carcinogens on mice from different genetic backgrounds has been a valuable model to define low penetrance loci that determine cancer susceptibility or resistance. Susceptibility determinants are multigenic, stage-specific, dependent on the carcinogenesis protocol, and in the case of initiating events, intrinsic properties of keratinocytes. In this study we examined the malignant conversion frequency of keratinocytes derived from FVB/N, inbred SENCARA/Pt, BALB/c or C57BL/6 mouse strains that differ substantially in the frequency of progression from papilloma to carcinoma. Keratinocytes were cultured from newborn mice and tested in an in vitro malignant conversion assay induced by a chemical carcinogen or immortalized by infection with replication defective human papillomavirus type 16 (HPV-16) E6/E7 retroviruses and tested for malignancy by grafting immortalized cell lines to nude mice. In vitro, FVB/N keratinocytes were 10-fold more sensitive to chemically induced malignant conversion than keratinocytes from other strains, consistent with the known sensitivity of this strain to pre-malignant progression in vivo. The E6/E7 genes induced immortalization of keratinocytes from FVB/N, SENCARA/Pt or C57BL/6 mice more efficiently than BALB/c, and HPV-16-immortalized FVB/N keratinocytes formed tumors more frequently (64%) than SENCARA/Pt (31%) BALB/c (1.9%) or C57BL/6 (2.5%). Furthermore, 78% of the tumors formed by FVB/N keratinocytes progressed to squamous carcinomas compared with 46% for SENCARA/Pt-derived cells and <3% for the others. In F-1 offspring of crosses from SENCARA/Pt and FVB/N mice, both the papilloma incidence and frequency of malignant conversion reflected the SENCARA/Pt parent indicating that predisposition to pre-malignant progression is not a dominant characteristic. This predisposition is an intrinsic property of the target keratinocytes and as such should be amenable to further study in isolated cells. C1 Clarkson Univ, Dept Biol, Potsdam, NY 13699 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Woodworth, CD (reprint author), Clarkson Univ, Dept Biol, Potsdam, NY 13699 USA. EM woodworth@clarkson.edu NR 45 TC 44 Z9 44 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2004 VL 25 IS 9 BP 1771 EP 1778 DI 10.1093/carcin/bgh170 PG 8 WC Oncology SC Oncology GA 850CM UT WOS:000223588800025 PM 15105299 ER PT J AU Chen, H Li, SF Liu, J Diwan, BA Barrett, JC Waalkes, MP AF Chen, H Li, SF Liu, J Diwan, BA Barrett, JC Waalkes, MP TI Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: implications for arsenic hepatocarcinogenesis SO CARCINOGENESIS LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; HUMAN BREAST-CANCER; DNA METHYLATION; HEPATOCELLULAR-CARCINOMA; DRINKING-WATER; FOLATE-DEFICIENCY; TRANSGENIC MICE; EXPRESSION; TUMORS; LIVER AB Inorganic arsenic is a human carcinogen that can target the liver, but its carcinogenic mechanisms are still unknown. Global DNA hypomethylation occurs during arsenic-induced malignant transformation in rodent liver cells. DNA hypomethylation can increase gene expression, particularly when occurring in the promoter region CpG sites, and may be a non-genotoxic mechanism of carcinogenesis. Thus, in the present study liver samples of male mice exposed to 0 (control) or 45 p.p.m. arsenic (as NaAsO2) in the drinking water for 48 weeks were analyzed for gene expression and DNA methylation. Chronic arsenic exposure caused hepatic steatosis, a lesion also linked to consumption of methyl-deficient diets. Microarray analysis of liver samples showed arsenic induced aberrant gene expression including steroid-related genes, cytokines, apoptosis-related genes and cell cycle-related genes. In particular, the expression of the estrogen receptor-alpha (ER-alpha), and cyclin D1 genes were markedly increased. RT-PCR and immunohistochemistry confirmed arsenic-induced increases in hepatic ER-alpha and cyclin D1 transcription and translation products, respectively. Arsenic induced hepatic global DNA hypomethylation, as evidenced by 5-methylcytosine content of DNA and by the methyl acceptance assay. Arsenic also markedly reduced the methylation within the ER-alpha gene promoter region, as assessed by methylation-specific PCR, and this reduction was statistically significant in 8 of 13 CpG sites within the promoter region. Overall, in controls 28.3% of the ER-alpha promoter region CpG sites were methylated, but only 2.9% were methylated after chronic arsenic exposure. Thus, long-term exposure of mice to arsenic in the drinking water can induce aberrant gene expression, global DNA hypomethylation, and the hypomethylation of the ER-alpha gene promoter, all of which could potentially contribute to arsenic hepatocarcinogenesis. C1 NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Waalkes, MP (reprint author), NIEHS, Comparat Carcinogenesis Lab, NCI, POB 12233, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 57 TC 163 Z9 172 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2004 VL 25 IS 9 BP 1779 EP 1786 DI 10.1093/carcin/bgh161 PG 8 WC Oncology SC Oncology GA 850CM UT WOS:000223588800026 PM 15073043 ER PT J AU Friedman, M Mikityansky, I Kam, A Libutti, SK Walther, MM Neeman, Z Locklin, JK Wood, BJ AF Friedman, M Mikityansky, I Kam, A Libutti, SK Walther, MM Neeman, Z Locklin, JK Wood, BJ TI Radiofrequency ablation of cancer SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Review DE radiofrequency ablation; tumor/neoplasm; colon carcinoma; hepatocellular carcinoma; hyperthermia ID SMALL HEPATOCELLULAR-CARCINOMA; RADIO-FREQUENCY ABLATION; THERMAL ABLATION; HEPATIC-TUMORS; TISSUE ABLATION; OSTEOID OSTEOMA; ETHANOL INJECTION; COLORECTAL-CANCER; LIVER METASTASES; CT AB Radiofrequency ablation (RFA) has been used for over 18 years for treatment of nerve-related chronic pain and cardiac arrhythmias. In the last 10 years, technical developments have increased ablation volumes in a controllable, versatile, and relatively inexpensive manner. The host of clinical applications for RFA have similarly expanded. Current RFA equipment, techniques, applications, results, complications, and research avenues for local tumor ablation are summarized. C1 NIH, Dept Diagnost Radiol, Special Procedures Div, Ctr Clin, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Diagnost Radiol, Rochester, NY 14642 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Dept Diagnost Radiol, Special Procedures Div, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM bwood@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 70 TC 37 Z9 40 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD SEP-OCT PY 2004 VL 27 IS 5 BP 427 EP 434 DI 10.1007/s00270-004-0062-0 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 856LW UT WOS:000224047700003 PM 15383844 ER PT J AU Varro, Z Locklin, JK Wood, BJ AF Varro, Z Locklin, JK Wood, BJ TI Laser navigation for radiofrequency ablation SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE radiofrequency ablation; laser guidance; renal cell carcinoma; von-Hippel Lindau disease ID GUIDANCE-SYSTEM; DEVICE; BIOPSY AB A 45-year-old male with renal cell carcinoma secondary to von-Hippel Lindau (VHL) disease presented for radiofrequency ablation (RFA) of kidney tumors. Due to his prior history of several partial nephrectomies and limited renal reserve, RFA was chosen because of its relatively nephron-sparing nature. A laser guidance device was used to help guide probe placement in an attempt to reduce procedure time and improve targeting accuracy. The device was successful at guiding needle placement, as both tumors were located with a single pass. Follow-up CT scan confirmed accurate needle placement, showing an area of coagulation necrosis covering the previously seen tumor. C1 NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Varro, Z (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. EM bwood@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 9 TC 14 Z9 14 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD SEP-OCT PY 2004 VL 27 IS 5 BP 512 EP 515 DI 10.1007/s00270-003-4033-7 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 856LW UT WOS:000224047700017 PM 15383857 ER PT J AU Smith, RM Suleman, N Lacerda, L Opie, LH Akira, S Chien, KR Sack, MN AF Smith, RM Suleman, N Lacerda, L Opie, LH Akira, S Chien, KR Sack, MN TI Genetic depletion of cardiac myocyte STAT-3 abolishes classical preconditioning SO CARDIOVASCULAR RESEARCH LA English DT Article DE ischemia; preconditioning; signal transduction ID NITRIC-OXIDE SYNTHASE; JAK-STAT; ISCHEMIA/REPERFUSION INJURY; ALPHA GENE; ACTIVATION; ISCHEMIA; PATHWAY; APOPTOSIS; CELLS; RAT AB Objective: To evaluate the functional requirement of signal transducer and activator of transcription-3 (STAT-3) in cardiac myocyte tolerance to ischemia (1) and in classical preconditioning. Methods: Cardiac myocyte STAT-3 was depleted in mice using Cre-lox p technology. Isolated cardiomyocytes from wild-type (WT) and STAT-3-deficient mice were evaluated for viability following simulated ischemia (SI; 26 h). Cardiomyocytes were then preconditioned by exposure to transient simulated ischemia or via the administration of preconditioning mimetics (100 muM adenosine, 100 muM diazoxide and 0.5 ng ml(-1) TNFalpha, individually and in combination) prior to index ischemia. To evaluate the effect of cardiac myocyte depletion of STAT-3 in the context of the intact heart, these experiments were performed in isolated perfused Langendorff heart preparations which were exposed to an index insult of 30-min global ischemia and 45-min reperfusion. Ischemic preconditioning was achieved by subjecting the hearts to four cycles of 5-min ischemia followed by 5-min reperfusion prior to index ischemia. Infarct size was measured following reperfusion. Results: Cell viability was diminished equally in wild-type and STAT-3-depleted cardiomyocytes. In contrast, ischemic and pharmacological preconditioning protected wild-type cardiomyocytes but not STAT-3-deficient cardiomyocytes. These results were mirrored in the intact heart. Conclusion: The depletion of functional STAT-3 does not modulate tolerance to ischemic injury in cardiomyocytes. This signaling molecule, however, is crucial for the ischemic and all the tested pharmacological preconditioning programs. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Univ Cape Town Observ, Hatter Inst Cardiol Res, Fac Hlth Sci, Cape Heart Ctr, ZA-7925 Cape Town, South Africa. Osaka Univ, Res Inst Microbial Dis, Osaka, Japan. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Smith, RM (reprint author), Univ Stellenbosch, Dept Physiol Sci, Private Bag X1, ZA-7602 Matieland, South Africa. EM rsmith@sun.ac.za RI Akira, Shizuo/C-3134-2009 NR 41 TC 79 Z9 89 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP 1 PY 2004 VL 63 IS 4 BP 611 EP 616 DI 10.1016/j.cardiores.2004.06.0019 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 850DM UT WOS:000223591400007 PM 15306216 ER PT J AU Sordet, O Khan, QA Pommier, Y AF Sordet, O Khan, QA Pommier, Y TI Apoptotic topoisomerase I-DNA complexes induced by oxygen radicals and mitochondrial dysfunction SO CELL CYCLE LA English DT Article DE topoisomerase I; apoptosis; Top1 cleavage complexes; reative oxygen species; oxidative DNA lesions; DNA fragmentation; mitochondria; arsenic trioxide; staurosporine; etoposide ID CELL-DEATH; DAMAGE; INDUCTION; CLEAVAGE; GENERATION; VITRO AB Topoisomerase I (Top1) is expressed throughout the cell cycle. Top1 forms reversible and transient DNA cleavage complexes as it relaxes DNA supercoiling generated by transcription and replication. Recent findings indicate that mechanistically different inducers of apoptosis, arsenic trioxide, staurosporine and etoposide, which are inactive on purified Top1, induce Top1 cleavage complexes. These apoptotic Top1 cleavage complexes result from oxidative DNA lesions generated by reactive oxygen species during apoptosis. Their functional role could be to directly fragment chromatin and to further activate ( amplify) apoptotic pathways. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014 NR 31 TC 33 Z9 35 U1 1 U2 4 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2004 VL 3 IS 9 BP 1095 EP 1097 PG 3 WC Cell Biology SC Cell Biology GA 877MD UT WOS:000225573800002 PM 15326388 ER PT J AU Yu, L Lenardo, MJ Baehrecke, EH AF Yu, L Lenardo, MJ Baehrecke, EH TI Autophagy and caspases - A new cell death program SO CELL CYCLE LA English DT Article DE programmed cell death; apoptosis; autophagy; Atg; caspase ID SACCHAROMYCES-CEREVISIAE; APOPTOSIS; DROSOPHILA; MUTANTS; PATHWAY; YEAST; MECHANISMS; UBIQUITIN AB Autophagy is used to degrade components of the cytoplasm and functions as a cell survival mechanism during nutrient deprivation. Autophagic structures have also been observed in many types of dying cells, but experimental evidence for autophagy playing a role in the regulation of programmed cell death is limited. We have recently shown that the autophagy genes Atg7 and Beclin1 are required for the death of certain cells, thus demonstrating that this mechanism of proteolysis is involved in both survival and death. The factors that enable autophagy to regulate distinct cell survival and death responses are not clear, and future work is needed to determine the mechanism(s) that regulate autophagic cell death. C1 Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20782 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Baehrecke, EH (reprint author), Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, 5115 Plant Sci Bldg, College Pk, MD 20782 USA. EM baehreck@umbi.und.edu NR 26 TC 81 Z9 87 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP PY 2004 VL 3 IS 9 BP 1124 EP 1126 PG 3 WC Cell Biology SC Cell Biology GA 877MD UT WOS:000225573800011 PM 15326383 ER PT J AU Wachira, SJ Hughes-Darden, CA Nicholas, HB Taylor, CV Robinson, TJ AF Wachira, SJ Hughes-Darden, CA Nicholas, HB Taylor, CV Robinson, TJ TI Neural melanocortin receptors are differentlally expressed and regulated by stress in rat hypothalamic-pituitary-adrenal axis SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE hypothalamic-pituitary-adrenal axis (HPA); proopiomelanocortin; melanocortin receptor; REM-sleep deprivation; stress ID CELL-SURFACE EXPRESSION; AGOUTI-RELATED PROTEIN; SLEEP-DEPRIVATION; SIGNALING PATHWAYS; PEPTIDES; PROOPIOMELANOCORTIN; SEQUENCE; HORMONE; OBESITY; CORTEX AB Genetic knockout and null mutations of melanocortin system components lead to phenotypes that recapitulate the metabolic syndrome such as obesity, hypertension and insulin resistance. Since stress is known to modify metabolic and cardiovascular function, we hypothesized the involvement of the neural melanocortin system in the stress response. Male rats were subjected to rapid-eye-movement sleep deprivation stress and the levels of proopiomelanocortin (POMC), MC3R, MC4R and MC5R transcripts in the hypothalamic-pituitary-adrenal axis (HPA) determined by real-time PCR. Increased levels of POMC transcripts were observed in the hypothalamus and adrenal gland tissues but there were no significant changes in the expression of the receptors genes. Whereas MOR and MOR are expressed in all HPA tissues, MC4R seems to be restricted mainly to the hypothalamus. It is possible that melanocortin receptors function in different aspects of the neuron. In vitro studies showed similar cellular distribution patterns for MOR and MC4R and sequence analyses revealed strong conservation of the putative G-protein coupled receptors (GPCR) C-terminal membrane localization signal, EX(3-7)II/L motif, in MC3R, MC4R and MC5R. These data suggest that the physiological roles of neural melanocortin receptors, MOR and MC4R, are likely determined by distinct tissue distribution patterns and suggest a role for hypothalamic and intra-adrenal melanocortin systems in the manifestation of stress related pathologies. C1 Morgan State Univ, Dept Biol, Baltimore, MD 21251 USA. NIH, Res Ctr, Pittsburgh Supercomp Ctr, Pittsburgh, PA 15213 USA. RP Wachira, SJ (reprint author), Morgan State Univ, Dept Biol, 1700 E Cold Spring Lane, Baltimore, MD 21251 USA. EM jwachir@morgan.edu FU NCRR NIH HHS [G12 RR 017581, P41 RR 06009]; NIGMS NIH HHS [2 S06 GM 051971-08, T36 GM 08789] NR 50 TC 10 Z9 10 U1 0 U2 2 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD SEP PY 2004 VL 50 IS 6 BP 703 EP 713 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 881UG UT WOS:000225894300004 PM 15641161 ER PT J AU Andersen, H Rossio, JL Coalter, V Poore, B Martin, MP Carrington, M Lifson, JD AF Andersen, H Rossio, JL Coalter, V Poore, B Martin, MP Carrington, M Lifson, JD TI Characterization of rhesus macaque natural killer activity against a rhesus-derived target cell line at the single-cell level SO CELLULAR IMMUNOLOGY LA English DT Article DE AIDS; rhesus macaque; NK cells; MHC; degranulation; intracellular cytokine; viral ID SIMIAN IMMUNODEFICIENCY VIRUS; CLASS-I MOLECULES; DENDRITIC CELLS; NK CELLS; NONHUMAN-PRIMATES; INFECTION; EXPRESSION; RESPONSES; MONKEY; CYTOTOXICITY AB Natural killer (NK) cells and NK cell activities in the rhesus macaque have been incompletely characterized. Using a recently developed rhesus NK target cell line with down-regulated MHC-I (B116(Lo)) as stimulators and FACS-sorted cells as effectors in a 4-h [Cr-51]-release assay we showed that the CD3(-)CD8(1o) subpopulation is the primary effector population for NK cell-mediated cytolysis. The majority of these cells co-express CD16, CD11b, NKG2D, and NKp46. To evaluate functional activity at the individual cell level, we employed intracellular cytokine staining and a flow cytometric assay for degranulation, based on cell surface CD107a expression. Flow cytometric analysis revealed that a greater proportion of NK cells degranulated than produced cytokines in response to B116(Lo) stimulation; the frequency of CD107a-expressing cells within the total NK cell population ranging from 5 to 39%. Somewhat surprisingly, we did not find a significant correlation between lysis, measured by [Cr-51]-release assay, and the size of the degranulating NK cell population, implying that additional mechanisms may regulate lytic activity. Use of these approaches should facilitate an improved understanding of NK activity in the rhesus macaque. (c) 2004 Elsevier Inc. All rights reserved. C1 SAIC Frederick Inc, AIDS Vaccine Program, NCI, Ft Detrick, MD 21702 USA. SAIC Frederick Inc, Lab Genom Divers, NCI, Ft Detrick, MD 21702 USA. RP Lifson, JD (reprint author), SAIC Frederick Inc, AIDS Vaccine Program, NCI, Ft Detrick, MD 21702 USA. EM lifson@ncifcrf.gov FU NCI NIH HHS [N01-CO-124000] NR 40 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP-OCT PY 2004 VL 231 IS 1-2 BP 85 EP 95 DI 10.1016/j.cellimm.2004.12.004 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 934CD UT WOS:000229683600011 PM 15919373 ER PT J AU Yoon, HY Jacques, K Nealon, B Stauffer, S Premont, RT Randazzo, PA AF Yoon, HY Jacques, K Nealon, B Stauffer, S Premont, RT Randazzo, PA TI Differences between AGAP1, ASAP1 and arf GAP1 in substrate recognition: interaction with the N-terminus of Arf1 SO CELLULAR SIGNALLING LA English DT Article DE ADP-ribosylation factor; GTPase-activating proteins; membrane traffic ID ADP-RIBOSYLATION-FACTOR; GTPASE-ACTIVATING PROTEIN; GUANINE-NUCLEOTIDE EXCHANGE; BINDING PROTEINS; AMINO-TERMINUS; FACTOR ARNO; FACTOR-I; FUNCTIONAL INTERACTION; DEPENDENT INTERACTION; TARGET PROTEIN AB The Arf GAPs are a structurally diverse group of proteins that catalyze the hydrolysis of GTP bound to Arf1. Here, we directly compare the role of amino acids 2-17 of Arf1, a GTP- and phospholipid-sensitive switch, for interaction with three Arf GAPs: Arf GAPI, AGAP1 and ASAP1. Sequestration of amino acids 2-17 with an antibody inhibited interaction with the three tested Arf GAPs. Examination of Arf1 mutants also indicated that [2-17]Arf1 is a critical structural determinant of interaction with all three Arf GAPs; however, the effect of specific mutations differed among the GAPs. Compared to wild-type Arf1, Arf1 with the amino terminal 13 ([Delta13]Arf1) and 17 amino acids ([Delta17]Arf1) deleted had 200- and 4000-fold reduced interaction with ASAP1 and 150-fold reduced interaction with AGAP1. In contrast, deletion of the amino terminus of Arf reduced interaction with Arf GAPI by 5-fold. By analysis of point mutants, we found that lysines 15 and 16 had a greater contribution to productive interaction between Arf1, ASAP1 and AGAP1 than between Arf1 and Arf GAT1. Leucine 8 contributed to the interaction with Arf GAPI but not with ASAP1 and AGAP1. Amino acids 2-17 of Arf1, isolated from the protein, inhibited GAP activity of Arf GAPI, ASAP1 and AGAP1 and bound directly to ASAP1. Taken together, our results indicate that (i) Arf GAPs interact with amino acids 2-17 of Arf1 and (ii) each subgroup of Arf GAPs has a unique interface with Arf1. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Canc Res Ctr, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Med Gastroenterol, Durham, NC 27710 USA. RP Randazzo, PA (reprint author), NCI, Canc Res Ctr, Cellular Oncol Lab, NIH, Bldg 37,Room 4118, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov OI Premont, Richard/0000-0002-8053-5026 FU NIGMS NIH HHS [GM 59989] NR 71 TC 21 Z9 22 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD SEP PY 2004 VL 16 IS 9 BP 1033 EP 1044 DI 10.1016/j.cellsig.2004.02.008 PG 12 WC Cell Biology SC Cell Biology GA 836GY UT WOS:000222545000007 PM 15212764 ER PT J AU Chu, C Alapat, D Wen, XP Timo, K Burstein, D Lisanti, M Shears, S Kohtz, DS AF Chu, C Alapat, D Wen, XP Timo, K Burstein, D Lisanti, M Shears, S Kohtz, DS TI Ectopic expression of murine diphosphoinositol polyphosphate phosphohydrolase 1 attenuates signaling through the ERK1/2 pathway SO CELLULAR SIGNALLING LA English DT Article DE diphosphoinositol polyphosphate phosphohydrolase; extracellular signal-regulated kinase; receptor tyrosine kinase ID GROWTH-FACTOR RECEPTOR; GUANINE-NUCLEOTIDE EXCHANGE; GTPASE-ACTIVATING PROTEIN; INOSITOL HEXAKISPHOSPHATE KINASE; SERUM RESPONSE ELEMENT; HIGH-AFFINITY BINDING; NIH 3T3 CELLS; TYROSINE KINASE; DNA-SYNTHESIS; IN-VITRO AB Signals from several receptor tyrosine kinases are transduced by activation of the Ras family of GTP-binding proteins. Activation of Ras initiates a kinase cascade that culminates in activation of the mitogen-activated protein kinases (MAPKs). The MAPKs include the c-jun NH2-terminal protein kinases (JNKs) and extracellular signal-regulated kinases (ERKs), both of which phosphorylate Elk-1/TCF, a factor that activates transcription of the c-fos gene. In this report, we identify a novel 19 kDa gene product as a negative regulator of signaling through the ERK1/2 pathway. While these studies were in progress, the human homologue of this gene was characterized as diphosphomositol polyphosphate phosphohydrolase (DIPP1) [EM130 J. 17 (1998) 6599], a phosphohydrolase that converts diphosphate groups on diphosphomositol polyphosphates to monophosphates. Ectopic expression of murine DIPP1 (muDIPP1) blocked activation of the c-fos promoter by the ERK 1/2 pathway. Inhibition of signal transduction through the ERK 1/2 pathway by muDIPP1 occurs at or downstream from activation of MEK. In vitro kinase studies suggest that muDIPP1 is not a direct inhibitor of MEK or ERK activity, although, ectopic expression at near physiological levels results in attenuation of ERK phosphorylation in vivo. Interestingly, a site mutant of muDIPP1 lacking phosphohydrolase activity blocked signaling through the ERK1/2 pathway with greater efficiency than wild-type muDIPP1. This result suggests that inhibition of signaling through the ERK1/2 pathway is a distinct function of muDIPP1 that is not dependent on, but may be regulated by, its activity as a phosphohydrolase. (C) 2004 Elsevier Inc. All rights reserved. C1 Mt Sinai Sch Med, Ruttenberg Canc Ctr, Dept Pathol 1194, New York, NY 10029 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA. NIEHS, Inositide Signaling Sect, Res Triangle Pk, NC 27709 USA. RP Kohtz, DS (reprint author), Mt Sinai Sch Med, Ruttenberg Canc Ctr, Dept Pathol 1194, 1 Gustave Levy Pl, New York, NY 10029 USA. EM stave.kohtz@mssm.edu FU NCI NIH HHS [CA 72775] NR 79 TC 13 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD SEP PY 2004 VL 16 IS 9 BP 1045 EP 1059 DI 10.1016/j.cellsig.2004.02.009 PG 15 WC Cell Biology SC Cell Biology GA 836GY UT WOS:000222545000008 PM 15212765 ER PT J AU Yoo, S McKee, BD AF Yoo, S McKee, BD TI Overexpression of Drosophila Rad51 protein (DmRad51) disrupts cell cycle progression and leads to apoptosis SO CHROMOSOMA LA English DT Article ID RECA-LIKE GENE; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; DNA; REPAIR; EXPRESSION; REAPER; DEATH; P53; BINDING AB Among proteins involved in homologous recombination, Rad51 is an essential enzyme in DNA repair and recombination. However, little is known about its role in cell cycle regulation and apoptosis. To examine the function of Drosophila Rad51 (DmRad51) in cell cycle regulation and apoptosis, DmRad51 protein was overexpressed using a heat shock-inducible promoter or the UAS-GAL4 binary expression system. We observed that ubiquitous expression of DmRad51 protein in flies carrying hsp26-Rad51 or UAS-Rad51 transgenes was lethal. Induction of DmRad51-more specifically in eye or wing imaginal discs-caused tissue-specific cell death in the domains of DmRad51 expression. Cell death was due to apoptosis, as shown by staining with the TdT-mediated dUTP nick-end labeling assay. Immunocytochemistry revealed that cells expressing DmRad51 colocalized with apoptotic cells. In addition, the phenotypes caused by the overexpression of DmRad51 were similar to those caused by ectopic expression of Reaper, a proapoptotic protein, and were partially suppressed by the coexpression of p35, an antiapoptotic protein. Using an antiphosphohistone H3 antibody, we also observed that the overexpression of DmRad51 protein disrupted normal cell cycle progression in eye imaginal discs. Taken together, these results show that ectopically expressed DmRad51 disrupts cell cycle regulation and induces apoptosis. C1 Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP McKee, BD (reprint author), Univ Tennessee, Dept Biochem & Cellular & Mol Biol, M407 Walters Life Sci Bldg,1414 Cumberland Ave, Knoxville, TN 37996 USA. EM bdmckee@utk.edu FU NIGMS NIH HHS [GM40489] NR 47 TC 13 Z9 14 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD SEP PY 2004 VL 113 IS 2 BP 92 EP 101 DI 10.1007/s00412-004-0300-x PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 857DW UT WOS:000224097400006 PM 15257466 ER PT J AU McLaren, PJ Mayne, M Rosser, S Moffatt, T Becker, KG Plummer, FA Fowke, KR AF McLaren, PJ Mayne, M Rosser, S Moffatt, T Becker, KG Plummer, FA Fowke, KR TI Antigen-specific gene expression profiles of peripheral blood mononuclear cells do not reflect those of T-lymphocyte subsets SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID DNA MICROARRAY ANALYSIS; VIRUS-INFECTION; RNA AMPLIFICATION; CDNA MICROARRAYS; EPITHELIAL-CELLS; HIV-1 INFECTION; HLA SYSTEM; 2 PARTS; PATHOGENESIS; INTERFERON AB Advances in microarray technology have allowed for the monitoring of thousands of genes simultaneously. This technology is of particular interest to immunologists studying infectious diseases, because it provides tremendous potential for investigating host-pathogen interactions at the level of immune gene expression. To date, many studies have focused either on cell lines, where the physiological relevance is questionable, or on mixed cell populations, where the contributions of individual subpopulations are unknown. In the present study, we perform an intrasubject comparison of antigen-stimulated immune gene expression profiles between a mixed population of peripheral blood mononuclear cells (PBMC) and the two predominant cell types found in PBMC, CD4(+) and CD8(+) T lymphocytes. We show that the microarray profiles of CD4(+) and CD8(+) T lymphocytes differ from each other as well as from that of the mixed cell population. The independence of the gene expression profiles of different cell types is demonstrated with a ubiquitous antigen (Candida albicans) as well as with a disease-specific antigen (human immunodeficiency virus p24). This study has important implications for microarray studies of host immunity and underscores the importance of profiling the expression of specific cell types. C1 Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Internal Med, Infect Dis Sect, Winnipeg, MB R3E 0W3, Canada. NIA, DNA Array Unit, Bethesda, MD USA. RP Fowke, KR (reprint author), Univ Manitoba, Dept Med Microbiol, 539-730 William Ave, Winnipeg, MB R3E 0W3, Canada. EM fowkekr@cc.umanitoba.ca OI Becker, Kevin/0000-0002-6794-6656; Fowke, Keith/0000-0001-8227-6649 NR 42 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 2004 VL 11 IS 5 BP 977 EP 982 DI 10.1128/CDLI.11.5.977-982.2004 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 856LJ UT WOS:000224046400025 PM 15358662 ER PT J AU Monitto, CL Dong, SM Jen, J Sidransky, D AF Monitto, CL Dong, SM Jen, J Sidransky, D TI Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia SO CLINICAL CANCER RESEARCH LA English DT Article ID MUSCLE PROTEIN-DEGRADATION; BREAST-CANCER; TUMOR-GROWTH; NUDE-MICE; CACHECTIC FACTOR; WEIGHT-LOSS; MODEL; CELLS; INDUCTION; PEPTIDE AB Cachexia is an important cause of secondary morbidity and mortality in patients with cancer. Previous studies have suggested that cancer-associated cachexia may be due in part to tumor-specific production and secretion of a glycosylated peptide, proteolysis-inducing factor, originally identified in a murine cancer cachexia model. We report here the cloning of a human cDNA that generates a peptide having high-sequence homology to this proteolysis-inducing factor. Constitutive expression of human proteolysis-inducing factor is low or absent in most normal human tissues but appears to be elevated in some human tumors. Stable forced expression of human proteolysis-inducing factor in multiple murine and human cell lines results in a secreted protein, but no glycosylation of the protein is detected. In addition, tumor xenografts engineered to overexpress human proteolysis-inducing factor protein do not induce cachexia in vivo. These findings raise important questions as to potential cross-species differences in protein sequence and processing of murine proteolysis-inducing factor and human proteolysis-inducing factor, as well as the nature of the relationship between human proteolysis-inducing factor and the development of cancer cachexia. C1 Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Sidransky, D (reprint author), Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. EM DSIDRANS@jhmi.edu NR 35 TC 22 Z9 23 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5862 EP 5869 DI 10.1158/1078-0432.CCR-04-0435 PG 8 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700033 PM 15355918 ER PT J AU de Jong, FA Marsh, S Mathijssen, RHJ King, C Verweij, J Sparreboom, A McLeod, HL AF de Jong, FA Marsh, S Mathijssen, RHJ King, C Verweij, J Sparreboom, A McLeod, HL TI ABCG2 pharmacogenetics: Ethnic differences in allele frequency and assessment of influence on irinotecan disposition SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-31, 2004 CL Orlando, FL SP Amer Assoc Canc Res ID CANCER RESISTANCE PROTEIN; MULTIDRUG-RESISTANCE; CLINICAL PHARMACOKINETICS; GENE; TRANSPORTER; METABOLISM; CPT-11; TOPOTECAN; SN-38; CELLS AB Purpose: The ATP-binding cassette transporter ABCG2 (breast cancer resistance protein) is an efflux protein that plays a role in host detoxification of various xenobiotic substrates, including the irinotecan metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). The ABCG2 421C>A polymorphism has been associated with reduced protein expression and altered function in vitro. The aim of this study was to evaluate the ethnic distribution and potential functional consequence of the ABCG2 421C>A genotype in cancer patients treated with irinotecan. Experimental Design: ABCG2 genotyping was performed using Pyrosequencing on DNA from 88 American Caucasians, 94 African Americans, 938 Africans, and 95 Han Chinese, as well as in 84 European Caucasian patients treated with irinotecan undergoing additional blood sampling for pharmacokinetic studies. Results: Significant differences in allele frequencies were observed between the given world populations (P < 0.001), the variant allele being most common in the Han Chinese population with a frequency as high as 34%. The mean area under the curve of irinotecan and SN-38 were 19,851 and 639 ng X hour/mL, respectively. The frequency of the variant allele (10.7%) was in line with results in American Caucasians. No significant changes in irinotecan pharmacokinetics were observed in relation to the ABCG2 421C>A genotype, although one of two homozygous variant allele carriers showed extensive accumulation of SN-38 and SN-38 glucuronide. dConclusions: The ABCG2 421C>A polymorphism appears to play a limited role in the disposition of irinotecan in European Caucasians. It is likely that the contribution of this genetic variant is obscured by a functional role of other polymorphic proteins. C1 NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Erasmus Univ MC, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Washington Univ, Sch Med, Dept Med, St Louis, MO 63130 USA. RP Sparreboom, A (reprint author), NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM SparrebA@mail.nih.gov RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011 FU NIGMS NIH HHS [U01 GM63340] NR 37 TC 137 Z9 144 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5889 EP 5894 DI 10.1158/1078-0432.CCR-04-0144 PG 6 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700036 PM 15355921 ER PT J AU Kelloff, GJ Schilsky, RL AF Kelloff, GJ Schilsky, RL TI Limitations of the adenoma - Carcinoma sequence in colorectum - Reply SO CLINICAL CANCER RESEARCH LA English DT Letter ID SURROGATE END-POINTS; CANCER; PREVENTION; PERSPECTIVES; DRUGS C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Univ Chicago, Div Biol Sci, Chicago, IL 60637 USA. RP Kelloff, GJ (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2004 VL 10 IS 17 BP 5970 EP 5970 PG 1 WC Oncology SC Oncology GA 851ZJ UT WOS:000223724700048 ER PT J AU Marciano, BE Wesley, R De Carlo, ES Anderson, VL Barnhart, LA Darnell, D Malech, HL Gallin, JI Holland, SM AF Marciano, BE Wesley, R De Carlo, ES Anderson, VL Barnhart, LA Darnell, D Malech, HL Gallin, JI Holland, SM TI Long-term interferon-gamma therapy for patients with chronic granulomatous disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FOLLOW-UP; SULFAMETHOXAZOLE-TRIMETHOPRIM; HEALTHY-SUBJECTS; INFECTIONS; CORTICOSTEROIDS; ITRACONAZOLE; PROPHYLAXIS; NEUTROPHILS; MANAGEMENT; SAFETY AB Background. Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absent production of superoxide and hydrogen peroxide in phagocytes predisposes patients to bacterial and fungal infections. Infections are dramatically reduced by prophylaxis with antibiotics, antifungals, and interferon-gamma (IFN-gamma). Methods. Seventy-six patients with CGD were enrolled in an uncontrolled, open-label follow-up study to assess the long-term clinical safety and efficacy of IFN-gamma therapy. Patients received IFN-gamma subcutaneously 3 times per week. Results. We observed patients for up to 9 years, for a total observation period of 328.4 patient-years. The incidence of serious infections was 0.30 infections per patient-year; for serious bacterial infections, the incidence was 0.18 cases per patient-year, and for serious fungal infections, it was 0.12 cases per patient-year. Thirty-seven percent of patients reported an adverse event, the most common of which was fever. Twenty-six patients withdrew from the study (3 because of adverse events, 15 because of patient preference, and 8 because of transfer to another trial). There were no life-threatening IFN-gamma-related adverse events and no discernible effects on growth. The overall mortality rate was 1.5% per patient-year. Conclusion. IFN-gamma prophylaxis for CGD appears to be effective and well tolerated over a prolonged period of time. C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, US Dept HHS, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), Bldg 10,Rm 11N103,10 Ctr Dr MSC 1886, Bethesda, MD 20892 USA. EM smh@nih.gov NR 41 TC 99 Z9 108 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2004 VL 39 IS 5 BP 692 EP 699 DI 10.1086/422993 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 847CU UT WOS:000223367500013 PM 15356785 ER PT J AU Putnam, SD Riddle, MS Wierzba, TF Pittner, BT Elyazeed, RA El-Gendy, A Rao, MR Clemens, JD Frenck, RW AF Putnam, SD Riddle, MS Wierzba, TF Pittner, BT Elyazeed, RA El-Gendy, A Rao, MR Clemens, JD Frenck, RW TI Antimicrobial susceptibility trends among Escherichia coli and Shigella spp. isolated from rural Egyptian paediatric populations with diarrhoea between 1995 and 2000 SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE antibiotic resistance; diarrhoea; Egypt; Escherichia coli; resistance; Shigella spp. ID STRAINS MULTIPLY RESISTANT; ANTIBIOTIC-RESISTANCE; TRIMETHOPRIM-SULFAMETHOXAZOLE; STREPTOCOCCUS-PNEUMONIAE; CHILDHOOD SHIGELLOSIS; IMMUNOSORBENT-ASSAY; NALIDIXIC-ACID; FECAL FLORA; INFECTION; CHILDREN AB Antimicrobial susceptibility testing was performed on 3627 isolates of Escherichia coli and 180 isolates of Shigella spp. collected in rural locations from 875 Egyptian children with diarrhoea between 1995 and 2000. The cumulative rates of resistance for E. coli and Shigella spp. were high (respectively, 68.2% and 54.8% for ampicillin, 24.2% and 23.5% for ampicillin-sulbactam, 57.2% and 42.5% for trimethoprim-sulphamethoxazole, and 50.9% and 75.4% for tetracycline). Non-enterotoxigenic E. coli (NETEC) isolates had a consistently higher level of antimicrobial resistance than did enterotoxigenic E. coli (ETEC) isolates. Trend testing showed significant decreases in resistance to ampicillin, ampicillin-sulbactam and tetracycline among all E. coli isolates. Increasing rates of resistance were observed for trimethoprim-sulphamethoxazole in ETEC isolates and Shigella spp., but not in NETEC isolates. Low levels of resistance were observed for all other antimicrobial agents tested. Overall, high levels, but decreasing trends, of resistance to commonly used antimicrobial agents were detected among isolates of E. coli and Shigella spp. from children in rural Egypt. C1 Naval Med Res Ctr, Enter Dis Dept, Silver Spring, MD USA. Naval Med Res Unit 3, Enter Dis Res Program, Cairo, Egypt. WHO, EPI & Polio Educ, Kathmandu, Nepal. Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. Int Vaccine Inst, Seoul, South Korea. RP Putnam, SD (reprint author), NAMRUZ, FPO, AP 96520 USA. EM putnam@namruz.019 RI Riddle, Mark/A-8029-2011 FU NICHD NIH HHS [Y1-HD-0026-01] NR 41 TC 24 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD SEP PY 2004 VL 10 IS 9 BP 804 EP 810 DI 10.1111/j.1469-0691.2004.00927.x PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 851UW UT WOS:000223712400006 PM 15355411 ER PT J AU Knight, DC Smith, CN Cheng, DT Stein, EA Helmstetter, FJ AF Knight, David C. Smith, Christine N. Cheng, Dominic T. Stein, Elliot A. Helmstetter, Fred J. TI Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article AB Previous functional magnetic resonance imaging (fMRI) studies have characterized brain systems involved in conditional response acquisition during Pavlovian fear conditioning. However, the functional neuroanatomy underlying the extinction of human conditional fear remains largely undetermined. The present study used fMRI to examine brain activity during acquisition and extinction of fear conditioning. During the acquisition phase, participants were either exposed to light (CS) presentations that signaled a brief electrical stimulation (paired group) or received light presentations that did not serve as a warning signal (control group). During the extinction phase, half of the paired group subjects continued to receive the same treatment, whereas the remainder received light alone. Control subjects also received light alone during the extinction phase. Changes in metabolic activity within the amygdala and hippocampus support the involvement of these regions in each of the procedural phases of fear conditioning. Hippocampal activity developed during acquisition of the fear response. Amygdala activity increased whenever experimental contingencies were altered, suggesting that this region is involved in processing changes in environmental relationships. The present data show learning-related amygdala and hippocampal activity during human Pavlovian fear conditioning and suggest that the amygdala is particularly important for forming new associations as relationships between stimuli change. C1 [Knight, David C.; Smith, Christine N.; Cheng, Dominic T.; Helmstetter, Fred J.] Univ Wisconsin, Milwaukee, WI 53201 USA. [Knight, David C.] NIMH, Bethesda, MD 20892 USA. [Smith, Christine N.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Stein, Elliot A.; Helmstetter, Fred J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Stein, Elliot A.] NIDA, Intramural Res Program, Baltimore, MD USA. RP Helmstetter, FJ (reprint author), Univ Wisconsin, Dept Psychol, POB 413, Milwaukee, WI 53201 USA. EM fjh@uwm.edu OI Smith, Christine/0000-0002-7760-4131; Helmstetter, Fred/0000-0003-3413-2418 FU NIMH [MH11722, MH50864]; NIDA [DA09465]; McDonnell Foundation; General Clinical Research Centers Grant [M01 RR00058] FX This work was supported by NIMH Fellowship MH11722 to D. C. K., NIDA Grant DA09465 to E. A. S., NIMH Grant MH50864 to F.J.H., a McDonnell Foundation grant to F.J.H., and General Clinical Research Centers Grant M01 RR00058 to the Medical College of Wisconsin. Correspondence should be addressed to F. J. Helmstetter, Department of Psychology, University of Wisconsin, P.O. Box 413, Milwaukee, WI 53201 (e-mail: fjh@uwm.edu). NR 51 TC 130 Z9 132 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD SEP PY 2004 VL 4 IS 3 BP 317 EP 325 DI 10.3758/CABN.4.3.317 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V32MO UT WOS:000208955500004 PM 15535167 ER PT J AU Braunschweig, T Chung, JY Hewitt, SM AF Braunschweig, T Chung, JY Hewitt, SM TI Perspectives in tissue microarrays SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE tissue microarray; tissue array; TMA; pathology; proteomics; histology; translational medicine; high throughput methodologies ID IN-SITU HYBRIDIZATION; PROSTATE-CANCER; BREAST-CANCER; PROTEIN EXPRESSION; GENE AMPLIFICATION; HUMAN GENOME; CARCINOMA; TUMORS; IMMUNOHISTOCHEMISTRY; OVEREXPRESSION AB Tissue microarrays (TMAs) are means of combining tens to hundreds of specimens of tissue onto a single slide for analysis at one time. TMAs are most frequently constructed from paraffin embedded tissue; however, they can be constructed from frozen tissue. The construction of TMAs is flexible, meeting the focused needs of the investigator. A TMA slide can be processed like an ordinary tissue section, and used for histochemical, immunohistochemical staining or in situ hybridization. Combined with automated new image analysis systems, TMAs are a powerful molecular profiling tool. By confirming the findings of microarray experiments or protein arrays, TMAs can be applied systematically to global cellular network analysis within tissue cell. TMAs are commonly used to confirm the results of expression microarrays as well as in the development of diagnostic and prognostics markers for clinical applications. This review will cover recent advancements in technology for the construction and use of TMAs. Because TMAs can be constructed from archival paraffin embedded tissue, they open up the vast archive of patient samples and make them accessible for medical research. TMAs play an ever increasing role in translational medicine, bridging the chasm of discovery at the research bench to the demonstration of clinical utility prior to implementation in patient care. C1 NCI, TARP Lab, Ctr Adv Technol, Lab Pathol,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Inje Univ, Coll Med, PharmacoGenom Res Ctr, Pusan 614735, South Korea. Inje Univ, Coll Med, Mol Cell Physiol Res Grp, Pusan 614735, South Korea. RP Hewitt, SM (reprint author), NCI, TARP Lab, Ctr Adv Technol, Lab Pathol,Ctr Canc Res,NIH, MSC 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 64 TC 29 Z9 31 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD SEP PY 2004 VL 7 IS 6 BP 575 EP 585 PG 11 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 851WC UT WOS:000223716000007 PM 15379629 ER PT J AU Kim-Shapiro, DB Hogg, N Patel, RP Gladwin, MT AF Kim-Shapiro, DB Hogg, N Patel, RP Gladwin, MT TI What's right about nitrite? SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Meeting Abstract C1 Wake Forest Univ, Coll Med, Winston Salem, NC 27109 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Alabama, Tuscaloosa, AL 35487 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kim-Shapiro, DB (reprint author), Wake Forest Univ, Coll Med, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD SEP PY 2004 VL 139 IS 1 BP 140 EP 140 PG 1 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 858DR UT WOS:000224171000029 ER PT J AU Yu, KF Yuan, W AF Yu, KF Yuan, W TI Regression models for unbalanced longitudinal ordinal data: computer software and a simulation study SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE longitudinal ordinal data; global odds ratio; generalized estimating equations; sample generating ID GENERALIZED ESTIMATING EQUATIONS AB A computer program GGOREX in the form of a SAS macro is developed for the analysis of longitudinal ordinal data. It is extended from GEECAT and GEEGOR developed by Williamson, Lipsitz and Kim in their paper in 1999. An illustrative example with some preliminary data from a study conducted by the National Institute of Child Health and Human Development and the University of Alabama at Birmingham is given. Another set of computer programs is developed to make it possible to conduct a simulation study to validate the GGOREX procedure in a finite sample. A simple computer program in FORTRAN using the IMSL software library is developed to solve for the probability distribution of the longitudinal ordinal responses according to the correlation specification. Published by Elsevier Ireland Ltd. C1 NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Glotech Inc, Rockville, MD 20850 USA. RP Yu, KF (reprint author), NICHHD, Dept Hlth & Human Serv, Bldg 6100,Room 7B05, Bethesda, MD 20892 USA. EM yukf@mail.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD SEP PY 2004 VL 75 IS 3 BP 195 EP 200 DI 10.1016/j.cmpb.2004.02.006 PG 6 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 846XV UT WOS:000223353700002 PM 15265618 ER PT J AU Klaunberg, BA O'Malley, J Clark, T Davis, JA AF Klaunberg, BA O'Malley, J Clark, T Davis, JA TI Euthanasia of mouse fetuses and neonates SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID EXPERIMENTAL-ANIMALS; RECOMMENDATIONS; EKLF AB We sought to determine whether any of the common methods of euthanasia for adult rodents would lead to an acceptable death for fetuses or neonates. We wanted to identify a method that was rapid, free of signs of pain or distress, reliable, and minimally distressful to the person performing the procedure and that minimized the amount of handling required to perform the procedure. We evaluated six methods of euthanasia, with and without anesthesia, in three age groups of mice: gravid mice (E14-20) and neonatal pups (P1-P7 and P8-P14). Euthanasia methods included: halothane inhalation, carbon dioxide inhalation, intraperitoneal sodium pentobarbital, intravenous potassium chloride, and cervical dislocation with and without anesthesia. Noninvasive echocardiography was used to assess heartbeat during euthanasia. With cardiac arrest as the definition of death, no method of euthanasia killed fetal mice. Halothane inhalation (5% by vaporizer) was not an acceptable method of euthanasia for mice of the age groups tested. Intraperitoneal administration of sodium pentobarbital for euthanasia required a higher dose than the previously established dose, and there is a risk of reduced efficacy in pregnant animals due to potential intrauterine injection. Carbon dioxide asphyxiation was the most efficient method of euthanasia for neonatal mouse pups P1-14. For pregnant adult mice, intravenous potassium chloride under anesthesia, carbon dioxide asphyxiation, and cervical dislocation alone or under anesthesia were excellent methods of euthanasia. C1 NINDS, AHCS, DIR, NIH,DHHS, Bethesda, MD 20892 USA. NINDS, NMRF, DIR, NIH,DHHS, Bethesda, MD 20892 USA. NIH, OACU, OIR, OD,DHHS, Bethesda, MD 20892 USA. RP Davis, JA (reprint author), NINDS, AHCS, DIR, NIH,DHHS, 36 Convent Dr,Bldg 36,Room B306, Bethesda, MD 20892 USA. NR 17 TC 15 Z9 15 U1 1 U2 12 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD SEP PY 2004 VL 43 IS 5 BP 29 EP 34 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 855LH UT WOS:000223974200006 PM 15461437 ER PT J AU Cappa, SF Grafman, J AF Cappa, SF Grafman, J TI Neuroimaging of higher cognitive function SO CORTEX LA English DT Editorial Material ID JUDGMENTS; FMRI C1 Univ Vita Salute San Raffaele, Cognit Neurosci Ctr, Milan, Italy. NINDS, Cognit Neurosci Sect, Bethesda, MD USA. RP Cappa, SF (reprint author), Univ Vita Salute San Raffaele, Cognit Neurosci Ctr, Milan, Italy. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 11 TC 1 Z9 1 U1 0 U2 0 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA FRATELLI BRESSAN 2, 20126 MILAN, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD SEP-DEC PY 2004 VL 40 IS 4-5 BP 591 EP 592 DI 10.1016/S0010-9452(08)70154-0 PG 2 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 864ZL UT WOS:000224671800001 PM 15505968 ER PT J AU Gajic, O Dara, SI Mendez, JL Adesanya, AO Festic, E Caples, SM Rana, R Sauver, JLS Lymp, JF Afessa, B Hubmayr, RD AF Gajic, O Dara, SI Mendez, JL Adesanya, AO Festic, E Caples, SM Rana, R Sauver, JLS Lymp, JF Afessa, B Hubmayr, RD TI Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; outcome assessment (health care), pulmonary edema; ventilator-associated lung injury; transfusion-related acute lung injury ID RESPIRATORY-DISTRESS-SYNDROME; INTENSIVE-CARE-UNIT; LOW TIDAL VOLUMES; PULMONARY-EDEMA; HYPERCAPNIC ACIDOSIS; CONSENSUS CONFERENCE; PRESSURES; OUTCOMES; TRIALS; ADULTS AB Objective. Although ventilation with small tidal volumes is recommended in patients with established acute lung injury, most others receive highly variable tidal volume aimed in part at normalizing arterial blood gas values. We tested the hypothesis that acute lung injury, which develops after the initiation of mechanical ventilation, is associated with known risk factors for ventilator-induced lung injury such as ventilation with large tidal volume. Design: Retrospective cohort study. Setting: Four intensive care units in a tertiary referral center. Patients: Patients who received invasive mechanical ventilation for greater than or equal to48 hrs between January and December 2001. Interventions: None. Measurements and Main Results. The main outcome of interest, acute lung injury, was assessed by independent review of daily digital chest radiographs and arterial blood gases. Ventilator settings, hemodynamics, and acute lung injury risk factors were extracted from the Acute Physiology and Chronic Health Evaluation III database and the patients' medical records. Of 332 patients who did not have acute lung injury from the outset, 80 patients (24%) developed acute lung injury within the first 5 days of mechanical ventilation. When expressed per predicted body weight, women were ventilated with larger tidal volume than men (mean 11.4 vs. 10.4 mL/kg predicted body weight, p < .001) and tended to develop acute lung injury more often (29% vs. 20%, p =.068). In a multivariate analysis, the main risk factors associated with the development of acute lung injury were the use of large tidal volume (odds ratio 1.3 for each mL above 6 mL/kg predicted body weight, p < .001), transfusion of blood products (odds ratio, 3.0; p < 0.001), acidemia (pH < 7.35; odds ratio, 2.0; p = .032) and a history of restrictive lung disease (odds ratio, 3.6; p = .044). Conclusions: The association between the initial tidal volume and the development of acute lung injury suggests that ventilator-associated lung injury may be an important cause of this syndrome. Height and gender should be considered when setting up the ventilator, Strong consideration should be given to limiting large tidal volume, not only in patients with established acute lung injury but also in patients at risk for acute lung injury. C1 NHLBI, St Louis, MO 63178 USA. Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA. Univ Texas, SW Med Ctr, Dept Anesthesiol & Crit Care, Dallas, TX 75230 USA. Mayo Clin, Div Pulm & Crit Care Med, Jacksonville, FL 32224 USA. RP Gajic, O (reprint author), Falk Med Res Trust Fellowship Clin Res Training, St Louis, MO 63178 USA. FU NHLBI NIH HHS [HL 63178] NR 40 TC 357 Z9 378 U1 2 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2004 VL 32 IS 9 BP 1817 EP 1824 DI 10.1097/01.CCM.0000133019.52531.30 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 854JH UT WOS:000223898400001 PM 15343007 ER PT J AU Kolobow, T AF Kolobow, T TI Volutrauma, barotrauma, and ventilator-induced lung injury: Lessons learned from the animal research laboratory SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE barotrauma; volutrauma; ventilator-states associated lung injury; mechanical ventilation; tidal volume; peak inspiratory pressure; tracheal gas insufflation ID ACUTE RESPIRATORY-FAILURE; INTRATRACHEAL PULMONARY VENTILATION; EXTRACORPOREAL MEMBRANE-OXYGENATION; MECHANICAL VENTILATION; AIRWAY PRESSURE; MODEL C1 NIH, Bethesda, MD 20892 USA. RP Kolobow, T (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 9 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2004 VL 32 IS 9 BP 1961 EP 1962 DI 10.1097/01.CCM.0000134405.71890.3A PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 854JH UT WOS:000223898400022 PM 15343028 ER PT J AU Brown, P Cervenakova, L AF Brown, P Cervenakova, L TI The modern landscape of transfusion-related iatrogenic Creutzfeldt-Jakob disease and blood screening tests SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE transmissible spongiform encephalopathy; Creutzfeldt-Jakob disease; variant Creutzfeldt-Jakob disease; prion disease; blood infectivity; blood screening tests ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; PATHOLOGICAL PRION PROTEIN; BUFFY COAT; INFECTIVITY; STRAINS; HUMANS; MICE; VCJD; BSE; COMPONENTS AB The idea that blood in naturally occurring transmissible spongiform encephalopathies is not infectious has imploded in the face of recent transmissions from the blood of naturally occurring scrapie in sheep and of variant Creutzfeldt-Jakob disease in humans. Although donor exclusion criteria ensure that the number of any further iatrogenic cases will be small, the risk of future blood-borne disease transmissions could be entirely eliminated by a diagnostic preclinical screening test. A variety of methodological approaches to blood testing are under development, with different levels of success, but no method has yet achieved the critical goal of discriminating transmissible spongiform encephalopathy-infected from healthy uninfected humans. C1 Natl Inst Hlth, Bethesda, MD USA. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Plasma Derivatives Dept, Rockville, MD 20855 USA. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Transmissible Dis Dept, Rockville, MD 20855 USA. RP Brown, P (reprint author), 7815 Exeter Rd, Bethesda, MD 20814 USA. EM paulwbrown@comcast.net NR 36 TC 8 Z9 9 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD SEP PY 2004 VL 11 IS 5 BP 351 EP 356 DI 10.1097/01.moh.0000143393.49202.f0 PG 6 WC Hematology SC Hematology GA 865UM UT WOS:000224729000007 PM 15666660 ER PT J AU Posadas, EM Davidson, B Kohn, EC AF Posadas, EM Davidson, B Kohn, EC TI Proteomics mind ovarian cancer: Implications for diagnosis and treatment: a critical review of the recent literature SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE ovarian cancer; proteomics; mass spectroscopy; combinatorial signaling therapy; ascites ID CLINICAL PROTEOMICS; SERUM; OSTEOPONTIN; PATTERNS; BIOMARKER AB Purpose of review Epithelial ovarian cancer is the leading cause of death from gynecologic malignancies amongst American women. Emerging proteomic technologies have promise for early diagnosis and in advancing treatment directions. Application of these technologies has produced new biomarkers, diagnostic approaches, and understanding of disease biology. Recent findings Mass spectral blood and tissue analysis has yielded new putative biomarkers that require further validation and assessment of diagnostic specificity and sensitivity. Protein signature patterns derived from mass spectrometry datastreams have been modeled and are moving into validation. Tissue-based protein analysis has led to identification of tumor and stromal protein and signal activation events in ovarian cancer. Clinical trials are now ascertaining tissue samples prior to and during therapy with molecularly targeted agents to evaluate modulation of targeted signaling pathways. Finally, proteomic analysis of tissues and metastases will outline biochemical events underlying the metastatic phenotype of ovarian cancer. Summary Proteomic approaches are experimental technologies applied to ovarian and other cancers. Proper validation and use of findings may advance our understanding of biochemical events that have complicated successful detection and intervention, This knowledge is the first step in fulfilling the promise of personalized molecular medicine. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, FDA Clin Prot Program, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, Bethesda, MD 20892 USA. EM kohne@mail.nih.gov NR 38 TC 33 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD SEP PY 2004 VL 16 IS 5 BP 478 EP 484 DI 10.1097/00001622-200409000-00012 PG 7 WC Oncology SC Oncology GA 851UQ UT WOS:000223711600011 PM 15314519 ER PT J AU Telford, WG AF Telford, WG TI Analysis of UV-excited fluorochromes by flow cytometry using near-ultraviolet laser diodes SO CYTOMETRY PART A LA English DT Article DE solid-state laser; near-UV laser diode; Nd-YAG AB Introduction: Violet laser diodes have become common and reliable laser sources for benchtop flow cytometers. While these lasers are very useful for a variety of violet and some ultraviolet-excited fluorochromes (e.g., DAPI), they do not efficiently excite most UV-stimulated probes. In this study, the next generation of InGaN near-UV laser diodes (NUVLDs) emitting in the 370 - 375-nm range have been evaluated as laser sources for cuvette-based flow cytometers. Methods: Several NUVLDs, ranging in wavelength from 370 to 374 nm and in power level from 1.5 to 10 mW, were mounted on a BD Biosciences LSR II and evaluated for their ability to excite cells labeled with the UV DNA binding dye DAPI, several UV phenotyping fluorochromes (including Alexa Fluor 350, Marina Blue, and quantum dots), and the fluorescent calcium chelator indo-1. Results: NUVLDs at the 8-10-mW power range gave detection sensitivity levels comparable to more powerful solid-state and ion laser sources, using low-fluorescence microsphere beads as measurement standards. NUVLDs at all tested power levels allowed extremely high-resolution DAPI cell cycle analysis, and sources in the 8-10-mW power range excited Alexa Fluor 350, Marina Blue, and a variety of quantum dots at virtually the same signal-to-noise ratios as more powerful UV sources. Conclusions: These evaluations indicate that near-UV laser diodes installed on a cuvette-based flow cytometer performed nearly as well as more powerful solid-state UV lasers on the same instrumentation, and comparably to more powerful ion lasers on a jet-in-air system, and. Despite their limited power, integration of these small and inexpensive lasers into benchtop flow cytometers should allow the use of flow cytometric applications requiring UV excitation on a wide variety of instruments. Published 2004 Wiley-Liss, Inc.(dagger) C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Telford, WG (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12C121,9000 Rockville, Bethesda, MD 20892 USA. EM telfordw@mail.nih.gov NR 13 TC 18 Z9 22 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2004 VL 61A IS 1 BP 9 EP 17 DI 10.1002/cyto.a.20032 PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 851VW UT WOS:000223715200002 PM 15351984 ER PT J AU Khan, SS Smith, MS Reda, D Suffredini, AF McCoy, JP AF Khan, SS Smith, MS Reda, D Suffredini, AF McCoy, JP TI Multiplex bead array assays for detection of soluble cytokines: Comparisons of sensitivity and quantitative values among kits from multiple manufacturers SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE luminex; multiplex bead array; cytokines ID HUMAN INFLAMMATORY RESPONSES; INTRAVENOUS ENDOTOXIN; TECHNOLOGY; RECEPTOR; SYSTEM AB Background: Multiplex bead array assays permit simultaneous cytometric quantitation of multiple cytokines in solution by capturing these to spectrally distinct beads. Because several manufacturers offer reagents to quantitate the same cytokines on a single instrument, a comparison should be made to determine whether these kits yield similar data and whether these data are comparable to enzyme-linked immunosorbent assay (ELISA). Methods: This study compared cytokine detection kits by using Luminex 100. Twenty-six serum samples from seven subjects were analyzed for interferon-gamma, interleukins 1beta, 6, and 8, and tumor necrosis factor-a by using multiplex kits from LINCO Research, Bio-Rad Laboratories, R&D Systems, and BioSource International. Each assay was performed according to the manufacturers' specifications. Standard curves were generated by using reference concentrations supplied by each manufacturer. ELISAs for interleukin-8 were performed by using kits from R&D and BioSource. Results: Cytokine levels followed similar patterns, although absolute concentrations differed among kits. ELISA and Luminex values for interleukin-8 were similar in kits from the same manufacturer. Conclusions: Because relative cytokine measurements are often valuable when performed serially, it may be possible to make interlaboratory comparisons by using different kits. When comparison of absolute values is crucial, kits from the same supplier should be used. Within-vendor, bead array, and ELISA values appear comparable. Published 2004 Wiley-Liss, Inc.(dagger) C1 NHLBI, NIH, Flow Cytometry Core, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP McCoy, JP (reprint author), NHLBI, NIH, Flow Cytometry Core, Bldg 10,Room 4A07, Bethesda, MD 20892 USA. EM mccoyj@nhlbi.nih.gov NR 14 TC 225 Z9 234 U1 1 U2 19 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2004 VL 61B IS 1 BP 35 EP 39 DI 10.1002/cyto.b.20021 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 853PO UT WOS:000223839700005 PM 15351980 ER PT J AU Barald, KF Kelley, MW AF Barald, KF Kelley, MW TI From placode to polarization: new tunes in inner ear development SO DEVELOPMENT LA English DT Review ID BONE MORPHOGENETIC PROTEINS; NEURAL CREST DEVELOPMENT; MYOSIN-VIIA GENE; OTIC PLACODE; HAIR-CELLS; TRANSCRIPTION FACTORS; MICE LACKING; SYSTEM DEVELOPMENT; MAMMALIAN COCHLEA; MATH1 EXPRESSION AB The highly orchestrated processes that generate the vertebrate inner ear from the otic placode provide an excellent and circumscribed testing ground for fundamental cellular and molecular mechanisms of development. The recent pace of discovery in developmental auditory biology has been unusually rapid, with hundreds of papers published in the past 4 years. This review summarizes studies addressing several key issues that shape our current thinking about inner ear development, with particular emphasis on early patterning events, sensory hair cell specification and planar cell polarity. C1 Natl Inst Deafness & Other Communicat Disorders, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA. Univ Michigan, Cell & Mol Biol Program, Dept Cell & Dev Biol, Sch Med, Ann Arbor, MI 48109 USA. RP Kelley, MW (reprint author), Natl Inst Deafness & Other Communicat Disorders, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA. EM kelleymt@nidcd.nih.gov NR 110 TC 149 Z9 154 U1 0 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 2004 VL 131 IS 17 BP 4119 EP 4130 DI 10.1242/dev.01339 PG 12 WC Developmental Biology SC Developmental Biology GA 857SG UT WOS:000224138000001 PM 15319325 ER PT J AU Chang, W Brigande, JV Fekete, DM Wu, DK AF Chang, W Brigande, JV Fekete, DM Wu, DK TI The development of semicircular canals in the inner ear: role of FGFs in sensory cristae SO DEVELOPMENT LA English DT Article DE FGF2; FGF3; FGF 10; sensory organ; semicircular canals; common crus; BMP2; BMP7 ID NEURAL DEVELOPMENT; EXPRESSION; CHICKEN; MORPHOGENESIS; RECEPTOR; ANTAGONIST; INDUCTION; PROTEINS; NOGGIN; DOMAIN AB In the vertebrate inner ear, the ability to detect angular head movements lies in the three semicircular canals and their sensory tissues, the cristae. The molecular mechanisms underlying the formation of the three canals are largely unknown. Malformations of this vestibular apparatus found in zebrafish and mice usually involve both canals and cristae. Although there are examples of mutants with only defective canals, few mutants have normal canals without some prior sensory tissue specification, suggesting that the sensory tissues, cristae, might induce the formation of their non-sensory components, the semicircular canals. We fate-mapped the vertical canal pouch in chicken that gives rise to the anterior and posterior canals, using a fluorescent, lipophilic dye (DiI), and identified a canal genesis zone adjacent to each prospective crista that corresponds to the Bone morphogenetic protein 2 (Bmp2)-positive domain in the canal pouch. Using retroviruses or beads to increase Fibroblast Growth Factors (FGFs) for gain-of-function and beads soaked with the FGF inhibitor SU5402 for loss-of-function experiments, we show that FGFs in the crista promote canal development by upregulating Bmp2. We postulate that FGFs in the cristae induce a canal genesis zone by inducing/upregulating Bmp2 expression. Ectopic FGF treatments convert some of the cells in the canal pouch from the prospective common crus to a canal-like fate. Thus, we provide the first molecular evidence whereby sensory organs direct the development of the associated non-sensory components, the semicircular canals, in vertebrate inner ears. C1 Natl Deafness & Other Commun Disorders, Rockville, MD 20850 USA. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. RP Wu, DK (reprint author), Natl Deafness & Other Commun Disorders, Rockville, MD 20850 USA. EM wud@nidcd.nih.gov RI Fekete, Donna/B-9170-2009 OI Fekete, Donna/0000-0003-0662-0246 FU NIDCD NIH HHS [F32 DC000437] NR 35 TC 73 Z9 74 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 2004 VL 131 IS 17 BP 4201 EP 4211 DI 10.1242/dev.01292 PG 11 WC Developmental Biology SC Developmental Biology GA 857SG UT WOS:000224138000008 PM 15280215 ER PT J AU Belsky, J Booth-LaForce, CL Bradley, R Brownell, CA Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasck, K Houts, RM Huston, A Jaeger, E Johnson, DJ Kelly, JF Knoke, B Marshall, N McCartney, K Morrison, FJ O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Randolph, SM Robeson, WW Spieker, S Vandell, DL Weinraub, M AF Belsky, J Booth-LaForce, CL Bradley, R Brownell, CA Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasck, K Houts, RM Huston, A Jaeger, E Johnson, DJ Kelly, JF Knoke, B Marshall, N McCartney, K Morrison, FJ O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Randolph, SM Robeson, WW Spieker, S Vandell, DL Weinraub, M CA NICHD Early Child Care Res Network TI Does class size in first grade relate to children's academic and social performance or observed classroom processes? SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID TENNESSEE; TEACHERS; SCHOOLS AB This study evaluated the extent to which first-grade class size predicted child outcomes and observed classroom processes for 651 children (in separate classrooms). Analyses examined observed child-adult ratios and teacher-reported class sizes. Smaller classrooms showed higher quality instructional and emotional support, although children were somewhat less likely to be engaged. Teachers in smaller classes rated typical children in those classes as more socially skilled and as showing less externalizing behavior and reported more closeness toward them. Children in smaller classes performed better on literacy skills. Larger classrooms showed more group activities directed by the teacher, teachers and children interacted more often, and children were more often engaged. Lower class sizes were not of more benefit (or harm) as a function of the child's family income. First-grade class size in the range typical of present-day classrooms in the United States predicts classroom social and instructional processes as well as relative changes in social and literacy outcomes from kindergarten to first grade. C1 NICHD, Early Child Care Res Network, Ctr Res Mothers & Children, Rockville, MD 20852 USA. RP Belsky, J (reprint author), NICHD, Early Child Care Res Network, Ctr Res Mothers & Children, 6100 Execut Blvd,4B05, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012; OI Belsky, Jay/0000-0003-2191-2503; Marshall, Nancy L/0000-0002-4799-2030; Pianta, Robert/0000-0002-6280-8051 NR 36 TC 44 Z9 44 U1 2 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD SEP PY 2004 VL 40 IS 5 BP 651 EP 664 DI 10.1037/0012-1649.40.5.651 PG 14 WC Psychology, Developmental SC Psychology GA 848QX UT WOS:000223483300001 ER PT J AU Speckman, RA Frankenfield, DL Roman, SH Eggers, PW Bedinger, MR Rocco, MV McClellan, WM AF Speckman, RA Frankenfield, DL Roman, SH Eggers, PW Bedinger, MR Rocco, MV McClellan, WM TI Diabetes is the strongest risk factor for lower-extremity amputation in new hemodialysis patients SO DIABETES CARE LA English DT Article ID STAGE RENAL-DISEASE; DIALYSIS THERAPY; QUALITY; MORTALITY; PRESCRIPTION; MELLITUS; PROJECT; UREMIA AB OBJECTIVE - End-stage renal disease (ESRD) patients, especially those With diabetes, have an increased risk of nontraumatic lower-extremity amputation (LEA). The present study aims to examine the association of demographic and clinical variables With the risk of hospitalization for LEA among incident hemodialysis patients. RESEARCH DESIGN AND METHODS - The study population consisted of incident hemodialysis patients from the study years 1996-1999 of the ESRD Core Indicator/Clinical Performance Measures (CPM) Project. Cox proportional hazard modeling was used to identify factors associated with LEA. RESULTS - Four percent (1.16 of 3,272) of noncensored incident patients had an LEA during the 12-month follow-up period. Factors associated with LEA included diabetes as the cause of ESRD or preexisting comorbidity (hazard ratio 6.4, 95% CI 3.4-12.0), cardiovascular comorbidity (1.8, 1.2-2.8), hemodialysis inadequacy (urea reduction ratio [URR] <58.5% (1.9, 1.1-3.3), and lower serum albumin level (1.6, 1.1-2.3). Among patients with diabetes, hemodialysis inadequacy and cardiovascular comorbidity were risk factors for LEA (2.6, 1.4-4.8, and 1.7, 1.1-2.6, respectively). CONCLUSIONS - These data suggest that diabetes is a potent risk factor for LEA in new hemodialysis patients. In ESRD patients with diabetes, a multipronged approach may reduce the rate of LEA. Potentially beneficial Strategies include adherence to hemodialysis adequacy guidelines, aggressive treatment of cardiovascular comorbidities, and the utilization of LEA prevention strategies recommended for the general population of patients with diabetes. C1 Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Ctr Medicare & Medicaid Serv, Ctr Beneficiary Choices, Baltimore, MD USA. NIH, NIDDKD, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Nephrol, Winston Salem, NC 27109 USA. RP McClellan, WM (reprint author), Georgia Med Care Fdn, 1455 Lincoln Pkwy,Suite 800, Atlanta, GA 30329 USA. EM bmcclellan@gmcf.org NR 24 TC 33 Z9 33 U1 2 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2004 VL 27 IS 9 BP 2198 EP 2203 DI 10.2337/diacare.27.9.2198 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 851JP UT WOS:000223681700016 PM 15333484 ER PT J AU Tulloch-Reid, MK Hanson, RL Saremi, A Looker, HC Williams, DE Krakoff, J Knowler, WC AF Tulloch-Reid, MK Hanson, RL Saremi, A Looker, HC Williams, DE Krakoff, J Knowler, WC TI Hematocrit and the incidence of type 2 diabetes in the pima Indians SO DIABETES CARE LA English DT Article ID MELLITUS; INSULIN; RISK; MEN C1 NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Knowler, WC (reprint author), NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM knowler@nih.gov RI Tulloch-Reid, Marshall/E-4383-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 13 TC 12 Z9 13 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2004 VL 27 IS 9 BP 2245 EP 2246 DI 10.2337/diacare.27.9.2245 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 851JP UT WOS:000223681700025 PM 15333493 ER PT J AU Simmonds, AC Reilly, CA Baldwin, RM Ghanayem, BI Lanza, DL Yost, GS Collins, KS Forkert, PG AF Simmonds, AC Reilly, CA Baldwin, RM Ghanayem, BI Lanza, DL Yost, GS Collins, KS Forkert, PG TI Bioactivation of 1,1-dichloroethylene to its epoxide by CYP2E1 and CYP2F enzymes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CDNA-DIRECTED EXPRESSION; VINYLIDENE-CHLORIDE; MURINE LUNG; GLUTATHIONE CONJUGATE; METABOLIC-ACTIVATION; LIVER-MICROSOMES; REACTIVE EPOXIDE; MOUSE LUNG; NAPHTHALENE; CYTOCHROME-P-450 AB 1,1-Dichloroethylene (DCE) exposure to mice elicits lung toxicity that selectively targets bronchiolar Clara cells. The toxicity is mediated by DCE metabolites formed via cytochrome P450 metabolism. The primary metabolites formed are DCE epoxide, 2,2-dichloroacetaldehyde, and 2-chloroacetyl chloride. The major metabolite detected is 2-S-glutathionyl acetate [C], a putative conjugate of DCE epoxide with glutathione. In this investigation, studies were undertaken to test the hypothesis that CYP2E1 and CYP2F2 are involved in bioactivation of DCE to the epoxide in murine lung. We have developed a method using liquid chromatography/mass spectrometry (LC/MS) to evaluate the kinetics of the rates of production of conjugate [C] by recombinant CYP2E1 and CYP2F enzymes and lung microsomes. Concentration-dependent formation of conjugate [C] was found in incubations of DCE with recombinant CYP2E1 and CYP2F enzymes and lung microsomes from CD-1, wild-type (mixed 129/Sv and C57BL), and CYP2E1-null mice. Recombinant rat CYP2E1 exhibited greater affinity and catalytic efficiency for DCE metabolism than did recombinant human CYP2E1, mouse CYP2F2, goat CYP2F3 or rat CYP2F4. In the lung microsomal incubations, the rates of conjugate [ C] production were higher in CD-1 mice than in either wild-type or CYP2E1-null mice; the level of [ C] in CYP2E1-null mice was about 66% of that in wild-type mice. These results demonstrated that LC/MS analysis is a suitable method for detection and quantitation of conjugate [C], and that CYP2E1 and CYP2F2 catalyze the bioactivation of DCE to the epoxide in murine lung. The results also demonstrated that CYP2E1 is the high-affinity enzyme involved in DCE bioactivation. C1 Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada. Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. RP Forkert, PG (reprint author), Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada. EM forkertp@post.queensu.ca RI Baldwin, Mike/E-8601-2015 OI Baldwin, Mike/0000-0002-6236-5000 FU NHLBI NIH HHS [HL60143, R01 HL060143, R01 HL013645, HL13645]; NIEHS NIH HHS [ES 08408] NR 39 TC 25 Z9 28 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 2004 VL 32 IS 9 BP 1032 EP 1039 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 847EM UT WOS:000223375500021 PM 15319346 ER PT J AU Brieba, LG Eichman, BF Kokoska, RJ Doublie, S Kunkel, TA Ellenberger, T AF Brieba, LG Eichman, BF Kokoska, RJ Doublie, S Kunkel, TA Ellenberger, T TI Structural basis for the dual coding potential of 8-oxoguanosine by a high-fidelity DNA polymerase SO EMBO JOURNAL LA English DT Article DE DNA damage; DNA polymerase; protein crystallography; replication fidelity ID STATE KINETIC-ANALYSIS; REPLICATION FIDELITY; STEADY-STATE; NUCLEOTIDE INSERTION; CRYSTAL-STRUCTURE; MAGNETIC-RESONANCE; ELECTRON-DENSITY; ACTIVE-SITE; MECHANISM; 8-OXO-7,8-DIHYDROGUANINE AB Accurate DNA replication involves polymerases with high nucleotide selectivity and proofreading activity. We show here why both fidelity mechanisms fail when normally accurate T7 DNA polymerase bypasses the common oxidative lesion 8-oxo-7, 8-dihydro-2-deoxyguanosine (8oG). The crystal structure of the polymerase with 8oG templating dC insertion shows that the 08 oxygen is tolerated by strong kinking of the DNA template. A model of a corresponding structure with dATP predicts steric and electrostatic clashes that would reduce but not eliminate insertion of dA. The structure of a postinsertional complex shows 8oG(syn) . dA (anti) in a Hoogsteen-like base pair at the 3' terminus, and polymerase interactions with the minor groove surface of the mismatch that mimic those with undamaged, matched base pairs. This explains why translesion synthesis is permitted without proofreading of an 8oG . dA mismatch, thus providing insight into the high mutagenic potential of 8oG. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Ellenberger, T (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM tome@hms.harvard.edu RI Bell, Tiffany/F-4403-2010; Brieba, Luis/I-8447-2016; OI Brieba, Luis/0000-0002-6073-5207; Eichman, Brandt/0000-0002-0965-2297; Doublie, Sylvie/0000-0002-6294-5304 FU NIGMS NIH HHS [F32 GM065714-02, F32 GM065714, GM55390, R01 GM055390] NR 50 TC 136 Z9 136 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 2004 VL 23 IS 17 BP 3452 EP 3461 DI 10.1038/sj.emboj.7600354 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852CM UT WOS:000223732800002 PM 15297882 ER PT J AU Eisenhofer, G Bornstein, SR Brouwers, FM Cheung, NKV Dahia, PL de Krijger, RR Giordano, TJ Greene, LA Goldstein, DS Lehnert, H Manger, WM Maris, JM Neumann, HPH Pacak, K Shulkin, BL Smith, DI Tischler, AS Young, WF AF Eisenhofer, G Bornstein, SR Brouwers, FM Cheung, NKV Dahia, PL de Krijger, RR Giordano, TJ Greene, LA Goldstein, DS Lehnert, H Manger, WM Maris, JM Neumann, HPH Pacak, K Shulkin, BL Smith, DI Tischler, AS Young, WF TI Malignant pheochromocytoma: current status and initiatives for future progress SO ENDOCRINE-RELATED CANCER LA English DT Review ID NEUROFIBROMATOSIS KNOCKOUT MICE; METASTATIC PHEOCHROMOCYTOMA; SPORADIC PHEOCHROMOCYTOMAS; ADRENAL PHEOCHROMOCYTOMA; REFRACTORY NEUROBLASTOMA; OCTREOTIDE SCINTIGRAPHY; NEUROENDOCRINE TUMORS; TARGETED RADIOTHERAPY; INCREASED EXPRESSION; CELL-LINES AB Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th-18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multicenter studies. C1 NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Erasmus Med Ctr, Rotterdam, Netherlands. Univ Michigan, Ann Arbor, MI 48109 USA. Columbia Univ, New York, NY USA. Univ Magdeburg, Sch Med, D-39106 Magdeburg, Germany. Natl Hypertens Assoc, New York, NY USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Med Univ Klin, Freiburg, Germany. Mayo Clin, Rochester, MN USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Eisenhofer, G (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov OI Giordano, Thomas/0000-0003-0641-8873 NR 91 TC 191 Z9 202 U1 0 U2 4 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2004 VL 11 IS 3 BP 423 EP 436 DI 10.1677/erc.1.00829 PG 14 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 860KR UT WOS:000224343000003 PM 15369446 ER PT J AU Chen, M Haluzik, M Wolf, NJ Lorenzo, J Dietz, KR Reitman, ML Weinstein, LS AF Chen, M Haluzik, M Wolf, NJ Lorenzo, J Dietz, KR Reitman, ML Weinstein, LS TI Increased insulin sensitivity in paternal Gnas knockout mice is associated with increased lipid clearance SO ENDOCRINOLOGY LA English DT Article ID PROTEIN ALPHA-SUBUNIT; STIMULATORY G-PROTEIN; ACTIVATED RECEPTOR-ALPHA; FATTY-ACID OXIDATION; ALBRIGHT HEREDITARY OSTEODYSTROPHY; TISSUE RESISTIN EXPRESSION; ADIPOSE-TISSUE; GLUCOSE-TRANSPORT; GENE-EXPRESSION; CARNITINE PALMITOYLTRANSFERASE AB The G protein alpha-subunit G(s)alpha is required for hormone-stimulated cAMP generation. The G(s)alpha gene Gnas is a complex gene with multiple imprinted gene products. Mice with heterozygous disruption of the Gnas paternal allele (+/p-) are partially G(s)alpha deficient and totally deficient in XLalphas, a neuroendocrine-specific G(s)alpha isoform. that is expressed only from the paternal Gnas allele. We previously showed that these mice are hypermetabolic and lean and have increased insulin sensitivity. We now performed hyperinsulinemic-euglycemic clamp studies, which confirmed the markedly increased whole body insulin sensitivity in +/p- mice. +/p- mice had 1.4-, 7- and 3.8-fold increases in insulin-stimulated glucose uptake in muscle and white and brown adipose tissue, respectively, and markedly suppressed endogenous glucose production from the liver. This was associated with increased phosphorylation of insulin receptor and a downstream effector (Akt kinase) in both liver and muscle in response to insulin. Triglycerides cleared more rapidly in +/p- mice after a bolus administered by gavage. This was associated with decreased liver and muscle triglyceride content and increased muscle acyl-CoA oxidase mRNA expression. Resistin and adiponectin were overexpressed in white adipose tissue of +/p- mice, although there was no difference in serum adiponectin levels. The lean phenotype and increased insulin sensitivity observed in +/p- mice is likely a consequence of increased lipid oxidation in muscle and possibly other tissues. Further studies will clarify whether XLalphas deficiency is responsible for these effects and if so, the mechanism by which XLalphas deficiency leads to this metabolic phenotype. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov RI Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; Weinstein, Lee/0000-0002-1899-5152; Dietz, Kelly/0000-0003-3670-2912 NR 58 TC 38 Z9 39 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2004 VL 145 IS 9 BP 4094 EP 4102 DI 10.1210/en.2004-0038 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847NG UT WOS:000223401600016 PM 15166122 ER PT J AU Nishi, H Nakada, T Hokamura, M Osakabe, Y Itokazu, O Huang, LE Isaka, K AF Nishi, H Nakada, T Hokamura, M Osakabe, Y Itokazu, O Huang, LE Isaka, K TI Hypoxia-inducible factor-1 transactivates transforming growth factor-beta 3 in trophoblast SO ENDOCRINOLOGY LA English DT Article ID C-MYC; EXPRESSION; TRANSCRIPTION; OXYGEN; ACTIVATION; DIFFERENTIATION; PREECLAMPSIA; ENDOMETRIAL; TGF-BETA(3); PREGNANCIES AB Hypoxia occurs during the development of placenta in the first trimester and is implicated in trophoblast differentiation. Intervillous blood flow increases after 10 wk of gestation and results in exposure of trophoblast cells to oxygen. Before this time, low oxygen appears to prevent trophoblast differentiation toward an invasive phenotype. The oxygen-regulated early events of trophoblast differentiation are mediated by TGF-beta3. TGF-beta3 plays a vital role in trophoblast differentiation, and its overexpression can be found in preeclamptic placenta. We sought to determine the mechanism of TGF-beta3 expression through hypoxia-inducible factor (HIF)-1. We show that HIF-1alpha and TGF-beta3 are overexpressed in preeclamptic placenta. Hypoxia not only transactivates the TGF-beta3 promoter activity but also enhances endogenous TGF-beta3 expression. Using the TGF-beta3 promoter deletion mutants, we show that the region between -90 and -60, which contains a putative HIF-1 consensus motif, is crucial for HIF-1-mediated transactivation. Electrophoretic mobility shift assays show that HIF-1 binds to the oligonucleotide containing the HIF-1 motif. Also, introduction of an antisense oligonucleotide for HIF-1 diminishes TGF-beta3 expression during hypoxia, indicating that the up-regulation of TGF-beta3 by hypoxia is mediated through HIF-1. Our results provide evidence that regulation of TGF-beta3 promoter activity by HIF-1 represents a mechanism for trophoblast differentiation during hypoxia. C1 Tokyo Med Univ, Dept Obstet & Gynecol, Shinjuku Ku, Tokyo 1600023, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Nishi, H (reprint author), Tokyo Med Univ, Dept Obstet & Gynecol, Shinjuku Ku, 6-7-1 Nishishinjuku, Tokyo 1600023, Japan. EM nishih@tokyo-med.ac.jp NR 28 TC 58 Z9 64 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2004 VL 145 IS 9 BP 4113 EP 4118 DI 10.1210/en.2003-1639 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847NG UT WOS:000223401600018 PM 15155569 ER PT J AU Yubero, P Hondares, E Carmona, MC Rossell, M Gonzalez, FJ Iglesias, R Giralt, M Villarroya, F AF Yubero, P Hondares, E Carmona, MC Rossell, M Gonzalez, FJ Iglesias, R Giralt, M Villarroya, F TI The developmental regulation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression in the liver is partially dissociated from the control of gluconeogenesis and lipid catabolism SO ENDOCRINOLOGY LA English DT Article ID GENE-EXPRESSION; MITOCHONDRIAL BIOGENESIS; HEPATIC GLUCONEOGENESIS; TRANSCRIPTIONAL COACTIVATOR; POSTNATAL-DEVELOPMENT; FATTY-ACIDS; RAT-LIVER; ERR-ALPHA; PGC-1; NUCLEAR AB The developmental regulation of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) gene expression was studied in mice and compared with that of marker genes of liver energy metabolism. The PGC-1alpha gene was highly expressed in fetal liver compared with that in adults and remained high in neonatal liver. The regulation of PGC-1alpha gene expression during the fetal and early neonatal periods was dissociated from that of gluconeogenic genes, i.e. the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) genes. Only under the effects of starvation was PGC-1alpha gene expression induced in parallel to phosphoenolpyruvate carboxykinase and G6Pase mRNAs during the perinatal period. Furthermore, the PGC-1alpha gene was not regulated as part of the developmental program of gene expression associated with the maturation of hepatic gluconeogenesis, as revealed by the impaired PEPCK and G6Pase gene expression but unaltered PGC-1alpha mRNA levels in CCAAT/enhancer-binding protein-alpha-null fetus and neonates. Regulation of the PGC-1alpha gene and that of mitochondrial 3-hydroxy-3-methyl-glutaryl-coenzyme A synthase, acyl-coenzyme A oxidase, and long-chain acyl-coenzyme dehydrogenase, marker genes of lipid catabolism, were dissociated in fetuses and neonates. The expression of lipid catabolism genes was down-regulated in fasted neonates, whereas PGC-1alpha was oppositely regulated. The independent regulation of PGC-1alpha and lipid catabolism genes was also found in peroxisome proliferator-activated receptor-alpha-null neonates, in which PGC-1alpha mRNA levels were unaffected whereas gene expression for 3-hydroxy-3-methyl-glutaryl-coenzyme A synthase and acyl-coenzyme A oxidase was impaired. Thus, regulation of the PGC-1alpha gene is partially dissociated from the patterns of regulation of hepatic genes encoding enzymes involved in gluconeogenesis and lipid catabolism during fetal ontogeny and in response to the initiation of lactation. C1 Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Villarroya, F (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Avda Diagonal 645, E-08028 Barcelona, Spain. EM gombau@porthos.bio.ub.es RI Giralt, Marta/A-4756-2013; Villarroya, Francesc/K-4357-2014; OI Giralt, Marta/0000-0001-7968-4190; Villarroya, Francesc/0000-0003-1266-9142 NR 32 TC 18 Z9 19 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2004 VL 145 IS 9 BP 4268 EP 4277 DI 10.1210/en.2004-0099 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847NG UT WOS:000223401600035 PM 15178647 ER PT J AU Yoshida, A Hisatome, I Taniguchi, S Sasaki, N Yamamoto, Y Miake, J Fukui, H Shimizu, H Okamura, T Okura, T Igawa, O Shigemasa, C Green, ED Kohn, LD Suzuki, K AF Yoshida, A Hisatome, I Taniguchi, S Sasaki, N Yamamoto, Y Miake, J Fukui, H Shimizu, H Okamura, T Okura, T Igawa, O Shigemasa, C Green, ED Kohn, LD Suzuki, K TI Mechanism of iodide/chloride exchange by pendrin SO ENDOCRINOLOGY LA English DT Article ID CARDIAC NA+-CA2+ EXCHANGER; NA/K PUMP CURRENT; THYROID-CELLS; FRTL-5 CELLS; CULTURED PORCINE; IODIDE EFFLUX; APICAL PORTER; GENE PDS; TRANSPORT; DEPENDENCE AB We performed an electrophysiological study to investigate ion transport of pendrin and thereby understand the pathogenesis of Pendred syndrome. Using pendrin-transfected COS-7 cells, we could show that pendrin transports both iodide and chloride measured as voltage-dependent inward and outward membrane currents. Chloride in the culture medium, [CI-](o), was efficiently exchanged with cytoplasmic iodide, [CI-](o), under physiological concentrations, indicating that pendrin is important for chloride uptake and iodide efflux. Although exchange of iodide in the medium, [I-](o), with cytoplasmic chloride, [Cl-](i), was observed, a significantly high concentration of iodide (10 mm) was required. In addition, either iodide or chloride was required on both sides of the cell membrane for the anion exchange activity of pendrin, indicating that iodide and chloride activate the exchange activity of pendrin while they are transported. The present study further supports that pendrin is responsible for the iodide efflux in thyroid cells where intracellular iodide concentration is high and that the general function of pendrin in other tissues is to transport chloride through exchange with other anions. C1 Tottori Univ, Fac Med, Dept Internal Med 1, Tottori 6838504, Japan. Tottori Univ, Grad Sch Med, Dept Genet & Regenerat Med, Div Regenerat Med & Therapeut, Tottori 6838504, Japan. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Ohio Univ, Sch Osteopath Med, Athens, OH 45701 USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Natl Inst Infect Dis, Leprosy Res Ctr, Dept Microbiol, Tokyo 1890002, Japan. RP Yoshida, A (reprint author), Tottori Univ, Fac Med, Dept Internal Med 1, 36-1 Nishimachi, Tottori 6838504, Japan. EM ayoshida@bronze.ocn.ne.jp NR 28 TC 51 Z9 53 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2004 VL 145 IS 9 BP 4301 EP 4308 DI 10.1210/en.2004-0048 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 847NG UT WOS:000223401600039 PM 15155570 ER PT J AU Kalra, P Srinivasan, S Ivey, S Greenlund, K AF Kalra, P Srinivasan, S Ivey, S Greenlund, K TI Knowledge and practice: The risk of cardiovascular disease among Asian Indians. Results from focus groups conducted in Asian Indian communities in northern California SO ETHNICITY & DISEASE LA English DT Article DE Asian Indians; cardiovascular risk; focus groups; interventions; stress ID CORONARY-HEART-DISEASE; ETHNIC-GROUPS; INSULIN-RESISTANCE; EUROPEAN ORIGIN; MEN; HYPERTENSION; AMERICANS; MORTALITY; CANADIANS; CHINESE AB Objective: The focus groups were utilized to gather information on the perceptions of cardiovascular risk within the Asian Indian community, and to identify opportunities to design health promotion and intervention programs for Asian Indian communities. Design: Qualitative methods were utilized to obtain perceptions of cardiovascular risk within 3 Asian Indian communities. Eight focus groups were conducted in either English or Punjabi. Setting: These focus groups were conducted as part of a 3-year community-based participatory research project examining cardiovascular risk factors among the Asian Indian population in Northern California. Participants: Focus group participants were selected through referrals from community-based organizations, postings in local community centers, and businesses. Fifty-seven men and women were recruited using snowball sampling. Results: Six themes emerged from the focus groups: knowledge of cardiovascular disease, health and cultural concerns regarding diet, physical activity levels, stress as a factor for cardiovascular disease, acculturation concerns, and cardiovascular prevention ideas. Conclusions: The use of focus groups was an effective method for gathering information on perceptions of cardiovascular risk, and collecting information on risk behaviors within these Asian Indian communities. In this study, we found that psychosocial and cultural factors, especially cultural issues concerning stress and acculturation, surfaced as key elements across all 8 focus groups. C1 VA Palo Alto Healthcare Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. Stanford Univ, Sch Med, Menlo Pk, CA USA. Univ Calif Berkeley, Sch Publ Hlth, Ctr Family & Community Hlth, Berkeley, CA USA. NIEHS, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Kalra, P (reprint author), VA Palo Alto Healthcare Syst, Ctr Hlth Care Evaluat, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM Preety.Kalra@med.va.gov FU ODCDC CDC HHS [U48/CCU909706-08] NR 36 TC 21 Z9 21 U1 0 U2 8 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2004 VL 14 IS 4 BP 497 EP 504 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 866GK UT WOS:000224761800006 PM 15724768 ER PT J AU Sundstrom, J Evans, JC Benjamin, EJ Levy, D Larson, MG Sawyer, DB Siwik, DA Colucci, WS Wilson, PWF Vasan, RS AF Sundstrom, J Evans, JC Benjamin, EJ Levy, D Larson, MG Sawyer, DB Siwik, DA Colucci, WS Wilson, PWF Vasan, RS TI Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart study SO EUROPEAN HEART JOURNAL LA English DT Article DE heart failure; left ventricular hypertrophy; metalloproteinases; remodelling; echocardiography ID LEFT-VENTRICULAR HYPERTROPHY; MATRIX-METALLOPROTEINASE INHIBITION; FAILING HUMAN HEART; TISSUE INHIBITOR; ESSENTIAL-HYPERTENSION; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; SERUM; DEGRADATION; REDUCTION AB Aims Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key regulator of extracellular matrix degradation. We examined relations of plasma total TIMP-1 to cardiovascular risk factors and echocardiographic Left ventricular (LV) structure and function in a community-based sample. Methods and results We studied 1069 Framingham Heart Study participants (mean age 56 years, 58% women) free of heart failure and previous myocardial infarction. Plasma TIMP-1 was higher in men compared with women, and increased with age, body mass index and total/HDL-cholesterol ratio, but decreased with alcohol intake. plasma TIMP-1 was also directly related to smoking, diabetes and use of anti-hypertensive treatment. Adjusting for age, sex and height, plasma TIMP-1 was positively associated with LV mass, watt thickness, relative watt thickness, end-systolic diameter, and left atrial diameter and the risk of having increased LV end-diastolic diameter or increased wall thickness, and negatively correlated with fractional shortening. Additional adjustment for clinical covariates attenuated the relations of plasma TIMP-1 to most echocardiographic measures. Conclusions In our cross-sectional investigation, plasma total TIMP-1 was related to major cardiovascular risk factors and to indices of LV hypertrophy and systolic dysfunction. This raises the possibility that cardiovascular risk factors may influence cardiovascular remodelling via extracellular matrix degradation, which may be reflected in plasma TIMP-1 levels. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 Boston Univ, Sch Med, Framingham Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Myocardial Biol Unit, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Boston Univ, Sch Med, Framingham Study, 73 Mt Wayte Ave Suite 2, Framingham, MA USA. EM vasan@bu.edu RI Sundstrom, Johan/A-6286-2009; OI Sundstrom, Johan/0000-0003-2247-8454; Siwik, Deborah/0000-0002-7166-327X; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1K24HL04334, 1R01HL67288-01, N01-HC-25195] NR 30 TC 88 Z9 91 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2004 VL 25 IS 17 BP 1509 EP 1516 DI 10.1016/j.ehj.2004.05.029 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 856JA UT WOS:000224040300010 PM 15342170 ER PT J AU Humphreys, SR Mantel, N Goldin, A AF Humphreys, SR Mantel, N Goldin, A TI Chemotherapy and surgery of spontaneous tumors of mice SO EUROPEAN JOURNAL OF CANCER LA English DT Article ID PROPHYLACTIC TREATMENT; CANCER; LEUKEMIA; INTERRELATIONSHIPS; ADJUVANT; AGENTS AB Daily treatment with 3'5'dichloromethotrexate, 6-mercaptopurine or Cytoxan retarded the growth of spontaneous mammary tumors in C3H/HeN mice. However, with possibly a few exceptions, no increases in survival time of the mice resulted. Surgical excision of the spontaneous tumors plus weekly treatment with Cytoxan did not result in any increases in survival time of the mice. The combination, nevertheless, appeared to be more effective than surgery alone or Cytoxan alone in controlling tumor growth. It increased the incidence of cases in which no tumor growth, whether excised tumor regrowth or new tumor formation, was evident at the time of death. In addition, there was a decrease in the number of mice that died with multiple tumors. However, with the combination of surgery and chemotherapy, new tumors arose despite the continuation of therapy. The data appear to lend support to the concept that reduction in tumor mass may augment therapeutic response. (C) 1966 Elsevier Ltd. All rights reserved. C1 NCI, Drug Evaluat Branch, Natl Serv Ctr, Bethesda, MD 20892 USA. NCI, Biometry Branch, Bethesda, MD 20892 USA. RP Humphreys, SR (reprint author), NCI, Drug Evaluat Branch, Natl Serv Ctr, Bethesda, MD 20892 USA. NR 29 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2004 VL 40 IS 13 BP 1968 EP 1973 DI 10.1016/j.ejca.2004.05.014 PG 6 WC Oncology SC Oncology GA 856BS UT WOS:000224019200010 PM 15315805 ER PT J AU Dreher, JC Koch, P Kohn, P Meyer-Lindenberg, AAS Weinberger, D Berman, KF AF Dreher, J. C. Koch, P. Kohn, P. Meyer-Lindenberg, A. A. S. Weinberger, D. Berman, K. F. TI Respective contributions of aging and performance to brain activation during working memory SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 CNRS, Inst Cognit Sci, Lyon, France. NIMH, NIH, CBDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2004 VL 11 SU 2 BP 28 EP 28 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GV UT WOS:000202992100088 ER PT J AU Sohn, YH Hallett, M AF Sohn, Y. H. Hallett, M. TI Corticospinal disinhibition during dual action SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Yonsei Univ, Med Ctr, Dept Neurol, Seoul 120749, South Korea. NIH, Human Motor Control Sect, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2004 VL 11 SU 2 BP 158 EP 158 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GV UT WOS:000202992100571 ER PT J AU Platonov, FA Vladimirtsev, VA Osakovskiy, VL Goldfarb, LG Gogolev, MP AF Platonov, F. A. Vladimirtsev, V. A. Osakovskiy, V. L. Goldfarb, L. G. Gogolev, M. P. TI Phenotypic variability of spinocerebellar ataxia type 1 SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Med Res Ctr, Yakutsk, Russia. Inst Hlth Sakha Republ, Yakutsk, Russia. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2004 VL 11 SU 2 BP 298 EP 298 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GV UT WOS:000202992101355 ER PT J AU Goldfarb, L AF Goldfarb, L. TI Genetics of desmin myopathies SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2004 VL 11 SU 2 BP 344 EP 344 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GV UT WOS:000202992101496 ER PT J AU Valente, EM Abou-Sleiman, PM Caputo, V Muqit, MMK Harvey, K Gispert, S Zeeshani, A Del Turco, D Bentivoglio, AR Healy, DG Albanese, A Nussbaum, R Gonzalez-Maldonado, R Deller, T Salvi, S Cortelli, P Gilks, WP Latchman, DS Harvey, RJ Dallapiccola, B Auburger, G Wood, NW AF Valente, E. M. Abou-Sleiman, P. M. Caputo, V. Muqit, M. M. K. Harvey, K. Gispert, S. Zeeshani, A. Del Turco, D. Bentivoglio, A. R. Healy, D. G. Albanese, A. Nussbaum, R. Gonzalez-Maldonado, R. Deller, T. Salvi, S. Cortelli, P. Gilks, W. P. Latchman, D. S. Harvey, R. J. Dallapiccola, B. Auburger, G. Wood, N. W. TI Identification of PINK1, the first mitochondrial gene causing Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. Mendel Inst Med Genet & Twin Res, IRCCS, CSS, Rome, Italy. Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy. Inst Child Hlth, Med Mol Biol Unit, London, England. Univ London, Sch Pharm, Dept Pharmacol, London WC1N 1AX, England. Inst Expt Neurobiol, London, England. Univ Frankfurt, Inst Clin Neuroanat, Frankfurt, Germany. Catholic Univ, Inst Neurol, Rome, Italy. Natl Neurol Inst Carlo Besta, Milan, Italy. NHGRI, NIH, Bethesda, MD 20892 USA. Hosp Univ San Cecilio, Dept Neurol, Granada, Spain. Univ Modena & Reggio Emilia, Dept Neurosci, Modena, Italy. Univ London Birkbeck Coll, London WC1E 7HX, England. Univ Frankfurt, Neurol Clin, Sect Mol Neurogenet, Frankfurt, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2004 VL 11 SU 2 BP 366 EP 367 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V44GV UT WOS:000202992101559 ER PT J AU Adcock, KH Brown, DJ Shearer, MC Shewan, D Schachner, M Smith, GM Geller, HM Fawcett, JW AF Adcock, KH Brown, DJ Shearer, MC Shewan, D Schachner, M Smith, GM Geller, HM Fawcett, JW TI Axon behaviour at Schwann cell astrocyte boundaries: manipulation of axon signalling pathways and the neural adhesion molecule L1 can enable axons to cross SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE axon guidance; axon regeneration; cAMP; FGF-2; L1; NGF; NT-3; rat; Rho ID ADULT SPINAL-CORD; ROOT ENTRY ZONE; CENTRAL-NERVOUS-SYSTEM; NEURITE OUTGROWTH; FUNCTIONAL REGENERATION; SENSORY AFFERENTS; SCIATIC-NERVE; CYCLIC-AMP; N-CAM; GROWTH AB Axon regeneration in vivo is blocked at boundaries between Schwann cells and astrocytes, such as occur at the dorsal root entry zone and around peripheral nerve or Schwann cell grafts. We have created a tissue culture model of these boundaries in Schwann cell - astrocyte monolayer co-cultures. Axon behaviour resembles that in vivo, with axons showing a strong preference for Schwann cells over astrocytes. At boundaries between the two cell types, axons growing on astrocytes cross readily onto Schwann cells, but only 15% of axons growing on Schwann cells are able to cross onto astrocytes. Treatment with chondroitinase or chlorate to reduce inhibition by proteoglycans did not change this behaviour. The neural adhesion molecule L1 is present on Schwann cells and not astrocytes, and manipulation of L1 by application of an antibody, L1-Fc in solution, or adenoviral transduction of L1 into astrocytes increased the proportion of axons able to cross onto astrocytes to 40-50%. Elevating cAMP levels increased crossing from Schwann cells onto astrocytes in live and fixed cultures, and had a co-operative effect with NT-3 but not with NGF. Inactivation of Rho with a cell-permeant form of C3 exoenzyme also increased crossing from Schwann cells to astrocytes. Our experiments indicate that the preference of axons for Schwann cells is largely mediated by the presence of L1 on Schwann cells but not astrocytes, and that manipulation of growth cone signalling pathways can allow axons to disregard boundaries between the two cell types. C1 Univ Cambridge, Ctr Brain Repair, Cambridge CB2 2PZ, England. Univ Cambridge, Dept Physiol, Cambridge CB2 2PZ, England. Univ Hamburg, Zentrum Mol Neurobiol, D-20246 Hamburg, Germany. Univ Kentucky, Albert B Chandler Med Ctr, Spinal Cord & Brain Injury Res Ctr, Dept Physiol, Lexington, KY 40536 USA. NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Fawcett, JW (reprint author), Univ Cambridge, Ctr Brain Repair, Robinson Way, Cambridge CB2 2PZ, England. EM jf108@cam.ac.uk OI Geller, Herbert/0000-0002-7048-6144; Fawcett, James/0000-0002-7990-4568 NR 57 TC 41 Z9 41 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2004 VL 20 IS 6 BP 1425 EP 1435 DI 10.1111/j.1460-9568.2004.03573.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 852GV UT WOS:000223744600001 PM 15355310 ER PT J AU Bowen, WD AF Bowen, WD TI Sigma receptors as novel target structures for cancer chemotherapeutics SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 1st International Meeting on Neurobiology of the Skin CY FEB 13-15, 2004 CL Munster, GERMANY C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD SEP PY 2004 VL 13 IS 9 BP 570 EP 570 PG 1 WC Dermatology SC Dermatology GA 850DG UT WOS:000223590800020 ER PT J AU Butts, CL Sternberg, EM AF Butts, CL Sternberg, EM TI Interaction between the immune and neuroendocrine system - focus on dendritic cells and skin SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 1st International Meeting on Neurobiology of the Skin CY FEB 13-15, 2004 CL Munster, GERMANY C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD SEP PY 2004 VL 13 IS 9 BP 574 EP 574 PG 1 WC Dermatology SC Dermatology GA 850DG UT WOS:000223590800034 ER PT J AU Hejtmancik, JF Wingfield, PT Sergeev, YV AF Hejtmancik, JF Wingfield, PT Sergeev, YV TI beta-Crystallin association SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE crystallin; lens; association; beta-crystallin ID X-RAY-ANALYSIS; EYE-LENS; GAMMA-CRYSTALLIN; DOMAIN INTERACTIONS; CATARACT; GENE; PROTEINS; MUTATION; BETA-A3-CRYSTALLIN; EVOLUTION AB beta-Crystallins are major protein constituents of the mammalian lens, where their stability and association into higher order complexes are critical for lens clarity and refraction. Dimerization is an initial step in formation of beta-crystallin complexes. beta-crystallin association into dimers is energetically highly favoured, but rapidly reversible under physiological conditions. beta-Crystallin dimers can exchange monomers, probably through a transient and energetically unfavoured monomer intermediate state. As predicted by molecular modelling, the fraction of beta-Crystallin present as dimers increases with increasing temperature, implying that beta-crystallin association is entropically driven. (C) 2004 Elsevier Ltd. All rights reserved. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bldg 10,Room 10B10,10 CTR DR MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov NR 42 TC 32 Z9 33 U1 1 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 2004 VL 79 IS 3 BP 377 EP 383 DI 10.1016/j.exer.2004.06.011 PG 7 WC Ophthalmology SC Ophthalmology GA 855KZ UT WOS:000223973400010 PM 15336500 ER PT J AU Poulain, M Pes, GM Grasland, C Carru, C Ferrucci, L Baggio, G Franceschi, C Deiana, L AF Poulain, M Pes, GM Grasland, C Carru, C Ferrucci, L Baggio, G Franceschi, C Deiana, L TI Identification of a geographic area characterized by extreme longevity in the Sardinia island: the AKEA study SO EXPERIMENTAL GERONTOLOGY LA English DT Article AB High prevalence and low female/male ratio for validated centenarians are observed in Sardinia and these findings appear to be thus far unique to this island. Moreover a specific region on the island is characterized by exceptional male longevity. We calculated the extreme longevity index (ELI), defined as the percentage of persons born in Sardinia between 1880 and 1900, who became centenarians. A gaussian smoothing method was used in order to identify the so-called 'Blue Zone', where longevity is concentrated in the central-eastern part of the island and covers all the mountainous areas of central Sardinia. The estimated life expectancy in the 'Blue Zone' is longer than in the remaining territory of the island especially for men and the male to female ratio among centenarians born in this area is 1.35 compared to 2.43 in the rest of Sardinia. The specific mechanism by which persons living in this territory were more likely to reach extreme longevity remains unknown but it is interesting to note that most of the 'longevity hot spots' identified in various regions of the world over the years have been located in mountainous geographical areas even if none of these longevity regions have been fully validated. An alternative and interesting hypothesis is that the high rate of inbreeding determined by frequent marriages between consanguineous individuals and low immigration rates have progressively decreased the variability of the genetic pool and facilitated the emergence of genetic characteristics that protect individuals from diseases that are major causes of mortality particularly in older individuals. Given the exceptionally high prevalence of male centenarians in the 'Blue Zone', it is reasonable to assume that either the environmental characteristics or the genetic factors, or both, exert their favorable effect more strongly in men than in women. Thus, the mechanism involved may be modulated by the hormonal milieu, or may be associated with genes located in the sex chromosomes. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Catholique Louvain, Grp Etudes Demog Appl, FNRS, GeDAP, B-1348 Louvain, Belgium. Univ Sassari, Inst Clin Biochem, I-07100 Sassari, Italy. Univ Paris 07, UMR Geog Cites, Paris, France. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. Univ Padua, Azienda Osped, Internal Med Unit, Sassari, Italy. Univ Sassari, I-07100 Sassari, Italy. Univ Bologna, Dept Expt Pathol, Ancona, Italy. Univ Bologna, CIG, Ancona, Italy. INRCA, Dept Gerontol Res, Ancona, Italy. RP Poulain, M (reprint author), UCL, GeDAP, Bd Devreux 6, B-6000 Charleroi, Belgium. EM poulain@sped.ucl.ac.be OI Carru, Ciriaco/0000-0002-6985-4907; Pes, Giovanni Mario/0000-0003-3265-2823 FU NCI NIH HHS [03-SC-NIH-1027] NR 13 TC 74 Z9 77 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP PY 2004 VL 39 IS 9 BP 1423 EP 1429 DI 10.1016/j.exger.2004.06.016 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 857UM UT WOS:000224144000019 PM 15489066 ER PT J AU Zeng, WH Kajigaya, S Chen, GB Risitano, AM Nunez, O Young, NS AF Zeng, WH Kajigaya, S Chen, GB Risitano, AM Nunez, O Young, NS TI Transcript profile of CD4(+) and CD8(+) T cells from the bone marrow of acquired aplastic anemia patients SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; DIFFERENTIAL GENE-EXPRESSION; SELECTIVE EXPRESSION; TH2 CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; MICROBIAL LIPOPROTEINS; OLIGONUCLEOTIDE ARRAYS; BACTERIAL LIPOPROTEINS; INTERFERON-GAMMA AB Objective. Immune-mediated destruction of hematopoietic stem and progenitor cells is pathophysiologic in most cases of aplastic anemia (AA). We have successfully determined the gene expression profile of the marrow CD34(+) target cells in AA. T cells producing IFN-gamma and TNF-alpha have been implicated in hematopoietic destruction in AA. We sought to characterize T cells as immune mediators using the microarray approach. Materials and Methods. We applied Affymetrix GeneChip techniques to determine the detailed profile of mRNA expression of CD4(+) and CD8(+) cells from the BM of newly diagnosed AA patients and healthy volunteers. For validation, we confirmed our microarray results using quantitative real-time PCR. Results. Compared to healthy controls, there were 178 and 183 differentially expressed genes in patients' CD4(+) cells and CD8(+) T cells, respectively; activities of 22 selected genes were confirmed using real-time PCR. Dysregulated genes included those encoding cytokines/chemokines, and involved in transcription regulation, calcium and ion channel formation, and cell adhesion. Unexpected findings were overexpression of toll-like receptor genes in marrow CD4(+) cells of patients and of genes for killer-cell immunoglobulin-like receptors (KIR) in AA marrow CD8(+) cells. Conclusions. Our detailed results at the mRNA level provide insights into the mechanism of AA. Both innate and adaptive immune responses of CD4(+) and CD8(+) T cells appear to be active in immune-mediated marrow destruction. A variety of cytokines and chemokines active in pathophysiologic cells likely play important roles in the recruitment and activation of lymphocytes to cytotoxic effectors for marrow hematopoietic target cells in AA. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, NIH, Hematol Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM youngn@nhlbi.nih.gov NR 56 TC 34 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2004 VL 32 IS 9 BP 806 EP 814 DI 10.1016/j.exphem.2004.06.004 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 857LG UT WOS:000224117500003 PM 15345281 ER PT J AU Brennan, MJ Morris, SL Sizemore, CF AF Brennan, MJ Morris, SL Sizemore, CF TI Tuberculosis vaccine development: research, regulatory and clinical strategies SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE Mycobacterium tuberculosis; tuberculosis vaccines; vaccine regulatory issues; vaccine trials ID BACILLUS-CALMETTE-GUERIN; MYCOBACTERIUM-TUBERCULOSIS; PROTECTIVE EFFICACY; BCG VACCINES; ENHANCED IMMUNOGENICITY; PANTOTHENATE AUXOTROPH; IMMUNE-RESPONSES; RECENT PROGRESS; DNA; MICE AB In the past decade, while the global tuberculosis (TB) epidemic has continued to devastate mankind, considerable progress has nevertheless been made in the development of new and improved vaccines for this ancient disease. Recombinant bacillus Calmette-Guerin strains, DNA-based vaccines, live attenuated Mycobacterium tuberculosis vaccines and subunit vaccines formulated with novel adjuvants have shown promise in preclinical animal challenge models. Three of these vaccines are being evaluated at present in human clinical studies, and several other vaccine preparations are being targeted for clinical trials in the near future. Although the preclinical characterisation and testing of new TB vaccines has clearly led to exciting new findings, complex regulatory and clinical trial design issues remain as a challenge to TB vaccine development. This report reviews some of the exciting advances in TB research that have led to the development of new TB vaccines, and addresses the unique regulatory and clinical issues associated with the testing of novel anti-TB preparations in human populations. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. NIAID, TB & Other Mycobacterial Dis Sect, Resp Dis Branch, Div Microbiol & Infect Dis,NIH, Bethesda, MD 20892 USA. RP Brennan, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Rm 503,HFM-431,29 Lincoln Dr, Bethesda, MD 20892 USA. EM brennan@cber.fda.gov; morris@cber.fda.gov NR 69 TC 10 Z9 11 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2004 VL 4 IS 9 BP 1493 EP 1504 DI 10.1517/14712598.4.9.1493 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 853RQ UT WOS:000223845600012 PM 15335316 ER PT J AU Walsh, SP Kling, MA AF Walsh, SP Kling, MA TI VNS and depression: current status and future directions SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Review DE epilepsy; neurostimulation; treatment-resistant depression; vagus nerve stimulation ID VAGUS NERVE-STIMULATION; TREATMENT-RESISTANT DEPRESSION; EPILEPSY; BRAIN AB Vagus nerve stimulation (VNS) Is an established anticonvulsant therapy In treatment-resistant patients with epilepsy. The known anatomical projections of the vagus nerve to many brain regions that have been implicated in mood disorders suggest that VNS may also have useful antidepressant effects. There has been growing Interest in the potential application of VNS In the nonpharmacological management of treatment-resistant depression. Results from an open-label study, In which 59 subjects with treatment-resistant depression were treated for 10 weeks with VNS therapy, reported a 31% response rate. In a recent controlled double-blind trial of VNS and depression, short-term treatment for 10 weeks failed to demonstrate statistical improvement over sham treatment. Results from the long-term phase of this trial may be more significant, however published data are awaited. C1 Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. NIMH, Child Neuroendocrinol Branch, Bethesda, MD 20092 USA. RP Walsh, SP (reprint author), Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. EM spw9@georgetown.edu; klingm@mail.nih.gov RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 51 TC 5 Z9 5 U1 0 U2 2 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD SEP PY 2004 VL 1 IS 1 BP 155 EP 160 DI 10.1586/17434440.1.1.155 PG 6 WC Engineering, Biomedical SC Engineering GA 018XC UT WOS:000235797100024 PM 16293018 ER PT J AU Reynolds, SJ Muwonga, J AF Reynolds, SJ Muwonga, J TI OraQuick((R)) ADVANCE rapid HIV-1/2 antibody test SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE diagnostics; HIV; rapid resting ID IMMUNODEFICIENCY-VIRUS TYPE-1 AB Rapid HIV antibody tests represent a key development in the current diagnosis and management of HIV infection. The OraQuick(R) ADVANCE Rapid HIV-1/2 antibody test (OraSure Technologies) has received US Food and Drug Administration approval on the basis of Its performance characteristics and a subsequent Clinical Laboratory Improvement Amendments waiver based on Its simplicity and accuracy. The test has been approved for use on oral mucosal transudate, whole blood or plasma. Clinical evaluation of the OraQuick ADVANCE Rapid HIV-1/2 antibody test has revealed high sensitivity and specificity. The test has many important applications, extending the opportunities for voluntary counseling and testing, and as a tool for the scale-up of antiretroviral therapy In resource-limited settings. C1 NIAID, NIH, ICER Program Uganda, Washington, DC 20521 USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Univ Kinshasa, Fac Med, Dept Med Biol, Kinshasa, Congo. Natl Reference Lab, HIV AIDS Natl Control Program, Kinshasa, Congo. RP Reynolds, SJ (reprint author), NIAID, NIH, ICER Program Uganda, 2190 Kampala Pl, Washington, DC 20521 USA. EM sjr@jhmi.edu NR 9 TC 14 Z9 16 U1 0 U2 6 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2004 VL 4 IS 5 BP 587 EP 591 DI 10.1586/14737159.4.5.587 PG 5 WC Pathology SC Pathology GA 853KD UT WOS:000223825500003 PM 15347252 ER PT J AU Dorritie, K Montagna, C Difilippantonio, MJ Ried, T AF Dorritie, K Montagna, C Difilippantonio, MJ Ried, T TI Advanced molecular cytogenetics in human and mouse SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE array CGH; comparative cytogenetics; comparative genomics; cytogenetic; DOP-PCR; fluorescent in situ hybridization; fluorochromes; hybridization; M-FISH; microarrays; mouse models; multiplex FISH; spectral karyotyping ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; FLUORESCENCE INSITU HYBRIDIZATION; DOUBLE MINUTE CHROMOSOMES; ACUTE MYELOID-LEUKEMIA; CANCER CELL-LINES; ACUTE LYMPHOBLASTIC-LEUKEMIA; UNIVERSAL DNA-AMPLIFICATION; ANALYSIS DETECTS FREQUENT; POLYMERASE-CHAIN-REACTION AB Fluorescence in situ hybridization, spectral karyotyping, multiplex fluorescence in situ hybridization, comparative genomic hybridization, and more recently array comparative genomic hybridization, represent advancements in the field of molecular cytogenetics. The application of these techniques for the analysis of specimens from humans, or mouse models of human diseases, enables one to reliably identify and characterize complex chromosomal rearrangements resulting in alterations of the genome. As each of these techniques has advantages and limitations, a comprehensive analysis of cytogenetic aberrations can be accomplished through the utilization of a combination approach. As such, analyses of specific tumor types have proven invaluable in the identification of new tumor-specific chromosomal aberrations and imbalances (aneuploidy), as well as regions containing tumor-specific gone targets. Application of these techniques has already improved the classification of tumors into distinct categories, with the hope that this will lead to more tailored treatment strategies. These techniques, in particular the application of tumor-specific fluorescence in situ hybridization probes to interphase, nuclei, are also powerful tools for the early identification of premalignant lesions. C1 NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. New York State Med Sch, New York, NY USA. RP Ried, T (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, Bldg 50,Rm 1408,50 South Dr, Bethesda, MD 20892 USA. EM riedt@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 163 TC 6 Z9 7 U1 0 U2 3 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2004 VL 4 IS 5 BP 663 EP 676 DI 10.1586/14737159.4.5.663 PG 14 WC Pathology SC Pathology GA 853KD UT WOS:000223825500011 PM 15347260 ER PT J AU Catalano, A Caprari, P Soddu, S Procopio, A Romano, M AF Catalano, A Caprari, P Soddu, S Procopio, A Romano, M TI 5-Lipoxygenase antagonizes genotoxic stress-induced apoptosis by altering p53 nuclear trafficking SO FASEB JOURNAL LA English DT Article; Proceedings Paper CT 8th International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Related Diseases CY SEP, 2003 CL Chicago, IL DE eicosanoids; mesothelioma ID CANCER-THERAPY; MALIGNANT MESOTHELIOMA; LEUKOTRIENE SYNTHESIS; CELL-SURVIVAL; EXPRESSION; PROTEIN; CYCLOOXYGENASE-2; OVEREXPRESSION; BIOSYNTHESIS; LINES AB 5-Lipoxygenase (5-LO) promotes cancer cell proliferation and survival by unclear mechanisms. Here, we show that 5-LO expression and activity were induced by genotoxic agents in a p53-independent manner and antagonized p53- or genotoxic drug-induced apoptosis in a variety of cancer cells. 5-LO inhibited p53- governed transactivation of the pro-apoptotic genes bax and pig3 but not of p21(WAF1/CIP1) or mdm2. This may be explained by 5-LO capability to inhibit the binding of p53 to promyelocytic leukemia protein (PML) and p53 subnuclear relocalization into PML-nuclear bodies in response to genotoxic stress. Interestingly, 5-LO activity appears to be involved in nuclear retention and inactivation of wild-type p53 in malignant mesothelioma cells. In these cells, genetic or pharmacological inhibition of 5-LO enabled suppression of in vitro tumorigenicity by low doses of chemotherapeutic drugs. Together, these results uncover novel functions of 5-LO and contribute to the understanding of 5-LO involvement in tumor progression. Moreover, they provide a rationale to the therapeutic use of 5-LO inhibitors to enhance cancer chemosensitivity in selected tumors. C1 Univ Politecn Marche, Dipartimento Patol Mol & Terapie Innovat, I-60131 Ancona, Italy. Regina Elena Inst Canc Res, Mol Oncogenesis Lab, Rome, Italy. Gabriele DAnnunzio Univ Fdn, CeSI, Dept Biomed Sci, Chieti, Italy. Gabriele DAnnunzio Univ Fdn, CeSI, Aging Res Ctr, Chieti, Italy. NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Catalano, A (reprint author), Univ Politecn Marche, Dipartimento Patol Mol & Terapie Innovat, Via Ranieri, I-60131 Ancona, Italy. EM catgfp@yahoo.it OI ROMANO, Mario/0000-0001-8512-1458 NR 35 TC 30 Z9 31 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2004 VL 18 IS 12 BP 1740 EP + DI 10.1096/fj.04-2258fje PG 25 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 859DQ UT WOS:000224243200022 PM 15375079 ER PT J AU von Kobbe, C May, A Grandori, C Bohr, VA AF von Kobbe, C May, A Grandori, C Bohr, VA TI Werner syndrome cells escape hydrogen peroxide-induced cell proliferation arrest SO FASEB JOURNAL LA English DT Article DE DNA damage; premature senescence ID NORMAL HUMAN FIBROBLASTS; DNA-DAMAGE; SYNDROME PROTEIN; MAMMALIAN-CELLS; EXONUCLEASE ACTIVITY; GENOMIC INSTABILITY; GROWTH ARREST; P53; SENESCENCE; REPAIR AB Werner syndrome (WS) is a rare disease caused by the lack of a functional nuclear WS protein (WRN). WS is characterized by the early onset of premature aging signs and a high incidence of sarcomas. WS diploid fibroblasts have a short life span and extensive genomic instability. Mammalian cells are continuously exposed to reactive oxygen species (ROS), which represent human mutagens and are thought to be a major contributor to the aging process. Hydrogen peroxide (H2O2) is a common ROS intermediate generated by various forms of oxidative stress. In response to H2O2-induced DNA damage, normal human diploid fibroblasts follow a pathway leading to irreversible proliferation arrest and premature senescence. Here we show that in contrast to normal human fibroblasts, WS diploid fibroblasts continue proliferating after extensive H2O2-induced DNA damage and accumulate oxidative DNA lesions. A direct role of WRN in this abnormal cellular response to H2O2 is demonstrated by interfering with WRN expression in normal human fibroblasts. We propose a role for WRN in the detection and/or processing of oxidative DNA lesions and in cellular responses to H2O2 as they relate to some of the phenotypical aspects of WS cells. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 57 TC 41 Z9 42 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2004 VL 18 IS 12 BP 1970 EP + DI 10.1096/fj.04-1895fje PG 26 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 859DQ UT WOS:000224243200001 PM 15459124 ER PT J AU Blood-Siegfried, J Nyska, A Geisenhoffer, K Lieder, H Moomaw, C Cobb, K Shelton, B Coombs, W Germolec, D AF Blood-Siegfried, J Nyska, A Geisenhoffer, K Lieder, H Moomaw, C Cobb, K Shelton, B Coombs, W Germolec, D TI Alteration in regulation of inflammatory response to influenza a virus and endotoxin in suckling rat pups: a potential relationship to sudden infant death syndrome SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE SIDS; endotoxin; influenza A; inflammatory cytokine ID NITRIC-OXIDE SYNTHASE; UPPER RESPIRATORY-TRACT; SYNDROME SIDS; CYTOKINE ANTAGONISTS; LETHAL SYNERGY; INFECTION; SEPSIS; BACTERIA; TOXINS; ANTIOXIDANT AB Data increasingly implicate a possible role of immune and inflammatory responses to infection in sudden infant death syndrome (SIDS). We have previously described a dual challenge model that results in pathology, organ damage, vascular collapse and unexplained death similar to that seen in SIDS. In this study, we examined changes in inflammatory cytokine mRNA in the lung and liver and regulation of pathways associated with nitric oxide production. Our data suggest that priming of the immune system by mild viral infection disturbs normal inflammatory response to endotoxin. This results in an increased nitric oxide synthase production, most likely the cause of liver pathology and clotting abnormalities. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NIEHS, Environm Immunol Lab, Res Triangle Pk, NC 27709 USA. Duke Univ, Sch Nursing, Durham, NC 27707 USA. RP Blood-Siegfried, J (reprint author), NIEHS, Environm Immunol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM blood002@mc.duke.edu OI Blood-Siegfried, Jane/0000-0003-1926-9758 NR 48 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD SEP 1 PY 2004 VL 42 IS 1 BP 85 EP 93 DI 10.1016/j.femsim.2004.06.004 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 851ON UT WOS:000223694500011 PM 15325401 ER PT J AU Alvero, R Armstrong, A Payson, M Segars, J Myers, E AF Alvero, R Armstrong, A Payson, M Segars, J Myers, E TI Costs and outcomes of day 3 versus blastocyst transfer in assisted reproductive technologies. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P221 BP S213 EP S213 DI 10.1016/j.fertnstert.2004.07.563 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800552 ER PT J AU Alvero, R Konowal, A Russell, D Rosario, M Kelk, D Phillips, T AF Alvero, R Konowal, A Russell, D Rosario, M Kelk, D Phillips, T TI Evaluation of products from embryo culture and their correlation with pregnancy outcome. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Univ Colorado, Ctr Hlth Sci, Aurora, CO USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA O141 BP S57 EP S57 DI 10.1016/j.fertnstert.2004.07.146 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800141 ER PT J AU Catherino, WH Mayers, C Morris, S Payson, M Leppert, PC Segars, JH AF Catherino, WH Mayers, C Morris, S Payson, M Leppert, PC Segars, JH TI Under-expression of alcohol dehydrogenase in uterine fibroids: Impact on retinoic acid pathway. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NICHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA O224 BP S90 EP S90 DI 10.1016/j.fertnstert.2004.07.229 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800224 ER PT J AU Gustofson, RL Segars, JH Larsen, FW AF Gustofson, RL Segars, JH Larsen, FW TI Cost analysis of ganirelix versus luteal-phase lupron downregulation per assisted reproductive technology, (ART) cycle and pregnancy achieved. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Natl Naval Med Res Inst, NIH, Walter Reed Army Med Ctr, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20307 USA. Walter Reed Army Med Ctr, ART Program, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA O296 BP S118 EP S119 DI 10.1016/j.fertnstert.2004.07.301 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800295 ER PT J AU Neithardt, AB Shah, BH Catt, KJ AF Neithardt, AB Shah, BH Catt, KJ TI Dependence of GnRH-induced CREB phosphorylation in hypothalamic neurons upon transactivation of the EGF receptor and activation of the phosphoinositide 3-kinase pathway SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P491 BP S308 EP S309 DI 10.1016/j.fertnstert.2004.07.833 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800815 ER PT J AU Parker, JD Baldwin, EL Catherino, WH Segars, JH Wu, TJ AF Parker, JD Baldwin, EL Catherino, WH Segars, JH Wu, TJ TI Ultrashortloop feedback regulation of GnRH in uterine tissue. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 NICHD, Combined Fed Fellowship REI, PREB, NNMC,WRAMC,USUHS,NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P495 BP S310 EP S310 DI 10.1016/j.fertnstert.2004.07.837 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800819 ER PT J AU Parker, JD Segars, JH Armstrong, AY Larsen, FW AF Parker, JD Segars, JH Armstrong, AY Larsen, FW TI The effects of extended oral contraceptive pills for cycle regulation among different ages and FSH levels prior to ART. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 NIH, Combined Fed Fellowship REI, NICHD, PREB,NNMC,WRAMC,USUHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA O327 BP S131 EP S132 DI 10.1016/j.fertnstert.2004.07.332 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800326 ER PT J AU Payson, M Armstrong, A Nielsen, P Robinson, R Ernest, J Alvero, R AF Payson, M Armstrong, A Nielsen, P Robinson, R Ernest, J Alvero, R TI Analysis of reproductive endocrinology & infertility CREOG subject scores: A multi-institution study. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. NIH, Washington, DC USA. Madigan Army Med Ctr, Tacoma, WA 98431 USA. San Antonio Uniformed Hlth Educ Consortium, San Antonio, TX USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P485 BP S307 EP S307 DI 10.1016/j.fertnstert.2004.07.827 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800809 ER PT J AU Payson, M Allard, J Alvero, R Segars, J Larsen, F AF Payson, M Allard, J Alvero, R Segars, J Larsen, F TI Methotrexate affects ovarian reserve in treatment of ectopic pregnancies resulting from ART. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. Univ Colorado, Aurora, CO USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P23 BP S143 EP S144 DI 10.1016/j.fertnstert.2004.07.366 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800359 ER PT J AU Potlog-Nahari, C Chapin, H Chang, R Feuillan, P Segars, J Nieman, L AF Potlog-Nahari, C Chapin, H Chang, R Feuillan, P Segars, J Nieman, L TI Ovarian venous sampling to guide localization and treatment of female hyperandrogenism. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. NIH, CC, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. USUHS, Combined Fed Program Reprod Endocrinol WRAMC, NNMC, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA P482 BP S305 EP S306 DI 10.1016/j.fertnstert.2004.07.824 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800806 ER PT J AU Zhang, J Gilles, J Barnhart, K Creinin, M Westhoff, C Frederick, M AF Zhang, J Gilles, J Barnhart, K Creinin, M Westhoff, C Frederick, M TI Medical management with misoprostol for early pregnancy failure: A multicenter, randomized equivalence trial. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med C1 Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Univ Miami, Miami, FL 33152 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA USA. Columbia Univ, New York, NY USA. Clin Trial & Survey Corp, Baltimore, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2004 VL 82 SU 2 MA O132 BP S53 EP S54 DI 10.1016/j.fertnstert.2004.07.137 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 855YM UT WOS:000224010800132 ER PT J AU Botta, D Franklin, CC White, CC Krejsa, CM Dabrowski, MJ Pierce, RH Fausto, N Kavanagh, TJ AF Botta, D Franklin, CC White, CC Krejsa, CM Dabrowski, MJ Pierce, RH Fausto, N Kavanagh, TJ TI Glutamate-cysteine ligase attenuates TNF-induced mitochondrial injury and apoptosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE glutathione; glutamate-cysteine ligase; tumor necrosis factor; apoptosis; mitochondria; free radicals ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; ADENINE-NUCLEOTIDE TRANSLOCATOR; PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; ACTIVATED PROTEIN-KINASE; CELL-DEATH; CATALYTIC SUBUNIT; GLUTATHIONE SYNTHESIS; REDOX REGULATION; CONDITIONAL EXPRESSION AB Glutathione (GSH) is important in free radical scavenging, maintaining cellular redox status, and regulating cell survival in response to a wide variety of toxicants. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), which is composed of catalytic (GCLC) and modifier (GCLM) subunits. To determine whether increased GSH biosynthetic capacity enhances cellular resistance to tumor necrosis factor-alpha- (TNF-alpha-) induced apoptotic cell death, we have established several mouse liver hepatoma (Hepa- 1) cell lines overexpressing GCLC and/or GCLM. Cells overexpressing GCLC alone exhibit modest increases in GCL activity, while cells overexpressing both subunits have large increases in GCL activity. Importantly, cells overexpressing both GCL subunits exhibit increased resistance to TNF-induced apoptosis as judged by a loss of redox potential; mitochondrial membrane potential; translocation of cytochrome c to the cytoplasm; and activation of caspase-3, caspase-8, and caspase-9. Analysis of the effects of TNF on these parameters indicates that maintaining mitochondrial integrity mediates this protective effect in GCL-overexpressing cells. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, UW NIEHS Ctr Ecogenet & Environm Hlth, Seattle, WA USA. RP Kavanagh, TJ (reprint author), Univ Washington, Dept Environm & Occupat Hlth Sci, Box 354695, Seattle, WA 98195 USA. EM tjkav@u.washington.edu FU NCI NIH HHS [1R29CA75316, 1R01CA90473, 1R01CA23226, 1R01CA74131]; NIA NIH HHS [1P01AG01751]; NIEHS NIH HHS [1T32ES07032, 1P30ES07033, 1P42ES04696] NR 53 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2004 VL 37 IS 5 BP 632 EP 642 DI 10.1016/j.freeradbiomed.2004.05.027 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 847QI UT WOS:000223409600008 PM 15288121 ER PT J AU Derse, D Heidecker, G Mitchell, M Hill, S Lloyd, P Princler, G AF Derse, D Heidecker, G Mitchell, M Hill, S Lloyd, P Princler, G TI Infectious transmission and replication of human T-cell leukemia virus type 1 SO FRONTIERS IN BIOSCIENCE LA English DT Article DE HTLV-1; T lymphocyte; leukemia; retrovirus; reverse transcriptase; antiviral; nucleoside analogs; review ID BLOOD MONONUCLEAR-CELLS; REVERSE-TRANSCRIPTASE INHIBITORS; IN-VITRO; HTLV-I; MOLECULAR CLONE; EXPRESSION; SUSCEPTIBILITY; LYMPHOCYTES; LAMIVUDINE; LINES AB Retrovirus infection proceeds by attachment of the envelope glycoprotein to a cell surface receptor, followed by fusion of the viral and cellular membranes. Once in the cell, the viral enzymes and structural proteins form a replication complex that converts the single-stranded viral genomic RNA into a double-stranded DNA, which is then integrated into the host cell chromosome. For HTLV-1, these events are not well characterized. We have developed cell culture systems, infectious molecular clones, and viral vectors that can be used to characterize the mechanisms of HTLV-1 infection and replication. Infection with cell-free HTLV-1 virions is orders of magnitude less efficient compared with other retroviruses. This inefficiency is the result of a block in the replication process after the virion is bound to the cell surface. We are determining whether this block is conferred by the viral replication enzymes, results from the actions of cellular restriction factors, reflects the need for cell-cell contact, or is caused by a combination of these factors. C1 NCI, Retrovirus Gene Express Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Derse, D (reprint author), NCI, Retrovirus Gene Express Sect, HIV Drug Resistance Program, Ctr Canc Res, Bldg 567 Rm 152, Frederick, MD 21702 USA. EM derse@ncifcrf.gov NR 30 TC 11 Z9 11 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2004 VL 9 SU S BP 2495 EP 2499 DI 10.2741/1411 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852NS UT WOS:000223763200038 PM 15353302 ER PT J AU Takenouchi, N Yao, K Jacobson, S AF Takenouchi, N Yao, K Jacobson, S TI Immunopathogensis of HTLV-I associated neurologic disease: Molecular, histopathologic, and immunologic approaches SO FRONTIERS IN BIOSCIENCE LA English DT Review DE HAM/TSP; molecular; histopathology; immunology; review ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; T-CELL LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD LESIONS; BLOOD MONONUCLEAR-CELLS; HTLV-1-ASSOCIATED MYELOPATHY HAM/TSP; CEREBROSPINAL-FLUID; PROVIRAL LOAD; MULTIPLE-SCLEROSIS AB Human T-cell lymphotropic virus type I (HTLV-I) infection is associated with a variety of human diseases including HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive inflammatory neurological disease. An important risk factor for the development of HAM/TSP is thought to be a high HTLV-I proviral load. Histopathological studies have demonstrated the presence of HTLV-I virus in the affected areas of spinal cords from HAM/TSP patients. Furthermore, T-cell infiltrations have been shown in spinal cord lesions. The precise mechanism for disease development is still unknown. Virus-host immune interactions are considered to play an important role in disease pathogenesis. This review focuses on current molecular, histopathological, and immunological approaches to understand the immunopathogenesis of HAM/TSP. C1 NINDS, Virol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, NIH, NIB, Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 110 TC 14 Z9 14 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2004 VL 9 SU S BP 2527 EP 2539 DI 10.2741/1414 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852NS UT WOS:000223763200041 PM 15353305 ER PT J AU Aladjem, MI AF Aladjem, MI TI The mammalian beta globin origin of DNA replication SO FRONTIERS IN BIOSCIENCE LA English DT Article DE beta globin; replication; cell cycle; replicator; review ID LOCUS-CONTROL REGION; CHROMOSOME CONDENSATION; NUCLEAR MATRIX; GENE LOCUS; INITIATION; ACTIVATION; SITES; CELLS; REPRESSION; SEQUENCES AB Initiation of DNA replication is a tightly regulated process aimed to insure that the entire genome is replicated at the appropriate time during each cell cycle. In the human beta-globin locus, replication initiates from a region between the two genes that encode the adult subunit of hemoglobin ( the beta-globin initiation region, or IR). Mammalian beta-globin loci replicate early during the S-phase of the cell cycle in pre-erythroid cells, in which the beta-globin locus is present in a euchromatin form. However, in cells that do not express globin and in which the locus is heterochromatic, these same loci replicate during the later stages of S-phase. Both early and late replication patterns utilize similar replication initiation regions. These features make the beta-globin locus an attractive model for studying the determinants of replication sites and replication timing, as well as the correlation between gene expression and DNA replication. Two genomic domains are essential for initiation of DNA replication within the locus: the initiation region ( IR), and a 40 kb region upstream of the globin gene cluster known as the locus control region (LCR). The IR meets the genetic requirements for a chromosomal replicator, since it can initiate DNA replication at ectopic sites. The LCR regulates transcriptional activity and chromatin structure, and may act as a determinant of replication timing. This review will summarize recent findings characterizing the sequence requirements for initiation of DNA replication in mammalian beta-globin loci and will discuss the specific influence of the location and the chromosomal environment in regulating DNA replication at the beta-globin IR. C1 NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Aladjem, MI (reprint author), NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. EM aladjemm@mail.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 NR 43 TC 11 Z9 12 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2004 VL 9 SU S BP 2540 EP 2547 DI 10.2741/1415 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852NS UT WOS:000223763200042 PM 15358579 ER PT J AU Friedman, FK Robinson, RC Dai, R AF Friedman, FK Robinson, RC Dai, R TI Molecular modeling of mammalian cytochrome P450s SO FRONTIERS IN BIOSCIENCE LA English DT Article DE computational modeling; homology models; protein structure; cytochrome P450; drug metabolism; review ID PROTEIN SECONDARY STRUCTURE; CO BINDING-KINETICS; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; SUBSTRATE-BINDING; STRUCTURE PREDICTION; NEURAL NETWORKS; ACTIVE-SITE; INHIBITION; HOMOLOGY AB The cytochrome P450 enzymes collectively metabolize a wide range of xenobiotic and endogenous compounds. The broad substrate specificity of this superfamily derives from the multiplicity of P450s whose unique substrate specificity profiles reflect underlying differences in primary sequence. Experimental structures of P450s, where available, have provided great insight into the basis of substrate recognition. However, for those mammalian P450s whose structures have not been determined, homology modeling has become an increasingly important tool for understanding substrate specificity and mechanism. P450 modeling is often a challenging task, owing to the rather low sequence identity between target and template proteins. Although mammalian P450 models have previously been based on bacterial P450 structures, the recent advent of mammalian P450 structures holds great potential for generating more accurate homology models. Consequently, the substrate recognition properties of several mammalian P450s have been rationalized using the predicted substrate binding site of recently developed models. This review summarizes the major concepts and current approaches of molecular modeling of P450s. C1 Bristol Myers Squibb Co, Pharmaceut Candidate Optimizat, Princeton, NJ 08543 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Dai, R (reprint author), Bristol Myers Squibb Co, Pharmaceut Candidate Optimizat, Princeton, NJ 08543 USA. EM renke.dai@bms.com RI Friedman, Fred/D-4208-2016 NR 56 TC 3 Z9 3 U1 1 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2004 VL 9 SU S BP 2796 EP 2806 DI 10.2741/1437 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852NS UT WOS:000223763200064 PM 15353315 ER PT J AU Borlongan, CV Wang, Y Su, TP AF Borlongan, CV Wang, Y Su, TP TI Delta opioid peptide (D-Ala 2, D-Leu 5) enkephalin: Linking hibernation and neuroprotection SO FRONTIERS IN BIOSCIENCE LA English DT Article DE opioid; hibernation; transplantation; neurological disorders; neuroprotection; review ID ACTIVE GROUND-SQUIRRELS; INDUCTION TRIGGERS; CEREBRAL-ISCHEMIA; PRESERVATION; SURVIVAL; METHAMPHETAMINE; BLOCKS; TIME AB Hibernation is a potential protective strategy for the peripheral, as well as for the central nervous system. A protein factor termed hibernation induction trigger ( HIT) was found to induce hibernation in summer-active ground squirrels. Purification of HIT yielded an 88-kD peptide that is enriched in winter hibernators. Partial sequence of the 88-kD protein indicates that it may be related to the inhibitor of metalloproteinase. Using opioid receptor antagonists to elucidate the mechanisms of HIT, it was found that HIT targeted the delta opioid receptors. Indeed, delta opioid (D-Ala 2, D-Leu 5) enkephalin (DADLE) was shown to induce hibernation. Specifically, HIT and DADLE were found to prolong survival of peripheral organs, such as the lung, the heart, liver, and kidney preserved en bloc or as a single preparation. In addition, DADLE has been recently demonstrated to promote survival of neurons in the central nervous system. Exposure to DADLE dose-dependently enhanced cell viability of cultured primary rat fetal dopaminergic cells. Subsequent transplantation of these DADLE-treated dopaminergic cells into the Parkinsonian rat brain resulted in a two-fold increase in surviving grafted cells. Interestingly, delivery of DADLE alone protected against dopaminergic depletion in a rodent model of Parkinson's disease. Similarly, DADLE blocked and reversed the dopaminergic terminal damage induced by methamphetamine ( METH). Such neuroprotective effects of DADLE against METH neurotoxicity was accompanied by attenuation of mRNA expressions of a tumor necrosis factor p53 and an immediate early gene c-fos. In parallel to these beneficial effects of DADLE on the dopaminergic system, DADLE also ameliorated the neuronal damage induced by ischemia-reperfusion following a transient middle cerebral artery occlusion. In vitro replication of this ischemia cell death by serum-deprivation of PC12 cells revealed that DADLE exerted neuroprotection in a naltrexone-sensitive manner. These results taken together suggest that DADLE stands as a novel therapeutic agent. In this review paper, we present laboratory evidence supporting the use of DADLE for protection of peripheral and central nervous system. C1 Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD 21224 USA. RP Borlongan, CV (reprint author), Med Coll Georgia, Dept Neurol, BI-3080,1120 15th St, Augusta, GA 30912 USA. EM cborlongan@mail.mcg.edu OI Borlongan, Cesar/0000-0002-2966-9782 NR 29 TC 58 Z9 66 U1 1 U2 12 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2004 VL 9 SU S BP 3392 EP 3398 DI 10.2741/1490 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852NS UT WOS:000223763200116 PM 15353366 ER PT J AU Chang, YC Tsai, HF Karos, M Kwon-Chung, KJ AF Chang, YC Tsai, HF Karos, M Kwon-Chung, KJ TI THTA, a thermotolerance gene of Aspergillus fumigatus SO FUNGAL GENETICS AND BIOLOGY LA English DT Article DE high temperature; hygromycin; nystatin; thermotolerance; THTA; virulence ID INVASIVE ASPERGILLOSIS; THERMOPHILIC FUNGI; ANTIFUNGAL THERAPY AB Aspergillus fumigatus grows optimally from 37 to 42degreesC but can grow at temperatures up to 55 degreesC. To study the genetic basis of thermotolerance and its role in virulence of A. fumigatus, temperature sensitive mutants were isolated. One of the mutants that grew at 42degreesC but not at 48degreesC was complemented and the gene, THTA. was identified. Deletion of THTA showed the same temperature sensitivity as the original mutant. THTA encodes a putative protein of 141 kDa with unknown function and the HA-tagged ThtAp accumulated to similar levels in cultures grown at either 37 or 48degreesC. Southern blot analysis and database searches revealed the presence of THTA-related sequences in several other ascomycetous fungi. No difference in virulence was observed between the DeltathtA and wild-type strains. Thus, THTA is essential for growth of A. fumigatus at high temperatures but does not contribute to the pathogenicity of the species. Published by Elsevier Inc. C1 Natl Inst Allergy & Infect Dis, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), Natl Inst Allergy & Infect Dis, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM june_kwon_chung@nih.gov NR 22 TC 25 Z9 29 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1087-1845 J9 FUNGAL GENET BIOL JI Fungal Genet. Biol. PD SEP PY 2004 VL 41 IS 9 BP 888 EP 896 DI 10.1016/j.fgb.2004.06.004 PG 9 WC Genetics & Heredity; Mycology SC Genetics & Heredity; Mycology GA 845RX UT WOS:000223263100007 PM 15338574 ER PT J AU Laskus, T Wilkinson, J Gallegos-Orozco, JF Radkowski, M Adair, DM Nowicki, M Operskalski, E Buskell, Z Seeff, LB Vargas, H Rakela, J AF Laskus, T Wilkinson, J Gallegos-Orozco, JF Radkowski, M Adair, DM Nowicki, M Operskalski, E Buskell, Z Seeff, LB Vargas, H Rakela, J TI Analysis of hepatitis C virus quasispecies transmission and evolution in patients infected through blood transfusion SO GASTROENTEROLOGY LA English DT Article ID HYPERVARIABLE REGION 1; UNITED-STATES; HEPATOCELLULAR-CARCINOMA; DYNAMIC BEHAVIOR; LIVER-DISEASE; IN-VITRO; NON-A; NON-B; GLYCOPROTEIN; RECIPIENTS AB Background & Aims: Studies on hepatitis C virus (HCV) quasispecies dynamics in the natural course of infection are rare owing to difficulties in obtaining samples from the early phase of infection. Methods: We studied 15 patients from the Transfusion-Transmitted Viruses Study who seroconverted to anti-HCV after receiving infected blood. Follow-up serum samples were collected every 2-3 weeks for 6 months, at 10 months, and at 11-16 years. Viral quasispecies in the second envelope hypervariable region 1 (E2/HVR1) and 5' untranslated region (5'UTR) were analyzed with single-strand conformation polymorphism (SSCP) and heteroduplex mobility assay (HMA). Results: Seven patients cleared infection within 7-24 weeks (mean, 14.0 wk) and 3 patients eventually became anti-HCV negative. In 6 patients with resolving hepatitis the SSCP band pattern remained stable, whereas in one patient minor changes appeared before clearance. In contrast, in all 8 patients progressing to chronicity, major changes in the E2/HVR1 quasispecies developed at 8-22 weeks (mean, 13.1 wk). Shannon entropy and medium mobility shift values derived from HMA gels remained stable in patients with resolving hepatitis but changed in those who developed chronic infection. Only 2 patients showed minor changes in 5'UTR. A decrease in E2/HVR1 complexity at the time of transmission (bottleneck) was found in 5 patients altogether. Conclusions: Changes in E2/HVR1 quasispecies 8-22 weeks after infection, likely caused by mounting immune pressure, were predictive of ensuing chronic infection, whereas stability was associated with resolution. Our study also showed that composition of HCV quasispecies may be preserved during transmission from host to host. C1 Mayo Clin, Dept Med, Scottsdale, AZ 85259 USA. Med Acad Warsaw, Inst Infect Dis, Warsaw, Poland. Univ So Calif, Maternal Child Virol Res Lab, Los Angeles, CA USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. NIDDKD, NIH, Bethesda, MD USA. RP Rakela, J (reprint author), Mayo Clin, Dept Med, SC Johnson Bldg Sj3, Scottsdale, AZ 85259 USA. EM rakela.Jorge@mayo.edu OI Vargas, Hugo/0000-0002-7802-688X NR 55 TC 48 Z9 50 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2004 VL 127 IS 3 BP 764 EP 776 DI 10.1053/j.gastro.2004.06.005 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 853NO UT WOS:000223834500014 PM 15362033 ER PT J AU Bassaganya-Riera, J Reynolds, K Martino-Catt, S Cui, YZ Hennighausen, L Gonzalez, F Rohrer, J Benninghoff, AU Hontecillas, R AF Bassaganya-Riera, J Reynolds, K Martino-Catt, S Cui, YZ Hennighausen, L Gonzalez, F Rohrer, J Benninghoff, AU Hontecillas, R TI Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease SO GASTROENTEROLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; RECEPTOR-GAMMA; FATTY-ACIDS; T-CELLS; GENE-EXPRESSION; PEROXISOME-PROLIFERATION; ULCERATIVE-COLITIS; IMMUNE-RESPONSES AB Background & Aims: The molecular targets for the protective actions of conjugated linoleic acid (CLA) on experimental inflammatory bowel disease (IBD) are unknown. We used a loss-of-function approach to investigate whether CLA ameliorated colitis through a peroxisome proliferator-activated receptor gamma (PPAR gamma)-dependent mechanism. Methods: The expression of PPAR gamma, delta, and their target genes in the colon of mice fed control or CLA-supplemented diets was assayed after a 7-day dextran sodium sulfate (DSS) challenge by quantitative real-time polymerase chain reaction (PCR). Additionally, nuclear factor-kappa B (NF-kappaB) p65 activation was quantified in the colon. To determine the involvement of PPAR gamma in the mechanism of action of CLA directly, specific deletions of PPAR gamma in the colon were performed in mice by using the Cre-lox recombination system. Colonic PPAR gamma null mice and wild-type littermates were fed either a CLA-supplemented or a control diet for 42 days and challenged with 2.5% DSS. The therapeutic efficacy of CLA also was examined by using the CD4(+)CD45RB(hi) transfer colitis model. Results: CLA induced PPAR gamma and delta, transcriptionally modulated PPAR gamma and delta-responsive gene clusters involved in lipid metabolism (uncoupling protein [UCP]1, UCP3, PPAR gamma coactivator 1alpha [PGC-1alpha], and CD36) and epithelial cell maturation (Gob-4 and Keratin 20). Additionally, CLA repressed tumor necrosis factor alpha (TNF-alpha) expression and NF-kappaB activation while inducing the immunoregulatory cytokine transforming growth factor a 1 (TGF-beta(1)). Clinically, CLA ameliorated DSS- and CD4(+)-induced colitis. Loss of the PPAR gamma gene in the colon abrogated the beneficial effects of CLA in DSS colitis. Conclusions: Our studies provide molecular evidence in vivo, suggesting that CLA ameliorates colitis through a PPAR gamma-dependent mechanism. C1 Virginia Polytech Inst & State Univ, Lab Nutrit Immunol & Mol Nutr, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA. Virginia Polytech Inst & State Univ, Bioinformat Inst, Blacksburg, VA USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD USA. NCI, Lab Metab, NIH, Bethesda, MD USA. BD Biosci Pharmingen, La Jolla, CA USA. RP Bassaganya-Riera, J (reprint author), Virginia Polytech Inst & State Univ, Lab Nutrit Immunol & Mol Nutr, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA. EM jbassaga@vt.edu NR 78 TC 208 Z9 215 U1 0 U2 20 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2004 VL 127 IS 3 BP 777 EP 791 DI 10.1053/j.gastro.2004.06.049 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 853NO UT WOS:000223834500015 PM 15362034 ER PT J AU Jacoby, RF Cole, CE Hawk, ET Lubet, RA AF Jacoby, RF Cole, CE Hawk, ET Lubet, RA TI Ursodeoxycholate/sulindac combination treatment effectively prevents intestinal adenomas in a mouse model of polyposis SO GASTROENTEROLOGY LA English DT Article ID PRIMARY SCLEROSING CHOLANGITIS; URSODEOXYCHOLIC ACID; COLON-CANCER; CYCLOOXYGENASE-2 INHIBITOR; ULCERATIVE-COLITIS; COLORECTAL-CANCER; F344 RATS; NEOPLASIA; MIN; CHEMOPREVENTION AB Background & Aims: Preclinical studies in animal models, human epidemiological data, and clinical trials in patients with adenomatous polyposis have consistently indicated that sulindac and other nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have the greatest potential efficacy among current candidates for colon tumor chemopreventive agents. However, at highly effective doses they all have some risk of toxicity, and their therapeutic profile might be improved by use at lower, more tolerable doses, in combination with a second agent acting via other mechanisms. Methods: Sulindac was tested in combination with ursodeoxycholic acid (ursodiol), a naturally occurring 7-B-epimer of the bile component chenodeoxycholic acid, for prevention of adenomas in the Min mouse model of adenomatous polyposis. Results: Ursodeoxycholic acid caused a dose-dependent decrease in the number of intestinal tumors. Unlike sulindac and other nonsteroidal anti-inflammatory drugs, which are quite beneficial in the distal intestine but are somewhat less effective in the proximal small intestine (especially the clinically important periampullary duodenum), ursodeoxycholate had equal efficacy throughout the entire intestine, both proximal and distal. Combined treatment with low-dose sulindac was less toxic, with normal weight gain and fewer gastrointestinal ulcerations than high-dose sulindac. Combined treatment with sulindac and ursodeoxycholate was more effective than either agent alone for the prevention of tumors throughout the entire intestine. Conclusions: These experiments provide the first evidence that ursodeoxycholic acid is effective for preventing adenomas in an animal model. Cyclooxygenase inhibition, when combined with this naturally occurring bile component, may become a promising approach for colon cancer prevention. C1 Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Univ Wisconsin, Gastroenterol Sect, Dept Med, Madison, WI USA. NCI, Chemoprevent Branch, Div Canc Prevent, Bethesda, MD USA. RP Jacoby, RF (reprint author), Ctr Clin Sci, 5124,600 Highland Ave, Madison, WI 53792 USA. EM rfjacoby@wisc.edu FU NCI NIH HHS [N01 CN 65122] NR 31 TC 34 Z9 34 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2004 VL 127 IS 3 BP 838 EP 844 DI 10.1053/j.gastro.2004.06.003 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 853NO UT WOS:000223834500020 PM 15362039 ER PT J AU Ghany, MG Doo, EC AF Ghany, MG Doo, EC TI Management of chronic hepatitis B SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID E-ANTIGEN; VIRUS-INFECTION; HBEAG SEROCONVERSION; PHYLOGENETIC RELATEDNESS; HEPATOCELLULAR-CARCINOMA; LAMIVUDINE THERAPY; ANTIVIRAL THERAPY; GENOTYPE-B; IN-VITRO; L-FMAU AB Chronic hepatitis B (CHB) is a major worldwide cause of chronic liver disease and a significant public health issue. Three predominant clinical presentations are recognized: hepatitis B e antigen (HBeAg) or typical CHB, HBeAg-negative or atypical CHB, and inactive CHB. The natural history of CHB infection in an individual may be dominated by one or a combination of these clinical presentations in a sequential fashion. These variations in clinical presentations reflect the viral-host immunology dynamics that form the basis for the development of liver disease. Therapy has been problematic in the past. There are three licensed drugs available for therapy of CHB with varied mechanisms of action. This has introduced the concept of tailored therapy for the individual patient. Many promising new agents and therapeutic approaches should become available in the near future. C1 NIDDKD, Liver Dis Sect, NIH, Bethesda, MD USA. Calif Pacific Med Ctr, Dept Transplantat, San Francisco, CA 94115 USA. RP Ghany, MG (reprint author), NIDDKD, Liver Dis Sect, NIH, Bldg 10,Room 9B-06,10 Ctr Dr,MSC 1800, Bethesda, MD USA. EM marcg@bldg10.niddk.nih.gov NR 59 TC 4 Z9 5 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2004 VL 33 IS 3 BP 563 EP + DI 10.1016/j.gtc.2004.04.007 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 852JU UT WOS:000223752400008 PM 15324944 ER PT J AU Zilberman-Peled, B Benhar, I Coon, SL Ron, B Gothilf, Y AF Zilberman-Peled, B Benhar, I Coon, SL Ron, B Gothilf, Y TI Duality of serotonin-N-acetyltransferase in the gilthead seabream (Sparus aurata): molecular cloning and characterization of recombinant enzymes SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article DE melatonin; serotonin; indoleethylamine; arylalkylamine-N-acetyltransferase; pineal gland; retina; seabream ID FISH PINEAL ORGAN; MELATONIN SYNTHESIS; PROTEASOMAL PROTEOLYSIS; DROSOPHILA-MELANOGASTER; CIRCADIAN REGULATION; TROUT RETINA; EC 2.3.1.87; ZEBRAFISH; GLAND; N-ACETYLTRANSFERASE-2 AB Serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase, AANAT) is the key enzyme in the biosynthesis of melatonin in the pineal gland and retinal photoreceptors. Rhythmic AANAT activity drives rhythmic melatonin production in these tissues. The presence of two AANATs, AANAT1 and AANAT2, has been previously demonstrated in three fresh water teleosts. This duality, the result of early gene duplication, is unique to teleost species. In this study, the cDNAs encoding for AANAT1 and AANAT2 were cloned from a marine fish, the gilthead seabream (sb, Sparus aurata). Northern blot hybridization analysis indicates that sbAANAT1 and sbAANAT2 are exclusively expressed in the retina and pineal gland, respectively. Bacterially expressed recombinant sbAANATs exhibit differential enzyme kinetics. Recombinant retinal sbAANAT1 has relatively high substrate affinity and low activity rate; it is inhibited by high substrate and product concentrations. In contrast, recombinant pineal sbAANAT2 exhibits low substrate affinity and high activity rate and is not inhibited by substrates or products. The two recombinant enzymes also exhibit differential substrate preference. Retinal sbAANAT1 acetylates a range of arylalkylamines while pineal sbAANAT2 preferentially acetylates indoleethylamines, especially serotonin. The different spatial expression patterns, enzyme kinetics, and substrate preferences of the two sbAANATs support the hypothesis that, as a consequence of gene duplication, teleosts have acquired two AANATs with different functions. Pineal AANAT2 specializes in the production of large amounts of melatonin that is released into the circulation and exerts an endocrine role. Retinal AANAT1, on the other hand, is involved in producing low levels of melatonin that execute a paracrine function. In addition, retinal AANAT1 may carry out an as yet unknown function that involves acetylation of arylalkylamines other than serotonin. (C) 2004 Elsevier Inc. All rights reserved. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Ctr Mariculture, Israel Oceanog & Limnol Res Inst, Elat, Israel. RP Gothilf, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. EM yoavg@tauex.tau.ac.il NR 28 TC 27 Z9 28 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD SEP 1 PY 2004 VL 138 IS 2 BP 139 EP 147 DI 10.1016/j.ygcen.2004.05.007 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 848RL UT WOS:000223484700006 PM 15302263 ER PT J AU Bernig, T Taylor, JG Foster, CB Staats, B Yeager, M Chanock, SJ AF Bernig, T Taylor, JG Foster, CB Staats, B Yeager, M Chanock, SJ TI Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection SO GENES AND IMMUNITY LA English DT Review DE mannose-binding lectin; innate immunity; genetic variation; recombination hot spot; gene conversion ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN LIPOPROTEIN-LIPASE; 3' UNTRANSLATED REGION; CLASS-II REGION; LINKAGE DISEQUILIBRIUM; HUMAN GENOME; PROTEIN GENE; HAPLOTYPE BLOCKS; COMPLEMENT ACTIVATION; SERINE-PROTEASE AB Human mannose-binding protein (MBL) is a component of innate immunity. To capture the common genetic variants of MBL2, we resequenced a 10.0 kb region that includes MBL2 in 102 individuals representing four major US ethnic groups. In all, 87 polymorphic sites were observed, indicating a high level of heterozygosity (total pi = 18.3 x 10(-4)). Estimates of linkage disequilibrium across MBL2 indicate that it is divided into two blocks, with a probable recombination hot spot in the 30 end. Three non-synonymous SNPs in exon 1 of the encoding MBL2 gene and three upstream SNPs form common 'secretor haplotypes' that can predict circulating levels. Common variants have been associated with increased susceptibility to infection and autoimmune diseases. The high frequencies of B, C and D alleles in certain populations suggest a possible selective advantage for heterozygosity. There is limited diversity of haplotype structure; the 'secretor haplotypes' lie on a restricted number of extended haplotypes, which could include additional linked SNPs, which might also have possible functional implications. There is evidence for gene conversion in the region between the two blocks, in the last exon. Our data should form the basis for conducting MBL2 candidate gene association studies using a locus-wide approach. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pediat, Div Infect Dis, Baltimore, MD 21218 USA. NCI, Core Genotypeing Facil, Ctr Adv Technol, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM sc83a@nih.gov OI Taylor, James/0000-0002-4421-1809 NR 117 TC 59 Z9 59 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD SEP PY 2004 VL 5 IS 6 BP 461 EP 476 DI 10.1038/sj.gene.6364116 PG 16 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 850QC UT WOS:000223626500004 PM 15306844 ER PT J AU Belfer, I Buzas, B Hipp, H Dean, M Evans, C Lorincz, I Max, MB Goldman, D AF Belfer, I Buzas, B Hipp, H Dean, M Evans, C Lorincz, I Max, MB Goldman, D TI Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans SO GENES AND IMMUNITY LA English DT Article DE single-nucleotide polymorphism; linkage disequilibrium; haplotype; IL1B; IL6; TNF/LTA ID NECROSIS-FACTOR-ALPHA; PROMOTER POLYMORPHISM; INTERLEUKIN-6 GENE; ASSOCIATION; DISEASE; LOCUS; ONSET; BRAIN; RISK AB The major inflammatory cytokines interleukin( IL)1beta, IL6 and tumor necrosis factor alpha (TNFalpha) play a crucial role in infection, inflammation and stress responses. Previously, three coding genes were resequenced, identifying promoter polymorphisms that were used in association studies of neurodegenerative diseases, metabolic disorders and cancer. These studies have produced intriguing but inconsistent results, potentially because the known functional variants: IL1B-511 C>T, IL6-174 G>C and TNF-308 G>A provided an incomplete picture of the total functional diversity at these genes. Therefore, we created marker panels for IL1B, IL6 and TNF/LTA that included the known functional marker but also other markers evenly spaced and with sufficient density to identify haplotype block structure and to maximize haplotype diversity. A total of 26 markers were genotyped in 96 US Caucasians and 96 African Americans. In both populations, a single block with little evidence of historical recombination was observed in IL1B, IL6 and TNF/LTA. For each gene, haplotypes captured the information content of each functional locus, even if that locus was not genotyped, and presumably haplotypes would capture the signal from unknown functional loci whose alleles are of moderate abundance. This study demonstrates the utility of using gene haplotype maps and marker panels as tools for linkage studies on related phenotypes. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, Bethesda, MD USA. NIAAA, Neurogenet Lab, Bethesda, MD USA. NCI, Lab Genom Divers, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Belfer, I (reprint author), NIH, 12420 Parklawn Dr,Suite 451,MSC 8110, Rockville, MD 20852 USA. EM ibelfer@mail.nih.gov RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010; OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405; Hipp, Heather/0000-0002-1089-3928 FU NIAAA NIH HHS [Z01 AA000301]; NIDCR NIH HHS [Z01 DE00366] NR 36 TC 23 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD SEP PY 2004 VL 5 IS 6 BP 505 EP 512 DI 10.1038/sj.gene.6364118 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 850QC UT WOS:000223626500008 PM 15306845 ER PT J AU Walker, GJ Indsto, JO Sood, R Faruque, MU Hu, P Pollock, PM Duray, P Holland, EA Brown, K Kefford, RF Trent, JM Mann, GJ Hayward, NK AF Walker, GJ Indsto, JO Sood, R Faruque, MU Hu, P Pollock, PM Duray, P Holland, EA Brown, K Kefford, RF Trent, JM Mann, GJ Hayward, NK TI Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval SO GENES CHROMOSOMES & CANCER LA English DT Article ID CUTANEOUS MALIGNANT MELANOMAS; CHROMOSOME ARM 1P; HETEROZYGOSITY ANALYSIS; ALLELIC DELETIONS; CELL LINES; REGION; NEUROBLASTOMA; PROGRESSION; 9P; TRANSLOCATION AB Loss of the short arm of chromosome I is frequently observed in many tumor types, including melanoma. We recently localized a third melanoma susceptibility locus to chromosome band Ip22. Critical recombinants in linked families localized the gene to a 15-Mb region between DIS430 and DIS2664. To map the locus more finely we have performed studies to assess allelic loss across the region in a panel of melanomas from Ip22-linked families, sporadic melanomas, and melanoma cell lines. Eighty percent of familial melanomas exhibited loss of heterozygosity (LOH) within the region, with a smallest region of overlapping deletions (SRO) of 9 Mb between DIS207 and DIS435. This high frequency of LOH makes it very likely that the susceptibility locus is a tumor suppressor. In sporadic tumors, four SROs were defined. SRO1 and SRO2 map within the critical recombinant and familial tumor region, indicating that one or the other is likely to harbor the susceptibility gene. However, SRO3 may also be significant because it overlaps with the markers with the highest 2-point LOD score (DIS2776), part of the linkage recombinant region, and the critical region defined in mesothelioma. The candidate genes PRKCL2 and GTF2B, within SRO2, and TGFBR3, CDC7, and EVI5, in a broad region encompassing SRO3, were screened in I p22-linked melanoma kindreds, but no coding mutations were detected. Allelic loss in melanoma cell lines was significantly less frequent than in fresh tumors, indicating that this gene may not be involved late in progression, such as in overriding cellular senescence, necessary for the propagation of melanoma cells in culture. (C) 2004 Wiley-Liss, Inc. C1 Queensland Inst Med Res, Human Genet Lab, Brisbane, Qld 4006, Australia. Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Westmead, NSW 2145, Australia. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Walker, GJ (reprint author), Queensland Inst Med Res, 300 Herston Red, Herston, Qld 4006, Australia. EM graemeW@qimr.edu.au RI Walker, Graeme/C-2548-2012; Mann, Graham/G-4758-2014; hayward, nicholas/C-1367-2015 OI Walker, Graeme/0000-0002-9392-8769; Mann, Graham/0000-0003-1301-405X; hayward, nicholas/0000-0003-4760-1033 NR 30 TC 26 Z9 26 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 2004 VL 41 IS 1 BP 56 EP 64 DI 10.1002/gcc.20056 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 840PA UT WOS:000222870200006 PM 15236317 ER PT J AU Williams, RD Hing, SN Greer, BT Whiteford, CC Wei, JS Natrajan, R Kelsey, A Rogers, S Campbell, C Pritchard-Jones, K Khan, J AF Williams, RD Hing, SN Greer, BT Whiteford, CC Wei, JS Natrajan, R Kelsey, A Rogers, S Campbell, C Pritchard-Jones, K Khan, J TI Prognostic classification of relapsing favorable histology Wilms tumor using cDNA microarray expression profiling and support vector machines SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE-EXPRESSION; BREAST-CANCER; DIFFERENTIAL EXPRESSION; NEPHROBLASTOMA; RECEPTOR; COMPARTMENTS; PREDICTION; PROTEINS; SURVIVAL; SYSTEM AB Treatment of Wilms tumor has a high success rate, with some 85% of patients achieving long-term survival. However, late effects of treatment and management of relapse remain significant clinical problems. If accurate prognostic methods were available, effective risk-adapted therapies could be tailored to individual patients at diagnosis. Few molecular prognostic markers for Wilms tumor are currently defined, though previous studies have linked allele loss on 1p or 16q, genomic gain of 1q, and overexpression from 1q with an increased risk of relapse. To identify specific patterns of gene expression that are predictive of relapse, we used high-density (30 k) cDNA microarrays to analyze RNA samples from 27 favorable histology Wilms tumors taken from primary nephrectomies at the time of initial diagnosis. Thirteen of these tumors relapsed within 2 years. Genes differentially expressed between the relapsing and nonrelapsing tumor classes were identified by statistical scoring (t test). These genes encode proteins with diverse molecular functions, including transcription factors, developmental regulators, apoptotic factors, and signaling molecules. Use of a support vector machine classifier, feature selection, and test evaluation using cross-validation led to identification of a generalizable expression signature, a small subset of genes whose expression potentially can be used to predict tumor outcome in new samples. Similar methods were used to identify genes that are differentially expressed between tumors with and without genomic 1q gain. This set of discriminators was highly enriched in genes on 1q, indicating close agreement between data obtained from expression profiling with data from genomic copy number analyses. (C) 2004 Wiley-Liss, Inc. C1 Inst Canc Res, Sect Paediat Oncol, Sutton SM2 5NG, Surrey, England. NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD USA. Royal Manchester Childrens Hosp, Dept Paediat Pathol, Manchester M27 1HA, Lancs, England. Univ Bristol, Dept Engn Math, Bristol BS8 1TH, Avon, England. RP Williams, RD (reprint author), Inst Canc Res, Sect Paediat Oncol, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England. EM richardw@icr.ac.uk RI Pritchard-Jones, Kathy/F-4286-2014; Khan, Javed/P-9157-2014 OI Pritchard-Jones, Kathy/0000-0002-2384-9475; Khan, Javed/0000-0002-5858-0488 FU NCI NIH HHS [Z01 SC010366-05] NR 53 TC 35 Z9 38 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 2004 VL 41 IS 1 BP 65 EP 79 DI 10.1002/gcc.20060 PG 15 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 840PA UT WOS:000222870200007 PM 15236318 ER PT J AU Schneider, A Guan, YF Zhang, YH Magnuson, MA Pettepher, C Loftin, CD Langenbach, R Breyer, RM Breyer, MD AF Schneider, A Guan, YF Zhang, YH Magnuson, MA Pettepher, C Loftin, CD Langenbach, R Breyer, RM Breyer, MD TI Generation of a conditional allele of the mouse prostaglandin Ep(4) receptor SO GENESIS LA English DT Article DE dinoprostone; ductus arteriosus ID PROSTANOID RECEPTORS; CRE RECOMBINASE; MICE LACKING; EXPRESSION; GENE; CLONING; CYCLOOXYGENASE; SUBTYPES AB Genetic disruption of the mouse EP4 receptor results in perinatal lethality associated with persistent patent ductus areteriosus (PDA). To circumvent this, an EP4 allele amenable to conditional deletion using the Cre/loxP system was generated. The targeting construct was comprised of a floxed exon2 in tandem with the neomycin-resistance gene in intron 2, flanked by third 3' LoxP site. Mice homozygous for the targeted allele (EP4lox+neo/lox+neo), or following its Cre-mediated deletion (EP4del/del), also die within hours of birth with PDA. In contrast, mice homozygous for a partially recombined allele, retaining exon2 but lacking neo (EP4flox/flox), are viable and show no overt phenotype. Postnatal deletion of the floxed EP4 gene is efficiently achieved in the liver and kidney in a transgenic mouse expressing the inducible Mx1Cre recombinase. The EP4flox mouse should provide a useful reagent with which to examine the physiologic roles of the EP4 receptor. (C) 2004 Wiley-Liss, Inc. C1 Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. NIEHS, Dept Canc Biol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Vet Adm Med Ctr, Dept Med, Nashville, TN 37203 USA. RP Breyer, MD (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, S-3223 MCN, Nashville, TN 37232 USA. EM matthew.breyer@vanderbilt.edu RI Magnuson, Mark/B-1335-2009 OI Magnuson, Mark/0000-0002-8824-6499 FU NIDDK NIH HHS [DK-37097] NR 21 TC 40 Z9 40 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD SEP PY 2004 VL 40 IS 1 BP 7 EP 14 DI 10.1002/gene.20048 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 859IV UT WOS:000224257500002 PM 15354288 ER PT J AU Zhang, XM Ng, AHL Tanner, JA Wu, WT Copeland, NG Jenkins, NA Huang, JD AF Zhang, XM Ng, AHL Tanner, JA Wu, WT Copeland, NG Jenkins, NA Huang, JD TI Highly restricted expression cerebellar Purkinje cells SO GENESIS LA English DT Article DE Pcp2; L7; Cre recombinase; BAC; transgenic mouse; cerebellum; Purkinje cells ID RETINAL BIPOLAR NEURONS; TRANSGENE EXPRESSION; DOUBLE REPORTER; MICE; PROTEIN; GENE; RECOMBINATION; CLONING AB The Purkinje neuron, one of the most fascinating components of the cerebellar cortex, is involved in motor learning, motor coordination, and cognitive function. Purkinje cell protein 2 (Pcp2/L7) expression is highly restricted to Purkinje and retinal bipolar cells, where it has been exploited to enable highly specific, Cre recombinase-mediated, site-specific recombination. Previous studies showed that mice carrying a Cre transgene produced by insertion of Cre cDNA into a small 2.88-kb Pcp2 DNA fragment expressed Cre in Purkinje cells; however, some Cre activity was also observed outside the target tissues. Here, we used Red-mediated recombineering to insert Cre cDNA into a 173-kb BAC carrying the entire intact Pcp2 gene, and characterize the resultant BAC/Cre transgenic mice for Cre expression. We show that BAC/Cre transgenic mice have exclusive Cre expression in Purkinje and bipolar cells and nowhere else. These mice will facilitate Purkinje cell and retinal bipolar cell-specific genetic manipulation. (C) 2004 Wiley-Liss, Inc. C1 Univ Hong Kong, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Anat, Hong Kong, Hong Kong, Peoples R China. NCI, Canc Res Ctr, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Huang, JD (reprint author), Univ Hong Kong, Dept Biochem, Fac Med Bldg,21 Sassoon Rd,Pokfulam, Hong Kong, Hong Kong, Peoples R China. EM jdhuang@hkucc.hku.hk RI Tanner, Julian/C-4412-2009 OI Tanner, Julian/0000-0002-5459-1526 NR 24 TC 27 Z9 27 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD SEP PY 2004 VL 40 IS 1 BP 45 EP 51 DI 10.1002/gene.20062 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 859IV UT WOS:000224257500007 PM 15354293 ER PT J AU Schneider, KA DiGianni, LM Patenaude, AF Klar, N Stopfer, JE Calzone, DA Li, FP Weber, BL Garber, JE AF Schneider, KA DiGianni, LM Patenaude, AF Klar, N Stopfer, JE Calzone, DA Li, FP Weber, BL Garber, JE TI Accuracy of cancer family histories: Comparison of two breast cancer syndromes SO GENETIC TESTING LA English DT Article ID COLORECTAL-CANCER; COLON-CANCER; VALIDATION AB Cancer risk programs rely on accurately reported family history information. This study compares the accuracy with which cancer sites and ages at diagnosis are reported by Li-Fraumeni syndrome (LFS) and hereditary breast-ovarian cancer syndrome (HBOCS) families undergoing genetic testing. We analyzed the accuracy of 191 cancer diagnoses among first-degree (FDRs) and second-degree (SDRs) relatives reported by 32 LFS and 52 HBOCS participants in genetic testing programs. Cancer diagnoses of relatives were more accurately reported in the HBOCS cohort (78%) than in the LFS cohort (52%). Almost all breast cancer diagnoses were accurately reported, whereas 74% of ovarian cancer diagnoses and only 55% of other LFS-related cancers were accurately reported. Age at diagnosis was accurate within 5 years for 60% of LFS relatives and 53% of HBOCS relatives. Factors correlating with accurate reporting of cancer history included: being member of BRCA1 family, higher education level, female historian, degree of closeness to affected relative, and having fewer than 5 affected FDRs and SDRs. Relying on verbal histories would not have altered eligibility for genetic testing among HBOCS historians, but fewer than half of LFS historians provided information that would have led to TP53 testing. Our data suggest that it may not be necessary to confirm breast cancer diagnoses routinely; however, documentation of other cancer types remains important for appropriate risk assessment and follow-up. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Care Ontario, Div Pediat Oncol, Toronto, ON M5G 2L7, Canada. Univ Penn, Canc Risk Evaluat Program, Philadelphia, PA 19104 USA. Univ Penn, Dept Med & Genet, Philadelphia, PA 19104 USA. NCI, CCR, Genet Branch, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Schneider, KA (reprint author), Dana Farber Canc Inst, 44 Binney St SM335, Boston, MA 02115 USA. EM Katherine_Schneider@dfci.harvard.edu FU NHGRI NIH HHS [5R01 HG00725, 5R01 HG01244] NR 19 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2004 VL 8 IS 3 BP 222 EP 228 DI 10.1089/gte.2004.8.222 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 875QR UT WOS:000225437300002 PM 15727243 ER PT J AU Ogino, S Wilson, RB Gold, B Hawley, P Grody, WW AF Ogino, S Wilson, RB Gold, B Hawley, P Grody, WW TI Bayesian analysis for cystic fibrosis risks in prenatal and carrier screening SO GENETICS IN MEDICINE LA English DT Article DE CFTR; counseling; cystic fibrosis; probability; screening AB Purpose: Risk assessment is an essential component of genetic counseling and testing, and Bayesian analysis plays a central role in complex risk calculations. We previously developed generalizable Bayesian methods to calculate the autosomal recessive disease risk of a fetus when one or no mutation is detected, and another, independent risk factor is present. Our methods are particularly useful for calculating the CF disease risk for a fetus with echogenic bowel. In genetics practice, however, there are other scenarios for which our previous methods are inadequate. Methods and Results: We provide herein methods for calculating genetic risks in a variety of common clinical scenarios. These scenarios include the following: (1) different mutation panels that have been used for the parents and for a fetus; (2) genetic testing results available on the proband or other relatives, in addition to the consultand; (3) fetal ultrasound negative for echogenic bowel with a positive family history; and (4) a consultand with a mixed ethnic background. Conclusion: Our Bayesian methods have proven their versatility through application to many different common genetic counseling scenarios. These methods permit autosomal recessive disease and carrier probabilities to be calculated accurately, taking into account all relevant information. Our methods allow accurate genetic risk estimates for patients and their family members for CF or other autosomal recessive disorders. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Penn, Ctr Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Human Genet Sect, Lab Genomic Divers, Frederick, MD 21701 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Lab Med Human Genet & Pediat, Los Angeles, CA 90024 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu NR 13 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD SEP-OCT PY 2004 VL 6 IS 5 BP 439 EP 449 DI 10.1097/01.GIM.0000139511.83336.8F PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 855HZ UT WOS:000223965400008 PM 15371910 ER PT J AU Templeton, TJ Iyer, LM Anantharaman, V Enomoto, S Abrahante, JE Subramanian, GM Hoffman, SL Abrahamsen, MS Aravind, L AF Templeton, TJ Iyer, LM Anantharaman, V Enomoto, S Abrahante, JE Subramanian, GM Hoffman, SL Abrahamsen, MS Aravind, L TI Comparative analysis of apicomplexa and genomic diversity in eukaryotes SO GENOME RESEARCH LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; PHYLOGENETIC ANALYSIS; HUMAN ERYTHROCYTES; TOXOPLASMA-GONDII; PROTEIN; EXPRESSION; CRYPTOSPORIDIUM; FAMILY; SEQUENCES; ENCODE AB The apicomplexans Plasmodium and Cryptosporidium have developed distinctive adaptations via lineage-specific gene loss and gene innovation in the process of diverging from a common parasitic ancestor. The two lineages have acquired distinct but overlapping sets of surface protein adhesion domains typical of animal proteins, but in no case do they share multidomain architectures identical to animals. Cryptosporidium, but not Plasmodium, possesses all animal-type O-linked glycosylation pathway, along with >30 predicted surface proteins having mucin-like segments. The two parasites have notable qualitative differences in conserved protein architectures associated with chromatin dynamics and transcription. Cryptosporidium shows considerable reduction in the number of introns and a concomitant loss of spliceosomal machinery components. We also describe additional molecular characteristics distinguishing Apicomplexa from other eukaryotes for which complete genome sequences are available. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY 10021 USA. Cornell Univ, Program Immunol & Microbial Pathogenesis, Weill Grad Sch Med Sci, New York, NY 10021 USA. Univ Minnesota, Dept Vet Pathobiol, St Paul, MN 55108 USA. Univ Minnesota, Biomed Genom Ctr, St Paul, MN 55108 USA. Human Genome Sci, Rockville, MD 20850 USA. Sanaria Inc, Rockville, MD 20852 USA. RP Templeton, TJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM tjt2001@med.cornell.edu; aravind@ncbi.nlm.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 NR 50 TC 123 Z9 134 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2004 VL 14 IS 9 BP 1686 EP 1695 DI 10.1101/gr.2615304 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 851HJ UT WOS:000223675900002 PM 15342554 ER PT J AU Casimiro, MC Knollmann, BC Yamoah, EN Nie, LP Vary, JC Sirenko, SG Greene, AE Grinberg, A Huang, SP Ebert, SN Pfeifer, K AF Casimiro, MC Knollmann, BC Yamoah, EN Nie, LP Vary, JC Sirenko, SG Greene, AE Grinberg, A Huang, SP Ebert, SN Pfeifer, K TI Targeted point mutagenesis of mouse Kcnq1: phenotypic analysis of mice with point mutations that cause Romano-Ward syndrome in humans SO GENOMICS LA English DT Article DE Romano-Ward syndrome; RWS; JLNS; long QT; Kcnq1; mice; genetics; deafness ID LONG-QT SYNDROME; VESTIBULAR DARK CELLS; POTASSIUM CHANNEL GENE; LANGE-NIELSEN-SYNDROME; CARDIAC-ARRHYTHMIA; MOLECULAR-BASIS; NULL MUTATION; SUDDEN-DEATH; K+ SECRETION; KVLQT1 AB Inherited long QT syndrome is most frequently associated with mutations in KCNQ1, which encodes the primary subunit of a potassium channel. Patients with mutations in KCNQ1 may show only the cardiac defect (Romano-Ward syndrome or RWS) or may also have severe deafness (Jervell and Lange-Nielsen syndrome or JLNS). Targeted disruption of mouse Kcnq1 models JLNS in that mice are deaf and show abnormal ECGs. However, the phenotype is broader than that seen in patients. Most dramatically, the inner ear defects result in a severe hyperactivity/circling behavior, which may influence cardiac function. To understand the etiology of the cardiac phenotype in these mice and to generate a potentially more useful model system, we generated new mouse lines by introducing point mutations associated with RWS. The A340E line phenocopies RWS: the repolarization phenotype is inherited in a dominant manner and is observed independent of any inner ear defect. The T3III line phenocopies JLNS, with deafness associated with inner hair cell malfunction. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHD, Lab Mammalian Genes & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Univ Calif Davis, Ctr Neurosci, Dept Otolaryngol, Davis, CA 95616 USA. Howard Hughes Med Inst, NIH, Res Scholar Program, Bethesda, MD 20872 USA. RP Pfeifer, K (reprint author), NICHD, Lab Mammalian Genes & Dev, Natl Inst Hlth, Bldg 6B,Room 2B-206,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pfeiferk@mail.nih.gov OI Knollmann, Bjorn/0000-0003-4956-9735; Pfeifer, Karl/0000-0002-0254-682X FU NHLBI NIH HHS [R01 HL071670]; NIDCD NIH HHS [DC04215, DC03828] NR 48 TC 34 Z9 34 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2004 VL 84 IS 3 BP 555 EP 564 DI 10.1016/j.ygeno.2004.06.007 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 847QD UT WOS:000223409100011 PM 15498462 ER PT J AU Tuohy, TMF Wallingford, N Liu, Y Chan, FH Rizvi, T Xing, RB Bebo, B Rao, MS Sherman, LS AF Tuohy, TMF Wallingford, N Liu, Y Chan, FH Rizvi, T Xing, RB Bebo, B Rao, MS Sherman, LS TI CD44 overexpression by oligodendrocytes: A novel mouse, model of inflammation-independent demyelination and dysmyelination SO GLIA LA English DT Article DE CD44; oligodendrocyte; Schwann cell; demyelination; dysmyelination ID INVASION IN-VITRO; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TUMOR-CELL INVASION; NERVOUS-SYSTEM; HYALURONAN-BINDING; WHITE-MATTER; MONOCLONAL-ANTIBODY; T-CELLS; EXPRESSION; GROWTH AB The CD44 transmembrane glycoprotein family has been implicated in cell-cell adhesion and cell signaling in response to components Of the extracellular matrix but its role in the nervous system is not understood. CD44 proteins are elevated in Schwann cells and oligodendrocytes following nervous system insults, in inflammatory demyelinating lesions, and in tumors. Here, we tested the hypothesis that elevated CD44 expression influences Schwann cell and oligodendrocyte functions by generating transgenic mice that express CD44 under the control of the 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) promoter. These mice failed to develop peripheral nerve or CNS tumors. However, they did develop severe tremors that were associated with CNS dysmyelination and progressive demyelination. Loss of CNS myelin was not due to alterations in early oligodendrocyte precursor differentiation, proliferation, or survival. Myelinatior. in the PNS appeared normal. In no instance was there and evidence of an inflammatory response that could account for the loss of CNS myelin. These findings suggest that CNPase-CD44 mice are a novel model for noninflammatory progressive demyelinating disease and support a potential role for CD44 proteins expressed by glial cells in promoting demyelination. (C) 2004 Wiley-Liss, Inc. C1 Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR 97006 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Univ Cincinnati, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH USA. Oregon Hlth & Sci Univ, Inst Neurol Sci, Beaverton, OR USA. RP Sherman, LS (reprint author), Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, 505 NW 185th Ave, Beaverton, OR 97006 USA. EM ShermanL@ohsu.edu RI Tuohy, Therese/A-8665-2009 FU NINDS NIH HHS [NS39550] NR 53 TC 28 Z9 28 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2004 VL 47 IS 4 BP 335 EP 345 DI 10.1002/glia.20042 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 849AB UT WOS:000223508500004 PM 15293231 ER PT J AU Bianco, C Normanno, N Salomon, DS Ciardiello, F AF Bianco, C Normanno, N Salomon, DS Ciardiello, F TI Role of the cripto (EGF-CFC) family in embryogenesis and cancer SO GROWTH FACTORS LA English DT Review ID MAMMARY EPITHELIAL-CELLS; CERVICAL-CARCINOMA CELLS; EMBRYONIC STEM-CELLS; GROWTH-FACTOR; VERTEBRATE DEVELOPMENT; TYROSINE PHOSPHORYLATION; BREAST-CANCER; TUMOR-GROWTH; GENE FAMILY; EXPRESSION C1 Univ Naples 2, Cattedra Oncol Med, Dipartimento Medicochirurg Internist Clin & Speri, I-80131 Naples, Italy. NCI, Tumor Growth Sect, Mammary Biol & Tumorgenesis Lab, NIH, Bethesda, MD 20892 USA. Ist Tumori Napoli Fdn Pascale, I-80131 Naples, Italy. RP Ciardiello, F (reprint author), Univ Naples 2, Cattedra Oncol Med, Dipartimento Medicochirurg Internist Clin & Speri, Via S Pansini 5, I-80131 Naples, Italy. EM fortunato.ciardiello@unina2.it OI Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 45 TC 21 Z9 24 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PD SEP PY 2004 VL 22 IS 3 BP 133 EP 139 DI 10.1080/08977190410001723290 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 863KN UT WOS:000224560600002 PM 15518236 ER PT J AU Prunier, C Hocevar, BA Howe, PH AF Prunier, C Hocevar, BA Howe, PH TI Wnt signaling: Physiology and pathology SO GROWTH FACTORS LA English DT Review DE Wnt signaling; axin; signal transduction; antagonists ID ADENOMATOUS POLYPOSIS-COLI; APC TUMOR-SUPPRESSOR; PROTEIN PHOSPHATASE 2A; CONVERGENT EXTENSION MOVEMENTS; BETA-CATENIN FUNCTION; KINASE I-EPSILON; F-BOX PROTEIN; AXIS FORMATION; NUCLEAR EXPORT; NEGATIVE REGULATOR AB Signaling by the Wnt family of secreted glycoproteins has been demonstrated to be essential both in normal embryonic development and in the pathogenesis of a variety of diseases, including cancer. This signaling pathway is exquisitely regulated by a large and complex array of proteins, which act as agonists or antagonists of signal transduction, modulating the Wnt signal extracellularly, in the cytoplasm and in the nucleus. Here, we will briefly review the canonical Wnt signaling pathway and consider molecular defects in Wnt signaling components known to promote uncontrolled cell growth following induction of Wnt signaling. We will also focus on two recently identified factors in this pathway, that seem to act as Wnt signaling antagonists, one functioning in the cytoplasm called Disabled-2 and the other in the nucleus named Chibby. C1 Cleveland Clin Fdn, Cleveland Clin Lerner Coll Med, Dept Cell Biol, NCI, Cleveland, OH 44195 USA. RP Howe, PH (reprint author), Cleveland Clin Fdn, Cleveland Clin Lerner Coll Med, Dept Cell Biol, NCI, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM howep@ccf.org FU NCI NIH HHS [CA55536, CA80095] NR 128 TC 66 Z9 72 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PD SEP PY 2004 VL 22 IS 3 BP 141 EP 150 DI 10.1080/08977190410001720860 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 863KN UT WOS:000224560600003 PM 15518237 ER PT J AU Theodore, D Fried, MW Kleiner, DE Kroner, BL Goedert, JJ Eyster, ME Faust, SP Sherman, KE Kessler, CM Francis, C Aledort, LM AF Theodore, D Fried, MW Kleiner, DE Kroner, BL Goedert, JJ Eyster, ME Faust, SP Sherman, KE Kessler, CM Francis, C Aledort, LM TI Liver biopsy in patients with inherited disorders of coagulation and chronic hepatitis C SO HAEMOPHILIA LA English DT Review DE complications; haemophilia; hepatitis C; liver biopsy ID INJECTION-DRUG USERS; BLEEDING DISORDERS; VIRUS-INFECTION; VIRAL-HEPATITIS; UNITED-STATES; NATURAL-HISTORY; PLUS RIBAVIRIN; HEMOPHILIA; COMPLICATIONS; DISEASE AB Liver biopsy plays a pivotal role in the management of patients with a variety of liver diseases, including chronic hepatitis C virus. The major risk of the procedure is the potential for significant haemorrhagic complications. Although the data are limited, the procedure does not appear to pose excessive risk to the patient with inherited disorders of coagulation, provided that adequate haemostasis can be achieved prior to the liver biopsy. This requires close coordination of care between the hepatologist and the haematologist. Indications for liver biopsy should be the same in patients with haemophilia as in other populations. C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ N Carolina, Chapel Hill, NC USA. NCI, Bethesda, MD 20892 USA. RTI Int, Rockville, MD USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. Hemophilia Georgia, Atlanta, GA USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Aledort, LM (reprint author), CUNY Mt Sinai Sch Med, 1 Gustave L Levy Pl,POB 1006, New York, NY 10029 USA. EM louis.aledort@mssm.edu OI Kleiner, David/0000-0003-3442-4453 FU NCI NIH HHS [N01-CP-01004]; NHLBI NIH HHS [R01 HL 64817-01]; NIAID NIH HHS [R01 AI 49508-01] NR 48 TC 15 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2004 VL 10 IS 5 BP 413 EP 421 DI 10.1111/j.1365-2516.2004.00919.x PG 9 WC Hematology SC Hematology GA 852ME UT WOS:000223758600001 PM 15357765 ER PT J AU Herrick, EK Nussbaum, R Holtzman, NA Wissow, L AF Herrick, EK Nussbaum, R Holtzman, NA Wissow, L TI Asking fathers: a study of psychosocial adaptation SO HAEMOPHILIA LA English DT Article DE haemophilia A/B; marital adjustment; Marital Adjustment Test; parenting satisfaction; Parenting Sense of Competence; paternal adaptation; psychosocial ID HEMOPHILIC BOYS; CHILDREN; PARENTS; BEHAVIOR; FAMILIES; STRESS AB Although few contemporary studies specifically address paternal adaptation, the theme of paternal estrangement from medical care and from family relationships is pervasive in the psychosocial literature on haemophilia. This estrangement has been shown to have a negative effect on fathers' psychological well-being, marital relationships and the adaptive outcome of their sons who have haemophilia. The goals of this study were to provide contemporary data on the psychosocial adaptation of fathers of boys with haemophilia and to examine specific variables that might influence their adjustment. Eighty-three eligible fathers returned a survey instrument that collected demographic and medical information, as well as scores on self-measures of adaptation in marital and parenting roles. Statistically significant direct correlations (P < 0.01) were found between fathers' scores on the Marital Adjustment Test and the Parenting Sense of Competence subscales (parenting efficacy and satisfaction). Variables specific to rearing a son with haemophilia that negatively affected fathers' marital adjustment scores included: feeling left out of medical decision making by their wives or partners, worry about their sons' having limited activity, and the presence of a secondary diagnosis in the affected child. Scores on the parenting efficacy subscale of the PSOC were statistically significantly reduced (i.e. fathers felt less effective in the parenting role) in men who 'rarely' or 'never' infused their sons (42/80, 53%). Variables that negatively affected scores on the parenting satisfaction subscale included frustrating interactions with medical staff and concern about their sons' potential to contract an infection or secondary diagnosis. This paper presents a model to examine the interrelationships among the data and discusses the clinical implications. C1 Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. NHGRI, Joint Masters Degree Program Genet Counseling, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. NHGRI, Inherited Dis Res Branch, Div Intramural Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. RP Herrick, EK (reprint author), Natl Coalit Hlth Profess Educ Genet, 2360 W Joppa Rd,Suite 320, Lutherville Timonium, MD 21093 USA. EM ekherrick@nchpeg.org NR 16 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2004 VL 10 IS 5 BP 582 EP 589 DI 10.1111/j.1365-2516.2004.00958.x PG 8 WC Hematology SC Hematology GA 852ME UT WOS:000223758600023 PM 15357787 ER PT J AU Bellg, AJ Borrelli, B Resnick, B Hecht, J Minicucci, DS Ory, M Ogedegbe, G Orwig, D Ernst, D Czajkowski, S AF Bellg, AJ Borrelli, B Resnick, B Hecht, J Minicucci, DS Ory, M Ogedegbe, G Orwig, D Ernst, D Czajkowski, S TI Enhancing treatment fidelity in health behavior change studies: Best practices and recommendations from the NIH behavior change consortium SO HEALTH PSYCHOLOGY LA English DT Article DE treatment fidelity; health behavior; translational research; reliability; validity AB Treatment fidelity refers to the methodological strategies used to monitor and enhance the reliability and validity of behavioral interventions. This article describes a multisite effort by the Treatment Fidelity Workgroup of the National Institutes of Health Behavior Change Consortium (BCC) to identify treatment fidelity concepts and strategies in health behavior intervention research. The work group reviewed treatment fidelity practices in the research literature, identified techniques used within the BCC, and developed recommendations for incorporating these practices more consistently. The recommendations cover study design, provider training, treatment delivery, treatment receipt, and enactment of treatment skills. Funding agencies, reviewers, and journal editors are encouraged to make treatment fidelity a standard part of the conduct and evaluation of health behavior intervention research. C1 Appleton Heart Inst, Appleton Cardiol Assoc, Appleton, WI 54911 USA. Brown Univ, Sch Med, Ctr Behav & Prevent Med, Providence, RI 02912 USA. Univ Maryland, Sch Nursing, College Pk, MD 20742 USA. Univ Rochester, Sch Nursing, Rochester, NY 14627 USA. NIA, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ New Mexico, Dept Family Practice, Albuquerque, NM 87131 USA. NHLBI, NIH, Bethesda, MD USA. RP Bellg, AJ (reprint author), Appleton Heart Inst, Appleton Cardiol Assoc, 1818 N Meade St, Appleton, WI 54911 USA. EM albert.bellg@thedacare.org FU NHLBI NIH HHS [R01 HL62165] NR 12 TC 542 Z9 545 U1 6 U2 47 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2004 VL 23 IS 5 BP 443 EP 451 DI 10.1037/0278-6133.23.5.443 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 849LY UT WOS:000223541300001 PM 15367063 ER PT J AU Lutgendorf, SK Russell, D Ullrich, P Harris, TB Wallace, R AF Lutgendorf, SK Russell, D Ullrich, P Harris, TB Wallace, R TI Religious participation, interleukin-6, and mortality in older adults SO HEALTH PSYCHOLOGY LA English DT Article DE religious participation; mortality; aging; interleukin-6; cytokines; Iowa 65+Rural Health Study ID C-REACTIVE PROTEIN; PITUITARY-ADRENAL AXIS; NECROSIS-FACTOR-ALPHA; SOCIAL RELATIONSHIPS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RHEUMATOID-ARTHRITIS; DEPRESSIVE SYMPTOMS; PHYSICAL HEALTH; RISK-FACTORS AB This study prospectively examined the relationship between religious attendance, interleukin-6 (IL-6) levels, and mortality rates in a community-based sample of 557 older adults. Attending religious services more than once weekly was a significant predictor of lower subsequent 12-year mortality and elevated IL-6 levels (> 3.19 pg/mL), with a mortality ratio of .32 (95% confidence interval [CI] = 0.15, 0.72; p < .01) and an odds ratio for elevated IL-6 of .34 (95% CI = 0.16, 0.73, p <. 01), compared with never attending religious services. Structural equation modeling indicated religious attendance was significantly related to lower mortality rates and IL-6 levels, and IL-6 levels mediated the prospective relationship between religious attendance and mortality. Results were independent of covariates including age, sex, health behaviors, chronic illness, social support, and depression. Findings are consistent with a role for IL-6 in processes mediating the relationship between religious attendance and mortality. C1 Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Iowa State Univ, Dept Human Dev & Family Studies, Ames, IA USA. Iowa State Univ, Inst Social & Behav Res, Ames, IA USA. NIA, Geriatr Epidemiol Sect, Lab Epidemiol Demograph & Biomet, Bethesda, MD 20892 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. RP Lutgendorf, SK (reprint author), Univ Iowa, Dept Psychol, E11 Seashore Hall, Iowa City, IA 52242 USA. EM susan-lutgendorf@uiowa.edu RI Russell, Daniel/A-7559-2013 OI Russell, Daniel/0000-0003-2264-861X FU NCI NIH HHS [1R21CA88293]; NIA NIH HHS [AG-0-2106]; NIMH NIH HHS [MH62666] NR 82 TC 55 Z9 56 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2004 VL 23 IS 5 BP 465 EP 475 DI 10.1037/0278-6133.23.5.465 PG 11 WC Psychology, Clinical; Psychology SC Psychology GA 849LY UT WOS:000223541300004 PM 15367066 ER PT J AU Davis, LL Vitale, KA Irmiere, CA Hackney, TA Belew, KM Chikowski, AMR Sullivan, CA Hellkamp, AS Schron, EB Lamas, GA AF Davis, LL Vitale, KA Irmiere, CA Hackney, TA Belew, KM Chikowski, AMR Sullivan, CA Hellkamp, AS Schron, EB Lamas, GA CA Mode Selection Trial Sinus Node TI Body image changes associated with dual-chamber pacemaker insertion in women SO HEART & LUNG LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; QUALITY-OF-LIFE; RECIPIENTS; ADAPTATION; ACCEPTANCE; PATIENT AB PURPOSE: The study's purpose was to examine body image changes in subjects participating in a long-term multicenter pacemaker trial. METHODS: At study closeout, 383 adults, all of whom had received a dual-chamber pacemaker, completed questionnaires evaluating what effect their pacemaker or pacemaker site and scar had on them or their spouses or significant others. RESULTS: Most reported that their pacemaker did not change the way they or their spouses or significant others felt about their body (73.2% and 93.5%, respectively). Most (87.1%) denied feeling differently because of the pacemaker site and scar. Most were not concerned how their clothes fit or about wearing a swimsuit (92.0% and 90.7%, respectively). Women were more concerned about how the pacemaker site and scar made them feel about their body (P =.001), clothes fitting (P =.002), and wearing a swimsuit (P =.004). Men were more concerned with how their spouses or significant others perceived them postimplantation (P =.021). CONCLUSIONS: Most subjects did not express undue concern about changes in body image. C1 Univ N Carolina, Chapel Hill, NC 27599 USA. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. St Josephs Hosp, Paterson, NJ USA. Alamance Reg Med Ctr, Burlington, NC USA. Univ Missouri, Columbia, MO USA. Main Line Hlth Heart Ctr, Wynnewood, PA USA. Univ Community Hosp, Tampa, FL USA. Duke Clin Res Inst, Durham, NC USA. NHLBI, Clin Trials Sci Res Grp, Bethesda, MD 20892 USA. RP Davis, LL (reprint author), Univ N Carolina, CB 7460,Carrington Hall, Chapel Hill, NC 27599 USA. NR 16 TC 9 Z9 9 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD SEP-OCT PY 2004 VL 33 IS 5 BP 273 EP 280 DI 10.1016/j.hrtlng.2004.04.005 PG 8 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 860FT UT WOS:000224328600001 PM 15454905 ER PT J AU Kresina, TF Seeff, LB Francis, H AF Kresina, TF Seeff, LB Francis, H TI Hepatitis C infection and injection drug use: The role of hepatologists in evolving treatment efforts SO HEPATOLOGY LA English DT Editorial Material ID VIRUS-INFECTION; ADDICTION TREATMENT; OPIOID DEPENDENCE; CARE; HIV; INDIVIDUALS; MANAGEMENT; PROGRAMS AB Treatment regimens for both substance abuse and hepatitis C infection are complex and evolving. New pharmacotherapy for opioid addiction allows for office-based treatment and, thus, an opportunity for expanded treatment in the context of hepatitis C infection. The current article addresses the newly evolving, complex issues in the medical management of hepatitis C and injection drug use. C1 NIDA, Ctr AIDS & Med Other Consequences Drug Abuse, Bethesda, MD 20892 USA. NIDDKD, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Kresina, TF (reprint author), NIDA, Ctr AIDS & Med Other Consequences Drug Abuse, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM tk13v@nih.gov NR 39 TC 4 Z9 4 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2004 VL 40 IS 3 BP 516 EP 519 DI 10.1002/hep.20367 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 851KR UT WOS:000223684500003 PM 15349886 ER PT J AU Kamiya, A Gonzalez, FJ AF Kamiya, A Gonzalez, FJ TI TNF-alpha regulates mouse fetal hepatic maturation induced by oncostatin M and extracellular matrices SO HEPATOLOGY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; NF-KAPPA-B; DEFICIENT LIVER-REGENERATION; MICE LACKING TYPE-1; EMBRYONIC LETHALITY; HEPATOCYTE DIFFERENTIATION; RAT HEPATOCYTES; KNOCKOUT MICE; IN-VITRO; GENE AB Fetal hepatic maturation consists of multisteps and is regulated by several cytokines and cell-cell or cell-matrices interactions. In the mid-to-late fetal stage, hepatocytes have few metabolic functions associated with adult liver homeostasis. Cultured fetal hepatocytes acquire the expression of several mature liver-specific genes through stimulation with hepatic maturation factor oncostatin M (OSM) and matrigel. Tumor necrosis factor-alpha (TNFalpha) regulates fetal hepatic maturation stimulated by OSM and matrigel. TNFalpha suppressed expression of mature liver-specific genes such as tyrosine aminotransferase and apolipoproteins. In addition, the expression of hematopoietic cytokines and cyclin A2, repressed by OSM and matrigel, is induced by TNFalpha in the fetal hepatic cultures coincident with cell division. TNFalpha inhibited the induction of hepatocyte nuclear factor 4alpha induced by OSM and matrigel, suggesting that down-regulation of hepatocyte nuclear factor 4alpha expression is involved in the mechanism of suppression of hepatic maturation by TNFalpha. Interestingly, TNFalpha is expressed in the prenatal and postnatal liver but not in adult liver, whereas TNFR1, a TNFalpha receptor, is expressed in both fetal and adult livers. In conclusion, TNFalpha is a suppressive factor of hepatic maturation. The balance between hepatic maturation factor (OSM and extracellular matrices) and TNFalpha is important for liver development. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106B,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 42 TC 29 Z9 32 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2004 VL 40 IS 3 BP 527 EP 536 DI 10.1002/hep.20362 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 851KR UT WOS:000223684500007 PM 15349890 ER PT J AU Sanchez, A Factor, VM Espinoza, LA Schroeder, I Thorgeirsson, SS AF Sanchez, A Factor, VM Espinoza, LA Schroeder, I Thorgeirsson, SS TI In vitro differentiation of rat liver derived stem cells results in sensitization to TNF alpha-mediated apoptosis SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; HEPATIC PROGENITOR CELLS; OVAL CELLS; GLUTATHIONE DEPLETION; OXIDATIVE STRESS; CYTOCHROME-C; HEPATOCYTE APOPTOSIS; MOUSE HEPATOCYTES; EPITHELIAL-CELLS AB Hepatic stem cells are activated after liver damage and have a critical role in tissue homeostasis and repair. Characterization of molecular and cellular events accompanying the expansion and differentiation of liver stem cells is essential for understanding the basic biology of stem cells and for facilitating clinical application of the stem cells. We assessed whether in vitro differentiation of putative hepatic progenitor (rat liver epithelial [RLE]) cells toward hepatocytic lineage affects the response to TNFalpha-mediated cytotoxicity, a common determinant of liver injury. The data show that 50% of differentiated cells underwent apoptosis after 6 hours of TNFalpha treatment whereas control RLE cells were resistant. Both cell types displayed mitochondrial depolarization and release of cytochrome c but the TNFalpha treatment resulted in activation of caspases 9 and 3 and the execution of apoptosis only in differentiated RLE cells. Apoptotic death was associated with increased ROS production and depletion of glutathione. Antioxidants completely prevented both glutathione depletion and apoptosis induced by TNFalpha in differentiated RLE cells. Conversely, glutathione-depleting agents sensitized control RLE cells to TNFalpha induced apoptosis. In conclusion, efficient antioxidant defense system involving glutathione renders hepatic progenitor cells resistant to TNFalpha-mediated apoptosis and acquisition of sensitivity to death stimuli is an implicit feature of the differentiation process. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr MSC 4258,Bldg 37,Room 3C28, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov RI Sanchez, Aranzazu/H-7810-2015 OI Sanchez, Aranzazu/0000-0001-9145-6633 NR 50 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2004 VL 40 IS 3 BP 590 EP 599 DI 10.1002/hep.20363 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 851KR UT WOS:000223684500014 PM 15349897 ER PT J AU Lee, JS Chu, IS Heo, J Calvisi, DF Sun, ZT Roskams, T Durnez, A Demetris, AJ Thorgeirsson, SS AF Lee, JS Chu, IS Heo, J Calvisi, DF Sun, ZT Roskams, T Durnez, A Demetris, AJ Thorgeirsson, SS TI Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling SO HEPATOLOGY LA English DT Article ID B-CELL LYMPHOMA; NATURAL-HISTORY; CANCER; PROGNOSIS; PROTEIN; SET; IDENTIFICATION; SURVEILLANCE; MICROARRAY; RECURRENCE AB We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods. We also identified the genes most strongly associated with survival by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification, suggesting an etiological involvement of these processes in accelerating the progression of HCC. In conclusion, the biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g., HIF1a) for selective treatment of HCC patients. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Natl Lab Mol Oncol, Beijing 100021, Peoples R China. Katholieke Univ Leuven, Dept Morphol, Louvain, Belgium. Katholieke Univ Leuven, Dept Mol Pathol & Hepatol, Louvain, Belgium. Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplant Inst, Pittsburgh, PA USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 39 TC 456 Z9 470 U1 1 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2004 VL 40 IS 3 BP 667 EP 676 DI 10.1002/hep.20375 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 851KR UT WOS:000223684500023 PM 15349906 ER PT J AU Eck, P Erichsen, HC Taylor, JG Yeager, M Hughes, AL Levine, M Chanock, SJ AF Eck, P Erichsen, HC Taylor, JG Yeager, M Hughes, AL Levine, M Chanock, SJ TI Comparison of the genomic structure and variation in the two human sodium-dependent vitamin C transporters, SLC23A1 and SLC23A2 SO HUMAN GENETICS LA English DT Article ID RECOMMENDED DIETARY ALLOWANCE; ASCORBIC-ACID; DEHYDROASCORBIC ACID; STATISTICAL-METHOD; HUMAN NEUTROPHILS; GENETIC-VARIATION; INDIVIDUALITY; EVOLUTIONARY; MUTATIONS; CLONING AB Vitamin C (L-ascorbic acid) is an essential co-factor for eight mammalian enzymes and quenches reactive oxygen species. Sodium-dependent vitamin C transport is mediated by two transporters, SVCT 1 and SVCT 2, encoded by SLC23A1 and SLC23A2. We characterized the genomic structures of SLC23A1 and SLC23A2, determined the extent of genetic variation and linkage disequilibrium across each gene, analyzed nucleotide diversity to estimate the effect of selective pressure, and compared sequence variation across species. In SLC23A1, the majority of single micleotide polymorphisms (SNPs) are population-specific in either African Americans or Caucasians, including three of four non-synonymous SNPs. In contrast, most SNPs in SLC23A2 are shared between African Americans and Caucasians, and there are no non-synonymous SNPs in SLC23A2. Our analysis, combined with previous in vitro and in vivo studies, suggests that non-synonymous variation appears to be tolerated in SLC23A1 but not SLC23A2, and that this may be a consequence of different selective pressures following past gene duplication of the sodium-dependent vitamin C transporters. Genetic association studies of these two genes will need to account for the differences in haplotype structure and the population-specific variants. Our data represent a fundamental step toward the application of genetics to refining nutrient recommendations, specifically for vitamin C, and may serve as a paradigm for other vitamins. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. NCI, Intramural Res Support Program, SAIC Frederick, FCRDC, Ft Detrick, MD 21702 USA. Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. RP Chanock, SJ (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, 8717 Grovement Circle, Bethesda, MD 20892 USA. EM sc83a@nih.gov OI Eck, Peter/0000-0003-2371-9774; Taylor, James/0000-0002-4421-1809 NR 43 TC 38 Z9 40 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 2004 VL 115 IS 4 BP 285 EP 294 DI 10.1007/s00439-004-1167-x PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 855EQ UT WOS:000223956400003 PM 15316768 ER PT J AU Carrington, M Gao, X Norman, P AF Carrington, M Gao, X Norman, P TI KIR gene Allele frequencies in populations from USA (African American) USA (European) and England SO HUMAN IMMUNOLOGY LA English DT Article C1 NCI, Frederick, MD 21702 USA. Guys Hosp, Tissue Typing Lab, London SE1 9RT, England. RP Gao, X (reprint author), NCI, Frederick, MD 21702 USA. EM goax@ncifcrf.gov; paul.norman@stanford.edu NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP-OCT PY 2004 VL 65 IS 9-10 SI SI BP 1191 EP 1191 DI 10.1016/j.humimm.2004.08.154 PG 1 WC Immunology SC Immunology GA 861HQ UT WOS:000224407100145 ER PT J AU Chanock, SJ Foster, CB Miller, FW O'Hanlon, TP AF Chanock, SJ Foster, CB Miller, FW O'Hanlon, TP TI HLA-A, -B, -Cw, -DQA1 and -DRB1 alleles in a Caucasian population from Bethesda, USA SO HUMAN IMMUNOLOGY LA English DT Article C1 NCI, NIH, Bethesda, MD 20892 USA. NIEHS, NIH, Bethesda, MD USA. RP Chanock, SJ (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM ohanlont@tzlehs.nih.gov NR 0 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP-OCT PY 2004 VL 65 IS 9-10 SI SI BP 1211 EP 1223 DI 10.1016/j.humimm.2004.08.162 PG 13 WC Immunology SC Immunology GA 861HQ UT WOS:000224407100153 ER PT J AU Chanock, SJ Foster, CB Miller, FW O'Hanlon, TP AF Chanock, SJ Foster, CB Miller, FW O'Hanlon, TP TI HLA-A, -B, -Cw,-DQA1 and DRB1 in an African American population from Bethesda, USA SO HUMAN IMMUNOLOGY LA English DT Article C1 NCI, NIH, Bethesda, MD 20892 USA. NIEHS, NIH, Bethesda, MD USA. RP Chanock, SJ (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM ohanlont@niehs.nih.gov OI Miller, Frederick/0000-0003-2831-9593 NR 0 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP-OCT PY 2004 VL 65 IS 9-10 SI SI BP 1223 EP 1235 DI 10.1016/j.humimm.2004.08.163 PG 13 WC Immunology SC Immunology GA 861HQ UT WOS:000224407100154 ER PT J AU Arnett, FC Reveille, JD O'Hanlon, TP AF Arnett, FC Reveille, JD O'Hanlon, TP TI HLA-DRB1 alleles in a Caucasian population from Houston, USA SO HUMAN IMMUNOLOGY LA English DT Article C1 Univ Texas, Hlth Sci Ctr, Houston, TX USA. NIEHS, NIH, Bethesda, MD USA. RP Arnett, FC (reprint author), Univ Texas, Hlth Sci Ctr, Houston, TX USA. EM ohanlont@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP-OCT PY 2004 VL 65 IS 9-10 SI SI BP 1238 EP 1241 DI 10.1016/j.humimm.2004.08.168 PG 4 WC Immunology SC Immunology GA 861HQ UT WOS:000224407100159 ER PT J AU Oddis, CV Morel, P O'Hanlon, TP AF Oddis, CV Morel, P O'Hanlon, TP TI HLA-DRB1 alleles in a Caucasian population from Pittsburgh, USA SO HUMAN IMMUNOLOGY LA English DT Article C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NIEHS, NIH, Bethesda, MD USA. RP Oddis, CV (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. EM ohanlont@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP-OCT PY 2004 VL 65 IS 9-10 SI SI BP 1241 EP 1244 DI 10.1016/j.humimm.2004.08.169 PG 4 WC Immunology SC Immunology GA 861HQ UT WOS:000224407100160 ER PT J AU de Leeuw, RJ Davies, JJ Rosenwald, A Bebb, G Gascoyne, RD Dyer, MJS Staudt, LM Martinez-Climent, JA Lam, WL AF de Leeuw, RJ Davies, JJ Rosenwald, A Bebb, G Gascoyne, RD Dyer, MJS Staudt, LM Martinez-Climent, JA Lam, WL TI Comprehensive whole genome array CGH profiling of mantle cell lymphoma model genomes SO HUMAN MOLECULAR GENETICS LA English DT Article ID NON-HODGKINS-LYMPHOMA; CYTOGENETIC ANALYSIS; FOLLICULAR LYMPHOMA; COMPLETE COVERAGE; COPY NUMBER; HYBRIDIZATION; CANCER; GENE; AMPLIFICATION; DISTINCT AB Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma with median patient survival times of similar to3 years. Although the characteristic t(11;14)(q13;q32) is found in virtually all cases, experimental evidence suggests that this event alone is insufficient to result in lymphoma and secondary genomic alterations are required. Using a newly developed DNA microarray of 32433 overlapping genomic segments spanning the entire human genome, we can for the first time move beyond marker based analysis and comprehensively search for secondary genomic alterations concomitant with the t(11;14) in eight commonly used cell models of MCL (Granta-519, HBL-2, NCEB-1, Rec-1, SP49, UPN-1, Z138C and JVM-2). Examining these genomes at tiling resolution identified an unexpected average of 35 genetic alterations per cell line, with equal numbers of amplifications and deletions. Recurrent high-level amplifications were identified at 18q21 containing BCL2, and at 13q31 containing GPC5. In addition, a recurrent homozygous deletion was identified at 9p21 containing p15 and p16. Alignment of these profiles revealed 14 recurrent losses and 21 recurrent gains as small as 130 kb. Remarkably, even the intra immunoglobulin gene deletions at 2p11 and 22q11 were detected, demonstrating the power of combining the detection sensitivity of array comparative genomic hybridization (CGH) with the resolution of an overlapping whole genome tiling-set. These alterations not only coincided with previously described aberrations in MCL, but also defined 13 novel regions. Further characterization of such minimally altered genomic regions identified using whole genome array CGH will define novel dominant oncogenes and tumor suppressor genes that play important roles in the pathogenesis of MCL. C1 British Columbia Canc Agcy, Dept Canc Genet, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. Univ Wurzburg, Inst Pathol, Wurzburg, Germany. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Leicester, MRC, Toxicol Unit, Leicester LE1 7RH, Leics, England. Univ Valencia, Hosp Clin, Dept Hematol & Med Oncol, E-46003 Valencia, Spain. RP de Leeuw, RJ (reprint author), British Columbia Canc Res Ctr, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM rdeleeuw@bccrc.ca RI Martinez-Climent, Jose/I-9199-2012; Dyer, Martin/F-2691-2014 OI Martinez-Climent, Jose/0000-0002-7938-3950; Dyer, Martin/0000-0002-5033-2236 NR 52 TC 96 Z9 96 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2004 VL 13 IS 17 BP 1827 EP 1837 DI 10.1093/hmg/ddh195 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 851XP UT WOS:000223720100001 PM 15229187 ER PT J AU Brinton, LA Scoccia, B Moghissi, KS Westhoff, CL Althuis, MD Mabie, JE Lamb, EJ AF Brinton, LA Scoccia, B Moghissi, KS Westhoff, CL Althuis, MD Mabie, JE Lamb, EJ TI Breast cancer risk associated with ovulation-stimulating drugs SO HUMAN REPRODUCTION LA English DT Article DE breast cancer; epidemiology; infertility; ovulation-stimulating medications; risk ID IN-VITRO FERTILIZATION; INFERTILE WOMEN; FERTILITY DRUGS; UNITED-STATES; COHORT; HISTORY; INCREASE AB BACKGROUND: Despite the recognized role of hormones in the aetiology of breast cancer, there has been little evaluation of hormonal preparations used to treat infertility. METHODS: A retrospective cohort study of 12 193 women evaluated for infertility between 1965 and 1988 at five clinical sites identified 292 in situ and invasive breast cancers in follow-up through 1999. Standardized incidence ratios (SIRs) compared breast cancer risks with those of the general population. Analyses within the cohort estimated rate ratios (RRs) associated with medications after adjustment for other breast cancer predictors. RESULTS: Infertile patients had a significantly higher breast cancer risk than the general population [SIR = 1.29, 95% confidence interval (CI) 1.1-1.4]. Analyses within the cohort showed adjusted RRs of 1.02 for clomiphene citrate and 1.07 for gonadotrophins, and no substantial relationships to dosage or cycles of use. Slight and non-significant elevations in risk were seen for both drugs after greater than or equal to20 years of follow-up (RRs = 1.39 for clomiphene and 1.54 for gonadotrophins). However, the risk associated with clomiphene for invasive breast cancers was statistically significant (RR = 1.60, 95% CI 1.0-2.5). CONCLUSIONS: Although there was no overall increase in breast cancer risk associated with use of ovulation-stimulating drugs, long-term effects should continue to be monitored. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Wayne State Univ, Detroit, MI USA. Columbia Univ, New York, NY USA. Informat Management Serv Inc, Rockville, MD USA. Stanford Univ, Stanford, CA 94305 USA. RP Brinton, LA (reprint author), 6120 Execut Blvd,Room 7068, Bethesda, MD 20892 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 44 TC 55 Z9 60 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD SEP PY 2004 VL 19 IS 9 BP 2005 EP 2013 DI 10.1093/humrep/deh371 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 852YG UT WOS:000223792100015 PM 15217997 ER PT J AU Li, KCP AF Li, KCP TI Molecular imaging II SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Li, KCP (reprint author), NIH, Ctr Clin, Bldg 10 1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. EM kingli@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD SEP-OCT PY 2004 VL 23 IS 5 BP 16 EP 17 DI 10.1109/MEMB.2004.1360404 PG 2 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 868WD UT WOS:000224942900004 PM 15565795 ER PT J AU Guccione, S Li, KCP Bednarski, MD AF Guccione, S Li, KCP Bednarski, MD TI Molecular imaging and therapy directed at the neovasculature in pathologies SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID PARAMAGNETIC POLYMERIZED LIPOSOMES; TUMOR ANGIOGENESIS; IN-VIVO; CLINICAL-APPLICATIONS; GENE DELIVERY; CANCER; INTEGRINS; CARCINOMA; MEDICINE; BREAST C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. Stanford Univ, Stanford, CA 94305 USA. RP Bednarski, MD (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM mbednarski@mail.cc.nih.gov NR 29 TC 13 Z9 13 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD SEP-OCT PY 2004 VL 23 IS 5 BP 50 EP 56 DI 10.1109/MEMB.2004.1360408 PG 7 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 868WD UT WOS:000224942900008 PM 15565799 ER PT J AU Mossop, BJ Barr, RC Zaharoff, DA Yuan, F AF Mossop, BJ Barr, RC Zaharoff, DA Yuan, F TI Electric fields within cells as a function of membrane resistivity - A model study SO IEEE TRANSACTIONS ON NANOBIOSCIENCE LA English DT Article DE intracellular electric field; membrane resistance; single cell in electric field; transmembrane potential ID THEORETICAL-ANALYSIS; STIMULATION; STRENGTH AB Externally applied electric fields play an important role in many therapeutic modalities, but the fields they produce inside cells remain largely unknown. This study makes use of a three-dimensional model to determine the electric field that exists in the intracellular domain of a 10-mum spherical cell exposed to an applied field of 100 V/cm. The transmembrane potential resulting from the applied field was also determined and its change was compared to those of the intracellular field. The intracellular field increased as the membrane resistance decreased over a wide range of values. The results showed that the intracellular electric field was about 1.1 mV/cm for R-m of 10 000 Omega (.) cm(2), increasing to about 111 mV/cm as R-m decreased to 100 Omega (.) cm(2). Over this range of R-m the transmembrane potential was nearly constant. The transmembrane potential declined only as R, decreased below 1 Omega (.) cm(2). The simulation results suggest that intracellular electric field depends on R-m in its physiologic range, and may not be negligible in understanding some mechanisms of electric field-mediated therapies. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yuan, F (reprint author), Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. EM fyuan@duke.edu RI Yuan, Fan/A-1287-2011; OI Zaharoff, David/0000-0001-6885-6727 FU NCI NIH HHS [CA94019] NR 17 TC 11 Z9 11 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1536-1241 J9 IEEE T NANOBIOSCI JI IEEE Trans. Nanobiosci. PD SEP PY 2004 VL 3 IS 3 BP 225 EP 231 DI 10.1109/TNB.2004.833703 PG 7 WC Biochemical Research Methods; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA 853AJ UT WOS:000223797900011 PM 15473075 ER PT J AU Campbell, SR Wang, DL Jayaprakash, C AF Campbell, SR Wang, DL Jayaprakash, C TI Synchronization rates in classes of relaxation oscillators SO IEEE TRANSACTIONS ON NEURAL NETWORKS LA English DT Article DE coupled oscillators; neural dynamics; relaxation oscillators; synchronization rate; synchrony ID COUPLED NEURAL OSCILLATORS; FIRE OSCILLATORS; NETWORKS; MODEL; INTEGRATE; SYSTEMS; NEURONS; POPULATIONS; MECHANISM; DELAYS AB Relaxation oscillators arise frequently in physics, electronics, mathematics, and biology. Their mathematical definitions possess a high degree of flexibility in the sense that through appropriate parameter choices relaxation oscillators can be made to exhibit qualitatively different kinds of oscillations. We study numerically four different classes of relaxation oscillators through their synchronization rates in one-dimensional chains with a Heaviside step function interaction and obtain the following results. Relaxation oscillators in the sinusoidal and relaxation regime both exhibit an average time to synchrony, similar to n, where n is the chain length. Relaxation oscillators in the singular limit exhibit similar to n(p), where p is a numerically obtained value less than 0.5. Relaxation oscillators in the singular limit with parameters modified so that they resemble spike oscillations exhibit similar to log(n) in chains and similar to log(L) in two-dimensional square networks of length L. Finally, using a sigmoid interaction results in similar to n(2), for relaxation oscillators in the sinusoidal and relaxation regimes, indicating that the form of the coupling is a controlling factor in the synchronization rate. C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Ohio State Univ, Dept Comp & Informat Sci, Columbus, OH 43210 USA. Ohio State Univ, Ctr Cognit Sci, Columbus, OH 43210 USA. Ohio State Univ, Dept Phys, Columbus, OH 43210 USA. RP Campbell, SR (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM SCamp-bell@cc.nih.gov NR 50 TC 10 Z9 11 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1045-9227 J9 IEEE T NEURAL NETWOR JI IEEE Trans. Neural Netw. PD SEP PY 2004 VL 15 IS 5 BP 1027 EP 1038 DI 10.1109/TNN.2004.833134 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Hardware & Architecture; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 853AN UT WOS:000223798400010 PM 18238085 ER PT J AU Huang, AYC Qi, H Germain, RN AF Huang, AYC Qi, H Germain, RN TI Illuminating the landscape of in vivo immunity: Insights from dynamic in situ imaging of secondary lymphoid tissues SO IMMUNITY LA English DT Review ID CD4 T-CELLS; EPIDERMAL LANGERHANS CELLS; MATURING DENDRITIC CELLS; IMMUNOLOGICAL SYNAPSE; EXTRACELLULAR-MATRIX; ANTIGEN PRESENTATION; 2-PHOTON MICROSCOPY; NODE CORTEX; B-CELLS; NAIVE AB A central feature of the immune system is the migratory behavior of its cellular components. Thus, fully understanding the generation and maintenance of immune responses must include consideration of how hematopoietic cells home to, interact within, and exit from secondary lymphoid organs as well as peripheral tissues. Recent advances in in situ imaging techniques now permit direct observation of these events in their physiologic settings with high spatiotemporal resolution. This review summarizes progress in this area of investigation from a lymphocentric perspective. We highlight controversies, point out key unanswered questions, and briefly outline what we believe are some of the near-term directions that in situ microscopic analysis of the immune system will take. C1 NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. EM rgermain@niaid.nih.gov RI Qi, Hai/A-3955-2009; OI Huang, Alex/0000-0002-5701-4521 NR 70 TC 22 Z9 22 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD SEP PY 2004 VL 21 IS 3 BP 331 EP 339 DI 10.1016/S1074-7613(04)00235-3 PG 9 WC Immunology SC Immunology GA 856GY UT WOS:000224034900004 ER PT J AU Ye, J AF Ye, J TI The immunoglobulin IGHD gene locus in C57BL/6 mice SO IMMUNOGENETICS LA English DT Article DE IGHD gene locus; immunoglobulin; germline ID B-CELL PROGENITORS; BALB/C MOUSE; MRL MICE; VH-GENE; RECOMBINATION; REARRANGEMENT; SELECTION; SIGNAL; FETAL; DIVERSITY AB Four immunoglobulin heavy chain diversity (IGHD) gene subgroups (DFL16, DSP2, DQ52, and DST4) have been identified previously in BALB/c mice. Although the locations of most IGHD genes have been established based on restriction map and Southern blot analysis, a complete mouse IGHD gene locus map at the sequence level is still not available. In addition, a previous restriction fragment length polymorphism study suggested that significant difference in the IGHD gene locus exists between C57BL/6 and BALB/c mice. The author has now analyzed the C57BL/6 mouse genomic data and established a complete map of the IGHD gene locus. All four IGHD subgroups previously identified in BALB/c mice were found to be present in C57BL/6 mice. However, unlike the BALB/c mice, which have at least 13 IGHD genes, the C57BL/6 genome contains only ten IGHD genes, which include one DFL16, six DSP2, one DQ52, and two DST4 genes. There are also differences in the coding regions of the DST4 and DQ52 genes between the two mouse strains. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Ye, J (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,Bldg 38A,Room 1003K, Bethesda, MD 20894 USA. EM jianye@ncbi.nlm.nih.gov NR 27 TC 20 Z9 21 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 2004 VL 56 IS 6 BP 399 EP 404 DI 10.1007/s00251-004-0712-z PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 863IS UT WOS:000224555500002 PM 15322776 ER PT J AU Chang, YC Stins, MF McCaffery, MJ Miller, GF Pare, DR Dam, T Paul-Satyasee, M Kim, KS Kwon-Chung, KJ AF Chang, YC Stins, MF McCaffery, MJ Miller, GF Pare, DR Dam, T Paul-Satyasee, M Kim, KS Kwon-Chung, KJ TI Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier SO INFECTION AND IMMUNITY LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; ESCHERICHIA-COLI INVASION; CAPSULE-ASSOCIATED GENE; RAT CEREBRAL-CORTEX; IN-VITRO; IMMUNODEFICIENCY-VIRUS; LISTERIA-MONOCYTOGENES; EPITHELIAL-CELLS; NEOFORMANS; MENINGITIS AB Cryptococcal meningoencephalitis develops as a result of hematogenous dissemination of inhaled Cryptococcus neoformans from the lung to the brain. The mechanism(s) by which C neoformans crosses the blood-brain barrier (BBB) is a key unresolved issue in cryptococcosis. We used both an in vivo mouse model and an in vitro model of the human BBB to investigate the cryptococcal association with and traversal of the BBB. Exposure of human brain microvascular endothelial cells (HBMEC) to C. neoformans triggered the formation of microvillus-like membrane protrusions within 15 to 30 min. Yeast cells of C. neoformans adhered to and were internalized by the HBMEC, and they crossed the HBMEC monolayers via a transcellular pathway without affecting the monolayer integrity. The histopathology of mouse brains obtained after intravenous injection of C. neoformans showed that the yeast cells either were associated with endothelial cells or escaped from the brain capillary vessels into the neuropil by 3 h. C. neoformans was found in the brain parenchyma away from the vessels by 22 h. Association of C. neoformans with the choroid plexus, however, was not detected during up to 10 days of observation. Our findings indicate that C. neoformans cells invade the central nervous system by transcellular crossing of the endothelium of the BBB. C1 NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. NIAID, Div Vet Resources, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Pediat Infect Dis, Baltimore, MD USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, LCI, NIH, Bldg 10,11C304, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU NIMH NIH HHS [MH63850, R01 MH063850]; NINDS NIH HHS [NS 26310, R01 NS026310, R56 NS026310]; PHS HHS [A1 47225] NR 42 TC 120 Z9 136 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2004 VL 72 IS 9 BP 4985 EP 4995 DI 10.1128/IAI.72.9.4985-4995.2004 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 849ZM UT WOS:000223580400007 PM 15321990 ER PT J AU Nyan, DC Welch, AR Dubois, A Coleman, WG AF Nyan, DC Welch, AR Dubois, A Coleman, WG TI Development of a noninvasive method for detecting and monitoring the time course of Helicobacter pylori infection SO INFECTION AND IMMUNITY LA English DT Article ID POLYMERASE CHAIN-REACTION; CAMPYLOBACTER-PYLORI; GASTRIC-CANCER; ANIMAL-MODELS; HUMAN-DISEASE; MOUSE MODEL; BREATH TEST; PCR; ANTIBODIES; DIAGNOSIS AB Helicobacter pylori infection status following experimental inoculation of mice presently requires euthanasia. The purpose of this study was to develop a method for following the time course of H. pylori infection in live experimental animals. Twenty-six C57BL/6, Helicobacter-free female mice were inoculated with H. pylori Sydney strain 1, and 16 mice were sham inoculated. The mice were repeatedly tested during a period of about 1 year with an H. pylori species-specific primer-based PCR analysis of DNA extracted from fecal pellets of mice. The mice were euthanized at 6 months (n = 15) and 10 months (n = 15) to determine their infection status by histology, culture, and PCR of gastric specimens. H. pylori-inoculated mice were tested via the PCR method at 6 and 10 months prior to necropsy. Nine of 13 (69%) and 10 of 13 (77%) mice tested at 6 and 10 months, respectively, were positive. All sham-inoculated mice were negative. These two PCR results suggested a specificity of 100% with a sensitivity range between 69 and 77%. In contrast, sensitivity and specificity rose to 90 and 100% if groups of mice were tested once daily for 4 days. Seventy-seven to 85% of the experimental mice were also positive for H. pylori by culture. The histopathology demonstrated mild to severe gastritis. These findings demonstrate that the persistence or transience of H. pylori infection in live mice can be repeatedly evaluated over time. This method could allow the determination of the time course of infection and the efficacy of medications and/or vaccine without necropsy. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Diagnon Corp, Gaithersburg, MD USA. RP Coleman, WG (reprint author), NIDDKD, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wc3z@NIH.GOV FU NCI NIH HHS [R01 CA082312-06, R01 CA082312, CA82312] NR 38 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2004 VL 72 IS 9 BP 5358 EP 5364 DI 10.1128/IAI.72.9.5358-5364.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 849ZM UT WOS:000223580400050 PM 15322033 ER PT J AU Manca, C Reed, MB Freeman, S Mathema, B Kreiswirth, B Barry, CE Kaplan, G AF Manca, C Reed, MB Freeman, S Mathema, B Kreiswirth, B Barry, CE Kaplan, G TI Differential monocyte activation underlies strain-specific Mycobacterium tuberculosis pathogenesis SO INFECTION AND IMMUNITY LA English DT Article ID MOLECULAR EPIDEMIOLOGY; MACROPHAGE ACTIVATION; GLOBAL DISSEMINATION; MEDIATED ACTIVATION; CLONE FAMILY; TRANSMISSION; LIPOARABINOMANNAN; INDUCTION; OUTBREAK; NECROSIS AB In vitro infection of monocytes with Mycobacterium tuberculosis HN878 and related W/Beijing isolates preferentially induced interleukin-4 (IL-4) and IL-13, which characterize Th2 polarized immunity. In contrast, CDC1551 induced more IL-12 and other molecules associated with phagocyte activation and Th1 protective immunity. The differential cytokine-chemokine response was mediated by extracted lipids, suggesting that these molecules regulate host responses to infection. C1 Publ Hlth Res Inst, Lab Mycobacterial Immun & Pathogenesis, Int Ctr Publ Hlth, Newark, NJ 07103 USA. Publ Hlth Res Inst, TB Ctr, Int Ctr Publ Hlth, Newark, NJ 07103 USA. NIAID, TB Res Sect, NIH, Rockville, MD USA. RP Kaplan, G (reprint author), Publ Hlth Res Inst, Lab Mycobacterial Immun & Pathogenesis, Int Ctr Publ Hlth, 225 Warren St, Newark, NJ 07103 USA. EM kaplan@phri.org RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11]; NIAID NIH HHS [AI-22616, AI-54361, R01 AI054361] NR 22 TC 145 Z9 147 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2004 VL 72 IS 9 BP 5511 EP 5514 DI 10.1128/IAI.72.9.5511-5514.2004 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 849ZM UT WOS:000223580400073 PM 15322056 ER PT J AU Park, Y Spouge, JL AF Park, Y Spouge, JL TI Searching for multiple words in a Markov sequence SO INFORMS JOURNAL ON COMPUTING LA English DT Article DE Markovian arrival processes; word occurrences; distance between occurrences; transition-probability matrix ID NUCLEOTIDE-SEQUENCES; RENEWAL THEORY; LIMIT-THEOREM; OCCURRENCES; CHAINS; PATTERNS; APPROXIMATIONS; POISSON; TRIALS; RUNS AB The theory of the discrete-time Markovian arrival process (DMAP) can be applied to some statistical problems encountered when searching for multiple words in a Markov sequence. Such word searches are often emphasized in studies of the human genome. There are several advantages to the DMAP approach we present. Most notably, its derivations are transparent, and they readily unify disparate results about the exact distributions of overlapping and nonoverlapping word counts. We also present several examples and applications of our theory, including a numerical study using a random DNA dataset from the human genome. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Park, Y (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM park@ncbi.nlm.nih.gov; spouge@ncbi.nlm.nih.gov NR 27 TC 2 Z9 2 U1 0 U2 3 PU INFORMS PI LINTHICUM HTS PA 901 ELKRIDGE LANDING RD, STE 400, AIPORT SQUARE, LINTHICUM HTS, MD 21090-2908 USA SN 1091-9856 J9 INFORMS J COMPUT JI INFORMS J. Comput. PD FAL PY 2004 VL 16 IS 4 BP 341 EP 347 DI 10.1287/ijoc.1040.0095 PG 7 WC Computer Science, Interdisciplinary Applications; Operations Research & Management Science SC Computer Science; Operations Research & Management Science GA 871ET UT WOS:000225113100003 ER PT J AU Pardigon, N Darche, S Kelsall, B Bennink, JR Yewdell, JW AF Pardigon, N Darche, S Kelsall, B Bennink, JR Yewdell, JW TI The TL MHC class lb molecule has only marginal effects on the activation, survival and trafficking of mouse small intestinal intraepithelial lymphocytes SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE intraepithelial lymphocytes; mouse small intestine; thymic leukemia ag ID THYMUS LEUKEMIA ANTIGEN; CLASS-I MOLECULE; MAJOR HISTOCOMPATIBILITY COMPLEX; EPITHELIAL-CELLS; E-CADHERIN; EXPRESSION; MICE; ALPHA(E)BETA(7); INTEGRIN; GAMMA AB Thymus leukemia antigen (TL) is an MHC class Ib molecule that is highly conserved in rats and mice with no obvious human homolog. TL is expressed in mouse small intestinal epithelial cells and is known to interact with CD8alphaalpha homodimers, which are expressed by intraepithelial lymphocytes (IELs), some other T cell subsets and some non-T cells such as a subset of dendritic cells. We show here that TL is abundantly expressed on the basolateral surface of mouse small intestinal epithelial cells and that expression is abrogated in beta(2)m-/- mice but unaffected in TCR-/- mice or CD8alpha chain-/- mice. We demonstrate that the interaction between TL and CD8alphaalpha is not necessary for IEL survival in vitro or in vivo and does not modulate IEL trafficking in vivo. TL co-stimulation of alpha-CD3 anti body-activated IELs resulted in modestly enhanced production of IFN-gamma in one subset of IELs. The lack of effect on IEL survival and trafficking and the modest effect on IFN-gamma production suggest that the functional consequences of TL interaction with CD8alphaalpha as well as the more general biological role of TL in mucosal immunity remains to be discovered. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Inst Pasteur, INSERM, U277, Lab Biol Mol Gene, F-75724 Paris, France. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Pardigon, N (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM npardigon@niaid.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 33 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 2004 VL 16 IS 9 BP 1305 EP 1313 DI 10.1093/intimm/dxh133 PG 9 WC Immunology SC Immunology GA 853KQ UT WOS:000223826900009 PM 15302846 ER PT J AU Reifen, R Mor, A Nyska, A AF Reifen, R Mor, A Nyska, A TI Vitamin a deficiency aggravates rotavirus infection in CD-1 mice through extensive involvement of the gut SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Article DE vitamin A deficiency; rotavirus infection; small intestinal and colonic damage ID EPIZOOTIC DIARRHEA; MURINE ROTAVIRUS; SUPPLEMENTATION; CHILDREN; RAT; EXPRESSION; INFANT; PATHOGENESIS; EPITHELIUM; INTESTINE AB rotavirus (RV) is one of the leading causes of life-threatening viral gastroenteritis in infants and animals. More than 100 million children live in endemic areas where they are at risk of rotavirus infection. In the western world, rotavirus is usually a self-limiting disease that involves no major sequelae; however, in the developing world it often leads to morbidity and mortality. One of the major components influencing the prognosis of rotavirus-infected children is their nutritional status. The prevalence of vitamin A deficiency in developing countries, where RV infection can be fatal, encompasses up to 40% of preschool children. We hypothesized, therefore, that vitamin A deficiency in an animal model would aggravate the course of rotavirus disease. CD-1 mice were infected with RV and fed either vitamin A-sufficient or vitamin A-deficient diets. Histological components of the small intestine and colon, stool samples from which rotavirus was recovered, and vitamin A levels were examined. Flattening of the villi along the duodenum was observed in both rotavirus-infected and non-infected vitamin A-deficient mise. Maximal effect was obtained with a combination of vitamin A deficiency and RV infection. The colon of vitamin A-deficient, infected mice displayed a significantly (p < 0.05) smaller glandular area and higher level of mucin, and viral excretion in the stool became significantly (p < 0.01) increased and lasted longer than in controls. We conclude that vitamin A deficiency aggravates the course of RV infection through both small intestinal and colonic damage. C1 Hebrew Univ Jerusalem, Fac Agr Food & Environm Qual Serv, Sch Nutrit Sci, IL-76100 Rehovot, Israel. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Reifen, R (reprint author), Hebrew Univ Jerusalem, Fac Agr Food & Environm Qual Serv, Sch Nutrit Sci, IL-76100 Rehovot, Israel. EM reifen@agri.huji.ac.il NR 38 TC 6 Z9 6 U1 0 U2 1 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PD SEP PY 2004 VL 74 IS 5 BP 355 EP 361 DI 10.1024/0300-9831.74.5.355 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 883TH UT WOS:000226038100008 PM 15628674 ER PT J AU Sarafianos, SG Hughes, SH Arnold, E AF Sarafianos, SG Hughes, SH Arnold, E TI Designing anti-AIDS drugs targeting the major mechanism of HIV-1 RT resistance to nucleoside analog drugs SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review ID TYPE-1 REVERSE-TRANSCRIPTASE; DINUCLEOSIDE POLYPHOSPHATES; FIREFLY LUCIFERASE; PRIMER UNBLOCKING; STERIC HINDRANCE; 3TC RESISTANCE; DNA; COMPLEX; AZT; TRANSLOCATION AB HIV reverse transcriptase (RT) is the target of a number of important anti-AIDS drugs. Drugs that inhibit RT are either nucleoside reverse transcriptase inhibitors (NRTIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). Combinations of various anti-AIDS drugs (highly active anti-retroviral therapies or HAART) can reduce the viral load to non-detectable levels. However, the development of drug resistance leads to the emergence of HINT strains that are resistant to multiple anti-AIDS drugs. The nucleotide analogs that are used as anti-HIV-1 drugs lack the normal 3'-OH and as a consequence act as chain-terminators when incorporated into DNA. One mechanism of nucleoside analog resistance involves ATP-based excision to unblock chain-terminated primers and allow HIV replication to continue. There is an urgent need for new drugs and for new therapies that can overcome the excision mechanism of resistance. Compounds that disrupt the binding of the excision reaction substrate(s) (the blocked primer and/or ATP and/or pyrophosphate), or mimic the dinucleoside tetraphosphate product of the ATP-based excision reaction are potential inhibitors of excision. Detailed understanding of drug resistance mechanisms can reveal novel targets for anti-viral agents. (C) 2004 Elsevier Ltd. All rights reserved. C1 Rutgers State Univ, CABM, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Sarafianos, SG (reprint author), Rutgers State Univ, CABM, 679 Hoes Lane, Piscataway, NJ 08854 USA. EM stefan@cabm.rutgers.edu; arnold@cabm.rutgers.edu OI Sarafianos, Stefan G/0000-0002-5840-154X NR 36 TC 34 Z9 34 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD SEP PY 2004 VL 36 IS 9 BP 1706 EP 1715 DI 10.1016/j.biocel.2004.02.027 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 832GR UT WOS:000222255900005 PM 15183339 ER PT J AU Rausch, JW Le Grice, SFJ AF Rausch, JW Le Grice, SFJ TI 'Binding, bending and bonding': polypurine tract-primed initiation of plus-strand DNA synthesis in human immunodeficiency virus SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE retrovirus; plus-strand synthesis; reverse transcriptase; RNA/DNA hybrid; ribonuclease H ID HIV-1 REVERSE-TRANSCRIPTASE; MURINE LEUKEMIA-VIRUS; SEQUENCE FEATURES IMPORTANT; AVIAN-MYELOBLASTOSIS VIRUS; RIBONUCLEASE-H ACTIVITY; RNASE-H; CLEAVAGE SPECIFICITY; LENTIVIRAL VECTORS; SARCOMA-VIRUS; IN-VIVO AB During the course of reverse transcription, human immunodeficiency virus type I reverse transcriptase (HIV-1 RT) initiates plus-strand DNA synthesis from two highly conserved, purine-rich RNA segments of the viral genome referred to as the 3' and central polypurine tracts (3' and cPPTs). Processing of these elements occurs in several sequential steps including (1) minus-strand DNA synthesis over the PPT(s), (2) ribonuclease H (RNase H) mediated cleavage at the PPT 3' terminus, (3) plus-strand DNA synthesis from the nascent RNA primer(s), and (4) primer removal. Completing each of these steps precisely and specifically is essential, as failure to do so can result in reduced virus replication and/or impaired integration of viral DNA into the host cell genome. In this review, plus-strand primer processing in HIV-1 is discussed from biochemical, structural, and historical perspectives. A comparative analysis of PPT-processing in different LTR-containing retroelements is also presented. (C) 2004 Elsevier Ltd. All rights reserved. C1 NCI, HIV Drug Resistance Program, Reverse Transcriptase Biochem Sect, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Reverse Transcriptase Biochem Sect, Bldg 535,Room 325, Frederick, MD 21702 USA. EM slegrice@nciferf.gov NR 73 TC 62 Z9 64 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD SEP PY 2004 VL 36 IS 9 BP 1752 EP 1766 DI 10.1016/j.biocel.2004.02.016 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 832GR UT WOS:000222255900008 PM 15183342 ER PT J AU Carroll, NM Elaraj, DM Puhlmann, M Weinreich, DM Turner, EM Xu, H Alexander, HR AF Carroll, NM Elaraj, DM Puhlmann, M Weinreich, DM Turner, EM Xu, H Alexander, HR TI Alterations in tumor necrosis factor-induced endothelial cell procoagulant activity by hyperthermia SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE tumor necrosis,factor; tissue factor; tissue factor pathway inhibitor-2; hyperthermia; endothelium; coagulation; isolated limb perfusion ID ISOLATED LIMB PERFUSION; FACTOR-PATHWAY INHIBITOR; TISSUE-FACTOR; FACTOR-ALPHA; INTERFERON-GAMMA; HUMAN-MELANOMA; MOLECULAR-CLONING; TNF-ALPHA; MELPHALAN; SARCOMA AB TNF is a cytokine with potent antitumor activity in murine models and when administered clinically via regional perfusion. There is substantial evidence that this antitumor activity depends in large part on TNF's procoagulant effect on tumor neovasculature, which is mediated by induction of endothelial cell tissue factor (TF), a component of the extrinsic clotting cascade. In regional perfusion of a cancer-bearing limb or organ, TNF is always administered under hyperthermic temperatures; however, little is known about the effect of hyperthermia on TNF-mediated procoagulant activity in endothelium. We examined the effects of hyperthermia on TNF-mediated procoagulant activity in human umbilical vein endothelial cells (HUVECs). HUVECs were exposed to TNF at normothermic (37degreesC) and hyperthermic (41degreesC) temperatures for 90 min, then assayed for clotting activity, TF protein production and mRNA production of TF and tissue factor pathway inhibitor-2 (TFPI-2), an endogenous inducible inhibitor of TF activity in HUVECs. TNF treatment at 41degreesC significantly reduced clotting activity, TF protein and mRNA as well as TFPI-2 mRNA compared to treatment at 37degreesC. These data show that hyperthermia significantly reduces the procoagulant effects of TNF on endothelial tissue compared to normothermia, which may have important clinical implications for the use of TNF in regional perfusion. (C) 2004 Wiley-Liss, Inc. 