FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Wang, H
   Lin, L
   Jiang, JG
   Wang, Y
   Lu, ZY
   Bradbury, JA
   Lih, FB
   Wang, DW
   Zeldin, DC
AF Wang, H
   Lin, L
   Jiang, JG
   Wang, Y
   Lu, ZY
   Bradbury, JA
   Lih, FB
   Wang, DW
   Zeldin, DC
TI Up-regulation of endothelial nitric-oxide synthase by
   endothelium-derived hyperpolarizing factor involves mitogen-activated
   protein kinase and protein kinase C signaling pathways
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ARACHIDONIC-ACID EPOXYGENASE; EPIDERMAL GROWTH-FACTOR;
   EPOXYEICOSATRIENOIC ACIDS; DIHYDROXYEICOSATRIENOIC ACIDS; TYROSINE
   PHOSPHORYLATION; EPOXIDE HYDROLASE; CORONARY-ARTERIES; SMOOTH-MUSCLE;
   CYTOCHROME-P450; CELLS
AB Cytochrome P450 (P450)-dependent metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs), are proposed to be endothelium-derived hyperpolarizing factors ( EDHF) that affect vascular tone; however, the effects of EDHF on endothelial-derived nitric oxide biosynthesis remain unknown. We examined the regulation of endothelial nitric-oxide synthase ( eNOS) by EDHF and investigated the relevant signaling pathways involved. The P450 epoxygenases CYP102 F87V mutant, CYP2C11-CYPOR, and CYP2J2 were transfected into cultured bovine aortic endothelial cells, and the effects of endogenously formed or exogenously applied EETs on eNOS expression and activity were assessed. Transfection with the P450 epoxygenases led to increased eNOS protein expression, an effect that was attenuated by cotreatment with the P450 inhibitor 17-ODYA. Northern analysis demonstrated that P450 transfection led to increased eNOS mRNA levels consistent with an effect at the pretranslational level. P450 epoxygenase transfection resulted in increased eNOS activity as measured by the conversion of L-arginine to L-citrulline. Addition of synthetic EETs (50 - 200 nM) to the culture media also increased eNOS expression and activity. Treatment with mitogen-activated protein kinase ( MAPK), MAPK kinase, and protein kinase C inhibitors apigenin, 2'-amino-3'-methoxyflavone (PD98059), and 1-(5-isoquinolinesulfonyl)- 2-methylpiperazine (H-7), respectively, significantly inhibited the effects of P450 transfection on eNOS expression. Overexpression of P450 epoxygenases or addition of synthetic EETs increased Thr495 phosphorylation of eNOS, an effect that was inhibited by both apigenin and PD98059. Overexpression of P450 epoxygenases in rats resulted in increased aortic eNOS expression, providing direct evidence that EDHF can influence vascular eNOS levels in vivo. Based on this data, we conclude that EDHF up-regulates eNOS via activation of MAPK and protein kinase C signaling pathways.
C1 Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiol, Wuhan 430030, Peoples R China.
   NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiol, 1095 Jie Fang Da Dao Ave, Wuhan 430030, Peoples R China.
NR 52
TC 64
Z9 82
U1 0
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD NOV
PY 2003
VL 307
IS 2
BP 753
EP 764
DI 10.1124/jpet.103.052787
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 734UP
UT WOS:000186076600040
PM 12975498
ER

PT J
AU Raje, S
   Cao, JJ
   Newman, AH
   Gao, HL
   Eddington, ND
AF Raje, S
   Cao, JJ
   Newman, AH
   Gao, HL
   Eddington, ND
TI Evaluation of the blood-brain barrier transport, population
   pharmacokinetics, and brain distribution of benztropine analogs and
   cocaine using in vitro and in vivo techniques
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID DOPAMINE UPTAKE INHIBITORS; P-GLYCOPROTEIN; ENAMINONE ANTICONVULSANTS;
   MULTIDRUG-RESISTANCE; RHESUS-MONKEYS; RAT PLASMA; ABUSE;
   PHARMACOTHERAPIES; REINFORCEMENT; METABOLITES
AB The N-substituted 3alpha- [bis(4'-fluorophenyl) methoxy] tropanes (AHN 2-003, AHN 1-055, AHN 2-005, and JHW 007) bind with high affinity to the dopamine transporter and inhibit dopamine uptake more potently than cocaine, but they demonstrate behavioral profiles in animal models of psychostimulant abuse that are unlike that of cocaine. The objective of this study was to characterize the in vitro permeability, brain distribution, and pharmacokinetics of the benztropine (BZT) analogs. Transport studies of cocaine and the BZT analogs (10(-4) M) were conducted across bovine brain microvessel endothelial cells. Male Sprague-Dawley rats (similar to300 g) were administered BZT analogs (10 mg/kg) or cocaine (5 mg/kg) via the tail vein. Blood and brain samples were collected over 36 h and assayed using UV-high-performance liquid chromatography. Transport of both AHN 1-055 (2.15 x 10(-4) cm/s) and JHW 007 (2.83 x 10(-4) cm/s) was higher (p < 0.05) than that of cocaine (1.63 x 10(-4) cm/s). The volume of distribution (12.3 - 30.5 l/kg) of the analogs was significantly higher than cocaine (0.9 l/kg). The BZT analogs displayed a &GE;8-fold higher elimination half-life (4.12 - 16.49 h) compared with cocaine (0.49 h). The brain-to-plasma partition coefficients were at least two-fold higher for the BZTs versus cocaine, except for AHN 2-003. The BZT analogs are highly permeable across the blood-brain barrier and possess a pharmacokinetic profile different from that of cocaine. These characteristics, in addition to their distinctive behavioral profiles, suggest that the BZT analogs may be promising candidates for the treatment of cocaine abuse.
C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA.
   NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, 20 Penn St,HSF II, Baltimore, MD 21201 USA.
FU NCI NIH HHS [CA 87654-02]
NR 39
TC 41
Z9 41
U1 1
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD NOV
PY 2003
VL 307
IS 2
BP 801
EP 808
DI 10.1124/jpet.103.053504
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 734UP
UT WOS:000186076600045
PM 12966155
ER

PT J
AU Coupland, NJ
   Singh, AJ
   Sustrik, RA
   Ting, P
   Blair, RJ
AF Coupland, NJ
   Singh, AJ
   Sustrik, RA
   Ting, P
   Blair, RJ
TI Effects of diazepam on facial emotion recognition
SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE
LA English
DT Article
DE diazepam; emotions; facial expression; gamma-aminobutyric acid;
   perception
ID SELECTIVE IMPAIRMENT; EXPRESSIONS; FACE; PERCEPTION; ATTENTION; DISGUST;
   ANGER; FMRI; IDENTIFICATION; EXPERIENCE
AB Objective: There have been few studies of the pharmacologic modulation of facial emotion recognition. The present study aimed to replicate and extend the finding that recognition of facial anger was selectively impaired by diazepam. The hypothesis was that, in comparison with placebo, diazepam would impair the recognition of facial anger in healthy volunteers, but not the recognition of 5 other basic emotions: happiness, surprise, fear, sadness and disgust. Design: A randomized, counterbalanced, double-blind, placebo-controlled, within-subjects comparison of diazepam with placebo. Setting: A university psychopharmacology research unit. Participants: Healthy male (n = 6) and female (n = 22) volunteers, aged 1845 years. Procedures: Subjects were tested on 2 tasks following the administration of diazepam, 15 mg, and placebo on separate occasions. In the first "multimorph" task, images of facial expressions were morphed to produce continua between the neutral and full expressions of 6 basic emotions. Accuracy and identification thresholds were assessed for stimuli in which the intensity of expression gradually increased. In the second "emotional hexagon" task, facial expressions were morphed between pairs of emotions. Single images were presented, and accuracy and speed of response were assessed. Results: Diazepam produced broad impairments in response accuracy, recognition thresholds and response speed on the facial emotion tasks that were not limited to angry expressions. Conclusions: The present study found that diazepam, 15 mg, impaired facial emotion recognition, but not selectively. In the emotional hexagon task, a reaction-time analysis suggested that the identification of facial anger might be differentially sensitive to variations in stimulus duration, complicating the interpretation of this paradigm.
C1 Univ Alberta, Dept Psychiat, Psychopharmacol Res Unit, Edmonton, AB T6G 2B7, Canada.
   St Georges Univ, Fac Med, St Georges, Grenada.
   NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
RP Coupland, NJ (reprint author), Univ Alberta, Dept Psychiat, Psychopharmacol Res Unit, 1E7-16 WMC,8440-112 St, Edmonton, AB T6G 2B7, Canada.
NR 37
TC 20
Z9 22
U1 14
U2 16
PU CANADIAN MEDICAL ASSOCIATION
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA
SN 1180-4882
J9 J PSYCHIATR NEUROSCI
JI J. Psychiatry Neurosci.
PD NOV
PY 2003
VL 28
IS 6
BP 452
EP 463
PG 12
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 745VZ
UT WOS:000186712500004
PM 14631456
ER

PT J
AU Newman, RB
   Johnson, F
   Das, A
   Goldenberg, RL
   Swain, M
   Moawad, A
   Sibai, BM
   Caritis, SN
   Miodovnik, M
   Paul, RH
   Dombrowski, MP
   Sharp, BAC
   Fischer, M
AF Newman, RB
   Johnson, F
   Das, A
   Goldenberg, RL
   Swain, M
   Moawad, A
   Sibai, BM
   Caritis, SN
   Miodovnik, M
   Paul, RH
   Dombrowski, MP
   Sharp, BAC
   Fischer, M
CA Natl Inst Child Hlth Human Dev
TI Uterine contraction frequency before and after successful tocolytic
   therapy for preterm uterine contractions
SO JOURNAL OF REPRODUCTIVE MEDICINE
LA English
DT Article
DE labor; premature; uterine contraction; tocolysis
ID RITODRINE HYDROCHLORIDE; MAGNESIUM-SULFATE; LABOR; BIRTH
AB OBJECTIVE: To examine the association between prelabor uterine contraction frequency (UCF) and the success of tocolytic therapy for preterm labor (PTL).
   STUDY DESIGN: Eleven centers conducted a prospective, observational study of UCF recorded between 22017 and 36617 weeks' gestational age or until delivery greater than or equal to2 times/d on greater than or equal to2 d/wk in women with singleton pregnancies with and without risk factors for preterm birth. Uterine contraction data obtained from patients diagnosed with PTL allowed comparison of mean UCF both before and after an acute episode of PTL treated with either intravenous, subcutaneous or oral tocolysis. The signed rank test was used to analyze differences in UCF before and after tocolytic therapy and between women who were or were not successfully treated with a labor-inhibiting agent.
   RESULTS: Of 454 enrolled women, 128 were diagnosed with PTL, and 74 were successfully treated with a labor-inhibiting agent. The mean UCF preceding PTL was not different between those women successfully treated and those who delivered as a consequence of the PTL episode. There was no difference (P = .653) in mean UCF between the week before PTL (UCF 0.60 +/- 0.8, median 0.30) and the first week of monitoring after successful tocolysis (UCF 0.82 +/- 1.4, median 0.27).
   CONCLUSION: The mean UCF immediately preceding PTL does not predict tocolytic success or failure.
C1 Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA.
   Ohio State Univ, Columbus, OH 43210 USA.
   Univ Alabama, Birmingham, AL USA.
   Wake Forest Univ, Winston Salem, NC 27109 USA.
   Univ Chicago, Chicago, IL 60637 USA.
   Univ Tennessee, Memphis, TN USA.
   Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA.
   Univ Cincinnati, Cincinnati, OH USA.
   Univ So Calif, Los Angeles, CA USA.
   Wayne State Univ, Detroit, MI USA.
   George Washington Univ, Ctr Biostat, Washington, DC USA.
   NICHHD, Bethesda, MD 20892 USA.
RP Newman, RB (reprint author), Med Univ S Carolina, Dept Obstet & Gynecol, 96 Jonathan Lucas St,Suite 634,POB 250619, Charleston, SC 29425 USA.
OI caritis, steve/0000-0002-2169-0712
FU NICHD NIH HHS [HD 21414, HD 19897, HD 21410, HD 21434, HD 27860, HD
   27861, HD 27869, HD 27883, HD 27889, HD 27905, HD 27915, HD 27917]
NR 17
TC 0
Z9 0
U1 0
U2 1
PU SCI PRINTERS & PUBL INC
PI ST LOUIS
PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA
SN 0024-7758
J9 J REPROD MED
JI J. Reprod. Med.
PD NOV
PY 2003
VL 48
IS 11
BP 843
EP 849
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 748QY
UT WOS:000186873600002
PM 14686015
ER

PT J
AU Pianta, RC
AF Pianta, RC
TI Untitled
SO JOURNAL OF SCHOOL PSYCHOLOGY
LA English
DT Editorial Material
C1 Univ Virginia, NICHD Study, Charlottesville, VA 22908 USA.
RP Pianta, RC (reprint author), Univ Virginia, NICHD Study, POB 800784, Charlottesville, VA 22908 USA.
OI Pianta, Robert/0000-0002-6280-8051
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-4405
J9 J SCHOOL PSYCHOL
JI J. Sch. Psychol.
PD NOV-DEC
PY 2003
VL 41
IS 6
BP 399
EP 400
DI 10.1016/j.jsp.2003.09.001
PG 2
WC Psychology, Educational
SC Psychology
GA 754UA
UT WOS:000187349000001
ER

PT J
AU Breslow, RA
   Faden, VB
   Smothers, B
AF Breslow, RA
   Faden, VB
   Smothers, B
TI Alcohol consumption by elderly Americans
SO JOURNAL OF STUDIES ON ALCOHOL
LA English
DT Article
ID POPULATION; DRINKING; ADULTS
AB Objective: The purpose of this study was to estimate the prevalence of alcohol consumption in Americans age 65 years and older using data from three nationally representative cross-sectional surveys: the National Health Interview Survey (NHIS-2000), the Behavioral Risk Factor Surveillance System (BRFSS-2001) and the National Household Survey on Drug Abuse (NHSDA-2000). Method: Alcohol consumption levels were defined as none, moderate (less than or equal to1 drink a day) and heavier (>1 drink a day). The NHIS assessed alcohol consumption in the past year, and the BRFSS and NHSDA assessed alcohol consumption in the past 30 days. Differences between the BRFSS and NHSDA were tested using multinomial logistic regression. Age trends in alcohol consumption (between age 65 and 84 years) were tested using logistic regression. All analyses were weighted to produce national estimates. Results: In men, the prevalence of moderate drinking was 37.6% (95% confidence interval [0]: 35.2-40.0) in the NHIS, 38.7% (CI: 37.3-40.1) in the BRFSS and 27.2% (CI: 23.6-30.8) in the NHSDA. The prevalence of heavier drinking among men was 10.1% (CL 8.7-11.5), 10.1% (CI: 9.3-10.9) and 0.2% (CI: 7.2-11.3), respectively In women, the prevalence of moderate drinking was 32.3% (CI: 30.4-34.2) in the NHIS, 27.7% (CI: 26.7-28.6) in the BRFSS and 21.5% (CI: 18.9-24.2) in the NHSDA. The prevalence of heavier drinking among women was 2.2% (CI: 1.6-2.7), 2.6% (CI: 2.3-2.9) and 2.4% (CI: 1.4-3.3), respectively In increasingly older groups of men, moderate drinking remained stable (all surveys, p for age trend [p trend] = NS), while heavier drinking significantly decreased in two of three surveys (NHIS and BRFSS, p trend < .05; NHSDA, p = NS). Conversely, in increasingly older groups of women, moderate drinking significantly decreased (all surveys, p trend = .001), while heavier drinking remained stable (all surveys, p trend = NS). Conclusions: In the years 2000 to 2001 approximately one third of the US. elderly population, about I I million persons, consumed alcohol. The risks and benefits of drinking by elderly Americans will become an increasingly important public health issue as this segment of the population expands over the coming decades.
C1 NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
RP Breslow, RA (reprint author), NIAAA, Div Epidemiol & Prevent Res, Willco Bldg,Suite 514,6000 Execut Blvd, Bethesda, MD 20892 USA.
NR 23
TC 49
Z9 50
U1 1
U2 2
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 0096-882X
J9 J STUD ALCOHOL
JI J. Stud. Alcohol
PD NOV
PY 2003
VL 64
IS 6
BP 884
EP 892
PG 9
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 758TD
UT WOS:000187665500018
PM 14743953
ER

PT J
AU Agelli, M
   Clegg, LX
AF Agelli, M
   Clegg, LX
TI Epidemiology of primary Merkel cell carcinoma in the United States
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
ID NEURON-SPECIFIC ENOLASE; END RESULTS PROGRAM; TRABECULAR CARCINOMA;
   NEUROENDOCRINE CARCINOMAS; SPONTANEOUS REGRESSION; SKIN; TUMORS;
   MANAGEMENT; FEATURES; MARKER
AB Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer.
   Objective: We sought to describe primary MCC incidence trends, epidemiology, and predictors of survival.
   Methods: The population covered by the Surveillance, Epidemiology, and End Results Program was analyzed as a prospective cohort. We measured age-adjusted incidence rates (per 100,000 person-years) and effect of age, anatomic site, and stage on survival.
   Results: Incidence was higher in males (0.34) than in females (0.17). Cases (n = 1034) occurred mostly in whites (94%), in people older than 65 years (76%), and at the head (48%). The 5-year relative Survival was 75%, 59%, and 25% for localized, regional, and distant MCC, respectively. Female sex, limb presentation, localized disease, and younger age were positive predictors of survival.
   Conclusion: The highest incidence of MCC was observed in whites, males, and in people older than 65 years. Only 49% of cases were reported as localized. Better survival was associated with limb localization, early-stage disease, younger age, and female sex.
C1 NCI, OCTR, Bethesda, MD 20892 USA.
   NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Agelli, M (reprint author), NCI, OCTR, 6116 Execut Blvd,Suite 7021, Bethesda, MD 20892 USA.
NR 71
TC 243
Z9 245
U1 2
U2 8
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 NOV
PY 2003
VL 49
IS 5
BP 832
EP 841
DI 10.1067/S0190-9622(03)02108-X
PG 10
WC Dermatology
SC Dermatology
GA 737NE
UT WOS:000186238000005
PM 14576661
ER

PT J
AU Gray, SL
   Penninx, BWJH
   Blough, DK
   Artz, MB
   Guralnik, JM
   Wallace, RB
   Buchner, DM
   LaCroix, AZ
AF Gray, SL
   Penninx, BWJH
   Blough, DK
   Artz, MB
   Guralnik, JM
   Wallace, RB
   Buchner, DM
   LaCroix, AZ
TI Benzodiazepine use and physical performance in community-dwelling older
   women
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE benzodiazepine; activities of daily living; aged; cohort studies
ID ELIMINATION HALF-LIFE; RISK-FACTORS; ESTABLISHED POPULATIONS; DEPRESSIVE
   SYMPTOMS; MEDICATION USE; DISABILITY; HEALTH; PEOPLE; SCALE; FALLS
AB OBJECTIVES: To determine whether benzodiazepine use in older women increased the risk of decline in physical function.
   DESIGN: A four-year prospective cohort study.
   SETTING: The communities of Iowa and Washington counties, Iowa.
   PARTICIPANTS: Eight hundred eighty-five women aged 70 and older who had completed physical performance tests in 1988 and 1992.
   MEASUREMENTS: Benzodiazepine use was determined during in-home interviews and classified by dose, duration, indication for use, and half-life. Physical performance tests included an assessment of standing balance, walking speed (8-foot distance), and repeated chair raises.
   RESULTS: Ninety (10.2%) reported benzodiazepine use at baseline. After adjustment for baseline physical performance score and potential confounders, benzodiazepine use was associated with a greater decline in physical performance over 4 years than nonuse (beta=-1.16; standard error (SE)=0.25; P<.001). The use of higher-than-recommended dose was related to decline (beta=-2.26; SE=0.47; P<.001), and use of lower doses was not (beta=-0.53; SE=0.46; P=.246). Long-term use (greater than or equal to3 years) was related to decline (beta=-1.65; SE=0.34; P<.001), whereas recent and past use were not. Similar results were obtained when restricting the sample to those without disability at baseline.
   CONCLUSION: This study provides evidence that older women who used benzodiazepines were at risk for decline in physical performance. Subgroup analyses indicated that risk was greater with use of higher-than-recommended doses or for long duration (greater than or equal to3 years). These findings highlight the importance of using benzodiazepines at the lowest effective dose for a limited duration in older women.
C1 Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
   Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
   Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA.
   NIA, Epidemiol & Demog Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA.
   Ctr Dis Control & Prevent, Phys Act & Hlth Branch, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
   Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA.
RP Gray, SL (reprint author), Univ Washington, Sch Pharm, Box 357630, Seattle, WA 98195 USA.
FU NIA NIH HHS [K08AG00808-01]
NR 40
TC 29
Z9 29
U1 1
U2 3
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 NOV
PY 2003
VL 51
IS 11
BP 1563
EP 1570
DI 10.1046/j.1532-5415.2003.51502.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 736KE
UT WOS:000186169300007
PM 14687385
ER

PT J
AU Newman, AB
   Kupelian, V
   Visser, M
   Simonsick, E
   Goodpaster, B
   Nevitt, M
   Kritchevsky, SB
   Tylavsky, FA
   Rubin, SM
   Harris, TB
AF Newman, AB
   Kupelian, V
   Visser, M
   Simonsick, E
   Goodpaster, B
   Nevitt, M
   Kritchevsky, SB
   Tylavsky, FA
   Rubin, SM
   Harris, TB
CA Hlth ABC Study Investigators
TI Sarcopenia: Alternative definitions and associations with lower
   extremity function
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE sarcopenia; muscle mass; physical function
ID SKELETAL-MUSCLE MASS; FAT-FREE MASS; BODY-COMPOSITION; PHYSICAL
   PERFORMANCE; MUSCULAR STRENGTH; HEALTH ABC; OLDER MEN; WOMEN;
   DISABILITY; AGE
AB OBJECTIVES: To compare two sarcopenia definitions and examine the relationship between them and lower extrem-ity function and other health related factors using data from the baseline examination of the Health Aging and Body Composition (Health ABC) Study.
   DESIGN: Observational cohort study.
   SETTING: Two U.S. communities in Memphis, Tennessee, and Pittsburgh, Pennsylvania.
   PARTICIPANTS: Participants were aged 70 to 79 (N=2,984, 52% women, 41% black).
   MEASUREMENTS: Participants were assessed using dual energy x-ray absorptiometry and were classified as sarcopenic using two different approaches to adjust lean mass for body size: appendicular lean mass divided by height-squared (aLM/ht(2)) and appendicular lean mass adjusted for height and body fat mass (residuals).
   RESULTS: These methods differed substantially in the classification of individuals as being sarcopenic, especially those who were more obese. The former method was highly correlated with body mass index and identified fewer overweight or obese individuals as sarcopenic. In both men and women, none of the obese group would be considered sarcopenic using the aLM/ht(2) method, compared with 11.5% of men and 21.0% of women using the residuals method. In men, both classifications of sarcopenia were associated with smoking, poorer health, lower activity, and impaired lower extremity function. Fewer associations with health factors were noted in women, but the classification based on both height and fat mass was more strongly associated with lower extremity functional limitations (odds ratio (OR)=0.9, 95% confidence interval (CI)=0.7-1.2 for low kg/ht(2); OR=1.9, 95% CI=1.4-2.5 for lean mass adjusted for height and fat mass).
   CONCLUSION: These findings suggest that fat mass should be considered in estimating prevalence of sarcopenia in women and in overweight or obese individuals.
C1 Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15213 USA.
   Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands.
   NIA, Intramural Res Program, Baltimore, MD 21224 USA.
   Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA.
   Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
   Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
   NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Newman, AB (reprint author), Univ Pittsburgh, Div Geriatr Med, 130 N Bellefield,Room 532, Pittsburgh, PA 15213 USA.
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]
NR 30
TC 302
Z9 313
U1 1
U2 23
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 NOV
PY 2003
VL 51
IS 11
BP 1602
EP 1609
DI 10.1046/j.1532-5415.2003.51534.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 736KE
UT WOS:000186169300012
PM 14687390
ER

PT J
AU Dams, R
   Huestis, MA
   Lambert, WE
   Murphy, CM
AF Dams, R
   Huestis, MA
   Lambert, WE
   Murphy, CM
TI Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: Influence
   of ionization type, sample preparation, and biofluid
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
ID CHROMATOGRAPHY-MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION;
   LIQUID-CHROMATOGRAPHY; MS-MS; METABOLITES; SUPPRESSION; DISCOVERY
AB The purpose of the present work was to evaluate the synergistic effect of ionization type, sample preparation technique, and bio-fluid on the presence of matrix effect in quantitative liquid chromatography (LC)-MS/MS analysis of illicit drugs by post-column infusion experiments with morphine (10-mug/mL solution). Three bio-fluids (urine, oral fluid, and plasma) were pretreated with four sample preparation procedures [direct injection, dilution, protein precipitation, solid-phase extraction (SPE)] and analyzed by both LC-electrospray ionization (ESI)-MS/MS and LC-atmospheric pressure chemical ionization (APCI)-MS/MS. Our results indicated that both ionization types showed matrix effect, but ESI was more susceptible than APCI. Sample preparation could reduce (clean up) or magnify (pre-concentrate) matrix effect. Residual matrix components were specific to each bio-fluid and interfered at different time points in the chromatogram. We evaluated matrix effect in an early stage of method development and combined optimal ionization type and sample preparation technique for each bio-fluid. Simple dilution of urine was sufficient to allow for the analysis of the analytes of interest by LC-APCI-MS/MS. Acetonitrile protein precipitation provided both sample clean up and concentration for oral fluid analysis, while SPE was necessary for extensive clean up of plasma prior to LC-APCI-MS/MS. (C) 2003 American Society for Mass Spectrometry.
C1 NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD 21224 USA.
   State Univ Ghent, Toxicol Lab, B-9000 Ghent, Belgium.
RP Murphy, CM (reprint author), NIDA, Chem & Drug Metab Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
NR 19
TC 362
Z9 389
U1 11
U2 82
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 NOV
PY 2003
VL 14
IS 11
BP 1290
EP 1294
DI 10.1016/S1044-0305(03)00574-9
PG 5
WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy
SC Chemistry; Spectroscopy
GA 739ZD
UT WOS:000186375700010
PM 14597119
ER

PT J
AU Rottman, JN
   Ni, G
   Koo, M
   Wang, ZZ
   Zhang, W
   Anderson, ME
   Madu, EC
AF Rottman, JN
   Ni, G
   Koo, M
   Wang, ZZ
   Zhang, W
   Anderson, ME
   Madu, EC
TI Temporal changes in ventricular function assessed echocardiographically
   in conscious and anesthetized mice
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
ID M-MODE ECHOCARDIOGRAPHY; CARDIAC-FUNCTION; DIASTOLIC FUNCTION; MOUSE
   MODEL; ANESTHESIA; HEART; MASS; HYPERTROPHY
AB The mouse is an important model system for cardiovascular biology, with echocardiography a critical tool for noninvasive measurement of cardiac morphology and function. The feasibility and short-term temporal consistency of repeated echocardiographic measurements in conscious mice has not been previously evaluated. We performed serial 2-dimensional guided M-mode transthoracic echocardiographic measurements at 5- to 10-minute intervals over 60 minutes in conscious mice and in mice treated with 1 of 3 anesthetic regimens: ketamine and acepromazine (n = 14); pentobarbital (n = 14); and ketamine and xylazine (n = 13). Unanesthetized mice received intraperitoneal saline (n = 6) or no injection (n = 7). in sequentially repeated measurements over 1 hour in conscious mice, none of the measured or derived echocardiographic parameters differed from baseline, whereas all 3 anesthetic regimens produced significant, prolonged, and temporally variable decreases in heart rate and fractional shortening. The relationship between heart rate and fractional shortening was not altered by anesthetic choice. Serial echocardiographic assessments of cardiac function, dimension, and mass can be performed with high reproducibility in conscious mice.
C1 Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, Nashville, TN 37232 USA.
   Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA.
   Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA.
RP Rottman, JN (reprint author), Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, 371 PRB,2220 Pierce Ave, Nashville, TN 37232 USA.
FU NHLBI NIH HHS [HL46681, HL70250]; NIDDK NIH HHS [U24-DK-59637]
NR 28
TC 66
Z9 68
U1 0
U2 0
PU MOSBY, INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD NOV
PY 2003
VL 16
IS 11
BP 1150
EP 1157
DI 10.1067/S0894-7317(03)00471-1
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 740KN
UT WOS:000186401700007
PM 14608286
ER

PT J
AU Cheung, AK
   Agodoa, L
   Daugirdas, JT
   Greene, T
   Levey, AS
   Milford, E
   Ornt, DB
   Rocco, M
   Sarnak, M
   Yan, G
   Eknoyan, G
AF Cheung, AK
   Agodoa, L
   Daugirdas, JT
   Greene, T
   Levey, AS
   Milford, E
   Ornt, DB
   Rocco, M
   Sarnak, M
   Yan, G
   Eknoyan, G
CA HEMO Study Grp
TI Predictive value of blood pressure (BP) for mortality in chronic
   hemodialysis (HD) patients changes with duration of follow-up
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Utah, NIDDK, Salt Lake City, UT 84112 USA.
NR 0
TC 5
Z9 5
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 2A
EP 2A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100008
ER

PT J
AU Simon, JF
   Agadoa, LY
   Abbott, KC
AF Simon, JF
   Agadoa, LY
   Abbott, KC
TI Predictors of delayed graft function in the era of modern
   immunosuppression.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Walter Reed Army Med Ctr, Serv Nephrol, Dept Med, Washington, DC 20307 USA.
   NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 11A
EP 11A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100047
ER

PT J
AU Mannon, RB
   Cheng, O
   Zhang, XJ
   Hoffmann, S
   Usinger, W
   Kirk, A
AF Mannon, RB
   Cheng, O
   Zhang, XJ
   Hoffmann, S
   Usinger, W
   Kirk, A
TI Connective tissue growth factor (CTGF): A biomarker of chronic allograft
   nephropathy (CAN).
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, TAB, DHHS, NIH, Bethesda, MD USA.
   FibroGen, San Francisco, CA 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 12A
EP 13A
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100054
ER

PT J
AU Thadhani, R
   Mutter, W
   Wolf, M
   Levine, R
   Ecker, J
   Karumanchi, A
AF Thadhani, R
   Mutter, W
   Wolf, M
   Levine, R
   Ecker, J
   Karumanchi, A
TI First trimester angiogenic growth factor (PIGF) and inhibitor (sFlt-1)
   and risk for precclampsia.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA.
   NICHD, NIH, Bethesda, MD USA.
   Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   Massachusetts Gen Hosp, Vincent Obstet Serv, Boston, MA 02114 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 21A
EP 21A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100094
ER

PT J
AU Hoffert, JD
   van Balkom, BWM
   Chou, CL
   Knepper, MA
AF Hoffert, JD
   van Balkom, BWM
   Chou, CL
   Knepper, MA
TI Identification of inner medullary collecting duct marker proteins by
   difference gel electrophoresis (DIGE).
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NHLBI, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 24A
EP 24A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100109
ER

PT J
AU Athirakul, K
   Bradbury, AJ
   Graves, J
   Miller, L
   Ma, JX
   Mao, L
   Rockman, H
   Spurney, RF
   Coffman, TM
   Zeldin, DC
AF Athirakul, K
   Bradbury, AJ
   Graves, J
   Miller, L
   Ma, JX
   Mao, L
   Rockman, H
   Spurney, RF
   Coffman, TM
   Zeldin, DC
TI Hypertension in Cyp2j5 null mice is estrogen responsive.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Duke Univ, Ctr Med, Durham, NC USA.
   NIH, NIEHS, Res Triangle Pk, NC 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 29A
EP 29A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100130
ER

PT J
AU van Balkom, BWM
   Hoffert, JD
   Chou, CL
   Knepper, MA
AF van Balkom, BWM
   Hoffert, JD
   Chou, CL
   Knepper, MA
TI Proteomic analysis of long-term vasopressin response in inner medullary
   collecting duct of Brattleboro rat.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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 NOV
PY 2003
VL 14
SU S
BP 32A
EP 32A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100147
ER

PT J
AU Mannon, RB
   Hoffman, S
   Fahle, G
   Kampen, R
   Kirk, A
AF Mannon, RB
   Hoffman, S
   Fahle, G
   Kampen, R
   Kirk, A
TI Assessing the damage: Characterization of the intragraft molecular
   signature of polyomavirus nephropathy (PVN)
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, TAB, DHHS, NIH, Bethesda, MD USA.
   NIH, CC, Lab Med, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 43A
EP 43A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100198
ER

PT J
AU Vallon, V
   Huang, DY
   Richter, K
   Schnermann, J
AF Vallon, V
   Huang, DY
   Richter, K
   Schnermann, J
TI Nephron function in adenosine A1 Receptor (A1R)-deficient mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Tubingen, Dept Pharmacol, Tubingen, Germany.
   NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 58A
EP 58A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100265
ER

PT J
AU Hoffmann, S
   Jacobson, LM
   Muehrer, R
   Park, J
   Lorentzen, D
   Chang, O
   Kleiner, D
   Kirk, A
   Mannon, R
   Becker, BN
AF Hoffmann, S
   Jacobson, LM
   Muehrer, R
   Park, J
   Lorentzen, D
   Chang, O
   Kleiner, D
   Kirk, A
   Mannon, R
   Becker, BN
TI Donor genomics affect graft events: Single nucleotide polymorphisms from
   the donor organ perspective
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, Transplantat & Autoimmun Branch, Bethesda, MD USA.
   Univ Wisconsin, Madison, WI USA.
   Henry Jackson Fdn, Rockville, MD USA.
   NCI, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 64A
EP 64A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100297
ER

PT J
AU Irarrazabal, CE
   Burg, MB
   Ferraris, JD
AF Irarrazabal, CE
   Burg, MB
   Ferraris, JD
TI ATM is activated by high NaCl, contributing to increased TonEBP-mediated
   transcription.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NHLBI, DHHS, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 72A
EP 72A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100334
ER

PT J
AU Kamijo, Y
   Hora, K
   Kiyosawa, K
   Gonzalez, FJ
   Aoyama, T
AF Kamijo, Y
   Hora, K
   Kiyosawa, K
   Gonzalez, FJ
   Aoyama, T
TI Renal constitutive expression of fatty acid-metabolizing enzymes and
   adaptive response to starvation in peroxisome proliferator-activated
   receptor alpha-null mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Shinshu Univ, Sch Med, Dept Metab Regulat, Nagano, Japan.
   Shinshu Univ, Sch Med, Dept Internal Med 2, Matsumoto, Nagano 390, Japan.
   NCI, Lab Metab, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 72A
EP 72A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100335
ER

PT J
AU Fenton, RA
   Chou, CL
   Stewart, GS
   Smith, CP
   Knepper, MA
AF Fenton, RA
   Chou, CL
   Stewart, GS
   Smith, CP
   Knepper, MA
TI Selective knockout of coliecting-duct specific urea transporter
   isoforms, UT-A1 and UT-A3.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NHLBI, LKEM, NIH, Bethesda, MD 20892 USA.
   Univ Manchester, Sch Biol Sci, Manchester M13 9PL, Lancs, England.
NR 0
TC 0
Z9 0
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 NOV
PY 2003
VL 14
SU S
BP 74A
EP 74A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100342
ER

PT J
AU Smith, CP
   Potter, EA
   Fenton, RA
   Stewart, GS
AF Smith, CP
   Potter, EA
   Fenton, RA
   Stewart, GS
TI Localization of UT-A3 to the basolateral membrane in mouse kidney inner
   medullary collecting duct.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Manchester, Sch Biol Sci, Manchester, Lancs, England.
   NHLBI, LKEM, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 75A
EP 75A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100347
ER

PT J
AU Lim, SW
   Li, C
   Sun, BK
   Yang, CW
   Kim, YS
   Knepper, MA
   Sands, JM
   Kim, J
   Bang, BK
AF Lim, SW
   Li, C
   Sun, BK
   Yang, CW
   Kim, YS
   Knepper, MA
   Sands, JM
   Kim, J
   Bang, BK
TI Long-term treatment of cyclosporine decreases aquaporins and urea
   transporters: The possible mechanism of urine concentration.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Catholic Univ Korea, Seoul, South Korea.
   YanBian Univ, Coll Med, Nephrol & Dialysis Unit, YanJi, JiLin, Peoples R China.
   NIH, Bethesda, MD 20892 USA.
   Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 76A
EP 76A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100354
ER

PT J
AU Zhang, Z
   Dmitrieva, N
   Levine, RL
   Burg, MB
AF Zhang, Z
   Dmitrieva, N
   Levine, RL
   Burg, MB
TI Urea causes oxidative damage to cellular DNA and protein.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NHLBI, DHHS, Bethesda, MD 20892 USA.
RI Levine, Rodney/D-9885-2011
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 76A
EP 76A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100356
ER

PT J
AU Morris, RG
   Knepper, MA
   Chou, CL
AF Morris, RG
   Knepper, MA
   Chou, CL
TI Aldosterone-responsive active Na+ transport in a distal tubule cell
   line.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NHLBI, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 81A
EP 81A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100378
ER

PT J
AU Connaire, JJ
   Aronow, BJ
   Chmielewski, D
   Kopp, JB
   Rosenberg, ME
AF Connaire, JJ
   Aronow, BJ
   Chmielewski, D
   Kopp, JB
   Rosenberg, ME
TI Clusterin functions as a progression factor in immune-mediated mesangial
   cell apoptosis.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Minnesota, Minneapolis, MN 55455 USA.
   NIDDK, NIH, Bethesda, MD 20892 USA.
   Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA.
RI Aronow, Bruce/F-8438-2012
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 96A
EP 96A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100452
ER

PT J
AU Orloff, MS
   Iyengar, S
   Briggs, W
   Dart, R
   Kobert, S
   Mokryzcki, M
   Kimmel, P
   Ahuja, T
   Berns, J
   Simon, E
   Trachtman, H
   Michel, M
   Vlahov, D
   Winkler, C
   Goddard, K
   Schelling, J
   Sedor, J
   Kopp, J
AF Orloff, MS
   Iyengar, S
   Briggs, W
   Dart, R
   Kobert, S
   Mokryzcki, M
   Kimmel, P
   Ahuja, T
   Berns, J
   Simon, E
   Trachtman, H
   Michel, M
   Vlahov, D
   Winkler, C
   Goddard, K
   Schelling, J
   Sedor, J
   Kopp, J
TI Single nucleotide polymorphism (SNP) analyses demonstrate that the
   Wilm's tumor gene (WT1) plays a role in thee pathophysiology of focal
   segmental glomerulosclerosis (FSGS).
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Case Western Reserve Univ, Cleveland, OH 44106 USA.
   NIDDK, NIH, Bethesda, MD 20892 USA.
   NIH, FSGS Genet Study, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 103A
EP 103A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100491
ER

PT J
AU Liu, Y
   Berthier-Schaad, Y
   Fallin, MD
   Fink, NE
   Tracy, RP
   Klag, MJ
   Smith, MW
   Coresh, J
AF Liu, Y
   Berthier-Schaad, Y
   Fallin, MD
   Fink, NE
   Tracy, RP
   Klag, MJ
   Smith, MW
   Coresh, J
TI Interleukin-6 haplotypes, inflammation, and risk of cardiovascular
   disease in a multiethnic dialysis cohort.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD USA.
   NCI, Lab Genome Divers, Frederick, MD USA.
   Univ Vermont, Lab Clin Biochem Res, Burlington, VT USA.
RI Smith, Michael/B-5341-2012
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 113A
EP 113A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100536
ER

PT J
AU Plantinga, LC
   Berthier-Schaud, Y
   Liu, Y
   Fink, NE
   Klag, MJ
   Smith, MW
   Coresh, J
AF Plantinga, LC
   Berthier-Schaud, Y
   Liu, Y
   Fink, NE
   Klag, MJ
   Smith, MW
   Coresh, J
TI Association of PPAR alpha haplotypes with inflammation and risk of
   cardiovascular disease and mortality in a dialysis cohort.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
   SAIC Frederick, NCI, Frederick, MD USA.
RI Smith, Michael/B-5341-2012
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 113A
EP 113A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100535
ER

PT J
AU Banikazemi, M
   Schiffmann, R
   Bultas, J
   Linthorst, GE
   Packman, S
   Sorensen, SA
   Wilcox, WR
   Desnick, RJ
AF Banikazemi, M
   Schiffmann, R
   Bultas, J
   Linthorst, GE
   Packman, S
   Sorensen, SA
   Wilcox, WR
   Desnick, RJ
TI Natural history of Fabry disease.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   Univ Copenhagen, Copenhagen, Denmark.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
   Acad Med Ctr, Amsterdam, Netherlands.
   Univ Hosp, Prague, Czech Republic.
   NIH, DMNB, Bethesda, MD 20892 USA.
   Mt Sinai Sch Med, New York, NY 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 115A
EP 115A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100544
ER

PT J
AU Nelson, RG
   Greene, T
   Beck, GJ
   Van Lente, F
   Wang, XL
   Knowler, WC
AF Nelson, RG
   Greene, T
   Beck, GJ
   Van Lente, F
   Wang, XL
   Knowler, WC
TI Estimating GFR by the MDRD and Cockroft-Gault equations in Pima Indians
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   NIDDK, Diabet & Arthrit Epidemiol Sect, Phoenix, AZ USA.
NR 0
TC 11
Z9 11
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 134A
EP 134A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100630
ER

PT J
AU Kawada, N
   Solis, G
   Dennehy, K
   Imai, E
   Lagenbach, R
   Welch, WJ
   Wilcox, CS
AF Kawada, N
   Solis, G
   Dennehy, K
   Imai, E
   Lagenbach, R
   Welch, WJ
   Wilcox, CS
TI Cyclooxygenase-1 deficient mice have non-dipper blood pressure pattern
   with renal vasoconstriction
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Georgetown Univ, Div Nephrol & Hypertens, Washington, DC USA.
   Georgetown Univ, Cardiovasc Kidney Inst, Washington, DC USA.
   Osaka Univ, Dept Med 1, Osaka, Japan.
   NIEHS, Res Triangle Pk, NC 27709 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 140A
EP 141A
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100661
ER

PT J
AU Bagrov, AY
   Fedorova, OV
   Agalakova, NI
   Lakatta, EG
   Shapiro, JI
AF Bagrov, AY
   Fedorova, OV
   Agalakova, NI
   Lakatta, EG
   Shapiro, JI
TI Atrial natriuretic peptide (ANP) differentially modulates sodium pump
   inihibitory effects of a putative natriuretic hormone, marinobufagenin,
   in rat aorta and renal medulla
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIA, NIH, Baltimore, MD 21224 USA.
   Med Coll Ohio, Toledo, OH 43699 USA.
NR 0
TC 0
Z9 0
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 NOV
PY 2003
VL 14
SU S
BP 144A
EP 144A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100676
ER

PT J
AU Barisoni, L
   Arend, L
   Bonsib, S
   Cohen, A
   Haas, M
   Stillman, I
   Walker, P
   Kessing, B
   Kopp, J
AF Barisoni, L
   Arend, L
   Bonsib, S
   Cohen, A
   Haas, M
   Stillman, I
   Walker, P
   Kessing, B
   Kopp, J
TI NIH/NYU Podocyte Disease Registry
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NYU, New York, NY 10012 USA.
   Univ Rochester, Rochester, NY USA.
   Indiana Univ, Indianapolis, IN 46204 USA.
   Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 151A
EP 151A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100712
ER

PT J
AU Shigehara, T
   Zaragoza, C
   Kitiyakara, C
   Lu, HY
   Kopp, J
AF Shigehara, T
   Zaragoza, C
   Kitiyakara, C
   Lu, HY
   Kopp, J
TI Conditional expression of HIV-1 gene Vpr in podocytes induces
   proteinuria in a transgenic mouse.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 153A
EP 153A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100720
ER

PT J
AU Mannon, RB
   Post, D
   Kowalski, R
   Hale, D
   Swanson, J
   Kirk, A
   Britz, J
AF Mannon, RB
   Post, D
   Kowalski, R
   Hale, D
   Swanson, J
   Kirk, A
   Britz, J
TI Monitoring immune cell reconstitution using the Cylex (R) immune cell
   function assay (ImmuKnow (TM))
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, TAB, DHHS, Bethesda, MD USA.
   Cylex Inc, Columbia, MD USA.
   WRAMC, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 1
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 NOV
PY 2003
VL 14
SU S
BP 180A
EP 181A
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100853
ER

PT J
AU Norris, K
   Greene, T
   Kopple, J
   Lea, J
   Lipkowitz, M
   Miller, E
   Richardson, A
   Rostand, S
   Wang, XL
AF Norris, K
   Greene, T
   Kopple, J
   Lea, J
   Lipkowitz, M
   Miller, E
   Richardson, A
   Rostand, S
   Wang, XL
CA AASK Study Grp
TI Baseline predictors of renal disease progression in the African American
   (AA) study of hypertension and kidney disease (AASK)
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 190A
EP 190A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100896
ER

PT J
AU Coresh, J
   Francis, ME
   Astor, B
   Briggs, JP
   Eggers, PW
   Lacher, DA
   Hostetter, TH
AF Coresh, J
   Francis, ME
   Astor, B
   Briggs, JP
   Eggers, PW
   Lacher, DA
   Hostetter, TH
TI Prevalence and trends in chronic kidney disease and reduced kidney
   function among US adults, 1988-2000
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Johns Hopkins Med Inst, Baltimore, MD USA.
   NIDDKD, NIH, Baltimore, MD USA.
   Social & Sci Syst, Silver Spring, MD USA.
   Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Nutr Examinat Surveys, Hyattsville, MD 20782 USA.
RI Briggs, Josephine/B-9394-2009
OI Briggs, Josephine/0000-0003-0798-1190
NR 0
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 192A
EP 192A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100904
ER

PT J
AU Sarnak, MJ
   Wang, XL
   Greene, T
   Beck, GJ
   Kusek, JW
   Collins, AJ
   Levey, AS
AF Sarnak, MJ
   Wang, XL
   Greene, T
   Beck, GJ
   Kusek, JW
   Collins, AJ
   Levey, AS
TI Effect of strict blood pressure control on long-term outcomes in the
   Modification of Diet in Renal Disease (MDRD) Study
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Tufts Univ, New England Med Ctr, Boston, MA 02111 USA.
   Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   Univ Minnesota, US Renal Data Syst, Minneapolis, MN USA.
   NIDDKD, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 192A
EP 192A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100905
ER

PT J
AU Meyer, TW
   Leeper, EC
   Bartlett, DW
   Depner, TA
   Lit, YZ
   Robertson, CR
   Hostetter, TH
AF Meyer, TW
   Leeper, EC
   Bartlett, DW
   Depner, TA
   Lit, YZ
   Robertson, CR
   Hostetter, TH
TI Increasing dialysate flow (QD) and dialyzer mass-transfer coefficient
   (K(0)A) to increase clearance of protein bound solutes.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 VAHCS & Stanford, Palo Alto, CA USA.
   Univ Calif Davis, Sacramento, CA 95817 USA.
   NIDDK, NIH, Bethesda, MD USA.
   Univ Minnesota, Minneapolis, MN 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 211A
EP 212A
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100992
ER

PT J
AU Greene, T
   Daugirdas, J
   Cheung, A
   Depner, T
   Gotch, F
   Levin, N
   Leypoldt, JK
   Schulman, G
AF Greene, T
   Daugirdas, J
   Cheung, A
   Depner, T
   Gotch, F
   Levin, N
   Leypoldt, JK
   Schulman, G
CA HEMO Study Grp
TI Indices derived from modeled urea distribution volume (Vm) are
   associated with mortality in the HEMO study.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 212A
EP 212A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219100996
ER

PT J
AU Daugirdas, J
   Allon, M
   Depner, T
   Greene, T
   Ornt, D
   Schwab, S
AF Daugirdas, J
   Allon, M
   Depner, T
   Greene, T
   Ornt, D
   Schwab, S
CA HEMO Study Grp
TI Effect of change in vascular access status on outcome in the HEMO study.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 238A
EP 238A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101111
ER

PT J
AU Abbott, KC
   Glanton, CW
   Trespalacios, FC
   Oliver, DK
   Ortiz, MI
   Agodoa, LY
   Cruess, D
   Kimmel, PL
AF Abbott, KC
   Glanton, CW
   Trespalacios, FC
   Oliver, DK
   Ortiz, MI
   Agodoa, LY
   Cruess, D
   Kimmel, PL
TI Body mass index, dialysis modality and survival: Analysis of the United
   States Renal Data System Dialysis Morbidity and Mortality Wave
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA.
   Wilford Hall USAF Med Ctr, Lackland AFB, TX USA.
   Madigan Army Med Ctr, Ft Lewis, WA USA.
   NIDDK, NIH, Bethesda, MD USA.
   Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   George Washington Univ, Washington, DC 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 255A
EP 255A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101186
ER

PT J
AU Mannon, RB
   Zhang, XJ
   Cheng, O
AF Mannon, RB
   Zhang, XJ
   Cheng, O
TI Connective tissue growth factor (CTGF): A novel mediator of ischemic
   injury and chronic allograft nephropathy (CAN).
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, TAB, NIH, DHHS, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 270A
EP 270A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101252
ER

PT J
AU Yuen, PS
   Dunn, SR
   Miyaji, T
   Sharma, K
   Star, RA
AF Yuen, PS
   Dunn, SR
   Miyaji, T
   Sharma, K
   Star, RA
TI A simplified method for HPLC determination of creatinine in mouse serum.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
   Thomas Jefferson Univ, Dept Med, Div Nephrol, Philadelphia, PA 19107 USA.
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 277A
EP 277A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101285
ER

PT J
AU Kim, SW
   Wang, WD
   Nielsen, J
   Praetorius, J
   Knepper, MA
   Frokiaer, J
   Nielsen, S
AF Kim, SW
   Wang, WD
   Nielsen, J
   Praetorius, J
   Knepper, MA
   Frokiaer, J
   Nielsen, S
TI Upregulation and increased trafficking of ENaC subunits in
   puromycin-induced nephrotic syndrome in rats
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark.
   NHLBI, LKEM, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 284A
EP 284A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101316
ER

PT J
AU Eggers, PW
   Francis, ME
   Astor, B
   Briggs, JP
   Coresh, J
   Lacher, DA
   Hostetter, TH
AF Eggers, PW
   Francis, ME
   Astor, B
   Briggs, JP
   Coresh, J
   Lacher, DA
   Hostetter, TH
TI Lack of racial disparities in CKD: Analysis of NHANES surveys
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
   Scoial & Sci Syst, Silver Spring, MD USA.
   Johns Hopkins Univ Hosp, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA.
   Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   Univ Minnesota, Minneapolis, MN USA.
   Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Nutr Surveys, Hyattsville, MD 20782 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 288A
EP 288A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101335
ER

PT J
AU Hostetter, TH
   Chawla, P
   Melcher, C
   Gladstone, E
   Stryer, D
   Mcclellan, WM
AF Hostetter, TH
   Chawla, P
   Melcher, C
   Gladstone, E
   Stryer, D
   Mcclellan, WM
TI A comprehensive survey of African Americans on kidney disease
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDKD, NIH, Bethesda, MD 20892 USA.
   Univ Minnesota, Minneapolis, MN USA.
   Equals Three Commun, Bethesda, MD USA.
   Agcy Healthcare Res & Qual, Rockville, MD USA.
   Emory Univ, Div Renal, Atlanta, GA 30322 USA.
   Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 289A
EP 289A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101338
ER

PT J
AU Hostetter, TH
   Francis, ME
   Briggs, JP
   Astor, B
   Eggers, PW
   Lacher, DA
   Coresh, J
AF Hostetter, TH
   Francis, ME
   Briggs, JP
   Astor, B
   Eggers, PW
   Lacher, DA
   Coresh, J
TI Awareness of CKD is low, especially in women
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDKD, NIH, Bethesda, MD 20892 USA.
   Social & Sci Syst, Silver Spring, MD USA.
   Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
   Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   Ctr Dis Control & Prevent, Div Hlth & Nutr Surveys, Natl Ctr Hlth Stat, Hyattsville, MD USA.
   Univ Minnesota, Minneapolis, MN 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 295A
EP 295A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101363
ER

PT J
AU Leal-Pinto, E
   Teixeira, A
   Henderson, SC
   Hawkins, ME
   Klotman, PE
   Hanss, B
AF Leal-Pinto, E
   Teixeira, A
   Henderson, SC
   Hawkins, ME
   Klotman, PE
   Hanss, B
TI New insight into cellular uptake of nucleic acids: a role for the
   nucleic acid-conducting channel
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Mt Sinai Sch Med, Dept Med, New York, NY USA.
   NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
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 NOV
PY 2003
VL 14
SU S
BP 305A
EP 305A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101408
ER

PT J
AU Leal-Pinto, E
   Abramson, RG
   Zhao, X
   Cohen, BE
   Lipkowitz, MS
AF Leal-Pinto, E
   Abramson, RG
   Zhao, X
   Cohen, BE
   Lipkowitz, MS
TI Mutation of amino- and carboxy-sugar binding sites differentially
   regulates urate channel activity of human hUAT/galectin 9
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Mt Sinai Sch Med, Dept Med, New York, NY USA.
   NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
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 NOV
PY 2003
VL 14
SU S
BP 306A
EP 306A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101413
ER

PT J
AU Frische, S
   Chou, CL
   Knepper, M
   Nielsen, S
AF Frische, S
   Chou, CL
   Knepper, M
   Nielsen, S
TI Immunohistochemical localization of myosin IIb, Va, and Vb in rat kidney
   collecting duct
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Aarhus Univ, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark.
   NHLBI, NIH, Bethesda, MD 20892 USA.
RI Frische, Sebastian/B-2332-2009
OI Frische, Sebastian/0000-0002-0270-3602
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 309A
EP 309A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101427
ER

PT J
AU Wall, SM
   Hassell, KA
   Royaux, IE
   Glapion, DM
   Wang, ME
   Everett, LA
   Green, ED
   Verlander, JW
AF Wall, SM
   Hassell, KA
   Royaux, IE
   Glapion, DM
   Wang, ME
   Everett, LA
   Green, ED
   Verlander, JW
TI Deoxycorticosterone upregulates pds (Slc26a4) in mouse kidney: role of
   pendrin in mineralocorticoid-induced hypertension
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Emory Univ, Sch Med, Atlanta, GA 30322 USA.
   Univ Texas, Houston, TX USA.
   NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
   Wellcome Trust Sanger Inst, Cambridge, England.
   Univ Florida, Gainesville, FL 32611 USA.
NR 0
TC 0
Z9 0
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 NOV
PY 2003
VL 14
SU S
BP 312A
EP 312A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101439
ER

PT J
AU Periyasamy, SM
   Liu, J
   Tanta, F
   Kabak, B
   Malhotra, D
   Fedorova, OV
   Xie, ZJ
   Bagrov, AY
   Shapiro, JI
AF Periyasamy, SM
   Liu, J
   Tanta, F
   Kabak, B
   Malhotra, D
   Fedorova, OV
   Xie, ZJ
   Bagrov, AY
   Shapiro, JI
TI Salt loading induces endocytosis of proximal tubule sodium pump in a
   process involving endogerious digitalis like substances
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Med Coll Ohio, Dept Med, Toledo, OH 43699 USA.
   Med Coll Ohio, Dept Pharmacol, Toledo, OH 43699 USA.
   NIA, Baltimore, MD 21224 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 315A
EP 315A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101457
ER

PT J
AU Castrop, H
   Huang, Y
   Mizel, D
   Briggs, J
   Schnermann, J
AF Castrop, H
   Huang, Y
   Mizel, D
   Briggs, J
   Schnermann, J
TI Effect of acute furosemide administration on plasma renin in adenosine 1
   receptor knockout mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 321A
EP 321A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101486
ER

PT J
AU Castrop, H
   Schweda, F
   Huang, Y
   Mizel, D
   Briggs, JP
   Kurtz, A
   Schnermann, J
AF Castrop, H
   Schweda, F
   Huang, Y
   Mizel, D
   Briggs, JP
   Kurtz, A
   Schnermann, J
TI Macula densa control of renin secretion in neuronal nitric oxide
   synthase deficient mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD 20892 USA.
   Univ Regensburg, Inst Physiol, D-8400 Regensburg, Germany.
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 322A
EP 322A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101491
ER

PT J
AU Miyaji, T
   Hu, XZ
   Yuen, PST
   Muramatsu, Y
   Iyer, S
   Hewitt, SM
   Star, RA
AF Miyaji, T
   Hu, XZ
   Yuen, PST
   Muramatsu, Y
   Iyer, S
   Hewitt, SM
   Star, RA
TI Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple
   organ damage in aged mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
   NCI, NIH, Bethesda, MD 20892 USA.
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
NR 0
TC 0
Z9 0
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 NOV
PY 2003
VL 14
SU S
BP 353A
EP 353A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101638
ER

PT J
AU Iyer, S
   Yuen, PST
   Hu, XZ
   Ekejiuba, S
   Yasuda, H
   Hewitt, SM
   Star, RA
AF Iyer, S
   Yuen, PST
   Hu, XZ
   Ekejiuba, S
   Yasuda, H
   Hewitt, SM
   Star, RA
TI Pirfenidone decreases sepsis-induced acute renal failure in aged mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
   NCI, NIH, Bethesda, MD 20892 USA.
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 354A
EP 354A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101643
ER

PT J
AU Miyaji, T
   Hu, X
   Yuen, PST
   Muramatsu, Y
   Iyer, S
   Hewitt, SM
   Star, RA
AF Miyaji, T
   Hu, X
   Yuen, PST
   Muramatsu, Y
   Iyer, S
   Hewitt, SM
   Star, RA
TI A new model of fluid- and antibiotic-treated sepsis-induced acute renal
   failure in aged mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 356A
EP 356A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101653
ER

PT J
AU Song, XW
   Ning, H
   Cattran, DC
   Kopp, J
   Der, S
   St George-Hyslop, P
   Pei, Y
AF Song, XW
   Ning, H
   Cattran, DC
   Kopp, J
   Der, S
   St George-Hyslop, P
   Pei, Y
TI Molecular classification of steroid-sensitive idiopathic nephrotic
   syndrome (INS) by global gene profiling.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Toronto, Dept Med, Toronto, ON, Canada.
   NIH, Kidney Dis Sect, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 366A
EP 366A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219101702
ER

PT J
AU Thornley-Brown, D
   Wang, XL
   Cheek, D
   Contreras, G
   Gassman, J
   Lash, JP
   Miller, ER
   Randall, OS
AF Thornley-Brown, D
   Wang, XL
   Cheek, D
   Contreras, G
   Gassman, J
   Lash, JP
   Miller, ER
   Randall, OS
CA AASK Study Grp
TI ACE inhibitor-based therapy reduces the' risk of incident diabetes in
   African Americans with hypertensive kidney disease: Results of the AASK
   clinical trial.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Alabama, Div Nephrol, Birmingham, AL USA.
   Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA.
   Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA.
   Univ Miami, Div Nephrol, Miami, FL 33152 USA.
   Rush Presbyterian St Lukes Med Ctr, Div Nephrol, Chicago, IL 60612 USA.
   Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
   Howard Univ, Coll Med, Div Cardiol, Washington, DC 20059 USA.
   NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 443A
EP 443A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102052
ER

PT J
AU Mcclellan, WM
   Chawla, P
   Melcher, C
   Gladstone, E
   Stryer, D
   Hostetter, TH
AF Mcclellan, WM
   Chawla, P
   Melcher, C
   Gladstone, E
   Stryer, D
   Hostetter, TH
TI Awareness and perceived severity of a family history of chronic kidney
   disease (FH-CKD) among primary care physicians (PCPs).
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Emory Univ, Div Renal, Atlanta, GA 30322 USA.
   Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
   Univ Minnesota, Minneapolis, MN USA.
   Equals Three Commun Inc, Bethesda, MD USA.
   Agcy Healthcare Res & Qual, Rockville, MD USA.
   NIDDKD, Natl Kidney Dis Educ Program, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 445A
EP 445A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102062
ER

PT J
AU Herzog, CA
   Li, SL
   Eggers, P
AF Herzog, CA
   Li, SL
   Eggers, P
TI A tale of two medicare populations: 30 day mortality after acute
   myocardial infarction has markedly decreased in general medicare
   patients but not dialysis patients from 1986 to 2000.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 USRDS, Cardiovasc Special Studies Ctr, Minnepolis Med Res Fdn, Minneapolis, MN USA.
   US Renal Data Syst, Minneapolis Med Res Fdn, Minneapolis, MN USA.
   NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 490A
EP 490A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102259
ER

PT J
AU Herzog, CA
   Littrell, K
   Arko, C
   Frederick, P
   Blaney, M
   Eggers, P
AF Herzog, CA
   Littrell, K
   Arko, C
   Frederick, P
   Blaney, M
   Eggers, P
TI The clinical characteristics of dialysis patients with acute myocardial
   infarction (AMI) in the United States: A collaborative project of the
   United States renal data system (USRDS)/NIH and the national registry of
   myocardial infarction (NRMI).
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 US Renal Data Syst, Minneapolis Med Res Fdn, Minneapolis, MN USA.
   Genentech Inc, San Francisco, CA 94080 USA.
   Ovat Res Grp, Seattle, WA USA.
   NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 493A
EP 493A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102276
ER

PT J
AU Leung, J
   Dwyer, J
   Cockram, D
   Rocco, M
   Larive, B
   Chumlea, C
   Burrowes, J
   Bergen, C
   Frydrych, A
   McLeroy, S
   Poole, D
AF Leung, J
   Dwyer, J
   Cockram, D
   Rocco, M
   Larive, B
   Chumlea, C
   Burrowes, J
   Bergen, C
   Frydrych, A
   McLeroy, S
   Poole, D
CA HEMO Study Grp
TI Association of nutritional parameters with mortality depends on length
   of follow-up.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, HEMO Study Grp, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 503A
EP 503A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102317
ER

PT J
AU Rocco, MV
   Dwyer, J
   Larive, B
   Cockram, D
   Chumlea, C
   Leung, J
   Bergen, C
   Burrowes, J
   Frydrych, A
   McLeroy, S
   Poole, D
AF Rocco, MV
   Dwyer, J
   Larive, B
   Cockram, D
   Chumlea, C
   Leung, J
   Bergen, C
   Burrowes, J
   Frydrych, A
   McLeroy, S
   Poole, D
CA HEMO Study Grp
TI Mortality risk as assessed by changes in nutritional parameters: Results
   from the HEMO Study.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, HEMO Study Grp, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 503A
EP 503A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102316
ER

PT J
AU Dember, L
   Allon, M
   Delmez, J
   Dixon, B
   Greenberg, A
   Himmelfarb, J
   Kaufman, J
   Vazquez, M
   Beck, G
   Gassman, J
   Radeva, M
   Kusek, J
   Feldman, H
AF Dember, L
   Allon, M
   Delmez, J
   Dixon, B
   Greenberg, A
   Himmelfarb, J
   Kaufman, J
   Vazquez, M
   Beck, G
   Gassman, J
   Radeva, M
   Kusek, J
   Feldman, H
CA DAC Study Grp
TI Dialysis access consortium (DAC) fistula trial: Progress report and
   baseline characteristics.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 506A
EP 506A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102329
ER

PT J
AU Dixon, BS
   Allon, M
   Delmez, J
   Dember, L
   Greenberg, A
   Himmelfarb, J
   Vazquez, M
   Beck, G
   Depner, T
   Greene, T
   Radeva, M
   Meyers, C
   Feldman, H
AF Dixon, BS
   Allon, M
   Delmez, J
   Dember, L
   Greenberg, A
   Himmelfarb, J
   Vazquez, M
   Beck, G
   Depner, T
   Greene, T
   Radeva, M
   Meyers, C
   Feldman, H
CA DAC Study Grp
TI Dialysis access consortium (DAC) graft trial: Progress report and
   baseline characteristics.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 506A
EP 506A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102328
ER

PT J
AU Xue, JL
   Daniels, FX
   Star, RA
   Kimmel, PL
   Eggers, PW
   Molitoris, BA
   Himmelfarb, J
   Collins, AJ
AF Xue, JL
   Daniels, FX
   Star, RA
   Kimmel, PL
   Eggers, PW
   Molitoris, BA
   Himmelfarb, J
   Collins, AJ
TI Incidence of hospital- and non-hospital-acquired acute renal failure in
   US medicare patients.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Mpls Med Res Fdn, US Renal Data Syst, Minneapolis, MN USA.
   Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
   NIDDK, KUH, Bethesda, MD USA.
   Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46204 USA.
   NIDDK, NIH, Bethesda, MD USA.
   Maine Med Ctr, Div Nephrol, Portland, ME 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 510A
EP 510A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102349
ER

PT J
AU Xue, JL
   Daniels, FX
   Star, RA
   Kimmel, PL
   Eggers, PW
   Molitoris, BA
   Himmelfarb, J
   Collins, AJ
AF Xue, JL
   Daniels, FX
   Star, RA
   Kimmel, PL
   Eggers, PW
   Molitoris, BA
   Himmelfarb, J
   Collins, AJ
TI Mortality and advancing to end-stage renal disease in patients with
   hospital- and non-hospital-acquired acute renal failure.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Mpls Med Res Fdn, Minneapolis, MN USA.
   Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
   NIDDK, KUH, Bethesda, MD USA.
   Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA.
   NIDDK, NIH, Bethesda, MD USA.
   Maine Med Ctr, Div Nephrol, Portland, ME 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 511A
EP 511A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102354
ER

PT J
AU Palevsky, PM
   O'Connor, TZ
   Zhang, JH
   Star, R
AF Palevsky, PM
   O'Connor, TZ
   Zhang, JH
   Star, R
CA VA NIH Acute Renal Failure Trial N
TI VA/NIH acute renal failure trial network: Study design.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
   CSPCC, VA Connecticut Healthcare Syst, West Haven, CT USA.
   NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 4
Z9 4
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 NOV
PY 2003
VL 14
SU S
BP 512A
EP 512A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102359
ER

PT J
AU Smith, D
   Branton, M
   Fervenza, F
   Kopp, J
AF Smith, D
   Branton, M
   Fervenza, F
   Kopp, J
TI Pulse dexamethasone for focal segmental glomerulosclerosis.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD USA.
   Mayo Clin, Rochester, MN 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 526A
EP 526A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102423
ER

PT J
AU Cai, Q
   Dmitrieva, NI
   Ferraris, JD
   Brooks, HL
   van Balkom, BWM
   Burg, MB
AF Cai, Q
   Dmitrieva, NI
   Ferraris, JD
   Brooks, HL
   van Balkom, BWM
   Burg, MB
TI Pax2 expression occurs in adult renal inner medulla and is
   osmolality-dependent.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 DHHS, NHLBI, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 544A
EP 544A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102506
ER

PT J
AU Dmitrieva, NI
   Cai, Q
   Burg, MB
AF Dmitrieva, NI
   Cai, Q
   Burg, MB
TI Adaptation to high NaCl is accompanied by increased DNA breaks and
   decreased DNA repair in renal inner medullary cells in cell culture and
   in vivo.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 DHHS, NHLBI, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 544A
EP 544A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102507
ER

PT J
AU Yang, ZW
   Yu, PY
   Asico, LD
   Wang, Z
   Bek, M
   Sibley, DR
   Jose, PA
AF Yang, ZW
   Yu, PY
   Asico, LD
   Wang, Z
   Bek, M
   Sibley, DR
   Jose, PA
TI D-5 dopamine receptor regulation of NADPH oxidase and blood pressure in
   mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Georgetown Univ, Dept Pediat, Washington, DC 20057 USA.
   NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 3
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 553A
EP 553A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102552
ER

PT J
AU Masereeuw, R
   Notenboom, S
   Kuik, LH
   Russel, FGM
   Miller, DS
AF Masereeuw, R
   Notenboom, S
   Kuik, LH
   Russel, FGM
   Miller, DS
TI Short-term gentamicin exposure results in long-term intracellular
   signaling in renal proximal tubule.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Nijmegen Ctr Mol Life Sci, Dept Pharmacol & Toxicol, Nijmegen, Netherlands.
   NIEHS, Pharmacol & Chem Lab, NIH, Res Triangle Pk, NC 27709 USA.
   Mt Desert Isl Biol Lab, Salsbury Cove, ME USA.
RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014
OI Russel, Frans/0000-0002-7959-2314; 
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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 566A
EP 566A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102615
ER

PT J
AU Shigehara, T
   Shrivastav, S
   Kopp, JB
AF Shigehara, T
   Shrivastav, S
   Kopp, JB
TI Mouse megsin gene promoter contains a mesangial cell-specific enhancer
   regulated by Oct-1: Activation by squelching the repressors.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 592A
EP 592A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102744
ER

PT J
AU Hansen, PB
   Huang, Y
   Briggs, J
   Schnermann, J
AF Hansen, PB
   Huang, Y
   Briggs, J
   Schnermann, J
TI Mechanisms of adnosine-induced vasoconstriction in mouse afferent
   arteribles.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 605A
EP 606A
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102804
ER

PT J
AU Hashimoto, S
   Huang, YG
   Briggs, JR
   Schnermann, JB
AF Hashimoto, S
   Huang, YG
   Briggs, JR
   Schnermann, JB
TI Tubular fluid reabsorption, filtration rate, and tubuloglomerular
   feedback in aquaporin-1 (AQP-1)/Adenosine 1 receptor (A1AR) double
   knockout mice.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 607A
EP 607A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102812
ER

PT J
AU Honeggar, M
   Mizel, D
   Briggs, JP
   Schnermann, JB
   Yang, T
AF Honeggar, M
   Mizel, D
   Briggs, JP
   Schnermann, JB
   Yang, T
TI Distinct regulation of COX-2 and NOSI expressions by PGE(2) in macula
   densa cells.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Utah, Salt Lake City, UT USA.
   VA Med Ctr, Salt Lake City, UT USA.
   NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 607A
EP 607A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102813
ER

PT J
AU Bagrov, AY
   Manusova, NB
   Egorova, IA
   Fedorova, OV
   Shapiro, JI
   Lakatta, EG
   Bagrov, YY
AF Bagrov, AY
   Manusova, NB
   Egorova, IA
   Fedorova, OV
   Shapiro, JI
   Lakatta, EG
   Bagrov, YY
TI Endogenous digitalis-like factors are linked to sodium pump inhibition
   in diabetes mellitus.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 IM Sechenov Evolutionary Physiol & Biochem Inst, Lab Pathophysiol Membrane Transport, St Petersburg 194223, Russia.
   NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
   Med Coll Ohio, Dept Med, Toledo, OH 43699 USA.
NR 0
TC 1
Z9 1
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 NOV
PY 2003
VL 14
SU S
BP 612A
EP 612A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219102833
ER

PT J
AU Norris, K
   Bourgoignie, J
   Gassman, J
   Hebert, L
   Middleton, J
   Phillips, R
   Randall, O
   Rostand, S
   Sherer, S
   Toto, R
   Wright, J
   Wang, XL
   Kopple, J
   Lewis, J
   Greene, T
AF Norris, K
   Bourgoignie, J
   Gassman, J
   Hebert, L
   Middleton, J
   Phillips, R
   Randall, O
   Rostand, S
   Sherer, S
   Toto, R
   Wright, J
   Wang, XL
   Kopple, J
   Lewis, J
   Greene, T
CA AASK Study Grp
TI Cardiovascular outcomes in the African American (AA) study of
   hypertension and kidney disease (AASK).
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIKKD, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 673A
EP 673A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103113
ER

PT J
AU Lash, JP
   Gadegbeku, C
   Greene, T
   Hall, Y
   Jones, K
   Kusek, JW
   Sika, M
   Wang, XL
AF Lash, JP
   Gadegbeku, C
   Greene, T
   Hall, Y
   Jones, K
   Kusek, JW
   Sika, M
   Wang, XL
CA AASK Study Grp
TI Longitudinal effects of blood pressure level and anti hypertensive
   regimen, on quality of life (QOL) in the AASK study.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 678A
EP 678A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103137
ER

PT J
AU Kao, WHL
   Parekh, R
   Meoni, LL
   Ipp, E
   Kimmel, PL
   Knowler, WC
   Klag, MJ
AF Kao, WHL
   Parekh, R
   Meoni, LL
   Ipp, E
   Kimmel, PL
   Knowler, WC
   Klag, MJ
TI Lack-of effect of freezer time on urinary albumin analysis: The FIND
   study.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Johns Hopkins Univ, Baltimore, MD USA.
   Univ Calif Los Angeles, Res & Educ Inst, Los Angeles, CA USA.
   NIDDK, Natl Inst Hlth, Bethesda, MD USA.
   NIDDK, Diabet & Arthrit Epidemiol Sect, NIH, Phoenix, AZ 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 679A
EP 679A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103140
ER

PT J
AU Curhan, GC
   Pearle, M
AF Curhan, GC
   Pearle, M
CA Urologic Dis Amer Project
TI Changes in national rates of hospitalization and outpatient visits for
   nephrolithiasis.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
   UT SW Med Ctr, Dept Urol, Dallas, TX USA.
   NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
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 NOV
PY 2003
VL 14
SU S
BP 698A
EP 698A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103221
ER

PT J
AU Daugirdas, J
   Levin, N
   Bailey, J
   Beck, G
   Cheung, A
   Greene, T
   Leypoldt, JK
   Martin, A
AF Daugirdas, J
   Levin, N
   Bailey, J
   Beck, G
   Cheung, A
   Greene, T
   Leypoldt, JK
   Martin, A
CA HEMO Study Grp
TI Occurrence of intradialytic hypotension (IH) as a risk factor for
   mortality in the HEMO study.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, HEMO Study Grp, NIH, Bethesda, MD USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 711A
EP 711A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103281
ER

PT J
AU Knecht, A
   Kaplan, B
   Cojocaru, M
   Unsworth, E
   Martin, B
AF Knecht, A
   Kaplan, B
   Cojocaru, M
   Unsworth, E
   Martin, B
TI Search for peptidic "Middle molecules" in uremic sera: Accumulation of
   fibrinogen fragments in uremia.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Sheba Med Ctr, Dept Hypertens & Nephrol, Tel Hashomer, Israel.
   Sheba Med Ctr, Heller Inst Med Res, Tel Hashomer, Israel.
   Bar Ilan Univ, Dept Chem, Ramat Gan, Israel.
   NIMH, Lab Neurotoxicol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
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 NOV
PY 2003
VL 14
SU S
BP 713A
EP 713A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103288
ER

PT J
AU McClellan, WM
   Frankenfield, DL
   Roman, SH
   Eggers, P
   Bedinger, MR
   Rocco, MV
AF McClellan, WM
   Frankenfield, DL
   Roman, SH
   Eggers, P
   Bedinger, MR
   Rocco, MV
TI Race and gender are not risk factors for lower; extremity amputation
   among incident dialysis patients: A report from the ESRD hemodialysis
   CPM project.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Emory Univ, Div Renal, Atlanta, GA USA.
   Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA USA.
   Ctr Benef Choices, Baltimore, MD USA.
   NIDDK, NIH, Bethesda, MD USA.
   Wake Forest Sch Med, Winston Salem, NC USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 715A
EP 715A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103296
ER

PT J
AU Allon, M
   Radeva, M
   Bailey, J
   Beddhu, S
   Butterly, D
   Coyne, DW
   Depner, TA
   Gassman, JJ
   Kaufman, AM
   Kaysen, GA
   Lewis, JA
   Schwab, SJ
AF Allon, M
   Radeva, M
   Bailey, J
   Beddhu, S
   Butterly, D
   Coyne, DW
   Depner, TA
   Gassman, JJ
   Kaufman, AM
   Kaysen, GA
   Lewis, JA
   Schwab, SJ
CA HEMO Study Grp
TI Association of serum albumin and disease category with severity of
   infection: Data from the HEMO study.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Alabama, Div Nephrol, HEMO Study Grp, Birmingham, AL USA.
   Cleveland Clin, Dept Biostat, Cleveland, OH USA.
   Emory Univ, Div Nephrol, Atlanta, GA USA.
   Univ Utah, Div Nephrol, Salt Lake City, UT USA.
   Duke Univ, Div Nephrol, Durham, NC USA.
   Washington Univ, Div Nephrol, St Louis, MO USA.
   Univ Calif Davis, Div Nephrol, Davis, CA USA.
   Beth Israel Med Ctr, Div Nephrol, New York, NY 10003 USA.
   Vanderbilt Univ, Div Nephrol, Nashville, TN USA.
   NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 720A
EP 720A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103318
ER

PT J
AU Hogg, RJ
   Lee, J
   Nardelli, NA
   Cattran, D
   Hirschman, G
   Julian, BA
AF Hogg, RJ
   Lee, J
   Nardelli, NA
   Cattran, D
   Hirschman, G
   Julian, BA
TI Multicenter, placebo-controlled trial of alternate-day prednisone
   (QOD-PRED) or daily omega-3 fatty acids (OM-3 FA) in. children and young
   adults with IgA nephropathy (IgAN). Report from the southwest pediatric
   nephrology study group.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Med City Dallas Hosp, Dallas, TX USA.
   Univ Alabama, Biostat Unit, Birmingham, AL USA.
   Toronto Hosp, Toronto, ON M5T 2S8, Canada.
   NIDDK, Div Kidney Urol & Hematol Dis, Washington, DC USA.
NR 0
TC 5
Z9 6
U1 0
U2 0
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 NOV
PY 2003
VL 14
SU S
BP 751A
EP 751A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103457
ER

PT J
AU Kleta, R
   Bernardini, I
   Gahl, WA
AF Kleta, R
   Bernardini, I
   Gahl, WA
TI Long-term follow-up of well treated nephropathic cystinosis patients.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NHGRI, Sect Human Biochem Genet, MGB, NIH, Bethesda, MD 20892 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 755A
EP 755A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103478
ER

PT J
AU Kimmel, PL
   Byrd-Holt, D
   Patel, SS
AF Kimmel, PL
   Byrd-Holt, D
   Patel, SS
TI Depression and urinary albumin excretion in the NHANES III population.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA.
   George Washington Univ, Dept Med, Washington, DC USA.
NR 0
TC 0
Z9 0
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 NOV
PY 2003
VL 14
SU S
BP 811A
EP 811A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103736
ER

PT J
AU Contreras, G
   Agodoa, LY
   Cheek, D
   Dowie, D
   Greene, T
   Lash, J
   Lipkowitz, M
   Miller, PR
   Ojo, A
   Sika, M
   Wilkening, B
   Toto, R
AF Contreras, G
   Agodoa, LY
   Cheek, D
   Dowie, D
   Greene, T
   Lash, J
   Lipkowitz, M
   Miller, PR
   Ojo, A
   Sika, M
   Wilkening, B
   Toto, R
CA AASK Study Grp
TI Lower blood pressure control and first line antihypertensives in the
   AASK trial.
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 NIDDK, NIH, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 815A
EP 815A
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219103755
ER