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 2B07, Bethesda, MD 20892 USA. EM ralexand@mail.nih.gov NR 39 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2004 VL 111 IS 3 BP 457 EP 462 DI 10.1002/ijc.20272 PG 6 WC Oncology SC Oncology GA 842BA UT WOS:000222976200021 PM 15221977 ER PT J AU Steinberg, E Tanofsky-Kraff, M Cohen, ML Elberg, J Freedman, RJ Semega-Janneh, M Yanovski, SZ Yanovski, JA AF Steinberg, E Tanofsky-Kraff, M Cohen, ML Elberg, J Freedman, RJ Semega-Janneh, M Yanovski, SZ Yanovski, JA TI Comparison of the child and parent forms of the questionnaire on eating and weight patterns in the assessment of children's eating-disordered behaviors SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE eating-disordered pathology; binge eating; questionnaires; child; parent ID X-RAY ABSORPTIOMETRY; PUBERTAL CHANGES; BODY-COMPOSITION; OBESE CHILDREN; ATTITUDES TEST; PSYCHOPATHOLOGY; ADOLESCENTS; INTERVIEW; DEPRESSION; VALIDATION AB Objective: The assessment of eating-disordered behaviors in middle childhood is challenging. Frequently, both child and parents are queried about the child's eating behavior. However, no direct comparisons between parent and child reports of child eating disturbance have been published. We compared results from the adolescent and parent versions of the Questionnaire on Eating and Weight Patterns (QEWP-A and QEWP-P, respectively) in a nontreatment sample of overweight and normal weight children. Method: The QEWP-A and QEWP-P were administered to 142 overweight (body mass index [BMI] greater than or equal to 85th percentile) and 121 normal weight (BMI 15th-84th percentile) children, age 9.7 +/- 1.9 years, recruited from the community. Results: The QEWP-A and QEWP-P showed good agreement for the absence of eating-disordered behavior but were not concordant in terms of the number or type of binge eating, overeating episodes, or compensatory weight control behaviors in the past 6 months. Children categorized by their own reports (QEWP-A) as engaging in no overeating, simple overeating, or binge eating behaviors did not differ significantly in body composition or in eating and general psychopathology. Children categorized according to their parents' reports (QEWP-P) as engaging in binge eating had significantly greater body adiposity, eating-disordered cognitions, body dissatisfaction, and parent-reported problems (all ps < .001) than children engaging in no overeating or simple overeating according to the QEWP-P. Discussion: Child and parent reports of eating behaviors are not concordant regarding the presence of binge eating or compensatory behaviors. Further investigation of the utility of these questionnaires is needed before either can serve as a surrogate for a clinical interview. Published 2004 by Wiley Periodicals, Inc. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tanofsky-Kraff, M (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM tanofskm@mail.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641] NR 34 TC 25 Z9 25 U1 5 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2004 VL 36 IS 2 BP 183 EP 194 DI 10.1002/eat.20022 PG 12 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 846OZ UT WOS:000223326500006 PM 15282688 ER PT J AU Chatterjee, I Somerville, GA Heilmann, C Herrmann, M AF Chatterjee, I Somerville, GA Heilmann, C Herrmann, M TI Staphylococcus aureus and very low ethanol concentrations: A sober attempt to correlate metabolism with post-death phase growth SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the DGHM CY SEP 26-29, 2004 CL Munster, GERMANY SP DGHM C1 Univ Saarland, Inst Med Microbiol & Hyg, D-6650 Homburg, Germany. NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Munster, Dept Med Microbiol, D-4400 Munster, Germany. RI Herrmann, Mathias/B-6475-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 1438-4221 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD SEP PY 2004 VL 294 SU 39 BP 160 EP 160 PG 1 WC Microbiology; Virology SC Microbiology; Virology GA 861ZA UT WOS:000224456000180 ER PT J AU Duerr, M Kristian, S Otto, M Peschel, A AF Duerr, M Kristian, S Otto, M Peschel, A TI Neutrophil chemotaxis by pathogen-associated molecular patterns - role of formylated peptides and novel bacterial chernoattractants SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the DGHM CY SEP 26-29, 2004 CL Munster, GERMANY SP DGHM C1 Univ Tubingen, Div Cellular & Mol Microbiol, Dept Med Microbiol & Hyg, Tubingen, Germany. Univ Basel Hosp, Dept Res, Div Infect Dis, CH-4031 Basel, Switzerland. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 1438-4221 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD SEP PY 2004 VL 294 SU 39 BP 168 EP 168 PG 1 WC Microbiology; Virology SC Microbiology; Virology GA 861ZA UT WOS:000224456000200 ER PT J AU Du, J Szabo, ST Gray, NA Manji, HK AF Du, J Szabo, ST Gray, NA Manji, HK TI Focus on CaMKII: a molecular switch in the pathophysiology and treatment of mood and anxiety disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article ID SYNAPTIC PLASTICITY; MESSENGER-RNA; KINASE-II; RECEPTORS; STRESS; BETA C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, 9000 Rockville Pike,Bldg 10,Unit 3 West,Room 3s25, Bethesda, MD 20892 USA. EM manjih@intra.nimh.nih.gov NR 22 TC 25 Z9 26 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2004 VL 7 IS 3 BP 243 EP 248 DI 10.1017/S1461145704004432 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 857FX UT WOS:000224102800001 PM 15154976 ER PT J AU Mirsky, AF AF Mirsky, AF TI Pathophysiology of mental illness SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Sect Clin & Expt Neuropsychol, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2004 VL 54 IS 1-2 BP 1 EP 2 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 842YF UT WOS:000223039900003 ER PT J AU Duncan, CC AF Duncan, CC TI Closed head injury-related information processing deficits SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Clin Psychophysiol & Psychopharmacol Lab, Bethesda, MD 20814 USA. NIMH, Sect Clin & Expt Neuropsychol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2004 VL 54 IS 1-2 BP 6 EP 6 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 842YF UT WOS:000223039900008 ER PT J AU Thayer, JF Ruiz-Padial, E Hansen, AL Johnsen, BH AF Thayer, JF Ruiz-Padial, E Hansen, AL Johnsen, BH TI Autonomic nervous system activity and its relationship to attention and working memory SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Univ Jaen, Jaen, Spain. Univ Bergen, N-5020 Bergen, Norway. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2004 VL 54 IS 1-2 BP 19 EP 19 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 842YF UT WOS:000223039900036 ER PT J AU Furey, ML AF Furey, ML TI Cholinergic modulation of attention and emotion in humans SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2004 VL 54 IS 1-2 BP 25 EP 25 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 842YF UT WOS:000223039900052 ER PT J AU Pietrini, P Ricciardi, E Furey, M AF Pietrini, P Ricciardi, E Furey, M TI Cholinergic enhancement during workjng memory improves information processing in the human brain: Effects of age and task difficulty SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Univ Pisa, I-56100 Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2004 VL 54 IS 1-2 BP 46 EP 47 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 842YF UT WOS:000223039900111 ER PT J AU Ricciardi, E Furey, ML Gobbini, MI Guazzelli, M Haxby, JV Pietrini, P AF Ricciardi, E Furey, ML Gobbini, MI Guazzelli, M Haxby, JV Pietrini, P TI Supramodal, topographic and category-related organization in the ventral visual pathway SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Pisa, Pisa, Italy. Princeton Univ, Princeton, NJ 08544 USA. NIMH, MADP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD SEP PY 2004 VL 54 IS 1-2 BP 58 EP 58 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 842YF UT WOS:000223039900142 ER PT J AU Wallner, PE Coleman, CN Brechbiel, M Milenic, D Tripuraneni, P AF Wallner, PE Coleman, CN Brechbiel, M Milenic, D Tripuraneni, P TI Are radiation oncologists serious about systemic radiation therapy and if not, should we be? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 NCI, Radiat Oncol Sci Program, Radiat Res Program, Bethesda, MD 20892 USA. ASTRO Targeted Radionuclide Therapy Task Force, Fairfax, VA USA. NCI, Radiat Oncol Sci Program, Radiat Oncol Branch, Bethesda, MD USA. Scripps Clin, La Jolla, CA USA. RP Wallner, PE (reprint author), NCI, Radiat Oncol Sci Program, Radiat Res Program, PN-6002,6130 Execut Blvd,MSC 7740, Bethesda, MD 20892 USA. EM wallnerp@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2004 VL 60 IS 1 BP 1 EP 2 DI 10.1016/j.ijrobp.2004.06.256 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UN UT WOS:000223854500001 PM 15337532 ER PT J AU Boccia, R Anne, PR Bourhis, J Brizel, D Daly, C Holloway, N Hymes, S Koukourakis, M Kozloff, M Turner, M Wasserman, T AF Boccia, R Anne, PR Bourhis, J Brizel, D Daly, C Holloway, N Hymes, S Koukourakis, M Kozloff, M Turner, M Wasserman, T TI Assessment and management of cutaneous reactions with amifostine administration: Findings of the Ethyol (amifostine) Cutaneous Treatment Advisory Panel (ECTAP) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE amifostine; Stevens-Johnson syndrome; toxic epidermal necrolysis; erythema multiforme ID STEVENS-JOHNSON-SYNDROME; TOXIC EPIDERMAL NECROLYSIS; CLINICAL-PRACTICE GUIDELINES; ERYTHEMA MULTIFORME; RADIATION-THERAPY; NECK-CANCER; RADIOTHERAPY PROTECTANTS; AMERICAN-SOCIETY; PHASE-II; CHEMOTHERAPY AB Purpose: To review reports of severe skin reactions during amifostine treatment. Methods and Material: The expert panel reviewed postmarketing reports of skin reactions and discussed strategies for evaluation and management. Results: Between 1994 and April 2002, 35 events were classified as severe skin reactions worldwide: erythema multiforme (8), Stevens-Johnson syndrome (10), toxic epidermal necrolysis (11), toxicoderma (3), and bullae (3). Unadjusted incidences were 6-9 per 10,000 radiotherapy patients and 0.8-1 per 10,000 chemotherapy patients. In 10 patients (29%) amifostine was continued after cutaneous signs and symptoms appeared. Conclusions: Practical recommendations for practicing clinicians were developed. Cutaneous evaluation for rash, ulceration, or lesions-particularly on lips/mucosa, palmar/plantar surfaces, and the trunk-should be performed before amifostine administration. Reactions can be classified as local injection site/radiation port reactions or non-injection site reactions; and non-injection site reactions with associated fever or constitutional symptoms must be differentiated from radiation-induced dermatitis or cutaneous reaction with another etiology. Amifostine should be permanently discontinued for severe skin reactions or reactions associated with constitutional symptoms not known to be due to any other etiology. Increased physician awareness, proper patient management, monitoring before administration, and early intervention/discontinuation for non-injection site reactions may reduce the incidence of cutaneous reactions and enhance amifostine safety. (C) 2004 Elsevier Inc. C1 Ctr Canc & Blood Disorders, Bethesda, MD USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Inst Gustave Roussy, Villejuif, France. Duke Univ, Med Ctr, Durham, NC USA. St Joseph Hosp, Chicago, IL USA. Cook Cty Hosp, Chicago, IL 60612 USA. MD Anderson Hosp & Tumor Inst, Houston, TX USA. Democritus Univ Thrace, Sch Med, Alexandroupolis, Greece. Ingalls Hosp, Harvey, IL USA. NIH, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. RP Boccia, R (reprint author), 6420 Rockledge Dr,4100, Bethesda, MD 20817 USA. EM boccia@dnamail.com NR 47 TC 25 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2004 VL 60 IS 1 BP 302 EP 309 DI 10.1016/j.ijrobp.2004.02.026 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 853UN UT WOS:000223854500038 PM 15337569 ER PT J AU Brown, DR Merritt, JL Jacobson, ER Klein, PA Tully, JG Brown, MB AF Brown, DR Merritt, JL Jacobson, ER Klein, PA Tully, JG Brown, MB TI Mycoplasma testudineum sp nov., from a desert tortoise (Gopherus agassizii) with upper respiratory tract disease SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID MOLLICUTES AB Mycoplasma testudineum sp. nov., first cultured from the upper respiratory tract of a clinically ill tortoise (Gopherus agassizii) in the Mohave Desert, was distinguished from previously described mollicutes serologically and by 16S rRNA gene sequence comparisons. It lacks a cell wall; ferments glucose, mannose, lactose and sucrose; does not produce 'film and spots'; does not hydrolyse arginine, aesculin or urea; is sensitive to digitonin; and lacks phosphatase activity. The organism causes chronic rhinitis and conjunctivitis of tortoises. The type strain of M. testudineum is BH29(T) ( = ATCC 700618(T) = MCCM 03231(T)). C1 Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32611 USA. Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, Gainesville, FL 32611 USA. Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. NIAID, Mycoplasma Sect, Frederick, MD 21702 USA. RP Brown, DR (reprint author), Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32611 USA. EM brownd@mail.vetmed.ufl.edu NR 17 TC 26 Z9 26 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD SEP PY 2004 VL 54 BP 1527 EP 1529 DI 10.1099/ijs.0.63072-0 PN 5 PG 3 WC Microbiology SC Microbiology GA 859JK UT WOS:000224259100015 PM 15388705 ER PT J AU Ahmed, F Torrado, M Zinovieva, RD Senatorov, VV Wistow, G Tomarev, SI AF Ahmed, F Torrado, M Zinovieva, RD Senatorov, VV Wistow, G Tomarev, SI TI Gene expression profile of the rat eye iridocorneal angle: NEIBank expressed sequence tag analysis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; GTPASE-ACTIVATING PROTEIN; HUMAN TRABECULAR MESHWORK; ELEVATED INTRAOCULAR-PRESSURE; 6000 NONREDUNDANT TRANSCRIPTS; ALPHA-LATROTOXIN RECEPTOR; OPTIC-NERVE HEAD; COUPLED RECEPTORS; EXPERIMENTAL GLAUCOMA; MEMBRANE-PROTEIN AB PURPOSE. To characterize gene expression pattern in the combined tissues of the rat iridocorneal angle by expressed sequence tag ( EST) analysis, as part of the NEIBank project. METHODS. RNA was extracted from dissected tissues of the rat iridocorneal angle ( iris, ciliary body, trabecular meshwork, and Schlemm's canal) and used to construct unamplified, nonnormalized cDNA libraries in the pSPORT1 vector. Approximately 5000 clones were sequenced from the 5'-end. Clones were clustered and identified using the GRIST software, a procedure based on BLAST comparisons. Complete sequences of several novel cDNAs showing eye-preferred expression patterns were obtained. The expression patterns of several genes have been investigated by Northern blot and in situ hybridization, as well as by RT-PCR. RESULTS. After analysis and removal of non-mRNA sequences, 2195 independent clusters, potentially representing individual eye angle-expressed clones were obtained. The expression profile of the combined rat eye angle tissues was more similar to that of the human iris than to human trabecular meshwork. Several cDNAs encoding transcription factors essential for normal eye development and function including Pax-6, Six3, c-Maf, Maf1, Sox-4, Foxc1, Rx, and Ldb2 were present among sequenced clones. A number of tested cDNAs showed eye-preferred expression patterns. Myocilin, which is abundant in human eye angle tissues, was not observed in the rat collection; however, transcripts for three other olfactomedin-domain proteins were seen. Latrotoxin receptor (CL1AA) and optimedin were shown to be expressed in the iris and ciliary body, as well as in the ganglion and inner nuclear cell layers of the retina, whereas the rat orthologue of the human HNOEL-iso gene was expressed in the iris and sclera and less actively in the trabecular meshwork, retina, and optic nerve. CONCLUSIONS. The iridocorneal libraries are a good source of novel uncharacterized genes and molecular markers for the tissues of the eye angle. Although myocilin is not abundantly expressed in rat eye angle, other olfactomedin-containing genes are expressed there and may play important roles in normal eye function and disease. C1 NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH,DHHS, Bethesda, MD 20814 USA. NEI, Sect Mol Struct & Funct, Bethesda, MD 20814 USA. RP Tomarev, SI (reprint author), NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH,DHHS, Bldg 7,Room 103, Bethesda, MD 20814 USA. EM tomarevs@nei.nih.gov RI Torrado, Mario/A-4889-2010 OI Torrado, Mario/0000-0001-9762-7018 NR 57 TC 18 Z9 25 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2004 VL 45 IS 9 BP 3081 EP 3090 DI 10.1167/iovs.04-0302 PG 10 WC Ophthalmology SC Ophthalmology GA 848XH UT WOS:000223500900029 PM 15326124 ER PT J AU Kim, BJ Li, ZQ Fariss, RN Shen, DF Mahesh, SP Egwuagu, C Yu, CR Nagineni, CN Chan, CC Nussenblatt, RB AF Kim, BJ Li, ZQ Fariss, RN Shen, DF Mahesh, SP Egwuagu, C Yu, CR Nagineni, CN Chan, CC Nussenblatt, RB TI Constitutive and cytokine-induced GITR ligand expression on human retinal pigment epithelium and photoreceptors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NITRIC-OXIDE SYNTHASE; INDUCED TNF RECEPTOR; EXPERIMENTAL AUTOIMMUNE UVEITIS; IMMUNOLOGICAL SELF-TOLERANCE; REGULATORY T-CELLS; INFLAMMATORY MEDIATORS; MURINE MACROPHAGE; GENE-EXPRESSION; FAMILY; LYMPHOCYTES AB PURPOSE. The glucocorticoid-induced TNF-related receptor ( GITR) plays a pivotal role in regulating the suppressive function of CD4(+) CD25(+) regulatory T cells. GITR is also involved in the inhibition of T-cell receptor-induced apoptosis and the upregulation of inducible nitric oxide synthase ( iNOS). GITR expression on CD4(+) T cells has been shown to correlate with the disease course of noninfectious uveitis. The current study was conducted to examine the expression of glucocorticoid-induced TNF-related receptor ligand (GITRL) and its regulation by ocular tissue. METHODS. Immunohistochemistry and confocal immunofluorescence microscopy were performed on human ocular tissue to examine the in vivo protein expression of GITRL. The regulation of GITRL was investigated by culturing retinal pigment epithelium (RPE) with proinflammatory cytokines and performing immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). The in vivo mRNA expression of GITRL was studied by RT-PCR on RNA from microdissected tissue sections. RESULTS. Both immunohistochemistry and confocal immunofluorescence microscopy demonstrated that GITRL was expressed constitutively on RPE and photoreceptor inner segments. Immunocytochemistry demonstrated that in vitro stimulated RPE cells expressed GITRL at the protein level, and RT-PCR showed that GITRL was upregulated at 24 hours by proinflammatory cytokines. Constitutive GITRL mRNA expression in vivo was confirmed by RT-PCR analysis of microdissected tissue. CONCLUSIONS. GITRL is expressed constitutively on RPE and in high levels on photoreceptor inner segments. The upregulation of GITRL by proinflammatory cytokines suggests that GITRL may play an important role in ocular immunity. The high level of constitutive GITRL expression on photoreceptor inner segments suggests that photoreceptors participate in the regulation of ocular inflammation. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10S219,10 Ctr Dr, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov NR 32 TC 24 Z9 25 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2004 VL 45 IS 9 BP 3170 EP 3176 DI 10.1167/iovs.03-0919 PG 7 WC Ophthalmology SC Ophthalmology GA 848XH UT WOS:000223500900042 PM 15326137 ER PT J AU Zeng, Y Takada, Y Kjellstrom, S Hiriyanna, K Tanikawa, A Wawrousek, E Smaoui, N Caruso, R Bush, RA Sieving, PA AF Zeng, Y Takada, Y Kjellstrom, S Hiriyanna, K Tanikawa, A Wawrousek, E Smaoui, N Caruso, R Bush, RA Sieving, PA TI RS-1 gene delivery to an adult Rs1h knockout mouse model restores ERG b-wave with reversal of the electronegative waveform of X-linked retinoschisis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID JUVENILE RETINOSCHISIS; MULLER CELLS; PHOTORECEPTOR; BIPOLAR; PROTEIN; ELECTRORETINOGRAM; HISTOPATHOLOGY; TRANSDUCTION; EXPRESSION; MUTATIONS AB PURPOSE. To create and evaluate a mouse model of human X-linked juvenile retinoschisis (XLRS) and then investigate whether supplementing with the retinoschisin protein by gene delivery can reverse the abnormal "electronegative" electroretinogram ( ERG) retinal response. METHODS. An X-linked retinoschisis mouse (Rs1h-KO) model was created by substituting a neomycin resistance cassette for exon 1 and 1.6 kb of intron 1 of Rs1h, the murine orthologue of the human RS-1 gene. RS protein was evaluated by immunohistochemistry and Western blot analysis with a polyclonal RS N-terminus antibody. Retinal function was evaluated by conventional, full-field flash ERG recordings. RS protein supplementation therapy was evaluated by gene transfer with an AAV(2/2)-CMV-Rs1h vector containing C57BL/6J Rs1h cDNA under the regulation of a CMV promoter, and ERG functional analysis was performed. RESULTS. No RS protein was detected by Western blot analysis or immunohistochemistry in the Rs1h-KO mouse. Dark-adapted ERG responses showed an electronegative configuration, with b-wave reduction in both Rs1h(-/Y) and Rs1h(-/-) mice, typical of XLRS in humans. Histologic examination of Rs1h-KO mice showed disorganization of multiple retinal layers, including duplication and mislocalization of ganglion cells, laminar dissection through the inner plexiform layer, disorganization of the outer plexiform layer, loss of regularity of the outer nuclear layer, and shortening of the inner/outer segments with mislocalization of photoreceptor nuclei into this layer. After intraocular administration of AAV(2/2)-CMV-Rs1h, immunohistochemistry showed retinoschisin expression in all retinal layers of Rs1h(-/Y) mice, and ERG recordings showed reversal of the electronegative waveform and restoration of the normal positive b- wave. CONCLUSIONS. The RS-KO mouse mimics structural features of human X-linked juvenile retinoschisis with dissection through, and disorganization of, multiple retinal layers. The Rs1h-KO functional deficit results in an electronegative ERG waveform that is characteristic of human retinoschisis disease and that implicates a synaptic transmission deficit in the absence of retinoschisin protein. Replacement therapy by supplementing normal Rs1h protein in the adult Rs1h-KO mouse restored the normal ERG configuration. This indicates that gene therapy is a viable strategy of therapeutic intervention even in the post-developmental adult stage of XLRS disease. C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Bldg 31,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov RI Wawrousek, Eric/A-4547-2008 NR 42 TC 116 Z9 120 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2004 VL 45 IS 9 BP 3279 EP 3285 DI 10.1167/iovs.04-0576 PG 7 WC Ophthalmology SC Ophthalmology GA 848XH UT WOS:000223500900057 PM 15326152 ER PT J AU Takada, Y Fariss, RN Tanikawa, A Zeng, Y Carper, D Bush, R Sieving, PA AF Takada, Y Fariss, RN Tanikawa, A Zeng, Y Carper, D Bush, R Sieving, PA TI A retinal neuronal developmental wave of retinoschisin expression begins in ganglion cells during layer formation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID X-LINKED RETINOSCHISIS; DEVELOPING MOUSE RETINA; ROD BIPOLAR CELLS; PROTEIN-KINASE-C; JUVENILE RETINOSCHISIS; MAMMALIAN RETINA; DIFFERENTIAL LOCALIZATION; POSTSYNAPTIC DENSITY; OUTER SEGMENTS; MESSENGER-RNA AB PURPOSE. Mutations in the retinoschisin gene, RS-1, cause juvenile X-linked retinoschisis (XLRS), a dystrophy characterized by delamination of the inner retinal layers, leading to visual impairment. Although the retinoschisin protein (RS) is expressed most abundantly in photoreceptors in the outer retina, XLRS disease affects the innermost retinal layers, including the nerve fiber layer that contains retinal ganglion cells (RGCs). Considering the histopathological and electrophysiological characteristics of the clinical disease, the present study was conducted to evaluate the local cellular expression of RS-1 during retinal development. METHODS. RS protein and RS-1 mRNA were localized to specific retinal cell types in embryonic to adult mice by immunohistochemistry, confocal immunofluorescence microscopy, catalyzed reporter deposition in situ hybridization, and laser capture microdissection/RT-PCR. RESULTS. RS-1 mRNA was expressed first in RGCs by postnatal day ( P) 1, after terminal differentiation. Expression then moved posteriorly through the retina in a spatial and temporal developmental wave, as additional neuronal classes were born and synaptic layers were formed. RS was expressed by bipolar cells at a time when these neurons were establishing functional synapses with photoreceptors, evidenced by the appearance of the electroretinogram b-wave between P12 and P14. CONCLUSIONS. All major classes of adult retinal neurons, with the possible exception of horizontal cells, express RS protein and mRNA, strongly suggesting that retinoschisin in the inner retina is synthesized locally rather than being transported, as earlier proposed, from distal retinal photoreceptors. Continued expression of RS by mature inner-retinal neurons supports the possibility of a therapeutic strategy of protein replacement to treat both infants and adults with XLRS. C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP Sieving, PA (reprint author), NEI, NIH, 31 Ctr Dr,Bldg 31,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov NR 77 TC 60 Z9 62 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2004 VL 45 IS 9 BP 3302 EP 3312 DI 10.1167/iovs.04-0156 PG 11 WC Ophthalmology SC Ophthalmology GA 848XH UT WOS:000223500900060 PM 15326155 ER PT J AU Kriebel, PW Parent, CA AF Kriebel, PW Parent, CA TI Adenylyl cyclase expression and regulation during the differentiation of Dictyostelium discoideum SO IUBMB LIFE LA English DT Review DE chemotaxis; development; cAMP; G proteins; PH domains; osmolarity; histidine kinase ID PROTEIN-MEDIATED ACTIVATION; SIGNAL-TRANSDUCTION; CHEMOATTRACTANT RECEPTOR; SPORE DORMANCY; LEADING-EDGE; CHEMOTAXIS; CAMP; INHIBITION; OSMOSENSOR; MUTANTS AB Cyclic AMP metabolism is essential for the survival of the social amoebae Dictyostelium discoideum . Three distinct adenylyl cyclases are expressed and required for the normal development of this simple eukaryote. The adenylyl cyclase expressed during aggregation, ACA, is related to the mammalian and Drosophila G protein-coupled enzymes and is responsible for the synthesis of cAMP that is required for cell-cell signaling in early development. ACB harbors histidine kinase and response-regulator domains and is required for terminal differentiation. Finally, the adenylyl cyclase expressed during germination, ACG, acts as an osmosensor and is involved in controlling spore germination. Together, these enzymes generate the various levels of cAMP that are required for D. discoideum to transition from uni- to multi-cellularity. This review will highlight the properties of these enzymes and describe the signaling cascades that lead to their activation. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37 Rm 2066, Bethesda, MD 20892 USA. EM parentc@helix.nih.gov NR 49 TC 26 Z9 27 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD SEP PY 2004 VL 56 IS 9 BP 541 EP 546 DI 10.1080/15216540400013887 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 875SU UT WOS:000225442800004 PM 15590560 ER PT J AU van den Bree, MBM Whitmer, MD Pickworth, WB AF van den Bree, MBM Whitmer, MD Pickworth, WB TI Predictors of smoking development in a population-based sample of adolescents: A prospective study SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; cigarettes; delinquency; gender differences; longitudinal; religion; risk factors; school; smoking stages; substance use ID HIGH-SCHOOL-STUDENTS; CIGARETTE-SMOKING; SUBSTANCE USE; DRUG-USE; YOUNG ADULTHOOD; LATE CHILDHOOD; UNITED-STATES; TOBACCO USE; FOLLOW-UP; RISK AB Purpose: To study the development of smoking behavior in adolescents using a longitudinal, multivariate design. Methods: Adolescents (n = 14,133, age range 12 to 18 years) took part in the longitudinal Add Health study (two waves, separated by 1 year, 56% smokers and 44% nonsmokers at Wave 1). Eight risk factor domains were established at Wave 1 (daily activities, psychological health, personality, school situation, family functioning, rough living, religion, and neighborhood status), which were further separated into subdomains by factor analysis. Subdomains were used to predict risk at Wave 2 of smoking initiation, progression, or failure to discontinue, using logistic regression analysis. Analyses were performed for boys and girls separately and results corrected for age, race, urbanicity, and socioeconomic status. Results: Use/abuse of other substances by self and peers influenced most stages of smoking, whereas trouble in school was associated with initiation and progression of smoking. Poor family relations predicted initiation of experimental smoking for girls, whereas low involvement in active pastimes predicted failure to discontinue experimental smoking. For boys, low religiosity predicted progression to regular smoking and failure to quit regular smoking, whereas delinquency also reduced success of regular smoking discontinuation. Conclusions: These findings may direct efforts for prevention and intervention of adolescent smoking behavior and may also provide guidance for future studies. (C) Society for Adolescent Medicine, 2004. C1 Univ Wales Coll Cardiff, Coll Med, Div Psychol Med, Cardiff CF14 4XN, S Glam, Wales. NIDA, Intramural Res Program, NIH, Baltimore, MD USA. RP van den Bree, MBM (reprint author), Univ Wales Coll Cardiff, Coll Med, Div Psychol Med, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. RI turton, miranda/F-4682-2011 FU NICHD NIH HHS [P01 HD 31921] NR 56 TC 68 Z9 73 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2004 VL 35 IS 3 BP 172 EP 181 DI 10.1016/j.jadohealth.2003.09.021 PG 10 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 849AK UT WOS:000223509400002 PM 15313498 ER PT J AU Robinson, MQL Berlin, I Moolchan, ET AF Robinson, MQL Berlin, I Moolchan, ET TI Tobacco smoking trajectory and associated ethnic differences among adolescent smokers seeking cessation treatment SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; cessation treatment; ethnic differences; smoking trajectory; tobacco dependence ID FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE PATCH THERAPY; CIGARETTE-SMOKING; YOUNG-ADULTS; DEVELOPMENTAL TRAJECTORIES; AFRICAN-AMERICANS; NATURAL-HISTORY; UNITED-STATES; FOLLOW-UP; DEPENDENCE AB Purpose: To examine smoking trajectories in a clinical sample of adolescent smokers seeking cessation treatment, including: (a) smoking onset (initial, daily) and time intervals from initial to daily smoking and from daily smoking to treatment request, (b) associations between current level of tobacco dependence and smoking history, and (c) differences in smoking trajectory between African-American and non-African-American youth. Methods: Four hundred and thirty-two adolescent smokers (aged 13-17 years, 61.8% female, 32% African-American) responding to various media advertisement completed a telephone interview as part of pre-eligibility screening for a smoking cessation trial. Smoking trajectory data included age at onset of initial and daily smoking, intervals between those time points, and cigarettes smoked per day (CPD). Tobacco dependence was assessed using the Fagerstrom Test for Nicotine Dependence (FTND). Data were analyzed using regression models and multiple analyses of covariance. Results: Initial smoking occurred at a mean age of less than 12 years and daily smoking at age 13 years. Earlier onset of daily smoking was associated with higher FTND scores and longer duration from daily smoking to treatment request. For the entire sample, the time interval from initial to daily smoking was 1.14 years. When the sample was divided into early (before age 14 years) and later (at or after age 14 years) initiators, early initiators showed it slower progression from initial to daily smoking compared with late initiators (16 months vs. 6 months). Compared with non-African-American teen smokers, African-American youth reported a 1-year delay in onset of both initial and daily smoking. Conclusions: Early age of daily smoking and short time interval from initial to daily smoking highlight a brief window of opportunity to prevent the development of tobacco addiction and its consequences. Ethnic differences in smoking trajectory uncovered in this report call for ethnically tailored interventions to reduce youth smoking, (C) Society for Adolescent Medicine, 2004. C1 NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, Teen Tobacco Addict Treatment Res Clin,NIH, Baltimore, MD 21224 USA. Pitie Salpetriere Med Sch, Dept Pharmacol, Paris, France. RP Moolchan, ET (reprint author), NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, Teen Tobacco Addict Treatment Res Clin,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov NR 61 TC 33 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2004 VL 35 IS 3 BP 217 EP 224 DI 10.1016/j.jadohealth.2003.10.005 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 849AK UT WOS:000223509400007 PM 15313503 ER PT J AU O'Connor, GT Walter, M Mitchell, H Kattan, M Morgan, WJ Gruchalla, RS Pongracic, JA Smartt, E Stout, JW Evans, R Crain, EF Burge, HA AF O'Connor, GT Walter, M Mitchell, H Kattan, M Morgan, WJ Gruchalla, RS Pongracic, JA Smartt, E Stout, JW Evans, R Crain, EF Burge, HA TI Airborne fungi in the homes of children with asthma in low-income urban communities: The Inner-City Asthma Study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE airborne fungi; indoor mold; home environmental characteristics; indoor air; inner-city pediatric asthma ID OUTDOOR AIR; MOLD EXPOSURE; INDOOR AIR; PREVALENCE; ENVIRONMENTS; PROPAGULES; ALLERGENS; POLLEN; SPORES; ATOPY AB Background: Despite growing evidence of the importance of exposure to fungi as an environmental risk factor for asthma, few data have been reported on the exposure to airborne fungi of asthmatic children living in US inner cities. Objective: We sought to examine the spectrum and concentration of fungi in the air inside and outside of the homes of mold-sensitive children with asthma living in US cities. We also analyzed the relationship of the concentration of fungi in indoor air to home characteristics. Methods: We performed a home environmental survey and measured the concentrations of culturable airborne fungi inside and outside the homes of 414 mold-sensitive children with asthma in 7 urban communities. Results: The airborne fungi encountered indoors generally paralleled those found outdoors, and the similarities between communities were more striking than the differences. Indoor fungal concentrations were correlated with outdoor concentrations measured on the same day, suggesting the need to adjust for the outdoor concentration in analyses by using the indoor concentration as an indicator of the relative moldiness of a home. The concentration of fungi in indoor air in excess of outdoor air-that is, the indoor-outdoor difference-was significantly related to home characteristics, including dampness, having a cat, and cockroach infestation. Conclusion: Mold-sensitive children with asthma living in urban communities across the US are exposed to airborne fungi in indoor and outdoor air. The concentrations of fungi are higher in homes with dampness problems, cockroach infestation, and cats. The indoor-outdoor difference in the concentration of airborne fungi may provide a valuable metric for investigations of the role of fungal exposure as a risk factor for asthma. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. Rho Inc, Chapel Hill, NC USA. CUNY Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. Univ Arizona, Resp Sci Ctr, Tucson, AZ USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA. Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. NIAID, Bethesda, MD 20892 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth Sci, Boston, MA 02115 USA. RP O'Connor, GT (reprint author), Boston Univ, Sch Med, Ctr Pulm, Room R304,715 Albany St, Boston, MA 02118 USA. EM goconnor@bu.edu OI O'Connor, George/0000-0002-6476-3926 FU NCRR NIH HHS [M01 RR00533]; NIAID NIH HHS [AI/ES-39785, AI/ES-39761, AI/ES-39769, AI/ES-39776, AI/ES-39789, AI/ES-39900, AI/ES-39901, AI/ES-39902] NR 25 TC 69 Z9 73 U1 1 U2 13 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2004 VL 114 IS 3 BP 599 EP 606 DI 10.1016/j.jaci.2004.05.064 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 853AX UT WOS:000223799600020 PM 15356564 ER PT J AU Orange, JS Levy, O Brodeur, SR Krzewski, K Roy, RM Niemela, JE Fleisher, TA Bonilla, FA Geha, RS AF Orange, JS Levy, O Brodeur, SR Krzewski, K Roy, RM Niemela, JE Fleisher, TA Bonilla, FA Geha, RS TI Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE NF-kappa B; I kappa B kinase; immunologic deficiency syndromes; X-chromosome-linked genetic diseases; innate immunity ID HYPER-IGM SYNDROME; INCONTINENTIA PIGMENTI; BACTERIAL-INFECTIONS; IMMUNE-DEFICIENCY; IKK-GAMMA; NEMO; PATHWAY; INTERLEUKIN-1; ACTIVATION AB Background: Many receptors rely on the appropriate activation of nuclear factor (NF)kappaB to induce cellular function. This process depends critically on the phosphorylation of the inhibitor of NF-kappaB (IkappaB) by the IkappaB kinase. This targets IkappaB for ubiquitination and degradation, allowing NF-kappaB to translocate to the nucleus, where it can direct transcription. Hypomorphic human mutations affecting one IkappaB kinase component, the NF-kappaB essential modulator (NEMO), result in impaired signaling from receptors required for ectodermal development and immune function. Male subjects with these mutant NEMO molecules have an X-linked syndrome known as ectodermal dysplasia with immunodeficiency, which is characterized by severe infections, with herpesviruses, bacteria, and mycobacterial susceptibility. Objective: We sought to genetically and biochemically characterize a patient with a mutant NEMO molecule without ectodermal abnormalities. Methods: We evaluated NEMO in a patient who had immunodeficiency and atypical mycobacterial infection but normal ectoderm. Results: We identified a novel NEMO mutant causing immunodeficiency without ectodermal dysplasia. The mutation, which altered the exon 9 splice site, was present in cells of ectodermal and hematopoetic origin and resulted in a heterogeneous mixture of mutant and wild-type cDNA species. Immunologic function was variably impaired, with reduced CD40-induced B-cell proliferation, partially reduced NF-kappaB p65 nuclear translocation, and variable Toll-like receptor-induced TNF production. This variability might be explained by an inconsistent ratio of mutant to wild-type NEMO. The lack of any ectodermal phenotype, however, suggested a separation in the hematopoetic and ectodermal function of NEMO that leads to NF-kappaB activation. Conclusion: Mutation of the gene encoding NEMO can result in immunodeficiency without ectodermal dysplasia. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA USA. Childrens Hosp, Div Infect Dis, Boston, MA USA. Childrens Hosp, Div Immunol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02138 USA. Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA USA. Warren G Magnuson Clin Ctr, Dept Lab Med, NIH, Bethesda, MD USA. RP Geha, RS (reprint author), Childrens Hosp, Div Immunol, New Res Bldg,1 Blackfan Circle, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu RI Orange, Jordan/D-5239-2009; OI Niemela, Julie/0000-0003-4197-3792; orange, jordan/0000-0001-7117-7725 FU NCRR NIH HHS [M01-RR02172]; NIAID NIH HHS [AI-50583, AI-55602, AI-31136, AI-31451] NR 25 TC 69 Z9 71 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2004 VL 114 IS 3 BP 650 EP 656 DI 10.1016/j.jaci.2004.06.052 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 853AX UT WOS:000223799600028 PM 15356572 ER PT J AU Hung, CH Chen, LC Zhang, ZJ Chowdhury, B Lee, WL Plunkett, B Chen, CH Myers, AC Huang, SK AF Hung, CH Chen, LC Zhang, ZJ Chowdhury, B Lee, WL Plunkett, B Chen, CH Myers, AC Huang, SK TI Regulation of T(H)2 responses by the pulmonary Clara cell secretory 10-kd protein SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE T(H)2; cytokine; Clara cell; CC10; asthma ID UTEROGLOBIN GENE; CUTTING EDGE; TH2 CELLS; GATA-3; ASTHMA; INHIBITION; MICE; RESPONSIVENESS; INFLAMMATION; POLYMORPHISM AB Background: Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T-cell responses remains unknown. Objective: The role of CC10 in the regulation of T(H)2 cytokine expression was investigated. Methods: The levels of cytokine and GATA-3 expression were determined by ELISA and RT-PCR, respectively. Bronchoalveolar lavage fluid cell counts were also determined by using a standard protocol. CC10 expression in vivo was determined by immunocytochemistry and Western blotting. Results: In vitro, a significant, dose-dependent suppressive effect of CC10 was found on T(H)2 cytokine expression, but not IFN-gamma, in splenocytes of antigen-sensitized mice. A similar suppressive effect was also noted in polarized CD4(+) T(H)2 cells, but not in naive CD4(+) T cells. In contrast, CC10 was able to induce IFN-gamma expression in naive CD4(+) T cells, but not in polarized T(H)1 cells. Furthermore, the suppression of T(H)2 cytokine expression was concomitant with reduction of a critical transcription factor, GATA-3. Of significance was the finding that although no significant change was found in the decay kinetics of T(H)2 cytokine transcripts, a significant decrease in mRNA stability of GATA-3 was seen in CC10-treated cells. In vivo, reconstitution of the CC10 gene in CC10-deficient mice resulted in significantly lower levels of T(H)2 cytokines, concomitant with a decrease in GATA-3 expression, after challenge with Ag compared with those seen in mock-transduced mice, which are associated with reduced levels of pulmonary eosinophilia. Conclusion: These results demonstrate, that CC10 plays a direct role in the regulation of T-cell-mediated inflammatory responses. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. Tri Serv Gen Hosp, Dept Pediat, Taipei, Taiwan. Natl Def Med Ctr, Taipei, Taiwan. Chang Gung Childrens Hosp, Dept Pediat, Div Allergy Asthma & Rheumatol, Tao Yuan, Taiwan. NICHHD, NIH, Bethesda, MD 20892 USA. Taipei Med Univ, Taipei, Taiwan. RP Huang, SK (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM skhuang@jhmi.edu RI Hung, Chih-Hsing/C-7296-2009; Huang, Shau-Ku/F-5509-2010 FU PHS HHS [R01-40274] NR 32 TC 46 Z9 49 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2004 VL 114 IS 3 BP 664 EP 670 DI 10.1016/j.jaci.2004.05.042 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 853AX UT WOS:000223799600030 PM 15356574 ER PT J AU Notarangelo, L Casanova, JL Fischer, A Puck, J Rosen, F Seger, R Geha, R AF Notarangelo, L Casanova, JL Fischer, A Puck, J Rosen, F Seger, R Geha, R CA Int Union Immunological Soc Primar TI Primary immunodeficiency diseases: An update SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE primary immunodeficiency diseases; T cells; B cells; phagocytes; complement; immune dysregulation syndromes; innate immunity ID CLASSIFICATION AB Although relatively rare, primary immune deficiency diseases (PIDs) provide an excellent window into the functioning of the immune system. In the late 1960s, observations on these diseases, with their associated infections and genetics, bisected the immune system into Immoral immunity and cell-mediated immunity. These diseases also represent a challenge in their diagnosis and treatment. Beginning in 1970, a unified nomenclature for the then-known primary immunodeficiency diseases was created by a committee convened by the World Health Organization. Since then, and later under the aegis of the International Union of Immunological Societies, an international committee of experts has met every 2 to 3 years to update the classification of PIDs. During the past 15 years, the molecular basis of more than 100 PIDs has been elucidated. This update results from the latest meeting of this committee in Sintra, Portugal, June 2003, which followed 2(1)/(2) days of scientific discussions. C1 Univ Brescia Spedali Civili, Dept Pediat, Brescia, Italy. Hop Necker Enfants Malad, Paris, France. NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Univ Kinderklin, Zurich, Switzerland. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Geha, R (reprint author), Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 4 TC 90 Z9 97 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2004 VL 114 IS 3 BP 677 EP 687 DI 10.1016/j.jaci.2004.06.044 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 853AX UT WOS:000223799600032 PM 15356576 ER PT J AU Cohen, SG Zelaya-Quesada, M AF Cohen, SG Zelaya-Quesada, M TI Prausnitz and Kustner phenomenon: The P-K reaction SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID PASSIVE TRANSFER; ATOPIC REAGIN; HYPERSENSITIVENESS; SKIN; ANTIBODY; SENSITIVITY; ASTHMA; SERUM C1 NIAID, NIH, Bethesda, MD 20892 USA. NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2004 VL 114 IS 3 BP 705 EP 710 DI 10.1016/j.jaci.2004.06.039 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 853AX UT WOS:000223799600041 PM 15356578 ER PT J AU Huestis, MA Cone, EJ AF Huestis, MA Cone, EJ TI Relationship of Delta(9)-tetrahydrocannabinol concentrations in oral fluid and plasma after controlled administration of smoked cannabis SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID MARIJUANA SMOKE; IMMUNOASSAY; EXCRETION; SALIVA; HUMANS; ABUSE; BLOOD; URINE; DRUGS C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 22 TC 103 Z9 111 U1 1 U2 8 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP PY 2004 VL 28 IS 6 BP 394 EP 399 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 850RQ UT WOS:000223630500002 PM 15516285 ER PT J AU Zhang, ZJ McCaffery, JM Spencer, RGS Francomano, CA AF Zhang, ZJ McCaffery, JM Spencer, RGS Francomano, CA TI Hyaline cartilage engineered by chondrocytes in pellet culture: histological, immunohistochemical and ultrastructural analysis in comparison with cartilage explants SO JOURNAL OF ANATOMY LA English DT Article DE aggrecan; chondrogenesis; collagen; differentiation; phenotype ID CHICK STERNAL CARTILAGE; ARTICULAR-CARTILAGE; TERMINAL DIFFERENTIATION; MATRIX PRODUCTION; HIGH-DENSITY; COLLAGEN-IX; IN-VITRO; TISSUE; REGENERATION; MICROSCOPY AB Cartilage engineering is a strategic experimental goal for the treatment of multiple joint diseases. Based on the process of embryonic chondrogenesis, we hypothesized that cartilage could be engineered by condensing chondrocytes in pellet culture and, in the present study, examined the quality of regenerated cartilage in direct comparison with native cartilage. Chondrocytes isolated from the sterna of chick embryos were cultured in pellets (4 x 10(6) cells per pellet) for 2 weeks. Cartilage explants from the same source were cultured as controls. After 2 weeks, the regenerated cartilage from pellet culture had a disc shape and was on average 9 mm at the longest diameter. The chondrocyte phenotype was stabilized in pellet culture as shown by the synthesis of type II collagen and aggrecan, which was the same intensity as in the explant after 7 days in culture. During culture, chondrocytes also continuously synthesized type IX collagen. Type X collagen was negatively stained in both pellets and explants. Except for fibril orientation, collagen fibril diameter and density in the engineered cartilage were comparable with the native cartilage. In conclusion, hyaline cartilage engineered by chondrocytes in pellet culture, without the transformation of cell phenotypes and scaffold materials, shares similarities with native cartilage in cellular distribution, matrix composition and density, and ultrastructure. C1 NIA, Genet Lab, NIH, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Biol, Integrated Imaging Ctr, Baltimore, MD 21218 USA. RP Zhang, ZJ (reprint author), NIA, Genet Lab, NIH, Intramural Res Program, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM zhangzj@grc.nia.nih.gov NR 34 TC 72 Z9 74 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0021-8782 J9 J ANAT JI J. Anat. PD SEP PY 2004 VL 205 IS 3 BP 229 EP 237 DI 10.1111/j.0021-8782.2004.00327.x PG 9 WC Anatomy & Morphology SC Anatomy & Morphology GA 855TV UT WOS:000223998400006 PM 15379928 ER PT J AU Poletto, CJ Verdun, LP Strominger, R Ludlow, CL AF Poletto, CJ Verdun, LP Strominger, R Ludlow, CL TI Correspondence between laryngeal vocal fold movement and muscle activity during speech and nonspeech gestures SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE correlation; electromyography; larynx; nasolaryngoscopy; muscle activation; intrinsic laryngeal muscles ID POSTERIOR CRICOARYTENOID MUSCLE; NORMAL ADULT HUMANS; THYROARYTENOID MUSCLE; CRICOTHYROID MUSCLE; VOLUNTARY HYPERVENTILATION; BOTULINUM TOXIN; SLEEP; ELECTROMYOGRAPHY; PHONATION; WAKEFULNESS AB To better understand the role of each of the laryngeal muscles in producing vocal fold movement, activation of these muscles was correlated with laryngeal movement during different tasks such as sniff, cough or throat clear, and speech syllable production. Four muscles [the posterior cricoarytenoid, lateral cricoarytenoid, cricothyroid (CT), and thyroarytenoid (TA)] were recorded with bipolar hooked wire electrodes placed bilaterally in four normal subjects. A nasoendoscope was used to record vocal fold movement while simultaneously recording muscle activity. Muscle activation level was correlated with ipsilateral vocal fold angle for vocal fold opening and closing. Pearson correlation coefficients and their statistical significance were computed for each trial. Significant effects of muscle (P less than or equal to 0.0005) and task (P = 0.034) were found on the r (transformed to Fisher's Z') values. All of the posterior cricoarytenoid recordings related significantly with vocal opening, whereas CT activity was significantly correlated with opening only during sniff. The TA and lateral cricoarytenoid activities were significantly correlated with vocal fold closing during cough. During speech, the CT and TA activity correlated with both opening and closing. Laryngeal muscle patterning to produce vocal fold movement differed across tasks; reciprocal muscle activity only occurred on cough, whereas speech and sniff often involved simultaneous contraction of muscle antagonists. In conclusion, different combinations of muscle activation are used for biomechanical control of vocal fold opening and closing movements during respiratory, airway protection, and speech tasks. C1 NINDS, Larynegeal & Speech Sect, Clin Neurosci Program, Bethesda, MD USA. RP Poletto, CJ (reprint author), NINDS, Larynegeal & Speech Sect, Clin Neurosci Program, Bldg 10,Rm 5D 38,10 Ctr Dr.MSC 1416, Bethesda, MD USA. EM polettoc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU Intramural NIH HHS [Z01 NS002980-08] NR 58 TC 28 Z9 30 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2004 VL 97 IS 3 BP 858 EP 866 DI 10.1152/japplphysiol.00087.2004 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 850EP UT WOS:000223594300009 PM 15133000 ER PT J AU Englander, J Klein, E Brumfeld, V Sharma, AK Doherty, AJ Minsky, A AF Englander, J Klein, E Brumfeld, V Sharma, AK Doherty, AJ Minsky, A TI DNA toroids: Framework for DNA repair in Deinococcus radiodurans and in germinating bacterial spores SO JOURNAL OF BACTERIOLOGY LA English DT Editorial Material ID ESCHERICHIA-COLI; RECA PROTEIN; IONIZING-RADIATION; STRAND EXCHANGE; IN-VIVO; RESISTANCE; GENOME; RECOMBINATION; CONDENSATION; TEMPERATURE C1 Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Chem Sci, IL-76100 Rehovot, Israel. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RH, E Sussex, England. RP Minsky, A (reprint author), Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. EM avi.minsky@weizmann.ac.il NR 52 TC 39 Z9 42 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2004 VL 186 IS 18 BP 5973 EP 5977 DI 10.1128/jb.186.18.5973-5977.2004 PG 5 WC Microbiology SC Microbiology GA 851QM UT WOS:000223699900001 PM 15342565 ER PT J AU Hattery, D Hattery, B Chernomordik, V Smith, P Loew, M Mulshine, J Gandjbakhche, A AF Hattery, D Hattery, B Chernomordik, V Smith, P Loew, M Mulshine, J Gandjbakhche, A TI Differential oblique angle spectroscopy of the oral epithelium SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE oral; cancer; spectroscopy; inflammation; diffuse reflectance; chemopreventive ID OPTICAL COHERENCE TOMOGRAPHY; PHOTON MIGRATION; IN-VIVO; LAYERED MEDIA; INFLAMMATION; DIFFUSION; TISSUE; SKIN AB Increasing evidence suggests that inflammation may contribute to the process of carcinogenesis. This is the basis of several clinical trials evaluating potential chemopreventive drugs. These trials require quantitative assessments of inflammation, which, for the oral epithelium, are traditionally provided by histopathological evaluation. To reduce patient discomfort and morbidity of tissue biopsy procedures, we develop a noninvasive alternative using diffuse reflectance spectroscopy to measure epithelial thickness as an index of tissue inflammation. Although any optical system has the potential for probing near-surface structures, traditional methods of accounting for scattering of photons are generally invalid for typical epithelia] thicknesses. We develop a single-scattering theory that is valid for typical epithelial thicknesses. The theory accurately predicts a distinctive feature that can be used to quantify epithelia[ thickness given intensity measurements with sources at two different angles relative to the tissue surface. This differential measure approach has acute sensitivity to small, layer-related changes in scattering coefficients. To assess the capability of our method to quantify epithelial thickness, detailed Monte Carlo simulations and measurements on phantom models of a two-layered structure are performed. The results show that the intensity ratio maximum feature can be used to quantify epithelial thickness with an error less than 30% despite fourfold changes in scattering coefficients and 10-fold changes in absorption coefficients. An initial study using a simple two-source, four-detector probe on patients shows that the technique has promise. We believe that this new method will perform well on patients with diverse tissue optical characteristics and therefore be of practical clinical value for quantifying epithelial thickness in vivo. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 NICHHD, NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Apogee Biodimens, Washington, DC 20011 USA. NIH, Off Res Serv, Bethesda, MD 20892 USA. George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Hattery, D (reprint author), NIH, 5630 16th St NW, Washington, DC 20011 USA. EM hattery@ieee.org NR 22 TC 6 Z9 6 U1 0 U2 1 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD SEP-OCT PY 2004 VL 9 IS 5 BP 951 EP 960 DI 10.1117/1.1781161 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 860PY UT WOS:000224356700012 PM 15447016 ER PT J AU O'Neil-Cabello, E Wu, ZR Bryce, DL Nikonowicz, EP Bax, A AF O'Neil-Cabello, E Wu, ZR Bryce, DL Nikonowicz, EP Bax, A TI Enhanced spectral resolution in RNA HCP spectra for measurement of (3)J(C2/P) and (3)J(C4/P) couplings and P-31 chemical shift changes upon weak alignment SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE CSA; Karplus equation; liquid crystal; Pf1; phosphodiester; RNA; torsion angle ID RESIDUAL DIPOLAR COUPLINGS; NMR-SPECTROSCOPY; NUCLEIC-ACIDS; STRUCTURE REFINEMENT; DNA DODECAMER; STEM-LOOP; PROTEINS; CONSTANTS; DYNAMICS; BACKBONE AB The 'out-and-back' 3D HCP experiment, using gradient- and sensitivity-enhanced detection, provides a convenient method for assignment of the P-31 NMR spectra and accurate measurement of the 31P chemical shifts of ribonucleic acids. The C-13 resolution in such spectra can be doubled, at the cost of a 50% reduction in sensitivity, by combining C-13 evolution during the C-13-{P-31} de- and rephasing periods. The multiple connectivities observable for a given P-31, including correlations to the intranucleotide C5'H-2 and C4'H groups, and the C2'H, C3'H and C4'H groups of the preceding nucleotide, permit independent measurements of the P-31 shift. The C-13 spectrum of these groups is typically crowded for an RNA molecule in isotropic solution and overlap becomes more problematic in media used to achieve partial alignment. However, many of these correlations are resolvable in the combined-evolution HCP spectrum. The difference in P-31 chemical shift between isotropic solution and a medium containing liquid crystalline Pf1 provides information on the orientation of phosphate groups. The intensities measured in the 3D HCP spectrum, obtained for an isotropic sample, yield values for the (3)J(C2'P) and (3)J(C4'P) couplings, thereby providing important restraints for the backbone torsion angles e and. The experiments are illustrated for a uniformly C-13-enriched, 24-residue stem-loop RNA sequence, and results for the helical stem region show close agreement between observed Deltadelta(P-31) values and those predicted for a model A-form RNA helix when using a uniform 31P CSA tensor. This confirms that Deltadelta(P-31) values can be used directly as restraints in refining nucleic acid structures. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77251 USA. RP O'Neil-Cabello, E (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RI Bryce, David/A-3534-2008 OI Bryce, David/0000-0001-9989-796X NR 52 TC 15 Z9 15 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2004 VL 30 IS 1 BP 61 EP 70 DI 10.1023/B:JNMR.0000042952.66982.38 PG 10 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 857EU UT WOS:000224099800006 PM 15452435 ER PT J AU Karadag, A Fedarko, NS Fisher, LW AF Karadag, A Fedarko, NS Fisher, LW TI Bone sialoprotein bridges MMP-2 to the cell surface, increasing metastatic properties of osteotropic cancer cells in vitro SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX C1 NIDCR, CSDB, DHHS, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1571 EP 1571 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500050 ER PT J AU Chirgwin, JM Martinez, A Wang, Z Mohammad, KS Guise, TA AF Chirgwin, JM Martinez, A Wang, Z Mohammad, KS Guise, TA TI Turnor adrenomedullin increases bone metastases in lung and prostate cancers SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 4th International Conference on Cancer-Induced Bone Diseases CY DEC 08, 2003 CL San Antonio, TX C1 Univ Virginia, Charlottesville, VA USA. Natl Canc Inst, Bethesda, MD USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2004 VL 19 IS 9 BP 1597 EP 1597 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 850JP UT WOS:000223607500141 ER PT J AU Chen, KL Ochalski, PG Tran, TS Sahir, N Schubert, M Pramatarova, A Howell, BW AF Chen, KL Ochalski, PG Tran, TS Sahir, N Schubert, M Pramatarova, A Howell, BW TI Interaction between Dab1 and CrkII is promoted by Reelin signaling SO JOURNAL OF CELL SCIENCE LA English DT Article DE Reelin; Dab1; brain development; Crk; Dock1 ID REGULATES CELL-MIGRATION; FOCAL ADHESION KINASE; APOE RECEPTOR 2; BRAIN-DEVELOPMENT; TYROSINE PHOSPHORYLATION; CRKII/DOCK180/RAC PATHWAY; DROSOPHILA HOMOLOG; STIMULATED NEURONS; APOPTOTIC CELLS; VLDL RECEPTOR AB Reelin-induced Dab1 tyrosine phosphorylation has been implicated in the regulation of neuronal positioning during brain development. The downstream consequences of Dab1 tyrosine phosphorylation are not fully understood, however. Here we identify CrkII, CrkL and Dock1 in complexes bound to tyrosine-phosphorylated Dab1, through mass spectrometry. The CrkII-Dab1 interaction requires tyrosine phosphorylation of Dab1 at residues 220 or 232 and is promoted by Reelin treatment of embryonic forebrain neurons. Unlike other CrkII binding proteins, such as paxillin and p130Cas, expression of Dab1 interfered with CrkII-dependent cell migration of Nara Bladder Tumor II (NBT-II) cells, in a tyrosine phosphorylation-site dependent manner. Overexpression of CrkIIGFP rescued the migration of these cells, suggesting that Dab1 makes Crk a limiting factor for migration. The Dock1-Dab1 association is indirect and requires CrkII. In organisms such as Drosophila melanogaster and Caenorhabditis elegans, signaling complexes, which contain Crk and Dock1 family members are conserved and act through Rac. We show that a rough-eye phenotype in Drosophila caused by exogenous expression of tyrosine-phosphorylated mouse Dab1RFP is partially rescued by a loss-of-function mutation in myoblast city, a Dock1-like gene in Drosophila. We propose a model that tyrosine-phosphorylated Dab1 engages the conserved Crk-Dock1-Rac signaling cassette, but when bound to Dab1 this signaling complex does not support migration. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NINDS, Mol Virol & Neurgenet Sect, NIH, Bethesda, MD 20892 USA. RP Howell, BW (reprint author), NINDS, Neurogenet Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM howellb@ninds.nih.gov NR 60 TC 57 Z9 62 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP 1 PY 2004 VL 117 IS 19 BP 4527 EP 4536 DI 10.1242/jcs.01320 PG 10 WC Cell Biology SC Cell Biology GA 862RD UT WOS:000224507600017 PM 15316068 ER PT J AU Sun, G Voigt, JH Filippov, IV Marquez, VE Nicklaus, MC AF Sun, G Voigt, JH Filippov, IV Marquez, VE Nicklaus, MC TI PROSIT: Pseudo-Rotational Online Service and Interactive Tool, applied to a conformational survey of nucleosides and nucleotides SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; CAMBRIDGE STRUCTURAL DATABASE; B-DNA DODECAMER; CRYSTAL-STRUCTURE; NUCLEIC-ACID; POLYPURINE TRACT; SUGAR; PSEUDOROTATION; BACKBONE; DUPLEX AB Pseudo-Rotational Online Service and Interactive Tool (PROSIT) designed to perform complete pseudorotational analysis of nucleosides and nucleotides is described. This service is freely available at http://cactus.nei.nih.gov/prosit/. Files containing nucleosides/nucleotides or DNA/RNA segments, isolated or bound to other molecules (e.g., a protein) can be uploaded to be processed by PROSIT. The service outputs the pseudorotational phase angle P, puckering amplitude v(max), and other related information for each nucleoside/nucleotide detected. The service was implemented using the chemoinformatics tooWt CACTVS. PROSIT was used for a survey of nucleosides contained in the Cambridge Structural Database and nucleotides in high-resolution crystal structures from the Nucleic Acid Database. Special cases discussed include nucleosides having constrained sugar moieties with extreme puckering amplitudes, and several specific DNA/RNA helices and protein-bound DNA oligonucleotides (Dickerson-Drew dodecamer, RNA/DNA hybrid viral plypurine tract, Z-DNA enantiomers, B-DNA containing (L)-alpha-threofuranosyl nucleotides, TATA-box binding protein/TATA-box complex, and DNA (cytosine C5)-methyltransferase complexed with an oligodeoxyribonucleotide containing transition state analogue 5,6-dihydro-5-azacytosine). When the puckering amplitude decreases to a small value, the sugar becomes increasingly planar, thus reducing the significance of the phase angle P. We introduce the term "central conformation" to describe this part of the pseudorotational hyperspace in contrast to the conventional north and south conformations. C1 NCI, Med Chem Lab, Ctr Canc Res, DHHS,NIH, Frederick, MD 21702 USA. RP Nicklaus, MC (reprint author), NCI, Med Chem Lab, Ctr Canc Res, DHHS,NIH, 376 Boyles St, Frederick, MD 21702 USA. EM mnl@helix.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU NCI NIH HHS [N01-CO-12400] NR 47 TC 42 Z9 42 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD SEP-OCT PY 2004 VL 44 IS 5 BP 1752 EP 1762 DI 10.1021/ci049881+ PG 11 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA 858IQ UT WOS:000224185900027 PM 15446834 ER PT J AU Tossell, JW Greenstein, DK Davidson, AL Job, SB Gochman, P Lenane, M Nugent, TF Gogtay, N Sporn, AL Rapoport, JL AF Tossell, JW Greenstein, DK Davidson, AL Job, SB Gochman, P Lenane, M Nugent, TF Gogtay, N Sporn, AL Rapoport, JL TI Stimulant drug treatment in childhood-onset schizophrenia with comorbid ADHD: An open-label case series SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID CHILDREN AB The administration of psychostimulants to children with psychotic symptoms is controversial. This study reports the stimulant drug response of 5 children, aged 8-15 years, with childhood-onset schizophrenia (COS) and comorbid attention deficit hyperactivity disorder (ADHD). Four COS inpatients were given stimulants for comorbid ADHD after stabilization of psychosis on antipsychotic medication. A fifth COS inpatient received stimulants while still actively psychotic, despite concurrent neuroleptic treatment. Data from the 10-item Brief Conners Teachers Ratings Scale (BCTRS) were examined the week before, and the week after, stimulant addition. A paired t test, conducted using Conners Teachers data from these 4 subjects, indicated significant improvement in ADHD symptoms (p = 0.02). Data obtained from a retrospective chart review indicated no significant worsening of psychosis. The 2 subjects treated with mixed salts of dextroamphetamine sulfate and amphetamine sulfate remained on that medication at 6 months and at the 2-year follow-up. Our results suggest that ADHD comorbid with COS may be safely treated with a stimulant, once the psychosis is stabilized. A systematic investigation of this question may be warranted. C1 NIMH, Child Psychiat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tossell, JW (reprint author), NIMH, Child Psychiat Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 3N202, Bethesda, MD 20892 USA. EM tossellj@intra.nimh.nih.gov RI Gogtay, Nitin/A-3035-2008 NR 14 TC 15 Z9 15 U1 0 U2 3 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 2004 VL 14 IS 3 BP 448 EP 454 DI 10.1089/1044546042389163 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 867JI UT WOS:000224838500020 PM 15650502 ER PT J AU Finkelstein, R AF Finkelstein, R TI Advances in tuberous sclerosis complex research: The October 1, 2003, Child Neurology Society Workshop SO JOURNAL OF CHILD NEUROLOGY LA English DT Editorial Material C1 NINDS, Bethesda, MD 20892 USA. RP Finkelstein, R (reprint author), NINDS, NSC Room 2143,6001 Execut Blvd, Bethesda, MD 20892 USA. EM rf45c@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2004 VL 19 IS 9 BP 734 EP 735 PG 2 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 938GT UT WOS:000229988600015 PM 15563021 ER PT J AU McDuffie, JR Riggs, PA Calis, KA Freedman, RJ Oral, EA DePaoli, AM Yanovski, JA AF McDuffie, JR Riggs, PA Calis, KA Freedman, RJ Oral, EA DePaoli, AM Yanovski, JA TI Effects of exogenous leptin on satiety and satiation in patients with lipodystrophy and leptin insufficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-WEIGHT; FOOD-INTAKE; EATING BEHAVIOR; OBESE GENE; WOMEN; CHOLECYSTOKININ; DEFICIENCY; BULIMIA; GHRELIN; MEAL AB To examine leptin's role in human appetite regulation, we studied recombinant methionyl human leptin's effects on satiation and satiety in a model of leptin insufficiency, lipodystrophy. Eight females with hypoleptinemia and lipodystrophy were given sc injections of A-100 ( maximal dose, 200% of that predicted to normalize serum leptin) for 4 months. Satiation and satiety were determined before and again during leptin treatment. Satiation was measured as the time to voluntary cessation of eating from a standardized food array after a 12-h fast. Satiety was determined as the time to hunger sufficient to consume a full meal after consumption of a standardized preload. During leptin treatment, satiation time decreased (41.2 +/- 18.2 to 19.5 +/- 10.6 min; P = 0.01), satiety time increased 62.9 +/- 64.8 to 137.8 +/- 91.6 min; P = 0.04), energy consumed to produce satiation decreased (2034 +/- 405 to 1135 +/- 432 kcal or 8.5 +/- 1.7 to 4.7 +/- 1.8 MJ; P < 0.01), and the amount of food desired in the postabsorptive state decreased ( P < 0.02). Ghrelin concentrations also decreased during leptin administration (284.3 +/- 127.9 to 140.6 +/- 104.5 pmol/liter; P < 0.002). We conclude that increased leptin in patients with lipodystrophy results in less caloric, shorter, more satiating meals and longer-lived satiety. These data support the hypothesis that leptin plays an important, permissive role in human appetite regulation. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nutr, Bethesda, MD 20892 USA. NIH, Drug Informat Serv, Dept Pharm, Bethesda, MD 20892 USA. Natl Inst Diabet Digest Disorders & Kidney Dis, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10N262,MSC 1862, Bethesda, MD 20892 USA. EM yanovskj@mail.nih.gov OI Oral, Elif/0000-0002-9171-1144; Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641, ZO1-HD-00641]; NIDDK NIH HHS [R01 DK054387, R01-DK-54387] NR 29 TC 46 Z9 47 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4258 EP 4263 DI 10.1210/jc.2003-031868 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600013 PM 15356018 ER PT J AU Malm, G Haugen, TB Henrichsen, T Bjorsvik, C Grotmol, T Saether, T Malm, J Figenschau, Y Hagmar, L Rylander, L Levine, RJ Giwercman, A AF Malm, G Haugen, TB Henrichsen, T Bjorsvik, C Grotmol, T Saether, T Malm, J Figenschau, Y Hagmar, L Rylander, L Levine, RJ Giwercman, A TI Reproductive function during summer and winter in Norwegian men living north and south of the Arctic Circle SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SEMEN QUALITY; SEASONAL-VARIATION; CIRCANNUAL RHYTHM; ABSTINENCE PERIOD; SPERM COUNTS; DANISH MEN; INHIBIN-B; SPERMATOGENESIS; POPULATION; PARAMETERS AB Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69degrees north latitude) and 112 in Oslo (60degrees north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49x10(6)/ml in summer and 54x10(6)/ml in winter. Corresponding values for Oslo were 59x10(6)/ml and 54x10(6)/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P=0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter). The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility. C1 Malmo Univ Hosp, Fertil Ctr, Scanian Androl Ctr, SE-20502 Malmo, Sweden. Rikshosp Univ Hosp, Androl Lab, Dept Obstet & Gynaecol, N-0027 Oslo, Norway. Inst Populat Based Canc Res, Canc Registry Norway, N-0310 Oslo, Norway. Univ Hosp MAS, Dept Clin Chem, SE-20502 Malmo, Sweden. Univ Hosp N Norway, Dept Clin Chem, N-9038 Tromso, Norway. Univ Lund Hosp, Dept Occupat & Environm Med, S-22185 Lund, Sweden. NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Giwercman, A (reprint author), Malmo Univ Hosp, Fertil Ctr, Scanian Androl Ctr, SE-20502 Malmo, Sweden. EM aleksander.giwercman@kir.mas.lu.se NR 38 TC 17 Z9 17 U1 2 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4397 EP 4402 DI 10.1210/jc.2004-0427 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600036 PM 15356037 ER PT J AU Vgontzas, AN Zoumakis, E Lin, HM Bixler, EO Trakada, G Chrousos, GP AF Vgontzas, AN Zoumakis, E Lin, HM Bixler, EO Trakada, G Chrousos, GP TI Marked decrease in sleepiness in patients with sleep apnea by etanercept, a tumor necrosis factor-alpha antagonist SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXCESSIVE DAYTIME SLEEPINESS; POSITIVE AIRWAY PRESSURE; INSULIN-RESISTANCE; VISCERAL OBESITY; IN-VIVO; DISORDERS; CYTOKINES; INTERLEUKIN-6; PREVALENCE; HORMONES AB The proinflammatory cytokines, TNFalpha and IL-6, are elevated in obstructive sleep apnea (OSA) and have been proposed as mediators of excessive daytime sleepiness in humans. We tested the effects of etanercept, a medication that neutralizes TNFalpha and is approved by the FDA for the treatment of rheumatoid arthritis, in eight obese male apneics. These patients participated in a pilot, placebo-controlled, double-blind study during which nighttime polysomnography, multiple sleep latency test, and fasting blood glucose and plasma levels of IL-6, C-reactive protein, insulin, and adiponectin were obtained. There was a significant and marked decrease in sleepiness by etanercept, which increased sleep latency during the multiple sleep latency test by 3.1+/-1.0 min (P<0.05) compared with placebo. Also, the number of apneas/hypopneas per hour was reduced significantly by the drug compared with placebo (52.8 +/- 9.1 vs. 44.3 +/- 10.3; adjusted difference, -8.4 +/- 2.3; P<0.05). Furthermore, IL-6 levels were significantly decreased after etanercept administration compared with placebo (3.8+/-0.9 vs. 1.9+/-0.4 pg/ml; adjusted difference, -1.9+/-0.5; P<0.01). However, no differences were observed in etanercept vs. placebo in the levels of fasting blood glucose and plasma C-reactive protein, insulin, and adiponectin. We conclude that neutralizing TNF alpha activity is associated with a significant reduction of objective sleepiness in obese patients with OSA. This effect, which is about 3-fold higher than the reported effects of continuous positive airway pressure on objective sleepiness in patients with OSA (0.9 vs. 3.1 min), suggests that proinflammatory cytokines contribute to the pathogenesis of OSA/sleepiness. C1 Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Hlth Evaluat Sci, Hershey, PA 17033 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, 500 univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu FU NHLBI NIH HHS [HL-64415] NR 33 TC 186 Z9 201 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4409 EP 4413 DI 10.1210/jc.2003-031929 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600038 PM 15356039 ER PT J AU Horne, MK Singh, KK Rosenfeld, KG Wesley, R Skarulis, MC Merryman, PK Cullinane, A Costello, R Patterson, A Eggerman, T Bernstein, DM Pucino, F Csako, G AF Horne, MK Singh, KK Rosenfeld, KG Wesley, R Skarulis, MC Merryman, PK Cullinane, A Costello, R Patterson, A Eggerman, T Bernstein, DM Pucino, F Csako, G TI Is thyroid hormone suppression therapy prothrombotic? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR; VENOUS THROMBOSIS; RISK-FACTOR; CARDIOVASCULAR-DISEASE; BLOOD-COAGULATION; THYROTOXICOSIS; HYPERTHYROIDISM; PLASMA; THROMBOEMBOLISM AB The purpose of this study was to determine whether chronic thyroid hormone suppression therapy (THST) is prothrombotic. We obtained blood samples from 14 thyroid cancer patients while on THST and after they had become hypothyroid for radioiodine whole-body scanning and therapy. Prothrombin fragment 1+2, fibrinogen, factor VIII, antithrombin, tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor 1 (PAI-1), PAI-1/tPA, and C-reactive protein were significantly (P<0.05) higher in the hyper- than in the hypothyroid state, whereas protein C and plasmin-antiplasmin complexes were significantly lower during the hyperthyroid period. When the 10 female patients were hyperthyroid, their levels of prothrombin fragment 1+2, fibrinogen, protein S, antithrombin, tPA, PAI-1, and PAI-1/tPA were significantly higher (P less than or equal to 0.05) than in healthy female controls, whereas when the female patients were hypothyroid, their antithrombin and plasmin-antiplasmin were lower and their protein S was higher than in controls. Factor II, plasminogen, and D-dimer were not significantly affected by the thyroid status in either assessment. In conclusion, we found evidence that the majority of patients treated with THST have a prothrombotic profile. C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Dept Pharm, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. NIDDKD, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Off Director, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Dept Lab Med, Bldg 10,Room 2C-306, Bethesda, MD 20892 USA. EM MHorne@mail.cc.nih.gov NR 29 TC 24 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4469 EP 4473 DI 10.1210/jc.2004-0536 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600048 PM 15356049 ER PT J AU Gupta, A Winer, K Econs, MJ Marx, SJ Collins, MT AF Gupta, A Winer, K Econs, MJ Marx, SJ Collins, MT TI FGF-23 is elevated by chronic hyperphosphatemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DOMINANT HYPOPHOSPHATEMIC RICKETS; VITAMIN-D METABOLISM; PHOSPHATE; FGF23; OSTEOMALACIA; LEVEL AB The identification and characterization of FGF-23 has provided an opportunity to gain new insight into phosphorus metabolism. Circulating FGF-23 promotes renal excretion of phosphorus, and FGF-23 is measurable in the serum of normal subjects. Serum levels of FGF-23 are elevated in patients with renal phosphate wasting disorders such as tumor induced osteomalacia, X-linked hypophosphatemia and fibrous dysplasia. However, the factors that alter its serum concentration are not known. The study of serum FGF-23 is confounded by the fact that high serum calcium, PTH, and any other putative phosphotonins, have similar effects on serum and urine phosphorus. To circumvent the confounding effect of serum PTH and calcium, we studied serum FGF-23 and phosphate levels in patients with chronic hypoparathyroidism and hyperphosphatemia. Serum was collected in the morning after an overnight fast from three groups: 1) 9 patients with chronic hypoparathyroidism on stable treatment with calcium and calcitriol, 2) 9 patients with primary hyperparathyroidism, and 3) 77 normal controls. Patients with hypoparathyroidism had predictably higher levels of serum phosphorus than patients with hyperparathyroidism or normal controls (5.6+/-1.1, 3.1+/-0.6, and 3.1+/-0.5 mg/dL, mean +/-1 SD, respectively (p<0.01) for hypoparathyroid vs: either group)). They also had higher levels of FGF-23 (150 +/- 120 vs: 70 +/- 60, or 55 +/- 20 RlU/ml, respectively (p<0.05 vs: either group)). In conclusion, serum FGF-23 levels are elevated in patients with hyperphosphatemia and chronic hypoparathyroidism, suggesting a feedback system in which serum FGF-23 responds to serum phosphorus and regulates it. However, in the setting of chronic hypoparathyroidism, the degree of elevation of FGF-23 is insufficient to normalize serum phosphorus. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD USA. NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Indianapolis, IN USA. RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. EM mcolllins@dir.nider.nih.gov OI Econs, Michael/0000-0003-0940-1911 NR 13 TC 93 Z9 95 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2004 VL 89 IS 9 BP 4489 EP 4492 DI 10.1210/jc.2004-0724 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 852GM UT WOS:000223743600052 PM 15356053 ER PT J AU Mertens, AC Walls, RS Taylor, L Mitby, PA Whitton, J Inskip, PD Potter, JD Robison, LL AF Mertens, AC Walls, RS Taylor, L Mitby, PA Whitton, J Inskip, PD Potter, JD Robison, LL TI Characteristics of childhood cancer survivors predicted their successful tracing SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE cohort studies; epidemiologic methods; tracing; bias; data collection ID LONG-TERM SURVIVORS; FOLLOW-UP; TRACKING; COHORT; ATTRITION AB Objective: The Childhood Cancer Survivor Study is a retrospective cohort study that was initiated to explore late effects of childhood cancer and its therapies. We evaluated the characteristics of those requiring tracing and factors that influenced tracing success. Study Design and Setting: Medical record review identified 20,051 eligible individuals from 25 institutions in the United States and Canada. Of these, 13,021 had a current address in the medical record at the treating institution, and 7,030 had an incorrect address and required tracing by a commercial firm. Results: Tracing was successful for 4,188 persons (60%). Younger age at contact, shorter length of time since last contact, having a middle initial available, an uncommon last name, and socioeconomic factors were found to predict successful tracing. Compared to those with a current address available in medical records, subjects successfully traced were less likely to have accessed health care during the previous 2 years; and more likely to be current smokers, obese, and to report moderate to severe impairments (pain, functional status, and activity). Conclusion: These findings provide an empirical basis concerning determinants and predictors of tracing success. If tracing had not been performed in this cohort, spurious associations may have been obtained for some health outcomes of interest. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Minnesota, Sch Med, Dept Pediat Epidemiol & Clin Res, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Bethesda, MD 20892 USA. RP Mertens, AC (reprint author), Univ Minnesota, Sch Med, Dept Pediat Epidemiol & Clin Res, 420 Delaware St SE, Minneapolis, MN 55455 USA. EM mertens@epi.umn.edu OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [CA 55727] NR 16 TC 38 Z9 38 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2004 VL 57 IS 9 BP 933 EP 944 DI 10.1016/j.jclinepi.2004.01.005 PG 12 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 870YB UT WOS:000225093700007 PM 15504636 ER PT J AU Shalowitz, D Emanuel, E AF Shalowitz, D Emanuel, E TI Euthanasia and physician-assisted suicide: Implications for physicians SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID TERMINALLY-ILL PATIENTS; ONCOLOGY PATIENTS; UNITED-STATES; ATTITUDES; DEPRESSION; CARE C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. EM dshalowitz@cc.nih.gov RI Shalowitz, David/A-7432-2009; OI Shalowitz, David/0000-0002-5189-4687 NR 14 TC 3 Z9 3 U1 0 U2 1 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD FAL PY 2004 VL 15 IS 3 BP 232 EP 236 PG 5 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 877IE UT WOS:000225560700003 PM 15630865 ER PT J AU Castrop, H Huang, YN Hashimoto, S Mizel, D Hansen, P Theilig, F Bachmann, S Deng, CX Briggs, J Schnermann, J AF Castrop, H Huang, YN Hashimoto, S Mizel, D Hansen, P Theilig, F Bachmann, S Deng, CX Briggs, J Schnermann, J TI Impairment of tubuloglomerular feedback regulation of GFR in ecto-5 '-nucleotidase/CD73-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ADENOSINE-DEAMINASE; ECTO-NUCLEOTIDASES; MESANGIAL CELLS; NITRIC-OXIDE; ATP; 5'-NUCLEOTIDASE; RECEPTORS; TISSUE; VASOCONSTRICTION; INHIBITION AB Adenosine coordinates organ metabolism and blood supply, and it modulates immune responses. In the kidney it mediates the vascular response elicited by changes in NaCl concentration in the macula densa region of the nephron, thereby serving as an important regulator of GFR. To determine whether adenosine formation depends on extracellular nucleotide hydrolysis, we studied NaCl-dependent GFR regulation (tubuloglomerular feedback) in mice with targeted deletion of ecto-5'-nucleotidase/CD73 (e-5'NT/CD73), the enzyme responsible for adenosine formation from AMP. e-5'NT/CD73(-/-) mice were viable and showed no gross anatomical abnormalities. Blood pressure, blood and urine chemistry, and renal blood flow were not different between e-5'NT/CD73(+/+) and e-5'NT/CD73(-/-) mice. e-5'NT/CD73(-/-) mice had a significantly reduced fall in stop flow pressure and superficial nephron glomerular filtration rate in response to a saturating increase of tubular perfusion flow. Furthermore, whereas tubuloglomerular feedback responses did not change significantly during prolonged loop of Henle perfusion in e-5'NT/CD73(+/+) mice, a complete disappearance of the residual feedback response was noted in e-5'NT/CD73(-/-) mice over 10 minutes of perfusion. The contractile response of isolated afferent arterioles to adenosine was normal in e-5'NT/CD73(-/-) mice. We conclude that the generation of adenosine at the glomerular pole depends to a major extent on e-5'NT/CD73-mediated dephosphorylation of 5'-AMP, presumably generated from released ATP. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Charite Univ Med Berlin, Inst Anat, Berlin, Germany. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Room 4 D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 38 TC 118 Z9 118 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2004 VL 114 IS 5 BP 634 EP 642 DI 10.1172/JCI200421851 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 851RQ UT WOS:000223703300009 PM 15343381 ER PT J AU Chan, KS Sano, S Kiguchi, K Anders, J Komazawa, N Takeda, J DiGiovanni, J AF Chan, KS Sano, S Kiguchi, K Anders, J Komazawa, N Takeda, J DiGiovanni, J TI Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID KERATINOCYTE STEM-CELLS; MOUSE SKIN; CYCLIN D1; C-MYC; IN-VIVO; CONSTITUTIVE ACTIVATION; ONCOGENIC RAS; HA-RAS; GROWTH; CANCER AB Constitutive activation of signal transducer and activator of transcription 3 (Stat3) has been found in a wide spectrum of human malignancies. Here, we have assessed the effect of Stat3 deficiency on skin tumor development using the 2-stage chemical carcinogenesis model. The epidermis of Stat3-deficient mice showed a significantly reduced proliferative response following treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) because of a defect in G1-to-S-phase cell cycle progression. Treatment with the tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA) resulted in a significant increase in the number of keratinocyte stem cells undergoing apoptosis in the bulge region of hair follicles of Stat3-deficient mice compared with nontransgenic littermates. Notably, Stat3-deficient mice were completely resistant to skin tumor development when DMBA was used as the initiator and TPA as the promoter. Abrogation of Stat3 function using a decoy oligonucleotide inhibited the growth of initiated keratinocytes possessing an activated Ha-ras gene, both in vitro and in vivo. In addition, injection of Stat3 decoy into skin tumors inhibited their growth. To our knowledge, these data provide the first evidence that Stat3 is required for de novo epithelial. carcinogenesis, through maintaining the survival of DNA-damaged stem cells and through mediating and maintaining the proliferation necessary for clonal expansion of initiated cells during tumor promotion. Collectively, these data suggest that, in addition to its emerging role as a target for cancer therapy, Stat3 may also be a target for cancer prevention strategies. C1 Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Smithville, TX 78957 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Osaka Univ, Grad Sch Med, Dept Social Environm Med, Osaka, Japan. RP DiGiovanni, J (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Sci Pk,POB 389, Smithville, TX 78957 USA. EM jdigiovanni@sprd1.mdacc.tmc.edu FU NCI NIH HHS [P30 CA016672, R01 CA076520, R01 CA76520]; NIEHS NIH HHS [ES07784, P30 ES007784, U01 ES011047, U01 ES11047] NR 53 TC 231 Z9 236 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2004 VL 114 IS 5 BP 720 EP 728 DI 10.1172/JCI200421032 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 851RQ UT WOS:000223703300019 PM 15343391 ER PT J AU Stapleton, JT Williams, CF Xiang, JH AF Stapleton, JT Williams, CF Xiang, JH TI GB virus type C: A beneficial infection? SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Editorial Material ID HEPATITIS-G VIRUS; HIV; SURVIVAL; PROGRESSION; COINFECTION; MEN C1 Univ Iowa, Dept Internal Med, UIHC, Iowa City, IA 52242 USA. Iowa City Vet Adm Med Ctr, Med & Res Serv, Iowa City, IA USA. NIAID, Epidemiol Branch, Div Aids, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Stapleton, JT (reprint author), Univ Iowa, Dept Internal Med, UIHC, SW34-P,GH,200 Hawkins Dr, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu FU NIAID NIH HHS [R01 AI058740, AI058740] NR 15 TC 49 Z9 54 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2004 VL 42 IS 9 BP 3915 EP 3919 DI 10.1128/JCM.42.9.3915-3919.2004 PG 5 WC Microbiology SC Microbiology GA 854KQ UT WOS:000223902000001 PM 15364968 ER PT J AU Brown, KE AF Brown, KE TI Detection and quantitation of parvovirus B19 SO JOURNAL OF CLINICAL VIROLOGY LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; BLOOD-DONORS; VIRAL-DNA; CELL-LINE; INFECTION; IDENTIFICATION; PERSISTENCE; TISSUE; ASSAY; PREVALENCE C1 NHLBI, Virus Discovery Grp, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Brown, KE (reprint author), NHLBI, Virus Discovery Grp, Hematol Branch, NIH, Bldg 10 Room 7C218,900 Rockville Pike, Bethesda, MD 20892 USA. EM brownk@nhlbi.nih.gov NR 36 TC 17 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD SEP PY 2004 VL 31 IS 1 BP 1 EP 4 DI 10.1016/j.jcv.2004.05.001 PG 4 WC Virology SC Virology GA 848GS UT WOS:000223456200001 PM 15288605 ER PT J AU Ogbureke, KUE Fisher, LW AF Ogbureke, KUE Fisher, LW TI Expression of SIBLINGs and their partner MMPs in salivary glands SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE SIBLING; MMP; bone sialoprotein; osteopontin; dentin matrix protein-1 ID DENTIN MATRIX PROTEIN-1; BONE SIALOPROTEIN BSP; HUMAN TISSUES; CDNA CLONING; OSTEOPONTIN; CANCER; GENE; PURIFICATION; INTEGRIN; TUMORS AB Three members of the SIBLING family of integrin- binding phosphoglycoproteins ( bone sialoprotein, BSP; osteopontin, OPN; and dentin matrix protein- 1, DMP1) were recently shown to bind with high affinity ( nM) and to activate 3 different matrix metalloproteinases ( MMP- 2, MMP- 3, and MMP- 9, respectively) in vitro. The current study was designed to document the possible biological relevance of the SIBLING-MMP activation pathway in vivo by showing that these 3 SIBLINGs and their known MMP partners are co- expressed in normal adult tissue. BSP, OPN, and DMP1 were invariably co- expressed with their partner MMPs in salivary glands of humans and mice. The 2 SIBLING proteins without known MMP partners, dentin sialophosphoprotein ( DSPP) and matrix extracellular phosphoglycoprotein ( MEPE), were also expressed in salivary glands. Expression of all SIBLINGs in this normal, non- mineralizing epithelial tissue suggests that they serve at least one function in vivo other than directly promoting matrix mineralization - a function we hypothesize involves local activation of MMPs. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Fisher, LW (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bldg 30,Room 228,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lfisher@dir.nidcr.nih.gov NR 30 TC 125 Z9 129 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2004 VL 83 IS 9 BP 664 EP 670 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 906TZ UT WOS:000227667700002 PM 15329369 ER PT J AU Griesenbach, U Kitson, C Escudero-Garcia, S Somerton, L Painter, H Farley, R Ogilvie, V Chow, YH Edbrooke, M Cheng, S Porteous, D Hu, J Hyde, S Geddes, D Caplen, N Alton, E AF Griesenbach, U Kitson, C Escudero-Garcia, S Somerton, L Painter, H Farley, R Ogilvie, V Chow, YH Edbrooke, M Cheng, S Porteous, D Hu, J Hyde, S Geddes, D Caplen, N Alton, E TI LacZ siRNA and antisense DNA decrease beta-galactosidase mRNA but not protein expression in the airways of K18-lacZ transgenic mice SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 1st Annual Conference of the British-Society-for-Gene-Therapy CY MAR 28-30, 2004 CL Keble Coll, Oxford, ENGLAND SP British Soc Gene Therapy, Schering Healthcare, AstraZeneca, Canc Res, Chron Granulomatous Disorder Res Trust, Gene Therapy Advisroy Comm, Gloria Miles Canc Fdn, Katherine Dormandy Trust haemophilia * Allied Disorders, Int Soc Canc Gene Therapy, Natl Translat Canc Res Network HO Keble Coll C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Gene Therapy, London SW7 2AZ, England. GlaxoSmithKline, Stevenage, Herts, England. Univ Oxford, Nuffield Dept Clin Lab Sci, Gene Med Grp, Oxford OX1 2JD, England. Univ Edinburgh, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Genzyme Corp, Framingham, MA 01701 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RI Porteous, David/C-7289-2013 OI Porteous, David/0000-0003-1249-6106 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD SEP PY 2004 VL 6 IS 9 MA 56 BP S21 EP S22 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 859IR UT WOS:000224257100066 ER PT J AU Nelson, DE Kreps, GL Hesse, BW Croyle, RT Willis, G Arora, NK Rimer, BK Viswanath, KV Weinstein, N Alden, S AF Nelson, DE Kreps, GL Hesse, BW Croyle, RT Willis, G Arora, NK Rimer, BK Viswanath, KV Weinstein, N Alden, S TI The Health Information National Trends Survey (HINTS): Development, design, and dissemination SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER CONTROL; COMMUNICATION; RISK; PERCEPTIONS; AMERICANS; KNOWLEDGE; INTERNET; IMPACT AB Little is known about access, sources, and trust of cancer-related information, or factors that facilitate or hinder communication on a populationwide basis. Through a careful developmental process involving extensive input from many individuals and organizations, the National Cancer Institute (NCI) developed the Health Information National Trends Survey ( HINTS) to help fill this gap. This nationally representative telephone survey of 6,369 persons aged greater than or equal to18 years among the general population was first conducted in 2002-2003, and will be repeated biennially depending on availability of funding. The purpose of creating a population survey to be repeated on a cyclical basis is to track trends in the public's rapidly changing use of new communication technologies while charting progress in meeting health communication goals in terms of the public's knowledge, attitudes, and behaviors. The HINTS survey instrument was built upon extant models of health communication and behavior change, taking into account the rapidly changing communication environment. Questions in the survey were drawn from an overall theoretical framework that juxtaposed the "push" aspects of traditional broadcast media against the "pull" aspects of new media. HINTS data will be made widely available for researchers and practitioners; it will help further research in health communication and health promotion and provide useful information for programs, policies, and practices in a variety of settings. C1 NCI, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Harvard Univ, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Cambridge, MA USA. Rutgers State Univ, Camden, NJ 08102 USA. NIH, Bethesda, MD 20892 USA. RP Hesse, BW (reprint author), NCI, 6131 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 NR 45 TC 245 Z9 247 U1 5 U2 36 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD SEP-OCT PY 2004 VL 9 IS 5 BP 443 EP 460 DI 10.1080/10810730490504233 PG 18 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 861OQ UT WOS:000224426900005 PM 15513791 ER PT J AU Acosta, CJ Galindo, CM Ochiai, RL Carolina, M Danovaro-Holliday, MC Page, AL Thiem, VD Park, JK Park, E Koo, H Wang, XY Abu-Elyazeed, R Ali, M Albert, MJ Ivanoff, B Pang, TK Xu, ZY Clemens, JD AF Acosta, CJ Galindo, CM Ochiai, RL Carolina, M Danovaro-Holliday, MC Page, AL Thiem, VD Park, JK Park, E Koo, H Wang, XY Abu-Elyazeed, R Ali, M Albert, MJ Ivanoff, B Pang, TK Xu, ZY Clemens, JD TI The role of epidemiology in the introduction of Vi polysaccharide typhoid fever vaccines in Asia SO JOURNAL OF HEALTH POPULATION AND NUTRITION LA English DT Article DE typhoid fever; vaccine; epidemiology; vaccinology; Salmonella typhi; Asia ID SALMONELLA-TYPHI; CAPSULAR POLYSACCHARIDE; IMMUNIZATION; EFFICACY; CHINA AB Despite the availability of at least two licensed typhoid fever vaccines-injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine-for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the programme, (b) generation of policy-relevant data, (c) providing the 'backbone' for the implementation of other multidisciplinary projects, and (d) generation of unexpected but useful information relevant for the introduction of vaccines. Epidemiological studies contribute to all stages of development of vaccine evaluation and introduction. C1 Int Vaccine Inst, Seoul 151818, South Korea. Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. US NAMRU 3, Enter Dis Res Program, Epidemiol Unit, Cairo, Egypt. GlaxoSmithKline BIol, Singapore, Singapore. Kuwait Univ, Fac Med, Dept Microbiol, Kuwait, Kuwait. WHO, Vaccines & Other Biol, CH-1211 Geneva, Switzerland. WHO, Res Policy & Cooperat, CH-1211 Geneva, Switzerland. NICHHD, Bethesda, MD 20892 USA. RP Acosta, CJ (reprint author), Int Vaccine Inst, San 4-8 Bongcheon 7 Dong, Seoul 151818, South Korea. EM Camilo_acosta2003@yahoo.com RI Ali, Mohammad/E-2365-2017; OI Ali, Mohammad/0000-0003-1410-388X; Ochiai, Leon/0000-0002-5079-6786 NR 21 TC 15 Z9 16 U1 0 U2 2 PU I C D D R B-CENTRE HEALTH POPULATION RESEARCH PI DHAKA PA MOHAKHALI, 1212 DHAKA, BANGLADESH SN 1606-0997 J9 J HEALTH POPUL NUTR JI J. Heatlh Popul. Nutr. PD SEP PY 2004 VL 22 IS 3 BP 240 EP 245 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 875TC UT WOS:000225443600003 PM 15609776 ER PT J AU Bahl, R Sinha, A Poulos, C Whittington, D Sazawal, S Kumar, R Mahalanabis, D Acosta, CJ Clemens, JD Bhan, MK AF Bahl, R Sinha, A Poulos, C Whittington, D Sazawal, S Kumar, R Mahalanabis, D Acosta, CJ Clemens, JD Bhan, MK TI Costs of illness due to typhoid fever in an Indian urban slum community: Implications for vaccination policy SO JOURNAL OF HEALTH POPULATION AND NUTRITION LA English DT Article DE typhoid fever; vaccination; typhoid and paratyphoid vaccines; cost of illness; costs and cost analysis; cost-benefit analysis; slums; prospective studies; India ID BONE-MARROW; VITAMIN-A; CHILDREN; CULTURES; BLOOD AB Data on the burden of disease, costs of illness, and cost-effectiveness of vaccines are needed to facilitate the use of available anti-typhoid vaccines in developing countries. This one-year prospective surveillance was carried out in an urban slum community in Delhi, India, to estimate the costs of illness for cases of typhoid fever. Ninety-eight culture-positive typhoid, 31 culture-positive paratyphoid, and 94 culture-negative cases with clinical typhoid syndrome were identified during the surveillance. Estimates of costs of illness were based on data collected through weekly interviews conducted at home for three months following diagnosis. Private costs included the sum of direct medical, direct non-medical, and indirect costs. Non-patient (public) costs included costs of outpatient visits, hospitalizations, laboratory tests, and medicines provided free of charge to the families. The mean cost per episode of blood culture-confirmed typhoid fever was 3,597 Indian Rupees (US$ 1 = INR 35.5) (SD 5,833); hospitalization increased the costs by several folds (INR 18,13 1, SD 11,218, p < 0.0001). The private and non-patient costs of illness were similar (INR 1,732, SD 1,589, and INR 1,865, SD 5,154 respectively, p = 0.8095). The total private and non-patient ex-ante costs, i.e. expected annual losses for each individual, were higher for children aged 2-5 years (INR 154) than for those aged 5-19 years (INR 32), 0-2 year(s) (INR 25), and 19-40 years (INR 2). The study highlights the need for affordable typhoid vaccines efficacious at 2-5 years of age. Currently-available Vi vaccine is affordable but is unlikely to be efficacious in the first two years of life. Ways must be found to make Vi-conjugate vaccine, which is efficacious at this age, available to children of developing-countries. C1 All India Inst Med Sci, Dept Paediat, Ctr Diarrhoeal Dis & Nutr Res, New Delhi 110029, India. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Johns Hopkins Univ, Dept Int Hlth, Baltimore, MD 21205 USA. Soc Appl Studies, Kolkata 700054, W Bengal, India. Int Vaccine Inst, Seoul 151600, South Korea. NICHHD, Bethesda, MD 20892 USA. RP Bhan, MK (reprint author), All India Inst Med Sci, Dept Paediat, Ctr Diarrhoeal Dis & Nutr Res, New Delhi 110029, India. EM Community.research@cih.uib.no NR 9 TC 32 Z9 33 U1 0 U2 3 PU ICDDR B PI DHAKA PA MOHAKHALI, 1212 DHAKA, BANGLADESH SN 1606-0997 EI 2072-1315 J9 J HEALTH POPUL NUTR JI J. Heatlh Popul. Nutr. PD SEP PY 2004 VL 22 IS 3 BP 304 EP 310 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 875TC UT WOS:000225443600010 PM 15609783 ER PT J AU Hirshfeld, AB Kahle, AL Clark, BJ Bridges, ND AF Hirshfeld, AB Kahle, AL Clark, BJ Bridges, ND TI Parent-reported health status after pediatric thoracic organ transplant SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID HEART-TRANSPLANTATION; LUNG-TRANSPLANTATION; CHILDREN; RECIPIENTS AB Background: Thoracic organ transplantation is a life-changing event for a child and family from both a physical and a psychosocial perspective. Accurate pre-transplantation counseling and effective post-transplantation follow-up depend on a good understanding of post-transplantation health status, especially as perceived by families. Methods: The Child Health Questionnaire-Parent Form 50 (CHQ-P50), an instrument that assesses parent-reported health status of pediatric patients, was administered to 47 pediatric thoracic organ transplant recipients (41 heart, 6 lung) 5 to 18 years of age. Results: Transplant recipients scored lower on the Physical Health Summary (PhS) score than the general population, as evidenced by a lower median score (50.6 vs 55.1, p<0.0001) and a difference in the distribution of quartiles (p = 0.001), skewed toward the lower quartiles of the general population. The distribution of PhS scores in transplant recipients was comparable to scores of 3 groups of pediatric patients with other chronic health conditions (juvenile rheumatoid arthritis, epilepsy and asthma). The distribution of the Psychosocial Health Summary (PsS) scores was similar to that of the general population, but the median score was lower (51.5 vs 53.2, p = 0.02). Transplant patients clearly scored lower than the general population on 4 of 12 sub-scales, including those assessing general health, physical functioning, family activities and parental emotional impact. No difference was found in sub-scales reflecting self-esteem, mental health, behavior, pain, peer interactions, family cohesion or parental time demands. Conclusions: Thoracic organ transplantation in children ages 5 to 18 years is associated with an ongoing deficit in parent-perceived physical health status. C1 Childrens Hosp Philadelphia, Div Cardiol, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Psychol, Philadelphia, PA 19104 USA. NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. RP Hirshfeld, AB (reprint author), Childrens Hosp Philadelphia, Div Cardiol, Dept Pediat, 2nd Floor Main Bldg,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM hirshfeld@email.chop.edu NR 18 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP PY 2004 VL 23 IS 9 BP 1111 EP 1118 DI 10.1016/j.healun.2003.08.016 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 858ZB UT WOS:000224230300014 PM 15454179 ER PT J AU Nagata, S Numata, Y Onda, M Ise, T Hahn, Y Lee, B Pastan, I AF Nagata, S Numata, Y Onda, M Ise, T Hahn, Y Lee, B Pastan, I TI Rapid grouping of monoclonal antibodies based on their topographical epitopes by a label-free competitive immunoassay SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE topographic mapping of epitopes; ELISA; monoclonal antibody; CD30; therapeutic antibody ID RECOMBINANT IMMUNOTOXINS; IN-VIVO; CELLS; ANTIGEN; CD30; SPECIFICITIES; VIRUS; THERAPY; DOMAIN; MAPS AB Topography of epitopes of monoclonal antibodies (MAbs), identified as the mutual competition of the MAbs, can be valuable indicators for the biological functions of MAbs. However, the determination of topographical epitopes is not performed before the functional screening of MAbs, because the requirement for purifying and labeling of MAbs makes the mapping experiment difficult, particularly in the early stage of MAb production. Here we describe a new label-free competitive enzyme-linked immunosorbent assay (LFC-ELISA) for the rapid grouping of MAbs based on the topography of their epitopes. In the LFC-ELISA, the immune complex formed by a competitor, MAb#2, and an antigen is challenged by an indicator, MAb#1 that had been captured on the ELISA plate through a secondary antibody. The MAb#2-antigen immune complex is trapped by MAb#1 only if MAb#1 reacts with an epitope different from that of MAb#2. The immune complex (MAb#2-antigen-MAb#1) is detected with an enzyme-labeled reagent specific to a tag on the antigen. Our experiments using different anti-CD30 MAbs and a CD30-Fc fusion protein as the antigen revealed that the LFC-ELISA performed well with MAbs of different isotypes (IgG1, IgG2a, and IgG2b), and in a practical range of MAb concentrations (0.3-10 mug/ml) and affinities (0.9-13 nM of Kd). We obtained pairwise competition data from all 26 anti-CD30 MAbs. We then utilized a cluster analysis and a bootstrap method to analyze the competition data for grouping of the MAbs. This objective and automated analysis identified eight distinct topographical epitopes on CD30. The reactivity of the anti-CD30 MAbs in immunoblot, and their inhibiting activity on CD30-CD30-ligand binding correlated with the topographical epitopes. The results show that the LFC-ELISA combined with cluster analysis is a useful new method for grouping MAbs based on their topographical epitopes and can be used in the early stage of MAb production. One useful application is to identify MAbs reacting with different epitopes from a large number of MAbs so that the most appropriate MAbs can be selected for therapeutic use. (C) 2004 Elsevier B.V. All rights reserved. C1 NCI, Ctr Canc Res, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Ctr Canc Res, Mol Biol Lab, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov NR 45 TC 16 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP PY 2004 VL 292 IS 1-2 BP 141 EP 155 DI 10.1016/j.jim.2004.06.009 PG 15 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 854WT UT WOS:000223935200013 PM 15350519 ER PT J AU Wolfraim, LA Walz, TM James, Z Fernandez, T Letterio, JJ AF Wolfraim, LA Walz, TM James, Z Fernandez, T Letterio, JJ TI p21(Cip1) and p27(Kip1) act in synergy to alter the sensitivity of naive T cells to TGF-beta-mediated G(1) arrest through modulation of IL-2 responsiveness SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN LYMPHOCYTES-T; GROWTH-FACTOR-BETA; MICE LACKING; INTERLEUKIN-2 RECEPTOR; TARGETED DISRUPTION; PROMOTES APOPTOSIS; CYCLE PROGRESSION; PROLIFERATION; TUMORIGENESIS; EXPRESSION AB Induction of G, arrest by TGF-beta correlates with the regulation of p21(clip1) and p27(Kip1), members of the Cip/Kip family of cyclin-dependent kinase inhibitors (cki). However, no definitive evidence exists that these proteins play a causal role in TGF-beta(1)-induced growth arrest in lymphocytes. In this report we show the suppression of cell cycle progression by TGF-beta is diminished in T cells from mice deficient for both p21(Cip1) and p27(Kip1) (double-knockout (DKO)) only when activated under conditions of optimal costimulation. Although there is an IL-2-dependent enhanced proliferation of CD8(+) T cells from DKO mice, TGF-beta is able to maximally suppress the proliferation of DKO T cells when activated under conditions of low costimulatory strength. We also show that the induction of p15(Ink4b) in T cells stimulated in the presence of TGF-beta is not essential, as TGF-beta also efficiently suppressed proliferation of T cells from p15(Ink4b-/-) mice. Finally, although these cki are dispensable for the suppression of T cell proliferation by TGF-beta, we now describe a Smad3-dependent down-regulation of cdk4, suggesting a potential mechanism underlying to resistance of Smad3(-/-) T cells to the induction of growth arrest by TGF-beta. In summary, the growth suppressive effects of TGF-beta in naive T cells are a function of the strength of costimulation, and alterations in the expression of cki modify the sensitivity to TGF-beta by lowering thresholds for a maximal mitogenic response. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Wolfraim, LA (reprint author), TolerGenics, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM wolfraim@tolergenics.com NR 27 TC 48 Z9 59 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2004 VL 173 IS 5 BP 3093 EP 3102 PG 10 WC Immunology SC Immunology GA 849HR UT WOS:000223529800031 PM 15322169 ER PT J AU Rutigliano, JA Graham, BS AF Rutigliano, JA Graham, BS TI Prolonged production of TNF-alpha exacerbates illness during respiratory syncytial virus infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; LYMPHOCYTE-MEDIATED CYTOTOXICITY; NECROSIS-FACTOR RECEPTOR; NATURAL-KILLER-CELLS; CYTOCHROME-C RELEASE; ACUTE LUNG INJURY; SPLENIC B-CELLS; GRANZYME-B; FAS LIGAND; IN-VIVO AB CD8(+) CTL are the main effector cells responsible for resolving viral infections. However, the CTL response to respiratory syncytial virus (RSV) infection in mice facilitates viral clearance at the expense of significant immunopathology. Previous reports have shown a strong correlation between the mechanism of CTL activity and the severity of RSV-induced illness. Furthermore, experiments in perforin knockout mice revealed that antiviral cytokine production temporally correlated with RSV-induced illness. In the current study, we show that TNF-alpha is the dominant mediator of RSV-associated illness, and it is also important for clearance of virus-infected cells during the early stages of infection. We also demonstrate that IFN-gamma plays a protective role in conjunction with perforin/granzyme-mediated killing. Preliminary experiments in gld mice that express nonfunctional Fas ligand (FasL) revealed that RSV-induced illness is significantly reduced in the absence of FasL-mediated killing. Antiviral cytokine production was not elevated in the absence of FasL, suggesting a possible link between FasL and antiviral cytokine activity. This work shows that multiple phenotypic subsets of CD8(+) CTLs respond to RSV infection, each with varying capacities for clearance of virus-infected cells and the induction of illness. In addition, the revelation that TNF-a is the principal mediator of RSV-induced illness means that administration of TNF receptor antagonists, in combination with antiviral therapy, may be an effective method to treat RSV infections. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 2502,40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU NIAID NIH HHS [R01-AI-33933] NR 82 TC 67 Z9 68 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 SEP 1 PY 2004 VL 173 IS 5 BP 3408 EP 3417 PG 10 WC Immunology SC Immunology GA 849HR UT WOS:000223529800067 PM 15322205 ER PT J AU Melchionda, F McKirdy, MK Medeiros, F Fry, TJ Mackall, CL AF Melchionda, F McKirdy, MK Medeiros, F Fry, TJ Mackall, CL TI Escape from immune surveillance does not result in tolerance to tumor-associated antigens SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE rodent; tumor immunity; T lymphocytes; tolerance/suppression/anergy; antigens/peptides/epitopes ID T-CELL REGENERATION; ELISPOT ASSAY; HOMEOSTATIC PROLIFERATION; H-Y; HISTOCOMPATIBILITY ANTIGEN; INTERFERON-GAMMA; SECRETING CELLS; LUNG-CANCER; IFN-GAMMA; IN-VIVO AB Despite expression of tumor-associated or tumor-specific antigens by most tumors, evasion of protective T-cell immunity is the rule rather than the exception. Understanding whether tumor immune escape primarily represents T-cell neglect, anergy/tolerance, or quantitative limits of an existent immune response is central to developing new strategies to enhance antitumor immunity. The authors studied the immune response to MB49, a tumor that naturally expresses HY. Immune surveillance was effective following low-dose tumor inocula, since normal female mice showed a diminished incidence and slower growth rate of MB49 compared with T-cell-depleted female mice and male mice. Following high-dose turner inoculation, females developed large, progressive tumors but continued to demonstrate immune responses to class I and class II restricted HY epitopes. The HY reactive T cells remained capable of executing HY immune responses since T cells adoptively transferred from MB49-bearing animals mediated accelerated HY skin graft rejection compared with those taken from naive mice. Thus, MB49 does not induce immune tolerance to HY but rather escapes immune surveillance largely due to quantitative limits of the immune response. Treatment of tumor-bearing animals with rhIL7 significantly increased the number of T cells responding to HY but did not alter tumor growth rate. These results demonstrate that escape from immune surveillance does not necessarily imply immune tolerance to tumor antigens and that immunotherapy need not overcome tumor-induced tolerance per se, and suggest that substantial opportunities remain in tumor-bearing hosts to amplify, weak but persistent antitumor immune responses. C1 NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Bologna, Dept Pediat Hematol Oncol, S Orsola Hosp, Bologna, Italy. Ist Portugues Oncol Francisco Gentil, Dept Anat Pathol, Lisbon, Portugal. RP Mackall, CL (reprint author), Bldg 10,Rm 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. EM cm35c@nih.gov FU NCI NIH HHS [N01-CO-56000] NR 59 TC 24 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD SEP-OCT PY 2004 VL 27 IS 5 BP 329 EP 338 DI 10.1097/00002371-200409000-00001 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 849SA UT WOS:000223559800001 PM 15314541 ER PT J AU Lee, D Graham, BS Chiu, YL Gilbert, PB McElrath, MJ Belshe, RB Buchbinder, SP Sheppard, HW Koblin, BA Mayer, KH Keefer, MC Mulligan, MJ Celum, CL AF Lee, D Graham, BS Chiu, YL Gilbert, PB McElrath, MJ Belshe, RB Buchbinder, SP Sheppard, HW Koblin, BA Mayer, KH Keefer, MC Mulligan, MJ Celum, CL TI Breakthrough infections during phase 1 and 2 prime-boost HIV-1 vaccine trials with canarypox vectors (ALVAC) and booster dose of recombinant gp120 or gp160 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; RHESUS-MONKEYS; VIRAL ESCAPE; AIDS; VIREMIA; SAFETY; IMMUNOGENICITY; PREPAREDNESS; VOLUNTEERS AB Candidate human immunodeficiency virus (HIV)-1 vaccines that elicit cytotoxic T lymphocytes may modulate HIV infection, requiring a prototype evaluation to assess participants who become infected with HIV. Of 1497 participants in canarypox HIV-1 vaccine prime-boost trials, 28 (1.9%) acquired HIV-1 infection after vaccination. Median plasma HIV-1 RNA levels (vaccinees, 4.78 log(10) copies/mL; placebo recipients, 4.27 log(10) copies/mL) and CD4 cell counts (vaccinees, 552 cells/mm(3); placebo recipients, 657 cells/mm(3)) before administration of antiretroviral therapy ( ART) and time to a composite end point (plasma HIV-1 RNA level 155,000 copies/mL, CD4 cell count <350 cells/mm(3), or initiation of ART) did not differ significantly between vaccinees and placebo recipients (P = .4, P = .1, and P = .7, respectively). Persons who acquire HIV-1 infection while enrolled in HIV-1 vaccine trials can be successfully followed after infection, to determine whether vaccines alter the course of HIV-1 infection. C1 Univ Washington, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Richmond, CA USA. New York Blood Ctr, New York, NY 10021 USA. Univ Rochester, Rochester, NY 14627 USA. Brown Univ, Providence, RI 02912 USA. Fenway Community Hlth Ctr, Boston, MA USA. Univ Alabama, Birmingham, AL USA. RP Celum, CL (reprint author), Univ Washington, 901 Boren Ave,Ste 1300, Seattle, WA 98104 USA. EM ccelum@u.washington.edu FU NIAID NIH HHS [AI-47976, AI-45202, N01 AI-45202, AI-45208, AI-48022, AI-45205, AI-47996, AI-45211, AI-48021, AI-47985, AI-48023, AI-45200, AI-45206, AI-47980, AI-48017, AI-46747, U01 AI-46725, AI-45207, AI-46703, AI-45210, AI-45209] NR 17 TC 29 Z9 30 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2004 VL 190 IS 5 BP 903 EP 907 DI 10.1086/423284 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 843VL UT WOS:000223114800005 PM 15295694 ER PT J AU Lin, FYC Weisman, LE Azimi, PH Philips, JB Clark, P Regan, J Rhoads, GG Frasch, CE Gray, BM Troendle, J Brenner, RA Moyer, P Clemens, JD AF Lin, FYC Weisman, LE Azimi, PH Philips, JB Clark, P Regan, J Rhoads, GG Frasch, CE Gray, BM Troendle, J Brenner, RA Moyer, P Clemens, JD TI Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TOXOID CONJUGATE VACCINE; POLYSACCHARIDE VACCINE; PREGNANT-WOMEN; HUMAN-SERA; INFECTION; IMMUNIZATION; IMMUNOGENICITY AB The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients ( neonates with EOD caused by GBS type III) and greater than or equal to43 matched control subjects ( neonates colonized by GBS type III who did not develop EOD) of greater than or equal to 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had greater than or equal to10 mug/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of <2 μg/mL. A vaccine that induces IgG anti-GBS type III levels of &GE;10 μg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen. C1 NICHHD, NIH, US Dept HHS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Res & Review, US Dept HHS, Bethesda, MD 20014 USA. Baylor Coll Med, Houston, TX 77030 USA. Childrens Hosp Med Ctr No Calif, Oakland, CA USA. Univ Alabama, Birmingham, AL USA. Univ Florida, Gainesville, FL USA. Columbia Univ Hlth Sci, New York, NY USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. RP Lin, FYC (reprint author), NICHHD, NIH, US Dept HHS, 6100 Execut Blvd,Rm 7B03,MSC 7510, Bethesda, MD 20892 USA. EM link@exchange.nih.gov FU NICHD NIH HHS [HD-53233, HD-43214, HD-43218, HD-43217, HD-43215, HD-43219, HD-43220] NR 31 TC 59 Z9 61 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2004 VL 190 IS 5 BP 928 EP 934 DI 10.1086/422756 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 843VL UT WOS:000223114800009 PM 15295698 ER PT J AU Winblad, B Palmer, K Kivipelto, M Jelic, V Fratiglioni, L Wahlund, LO Nordberg, A Backman, L Albert, M Almkvist, O Arai, H Basun, H Blennow, K de Leon, M DeCarli, C Erkinjuntti, T Giacobini, E Graff, C Hardy, J Jack, C Jorm, A Ritchie, K van Duijn, C Visser, P Petersen, RC AF Winblad, B Palmer, K Kivipelto, M Jelic, V Fratiglioni, L Wahlund, LO Nordberg, A Backman, L Albert, M Almkvist, O Arai, H Basun, H Blennow, K de Leon, M DeCarli, C Erkinjuntti, T Giacobini, E Graff, C Hardy, J Jack, C Jorm, A Ritchie, K van Duijn, C Visser, P Petersen, RC TI Mild cognitive impairment - beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment SO JOURNAL OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 1st Key Symposium on Mild Cognitive Impairment* CY SEP, 2003 CL Stockholm, SWEDEN DE MCI; consensus; mild cognitive impairment; definition; clinical criteria; pre-clinical dementia; Alzheimer's disease AB The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired. C1 Karolinska Inst, Aging Res Ctr, Div Geriatr Epidemiol, Neurotec Dept, S-11382 Stockholm, Sweden. Karolinska Inst, Neurotec Dept, Div Geriatr Med, Stockholm, Sweden. Karolinska Inst, Neurotec Dept, Div Mol Neuropharmacol, Stockholm, Sweden. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Tohoku Univ, Grad Sch Med, Dept Geriatr & Complementary Med, Sendai, Miyagi 980, Japan. Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala, Sweden. Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden. NYU, Sch Med, Ctr Brain Hlth, New York, NY USA. Univ Calif Davis, Alzheimers Dis Ctr, Dept Neurol, Sacramento, CA 95817 USA. Helsinki Univ Hosp, Dept Clin Neurosci, Helsinki, Finland. Univ Geneva, Sch Med, Dept Geriatr, CH-1211 Geneva 4, Switzerland. Karolinska Inst, Neurotec Dept, Div Expt Geriatr, Stockholm, Sweden. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Mayo Clin, Dept Diagnost Radiol, Rochester, MN USA. Mayo Clin, MR Res Lab, Rochester, MN USA. Australian Natl Univ, Mental Hlth Res Ctr, Canberra, ACT, Australia. INSERM, Dept Nervous Syst Pathol, Montpellier, France. Erasmus Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Erasmus Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. Univ Maastricht, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. Mayo Clin, Dept Neurol, Rochester, MN USA. RP Winblad, B (reprint author), Karolinska Inst, Aging Res Ctr, Div Geriatr Epidemiol, Neurotec Dept, Box 6401, S-11382 Stockholm, Sweden. EM bengt.winblad@neurotec.ki.se RI graff, caroline/A-2545-2009; Jorm, Anthony/B-5555-2009; DeCarli, Charles/B-5541-2009; Jack, Clifford/F-2508-2010; Hardy, John/C-2451-2009; Palmer, Katie/A-1430-2016; Ritchie, Karen/G-3571-2013; Visser, Pieter/C-8541-2015; OI Jack, Clifford/0000-0001-7916-622X; Palmer, Katie/0000-0001-8783-016X; Visser, Pieter/0000-0001-8008-9727; Jorm, Anthony/0000-0002-1424-4116 NR 0 TC 1877 Z9 1953 U1 13 U2 117 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD SEP PY 2004 VL 256 IS 3 BP 240 EP 246 DI 10.1111/j.1365-2796.2004.01380.x PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 848MD UT WOS:000223470900008 PM 15324367 ER PT J AU Simon, A Bijzet, J Voorbij, HAM Mantovani, A van der Meer, JWM Drenth, JPH AF Simon, A Bijzet, J Voorbij, HAM Mantovani, A van der Meer, JWM Drenth, JPH TI Effect of inflammatory attacks in the classical type hyper-IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE acute phase response; ferritin; hyper-IgD syndrome; immunoglobulin D; pentraxin-3; procalcitonin ID PERIODIC FEVER SYNDROME; FAMILIAL MEDITERRANEAN FEVER; DENSITY-LIPOPROTEIN CHOLESTEROL; HYPERIMMUNOGLOBULINEMIA-D; SERUM FERRITIN; ALPHA(1)-ACID GLYCOPROTEIN; BACTERIAL-INFECTION; DISEASE-ACTIVITY; STILL DISEASE; PROCALCITONIN AB Background. Classical type hyper-immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto-inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency. Objective. To further characterize the acute phase response during fever attacks in HIDS in order to improve diagnosis. Subjects. Twenty-two mevalonate kinase-deficient HIDS patients. Methods. Blood samples were drawn during and in between febrile attacks, and concentrations ofC-reactive protein (CRP), ferritin, procalcitonin, pentraxin 3, IgD and cholesterol in several lipoprotein fractions were determined. Results. The marked acute phase response at the time of a fever attack in classical type HIDS is reflected by a rise in CRP accompanied by a moderate but statistically significant rise in procalcitonin and pentraxin 3. In only two of 22 patients, procalcitonin concentration rose above 2 ng mL(-1) during fever attack, compatible with the noninfectious nature of these attacks. Ferritin does not reach the high concentrations found in adult-onset Still's disease. Despite the defect in mevalonate kinase, a component of cholesterol metabolism, serum cholesterol did not change during attacks. IgD concentration is elevated regardless of disease activity, although there is appreciable variation during life. Its role in HIDS remains unclear. Conclusion. The combination of high CRP concentration plus procalcitonin concentration <2 ng mL(-1) in a symptomatic HIDS patient might indicate a febrile attack without (bacterial) infection; this observation warrants further investigation for its usefulness as a marker in clinical practice. C1 Univ Med Ctr St Radboud, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. Univ Groningen Hosp, Dept Rheumatol, Groningen, Netherlands. Univ Med Ctr Utrecht, Dept Clin Chem, Utrecht, Netherlands. Mario Negri Inst Pharmacol Res, Dept Immunol & Cell Biol, I-20157 Milan, Italy. Univ Med Ctr St Radboud, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Simon, A (reprint author), Univ Med Ctr St Radboud, Dept Gen Internal Med, 541 POB 9101, NL-6500 HB Nijmegen, Netherlands. EM a.simon@aig.umcn.nl RI Simon, Anna/D-3757-2009; Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013; OI Simon, Anna/0000-0002-6141-7921; van der Meer, Jos/0000-0001-5120-3690; Mantovani, Alberto/0000-0001-5578-236X NR 31 TC 19 Z9 20 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD SEP PY 2004 VL 256 IS 3 BP 247 EP 253 DI 10.1111/j.1365-2796.2004.01359.x PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 848MD UT WOS:000223470900009 PM 15324368 ER PT J AU Hurst, SA Teagarden, JR Garrett, E Emanuel, EJ AF Hurst, SA Teagarden, JR Garrett, E Emanuel, EJ TI Conserving scarce resources: Willingness of health insurance enrollees to choose cheaper options SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID CARE; COMMONS; COPAY AB One of the least controversial mechanisms to conserve health care resources is allowing patients to choose cheaper options themselves. This survey of pharmacy benefit plan enrolees suggests that people are resistant to choosing a cheaper, clinically equivalent option except when they either believe that others are doing the same, or have a personal financial interest. C1 Univ Hosp Geneva, Sch Med, Geneva, Switzerland. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Hurst, SA (reprint author), Univ Hosp Geneva, Sch Med, Geneva, Switzerland. RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 22 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, SUITE 1634, BOSTON, MA 02215 USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 2004 VL 32 IS 3 BP 496 EP + DI 10.1111/j.1748-720X.2004.tb00162.x PG 5 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 854KT UT WOS:000223902400017 PM 15490596 ER PT J AU Peters, DC Ennis, DB Rohatgi, P Syed, MA McVeigh, ER Arai, AE AF Peters, DC Ennis, DB Rohatgi, P Syed, MA McVeigh, ER Arai, AE TI 3D breath-held cardiac function with projection reconstruction in steady state free precession validated using 2D cine MRI SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE radial imaging : projection reconstruction; cardiac function; validation : 3D SSFP; left ventricle; global function; magnetic resonance imaging ID LEFT-VENTRICULAR FUNCTION; SEGMENTED K-SPACE; FIELD-OF-VIEW; REAL-TIME; T BLAST; ANGIOGRAPHY; ARTIFACTS; UNFOLD; HEART; ECHO AB Purpose: To develop and validate a three-dimensional (3D) single breath-hold. projection reconstruction (PR), balanced steady state free precession (SSFP) method for cardiac function evaluation against a two-dimensional (2D) multislice Fourier (Cartesian) transform (FT) SSFP method. Materials and Methods: The 3D PR SSFP sequence used projections in the x-y plane and partitions in z, providing 70 - 80 msec temporal resolution and 1.7 x 1.7 x 8 - 10 mm in a 24-heartbeat breath hold. A total of 10 volunteers were imaged with both methods, and the measurements of global cardiac function were compared. Results: Mean signal-to-noise ratios (SNRs) for the blood and myocardium were 114 and 42 (213) and 59 and 21 (3D). Bland-Altman analysis comparing the 2D and 3D ejection fraction (EF), left ventricular end diastolic volume (LVEDV) and end systolic volume (LVESV). and end diastolic myocardial mass (LVEDM) provided values of bias +/-2 SD of 0.6% +/- 7.7% for LVEF, 5.9 mL +/- 20 mL for LVEDV, -2.8 mL +/- 12 mL for LVESV. and -0.61 g +/- 13 g for LVEDM. 3D interobserver variability was greater than 2D for LVEDM and LVESV. Conclusion: In a single breath hold, the 3D PR method provides comparable information to the standard 2D FT method, which employs 10-12 breath holds. C1 Beth Israel Deaconess Med Ctr, Cardiac MR Ctr, Boston, MA 02215 USA. NHLBI, Cardiac Energet Lab, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. RP Peters, DC (reprint author), Beth Israel Deaconess Med Ctr, Cardiac MR Ctr, RW457,330 Brookline Ave, Boston, MA 02215 USA. EM depeters@bidmc.harvard.edu OI Rohatgi, Pratik/0000-0003-4175-5293 FU Intramural NIH HHS [Z01 HL004608-08] NR 31 TC 33 Z9 33 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2004 VL 20 IS 3 BP 411 EP 416 DI 10.1002/jmri.20145 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849ET UT WOS:000223522200009 PM 15332248 ER PT J AU Kobayashi, H Jo, SK Kawamoto, S Yasuda, H Hu, XZ Knopp, MV Brechbiel, MW Choyke, PL Star, RA AF Kobayashi, H Jo, SK Kawamoto, S Yasuda, H Hu, XZ Knopp, MV Brechbiel, MW Choyke, PL Star, RA TI Polyamine dendrimer-based MRI contrast agents for functional kidney imaging to diagnose acute renal failure SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; kidney; polyamine dendrimer; contrast media; acute renal failure ID POLYAMIDOAMINE DENDRIMER; CORE; PHARMACOKINETICS; ANGIOGRAPHY; SIZES; MICE AB Purpose: To choose an efficacious renal functional MRI contrast agent to image early renal tubular damage. We synthesized and compared smaller polyamine dendrimer-based MRI contrast agents (<60 kD) that, unlike Gd-[DTPA], transiently accumulate in renal tubules and can be used to visualize renal structural and functional damage. Materials and Methods: Six dendrimer-based MRI contrast agents smaller than 60 kD were studied by high resolution dynamic micro-MRI and compared to Gd-[DTPA]-dimeglumine and Gadomer-17. The best agent, DAB-G2, was further tested in a mouse ischemia/reperfusion model to validate its efficacy. Results: Despite unequal renal clearance rates, all polyamine dendrimer agents visualized the renal functional anatomy of the mice better than Gd-[DTPA]-dimeglumine and Gadomer-17. DAB-G2 was excreted most rapidly, yet was able to visualize mild renal tubular injury very early after injury. Conclusion: DAB-G2 was found to be the best candidate for functional kidney imaging and enabled early diagnosis of acute renal injury. C1 NCI, Canc Res Ctr, Natl Inst Hlth, Metab Branch, Bethesda, MD 20892 USA. NIDDK, Renal Diagnost & Therapeut Unit, Natl Inst Hlth, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD USA. RP Kobayashi, H (reprint author), NCI, Canc Res Ctr, Natl Inst Hlth, Metab Branch, Bldg 10,Room B3B69,MSC1002,10 Ctr Dr, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov NR 19 TC 47 Z9 49 U1 1 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2004 VL 20 IS 3 BP 512 EP 518 DI 10.1002/jmri.20147 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849ET UT WOS:000223522200022 PM 15332261 ER PT J AU Shen, J Chen, ZG Yang, JH AF Shen, J Chen, ZG Yang, JH TI New FOCI pulses with reduced radiofrequency power requirements SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE RF pulse; RF power deposition; adiabaticity; spin echo imaging ID SELECTIVE EXCITATION; INVERSION; BRAIN; SPECTROSCOPY AB Purpose: To propose new frequency offset corrected inversion (FOCI) pulses with significantly reduced radiofrequency (RF) power deposition for spin echo imaging by incorporating the variable-rate selective excitation (VERSE) schemes into the pulse design. Materials and Methods: Two schemes are proposed to design the new FOCI pulses with dramatically reduced peak RF power requirements. In scheme A, the time-dilation function is derived from a predefined adiabaticity factor modulation function. In scheme B, the time-dilation function is predefined. while the adiabaticity factor is conserved. Results: The new FOCI pulses are shown to be able to operate at reduced specific absorption rate (SAR), specifically at the same peak RF power as that of a five- or seven-lobe sine inversion pulse of the same duration. Using the new FOCI pulse, significant gain in sensitivity was observed in in vivo spin-echo echo-planar imaging, which was attributed to the improved refocusing slice profile. Conclusion: The new FOCI pulses can replace the 180degrees five- or seven-lobe sine pulses in spin-echo imaging with the same peak RF power requirement and significantly improved slice profile. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov NR 15 TC 16 Z9 16 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2004 VL 20 IS 3 BP 531 EP 537 DI 10.1002/jmri.20134 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849ET UT WOS:000223522200025 PM 15332264 ER PT J AU Frattali, C AF Frattali, C TI An errorless learning approach to treating dysnomia in frontotemporal dementia SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID SEMANTIC DEMENTIA; FUNCTIONAL COMMUNICATION; LIVING THINGS; NEURAL BASIS; TOKEN TEST; VERBS; NOUNS; KNOWLEDGE; LANGUAGE; THERAPY AB This case study describes an errorless learning approach to naming treatment for an adult with temporal-variant frontotemporal dementia. The patient's severe dysnomia was characterized by between- (verbs better than nouns) and within-class (biological motion better than tool use verbs; living better than nonliving nouns) grammatical dissociations. A treatment method was designed to improve naming within specific semantic categories using an interactional discourse approach that required use of analytical and associative skills, with confrontation naming expected as a byproduct of the direct treatment. The predictions were that significant improvements would occur during the active course of treatment, with steeper learning curves achieved for more relatively preserved semantic categories, but with no generalization to novel stimuli and no maintenance of gain at 3-months follow-up. Results were largely as predicted, with significant improvements in naming during the active phases of treatment, with no generalization of naming ability to novel stimuli, and no maintenance of gain at follow-up. Findings coincide with other studies in the literature. Findings also suggest the value of errorless learning approaches to naming and the facilitation of neurobehavioral effect during active phases of treatment. C1 NIH, WG Magnuson Clin Ctr, Dept Rehabil Med, Speech Language Pathol Sect, Bethesda, MD 20892 USA. RP Frattali, C (reprint author), Florida State Univ, Dept Commun Disorders, Tallahassee, FL 32306 USA. NR 55 TC 13 Z9 14 U1 1 U2 4 PU DELMAR LEARNING PI CLIFTON PARK PA EXECUTIVE WOODS, 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD SEP PY 2004 VL 12 IS 3 BP XI EP XXIV PG 14 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 853RZ UT WOS:000223846600003 ER PT J AU Imahashi, K London, RE Steenbergen, C Murphy, E AF Imahashi, K London, RE Steenbergen, C Murphy, E TI Male-female differences in intracellular Na+ regulation during ischemia/reperfusion in mouse heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE ischemia; sodium; sexual dimorphisms; nuclear magnetic resonance spectroscopy ID BETA-ADRENERGIC STIMULATION; VENTRICULAR MYOCYTES; METABOLIC INHIBITION; NA+-CA2+ EXCHANGER; REPERFUSION INJURY; CARDIAC MYOCYTES; NA/CA EXCHANGE; RAT HEARTS; ISCHEMIA; CALCIUM AB We previously showed that P-adrenergic stimulation revealed male/female differences in susceptibility to ischemia/reperfusion (I/R) injury. To explore whether altered [Na+](i) regulation is involved in the mechanism of this sex difference, we measured [Na+](i) by Na-23 NMR spectroscopy in isolated perfused mouse hearts. [Na+](i) increased to 195 +/- 3% (mean +/- S.E.) of the pre-ischemic level at 20 min of ischemia in male hearts, whereas [Na+](i) accumulation was slightly less in female hearts (176 +/- 2%, P < 0.05). There was no significant difference in the recovery of contractile function after reperfusion (male: 30.6 +/- 3.8%; female: 35.0 +/- 1.9%; P > 0.05). If hearts were treated with isoproterenol (ISO, 10 nmol/l), males exhibited significantly poorer recovery of post-ischemic contractile function than females (male: 13.0 +/- 1.9%; female: 28.1 +/- 1.2%; P < 0.05), and a significantly higher [Na+](i) accumulation during ischemia (male: 218 +/- 8%; female: 171 +/- 2%; P < 0.05). This ISO-induced male/female difference in [Na+](i) accumulation or contractile function was blocked by the nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (1 mumol/l). Furthermore, in ISO-treated hearts, the Na+/K+-ATPase inhibitor, ouabain (200 mumol/l) did not abolish the male/female difference in [Na+](i) accumulation during I/R or functional protection. Thus the data show that the sex difference in the [Na+](i) regulation is mediated through a NO-dependent mechanism, and the difference in susceptibility to I/R injury appears to result from a difference in Na+ influx. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Murphy, E (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM murphy1l@niehs.nih.gov FU NHLBI NIH HHS [R01 HL039752] NR 27 TC 20 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2004 VL 37 IS 3 BP 747 EP 753 DI 10.1016/j.yjmcc.2004.06.010 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 856JO UT WOS:000224041700014 PM 15350847 ER PT J AU Ellis, RJ Minton, AP Rivas, G AF Ellis, RJ Minton, AP Rivas, G TI Special issue: EMBO workshop on biological implications of macromolecular crowding held on 14-18 June 2003 Las Navas de Marques, Avila, Spain - Foreword SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Editorial Material C1 Univ Warwick, Dept Sci Biol, Coventry CV4 7AL, W Midlands, England. NIH, Bethesda, MD 20892 USA. CSIC, Ctr Invest Biol, Madrid, Spain. RP Ellis, RJ (reprint author), Univ Warwick, Dept Sci Biol, Coventry CV4 7AL, W Midlands, England. EM jellis@bio.warwick.ac.uk; minton@helix.nih.gov; grivas@cib.csic.es NR 5 TC 0 Z9 0 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD SEP-OCT PY 2004 VL 17 IS 5 BP 349 EP 349 DI 10.1002/jmr.717 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 857YR UT WOS:000224157400001 ER PT J AU Rivas, G Minton, AP AF Rivas, G Minton, AP TI Non-ideal tracer sedimentation equilibrium: a powerful tool for the characterization of macromolecular interactions in crowded solutions SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Article; Proceedings Paper CT EMBO Workshop on Biological Implications of Macromolecular Crowding CY JUN 14-18, 2003 CL Avila, SPAIN SP EMBO DE analytical ultracentrifugation; self-association; hetero-association; macromolecular crowding ID SELF-ASSOCIATION; ANALYTICAL ULTRACENTRIFUGATION; QUANTITATIVE CHARACTERIZATION; PROTEIN INTERACTIONS AB Non-ideal tracer sedimentation equilibrium is a technique devised to quantify the effect of high concentrations of unrelated macromolecules on the self- or hetero-associations of dilute macromolecules. Principles and experimental techniques are reviewed, and previous experimental work summarized. A new analysis of experimental data is presented that requires no a priori assumptions regarding the nature of weak repulsive interactions between solute species and the concentrated (crowding) species. Published in 2004 by John Wiley Sons, Ltd. C1 NIDDKD, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. CSIC, Ctr Invest Biol, E-28040 Madrid, Spain. RP Minton, AP (reprint author), NIDDKD, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247; Rivas, German/0000-0003-3450-7478 NR 21 TC 16 Z9 16 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD SEP-OCT PY 2004 VL 17 IS 5 BP 362 EP 367 DI 10.1002/jmr.708 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 857YR UT WOS:000224157400003 PM 15362093 ER PT J AU DiProspero, NA Chen, EY Charles, V Plomann, M Kordower, JH Tagle, DA AF DiProspero, NA Chen, EY Charles, V Plomann, M Kordower, JH Tagle, DA TI Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEIN-2; AXONAL-TRANSPORT; MOUSE MODEL; NEUROTRANSMITTER RELEASE; NEUROFILAMENT SUBUNIT; WIDESPREAD EXPRESSION; STRIATAL NEURONS; QUINOLINIC ACID; TRANSGENIC MICE; COMPLEXIN-II AB Huntingtons disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions. To investigate whether early degenerative changes in HD involve alterations of cytoskeletal and vesicular components, we examined early cellular changes in the frontal cortex of HD presymptomatic (PS), early pathological grade (grade 1) and late-stage (grade 3 and 4) patients as compared to age-matched controls. Morphologic analysis using silver impregnation revealed a progressive decrease in neuronal fiber density and organization in pyramidal cell layers beginning in presymptomatic HD cases. Immunocytochemical analyses for the cytoskeletal markers α-tubulin, microtubule-associated protein 2, and phosphorylated neurofilament demonstrated a concomitant loss of staining in early grade cases. Immunoblotting for synaptic proteins revealed a reduction in complexin 2, which was marked in some grade 1 HD cases and significantly reduced in all late stage cases. Interestingly, we demonstrate that two synaptic proteins, dynamin and PACSIN 1, which were unchanged by immunoblotting, showed a striking loss by immunocytochemistry beginning in early stage HD tissue suggesting abnormal distribution of these proteins. We propose that mutant huntingtin affects proteins involved in synaptic function and cytoskeletal integrity before symptoms develop which may influence early disease onset and/or progression. C1 Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Rush Presbyterian Med Ctr, Chicago, IL 60612 USA. Univ Cologne, Inst Biochem 2, D-50931 Cologne, Germany. Univ Cologne, CMMC, D-50931 Cologne, Germany. RP DiProspero, NA (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM diprospern@ninds.nih.gov FU NIMH NIH HHS [MH/NS 31862] NR 81 TC 79 Z9 82 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD SEP PY 2004 VL 33 IS 5 BP 517 EP 533 DI 10.1007/s11068-004-0514-8 PG 17 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 928KW UT WOS:000229271400004 PM 15906159 ER PT J AU Shevach, E AF Shevach, E TI Activation and deactivation of regulatory T cell function SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA IS7 BP 6 EP 6 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200011 ER PT J AU Mattson, MP AF Mattson, MP TI Detrimental and beneficial cytokine signaling in Alzheimer's disease SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIA, Neurosci Lab, IRP, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA IS20 BP 9 EP 9 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200024 ER PT J AU Martin, R AF Martin, R TI Antigen recognition patterns of autoreactive T cells in multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA IS28 BP 11 EP 11 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200032 ER PT J AU Chrousos, GP AF Chrousos, GP TI Inflammatory stress SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NICHD, PREB, NIH, Bethesda, MD USA. Univ Athens, Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA IS54 BP 18 EP 18 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200058 ER PT J AU Alesci, S Martinez, P Kelkar, S Ilias, I Ayala, AR Licinio, J Chrousos, GP Gold, PW AF Alesci, S Martinez, P Kelkar, S Ilias, I Ayala, AR Licinio, J Chrousos, GP Gold, PW TI Multiple IL-6 anomalies in patients with major depression SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 119 BP 37 EP 37 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200123 ER PT J AU Schreiner, B Voss, J Dalakas, M Lochmuller, H Melms, A Wiendl, H AF Schreiner, B Voss, J Dalakas, M Lochmuller, H Melms, A Wiendl, H TI Expression of Toll-like receptors by human muscle cells in vitro and in vivo: TLR3 is highly expressed in HIV myopathies and mediates NF-kappaB activation and IL-8 secretion upon stimulation with Poly(I : C) SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 Univ Tubingen, Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Univ Munich, Genzentrum, Friedrich Baur Inst, Munich, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 161 BP 48 EP 48 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200165 ER PT J AU Herkenham, M Kassed, C AF Herkenham, M Kassed, C TI NF-kappaB1 (p50) knockout mice show reduced anxiety SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 426 BP 128 EP 128 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200431 ER PT J AU Pert, A Weber, R AF Pert, A Weber, R TI Electrical stimulation of the mesencephalic periaqueductal gray matter in rats alters NK cell function SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIH, Bethesda, MD 20892 USA. Univ Illinois, Coll Med, Peoria, IL 61656 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 442 BP 132 EP 132 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200447 ER PT J AU Schmidt, J Voss, JG Raju, R Dalakas, MC AF Schmidt, J Voss, JG Raju, R Dalakas, MC TI Sporadic inclusion body myositis: immunotherapy downregulates inflammation and beta-amyloid associated factors in repeated muscle biopsies SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIH, Bethesda, MD 20892 USA. RI Raju, Raghavan/E-9219-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 494 BP 148 EP 148 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200499 ER PT J AU Sospedra, M Zhao, Y Muraro, P Jacobson, S Pinilla, C Martin, R AF Sospedra, M Zhao, Y Muraro, P Jacobson, S Pinilla, C Martin, R TI Identification of putative trigger agents in multiple sclerosis using an unbiased approach SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIH, Bethesda, MD 20892 USA. Torrey Pines Inst, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 597 BP 182 EP 182 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200602 ER PT J AU Muraro, PA Chung, K Douek, D McFarland, HF Burt, RK Martin, R AF Muraro, PA Chung, K Douek, D McFarland, HF Burt, RK Martin, R TI Immunological mechanisms of autologous hematopoietic stem cell transplantation as a therapy for multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIH, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 692 BP 210 EP 210 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200697 ER PT J AU Bielekova, B Reichert-Scrivner, S Cerna, A McFarland, H Martin, R AF Bielekova, B Reichert-Scrivner, S Cerna, A McFarland, H Martin, R TI CD56bright NK cells mediate immunomodulatory effects of IL-2R-alpha-targeted therapy in multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 699 BP 211 EP 211 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200704 ER PT J AU Park, DM Sospedra, M Wang, X Quandt, J Raine, C McFarland, HF Martin, R AF Park, DM Sospedra, M Wang, X Quandt, J Raine, C McFarland, HF Martin, R TI Multiple sclerosis brain-derived cDNA expression libraries allow the identification of novel autoantigens for CSF-infiltrating CD4+ T lymphocytes SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, New York, NY USA. RI Park, Deric/C-5675-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 745 BP 226 EP 226 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200750 ER PT J AU Quandt, JA Huh, J Park, D Pinilla, C Ito, K Martin, R AF Quandt, JA Huh, J Park, D Pinilla, C Ito, K Martin, R TI Pathologic relevance of degenerate foreign and self antigen recognition by a myelin-specific HLA-DR2-restricted T cell receptor SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 7th International Congress of the International-Society-of-Neuroimmunology CY SEP 28-OCT 02, 2004 CL Venice, ITALY SP Int Soc Neuroimmunol C1 NIH, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies, San Diego, CA USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2004 VL 154 IS 1-2 SI SI MA 748 BP 226 EP 226 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 855VO UT WOS:000224003200753 ER PT J AU Hasegawa, RP Blitz, AM Goldberg, ME AF Hasegawa, RP Blitz, AM Goldberg, ME TI Neurons in monkey prefrontal cortex whose activity tracks the progress of a three-step self-ordered task SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL NEURONS; VISUAL WORKING-MEMORY; INFEROTEMPORAL CORTEX; REWARD MAGNITUDE; PARIETAL CORTEX; UNIT-ACTIVITY; PRIMATE; PERFORMANCE; MACAQUE; LESIONS AB The self-ordered task is a powerful tool for the analysis of dorsal prefrontal deficits. Each trial consists of a number of steps, and subjects must remember their choices in previous steps. The task becomes more difficult as the number of objects to be remembered increases. We recorded the activity of 156 neurons in the mid-dorsal prefrontal cortex of two rhesus monkeys performing an oculomotor version of the task. Although the task requires working memory, there was no convincing evidence for activity selective for the working memory of the objects that the monkey had to remember. Instead, nearly one-half of neurons (47%, 74/156) showed activity that was modulated according to the step of the task in any one or more task periods. Although the monkey's reward also increased with step, the neurons exhibited little or no step modulation in a reward control task in which reward increased without a concurrent increase in task difficulty. The activity of some neurons was also selective for the location of saccade target that the monkey voluntarily chose. Neurons showed less step modulation in error trials, and there was no increase between the second and third step responses on trials in which the error was on the third step. These results suggest that the mid-dorsal prefrontal cortex contributes to the self-ordered task, not by providing an object working memory signal, but by regulating some general aspect of the performance in the difficult task. C1 Natl Inst Adv Ind Sci & Technol, Neurosci Res Inst, Tsukuba, Ibaraki 3058568, Japan. NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Mahoney Ctr Brain & Behav, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Hasegawa, RP (reprint author), Natl Inst Adv Ind Sci & Technol, Neurosci Res Inst, 1-1-1 Umezono, Tsukuba, Ibaraki 3058568, Japan. EM r-hasegawa@aist.go.jp FU NEI NIH HHS [R01 EY014978, R01 EY017039] NR 44 TC 26 Z9 26 U1 4 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2004 VL 92 IS 3 BP 1524 EP 1535 DI 10.1152/jn.01110.2003 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 849LF UT WOS:000223539400025 PM 15152025 ER PT J AU Krug, K Cumming, BG Parker, AJ AF Krug, K Cumming, BG Parker, AJ TI Comparing perceptual signals of single V5/MT neurons in two binocular depth tasks SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; VERGENCE EYE-MOVEMENTS; CORTICAL AREA V1; VISUAL-CORTEX; ANTICORRELATED STEREOGRAMS; STEREOSCOPIC DEPTH; MOTION DIRECTION; MT NEURONS; DISPARITY; MACAQUE AB Neurons in the extrastriate visual area V5/MT show perceptually relevant signals in binocular depth tasks, which can be measured as a choice probability (CP) for the neuron. The presence of a CP in a particular paradigm may be an indicator that the neuron is generally part of the substrate for the perception of binocular depth. We compared the responses of those single neurons that show CPs in one stereoscopic depth task with their responses in another stereo task. Each neuron was tested for the presence of 1) CPs during a task in which macaques responded to the sign of binocular depth in a structure-from-motion stimulus, to judge its direction of three-dimensional rotation and 2) a consistent response to the stereo disparity of binocularly anti-correlated stimuli. Previous work, confirmed here, shows that changing the disparity of these binocularly anti-correlated stimuli often fails to yield a coherent change in the depth percept. For each test alone, there are V5/MT neurons that carry signals that are congruent with the perceptual effects. However, on comparing tests, there is no fixed pool of neurons that can account for the binocular depth percept. Excitation of neurons with a measurable CP does not necessarily lead to a change in perception. The cortical circuitry must be able to make dynamic changes in the pools of neurons that underlie perceptual judgments according to the demands of the task. C1 Univ Oxford, Univ Lab Physiol, Oxford OX1 3PT, England. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Krug, K (reprint author), Univ Oxford, Univ Lab Physiol, Parks Rd, Oxford OX1 3PT, England. EM kristine.krug@physiol.ox.ac.uk RI Parker, Andrew/I-7867-2013; OI Parker, Andrew/0000-0001-5800-0407; Krug, Kristine/0000-0001-7119-9350 NR 44 TC 66 Z9 68 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2004 VL 92 IS 3 BP 1586 EP 1596 DI 10.1152/jn.00851.2003 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 849LF UT WOS:000223539400031 PM 15102899 ER PT J AU Bolla, K Ernst, M Kiehl, K Mouratidis, M Eldreth, D Contoreggi, C Matochik, J Kurian, V Cadet, J Kimes, A Funderburk, F London, E AF Bolla, K Ernst, M Kiehl, K Mouratidis, M Eldreth, D Contoreggi, C Matochik, J Kurian, V Cadet, J Kimes, A Funderburk, F London, E TI Prefrontal cortical dysfunction in abstinent cocaine abusers SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ANTERIOR CINGULATE CORTEX; POSITRON EMISSION TOMOGRAPHY; STROOP TASK-PERFORMANCE; SELECTIVE ATTENTION; FUNCTIONAL MRI; SCHIZOPHRENIA; DISORDER; INTERFERENCE; CONFLICT; DEFICITS AB The anterior cingulate cortex (ACC) and lateral prefrontal (LPFC) cortex are brain regions important to executive cognitive functions (ECF). We determined ACC and LPFC function in 23-day abstinent cocaine abusers using positron emission tomography (PET (H2O)-O-15) during performance of a modified version of the Stroop Task. Cocaine abusers showed less activation than non-drug-using comparison subjects in the left ACC and the right LPFC and greater activation in the right ACC. Average amount of cocaine used per week was negatively correlated with activity in the rostral ACC and right LPFC. Disruption of ECF in substance abusers could interfere with attempts to stop drug use and undermine treatment. Since impairment in ECF may be a common feature of various neuropsychiatric disorders, these findings have applicability beyond the neurobiology of addiction. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. NIMH, Mood & Anxiety Disorders Program, New Haven, CT USA. Hartford Hosp, Inst Living, New Haven, CT USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. NIDA, Brain Imaging Ctr, Intramural Res Program, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. RP Bolla, K (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM kbolla@jhmi.edu FU NCRR NIH HHS [M01 RR002719, M01 RR02719]; NIDA NIH HHS [DA11426, R01 DA011426-02]; NIMH NIH HHS [R01 MH085010] NR 39 TC 153 Z9 163 U1 3 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2004 VL 16 IS 4 BP 456 EP 464 DI 10.1176/appi.neuropsych.16.4.456 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 881VN UT WOS:000225897600008 PM 15616172 ER PT J AU Stein, TD Anders, NJ DeCarli, C Chan, SL Mattson, MP Johnson, JA AF Stein, TD Anders, NJ DeCarli, C Chan, SL Mattson, MP Johnson, JA TI Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APP(Sw) mice resulting in tau phosphorylation and loss of hippocampal neurons: Support for the amyloid hypothesis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; alpha-secretase; neuropathology; neurotrophic; neurodegeneration; neuroprotection; organotypic slice culture; beta-amyloid ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; A-BETA; CEREBROSPINAL-FLUID; ALPHA-SECRETASE; NEUROFIBRILLARY TANGLES; TIME-COURSE; MUTANT; BAD; APOPTOSIS AB Alzheimer's disease (AD) may be caused by the abnormal processing of the amyloid precursor protein (APP) and the accumulation of beta-amyloid (Abeta). The amyloid precursor protein can be proteolytically cleaved into multiple fragments, many of which have distinct biological actions. Although a high level of Abeta can be toxic, the alpha-secretase cleaved APP (sAPPalpha) is neuroprotective. However, the mechanism of sAPPalpha protection is unknown. Here, we show that sAPPalpha increases the expression levels of several neuroprotective genes and protects organotypic hippocampal cultures from Abeta-induced tau phosphorylation and neuronal death. Antibody interference and small interfering RNA knock-down demonstrate that the sAPPalpha-driven expression of transthyretin and insulin-like growth factor 2 is necessary for protection against Abeta-induced neuronal death. Mice overexpressing mutant APP possess high levels of sAPPalpha and transthyretin and do not develop the tau phosphorylation or neuronal loss characteristic of human AD. Chronic infusion of an antibody against transthyretin into the hippocampus of mice overexpressing APP with the Swedish mutation (APP(Sw)) leads to increased Abeta, tau phosphorylation, and neuronal loss and apoptosis within the CA1 neuronal field. Therefore, the elevated expression of transthyretin is mediated by sAPPalpha and protects APP(Sw) mice from developing many of the neuropathologies observed in AD. C1 Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. Univ Wisconsin, Neurosci Training Program, Madison, WI 53705 USA. Univ Wisconsin, Ctr Environm Toxicol, Madison, WI 53705 USA. Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA. NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Johnson, JA (reprint author), Univ Wisconsin, Sch Pharm, 6125 Rennebohm Hall,777 Highland Ave, Madison, WI 53705 USA. EM jajohnson@pharmacy.wisc.edu RI DeCarli, Charles/B-5541-2009; Mattson, Mark/F-6038-2012 FU CSRD VA [I01 CX001038]; NIA NIH HHS [P30 AG10129]; NIEHS NIH HHS [ES08089, ES10042] NR 44 TC 152 Z9 166 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 2004 VL 24 IS 35 BP 7707 EP 7717 DI 10.1523/JNEUROSCI.2211-04.2004 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 851ZL UT WOS:000223724900014 PM 15342738 ER PT J AU Yabe, T Herbert, JT Takanohashi, A Schwartz, JP AF Yabe, T Herbert, JT Takanohashi, A Schwartz, JP TI Treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor in vitro enhances expression of other neurotrophic factors as well as cytokines and chemokines SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE microarray; MIP (macrophage inflammatory protein); BDNF ID FACTOR-KAPPA-B; FACTOR PEDF; MOTOR-NEURONS; HIPPOCAMPAL-NEURONS; GROWTH-FACTOR; APOPTOSIS; SURVIVAL; DEATH; RAT; GLUTAMATE AB Microarray analyses demonstrated that a variety of genes was affected by treatment of cerebellar granule cell neurons with the neurotrophic factor pigment epithelium-derived factor (PEDF). The genes for neurotrophins, glial cell-derived neurotrophic factor (GDNF), and their receptors were regulated differentially in immature versus mature neurons; however, nerve growth factor (NGF), neurotrophin (NT)-3, and GDNF did not contribute to the protective effect of PEDF. Brain-derived neurotrophic factor (BDNF) seemed capable of inducing apoptosis, because a blocking antibody enhanced the protective effect of PEDF In addition, PEDF exposure also stimulated expression of several cytokine and chemokine genes. Removal of the less than 1% of microglia in the cultures by treatment with L-leucine methyl ester, combined with enzyme-linked immunosorbent assays (ELISAs), demonstrated that the cerebellar granule cells constitutively produce three chemokines, macrophage inflammatory protein (MIP)-1alpha, MIP-2, and MIP-3alpha, whose production is enhanced further by treatment with PEDF. Blocking antibodies to each of the chemokines was protective under control conditions, suggesting that they may contribute to the "natural" apoptosis occurring in the cultures, and enhanced the effects of PEDF. Although PEDF enhanced production of all three chemokines, the blocking antibodies did not increase its protective effect against induced apoptosis. These results suggest that although PEDF enhances expression of other neurotrophic factors or chemokines, it does not exert its neuroprotective effect on cerebellar granule cells through their production. (C) 2004 Wiley-Liss, Inc. C1 NINDS, Neurotroph Factors Sect, OIR, OD,NIH, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINDS, Neurotroph Factors Sect, OIR, OD,NIH, Bldg 1,Room 135, Bethesda, MD 20892 USA. EM jps@helix.nih.gov OI Takanohashi, Asako/0000-0003-3292-1595; Herbert, James Taylor/0000-0002-9077-2391 NR 33 TC 17 Z9 18 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 2004 VL 77 IS 5 BP 642 EP 652 DI 10.1002/jnr.20196 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 852DL UT WOS:000223735300003 PM 15352210 ER PT J AU Israelsson, C Lewen, A Kylberg, A Althini, S Mishina, K Hillered, L Ebendal, T AF Israelsson, C Lewen, A Kylberg, A Althini, S Mishina, K Hillered, L Ebendal, T TI Transcriptional changes in hippocampus and neocortex following traumatic brain injury (TBI) in the mouse SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 22nd Annual National-Neurotrauma-Society Symposium CY OCT 20-22, 2004 CL San Diego, CA SP Natl Neurotrauma Soc DE gene expression; RT-PCR; GFAP; MAP kinase; transgenic mouse C1 Dept Neurosci, Uppsala, Sweden. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RI Lewen, Anders/A-5156-2013 OI Lewen, Anders/0000-0003-4925-1348 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2004 VL 21 IS 9 MA P321 BP 1343 EP 1343 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 855HC UT WOS:000223962900320 ER PT J AU Pettigrew, R Fee, CA Li, KC AF Pettigrew, R Fee, CA Li, KC TI INM - Comments and perspectives SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Pettigrew, R (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 2004 VL 45 IS 9 BP 1427 EP 1427 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 853EM UT WOS:000223809500005 PM 15452962 ER PT J AU Giovacchini, G Lerner, A Toczek, MT Fraser, C Ma, KZ DeMar, JC Herscovitch, P Eckelman, WC Rapoport, SI Carson, RE AF Giovacchini, G Lerner, A Toczek, MT Fraser, C Ma, KZ DeMar, JC Herscovitch, P Eckelman, WC Rapoport, SI Carson, RE TI Brain incorporation of C-11-arachidonic acid, blood volume, and blood flow in healthy aging: A study with partial-volume correction SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE arachidonic acid; blood volume; aging; partial-volume correction; PET ID POSITRON-EMISSION-TOMOGRAPHY; PHOSPHOLIPASE A(2); ARACHIDONIC-ACID; PET; IMAGES; CHROMATOGRAPHY; SEGMENTATION; ALGORITHM; TURNOVER; RELEASE AB PET with C-11-arachidonic acid (AA) can be used to quantify neural signaling related to phospholipase A(2) (PLA(2)). Animal studies suggest reduction in the activity of this signaling system with age. The aim of this study was to evaluate the effect of healthy aging on brain incorporation of C-11-AA, before and after partial-volume correction (PVC). Methods: Absolute measurements of cerebral blood flow (CBF) were obtained in 8 young and 7 old healthy subjects (mean age +/- SD, 27 +/- 5 y and 65 +/- 9 y) with bolus injection of O-15-water. About 15 min later, dynamic 60-min 3-dimensional scans were acquired after the injection of C-11-AA. Radioactivity frames of C-11-AA were corrected for head motion and registered to magnetic resonance (MR) images. A 3-segment (3S) and a 2-segment (2S) PVC was applied pixel-by-pixel to the activity frames. For the 3S method, the white matter value was estimated using a new automatic method by extrapolating the activity values of pixels with white matter membership > 0.99. Parametric images of the brain incorporation rate of C-11-AA (K*) and cerebral blood volume (V-b), as well as CBF, were generated and regional gray matter values were obtained. Results: Among cortical areas, there were no significant differences (uncorrected P < 0.05) in K* or V-b absolute values between young and old subjects before or after PVC. A significant reduction of CBF was detected in the frontal cortex of the elderly group. After normalization to the global gray average, K*, Vb, and CBF values revealed significant reductions in the frontal lobe of old subjects; none of these differences were significant after PVC. Conclusion: These results confirm previous PET findings that brain function at rest is minimally affected by healthy aging. Proper PVC methodology is of critical importance in accurate quantitative assessment of PET physiologic measures. C1 NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Univ Pisa, Sch Med, Postgrad Specialty Sch Nucl Med, I-56100 Pisa, Italy. RP Carson, RE (reprint author), NIH, Ctr Clin, PET Dept, Bldg 10,Room 1C-401,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. EM richard-e-carson@nih.gov RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 32 TC 63 Z9 65 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 2004 VL 45 IS 9 BP 1471 EP 1479 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 853EM UT WOS:000223809500013 PM 15347713 ER PT J AU Lu, JQ Ichise, M Liow, JS Ghose, S Vines, D Innis, RB AF Lu, JQ Ichise, M Liow, JS Ghose, S Vines, D Innis, RB TI Biodistribution and radiation dosimetry of the serotonin transporter ligand C-11-DASB determined from human whole-body PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE C-11-DASB; serotonin transporter; dosimetry; whole-body biodistribution; PET ID POSITRON-EMISSION-TOMOGRAPHY; NONHUMAN-PRIMATES; HUMAN BRAIN; IN-VITRO; DEPRESSION; PATHOPHYSIOLOGY; RADIOTRACERS; -DASB; PROBE; RAT AB C-11-Labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile (DASB) is a selective radioligand for the in vivo quantitation of serotonin transporters (SERTs) using PET. The goal of this study was to provide dosimetry estimates for C-11-DASB based on human whole-body PET. Methods: Dynamic whole-body PET scans were acquired for 7 subjects after the injection of 669 +/- 97 MBq (18.1 +/- 2.6 mCi) of C-11-DASB. The acquisition for each subject was obtained at 14 time points for a total of 115 min after injection of the radioligand. Regions of interest were placed over compressed planar images of source organs that could be visually identified to generate time-activity curves. Radiation burden to the body was calculated from residence times of these source organs using the MIRDOSE3.1 program. Results: The organs with high radiation burden included the lungs, urinary bladder wall, kidneys, gallbladder wall, heart wall, spleen, and liver. The activity peaked within 10 min after the injection of C-11-DASB for all these organs except two-the excretory organs gallbladder and urinary bladder wall, which had peak activities at 32 and 22 min, respectively. Monoexponential fitting of activity overlying the urinary bladder suggested that approximately 12% of activity was excreted via the urine. Simulations in which the urinary voiding interval was decreased from 4.8 to 0.6 h produced only modest effects on the dose to the urinary bladder wall. With a 2.4-h voiding interval, the calculated effective dose was 6.98 muGy/MBq (25.8 mrem/mCi). Conclusion: The estimated radiation burden of C-11-DASB is relatively modest and would allow multiple PET examinations of the same research subject per year. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Lu, JQ (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 1,Room B3-10,1 Ctr Dr,MSC 0135, Bethesda, MD 20892 USA. EM lujq@intra.nimh.nih.gov RI Ghose, Subroto/J-6732-2016 NR 25 TC 27 Z9 27 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 2004 VL 45 IS 9 BP 1555 EP 1559 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 853EM UT WOS:000223809500024 PM 15347724 ER PT J AU Gruber, M Chappell, R Millen, A LaRowe, T Moeller, SM Iannaccone, A Kritchevsky, SB Mares, J AF Gruber, M Chappell, R Millen, A LaRowe, T Moeller, SM Iannaccone, A Kritchevsky, SB Mares, J TI Correlates of serum lutein plus zeaxanthin: Findings from the Third National Health and Nutrition Examination Survey SO JOURNAL OF NUTRITION LA English DT Article DE body mass; carotenoids; diet; lutein; smoking; zeaxanthin ID MACULAR PIGMENT DENSITY; PLASMA CAROTENOID CONCENTRATIONS; LIFE-STYLE FACTORS; TISSUE CONCENTRATIONS; ALPHA-TOCOPHEROL; DIETARY; QUESTIONNAIRE; DEGENERATION; VARIABILITY; VEGETABLES AB The determinants of blood levels of carotenoids were previously investigated in small or select samples. The relations of serum lutein + zeaxanthin to possible diet, lifestyle, and physiological determinants in 7059 participants of the Third National Health and Nutrition Examination Survey (1988-1994), greater than or equal to 40 y old, were examined. In a fully adjusted, multiple linear regression model, lower serum lutein + zeaxanthin was significantly associated with smoking, heavy drinking, being white, female, or not being physically active, having lower dietary lutein + zeaxanthin, higher fat-free mass, a higher percentage of fat mass, a higher waist-hip ratio, lower serum cholesterol, a higher white blood cell count, and high levels of C-reactive protein (P < 0.05). The model explained 24% of the variation present in serum lutein + zeaxanthin for the current sample. The correlation between dietary and serum lutein + zeaxanthin was 0.17 and increased to 0.18 after adjusting for the effects of given covariates. Each 10% increase in dietary lutein + zeaxanthin was associated with a 1% increase in serum conditional on other terms in the model. Many factors that influence the level of serum lutein + zeaxanthin remain unknown. C1 Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Nutrit Sci, Madison, WI USA. Univ Tennessee, Hlth Sci Ctr, Dept Ophthalmol, Memphis, TN USA. Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. RP Gruber, M (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. EM mgruber@facstaff.wisc.edu FU NEI NIH HHS [EY 11722, EY 13018] NR 39 TC 39 Z9 43 U1 0 U2 5 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2004 VL 134 IS 9 BP 2387 EP 2394 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 852KE UT WOS:000223753400035 PM 15333733 ER PT J AU Hursting, SD Lavigne, JA Berrigan, D Donehower, LA Davis, BJ Phang, JM Barrett, JC Perkins, SN AF Hursting, SD Lavigne, JA Berrigan, D Donehower, LA Davis, BJ Phang, JM Barrett, JC Perkins, SN TI Diet-gene interactions in p53-deficient mice: Insulin-like growth factor-1 as a mechanistic target SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutrition and Gene Regulation CY 2003 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch DE nutrition; chemoprevention; transgenics; calorie restriction; insulin-like growth factor-1; leptin ID BREAST-CANCER RISK; CALORIE RESTRICTION; LIFE-SPAN; SPONTANEOUS TUMORIGENESIS; BINDING PROTEIN-3; TRANSGENIC MICE; PLASMA-LEVELS; CELL-PROLIFERATION; APC(MIN) MICE; US ADULTS AB Progress in cancer prevention research is being facilitated by the use of animal models displaying specific genetic susceptibilities for cancer, such as mice deficient in one (+/-) or both (-/-) alleles of the p53 tumor suppressor gene. Our lab, which focuses on nutrition (particularly energy balance/obesity) and molecular carcinogenesis, has shown in p53-/- mice that calorie restriction (CR) increases the latency of spontaneous tumor development (mostly lymphomas) similar to75%, decreases serum insulin-like growth factor (IGF)-1 and leptin levels, and induces apoptosis in immature (lymphoma-susceptible) thymocytes. In heterozygous p53-deficient (p53+/-) mice, CR and a one day/wk fast each significantly delay spontaneous tumor development (a mix of lymphomas, sarcomas, and epithelial tumors) and decreases serum IGF-1 and leptin levels, even when begun late in life. We are presently comparing and combining CR and exercise (treadmill and running wheel) to further elucidate the relationships between energy balance, p53, and tumorigenesis in these models. Furthermore, we have capitalized on the susceptibility of p53+/- mice to chronic, low-dose aromatic amine-induced bladder carcinogenesis to develop a model for evaluating bladder cancer prevention approaches. Using this model, we have established that IGF-1 mediates many of the anti-cancer effects of CR. We are currently conducting oligonucleotide microarray studies to further characterize diet-gene interactions underlying the anti-cancer effects of CR and to determine which of the CR-responsive genes are IGF-1 dependent. C1 NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Hursting, SD (reprint author), NCI, Canc Res Ctr, Bethesda, MD 20892 USA. EM hurstins@mail.nih.gov NR 61 TC 17 Z9 17 U1 1 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2004 VL 134 IS 9 BP 2482S EP 2486S PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 852KE UT WOS:000223753400047 PM 15333746 ER PT J AU Milner, JA AF Milner, JA TI Molecular targets for bioactive food components SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutrition and Gene Regulation CY 2003 CL Harvard Med Sch, Boston, MA HO Harvard Med Sch DE bioactive; nutrigenomics; nutrigenetics; proteomics; metabolomics ID METHYLENETETRAHYDROFOLATE-REDUCTASE GENE; CDNA MICROARRAY ANALYSIS; CANCER PREVENTION; BREAST-CANCER; SELENIUM SUPPLEMENTATION; MAMMARY CARCINOGENESIS; DIALLYL DISULFIDE; TEA POLYPHENOLS; DEFICIENT MICE; LUNG-CANCER AB Mounting evidence points to dietary habits as an important determinant of cancer risk and tumor behavior. Although the linkages with diet are intriguing, the literature is also laden with inconsistencies. The reasons for these inconsistencies are likely multi-factorial, but probably reflect variations in the ability of bioactive constituents to reach or affect critical molecular targets. Fluctuations in the foods consumed not only influence the intake of particular bioactive components, but may alter metabolism and potentially influence the sites of action of both essential and nonessential nutrients. Genetic polymorphisms are increasingly recognized as another factor that can alter the response to dietary components (nutritional transcriptomic effect) by influencing the absorption, metabolism, or sites of action. Likewise, variation in DNA methylation patterns and other epigenetic events that influence overall gene expression can be influenced by dietary intakes. Furthermore, variation in the ability of food components to increase or depress gene expression (nutrigenomic effect) may account for some of the observed inconsistencies in the response to dietary change. Because a host of food components are recognized to influence phosphorylation and other posttranslational events, it is also likely that these and other proteomic modifications account for at least part of the response and variation that is reported in the literature. Collectively, it is clear that bioactive food components can influence a number of key molecular events that are involved in health and disease resistance. As the era of molecular nutrition unfolds, a greater understanding of how these foods and components influence cancer will surely arise. Such information will be critical in the development of effective tailored strategies for reducing cancer burden. Just as important, however, is that as this information unfolds it is utilized within a responsible bioethical framework. C1 NCI, Div Canc Prevent, Nutrit Sci Res Grp, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Milner, JA (reprint author), NCI, Div Canc Prevent, Nutrit Sci Res Grp, Dept Hlth & Human Serv, Rockville, MD 20852 USA. EM milnerj@mail.nih.gov NR 67 TC 64 Z9 68 U1 1 U2 20 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2004 VL 134 IS 9 BP 2492S EP 2498S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 852KE UT WOS:000223753400049 PM 15333748 ER PT J AU Buchanan, D AF Buchanan, D TI Advocates of scientific method still miss the point SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Letter C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Buchanan, D (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD SEP-OCT PY 2004 VL 36 IS 5 BP 226 EP 227 DI 10.1016/S1499-4046(06)60384-9 PG 2 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 877WD UT WOS:000225604300005 ER PT J AU Debski, B Milner, JA AF Debski, B Milner, JA TI Dietary selenium supplementation prolongs pentobarbital induced hypnosis SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE selenium; hypnosis; cytochrome; pentobarbital; glutathione peroxidase ID PHENOBARBITAL INDUCTION; GABA(A) RECEPTORS; MALE-RAT; CYTOCHROME-P-450; DEFICIENCY; BINDING; LIVER; SYSTEM; CYP2B2 AB The present studies characterized the influence of dietary selenium (Na2SeO3) on the duration of pentobarbital (PB) induced hypnosis (sleep) in the rat. Rats were fed semipurified diets varying from 0.01 to 2.0 mg Se/kg for up to 4 weeks. Consumption of diets containing 1.0 and 2.0 mg Se/kg significantly prolonged PB induced hypnosis. Hepatic selenium, but not hepatic glutathione peroxidase activity, correlated with the length of PB induced hypnosis. The prolongation of hypnosis caused by diets containing 1.0 mg Se/kg was substantially reduced or eliminated by repeated exposure to PB. Although single exposure to increasing quantities of PB (60-100 mg/kg body weight) led to a progressive increase in sleep duration, the proportional increase caused by supplemental selenium (2.0 vs 0.1 mug Se/g) remained relatively constant (similar to25%). Increasing maturity was inversely related to the duration of PB induced hypnosis, regardless of dietary selenium provided. Consumption of the 2.0 mg Se/kg diet prolonged PB induced hypnosis to a greater degree in immature than in mature rats (P < 0.05). Consumption of the selenium enriched diet (2 mug Se/g) resulted in an increase in cytochrome 2B, but had no effect on cytochrome 1A compared to controls (0.1 mug Se/g). Pretreatment of rats with P-450 enzymes activators (i.e., PB, Aroclor 1254, or 3-methylcholanthrene) shortened the duration of PB induced sleep and masked the effects of dietary selenium. The current studies document that dietary selenium can influence the response to pentobarbital induced hypnosis and likely relates to changes in drug detoxification enzymes. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Illinois, Dept Food Sci, Urbana, IL 61801 USA. Agr Univ Warsaw, Fac Med Vet, Dept Physiol Sci, Warsaw, Poland. NCI, Nutrit Sci Res Grp, Div Canc Prevent, Rockville, MD 20854 USA. RP Milner, JA (reprint author), Univ Illinois, Dept Food Sci, Urbana, IL 61801 USA. NR 25 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD SEP PY 2004 VL 15 IS 9 BP 548 EP 553 DI 10.1016/j.nutbio.2004.04.002 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 856JP UT WOS:000224041800007 PM 15350987 ER PT J AU Kim, H Neubert, JK Rowan, JS Brahim, JS Iadarola, MJ Dionne, RA AF Kim, H Neubert, JK Rowan, JS Brahim, JS Iadarola, MJ Dionne, RA TI Comparison of experimental and acute clinical pain responses in humans as pain phenotypes SO JOURNAL OF PAIN LA English DT Article DE pain; phenotype; thermal testing; cold pressor; clinical inflammatory pain ID SEX-DIFFERENCES; POSTOPERATIVE PAIN; ETHNIC-DIFFERENCES; MENSTRUAL-CYCLE; SENSITIVITY; PREDICTION; NOCICEPTION; TOLERANCE; ANALGESIA; GENOTYPE AB This study evaluates the sensitivity of normal subjects (N = 617; 369 women, 248 men) to experimentally induced pain including thermal stimuli and the cold pressor test to delineate individual response patterns and pain phenotypes. A subset of subjects (n = 157; 99 women and 58 men) also underwent standardized oral surgery, and the responses to clinically induced acute inflammatory pain were evaluated. A wide range of pain responses was found in both the experimental and clinical situations. The latency for withdrawal in the cold pressor test exhibited a dichotomous distribution of short and long times. Women exhibited higher responses to cold (P < .001) and thermal stimuli (P < .05) than men. Ethnicity affected pain responses to thermal stimuli ranging from 43degreesC to 47degreesC (P < .05) and cold stimuli (P < .001). However, neither gender nor ethnicity affected pain responses to clinically induced acute inflammatory stimuli. Cross-modality comparisons of responses within experimental pain showed strong correlations (P < .01) but weaker relationships with clinical inflammatory pain. These data suggest that the background factors and characteristics of experimental pain responses differ from those of clinical pain; therefore, experimental pain ratings alone are not sufficient to predict responses to clinically induced acute pain. Perspective: The findings of the present study suggest that investigations of pain phenotypes should take into consideration the subjects' gender and ethnicity and the pain-inducing stimuli. The predictive value of experimental pain for clinically induced pain is weak and not reliable. (C) 2004 by the American Pain Society. C1 NIDCR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), NIDCR, Pain & Neurosensory Mechanisms Branch, NIH, 10 Ctr Dr,Room 1N-103, Bethesda, MD 20892 USA. EM rdionne@dir.nidcr.nih.gov NR 28 TC 42 Z9 43 U1 3 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD SEP PY 2004 VL 5 IS 7 BP 377 EP 384 DI 10.1016/j.jpain.2004.06.003 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 865BX UT WOS:000224678600003 PM 15501195 ER PT J AU Fuemmeler, BF AF Fuemmeler, BF TI Bridging disciplines: An introduction to the special issue on public health and pediatric psychology SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE public health; prevention; health promotion ID EMPIRICALLY SUPPORTED TREATMENTS; PHYSICAL-ACTIVITY; RISK BEHAVIOR; PRIMARY-CARE; VALE DICTUM; INTERVENTION; PROMOTION; CHILDREN; FRAMEWORK; SMOKING C1 NCI, Div Canc Control & Populat Sci, Hlth Promot Res Branch, Bethesda, MD 20892 USA. RP Fuemmeler, BF (reprint author), NCI, Div Canc Control & Populat Sci, Hlth Promot Res Branch, 6130 Execut Blvd,EPN 4080,MSC 7335, Bethesda, MD 20892 USA. EM fuemmelb@mail.nih.gov NR 72 TC 8 Z9 8 U1 4 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD SEP PY 2004 VL 29 IS 6 BP 405 EP 414 DI 10.1093/jpepsy/jsho45 PG 10 WC Psychology, Developmental SC Psychology GA 844FT UT WOS:000223143900001 PM 15277584 ER PT J AU Wiecha, JL El Ayadi, AM Fuemmeler, BF Carter, JE Handler, S Johnson, S Strunk, N Korzec-Ramirez, D Gortmaker, SL AF Wiecha, JL El Ayadi, AM Fuemmeler, BF Carter, JE Handler, S Johnson, S Strunk, N Korzec-Ramirez, D Gortmaker, SL TI Diffusion of an integrated health education program in an urban school system: Planet health SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE school-based health promotion; obesity prevention; diffusion; dissemination; community-based participatory research ID ADOLESCENT TRIAL; PREVENTION; INTERVENTION; CHILDREN; OBESITY; CATCH; IMPLEMENTATION; INNOVATIONS; OVERWEIGHT; PREVALENCE AB Objective Assessed the feasibility, acceptability, and sustainability of Planet Health, an interdisciplinary, integrated health education curriculum implemented in six public middle schools. Methods Workshops on Planet Health implementation were attended by 129 teachers (language arts, math, science, and social studies) over three school years (1999-2000, 2000-2001, and 2001-2002). Questionnaires were administered post-implementation and in the fall and spring of each year. Outcomes were dose, acceptability, feasibility, and intent to continue use. Results The average number of lessons taught per teacher per year was 1.7 to 3.1, compared to a goal of 2 to 3. Each year, teachers reported high acceptability and perceived feasibility of the intervention, and the majority indicated they intended to continue using the curriculum. Conclusions Planet Health was feasible and acceptable in a participatory research model involving a public school-university partnership, and it was also sustainable independent of the research effort. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA. Boston Publ Sch Syst, Boston, MA USA. RP Wiecha, JL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,7th Floor, Boston, MA 02115 USA. EM jwiecha@hsph.harvard.edu FU ODCDC CDC HHS [U48/CCU115807] NR 31 TC 31 Z9 32 U1 0 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD SEP PY 2004 VL 29 IS 6 BP 467 EP 474 DI 10.1093/jpepsy/jsho50 PG 8 WC Psychology, Developmental SC Psychology GA 844FT UT WOS:000223143900006 PM 15277589 ER PT J AU Taylor, HA Wilfond, BS AF Taylor, HA Wilfond, BS TI Ethical issues in newborn screening research: Lessons from the Wisconsin cystic fibrosis trial SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID INFORMED-CONSENT; GENOMIC MEDICINE; DIAGNOSIS; CHILDHOOD; PROGRAM; POLICY; FORMS C1 Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Phoebe R Berman Bioeth Inst, Baltimore, MD 21218 USA. NHGRI, Social & Behav Res Branch, NIH, Baltimore, MD USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Baltimore, MD USA. RP Wilfond, BS (reprint author), NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM Wilfond@nih.gov NR 35 TC 15 Z9 15 U1 3 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2004 VL 145 IS 3 BP 292 EP 296 DI 10.1016/j.jpeds.2004.04.010 PG 5 WC Pediatrics SC Pediatrics GA 853VQ UT WOS:000223857400007 PM 15343177 ER PT J AU Wu, Z Ericksen, B Tucker, K Lubkowski, J Lu, W AF Wu, Z Ericksen, B Tucker, K Lubkowski, J Lu, W TI Synthesis and characterization of human alpha-defensins 4-6 SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE antimicrobial peptide/protein; defensin; HD5; HD6; HNP4; solid-phase peptide synthesis ID ANTIMICROBIAL PEPTIDES; NEUTROPHIL DEFENSINS; CHEMICAL SYNTHESIS; DENDRITIC CELLS; BETA-DEFENSINS; PANETH CELLS; ALPHA-DEFENSIN-1; PURIFICATION; PROTEINS; IMMUNITY AB Human alpha-defensins are small, Cys-rich, cationic proteins expressed predominantly in neutrophils and intestinal epithelia. They play important roles in innate and adaptive immunity against infection. Progress in studying these molecules can be accelerated by access to large quantities of high-quality materials, which have been obtained mainly from natural sources. Here, we report total synthesis of human alpha-defensins 4, 5, and 6, also known as HNP4, HD5, and HD6, using the optimized N,N-diisopropylethylamine (DIEA) in situ neutralization/2-(1 H-benzotriazolyl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HBTU) activation protocol for solid-phase Boc chemistry. Oxidative folding/disulfide formation was achieved directly using crude peptides, resulting in an overall synthetic yield of 10-16% with high purity. Antimicrobial activity assays were performed with Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, using colony-counting methods, and the results demonstrated differential activity against these strains. Our report describes a highly efficient synthetic approach that enables thorough structural and functional studies of these three important immunologic molecules. C1 Univ Maryland, Maryland Biotechnol Inst, Inst Human Virol, Baltimore, MD 21201 USA. NCI, Opportunist Infect Lab, Frederick, MD 21702 USA. NCI, Macromol Assembly Struct & Cell Signaling Sect, Frederick, MD 21702 USA. RP Lu, W (reprint author), Univ Maryland, Maryland Biotechnol Inst, Inst Human Virol, 725 W Lombard St, Baltimore, MD 21201 USA. EM luw@umbi.umd.edu RI Lu, Wuyuan/B-2268-2010; Ericksen, Bryan/F-9047-2012 FU NCI NIH HHS [N01-CO-1240]; NIAID NIH HHS [AI056264] NR 30 TC 69 Z9 70 U1 0 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD SEP PY 2004 VL 64 IS 3 BP 118 EP 125 DI 10.1111/j.1399-3011.2004.00179.x PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 845YG UT WOS:000223280800005 PM 15317502 ER PT J AU DeLozier, TC Tsao, CC Coulter, SJ Foley, J Bradbury, JA Zeldin, DC Goldstein, JA AF DeLozier, TC Tsao, CC Coulter, SJ Foley, J Bradbury, JA Zeldin, DC Goldstein, JA TI CYP2C44, a new murine CYP2C that metabolizes arachidonic acid to unique stereospecific products SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID EXTRAHEPATIC TISSUES; IMMUNOHISTOCHEMICAL LOCALIZATION; ENZYMATIC CHARACTERIZATION; MOLECULAR-CLONING; CYTOCHROME P450S; ESCHERICHIA-COLI; RAT-KIDNEY; EXPRESSION; EPOXYGENASE; IDENTIFICATION AB The human CYP2Cs have been studied extensively with respect to the metabolism of clinically important drugs and endogenous chemicals such as arachidonic acid ( AA). Five members of the mouse CYP2C family have previously been described that metabolize arachidonic acid into regio- and stereospecific epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids, which have many important physiological roles. Herein, we describe the cloning and characterization of a new mouse cytochrome P450 ( P450), CYP2C44, which has the lowest homology with other known mouse CYP2Cs. Western blotting and real-time polymerase chain reaction detected CYP2C44 mRNA and protein in liver >> kidney > adrenals. Kidney contained approximately 10% of the CYP2C44 mRNA content of liver. CYP2C44 metabolized AA to unique stereospecific products, 11R, 12S-EET and 8R, 9S-EET, which are similar to those produced by rat CYP2C23. CY2C23 is highly expressed in rat kidney and has been suggested to be important in producing compensatory renal artery vasodilation in response to salt-loading in this species. Immunohistochemistry showed the presence of CYP2C44 in hepatocytes, biliary cells of the liver, and the proximal tubules of the kidney. Unlike mouse CYP2C29, CYP2C38, and CYP2C39, CYP2C44 did not metabolize the common CYP2C substrate tolbutamide. CYP2C44 was not induced by phenobarbital or pregnenolone-16alpha-carbonitrile, two prototypical inducers of hepatic P450s. The presence of CYP2C44 in mouse liver, kidney, and adrenals and the unique stereospecificity of its arachidonic acid metabolites are consistent with the possibility that it may have unique physiological roles within these tissues, such as modulation of electrolyte transport or vascular tone. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Goldstein, JA (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,111 TW Alexander Dr,Bldg 101, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012; OI Coulter, Sherry/0000-0002-2732-3470 NR 47 TC 49 Z9 52 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2004 VL 310 IS 3 BP 845 EP 854 DI 10.1124/jpet.104.067819 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848BU UT WOS:000223442900001 PM 15084647 ER PT J AU Simmonds, AC Ghanayem, BI Sharma, A Reilly, CA Millen, B Yost, GS Forkert, PG AF Simmonds, AC Ghanayem, BI Sharma, A Reilly, CA Millen, B Yost, GS Forkert, PG TI Bioactivation of 1,1-dichloroethylene by CYP2E1 and CYP2F2 in murine lung SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GLUTATHIONE CONJUGATE; CYTOCHROME P4502E1; LIVER-MICROSOMES; REACTIVE EPOXIDE; PARA-NITROPHENOL; TOXICITY; BINDING; MICE; RAT; 2E1 AB 1,1-Dichloroethylene (DCE) exposure evokes lung toxicity with selective damage to bronchiolar Clara cells. Recent in vitro studies have implicated CYP2E1 and CYP2F2 in the bioactivation of DCE to 2-S-glutathionyl acetate [ C], a putative conjugate of DCE epoxide with glutathione. An objective of this study was to test the hypothesis that bioactivation of DCE is catalyzed by both CYP2E1 and CYP2F2 in murine lung. Western blot analysis of lung microsomal proteins from DCE-treated CD-1 mice showed time-dependent loss of immunodetectable CYP2F2 and CYP2E1 protein. Dose-dependent formation of conjugate [ C] was observed in the lungs of CD-1 mice treated with DCE ( 75 - 225 mg/kg), but it was not detected after pretreatment with 5-phenyl-1-pentyne (5-PIP). Treatment of mice with 5-PIP and also with diallyl sulfone (DASO(2)) significantly inhibited hydroxylation of p-nitrophenol (PNP) and chlorzoxazone (CHZX). Incubation of recombinant CYP2F3 ( a surrogate for CYP2F2) and recombinant CYP2E1 with PNP and CHZX confirmed that they are substrates for both of the recombinant enzymes. Incubation of the recombinant enzymes with DASO(2) or 5-PIP significantly inhibited hydroxylation of both PNP and CHZX. Bronchiolar injury was elicited in CD-1 mice treated with DCE ( 75 mg/kg), but it was abrogated with 5-PIP pretreatment. Bronchiolar toxicity also was manifested in the lungs of CYP2E1-null and wild-type mice treated with DCE ( 75 mg/kg), but protection ensued after pretreatment with 5-PIP or DASO(2). These results showed that bioactivation of DCE in murine lung occurred via the catalytic activities of both CYP2E1 and CYP2F2 and that bioactivation by these enzymes mediated the lung toxicity. C1 Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. RP Forkert, PG (reprint author), Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada. EM forkertp@post.queensu.ca FU NHLBI NIH HHS [R01 HL013645, R01 HL060143] NR 39 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2004 VL 310 IS 3 BP 855 EP 864 DI 10.1124/jpet.104.068171 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848BU UT WOS:000223442900002 PM 15123768 ER PT J AU Matsumoto, K Krishna, MC Mitchell, JB AF Matsumoto, K Krishna, MC Mitchell, JB TI Novel pharmacokinetic measurement using electron paramagnetic resonance spectroscopy and simulation of in vivo decay of various nitroxyl spin probes in mouse blood SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RADICAL REACTIONS; ESR SPECTROSCOPY; REDOX STATUS; OXYGEN; MICE; SUPEROXIDE; REDUCTION; TEMPOL; HYDROXYLAMINES; METABOLISM AB A novel approach to measure the time course of paramagnetic spin probe concentration in the circulating blood of a living mouse using X-band (9.4 GHz) electron paramagnetic resonance spectrometer is described. Using this technique, the pharmacokinetics of several nitroxyl spin probes was examined. The decay profiles were also independently simulated using pharmacokinetic properties as well as redox-mediated factors responsible in converting the nitroxyl radicals to the corresponding hydroxylamines. Finally, suitability of nitroxyl radicals as the probes of in vivo redox status and for radioprotection was described. The studies indicate that the six-member piperidine nitroxyls are suitable for estimating redox status in the circulation, whereas the five-member pyrrolidine nitroxyl radicals are suited for tissue redox status determination. For selective protection against radiation of normal tissues rather than cancer/tumor, efficient reoxidation of the hydroxylamine in normal tissue is preferable. Simulation results showed that for carbamoyl-PROXYL, only administration of the radical form might give radioprotection and not the hydroxylamine. However, the hydroxylamine form of TEMPOL, i.e., TEMPOL-H, may give similar radioprotection as the radical form due to efficient reoxidation in vivo. C1 NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Rm B3B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 31 TC 32 Z9 33 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2004 VL 310 IS 3 BP 1076 EP 1083 DI 10.1124/jpet.104.066647 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848BU UT WOS:000223442900027 PM 15105413 ER PT J AU Oz, M Zhang, L Ravindran, A Morales, M Lupica, CR AF Oz, M Zhang, L Ravindran, A Morales, M Lupica, CR TI Differential effects of endogenous and synthetic cannabinoids on (alpha 7)-nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID 5-HT3 RECEPTOR; NONCOMPETITIVE INHIBITION; METABOTROPIC GLUTAMATE; SYNAPTIC TRANSMISSION; ARACHIDONIC-ACID; LAEVIS OOCYTES; ANANDAMIDE; CHANNELS; CA2+; 2-ARACHIDONOYLGLYCEROL AB The effects of endogenous and synthetic cannabinoid receptor agonists, including 2-arachidonoylglycerol (2-AG), R-methanandamide, WIN55,212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)1-( 1-naphthalenylcarbonyl)-6H-pyrrolo[3,2,1ij] quinolin-6-one], and CP 55,940 [1alpha, 2beta-(R)-5alpha]-(-)-5-(1,1-dimethyl)-2-[5-hydroxy- 2-(3-hydroxypropyl) cyclohexyl- phenol], and the psychoactive constituent of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), on the function of homomeric alpha(7)-nicotinic acetylcholine (nACh) receptors expressed in Xenopus oocytes was investigated using the two-electrode voltage-clamp technique. The endogenous cannabinoid receptor ligands 2-AG and the metabolically stable analog of anandamide ( arachidonylethanolamide), R-methanandamide, reversibly inhibited currents evoked with ACh ( 100 muM) in a concentration-dependent manner (IC50 values of 168 and 183 nM, respectively). In contrast, the synthetic cannabinoid receptor agonists CP 55,940, WIN55,212-2, and the phytochemical Delta(9)-THC did not alter alpha(7)-nACh receptor function. The inhibition of alpha(7)-mediated currents by 2-AG was found to be noncompetitive and voltage-independent. Additional experiments using endocannabinoid metabolites suggested that arachidonic acid, but not ethanolamine or glycerol, could also inhibit the alpha(7)-nACh receptor function. Whereas the effects of arachidonic acid were also noncompetitive and voltage-independent, its potency was much lower than 2-AG and anandamide. Results of studies with chimeric alpha(7)-nACh-5-hydroxytryptamine (5-HT)(3) receptors comprised of the amino-terminal domain of the alpha(7)-nACh receptor and the transmembrane and carboxyl-terminal domains of 5-HT3 receptors indicated that the site of interaction of the endocannabinoids with the alpha(7)-nAChR was not located on the N-terminal region of the receptor. These data indicate that cannabinoid receptor ligands that are produced in situ potently inhibit alpha(7)-nACh receptor function, whereas the synthetic cannabinoid ligands, and Delta(9)-THC, are without effect, or are relatively ineffective at inhibiting these receptors. C1 NIDA, Intramural Res Program, Cellular Neurobiol Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIDA, Behav Neurobiol Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIAAA, NIH, Dept Hlth & Human Serv, Mol & Cellular Biol Lab, Bethesda, MD USA. RP Oz, M (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Branch, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 53 TC 39 Z9 41 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2004 VL 310 IS 3 BP 1152 EP 1160 DI 10.1124/jpet.104.067751 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848BU UT WOS:000223442900035 PM 15102930 ER PT J AU Mantey, SA Coy, DH Entsuah, LK Jensen, RT AF Mantey, SA Coy, DH Entsuah, LK Jensen, RT TI Development of bombesin analogs with conformationally restricted amino acid substitutions with enhanced selectivity for the orphan receptor human bombesin receptor subtype 3 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GASTRIN-RELEASING-PEPTIDE; NEUROMEDIN-B RECEPTOR; LUNG-CANCER CELLS; HIGH-AFFINITY; MOLECULAR-CLONING; GUINEA-PIG; MESSENGER-RNA; BRS-3; EXPRESSION; RAT AB The human bombesin receptor subtype 3 (hBRS-3) orphan receptor, which has a high homology to bombesin (Bn) receptors [gastrin-releasing peptide (GRP) and neuromedin B (NMB) receptors], is widely distributed in the rat central nervous system. Its natural ligand or role in physiology is unknown due to lack of selective ligands. Its target disruption leads to obesity, diabetes, and hypertension. A synthetic high-affinity agonist, [D-Tyr(6),beta-Ala(11), Phe(13), Nle(14)] Bn(6-14), has been described, but it is nonselective for hBRS-3 over other Bn receptors; however, substitution of (R)- or (S)-amino-3-phenylpropionic acid (Apa) for beta-Ala(11) resulted in a modestly selective ligand. In the present study, we have attempted to develop a more selective hBRS-3 ligand by using two strategies: substitutions on phenyl ring of Apa(11) and the substitution of other conformationally restricted amino acids into position 11 of [D-Tyr(6),beta-Ala(11), Phe(13), Nle(14)] Bn(6-14). Fifteen analogs were synthesized and affinities were determined for hBRS-3 and Bn receptors (hGRP-R and hNMB-R). Selective analogs were tested for their ability to activate each receptor by stimulating phospholipase C. One analog, [D-Tyr(6), Apa-4Cl, Phe(13), Nle(14)] Bn(6-14), retained high affinity for the hBRS-3 (K-i = 8 nM) and had enhanced selectivity (> 230-fold) for hBRS-3 over hGRP-R or hNMB-R. This analog specifically interacted with hBRS- 3, fully activated hBRS- 3 receptors, and was a potent agonist at the hBRS- 3 receptor. This enhanced selectivity should allow this analog to be useful for investigating the possible role of hBRS- 3 in physiological or pathological processes. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Tulane Univ, Dept Med, Peptide Res Labs, Hlth Sci Ctr, New Orleans, LA 70118 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 48 TC 30 Z9 31 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2004 VL 310 IS 3 BP 1161 EP 1170 DI 10.1124/jpet.104.066761 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848BU UT WOS:000223442900036 PM 15102928 ER PT J AU Newman, DJ AF Newman, D. J. TI Mother nature's pharmacopoeia; the search for pharmacophores SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Meeting Abstract C1 [Newman, D. J.] NCI, Nat Prod Branch, Dev Therapeut Program, DCTD, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD SEP PY 2004 VL 56 SU S MA 243 BP S90 EP S90 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V50KV UT WOS:000203408100243 ER PT J AU Geer, LY Markey, SP Kowalak, JA Wagner, L Xu, M Maynard, DM Yang, XY Shi, WY Bryant, SH AF Geer, LY Markey, SP Kowalak, JA Wagner, L Xu, M Maynard, DM Yang, XY Shi, WY Bryant, SH TI Open mass spectrometry search algorithm SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE protein identification; algorithm; bioinformatics; mass spectrometry; proteomics; significance testing ID PROTEIN IDENTIFICATION; SEQUENCE DATABASES; SPECTRAL DATA; PEPTIDES; MODEL; VALIDATION; BLAST AB Large numbers of MS/MS peptide spectra generated in proteomics experiments require efficient, sensitive and specific algorithms for peptide identification. In the Open Mass Spectrometry Search Algorithm (OMSSA), specificity is calculated by a classic probability score using an explicit model for matching experimental spectra to sequences. At default thresholds, OMSSA matches more spectra from a standard protein cocktail than a comparable algorithm. OMSSA is designed to be faster than published algorithms in searching large MS/MS datasets. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. RP Geer, LY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM lewisg@mail.nih.gov RI Geer, Lewis/H-2714-2014 NR 28 TC 839 Z9 858 U1 4 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP-OCT PY 2004 VL 3 IS 5 BP 958 EP 964 DI 10.1021/pr0499491 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 865HR UT WOS:000224693800005 PM 15473683 ER PT J AU Yang, XY Dondeti, V Dezube, R Maynard, DM Geer, LY Epstein, J Chen, XF Markey, SP Kowalak, JA AF Yang, XY Dondeti, V Dezube, R Maynard, DM Geer, LY Epstein, J Chen, XF Markey, SP Kowalak, JA TI DBParser: Web-based software for shotgun proteomic data analyses SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomics; data analysis; peptides; mass spectrometry; software; bioinformatics ID TANDEM MASS-SPECTROMETRY; PROTEIN IDENTIFICATIONS; STATISTICAL-MODEL; PEPTIDE; VALIDATION; SEQUENCES; SEARCH; TOOLS AB We describe a web-based program called 'DBParser' for rapidly culling, merging, and comparing sequence search engine results from multiple LC-MS/MS peptide analyses. DBParser employs the principle of parsimony to consolidate redundant protein assignments and derive the most concise set of proteins consistent with all of the assigned peptide sequences observed in an experiment or series of experiments. The resulting reports summarize peptide and protein identifications from multidimensional experiments that may contain a single data set or combine data from a group of data sets, all related to a single analytical sample. Additionally, the results of multiple experiments, each of which may contain several data sets, can be compared in reports that identify features that are common or different. DBParser actively links to the primary mass spectral data and to public online databases such as NCBI, GO, and Swiss-Prot in order to structure contextually specific reports for biologists and biochemists. C1 NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Biol Computat, NIH, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Kowalak, JA (reprint author), NIMH, Lab Neurotoxicol, NIH, 10 Ctr Dr,Room 3D42, Bethesda, MD 20892 USA. EM jeffrey.kowalak@nih.gov RI Geer, Lewis/H-2714-2014 NR 17 TC 68 Z9 71 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP-OCT PY 2004 VL 3 IS 5 BP 1002 EP 1008 DI 10.1021/pr049920x PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 865HR UT WOS:000224693800011 PM 15473689 ER PT J AU Grillon, C AF Grillon, C TI Fear-potentiated startle: A translational tool for research on anxiety SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 25-28, 2004 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. EM Christian.Grillon@ninh.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2004 VL 18 IS 3 SU S BP A9 EP A9 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 863HC UT WOS:000224550800036 ER PT J AU Law, AJ Lipska, B Weickert, SC Hyde, TM Hashimoto, R Weinberger, DR Harrison, PJ Kleinman, JE AF Law, AJ Lipska, B Weickert, SC Hyde, TM Hashimoto, R Weinberger, DR Harrison, PJ Kleinman, JE TI Splice variant-specific alterations of neuregulin-1 gene expression in the hippocampus in schizophrenia identified using real-time quantitative RT-PCR. SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 25-28, 2004 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Univ Oxford, Dept Psychiat, Oxford, England. NIH, Clin Brain Disorders Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2004 VL 18 IS 3 SU S BP A72 EP A72 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 863HC UT WOS:000224550800283 ER PT J AU Law, AJ Lipska, B Weickert, SC Hyde, TM Hashimoto, R Weinberger, DR Harrison, PJ Kleinman, JE AF Law, AJ Lipska, B Weickert, SC Hyde, TM Hashimoto, R Weinberger, DR Harrison, PJ Kleinman, JE TI Splice variant-specific alterations of Neuregulin-1 gene expression in the hippocampus in schizophrenia identified using real-time quantitative RT-PCR. SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Summer Meeting of the British-Association-for-Psychopharmacology CY JUL 25-28, 2004 CL Harrogate, ENGLAND SP British Assoc Psychopharmacol C1 Univ Oxford, Dept Psychiat, Oxford, England. NIH, Clin Brain Disorders Branch, Bethesda, MD USA. RI Law, Amanda/G-6372-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD SEP PY 2004 VL 18 IS 3 SU S BP A67 EP A67 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 863HC UT WOS:000224550800264 ER PT J AU Woodside, DB Bulik, CM Thornton, L Klump, KL Tozzi, F Fichter, MM Halmi, KA Kaplan, AS Strober, M Devlin, B Bacanu, SA Ganjei, K Crow, S Mitchell, J Rotondo, A Mauri, M Cassano, G Keel, P Berrettini, WH Kaye, WH AF Woodside, DB Bulik, CM Thornton, L Klump, KL Tozzi, F Fichter, MM Halmi, KA Kaplan, AS Strober, M Devlin, B Bacanu, SA Ganjei, K Crow, S Mitchell, J Rotondo, A Mauri, M Cassano, G Keel, P Berrettini, WH Kaye, WH TI Personality in men with eating disorders SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE eating disorders; men; personality ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; MALES; TEMPERAMENT; CHARACTER; ROCHESTER; FEMALES; SCALE AB Objective: This study compares personality variables of men with eating disorders to women with eating disorders. Method: Data were obtained from an international study of the genetics of eating disorders. Forty-two mate participants were age-band matched at 1:2 ratio to females from the same study. Personality features were compared between males and females controlling for diagnostic subgroup. Results: Males with eating disorders appear to be slightly less at risk for perfectionism, harm avoidance, reward dependence, and cooperativeness than females. Few differences were found when diagnostic Subgroup was considered. Conclusion: Observed differences in personality variables may help explain the difference in incidence and prevalence of eating disorders in men and women. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Toronto, Toronto Gen Hosp, Hlth Network, Program Eating Disorders, Toronto, ON M5G 2C4, Canada. Univ Toronto, Toronto Gen Hosp, Hlth Network, Dept Psychiat, Toronto, ON M5G 2C4, Canada. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23298 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Univ Roma Tor Vergata, Rome, Italy. Univ Munich, Roseneck Hosp Behav Med, Prien Am Chiemsee, Germany. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, White Plains, NY 10605 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD 20877 USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. Neuropsychiat Res Inst, Fargo, ND USA. Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. RP Woodside, DB (reprint author), Toronto Gen Hosp, Inpatient Eating Disorders Program, 8EN-219,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM b.woodside@utoronto.ca; kayewh@nisx.upmc.edu OI Tozzi, Federica/0000-0002-3536-2920 NR 22 TC 18 Z9 19 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD SEP PY 2004 VL 57 IS 3 BP 273 EP 278 DI 10.1016/j.jpsychores.2004.02.011 PG 6 WC Psychiatry SC Psychiatry GA 875SW UT WOS:000225443000011 PM 15507254 ER PT J AU Graham, JA Horowitz, AM Canto, MT AF Graham, JA Horowitz, AM Canto, MT TI Coverage and quality of oral cancer information in selected popular press: May 1998 to July 2003 SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT Montgomery College Student Research Symposium CY OCT 04, 2003 CL Rockville, MD DE oral cancer; popular press; prevention; public knowledge ID BREAST-CANCER; MEDIA COVERAGE; ADULTS; PREVENTION; KNOWLEDGE; ASSOCIATION; MAGAZINES; WOMEN; OLDER; RISK AB Objectives: A 1998 study demonstrated a lack of coverage about oral cancer in the popular press between April 1987 and April 1997. Since that study, several oral cancer-related activities took place, many of which could have increased the media's attention to oral cancer. Therefore, this study analyzed coverage and quality of oral cancer information in selected popular press between May 1998 and July 2003. Methods: Articles from magazines and newspapers were retrieved from three databases and were analyzed by specific topics and subtopics for adequacy of content and accuracy of information. Articles were categorized as either 'primarily oral cancer-related" or 'primarily tobacco-related." Results: Sixty articles were identified, 39 of which were included in the analysis (14 magazines; 25 newspapers). Seventeen articles were `primarily oral cancer-related, "and 22 were 'primarily tobacco-related. "Seventy-two percent of the articles mentioned at least one risk factor for oral cancer, the most common being tobacco use (69%). Far fewer articles noted alcohol (10%) or the combined use of tobacco and alcohol (5%) as risk factors. Only 8 percent of the articles recommended an oral cancer examination. Conclusion: Despite local and limited national efforts and activities aimed at increasing public awareness of oral cancer, the popular press coverage of those activities was minimal or nonexistent. C1 Natl Inst Dent & Craniofacial Res, Div Populat & Hlth Promot Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Horowitz, AM (reprint author), 45 Ctr Dr,Room 4AS-37A, Bethesda, MD 20892 USA. EM Alice.Horowitz@nih.gov NR 24 TC 2 Z9 2 U1 0 U2 1 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 2004 VL 64 IS 4 BP 231 EP 236 PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 867CI UT WOS:000224819300007 PM 15562946 ER PT J AU Douglas, G Reilly, C Dooley, MA Page, G Cooper, G Gilkeson, G AF Douglas, G Reilly, C Dooley, MA Page, G Cooper, G Gilkeson, G TI Angiotensin-converting enzyme (insertion/deletion) and endothelial nitric oxide synthase polymorphisms in patients with systemic lupus erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; nitric oxide; genetics; predisposition; angiotensin-converting enzyme; African American; polymorphism ID CORONARY-ARTERY-DISEASE; GENE POLYMORPHISM; DELETION POLYMORPHISM; DIABETIC-NEPHROPATHY; ESSENTIAL-HYPERTENSION; MYOCARDIAL-INFARCTION; 5'-FLANKING REGION; HEART-DISEASE; ACE GENE; ASSOCIATION AB Objective. Genetic polymorphisms in the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) are linked with expression and/or progression of renal disease. We hypothesized that polymorphisms in the genes coding for ACE and eNOS may influence the development and/or progression of systemic lupus erythematosus (SLE) and lupus nephritis given their linkage with other renal diseases. Methods. DNA from patients with SLE (n = 227) and their age and sex matched controls (n = 275) from the Carolina Lupus (CLU) Study cohort was assessed for ACE and eNOS polymorphisms. Seventy patients had biopsy-proven lupus nephritis. Two different eNOS polymorphisms (eNOS promoter T-786-->C nucleotide substitution and eNOS 27 base pair tandem repeat in intron 4) and the ACE insertion/deletion (I/D) polymorphism in intron 16 were examined by restriction fragment length polymorphism-polymerase chain reaction. Results. Allele frequency of the eNOS polymorphisms varied significantly between SLE patients and controls. There was no association of these polymorphisms with lupus within ethnic groups. We found no association of the polymorphism with the development of renal disease. No association was observed for the ACE I/D polymorphism with SLE or nephritis, or with ethnicity or sex. Conclusion. eNOS genetic polymorphisms differed significantly across ethnic groups. There was no significant increased risk of SLE and/or lupus nephritis associated with eNOS or ACE polymorphisms in either the African American or Caucasian groups compared to ethnically matched controls. These studies emphasize the need to control for ethnicity when investigating genetic polymorphisms and disease. C1 Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Edward Via Virginia Coll Osteopath Med, Dept Physiol, Blacksburg, VA USA. Univ N Carolina, Affiliated Hosp, Dept Med, Chapel Hill, NC USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Gilkeson, G (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. EM gilkeson@musc.edu FU NIAID NIH HHS [AI41764]; NIAMS NIH HHS [AR39162, AR45476] NR 43 TC 22 Z9 22 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 2004 VL 31 IS 9 BP 1756 EP 1762 PG 7 WC Rheumatology SC Rheumatology GA 852ZS UT WOS:000223796200016 PM 15338496 ER PT J AU Zheng, G Park, S AF Zheng, G Park, S TI A note on time savings in censored life testing SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE equivalence size; fisher information; life testing; maximum likelihood estimate; time saving; type I and type II censoring ID EXPONENTIATED EXPONENTIAL FAMILY; FISHER INFORMATION; WEIBULL-DISTRIBUTION; HAZARD RATE AB In life testing, Type I or Type II censored data are usually observed. An important feature of censored life testing is time saving. Several measures of time saving have appeared in the literature for Type II censored data. The purposes of this note are to review different measures of time saving and discuss their different roles in planning censored life testing, to generalize one measure of time saving to a general distribution, to extend some results to the multi-parameter case and Type I censoring case, respectively, and to show by an example how the method is used to demonstrate the time saving in planning censored life testing. (C) 2003 Elsevier B.V. All rights reserved. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Yonsei Univ, Dept Appl Stat, Seoul, South Korea. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Rockledge 2,Room 8223,6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 19 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD SEP 1 PY 2004 VL 124 IS 2 BP 289 EP 300 DI 10.1016/S0378-3758(03)00208-8 PG 12 WC Statistics & Probability SC Mathematics GA 837PM UT WOS:000222647700003 ER PT J AU Korn, EL Troendle, JF McShane, LM Simon, R AF Korn, EL Troendle, JF McShane, LM Simon, R TI Controlling the number of false discoveries: application to high-dimensional genomic data SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE false discovery; multiple comparisons; stepwise procedure; permutation method; gene expression; microarray ID MICROARRAY; EXPRESSION AB Researchers conducting gene expression microarray experiments often are interested in identifying genes that are differentially expressed between two groups of specimens. A straightforward approach to the identification of such "differentially expressed" genes is to perform a univariate analysis of group mean differences for each gene, and then identify those genes that are most statistically significant. However, with the large number of genes typically represented on a microarray, using nominal significance levels (unadjusted for the multiple comparisons) will lead to the identification of many genes that truly are not differentially expressed, "false discoveries." A reasonable strategy in many situations is to allow a small number of false discoveries, or a small proportion of the identified genes to be false discoveries. Although previous work has considered control for the expected proportion of false discoveries (commonly known as the false discovery rate), we show that these methods may be inadequate. We propose two stepwise permutation-based procedures to control with specified confidence the actual number of false discoveries and approximately the actual proportion of false discoveries. Limited simulation studies demonstrate substantial gain in sensitivity to detect truly differentially expressed genes even when allowing as few as one or two false discoveries. We apply these new methods to analyze a microarray data set consisting of measurements on approximately 9000 genes in paired tumor specimens, collected both before and after chemotherapy on 20 breast cancer patients. The methods described are broadly applicable to the problem of identifying which variables of any large set of measured variables differ between pre-specified groups. Published by Elsevier B.V. C1 NCI, Biometr Res Branch, EPN 8128, Bethesda, MD 20892 USA. NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN 8128, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov NR 12 TC 131 Z9 135 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD SEP 1 PY 2004 VL 124 IS 2 BP 379 EP 398 DI 10.1016/S0378-3758(03)00211-8 PG 20 WC Statistics & Probability SC Mathematics GA 837PM UT WOS:000222647700008 ER PT J AU Schotte, F Soman, J Olson, JS Wulff, M Anfinrud, PA AF Schotte, F Soman, J Olson, JS Wulff, M Anfinrud, PA TI Picosecond time-resolved X-ray crystallography: probing protein function in real time SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE myoglobin; protein dynamics; protein function; time-resolved X-ray crystallography; Laue; picosecond ID LIGAND-BINDING; CARBONMONOXY-MYOGLOBIN; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; HEME POCKET; PHOTODISSOCIATION; RECOMBINATION; NANOSECOND; MONOXIDE; COMPLEX AB A detailed mechanistic understanding of how a protein functions requires knowledge not only of its static structure, but also how its conformation evolves as it executes its function. The recent development of picosecond time-resolved X-ray crystallography has allowed us to visualize in real time and with atomic detail the conformational evolution of a protein. Here, we report the photolysis-induced structural evolution of wild-type and L29F myoglobin over times ranging from 100 ps to 3 mus. The sub-ns structural rearrangements that accompany ligand dissociation in wild-type and the mutant form differ dramatically, and lead to vastly different ligand migration dynamics. The correlated protein displacements provide a structural explanation for the kinetic differences. Our observation of functionally important protein motion on the sub-ns time scale was made possible by the 150-ps time resolution of the measurement, and demonstrates that picosecond dynamics are relevant to protein function. To visualize subtle structural changes without modeling, we developed a novel method for rendering time-resolved electron density that depicts motion as a color gradient across the atom or group of atoms that move. A sequence of these time-resolved images have been stitched together into a movie, which allows one to literally "watch" the protein as it executes its function. Published by Elsevier Inc. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Rice Univ, Dept Biochem & Cell Biol, WM Keck Ctr Computat Biol, Houston, TX 77251 USA. European Synchrotron Radiat Facil, Expt Div, F-38000 Grenoble, France. RP Anfinrud, PA (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM anfinrud@nih.gov OI Olson, John/0000-0002-0760-5403 FU NHLBI NIH HHS [HL47020]; NIGMS NIH HHS [GM35649] NR 44 TC 121 Z9 126 U1 1 U2 32 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 2004 VL 147 IS 3 BP 235 EP 246 DI 10.1016/j.jsb.2004.06.009 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 851DT UT WOS:000223666400004 PM 15450293 ER PT J AU Danino, D Moon, KH Hinshaw, JE AF Danino, D Moon, KH Hinshaw, JE TI Rapid constriction of lipid bilayers by the mechanochemical enzyme dynamin SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE dynamin; time-resolved cryo-EM; GTPase; endocytosis; self-assembly; membrane fission ID CLATHRIN-MEDIATED ENDOCYTOSIS; TRANSMISSION ELECTRON-MICROSCOPY; DEPENDENT CONFORMATIONAL-CHANGES; SYNAPTIC VESICLE ENDOCYTOSIS; PLECKSTRIN HOMOLOGY DOMAIN; PROLINE-RICH DOMAIN; GTPASE ACTIVITY; NERVE-TERMINALS; PINCHASE ACTION; COATED PITS AB Dynamin, a large GTPase, is located at the necks of clathrin-coated pits where it facilitates the release of coated vesicles from the plasma membrane upon GTP binding, and hydrolysis. Previously, we have shown by negative stain electron microscopy that wildtype dynamin and a dynamin mutant lacking the C-terminal proline-rich domain, DeltaPRD, form protein-lipid tubes that constrict and vesiculate upon addition of GTP. Here, we show by time-resolved cryo-electron microscopy (cryo-EM) that DeltaPRD dynamin in the presence of GTP rapidly constricts the underlying lipid bilayer, and then gradually disassembles from the lipid. In agreement with the negative stain results, the dynamin tubes constrict from 50 to 40 nm, and their helical pitch decreases from similar to13 to 9.4 nm. However, in contrast to the previous results, examination by cryo-EM shows that the lipid bilayer remains intact and small vesicles or fragments do not form upon GTP binding and hydrolysis. Therefore, the vesicle formation seen by negative stain may be due to the lack of mobility of the dynamin tubes on the grid during the GTP-induced conformational changes. Our results confirm that dynamin is a mechanochemical enzyme and suggest that during endocytosis dynamin is directly responsible for membrane constriction. In the cell, other proteins may enhance the activity of dynamin or the constraints induced by the surrounding coated pit and plasma membrane during constriction may cause the final membrane fission event. Published by Elsevier Inc. C1 NIH, Lab Cell Biochem & Biol, Rockville, MD 20852 USA. Technion Israel Inst Technol, Dept Food Engn & Biotechnol, IL-32000 Haifa, Israel. RP Hinshaw, JE (reprint author), NIH, Lab Cell Biochem & Biol, MSC 0851,8 Ctr Dr, Rockville, MD 20852 USA. EM jennyh@helix.nih.gov RI Danino, Dganit/D-6832-2016 OI Danino, Dganit/0000-0002-9782-4940 NR 52 TC 99 Z9 99 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 2004 VL 147 IS 3 BP 259 EP 267 DI 10.1016/j.jsb.2004.04.005 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 851DT UT WOS:000223666400006 PM 15450295 ER PT J AU Heymann, JB Conway, JF Steven, AC AF Heymann, JB Conway, JF Steven, AC TI Molecular dynamics of protein complexes from four-dimensional cryo-electron microscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE conformational change; molecular movie; molecular dynamics; image classification; single particle analysis; multiple particle analysis ID HERPES-SIMPLEX-VIRUS; ELECTRON-MICROSCOPY; BIOLOGICAL MACROMOLECULES; CAPSID MATURATION; DNA; IDENTIFICATION; CELL AB Cryo-electron microscopy of single particles offers a unique opportunity to detect and quantify conformational variation of protein complexes. Different conformers may, in principle, be distinguished by classification of individual projections in which image differences arising from viewing geometry are disentangled from variability in the underlying structures by "multiple particle analysis"-MPA. If the various conformers represent dynamically related states of the same complex, MPA has the potential to visualize transition states, and eventually to yield movies of the dynamic process. Ordering the various conformers into a time series is facilitated if cryo-EM data are taken at successive times from a system that is known to be developing in time. Virus maturation represents a relatively tractable dynamic process because the changes are large and irreversible and the rate of the natural process may be conveniently slowed in vitro by adjusting the environmental conditions. We describe the strategy employed in a recent analysis of herpes simplex virus procapsid maturation (Nat. Struct. Biol. 10 (2003) 334-341), compare it with previous work on the maturation of bacteriophage HK97 procapsid, and discuss various factors that impinge on the feasibility of performing similar experimental analyses of molecular dynamics in the general case. Published by Elsevier Inc. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Inst Biol Struct JP Ebel, F-38027 Grenoble, France. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov RI Heymann, Bernard/F-6825-2011; Conway, James/A-2296-2010; OI Conway, James/0000-0002-6581-4748; Heymann, Bernard/0000-0002-8872-5326 NR 30 TC 24 Z9 25 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 2004 VL 147 IS 3 BP 291 EP 301 DI 10.1016/j.jsb.2004.02.006 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 851DT UT WOS:000223666400009 PM 15450298 ER PT J AU Montgomery, JR White, TW Martin, BL Turner, ML Holland, SM AF Montgomery, JR White, TW Martin, BL Turner, ML Holland, SM TI A novel connexin 26 gene mutation associated with features of the keratitis-ichthyosis-deafness syndrome and the follicular occlusion triad SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID HEARING-LOSS; SKIN; DIFFERENTIATION; FAMILIES; DATABASE AB We report the case of a congenitally deaf white mate with mild palmoplantar keratoderma, ichthyosiform scaling, follicular hyperkeratosis, and mild keratitis, features consistent with keratitis-ichthyosis-deafness syndrome. His major problem was severe, disfiguring, inflammatory dissecting folliculitis of the scalp, hidradenitis suppurativa, and cystic acne, features comprising the follicular occlusion triad. This unusual phenotype is associated with a novel heterozygous point mutation (C119T) in the gap junction beta2 gene that substitutes a valine for alanine at codon 40 (A40V) in the connexin 26 protein. Through Xenopus oocyte expression studies, this mutant protein was shown to significantly disrupt the function of the specialized gap junctions connecting the cytoplasm of adjacent cells critical for tissue homeostasis. Mutations within the connexin 26 protein are associated with syndromes involving both sensorineural deafness and hyperkeratotic skin disorders. This is the first report of an association between a connexin 26 protein mutation, follicular hyperkeratosis of keratitis-ichthyosis-deafness syndrome, and severe follicular occlusion triad. C1 USN, Natl Naval Med Ctr, Bethesda, MD 20889 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Walter Reed Army Inst Res, Washington, DC USA. NIAID, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Montgomery, JR (reprint author), USN, Natl Naval Med Ctr, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM jrmontgomery@bethesda.med.navy.mil OI White, Thomas/0000-0002-3285-7434 NR 21 TC 42 Z9 43 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2004 VL 51 IS 3 BP 377 EP 382 DI 10.1016/j.jaad.2003.12.042 PG 6 WC Dermatology SC Dermatology GA 851RX UT WOS:000223704100009 PM 15337980 ER PT J AU Olsen, EA Hordinsky, MK Price, VH Roberts, JL Shapiro, J Canfield, D Duvic, M King, LE McMichael, AJ Randall, VA Turner, ML Sperling, L Whiting, DA Norris, D AF Olsen, EA Hordinsky, MK Price, VH Roberts, JL Shapiro, J Canfield, D Duvic, M King, LE McMichael, AJ Randall, VA Turner, ML Sperling, L Whiting, DA Norris, D TI Alopecia areata investigational assessment guidelines - Part II SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID TOPICAL MINOXIDIL; ANTHRALIN AB Alopecia areata is an immunologically mediated disease characterized by extreme variability not only in the time of initial onset of hair loss but in the duration, extent and pattern of hair loss during any given episode of active loss. These variables, as well as the unpredictable nature of spontaneous regrowth and lack of a uniform response to various therapies, has made clinical trials in alopecia areata difficult to plan and implement. In fact, there are currently no drugs FDA-approved specifically for the indication of alopecia areata. To help facilitate well-controlled clinical trials for alopecia areata, this National Alopecia Areata Foundation (NAAF) sponsored subgroup of investigators/clinicians experienced in clinical trials and/or in the clinical care of patients with alopecia areata has outlined some general principles and potential endpoints for clinical studies in alopecia areata. These guidelines build on the Alopecia Areata Investigational Assessment Guidelines published in 1999(1) which established baseline clinical staging and background information important to gather on any alopecia areata patient involved in clinical research. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. Univ Minnesota, Minneapolis, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Skin Care Ctr, Vancouver, BC, Canada. Canfield Sci, Fairfield, NJ USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Nashville, TN USA. Wake Forest Univ, Med Ctr, Winston Salem, NC 27109 USA. Univ Bradford, Bradford BD7 1DP, W Yorkshire, England. NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Baylor Hair Res & Treatment Ctr, Dallas, TX USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Olsen, EA (reprint author), Duke Univ, Med Ctr, Box 3294, Durham, NC 27710 USA. EM olsen001@mc.duke.edu NR 14 TC 146 Z9 158 U1 1 U2 11 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2004 VL 51 IS 3 BP 440 EP 447 DI 10.1016/j.jaad.2003.09.032 PG 8 WC Dermatology SC Dermatology GA 851RX UT WOS:000223704100019 PM 15337988 ER PT J AU Miclet, E Williams, DC Clore, GM Bryce, DL Boisbouvier, J Bax, A AF Miclet, E Williams, DC Clore, GM Bryce, DL Boisbouvier, J Bax, A TI Relaxation-optimized NMR spectroscopy of methylene groups in proteins and nucleic acids SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID E.COSY-TYPE MEASUREMENT; SELECTIVE COHERENCE TRANSFER; CROSS-CORRELATED RELAXATION; MOLECULAR-WEIGHT PROTEINS; PULSED-FIELD GRADIENTS; J-COUPLING-CONSTANTS; MULTIDIMENSIONAL NMR; POLARIZATION TRANSFER; IMPROVED SENSITIVITY; DIPOLAR COUPLINGS AB A large fraction of hydrogens in proteins and nucleic acids is of the methylene type. Their detailed study, however, in terms of structure and dynamics by NMR spectroscopy is hampered by their fast relaxation properties, which give rise to low sensitivity and resolution. It is demonstrated that six different relaxation interference processes, involving H-1-C-13 and H-1-H-1 dipolar interactions and H-1 and C-13 chemical shift anisotropy, can be used simultaneously to mitigate these problems effectively. The approach is applicable to the majority of NMR experiments commonly used to study side chain and backbone conformation. For proteins, its efficiency is evaluated quantitatively for two samples: the third IgG-bincling domain from Streptococcal Protein G and the protein calmodulin complexed with a 26-residue target peptide. Gains in both resolution and sensitivity by up to factors of 3.2 and 2.0, respectively, are observed for Gly residues at high magnetic field strengths, but even at much lower fields gains remain substantial. The resolution enhancement obtained for methylene groups makes possible a detailed analysis of spectral regions commonly considered inaccessible due to spectral crowding. For DNA, the high resolution now obtainable for C-5' sites permits an H-5'/H-5"-based sequential NOE assignment procedure, complementary to the conventional base-H-1'/H-2'/H-2" pathway. C1 NIDDKD, Phys Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Boisbouvier, J (reprint author), NIDDKD, Phys Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. EM jerome.boisbouvier@ibs.fr; bax@nih.gov RI Bryce, David/A-3534-2008; Clore, G. Marius/A-3511-2008 OI Bryce, David/0000-0001-9989-796X; Clore, G. Marius/0000-0003-3809-1027 NR 41 TC 52 Z9 52 U1 1 U2 8 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 SEP 1 PY 2004 VL 126 IS 34 BP 10560 EP 10570 DI 10.1021/ja047904v PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 849RU UT WOS:000223559100033 PM 15327312 ER PT J AU Dhanireddy, KK Xu, H Zhang, XJ Leopardi, FV Johnson, LB Hale, DA Kirk, AD AF Dhanireddy, KK Xu, H Zhang, XJ Leopardi, FV Johnson, LB Hale, DA Kirk, AD TI Pretransplant portal venous adoptive transfer in conjunction with sirolimus prolongs renal allograft survival in non-human primates SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 NIH, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S96 EP S97 PG 2 WC Surgery SC Surgery GA 852NA UT WOS:000223760800213 ER PT J AU Finkelstein, S Klebanoff, C Antony, P Gattinoni, L Heimann, D Hinrichs, C Hwang, L Palmer, D Spiess, P Rosenberg, S Restifo, N AF Finkelstein, S Klebanoff, C Antony, P Gattinoni, L Heimann, D Hinrichs, C Hwang, L Palmer, D Spiess, P Rosenberg, S Restifo, N TI IFN-gamma production by adoptively transferred CD8+T lymphocytes and host cells contributes to successful tumor immunotherapy SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S90 EP S91 PG 2 WC Surgery SC Surgery GA 852NA UT WOS:000223760800198 ER PT J AU Pearl, JP Xu, H Kirk, AD AF Pearl, JP Xu, H Kirk, AD TI Nonhuman primates have a high proportion of regulatory T-cells after lymphocyte depletion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 90th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-14, 2004 CL New Orleans, LA SP Amer Coll Surg C1 NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2004 VL 199 IS 3 SU S BP S94 EP S94 PG 1 WC Surgery SC Surgery GA 852NA UT WOS:000223760800206 ER PT J AU Braam, L McKeown, N Jacques, P Lichtenstein, A Vermeer, C Wilson, P Booth, S AF Braam, L McKeown, N Jacques, P Lichtenstein, A Vermeer, C Wilson, P Booth, S TI Dietary phylloquinone intake as a potential marker for a heart-healthy dietary pattern in the Framingham offspring cohort SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; VITAMIN-K; CARDIOVASCULAR-DISEASE; VEGETABLE INTAKE; WOMEN; RISK; CONSUMPTION; PLASMA; MEN; ATHEROSCLEROSIS AB Associations were evaluated among self-reported dietary intakes of phylloquinone (vitamin K-1), lifestyle characteristics, and intermediary markers of cardiovascular disease risk in a population-based cohort of men and women. Dietary phylloquinone intakes were assessed by food frequency questionnaire in 1,338 men and 1,603 women (mean age, 54 years) participating in the Framingham Heart Study. Cross-sectional associations with lifestyle characteristics and lipid profiles, including total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride concentrations, were estimated across increasing quintile categories of phylloquinone intakes. Participants in the highest quintile category of phylloquinone intake consumed more fruit, vegetables, fish, dietary fiber, and dietary supplements (P<.001), and consumed less meat and less saturated fat (P<.001). Higher phylloquinone intakes were also associated with lower triglyceride concentrations (P<.001). In conclusion, a high phylloquinone intake may be a marker for an overall heart-healthy dietary pattern. C1 Tufts Univ, Jean Mayer Human Nutr Res Ctr Aging, USDA, Boston, MA 02111 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NHLBI, Framingham MA Heart Study, Framingham, MA USA. Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. RP Booth, S (reprint author), Tufts Univ, Jean Mayer Human Nutr Res Ctr Aging, USDA, 711 Washington St, Boston, MA 02111 USA. EM sarah.booth@tufts.edu OI Vermeer, Cees/0000-0002-2300-8561 FU NHLBI NIH HHS [N01 HC 38038]; NIDDK NIH HHS [T32 DK 07651] NR 33 TC 22 Z9 23 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2004 VL 104 IS 9 BP 1410 EP 1414 DI 10.1016/j.jada.2004.06.021 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 852LG UT WOS:000223756200017 PM 15354158 ER PT J AU Chodosh, J Seeman, TE Keeler, E Sewall, A Hirsch, SH Guralnik, JM Reuben, DB AF Chodosh, J Seeman, TE Keeler, E Sewall, A Hirsch, SH Guralnik, JM Reuben, DB TI Cognitive decline in high-functioning older persons is associated with an increased risk of hospitalization SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive impairment; dementia; health service utilization ID MENTAL STATUS QUESTIONNAIRE; ALZHEIMERS-DISEASE; DEPRESSIVE SYMPTOMATOLOGY; ELDERLY POPULATION; UNITED-STATES; DEMENTIA; COMMUNITY; IMPAIRMENT; HEALTH; COSTS AB Objectives: To examine hospital use for patients with evidence of cognitive decline indicative of early cognitive impairment. Design: Medicare Part A hospital utilization data were linked to data from the MacArthur Research Network on Successful Aging Community Study to examine the association between baseline cognition and decline in cognitive function over a 3-year period and any hospitalization over that same period. Setting: New Haven, Connecticut, and East Boston, Massachusetts. Participants: Subjects (N=598) were from two sites of the MacArthur Research Network on Successful Aging Community Study, a 7-year cohort study of community-dwelling older persons with high physical and cognitive functioning. Measurements: Multivariate logistic regression was used to determine the association between any hospitalization over 3 years (1988-91) as the outcome variable and baseline cognitive function and decline in cognition over 3 years as primary predictor variables. Decline was based upon repeated (1988 and 1991) measures of delayed verbal recall and the Short Portable Mental Status Questionnaire (SPMSQ). Results: Of 598 subjects, 48 died between 1988 and 1991. No baseline (1988) delayed recall scores or change in recall scores (1988-91) were associated with hospitalization. Although 48.2% declined on verbal memory scores, decline was not associated with risk of hospitalization. Of 494 subjects with complete 3-year data, 31.2% declined at least one point on the SPMSQ, and 4.7% declined more than two points. Among individuals aged 75 and older at baseline, the adjusted odds ratio for hospitalization for those who declined more than 2 points compared with those who declined less was 7.8 (95% confidence interval=2.0-30.8). Conclusion: Although specific memory tests were not associated with hospitalization, high-functioning older persons who experienced decline in overall cognitive function were more likely to be hospitalized. Variation in baseline cognitive function in this high-functioning cohort did not affect hospitalization, but additional research is needed to evaluate associations with other healthcare costs. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Sewall Inc, Bethesda, MD USA. NIA, Bethesda, MD 20892 USA. RP Chodosh, J (reprint author), 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM jchodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU NIA NIH HHS [AG16677] NR 40 TC 40 Z9 40 U1 3 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2004 VL 52 IS 9 BP 1456 EP 1462 DI 10.1111/j.1532-5415.2004.52407.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 847CQ UT WOS:000223366900007 PM 15341546 ER PT J AU Sayers, SP Jette, AM Haley, SM Heeren, TC Guralnik, JM Fielding, RA AF Sayers, SP Jette, AM Haley, SM Heeren, TC Guralnik, JM Fielding, RA TI Validation of the Late-Life Function and Disability Instrument SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; mobility; functional ability; physical disability ID OLDER ADULTS; PERFORMANCE; COMPONENT; HEALTH AB Objectives: To assess the concurrent and predictive validity of the Late-Life Function and Disability Instrument (LLFDI). Design: Cross-sectional. Setting: University-based human physiology laboratory. Participants: One hundred one men and women aged 80.8+/-0.4. Measurements: A short physical performance battery (SPPB) and a self-paced 400-m walk (400-m W) were used as performance tests of lower extremity function. The LLFDI was used to assess self-reported function and physical disability. Partial correlations adjusted for age and body mass index were used to determine the concurrent and predictive validity of the LLFDI. Statistical significance was accepted at P<.004 using a testwise correction. Results: LLFDI Overall Function scores were moderately associated with the SPPB (r=0.65, P<.001), 400-m W gait speed (r=0.69, P<.001), and measures of lower extremity function. Correlations of the two lower extremity subscores of the LLFDI (correlation coefficient (r)=0.63-0.73, P<.001) were greater than for the LLFDI upper extremity subscores (r=0.19-0.26, P>.004). Performance measures of function predicted disability limitations in the range of r=0.37-0.44 (P<.001) and disability frequency in the range of r=0.16-0.20 (P>.004). Conclusion: These findings support the concurrent and predictive validity of the LLFDI. Results support the use of the LLFDI scales as a substitute for physical performance tests when self-report is a preferred data-collection format. C1 Boston Univ, Dept Hlth Sci, Human Physiol Lab, Boston, MA 02215 USA. Boston Univ, Sargent Coll Hlth & Rehabil Sci, Roybal Ctr Enhancement Late Life Funct, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol Biostat, Boston, MA USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Sayers, SP (reprint author), Univ Missouri, Sch Hlth Profess, Dept Phys Therapy, 114 Lewis Hall, Columbia, MO 65211 USA. EM sayerss@missouri.edu FU NIA NIH HHS [R01-AG-18844]; PHS HHS [263-MA-202876, P50-A11669, H133P99004] NR 15 TC 103 Z9 104 U1 2 U2 14 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2004 VL 52 IS 9 BP 1554 EP 1559 DI 10.1111/j.1532-5415.2004.52422.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 847CQ UT WOS:000223366900022 PM 15341561 ER PT J AU Williams, JG Tomer, KB AF Williams, JG Tomer, KB TI Disposable chromatography for a high-throughput nano-ESI/MS and nano-ESI/MS-MS platform SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; SAMPLE PREPARATION; PROTEOMICS; IDENTIFICATION; IONIZATION; DIGESTION; PROTEINS AB High-throughput proteomics has typically relied on protein identification based on MALDI-MS peptide maps of proteolytic digests of 2D-gel-separated proteins. This technique, however, requires significant sequence coverage in order to achieve a high level of confidence in the identification. Tandem MS data have the advantage of requiring fewer peptides (2) for high confidence identification, assuming adequate MS/MS sequence coverage. MALDI-MS/MS techniques are becoming available, but can still be problematic because of the difficulty of inducing fragment ions of a singly charged parent ion. Electrospray ionization, however, has the advantage of generating multiply charged species that are more readily fragmented during MS/MS analysis. Two electrospray/tandem mass spectrometry-based approaches, nanovial-ESI-MS/MS and LC-MS/MS, are used for high throughput proteomics, but much less often than MALDI-MS and peptide mass fingerprinting. Nanovial introduction entails extensive manual manipulation and often shows significant chemical background from the in-gel digest. LC-MS has the advantages that the chemical background can be removed prior to analysis and the analytes are concentrated during the separation, resulting in more abundant analyte signals. On the other hand, LC-MS can often be time intensive. Here, we report the incorporation of on-line sample clean-up and analyte concentration with a high-throughput, chip-based, robotic nano-ESI-MS platform for proteomics studies. (C) 2004 American Society for Mass Spectrometry. C1 Natl Inst Environm Hlth Sci, Lab Struct Biol, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Tomer, KB (reprint author), Natl Inst Environm Hlth Sci, Lab Struct Biol, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233,MD-F0-03, Res Triangle Pk, NC 27709 USA. EM tomer@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 NR 16 TC 13 Z9 14 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD SEP PY 2004 VL 15 IS 9 BP 1333 EP 1340 DI 10.1016/j.jasms.2004.06.007 PG 8 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 853RD UT WOS:000223844200009 PM 15337514 ER PT J AU Fox, CS Yang, Q Cupples, LA Guo, CY Larson, MG Leip, EP Wilson, PWF Levy, D AF Fox, CS Yang, Q Cupples, LA Guo, CY Larson, MG Leip, EP Wilson, PWF Levy, D TI Genomewide linkage analysis to serum creatinine, GFR, and creatinine clearance in a community-based population: The Framingham Heart Study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; QUANTITATIVE-TRAIT; CARDIOVASCULAR-DISEASE; CLINICAL EPIDEMIOLOGY; VARIANCE-COMPONENTS; PEDIGREES; FAILURE; INSUFFICIENCY; PREDICTION; CELLS AB Kidney disease is a risk factor for the development of cardiovascular disease, all-cause mortality, and ESRD. It is not known to what extent genetic factors play a role in the development of kidney disease in the general population. Multipoint variance components linkage analysis was performed using Gene-hunter on 330 families from the Framingham Heart Study offspring cohort, using a 10-cM genomewide scan for serum creatinine, GFR, and creatinine clearance (CRCL) measured from 1998 to 2001. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation, and CRCL was estimated using the Cockcroft-Gault equation. Covariates in the adjustment included age, gender, body mass index, diabetes, systolic BP, hypertension treatment, tobacco use, and HDL cholesterol. Overall, 1224 subjects (52% women), mean age 59, were available for analysis. Mean creatinine was 0.87 mg/dl, mean GFR was 87 ml/min per 1.73 m(2), and mean creatinine clearance was 100 ml/min. The multivariable-adjusted heritability estimates for creatinine, GFR, and CRCL were 0.29, 0.33, and 0.46, respectively. The peak log of the odds ratio (LOD) scores for serum creatinine, GFR, and CRCL were 2.28 at 176 cM on chromosome 4, 2.19 at 78 cM on chromosome 4, and 1.91 at 103 cM on chromosome 3, respectively. In a community-based sample, measures of serum creatinine, GFR, and CRCL are heritable, suggesting an underlying genetic component. These results also provide suggestive evidence for linkage to measures of kidney function. Further research is necessary to identify the genes involved in the development of kidney disease and to understand their roles in this complex process. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014; OI Larson, Martin/0000-0002-9631-1254; Cupples, L. Adrienne/0000-0003-0273-7965 FU NHLBI NIH HHS [N01-HC-25195] NR 34 TC 98 Z9 99 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2004 VL 15 IS 9 BP 2457 EP 2461 DI 10.1097/01.ASN.0000135972.13396.6F PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 851EK UT WOS:000223668200024 PM 15339995 ER PT J AU Eggers, PW Kimmel, PL AF Eggers, PW Kimmel, PL TI Is there an epidemic of HIV infection in the US ESRD program? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; STAGE RENAL-DISEASE; DIALYSIS-ASSOCIATED DISEASES; CHEMOKINE RECEPTOR CCR5; UNITED-STATES; NATIONAL SURVEILLANCE; HIV-1-ASSOCIATED NEPHROPATHY; PROTEASE INHIBITORS; SURVIVAL AB Surveys revealed increases in the prevalence of HIV-infected patients in the US end-stage renal disease (ESRD) program in the 1980s and early 1990s, with clustering in young black men 25 to 44 yr old. Since the availability of highly active antiretroviral therapy in 1996, the prognosis of HIV-infected patients has improved, and therapy has been shown to change the course of classic HIV-associated nephropathy. We used the United States Renal Data System database to determine if the incidence and prevalence of HIV-infected patients with renal disease has increased in the ESRD program, by means of principal diagnoses and comorbid AIDS-defining diagnoses. As the number of US patients living with AIDS increased 57% from 214,711 in 1995 to 337,017 in 2000, and the number of incident ESRD patients increased 29.9% from 72,827 to 94,602, the number of incident HIV-infected patients increased only by 3.5%, from 1133 to 1171. Over this time, the percentage of incident ESRD patients with HIV infection fell from 1.56% to 1.24%. Among black men 25 to 44 yr of age, HIV infection as a proportion of incident ESRD cases fell from 8.5% to 6.2% from 1995 to 2000. The incident rate per million of AIDS or HIV infection in black men aged 25 to 44 fell from 107 in 1995 to 78 per million in 2000. The incidence rate for HIV-infected women in the ESRD program rose 14% while it declined 7% in men. Almost 2000 HIV-infected women, or 28.8% of the population, have initiated therapy for ESRD with hemodialysis. The number of prevalent cases increased in absolute numbers 81.3% from 2687 to 4871 (0.90% to 1.16% of the ESRD program). One-year survival rates for HIV-infected incident ESRD patients increased from 53.1% to 67.1% from 1995 to 2000. Although these values may be underestimates because of underreporting due to confidentiality concerns and lack of biopsy confirmation, we conclude that although the prevalence of HIV infection is increasing in the US ESRD population, the increase as a proportion of the program is minimal and is due to better survival after development of renal failure. The incidence of HIV infection in the US ESRD program is stable. Highly active antiretroviral therapy may be responsible for the change in epidemiology of HIV infection in the US ESRD program. C1 George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Kimmel, PL (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, 2150 Penn Ave NW, Washington, DC 20037 USA. EM pkimme1@mfa.gwu.edu NR 38 TC 65 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2004 VL 15 IS 9 BP 2477 EP 2485 DI 10.1097/01.ASN.0000138546.53152.A7 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 851EK UT WOS:000223668200027 PM 15339998 ER PT J AU Prentice, RL Willett, WC Greenwald, P Alberts, D Bernstein, L Boyd, NF Byers, T Clinton, SK Fraser, G Freedman, L Hunter, D Kipnis, V Kolonel, LN Kristal, BS Kristal, A Lampe, JW McTiernan, A Milner, J Patterson, RE Potter, JD Riboli, E Schatzkin, A Yates, A Yetley, E AF Prentice, RL Willett, WC Greenwald, P Alberts, D Bernstein, L Boyd, NF Byers, T Clinton, SK Fraser, G Freedman, L Hunter, D Kipnis, V Kolonel, LN Kristal, BS Kristal, A Lampe, JW McTiernan, A Milner, J Patterson, RE Potter, JD Riboli, E Schatzkin, A Yates, A Yetley, E TI Nutrition and physical activity and chronic disease prevention: Research strategies and recommendations SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED TRIAL; ESTROGEN PLUS PROGESTIN; SURROGATE END-POINTS; BREAST-CANCER RISK; DIETARY-FAT INTAKE; POSTMENOPAUSAL WOMEN; COLORECTAL ADENOMAS; BETA-CAROTENE; LUNG-CANCER AB A shortage of credible information exists on practical dietary and physical activity patterns that have potential to reverse the national obesity epidemic and reduce the risk of major cancers and other chronic diseases. Securing such information is a challenging task, and there is considerable diversity of opinion concerning related research designs and priorities. Here, we put forward some perspectives on useful methodology and infrastructure developments for progress in this important area, and we list high-priority research topics in the areas of 1) assessment of nutrient intake and energy expenditure; 2) development of intermediate outcome biomarkers; 3) enhancement of cohort and cross-cultural studies; and 4) criteria for and development of full-scale nutrition and physical activity intervention trials. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Colorado, Sch Med, Denver, CO USA. Ohio State Univ, Dept Hematol & Oncol, Columbus, OH 43210 USA. Loma Linda Univ, Dept Epidemiol & Biostat, Loma Linda, CA 92350 USA. Bar Ilan Univ, Dept Math & Comp Sci, Tel Aviv, Israel. Univ Hawaii, Canc Res Ctr, Dept Epidemiol, Honolulu, HI 96813 USA. Cornell Univ, Coll Med, Burke Med Res Inst, Dementia Res Serv, White Plains, NY 10605 USA. Cornell Univ, Dept Biochem, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Neurosci, New York, NY USA. San Diego Fdn, San Diego, CA USA. Int Agcy Res Canc, F-69372 Lyon, France. Natl Acad Sci, Inst Med, Food & Nutr Board, Washington, DC 20418 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M3-A410, Seattle, WA 98109 USA. EM rprentic@fhcrc.org RI Kristal, Alan/A-8779-2008; OI Potter, John/0000-0001-5439-1500; Kristal, Alan/0000-0002-7329-1617 FU NCI NIH HHS [CA53996] NR 81 TC 44 Z9 48 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 1 PY 2004 VL 96 IS 17 BP 1276 EP 1287 DI 10.1093/jnci/djh240 PG 12 WC Oncology SC Oncology GA 850JS UT WOS:000223607800008 PM 15339966 ER PT J AU Schairer, C Mink, PJ Carroll, L Devesa, SS AF Schairer, C Mink, PJ Carroll, L Devesa, SS TI Probabilities of death from breast cancer and other causes among female breast cancer patients SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CARCINOMA SURVIVAL; COMPETING RISKS; ELDERLY-WOMEN; TUMOR CHARACTERISTICS; RACIAL-DIFFERENCES; MORTALITY; COMORBIDITY; DISPARITIES; OLDER; CHEMOTHERAPY AB Background: Among cancer patients, probabilities of death from that cancer and other causes in the presence of competing risks are optimal measures of prognosis and of mortality across demographic groups. We used data on breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) Program in a competing-risk analysis. Methods: We determined vital status and cause of death for 395 251 white and 35 259 black female patients with breast cancer diagnosed from January 1, 1973, through December 31, 2000, by use of SEER data. We calculated probabilities of death from breast cancer and other causes according to stage, race, and age at diagnosis; for cases diagnosed from January 1, 1990, to December 31, 2000, we also calculated some such probabilities according to tumor size and estrogen receptor (ER) status. All statistical tests were two-sided. Results: The probability of death from breast cancer after nearly 28 years of follow-up ranged from 0.03 to 0.10 for patients with in situ disease to 0.70 to 0.85 for patients with distant disease, depending on race and age. The probability of death from breast cancer at the end of the follow-up period generally declined with age at diagnosis; the probability among the oldest (2:70 years) compared with the youngest (<50 years) patients was 33% lower for white and 46% lower for black patients with localized disease and 14% lower for white patients and 13% lower for black patients with distant disease. The probability of death from breast cancer exceeded that from all other causes for patients diagnosed with localized disease before age 50 years, with regional disease before age 60 years, and with distant disease at any age. The probability of death from breast cancer for patients diagnosed with localized or regional disease was statistically significantly greater in black patients than in white patients (all six P values less than or equal to.01 for age groups 30-49 to 60-69 years; two P values less than or equal to.04 for ages greater than or equal to70 years). Among patients with localized or regional disease and known ER status, the probability of death from breast cancer after nearly 11 years of follow-up ranged from 0.04 to 0.11 for patients with localized ER-positive tumors of 2 cm or less to 0.37 to 0.53 for patients with regional ER-negative tumors. Conclusions: The probability of death from breast cancer versus other causes varied substantially according to stage, tumor size, ER status, and age at diagnosis in both white and black patients. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Exponent Hlth Grp, Washington, DC USA. Informat Management Serv Inc, Rockville, MD USA. RP Schairer, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS Rm 8020,MSC 7234, Rockville, MD 20852 USA. EM schairec@exchange.nih.gov NR 36 TC 143 Z9 149 U1 2 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 1 PY 2004 VL 96 IS 17 BP 1311 EP 1321 DI 10.1093/jnci/djh253 PG 11 WC Oncology SC Oncology GA 850JS UT WOS:000223607800011 PM 15339969 ER PT J AU Yabroff, KR Lawrence, WF Clauser, S Davis, WW Brown, ML AF Yabroff, KR Lawrence, WF Clauser, S Davis, WW Brown, ML TI Burden of illness in cancer survivors: Findings from a population-based national sample SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID QUALITY-OF-LIFE; STAGE BREAST-CANCER; TIME TRADE-OFF; LONG-TERM; PROSTATE-CANCER; PATIENTS PREFERENCES; PATIENT PREFERENCES; RANDOMIZED-TRIALS; LIMITATION INDEX; HEALTH UTILITIES AB Background: Population trends in aging and improved cancer survival are likely to result in increased cancer prevalence in the United States, but few estimates of the burden of illness among cancer survivors are currently available. The purpose of this study was to estimate the burden of illness in cancer survivors in a national, population-based sample. Methods: A total of 1823 cancer survivors and 5469 age-, sex-, and educational attainment-matched control subjects were identified from the 2000 National Health Interview Survey. Multiple measures of burden, including utility, a summary measure of health, and days lost from work, were compared using two-sided tests of statistical significance for the two groups overall and for subgroups stratified by tumor site and time since diagnosis. Results: Compared with matched control subjects, cancer survivors had poorer outcomes across all burden measures (P<.01). Cancer survivors had lower utility values (0.74 versus 0.80; P<.001) and higher levels of lost productivity and were more likely to report their health as fair or poor (31.0% versus 17.9%; P<.001) than matched control subjects. Cancer survivors reported statistically significantly higher burden than did control subjects across tumor sites and across time since diagnosis (i.e., within the past year, 2-5 years, 6-10 years, and greater than or equal to11 years for the majority of measures. Conclusions: Cancer survivors have poorer health outcomes than do similar individuals without cancer across multiple burden measures. These decrements are consistent across tumor sites and are found in patients many years following reported diagnosis. Improved measurement of long-term burden of illness will be important for future prospective research. C1 NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA. RP Yabroff, KR (reprint author), NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 65 TC 290 Z9 293 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 1 PY 2004 VL 96 IS 17 BP 1322 EP 1330 DI 10.1093/jnci/djh255 PG 9 WC Oncology SC Oncology GA 850JS UT WOS:000223607800012 PM 15339970 ER PT J AU Primm, BJ Perez, L Dennis, GC Benjamin, L Clark, HW Keough, K Leak, WD Payne, R Smith, D Sullivan, LW AF Primm, BJ Perez, L Dennis, GC Benjamin, L Clark, HW Keough, K Leak, WD Payne, R Smith, D Sullivan, LW TI Managing pain: The challenge in underserved populations: Appropriate use versus abuse and diversion SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE pain; opiods; substance abuse; cancer; race ID OF-LIFE CARE; OPIOID ANALGESICS; ELDERLY-PATIENTS; PALLIATIVE CARE; MANAGEMENT; CANCER; END; PERSPECTIVES; ETHNICITY; PATIENT AB This Consensus Report was made possible in part by an educational grant from Purdue Pharma, LLP. The National Medical Association and consensus panel members (Primm, chairperson; Perez, cochairperson; Dennis, consultant; Benjamin; Clark; Keough; Leak; Payne; Smith; and Sullivan) do not support or endorse any specific medication or modality discussed in this paper. The consensus report is not intended to substitute medical advice from a healthcare provider. C1 Addict Res & Treatment Corp, Brooklyn, NY USA. Natl Med Assoc, Bethesda, MD USA. Howard Univ Hosp, Washington, DC USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Ctr Subst Abuse Treatment, Rockville, MD USA. Natl Assoc State Controlled Subst Author, Waltham, MA USA. Case Western Reserve Univ, Sch Med, Dept Anesthesiol, Columbus, OH USA. Pain Control Consultants Inc, Columbus, OH USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NIDA, Bethesda, MD 20892 USA. Morehouse Sch Med, Atlanta, GA 30310 USA. Natl Med Assoc, Off Hlth Policy Res & Profess Med Affairs, Washington, DC USA. RP Primm, BJ (reprint author), Addict Res & Treatment Corp, Brooklyn, NY USA. NR 44 TC 15 Z9 15 U1 2 U2 6 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD SEP PY 2004 VL 96 IS 9 BP 1152 EP 1161 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 854CA UT WOS:000223876600001 PM 15481743 ER PT J AU Tripodi, A Chantarangkul, V Bohm, M Budde, U Dong, JF Friedman, KD Galbusera, M Girma, JP Moake, J Rick, ME Studt, JD Turecek, PL Mannucci, PM AF Tripodi, A Chantarangkul, V Bohm, M Budde, U Dong, JF Friedman, KD Galbusera, M Girma, JP Moake, J Rick, ME Studt, JD Turecek, PL Mannucci, PM TI Measurement of von Willebrand factor cleaving protease (ADAMTS-13): results of an international collaborative study involving 11 methods testing the same set of coded plasmas SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE ADAMTS-13; hemolytic uremic syndrome; thrombotic; microangiopathy; thrombotic tbrombocytopenic purpura (TTP); von Willebrand factor; von Willebrand factor; cleaving protease ID THROMBOTIC THROMBOCYTOPENIC PURPURA; HEMOLYTIC-UREMIC SYNDROME; METALLOPROTEASE ADAMTS13; VONWILLEBRAND-FACTOR; ASSAY; VWF; DEFICIENCY; CLEAVAGE; DOMAIN; TTP AB Background: ADAMTS-13 is a von Willebrand factor (VFW)-cleaving protease. Its congenital or acquired deficiency is associated with thrombotic thrombocytopenic purpura (TTP) and more rarely with the hemolytic uremic syndrome. We report on a survey evaluating I I methods for ADAMTS-13 measurement performed in different labs. Design: Two plasmas, one normal and one from a patient with familial TTP, were mixed at the co-ordinating center to prepare 6 plasmas with 0%, 100%, 20%, 40%, 80% and 100% ADAMTS-13 levels. Each plasma was aliquoted and assembled into sets of 60 (coded from I to 60), each containing 10 copies of the original 6 plasmas. Plasmas were frozen and shipped in dry ice to 10 labs with a common frozen reference plasma. Laboratories were asked to measure ADAMTS-13 with their methods. Results were sent to the coordinating center for statistical analysis. Results: Of the 10 methods performed under static conditions 9 were quantitative and one was semiquantitative. One method performed under flow conditions evaluated the extent of cleavage of endothelial cell-derived ultralarge VWF string-like structures and expressed results as deficient, normal, or borderline. Linearity (expected-vs-observed levels), assessed as the squared correlation coefficient, ranged from 0.98 to 0.39. Reproducibility, expressed as the coefficient of variation for repeated measurements, ranged from < 10% to 83%. The majority of methods were able to discriminate between different ADAMTS-13 levels. The majority were able to detect the plasma with 0% level and some of them to discriminate between 0% and 10%. Overall the best performance was observed for three methods measuring cleaved VWF by ristocetin cofactor, collagen binding, and iminunoblotting of degraded multimers of VWF substrate, respectively. The poor interlaboratory agreement of results was hardly affected by the us,2 of the common standard. The method performed under flow conditions identified the plasmas with 0%, 10%, 20% and 40% activity as deficient in 7, 5, 1 and 3 of the 10 replicate measurements. The plasmas with 80% and 100% were identified as normal in all of the 10 replicate measurements. Conclusions: The survey shows varied performance, but supports an optimistic view about the reliability of current methods for ADAMTS-13. C1 Univ Milan, Dept Internal Med, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy. IRCCS Maggiore Hosp, Milan, Italy. JW Goethe Univ Hosp, Dept Hemostaseol, Frankfurt, Germany. Lab Assoc Prof Arndt & Partners, Hamburg, Germany. Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. Med Coll Wisconsin, Dept Med, Blood Ctr S Eastern Wisconsin, Milwaukee, WI USA. Mario Negri Inst Pharmacol Res, Bergamo, Italy. Hop Bicetre, INSERM, U143, Paris, France. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. Univ Hosp, Inselspital, Dept Hematol, Bern, Switzerland. Univ Hosp, Inselspital, Cent Hematol Lab, Bern, Switzerland. Baxter Biosci, Vienna, Austria. RP Mannucci, PM (reprint author), Via Pace 9, I-20122 Milan, Italy. EM pmmannucci@libero.it RI Mannucci, Pier/C-3102-2014 NR 28 TC 65 Z9 66 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD SEP PY 2004 VL 2 IS 9 BP 1601 EP 1609 DI 10.1111/j.1538-7836.2004.00879.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 852MN UT WOS:000223759500017 PM 15333037 ER PT J AU Sevransky, JE Parent, C Cui, XZ Karzai, W Fitz, Y Banks, SM Gerstenberger, E Danner, RL Natanson, C Eichacker, PQ AF Sevransky, JE Parent, C Cui, XZ Karzai, W Fitz, Y Banks, SM Gerstenberger, E Danner, RL Natanson, C Eichacker, PQ TI Granulocyte colony-stimulating factor has differing effects comparing intravascular versus extravascular models of sepsis SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE granulocyte colony-stimulating factor; neutrophil; pretreatment; Escherichia coli; Staphylococcus aureus ID ESCHERICHIA-COLI PNEUMONIA; STAPHYLOCOCCUS-AUREUS PNEUMONIA; NECROSIS-FACTOR-ALPHA; SEPTIC SHOCK; G-CSF; PLASMA CYTOKINE; CANINE MODEL; LUNG INJURY; RG-CSF; ENDOTOXIN AB Background. Previously, neutrophil stimulation with granulocyte colony-stimulating factor (G-CSF) pretreatment increased survival rates in canines challenged with intraperitoneal or intrabronchial Escherichia coli and in rats challenged with intrabronchial Staphylococcus aureus. We investigated whether G-CSF pretreatment would be beneficial with intravascular challenge in these models. Methods: Animals were randomized to G-CSF or placebo pretreatment followed by intravenous E. coli challenge in canines (n=24) or intravenous or intrabronchial S. aureus challenge in rats (n=273). All animals were treated with antibiotics. Results: In canines, G-CSF before intravenous E. coli did not decrease mortality rates (7 of 12 [58%] G-CSF vs. 5 of 12 [42%] controls), which contrasted with prior reductions during extravascular infection (10 of 35 [29%] G-CSF vs. 37 of 65 [57%] controls). Consistent with the present and previously published studies in canines, in rats, G-CSF decreased mortality rates with intrabronchial S. aureus (22 of 90 [24%] G-CSF vs. 26 of 51 [51%] controls, p=0.009) but did not decrease them with intravenous infection (34 of 67 [50%] G-CSF vs. 27 of 65 [42%] controls, p=0.2) in patterns that were very different (p=0.005 for the effects of G-CSF with intravascular vs. intrabronchial S. aureus). Conclusion: In contrast to extravascular infection, sepsis with intravascular E. coli in canines and S. aureus in rats may not provide a compartmentalized nidus of bacteria on which G-CSF-stimulated neutrophils can exert a beneficial antimicrobial effect. Extrapolated clinically, a proinflammatory agent like G-CSF may be most beneficial with sepsis related primarily to a compartmentalized extravascular site of infection. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Ctr Asthma & Allergy, Baltimore, MD USA. Zent Klin Bad Berka, Dept Anesthesia & Intens Care, Bad Berka, Germany. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 7D43,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ludwig.labler@chi.usz.ch NR 38 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD SEP PY 2004 VL 57 IS 3 BP 618 EP 625 DI 10.1097/01.TA.0000105884.75782.4D PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 859YH UT WOS:000224303800031 PM 15454812 ER PT J AU Goncalves, LF Espinoza, J Romero, R Lee, W Beyer, B Treadwell, MC Humes, R AF Goncalves, LF Espinoza, J Romero, R Lee, W Beyer, B Treadwell, MC Humes, R TI A systematic approach to prenatal diagnosis of transposition of the great arteries using 4-dimensional ultrasonography with spatiotemporal image correlation SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID CONGENITAL HEART-DISEASE; FETAL HEART; DEFECTS; EXPERIENCE; ULTRASOUND; POPULATION; MORTALITY; VESSELS; TERM AB Spatiotemporal image correlation (STIC) is a recent technological advance in ultrasonographic imaging that allows dynamic multiplanar slicing and surface rendering of the fetal heart.(1-5) In a previous study, a technique was developed to systematically visualize the outflow tracts from volume data sets acquired with STIC.(3,4) The addition of color and power Doppler imaging to STIC technology made it possible to dynamically display rendered views of the outflow tracts with minimal manipulation of the volume data set.(5) Prenatal diagnosis of transposition of the great arteries (TGA) is associated with a significant reduction in both preoperative and postoperative mortality, a decrease in the rate of metabolic acidosis and multiorgan failure during the neonatal period, reduced need for ventilatory support, and shorter hospitalization time.(6,7) Unfortunately, prenatal detection rates for TGA have been low in most of the studies published to date.(8-15) Among the reasons for failure to prenatally detect most cases of TGA are the absence of risk factors to identify a target population for screening and the need to systematically examine the outflow tracts to establish the diagnosis.(6,16) Despite recommendations; by scientific societies such as the American Institute of Ultrasound in Medicine to extend the basic fetal cardiac examination to include visualization of the outflow tracts whenever technically feasible,(17) this examination remains a technical challenge for many sonographers.(6,18) Four-dimensional volume data set acquisition followed by a systematic approach to image the outflow tracts may reduce the operator dependency of prenatal ultrasonography, Volume acquisition is still operator dependent with current commercially available technology. However, once a good-quality volume data set is acquired, the outflow tracts can be systematically imaged by following algorithms developed for gray scale,(3,4) color, or power Doppler(5) imaging. It is anticipated that algorithms developed to image specific cardiac structures with 3- or 4-dimensional volume data sets may eventually become automated by computer software (automated multiplanar imaging).(19) The objective of this report was to describe the ultrasonographic findings of TGA on the basis of a systematic approach of 4-dimensional echocardiography with STIC. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHHD, NIH, Perinatol Res Branch, Dept Hlth & Human Serv, Bethesda, MD USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. Wayne State Univ, Childrens Hosp, Div Cardiol, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, Natl Inst Child Hlth & Human Dev,Dept Obstet & Gy, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 26 TC 28 Z9 30 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD SEP PY 2004 VL 23 IS 9 BP 1225 EP 1231 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 850RK UT WOS:000223629900012 PM 15328439 ER PT J AU Balter, S Schueler, BA Miller, DL Cole, PE Lu, HT Berenstein, A Albert, R Georgia, JD Noonan, PT Russell, EJ Malisch, TW Vogelzang, RL Geisinger, M Cardella, JF St George, J Miller, GL Anderson, J AF Balter, S Schueler, BA Miller, DL Cole, PE Lu, HT Berenstein, A Albert, R Georgia, JD Noonan, PT Russell, EJ Malisch, TW Vogelzang, RL Geisinger, M Cardella, JF St George, J Miller, GL Anderson, J TI Radiation doses in interventional radiology procedures: The RAD-IR study Part III: Dosimetric performance of the interventional fluoroscopy units SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article AB PURPOSE: To present the physics data supporting the validity of the clinical dose data from the RAD-IR study and to document the performance of dosimetry-components of these systems over time. MATERIALS AND METHODS: Sites at seven academic medical centers in the United States prospectively contributed data for each of 12 fluoroscopic units. All units were compatible with International Electrotechnical Commission (IEC) standard 60601-2-43. Comprehensive evaluations and periodic consistency checks were performed to verify the performance of each unit's dosimeter. Comprehensive evaluations compared system performance against calibrated ionization chambers under nine combinations of operating conditions. Consistency checks provided more frequent dosimetry data, with use of each unit's built-in dosimetry equipment and a standard water phantom. RESULTS: During the 3-year study, data were collected for 48 comprehensive evaluations and 581 consistency checks. For the comprehensive evaluations, the mean (95% confidence interval range) ratio of system to external measurements was 1.03 (1.00-1.05) for fluoroscopy and 0.93 (0.90-0.96) for acquisition. The expected ratio was 0.93 for both. For consistency checks, the values were 1.00 (0.98-1.02) for fluoroscopy and 1.00 (0.98-1.02) for acquisition. Each system was compared across time to its own mean value. Overall uncertainty was estimated by adding the standard deviations of the comprehensive and consistency measurements in quadrature. The authors estimate that the overall error in clinical cumulative dose measurements reported in RAD-IR is 24%. CONCLUSION: Dosimetric accuracy was well within the tolerances established by IEC standard 60601-2-43. The clinical dose data reported in the RAD-IR study are valid. C1 Natl Naval Med Ctr, Dept Radiol, Bethesda, MD 20889 USA. Lenox Hill Hosp, Dept Med, New York, NY 10021 USA. Mayo Clin, Rochester, MN USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. NCI, Med Oncol Clin Res Unit, Canc Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Beth Israel Deaconess Med Ctr, Ctr Endovasc Surg, Hyman Newman Inst Neurol & Neurosurg, New York, NY 10003 USA. NW Mem Hosp, Dept Radiol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Radiol, Chicago, IL 60611 USA. Cleveland Clin Fdn, Dept Radiol, Cleveland, OH 44195 USA. SUNY Upstate Med Univ, Dept Radiol, Syracuse, NY USA. Univ Texas, SW Med Ctr, Dept Radiol, Dallas, TX 75235 USA. Lahey Clin Fdn, Dept Radiol, Burlington, MA USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. RP Miller, DL (reprint author), Natl Naval Med Ctr, Dept Radiol, Bethesda, MD 20889 USA. EM dm72v@nih.gov NR 9 TC 34 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2004 VL 15 IS 9 BP 919 EP 926 DI 10.1097/01.RVI.0000130864.68139.08 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XQ UT WOS:000227678600004 PM 15361559 ER PT J AU Steinmann, D Barth, H Gissler, B Schurmann, P Adah, MI Gerlach, JT Pape, GR Depla, E Jacobs, D Maertens, G Patel, AH Inchauspe, G Liang, TJ Blum, HE Baumert, TF AF Steinmann, D Barth, H Gissler, B Schurmann, P Adah, MI Gerlach, JT Pape, GR Depla, E Jacobs, D Maertens, G Patel, AH Inchauspe, G Liang, TJ Blum, HE Baumert, TF TI Inhibition of hepatitis c virus-like particle binding to target cells by antiviral antibodies in acute and chronic hepatitis C SO JOURNAL OF VIROLOGY LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; CELLULAR IMMUNE-RESPONSES; IN-VITRO; E2 GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; ENVELOPE PROTEINS; INSECT CELLS; CD81 BINDING; INFECTION; REPLICATION AB Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis worldwide. The study of antibody-mediated virus neutralization has been hampered by the lack of an efficient and high-throughput cell culture system for the study of virus neutralization. The HCV structural proteins have been shown to assemble into noninfectious HCV-like particles (HCV-LPs). Similar to serum-derived virions, HCV-LPs bind and enter human hepatocytes and hepatoma cell lines. In this study, we developed an HCV-LP-based model system for a systematic functional analysis of antiviral antibodies from patients with acute or chronic hepatitis C. We demonstrate that cellular HCV-LP binding was specifically inhibited by antiviral antibodies from patients with acute or chronic hepatitis C in a dose-dependent manner. Using a library of homologous overlapping envelope peptides covering the entire HCV envelope, we identified an epitope in the N-terminal E2 region (SQKIQLVN TNGSWHI; amino acid positions 408 to 422) as one target of human antiviral antibodies inhibiting cellular particle binding. Using a large panel of serum samples from patients with acute and chronic hepatitis C, we demonstrated that the presence of antibodies with inhibition of binding activity was not associated with viral clearance. In conclusion, antibody-mediated inhibition of cellular HCV-LP binding represents a convenient system for the functional characterization of human anti-HCV antibodies, allowing the mapping of envelope neutralization epitopes targeted by naturally occurring antiviral antibodies. C1 Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany. Univ Munich, Klinikum Grosshadern, Dept Med 2, D-8000 Munich, Germany. Innogenet, Ghent, Belgium. Univ Glasgow, MRC, Virol Unit, Inst Virol, Glasgow, Lanark, Scotland. CNRS Biomerieux, Lyon, France. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Baumert, TF (reprint author), Univ Freiburg, Dept Med 2, Hugstetter Str 55, D-79106 Freiburg, Germany. EM Thomas.Baumert@uniklinik-freiburg.de NR 53 TC 58 Z9 63 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 17 BP 9030 EP 9040 DI 10.1128/JVI.78.17.9030-9040.2004 PG 11 WC Virology SC Virology GA 847IT UT WOS:000223386600008 PM 15308699 ER PT J AU Zhang, MY Xiao, XD Sidorov, IA Choudhry, V Cham, F Zhang, PF Bouma, P Zwick, M Choudhary, A Montefiori, DC Broder, CC Burton, DR Quinnan, GV Dimitrov, DS AF Zhang, MY Xiao, XD Sidorov, IA Choudhry, V Cham, F Zhang, PF Bouma, P Zwick, M Choudhary, A Montefiori, DC Broder, CC Burton, DR Quinnan, GV Dimitrov, DS TI Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZATION RESISTANCE PHENOTYPE; HIV-1 ENVELOPE GLYCOPROTEINS; PHAGE DISPLAY LIBRARIES; CD4 BINDING-SITE; CD4-BINDING SITE; PHASE-I; COMBINATORIAL LIBRARIES; PASSIVE-IMMUNIZATION; ANTIVIRAL ACTIVITY; HIGH INFECTIVITY AB The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and neutralization and in the development of entry inhibitors and vaccines. For enhanced selection of broadly cross-reactive antibodies, soluble HIV-1 envelope glycoproteins (Envs proteins) from two isolates complexed with two-domain soluble CD4 (sCD4) were alternated during panning of a phage-displayed human antibody library; these two Env proteins (89.6 and IIIB gp140s), and one additional Env (JR-FL gp120) alone and complexed with sCD4 were used for screening. An antibody with relatively long HCDR3 (17 residues), designated m14, was identified that bound to all antigens and neutralized heterologous HIV-1 isolates in multiple assay formats. Fab m14 potently neutralized selected well-characterized subtype B isolates, including JRCSF, 89.6, IIIB, and Yu2. Immunoglobulin G1 (IgG1) m14 was more potent than Fab m14 and neutralized 7 of 10 other clade B isolates; notably, although the potency was on average significantly lower than that of IgG1 b12, IgG1 m14 neutralized two of the isolates with significantly lower 50% inhibitory concentrations than did IgG1 b12. IgG1 m14 neutralized four of four selected clade C isolates with potency higher than that of IgG1 b12. It also neutralized 7 of 17 clade C isolates from southern Africa that were difficult to neutralize with other hMAbs and sCD4. IgG1 m14 neutralized four of seven primary HIV-1 isolates from other clades (A, D, E, and F) much more efficiently than did IgG1 b12; for the other three isolates, IgG b12 was much more potent. Fab m14 bound with high (nanomolar range) affinity to gp120 and gp140 from various isolates; its binding was reduced by soluble CD4 and antibodies recognizing the CD4 binding site (CD4bs) on gp120, and its footprint as defined by alanine-scanning mutagenesis overlaps that of b12. These results suggest that m14 is a novel CD4bs cross-reactive HIV-1-neutralizing antibody that exhibits a different inhibitory profile compared to the only known potent broadly neutralizing CD4bs human antibody, b12, and may have implications for our understanding of the mechanisms of immune evasion and for the development of inhibitors and vaccines. C1 NCI, LECB, CCR, Human Immunivirol Grp, Ft Detrick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med, Bethesda, MD USA. Scripps Res Inst, Dept Immunol, La Jolla, CA USA. Scripps Res Inst, Dept Biol Mol, La Jolla, CA USA. Duke Univ, Ctr Med, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC USA. RP Dimitrov, DS (reprint author), NCI, LECB, CCR, Human Immunivirol Grp, Bldg 469,Rm 105,POB B,Miller Dr, Ft Detrick, MD 21702 USA. EM dimitrov@ncifcrf.gov OI Sidorov, Igor/0000-0001-6519-4983 FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [AI47438, AI48280, AI48380, P01 AI048280] NR 76 TC 66 Z9 72 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 17 BP 9233 EP 9242 DI 10.1128/JVI.78.17.9233-9242.2004 PG 10 WC Virology SC Virology GA 847IT UT WOS:000223386600027 PM 15308718 ER PT J AU Nam, JH Faulk, K Engle, RE Govindarajan, S St Claire, M Bukh, J AF Nam, JH Faulk, K Engle, RE Govindarajan, S St Claire, M Bukh, J TI In vivo analysis of the 3 ' untranslated region of GB virus B after in vitro mutagenesis of an infectious cDNA clone: Persistent infection in a transfected tamarin SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-C VIRUS; RIBOSOME ENTRY SITE; NEW-WORLD MONKEYS; NONSTRUCTURAL PROTEIN-3; NONTRANSLATED REGION; SURROGATE MODEL; RNA; REPLICATION; AGENT; IDENTIFICATION AB GB virus B (GBV-B), the virus most closely related to hepatitis C virus (HCV), infects tamarins and causes acute hepatitis. The 3' untranslated region (UTR) of an infectious GBV-B clone (pGBB) has a proximal short sequence followed by a poly(U) tract and a 3' terminal sequence. Our investigators previously demonstrated that the 3' terminal sequence was critical for in vivo infectivity. Here, we tested the effect of deleting the short sequence and/or the poly(U) tract from pGBB; infectivity of each mutant was tested by intrahepatic transfection of two tamarins with transcribed RNA. A mutant lacking both regions was not viable. However, mutants lacking either the short sequence or the poly(U) tract were viable. All four tamarins had a wild-type-like acute infection and developed acute hepatitis. Whereas we found that five tamarins transfected with the wild-type clone pGBB had acute resolving infection, one tamarin transfected with the poly(U) deletion mutant became persistently infected. This animal had viremia and hepatitis until its death at week 90. The genomes recovered at weeks 2, 7, 15, 20, 60, and 90 lacked the poly(U) stretch. Eight amino acid changes were identified at week 90. One change, in the putative p7 protein, was dominant at week 15. Thus, persistence of GBV-B, like persistence of HCV, was associated with the emergence of virus variants. Four tamarins inoculated with serum collected at weeks 2 and 90 from the tamarin with persistent infection had an acute resolving infection. Nonetheless, the demonstration that GBV-B can persist in tamarins strengthens its relevance as a surrogate model for the study of HCV. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. BIOQUAL Inc, Rockville, MD USA. Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 50,Room 6529,50 S Dr,MSC 8009, Bethesda, MD 20892 USA. EM jbukh@maid.nih.gov NR 35 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 17 BP 9389 EP 9399 DI 10.1128/JVI.78.17.9389-9399.2004 PG 11 WC Virology SC Virology GA 847IT UT WOS:000223386600042 PM 15308733 ER PT J AU Krishnan, V Zeichner, SL AF Krishnan, V Zeichner, SL TI Host cell gene expression during human immunodeficiency virus type I latency and reactivation and effects of targeting genes that are differentially expressed in viral latency SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; HIV-1 INFECTION; HUMAN CYTOMEGALOVIRUS; MICROARRAY ANALYSIS; TRANSCRIPTIONAL ACTIVATION; ANTIRETROVIRAL THERAPY; PROTEASOME INHIBITION; CDNA MICROARRAYS; RNA-SYNTHESIS; ANTIGEN AB The existence of reservoirs of cells latently infected with human immunodeficiency virus (HIV) is a major obstacle to the elimination of HIV infection. We studied the changes in cellular gene expression that accompany the reactivation and completion of the lytic viral cycle in cell lines chronically infected with HIV-1. We found that several genes exhibited altered expression in the chronically infected cells compared to the uninfected parental cells prior to induction into lytic replication. A number of gene classes showed increased expression in the chronically infected cells, notably including genes encoding proteasomes, histone deacetylases, and many transcription factors. Following induction of the lytic replication cycle, we observed ordered, time-dependent changes in the cellular gene expression pattern. Approximately 1,740 genes, many of which fall into 385 known pathways, were differentially expressed (P < 0.001), indicating that completion of the HIV replication cycle is associated with distinct, temporally ordered changes in host cell gene expression. Maximum changes were observed in the early and intermediate phases of the lytic replication cycle. Since the changes in gene expression in chronically infected cells suggested that cells latently infected with HIV have a different gene expression profile than corresponding uninfected cells, we studied the expression profiles of three different chronically infected cell lines to determine whether they showed similar changes in common cellular genes and pathways. Thirty-two genes showed significant differential expression in all cell lines studied compared to their uninfected parental cell lines. Notable among them were cdc42 and lyn, which were downregulated and are required for HIV Nef binding and viral replication. Other genes previously unrelated to HIV latency or pathogenesis were also differentially expressed. To determine the effects of targeting products of the genes that were differentially expressed in latently infected cells, we treated the latently infected cells with a proteasome inhibitor, clastolactacystin-beta-lactone (CLBL), and an Egr1 activator, resveratrol. We found that treatment with CLBL and resveratrol stimulated lytic viral replication, suggesting that treatment of cells with agents that target cellular genes differentially expressed in latently infected cells can stimulate lytic replication. These findings may offer new insights into the interaction of the latently infected host cell and HIV and suggest therapeutic approaches for inhibiting HIV infection and for manipulating cells latently infected with HIV so as to trigger lytic replication. C1 NCI, HIV & AIDS Malignancy Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Zeichner, SL (reprint author), NCI, HIV & AIDS Malignancy Branch, Natl Inst Hlth, Bldg 10,Room 10S255,MSC 1868,10 Ctr Dr, Bethesda, MD 20892 USA. EM zeichner@nih.gov NR 72 TC 73 Z9 79 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 17 BP 9458 EP 9473 DI 10.1128/JVI.78.17.9458-9473.2004 PG 16 WC Virology SC Virology GA 847IT UT WOS:000223386600048 PM 15308739 ER PT J AU Moniuszko, M Fry, T Tsai, WP Morre, M Assouline, B Cortez, P Lewis, MG Cairns, S Mackall, C Franchini, G AF Moniuszko, M Fry, T Tsai, WP Morre, M Assouline, B Cortez, P Lewis, MG Cairns, S Mackall, C Franchini, G TI Recombinant interleukin-7 induces proliferation of naive macaque CD4(+) and CD8(+) T cells in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID MEMORY-LIKE PHENOTYPE; HOMEOSTATIC PROLIFERATION; DRIVEN PROLIFERATION; LYMPHOPENIC HOSTS; IL-7; CYTOKINES; SUBSETS; DIFFERENTIATION; SURVIVAL; ANTIGEN AB Interleukin-7 (IL-7) regulates T-cell homeostasis, and its availability is augmented in lymphopenic hosts. Naive CD8(+) T cells transferred to lymphopenic mice acquire a memory-like phenotype, raising the possibility that IL-7 is the biological mediator of this effect. Here, we provide direct evidence that IL-7 induces the acquisition of memory-cell markers not only in CD8(+) T cells but also in CD4(+) T-cell subsets in immune-competent Indian rhesus macaques. The increase of these memory-like populations was dependent on the dose of the cytokine, and these cells were found in the blood as well as secondary lymphoid organs. Memory-like CD4(+) and CD8(+) T cells acquired the ability to secrete tumor necrosis factor alpha and, to a lesser extent, gamma interferon following stimulation with a cognate antigen. The phenotypic change observed in naive T cells was promptly reversed after discontinuation of IL-7. Importantly, IL-7 induced cycling of both CD4(+) and CD8(+) central memory and effector memory T cells, demonstrating its contribution to the maintenance of the entire T-cell pool. Thus, IL-7 may be of benefit in the treatment of iatrogenic or virus-induced T-cell depletion. C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NCI, Immunol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Henry Jackson Fdn, Bethesda, MD USA. Cytheris, Vanves, France. Bioqual, Rockville, MD USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Bldg 41,Rm D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov NR 32 TC 64 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 18 BP 9740 EP 9749 DI 10.1128/JVI.78.18.9740-9749.2004 PG 10 WC Virology SC Virology GA 851QY UT WOS:000223701100018 PM 15331707 ER PT J AU Prentice, E McAuliffe, J Lu, XT Subbarao, K Denison, MR AF Prentice, E McAuliffe, J Lu, XT Subbarao, K Denison, MR TI Identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins SO JOURNAL OF VIROLOGY LA English DT Article ID MOUSE HEPATITIS-VIRUS; LENGTH INFECTIOUS CDNA; SARS-CORONAVIRUS; GENE POLYPROTEIN; REVERSE GENETICS; RNA-POLYMERASE; VIRAL-RNA; IN-VITRO; GENOME; LOCALIZATION AB The severe acute respiratory syndrome coronavirus (SARS-CoV) encodes proteins required for RNA transcription and genome replication as large polyproteins that are proteolytically processed by virus-encoded proteinases to produce mature replicase proteins. In this report, we generated antibodies against SARS-CoV predicted replicase protein and used the antibodies to identify and characterize 12 of the 16 predicted mature replicase proteins (nsp1, nsp2, nsp3, nsp4, nsp5, nsp8, nsp9, nsp12, nsp13, nsp14, nsp15, and nsp16) in SARS-CoV-infected Vero cells. Immunoblot analysis of infected-cell lysates identified proteins of the predicted sizes. Immunofluorescence microscopy detected similar patterns of punctate perinuclear and distributed cytoplasmic foci with all replicase antibodies and as early as 6 h postinfection. Dual-labeling studies demonstrated colocalization of replicase protein nsp8 with nsp2 and nsp3 in cytoplasmic complexes and also with LC3, a protein marker for autophagic vacuoles. Antibodies directed against mouse hepatitis virus (MHV) virions and against the putative RNA-dependent RNA polymerase (Pol) detected SARS-CoV nucleocapsid and nsp12 (Pol), respectively, in SARS-CoV-infected Vero cells. These results confirm the predicted protein processing pattern for mature SARS-CoV replicase proteins, demonstrate localization of replicase proteins to cytoplasmic complexes containing markers for autophagosome membranes, and suggest conservation of protein epitopes in the replicase and nucleocapsid of SARS-CoV and the group II coronavirus, MHV. Further, the results demonstrate the ability of replicase antibodies to detect SARS-CoV-infected cells as early as 6 h postinfection and thus represent important tools for studies of SARS-CoV replication, inhibition, and diagnosis. C1 Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Denison, MR (reprint author), Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, D6217 MCN, Nashville, TN 37232 USA. EM mark.denison@vanderbilt.edu FU NCI NIH HHS [CA68485, P30 CA068485]; NHLBI NIH HHS [5 T32 HL07751, T32 HL007751]; NIAID NIH HHS [AI50083-S1, R01 AI050083]; NIDDK NIH HHS [P30 DK020593, DK20593, P60 DK020593] NR 39 TC 120 Z9 131 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 18 BP 9977 EP 9986 DI 10.1128/JVI.78.18.9977-9986.2004 PG 10 WC Virology SC Virology GA 851QY UT WOS:000223701100042 PM 15331731 ER PT J AU Boyer, PL Imamichi, T Sarafianos, SG Arnold, E Hughes, SH AF Boyer, PL Imamichi, T Sarafianos, SG Arnold, E Hughes, SH TI Effects of the Delta 67 complex of mutations in human immunodeficiency virus type 1 reverse transcriptase on nucleoside analog excision SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-ACID DELETION; ZIDOVUDINE RESISTANCE MUTATIONS; BETA-3-BETA-4 HAIRPIN LOOP; PRIMER UNBLOCKING; DRUG-RESISTANCE; PHENOTYPIC SUSCEPTIBILITY; MOLECULAR-MECHANISMS; SELECTIVE EXCISION; THYMIDINE ANALOG; T-LYMPHOCYTES AB Long-term use of combination therapy against human immunodeficiency virus type (HIV-1) provides strong selective pressure on the virus, and HIV-1 variants that are resistant to multiple inhibitors have been isolated. HIV-1 variants containing amino acid substitutions within the coding region of HIV-1 reverse transcriptase (RT), such as the 3'-azido-3'-deoxythymidine (AZT)-resistant variant AZT-R (M41L/D67N/K70R/T215Y/K219Q) and a variant containing an insertion in the fingers domain (S(69)SGR(70)/T215Y), are resistant to the nucleoside RT inhibitor (NRTI) AZT because of an increase in the level of excision of AZT monophosphate (AZTMP) from the primer. While rare, variants have also been isolated which contain deletions in the RT coding region. One such virus, described by Imamichi et al. (J. Virol 74:10958-10964, 2000; J. Virol. 74:10231028, 2000; J. Virol. 75:3988-3992, 2001), contains numerous amino acid substitutions and a deletion of codon 67, which we have designated the Delta67 complex of mutations. We have expressed and purified HIV-1 RT containing these mutations. We compared the polymerase and pyrophosphorolysis (excision) activity of an RT with the Delta67 complex of mutations to wild-type RT and the two other AZT-resistant variants described above. All of the AZT-resistant variants we tested excise AZTMP and 9- [2-(R)-(phosphonomethoxy)propyl] adenine (PMPA [tenofovir]) from the end of a primer more efficiently than wild-type RT. Although the variant RTs excised d4TMP less efficiently than AZTMP and PMPA, they were able to excise d4TMP more efficiently than wild-type RT. HIV-1 RT containing the Delta67 complex of mutations was not able to excise as broad a range of NRTIs as the fingers insertion variant SSGR/T215Y, but it was able to polymerize efficiently with low concentrations of deoxynucleoside triphosphates and seems to be able to excise AZTMP and PMPA at lower ATP concentrations than AZT-R or SSGR/T215Y, suggesting that a virus containing the Delta67 complex of mutations would replicate reasonably well in quiescent cells, even in the presence of AZT. C1 NCI, FCRDC, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, SAIC Frederick, Frederick, MD 21702 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ USA. RP Hughes, SH (reprint author), NCI, FCRDC, HIV Drug Resistance Program, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov NR 38 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 18 BP 9987 EP 9997 DI 10.1128/JVI.78.18.9987-9997.2004 PG 11 WC Virology SC Virology GA 851QY UT WOS:000223701100043 PM 15331732 ER PT J AU Rucker, E Munch, J Wildum, S Brenner, M Eisemann, J Margolis, L Kirchhoff, F AF Rucker, E Munch, J Wildum, S Brenner, M Eisemann, J Margolis, L Kirchhoff, F TI A naturally occurring variation in the proline-rich region does not attenuate human immunodeficiency virus type 1 Nef function SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-SURFACE CD4; DOWN-REGULATION; HIV-1 NEF; VIRAL REPLICATION; ENV INCORPORATION; CLASS-II; T-CELLS; EXPRESSION; INFECTIVITY; MODULATION AB We analyzed human immunodeficiency virus type 1 (HIV-1) Nef variants to further evaluate the functional relevance of the R71T substitution previously proposed to attenuate viral replication (Fackler et al., Curr. Biol. 11:1294-1299, 2001). Our results demonstrate that this variation in the proline-rich region does not significantly affect the functional activity of Nef or HIV-1 infectivity or replication. C1 Univ Ulm Klinikum, Dept Virol, D-89081 Ulm, Germany. Univ Erlangen Nurnberg, Dept Dermatol, Erlangen, Germany. NICHHD, Lab Mol & Cellular Biophys, NIH, Bethesda, MD 20892 USA. RP Kirchhoff, F (reprint author), Univ Ulm Klinikum, Dept Virol, Albert Einstein Allee 11, D-89081 Ulm, Germany. EM frank.kirchhoff@medizin.uni-ulm.de NR 29 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2004 VL 78 IS 18 BP 10197 EP 10201 DI 10.1128/JVI.78.18.10197-10201.2004 PG 5 WC Virology SC Virology GA 851QY UT WOS:000223701100064 PM 15331753 ER PT J AU Antani, S Lee, DJ Long, LR Thoma, GR AF Antani, S Lee, DJ Long, LR Thoma, GR TI Evaluation of shape similarity measurement methods for spine X-ray images SO JOURNAL OF VISUAL COMMUNICATION AND IMAGE REPRESENTATION LA English DT Article DE content-based image retrieval; medical image databases; shape representation; performance evaluation ID CONTENT-BASED RETRIEVAL; PATTERN-RECOGNITION; PLANAR CURVES; REPRESENTATION; DATABASES; MULTISCALE; DESCRIPTORS AB Efficient content-based image retrieval (CBIR) of biomedical images is a challenging problem. Feature representation algorithms used in indexing medical images on the pathology of interest have to address conflicting goals of reducing feature dimensionality while retaining important and often subtle biomedical features. At the Lister Hill National Center for Biomedical Communications, an intramural R&D division of the U.S. National Library of Medicine, we are developing CBIR prototype for digitized images of a collection of 17,000 cervical and lumbar spine X-rays taken as a part of the second National Health and Nutrition Examination Survey (NHANES 11). The vertebra shape effectively describes various pathologies identified by medical experts as being consistently and reliably found in the image collection. A suitable shape algorithm must represent shapes in low dimension, be invariant to rotation, translation, and scale transforms, and retain relevant pathology. Additionally, supported similarity algorithms must be useful in retrieving images that are relevant to the queries posed by the intended target community, viz. medical researchers, physicians, etc. This paper describes an evaluation of two popular shape similarity methods from the literature on a set of 250 vertebra boundary shapes. The polygon approximation method achieved a performance score of 55.94% and bettered the Fourier descriptor algorithm which had a performance score of 46.96%. (C) 2004 Elsevier Inc. All rights reserved. C1 US Dept HHS, Natl Lib Med, NIH, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. Brigham Young Univ, Dept Elect & Comp Engn, Provo, UT 84602 USA. RP US Dept HHS, Natl Lib Med, NIH, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. EM antani@nlm.nih.gov RI Rohlf, F/A-8710-2008; OI Antani, Sameer/0000-0002-0040-1387 NR 38 TC 26 Z9 28 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-3203 EI 1095-9076 J9 J VIS COMMUN IMAGE R JI J. Vis. Commun. Image Represent. PD SEP PY 2004 VL 15 IS 3 BP 285 EP 302 DI 10.1016/j.jvcir.2004.04.005 PG 18 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA 863WC UT WOS:000224593100003 ER PT J AU Burkholder, TH Jensen, J Chen, H Junkins, K Chatfield, J Boothe, D AF Burkholder, TH Jensen, J Chen, H Junkins, K Chatfield, J Boothe, D TI Plasma evaluation for ivermectin in llamas (Lama glama) after standard subcutaneous dosing SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE Iverinectin; llama; Lama glama; pharmacokinetic; parasites ID PHARMACOKINETICS; CATTLE AB Plasma levels of the parasiticide ivermectin were studied by high-performance liquid chromatography in five llamas (Lama glama) after single 200 mug/kg s.c. injections. Ivermectin levels were undetectable in plasma samples drawn up to 4 wk after injection, suggesting that the dosage used was insufficient to reach therapeutic concentrations in this species. C1 Texas A&M Univ, Dept Large Anim Med & Surg, College Stn, TX 77843 USA. Texas A&M Univ, Vet Teaching Hosp, College Stn, TX 77843 USA. Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. RP Burkholder, TH (reprint author), NIH, Div Vet Resources, 9000 Rockville Pike,Bldg 28,Room 104, Bethesda, MD 20892 USA. NR 8 TC 11 Z9 12 U1 0 U2 3 PU AMER ASSOC ZOO VETERINARIANS PI MEDIA PA 6 NORTH PENNELL ROAD, MEDIA, PA 19063 USA SN 1042-7260 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD SEP PY 2004 VL 35 IS 3 BP 395 EP 396 DI 10.1638/03-047 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 857UH UT WOS:000224143400017 PM 15526897 ER PT J AU Bleyer, AJ Hart, TC Shihabi, Z Robins, V Hoyer, JR AF Bleyer, AJ Hart, TC Shihabi, Z Robins, V Hoyer, JR TI Mutations in the uromodulin gene decrease urinary excretion of Tamm-Horsfall protein SO KIDNEY INTERNATIONAL LA English DT Article DE Tamm-Horsfall protein; familial juvenile hyperuricemic nephropathy; medullary cystic kidney disease; uromodulin-associated kidney disease; human ID JUVENILE HYPERURICEMIC NEPHROPATHY; RENAL-DISEASE; UMOD GENE; GLYCOPROTEIN; RADIOIMMUNOASSAY; UROPONTIN; CLUSTER; MCKD; ACID AB Background. Mutations in the uromodulin (UMOD) gene that encodes Tamm-Horsfall protein (THP) cause an autosomal-dominant form of chronic renal failure. We have now investigated effects of UMOD gene mutations on protein expression by quantitatively measuring THP excretion. Methods. THP excretion was determined by enzyme-linked immunosorbent assay (ELISA) of urine collections obtained from 16 related individuals with a 27 bp deletion in the UMOD gene and seven individuals with other UMOD mutations. THP excretion of 22 control subjects (18 genetically related individuals and four spouses in the UMOD deletion family) was also determined. Results. The 16 individuals carrying the deletion mutation excreted 5.8 +/- 6.3 mg THP/g creatinine into their urine. The 18 unaffected relatives from the same family excreted 40.8 +/- 9.7 mg THP/g creatinine (P < 0.0001) and the four spouses excreted 43.9 +/- 25.1 mg THP/g creatinine (P < 0.0001 vs. individuals with the deletion mutation). THP excretion of sevem individuals with other UMOD gene mutations was also extremely low (range of 0.14 to 5.9 mg THP/g creatinine). All individuals with UMOD mutations had low THP excretion, irrespective of gender, glomerular filtration rate (GFR), or age. Conclusion. These studies quantitatively show that the autosomal-dominant gene mutations responsible for UMOD-associated kidney disease cause a profound reduction of THP excretion. We speculate that this suppression of normal THP excretion reflects deleterious effects of mutated THP within the kidney. Such effects may also play an important role in the pathogenesis of the progressive renal failure observed in patients with UMOD gene mutations. C1 Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC 27157 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. Natl Inst Dent & Craniofacial Res, Human & Craniofacial Genet Sect, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Med Ctr, Dept Pathol, Winston Salem, NC 27103 USA. Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Bleyer, AJ (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM ableyer@wfubmc.edu; hoyer@email.chop.edu FU NIDDK NIH HHS [DK62252, DK33501] NR 24 TC 55 Z9 57 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2004 VL 66 IS 3 BP 974 EP 977 DI 10.1111/j.1523-1755.2004.00845.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 845EB UT WOS:000223217700015 PM 15327389 ER PT J AU Ries, M Bettis, KEB Choyke, P Kopp, JB Austin, HA Brady, RO Schiffmann, R AF Ries, M Bettis, KEB Choyke, P Kopp, JB Austin, HA Brady, RO Schiffmann, R TI Parapelvic kidney cysts: A distinguishing feature with high prevalence in Fabry disease SO KIDNEY INTERNATIONAL LA English DT Article DE male; genetics; kidney; sinus; cyst; lyososmal; Fabry disease ID NATURAL-HISTORY; CLINICAL MANIFESTATIONS; REPLACEMENT THERAPY; INVOLVEMENT; HETEROZYGOTES; ANGIOKERATOMA; DIAGNOSIS AB Backgound. Fabry disease is an X-linked generalized progressive debilitating lysosomal storage disorder. The disease usually manifests in childhood, but the diagnosis is often made following the occurrence of late-stage complications such as progressive kidney failure. In order to identify key novel renal diagnostic imaging features of Fabry disease, we conducted a cross sectional case-control study of kidney involvement in patients with Fabry disease. Methods. Twenty-four patients (mean age 36.1 +/- 8.1 years, median 37 years, range 20 to 48 years) with chronic neuropathic pain who were enrolled in an enzyme replacement trial underwent prospective renal imaging evaluation with magnetic resonance imaging (MRI) and computed tomography (CT) at the National Institutes of Health, Bethesda, Maryland. We concurrently enrolled 19 age-matched healthy controls (mean age 34.6 +/- 12.0 years, median 33 years, range 18 to 61 years). The presence and localization of kidney cysts as well as the ratio of the signal intensity between medulla and cortex were determined. Results. Fifty percent of the Fabry disease patients had renal sinus cysts, compared to one individual (7%) in the control group. The ratio of the signal intensity between medulla and cortex on T2-weighted scans in Fabry disease patients with sinus cysts was elevated compared with Fabry disease patients without cysts (P= 0.0083), and elevated in Fabry disease patients without cysts compared with normal controls without cysts (P= 0.0173). Conclusion. The finding of multiple renal sinus cysts in the workup of a patient with kidney disease patient should strongly suggest the consideration of Fabry disease in the differential diagnosis. The cause of such cysts in Fabry disease remains to be elaborated. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Funct MR Facil, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Ries, M (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mr380t@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X NR 32 TC 23 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2004 VL 66 IS 3 BP 978 EP 982 DI 10.1111/j.1523-1755.2004.00846.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 845EB UT WOS:000223217700016 PM 15327390 ER PT J AU Cusick, M Chew, EY Hoogwerf, B Agron, E Wu, L Lindley, A Ferris, FL AF Cusick, M Chew, EY Hoogwerf, B Agron, E Wu, L Lindley, A Ferris, FL TI Risk factors for renal replacement therapy in the Early Treatment Diabetic Retinopathy Study (ETDRS), Early Treatment Diabetic Retinopathy Study Report No. 26 SO KIDNEY INTERNATIONAL LA English DT Article DE diabetic nephropathy; renal replacement therapy ID VASCULAR-DISEASE; BLOOD-PRESSURE; NEPHROPATHY; MICROALBUMINURIA; PROGRESSION; MELLITUS; ALBUMINURIA; COMPLICATIONS; PROTEINURIA; INSUFFICIENCY AB Background. Diabetes is a leading cause of end-stage renal disease (ESRD). The purpose of this study is to assess the risk factors for renal replacement therapy (RRT) in the Early Treatment Diabetic Retinopathy Study (ETDRS). Methods. We examined demographic, clinical, and laboratory characteristics of the 2226 subjects with complete laboratory data enrolled in the ETDRS. The primary renal variable evaluated was the time to development of renal replacement therapy, defined as the need for dialysis or transplantation. Multivariable Cox proportional hazards regression was used to assess risk factors for type 1 and type 2 diabetes separately. Results. The 5-year estimated incidence of RRT in the entire ETDRS population was 10.2% and 9.8% for patients with type 1 and type 2 diabetes, respectively. Of those patients with complete data, 127 of 934 (14%) of patients with type 1 diabetes, and 150 of 1292 (12%) patients with type 2 diabetes required RRT during the study. Baseline risk factors common to type 1 and type 2 diabetes included elevated total cholesterol, and serum creatinine; and low serum albumin and anemia. Other risk factors significant in type 1 diabetes included body mass index (BMI), shorter duration of diabetes, elevated hemoglobin A(1c) (HbA(1c)), elevated systolic blood pressure, and the development of proliferative diabetic retinopathy. Risk factors significant in type 2 diabetes, but not type 1 diabetes, included younger age, proteinuria, and elevated triglycerides. Conclusion. In this study, major modifiable risk factors such as hypertension, dyslipidemia, and hyperglycemia were found to be predictive of RRT. Other predictors were markers of vascular pathology and inflammation, proteinuria, hypoalbuminemia, and increased serum creatinine. Controlled clinical trials with treatment strategies that improve serum lipid levels, systemic blood pressure, glycemic control, and markers of inflammation may be important in furthering our knowledge on the pathogenesis of diabetic complications such as nephropathy and ESRD. C1 NEI, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Natl Inst Hlth Res Scholar, Bethesda, MD 20817 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. EMMES Corp, Potomac, MD USA. RP Chew, EY (reprint author), NEI, NIH, Bldg 31,Room 6A52,31 Ctr Dr MSC-2510, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 39 TC 37 Z9 38 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2004 VL 66 IS 3 BP 1173 EP 1179 DI 10.1111/j.1523-1755.2004.00869.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 845EB UT WOS:000223217700040 PM 15327414 ER PT J AU Nadon, NL AF Nadon, NL TI Maintaining aged rodents for biogerontology research SO LAB ANIMAL LA English DT Article ID ENVIRONMENTAL ENRICHMENT; SURVIVAL CHARACTERISTICS; STEREOTYPED BEHAVIOR; DIETARY RESTRICTION; C57BL/6 MICE; ACTIVE-RATS; DISEASE; MOUSE; STRAINS; MODELS AB Aged rodents present unique concerns for both husbandry staff and investigators. Choosing the correct rodent model and providing the appropriate care are important elements for successful use of rodent models in biogerontology research programs. The author discusses issues to be evaluated when housing and using aged rodents. C1 NIA, Off Biol Resources & Resource Dev, Bethesda, MD 20892 USA. RP Nadon, NL (reprint author), NIA, Off Biol Resources & Resource Dev, 7201 Wisconsin Ave,Ste 2C231, Bethesda, MD 20892 USA. EM nadonn@nia.nih.gov NR 28 TC 20 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2004 VL 33 IS 8 BP 36 EP 41 DI 10.1038/laban0904-36 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 852AK UT WOS:000223727400009 PM 15334110 ER PT J AU Calvisi, DF Ladu, S Conner, EA Factor, VM Thorgeirsson, SS AF Calvisi, DF Ladu, S Conner, EA Factor, VM Thorgeirsson, SS TI Disregulation of E-cadherin in transgenic mouse models of liver cancer SO LABORATORY INVESTIGATION LA English DT Article DE angiogenesis; beta-catenin; E-cadherin; HCC; hypoxia; transgenic mice ID HUMAN HEPATOCELLULAR-CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; BETA-CATENIN; C-MYC; FACTOR EXPRESSION; CELL-ADHESION; ANGIOGENESIS; PROGRESSION; CARCINOGENESIS AB E-cadherin is a cell-cell adhesion molecule that plays a pivotal role in the development and maintenance of cell polarity. Disruption of E-cadherin-mediated adhesion represents a key step toward the invasive phenotype in a variety of solid tumors, including hepatocellular carcinoma (HCC). Here, we investigate whether deregulation of E-cadherin occurs along the multistep process of hepatocarcinogenesis in transgenic mouse models, including c-Myc, E2F1, c-Myc/TGF-alpha and c-Myc/E2F1 mice. Liver tumors from the transgenic mouse lines could be divided into two categories based on E-cadherin levels. Of 28, 20 (71.4%) c-Myc HCCs showed marked reduction of E-cadherin expression when compared with wild-type livers. In contrast, all of c-Myc/TGF-alpha and the majority of E2F1 and c-myc/E2F1 preneoplastic and neoplastic lesions exhibited overexpression of E-cadherin. Downregulation of E-cadherin was associated with promoter hypermethylation in seven of 20 c-Myc HCCs (35%), while no loss of heterozygosity at the E-cadherin locus was detected. Nuclear accumulation of beta-catenin did not correlate with E-cadherin downregulation. Furthermore, c-Myc HCCs with reduced E-cadherin displayed upregulation of hypoxia-inducible factor-la and vascular endothelial growth factor proteins. Importantly, loss of E-cadherin was associated with increased cell proliferation and higher microvessel density in c-Myc tumors. Taken together, these data suggest that loss of E-cadherin might favor tumor progression in relatively more benign HCC from c-Myc transgenic mice by stimulating neoplastic proliferation and angiogenesis under hypoxic conditions. C1 NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, 37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 59 TC 35 Z9 41 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 2004 VL 84 IS 9 BP 1137 EP 1147 DI 10.1038/labinvest.3700147 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 847WY UT WOS:000223429900008 PM 15220935 ER PT J AU Donoghue, HD Spigelman, M Greenblatt, CL Lev-Maor, G Bar-Gal, GK Matheson, C Vernon, K Nerlich, AG Zink, AR AF Donoghue, HD Spigelman, M Greenblatt, CL Lev-Maor, G Bar-Gal, GK Matheson, C Vernon, K Nerlich, AG Zink, AR TI Tuberculosis: from prehistory to Robert Koch, as revealed by ancient DNA SO LANCET INFECTIOUS DISEASES LA English DT Review ID POLYMERASE-CHAIN-REACTION; COMPLETE GENOME SEQUENCE; 1918 SPANISH INFLUENZA; MYCOBACTERIUM-TUBERCULOSIS; MOLECULAR ANALYSIS; COMPLEX DNA; GENETIC DIVERSITY; OLD; REMAINS; IDENTIFICATION AB During the past 10 years palaeomicrobiology, a new scientific discipline, has developed. The study of ancient pathogens by direct detection of their DNA has answered several historical questions and shown changes to pathogens over time. However, ancient DNA (aDNA) continues to be controversial and great care is needed to provide valid data. Here we review the most successful application of the technology, which is the study of tuberculosis. This has provided direct support for the current theory of Mycobacterium tuberculosis evolution, and suggests areas of investigation for the interaction of M tuberculosis with its host. C1 UCL, Ctr Infect Dis & Int Hlth, London W1T 4JF, England. Hebrew Univ Jerusalem, Hadassah Med Sch, Kuvin Ctr Study Infect & Trop Dis, IL-91010 Jerusalem, Israel. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Lakehead Univ, Paleo DNA Lab, Fac Sci & Environm Studies, Thunder Bay, ON P7B 5E1, Canada. Univ Queensland, Dept Zool, Brisbane, Qld, Australia. Acad Teaching Hosp, Div Palaeopathol, Inst Pathol, Munich, Germany. RP Donoghue, HD (reprint author), UCL, Ctr Infect Dis & Int Hlth, 46 Cleveland St, London W1T 4JF, England. EM h.donoghue@ucl.ac.uk RI Donoghue, Helen/D-6805-2013; Zink, Albert/P-4024-2015 OI Zink, Albert/0000-0002-1461-747X NR 84 TC 88 Z9 97 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2004 VL 4 IS 9 BP 584 EP 592 DI 10.1016/S1473-3099(04)01133-8 PG 9 WC Infectious Diseases SC Infectious Diseases GA 851QI UT WOS:000223699500024 PM 15336226 ER PT J AU Miller, N Tyler, RJ Backus, JEB AF Miller, N Tyler, RJ Backus, JEB TI MedlinePlus (R): The National Library of Medicine (R) brings quality information to health consumers SO LIBRARY TRENDS LA English DT Article ID INTERNET AB The National Library of Medicine's (NLM(R)) MedlinePlus(R) is a high-quality gateway to consumer health information from NLM, the National Institutes of Health (NIH), and other authoritative organizations. For decades, NLM has been a leader in indexing, organizing, and distributing health information to health professionals. In creating MedlinePlus, NLM uses years of accumulated expertise and technical knowledge to produce an authoritative, reliable consumer health Web site. This article describes the development of MedlinePlus-its quality control processes, the integration of NLM and NIH information, NLM's relationship to other institutions, the technical and staffing infrastructures, the use of feedback for quality improvement, and future plans. C1 Natl Lib Med, Publ Hlth Div, Bethesda, MD 20892 USA. Natl Lib Med, Reference & Customer Serv Sect, Bethesda, MD 20892 USA. RP Miller, N (reprint author), Natl Lib Med, Publ Hlth Div, 8600 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 5 U1 0 U2 1 PU GSLIS PUBLICATIONS PI CHAMPAIGN PA 501 E DANIEL ST, CHAMPAIGN, IL 61820-6211 USA SN 0024-2594 J9 LIBR TRENDS JI Libr. Trends PD FAL PY 2004 VL 53 IS 2 BP 375 EP 388 PG 14 WC Information Science & Library Science SC Information Science & Library Science GA 893IG UT WOS:000226711900009 ER PT J AU Belvedere, O Fasola, G Rossetto, C Sibau, A Vigevani, E Adami, G Rizzato, S Spizzo, R Tumolo, S Grossi, F AF Belvedere, O Fasola, G Rossetto, C Sibau, A Vigevani, E Adami, G Rizzato, S Spizzo, R Tumolo, S Grossi, F TI A phase II study of irinotecan plus docetaxel in previously treated advanced non-small-cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary Group Study (ATOM 007) SO LUNG CANCER LA English DT Meeting Abstract CT 9th Central European Lung Cancer Conference CY SEP 23-25, 2004 CL Gdansk, POLAND SP Int Assoc Study Lung Canc, European Org Res & Treatment Canc, Polish Oncol Soc, Polish Phthisiopneumon Soc C1 AOSMM PUGD, Dept Med Oncol, Udine, Italy. Unit Oncol, Tolmezzo, Italy. Unit Oncol, San Daniele del Friuli, Italy. Unit Oncol, S Vito Tagliamento, Italy. Dept Med Oncol, Pordenone, Italy. Natl Canc Inst, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD SEP PY 2004 VL 45 SU 3 BP S78 EP S79 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 860CH UT WOS:000224315400161 ER PT J AU Grossi, F Fasola, G Meduri, S Barbone, F Rossetto, C Follador, A Zanin, T Cassetti, R Pignata, G Belvedere, O AF Grossi, F Fasola, G Meduri, S Barbone, F Rossetto, C Follador, A Zanin, T Cassetti, R Pignata, G Belvedere, O TI Screening for mesothelioma and lung cancer with low-dose spiral computed tomography (LDCT) in asbestos-exposed subjects: an Alpe-Adria Thoracic Oncology Multidisciplinary Group Study (ATOM 002) SO LUNG CANCER LA English DT Meeting Abstract CT 9th Central European Lung Cancer Conference CY SEP 23-25, 2004 CL Gdansk, POLAND SP Int Assoc Study Lung Canc, European Org Res & Treatment Canc, Polish Oncol Soc, Polish Phthisiopneumon Soc C1 Natl Canc Inst, Genoa, Italy. AOSMM PUGD, Dept Med Oncol, Udine, Italy. AOSMM, Dept Radiol, Udine, Italy. Univ Udine, Epidemiol Unit, I-33100 Udine, Italy. Unit Occupat Hlth, Monfalcone, Italy. Unit Radiol, Monfalcone, Italy. Div Surg, Monfalcone, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD SEP PY 2004 VL 45 SU 3 BP S69 EP S69 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 860CH UT WOS:000224315400143 ER PT J AU Thompson, RB McVeigh, ER AF Thompson, RB McVeigh, ER TI Flow-gated phase-contrast MRI using radial acquisitions SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE gating; flow; MRI; phase contrast; complex difference ID ANGIOGRAPHY; DIFFERENCE AB Phase-contrast (PC) MRI is a noninvasive method for imaging blood and tissue velocity. PC experiments are typically segmented into many cardiac cycles in order to obtain sufficient spatial and temporal resolution, and thus require a gating signal to properly combine the data from multiple cardiac cycles. Although the surface electrode ECG is the gating waveform of choice for cardiovascular MRI, alternative gating methods are required for fetal cardiac imaging (due to the unavailability of fetal ECG signals) and for cases of ECG contamination via the strong magnetic fields within the MR scanner. This study demonstrates the feasibility of using imaging data from flow-encoded MRI experiments to derive times for cardiac gating. An undersampled radial k-space acquisition method is used to measure an image-derived flow-gating waveform in real-time, from which the gating times are derived. These gating times are used to reconstruct a conventional gated-segmented image series by combining the real-time data from multiple heartbeats. Flow-gated PC experiments were performed on five normal volunteers with slice prescriptions in four anatomic regions. The standard deviation (SD) of the difference between the flow-gating and ECG gating times ranged from 5 ms to 12 ms. Published 2004 Wiley-Liss, Inc(dagger). C1 NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Thompson, RB (reprint author), NIH, Cardiac Energet Lab, Bldg 10,10 Ctr Dr,Room B1D 416, Bethesda, MD 20892 USA. EM thompsor@nhlbi.nih.gov RI Thompson, Richard/E-9821-2011 FU Intramural NIH HHS [Z01 HL004608-08] NR 11 TC 30 Z9 30 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2004 VL 52 IS 3 BP 598 EP 604 DI 10.1002/mrm.20187 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849HL UT WOS:000223529200021 PM 15334580 ER PT J AU Susil, RC Camphausen, K Choyke, P McVeigh, ER Gustafson, GS Ning, H Miller, RW Atalar, E Coleman, CN Menard, C AF Susil, RC Camphausen, K Choyke, P McVeigh, ER Gustafson, GS Ning, H Miller, RW Atalar, E Coleman, CN Menard, C TI System for prostate brachytherapy and biopsy in a standard 1.5 T MRI scanner SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; brachytherapy; prostate; prostatic neoplasms; biopsy; interventional MRI ID CANCER; REGISTRATION; FEASIBILITY AB A technique for transperineal high-dose-rate (HDR) prostate brachytherapy and needle biopsy in a standard 1.5 T MRI scanner is demonstrated. In each of eight procedures (in four patients with intermediate to high risk localized prostate cancer), four MRI-guided transperineal prostate biopsies were obtained followed by placement of 14-15 hollow transperineal catheters for HDR brachytherapy. Mean needle-placement accuracy was 2.1 mm, 95% of needle-placement errors were less than 4.0 mm, and the maximum needle-placement error was 4.4 mm. In addition to guiding the placement of biopsy needles and brachytherapy catheters, MR images were also used for brachytherapy treatment planning and optimization. Because 1.5 T MR images are directly acquired during the interventional procedure, dependence on deformable registration is reduced and online image quality is maximized. (C) Published 2004 Wiley-Liss, Inc(dagger). C1 NCI, Radiat Oncol Branch, NIH, DHHS, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. DHHS, Dept Radiol, Ctr Clin, NIH, Bethesda, MD USA. NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD USA. William Beaumont Hosp, Dept Radiat Oncol, Royal Oak, MI USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Bilkent Univ, Dept Elect & Elect Engn, TR-06533 Ankara, Turkey. RP Menard, C (reprint author), NCI, Radiat Oncol Branch, NIH, DHHS, Bldg 10,Rm B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM menardc@mail.nih.gov RI Atalar, Ergin/D-3184-2012 OI Atalar, Ergin/0000-0002-6874-6103 FU Intramural NIH HHS [Z01 HL004608-08] NR 18 TC 83 Z9 83 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2004 VL 52 IS 3 BP 683 EP 687 DI 10.1002/mrm.20138 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 849HL UT WOS:000223529200033 PM 15334592 ER PT J AU Al Shehadat, S Smego, RA AF Al Shehadat, S Smego, RA TI Medicare reform needed for home-based low-molecular-weight heparin therapy SO MAYO CLINIC PROCEEDINGS LA English DT Letter ID DEEP-VEIN THROMBOSIS C1 Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. NIAID, Rockville, MD 20852 USA. RP Al Shehadat, S (reprint author), Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD SEP PY 2004 VL 79 IS 9 BP 1209 EP 1209 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 851UT UT WOS:000223711900019 PM 15357046 ER PT J AU Nguyen, DH Espinoza, JC Taub, DD AF Nguyen, DH Espinoza, JC Taub, DD TI Cellular cholesterol enrichment impairs T cell activation and chemotaxis SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE cholesterol enrichment; T cell activation; chemotaxis ID LIPID RAFTS; SIGNAL-TRANSDUCTION; MEMBRANE MICRODOMAINS; RECEPTOR; LYMPHOCYTES; AGE; REDISTRIBUTION; REORGANIZATION; PATHOGENESIS; MODULATION AB Human aging is associated with an increase in immune cell cholesterol levels, independent of circulating cholesterol levels. The effects of such an increase in membrane cholesterol on lipid raft-associated immune cell function have not been investigated. We sought to examine the effects of in vitro cholesterol loading on two known lipid raft-associated pathways of T cells, namely T cell activation and chemokine stimulation. Using beta-cyclodextrin (BCD) as a vehicle, we were able to rapidly load cholesterol onto human T cell lines and primary peripheral blood T cells without inducing significant cell toxicity. Loading of cholesterol to four-fold that of normal levels induced significant inhibition of intracellular calcium mobilization by both alphaCD3 and SDF-1alpha. Cholesterol-loaded peripheral T cells were completely unresponsive to alphaCD3/alphaCD28 stimulation, demonstrating no increase in IL-2, GM 1 expression or cell size. T cell polarization of lipid rafts to alphaCD3/alphaCD28 beads was also impaired. In addition, cholesterol loading potently inhibited SDF-1alpha-induced chemotaxis. We propose that excess membrame cholesterol could potentially disrupt raft-related cell functions downstream of receptor triggering and that the loss of cholesterol regulation of aging immune cells could contribute to immune cell senescence. Published by Elsevier Ireland Ltd. C1 NIA, Immunol Lab, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Nguyen, DH (reprint author), NIA, Immunol Lab, NIH, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM taubd@grc.nia.nih.gov NR 42 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD SEP PY 2004 VL 125 IS 9 BP 641 EP 650 DI 10.1016/j.mad.2004.08.002 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 873BU UT WOS:000225254600009 PM 15491683 ER PT J AU Kannel, WB AF Kannel, WB TI Lessons from curbing the coronary artery disease epidemic for confronting the impending epidemic of heart failure SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID CARDIAC-FAILURE; FRAMINGHAM; RISK; HYPERTENSION; PREVENTION; POPULATION; AWARENESS; SURVIVAL; PROFILE; TRENDS AB This article describes five decades of epidemiologic research that has contributed to an explosive expansion of knowledge about the causes and evolution of cardiovascular disease. Cardiovascular epidemiology has become a basic science of preventive cardiology and has provided vital information about predisposing but modifiable risk factors to public health workers, physicians, scientists, and basic researchers. This research also has stimulated national public health initiatives, global attention to cardiovascular disease prevention, and pharmacologic development of agents to control hypertension and dyslipidemia and controlled trials that demonstrate their efficacy. C1 Boston Univ, Sch Med, Framingham Heart Study, NHLBI, Framingham, MA 01702 USA. RP Kannel, WB (reprint author), Boston Univ, Sch Med, Framingham Heart Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM billkannel@yahoo.com FU NHLBI NIH HHS [N01-HC-38038] NR 22 TC 5 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2004 VL 88 IS 5 BP 1129 EP + DI 10.1016/j.mcna.2004.02.002 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 853TX UT WOS:000223852900002 PM 15331309 ER PT J AU Kenchaiah, S Narula, J Vasan, RS AF Kenchaiah, S Narula, J Vasan, RS TI Risk factors for heart failure SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID GROWTH-FACTOR-I; LEFT-VENTRICULAR HYPERTROPHY; OBSTRUCTIVE SLEEP-APNEA; TUMOR-NECROSIS-FACTOR; DENSITY-LIPOPROTEIN CHOLESTEROL; MODERATE ALCOHOL-CONSUMPTION; POSITIVE AIRWAY PRESSURE; DIETARY-SODIUM INTAKE; US MALE PHYSICIANS; ISOLATED SYSTOLIC HYPERTENSION AB Despite remarkable therapeutic advances in the management of patients with heart failure (HF), the mortality due to this syndrome remains high. Identifying free-living individuals who are at high risk for developing HF may allow implementing strategies that can prevent HE Prospective epidemiologic studies have identified several risk factors and risk markers for HE This article reviews current knowledge regarding conventional and newer risk markers for HE outlines possible underlying mechanisms for the increased HF risk, and provides a framework for clinical multivariate risk prediction using HF risk factors. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Calif Irvine, Coll Med, Orange, CA 92668 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Kenchaiah, Satish/A-1519-2016; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24 HL04334, N01-HC-25195] NR 221 TC 58 Z9 62 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2004 VL 88 IS 5 BP 1145 EP + DI 10.1016/j.mcan.2004.04.016 PG 30 WC Medicine, General & Internal SC General & Internal Medicine GA 853TX UT WOS:000223852900004 PM 15331311 ER PT J AU Kenchaiah, S Gaziano, JM Vasan, RS AF Kenchaiah, S Gaziano, JM Vasan, RS TI Impact of obesity on the risk of heart failure and survival after the onset of heart failure SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID OBSTRUCTIVE SLEEP-APNEA; TUMOR-NECROSIS-FACTOR; LEFT-VENTRICULAR MASS; NATRIURETIC PEPTIDE LEVELS; C-REACTIVE PROTEIN; WEIGHT-LOSS; ADIPOSE-TISSUE; INSULIN-RESISTANCE; BODY-COMPOSITION; PULMONARY-EDEMA AB Obesity has reached epidemic proportions in the United States and worldwide. Heart failure (HF) is also a major public health problem, which, despite therapeutic advances, is associated with substantial mortality The adverse impact of obesity on the cardiovascular system is being increasingly recognized, and includes a hyperdynamic circulation, subclinical cardiac structural and functional changes, and overt HE At the same time, the possible protective effect of obesity in patients with established HF has been emphasized in recent studies. This article reviews evidence from epidemiologic studies evaluating the impact of over-weight and obesity on the risk of HF, appraises published data on the prognostic significance of overweight and obesity after the onset of HE, describes the potential mechanisms underlying these associations, speculates on the clinical implications of current evidence, and suggests directions for future research. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kenchaiah, S (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM skenchaiah@rics.bwh.harvard.edu RI Kenchaiah, Satish/A-1519-2016; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24 HL04334, N01-HC-25195] NR 114 TC 59 Z9 63 U1 0 U2 12 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 2004 VL 88 IS 5 BP 1273 EP + DI 10.1016/j.mcna.2004.04.011 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA 853TX UT WOS:000223852900010 PM 15331317 ER PT J AU Tosun, D Rettmann, ME Prince, JL AF Tosun, D Rettmann, ME Prince, JL TI Mapping techniques for aligning sulci across multiple brains SO MEDICAL IMAGE ANALYSIS LA English DT Article; Proceedings Paper CT 6th International Conference on Medical Image Computing and Computer-Assisted Intervention CY NOV 15-18, 2003 CL MONTREAL, CANADA SP Robarts Res Inst, No Digital Inc DE brain; cortex; MRI; mapping; flattening; conformal mapping; partially flattened maps; mean curvature; sulci labelling ID MAGNETIC-RESONANCE IMAGES; CEREBRAL-CORTEX; COORDINATE SYSTEM; CORTICAL SURFACE; SEGMENTATION; MRI AB Visualization and mapping of function on the cortical surface is difficult because of its sulcal and gyral convolutions. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in the literature. This makes visualization and measurement possible, but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. In this paper, we describe two methods that map each hemisphere of the cortex to a portion of a sphere in a standard way. To quantify how accurately the geometric features of the cortex - i.e., sulci and gyri - are mapped into the same location, sulcal alignment across multiple brains is analyzed, and probabilistic maps for different sulcal regions are generated to be used in automatic labelling of segmented sulcal regions. (C) 2004 Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. EM dtosun@jhu.edu; rettmann@nih.gov; prince@jhu.edu RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 FU NINDS NIH HHS [R01 NS037747, R01NS37747] NR 37 TC 63 Z9 63 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 EI 1361-8423 J9 MED IMAGE ANAL JI Med. Image Anal. PD SEP PY 2004 VL 8 IS 3 BP 295 EP 309 DI 10.1016/j.media.2004.06.020 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 857AS UT WOS:000224088300014 PM 15450224 ER PT J AU Irwin, ML Mctiernan, A Bernstein, L Gilliland, FD Baumgartner, R Baumgartner, K Ballard-Barbash, R AF Irwin, ML Mctiernan, A Bernstein, L Gilliland, FD Baumgartner, R Baumgartner, K Ballard-Barbash, R TI Physical activity levels among breast cancer survivors SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE exercise; fitness; patient; treatment; weight; race ID WOMEN; DIAGNOSIS; OBESITY; ADULTS; HEALTH; RISK AB Introduction: Obesity and weight gain are negative prognostic factors for breast cancer survival. Physical activity (PA) prevents weight gain and may decrease obesity. Little information exists on PA levels among cancer survivors. We assessed PA, including the proportion of breast cancer survivors engaging in recommended levels, by categories of adiposity, age, disease stage, and ethnicity in 806 women with stage 0-IIIA breast cancer participating in the Health, Eating, Activity, and Lifestyle Study. Methods: Black, non-Hispanic white, and Hispanic breast cancer survivors were recruited into the study through Surveillance Epidemiology End Results registries in New Mexico, Western Washington, and Los Angeles County, CA. Types of sports and household activities and their frequency and duration within the third yr after diagnosis were assessed during an in-person interview. Results: Thirty-two percent of breast cancer survivors participated in recommended levels of PA defined as 150 min(.)wk(-1) of moderate- to vigorous-intensity sports/recreational PA. When moderate-intensity household and gardening activities were included in the definition, 73% met the recommended level of PA. Fewer obese breast cancer survivors met the recommendation than overweight and lean breast cancer survivors (P < 0.05). Fewer black breast cancer survivors met the recommendation compared with non-Hispanic white and Hispanic breast cancer survivors (P < 0.05). Conclusions: Most of the breast cancer survivors were not meeting the PA recommendations proposed for the general adult population. Efforts to encourage and facilitate PA among these women would be an important tool to decrease obesity, prevent postdiagnosis weight gain, and improve breast cancer prognosis. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Irwin, ML (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu FU NCI NIH HHS [N01 CN005228, N01 PC035138-22, N01 PC067010, N01-CN-05228, N01-CN-75036-20, T32 CA009661, T32 CA09661]; NCRR NIH HHS [M01 RR000037, M01-RR-00037]; NICHD NIH HHS [N01-HD-3-3175] NR 24 TC 169 Z9 171 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD SEP PY 2004 VL 36 IS 9 BP 1484 EP 1491 DI 10.1249/01.MSS.0000074670.03001.98 PG 8 WC Sport Sciences SC Sport Sciences GA 855IP UT WOS:000223967100004 PM 15354027 ER PT J AU Dimitrakakis, C Jones, RA Liu, A Bondy, CA AF Dimitrakakis, C Jones, RA Liu, A Bondy, CA TI Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE menopause; hormone therapy; estrogen; androgen ID REPLACEMENT THERAPY; ESTROGEN; PROGESTIN; BENEFITS; RISKS AB Objective: There is now convincing evidence that usual hormone therapy for ovarian failure increases the risk for breast cancer. We have previously shown that ovarian androgens normally protect mammary epithelial cells from excessive estrogenic stimulation, and therefore we hypothesized that the addition of testosterone to usual hormone therapy might protect women from breast cancer. Design: This was a retrospective, observational study that followed 508 postmenopausal women receiving testosterone in addition to usual hormone therapy in South Australia. Breast cancer status was ascertained by mammography at the initiation of testosterone treatment and biannually thereafter. The average age at the start of follow-up was 56.4 years, and the mean duration of follow-up was 5.8 years. Breast cancer incidence in this group was compared with that of untreated women and women using usual hormone therapy reported in the medical literature and to age-specific local population rates. Results: There were seven cases of invasive breast cancer in this population of testosterone users, for an incidence of 23 8 per 100,000 woman-years. The rate for estrogen/progestin and testosterone users was 293 per 100,000 woman-years-substantially less than women receiving estrogen/progestin in the Women's Health Initiative study (380 per 100,000 woman-years) or in the "Million Women" Study (521 per 100,000 woman-years). The breast cancer rate in our testosterone users was closest to that reported for hormone therapy never-users in the latter study (283 per 100,000 woman-years), and their age-standardized rate was the same as for the general population in South Australia. Conclusions: These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Mem Med Ctr, Adelaide, SA, Australia. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 13 TC 67 Z9 68 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP-OCT PY 2004 VL 11 IS 5 BP 531 EP 535 DI 10.1097/01.GME.0000119983.48235.D3 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 853MB UT WOS:000223830600006 PM 15356405 ER PT J AU Sumner, AE Bergman, RN Vega, GL Genovese, DJ Cochran, CS Pacak, K Watanabe, RM Boston, RC AF Sumner, AE Bergman, RN Vega, GL Genovese, DJ Cochran, CS Pacak, K Watanabe, RM Boston, RC TI The multiphasic profile of free fatty acids during the intravenous glucose tolerance test is unresponsive to exogenous insulin SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID MINIMAL-MODEL; GENDER-DIFFERENCES; DIABETES-MELLITUS; RESISTANCE; SENSITIVITY; SUPPRESSION; METABOLISM; SECRETION; MEN AB As small increments in insulin concentration profoundly affect lipolysis, our goal was to describe the free fatty acid (FFA) profile during the frequently sampled intravenous glucose tolerance test (FSIGT) and determine if both endogenous and exogenous insulin influenced the FFA profile. Thirteen subjects had both a glucose-only (GO-FSIGT) and insulin-modified FSIGT (IM-FSIGT). Both protocols were of 6 hours duration. At baseline an intravenous glucose bolus (0.3 g/kg) was given. In the IM-FSIGT, insulin was infused from 20 to 25 minutes (4 mU/kg . min). Six additional subjects had both an IM-FSIGT and a normal saline study (NS-Study). For the NS-Study, normal saline solution was infused instead of glucose and insulin. Fasting glucose, insulin, FFA and epinephrine concentrations were similar for all tests. Endogenous insulin peaked at 4 +/- 1 minute in both FSIGTs. The mean calculated peak time of exogenous insulin in the IM-FSIGT was 26 +/- 1 minute. Glucose concentrations were lower and epinephrine concentrations higher in the IM-FSIGT versus GO-FSIGT. During the FSIGTs, the FFA time course revealed four distinct phases, which did not differ between protocols. In phase I (0 to 11 minutes), FFA levels remained near basal (491 +/- 183 mumol/L); in phase II (11 to 79 minutes), FFA levels declined achieving a nadir of 139 +/- 63 mumol/L; in phase III (79 to 188 minutes), FFA levels rose linearly and reattained basal levels; and in phase IV (188 to 360 minutes), FFA levels rose above basal and plateaued at 732 +/- 214 mumol/L (P<.001). In the NS-Study, FFA levels remained near baseline (388 +/- 118 mEq/L) until 180 minutes and then trended upward to 618 +/- 258 mumol/L at 360 minutes. FFA concentrations from 180 to 360 minutes did not differ in the IM-FSIGT versus NS-Study. As the 4 FFA phases did not differ between protocols, the insulin effect on FFA levels in the FSIGT can be attributed to endogenous insulin. But the similarity in FFA levels from 180 to 360 minutes in the IM-FSIGT and NS-Study suggests diurnal variation and not a dynamic related to insulin or the FSIGT protocol is responsible for the final suprabasal FFA plateau. (C) 2004 Elsevier Inc. All rights reserved. C1 NIH, Clin Endocrinol Branch, NIDDKD, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ So Calif, Keck Sch Med, Dept Physiol & Prevent Med, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75230 USA. Univ Penn, Sch Vet Med, Biomath Unit, Philadelphia, PA 19104 USA. RP Sumner, AE (reprint author), NIH, Clin Endocrinol Branch, NIDDKD, Bldg 10,Room 8S235D, Bethesda, MD 20892 USA. NR 27 TC 15 Z9 15 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2004 VL 53 IS 9 BP 1202 EP 1207 DI 10.1016/j.metabol.2004.03.020 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 856LU UT WOS:000224047500020 PM 15334385 ER PT J AU Laurentino, EC Ruiz, JC Fazelinia, G Myler, PJ Degrave, W Alves-Ferreira, M Ribeiro, JMC Cruz, AK AF Laurentino, EC Ruiz, JC Fazelinia, G Myler, PJ Degrave, W Alves-Ferreira, M Ribeiro, JMC Cruz, AK TI A survey of Leishmania braziliensis genome by shotgun sequencing SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Leishmania braziliensis; genome survey sequencing (GSS); gene discovery; comparative genomics ID DNA; REGION; CHROMOSOME-1; REPLICATION; EXPRESSION; PROJECT; PROGRAM; GENES AB We have carried out a survey of the genome of Leishmania (Viannia) braziliensis by shotgun sequencing. Approximately 15% of the haploid genome of the parasite (5.15 Mb of genomic sequence) was obtained. A large number of known and putative genes, predicted to be involved in several cellular processes, were identified. Some genomic features were investigated, such as the general G + C content, which was found to be lower than L. major (57% versus 63%). BlastN searches revealed that 60.2% of the clusterized GSS sequences displayed similarity to L. major genomic sequences, while a BlastX search showed that 45.3% of the thus obtained predicted protein sequences showed similarity to annotated proteins of L. major. Further comparison of the degree of conservation between L major and L. braziliensis revealed that coding regions are much more conserved than non-coding ones. The shotgun sequence analysis of Leishmania braziliensis appears to be an efficient and suitable strategy contributing to the search for vaccines and novel drug targets. The sequence data described in this paper have been submitted to the dbGSS database under the following accession numbers (BX530413 to BX530454; BX530456 to BX530718; BX538354 to BX539305; BX539350 to BX540325; BX541002 to BX544869; BX544893 to BX545685; BX897701 to BX897710; BX905184 to BX907797; BX907798 to BX908381; BX908403 to BX908718). All data including sequences are also available at (www.ebi.ac.uk/embl/). (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP, Brazil. Seattle Biomed Res Inst, Seattle, WA 98109 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Univ Washington, Div Biomed & Hlth Informat, Seattle, WA 98195 USA. Fiocruz MS, Inst Oswaldo Cruz, Dept Bioquim & Biol Mol, BR-21045900 Rio De Janeiro, Brazil. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Cruz, AK (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM akcruz@fmrp.usp.br RI Degrave, Wim/B-4162-2009; Ferreira, Marcelo/C-2770-2014; Cruz, Angela/N-8445-2014; OI Cruz, Angela/0000-0002-4260-4713; Myler, Peter/0000-0002-0056-0513; Ribeiro, Jose/0000-0002-9107-0818 NR 37 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD SEP PY 2004 VL 137 IS 1 BP 81 EP 86 DI 10.1016/j.molbiopara.2004.05.001 PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 847EZ UT WOS:000223376800009 PM 15279954 ER PT J AU Shuman, JD Sebastian, T Kaldis, P Copeland, TD Zhu, SY Smart, RC Johnson, PF AF Shuman, JD Sebastian, T Kaldis, P Copeland, TD Zhu, SY Smart, RC Johnson, PF TI Cell cycle-dependent phosphorylation of C/EBP beta mediates oncogenic cooperativity between C/EBP beta and H-Ras(V12) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING PROTEIN-BETA; SIGNAL-TRANSDUCTION; RAS EFFECTORS; ACTIVATION; KINASE; PATHWAYS; TRANSFORMATION; TRANSCRIPTION; CANCER; CDK2 AB CCAAT/enhancer binding protein beta (C/EBPbeta) is a widely expressed transcription factor whose activity is regulated by oncogenic Ha-Ras(V12) signaling. C/EBPbeta is essential for the development of mouse skin tumors containing Ras mutations and can cooperate with Ras(V12) to transform NIH 3T3 cells. Here we have investigated Ras-induced phosphorylation of C/EBPbeta in fibroblasts and report a novel proline-directed phosphoacceptor site at Ser64 within the transactivation domain. Ser64 phosphorylation was induced by activated Ras and Raf but was not blocked by chemical inhibitors of MEK1/2, phosphatidylinositol 3-kinase, JNK, or p38 mitogen-activated protein kinases. Ser64 was efficiently phosphorylated in vitro by the cyclin-dependent kinases Cdk2 and Cdc2. Thr189, previously identified as an ERK1/2 phosphorylation site that regulates C/EBPbeta activity, was also a substrate for Cdk phosphorylation. Ser64 and Thr189 phosphorylation was low in serum-starved (G(0)) cells but was strongly increased in mid-G, cells and in cells arrested in S or M phase. In addition, phosphorylation on both sites was blocked by treating cells with the Cdk inhibitor roscovitine. In contrast to wild-type C/EBPbeta, which enhances transformation of NIH 3T3 cells, mutants bearing alanine substitutions at Ser64 and/or Thr189 inhibited Ras(V12)-induced focus formation. Our findings support a role for C/EBPbeta as a nuclear effector of Ras signaling and transformation, and they indicate that cell cycle-dependent phosphorylation of C/EBPbeta on Ser64 and Thr189 is required to promote Ras-induced transformation of NIH 3T3 cells. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Johnson, PF (reprint author), NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012; Kaldis, Philipp/G-2714-2010; OI Johnson, Peter/0000-0002-4145-4725; Kaldis, Philipp/0000-0002-7247-7591; Shuman, Jon/0000-0001-8412-9087 FU NCI NIH HHS [CA46637-RCS, R01 CA046637] NR 39 TC 61 Z9 62 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2004 VL 24 IS 17 BP 7380 EP 7391 DI 10.1128/MCB.24.17.7380-7391.2004 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 848CD UT WOS:000223443800007 PM 15314150 ER PT J AU Elagib, KE Xiao, M Hussaini, IM Delehanty, LL Palmer, LA Racke, FK Birrer, MJ Shanmugasundaram, G McDevitt, MA Goldfarb, AN AF Elagib, KE Xiao, M Hussaini, IM Delehanty, LL Palmer, LA Racke, FK Birrer, MJ Shanmugasundaram, G McDevitt, MA Goldfarb, AN TI Jun blockade of erythropoiesis: Role for repression of GATA-1 by HERP2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; PROTEIN-PROTEIN INTERACTION; KINASE C-EPSILON; MEGAKARYOCYTIC DIFFERENTIATION; ERYTHROID-DIFFERENTIATION; DNA-BINDING; CELL-LINE; MEGAKARYOBLASTIC LEUKEMIA; ERYTHROLEUKEMIC CELLS; STROMAL INHIBITION AB Although Jun upregulation and activation have been established as critical to oncogenesis, the relevant downstream pathways remain incompletely characterized. In this study, we found that c-Jun blocks erythroid differentiation in primary human hematopoietic progenitors and, correspondingly, that Jun factors block transcriptional activation by GATA-1, the central regulator of erythroid differentiation. Mutagenesis of c-Jun suggested that its repression of GATA-1 occurs through a transcriptional mechanism involving activation of downstream genes. We identified the hairy-enhancer-of-split-related factor HERP2 as a novel gene upregulated by c-Jun. HERP2 showed physical interaction with GATA-1 and repressed GATA-1 transcriptional activation. Furthermore, transduction of HERP2 into primary human hematopoietic progenitors inhibited erythroid differentiation. These results thus define a novel regulatory pathway linking the transcription factors c-Jun, HERP2, and GATA-1. Furthermore, these results establish a connection between the Notch signaling pathway, of which the HERP factors are a critical component, and the GATA family, which participates in programming of cellular differentiation. C1 Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NCI, Mol Mechanism Sect, Rockville, MD USA. RP Goldfarb, AN (reprint author), Univ Virginia, Sch Med, Dept Pathol, POB 800904, Charlottesville, VA 22908 USA. EM ang3x@virginia.edu FU NCI NIH HHS [R56 CA100057, R01 CA100057, R01 CA093735, CA93735, CA100057]; NHLBI NIH HHS [K08 HL04017, K08 HL004017] NR 72 TC 50 Z9 50 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2004 VL 24 IS 17 BP 7779 EP 7794 DI 10.1128/MCB.24.17.7779-7794.2004 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 848CD UT WOS:000223443800040 PM 15314183 ER PT J AU Kodama, S Koike, C Negishi, M Yamamoto, Y AF Kodama, S Koike, C Negishi, M Yamamoto, Y TI Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PREGNANE-X-RECEPTOR; FACTOR-BINDING PROTEIN-1; INSULIN-RESPONSE SEQUENCES; TRANSCRIPTION FACTOR FOXO1; DISTAL ENHANCER MODULE; MOUSE CYP2B10 GENE; ANDROSTANE-RECEPTOR; KINASE B; PROMOTER ACTIVITY; GROWTH-HORMONE AB The nuclear receptors CAR and PXR activate hepatic genes in response to therapeutic drugs and xenobiotics, leading to the induction of drug-metabolizing enzymes, such as cytochrome P450. Insulin inhibits the ability of FOXO1 to express genes encoding gluconeogenic enzymes. Induction by drugs is known to be decreased by insulin, whereas gluconeogenic activity is often repressed by treatment with certain drugs, such as phenobarbital (PB). Performing cell-based transfection assays with drug-responsive and insulin-responsive enhancers, glutathione S-transferase pull down, RNA interference (RNAi), and mouse primary hepatocytes, we examined the molecular mechanism by which nuclear receptors and FOXO1 could coordinately regulate both enzyme pathways. FOXO1 was found to be a coactivator to CAR- and PXR-mediated transcription. In contrast, CAR and PXR, acting as corepressors, downregulated FOXO1-mediated transcription in the presence of their activators, such as 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) and pregnenolone 16alpha-carbonitrile, respectively. A constitutively active mutant of the insulin-responsive protein kinase Akt, but not the kinase-negative mutant, effectively blocked FOXO1 activity in cell-based assays. Thus, insulin could repress the receptors by activating the Akt-FOXO1 signal, whereas drugs could interfere with FOXO1-mediated transcription by activating CAR and/or PXR. Treatment with TCPOBOP or PB decreased the levels of phosphoenolpyruvate carboxykinase 1 mRNA in mice but not in Car(-/-) mice. We conclude that FOXO1 and the nuclear receptors reciprocally coregulate their target genes, modulating both drug metabolism and gluconeogenesis. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 60 TC 185 Z9 197 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2004 VL 24 IS 18 BP 7931 EP 7940 DI 10.1128/MCB.24.18.7931.7940.2004 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852MY UT WOS:000223760600010 PM 15340055 ER PT J AU Cui, Y Riedlinger, G Miyoshi, K Tang, W Li, CL Deng, CX Robinson, GW Hennighausen, L AF Cui, Y Riedlinger, G Miyoshi, K Tang, W Li, CL Deng, CX Robinson, GW Hennighausen, L TI Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIGNAL TRANSDUCER; GENE-EXPRESSION; TRANSGENIC MICE; PHOSPHATIDYLINOSITOL 3-KINASE; GLAND DEVELOPMENT; KNOCKOUT MICE; ACTIVATION; GROWTH; COTRANSPORTER; APOPTOSIS AB This study explored the functions of the signal transducers and activators of transcription 5a and 5b (referred to as Stat5 here) during different stages of mouse mammary gland development by using conditional gene inactivation. Mammary gland morphogenesis includes cell specification, proliferation and differentiation during pregnancy, cell survival and maintenance of differentiation throughout lactation, and cell death during involution. Stat5 is activated by prolactin, and its presence is mandatory for the proliferation and differentiation of mammary epithelium during pregnancy. To address the question of whether Stat5 is also necessary for the maintenance and survival of the differentiated epithelium, the two genes were deleted at different time points. The 110-kb Stat5 locus in the mouse was bracketed with loxP sites, and its deletion was accomplished by using two Cre-expressing transgenic lines. Loss of Stat5 prior to pregnancy prevented epithelial proliferation and differentiation. Deletion of Stat5 during pregnancy, after mammary epithelium had entered Stat5-mediated differentiation, resulted in premature cell death, indicating that at this stage epithelial cell proliferation, differentiation, and survival require Stat5. C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima 770, Japan. RP Hennighausen, L (reprint author), NIDDK, Lab Genet & Physiol, NIH, Bldg 8,Room 101, Bethesda, MD 20892 USA. EM hennighausen@nih.gov RI Robinson, Gertraud/I-2136-2012; deng, chuxia/N-6713-2016 NR 40 TC 299 Z9 303 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2004 VL 24 IS 18 BP 8037 EP 8047 DI 10.1128/MCB.24.18.8037-8047.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852MY UT WOS:000223760600021 PM 15340066 ER PT J AU Trushina, E Dyer, RB Badger, JD Ure, D Eide, L Tran, DD Vrieze, BT Legendre-Guillemin, V McPherson, PS Mandavilli, BS Van Houten, B Zeitlin, S McNiven, M Aebersold, R Hayden, M Parisi, JE Seeberg, E Dragatsis, I Doyle, K Bender, A Chacko, C McMurray, CT AF Trushina, E Dyer, RB Badger, JD Ure, D Eide, L Tran, DD Vrieze, BT Legendre-Guillemin, V McPherson, PS Mandavilli, BS Van Houten, B Zeitlin, S McNiven, M Aebersold, R Hayden, M Parisi, JE Seeberg, E Dragatsis, I Doyle, K Bender, A Chacko, C McMurray, CT TI Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DISEASE GENE HOMOLOG; NEURODEGENERATIVE DISEASES; REPRESSES TRANSCRIPTION; MEDIATED TRANSCRIPTION; EMBRYONIC LETHALITY; INCREASED APOPTOSIS; PROJECTION NEURONS; BINDING-PROTEIN; MOUSE MODEL; CELL-DEATH AB Recent data in invertebrates demonstrated that huntingtin (htt) is essential for fast axonal trafficking. Here, we provide direct and functional evidence that htt is involved in fast axonal trafficking in mammals. Moreover, expression of full-length mutant htt (mhtt) impairs vesicular and mitochondrial trafficking in mammalian neurons in vitro and in whole animals in vivo. Particularly, mitochondria become progressively immobilized and stop more frequently in neurons from transgenic animals. These defects occurred early in development prior to the onset of measurable neurological or mitochondrial abnormalities. Consistent with a progressive loss of function, wild-type htt, trafficking motors, and mitochondrial components were selectively sequestered by mhtt in human Huntington's disease-affected brain. Data provide a model for how loss of htt function causes toxicity; mhtt-mediated aggregation sequesters htt and components of trafficking machinery leading to loss of mitochondrial motility and eventual mitochondrial dysfunction. C1 Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Mayo Clin & Mayo Grad Sch Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA. Mayo Clin & Mayo Grad Sch Med, Div Neuroimmunol, Neurosci Program, Rochester, MN USA. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Univ Virginia, Dept Neurosci, Charlottesville, VA USA. Inst Syst Biol, Seattle, WA USA. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. Univ Oslo, Natl Hosp, Ctr Mol Biol & Neurosci, Oslo, Norway. Univ Oslo, Natl Hosp, Inst Med Microbiol, Dept Mol Biol, Oslo, Norway. NIEHS, NIH, Raleigh, NC USA. Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA. RP McMurray, CT (reprint author), Mayo Clin & Mayo Fdn, Dept Mol Pharmacol, 200 1st St SW, Rochester, MN 55905 USA. EM mcmurray.cynthia@mayo.edu RI Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 FU NIDDK NIH HHS [DK 43694-01]; NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [NS40738, R01 NS040738] NR 54 TC 280 Z9 288 U1 0 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2004 VL 24 IS 18 BP 8195 EP 8209 DI 10.1128/MCB.24.18.8195-8209.2004 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 852MY UT WOS:000223760600034 PM 15340079 ER PT J AU Yamagiwa, H Yamada, Y Bolander, ME Sarkar, G AF Yamagiwa, H Yamada, Y Bolander, ME Sarkar, G TI Oligonucleotide decoy mimicking alpha A-crystallin-binding protein 1 binding site on mouse Col2a1 enhancer stimulates transcription from the adjacent Col2a1 promoter in chondrogenic ATDC5 cell SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE oligonucleotide decoy; ATDC5; transcription factor; CRYBP1; SOX9; type 11 collagen; oligomimetics ID CHONDROCYTE-SPECIFIC ENHANCER; COLLAGEN GENE; II COLLAGEN; OSTEOARTHRITIS; CARTILAGE; DAMAGE; SOX9; METALLOPROTEINASE; INHIBITION; EXPRESSION AB A 48-bp sequence element in intron 1 of the alpha1(II) collagen gene (Col2a1) acts as an enhancer of Col2a1 transcription and contains binding sites for the transcription activator SOX9 and repressor alphaA-crystallin-binding protein 1 (CRYBP1). We hypothesized that abrogating CRYBP1 binding should increase transcription from a promoter associated with the Col2a1 enhancer. We tested this hypothesis by cotransfecting an oligonucleotide (ODN) decoy for CRYBP1 and a luciferase-based reporter vector under the transcriptional control of the Col2a1 promoter linked to the 100-bp enhancer in chondrogenic ATDC5 cells. As a control, we used decoy ODN corresponding to the SOX9 binding site. Transfection with CRYBP1 decoy increased luciferase activity by >2.5-fold in the absence or presence of insulin, whereas SOX9 decoy ODN decreased luciferase activity to about 50% under similar conditions. In addition, the repressive effect of interleukin-1 on Col2a1 transcription through decreasing SOX9 messenger ribonucleic acid (mRNA) expression and increasing CRYBP1 mRNA expression, was counteracted by CRYBP1 decoy ODN. These results provide a rationale for gene therapy in degenerative joint diseases by elevating Col2a1 expression in chondrocytes through oligomimetics of repressor binding sites. C1 Mayo Clin & Mayo Fdn, Dept Orthoped Surg, Rochester, MN 55905 USA. Niigata Univ, Grad Sch Med & Dent Sci, Dept Regenerat & Transplant Med, Div Orthopaed Surg, Niigata 9518510, Japan. Natl Inst Dental & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Sarkar, G (reprint author), Mayo Clin & Mayo Fdn, Dept Orthoped Surg, 200 1st St SW, Rochester, MN 55905 USA. EM sarkar.gobinda@mayo.edu NR 16 TC 3 Z9 6 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD SEP PY 2004 VL 28 IS 1 BP 1 EP 7 DI 10.1385/MB:28:1:01 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 855ZF UT WOS:000224012700001 PM 15456958 ER PT J AU Danielson, KG Kanthala, S Tuli, R Tuan, RS AF Danielson, KG Kanthala, S Tuli, R Tuan, RS TI Fluorescent detection of differentially expressed cDNA using SYBR gold nucleic acid gel stain SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE mRNA differential display PCR; polyacrylamide gel; SYBR Gold staining ID MESENCHYMAL STEM-CELLS; MESSENGER-RNA; PROGENITOR CELLS; DISPLAY; MARROW; GENES; BONE; IDENTIFICATION; CLONING; PCR AB We describe herein a modified differential gene display (DGD) technique that can be rapidly and simply performed and that eliminates the need for radioactivity by fluorescent visualization of complementary deoxyribonucleic acid (cDNA) bands with SYBR gold nucleic acid gel stain. To streamline the DGD procedure, a number of modifications were employed. Ribonucleic acid isolated from differentially treated populations of human trabecular bone-derived mesenchymal progenitor cells was reverse-transcribed into cDNA using oligo-dT primer, and subsequent amplification of differentially expressed cDNAs was done using arbitrary 25-mer primers and oligo-dT(9) 30-mer primers. Moderate-sized nondenaturing 6% polyacrylamide gels (30 x 20 cm) of 1.5-mm thickness were used for easier handling and increased sample loading capacity. Gels were subjected to electrophoresis overnight, stained with SYBR gold, and visualized and photographed using a commercially available gel imager. DNA bands ranging in size from 100 to 400 bp were visualized directly on an ultraviolet transilluminator, excised from the gel, and reamplified. The cDNA amplicons were subcloned, sequenced, and gene sequences were identified by a Basic Local Alignment Search Tool of genomic databases. Overall, this rapid and functional method proved quite effective for identification of novel genes that may be of interest in studies of cartilage and bone differentiation. C1 Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Danielson, KG (reprint author), Thomas Jefferson Univ, Dept Orthopaed Surg, Room 501 Curtis Bldg,1015 Walnut St, Philadelphia, PA 19107 USA. EM keith.danielson@jefferson.edu FU NIAMS NIH HHS [AR 47396]; NIDCR NIH HHS [DE 12864] NR 20 TC 2 Z9 2 U1 2 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD SEP PY 2004 VL 28 IS 1 BP 41 EP 45 DI 10.1385/MB:28:1:41 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 855ZF UT WOS:000224012700005 PM 15456962 ER PT J AU Krop, I Player, A Tablante, A Taylor-Parker, M Lahti-Domenici, J Fukuoka, J Batra, SK Papadopoulos, N Richards, WG Sugarbaker, DJ Wright, RL Shim, J Stamey, TA Sellers, WR Loda, M Meyerson, M Hruban, R Jen, J Polyak, K AF Krop, I Player, A Tablante, A Taylor-Parker, M Lahti-Domenici, J Fukuoka, J Batra, SK Papadopoulos, N Richards, WG Sugarbaker, DJ Wright, RL Shim, J Stamey, TA Sellers, WR Loda, M Meyerson, M Hruban, R Jen, J Polyak, K TI Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types SO MOLECULAR CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; NORMAL-1 HIN-1; PCR ASSAY; GENE; HYPERMETHYLATION; ADENOCARCINOMA; MORPHOGENESIS; PROTEIN AB HIN-1 (high in normal-1) is a candidate tumor suppressor identified as a gene silenced by methylation in the majority of breast carcinomas. HIN-1 is highly expressed in the mammary gland, trachea, lung, prostate, pancreas, and salivary gland, and in the lung, its expression is primarily restricted to bronchial epithelial cells. In this report, we show that, correlating with the secretory nature of HIN-1, high levels of HIN-1 protein are detected in bronchial lavage, saliva, plasma, and serum. To determine if, similar to breast carcinomas, HIN-1 is also silenced in tumors originating from other organs with high HIN-1 expression, we analyzed its expression and promoter methylation status in lung, prostate, and pancreatic carcinomas. Nearly all prostate and a significant fraction of lung and pancreatic carcinomas showed HIN-1 hypermethylation, and the majority of lung and prostate tumors lacked HIN-1 expression. In lung carcinomas, the degree of HIN-1 methylation differed among tumor subtypes (P = 0.02), with the highest level of HIN-1 methylation observed in squamous cell carcinomas and the lowest in small cell lung cancer. In lung adenocarcinomas, the expression of HIN-1 correlated with cellular differentiation status. Hypermethylation of the HIN-1 promoter was also frequently observed in normal tissue adjacent to tumors but not in normal tissue from noncancer patients, implying that HIN-1 promoter methylation may be a marker of premalignant changes. Thus, silencing of HIN-1 expression and methylation of its promoter occurs in multiple human cancer types, suggesting that elimination of HIN-1 function may contribute to several forms of epithelial tumorigenesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Columbia Univ, Dept Pathol, Inst Canc Genet, New York, NY USA. Stanford Univ, Stanford, CA 94305 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; Papadopoulos, Nickolas/K-7272-2012 FU NCI NIH HHS [CA89393, CA94787-01, R01 CA94074-01A1] NR 20 TC 35 Z9 36 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2004 VL 2 IS 9 BP 489 EP 494 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 857AM UT WOS:000224087600001 PM 15383627 ER PT J AU Bacolod, MD Johnson, SP Pegg, AE Dolan, ME Moschel, RC Bullock, NS Fang, QM Colvin, OM Modrich, P Bigner, DD Friedman, HS AF Bacolod, MD Johnson, SP Pegg, AE Dolan, ME Moschel, RC Bullock, NS Fang, QM Colvin, OM Modrich, P Bigner, DD Friedman, HS TI Brain tumor cell lines resistant to O-6-benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea chemotherapy have O-6 -alkylguanine-DNA alkyltransferase mutations SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CARMUSTINE PLUS O-6-BENZYLGUANINE; PROGRESSIVE MALIGNANT GLIOMA; DEFICIENT COLON-CANCER; MISMATCH REPAIR; O(6)-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CROSS-LINKING; HPRT LOCUS; GENE; P53 AB The chemotherapeutic activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU or carmustine) may be improved by the addition of O-6-benzylguanine (O-6 -BG). The reaction of O-6-BG with O-6-alkylguanine-DNA alkyltransferase (AGT) prevents the repair of O-6-chloroethyl lesions caused by BCNU. In clinics, the combination of O-6-BG and BCNU is now being tested for the treatment of brain tumors. However, the effectiveness of this drug regimen may be limited by drug resistance acquired during treatment. To understand the possible mechanisms of resistance of brain tumor cells to the O-6-BG/BCNU combination, we generated medulloblastoma cell lines (D283 MED, D341 MED, and Daoy) resistant to the combination of O-6-BG and BCNU [O-6-BG/BCNU resistant (OBR)]. DNA sequencing showed that all of the parent cell lines express wild-type AGTs, whereas every OBR cell line exhibited mutations that potentially affected the binding of O-6-BG to the protein as evidenced previously by in vitro mutagenesis and structural studies of AGT. The D283 MED (OBR), Daoy (OBR), and D341 MED (OBR) cell lines expressed G156C, Y114F, and K165T AGT mutations, respectively. We reported previously that rhabdomyosarcoma TE-671 (OBR) also expresses a G156C mutation. These data suggest that the clonal selection of AGT mutants during treatment with O-6-BG plus an alkylator may produce resistance to this intervention in clinical settings. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Penn State Univ, Coll Med, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Hershey, PA USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Natl Canc Inst, Comparat Carcinogenesis Lab, Frederick, MD USA. RP Friedman, HS (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 3624, Durham, NC 27710 USA. EM fried003@mc.duke.edu RI Fang, Qingming/B-6839-2008 OI Fang, Qingming/0000-0002-4006-0636 FU NCI NIH HHS [CA-71976]; NINDS NIH HHS [NS-20023, NS-30245] NR 47 TC 24 Z9 24 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2004 VL 3 IS 9 BP 1127 EP 1135 PG 9 WC Oncology SC Oncology GA 854MM UT WOS:000223907300010 PM 15367707 ER PT J AU Yu, LR Conrads, TP Uo, T Kinoshita, Y Morrison, RS Lucas, DA Chan, KC Blonder, J Issaq, HJ Veenstra, TD AF Yu, LR Conrads, TP Uo, T Kinoshita, Y Morrison, RS Lucas, DA Chan, KC Blonder, J Issaq, HJ Veenstra, TD TI Global analysis of the cortical neuron proteome SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID CYCLE-REGULATED PROTEIN; MASS-SPECTROMETRY; IDENTIFICATION; PESCADILLO; SEPARATION; PEPTIDES AB In this study, a multidimensional fractionation approach was combined with MS/MS to increase the capability of characterizing complex protein profiles of mammalian neuronal cells. Proteins extracted from primary cultures of cortical neurons were digested with trypsin followed by fractionation using strong cation exchange chromatography. Each of these fractions was analyzed by microcapillary reversed-phase LC-MS/MS. The analysis of the MS/MS data resulted in the identification of over 15,000 unique peptides from which 3,590 unique proteins were identified based on protein-specific peptide tags that are unique to a single protein in the searched database. In addition, 952 protein clusters were identified using cluster analysis of the proteins identified by the peptides not unique to a single protein. This identification revealed that a minimum of 4,542 proteins could be identified from this experiment, representing similar to16% of all known mouse proteins. An evaluation of the number of false-positive identifications was undertaken by searching the entire MS/MS dataset against a database containing the sequences of over 12,000 proteins from archaea. This analysis allowed a systematic determination of the level of confidence in the identification of peptides as a function of SEQUEST cross correlation (X-corr) and delta correlation (DeltaCn) scores. Correlation charts were also constructed to show the number of unique peptides identified for proteins from specific classes. The results show that low-abundance proteins involved in signal transduction and transcription are generally identified by fewer peptides than high-abundance proteins that play a role in maintaining mammalian cellular structure and motility. The results presented here provide the broadest proteome coverage for a mammalian cell to date and show that MS-based proteomics has the potential to provide high coverage of the proteins expressed within a cell. C1 NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, POB B,Bldg 469,Room 160, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400]; NINDS NIH HHS [NS35533, NS42699] NR 23 TC 60 Z9 62 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2004 VL 3 IS 9 BP 896 EP 907 DI 10.1074/mcp.M400034-MCP200 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 855GQ UT WOS:000223961700005 PM 15231876 ER PT J AU Sidransky, E AF Sidransky, E TI Gaucher disease: complexity in a "simple" disorder SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Gaucher disease; Mendelian disorder; glucocerebrosidase; glucosylsphingosine; genotype-phenotype correlation; recombination; animal models; parkinsonism; risk factor; modifier ID BETA-GLUCOCEREBROSIDASE DEFICIENCY; SIMPLE MENDELIAN DISORDERS; CYSTIC-FIBROSIS; GLUCOSYLSPHINGOSINE ACCUMULATION; GENOTYPE/PHENOTYPE CORRELATIONS; TARGETED DISRUPTION; PARKINSONS-DISEASE; MUTATION ANALYSIS; GLUCOSIDASE GENE; UNIQUE GENOTYPE AB Gaucher disease, the recessively inherited deficiency of the enzyme glucoccrebrosidase and the most common sphingolipidosis, has both non-neurological and neuronopathic forms and a continuum of diverse clinical manifestations. Studies of genotype-phenotype correlations reveal significant genotypic heterogeneity among clinically similar patients, and vastly different phenotypes among patients with the same mutations. The region surrounding the glucocerebrosidase gene (GBA) on chromosome 1q is particularly gene-rich, with a highly homologous pseudogene sequence 16 kb downstream. Recombination events within the GBA locus contribute to the etiology of some mutations in Gaucher disease. Studies of patients with Gaucher disease and atypical manifestations, including parkinsonism, myoclonic epilepsy, cardiac involvement and collodion skin, seek to define other genetic or environmental factors contributing to the phenotypes. Recent reports demonstrating an association between Gaucher disease and parkinsonism provide an example of heterozygosity for a Mendelian disorder acting as a risk factor for a complex disease. There are rare patients with Gaucher disease and differing genotypes who develop early onset, treatment-refractory parkinsonism. Neuropathology in a group of these patients showed alpha-synuclein-reaciive Lewy bodies in brain regions specifically associated with Gaucher disease. Family studies of these probands suggested that the incidence of parkinsonism might be more frequent in obligate heterozygotes. In a complementary finding, the examination of GBA in autopsy samples from individuals with sporadic Parkinson disease identified alterations in the GBA sequence in 14% of the cohort. These studies provide evidence that altered glucocerebrosidase may contribute to a vulnerability to parkinsonism. Moreover, this research demonstrates how insights from rare, single gene disorders like Gaucher disease can provide a window into the etiology of more common, multifactorial genetic diseases. Published by Elsevier Inc. C1 NHGRI, Sect Mol Neurogenet, NIMH, NIH, Bethesda, MD 20892 USA. NHGRI, MGB, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, NIMH, NIH, 35 Convent Dr MSC 3708,1A-213, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 76 TC 188 Z9 197 U1 3 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2004 VL 83 IS 1-2 BP 6 EP 15 DI 10.1016/j.ymgme.2004.08.015 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 863UV UT WOS:000224589800001 PM 15464415 ER PT J AU Chang, YC Wright, LC Tscharke, RL Sorrell, TC Wilson, CF Kwon-Chung, KJ AF Chang, YC Wright, LC Tscharke, RL Sorrell, TC Wilson, CF Kwon-Chung, KJ TI Regulatory roles for the homeodomain and C2H2 zinc finger regions of Cryptococcus neoformans Ste12 alpha p SO MOLECULAR MICROBIOLOGY LA English DT Article ID YEAST STE12 PROTEIN; MAP KINASE CASCADE; SACCHAROMYCES-CEREVISIAE; CANDIDA-ALBICANS; SIGNAL-TRANSDUCTION; MATING-TYPE; CELL-TYPE; PHOSPHOLIPASE-ACTIVITY; TRANSCRIPTION FACTORS; PHEROMONE RECEPTOR AB The STE12alpha gene of Cryptococcus neoformans encodes a protein containing both homeodomain and zinc finger regions. As homeodomains and zinc finger regions are important domains for the function of many transcription factors, we used site-specific mutagenesis to delineate the roles of these two domains. The homeodomain and zinc finger regions are each important for the function of Ste12alphap. DNA binding ability, mating frequency, and haploid fruiting capability were reduced in strains with mutations in the homeodomain, whereas virulence and capsule size in the mouse brain were increased. In contrast, mutations in the zinc fingers region resulted in decreased virulence, reduced capsule size in the mouse brain and decreased gene expression of capsule associated genes. In addition, phospholipase activity was increased in the zinc finger mutants. Taken together, most of the phenotypes previously observed in the ste12alpha deletion strains were reproduced in these two types of mutants. However, unlike mutations in the homeodomain/zinc finger region, complete deletion of STE12alpha caused a severe reduction in virulence and a decrease in phospholipase activity. These data suggest that region(s) other than the homeodomain and zinc finger regions of Ste12alphap contribute to the variable influences on the different phenotypes observed in C. neoformans. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, Westmead, NSW 2145, Australia. RP Kwon-Chung, KJ (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM June_Kwon-Chung@nih.gov NR 58 TC 18 Z9 19 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2004 VL 53 IS 5 BP 1385 EP 1396 DI 10.1111/j.1365-2958.2004.04188.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 848VB UT WOS:000223495100009 PM 15387817 ER PT J AU Su, XZ Wootton, JC AF Su, XZ Wootton, JC TI Genetic mapping in the human malaria parasite Plasmodium falciparum SO MOLECULAR MICROBIOLOGY LA English DT Review ID VITRO CHLOROQUINE SUSCEPTIBILITY; MULTIDRUG-RESISTANCE GENE; MICROSATELLITE MARKERS; DRUG-RESISTANCE; MEFLOQUINE RESISTANCE; MALE GAMETOGENESIS; PFMDR1 GENE; POLYMORPHISMS; MUTATIONS; PFCRT AB The Plasmodium falciparum genome sequence has boosted hopes for a new era of malaria research and for the application of comprehensive molecular knowledge to disease control, but formidable obstacles remain: approximate to 60% of the predicted P. falciparum proteins have no known functions or homologues, and most life cycle stages of this haploid eukaryotic parasite are relatively intractable to cultivation and biochemical manipulation. Genetic mapping based on high-resolution maps saturated with single-nucleotide polymorphisms or microsatellites is now providing effective strategies for discovering candidate genes determining important parasite phenotypes. Here we review classical linkage studies using laboratory crosses and population associations that are now amenable to genome-wide approaches and are revealing multiple candidate genes involved in complex drug responses. Moreover, mapping by linkage disequilibrium is practicable in cases where chromosomal segments flanking drug-selected genes have been preserved in populations during relatively recent P. falciparum evolution. We discuss the advantages and limitations of these various genetic mapping strategies, results from which offer complementary insights to those emerging from gene knockout experiments and/or high-throughput genomic technologies. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20850 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3E-24B,12735 Twinbrook Pkwy, Rockville, MD 20850 USA. EM xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 NR 56 TC 24 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2004 VL 53 IS 6 BP 1573 EP 1582 DI 10.1111/j.1365-2958.2004.04270.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 851CD UT WOS:000223662100003 PM 15341640 ER PT J AU Hartz, AMS Bauer, B Fricker, G Miller, DS AF Hartz, AMS Bauer, B Fricker, G Miller, DS TI Rapid regulation of P-glycoprotein at the blood-brain barrier by endothelin-1 SO MOLECULAR PHARMACOLOGY LA English DT Article ID RENAL PROXIMAL TUBULE; MULTIDRUG-RESISTANCE PROTEIN; XENOBIOTIC TRANSPORT; MDR1A EXPRESSION; IN-VITRO; NEPHROTOXICANTS; PERMEABILITY; DISRUPTION; SECRETION; DISEASE AB The ATP-driven xenobiotic transporter P-glycoprotein is a critical element of the blood-brain barrier. To study regulation of P-glycoprotein function, we measured specific transport [(3'-oxo-4-butenyl-4-methyl-threonine(1), (valine(2)) cyclosporin (PSC833)-sensitive] of the fluorescent cyclosporin A derivative [N-epsilon(4-nitrobenzofurazan-7-yl)-D-Lys(8)]-cyclosporin A (NBDL-CSA) into the lumens of isolated rat brain capillaries using confocal microscopy and quantitative image analysis. Luminal NBDL-CSA accumulation was rapidly and reversibly reduced in a concentration-dependent manner by 0.1 to 100 nM endothelin-1 (ET-1). In this concentration range, ET-1 did not affect junctional permeability. The ETB receptor agonist sarafotoxin 6c also reduced transport. An ETB receptor antagonist blocked effects of ET-1 and sarafotoxin 6c; an ETA receptor antagonist was without effect. Consistent with this, immunostaining and Western blotting showed expression of the ETB receptor in brain capillary membranes. NBDL-CSA transport was also reduced by sodium nitroprusside, a NO donor, and by phorbol ester, a protein kinase C (PKC) activator. Inhibition of NO synthase (NOS) or PKC abolished the ET-1 effects. Thus, ET-1, acting through an ETB receptor, NOS, and PKC rapidly and reversibly reduced transport mediated by P-glycoprotein at the blood-brain barrier. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov NR 32 TC 88 Z9 90 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2004 VL 66 IS 3 BP 387 EP 394 DI 10.1124/mol.104.001503 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848CA UT WOS:000223443500004 PM 15322229 ER PT J AU Bauer, B Hartz, AMS Fricker, G Miller, DS AF Bauer, B Hartz, AMS Fricker, G Miller, DS TI Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier SO MOLECULAR PHARMACOLOGY LA English DT Article ID NUCLEAR RECEPTOR; MULTIDRUG TRANSPORTERS; XENOBIOTIC RECEPTOR; DRUG-METABOLISM; GENE-EXPRESSION; RESISTANCE; INDUCTION; PREGNENOLONE-16-ALPHA-CARBONITRILE; PHARMACORESISTANCE; MODULATION AB P-glycoprotein, an ATP-driven drug export pump, is a critical, selective component of the blood-brain barrier responsible for the poor penetration of many therapeutic drugs. In liver, ligand-activated, nuclear receptors are transcriptional regulators of drug metabolizing enzymes and drug export pumps, but only one, the pregnane X receptor (PXR in rodents, SXR in humans), regulates p-glycoprotein expression. We report for the first time that PXR is expressed in rat brain capillaries. Moreover, exposing isolated capillaries to the PXR ligands pregnenolone-16alpha-carbonitrile (PCN) and dexamethasone increased p-glycoprotein expression and p-glycoprotein-specific transport of a fluorescent cyclosporine A derivative into capillary lumens. Dosing rats with PCN and dexamethasone increased p-glycoprotein expression in liver plasma membranes and in brain capillaries and up-regulated specific transport in capillaries. This is the first evidence for PXR expression in brain and for regulation by nuclear receptors of a xenobiotic export pump at the blood-brain barrier. These results imply selective tightening of the barrier in patients exposed to the wide range of xenobiotics that are PXR/SXR ligands, including drugs, dietary constituents, and toxicants. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany. RP Miller, DS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov NR 30 TC 181 Z9 188 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2004 VL 66 IS 3 BP 413 EP 419 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848CA UT WOS:000223443500007 PM 15322232 ER PT J AU Fayuk, D Yakel, JL AF Fayuk, D Yakel, JL TI Regulation of nicotinic acetylcholine receptor channel function by acetylcholinesterase inhibitors in rat hippocampal CA1 interneurons SO MOLECULAR PHARMACOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; SYNAPTIC-TRANSMISSION; ACH RECEPTORS; NEURONS; SUBTYPES; DIISOPROPYLFLUOROPHOSPHATE; ACTIVATION; BRAIN; DIVERSITY; DEFICITS AB Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in cognition and may play a role in Alzheimer's disease ( AD). Known inhibitors of acetylcholinesterase (AChE) are used to treat AD and are known cognitive enhancers; however, their mechanism of action relating to AD is not fully understood. We tested several AChE inhibitors, including huperzine A, tacrine, and 1,5-bis(4-allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284c51), on nAChRs in rat hippocampal CA1 interneurons in slices using patch-clamp techniques. These interneurons express both alpha7 and non-alpha7 subunit-containing nAChRs and were activated with pressure applications of acetylcholine (ACh), choline, or carbachol. These AChE inhibitors had no significant effect on either the amplitude or kinetics of alpha7 nAChRs activated by ACh, but they slowed the rate of recovery from desensitization through an indirect mechanism; responses activated with either choline or carbachol were unaffected. For non-alpha7 receptors, these inhibitors significantly increased the amplitude and decay phase for responses induced by ACh ( but not carbachol), also through an indirect mechanism. Slices preincubated with diisopropylflurophosphate ( to permanently inactivate AChE) mimicked the effect of these AChE inhibitors on both alpha7 and non-alpha7 nAChRs. In addition, galantamine, which is both an inhibitor of AChE and an allosteric potentiator of nAChRs, had similar effects. Therefore, various AChE inhibitors are having significant and indirect effects on nAChRs through direct inhibition of AChE; this results in an enhanced amount and/or duration of ACh in slices, with no effect on the levels of choline or carbachol. Therefore, drugs that target AChE are likely to be important regulators of cholinergic signaling in the hippocampus. C1 NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov NR 40 TC 46 Z9 47 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2004 VL 66 IS 3 BP 658 EP 666 DI 10.1124/mol.104.000042 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848CA UT WOS:000223443500033 PM 15322258 ER PT J AU Palmatier, MA Pakstis, AJ Speed, W Paschou, P Goldman, D Odunsi, A Okonofua, F Kajuna, S Karoma, N Kungulilo, S Grigorenko, E Zhukova, OV Bonne-Tamir, B Lu, RB Parnas, J Kidd, JR DeMille, MMC Kidd, KK AF Palmatier, MA Pakstis, AJ Speed, W Paschou, P Goldman, D Odunsi, A Okonofua, F Kajuna, S Karoma, N Kungulilo, S Grigorenko, E Zhukova, OV Bonne-Tamir, B Lu, RB Parnas, J Kidd, JR DeMille, MMC Kidd, KK TI COMT haplotypes suggest P2 promoter region relevance for schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE COMT; haplotypes; schizophrenia; linkage disequilibrium; functional variation; P2 promoter; population variation ID CATECHOL-O-METHYLTRANSFERASE; DORSOLATERAL PREFRONTAL CORTEX; MESSENGER-RNA EXPRESSION; LINKAGE DISEQUILIBRIUM; POLYMORPHISM; ASSOCIATION; SUSCEPTIBILITY; CLONING; ENZYME; BRAIN AB A recent study found, in a large sample of Ashkenazi Jews, a highly significant association between schizophrenia and a particular haplotype of three polymorphic sites in the catechol-O-methyl transferase, COMT, gene: an IVS 1 SNP (dbSNP rs737865), the exon 4 functional SNP (Val158Met, dbSNP rs165688), and a downstream SNP (dbSNP rs165599). Subsequently, this haplotype was shown to be associated with lower levels of COMT cDNA derived from normal cortical brain tissue, most likely due to cis-acting element(s). As a first step toward evaluating whether this haplotype may be relevant to schizophrenia in populations other than Ashkenazi Jews, we have studied this haplotype in 38 populations representing all major regions of the world. Adding to our previous data on four polymorphic sites in the COMT gene, including the Val158Met polymorphism, we have typed the IVS 1 rs737865 and 3' rs615599 sites and also included a novel IVS 1 indel polymorphism, yielding seven-site haplotype frequencies for normal individuals in the 38 globally distributed populations, including a sample of Ashkenazi Jews. We report that the schizophrenia-associated haplotype is significantly heterogeneous in populations worldwide. The three-site, schizophrenia-associated haplotype frequencies range from 0% in South America to 37.1% in Southwest Asia, despite the fact that schizophrenia occurs at roughly equal frequency around the world. Assuming that the published associations found between the exon 4 Val158Met SNP and schizophrenia are due to linkage disequilibrium, these new haplotype data support the hypothesis of a relevant cis variant linked to the rs737865 site, possibly just upstream in the P2 promoter driving transcription of the predominant form of COMT in the brain. The previously described HindIII restriction site polymorphism, located within the P2 promoter, varies within all populations and may provide essential information in future studies of schizophrenia. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. Univ Benin, Fac Med, Dept Obstet & Gynecol, Benin, Nigeria. Hubert Kairuki Mem Univ, Dar Es Salaam, Tanzania. Muhimbili Univ Coll Hlth Sci, Dar Es Salaam, Tanzania. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RAS, NI Vavilov Gen Genet Res Inst, Moscow 117901, Russia. Tel Aviv Univ, Sackler Sch Med, Dept Genet, IL-69978 Tel Aviv, Israel. Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Psychiat, Taipei, Taiwan. Univ Copenhagen, Hvidovre Hosp, Dept Psychiat, DK-2650 Hvidovre, Denmark. RP Kidd, KK (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA. EM Kidd@biomed.med.yale.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; DeMille, Mellissa/0000-0001-7068-395X; Paschou, Peristera/0000-0002-9783-1024 FU NIAAA NIH HHS [AA09379]; NIGMS NIH HHS [GM57672]; NIMH NIH HHS [MH62495]; NINDS NIH HHS [NS01795] NR 33 TC 52 Z9 57 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2004 VL 9 IS 9 BP 859 EP 870 DI 10.1038/sj.mp.4001496 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 850LL UT WOS:000223612800005 PM 15098000 ER PT J AU Reist, C Mazzanti, C Vu, R Fujimoto, K Goldman, D AF Reist, C Mazzanti, C Vu, R Fujimoto, K Goldman, D TI Inter-relationships of intermediate phenotypes for serotonin function, impulsivity, and a 5-HT2A candidate allele: His452Tyr SO MOLECULAR PSYCHIATRY LA English DT Article DE serotonin; platelet; calcium; T102C; His452Tyr; impulsivity; fenfluramine ID ANXIETY-RELATED TRAITS; CALCIUM MOBILIZATION; T102C POLYMORPHISM; D-FENFLURAMINE; PLATELET; TRANSPORTER; AGGRESSION; RECEPTOR; GENE; ASSOCIATION AB Central serotonin (5-hydroxytryptamine, 5-HT) function has a role in a range of genetically influenced psychiatric diagnoses and behaviors. Several human 5-HT receptor polymorphisms are 'candidate alleles', altering in vitro function, and potentially affecting behavior and drug response. The 5-HT2A His452Tyr polymorphism alters signal transduction, and has been associated with diminished efficacy of clozapine in schizophrenia. Another 5-HT2A receptor polymorphism consists of the silent thymidine-cytosine substitution (102T4C), which has been controversially associated with schizophrenia. We investigated the role of His452Tyr and the 102T4C in behavior and in vivo intermediate biochemical phenotypes. Intracellular 5-HT-induced Ca(2+)release by platelets and fenfluramine-induced prolactin release by pituitary were evaluated in 27 psychiatrically interviewed subjects (including both impulsive patients and controls) stratified by His452Tyr genotype and also genotyped for a second 5-HT2A polymorphism, 102T4C. Subjects with increased measures of impulsivity showed decreased postreceptor 5-HT function, as indicated by reduced 5-HT-induced Ca2+ release, but no alteration in net 5-HT function, as measured by fenfluramine response. No significant effects of either polymorphism were associated with altered 5-HT-induced calcium response or fenfluramine-stimulated prolactin release. One available Tyr452/Tyr452 homozygote had diminished Ca2+ release and one of the highest levels of fenfluramine response. Although not statistically significant, the effect of the T102C, but not the His452Tyr, genotype on prolactin level change over time was associated with a medium to large strength of association ( treatment magnitude of T-2=0.10), suggesting that further study is warranted. C1 Long Beach Vet Affairs Med Ctr, Dept Psychiat, Long Beach, CA 90822 USA. Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Reist, C (reprint author), Long Beach Vet Affairs Med Ctr, Dept Psychiat, 5901 E 7th St, Long Beach, CA 90822 USA. EM creist@uci.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 43 TC 17 Z9 17 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2004 VL 9 IS 9 BP 871 EP 878 DI 10.1038/sj.mp.4001495 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 850LL UT WOS:000223612800006 PM 15037867 ER PT J AU McCart, JA Mehta, N Scollard, D Reilly, RM Carrasquillo, JA Tang, N Deng, H Miller, M Xu, H Libutti, SK Alexander, HR Bartlett, DL AF McCart, JA Mehta, N Scollard, D Reilly, RM Carrasquillo, JA Tang, N Deng, H Miller, M Xu, H Libutti, SK Alexander, HR Bartlett, DL TI Oncolytic vaccinia virus expressing the human somatostatin receptor SSTR2: Molecular imaging after systemic delivery using In-111-Pentetreotide SO MOLECULAR THERAPY LA English DT Article DE gene therapy; molecular imaging; reporter genes; vaccinia virus; somatostatin receptor ID POSITRON-EMISSION-TOMOGRAPHY; REPORTER GENE-EXPRESSION; SODIUM-IODIDE SYMPORTER; IN-VIVO; THYMIDINE KINASE; LIVING ANIMALS; TRANSGENE EXPRESSION; ADENOVIRAL VECTOR; TUMOR XENOGRAFTS; THERAPY AB Oncolytic vaccinia viruses (VV) have demonstrated tumor specificity, high levels of transgene expression, and anti-tumor effects. The ability to visualize vector biodistribution noninvasively will be necessary as gene therapy vectors come to clinical trials, and the creation of a VV that can both treat tumors and permit noninvasive imaging after systemic delivery is therefore an exciting concept. To facilitate imaging, a VV expressing the human somatostatin receptor type 2 (SSTR2) was created. Cells infected with the SSTR2-expressing VV or controls were incubated with the somatostatin analog In-111-pentetreotide with or without an excess of nonradiolabeled pentetreotide. The SSTR2-infected cells bound In-111-pentetreotide sixfold more efficiently than control virus-infected cells and this binding was specifically blocked by nonradiolabeled pentetreotide. Nude mice bearing subcutaneous murine colon CA xenografts were injected intra peritoneally with the SSTR2-expressing VV or control VV. After 6 days, mice were injected with In-111-pentetreotide and imaged. Mice were sacrificed and organs collected and counted in a gamma counter. The uptake of radioactivity in tumors and normal tissues (percentage injected dose per gram) and tumor-to-normal tissue ratios were determined. Tumors infected with the SSTR2-expressing VV accumulated significantly higher concentrations of radioactivity compared to tumors in animals receiving the control virus. SSTR2-infected tumors were visible on imaging 6 days after VV injection and could be visualized for up to 3 weeks post-viral injection using repeat injections of In-111-pentetreotide. This reporter gene imaging strategy could be a very effective method to visualize vector distribution, expression, and persistence over time and enhances the potential of VV as a novel anti-cancer therapeutic. C1 Toronto Gen Res Inst, Div Expt Therapeut, Toronto, ON M5G 2M1, Canada. Univ Toronto, Dept Surg, Toronto, ON M5G 1V7, Canada. Univ Toronto, Dept Pharmaceut Sci, Toronto, ON M5G 1V7, Canada. Univ Toronto, Dept Med Imaging, Toronto, ON M5G 1V7, Canada. Toronto Gen Hosp, Div Nucl Med, Toronto, ON M5G 2C4, Canada. NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP McCart, JA (reprint author), Toronto Gen Res Inst, Div Expt Therapeut, 67 Coll St,Room 4-408, Toronto, ON M5G 2M1, Canada. EM amccart@uhnres.utoronto.ca RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 48 TC 46 Z9 48 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2004 VL 10 IS 3 BP 553 EP 561 DI 10.1016/j.ymthe.2004.06.158 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 862HC UT WOS:000224480600020 PM 15336655 ER PT J AU Olanow, CW Agid, Y Mizuno, Y Albanese, A Bonucelli, U Damier, P De Yebenes, J Gershanik, O Guttman, M Grandas, F Hallett, M Hornykiewicz, O Jenner, P Katzenschlager, R Langston, WJ LeWitt, P Melamed, E Mena, MA Michel, PP Mytilineou, C Obeso, JA Poewe, W Quinn, N Rajput, AH Rascol, O Sampaio, C Stocchi, F AF Olanow, CW Agid, Y Mizuno, Y Albanese, A Bonucelli, U Damier, P De Yebenes, J Gershanik, O Guttman, M Grandas, F Hallett, M Hornykiewicz, O Jenner, P Katzenschlager, R Langston, WJ LeWitt, P Melamed, E Mena, MA Michel, PP Mytilineou, C Obeso, JA Poewe, W Quinn, N Rajput, AH Rascol, O Sampaio, C Stocchi, F TI Levodopa in the treatment of Parkinson's disease: Current controversies SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; levodopa; neurotoxicity; dyskinesia; motor complications ID GLOBUS-PALLIDUS NEURONS; MPTP-TREATED MONKEY; CONTROLLED-RELEASE CARBIDOPA/LEVODOPA; PRIMATE SUBTHALAMIC NUCLEUS; MESENCEPHALIC CELL-CULTURES; HYDROGEN-PEROXIDE TOXICITY; MIDBRAIN DOPAMINE NEURONS; OXIDATIVE DNA-DAMAGE; NIGRAL IRON CONTENT; LONG-TERM TREATMENT AB Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease (PD) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to Cultured dopamine neurons, and this may be a problem in PD where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to Suggest that levodopa is toxic in vivo or in PD. Clinical trials have not clarified this situation. Levodopa is also associated with rnotor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce Pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule. Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in MPTP monkeys and PD patients. These studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Clinical trials to test this hypothesis are underway. We review current evidence relating to these areas of controversy. (C) 2004 Movement Disorder Society. C1 Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Hop La Pitie Salpetriere, Paris, France. Jutendo Univ, Sch Med, Dept Neurol, Bunkyo Ku, Tokyo, Japan. Ist Nazl Neurol, Milan, Italy. Univ Pisa, Dept Neurosci, I-56100 Pisa, Italy. Hop Laennec, Neurol Clin, Nantes, France. Univ Autonoma Madrid, Fdn Jimenez Diaz, Madrid, Spain. Hop Frances, Ctr Neuroldgico, Buenos Aires, DF, Argentina. Univ Toronto, Markham, ON, Canada. Hop Gen G Maranon, Madrid, Spain. Natl Inst Neurol Dis Ctr, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Univ Vienna, Sch Med, Brain Res Inst, Vienna, Austria. Univ London Kings Coll, London WC2R 2LS, England. Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. Parkinsons Inst, Sunnyvale, CA USA. Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. Rabin Med Ctr, Dept Neurol, Petah Tiqwa, Israel. Hosp Ramon y Cajal, Dept Neurobiol Invest, Ctr Colmenar, E-28034 Madrid, Spain. Hop La Pitie Salpetriere, INSERM, Paris, France. Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Univ Navarra, E-31080 Pamplona, Spain. Univ Innsbruck Hosp, Dept Neurol, A-6020 Innsbruck, Tyrol, Austria. Neurol Inst, Dept Clin Neurol, London, England. Hop La Pitie Salpetriere, Paris, France. Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada. Clin Univ Ctr, Fac Med, Toulouse, France. R Dr Antonio Loureiro Borges, Lisbon, Portugal. Univ Roma La Sapienza, Hosp San Raffaele, Dept Neurosci, Rome, Italy. RP Olanow, CW (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. EM warren.olanow@mssm.edu OI Michel, Patrick Pierre/0000-0001-5607-3119 NR 131 TC 193 Z9 201 U1 3 U2 33 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2004 VL 19 IS 9 BP 997 EP 1005 DI 10.1002/mds.20243 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 853LX UT WOS:000223830200001 ER PT J AU Ravina, B Putt, M Siderowf, A Farrar, JT Gillespie, M Crawley, A Fernandez, H Treischmann, M Reichwein, S Simuni, T AF Ravina, B Putt, M Siderowf, A Farrar, JT Gillespie, M Crawley, A Fernandez, H Treischmann, M Reichwein, S Simuni, T TI Donepezil for dementia in Parkinson's disease: A randomized, double-blind, placebo-controlled, crossover study. SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 18th Annual Symposium on Etiology, Pathogenesis and Treatment of Parkinsons Disease and Other Movement Disorders CY OCT 03, 2004 CL Toronto, CANADA SP Parkinson Study Grp, Huntington Study Grp, Dystonia Study Grp, Myoclonus Study Grp, Tourettes Syndrome Study Grp, Gooperat Ataxia Grp, Movement Disorder Soc C1 NINDS, Rockville, MD USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Florida, Dept Neurol, Gainesville, FL 32611 USA. Brown Univ, Dept Neurol, Pawtucket, RI 02860 USA. Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2004 VL 19 IS 9 BP 1132 EP 1133 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 853LX UT WOS:000223830200074 ER PT J AU Bagnato, F Gupta, S Pezawas, L Ohayon, J Stone, R Frank, J Richert, N Butman, J McFarland, H AF Bagnato, F Gupta, S Pezawas, L Ohayon, J Stone, R Frank, J Richert, N Butman, J McFarland, H TI Cortical lesions in patients with multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 20th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple- Sclerosis/9th Annual Meeting of Rehabilitation in MS CY OCT 06-09, 2004 CL Vienna, AUSTRIA C1 NIH, Bethesda, MD USA. RI Butman, John/A-2694-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2004 VL 10 IS 7032 SU 2 BP S223 EP S224 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 875YS UT WOS:000225459800468 ER PT J AU Gupta, S Bagnato, E Solomon, J Tasciyan, T Stone, R Richert, N Frank, J McFarland, H AF Gupta, S Bagnato, E Solomon, J Tasciyan, T Stone, R Richert, N Frank, J McFarland, H TI Characterisation of contrast-enhancing lesion sizes and re-enhancements with and without interferon-beta therapy SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 20th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple- Sclerosis/9th Annual Meeting of Rehabilitation in MS CY OCT 06-09, 2004 CL Vienna, AUSTRIA C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2004 VL 10 IS 7032 SU 2 BP S244 EP S244 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 875YS UT WOS:000225459800541 ER PT J AU Scagnolari, G Duda, P Alberelli, A Lavolpe, V Bagnato, F Girardi, E Trojano, M Kappos, L Antonelli, G AF Scagnolari, G Duda, P Alberelli, A Lavolpe, V Bagnato, F Girardi, E Trojano, M Kappos, L Antonelli, G TI Pharmacodynamics of interferon-beta in relapsing-remitting multiple sclerosis with and without neutralising antibodies SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 20th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple- Sclerosis/9th Annual Meeting of Rehabilitation in MS CY OCT 06-09, 2004 CL Vienna, AUSTRIA C1 Univ Roma La Sapienza, Rome, Italy. Univ Basel Hosp, CH-4031 Basel, Switzerland. Univ Bari, Bari, Italy. NINDS, NIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2004 VL 10 IS 7032 SU 2 BP S255 EP S255 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 875YS UT WOS:000225459800578 ER PT J AU Tovar-Moll, FF Lent, R de Freitas, GR Moll, J Bramati, I Oliveira-Souza, R Souzo-Lima, E Bagnato, F McFarland, H AF Tovar-Moll, FF Lent, R de Freitas, GR Moll, J Bramati, I Oliveira-Souza, R Souzo-Lima, E Bagnato, F McFarland, H TI Remote effects of MS plaques on fibre bundles: preliminary DTI tractography findings SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 20th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple- Sclerosis/9th Annual Meeting of Rehabilitation in MS CY OCT 06-09, 2004 CL Vienna, AUSTRIA C1 UFRI, Neuroimmunol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2004 VL 10 IS 7032 SU 2 BP S231 EP S231 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 875YS UT WOS:000225459800495 ER PT J AU Lin, JZ Floeter, MK AF Lin, JZ Floeter, MK TI Do F-wave measurements detect changes in motor neuron excitability? SO MUSCLE & NERVE LA English DT Article DE backfiring; F response; motor neuron excitability; persistence; reflex methods ID CUTANEOUS SILENT PERIOD; MOTONEURONAL EXCITABILITY; H-REFLEXES; CORTEX EXCITABILITY; RESPONSES; MUSCLES; SIZE; SENSITIVITY; STIMULATION; DISCHARGE AB The use of F waves to assess motor neuron excitability in experimental paradigms has never been validated. Our objective was to determine whether F-wave area, amplitude, and persistence measurements change in response to manipulations known to alter the excitability of motor neurons. The effects of muscle vibration, contraction of a remote muscle, and high-intensity stimulation of ipsilateral o, contralateral fingers were assessed in 12 healthy volunteers. F-wave area, amplitude, and persistence all declined with ipsilateral cutaneous stimulation. The other maneuvers facilitated some, but not all, of the F-wave measurements. Changes in F-wave area and amplitude were correlated, but neither correlated with changes in persistence. A sample size of 50-75 F waves was needed to approximate amplitude and area results from 100 F waves with an accuracy of +/-25%. We conclude that changes in F waves are better at detecting inhibition than facilitation of motor neurons. F waves reflect motor neuron excitability in a general way but do not allow for accurate measures of short-term changes in excitability. C1 NINDS, Electromyog Sect, NIH, Bethesda, MD 20892 USA. RP NINDS, Electromyog Sect, NIH, Bldg 10,Room 5C101,10 Ctr Dr MSC 1404, Bethesda, MD 20892 USA. EM floeterm@ninds.nih.gov NR 37 TC 39 Z9 39 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 2004 VL 30 IS 3 BP 289 EP 294 DI 10.1002/mus.20110 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 849HO UT WOS:000223529500004 PM 15318339 ER PT J AU Chen, KH Guo, XM Ma, DL Guo, YH Li, QA Yang, DM Li, PF Qiu, XY Wen, SJ Xiao, RP Tang, JA AF Chen, KH Guo, XM Ma, DL Guo, YH Li, QA Yang, DM Li, PF Qiu, XY Wen, SJ Xiao, RP Tang, JA TI Dysregulation of HSG triggers vascular proliferative disorders SO NATURE CELL BIOLOGY LA English DT Article ID MUSCLE CELL-PROLIFERATION; SPONTANEOUSLY HYPERTENSIVE RAT; DEPENDENT KINASE INHIBITOR; SMOOTH-MUSCLE; GENE-THERAPY; IN-VIVO; CARDIOVASCULAR-DISEASE; MITOCHONDRIAL FUSION; INTIMAL HYPERPLASIA; NEOINTIMA FORMATION AB Vascular proliferative disorders, such as atherosclerosis and restenosis, are the most common causes of severe cardiovascular diseases, but a common molecular mechanism remains elusive. Here, we identify and characterize a novel hyperplasia suppressor gene, named HSG (later re-named rat mitofusin-2). HSG expression was markedly reduced in hyper-proliferative vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rat arteries, balloon-injured Wistar Kyoto rat arteries, or ApoE-knockout mouse atherosclerotic arteries. Overexpression of HSG overtly suppressed serum-evoked VSMC proliferation in culture, and blocked balloon injury induced neointimal VSMC proliferation and restenosis in rat carotid arteries. The HSG anti-proliferative effect was mediated by inhibition of ERK/MAPK signalling and subsequent cell-cycle arrest. Deletion of the p21(ras) signature motif, but not the mitochondrial targeting domain, abolished HSG-induced growth arrest, indicating that rHSG-induced anti-proliferation was independent of mitochondrial fusion. Thus, rHSG functions as a cell proliferation suppressor, whereas dysregulation of rHSG results in proliferative disorders. C1 Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China. Peking Univ, Inst Mol Med, Beijing 100083, Peoples R China. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Peking Univ, Ctr Human Dis Gen, Beijing 100083, Peoples R China. Peking Univ, Dept Immunol, Ctr Hlth, Beijing 100083, Peoples R China. RP Xiao, RP (reprint author), Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China. EM xiaor@grc.nia.nih.gov RI GUO, Yanhong/B-5325-2012; Guo, Yanhong/D-9764-2012 NR 49 TC 187 Z9 262 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2004 VL 6 IS 9 BP 872 EP U8 DI 10.1038/ncb/1161 PG 16 WC Cell Biology SC Cell Biology GA 852IZ UT WOS:000223750300017 PM 15322553 ER PT J AU Austin, CP Battey, JF Bradley, A Bucan, M Capecchi, M Collins, FS Dove, WF Duyk, G Dymecki, S Eppig, JT Grieder, FB Heintz, N Hicks, G Insel, TR Joyner, A Koller, BH Lloyd, KCK Magnuson, T Moore, MW Nagy, A Pollock, JD Roses, AD Sands, AT Seed, B Skarnes, WC Snoddy, J Soriano, P Stewart, DJ Stewart, F Stillman, B Varmus, H Varticovski, L Verma, IM Vogt, TF von Melchner, H Witkowski, J Woychik, RP Wurst, W Yancopoulos, GD Young, SG Zambrowicz, B AF Austin, CP Battey, JF Bradley, A Bucan, M Capecchi, M Collins, FS Dove, WF Duyk, G Dymecki, S Eppig, JT Grieder, FB Heintz, N Hicks, G Insel, TR Joyner, A Koller, BH Lloyd, KCK Magnuson, T Moore, MW Nagy, A Pollock, JD Roses, AD Sands, AT Seed, B Skarnes, WC Snoddy, J Soriano, P Stewart, DJ Stewart, F Stillman, B Varmus, H Varticovski, L Verma, IM Vogt, TF von Melchner, H Witkowski, J Woychik, RP Wurst, W Yancopoulos, GD Young, SG Zambrowicz, B CA Comprehensive Knockout Mouse Proje TI The knockout mouse project SO NATURE GENETICS LA English DT Article ID EMBRYONIC STEM-CELLS; GENE-TRAP MUTAGENESIS; GENOME; MICE; SEQUENCE; IDENTIFICATION; DEFICIENCY; PHENOTYPE; INSIGHTS; RESOURCE AB Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT 85112 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. TPG Ventures, San Francisco, CA 94104 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NIH, Natl Ctr Res Resources, Bethesda, MD 20817 USA. Rockefeller Univ, Mol Biol Lab, New York, NY 10021 USA. Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. NIMH, Bethesda, MD 20892 USA. Skirball Inst Biomol Med, New York, NY 10016 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. Deltagen, Redwood City, CA 94063 USA. Univ Toronto, Samuel Lumenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Natl Inst Drug Abuse, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. Lexicon Genet, The Woodlands, TX 77381 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Oak Ridge Natl Lab, Univ Tennessee ORNL Grad Sch Genome Sci & Technol, Oak Ridge, TN 37831 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Cold Spring Harbor Lab, Banbury Ctr, Cold Spring Harbor, NY 11724 USA. Univ Technol, Bioz, MPI CBG, D-1307 Dresden, Germany. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Mol Biol & Virol Lab, La Jolla, CA 92037 USA. Merck Res Labs, West Point, PA 19486 USA. Goethe Univ Frankfurt, Sch Med, Lab Mol Hematol, D-60590 Frankfurt, Germany. Jackson Lab, Bar Harbor, ME 04609 USA. Max Planck Inst Psychiat, GSF Res Ctr, Inst Dev Genet, D-85764 Munich, Germany. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. Univ Calif San Francisco, Gladstone Fdn Cardiovasc Dis, San Francisco, CA 94143 USA. RP Austin, CP (reprint author), NHGRI, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. EM austinc@mail.nih.gov RI Pollock, Jonathan/B-1554-2009; Stewart, A. Francis/E-7789-2010; Nagy, Andras/G-6465-2013; Soriano, Philippe/E-5797-2015; OI Soriano, Philippe/0000-0002-0427-926X; Witkowski, Jan/0000-0002-8159-2874; Stillman, Bruce/0000-0002-9453-4091 FU Wellcome Trust [077188] NR 25 TC 359 Z9 385 U1 4 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2004 VL 36 IS 9 BP 921 EP 924 DI 10.1038/ng0904-921 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 851AY UT WOS:000223658100005 PM 15340423 ER PT J AU Huusko, P Ponciano-Jackson, D Wolf, M Kiefer, JA Azorsa, DO Tuzmen, S Weaver, D Robbins, C Moses, T Allinen, M Hautaniemi, S Chen, YD Elkahloun, A Basik, M Bova, GS Bubendorf, L Lugli, A Sauter, G Schleutker, J Ozcelik, H Elowe, S Pawson, T Trent, JM Carpten, JD Kallioniemi, OP Mousses, S AF Huusko, P Ponciano-Jackson, D Wolf, M Kiefer, JA Azorsa, DO Tuzmen, S Weaver, D Robbins, C Moses, T Allinen, M Hautaniemi, S Chen, YD Elkahloun, A Basik, M Bova, GS Bubendorf, L Lugli, A Sauter, G Schleutker, J Ozcelik, H Elowe, S Pawson, T Trent, JM Carpten, JD Kallioniemi, OP Mousses, S TI Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer SO NATURE GENETICS LA English DT Article ID GENE-EXPRESSION PATTERNS; BREAST-CANCER; COPY-NUMBER; RECEPTORS; EPHRIN-B2 AB The identification of tumor-suppressor genes in solid tumors by classical cancer genetics methods is difficult and slow. We combined nonsense-mediated RNA decay microarrays(1) and array-based comparative genomic hybridization(2,3) for the genome-wide identification of genes with biallelic inactivation involving nonsense mutations and loss of the wild-type allele. This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EPHB2. The DU 145 prostate cancer cell line, originating from a brain metastasis, carries a truncating mutation of EPHB2 and a deletion of the remaining allele. Additional frameshift, splice site, missense and nonsense mutations are present in clinical prostate cancer samples. Transfection of DU 145 cells, which lack functional EphB2, with wild-type EPHB2 suppresses clonogenic growth. Taken together with studies indicating that EphB2 may have an essential role in cell migration and maintenance of normal tissue architecture, our findings suggest that mutational inactivation of EPHB2 may be important in the progression and metastasis of prostate cancer. C1 Translat Genom Res Inst, Genet Basis Human Dis Res Div, Phoenix, AZ 85004 USA. Univ Turku, Turku 20521, Finland. VTT Tech Res Ctr Finland, Turku 20521, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Tampere Univ Technol, Inst Signal Proc, FIN-33101 Tampere, Finland. Jewish Gen Hosp, Dept Oncol, Montreal, PQ H3T 1E2, Canada. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. Univ Tampere, Inst Med Technol, Canc Genet Lab, Tampere 33520, Finland. Tampere Univ Hosp, Tampere 33520, Finland. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Kallioniemi, OP (reprint author), Translat Genom Res Inst, Canc Durg Dev Lab, 20 Firstfield Rd,Suite 110, Gaithersburg, MD 20878 USA. EM smousses@tgen.org; olli.kallioniemi@vtt.fi RI Hautaniemi, Sampsa/A-3122-2009; Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011; Pawson, Tony/E-4578-2013; Tuzmen, Sukru/I-5663-2013; Kallioniemi, Olli/H-4738-2012; OI Hautaniemi, Sampsa/0000-0002-7749-2694; Kallioniemi, Olli/0000-0002-3231-0332; Tuzmen, Sukru/0000-0003-4822-396X; Kallioniemi, Olli/0000-0002-3231-0332; Kiefer, Jeff/0000-0002-1238-3120 NR 21 TC 124 Z9 137 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2004 VL 36 IS 9 BP 979 EP 983 DI 10.1038/ng1408 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 851AY UT WOS:000223658100024 PM 15300251 ER PT J AU Kleta, R Romeo, E Ristic, Z Ohura, T Stuart, C Arcos-Burgos, M Dave, MH Wagner, CA Camargo, SRM Inoue, S Matsuura, N Helip-Wooley, A Bockenhauer, D Warth, R Bernardini, I Visser, G Eggermann, T Lee, P Chairoungdua, A Jutabha, P Babu, E Nilwarangkoon, S Anzai, N Kanai, Y Verrey, F Gahl, WA Koizumi, A AF Kleta, R Romeo, E Ristic, Z Ohura, T Stuart, C Arcos-Burgos, M Dave, MH Wagner, CA Camargo, SRM Inoue, S Matsuura, N Helip-Wooley, A Bockenhauer, D Warth, R Bernardini, I Visser, G Eggermann, T Lee, P Chairoungdua, A Jutabha, P Babu, E Nilwarangkoon, S Anzai, N Kanai, Y Verrey, F Gahl, WA Koizumi, A TI Mutations in SLC6A19, encoding B(0)AT1, cause Hartnup disorder SO NATURE GENETICS LA English DT Article ID RECESSIVE TRAITS; TRANSPORTER; NEPHRON AB Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), cerebellar ataxia and psychosis(1,2). Using homozygosity mapping in the original family in whom Hartnup disorder was discovered, we confirmed that the critical region for one causative gene was located on chromosome 5p15 (ref. 3). This region is homologous to the area of mouse chromosome 13 that encodes the sodium-dependent amino acid transporter B(0)AT1 (ref. 4). We isolated the human homolog of B(0)AT1, called SLC6A19, and determined its size and molecular organization. We then identified mutations in SLC6A19 in members of the original family in whom Hartnup disorder was discovered and of three Japanese families. The protein product of SLC6A19, the Hartnup transporter, is expressed primarily in intestine and renal proximal tubule and functions as a neutral amino acid transporter. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Off Rare Dis, Intramural Program, Off Director, Bethesda, MD 20892 USA. Univ Zurich, Inst Physiol, Zurich, Switzerland. Tohoku Univ, Sch Med, Dept Pediat, Sendai, Miyagi 980, Japan. Kyoto Univ, Grad Sch Med, Kyoto, Japan. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Univ Regensburg, Inst Physiol, D-8400 Regensburg, Germany. Univ Utrecht Hosp, Wilhelmina Childrens Hosp, Dept Metab Dis, Utrecht, Netherlands. Aachen Univ Hosp, Inst Human Genet, Aachen, Germany. UCL Natl Hosp Neurol & Neurosurg, Charles Dent Metab Unit, London, England. Kyorin Univ, Sch Med, Dept Pharmacol & Toxicol, Tokyo, Japan. RP Kleta, R (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-107, Bethesda, MD 20892 USA. EM kletar@mail.nih.gov RI Bockenhauer, Detlef/C-5951-2008; Warth, Richard/N-7119-2014; Eggermann, Thomas/F-3807-2014 OI Bockenhauer, Detlef/0000-0001-5878-941X; Warth, Richard/0000-0001-6084-0659; NR 17 TC 122 Z9 125 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD SEP PY 2004 VL 36 IS 9 BP 999 EP 1002 DI 10.1038/ng1405 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 851AY UT WOS:000223658100028 PM 15286787 ER PT J AU O'Shea, JJ Watford, W AF O'Shea, JJ Watford, W TI A peek at PIAS SO NATURE IMMUNOLOGY LA English DT Editorial Material ID SIGNAL-TRANSDUCTION; PROTEINS; SUMO AB Members of the PIAS family can negatively regulate the cytokine-activated Jak-STAT pathway in vitro. One member of this family, PIAS1, is a nonredundant and physiologic regulator of certain STAT1-dependent interferon-induced genes. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Rockville, MD 20852 USA. RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Rockville, MD 20852 USA. EM osheajo@mail.nih.gov NR 13 TC 17 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2004 VL 5 IS 9 BP 875 EP 876 DI 10.1038/ni0904-875 PG 2 WC Immunology SC Immunology GA 850LI UT WOS:000223612500006 PM 15334080 ER PT J AU Strober, W AF Strober, W TI Epithelial cells pay a Toll for protection SO NATURE MEDICINE LA English DT Editorial Material ID MURINE COLITIS AB Ligands from commensal microflora can stimulate Toll-like receptors on the surface of intestinal epithelial cells. Work in mice now assigns a surprising role to such signals: cell survival and repair during inflammation. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 12 TC 41 Z9 42 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2004 VL 10 IS 9 BP 898 EP 900 DI 10.1038/nm0904-898 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 851AZ UT WOS:000223658400013 PM 15340409 ER PT J AU Shevach, EM AF Shevach, EM TI Fatal attraction: tumors beckon regulatory T cells SO NATURE MEDICINE LA English DT Editorial Material ID CANCER AB Tumor tissue and ascites from patients with ovarian cancer contain high levels of cells with all the hallmarks of regulatory T cells. These cells migrate into the tumor microenvironment in a process mediated by the chemokine CCL22, and are capable of suppressing antitumor responses ( pages 942 - 949). C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 11 TC 68 Z9 75 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2004 VL 10 IS 9 BP 900 EP 901 DI 10.1038/nm0904-900 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 851AZ UT WOS:000223658400014 PM 15340410 ER EF