PT J
AU Grantham, JJ
   Zheng, DX
   Torres, VE
   Chapman, AB
   Guay-Woodford, LM
   Bae, KT
   Miller, JP
   Bennett, W
   Hirschman, GH
AF Grantham, JJ
   Zheng, DX
   Torres, VE
   Chapman, AB
   Guay-Woodford, LM
   Bae, KT
   Miller, JP
   Bennett, W
   Hirschman, GH
TI A prospective examination of the relation between MCP-1 and disease
   status in non-azotemic patients with autosomal dominant PKD
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the American-Society-of-Nephrology
CY NOV 12-17, 2003
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Nephrol
C1 Univ Kansas, Med Ctr, Kidney Inst, Kansas City, KS 66103 USA.
   Mayo Clin, Rochester, MI USA.
   Emory Univ, Atlanta, GA 30322 USA.
   Univ Alabama, Birmingham, AL USA.
   Washington Univ, Malinckrodt Inst Radiol, St Louis, MO USA.
   Hosp Good Samaritan, Dept Transplantat, Portland, OR USA.
   NIDDK, Bethesda, 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 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2003
VL 14
SU S
BP 875A
EP 876A
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 737FE
UT WOS:000186219104032
ER

PT J
AU Abbott, KC
   Bucci, JR
   Matsumoto, CS
   Swanson, SJ
   Agodoa, LYC
   Holtzmuller, KC
   Cruess, DF
   Peters, TG
AF Abbott, KC
   Bucci, JR
   Matsumoto, CS
   Swanson, SJ
   Agodoa, LYC
   Holtzmuller, KC
   Cruess, DF
   Peters, TG
TI Hepatitis C and renal transplantation in the era of modern
   immunosuppression
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID MYCOPHENOLATE-MOFETIL; LIVER-TRANSPLANTATION; PATIENT SURVIVAL;
   VIRUS-INFECTION; EARLY GRAFT; ANTI-HCV; RECIPIENTS; DONORS; DISEASE;
   IMPACT
AB Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.
C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA.
   Uniformed Serv Univ Sch Hlth Sci, Bethesda, MD USA.
   WRAMC, Organ Transplant Serv, Washington, DC USA.
   NIH, Bethesda, MD 20892 USA.
   NIDDKD, NIH, Bethesda, MD 20892 USA.
   WRAMC, Serv Gastroenterol, Washington, DC USA.
   Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
   Jacksonville Transplant Ctr Shands, Jacksonville, FL USA.
RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA.
OI Abbott, Kevin/0000-0003-2111-7112
NR 49
TC 58
Z9 60
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 NOV
PY 2003
VL 14
IS 11
BP 2908
EP 2918
DI 10.1097/01.ASN.0000090743.43034.72
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 734TF
UT WOS:000186073500025
PM 14569101
ER

PT J
AU DeVore, GR
   Romero, R
AF DeVore, GR
   Romero, R
TI Genetic sonography - An option for women of advanced maternal age with
   negative triple-marker maternal serum screening results
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
DE genetic sonography; maternal serum screening; trisomy 21
ID 2ND-TRIMESTER ULTRASOUND MARKERS; SCORING INDEX; RISK-ASSESSMENT;
   DOWNS-SYNDROME; FETAL LOSS; TRISOMY-21; AMNIOCENTESIS; FETUSES;
   ULTRASONOGRAPHY
AB Objective. To determine whether offering genetic sonography to patients 35 years of age and older with negative maternal serum triple-marker screening results will result in an increase in the detection rate of trisomy 21. Methods. The detection rate of trisomy 21 was determined in women 35 years of age and older whose pregnancies were managed according to the following 3 policies: policy 1, universal amniocentesis; policy II, maternal serum triple-marker screening followed by amniocentesis only in high-risk women (risk >1:190),- and policy III, genetic sonography in women with negative maternal serum screening results (policy II). Policy III included the offering of genetic amniocentesis to patients with abnormal genetic sonographic findings. The rate of acceptance of genetic amniocentesis was modeled, as was the sensitivity (50%-90%) and false-positive rate (5%-25%) of genetic sonography. Results. The number of fetuses expected to have trisomy 21 was 784. For patients evaluated under policy II, 86.3% of fetuses with trisomy 21 were detected. On the basis of the detection rate for trisomy 21 of policy II, the addition of fetuses with trisomy 21 identified under policy III was significantly (P <.01) increased (93.2% to 98.6%) for genetic sonographic sensitivities ranging between 50% and 90%. Conclusions. A policy of offering genetic sonography followed by amniocentesis to patients 35 years of age and older who originally had triple-marker maternal serum screening findings that were negative for the diagnosis of trisomy 21 results in a higher overall detection rate of trisomy 21.
C1 NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
RP DeVore, GR (reprint author), 301 S Fair Oaks Ave,Suite 206, Pasadena, CA USA.
NR 27
TC 8
Z9 10
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 NOV
PY 2003
VL 22
IS 11
BP 1191
EP 1199
PG 9
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 738JT
UT WOS:000186284000008
PM 14620890
ER

PT J
AU Kao, S
   Khan, MA
   Miyagi, E
   Plishka, R
   Buckler-White, A
   Strebel, M
AF Kao, S
   Khan, MA
   Miyagi, E
   Plishka, R
   Buckler-White, A
   Strebel, M
TI The human immunodeficiency virus type 1 Vif protein reduces
   intracellular expression and inhibits packaging of APOBEC3G (CEM15), a
   cellular inhibitor of virus infectivity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRION INCORPORATION; MUTATIONAL ANALYSIS; RESTRICTIVE CELLS; HIV-1
   INFECTION; SOR GENE; DNA; RNA; GAG; REPLICATION; HYPERMUTATION
AB Replication of human immunodeficiency virus type 1 (HIV-1) in most primary cells and some immortalized T-cell lines depends on the activity of the viral infectivity factor (Vif). Vif has the ability to counteract a cellular inhibitor, recently identified as CEM15, that blocks infectivity of Vif-defective HIV-1 variants. CEM15 is identical to APOBEC3G and belongs to a family of proteins involved in RNA and DNA deamination. We cloned APOBEC3G from a human kidney cDNA library and confirmed that the protein acts as a potent inhibitor of HIV replication and is sensitive to the activity of Vif. We found that wild-type Vif inhibits packaging of APOBEC3G into virus particles in a dose-dependent manner. In contrast, biologically inactive variants carrying in-frame deletions in various regions of Vif or mutation of two highly conserved cysteine residues did not inhibit packaging of APOBEC3G. Interestingly, expression of APOBEC3G in the presence of wild-type Vif not only affected viral packaging but also reduced its intracellular expression level. This effect was not seen in the presence of biologically inactive Vif variants. Pulse-chase analyses did not reveal a significant difference in the stability of APOBEC3G in the presence or absence of Vif. However, in the presence of Vif, the rate of synthesis of APOBEC3G was slightly reduced. The reduction of intracellular APOBEC3G in the presence of Vif does not fully account for the Vif-induced reduction of virus-associated APOBEC3G, suggesting that Vif may function at several levels to prevent packaging of APOBEC3G into virus particles.
C1 NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA.
RP Strebel, M (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, 4-312,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA.
NR 47
TC 229
Z9 242
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 NOV
PY 2003
VL 77
IS 21
BP 11398
EP 11407
DI 10.1128/JVI.77.21.11398-11407.2003
PG 10
WC Virology
SC Virology
GA 733HY
UT WOS:000185995300010
PM 14557625
ER

PT J
AU Fogg, MH
   Teterina, NL
   Ehrenfeld, E
AF Fogg, MH
   Teterina, NL
   Ehrenfeld, E
TI Membrane requirements for uridylylation of the poliovirus VPg protein
   and viral RNA synthesis in vitro
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID REPLICATION COMPLEX; BREFELDIN-A; CELL-FREE; ENDOPLASMIC-RETICULUM;
   POLYMERASE 3D(POL); LIPID-SYNTHESIS; INFECTED-CELLS; FATTY-ACIDS;
   HELA-CELLS; VIRUS
AB Efficient translation of poliovirus (PV) RNA in uninfected HeLa cell extracts generates all of the viral proteins required to carry out viral RNA replication and encapsidation and to produce infectious virus in vitro. In infected cells, viral RNA replication occurs in ribonucleoprotein complexes associated with clusters of vesicles that are formed from preexisting intracellular organelles, which serve as a scaffold for the viral RNA replication complex. In this study, we have examined the role of membranes in viral RNA replication in vitro. Electron microscopic and biochemical examination of extracts actively engaged in viral RNA replication failed to reveal a significant increase in vesicular membrane structures or the protective aggregation of vesicles observed in PV-infected cells. Viral, nonstructural replication proteins, however, bind to heterogeneous membrane fragments in the extract. Treatment of the extracts with nonionic detergents, a membrane-altering inhibitor of fatty acid synthesis (cerulenin), or an inhibitor of intracellular membrane trafficking (brefeldin A) prevents the formation of active replication complexes in vitro, under conditions in which polyprotein synthesis and processing occur normally. Under all three of these conditions, synthesis of uridylylated VPg to form the primer for initiation of viral RNA synthesis, as well as subsequent viral RNA replication, was inhibited. Thus, although organized membranous structures morphologically similar to the vesicles observed in infected cells do not appear to form in vitro, intact membranes are required for viral RNA synthesis, including the first step of forming the uridylylated VPg primer for RNA chain elongation.
C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Ehrenfeld, E (reprint author), NIAID, Infect Dis Lab, NIH, 50,Room 6120,9000 Rockville Pk, Bethesda, MD 20892 USA.
NR 52
TC 26
Z9 26
U1 0
U2 2
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 NOV
PY 2003
VL 77
IS 21
BP 11408
EP 11416
DI 10.1128/JVI.77.21.11408-11416.2003
PG 9
WC Virology
SC Virology
GA 733HY
UT WOS:000185995300011
PM 14557626
ER

PT J
AU Husain, M
   Moss, B
AF Husain, M
   Moss, B
TI Evidence against an essential role of COPII-mediated cargo transport to
   the endoplasmic reticulum-Golgi intermediate compartment in the
   formation of the primary membrane of vaccinia virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SWINE-FEVER VIRUS; TYROSINE PHOSPHORYLATION; VIRION MORPHOGENESIS;
   ENVELOPE PROTEIN; GENE PROVIDES; F10 KINASE; EXPRESSION; BIOGENESIS;
   COMPONENT; PATHWAY
AB Vaccinia virus assembles two distinct lipoprotein membranes. The primary membrane contains nonglycosylated proteins, appears as crescents in the cytoplasm, and delimits immature and mature intracellular virions. The secondary or wrapping membrane contains glycoproteins, is derived from virus-modified trans-Golgi or endosomal cisternae, forms a loose coat around some intracellular mature virions, and becomes the envelope of extracellular virions. Although the mode of formation of the wrapping membrane is partially understood, we know less about the primary membrane. Recent reports posit that the primary membrane originates from the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). According to this model, viral primary membrane proteins are cotranslationally inserted into the ER and accumulate in the ERGIC. To test the ERGIC model, we employed Sar1(H79G), a dominant negative form of the Sar1 protein, which is an essential component of coatomer protein II (COPII)-mediated cargo transport from the ER to the ERGIC and other post-ER compartments. Overexpression of Sar1(H79G) by transfection or by a novel recombinant vaccinia virus with an inducible Sar1(H79G), gene resulted in retention of ERGIC 53 in the ER but did not interfere with localization of viral primary membrane proteins in factory regions or with formation of viral crescent membranes and infectious intracellular mature virions. Wrapping of intracellular mature virions and formation of extracellular virions did not occur, however, because some proteins that are essential for the secondary membrane were retained in the ER as a consequence of Sar1(H79G) overexpression. Our data argue against an essential role of COPII-mediated cargo transport and the ERGIC in the formation of the viral primary membrane. Instead, viral membranes may be derived directly from the ER or by a novel mechanism.
C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA.
NR 48
TC 38
Z9 38
U1 0
U2 3
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 NOV
PY 2003
VL 77
IS 21
BP 11754
EP 11766
DI 10.1128/JVI.77.21.11754-11766.2003
PG 13
WC Virology
SC Virology
GA 733HY
UT WOS:000185995300045
PM 14557660
ER

PT J
AU Bouamr, F
   Melillo, JA
   Wang, MQ
   Nagashima, K
   Los Santos, MD
   Rein, A
   Goff, SP
AF Bouamr, F
   Melillo, JA
   Wang, MQ
   Nagashima, K
   Los Santos, MD
   Rein, A
   Goff, SP
TI PPPYEPTAP motif is the late domain of human T-Cell leukemia virus type 1
   GaG and mediates its functional interaction with cellular proteins Nedd4
   and Tsg101
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INFECTIOUS-ANEMIA VIRUS; ROUS-SARCOMA VIRUS; LATE ASSEMBLY DOMAIN;
   UBIQUITIN-PROTEASOME SYSTEM; PLASMA-MEMBRANE PROTEINS; N-TERMINAL
   DOMAIN; IMMUNODEFICIENCY-VIRUS; PARTICLE-PRODUCTION; MAMMALIAN-CELLS;
   DOWN-REGULATION
AB The human T-cell leukemia virus type 1 (HTLV-1) Gag polyprotein contains two adjacent proline-rich motifs (sequence PPPYEPTAP) in the C terminus of the matrix domain. Proline-to-alanine mutations were introduced into either or both motifs of HTLV-1 to determine the effect on the release of HTLV-1 virus-like particles from 293T cells. The release of both single mutants was significantly reduced, whereas a double mutation in both motifs abolished the release of the HTLV-1 particles. Two-hybrid and in vitro binding assays showed that the HTLV-1 Gag polyprotein binds both Tsg101 and Nedd4 proteins. The interaction with HTLV-1 Gag required the central WW domain of Nedd4 and the ubiquitin enzyme variant (UEV) domain of Tsg101. We expressed various fragments of Nedd4 and Tsg101 proteins in 293T cells and tested for their ability to interfere with virion release mediated by the HTLV-1 Gag-Pro polyprotein. Fragments consisting of the N-terminal UEV domain of Tsg101 and the central WW and C-terminal Hect domains of Nedd4 protein all caused transdominant inhibition of HTLV-1 particle release. Similarly, inhibition of the proteasome significantly decreased HTLV-1 particle release. Furthermore, the WW domain overexpression caused an early arrest of HTLV-1 particle morphogenesis before the membrane is deformed into the typical half-shell structure. This result suggests that Nedd4 is involved early in budding of HTLV-1.
C1 Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, Coll Phys & Surg, New York, NY 10032 USA.
   Columbia Univ, Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA.
   Howard Hughes Med Inst, New York, NY USA.
   SAIC, Frederick, MD USA.
   NCI, HIV Drug Resistance Program, Frederick, MD USA.
RP Goff, SP (reprint author), Columbia Univ, Dept Biochem, Howard Hughes Med Inst, Coll Phys & Surg, HHSC1310,701 W 168 St, New York, NY 10032 USA.
RI Goff, Stephen/K-6337-2014
OI Goff, Stephen/0000-0003-0693-5547
FU NCI NIH HHS [N01CO12400]; PHS HHS [N01-C0-12400]
NR 68
TC 93
Z9 98
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 NOV
PY 2003
VL 77
IS 22
BP 11882
EP 11895
DI 10.1128/JVI.77.22.11882-11895.2003
PG 14
WC Virology
SC Virology
GA 738NG
UT WOS:000186294300003
PM 14581525
ER

PT J
AU Thio, CL
   Thomas, DL
   Karacki, P
   Gao, XJ
   Marti, D
   Kaslow, RA
   Goedert, JJ
   Hilgartner, M
   Strathdee, SA
   Duggal, P
   O'Brien, SJ
   Astemborski, J
   Carrington, M
AF Thio, CL
   Thomas, DL
   Karacki, P
   Gao, XJ
   Marti, D
   Kaslow, RA
   Goedert, JJ
   Hilgartner, M
   Strathdee, SA
   Duggal, P
   O'Brien, SJ
   Astemborski, J
   Carrington, M
TI Comprehensive analysis of class I and class IIHLA antigens and chronic
   hepatitis B virus infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MULTICENTER AIDS COHORT; VIRAL-HEPATITIS; HLA ANTIGENS; T-CELLS;
   ASSOCIATION; VACCINE; DISEASES; INHERITANCE; HEMOPHILIA; CLEARANCE
AB Following an acute hepatitis B virus (HBV) infection, clearance or persistence is determined in part by the vigor and breadth of the host immune response. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance. HLA class I and II genes were molecularly typed in 194 Caucasian individuals with viral persistence and 342 matched controls who had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral clearance. The class II allele DRB1*1302 was also associated with clearance (OR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a multivariate model that included other alleles associated with disease outcome as covariates. B*08 was associated with viral persistence both independently (OR, 1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian haplotype A*01-B*08-DPB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% Cl, 1.22 to 3.24; P = 0.006) haplotypes were also associated with viral persistence. Interestingly, both the B*08 haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been associated with nonresponse to the HBV vaccine. The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.
C1 Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
   Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA.
   NCI, Lab Genome Divers, Frederick, MD 21701 USA.
   NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
   Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
   New York Presbyterian Hosp, Cornell Med Ctr, Dept Pediat, New York, NY USA.
RP Thio, CL (reprint author), Johns Hopkins Univ, 1503 E Jefferson St, Baltimore, MD 21231 USA.
RI Strathdee, Steffanie/B-9042-2009
FU NCI NIH HHS [N01-CP-33002]; NCRR NIH HHS [M01 RR000059, 5-M01-RR-00722,
   M01 RR000071, M01 RR000722, M01 RR002558, M01-RR00059, M01-RR00071,
   M01-RR02558, M01-RR06020]; NIAID NIH HHS [U01 AI035039, U01 AI035040,
   U01 AI035041, U01 AI035042, U01 AI035043, U01 AI037613, U01 AI037984,
   U01-AI-35039, U01-AI-35040, U01-AI-35041, U01-AI-35042, U01-AI-35043,
   U01-AI-37613, U01-AI-37984]; NICHD NIH HHS [N01-HD-4-3200]; NIDA NIH HHS
   [DA00441, DA04334, DA13324, K08 DA000441, R01 DA004334, R01 DA013324,
   R37 DA004334, R56 DA004334]; PHS HHS [MCJ-060570, N01-C0-56000]
NR 35
TC 87
Z9 104
U1 0
U2 1
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 NOV
PY 2003
VL 77
IS 22
BP 12083
EP 12087
DI 10.1128/JVI.77.22.12083-12087.2003
PG 5
WC Virology
SC Virology
GA 738NG
UT WOS:000186294300023
PM 14581545
ER

PT J
AU Mohan, KVK
   Muller, J
   Atreya, CD
AF Mohan, KVK
   Muller, J
   Atreya, CD
TI The N- and C-terminal regions of rotavirus NSP5 are the critical
   determinants for the formation of viroplasm-like structures independent
   of NSP2
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IN-VIVO; PHOSPHOPROTEIN NSP5; SEQUENCE-ANALYSIS; PHOSPHORYLATION;
   PROTEIN; LOCALIZATION; MUTATIONS; DOMAIN; RNA
AB Molecular events and the interdependence of the two rotavirus nonstructural proteins, NSP5 and NSP2, in producing viroplasm-like structures (VLS) were previously evaluated by using transient cellular coexpression of the genes for the two proteins, and VLS domains as well as the NSP2-binding region of NSP5 were mapped in the context of NSP2. Review of the previous studies led us to postulate that NSP2 binding of NSP5 may block the N terminus of NSP5 or render it inaccessible and that any similar N-terminal blockage may render NSP5 alone capable of producing VLS independent of NSP2. This possibility was addressed in this report by using two forms of NSP5-green fluorescent protein (GFP) chimeras wherein GFP is fused at either the N or the C terminus of NSP5 (GFP-NSP5 and NSP5-GFP) and evaluating their VLS-forming capability (by light and electron microscopy) and phosphorylation and multimerization potential independent of NSP2. Our results demonstrate that NSP5 alone can form VLS when the N terminus is blocked by fusion with a nonrotavirus protein (GFP-NSP5) but the C terminus is unmodified. Only GFP-NSP5 was able to undergo hyperphosphorylation and multimerization with the native form of NSP5, emphasizing the importance of an unmodified C terminus for these events. Deletion analysis of NSP5 mapped the essential signals for VLS formation to the C terminus and clearly suggested that hyperphosphorylation of NSP5 is not required for VLS formation. The present study emphasizes in general that when fusion proteins are used for functional studies, constructs that represent fusions at both the N and the C termini of the protein should be evaluated.
C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod,Lab Pediat & Resp Viral Dis, Sect Viral Pathogenesis & Vaccine Adverse React, Bethesda, MD 20892 USA.
   US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Vector Borne Viral Dis, Bethesda, MD 20892 USA.
RP Atreya, CD (reprint author), NIH, CBER, FDA, Bldg 29A,Room 2C-11,HFM-460,8800 Rockville Pike, Bethesda, MD 20892 USA.
NR 23
TC 33
Z9 35
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 NOV
PY 2003
VL 77
IS 22
BP 12184
EP 12192
DI 10.1128/JVI.77.22.12184-12192.2003
PG 9
WC Virology
SC Virology
GA 738NG
UT WOS:000186294300033
PM 14581555
ER

PT J
AU Katz, E
   Ward, BM
   Weisberg, AS
   Moss, B
AF Katz, E
   Ward, BM
   Weisberg, AS
   Moss, B
TI Mutations in the vaccinia virus A33R and B5R envelope proteins that
   enhance release of extracellular virions and eliminate formation of
   actin-containing microvilli without preventing tyrosine phosphorylation
   of the A36R protein
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TO-CELL SPREAD; INTRACELLULAR MOVEMENT; PROGENY VACCINIA; TAIL
   FORMATION; GLYCOPROTEIN; MEMBRANE; GENE; MOTILITY; MICROTUBULES;
   IDENTIFICATION
AB The spread of vaccinia virus in cell cultures is mediated by virions that adhere to the tips of specialized actin-containing microvilli and also by virions that are released into the medium. The use of a small plaque-forming A36R gene deletion mutant to select spontaneous second-site mutants exhibiting enhanced virus release was described previously. Two types of mutations were found: C-terminal truncations of the A33R envelope protein and a single amino acid substitution of the B5R envelope protein. In the present study, we transferred each type of mutation into a wild-type virus background in order to study their effects in vitro and in vivo. The two new mutants conserved the enhanced virus release properties of the original isolates; the A33R mutant produced considerably more extracellular virus than the B5R mutant. The extracellular virus particles contained the truncated A33R protein in one case and the mutated B5R protein in the other. Remarkably, both mutants failed to form actin tails and specialized microvilli, despite the presence of an intact A36R gene. The synthesis of the A36R protein as well as its physical association with the mutated or wild-type A33R protein was demonstrated. Moreover, the A36R protein was tyrosine phosphorylated, a step mediated by a membrane-associated Src kinase that regulates the nucleation of actin polymerization. The presence of large numbers of adherent virions on the cell surface argued against rapid dissociation as having a key role in preventing actin tail formation. Thus, the A33R and B5R proteins may be more directly involved in the formation or stabilization of actin tails than had been previously thought. When mice were inoculated intranasally, the A33R mutant was highly attenuated and the B5R mutant was mildly attenuated compared to wild-type virus. Enhanced virus release, therefore, did not compensate for the loss of actin tails and specialized microvilli.
C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
NR 36
TC 31
Z9 33
U1 0
U2 2
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 NOV
PY 2003
VL 77
IS 22
BP 12266
EP 12275
DI 10.1128/JVI.77.22.12266-12275.2003
PG 10
WC Virology
SC Virology
GA 738NG
UT WOS:000186294300041
PM 14581563
ER

PT J
AU Kunstman, KJ
   Puffer, B
   Korber, BT
   Kuiken, C
   Smith, UR
   Kunstman, J
   Stanton, J
   Agy, M
   Shibata, R
   Yoder, AD
   Pillai, S
   Doms, RW
   Marx, P
   Wolinsky, SM
AF Kunstman, KJ
   Puffer, B
   Korber, BT
   Kuiken, C
   Smith, UR
   Kunstman, J
   Stanton, J
   Agy, M
   Shibata, R
   Yoder, AD
   Pillai, S
   Doms, RW
   Marx, P
   Wolinsky, SM
TI Structure and function of CC-chemokine receptor 5 homologues derived
   from representative primate species and subspecies of the taxonomic
   suborders Prosimii and Anthropoidea
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; ENVELOPE GLYCOPROTEINS;
   MAXIMUM-LIKELIHOOD; CORECEPTOR USAGE; TYPE-1 ENTRY; HIV-1 ENTRY; GENE
   CCR5; PHYLOGENY; INFECTION; STRAINS
AB A chemokine receptor from the seven-transmembrane-domain G-protein-coupled receptor superfamily is an essential coreceptor for the cellular entry of human immunodeficiency virus type 1 (HW-1) and simian immunodeficiency virus (SIV) strains. To investigate nonhuman primate CC-chemokine receptor 5 (CCR5) homologue structure and function, we amplified CCR5 DNA sequences from peripheral blood cells obtained from 24 representative species and subspecies of the primate suborders Prosimii (family Lemuridae) and Anthropoidea (families Cebidae, Callitrichidae, Cercopithecidae, Hylobatidae, and Pongidae) by PCR with primers flanking the coding region of the gene. Full-length CCR5 was inserted into pCDNA3.1, and multiple clones were sequenced to permit discrimination of both alleles. Compared to the human CCR5 sequence, the CCR5 sequences of the Lemuridae, Cebidae, and Cercopithecidae shared 87,91 to 92, and 96 to 99% amino acid sequence homology, respectively. Amino acid substitutions tended to cluster in the amino and carboxy termini, the first transmembrane domain, and the second extracellular loop, with a pattern of species-specific changes that characterized CCR5 homologues from primates within a given family. At variance with humans, all primate species examined from the suborder Anthropoidea had amino acid substitutions at positions 13 (N to D) and 129 (V to I); the former change is critical for CD4-independent binding of SIV to CCR5. Within the Cebidae, Cercopithecidae, and Pongidae (including humans), CCR5 nucleotide similarities were 95.2 to 97.4, 98.0 to 99.5, and 98.3 to 99.3%, respectively. Despite this low genetic diversity, the phylogeny of the selected primate CCR5 homologue sequences agrees with present primate systematics, apart from some intermingling of species of the Cebidae and Cercopithecidae. Constructed HOS.CD4 cell lines expressing the entire CCR5 homologue protein from each of the Anthropoidea species and subspecies were tested for their ability to support HIV-1 and SIV entry and membrane fusion. Other than that of Cercopithecus pygerythrus, all CCR5 homologues tested were able to support both SIV and HIV-1 entry. Our results suggest that the shared structure and function of primate CCR5 homologue proteins would not impede the movement of primate immunodeficiency viruses between species.
C1 Northwestern Univ, Feinberg Sch Med, Dept Med, Div Infect Dis Med, Chicago, IL 60611 USA.
   Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA.
   Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA.
   Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA.
   Univ Washington, Natl Prime Res Ctr, Seattle, WA 98195 USA.
   NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
   Tulane Univ, Ctr Med, Tulane Reg Primate Ctr, Dept Zool, Covington, LA 70433 USA.
   Tulane Univ, Ctr Med, Tulane Reg Primate Ctr, Dept Trop Med, Covington, LA 70433 USA.
RP Wolinsky, SM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, Div Infect Dis Med, Suite 200,676 N St Clair, Chicago, IL 60611 USA.
RI Wolinsky, Steven/B-2893-2012; 
OI Wolinsky, Steven/0000-0002-9625-6697; Korber, Bette/0000-0002-2026-5757
FU NIAID NIH HHS [AI40880, AI41420, R01 AI040880, R01 AI041420]; NICHD NIH
   HHS [R01 HD037356, HD37356]
NR 52
TC 15
Z9 15
U1 0
U2 2
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 NOV
PY 2003
VL 77
IS 22
BP 12310
EP 12318
DI 10.1128/JVI.77.22.12310-12318.2003
PG 9
WC Virology
SC Virology
GA 738NG
UT WOS:000186294300045
PM 14581567
ER

PT J
AU Moniuszko, M
   Brown, C
   Pal, R
   Tryniszewska, E
   Tsai, WP
   Hirsch, VM
   Franchini, G
AF Moniuszko, M
   Brown, C
   Pal, R
   Tryniszewska, E
   Tsai, WP
   Hirsch, VM
   Franchini, G
TI High frequency of virus-specific CD8(+) T cells in the central nervous
   system of macaques chronically infected with simian immunodeficiency
   virus SIVmac251
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID I-ASSOCIATED MYELOPATHY; RHESUS-MONKEYS; CEREBROSPINAL-FLUID; VIRAL
   PERSISTENCE; BRAIN; LYMPHOCYTES; SIV; ENCEPHALITIS; NEUROPATHOGENESIS;
   RESPONSES
AB Infection with human immunodeficiency virus or simian immunodeficiency virus (SIV) induces virus-specific CD8(+) T cells that traffic to lymphoid and nonlymphoid tissues. In this study, we used Gag-specific tetramer staining to investigate the frequency of CD8+ T cells in peripheral blood and the central nervous system of Mamu-A*01-positive SIV-infected rhesus macaques. Most of these infected macaques were vaccinated prior to SIVmac251 exposure. The frequency of Gag(181-189) CM9 tetramer-positive cells was consistently higher in the cerebrospinal fluid and the brain than in the blood of all animals studied and did not correlate with either plasma viremia or CD4(+)-T-cell level. Little or no infection in the brain was documented for most animals by nucleic acid sequence-based amplification or in situ hybridization. These data suggest that this Gag-specific response may contribute to the containment of viral replication in this locale.
C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
   NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA.
   Adv BioSci Labs Inc, Kensington, MD 20895 USA.
RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA.
NR 48
TC 11
Z9 11
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 NOV
PY 2003
VL 77
IS 22
BP 12346
EP 12351
DI 10.1128/JVI.77.22.12346-12351.2003
PG 6
WC Virology
SC Virology
GA 738NG
UT WOS:000186294300049
PM 14581571
ER

PT J
AU Wang, ZY
   Wang, Y
   Lu, JP
   Kung, SY
   Zhang, JY
   Lee, R
   Xuan, JH
   Khan, JV
AF Wang, ZY
   Wang, Y
   Lu, JP
   Kung, SY
   Zhang, JY
   Lee, R
   Xuan, JH
   Khan, JV
TI Discriminatory mining of gene expression microarray data
SO JOURNAL OF VLSI SIGNAL PROCESSING SYSTEMS FOR SIGNAL IMAGE AND VIDEO
   TECHNOLOGY
LA English
DT Article; Proceedings Paper
CT 12th IEEE Workshop on Neural Networks for Signal Processing
CY SEP 04-06, 2002
CL MARTIGNY, SWITZERLAND
SP IEEE Signal Processing Soc, IEEE Neural Network Council, Swiss Natl Sci Fdn
DE computational bioinformatics; gene microarrays; finite normal mixture;
   cluster visualization and selection; machine learning
ID MOLECULAR CLASSIFICATION; DIMENSIONALITY REDUCTION; COMPONENT ANALYSIS;
   PREDICTION; NETWORKS; CANCER
AB Recent advances in machine learning and pattern recognition methods provide new analytical tools to explore high dimensional. gene expression microarray data. Our data mining software, VISual Data Analyzer for cluster discovery (VISDA), reveals many distinguishing patterns among gene expression profiles, which are responsible for the cell's phenotypes. The model-supported exploration of high-dimensional data space is achieved through two complementary schemes: dimensionality reduction by discriminatory data projection and cluster decomposition by soft data clustering. Reducing dimensionality generates the visualization of the complete data set at the top level. This data set is then partitioned into subclusters that can consequently be visualized at lower levels and if necessary partitioned again. In this paper, three different algorithms are evaluated in their abilities to reduce dimensionality and to visualize data sets: Principal Component Analysis (PCA), Discriminatory Component Analysis (DCA), and Projection Pursuit Method (PPM). The partitioning into subclusters uses the Expectation-Maximization (EM) algorithm and the hierarchical normal mixture model that is selected by the user and verified "optimally" by the Minimum Description Length (MDL) criterion. These approaches produce different visualizations that are compared against known phenotypes from the microarray experiments. Overall, these algorithms and user-selected models explore the high dimensional data where standard analyses may not be sufficient.
C1 Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
   Virginia Polytech Inst & State Univ, Dept Elect & Comp Engn, Alexandria, VA 22314 USA.
   Princeton Univ, Dept Elect Engn, Princeton, NJ 08544 USA.
   Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA.
   NHGRI, NIH, Bethesda, MD 20892 USA.
RP Wang, ZY (reprint author), Childrens Natl Med Ctr, Ctr Genet Res, Washington, DC 20010 USA.
RI Clarke, Robert/A-6485-2008; Khan, Javed/P-9157-2014
OI Clarke, Robert/0000-0002-9278-0854; Khan, Javed/0000-0002-5858-0488
NR 29
TC 15
Z9 15
U1 0
U2 5
PU KLUWER ACADEMIC PUBL
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0922-5773
J9 J VLSI SIG PROC SYST
JI J. VLSI Signal Process. Syst. Signal Image Video Technol.
PD NOV
PY 2003
VL 35
IS 3
BP 255
EP 272
DI 10.1023/B:VLSI.0000003024.13494.40
PG 18
WC Computer Science, Information Systems; Engineering, Electrical &
   Electronic
SC Computer Science; Engineering
GA 733ZW
UT WOS:000186031600004
ER

PT J
AU McCrae, RR
AF McCrae, RR
TI Expansion, integration, and omission: Some thoughts on a new agenda
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
   SCIENCES
LA English
DT Editorial Material
ID PERSONALITY
AB Hooker and McAdams (2003) have expanded a structural personality model to include personality processes and the interactions among all six resulting foci. This explicit model can usefully enlarge the scope of research on aging and personality. Additional thought, however, is needed on the definition of processes and on the selection of phenomena to be studied at the level of characteristic adaptations.
C1 NIA, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA.
RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
NR 10
TC 1
Z9 1
U1 0
U2 0
PU GERONTOLOGICAL SOCIETY AMER
PI WASHINGTON
PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA
SN 1079-5014
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD NOV
PY 2003
VL 58
IS 6
BP P307
EP P308
PG 2
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
   Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA 745WC
UT WOS:000186712900003
PM 14614112
ER

PT J
AU Miyaji, T
   Hu, XZ
   Yuen, PST
   Muramatsu, Y
   Iyer, S
   Hewitt, SM
   Star, RA
AF Miyaji, T
   Hu, XZ
   Yuen, PST
   Muramatsu, Y
   Iyer, S
   Hewitt, SM
   Star, RA
TI Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple
   organ damage in aged mice
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE acute renal failure; inflammation; TNF-alpha; coagulation;
   lipopolysaccharide
ID TUMOR-NECROSIS-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; CECAL
   LIGATION; REPERFUSION INJURY; EXPERIMENTAL-MODEL; INDUCED THROMBOSIS;
   PROGNOSTIC FACTORS; HEMORRHAGIC-SHOCK; IMPROVES SURVIVAL; SERUM
   CREATININE
AB Background. Sepsis is a common cause of acute renal failure (ARF). The incidence of sepsis increases dramatically after 50 years of age; however, most ARF studies are performed in young mice.
   Methods. We performed two common sepsis models, lipopolysaccharide (LPS) administration and cecal ligation puncture (CLP) in aged mice. We developed a fully treated CLP model in aged mice by treating mice with fluid resuscitation and antibiotics.
   Results. LPS induced renal injury in aged but not young mice. However, volume resuscitation starting within 6 hours decreased renal injury. We then used this fluid resuscitation scheme, along with antibiotics, to develop a fully treated CLP model in aged mice. Mice subjected to CLP developed functional and histologic ARF and multiple organ damage. Treatment with ethyl pyruvate, even when started 12 hours after surgery, decreased serum creatinine, tubular damage, and multiple organ injury at 24 hours. Ethyl pyruvate decreased plasma tumor necrosis factor-alpha (TNF-alpha), and kidney mRNA for TNFalpha, tissue factor, and plasminogen activator inhibitor-1 (PAI-1), and increased mRNA for urokinase-like plasminogen activator.
   Conclusion. CLP in aged mice causes functional and histologic changes consistent with human ARF. A single dose of ethyl pyruvate inhibits renal and multiple organ damage, and is still effective when given 12 hours after surgery.
C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA.
   NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA.
RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bldg 10,Room 3N108,10 Ctr Dr MSC 1268, Bethesda, MD 20892 USA.
RI Yuen, Peter/B-1954-2008; 
OI Yuen, Peter/0000-0001-9557-3909; Hewitt, Stephen/0000-0001-8283-1788
NR 60
TC 151
Z9 160
U1 0
U2 10
PU BLACKWELL PUBLISHING INC
PI MALDEN
PA 350 MAIN ST, MALDEN, MA 02148 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD NOV
PY 2003
VL 64
IS 5
BP 1620
EP 1631
DI 10.1046/j.1523-1755.2003.00268.x
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 730HH
UT WOS:000185824300007
PM 14531793
ER

PT J
AU Shiao, YH
   Forsti, A
   Egevad, L
   Anderson, LM
   Lindblad, P
   Hemminki, K
AF Shiao, YH
   Forsti, A
   Egevad, L
   Anderson, LM
   Lindblad, P
   Hemminki, K
TI VHL down-regulation and differential localization as mechanisms in
   tumorigenesis
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE von Hippel-Lindau; immunohistochemistry; down-regulation; localization;
   membrane; renal tumor
ID VON-HIPPEL-LINDAU; TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; HUMAN
   TISSUES; MUTATIONS; PROTEIN; EXPRESSION
AB Background. The von Hippel-Lindau (VHL) gene has been widely analyzed in many tumors. Early studies in animal tumors suggest that changes in VHL protein level and localization may be also important in tumorigenesis. In this study, we determined the role of VHL protein in human renal cell carcinomas.
   Methods. Seventy-five human renal cell carcinomas, predominantly of clear cell type (60 of 75), were examined for VHL protein by immunohistochemistry. The level and pattern of protein expression were then compared to VHL mutations and tumor characteristics.
   Results. An apparent decline of VHL level (positive in <50% of tumor cells) was observed in 49 (65%) tumors, a change more frequent than VHL mutations (28 of 75) (37%). In tumors, VHL was localized to the cytoplasm and/or the cell membrane. The occurrence of a predominantly membranous signal was significantly associated with missense mutations (9 of 14 tumors with missense mutations versus 14 of 61 tumors with no or nonmissense mutations, P = 0.0025) and tumor stage (23 of 60 tumors with stage TI versus 0 of 15 tumors with TII and TIII, P = 0.0034).
   Conclusion. This study provides the first evidence of the role of VHL protein level and intracellular localization in tumorigenesis in humans.
C1 NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA.
   Karolinska Inst, Novum, Dept Biosci, Huddinge, Sweden.
   German Canc Res Ctr, D-6900 Heidelberg, Germany.
   Karolinska Hosp, Dept Pathol & Cytol, S-10401 Stockholm, Sweden.
   Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.
RP Shiao, YH (reprint author), NCI, Comparat Carcinogenesis Lab, NIH, Bldg 538,Room 205, Frederick, MD 21702 USA.
NR 22
TC 3
Z9 3
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 NOV
PY 2003
VL 64
IS 5
BP 1671
EP 1674
DI 10.1046/j.1523-1755.2003.00257.x
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 730HH
UT WOS:000185824300013
PM 14531799
ER

PT J
AU Goldstein, DS
AF Goldstein, DS
TI Dysautonomia in Parkinson's disease: neurocardiological abnormalities
SO LANCET NEUROLOGY
LA English
DT Review
ID SYMPATHETIC SKIN-RESPONSE; MULTIPLE SYSTEM ATROPHY; NEUROGENIC
   ORTHOSTATIC HYPOTENSION; AUTONOMIC FUNCTION-TESTS; AGE-RELATED-CHANGES;
   I-123 MIBG UPTAKE; BAROREFLEX SENSITIVITY; BLOOD-PRESSURE;
   NEUROCIRCULATORY FAILURE; PLASMA NOREPINEPHRINE
AB Symptoms of abnormal autonomic-nervous-system function occur commonly in Parkinson's disease (PD). Orthostatic hypotension in patients with parkinsonism has been thought to be a side-effect of treatment with levodopa, a late stage in the disease progression, or, if prominent and early with respect to disordered movement, an indication of a different disease, such as multiple system atrophy. Instead, patients with PD and orthostatic hypotension have clear evidence for baroreflex failure and loss of sympathetic innervation, most noticeably in the heart. By contrast, patients with multiple system atrophy, which is difficult to distinguish clinically from PD, have intact cardiac sympathetic innervation. Postmortem studies confirm this distinction. Because PD involves postganglionic sympathetic noradrenergic lesions, the disease seems to be not only a movement disorder with dopamine loss in the nigrostriatal system of the brain, but also a dysautonomia, with norepinephrine loss in the sympathetic nervous system of the heart.
C1 NINDS, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, NIH, Clin Neurocardiol Sect, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA.
NR 94
TC 161
Z9 163
U1 1
U2 8
PU LANCET LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD NOV
PY 2003
VL 2
IS 11
BP 669
EP 676
DI 10.1016/S1474-4422(03)00555-6
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 734ZN
UT WOS:000186088000015
PM 14572735
ER

PT J
AU Rotem, R
   Fingrut, O
   Moskovitz, J
   Flescher, E
AF Rotem, R
   Fingrut, O
   Moskovitz, J
   Flescher, E
TI The anticancer plant stress-protein methyl jasmonate induces activation
   of stress-regulated c-Jun N-terminal kinase and p38 protein kinase in
   human lymphoid cells
SO LEUKEMIA
LA English
DT Letter
ID SIGNAL; EXPRESSION
C1 Tel Aviv Univ, Sackler Fac Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel.
   NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Rotem, R (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Human Microbiol, IL-69978 Tel Aviv, Israel.
NR 8
TC 19
Z9 22
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD NOV
PY 2003
VL 17
IS 11
BP 2230
EP 2234
DI 10.1038/sj.leu.2403107
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 735VT
UT WOS:000186135800026
PM 12931224
ER

PT J
AU Little, RF
AF Little, RF
TI AIDS-related non-Hodgkin's lymphoma: Etiology, epidemiology, and impact
   of highly active antiretroviral therapy
SO LEUKEMIA & LYMPHOMA
LA English
DT Article; Proceedings Paper
CT 1st International Workshop on Non-Hodgkins Lymphoma
CY NOV, 2002
CL CHANTILLY, FRANCE
DE AIDS-related non-Hodgkin's lymphoma; etiology; epidemiology; HAART
ID B-CELL LYMPHOMA; IMMUNODEFICIENCY-VIRUS INFECTION; COLONY-STIMULATING
   FACTOR; M-BACOD; INTENSIVE CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE;
   MOLECULAR PATHOGENESIS; HISTOGENETIC SUBSETS; MYC REARRANGEMENTS;
   KAPOSIS-SARCOMA
AB Lymphoproliferative disorders (LPD) occur more frequently in the immunosuppressed host compared to those who are immunocompetent. The biological and clinical characteristics of a particular LPD are specific to the underlying immune defect, though there are clear similarities in the various tumor types that occur. Immunosuppression-related LPD are more frequently associated with gammaherpesviruses suggesting that the immunologic environment influences tumorigenesis. Clinical outcomes may be optimized when appropriate treatment strategies are based on consideration of the underlying immunodeficiency and on the tumor biology. Consistent with this observation, in AIDS-related lymphomas (ARL), tumor biology, clinical presentations, and treatment outcomes are correlated with the CD4 cell count. This review will consider the role of immune deficiency in HIV disease on ARL pathogenesis and epidemiology, and the impact that highly active antiretroviral therapy has had in this disease.
C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Little, RF (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bldg 10,Room 10S255,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rlittle@helix.nih.gov
NR 58
TC 5
Z9 5
U1 1
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD NOV
PY 2003
VL 44
SU 3
BP S63
EP S68
DI 10.1080/10428190310001623748
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA 763YL
UT WOS:000188128000010
PM 15202527
ER

PT J
AU Rosenwald, A
   Staudt, LM
AF Rosenwald, A
   Staudt, LM
TI Gene expression profiling of diffuse large B-cell lymphoma
SO LEUKEMIA & LYMPHOMA
LA English
DT Article; Proceedings Paper
CT 1st International Workshop on Non-Hodgkins Lymphoma
CY NOV, 2002
CL CHANTILLY, FRANCE
DE diffuse large B-cell lymphoma (DBLCL); gene expression profiling
   diagnosis
ID NON-HODGKINS-LYMPHOMA; CDNA MICROARRAY; COMPLEMENTARY-DNA; PATTERNS;
   CHEMOTHERAPY; CANCER
AB Initial gene expression profiling studies of diffuse large B-cell lymphoma (DLBCL) revealed that this single diagnosis actually encompasses two distinct diseases that differ in the expression of hundreds of genes. One subtype, germinal center B-cell-like (GCB) DLBCL, strongly resembles normal germinal center B-cells and has a good prognosis following chemotherapy, whereas activated B-cell-like (ABC) DLBCL resembles mitogenically activated blood B cells and has a poor outcome. An expanded analysis of 274 DLBCL cases confirmed the existence of the GCB and ABC subgroups, but demonstrated that additional subgroups exist. Furthermore, two recurrent oncogenic events in DLBCL, t(14;18) and amplification of the c-rel locus on chromosome 2p, were only observed in GCB DLBCL, whereas constitutive activation of NF-kappaB was seen in ABC DLBCL, showing that the gene expression subgroups represent pathogenetically distinct diseases. Gene expression profiling has also been used to identify individual genes that predict overall survival in DLBCL, the majority coming from gene expression signatures that reflect the cell of origin, proliferation rate, and host immune response to the tumor. A multivariate model including 17 genes representing these biological features divided patients with DLBCL into quartiles with strikingly distinct 5-year survival rates, ranging from 73% to 15%. The use of gene expression profiling should eventually lead to an integration of molecular diagnosis and consequent selection of the most appropriate treatment.
C1 NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Rosenwald, A (reprint author), NCI, Metab Branch, Ctr Canc Res, Bldg 10,4N114,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM aroswald@mail.nih.gov
NR 22
TC 53
Z9 55
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD NOV
PY 2003
VL 44
SU 3
BP S41
EP S47
DI 10.1080/10428190310001623775
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 763YL
UT WOS:000188128000007
PM 15202524
ER

PT J
AU Waldmann, T
AF Waldmann, T
TI ABCs of radioisotopes used for radioimmunotherapy: alpha- and
   beta-emitters
SO LEUKEMIA & LYMPHOMA
LA English
DT Article; Proceedings Paper
CT 1st International Workshop on Non-Hodgkins Lymphoma
CY NOV, 2002
CL CHANTILLY, FRANCE
DE non-Hodgkin's lymphoma; radiolabeled monoclonal antibodies;
   radionuclides; radioimmunotherapy
ID NON-HODGKINS-LYMPHOMA; T-CELL LEUKEMIA; ANTI-CD20 MONOCLONAL-ANTIBODY;
   REFRACTORY LOW-GRADE; IBRITUMOMAB TIUXETAN RADIOIMMUNOTHERAPY; IODINE
   I-131 TOSITUMOMAB; STREPTAVIDIN FUSION PROTEIN; MULTICENTER PHASE-II;
   PRETARGETED RADIOIMMUNOTHERAPY; MURINE MODEL
AB Although the introduction of the monoclonal antibody rituximab 5 years ago led to a marked improvement in the treatment of non-Hodgkin's lymphoma (NHL), most patients do not experience a complete response to therapy, and many who do respond relapse. One way of improving the efficacy of monoclonal antibodies is to use them to deliver cytotoxic agents, such as radionuclides, to the tumor. Monoclonal antibodies armed with radionuclides provide a means of targeting radiation therapy specifically to tumor cells that express the antigen to which the antibody was originally raised. Subsequently, in 2002, the first radiolabeled monoclonal antibody, 90 Y-ibritumomab tiuxetan was approved for the treatment of patients with relapsed or refractory low-grade follicular or transformed B-cell NHL, including patients with follicular lymphoma refractory to rituximab. Attempts to optimize the efficacy of radioimmunotherapy are ongoing, however, and there are three factors that need to be considered: choice of antibody/antigen, choice of delivery of system to be used, and choice of radionuclide. CD25 (IL-2Ralpha) is an ideal choice for a target antigen as it is over-expressed by a number of tumor cells, including adult T-cell leukemia (ATL); 9 of 16 patients with ATL responded to treatment with anti-Tac (which targets the interleukin-2 receptor-alpha [IL-2Ralpha]), conjugated to 90 Y. The dose of radionuclide that can be delivered to a tumor can be increased dramatically by using a three-step process in which the antibody and radioactivity are delivered separately to the antigen in order to improve tumor-to-normal tissue ratios. The most commonly used radionuclides in radioimmunotherapy to date are beta-emitters. However, the pretargeting process makes the use of short-lived alpha-emitters more feasible. The results of experiments involving this pretargeting process and alpha- and beta-emitting radionuclides in leukemia and lymphoma models suggest that alpha-emitters may be more effective in the treatment of small tumors, micrometastases and isolated cells, and that beta-emitters may be more suitable for use in large tumor masses, such as lymphomas.
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Waldmann, T (reprint author), NCI, NIH, Bldg 10,Room 4N115,10 Ctr Dr 1374, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov
NR 49
TC 12
Z9 13
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD NOV
PY 2003
VL 44
SU 3
BP S107
EP S113
DI 10.1080/10428190310001623685
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 763YL
UT WOS:000188128000016
PM 15202533
ER

PT J
AU He, QC
   Fyfe, JC
   Schaffer, AA
   Kilkenney, A
   Werner, P
   Kirkness, EF
   Henthorn, PS
AF He, QC
   Fyfe, JC
   Schaffer, AA
   Kilkenney, A
   Werner, P
   Kirkness, EF
   Henthorn, PS
TI Canine Imerslund-Grasbeck syndrome maps to a region orthologous to
   HSA14q
SO MAMMALIAN GENOME
LA English
DT Article
ID SELECTIVE VITAMIN-B12 MALABSORPTION; INTESTINAL COBALAMIN MALABSORPTION;
   HEREDITARY MEGALOBLASTIC-ANEMIA; BRUSH-BORDER EXPRESSION; RADIATION
   HYBRID MAP; LINKAGE ANALYSIS; MOUSE GASTRULATION; CUBILIN; PROTEIN;
   RECEPTOR
AB Selective malabsorption of cobalamin (vitamin B-12) accompanied by proteinuria, known as Imerslund-Grasbeck syndrome or megaloblastic anemia 1 (I-GS, MGAq; OMIM 261100), is a rare autosomal recessive disorder. In Finnish kindreds, I-GS is caused by mutations in the cubilin gene (CUBN), located on human Chromosome (Chr) 10. However, not all patients have CUBN mutations, and three distinct mutations in the amnionless gene, AMN, were very recently identified in patients from Norwegian and Israeli families. The present study demonstrates that in a large canine I-GS pedigree, the disease is genetically linked (peak multipoint LOD score 11.74) to a region on dog Chr 8 that exhibits conserved synteny with human Chr 14q. Multipoint analysis indicates that the canine disease gene lies in an interval between the echinoderm microtubule-associated, protein-like 1 (EML1) gene and the telomere. A single critical recombinant further suggests that the disease gene is between markers in EML1 and the G protein-coupled receptor (G2A) gene, defining an I-GS interval in the human genome that contains the AMN gene. Thus, these comparative-mapping data provide evidence that canine I-GS is a homologue of one form of the human disease and will provide a useful system for understanding the molecular mechanisms underlying the disease in humans.
C1 Univ Penn, Sch Vet Med, Sch Med Genet, Philadelphia, PA 19104 USA.
   Michigan State Univ, Coll Vet Sci, Lab Comparat Med Genet, E Lansing, MI 48824 USA.
   Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
   Inst Genom Res, Rockville, MD 20850 USA.
RP Henthorn, PS (reprint author), Univ Penn, Sch Vet Med, Sch Med Genet, 3900 Delancey St, Philadelphia, PA 19104 USA.
RI Schaffer, Alejandro/F-2902-2012
FU NCRR NIH HHS [RR02512]; NIDDK NIH HHS [DK064161, DK45341]
NR 46
TC 20
Z9 21
U1 0
U2 3
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0938-8990
J9 MAMM GENOME
JI Mamm. Genome
PD NOV
PY 2003
VL 14
IS 11
BP 758
EP 764
DI 10.1007/s00335-003-2280-1
PG 7
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
GA 739BB
UT WOS:000186321400004
PM 14722725
ER

PT J
AU Hemila, H
   Virtamo, J
   Albanes, D
   Kaprio, J
AF Hemila, H
   Virtamo, J
   Albanes, D
   Kaprio, J
TI Physical activity and the common cold in men administered vitamin E and
   beta-carotene
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE alpha-tocopherol; ascorbic acid; beta-carotene; exercise; oxidative
   stress; smoking; upper respiratory infections
ID RESPIRATORY-TRACT INFECTIONS; ELITE SWIMMERS; IMMUNE-SYSTEM; MALE
   SMOKERS; EXERCISE; RUNNERS; EPISODES; OXIDANTS; STRESS; WOMEN
AB HEMILA, H., J. VIRTAMO, D. ALBANES, and J. KAPRIO. Physical Activity and the Common Cold in Men Administered Vitamin E and beta-Carotene. Med. Sci. Sports Exerc., Vol. 35, No. 11, pp. 1815-1820, 2003. Background and Purpose: It has been proposed that moderate regular aerobic training may enhance immunocompetence, whereas excessive training may cause immunosuppression. We evaluated whether physical activity at work, or at leisure, is associated with the risk of the common cold, and whether the antioxidants vitamin E and beta-carotene affect common cold risk in physically active people. Methods: A cohort of 14,401 men aged 50-69 yr and working at study entry was drawn from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which examined the effect of vitamin E, 50 mg(.)d(-1), and beta-carotene, 20 mg(.)d(-1), on lung cancer in smokers using a 2 X 2 factorial design. The trial was conducted in southwestern Finland in 1985-1993; the intervention lasted for 6.1 yr (median). Physical activity at work, and the type and frequency of leisure-time exercise were recorded at study entry. The subjects were questioned about common cold episodes 3 X yr(-1). We modeled the cumulative incidence of colds during a 2-yr follow-up period with Poisson regression, adjusting for potential confounders. Results: Physical activity at work and at leisure had no association with common cold risk. In subjects with physically load-bearing jobs, neither vitamin E nor beta-carotene affected significantly the risk of common cold. In subjects carrying out heavy exercise at leisure, vitamin E and beta-carotene increased the risk of colds when compared with placebo. Conclusions: Contrary to previous suggestions, moderate physical activity is not associated with lower risk of common cold in middle-aged male smokers. It has been previously proposed that antioxidant supplementation might be beneficial for subjects carrying out heavy exercise, but in our study vitamin E and beta-carotene increased the risk of colds in subjects carrying out heavy exercise at leisure.
C1 Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland.
   Natl Publ Hlth Inst, Dept Mental Hlth, Helsinki, Finland.
   Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland.
   NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Hemila, H (reprint author), Univ Helsinki, Dept Publ Hlth, POB 41, FIN-00014 Helsinki, Finland.
RI Kaprio, Jaakko/A-1820-2008; Albanes, Demetrius/B-9749-2015; 
OI Hemila, Harri/0000-0002-4710-307X; Kaprio, Jaakko/0000-0002-3716-2455
FU NCI NIH HHS [N01-CN-45165]
NR 30
TC 19
Z9 20
U1 1
U2 7
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 NOV
PY 2003
VL 35
IS 11
BP 1815
EP 1820
DI 10.1249/01.MSS.0000093616.60899.92
PG 6
WC Sport Sciences
SC Sport Sciences
GA 741WH
UT WOS:000186483000005
PM 14600543
ER

PT J
AU Keenan, NL
   Mark, S
   Fugh-Berman, A
   Browne, D
   Kaczmarczyk, J
   Hunter, C
AF Keenan, NL
   Mark, S
   Fugh-Berman, A
   Browne, D
   Kaczmarczyk, J
   Hunter, C
TI Severity of menopausal symptoms and use of both conventional and
   complementary/alternative therapies
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE menopause; honnone therapy; complementary and alternative therapy;
   estrogen; hot flashes; telephone survey
ID POPULATION-BASED SURVEY; QUALITY-OF-LIFE; ALTERNATIVE MEDICINE;
   POSTMENOPAUSAL WOMEN; CONTROLLED TRIAL
AB Objectives: To describe the prevalence and correlates of using conventional therapies, complementary and alternative therapies, or a combination of both types of therapies for menopausal symptoms and to examine the association between severity of symptoms and type of therapy use.
   Design: Data on 2,602 women aged 45 years or older were gathered through a cross-sectional telephone survey conducted in Florida, Minnesota, and Tennessee during 1997 and 1998 using the Behavioral Risk Factor Surveillance System. Participants were asked a series of questions about their menopausal status, menopausal symptoms, healthcare provider selection in relation to menopause, and therapies used for menopausal symptoms.
   Results: Of the eight menopausal symptoms assessed, the highest prevalence estimates were reported for hot flashes (62.9%), night sweats (48.3%), and trouble sleeping (41. 1%). The average number of symptoms (range 0- 8) was 3. 10 (SD +/- 2.25) and, for women reporting symptoms, the average symptom severity score (range 1-24) was 6.78 (SD +/- 4.63). About 45% of the women had not consulted with a healthcare provider for treatment of menopausal symptoms or for medical conditions related to menopause even though only 16.3% did not report any of the symptoms included in the survey. Forty-six percent of the women used complementary/alternative therapy either alone or in combination with conventional therapies. Age-adjusted average symptom severity scores were significantly higher among women who had undergone a hysterectomy, with removal of the ovaries (7.73; 95% Cl 7.33,8.12) or without (7.60; 95% CI 7.16,8.05), than among women who experienced a natural menopause (6.42; 95% Cl 6.14,6.71). Average severity scores were significantly higher among women who used both conventional and complementary/alternative therapies in relation to menopause (8.61; 95% Cl 8.26,8.96) than among women who used only conventional therapies (7.09; 95% CI 6.67,7.50). This statistically significant association persisted when adjusted for age, education, income, race/ethnicity, state of residence, and menopausal category.
   Conclusions: In this sample, 46% of the women used complementary/alternative therapy either alone or in combination with conventional therapies, whereas a third of the women did not use any therapy in relation to menopause. Although causal inferences cannot be made, the menopausal symptom severity score was significantly higher among women who reported using a combination of conventional and complementary/alternative therapies than among women who used only conventional therapy, only complementary/alternative, or no therapy.
C1 CDCP, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA.
   Dept Hlth & Human Serv, Off Womens Hlth, Washington, DC USA.
   George Washington Univ, Sch Med, Washington, DC USA.
   US Dept Def, Ft Detrick, MD USA.
   US Hlth Resources & Serv Adm, Bethesda, MD USA.
   NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
RP Keenan, NL (reprint author), CDCP, Natl Ctr Chron Dis Prevent & Hlth Promot, Mailstop K47,1445 Buford Hwy NE, Atlanta, GA 30341 USA.
NR 27
TC 62
Z9 63
U1 3
U2 5
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 NOV-DEC
PY 2003
VL 10
IS 6
BP 507
EP 515
DI 10.1097/01.GME.0000064865.58809.3E
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 743TE
UT WOS:000186589000003
PM 14627858
ER

PT J
AU Sherman, SS
AF Sherman, SS
TI Study of women's health across the nation (SWAN): Recent key findings
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the North-American-Menopause-Society
CY SEP 17-20, 2003
CL MIAMI, FLORIDA
SP N Amer Menopause Soc
C1 NIA, NIH, Bethesda, MD 20892 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 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2003
VL 10
IS 6
BP 561
EP 561
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 743TE
UT WOS:000186589000023
ER

PT J
AU Johnson, BD
   Merz, CNB
   Sharaf, BL
   Berga, SL
   Braunstein, G
   Bittner, V
   Gierach, G
   Reis, SE
   Pepine, CJ
   Mankad, S
   Sopko, G
   Pohost, GM
   Kelsey, SF
AF Johnson, BD
   Merz, CNB
   Sharaf, BL
   Berga, SL
   Braunstein, G
   Bittner, V
   Gierach, G
   Reis, SE
   Pepine, CJ
   Mankad, S
   Sopko, G
   Pohost, GM
   Kelsey, SF
TI Bilateral salpingo-oophorectomy (BSO) and coronary artery disease (CAD):
   The NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the North-American-Menopause-Society
CY SEP 17-20, 2003
CL MIAMI, FLORIDA
SP N Amer Menopause Soc
C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   Rhode Isl Hosp, Providence, RI 02903 USA.
   Magee Womens Hosp, Pittsburgh, PA USA.
   Univ Alabama, Birmingham, AL USA.
   Univ Florida, Gainesville, FL 32611 USA.
   Western PA Allegheny Hosp, Pittsburgh, PA USA.
   NHLBI, NIH, Bethesda, MD USA.
   Univ So Calif, Los Angeles, CA USA.
RI Reis, Steven/J-3957-2014; Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
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 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2003
VL 10
IS 6
BP 568
EP 568
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 743TE
UT WOS:000186589000048
ER

PT J
AU Merz, CNB
   Johnson, BD
   Sharaf, B
   Berga, S
   Braunstein, G
   Bittner, V
   Reis, S
   Pepine, CJ
   Mankad, S
   Pohost, G
   Sopko, G
   Kelsey, SF
AF Merz, CNB
   Johnson, BD
   Sharaf, B
   Berga, S
   Braunstein, G
   Bittner, V
   Reis, S
   Pepine, CJ
   Mankad, S
   Pohost, G
   Sopko, G
   Kelsey, SF
TI Prior oral contraceptive use and coronary artery disease (CAD): Data
   from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)
   study
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Meeting Abstract
CT 14th Annual Meeting of the North-American-Menopause-Society
CY SEP 17-20, 2003
CL MIAMI, FLORIDA
SP N Amer Menopause Soc
C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   Univ Pittsburgh, Sch Publ Hlth, Pittsburgh, PA 15260 USA.
   Brown Univ, Providence, RI USA.
   Univ Alabama, Birmingham, AL USA.
   Univ Florida, Gainesville, FL USA.
   Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
   Univ So Calif, Los Angeles, CA USA.
   NHLBI, Bethesda, MD 20892 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 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD NOV-DEC
PY 2003
VL 10
IS 6
BP 582
EP 582
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 743TE
UT WOS:000186589000105
ER

PT J
AU Theodorakis, MJ
   Muller, DC
   Carlson, O
   Egan, JM
AF Theodorakis, MJ
   Muller, DC
   Carlson, O
   Egan, JM
TI Assessment of insulin sensitivity and secretion indices from oral
   glucose tolerance testing in subjects with fasting euglycemia but
   impaired 2-hour plasma glucose
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Letter
C1 NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA.
RP Theodorakis, MJ (reprint author), NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA.
NR 2
TC 2
Z9 2
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 NOV
PY 2003
VL 52
IS 11
BP 1523
EP 1524
DI 10.1016/S0026-0495(03)00353-6
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 741JQ
UT WOS:000186455300026
PM 14635635
ER

PT J
AU Kobayashi, SD
   Voyich, JM
   DeLeo, FR
AF Kobayashi, SD
   Voyich, JM
   DeLeo, FR
TI Regulation of the neutrophil-mediated inflammatory response to infection
SO MICROBES AND INFECTION
LA English
DT Article
DE inflammation; neutrophils; phagocytosis; apoptosis
ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; GROUP-A STREPTOCOCCUS; APOPTOSIS;
   PROTEIN; LIPOPOLYSACCHARIDE; EXPRESSION; GRANULOCYTES; RECOGNITION;
   DESTRUCTION; MACROPHAGES
AB Human polymorphonuclear leukocytes (PMNs) are the first line of defense against invading microorganisms and contribute significantly to inflammation. Recent evidence suggests that resolution of neutrophil-mediated inflammation is facilitated by an apoptosis differentiation program, a final stage of transcriptionally regulated PMN maturation that is accelerated significantly by phagocytosis. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA.
RP DeLeo, FR (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
OI DeLeo, Frank/0000-0003-3150-2516
NR 31
TC 82
Z9 87
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD NOV
PY 2003
VL 5
IS 14
BP 1337
EP 1344
DI 10.1016/j.micinf.2003.09.013
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 748FM
UT WOS:000186851900007
PM 14613777
ER

PT J
AU Cohn, JV
   Alkhalil, A
   Wagner, MA
   Rajapandi, T
   Desai, SA
AF Cohn, JV
   Alkhalil, A
   Wagner, MA
   Rajapandi, T
   Desai, SA
TI Extracellular lysines on the plasmodial surface anion channel involved
   in Na+ exclusion
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE Plasmodium falciparum; chloride channels; nutrients; ion channel
   selectivity; pH; antimalarial development
ID MALARIA-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; FALCIPARUM; TRANSPORT;
   PERMEATION; PARASITE; PERMEABILITY; MEMBRANE; SOLUTES
AB The human malaria parasite, Plasmodium falciparum, induces an unusual ion channel, the plasmodial surface anion channel (PSAC), on its host red blood cell (RBC) membrane. PSAC has a broad selectivity with permeability to anions, sugars, amino acids, purines, and certain vitamins, suggesting a role in nutrient acquisition by the intracellular parasite. Permeating solutes cover a range of molecular sizes and may be either neutral or carry a net negative or positive charge. Despite this broad selectivity, PSAC must efficiently exclude Na+ to avoid osmotic lysis of infected RBCs in the bloodstream. Here, we used amine-reactive N-hydroxysulfosuccinimide esters to probe PSAC's unusual selectivity. PSAC permeation rates, measured with both a kinetic osmotic lysis assay and single-channel patch-clamp, irreversibly decrease after treatment with these reagents. Sequential labelings with different esters and the effects of their chain length suggest that PSAC has multiple lysine residues near its extracellular pore mouth and that inhibition occurs via steric hindrance of its pore by the amide-linked side chain. When combined with the effects of pH on permeation, these findings implicate a combination of cation repulsion by pore mouth charges and a weak binding site for permeant solutes in PSAC's broad selectivity yet effective exclusion of Na+. 2003 Elsevier B.V. All rights reserved.
C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RI Desai, Sanjay/B-7110-2009; 
OI Mery, Marissa/0000-0001-5819-6008
FU Intramural NIH HHS [Z01 AI000882-07]
NR 23
TC 47
Z9 48
U1 0
U2 3
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 NOV
PY 2003
VL 132
IS 1
BP 27
EP 34
DI 10.1016/j.molbiopara.2003.08.001
PG 8
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA 737HE
UT WOS:000186223700003
PM 14563534
ER

PT J
AU Griffiths, EK
   Sanchez, O
   Mill, P
   Krawczyk, C
   Hojilla, CV
   Rubin, E
   Nau, MM
   Khokha, R
   Lipkowitz, S
   Hui, CC
   Penninger, JM
AF Griffiths, EK
   Sanchez, O
   Mill, P
   Krawczyk, C
   Hojilla, CV
   Rubin, E
   Nau, MM
   Khokha, R
   Lipkowitz, S
   Hui, CC
   Penninger, JM
TI Cbl-3-deficient mice exhibit normal epithelial development
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; PROTEIN-TYROSINE KINASES; SKIN
   TUMOR-DEVELOPMENT; C-CBL; TRANSGENIC MICE; EGF RECEPTOR; NEGATIVE
   REGULATOR; SIGNAL-TRANSDUCTION; ADAPTER PROTEIN; PHOSPHORYLATION
AB Cbl family proteins are evolutionarily conserved ubiquitin ligases that negatively regulate signaling from tyrosine kinase-coupled receptors. The mammalian cbl family consists of c-Cbl, Cbl-b, and the recently cloned Cbl-3 (also known as Cbl-c). In this study, we describe the detailed expression pattern of murine Cbl-3 and report the generation and characterization of Cbl-3-deficient mice. Cbl-3 exhibits an expression pattern distinct from those of c-Cbl and Cbl-b, with high levels of Cbl-3 expression in epithelial cells of the gastrointestinal tract and epidermis, as well as the respiratory, urinary, and reproductive systems. Cbl-3 expression was not detected in nonepithelial cells, but within epithelial tissues, the levels of Cbl-3 expression varied from undetectable in the alveoli of the lungs to very strong in the cecum and colon. Despite this restricted expression pattern, Cbl-3-deficient mice were viable, healthy, and fertile and displayed no histological abnormalities up to 18 months of age. Proliferation of epithelial cells in the epidermises and gastrointestinal tracts was unaffected by the loss of Cbl-3. Moreover, Cbl-3 was not required for attenuation of epidermal growth factor-stimulated Erk activation in primary keratinocytes. Thus, Cbl-3 is dispensable for normal epithelial development and function.
C1 Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria.
   Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2C1, Canada.
   Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada.
   Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada.
   NCI, Regulat Protein Funct Lab, NIH, Ft Detrick, MD 21702 USA.
RP Penninger, JM (reprint author), Austrian Acad Sci, Inst Mol Biotechnol, IMBA, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
RI Penninger, Josef/I-6860-2013; 
OI Penninger, Josef/0000-0002-8194-3777; Mill,
   Pleasantine/0000-0001-5218-134X
NR 53
TC 30
Z9 31
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 NOV
PY 2003
VL 23
IS 21
BP 7708
EP 7718
DI 10.1128/MCB.23.21.7708-7718.2003
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 734KQ
UT WOS:000186055400024
PM 14560016
ER

PT J
AU Kim, A
   Dean, A
AF Kim, A
   Dean, A
TI A human globin enhancer causes both discrete and widespread alterations
   in chromatin structure
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID LOCUS-CONTROL REGION; RNA-POLYMERASE-II; HISTONE ACETYLTRANSFERASE
   ACTIVITY; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; REMODELING ENZYMES; GENE
   ACTIVATION; ACETYLATION; PROMOTER; RECRUITMENT
AB Gene activation requires alteration of chromatin structure to facilitate active transcription complex formation at a gene promoter. Nucleosome remodeling complexes and histone modifying complexes each play unique and interdependent roles in bringing about these changes. The role of distant enhancers in these structural alterations is not well understood. We studied nucleosome remodeling and covalent histone modification mediated by the beta-globin locus control region HS2 enhancer at nucleosome-level resolution throughout a 5.5-kb globin gene model locus in vivo in K562 cells. We compared the transcriptionally active locus to one in which HS2 was inactivated by mutations in the core NF-E2 sites. In contrast to inactive templates, nucleosomes were mobilized in discrete areas of the active locus, including the HS2 core and the proximal promoter. Large differences in restriction enzyme accessibility between the active and inactive templates were limited to the regions of nucleosome mobilization, which subsumed the DNase I hypersensitive sites. In contrast to this discrete pattern, histone H3 and H4 acetylation and H3 K4 methylation were elevated across the entire active locus, accompanied by depletion of linker histone H1. The coding region of the gene differed from the regulatory regions, demonstrating both nucleosome mobilization and histone hyperacetylation, but lacked differences in restriction enzyme accessibility between transcriptionally active and inactive genes. Thus, although the histone modification pattern we observe is consistent with the spreading of histone modifying activity from the distant enhancer, the pattern of nucleosome mobilization is more compatible with direct contact between an enhancer and promoter.
C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Dean, A (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3154,50 South Dr,MSC 8028, Bethesda, MD 20892 USA.
NR 55
TC 34
Z9 34
U1 0
U2 1
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 NOV
PY 2003
VL 23
IS 22
BP 8099
EP 8109
DI 10.1128/MCB.23.22.8099.8109.2003
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 739PC
UT WOS:000186354800016
PM 14585970
ER

PT J
AU Nishikawa, K
   Kobayashi, M
   Masumi, A
   Lyons, SE
   Weinstein, BM
   Liu, PP
   Yamamoto, M
AF Nishikawa, K
   Kobayashi, M
   Masumi, A
   Lyons, SE
   Weinstein, BM
   Liu, PP
   Yamamoto, M
TI Self-association of Gata1 enhances transcriptional activity in vivo in
   zebra fish embryos
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ZINC-FINGER PROTEIN; BINDING PROTEIN; DNA-BINDING; CELL-DEVELOPMENT;
   GENE-EXPRESSION; FAMILY; DIFFERENTIATION; REPRESSOR; COFACTOR; ELEMENTS
AB Gata1 is a prototype transcription factor that regulates hematopoiesis, yet the molecular mechanisms by which Gata1 transactivates its target genes in vivo remain unclear. We previously showed, in transgenic zebra fish, that Gata1 autoregulates its own expression. In this study, we characterized the molecular mechanisms for this autoregulation by using mutations in the Gata1 protein which impair autoregulation. Of the tested mutations, replacement of six lysine residues with alanine (Gata1KA6), which inhibited self-association activity of Gata1, reduced the Gata1-dependent induction of reporter gene expression driven by the zebra fish gata1 hematopoietic regulatory domain (gata1 HRD). Furthermore, overexpression of wild-type Gata1 but not Gata1KA6 rescued the expression of Gata1 downstream genes in Wad tepes, a germ line gata1 mutant fish. Interestingly, both GATA sites in the double GATA motif in gata1 HRD were critical for the promoter activity and for binding of the self-associated Gata1 complex, whereas only the 3'-GATA site was required for Gata1 monomer binding. These results thus provide the first in vivo evidence that the ability of Gata1 to self-associate critically contributes to the autoregulation of the gata1 gene.
C1 Univ Tsukuba, Ctr TARA, Tsukuba, Ibaraki 3058577, Japan.
   Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 3058577, Japan.
   Japan Sci & Technol Corp, ERATO, Yamamoto Environm Response Project, Tsukuba, Ibaraki 3002635, Japan.
   Natl Inst Infect dis, Dept Safety Res Biol, Musashimurayama 2080011, Japan.
   Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
   NICHD, Bethesda, MD 20892 USA.
   NHGRI, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, M (reprint author), Univ Tsukuba, Ctr TARA, Tsukuba, Ibaraki 3058577, Japan.
RI Yamamoto, Masayuki/A-4873-2010; Liu, Paul/A-7976-2012; Kobayashi,
   Makoto/B-2537-2008
OI Liu, Paul/0000-0002-6779-025X; 
NR 61
TC 32
Z9 34
U1 1
U2 1
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 NOV
PY 2003
VL 23
IS 22
BP 8295
EP 8305
DI 10.1128/MCB.23.22.8295-8305.2003
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 739PC
UT WOS:000186354800032
PM 14585986
ER

PT J
AU Kanemitsu, Y
   Hosoi, M
   Zhu, PJ
   Weight, FF
   Peoples, RW
   McLaughlin, JS
   Zhang, L
AF Kanemitsu, Y
   Hosoi, M
   Zhu, PJ
   Weight, FF
   Peoples, RW
   McLaughlin, JS
   Zhang, L
TI Dynorphin A inhibits NMDA receptors through a pH-dependent mechanism
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
ID OPIOID PEPTIDE DYNORPHIN; D-ASPARTATE RECEPTOR; RAT-BRAIN;
   CEREBRAL-ISCHEMIA; GLUTAMATE-RECEPTOR; CORTICAL-NEURONS; POTENTIATION;
   SPERMINE; CHANNELS; HIPPOCAMPUS
AB Dynorphin A (DynA), an endogenous agonist Of K-opioid receptors, has also been reported to directly interact with the NMDA receptor. DynA inhibition of NMDA receptor function has been suggested to be involved in its neuroprotective action during ischemic and acidic conditions. However, the effect of external pH on DynA inhibition of the NMDA receptor has not been reported. Here, we show that DynA inhibition of the NMDA receptor is dependent on extracellular pH over the range of pH 6.7-8.3, and the inhibition by 10 muM DynA increases at low pH by three- to four-fold in hippocampal neurons and in Xenopus oocytes expressing NR1-1a/2B subunits. Molecular studies showed that the interacting site for DynA on the NMDA receptor is distinct from that of proton or redox sites. Peptide mapping demonstrated important contributions of positively charged residues and specific structural organization of the peptide to the potency of DynA inhibition. Thus, DynA inhibits NMDA receptors through an allosteric mechanism, which is pH dependent and involves the specific structural features of the peptide. (C) 2003 Elsevier Inc. All rights reserved.
C1 NIAAA, Lab Mol & Cellular Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Zhang, L (reprint author), NIAAA, Lab Mol & Cellular Neurobiol, NIH, Pk Bldg,Rm 150, Bethesda, MD 20892 USA.
NR 54
TC 9
Z9 9
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 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD NOV
PY 2003
VL 24
IS 3
BP 525
EP 537
DI 10.1016/S1044-7431(03)00214-8
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 751YH
UT WOS:000187117700001
PM 14664805
ER

PT J
AU Arnaoutova, I
   Jackson, CL
   Al-Awar, MS
   Donaldson, JG
   Loh, YP
AF Arnaoutova, I
   Jackson, CL
   Al-Awar, MS
   Donaldson, JG
   Loh, YP
TI Recycling of raft-associated prohormone sorting receptor
   carboxypeptidase E requires interaction with ARF6
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID GPI-ANCHORED PROTEINS; PLASMA-MEMBRANE; CELL-SURFACE; DEPENDENT
   RETENTION; SECRETORY GRANULES; GOLGI-COMPLEX; CPE(FAT) MICE; SHIGA
   TOXIN; CLATHRIN; PATHWAY
AB Little is known about the molecular mechanism of recycling of intracellular receptors and lipid raft-associated proteins. Here, we have investigated the recycling pathway and internalization mechanism of a transmembrane, lipid raft-associated intracellular prohormone sorting receptor, carboxypeptidase E (CPE). CPE is found in the trans-Golgi network (TGN) and secretory granules of (neuro)endocrine cells. An extracellular domain of the IL2 receptor alpha-subunit (Tac) fused to the transmembrane domain and cytoplasmic tail of CPE (Tac-CPE25) was used as a marker to track recycling of CPE. We show in (neuro) endocrine cells, that upon stimulated secretory granule exocytosis, raft-associated Tac-CPE25 was rapidly internalized from the plasma membrane in a clathrin-independent manner into early endosomes and then transported through the endocytic recycling compartment to the TGN. A yeast two-hybrid screen and in vitro binding assay identified the CPE cytoplasmic tail sequence S472ETLNF477 as an interactor with active small GTPase ADP-ribosylation factor (ARF) 6, but not ARF1. Expression of a dominant negative, inactive ARF6 mutant blocked this recycling. Mutation of residues S-472 or E-473 to A in the cytoplasmic tail of CPE obliterated its binding to ARF6, and internalization from the plasma membrane of Tac-CPE25 mutated at S-472 or E-473 was significantly reduced. Thus, CPE recycles back to the TGN by a novel mechanism requiring ARF6 interaction and activity.
C1 NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
   NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
   NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
RI Jackson, Catherine/A-3421-2013
OI Jackson, Catherine/0000-0002-0843-145X
NR 33
TC 28
Z9 28
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD NOV
PY 2003
VL 14
IS 11
BP 4448
EP 4457
DI 10.1091/mbc.E02-11-0758
PG 10
WC Cell Biology
SC Cell Biology
GA 746GH
UT WOS:000186738300011
PM 12960436
ER

PT J
AU Kong, HJ
   Yu, HJ
   Hong, SH
   Park, MJ
   Choi, YH
   An, WG
   Lee, JW
   Cheong, JH
AF Kong, HJ
   Yu, HJ
   Hong, SH
   Park, MJ
   Choi, YH
   An, WG
   Lee, JW
   Cheong, JH
TI Interaction and functional cooperation of the cancer-amplified
   transcriptional coactivator activating signal cointegrator-2 and E2F-1
   in cell proliferation
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID S-PHASE; RETINOBLASTOMA PROTEIN; IN-VIVO; HISTONE ACETYLTRANSFERASES;
   DEPENDENT TRANSACTIVATION; BINDING PROTEIN; CBP COACTIVATOR; FAMILY
   PROTEINS; NUCLEAR-FACTOR; ACETYLATION
AB Activating signal cointegrator-2 (ASC-2), a novel coactivator, is amplified in several cancer cells and known to interact with mitogenic transcription factors, including serum response factor, activating protein-1, and nuclear factor-kappaB, suggesting the physiological role of ASC-2 in the promotion of cell proliferation. Here, we show that the expression pattern of ASC-2 was correlated with that of E2F-1 for protein increases at G(1) and S phase. Furthermore, cells stably overexpressing ASC-2 had an increased cell proliferation profile. These results prompted us to examine the functional interaction of ASC-2 and E2F-1. Biochemical evidence of protein interaction indicated that the transactivation domain of E2F-1 interacted with the COOH-terminal region of ASC-2. The importance of the E2F-1-ASC-2 interaction was supported by the demonstration that the coexpression of ASC-2 and E2F-1 synergistically transactivated E2F-1-driven gene transcription and the acetylation of E2F-1 protein was necessary for ASC-2-mediated transcriptional coactivation. Interestingly, overexpression of ASC-2 increased the endogenous protein level of E2F-1 in cells, resulting from the prolonged protein stability of E2F-1. Taken together, these results suggest that the cancer-amplified transcriptional coactivator ASC-2 may promote cell proliferation through enhancement of E2F-1-dependent transactivation of the expression of genes associated with cell cycle progression that may be available to favor tumor growth in vivo.
C1 Pusan Natl Univ, Dept Mol Biol, Pusan 609735, South Korea.
   NIH, Lab Mol Growth Regulat, Bethesda, MD 20892 USA.
   Dong Eui Univ, Dept Biochem, Coll Oriental Med, Pusan, South Korea.
   Kyungpook Natl Univ, Dept Biol, Taegu 702701, South Korea.
   Baylor Coll Med, Dept Med Endocrinol, Houston, TX 77030 USA.
RP Cheong, JH (reprint author), Pusan Natl Univ, Dept Mol Biol, Pusan 609735, South Korea.
NR 45
TC 12
Z9 12
U1 0
U2 0
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 NOV
PY 2003
VL 1
IS 13
BP 948
EP 958
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 747DB
UT WOS:000186789000003
PM 14638867
ER

PT J
AU Kondapaka, SB
   Singh, SS
   Dasmahapatra, GP
   Sausville, EA
   Roy, KK
AF Kondapaka, SB
   Singh, SS
   Dasmahapatra, GP
   Sausville, EA
   Roy, KK
TI Perifosine, a novel alkylphospholipid, inhibits protein kinase B
   activation
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID PHOSPHATIDYLINOSITOL 3-KINASE; PROSTATE-CANCER; DEPENDENT
   PHOSPHORYLATION; ALKYL-LYSOPHOSPHOLIPIDS; MILTEFOSINE SOLUTION; COUPLED
   RECEPTORS; CELL-SURVIVAL; AKT2 ONCOGENE; BREAST-CANCER; PHASE-II
AB Perifosine is a novel p.o. bioavailable alkylphospholipid. Perifosine has displayed significant antiproliferative activity in vitro and in vivo in several human tumor model systems and has recently entered phase I clinical trials. Recent studies have identified that perifosine could cause cell cycle arrest with induction of p21(WAF1/CIP1) in a p53-independent fashion; however, the basis for that effect is not known. Structurally, perifosine resembles naturally occurring phospholipids. Therefore, we hypothesized that perifosine might perturb pathways related to phospholipids modulated by growth factor action. We demonstrate here that perifosine causes dose-dependent inhibition of protein kinase B/Akt phosphorylation and thus activation at concentrations causing growth inhibition of PC-3 prostate carcinoma cells. Only the myristoylated form of Akt (MYR-Akt), which bypasses the requirement for pleckstrin homology (PH) domain-mediated membrane recruitment, abrogated perifosine-mediated decrease of Akt phosphorylation and cell growth inhibition by perifosine. We demonstrate further that perifosine decreases the plasma membrane localization of Akt, and this is substantially relieved by MYR-Akt along with relief of downstream drug effect on induction of p21(WAF1/CIP1). Perifosine does not directly affect phosphoinositide 3-kinase (PI3K), phosphoinositide-dependent kinase 1, or Akt activity at concentrations inhibiting Akt phosphorylation and membrane localization. Our results demonstrate that Akt is an important cellular target of perifosine action. In addition, these studies show that the membrane translocation of certain PH domain-containing molecules can be greatly perturbed by the alkylphospholipid class of drugs and imply further that the PI3K/Akt pathway contributes to regulation of p21(WAF1/CIP1) expression.
C1 NCI, Clin Trials Unit, Dev Therapeut Program, Bethesda, MD 20892 USA.
RP Roy, KK (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 6N 113, Bethesda, MD 20892 USA.
NR 56
TC 300
Z9 311
U1 0
U2 8
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 NOV
PY 2003
VL 2
IS 11
BP 1093
EP 1103
PG 11
WC Oncology
SC Oncology
GA 742TN
UT WOS:000186534300002
PM 14617782
ER

PT J
AU Intine, RV
   Tenenbaum, SA
   Sakulich, AL
   Keene, JD
   Maraia, RJ
AF Intine, RV
   Tenenbaum, SA
   Sakulich, AL
   Keene, JD
   Maraia, RJ
TI Differential phosphorylation and subcellular localization of and La RNPs
   associated with precursor tRNAs and translation-related mRNAs
SO MOLECULAR CELL
LA English
DT Article
ID SS-B AUTOANTIGEN; POLYMERASE-III TRANSCRIPTS; IN-VIVO; PROTEIN; ANTIGEN;
   NUCLEAR; BINDING; RECOGNITION; APOPTOSIS; ELEMENT
AB The La protein facilitates the production of tRNAs in the nucleus and the translation of specific mRNAs in the cytoplasm. We report that human La that is phosphorylated on serine 366 (pLa) is nucleoplasmic and associated with precursor tRNAs and other nascent RNA polymerase III transcripts while nonphosphorylated (np)La is cytoplasmic and associated with a subset of mRNAs that contain 5'-terminal oligopyrimidine (5'TOP) motifs known to control protein synthesis. Thus, La ribonucleoproteins (RNP) exist in distinct states that differ in subcellular localization, serine 366 phosphorylation, and associated RNAs. These results are consistent with a model in which the relative concentrations of the La S366 isoforms in different subcellular compartments in conjunction with the relative concentrations of specific RNA ligands in these compartments determine the differential association of npLa and pLa with their respective classes of associated RNAs.
C1 NICHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA.
   Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
RP Maraia, RJ (reprint author), NICHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA.
EM maraiar@mail.nih.gov
FU NCI NIH HHS [CA79907]; NIAID NIH HHS [AI46451]
NR 32
TC 64
Z9 66
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD NOV
PY 2003
VL 12
IS 5
BP 1301
EP 1307
DI 10.1016/S1097-2765(03)00429-5
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 746TX
UT WOS:000186764700024
PM 14636586
ER

PT J
AU Moeller, LC
   Kimura, S
   Kusakabe, T
   Liao, XH
   Van Sande, J
   Refetoff, S
AF Moeller, LC
   Kimura, S
   Kusakabe, T
   Liao, XH
   Van Sande, J
   Refetoff, S
TI Hypothyroidism in thyroid transcription factor 1 haploinsufficiency is
   caused by reduced expression of the thyroid-stimulating hormone receptor
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID FACTOR-I; RESPIRATORY-FAILURE; GENE-EXPRESSION; TSH RECEPTOR;
   THYROTROPIN; MUTATIONS; RADIOIMMUNOASSAY; DELETION; BINDING; MICE
AB Humans expressing one allele of the thyroid transcription factor 1 (TTF1) gene have neurological symptoms and increased serum TSH with variable degrees of hypothyroidism. Ttf1(+/-) mice have also poor coordination and increased serum TSH concentration (205 +/- 22 vs. 92 +/- 12 mU/liter; P < 0.001) and slightly lower T-4 (46 +/- 3 vs. 63 +/- 6 nmol/liter; P < 0.02) as compared with Ttf1(+/+) mice. To determine whether the hypothyroidism is of central or primary origin, we examined the bioactivity of TSH, thyroidal response to exogenous TSH and the expression of genes regulated by TTF1. TSH bioactivity was normal, but T-4 response to a low but not high dose of TSH was significantly reduced in the Ttf1(+/-) mice (5.5 +/- 2.2 vs. 15.3 +/- 4.1 nmol/liter; P < 0.03), indicating a reduced thyroidal response. Thyroid mRNAs were measured by real-time PCR (Ttf1(+/+) littermates = 100%). Ttf1(+/-) mice had half the levels of TTF1 mRNA (54 +/- 9; P < 0.01) and protein, confirming their haploinsufficiency. Significantly lower levels of mRNAs were observed for two of the three genes with TTF1 cis elements: TSH receptor (TSHr, 57 +/- 4%; P < 0.002), thyroglobulin (63 +/- 7%; P < 0.005), but not thyroid peroxidase (81 +/- 12%; P > 0.05). No significant difference between the two genotypes was found for Pax8, sodium iodide symporter, and iodothyronine deiodinase 1. These results show that Ttf1 haploinsufficiency causes a reduction in the expression of TSHr and thyroglobulin, genes with TTF1 binding sites in their promoter regions. The low TSHr is only partially compensated by an increase in TSH secretion because T 4 remains mildly reduced. However, administration of a larger amount of TSH obliterates the response differences by saturating a reduced amount of receptor.
C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA.
   Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
   Univ Chicago, Comm Genet, Chicago, IL 60637 USA.
   NCI, NIH, Bethesda, MD 20892 USA.
   Free Univ Brussels, Erasme Hosp, Sch Med, Inst Rech Interdisciplinaire Biol Humaine & Mol, B-1070 Brussels, Belgium.
RP Refetoff, S (reprint author), Univ Chicago, Dept Med, MC3090,5841 S Maryland Ave, Chicago, IL 60637 USA.
OI Moeller, Lars/0000-0002-9330-9036
FU NIDDK NIH HHS [DK 15070]
NR 23
TC 44
Z9 44
U1 0
U2 1
PU ENDOCRINE SOC
PI BETHESDA
PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD NOV 1
PY 2003
VL 17
IS 11
BP 2295
EP 2302
DI 10.1210/me.2003-0175
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 738EL
UT WOS:000186273700014
PM 12907760
ER

PT J
AU Wolford, JK
   Colligan, PB
   Gruber, JD
   Bogardus, C
AF Wolford, JK
   Colligan, PB
   Gruber, JD
   Bogardus, C
TI Variants in the interleukin 6 receptor gene are associated with obesity
   in Pima Indians
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE single nucleotide polymorphisms; candidate gene analysis; BMI;
   chromosome 1q; proteolytic cleavage
ID DIABETES-SUSCEPTIBILITY GENES; SUBCUTANEOUS ADIPOSE-TISSUE; BODY-MASS
   INDEX; IL-6 RECEPTOR; GENOME-WIDE; INDEPENDENT REPLICATION; CHROMOSOME
   1Q21-Q24; ACTIVATION; MELLITUS; LOCUS
AB Circulating levels of the cytokine interleukin 6 (IL-6) are elevated in obesity, correlate with body mass index (BMI), and predict the development of type 2 diabetes mellitus (T2DM). A promoter polymorphism in the IL6 gene is associated with obesity, altered levels of insulin sensitivity, and T2DM. IL-6 exerts its effects by binding to the IL-6 receptor (IL-6R) and levels of IL-6R have been correlated with BMI. It is possible that IL6R variants may also be related to obesity, but to our knowledge, no study has yet examined this relationship. The objective of this study was to examine the relationship between genetic variants in the IL6R gene and obesity in Pima Indians, a population prone to excess adiposity. We sequenced 6 kb of the IL6R gene, corresponding to all exons, exon-intron boundaries, and 2 kb of promoter in 30 Pima Indians. We identified six single nucleotide polymorphisms (SNPs) in the IL6R gene: a predicted Asp --> Ala substitution at position 358, a variant in the 3'-untranslated region, and 4 intronic SNPs. All SNPs were in strong linkage disequilibrium (D' greater than or equal to 0.90) and varied in minor allele frequency from 0.33 to 0.48. Association between IL6R genotype and BMI (kg/m(2)) was assessed in approximately 700 nondiabetic, full-heritage Pima Indians. For each SNP, individuals carrying the variant allele had a higher mean BMI compared to those with the wild-type allele (range: [37.3 +/- 7.2-38.2 +/- 7.0] vs. [35.5 +/- 7.3-36.0 +/- 7.5]; P = 0.02-0.004). Our findings suggest that genetic variants in the IL6R gene may play a role in susceptibility to obesity. Assessment of these SNPs in other populations will be useful to determine the magnitude of obesity risk. (C) 2003 Elsevier Inc. All rights reserved.
C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA.
RP Wolford, JK (reprint author), Translat Genom Res Inst, 400 N 5th St,Suite 1600, Phoenix, AZ 85004 USA.
NR 33
TC 55
Z9 62
U1 0
U2 4
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 NOV
PY 2003
VL 80
IS 3
BP 338
EP 343
DI 10.1016/j.ymgme.2003.07.003
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 742JP
UT WOS:000186513900009
PM 14680981
ER

PT J
AU Koonin, EV
AF Koonin, EV
TI Horizontal gene transfer: the path to maturity
SO MOLECULAR MICROBIOLOGY
LA English
DT Editorial Material
ID EVOLUTION; GENOMES; CLASSIFICATION; PROKARYOTES; SEQUENCE; ARCHAEAL;
   BACTERIA
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
NR 17
TC 37
Z9 40
U1 0
U2 0
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 NOV
PY 2003
VL 50
IS 3
BP 725
EP 727
DI 10.1046/j.1365-2958.2003.03808.x
PG 3
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 733FC
UT WOS:000185988400001
PM 14617135
ER

PT J
AU Li, YF
   Youngren, B
   Sergueev, K
   Austin, S
AF Li, YF
   Youngren, B
   Sergueev, K
   Austin, S
TI Segregation of the Escherichia coli chromosome terminus
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID CELL-DIVISION; DNA-REPLICATION; DIMER RESOLUTION; P1 PLASMID; FTSK;
   RECOMBINATION; PROTEIN; CAPTURE; ORIGIN; MODEL
AB We studied the segregation of the replication terminus of the Escherichia coli chromosome by time-lapse and still photomicroscopy. The replicated termini lie together at the cell centre. They rapidly segregate away from each other immediately before cell division. At fast growth rate, the copies move progressively and quickly toward the centres of the new-born cells. At slow growth rate, the termini usually remain near the inner cell pole and migrate to the cell centre in the middle of the cell cycle. A terminus domain of about 160kb, roughly centred on the dif recombination site, segregated as a unit at cell division. Sequences outside this domain segregated before division, giving two separate foci in predivision cells. Resolution of chromosome dimers via the terminus dif site requires the XerC recombinase and an activity of the FtsK protein that is thought to align the dif sequences at the cell centre. We found that anchoring of the termini at the cell centre and proper segregation at cell division occurred normally in the absence of recombination via the XerC recombinase. Anchoring and proper segregation were, however, frequently disrupted when the C-terminal domain of FtsK was truncated.
C1 NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA.
RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA.
NR 30
TC 39
Z9 39
U1 0
U2 0
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 NOV
PY 2003
VL 50
IS 3
BP 825
EP 834
DI 10.1046/j.1365-2958.2003.03746.x
PG 10
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 733FC
UT WOS:000185988400010
PM 14617144
ER

PT J
AU Welty, DM
   Snyder, DS
AF Welty, DM
   Snyder, DS
TI Internalization of OspA in rsCD14 complex and aggregated forms
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; BORRELIA-BURGDORFERI; CELL-SURFACE; CUTTING EDGE;
   CPG-DNA; LIPOPOLYSACCHARIDE; CD14; LIPOPROTEINS; ACTIVATION; TLR4
AB Although the spirochetal protein OspA is capable of stimulating immune cells in a CD14- and TLR2-dependent manner, little is known about how TLR2 receptor complex ligands, such as OspA, are handled by the cell once delivered. We examine here the internalization of the fluorescently derivatized forms of both the full length OspA lipoprotein delivered as a recombinant soluble CD14 (rsCD14) complex and the corresponding lipohexapeptide given to the cells as an aggregate. Both forms of OspA are internalized in a similar manner to acetylated low density lipoprotein (AcLDL), a scavenger receptor ligand. Acetylated low density lipoprotein is capable of competing for internalization with OspA even when OspA is delivered as a rsCD14 complex. We observe co-localization of OspA with lysosomes but not with the Golgi complex. These phenomena are similar between RAW264.7 macrophages and endothelial cells but change drastically when the cells are deprived of serum. Upon serum starvation, OspA shows some localization to the Golgi apparatus whereas the lipohexapeptide remains on the cell surface. Inhibition of internalization of OspA via treatment with cytochalasin D or of the lipohexapeptide via serum starvation does not interfere with TNF induction activity, consistent with signalling from the cell surface.
C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Snyder, DS (reprint author), Baylor Coll Med, 1 Baylor Plaza, Houston, TX 77030 USA.
NR 20
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2003
VL 50
IS 3
BP 835
EP 843
DI 10.1046/j.1365-2958.2003.03769.x
PG 9
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 733FC
UT WOS:000185988400011
PM 14617145
ER

PT J
AU Zhang, AX
   Wassarman, KM
   Rosenow, C
   Tjaden, BC
   Storz, G
   Gottesman, S
AF Zhang, AX
   Wassarman, KM
   Rosenow, C
   Tjaden, BC
   Storz, G
   Gottesman, S
TI Global analysis of small RNA and mRNA targets of Hfq
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID SM-LIKE PROTEIN; HOST FACTOR-I; PHAGE Q-BETA; ESCHERICHIA-COLI;
   SALMONELLA-TYPHIMURIUM; COMPARATIVE GENOMICS; RPOS TRANSLATION;
   NONCODING RNAS; ENCODING GENES; ANTISENSE RNA
AB Hfq, a bacterial member of the Sm family of RNA-binding proteins, is required for the action of many small regulatory RNAs that act by basepairing with target mRNAs. Hfq binds this family of small RNAs efficiently. We have used co-immunoprecipitation with Hfq and direct detection of the bound RNAs on genomic microarrays to identify members of this small RNA family. This approach was extremely sensitive; even Hfq-binding small RNAs expressed at low levels were readily detected. At least 15 of 46 known small RNAs in E. coli interact with Hfq. In addition, high signals in other intergenic regions suggested up to 20 previously unidentified small RNAs bind Hfq; five were confirmed by Northern analysis. Strong signals within genes and operons also were detected, some of which correspond to known Hfq targets. Within the argX-hisR-leuT-proM operon, Hfq appears to compete with RNase E and modulate RNA processing and degradation. Thus Hfq immunoprecipitation followed by microarray analysis is a highly effective method for detecting a major class of small RNAs as well as identifying new Hfq functions.
C1 Natl Inst Child Hlth & Dev, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
   Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA.
   Affymetrix, Santa Clara, CA 95051 USA.
   Univ Washington, Dept Comp Sci, Seattle, WA 98195 USA.
   NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Storz, G (reprint author), Natl Inst Child Hlth & Dev, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
OI Storz, Gisela/0000-0001-6698-1241
NR 46
TC 324
Z9 337
U1 4
U2 28
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 NOV
PY 2003
VL 50
IS 4
BP 1111
EP 1124
DI 10.1046/j.1365-2958.2003.03734.x
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 740YJ
UT WOS:000186430500006
PM 14622403
ER

PT J
AU Chakir, K
   Xiang, Y
   Yang, DM
   Zhang, SJ
   Cheng, HP
   Kobilka, BK
   Xiao, RP
AF Chakir, K
   Xiang, Y
   Yang, DM
   Zhang, SJ
   Cheng, HP
   Kobilka, BK
   Xiao, RP
TI The third intracellular loop and the carboxyl terminus of
   beta(2)-adrenergic receptor confer spontaneous activity of the receptor
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID BETA-ADRENERGIC-RECEPTOR; HUMAN BETA(1)-ADRENERGIC RECEPTOR; HUMAN
   BETA-2-ADRENERGIC RECEPTOR; LUTEINIZING-HORMONE RECEPTOR;
   SUBTYPE-SELECTIVE AGONISTS; DOPAMINE D1B RECEPTOR; HIGH-AFFINITY
   BINDING; TRANSGENIC MICE; CARDIAC MYOCYTES; CONSTITUTIVE ACTIVITY
AB It is well established that the beta(2)-adrenergic receptor (beta(2)-AR) exhibits a robust ligand-independent activity, whereas this property is considerably weaker in the closely related beta(1)-AR subtype. To identify the potential domain(s) of beta(2)-AR responsible for the spontaneous receptor activation, we created three chimeras in which the third intracellular loop (beta(1)/beta(2-Li3)) or the carboxyl terminus (beta(1)/beta(2-CT)) or both domains (beta(1)/beta(2-Li3CT)) of beta1-AR are replaced by the corresponding parts of the beta(2)-AR. Using adenoviral gene transfer, we individually expressed these beta(1)/beta(2)-AR chimeras in mouse cardiomyocytes lacking both native beta(1)-AR and beta(2)-AR (beta(1)/beta(2) double knockout), and examined their possible spontaneous activities. Overexpression of these beta(1)/beta(2)-AR chimeras markedly elevated basal cAMP accumulation and myocyte contractility in the absence of agonist stimulation compared with those infected by a control adenovirus expressing beta-galactosidase or an adenovirus expressing wild type beta(1)-AR. These effects were fully reversed by a beta(2)-AR inverse agonist, (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551; 5 x 10(-7) M), regardless of inhibition of G(i) with pertussis toxin, but not by a panel of beta(1)-AR antagonists, including [2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1-methyl-4-trifluormethyl-2-imidazolyl)-phenoxy]-2-propanolmethanesulfonate (CGP20712A), betaxolol, biso-prolol, and metoprolol. Furthermore, we have shown that the C-terminal postsynaptic density 95/disc-large/ZO-1 (PDZ) motif of beta(1)-AR is not responsible for the lack of beta(1)-AR spontaneous activation, although it has been known that the beta(1)-AR PDZ motif prevents the receptor from undergoing agonist-induced trafficking and G(i) coupling in cardiomyocytes. Taken together, the present results indicate that both the third intracellular loop and the C terminus are involved in beta(2)-AR spontaneous activation and that either domain seems to be sufficient to confer the receptor spontaneous activity.
C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
   Stanford Univ, Med Ctr, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
RP Xiao, RP (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
NR 68
TC 15
Z9 17
U1 0
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD NOV
PY 2003
VL 64
IS 5
BP 1048
EP 1058
DI 10.1124/mol.64.5.1048
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 734UL
UT WOS:000186076300006
PM 14573753
ER

PT J
AU Kobayashi, K
   Sueyoshi, T
   Inoue, K
   Moore, R
   Negishi, M
AF Kobayashi, K
   Sueyoshi, T
   Inoue, K
   Moore, R
   Negishi, M
TI Cytoplasmic accumulation of the nuclear receptor CAR by a
   tetratricopeptide repeat protein in HepG2 cells
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID ARYL-HYDROCARBON RECEPTOR; HEAT-SHOCK-PROTEIN; GLUCOCORTICOID-RECEPTOR;
   PROGESTERONE-RECEPTOR; ENHANCER MODULE; DIOXIN RECEPTOR; AH RECEPTOR;
   MOUSE-LIVER; CYP2B GENE; 1ST STEP
AB The nuclear constitutive active receptor (CAR) is a key transcription factor regulating phenobarbital (PB)-inducible transcription of various hepatic genes that encode xenobiotic/steroid-metabolizing enzymes. CAR is retained in the cytoplasm of noninduced livers and translocates into the nucleus after PB induction (Mol Cell Biol 19:6318-6322, 1999). HepG2 cells lack the capability of retaining CAR in the cytoplasm; thus, the receptor spontaneously accumulates in the nucleus. We have now cloned and characterized a tetratricopeptide repeat (TPR) protein, designated cytoplasmic CAR retention protein (CCRP), for its ability to accumulate the receptor in the cytoplasm of cotransfected HepG2 cells. CCRP directly interacts with the ligand-binding domain of CAR and mediates the formation of a cytoplasmic CAR-CCRP-90-kDa heat shock protein (hsp90) ternary complex. Simultaneous expression of fluorescent protein-tagged CAR and CCRP reveals their colocalization with tubulin in mouse liver in vivo. Thus, these results indicate that CCRP may be a component of the CAR-hsp90 complex and involved in retaining the receptor in the cytoplasm of both HepG2 cells and probably in vivo liver cells.
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, Res Triangle Pk, NC 27709 USA.
NR 34
TC 129
Z9 140
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD NOV
PY 2003
VL 64
IS 5
BP 1069
EP 1075
DI 10.1124/mol.64.5.1069
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 734UL
UT WOS:000186076300008
PM 14573755
ER

PT J
AU Maraganore, DM
   Farrer, MJ
   Lesnick, TG
   de Andrade, M
   Bower, JH
   Hernandez, D
   Hardy, JA
   Rocca, WA
AF Maraganore, DM
   Farrer, MJ
   Lesnick, TG
   de Andrade, M
   Bower, JH
   Hernandez, D
   Hardy, JA
   Rocca, WA
TI Case-control study of the alpha-synuclein interacting protein gene and
   Parkinson's disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; synphilin-1; alphasynuclein; parkin; susceptibility
   genes; association; interactions
ID SYNPHILIN-1 GENE; ASSOCIATION; SUSCEPTIBILITY; POLYMORPHISMS; MUTATIONS;
   HAPLOTYPES; SCREEN
AB We conducted a case-control study of the alpha-synuclein-interacting protein gene (SNCAIP, also known as synphilin-1) and Parkinson's disease (PD). A total of 319 PD cases and 195 controls were genotyped for four SNCAIP variants, including a microsatellite repeat in intron 4 and three restriction fragment length polymorphisms (RFLP) proximal to the 5' terminal of exons 1, 4, and 6. None of the variants were found associated with PD, overall. Global score statistics were not significant for four, three, and two loci haplotypes. All four loci were in linkage disequilibrium for cases, controls, or both groups combined (P < 0.0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene. (C) 2003 Movement Disorder Society.
C1 Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA.
   Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA.
   Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
   NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Maraganore, DM (reprint author), Mayo Clin & Mayo Fdn, Dept Neurol, 200 1st St SW, Rochester, MN 55905 USA.
RI Hardy, John/C-2451-2009
FU NIEHS NIH HHS [ES10751]; NINDS NIH HHS [NS33978]
NR 36
TC 13
Z9 14
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD NOV
PY 2003
VL 18
IS 11
BP 1233
EP 1239
DI 10.1002/mds.10547
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 746FY
UT WOS:000186737400003
PM 14639662
ER

PT J
AU Zeuner, KE
   Molloy, FM
   Shoge, RO
   Goldstein, SR
   Wesley, R
   Hallett, M
AF Zeuner, KE
   Molloy, FM
   Shoge, RO
   Goldstein, SR
   Wesley, R
   Hallett, M
TI Effect of ethanol on the central oscillator in essential tremor
SO MOVEMENT DISORDERS
LA English
DT Article
DE ethanol in essential tremor; accelerometry; mechanical (reflex)
   component; central oscillator
ID ALCOHOL; FREQUENCY; TIME
AB We investigated the effects of ethanol and diazepam on the central, mechanical, and mechanical reflex components of tremor in patients with essential tremor (ET). A double-blind crossover study (ethanol or diazepam) was conducted on 2 separate days. Dose of ethanol or diazepam was calculated in each individual according to height, weight, and age in 10 patients with ET. The postural tremor amplitude at the wrist was recorded using a three-dimensional accelerometer placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface electrodes placed on the forearm extensors and flexors. To separate central and mechanical (reflex) components, a 500-g weight was placed on the dorsum of the hand during a second tremor measurement. Tremor recordings were done at baseline and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude of the central component 60 minutes after ingestion of ethanol was decreased significantly (P = 0.029) compared with diazepam. Our findings suggest that the improvement in tremor after ethanol ingestion was due, at least in part, to an effect on a central oscillator.
C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
   NIH, Biostat Serv, Ctr Clin, Bethesda, MD USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA.
NR 25
TC 19
Z9 20
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD NOV
PY 2003
VL 18
IS 11
BP 1280
EP 1285
DI 10.1002/mds.10553
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 746FY
UT WOS:000186737400009
PM 14639668
ER

PT J
AU Au, WW
   Ribeiro, LR
   Waters, MD
AF Au, WW
   Ribeiro, LR
   Waters, MD
TI The Fourth International Conference on Environmental Mutagens in Human
   Populations
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Editorial Material
C1 Univ Texas, Dept Prevent Med & Community Hlth, Med Branch, Galveston, TX 77555 USA.
   Univ Estadual Paulista, Fac Med, Program Post Grad Pathol, Botucatu, SP, Brazil.
   Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
RP Au, WW (reprint author), Univ Texas, Dept Prevent Med & Community Hlth, Med Branch, Galveston, TX 77555 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 1383-5742
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD NOV
PY 2003
VL 544
IS 2-3
BP 89
EP 91
DI 10.1016/j.mrrev.2003.09.004
PG 3
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 754VR
UT WOS:000187353400002
ER

PT J
AU Suk, WA
   Murray, K
   Avakian, MD
AF Suk, WA
   Murray, K
   Avakian, MD
TI Environmental hazards to children's health in the modem world
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Article; Proceedings Paper
CT 4th International Conference on Environmental Mutagens in Human
   Populations (ICEMHP)
CY MAY 04-08, 2003
CL FLORIANOPOLIS, BRAZIL
DE children; environmental health; disease; exposure; chemical; genetic
ID PREVENTION; THREATS; DISEASE
AB Patterns of illness in children have changed dramatically in the last century, and will continue to change in this century. The major diseases confronting children are now chronic and disabling conditions termed the "new pediatric morbidity"-asthma, leukemia and brain cancer, neurodevelopmental dysfunction and neurobehavioral abnormality, reproductive and systemic developmental problems. Chemical toxicants in the environment, poverty, and little or no access to health care are all factors contributing to life-threatening pediatric diseases; children are uniquely vulnerable to chemical toxicants because of their disproportionately heavy exposures and their inherent biological growth and development. Genetic susceptibility and environmental exposures during vulnerable periods of development are also important contributors to the etiologies of many diseases of childhood.
   It is vital that we develop a better understanding of the mechanisms and interactions between nutrition, infectious disease, environmental exposures, and genetic predisposition in order to develop better prevention methods. This paper briefly examines modem contributors to children's environmental health problems, efforts to date on both the regional and international level to address these challenges, and reflects upon major research needs that must be addressed in order to close the gaps that exist in our understanding of the relationship between environmental exposures and children's health. (C) 2003 Published by Elsevier B.V.
C1 NIEHS, Ctr Risk & Integrated Sci, Res Triangle Pk, NC 27709 USA.
RP Suk, WA (reprint author), NIEHS, Ctr Risk & Integrated Sci, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 24
TC 42
Z9 44
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5742
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD NOV
PY 2003
VL 544
IS 2-3
BP 235
EP 242
DI 10.1016/j.mrrev.2003.06.007
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 754VR
UT WOS:000187353400017
PM 14644325
ER

PT J
AU Waters, MD
   Selkirk, JK
   Olden, K
AF Waters, MD
   Selkirk, JK
   Olden, K
TI The impact of new technologies on human population studies
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Article; Proceedings Paper
CT 4th International Conference on Environmental Mutagens in Human
   Populations (ICEMHP)
CY MAY 04-08, 2003
CL FLORIANOPOLIS, BRAZIL
DE toxicogenomics; microarray; gene expression; proteomics; metabononics;
   bioinformatics; phenotypic anchoring; phenotype; molecular expression;
   systems biology; systems toxicology; database; knowledge base;
   compendia; ontologies; global query; sequence; transcription factors;
   single nucleotide polymorphisms
ID 2-DIMENSIONAL GEL DATABASE; LIVER PROTEINS USEFUL; GENE-EXPRESSION;
   SERIAL ANALYSIS; RISK-ASSESSMENT; OLIGONUCLEOTIDE MICROARRAYS;
   ENVIRONMENTAL EXPOSURES; DRUG DISCOVERY; SAGE LIBRARIES; DNA MICROARRAY
AB Human population studies involve clinical or epidemiological observations that associate environmental exposures with health endpoints and disease. Clearly, these are the most sought after data to support assessments of human health risk from environmental exposures. However, the foundations of many health risk assessments rest on experimental studies in rodents performed at high doses that elicit adverse outcomes, such as organ toxicity or tumors. Using the results of human studies and animal data, risk assessors define the levels of environmental exposures that may lead to disease in a portion of the population. These decisions on potential health risks are frequently based on the use of default assumptions that reflect limitations in our scientific knowledge. An important immediate goal of toxicogenomics, including proteomics and metabonomics, is to offer the possibility of making decisions affecting public health and public based on detailed toxicity, mechanistic, and exposure data in which many of the uncertainties have been eliminated. Ultimately, these global technologies will dramatically impact the practice of public health and risk assessment as applied to environmental health protection. The impact is already being felt in the practice of toxicology where animal experimentation using highly controlled dose-time parameters is possible. It is also being seen in human population studies where understanding human genetic variation and genomic reactions to specific environmental exposures is enhancing our ability to uncover the causes of variations in human response to environmental exposures. These new disciplines hold the promise of reducing the costs and time lines associated with animal and human studies designed to assess both the toxicity of environmental pollutants and efficacy of therapeutic drugs. However, as with any new science, experience must be gained before the promise can be fulfilled. Given the numbers and diversity of drugs, chemicals and environmental agents; the various species in which they are studied and the time and dose factors that are critical to the induction of beneficial and adverse effects, it is only through the development of a profound knowledge base that toxicology and environmental health can rapidly advance. The National Institute of Environmental Health Sciences (NIEHS), National Center for Toxicogenomics and its university-based Toxicogenomics Research Consortium (TRC), and resource contracts, are engaged in the development, application and standardization of the science upon which to the build such a knowledge base on Chemical Effects in Biological Systems (CEBS). In addition, the NIEHS Environmental Genome Project (EGP) is working to systematically identify and characterize common sequence polymorphisms in many genes with suspected roles in determining chemical sensitivity. The rationale of the EGP is that certain genes have a greater than average influence over human susceptibility to environmental agents. If we identify and characterize the polymorphism in those genes, we will increase our understanding of human disease susceptibility. This knowledge can be used to protect susceptible individuals from disease and to reduce adverse exposure and environmentally induced disease. (C) 2003 Published by Elsevier B.V.
C1 Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA.
   NIEHS, Res Triangle Pk, NC 27709 USA.
RP Waters, MD (reprint author), Natl Ctr Toxicogenom, 3 Alexander Dr,POB 12233,MD F1-05, Res Triangle Pk, NC 27709 USA.
NR 111
TC 15
Z9 16
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5742
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD NOV
PY 2003
VL 544
IS 2-3
BP 349
EP 360
DI 10.1016/jmrrev.2003.06.022
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 754VR
UT WOS:000187353400029
PM 14644337
ER

PT J
AU Waters, MD
   Olden, K
   Tennant, RW
AF Waters, MD
   Olden, K
   Tennant, RW
TI Toxicogenomic approach for assessing toxicant-related disease
SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
LA English
DT Article; Proceedings Paper
CT 4th International Conference on Environmental Mutagens in Human
   Populations (ICEMHP)
CY MAY 04-08, 2003
CL FLORIANOPOLIS, BRAZIL
DE toxicogenomics; microarray; gene expression; proteomics; metabonomics;
   bioinformatics; phenotypic anchoring; phenotype; molecular expression;
   systems biology; systems toxicology; database knowledge base; compendia;
   ontologies; global query; sequence; single nucleotide polymorphisms
ID GENE-EXPRESSION PATTERNS; MICROARRAY DATA; MOUSE-LIVER; TOXICITY;
   CHALLENGES; GENOME; ARRAYS; METABONOMICS; TOXICOLOGY; DISCOVERY
AB The problems of identifying environmental factors involved in the etiology of human disease and performing safety and risk assessments of drugs and chemicals have long been formidable issues. Three principal components for predicting potential human health risks are: (1) the diverse structure and properties of thousands of chemicals and other stressors in the environment; (2) the time and dose parameters that define the relationship between exposure and disease; and (3) the genetic diversity of organisms used as surrogates to determine adverse chemical effects. The global techniques evolving from successful genomics efforts are providing new exciting tools with which to address these intractable problems of environmental health and toxicology. In order to exploit the scientific opportunities, the National Institute of Environmental Health Sciences has created the National Center for Toxicogenomics (NCT). The primary mission of the NCT is to use gene expression technology, proteomics and metabolite profiling to create a reference knowledge base that will allow scientists to understand mechanisms of toxicity and to be able to predict the potential toxicity of new chemical entities and drugs. A principal scientific objective underpinning the use of microarray analysis of chemical exposures is to demonstrate the utility of signature profiling of the action of drugs or chemicals and to utilize microarray methodologies to determine biomarkers of exposure and potential adverse effects. The initial approach of the NCT is to utilize proof-of-principle experiments in an effort to "phenotypically anchor" the altered patterns of gene expression to conventional parameters of toxicity and to define dose and time relationships in which the expression of such signature genes may precede the development of overt toxicity. The microarray approach is used in conjunction with proteomic techniques to identify specific proteins that may serve as signature biomarkers. The longer-range goal of these efforts is to develop a reference relational database of chemical effects in biological systems (CEBS) that can be used to define common mechanisms of toxicity, chemical and drug actions, to define cellular pathways of response, injury and, ultimately, disease. In order to implement this strategy, the NCT has created a consortium of research organizations and private sector companies to actively collaborative in populating the database with high quality primary data. The evolution of discrete databases to a knowledge base of toxicogenomics will be accomplished through establishing relational interfaces with other sources of information on the structure and activity of chemicals such as that of the National Toxicology Program (NTP) and with databases annotating gene identity, sequence, and function. (C) 2003 Published by Elsevier B.V.
C1 NIEHS, Natl Ctr Toxigenom, Res Triangle Pk, NC 27709 USA.
RP Waters, MD (reprint author), NIEHS, Natl Ctr Toxigenom, POB 12233,MD F1-05,3 Alexander Dr, Res Triangle Pk, NC 27709 USA.
NR 41
TC 64
Z9 69
U1 2
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5742
J9 MUTAT RES-REV MUTAT
JI Mutat. Res.-Rev. Mutat. Res.
PD NOV
PY 2003
VL 544
IS 2-3
BP 415
EP 424
DI 10.1016/j.mrrev.2003.06.014
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 754VR
UT WOS:000187353400036
PM 14644344
ER

PT J
AU Del Val, M
   Yewdell, JW
AF Del Val, M
   Yewdell, JW
TI The latest killer AP
SO NATURE IMMUNOLOGY
LA English
DT Editorial Material
ID MHC CLASS-II; TRANSPORT; TRAFFICKING; LYSOSOMES; DEFICIENT; PERFORIN;
   MEMBRANE; CELLS
AB Patients with type 2 Hermansky-Pudlak syndrome are immunodeficient. Mutations in AP-3 that prevent movement of lytic granules along microtubules in CD8(+) T cells help explain these patients' susceptibility to infection.
C1 Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Immunol Viral, Madrid, Spain.
   NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Del Val, M (reprint author), Inst Salud Carlos III, Ctr Nacl Microbiol, Unidad Immunol Viral, Madrid, Spain.
RI Del Val, Margarita/E-4769-2010; yewdell, jyewdell@nih.gov/A-1702-2012
OI Del Val, Margarita/0000-0001-6769-4279; 
NR 12
TC 0
Z9 0
U1 0
U2 1
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 NOV
PY 2003
VL 4
IS 11
BP 1049
EP 1050
DI 10.1038/ni1103-1049
PG 2
WC Immunology
SC Immunology
GA 737PN
UT WOS:000186241100006
PM 14586420
ER

PT J
AU Rubio, V
   Stuge, TB
   Singh, N
   Betts, MR
   Weber, JS
   Roederer, M
   Lee, PP
AF Rubio, V
   Stuge, TB
   Singh, N
   Betts, MR
   Weber, JS
   Roederer, M
   Lee, PP
TI Ex vivo identification, isolation and analysis of tumor-cytolytic T
   cells
SO NATURE MEDICINE
LA English
DT Article
ID FUNCTIONAL AVIDITY; MULTIPEPTIDE VACCINE; METASTATIC MELANOMA; CYTOKINE
   PRODUCTION; TCR; LYMPHOCYTES; TETRAMERS; ESCAPE; CTL; SELECTION
AB We isolated pure, viable populations of tumor-cytolytic T cells directly from patient blood samples using flow cytometric quantification of the surface mobilization of CD107a-an integral membrane protein in cytolytic granules-as a marker for degranulation after tumor stimulation. We show that tumor-cytolytic T cells are indeed elicited in patients after cancer vaccination, and that tumor reactivity is strongly correlated with efficient T-cell recognition of peptide-bearing targets. We combined CD107a mobilization with peptide-major histocompatibility complex (P-MHC) tetramer staining to directly correlate antigen specificity and cytolytic ability on a single-cell level. This showed that tumor-cytolytic T cells with high recognition efficiency represent only a minority of peptide-specific T cells elicited in patients after heteroclitic peptide vaccination. We were also able to expand these cells to high numbers ex vivo while maintaining their cytolytic potential. These techniques will be useful not only for immune monitoring of cancer vaccine trials, but also for adoptive cellular immunotherapy after ex vivo expansion. The ability to rapidly identify and isolate tumor-cytolytic T cells would be very useful in cancer immunotherapy.
C1 Stanford Univ, Dept Med, Stanford, CA 94305 USA.
   NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   Univ So Calif, Norris Canc Ctr, Los Angeles, CA 90033 USA.
   NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Lee, PP (reprint author), Stanford Univ, Dept Med, 269 Campus Dr, Stanford, CA 94305 USA.
RI Roederer, Mario/G-1887-2011; 
OI Stuge, Tor B/0000-0002-6933-8419
FU NCI NIH HHS [R01CA 090809]
NR 26
TC 283
Z9 288
U1 1
U2 10
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 NOV
PY 2003
VL 9
IS 11
BP 1377
EP 1382
DI 10.1038/nm942
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 739AH
UT WOS:000186319700027
PM 14528297
ER

PT J
AU Liegeois, F
   Baldeweg, T
   Connelly, A
   Gadian, DG
   Mishkin, M
   Vargha-Khadem, F
AF Liegeois, F
   Baldeweg, T
   Connelly, A
   Gadian, DG
   Mishkin, M
   Vargha-Khadem, F
TI Language fMRI abnormalities associated with FOXP2 gene mutation
SO NATURE NEUROSCIENCE
LA English
DT Article
ID INHERITED SPEECH; BRAIN ABNORMALITIES; COGNITIVE DEFICITS; PREFRONTAL
   CORTEX; WORD GENERATION; FRONTAL LESIONS; VERB GENERATION; BASAL
   GANGLIA; MRI-ANALYSIS; DISORDER
AB Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.
C1 UCL, Inst Child Hlth, Dev Cognit Neurosci Unit, Wolfson Ctr, London WC1N 2AP, England.
   Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
   UCL, Inst Child Hlth, Radiol & Phys Unit, London WC1N 1EH, England.
   NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Liegeois, F (reprint author), UCL, Inst Child Hlth, Dev Cognit Neurosci Unit, Wolfson Ctr, Mecklenburgh Sq, London WC1N 2AP, England.
EM F.Liegeois@ich.ucl.ac.uk
RI Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008; Liegeois,
   Frederique/A-6351-2009; Connelly, Alan/A-9065-2013
NR 34
TC 175
Z9 180
U1 1
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD NOV
PY 2003
VL 6
IS 11
BP 1230
EP 1237
DI 10.1038/nn1138
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 737KH
UT WOS:000186229200024
PM 14555953
ER

PT J
AU Koonin, EV
AF Koonin, EV
TI Comparative genomics, minimal gene-sets and the last universal common
   ancestor
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID PHYLOGENETIC CLASSIFICATION; HAEMOPHILUS-INFLUENZAE; BACILLUS-SUBTILIS;
   LIFE; EVOLUTION; TREE; PROTEINS; IDENTIFICATION; DISPLACEMENT; SEQUENCE
AB Comparative genomics, using computational and experimental methods, enables the identification of a minimal set of genes that is necessary and sufficient for sustaining a functional cell. For most essential cellular functions, two or more unrelated or distantly related proteins have evolved; only about 60 proteins, primarily those involved in translation, are common to all cellular life. The reconstruction of ancestral life-forms is based on the principle of evolutionary parsimony, but the size and composition of the reconstructed ancestral gene-repertoires depend on relative rates of gene loss and horizontal gene-transfer. The present estimate suggests a simple last universal common ancestor with only 500-600 genes.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
NR 71
TC 264
Z9 283
U1 7
U2 59
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD NOV
PY 2003
VL 1
IS 2
BP 127
EP 136
DI 10.1038/nrmicro751
PG 10
WC Microbiology
SC Microbiology
GA 805YV
UT WOS:000220402500014
PM 15035042
ER

PT J
AU Dufour, EM
   Nandrot, E
   Marchant, D
   Van Den Berghe, L
   Gadin, S
   Issilame, M
   Dufier, JL
   Marsac, U
   Carper, D
   Menasche, M
   Abitbol, M
AF Dufour, EM
   Nandrot, E
   Marchant, D
   Van Den Berghe, L
   Gadin, S
   Issilame, M
   Dufier, JL
   Marsac, U
   Carper, D
   Menasche, M
   Abitbol, M
TI Identification of novel genes and altered signaling pathways in the
   retinal pigment epithelium during the Royal College of Surgeons rat
   retinal degeneration
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE RCS rat; phagocytosis; differential display; microarray; retinal pigment
   epithelium; gene expression
ID SCAFFOLD PROTEIN; PHAGOCYTOSIS; DYSTROPHY; MACROPHAGES; PHAGOSOMES;
   MECHANISMS; CAVEOLAE; RECEPTOR; LOCALIZATION; NEUTROPHILS
AB Shed photoreceptor outer segments (POS) are phagocytosed by RPE cells in a circadian manner. The homozygous deletion of the c-mer gene abolishes the ingestion phase of this phagocytosis in the Royal College of Surgeons (RCS) rat strain, which in turn leads to the death of photoreceptor cells. We identified RPE transcripts for which the expression is modulated by the abrogation of POS phagocytosis. A microarray approach and the differential display (DDRT-PCR) technique revealed 116 modulated known genes, 4 modulated unknown genes, and 15 expressed sequenced tags (ESTs) corresponding to unknown genes. The microarray and DDRT-PCR analyses detected alterations in signaling pathways such as the phosphatidylinositol 3-kinase-Akt-mTOR pathway and the DLK/JNK/SAPK pathway. The abrogation of POS phagocytosis caused a decrease in endomembrane biogenesis and altered endocytosis, exocytosis, transcytosis, and several metabolic and signaling pathways in RCS RPE cells. We also found differential levels of transcripts encoding proteins involved in phagocytosis, vesicle trafficking, the cytoskeleton, retinoic acid, and general metabolism. (C) 2003 Elsevier Inc. All rights reserved.
C1 Univ Paris 05, Fac Med Necker, CERTO,Minist Rech, Equipe 2502, F-75015 Paris, France.
   NEI, Sect Mol Therapeut, NIH, Bethesda, MD 20892 USA.
RP Abitbol, M (reprint author), Univ Paris 05, Fac Med Necker, CERTO,Minist Rech, Equipe 2502, 156 Rue Vaugirard, F-75015 Paris, France.
NR 43
TC 13
Z9 13
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 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD NOV
PY 2003
VL 14
IS 2
BP 166
EP 180
DI 10.1016/S0969-9961(03)00102-5
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 735HM
UT WOS:000186107200002
PM 14572440
ER

PT J
AU Mattson, MP
AF Mattson, MP
TI Adventures in neural plasticity, aging, and neurodegenerative disorders
   aboard the CWC beagle
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Alzheimer's disease; apoptosis; glutamate; neurotrophic factor; synaptic
   plasticity
ID AMYLOID BETA-PEPTIDE; FIBROBLAST GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM;
   PROTECTS HIPPOCAMPAL-NEURONS; RECEPTOR SUBUNIT GLUR1; HUMAN
   CORTICAL-NEURONS; DIETARY RESTRICTION; NEUROTROPHIC FACTOR;
   LIPID-PEROXIDATION; MITOCHONDRIAL DYSFUNCTION
AB This article recounts some of the scientific endeavors of Carl W. Cotman (CWC) during his journeys through the cellular circuitry of the mammalian brain. I have selected for consideration his findings that have been an important impetus for my own research; in several cases our different experiments have provided complementary data to support an hypothesis. Three examples are (i) Carl's studies of the roles of glutamate in synaptic transmission and plasticity in the adult brain and my studies of how glutamate regulates neurite outgrowth and cell survival in brain development; (ii) his and our studies of the mechanisms whereby amyloid beta-peptide damages and kills neurons; and (iii) Carl's evidence that physical activity regulates neurotrophin levels in the brain and our evidence that dietary restriction has similar effects and is neuroprotective. In case you have not yet realized how I chose a title for this article it is because Carl has a (very distant) connection with Charles Darwin-Darwin sailed on a vessel called the Beagle and Carl has studied beagle dogs, establishing them as a model for understanding the neurobiology of human brain aging.
C1 NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Gerontol Res Ctr, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
RI Mattson, Mark/F-6038-2012
NR 68
TC 4
Z9 4
U1 0
U2 0
PU KLUWER ACADEMIC/PLENUM PUBL
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD NOV
PY 2003
VL 28
IS 11
BP 1631
EP 1637
DI 10.1023/A:1026000703290
PG 7
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 730JK
UT WOS:000185827500006
PM 14584817
ER

PT J
AU Ernst, M
   Kimes, AS
   Jazbec, S
AF Ernst, M
   Kimes, AS
   Jazbec, S
TI Neuroimaging and mechanisms of drug abuse: interface of molecular
   imaging and molecular genetics
SO NEUROIMAGING CLINICS OF NORTH AMERICA
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; NICOTINIC ACETYLCHOLINE-RECEPTORS; INDUCED
   DOPAMINE RELEASE; IN-VIVO; HUMAN-BRAIN; SUBSTANCE-ABUSE; LONG-TERM;
   TRANSCRIPTIONAL REGULATION; BENZODIAZEPINE RECEPTORS; METHAMPHETAMINE
   ABUSERS
AB Substance abuse disorders are a huge burden at the individual and societal levels. Today, nuclear medical imaging techniques, positron emission tomography (PET) and single-photon emission computed tomography (SPECT), offer the most promising tools to help unravel the cellular and molecular mechanisms of addiction. These promises can be fulfilled only through an intimate integration of molecular biology and molecular imaging. Although not yet actualized for the purpose of human studies of complex disorders, the basic elements of this integration is in place. This article addresses the latest achievements of classic molecular imaging (ligand studies) and walks through the premises and the description of the still futuristic application of PET and SPECT to imaging gene expression. This latter approach promises to advance our understanding of the pathophysiology of addiction, one of the most baffling clinical disorders.
C1 NIMH, Dept Hlth & Human Serv, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
   NIDA, Neuroimaging Branch, Intramural Res Program, Brain Imaging Sect, Baltimore, MD 21224 USA.
RP Ernst, M (reprint author), NIMH, Dept Hlth & Human Serv, Mood & Anxiety Disorders Program, NIH, 15K N Dr,Room 118,MSC 2670, Bethesda, MD 20892 USA.
NR 114
TC 3
Z9 3
U1 2
U2 9
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 1052-5149
J9 NEUROIMAG CLIN N AM
JI Neuroimaging Clin. N. Am.
PD NOV
PY 2003
VL 13
IS 4
BP 833
EP +
DI 10.1016/S1052-5149(03)00109-6
PG 18
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 745FE
UT WOS:000186678000016
PM 15024965
ER

PT J
AU Lavezzari, G
   McCallum, J
   Lee, R
   Roche, KW
AF Lavezzari, G
   McCallum, J
   Lee, R
   Roche, KW
TI Differential binding of the AP-2 adaptor complex and PSD-95 to the
   C-terminus of the NMDA receptor subunit NR2B regulates surface
   expression
SO NEUROPHARMACOLOGY
LA English
DT Article
ID ER RETENTION SIGNAL; IONOTROPIC GLUTAMATE RECEPTORS; KV1.4 POTASSIUM
   CHANNEL; DENSITY PROTEIN PSD-95; DEVELOPMENTAL-CHANGES; SYNAPTIC
   PLASTICITY; GUANYLATE KINASES; SORTING SIGNALS; AMPA RECEPTORS;
   CELL-SURFACE
AB NMDA receptor expression on the plasma membrane and at synaptic sites is tightly regulated. We have recently shown that the NMDA receptor subunit NR2B has an endocytic motif contained within its C-terminus. We now identify this motif as a consensus tyrosine-based motif (YEKL) and demonstrate that this sequence binds directly to the medium chain of the AP-2 adaptor, a protein complex that links internalized proteins to clathrin. Although the AP-2 binding site on NR2B is adjacent to the PSD-95 binding site, it is distinct, as mutation of tyrosine 1472 of the endocytic motif disrupts AP-2 binding but not binding to PSD-95. Internalization assays reveal that like PSD-95, both SAP97 and PSD-93 inhibit NR2B-mediated endocytosis. Furthermore, we find that coexpression of a PSD-95 mutant that is unable to cluster NMDA receptors also inhibits NR2B-mediated endocytosis. Together, these data demonstrate that AP-2 and PSD-95 bind to unique sites on the C-terminus of NR2B and have antagonistic functional consequences that are independent of the ability of the PSD-95 to cluster receptors on the plasma membrane. Published by Elsevier Ltd.
C1 NINDS, NIH, Bethesda, MD 20892 USA.
RP Roche, KW (reprint author), NINDS, NIH, Bldg 36,Room 5B20,9000 Rockville Pike, Bethesda, MD 20892 USA.
OI Roche, Katherine/0000-0001-7282-6539
NR 42
TC 108
Z9 113
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD NOV
PY 2003
VL 45
IS 6
BP 729
EP 737
DI 10.1016/S0028-3908(03)00308-3
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 738PR
UT WOS:000186297500004
PM 14529712
ER

PT J
AU Krystal, JH
   Petrakis, IL
   Limoncelli, D
   Webb, E
   Gueorgueva, R
   D'Souza, DC
   Boutros, NN
   Trevisan, L
   Charney, DS
AF Krystal, JH
   Petrakis, IL
   Limoncelli, D
   Webb, E
   Gueorgueva, R
   D'Souza, DC
   Boutros, NN
   Trevisan, L
   Charney, DS
TI Altered NMDA glutamate receptor antagonist response in recovering
   ethanol-dependent patients
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE ethanol; ethanol dependence; tolerance; reward; alcoholism; glutamate;
   N-methyl-D-aspartate (NMDA); executive cognitive function; psychosis
ID SUBUNIT GENE-EXPRESSION; MOUSE CORTICAL-NEURONS; UP-REGULATION;
   SUSTAINED ATTENTION; HEALTHY-VOLUNTEERS; IONOPHORE COMPLEX; KETAMINE;
   WITHDRAWAL; NEUROTRANSMISSION; ALCOHOLISM
AB Ethanol is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. Ethanol dependence upregulates NMDA receptors and contributes to crosstolerance with selective NMDA receptor antagonists in animals. This study evaluated whether recovering ethanol-dependent patients show evidence of a reduced level of response to the effects of the NMDA receptor antagonist, ketamine. In this double-blind study, 34 recently detoxified alcohol-dependent patients and 26 healthy comparison subjects completed 3 test days involving a 40-min infusion of saline, ketamine 0.1 mg/kg, or ketamine 0.5 mg/kg in a randomized order. Recovering ethanol-dependent patients showed reduced perceptual alterations, dysphoric mood, and impairments in executive cognitive functions during ketamine infusion relative to the healthy comparison group. No attenuation of ketamine-induced amnestic effects, euphoria, or activation was observed. The alterations in NMDA receptor function observed in recovering ethanol-dependent patients may have important implications for ethanol tolerance, ethanol dependence, and the treatment of alcoholism.
C1 VA Connecticut Healthcare Syst, Dept Vet Affairs, Alcohol Res Ctr, Psychiat Serv 116A, West Haven, CT 06516 USA.
   Yale Univ, Sch Med, Dept Psychiat, NIAAA,Ctr Translat Neurosci Alcoholism, New Haven, CT USA.
   Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, Clin Neurosci Res Unit, New Haven, CT 06519 USA.
   NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA.
RP Krystal, JH (reprint author), VA Connecticut Healthcare Syst, Dept Vet Affairs, Alcohol Res Ctr, Psychiat Serv 116A, 950 Campbell Ave, West Haven, CT 06516 USA.
FU NIAAA NIH HHS [K02 AA00261-01, R01 AA12308-01, 1R01 AA10121-01, P50
   AA12870-01]
NR 53
TC 48
Z9 49
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2003
VL 28
IS 11
BP 2020
EP 2028
DI 10.1038/sj.npp.1300252
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 743AU
UT WOS:000186550900013
PM 12888778
ER

PT J
AU Handa, V
   Saha, T
   Usdin, K
AF Handa, V
   Saha, T
   Usdin, K
TI The fragile X syndrome repeats form RNA hairpins that do not activate
   the interferon-inducible protein kinase, PKR, but are cut by Dicer
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID TRIPLET REPEATS; CGG REPEATS; INSTABILITY; LENGTH; GENE
AB We show here that under physiologically reasonable conditions, CGG repeats in RNA readily form hairpins. In contrast to its DNA counterpart that forms a complex mixture of hairpins and tetraplexes, r(CGG)(22) forms a single stable hairpin with no evidence for any other folded structure even at low pH. RNA with the sequence (CGG)(9)AGG (CGG)(12)AGG(CGG)(97), found in a fragile X syndrome pre-mutation allele, forms a number of different hairpins. The most prominent hairpin forms in the 3' part of the repeat and involves the 97 uninterrupted CGG repeats. In contrast to the CUG-RNA hairpins formed by myotonic dystrophy type 1 repeats, we found no evidence that CGG-RNA hairpins activate PKR, the interferon-inducible protein kinase that is activated by a wide range of double-stranded RNAs. However, we do show that the CGG-RNA is digested, albeit inefficiently, by the human Dicer enzyme, a step central to the RNA interference effect on gene expression. These data provide clues to the basis of the toxic effect of CGG-RNA that is thought to occur in fragile X pre-mutation carriers. In addition, RNA hairpins may also account for the stalling of the 40S ribosomal subunit that is thought to contribute to the translation deficit in fragile X pre-mutation and full mutation alleles.
C1 NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Usdin, K (reprint author), NIDDKD, Sect Genom Struct & Funct, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 23
TC 75
Z9 80
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV 1
PY 2003
VL 31
IS 21
BP 6243
EP 6248
DI 10.1093/nar/gkg818
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 738XC
UT WOS:000186312300030
PM 14576312
ER

PT J
AU Field, AE
   Laird, N
   Steinberg, E
   Fallon, E
   Semega-Janneh, M
   Yanovski, JA
AF Field, AE
   Laird, N
   Steinberg, E
   Fallon, E
   Semega-Janneh, M
   Yanovski, JA
TI Which metric of relative weight best captures body fatness in children?
SO OBESITY RESEARCH
LA English
DT Article
DE BMI; body fat; BMI percentile; z scores of BMI; measurement
ID X-RAY ABSORPTIOMETRY; OPERATING CHARACTERISTIC CURVES; MASS INDEX;
   ADOLESCENTS; FAT; OBESITY; GIRLS; PERCENTAGE; ADIPOSITY; VALIDITY
AB Objective: To evaluate the relative merits of BMI (kilograms per meter squared) and age- and gender-adjusted BMI, age- and gender-specific z score of BMI, and age- and gender-specific percentiles of BMI as surrogate measures of body fatness among a sample of youth.
   Research Methods and Procedures: The sample comprised 596 children and adolescents 5 to 18.7 years old and was 40% male and 55% white. Height and weight were measured by trained research staff. DXA was used to determine body fat mass. BMI, age- and gender-specific percentile of BMI, and age- and gender-specific z scores of BMI were computed, and these metrics were compared with measured body fatness.
   Results: The BMI values in the sample ranged from 12.9 to 55.0 kg/m(2), with a mean of 24.9 kg/m(2). The Spearman correlations with percentage body fat were similar for all of the BMI metrics (r = 0.82 to 0.88). Linear regression models with age- and gender-specific percentiles of BMI explained significantly less of the variance (65%) than models with log-transformed BMI (81%) or age- and gender-specific z scores of BMI (75% to 79%). z scores were the most accurate at classifying children who were overfat (sensitivity = 0.84, specificity = 0.96 for z score greater than or equal to 1). However,using a BMI greater than or equal to85th percentile or a BMI 20 kg/m(2) was also accurate at classifying youth.
   Discussion: The BMI metrics had similar correlations with body fatness, but age- and gender-specific percentiles of BMI were the least accurate proxy measure of body fatness. However, a BMI z score greater than or equal to1, BMI percentile greater than or equal to85, and BMI greater than or equal to20 kg/m(2) are all useful for identifying children who may be overfat.
C1 Childrens Hosp, Div Adolescent Med, Dept Med, Boston, MA 02115 USA.
   Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   NICHHD, Dev Endocrinol Branch, Unit Growth & Obes, NIH, Bethesda, MD 20892 USA.
RP Field, AE (reprint author), Childrens Hosp, Div Adolescent Med, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA.
FU NICHD NIH HHS [HD 000641]; NIDDK NIH HHS [DK 42600]; PHS HHS [6T71 MC
   00009-1101]
NR 24
TC 62
Z9 63
U1 0
U2 8
PU NORTH AMER ASSOC STUDY OBESITY
PI SILVER SPRING
PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA
SN 1071-7323
J9 OBES RES
JI Obes. Res.
PD NOV
PY 2003
VL 11
IS 11
BP 1345
EP 1352
DI 10.1038/oby.2003.182
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 745ZL
UT WOS:000186721400010
PM 14627755
ER

PT J
AU Wan, XS
   Zhou, ZZ
   Kennedy, AR
   Kopelovich, L
AF Wan, XS
   Zhou, ZZ
   Kennedy, AR
   Kopelovich, L
TI In vitro evaluation of chemopreventive agents using cultured human
   prostate epithelial cells
SO ONCOLOGY REPORTS
LA English
DT Article
DE chemopreventive agents; prostate epithelial cells
ID CANCER PREVENTION; RETINOIC ACID; BREAST-CANCER; COLON-CANCER;
   SELENOMETHIONINE; CARCINOGENESIS; CARCINOMA; RATS; LUNG;
   1,4-PHENYLENEBIS(METHYLENE)SELENOCYANATE
AB The effects of nine potential cancer chemopreventive agents on cell growth or clonogenic survival were evaluated in normal human prostate epithelial cells, an immortalized but non-tumorigenic human prostate epithelial cell line (267131), a human benign prostatic hyperplasia (BPH) cell line (BRF-55T), and a human prostate cancer cell line (267B1/Ki-ras). Of the nine agents tested, 9-cis retinoic acid, liarozole fumarate, phenylenebis(methylene)-selenocyanate (p-XSC), and L-selenomethionine demonstrated much stronger growth inhibitory effects on prostate cancer cells than on the normal prostate epithelial cells, suggesting that these agents may be useful as prostate cancer chemopreventive agents. 9-cis retinoic acid. genistein, liarozole fumarate, p-XSC, L-selenomethionine and vitamin E also showed much stronger growth inhibitory effects on BRF-55T cells than on the normal prostate epithelial cells, indicating that these agents may also be useful for the prevention and treatment of BPH. Difluoromethylornithine (DFMO), DHEA analogue 8354 (fluasterone), and oltipraz did not show strong inhibitory effects on the growth or survival of normal prostate epithelial cells, 267B1 or 267B1/Ki-ras cells, suggesting that these agents may not be effective as prostate cancer preventive or therapeutic agents.
C1 Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
   NCI, Div Canc Prevent, Bethesda, MD 20892 USA.
RP Wan, XS (reprint author), Univ Penn, Sch Med, Dept Radiat Oncol, 195 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA.
FU NCI NIH HHS [N01-CN-95105]
NR 42
TC 5
Z9 6
U1 0
U2 1
PU PROFESSOR D A SPANDIDOS
PI ATHENS
PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD NOV-DEC
PY 2003
VL 10
IS 6
BP 2009
EP 2014
PG 6
WC Oncology
SC Oncology
GA 740AT
UT WOS:000186379200057
PM 14534735
ER

PT J
AU Hertle, RW
   Dell'Osso, LF
   FitzGibbon, EJ
   Thompson, D
   Yang, DS
   Mellow, SD
AF Hertle, RW
   Dell'Osso, LF
   FitzGibbon, EJ
   Thompson, D
   Yang, DS
   Mellow, SD
TI Horizontal rectus tenotomy in patients with congenital nystagmus -
   Results in 10 adults
SO OPHTHALMOLOGY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
   Association-for-Research-in-Vision-and-Ophthalmology
CY APR 29-MAY 04, 2001
CL FT LAUDERDALE, FLORIDA
SP Assoc Res Vis & Ophthalmol
ID VISUAL FUNCTION QUESTIONNAIRE; EYE-MOVEMENTS; IDIOPATHIC NYSTAGMUS;
   SURGERY; PROPRIOCEPTION; STIMULATION
AB Objective: We wished to determine the effectiveness of horizontal rectus tenotomy in changing the nystagmus of patients with congenital nystagmus and, secondarily, how their visual function changed.
   Design: This was a prospective, noncomparative, interventional case series.
   Participants: Ten adult patients with varied associated sensory defects and oculographic subtypes of congenital nystagmus (including asymmetric periodic or aperiodic alternating nystagmus) and no nystagmus treatment options.
   Methods: By using standard surgical techniques, simple tenotomy of all four horizontal recti with reattachment at the original insertion was accomplished. Search-coil eye movement recordings and clinical examinations were performed before and 1, 6, 24, and 52 weeks after surgery.
   Main Outcome Measures: The primary outcome measure was the expanded nystagmus acuity function, obtained in "masked" fashion directly from ocular motility recordings. Secondary outcomes included breadth of null zones, preoperative and postoperative masked measures of visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] chart), and the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25).
   Results: At 1 year after tenotomy and under binocular conditions, 9 of 10 patients had persistent, significant postoperative increases in the expanded nystagmus acuity function of their fixing (preferred) eye; 1 remained high, and 1 was not tested under the same conditions. Average foveation times increased in all 9 fixing (preferred) eyes. Binocular visual acuity measured with the ETDRS chart increased in 5 patients and was unaffected in five, whereas the NEI-VFQ-25 showed an improvement in vision-specific mental health in 9 patients. There were no adverse events. Tenotomy also radically changed the periodicity of one patient's asymmetric periodic or aperiodic alternating nystagmus. Conclusions: In 9 of 10 adult patients with clinical and oculographic variations in their congenital nystagmus, tenotomy resulted in significant improvements in a nystagmus measure and subjective visual functions. (C) 2003 by the American Academy of Ophthalmology.
C1 Ohio State Univ, Pediat Ophthalmol Associates Inc, Columbus Childrens Hosp, Columbus, OH 43205 USA.
   Ohio State Univ, Lab Visual Ocular Motor Physiol, Columbus Childrens Hosp, Columbus, OH 43205 USA.
   NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
   NEI, NIH, Bethesda, MD 20892 USA.
   Case Western Reserve Univ, Ocular Motor Neurophysiol Lab, Vet Adm Med Ctr, Cleveland, OH 44106 USA.
   Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA.
   Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA.
   EMMES Corp, Natl Eye Inst Sci Coordinating Ctr, Potomac, MD USA.
RP Hertle, RW (reprint author), Ohio State Univ, Pediat Ophthalmol Associates Inc, Columbus Childrens Hosp, 555 S 18th St,Suite 4C, Columbus, OH 43205 USA.
NR 46
TC 58
Z9 63
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2003
VL 110
IS 11
BP 2097
EP 2105
DI 10.1016/S0161-6420(03)00802-9
PG 9
WC Ophthalmology
SC Ophthalmology
GA 737VR
UT WOS:000186252900005
PM 14597515
ER

PT J
AU Cusick, M
   Chew, EY
   Chan, CC
   Kruth, HS
   Murphy, RP
   Ferris, FL
AF Cusick, M
   Chew, EY
   Chan, CC
   Kruth, HS
   Murphy, RP
   Ferris, FL
TI Histoplathology and regression of retinal hard exudates in diabetic
   retinopathy after reduction of elevated serum lipid levels
SO OPHTHALMOLOGY
LA English
DT Article
ID BLOOD-GLUCOSE CONTROL; HUMAN ATHEROSCLEROTIC LESIONS; MACULAR EDEMA;
   RENAL-DISEASE; MELLITUS; COMPLICATIONS; MECHANISMS; TRIAL
AB Purpose: To describe a regression of retinal hard exudates in 2 patients with diabetic maculopathy, and to report immunohistologic findings reflecting lipid deposition in the retina.
   Design: Two interventional case reports.
   Methods: Two patients with exudative diabetic maculopathy were treated to normalize serum lipids. Histologic examination and immunohistochemistry of each patient's eyes were performed to assess the localization of apolipoprotein B and cholesteryl ester, both of which are principal components of low-density lipoprotein.
   Results: Both patients showed a dramatic regression of retinal hard exudates after correction of dyslipidemia. Histopathology revealed diffuse lipids and cholesteryl ester in the retina. Apolipoprotein B and macrophages were colocalized in the perivascular space.
   Conclusions: The regression of hard exudates was most likely due to the aggressive lipid lowering in both patients. The novel histopathologic findings of hard exudate and diabetic maculopathy are similar to the pathologic changes observed in larger atherosclerotic lesions, except that they occur in the intraretinal perivascular space. (C) 2003 by the American Academy of Ophthalmology.
C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
   Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD USA.
   NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   Natl Heart Lung & Blood Inst, Sect Expt Atherosclerosis, NIH, Bethesda, MD USA.
   Retina Grp Washington, Fairfax, VA USA.
RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Res, NIH, Bldg 31,Rm 6A52,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU Intramural NIH HHS [Z99 EY999999]
NR 32
TC 59
Z9 62
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2003
VL 110
IS 11
BP 2126
EP 2133
DI 10.1016/S0161-6420(03)01017-0
PG 8
WC Ophthalmology
SC Ophthalmology
GA 737VR
UT WOS:000186252900009
PM 14597519
ER

PT J
AU Scher, AI
   Stewart, WF
   Ricci, JA
   Lipton, RB
AF Scher, AI
   Stewart, WF
   Ricci, JA
   Lipton, RB
TI Factors associated with the onset and remission of chronic daily
   headache in a population-based study
SO PAIN
LA English
DT Article
DE chronic daily headache; incidence; remission; prognosis; epidemiology
ID FOLLOW-UP; INPATIENT TREATMENT; GENERAL-POPULATION; FREQUENT HEADACHE;
   PREVALENCE; WITHDRAWAL; MEDICATION; MIGRAINE; ADULTS; NORWAY
AB The etiology and prognosis of chronic daily headache (CDH) are not well understood.
   The aim of this study is to describe factors that predict CDH onset or remission in an adult population.
   Potential cases (180 + headaches per year, n = 1134) and controls (two to 104 headaches per year, it = 798) were interviewed two times over an average I I months of follow-up. Factors associated with CDH prevalence at baseline were evaluated. The incidence of CDH and risk factors for onset were assessed in controls whose headache frequency increased to 180 + per year at follow-up. Prognostic factors were assessed in CDH cases whose headache frequency fell at follow-up.
   CDH was more common in women, in whites, and those of less education. CDH cases were more likely to be previously married (divorced, widowed, separated). obese, and report a physician diagnosis of diabetes or arthritis.
   At follow-up. 3% of the controls reported 180 or more headaches per year. Obesity and baseline headache frequency were significantly associated with new onset CDH.
   In CDH cases. the projected 1-year remission rate to less than one headache per week was 14% and to less than 180 headaches per year was 57%. A better prognosis was associated with higher education, non-white race, being married, and with diagnosed diabetes.
   Individuals with less than a high-school education, whites, and those who were previously married had a higher risk of CDH at baseline and reduced likelihood of remission at follow-up. New onset CDH was associated with baseline headache frequency and obesity. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
   Geisinger Hlth Syst, Outcomes Res Inst, Danville, PA USA.
   AdvancePCS Co, IMR, Hunt Valley, MD USA.
   Albert Einstein Coll Med, Dept Neurol Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Scher, AI (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave,MSC, Bethesda, MD 20892 USA.
NR 21
TC 350
Z9 362
U1 3
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD NOV
PY 2003
VL 106
IS 1-2
BP 81
EP 89
DI 10.1016/S0304-3959(03)00293-8
PG 9
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 745MX
UT WOS:000186693400012
PM 14581114
ER

PT J
AU Tambeli, CH
   Young, A
   Levine, JD
   Gear, RW
AF Tambeli, CH
   Young, A
   Levine, JD
   Gear, RW
TI Contribution of spinal glutamatergic mechanisms in heterosegmental
   antinociception induced by noxious stimulation
SO PAIN
LA English
DT Article
DE glutamate; noxious stimulus-induced antinociception; NMDA and mGluR(5)
   receptors
ID JAW-OPENING REFLEX; ASPARTATE RECEPTOR ANTAGONIST; SUBSTANCE-P; RAT
   MODEL; NEUROKININ-1 RECEPTOR; POSTOPERATIVE PAIN; NEUROPATHIC PAIN;
   DORSAL HORN; NEURONS; CORD
AB We evaluated the role of spinal glutamate and substance P receptors in noxious stimulus-induced antinociception (NSIA). NSIA was produced by subdermal capsaicin administration in the hind paw of the rat and measured as attenuation of the jaw-opening reflex. NSIA was completely blocked by spinal intrathecal administration of the selective NMDA receptor antagonist LY235959 as well as the mGluR(5) antagonists MPEP and SIB-1757 and partially attenuated by the selective AMPA/kainate receptor antagonist NBQX; however, neither the mGluR(1) receptor antagonist LY367385 nor the NK1 antagonist L-703,606 affected NSIA. These results suggest that NSIA depends on glutamate. released from the central terminals of the primary afferent nociceptors, acting primarily on NMDA and mGluR(5) receptors. Although substance P is also known to be released by similar stimuli, NK1 receptors do not appear to play a role in NSIA. The implications of these findings in the context of a proposed spinal circuit that mediates NSIA are discussed. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 Univ Calif San Francisco, Sch Dent, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA.
   Univ Campinas, Fac Dent Piracicaba, Piracicaba, Brazil.
RP Gear, RW (reprint author), Univ Calif San Francisco, Sch Dent, Dept Oral & Maxillofacial Surg, POB 0440,707 Parnassuss Ave, San Francisco, CA 94143 USA.
RI Tambeli, Claudia/D-4356-2012
NR 41
TC 12
Z9 12
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD NOV
PY 2003
VL 106
IS 1-2
BP 173
EP 179
DI 10.1016/S0304-3959(03)00332-4
PG 7
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 745MX
UT WOS:000186693400023
PM 14581125
ER

PT J
AU Purohit, V
   Russo, D
   Salin, M
   Brown, R
AF Purohit, V
   Russo, D
   Salin, M
   Brown, R
TI Mechanisms of alcoholic pancreatitis: Introduction and summary of the
   symposium
SO PANCREAS
LA English
DT Article
DE alcohol; pancreatitis; cholecystokinin; zymogen activation; alcohol
   metabolism
ID MEDICAL PROGRESS; STELLATE CELLS; ACINAR-CELLS; ETHANOL; RAT; METABOLISM
AB Long-term, heavy alcohol consumption is associated with both acute and chronic pancreatitis. Progression of pancreatitis may lead to multiple comorbidities including maldigestion, diabetes, and pancreatic cancer. Understanding the underlying molecular, biochemical, and cellular mechanisms by which alcohol ingestion leads to the development of pancreatitis may help to develop strategies for the treatment and prevention of the disease. The National Institute on Alcohol Abuse and Alcoholism and the Office of Rare Diseases of National Institutes of Health sponsored a satellite symposium on "Mechanisms of Alcoholic Pancreatitis" at the annual meeting of the American Pancreatic Association, Chicago, IL, November 2002. For this symposium, 8 speakers were invited to address the following issues: ( 1) epidemiology of alcoholic pancreatitis; ( 2) pathophysiology of alcoholic pancreatitis; ( 3) animal models of alcoholic pancreatitis - roles of cholecystokinin (CCK) and viral infections; ( 4) alcohol and zymogen activation in the pancreatic acinar cell; ( 5) role of alcohol metabolism in alcoholic pancreatitis; ( 6) pancreatic stellate cell activation in alcoholic pancreatitis; and ( 7) genetic predisposition to alcoholic chronic pancreatitis. It was concluded that alcohol abuse is a major contributory factor to the development of both acute and chronic pancreatitis. The injurious effects of ethanol on the pancreas may be mediated through ( 1) sensitization of acinar cells to CCK-induced premature activation of zymogens; (2) potentiation of the effect of CCK on the activation of transcription factors, nuclear factor kappaB (NF-kappaB) and activating protein-1 (AP-1); (3) generation of toxic metabolites such as acetaldehyde and fatty acid ethyl esters; ( 4) sensitization of the pancreas to the toxic effects of coxsackievirus B3; and ( 5) activation of pancreatic stellate cells by acetaldehyde and oxidative stress and subsequent increased production of collagen and other matrix proteins.
C1 NIAAA, Biomed Res Branch, Div Basic Res, NIH, Bethesda, MD 20892 USA.
RP Purohit, V (reprint author), 6000 Execut Blvd,Suite 402, Bethesda, MD 20892 USA.
NR 14
TC 17
Z9 18
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2003
VL 27
IS 4
BP 281
EP 285
DI 10.1097/00006676-200311000-00001
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 737GV
UT WOS:000186222800001
ER

PT J
AU Dufour, MC
   Adamson, MD
AF Dufour, MC
   Adamson, MD
TI The epidemiology of alcohol-induced pancreatitis
SO PANCREAS
LA English
DT Article
DE alcoholic pancreatitis; alcohol consumption; pancreas; epidemiology
ID RISK FACTOR; PATHOGENESIS; ETIOLOGY; MORTALITY; DISEASES; CANCER
AB Although the association between alcohol and pancreatitis has been recognized for centuries, the precise magnitude of the impact of alcohol remains poorly quantified. Epidemiologic research on this condition has been seriously handicapped by several factors. Classifications are based on morphology rather than on etiology; the diagnostic differences between acute and chronic pancreatitis are imprecise and confusing; and coding by the International Classification of Diseases (ICD) has been inadequate. The current ICD (ICD-10), used in the United States since 1999, identifies alcohol-induced chronic pancreatitis as a separate code for the first time, an enhancement that will greatly improve the quality of data collected in current and future studies. Unfortunately, no code yet exists for acute alcoholic pancreatitis. Of the approximately 2.4 million deaths in the United States in 1999, pancreatitis was listed as the underlying cause for 3289 deaths, making it the 235th leading cause of death. Acute pancreatitis accounted for 84% of these deaths, and chronic pancreatitis the remaining 16%. Alcohol is a primary cause of both acute and chronic pancreatitis in most developed countries. About one-third of acute pancreatitis in the United States is alcohol-induced. In the United States and other developed countries, 60% - 90% of chronic pancreatitis is alcohol induced. Both forms are more common in men. The development of chronic pancreatitis is proportional to the dose and duration of alcohol consumption ( minimum, 6 - 12 years of approximately 80g of alcohol per day). Autopsy studies reveal subclinical chronic pancreatitis in another 10% of alcohol abusers. Yet, since < 10% of chronic alcoholics develop chronic pancreatitis, clearly other predisposing factors besides alcohol are involved. Genetic variability and environmental exposures, such as diet, are prime candidates for further investigation. To date, there have been few large epidemiological studies of alcoholic pancreatitis in the United States or other developed countries. Additional studies are needed to improve the quality of existing baseline epidemiologic data and allow better assessment of risk. Improved diagnostic precision, more complete and specific coding, and greater understanding of covariables and mechanisms would also advance the field.
C1 NIAAA, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA.
RP Adamson, MD (reprint author), NIAAA, Div Biometry & Epidemiol, NIH, 6000 Execut Blvd,Wilco Bldg,Suite 514, Bethesda, MD 20892 USA.
NR 39
TC 98
Z9 111
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD NOV
PY 2003
VL 27
IS 4
BP 286
EP 290
DI 10.1097/00006676-200311000-00002
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 737GV
UT WOS:000186222800002
PM 14576488
ER

PT J
AU DiFurio, MJ
   Auerbach, A
   Kaplan, KJ
AF DiFurio, MJ
   Auerbach, A
   Kaplan, KJ
TI Well-differentiated fetal adenocarcinoma: Rare tumor in the pediatric
   population
SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY
LA English
DT Article
DE lung cancer; neuroendocrine differentiation; pulmonary blastoma;
   pulmonary endodermal tumor; well-differentiated fetal adenocarcinoma
ID PULMONARY BLASTOMA; LUNG; FEATURES
AB Well-differentiated fetal adenocarcinoma (WDFA) is a rare tumor of the lung, which has gone by many names over the years. The lesion was first described by Kradin et al., in 1982, who called it "pulmonary blastoma with argyrophil cells and lacking sarcomatous features (pulmonary endodermal tumor resembling fetal lung)." Since then, there have been at least 65 cases reported in the literature. Although there has been no consensus in the literature as to the best pathological term for this entity, the most recent World Health Organization classification of lung and pleural tumors uses the term well-differentiated fetal adenocarcinoma. Characteristically, this lesion consists of an epithelium, which recapitulates fetal lung at 3-5 months of gestation and demonstrates neuroendocrine differentiation. Although the classic age range is 30-40 years, there have been seven reports of WDFA in the pediatric age. We report an additional pediatric case of this tumor and review the pediatric cases in the existing literature.
C1 Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA.
   NCI, NIH, Bethesda, MD 20892 USA.
RP DiFurio, MJ (reprint author), Walter Reed Army Med Ctr, Dept Pathol, Ward 47,Bldg 2,6900 Georgia Ave NW, Washington, DC 20307 USA.
NR 13
TC 4
Z9 7
U1 1
U2 2
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 1093-5266
J9 PEDIATR DEVEL PATHOL
JI Pediatr. Dev. Pathol.
PD NOV-DEC
PY 2003
VL 6
IS 6
BP 564
EP 567
DI 10.1007/s10024-003-4046-x
PG 4
WC Pathology; Pediatrics
SC Pathology; Pediatrics
GA 757AK
UT WOS:000187526500013
PM 15018457
ER

PT J
AU Venditti, LN
   Venditti, CP
   Berry, GT
   Kaplan, PB
   Kaye, EM
   Glick, H
   Stanley, CA
AF Venditti, LN
   Venditti, CP
   Berry, GT
   Kaplan, PB
   Kaye, EM
   Glick, H
   Stanley, CA
TI Newborn screening by tandem mass spectrometry for medium-chain acyl-CoA
   dehydrogenase deficiency: A cost-effectiveness analysis
SO PEDIATRICS
LA English
DT Article
DE cost-utility; cost-effectiveness; newborn screening; inborn errors of
   metabolism; MCADD
ID BIRTH-WEIGHT INFANTS; SICKLE-CELL-DISEASE; INBORN-ERRORS; MCAD
   DEFICIENCY; ECONOMIC-EVALUATION; INTENSIVE-CARE; BLOOD SPOTS;
   METABOLISM; PHENYLKETONURIA; CHILDREN
AB Objective. To determine whether newborn screening by tandem mass spectrometry (MS/MS) for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is cost-effective versus not screening and to define the contributions of disease, test, and population parameters on the decision.
   Methods. A decision-analytic Markov model was designed to perform cost-effectiveness and cost-utility analyses measuring the discounted, incremental cost per life-year saved and per quality-adjusted life-year saved of newborn screening for MCADD compared with not screening. A hypothetical cohort of neonates made transitions among a set of health states that reflected clinical status, morbidity, and cost. Outcomes were estimated for time horizons of 20 and 70 years. Probabilities and costs were derived from a retrospective chart review of a 32-patient cohort treated over the past 30 years at the Children's Hospital of Philadelphia, clinical experience with MCADD patient management, patient-family interviews, cost surveys, state sources, and published studies. In addition to older patients who came to medical attention by symptomatic presentation, our patient group included 6 individuals whose MCADD had been diagnosed by supplemental newborn screening. Estimates of the expected net changes in costs and life expectancy for MCADD screening were used to compute the incremental cost-effectiveness ratios. Sensitivity analyses were performed on key input variables, and 95% confidence intervals (CIs) were computed through second-order Monte Carlo simulations.
   Results. In our base-case analysis over the first 20 years of life, the cost of newborn screening for MCADD was approximately $11000 (2001 US dollars; 95% CI: <$0-$33800) per life-year saved, or $5600 (95% CI: <$0-$17100) per quality-adjusted life-year saved compared with not screening. Over a 70-year horizon, the respective ratios were approximately $300 (95% CI: <$0-$13000) and $100 (95% CI: <$0-$6900). The results were robust when tested over plausible ranges for diagnostic test sensitivity and specificity, MCADD prevalence, asymptomatic rate, and screening cost.
   Conclusions. Simulation modeling indicates that newborn screening for MCADD reduces morbidity and mortality at an incremental cost below the range for accepted health care interventions. At the 70-year horizon, the model predicts that almost all of the additional costs of screening would be offset by avoided sequelae.
C1 Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA.
   Univ Penn, Sch Med, Dept Gen Internal Med, Philadelphia, PA 19104 USA.
   Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA.
   Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
RP Venditti, CP (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg49,Rm 4A56A, Bethesda, MD 20892 USA.
OI STANLEY, CHARLES/0000-0003-4881-9392; Berry, Gerard/0000-0001-5299-3313
NR 66
TC 66
Z9 67
U1 3
U2 8
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD NOV 1
PY 2003
VL 112
IS 5
BP 1005
EP 1015
DI 10.1542/peds.112.5.1005
PG 11
WC Pediatrics
SC Pediatrics
GA 738XA
UT WOS:000186312100001
PM 14595039
ER

PT J
AU Heinz, A
   Schafer, M
   Higley, JD
   Krystal, JH
   Goldman, D
AF Heinz, A
   Schafer, M
   Higley, JD
   Krystal, JH
   Goldman, D
TI Neurobiological correlates of the disposition and maintenance of
   alcoholism
SO PHARMACOPSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 1st International Charite Conference on Psychiatric Research: Challenges
   and Goals
CY OCT, 2002
CL BERLIN, GERMANY
DE alcoholism; neuroadaptation; sensitization; alcohol cues; candidate
   genes
ID SEROTONIN TRANSPORTER AVAILABILITY; RHESUS-MONKEYS; DRUG-ABUSE;
   CEREBROSPINAL-FLUID; RELAPSE PREVENTION; NONHUMAN-PRIMATES; FOLLOW-UP;
   RECEPTORS; ETHANOL; REWARD
AB The last decade witnessed a rapid increase in the knowledge of the etiopathology and treatment of alcoholism. The current disease concept includes psychosocial and neurobiological foundations and consequences of alcoholism. Neurobiological research points to dispositional factors such as a low level of response to alcohol, which is partly heritable and seems to be associated with monoaminergic dysfunction and reduced GABAergic alcohol effects. Chronic alcohol intake stimulates counteradaptive neuroadaptation in central GABAergic and glutamatergic neurotransmission, which increases alcohol tolerance. Neuroadaptation to chronic alcohol effects is not immediately reversed during detoxification and can cause clinical withdrawal once alcohol intake is terminated. Sensitization of the dopaminergic and opioidergic reward system may contribute to alcohol craving and reduced control of alcohol intake. New treatment options include pharmacological approaches and indicate that behavior or motivational therapy and the attendance of patient groups may equally reduce the relapse risk.
C1 Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany.
   NIAAA, NIH, Bethesda, MD USA.
   Yale Univ, NIAAA, Ctr Translat Neurosci Alcohism, New Haven, CT USA.
RP Heinz, A (reprint author), Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, CCM, Schumannstr 20-21, D-10117 Berlin, Germany.
EM andreas.heinz@charite.de
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU NIAAA NIH HHS [K02 AA 00261-01, P50 AA12870-01]
NR 51
TC 37
Z9 38
U1 2
U2 2
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0176-3679
J9 PHARMACOPSYCHIATRY
JI Pharmacopsychiatry
PD NOV
PY 2003
VL 36
SU 3
BP S255
EP S258
PG 4
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 763JG
UT WOS:000188081200018
PM 14677088
ER

PT J
AU Heinz, A
   Romero, B
   Gallinat, J
   Juckel, G
   Weinberger, DR
AF Heinz, A
   Romero, B
   Gallinat, J
   Juckel, G
   Weinberger, DR
TI Molecular brain imaging and the neurobiology and genetics of
   schizophrenia
SO PHARMACOPSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 1st International Charite Conference on Psychiatric Research: Challenges
   and Goals
CY OCT, 2002
CL BERLIN, GERMANY
DE dopamine; PET; SPECT; fMRI; COMT genotype; neurodevelopment
ID POSITRON-EMISSION-TOMOGRAPHY; DORSOLATERAL PREFRONTAL CORTEX; CEREBRAL
   BLOOD-FLOW; STRIATAL DOPAMINE; CONSCIOUS RECOLLECTION; SYNAPTIC
   DOPAMINE; WORKING-MEMORY; P300; DYSFUNCTION; AMPHETAMINE
AB It has been hypothesized that schizophrenia is related to dysfunction in temporolimbic-prefrontal neuronal networks, which is acquired early in an individual's development. After puberty, relatively reduced prefrontal control of striatal dopaminergic neurotransmission may lead to unmodulated striatal dopamine (DA) activity, and the positive symptoms of acute psychosis. Brain imaging studies support the notion of prefrontal dysfunction in schizophrenia and correlated upregulation of presynaptic striatal DA activity. Recent molecular brain imaging studies have combined genetic assessments with a multimodal neuroimaging approach to further refine our understanding of the pathophysiologic architecture of the disorder. We review the literature on functional brain imaging in schizophrenia and discuss genotype effects on core psychotic symptoms. A promising research strategy is the identification of genetic and environmental factors that contribute to intermediate phenotypes such as working memory deficits in schizophrenia. Molecular brain imaging can help to unravel the complex interactions between genes and environment and its association with neuronal network dysfunction in schizophrenia.
C1 Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany.
   NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Heinz, A (reprint author), Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, CCM, Schumannstr 20-21, D-10117 Berlin, Germany.
EM andreas.heinz@charite.de
NR 55
TC 30
Z9 30
U1 1
U2 4
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0176-3679
J9 PHARMACOPSYCHIATRY
JI Pharmacopsychiatry
PD NOV
PY 2003
VL 36
SU 3
BP S152
EP S157
PG 6
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 763JG
UT WOS:000188081200002
PM 14677072
ER

PT J
AU Figg, WD
   Cox, MC
AF Figg, WD
   Cox, MC
TI Pharmacy education: Back to the basics?
SO PHARMACOTHERAPY
LA English
DT Editorial Material
C1 NCI, Mol Pharmacol Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Canc Res Ctr, NIH, Bldg 10,room 5A01,MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 2
TC 12
Z9 12
U1 0
U2 2
PU PHARMACOTHERAPY PUBLICATIONS INC
PI BOSTON
PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA
SN 0277-0008
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD NOV
PY 2003
VL 23
IS 11
BP 1381
EP 1390
DI 10.1592/phco.23.14.1381.31946
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 736VF
UT WOS:000186193300001
PM 14620384
ER

PT J
AU Matuszak, Z
   Bilska, MA
   Reszka, KJ
   Chignell, CF
   Bilski, P
AF Matuszak, Z
   Bilska, MA
   Reszka, KJ
   Chignell, CF
   Bilski, P
TI Interaction of singlet molecular oxygen with melatonin and related
   indoles
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID PHOTOSENSITIZED OXIDATION; DNA-DAMAGE; IN-VITRO; A2E; O2(1-DELTA-G);
   DERIVATIVES; REACTIVITY; CHEMISTRY; DECAY; CELLS
AB Singlet molecular oxygen (O-1(2)) is one of the major agents responsible for (photo)oxidative damage in biological systems including human skin and eyes. It has been reported that the neural hormone melatonin (MLT) can abrogate O-1(2)-mediated cytotoxicity through its purported high antioxidant activity. We studied the interaction of MLT with O-1(2) in deuterium oxide (D2O), acetonitrile and methanol by measuring the phosphorescence lifetime of O-1(2) in the presence of MLT and related indoles for comparison. Rose bengal (RB) was used as the main O-1(2) photosensitizer. The rate constant (k(q)) for the total (physical and chemical) quenching of O-1(2) by MLT was determined to be 4.0 X 10(7) M-1 s(-1) in D2O (pl) 7), 6.0 X 10(7) M-1 s(-1) in acetonitrile, and 6.1 X 10(7) M-1 s(-1) in methanol-di. The related indoles, tryptophan, 5-hydroxyindole, 5-rriethoxytryptamine, 5-hydroxytryptamine (5-OH-T, serotonin), 6hydroxymelatonin (6-OH-MLT) and 6-chloromelatonin quenched O-1(2) phosphorescence with similar kq values. We also compared the photosensitized photobleaching rate of NILT with that of other indoles, which revealed that MLT is the most sensitive to O-1(2) bleaching. Hydroxylation of the indole moiety in 5-OH-T and 6-OH-MLT makes them more sensitive to photodegradation. In the absence of exogenous photosensitizers NILT itself can generate O-1(2) with low quantum yield (0.1 in CH3CN) upon UV excitation. Thus, the processes we investigated may occur in the skin and eyes during physiological circadian rhythm (photo)signaling involving NILT and other indoles. Our results indicate that all the indoles studied, including NILT, are quite efficient yet very similar O-1(2) quenchers. This directly shows that the exceptional antioxidant ability proposed for MLT is unsubstantiated when merely chemical mechanism(s) are considered in vivo, and it must predominantly involve humoral regulation that mobilizes other antioxidant defenses in living organisms.
C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
RP Bilski, P (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RI Strid, Ake/E-5309-2012
OI Strid, Ake/0000-0003-3315-8835
NR 39
TC 32
Z9 32
U1 0
U2 11
PU AMER SOC PHOTOBIOLOGY
PI AUGUSTA
PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD NOV
PY 2003
VL 78
IS 5
BP 449
EP 455
DI 10.1562/0031-8655(2003)078<0449:IOSMOW>2.0.CO;2
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 744RV
UT WOS:000186646900005
PM 14653575
ER

PT J
AU Soltis, J
   Wegner, FH
   Newman, JD
AF Soltis, J
   Wegner, FH
   Newman, JD
TI Adult cortisol response to immature offspring play in captive squirrel
   monkeys
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Saimiri sciureus; urinary cortisol; adult affiliation; play; animal
   welfare
ID MARMOSETS CALLITHRIX KUHLI; PITUITARY-ADRENAL ACTIVITY;
   SAIMIRI-SCIUREUS; PLASMA-CORTISOL; BEHAVIORAL-RESPONSES;
   SOCIAL-ENVIRONMENT; URINARY CORTISOL; TITI MONKEYS; GUINEA-PIGS;
   SEPARATION
AB Variable environmental and social conditions influence hypothalamic-pituitary-adrenal activity in captive animals. Socially separated and individually housed animals generally experience increased cortisol secretion compared to animals housed with conspecifics, and social companionship can buffer the stress response when exposed to challenges such as introduction to novel environments. Nevertheless, the presence of conspecifics may also be the cause of stress because social dynamics impact individuals. Squirrel monkeys (Saimiri spp.) readily form same-sex affiliative social relationships, but in captivity, the presence of immature offspring severely disrupts affiliative associations among adults. We examined behavioral and physiological effects of the presence of immature offspring on adults by comparing two groups of adults with immature offspring to an all-adult group. We conducted behavioral observations and collected urine from adult members, and urine was assayed for cortisol at the Wisconsin National Primate Research Center. Adults in groups with immature offspring received an average of 18 play attempts per hour from the offspring, experienced a fivefold decrease in adult affiliation, and showed higher urinary cortisol levels compared to the all-adult group. A principal components analysis showed that adults characterized by receiving play attempts, rejecting play attempts, and lacking affiliative contact with other adults showed the highest mean urinary cortisol levels. Further analyses demonstrated that the persistent play attempts by immature offspring, not the resulting lack of adult huddling, were primarily responsible for the observed increase in urinary cortisol levels. Taken together, these data suggest that the disruptive effect of immature offspring produces a chronic cortisol increase in captive adult squirrel monkeys. Published by Elsevier Inc.
C1 NICHHD, Comparat Ethol Lab, NIH, Dept Hlth & Human Serv, Poolesville, MD 20837 USA.
   Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
RP Newman, JD (reprint author), NICHHD, Comparat Ethol Lab, NIH, Dept Hlth & Human Serv, POB 529, Poolesville, MD 20837 USA.
NR 57
TC 6
Z9 6
U1 3
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD NOV
PY 2003
VL 80
IS 2-3
BP 217
EP 223
DI 10.1016/j.physbeh.2003.07.009
PG 7
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 750DT
UT WOS:000186976600007
PM 14637219
ER

PT J
AU Sunthitikawinsakul, A
   Kongkathip, N
   Kongkathip, B
   Phonnakhu, S
   Daly, JW
   Spande, TF
   Nimit, Y
   Napaswat, C
   Kasisit, J
   Yoosook, C
AF Sunthitikawinsakul, A
   Kongkathip, N
   Kongkathip, B
   Phonnakhu, S
   Daly, JW
   Spande, TF
   Nimit, Y
   Napaswat, C
   Kasisit, J
   Yoosook, C
TI Anti-HIV-1 limonoid: First isolation from Clausena excavata
SO PHYTOTHERAPY RESEARCH
LA English
DT Article
DE Clausena excavata; limonoid; anti-HIV-1 activity; clausenolide-1-ethyl
   ether; coumarin
ID NATURAL-PRODUCTS; ROOT BARK; COUMARINS; ASSAY; VIRUS; CONSTITUENTS;
   CARBAZOLES; ALKALOIDS; DISCOVERY
AB A limonoid, clausenolide-1-ethyl ether (1) and two coumarins, dentatin (2) and nor-dentatin (3), were isolated from Clausena excavata. Limonoid I was obtained from the crude ethanol extract of the rhizomes and the roots but had not previously been isolated from C. excavata and exhibited HIV-1 inhibitory activity. Coumarins 2 and 3, with their structures related to an anti-HIV-1 substance, (+)-calanolide A (4), were obtained from the crude chloroform extract of the rhizomes. Both induced toxicity to cells used in a syncytium assay for anti-HIV-1 activity. These compounds, 1-3, did not show any cytotoxic effect against KB and BC-1 cell lines (IC50 value > 20 mug/mL). Copyright (C) 2003 John Wiley Sons, Ltd.
C1 Kasetsart Univ, Fac Sci, Dept Chem, Nat Prod & Organ Synth Res Unit,NPOS, Bangkok 10900, Thailand.
   NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA.
   Mahidol Univ, Fac Sci, Dept Microbiol, Bangkok 10400, Thailand.
RP Kongkathip, N (reprint author), Kasetsart Univ, Fac Sci, Dept Chem, Nat Prod & Organ Synth Res Unit,NPOS, Chatujak, Bangkok 10900, Thailand.
NR 14
TC 25
Z9 28
U1 2
U2 9
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0951-418X
J9 PHYTOTHER RES
JI Phytother. Res.
PD NOV
PY 2003
VL 17
IS 9
BP 1101
EP 1103
DI 10.1002/ptr.1381
PG 3
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 740AJ
UT WOS:000186378400022
PM 14595596
ER

PT J
AU Stein, LD
   Bao, ZR
   Blasiar, D
   Blumenthal, T
   Brent, MR
   Chen, NS
   Chinwalla, A
   Clarke, L
   Clee, C
   Coghlan, A
   Coulson, A
   D'Eustachio, P
   Fitch, DHA
   Fulton, LA
   Fulton, RE
   Griffiths-Jones, S
   Harris, TW
   Hillier, LW
   Kamath, R
   Kuwabara, PE
   Mardis, ER
   Marra, MA
   Miner, TL
   Minx, P
   Mullikin, JC
   Plumb, RW
   Rogers, J
   Schein, JE
   Sohrmann, M
   Spieth, J
   Stajich, JE
   Wei, CC
   Willey, D
   Wilson, RK
   Durbin, R
   Waterston, RH
AF Stein, LD
   Bao, ZR
   Blasiar, D
   Blumenthal, T
   Brent, MR
   Chen, NS
   Chinwalla, A
   Clarke, L
   Clee, C
   Coghlan, A
   Coulson, A
   D'Eustachio, P
   Fitch, DHA
   Fulton, LA
   Fulton, RE
   Griffiths-Jones, S
   Harris, TW
   Hillier, LW
   Kamath, R
   Kuwabara, PE
   Mardis, ER
   Marra, MA
   Miner, TL
   Minx, P
   Mullikin, JC
   Plumb, RW
   Rogers, J
   Schein, JE
   Sohrmann, M
   Spieth, J
   Stajich, JE
   Wei, CC
   Willey, D
   Wilson, RK
   Durbin, R
   Waterston, RH
TI The genome sequence of Caenorhabditis briggsae: A platform for
   comparative genomics
SO PLOS BIOLOGY
LA English
DT Review
ID CELL-SPECIFIC EXPRESSION; CIS REGULATORY REQUIREMENTS; C-ELEGANS;
   LARGE-SCALE; DROSOPHILA-MELANOGASTER; GENUS CAENORHABDITIS; REPETITIVE
   ELEMENTS; PROTEIN FAMILIES; NEMATODES; EVOLUTION
AB The soil nematodes Caenorhabditis briggsae and Caenorhabditis elegans diverged from a common ancestor roughly 100 million years ago and yet are almost indistinguishable by eye. They have the same chromosome number and genome sizes, and they occupy the same ecological niche. To explore the basis for this striking conservation of structure and function, we have sequenced the C. briggsae genome to a high-quality draft stage and compared it to the finished C. elegans sequence. We predict approximately 19,500 protein-coding genes in the C. briggsae genome, roughly the same as in C. elegans. Of these, 12,200 have clear C. elegans orthologs, a further 6,500 have one or more clearly detectable C. elegans homologs, and approximately 800 C. briggsae genes have no detectable matches in C. elegans. Almost all of the noncoding RNAs (ncRNAs) known are shared between the two species. The two genomes exhibit extensive colinearity, and the rate of divergence appears to be higher in the chromosomal arms than in the centers. Operons, a distinctive feature of C. elegans, are highly conserved in C. briggsae, with the arrangement of genes being preserved in 96% of cases. The difference in size between the C briggsae (estimated at approximately 104 Mbp) and C. elegans (100.3 Mbp) genomes is almost entirely due to repetitive sequence, which accounts for 22.4% of the C. briggsae genome in contrast to 16.5% of the C. elegans genome. Few, if any, repeat families are shared, suggesting that most were acquired after the two species diverged or are undergoing rapid evolution. Coclustering the C. elegans and C. briggsae proteins reveals 2,169 protein families of two or more members. Most of these are shared between the two species, but some appear to be expanding or contracting, and there seem to be as many as several hundred novel C. briggsae gene families. The C. briggsae draft sequence will greatly improve the annotation of the C. elegans genome. Based on similarity to C. briggsae, we found strong evidence for 1,300 new C. elegans genes. In addition, comparisons of the two genomes will help to understand the evolutionary forces that mold nematode genomes.
C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
   Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63110 USA.
   Univ Colorado, Denver, CO 80202 USA.
   Washington Univ, Dept Comp Sci & Engn, St Louis, MO USA.
   Wellcome Trust Sanger Inst, Hinxton, England.
   Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland.
   NYU, Sch Med, New York, NY USA.
   Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
   British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
   NIH, Bethesda, MD 20892 USA.
   Duke Univ, Dept Mol Genet & Microbiol, Durham, NC USA.
   MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
   NYU, Dept Biol, New York, NY 10003 USA.
RP Stein, LD (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.
EM lstein@cshi.org
RI Stajich, Jason/C-7297-2008; Chen, Nansheng/E-6450-2012; Tang,
   Macy/B-9798-2014; Griffiths-Jones, Sam/H-2998-2014; Schein,
   Jacquie/G-3674-2015; Marra, Marco/B-5987-2008; 
OI Stajich, Jason/0000-0002-7591-0020; Griffiths-Jones,
   Sam/0000-0001-6043-807X; Durbin, Richard/0000-0002-9130-1006;
   D'Eustachio, Peter/0000-0002-5494-626X; Wei,
   Chaochun/0000-0002-1031-034X; Clarke, Laura/0000-0002-5989-6898
FU NHGRI NIH HHS [P41 HG02223, 5P01 HG00956, 5U01 HG02042, P01 HG000956,
   P41 HG002223]; NIGMS NIH HHS [R01 GM042432, R01 GM42432, T32 GM007754,
   T32 GM07754-22]
NR 118
TC 557
Z9 1155
U1 6
U2 54
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD NOV
PY 2003
VL 1
IS 2
BP 166
EP +
AR e45
DI 10.1371/journal.pbio.0000045
PG 29
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics
GA 772GZ
UT WOS:000188835200010
PM 14624247
ER

PT J
AU Klassen, AC
   Juon, HS
   Alberg, AJ
   Reid, BC
   Meissner, HI
AF Klassen, AC
   Juon, HS
   Alberg, AJ
   Reid, BC
   Meissner, HI
TI Opportunities for oral cancer screening among older African-American
   women
SO PREVENTIVE MEDICINE
LA English
DT Article
DE oral cancer; screening; African-Americans; preventive care
ID NECK-CANCER; CIGARETTE-SMOKING; HEALTH; HEAD; SERVICES; ADULTS; CARDIA;
   GENDER; TRENDS
AB Background. Older persons with smoking histories are important targets for oral cancer screening. Although older persons in low-income communities often lack regular dental care, little is known about the characteristics of groups at greatest risk for poor screening.
   Methods. Survey data from 576 African-American women aged 45-93 were used to identify predictors of smoking and recency and type of dental care.
   Results. Fifty-nine percent of respondents were current or former smokers, and 62% reported dental care within the past 3 years. Among smokers. no recent dental care was associated with older age, worse health, not working, no regular medical provider, and no recent mammography.
   Conclusions. These results suggest that episodic visits to nondentist providers offer opportunities for oral screening in high-risk populations. (C) 2003 American Health Foundation and Elsevier Inc. All rights reserved.
C1 Johns Hopkins Univ, Sch Publ Adm, Dept Hlth Policy & Management, Baltimore, MD 21205 USA.
   Univ Maryland, Sch Dent, Baltimore, MD 21201 USA.
   NCI, Bethesda, MD 20892 USA.
RP Klassen, AC (reprint author), Johns Hopkins Univ, Sch Publ Adm, Dept Hlth Policy & Management, 624 N Broadway,Room 745, Baltimore, MD 21205 USA.
FU NCI NIH HHS [CA73790, R01 CA66065]
NR 31
TC 10
Z9 10
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 0091-7435
J9 PREV MED
JI Prev. Med.
PD NOV
PY 2003
VL 37
IS 5
BP 499
EP 506
DI 10.1016/S0091-7435(03)00176-2
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 737UQ
UT WOS:000186250500013
PM 14572434
ER

PT J
AU Dror, O
   Benyamini, H
   Nussinov, R
   Wolfson, HJ
AF Dror, O
   Benyamini, H
   Nussinov, R
   Wolfson, HJ
TI Multiple structural alignment by secondary structures: Algorithm and
   applications
SO PROTEIN SCIENCE
LA English
DT Article
DE multiple structural comparison; nonsequential alignment; tiontopological
   motif; supersecondary structural motif; docking; protein structure
   classification; large-scale structure comparison
ID PROTEIN-STRUCTURE COMPARISONS; TERTIARY STRUCTURE; INTEGRATED APPROACH;
   SEQUENCE ALIGNMENT; MOTIFS; EFFICIENT; SETS; IDENTIFICATION;
   SIMILARITIES; CONSERVATION
AB We present MASS (Multiple Alignment by Secondary Structures), a novel highly efficient method for structural alignment of multiple protein molecules and detection of common structural motifs. MASS is based on a two-level alignment, using both secondary structure and atomic representation. Utilizing secondary structure information aids in filtering out noisy solutions and achieves efficiency and robustness. Currently, only a few methods are available for addressing the multiple structural alignment task. In addition to using secondary structure information, the advantage of MASS as compared to these methods is that it is a combination of several important characteristics: (1) While most existing methods are based on series of pairwise comparisons, and thus might miss optimal global solutions, MASS is truly multiple, considering all the molecules simultaneously; (2) MASS is sequence order-independent and thus capable of detecting nontopological structural motifs; (3) MASS is able to detect not only structural motifs, shared by all input molecules, but also motifs shared only by subsets of the molecules. Here, we show the application of MASS to various protein ensembles. We demonstrate its ability to handle a large number (order of tens) of molecules, to detect nontopological motifs and to find biologically meaningful alignments within nonpredefined subsets of the input. In particular, we show how by using conserved structural motifs, one can guide protein-protein docking, which is a notoriously difficult problem. MASS is freely available at http://bioinfo3d.cs.tau.ac.il/MASS/.
C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
   Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
   NCI, FCRDC, Lab Expt & Computat Biol, Frederick, MD 21702 USA.
   SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA.
RP Dror, O (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
RI Wolfson, Haim/A-1837-2011
FU NCI NIH HHS [N01-CO-12400, N01CO12400]
NR 46
TC 49
Z9 51
U1 1
U2 3
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD NOV
PY 2003
VL 12
IS 11
BP 2492
EP 2507
DI 10.1110/ps.03200603
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 739FJ
UT WOS:000186333800010
PM 14573862
ER

PT J
AU Lebowitz, J
   Lewis, MS
   Schuck, P
AF Lebowitz, J
   Lewis, MS
   Schuck, P
TI Back to the future: A rebuttal to Henryk Eisenberg
SO PROTEIN SCIENCE
LA English
DT Editorial Material
C1 NIH, Div Bioengn & Phys Sci, ORS, OD, Bethesda, MD 20892 USA.
RP Lebowitz, J (reprint author), NIH, Div Bioengn & Phys Sci, ORS, OD, 13 S Dr,Bldg 13,Room 3N17, Bethesda, MD 20892 USA.
OI Schuck, Peter/0000-0002-8859-6966
NR 7
TC 5
Z9 5
U1 2
U2 5
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD NOV
PY 2003
VL 12
IS 11
BP 2649
EP 2650
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 739FJ
UT WOS:000186333800026
ER

PT J
AU Xie, XQ
   Chen, JZ
   Billings, EM
AF Xie, XQ
   Chen, JZ
   Billings, EM
TI 3D structural model of the G-protein-coupled cannabinoid CB2 receptor
SO PROTEINS-STRUCTURE FUNCTION AND GENETICS
LA English
DT Article
DE cannabinoid receptor subtype 2 (CB2); G-protein-coupled receptor (GPCR);
   3D structure; homology; sequence alignment; computer modeling
ID 3-DIMENSIONAL STRUCTURE; FUNCTIONAL EXPRESSION; TRANSMEMBRANE DOMAIN;
   CIRCULAR-DICHROISM; MOLECULAR-CLONING; LYSINE RESIDUE; DISULFIDE BOND;
   MASTOPARAN-X; BINDING; ACTIVATION
AB The potential for therapeutic specificity in regulating diseases and for reduced side effects has made cannabinoid (CB) receptors one of the most important G-protein-coupled receptor (GPCR) targets for drug discovery. The cannabinoid (CB) receptor subtype CB2 is of particular interest due to its involvement in signal transduction in the immune system and its increased characterization by mutational and other studies. However, our understanding of their mode of action has been limited by the absence of an experimental receptor structure. In this study, we have developed a 3D model of the CB2 receptor based on the recent crystal structure of a related GPCR, bovine rhodopsin. The model was developed using multiple sequence alignment of homologous receptor sub-types in humans and mammals, and compared with other GPCRs. Alignments were analyzed with mutation scores, pairwise hydrophobicity profiles and Kyte-Doolittle plots. The 3D model of the transmembrane segment was generated by mapping the CB2 sequence onto the homologous residues of the rhodopsin structure. The extra- and intracellular loop regions of the CB2 were generated by searching for homologous C. backbone sequences in published structures in the Brookhaven Protein Databank (PDB). Residue side chains were positioned through a combination of rotamer library searches, simulated annealing and minimization. Intermediate models of the 7TM helix bundles were analyzed in terms of helix tilt angles, hydrogen-bond networks, conserved residues and motifs, possible disulfide bonds. The amphipathic cytoplasmic helix domain was also correlated with biological and site-directed mutagenesis data. Finally, the model receptor-binding cavity was characterized using solvent-accessible surface approach. (C) 2003 Wiley-Liss, Inc.
C1 Univ Connecticut, IMS, Storrs, CT 06269 USA.
   Univ Connecticut, Dept Pharmaceut Sci, Sch Pharm, Storrs, CT 06269 USA.
   NHLBI, Bioinformat Core Facil, NIH, Bethesda, MD 20892 USA.
RP Xie, XQ (reprint author), Univ Connecticut, IMS, U-3136, Storrs, CT 06269 USA.
FU NIDA NIH HHS [DA11510, DA15770]
NR 64
TC 76
Z9 80
U1 0
U2 6
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD NOV 1
PY 2003
VL 53
IS 2
BP 307
EP 319
DI 10.1002/prot.10511
PG 13
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 749WD
UT WOS:000186951800016
PM 14517981
ER

PT J
AU Obmolova, G
   Teplyakov, A
   Khil, PP
   Howard, AJ
   Camerini-Otero, RD
   Gilliland, GL
AF Obmolova, G
   Teplyakov, A
   Khil, PP
   Howard, AJ
   Camerini-Otero, RD
   Gilliland, GL
TI Crystal structure of the Escherichia coli Tas protein, an
   NADP(H)-dependent aldo-keto reductase
SO PROTEINS-STRUCTURE FUNCTION AND GENETICS
LA English
DT Article
ID ALDEHYDE REDUCTASE; BINDING SITE; DEHYDROGENASE; SUPERFAMILY; COMPLEX;
   GENES
C1 Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA.
   NIST, Rockville, MD 20850 USA.
   NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA.
   IIT, Chem & Phys Sci Dept, Ctr Synchrotron Radiat Res & Instrumentat, Chicago, IL 60616 USA.
RP Gilliland, GL (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
OI Khil, Pavel/0000-0002-4903-8777; Teplyakov, Alexey/0000-0003-0296-0016
FU NIGMS NIH HHS [P01-GM57890]
NR 22
TC 6
Z9 7
U1 0
U2 1
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD NOV 1
PY 2003
VL 53
IS 2
BP 323
EP 325
DI 10.1002/prot.10367
PG 3
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 749WD
UT WOS:000186951800018
PM 14517983
ER

PT J
AU Wulfkuhle, JD
   Aquino, JA
   Calvert, VS
   Fishman, DA
   Coukos, G
   Liotta, LA
   Petricoin, EF
AF Wulfkuhle, JD
   Aquino, JA
   Calvert, VS
   Fishman, DA
   Coukos, G
   Liotta, LA
   Petricoin, EF
TI Signal pathway profiling of ovarian cancer from human tissue specimens
   using reverse-phase protein microarrays
SO PROTEOMICS
LA English
DT Article
DE ovarian cancer; protein microarrays; signal transduction profiling
ID HUMAN-BREAST; ONCOGENE; TUMORS; CARCINOMAS; ACTIVATION; AKT2
AB Defects in cell signaling pathways play a central role in cancer cell growth, survival, invasion and metastasis. An important goal of proteomics is to characterize and develop "circuit maps" of these signaling pathways in normal and diseased cells. We have used reverse-phase protein array technology coupled with laser capture microdissection and phospho-specific antibodies to examine the activation status of several key molecular "gates" involved in cell survival and proliferation signaling in human ovarian tumor tissue. The levels of activated extracellular-regulated kinase (ERK1/2) varied considerably in tumors of the same histotype, but no significant differences between histotypes were observed. Advanced stage tumors had slightly higher levels of phosphorylated ERK1/2 compared to early stage tumors. The activation status of Akt and glycogen synthase kinase 3beta, key proteins and indicators of the state of the phosphatidylinositol 3-kinase/Akt pro-survival pathway also showed more variation within each histotype than between the histoypes studied. Our results demonstrate the utility of reverse phase protein microarrays for the multiplexed analysis of signal transduction from discreet cell populations of cells procured directly from human ovarian tumor specimens and suggest that patterns in signal pathway activation in ovarian tumors may be patient-specific rather than type or stage specific.
C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
   Food & Drug Adm, Bethesda, MD USA.
   Northwestern Univ, Sch Med, Chicago, IL 60611 USA.
   Univ Penn, Philadelphia, PA 19104 USA.
RP Wulfkuhle, JD (reprint author), NCI, Ctr Canc Res, Bldg 29A Room 2B20,8800 Rockville Pike, Bethesda, MD 20892 USA.
NR 18
TC 167
Z9 175
U1 1
U2 9
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD NOV
PY 2003
VL 3
IS 11
BP 2085
EP 2090
DI 10.1002/pmic.200300591
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 743PJ
UT WOS:000186582500003
PM 14595806
ER

PT J
AU Espina, V
   Mehta, AI
   Winters, ME
   Calvert, V
   Wulfkuhle, J
   Petricoin, EF
   Liotta, LA
AF Espina, V
   Mehta, AI
   Winters, ME
   Calvert, V
   Wulfkuhle, J
   Petricoin, EF
   Liotta, LA
TI Protein microarrays: Molecular profiling technologies for clinical
   specimens
SO PROTEOMICS
LA English
DT Review
DE catalyzed reporter deposition; individual targeted therapy; laser
   capture microdissection; molecular profiling; protein microarray; review
ID CATALYZED REPORTER DEPOSITION; LASER CAPTURE MICRODISSECTION; SIGNAL
   AMPLIFICATION; PROTEOMICS; CANCER; IMMUNOASSAY; MICROENVIRONMENT;
   DISEASE
AB Proteomics, the study of protein function within biologic systems, will further our understanding of cancer pathogenesis. Coupled with transcript profiling, proteomics can herald the advent of molecular therapy tailored to the individual patient's neoplasm. Protein microarrays, one emerging class of proteomic technologies, have broad applications for discovery and quantitative analysis. This technology is uniquely suited to gather information about the post-translational modifications of proteins reflecting the activity state of signal pathways and networks. Protein microarrays now make it feasible to conduct signal network profiling within cellular samples. Nevertheless, to be successful, design and use of protein microarrays must take into consideration enormous analytical challenges. A subclass of protein microarrays, Reverse Phase Arrays, created to meet these challenges, has been optimized for use with tissue specimens, and is now in use for the analysis of biopsy samples for clinical trial research.
C1 NCI, Pathol Lab, Ctr Canc Res,Food & Drug Adm, FDA,Clin Proteom Program,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
   Howard Hughes Med Inst, Bethesda, MD 20817 USA.
RP Espina, V (reprint author), NCI, Pathol Lab, Ctr Canc Res,Food & Drug Adm, FDA,Clin Proteom Program,Ctr Biol Evaluat & Res, Bldg 10 Room B1B53,9000 Rockville Pike, Bethesda, MD 20892 USA.
OI Espina, Virginia/0000-0001-5080-5972
NR 58
TC 163
Z9 172
U1 0
U2 15
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD NOV
PY 2003
VL 3
IS 11
BP 2091
EP 2100
DI 10.1002/pmic.200300592
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 743PJ
UT WOS:000186582500004
PM 14595807
ER

PT J
AU Grubb, RL
   Calvert, VS
   Wulkuhle, JD
   Paweletz, CP
   Linehan, WM
   Phillips, JL
   Chuaqui, R
   Valasco, A
   Gillespie, J
   Emmert-Buck, M
   Liotta, LA
   Petricoin, EF
AF Grubb, RL
   Calvert, VS
   Wulkuhle, JD
   Paweletz, CP
   Linehan, WM
   Phillips, JL
   Chuaqui, R
   Valasco, A
   Gillespie, J
   Emmert-Buck, M
   Liotta, LA
   Petricoin, EF
TI Signal pathway profiling of prostate cancer using reverse phase protein
   arrays
SO PROTEOMICS
LA English
DT Article
DE prostate cancer; protein microarrays; signal transduction profiling
AB Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phosphospecific endpoints revealed changes in cellular signaling events through disease progression and, between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy.
C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
   NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
   NCI, Ctr Canc Res, Pathol Lab, FDA Clin Proteom Program, Bethesda, MD 20892 USA.
   NCI, Pathol Lab, Clin Pathogenet Unit, Bethesda, MD 20892 USA.
   Catholic Univ Chile, Dept Urol, Santiago, Chile.
RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A Room 2D12,8800 Rockville Pike, Bethesda, MD 20892 USA.
NR 19
TC 143
Z9 155
U1 0
U2 5
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD NOV
PY 2003
VL 3
IS 11
BP 2142
EP 2146
DI 10.1002/pmic.200300598
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 743PJ
UT WOS:000186582500010
PM 14595813
ER

PT J
AU Seong, SY
   Choi, CY
AF Seong, SY
   Choi, CY
TI Current status of protein chip development in terms of fabrication and
   application
SO PROTEOMICS
LA English
DT Review
DE application; expression profiling; fabrication; immunodiagnosis;
   interaction profiling; microarray; protein chip; review
ID IN-VITRO SELECTION; MOLECULARLY IMPRINTED POLYMERS; ROLLING-CIRCLE
   AMPLIFICATION; LINKED-IMMUNOSORBENT-ASSAY; FREE TRANSLATION SYSTEM;
   AFFINITY RNA LIGANDS; ORIENTED IMMOBILIZATION; ANTIBODY MICROARRAY;
   BINDING-PROTEINS; SURFACE
AB Sequencing of the human genome revealed that more than 30 000 genes encode proteins comprising the human proteome. "Proteomics" can be defined as a field of research studying proteins in terms of their function, expression, structure, modification and their interaction in physiological and in pathological states. The concentration,. crucial in modification and interaction of proteins in cells, plasma, and in tissues are determining the phenotype of living organisms. Although fluctuation of protein concentration is essential to maintain homeostasis, protein expression levels are also pathognomonic features. Estimating protein concentration by analyzing the quantity of mRNA in cells through conventional technologies, such as DNA chips, does not provide precise values since the half-life and translation efficacy of mRNA is variable. In addition, polypeptides undergo post-translational modification. For these reasons, novel techniques are needed to analyze multiple proteins simultaneously using protein microarrays. In the near future, protein chips may allow construction of complete relational databases for metabolic and signal transduction pathways. This article reviews the current status of technologies for fabricating protein microarrays and their applications.
C1 Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul 110799, South Korea.
   NIAID, Cellular & Mol Immunol Lab, Bethesda, MD USA.
   NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Seong, SY (reprint author), Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul 110799, South Korea.
RI Seong, Seung Yong /J-2764-2012
NR 107
TC 63
Z9 66
U1 2
U2 27
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD NOV
PY 2003
VL 3
IS 11
BP 2176
EP 2189
DI 10.1002/pmic.200300609
PG 14
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 743PJ
UT WOS:000186582500014
PM 14595817
ER

PT J
AU Chesney, MA
   Chambers, DB
   Taylor, JM
   Johnson, LM
   Folkman, S
AF Chesney, MA
   Chambers, DB
   Taylor, JM
   Johnson, LM
   Folkman, S
TI Coping effectiveness training for men living with HIV: Results from a
   randomized clinical trial testing a group-based intervention
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE HIV; AIDS; coping; intervention; stress
ID STRESS-MANAGEMENT INTERVENTION; HUMAN-IMMUNODEFICIENCY-VIRUS; GAY MEN;
   POSITIVE EMOTIONS; UNITED-STATES; DISTRESS; EDUCATION; SURVIVAL;
   SUPPORT; PREDICTORS
AB Objective: This randomized clinical trial was designed to compare the effects of a theory-based coping effectiveness training (CET) intervention with an active informational control (HIV-Info) condition and a waiting-list control (WLC) condition on psychological distress and positive mood in HIV-seropositive gay men. Materials and Methods: The authors recruited 149 self-identified gay or bisexual men who were 21 to 60 years of age, reported depressed mood, and had CD4 levels of 200 to 700 cells/mm(3). CET and HIV-Info participants attended 10 90-minute group sessions during the 3-month intervention phase and six maintenance sessions over the remainder of the year. Participants were assessed at baseline and at 3, 6, and 12 months. Data were collected 1992 to 1994, before the introduction of HAART. Analyses were based on the 128 participants who completed the 3-month assessment. Results: After the 3-month intervention phase, when compared with HIV-Info, CET participants showed significantly greater decreases in perceived stress and burnout, and regression analyses indicated that significant increases in coping self-efficacy mediated the improvements in perceived stress and burnout. Compared with WLC, CET participants also showed significantly greater decreases in anxiety, and regression analyses indicated that significant increases in positive states of mind mediated the improvements in anxiety. Significant treatment group differences for positive morale were maintained at 6 and 12 months. In addition, optimism continued to increase in the CET and HIV-Info treatment groups during the maintenance phase. Conclusions: CET can be an effective strategy for managing psychological distress and improving positive psychological states in patients confronting chronic illness.
C1 Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA USA.
   Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
   Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA USA.
RP Chesney, MA (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
EM chesneym@mail.nih.gov
FU NIMH NIH HHS [R01-MH46805]
NR 54
TC 139
Z9 145
U1 2
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD NOV-DEC
PY 2003
VL 65
IS 6
BP 1038
EP 1046
DI 10.1097/01.PSY.0000097344.78697.ED
PG 9
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 748QK
UT WOS:000186872400016
PM 14645783
ER

PT J
AU Hall, HI
   Saraiya, M
   Thompson, T
   Hartman, A
   Glanz, K
   Rimer, B
AF Hall, HI
   Saraiya, M
   Thompson, T
   Hartman, A
   Glanz, K
   Rimer, B
TI Correlates of sunburn experiences among US adults: Results of the 2000
   National Health Interview Survey
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID SUN EXPOSURE; PROTECTION BEHAVIORS; MALIGNANT-MELANOMA; UNITED-STATES;
   SKIN-CANCER; POPULATION; SUNSCREENS; ATTITUDES
AB Objective. The purpose of this study was to determine the rate of sunburns in the U.S. adult population and the correlates of sunburns.
   Methods. Data from the 2000 National Health Interview Survey Cancer Control Module were used to calculate the number of sunburns (0, 1, 2, or greater than or equal to3) experienced during the past year by age, sex, race/ethnicity, and skin sensitivity to sun exposure. The relationship between no sunburns vs. one or more sunburns and additional demographic, health, and behavioral factors for adults who self-identify as white Hispanic or white non-Hispanic was assessed using general linear contrasts. Multivariate logistic regression modeling was conducted to determine the most important covariates associated with sunburns. All analyses were weighted for the complex sampling design.
   Results. The study data suggest that overall, 18.5% (95% confidence interval [CI] 17.9, 19.1) of U.S. adults experience one sunburn a year, 9.7% (95% CI 9.3, 10.1) experience two, and 8.0% (95% CI 7.6, 8.4) experience greater than or equal to3 sunburns. The data also indicate that adults who self-identify as white non-Hispanic experience sunburns more frequently than (in order of prevalence) those who identify as American Indian/Alaska Native, white Hispanic, Asian/Pacific Islander, or black. Sunburns were found to be more common among men than among women, more common among younger age groups than among older age groups, and more common among those with skin more prone to sunburn than among those with skin less prone to sunburn. Among individuals who self-identify as white Hispanic or white non-Hispanic, protective behaviors associated with lower rates of one or more sunburns in multivariate analyses are staying in the shade (odds ratio [OR] 0.73, 95% CI 0.66, 0.80) and wearing long-sleeved shirts (OR 0.86, 95% CI 0.75, 0.99).
   Conclusions. Many American adults have one or more sunburns per year. Methods to protect from sun exposure may not be used as needed to prevent sunburn.
C1 Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
   NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   Univ Hawaii, Canc Res Ctr Hawaii, Social & Behav Sci Program, Honolulu, HI 96822 USA.
RP Hall, HI (reprint author), CDC, Natl Ctr HIV STD & TB Prevent, 1600 Clifton Rd,MS E-47, Atlanta, GA 30333 USA.
NR 29
TC 28
Z9 31
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD NOV-DEC
PY 2003
VL 118
IS 6
BP 540
EP 549
DI 10.1016/S0033-3549(04)50290-X
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 754AT
UT WOS:000187281100007
PM 14563911
ER

PT J
AU Gray, LE
   Foster, PMD
AF Gray, LE
   Foster, PMD
TI Significance of experimental studies for assessing adverse effects of
   endocrine-disrupting chemicals
SO PURE AND APPLIED CHEMISTRY
LA English
DT Article; Proceedings Paper
CT Symposium on Implications of Endocrine Active Substances for Humans and
   Wildlife
CY NOV 17-21, 2002
CL YOKOHAMA, JAPAN
ID RAT UTEROTROPHIC BIOASSAY; ALTERS SEXUAL-DIFFERENTIATION; MALE
   REPRODUCTIVE DEVELOPMENT; ANDROGEN-RECEPTOR ANTAGONIST; MINNOW
   PIMEPHALES-PROMELAS; IN-UTERO EXPOSURE; DI(N-BUTYL) PHTHALATE;
   DOSE-RESPONSE; OECD PROGRAM; CELL-LINE
AB The U.S. Environmental Protection Agency (USEPA) is developing an endocrine disruptor screening and testing program to detect chemicals that alter hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen, and thyroid (EAT) hormone synthesis or metabolism and induce androgen (AR) and estrogen (ER) receptor-mediated effects in mammals and other animals. The utility of this approach is based upon the knowledge that mechanisms of endocrine-disrupting chemical (EDC) action are highly conserved at the cellular and molecular levels among vertebrates. Some EDC mechanisms also are shared with invertebrates. High-priority chemicals would be evaluated in a Tier 1 screening (T1S) battery, and chemicals that are positive in T1S would then be tested in Tier 2 (T2). T1S includes in vitro ER and AR receptor binding and/or gene expression, an assessment of steroidogenesis and mammalian (rat) and nonmammalian (fish) in vivo assays. In vivo, the uterotropic assay detects estrogens and antiestrogens, while steroidogenesis, antithyroid activity, antiestrogenicity, and HPG function are assessed in a pubertal female assay. Antiandrogens are detected in the Hershberger assay (weight of androgen-dependent tissues in castrate-immature-male rats). Fish and amphibian assays are also being developed to identify EDCs. Several alternative mammalian in vivo assays have been proposed. Of these, a short-term pubertal male rat assay appears most promising. T1S is designed to be sensitive to EAT activities, but many of the effects detected at the screening level would not be considered adverse, the dosage levels may be high, and the route of administration used may not be the most relevant. However, issues of adversity, dose response, and route(s) of exposure would be resolved in the testing phase. In addition to using an enhanced multigenerational test for Tier 2, an in utero-lactational screening protocol is also being evaluated by the USEPA for use in T2 or T1S. For T2, the numbers of endocrine-sensitive endpoints and offspring (F1) examined in multigenerational tests need to be expanded for EDCs in a thoughtful manner, based in part upon the results of T1S. In addition, for some chemicals histological examination of 10 adult F1 per sex in only the control and high-dose groups provides inadequate statistical power to detect low-dose lesions induced during development. In these cases, we propose that all the offspring be examined after puberty for gross and histological reproductive abnormalities. Since EDCs, like the phthalates and AR-antagonists, produce characteristic profiles, or syndromes, of adverse effects, data need to be reported in a manner that clearly identifies the proportion of animals displaying one or more of the abnormalities in a syndrome. Consideration should be given to tailoring T2, based on the results of T1S, to assure that all of the effects in such chemically induced developmental syndromes are included in the study.
C1 US EPA, Reprod Toxicol Div, NHEERL, Endocrinol Branch, Res Triangle Pk, NC 27711 USA.
   NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Gray, LE (reprint author), US EPA, Reprod Toxicol Div, NHEERL, Endocrinol Branch, 2525 Highway 54,MD 72, Res Triangle Pk, NC 27711 USA.
EM gray.earl@epa.gov
NR 60
TC 17
Z9 18
U1 0
U2 8
PU INT UNION PURE APPLIED CHEMISTRY
PI RES TRIANGLE PK
PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA
SN 0033-4545
J9 PURE APPL CHEM
JI Pure Appl. Chem.
PD NOV-DEC
PY 2003
VL 75
IS 11-12
BP 2125
EP 2141
DI 10.1351/pac200375112125
PG 17
WC Chemistry, Multidisciplinary
SC Chemistry
GA 764YG
UT WOS:000188233800037
ER

PT J
AU Selkirk, JK
   Tennant, RW
AF Selkirk, JK
   Tennant, RW
TI Toxicogenomics: Impact on human health
SO PURE AND APPLIED CHEMISTRY
LA English
DT Article; Proceedings Paper
CT Symposium on Implications of Endocrine Active Substances for Humans and
   Wildlife
CY NOV 17-21, 2002
CL YOKOHAMA, JAPAN
AB Toxicology is the science of adverse effects of chemicals, drugs, environmental agents, and stressors. Genomics defines the structure, sequence (code), and function of the entire DNA complement of organisms. The interface of these diverse disciplines is called toxicogenomics and is based upon the application of genomic technologies to define globally the changes in gene expression (both mRNA and proteins) as a consequence of exposures. DNA microarray technology enables the simultaneous measurement of transcription of thousands of genes using microchips containing thousands of probes of complementary DNA (cDNA) immobilized in a predetermined array. The ultimate application of this technology to toxicology holds great promise but faces several formidable problems. With the solution to these problems, it will be possible to develop a substantial database of Chemical Effects in Biological Systems (CEBS). Such a database will provide the capacity to relate specific changes in gene expression to specific adverse effects and to look for similar pathways in different organisms. Such data will provide an objective way of assessing surrogate systems for reporting or predicting potential adverse effects in humans. While the potential for toxicogenomics is thus very high for studying active substances, the task must be approached in a deliberate, incremental manner to insure that only high-quality data are compiled and analyzed. This workshop will present the latest results of research conducted in leading international laboratories studying endocrine-mediated toxicity.
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Selkirk, JK (reprint author), NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU INT UNION PURE APPLIED CHEMISTRY
PI RES TRIANGLE PK
PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA
SN 0033-4545
J9 PURE APPL CHEM
JI Pure Appl. Chem.
PD NOV-DEC
PY 2003
VL 75
IS 11-12
BP 2413
EP 2414
DI 10.1351/pac200375112413
PG 2
WC Chemistry, Multidisciplinary
SC Chemistry
GA 764YG
UT WOS:000188233800061
ER

PT J
AU Neeman, Z
AF Neeman, Z
TI Occipital condyle fractures in the pediatric population
SO RADIOGRAPHICS
LA English
DT Letter
ID LIGAMENT INJURY; CT; TRAUMA
C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA.
   Hadassah Univ Hosp, Dept Radiol, IL-91120 Jerusalem, Israel.
RP Neeman, Z (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, 10 Ctr Dr,Rm 1C 660, Bethesda, MD 20892 USA.
NR 15
TC 1
Z9 1
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0271-5333
J9 RADIOGRAPHICS
JI Radiographics
PD NOV-DEC
PY 2003
VL 23
IS 6
BP 1699
EP 1700
DI 10.1148/rg.236035138
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 741FG
UT WOS:000186447600028
PM 14615574
ER

PT J
AU Job, DE
   Whalley, HC
   McConnell, S
   Glabus, M
   Johnstone, EC
   Lawrie, SM
AF Job, DE
   Whalley, HC
   McConnell, S
   Glabus, M
   Johnstone, EC
   Lawrie, SM
TI Voxel-based morphometry of grey matter densities in subjects at high
   risk of schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE schizophrenia; grey matter; magnetic resonance imaging; voxel-based
   morphometry; statistical parametric mapping
ID EDINBURGH HIGH-RISK; GRAY-MATTER; HIPPOCAMPAL VOLUME; WHITE-MATTER;
   UNAFFECTED SIBLINGS; PSYCHOTIC SYMPTOMS; TWINS DISCORDANT; BRAIN
   VOLUMES; FETAL HYPOXIA; ABNORMALITIES
AB The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n = 146) were compared with normal control subjects (n = 36) and first episode schizophrenic subjects (n = 34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis. (C) 2003 Elsevier B.V. All rights reserved.
C1 Univ Edinburgh, Royal Edinburgh Hosp, Dept Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland.
   NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Job, DE (reprint author), Univ Edinburgh, Royal Edinburgh Hosp, Dept Psychiat, Moringside Pk, Edinburgh EH10 5HF, Midlothian, Scotland.
OI Job, Dominic/0000-0002-7829-7217; Whalley, Heather/0000-0002-4505-8869
NR 49
TC 148
Z9 149
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD NOV 1
PY 2003
VL 64
IS 1
BP 1
EP 13
DI 10.1016/S0920-9964(03)00158-0
PG 13
WC Psychiatry
SC Psychiatry
GA 729ZK
UT WOS:000185804600001
PM 14511796
ER

PT J
AU Bokat, CE
   Goldberg, TE
AF Bokat, CE
   Goldberg, TE
TI Letter and category fluency in schizophrenic patients: a meta-analysis
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE letter and category fluency; schizophrenia; meta-analysis
ID VERBAL FLUENCY; SEMANTIC FLUENCY; THOUGHT-DISORDER; MEMORY; DEFICITS;
   TASKS
AB Patients with schizophrenia typically demonstrate impairments on semantic and letter fluency tasks but it is possible that these tests demand subtly different cognitive processing: a lexical search based on phonology or orthography or a semantic search based on organization of semantic networks by dimension or attribute. Differences in the performance between these two tasks may imply whether deficits involve difficulties in accessing or traversing connectivities in the semantic system, as opposed to those based on linguistic units. In this meta-analysis, we reviewed 13 studies (N = 915) in an attempt to clarify whether schizophrenic patients are in fact differentially impaired in semantic fluency. Results from analyses indicated that schizophrenic patients are disproportionately deficient in category fluency (d = 1.23 for semantic and 1.01 for letter fluency with minimal overlap of confidence intervals of weighted d's) suggesting that compromises the semantic system may be present in schizophrenia and perhaps play a role in the symptomatic anomalies exhibited in this patient population. (C) 2002 Elsevier Science B.V. All rights reserved.
C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Room 4S 235,10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA.
NR 27
TC 123
Z9 125
U1 3
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD NOV 1
PY 2003
VL 64
IS 1
BP 73
EP 78
DI 10.1016/S0920-9964(02)00282-7
PG 6
WC Psychiatry
SC Psychiatry
GA 729ZK
UT WOS:000185804600008
PM 14511803
ER

PT J
AU Thorgeirsson, SS
   Grisham, JW
AF Thorgeirsson, SS
   Grisham, JW
TI Hepatic stem cells - Foreword
SO SEMINARS IN LIVER DISEASE
LA English
DT Editorial Material
C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 3
Z9 5
U1 0
U2 0
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0272-8087
J9 SEMIN LIVER DIS
JI Semin. Liver Dis.
PD NOV
PY 2003
VL 23
IS 4
BP 301
EP 301
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 757XZ
UT WOS:000187602400001
ER

PT J
AU Thorgeirsson, SS
   Grisham, JW
AF Thorgeirsson, SS
   Grisham, JW
TI Overview of recent experimental studies on liver stem cells
SO SEMINARS IN LIVER DISEASE
LA English
DT Review
DE liver stem cells; hepatocytes; cholangiocytes
ID EPITHELIAL PROGENITOR CELLS; HEPATOCYTE-LIKE CELLS; WB-F344 RAT-LIVER;
   BONE-MARROW TRANSPLANTATION; IN-VITRO DIFFERENTIATION;
   RETRORSINE-EXPOSED RATS; OVAL CELLS; FETAL LIVER; MOUSE EMBRYOS;
   ADULT-RAT
C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bldg 37,Rm 4146A1,37 Convent Dr,MSC4262, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
NR 80
TC 51
Z9 56
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0272-8087
J9 SEMIN LIVER DIS
JI Semin. Liver Dis.
PD NOV
PY 2003
VL 23
IS 4
BP 303
EP 312
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 757XZ
UT WOS:000187602400002
PM 14722808
ER

PT J
AU Jonas, BS
   Brody, D
   Roper, M
   Narrow, WE
AF Jonas, BS
   Brody, D
   Roper, M
   Narrow, WE
TI Prevalence of mood disorders in a national sample of young American
   adults
SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
LA English
DT Article
DE mood disorders; prevalence; depression; dysthymia; bipolar disorder;
   Diagnostic Interview Schedule; NHANES III
ID RESEARCH DIAGNOSTIC-CRITERIA; PROSPECTIVE RISK-FACTOR; UNITED-STATES
   ADULTS; MAJOR DEPRESSION; MENTAL-DISORDERS; GENERAL-POPULATION;
   FOLLOW-UP; DSM-III; SYMPTOMS; HYPERTENSION
AB Background Availability of nationally representative mood disorder prevalence estimates in the United States, based on structured psychiatric interviews is limited. This report estimates overall lifetime prevalence of major depressive episode, dysthymia, and bipolar disorder using the Third National Health and Nutrition Examination Survey (NHANES III) and compares these estimates to the Epidemiologic Catchment Area Study (ECA) conducted 10 years earlier. Additionally, prevalence estimate breakdowns by selected sociodemographic and health characteristics are investigated. Methods NHANES III, conducted from 1988 to 1994, is a large nationally representative cross-sectional sample of the United States. A population-based sample of 8,602 men and women 17-39 years of age were eligible to participate, of whom 7,667 (89.1 %) completed interviews. Mood disorder assessments came from the Diagnostic Interview Schedule (DIS) administered as one component of the NHANES III. Results Lifetime prevalence estimates were assessed for six mood measures: 1) major depressive episode (MDE) 8.6%, 2) major depressive episode with severity (MDE-s) 7.7%, 3) dysthymia 6.2%, 4) MDE-s with dysthymia 3.4%, 5) any bipolar disorder 1.6%, and 6) any mood disorder 11.5%. All estimates except for MDE and MDE-s were significantly higher than comparable ECA estimates. Conclusions These data provide recent national prevalence estimates. Based on their overall magnitudes, subgroup excesses, and observed increases compared to the ECA, continued monitoring of these estimates is warranted.
C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Off Anal Epidemiol & Hlth Promot, Hyattsville, MD 20782 USA.
   NIMH, Bethesda, MD 20892 USA.
   Amer Psychiat Inst Res & Educ, Arlington, VA USA.
RP Jonas, BS (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Off Anal Epidemiol & Hlth Promot, Room 6433,3311 Toledo Rd, Hyattsville, MD 20782 USA.
RI Langan Martin, Julie/M-4658-2015
NR 42
TC 50
Z9 54
U1 1
U2 5
PU DR DIETRICH STEINKOPFF VERLAG
PI DARMSTADT
PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY
SN 0933-7954
J9 SOC PSYCH PSYCH EPID
JI Soc. Psychiatry Psychiatr. Epidemiol.
PD NOV
PY 2003
VL 38
IS 11
BP 618
EP 624
DI 10.1007/s00127-003-0682-8
PG 7
WC Psychiatry
SC Psychiatry
GA 742XF
UT WOS:000186542800003
PM 14614549
ER

PT J
AU Dyda, F
   Hickman, AB
AF Dyda, F
   Hickman, AB
TI A mob of reps
SO STRUCTURE
LA English
DT Editorial Material
ID PROTEINS; BINDING; DNA
AB Emerging structural results confirm that the large Rolling Circle Replication initiator superfamily is composed of two classes of proteins that are circularly permutated with respect to each other, as initially suggested by sequence analysis. The two classes are united by the same endonucleolytic mechanism and a conserved Mg2+ binding site containing multiple histidine ligands unique to this superfamily.
C1 NIDDK, Mol Biol Lab, HHS, NIH, Bethesda, MD 20892 USA.
RP Dyda, F (reprint author), NIDDK, Mol Biol Lab, HHS, NIH, Bldg 5,Room 303, Bethesda, MD 20892 USA.
NR 7
TC 9
Z9 10
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD NOV
PY 2003
VL 11
IS 11
BP 1310
EP 1311
DI 10.1016/j.str.2003.10.010
PG 2
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 741RQ
UT WOS:000186472500002
PM 14604517
ER

PT J
AU Lovblad, KO
   El-Koussy, M
   Oswald, H
   Baird, AE
   Schroth, G
   Mattle, H
AF Lovblad, KO
   El-Koussy, M
   Oswald, H
   Baird, AE
   Schroth, G
   Mattle, H
TI Magnetic resonance imaging of the ischaemic penumbra
SO SWISS MEDICAL WEEKLY
LA English
DT Review
DE penumbra; ischaemia; stroke thrombolysis; magnetic resonance imaging;
   diffusion; perfusion
ID APPARENT DIFFUSION-COEFFICIENT; CEREBRAL-BLOOD-FLOW; TISSUE-PLASMINOGEN
   ACTIVATOR; PERFUSION-WEIGHTED MRI; LOCAL INTRAARTERIAL THROMBOLYSIS;
   POSITRON-EMISSION-TOMOGRAPHY; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS
   PASSAGES; ACUTE STROKE PATIENTS; COMPUTED-TOMOGRAPHY
AB Acute cerebral ischaemia should no longer be considered a tragic untreatable event but a medical emergency. To be able to start therapy, imaging is needed to assess the presence of a potential penumbra, i.e. an area of the brain which is bypoperfused but not yet definitively infarcted. With the development of diffilsion and perfusion MR techniques, the concept of a penumbra model has been developed in which it corresponds to the acute mismatch between diffusion and perfusion volumes. This penumbra should constitute the target for potential therapies.
C1 Univ Bern, Inselspital, Dept Neuroradiol, CH-3010 Bern, Switzerland.
   TSyst, Bern, Switzerland.
   Univ Bern, Inselspital, Dept Neurol, CH-3010 Bern, Switzerland.
   NINDS, Stroke Neurosci Unit, Bethesda, MD 20892 USA.
RP Lovblad, KO (reprint author), Univ Geneva, Hop Cantonal, 24 Rue Micheli Du Crest, CH-1211 Geneva 14, Switzerland.
NR 70
TC 6
Z9 11
U1 0
U2 0
PU E M H SWISS MEDICAL PUBLISHERS LTD
PI BASEL
PA STEINENTORSTRASSE 13, CH-4-10 BASEL, SWITZERLAND
SN 1424-7860
J9 SWISS MED WKLY
JI Swiss Med. Wkly.
PD NOV 1
PY 2003
VL 133
IS 41-42
BP 551
EP 559
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 757DA
UT WOS:000187532500001
PM 14691726
ER

PT J
AU Shimoji, K
   Esaki, T
   Itoh, Y
   Ravasi, L
   Cook, M
   Jehle, J
   Jagoda, EM
   Kiesewetter, DO
   Schmidt, K
   Sokoloff, L
   Eckelman, WC
AF Shimoji, K
   Esaki, T
   Itoh, Y
   Ravasi, L
   Cook, M
   Jehle, J
   Jagoda, EM
   Kiesewetter, DO
   Schmidt, K
   Sokoloff, L
   Eckelman, WC
TI Inhibition of [F-18]FP-TZTP binding by loading doses of muscarinic
   agonists P-TZTP or FP-TZTP in vivo is not due to agonist-induced
   reduction in cerebral blood flow
SO SYNAPSE
LA English
DT Article
DE M2 muscarinic receptors; [(18F)]FP-TZTP; inhibition study;
   [(14)-C]iodo-antipyrine method
ID RAT-BRAIN; ALZHEIMERS-DISEASE; CHOLINERGIC SYSTEMS; RECEPTOR SUBTYPES;
   NUCLEUS BASALIS; M2; AUTOREGULATION; ACETYLCHOLINE; LOCALIZATION;
   STIMULATION
AB [F-18][3-(3-(3-Fluoropropyl)thio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine ( [F-18]FP-TZTP) is an M2 selective muscarinic agonist that may allow noninvasive studies of Alzheimer's disease with PET. 3-(3-(Propylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpylidine (P-TZTP), a nonfluorinated analog of FPT-ZTP, and unlabeled FP-TZTP inhibited [F-18] FP-TZTP binding in vivo. Because muscarinic action of the loading dose of P-TZTP administered might have had pharmacological effects, the apparent inhibition might have resulted from reduced delivery rather than competition with receptor-binding. Therefore, we examined the effects of P-TZTP or FP-TZTP administration on cerebral blood flow (CBF) measured by the [C-14]iodoantipyrine method and laser-Doppler flowmetry in rats. Statistically significant synchronous decreases in both CBF and mean arterial blood pressure (MABP) were observed within the first minute following administration. The decreases in both CBF and MABP were prevented by pretreatment With atropine methyl bromide (M-At), a peripheral muscarinic antagonist, and coadministration of M-At with either FP-TZTP or P-TZTP resulted in the same degree of inhibition of cerebral [F-18]FP-TZTP-uptake 30 min after administration as observed without M-At. Also, with programmed infusions designed to produce constant arterial concentrations of [F-18]FP-TZTP-and FP-TZTP, which avoid changes in CBF, significant inhibition of [F-18]FP-TZTP-binding by FP-TZTP was observed. These results indicate that inhibition of [F-18]FP-TZTP-binding in the brain by P-TZTP or FP-TZTP in vivo occurs independently of their effects on CBF. The methods employed here may also be of interest to evaluate physiological effects of blocking agents utilized to validate other radiopharmaceuticals. Published 2003 Wiley-Liss, Inc.(dagger).
C1 NIMH, Positron Emiss Tomog Dept, Ctr Clin, NIH, Bethesda, MD 20892 USA.
   NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA.
   Univ Milan, Inst Sci Radiol, Milan, Italy.
RP Eckelman, WC (reprint author), NIMH, Positron Emiss Tomog Dept, Ctr Clin, NIH, Bldg 10,Room 1C495,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA.
NR 39
TC 8
Z9 8
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD NOV
PY 2003
VL 50
IS 2
BP 151
EP 163
DI 10.1002/syn.10257
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 723NY
UT WOS:000185439500008
PM 12923818
ER

PT J
AU Aikens, CM
   Webb, SP
   Bell, RL
   Fletcher, GD
   Schmidt, MW
   Gordon, MS
AF Aikens, CM
   Webb, SP
   Bell, RL
   Fletcher, GD
   Schmidt, MW
   Gordon, MS
TI A derivation of the frozen-orbital unrestricted open-shell and
   restricted closed-shell second-order perturbation theory analytic
   gradient expressions
SO THEORETICAL CHEMISTRY ACCOUNTS
LA English
DT Article
DE analytic derivative; Moller-Plesset perturbation theory; frozen core
ID CORRELATED WAVE-FUNCTIONS; MAIN-GROUP ELEMENTS; COUPLED-CLUSTER;
   ELECTRONIC-STRUCTURE; ENERGY GRADIENTS; EXCITED-STATES; BASIS SETS;
   IMPLEMENTATION; SILICOCENE; COMPOUND
AB A detailed derivation of the frozen-orbital second-order perturbation theory (MP2) analytic gradient in the spin-orbital basis is presented. The summation ranges and modification of the MP2 gradient terms that result from the frozen-orbital approximation are clearly identified. The frozen-orbital analytic gradients for unrestricted MP2 and closed-shell MP2 are determined from the spin-orbital derivation. A discussion of useful implementation procedures is included. Timings from full and frozen-orbital MP2 gradient calculations on the molecule silicocene (the silicon analog of the sandwich compound ferrocene) are also presented.
C1 Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
   Iowa State Univ, Ames Lab, Ames, IA 50011 USA.
   NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA.
   Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA.
   NASA, ELORET Corp, Ames Res Ctr, Moffett Field, CA 94035 USA.
RP Gordon, MS (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
EM mark@si.fi.ameslab.gov
OI Aikens, Christine/0000-0002-0854-7997
NR 35
TC 117
Z9 118
U1 3
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1432-881X
J9 THEOR CHEM ACC
JI Theor. Chem. Acc.
PD NOV
PY 2003
VL 110
IS 4
BP 233
EP 253
DI 10.1007/s00214-003-0453-3
PG 21
WC Chemistry, Physical
SC Chemistry
GA 742XH
UT WOS:000186543000001
ER

PT J
AU Heindel, JJ
   Zoeller, RT
AF Heindel, JJ
   Zoeller, RT
TI Thyroid hormone and brain development: Translating molecular mechanisms
   to population risk
SO THYROID
LA English
DT Editorial Material
ID FETAL-RAT BRAIN; POLYCHLORINATED-BIPHENYLS; PCB EXPOSURE; EXPRESSION;
   RECEPTOR; RC3/NEUROGRANIN; DEFICIENCY; DEIODINASE; PREGNANCY; CHILDREN
C1 NIEHS, Div Extramural Res & Training, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
   Univ Massachusetts, Dept Biol, Amherst, MA USA.
RP Heindel, JJ (reprint author), NIEHS, Div Extramural Res & Training, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 31
TC 9
Z9 9
U1 1
U2 2
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD NOV
PY 2003
VL 13
IS 11
BP 1001
EP 1004
DI 10.1089/105072503770867165
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 746TC
UT WOS:000186762900001
PM 14651783
ER

PT J
AU Tchounwou, PB
   Patlolla, AK
   Centeno, JA
AF Tchounwou, PB
   Patlolla, AK
   Centeno, JA
TI Carcinogenic and systemic health effects associated with arsenic
   exposure - A critical review
SO TOXICOLOGIC PATHOLOGY
LA English
DT Review
DE arsenic pollution; human exposure; molecular mechanisms; systemic health
   effects; carcinogenicity
ID TUMOR-SUPPRESSOR GENE; MONOMETHYLARSONOUS ACID MMA(III); INDUCED
   CELL-TRANSFORMATION; HAMSTER EMBRYO CELLS; DISEASE ENDEMIC AREA;
   ARTESIAN WELL WATER; DRINKING-WATER; SODIUM ARSENITE; WEST-BENGAL;
   DIMETHYLARSINIC ACID
AB Arsenic and arsenic containing compounds are human carcinogens. Exposure to arsenic occurs occupationally in several industries, including mining, pesticide, pharmaceutical, glass and microelectronics, as well as environmentally from both industrial and natural sources. Inhalation is the principal route of arsenic exposure in occupational settings, while ingestion of contaminated drinking water is the predominant source of significant environmental exposure globally. Drinking water contamination by arsenic remains a major public health problem. Acute and chronic arsenic exposure via drinking water has been reported in many countries of the world, where a large proportion of drinking water is contaminated with high concentrations of arsenic. General health effects that are associated with arsenic exposure include cardiovascular and peripheral vascular disease, developmental anomalies, neurologic and neurobehavioural disorders, diabetes, hearing loss, portal fibrosis, hematologic disorders ( anemia, leukopenia and eosinophilia) and multiple cancers: significantly higher standardized mortality rates and cumulative mortality rates for cancers of the skin, lung, liver, urinary bladder, kidney, and colon in many areas of arsenic pollution. Although several epidemiological studies have documented the sources of exposure and the global impact of arsenic contamination, the mechanisms by which arsenic induces health effects, including cancer, are not well characterized. Further research is needed to provide a better understanding of the pathobiology of arsenic-induced diseases and to better define the toxicologic pathology of arsenic in various organ systems. In this review, we provide and discuss the underlying pathology and nature of arsenic-induced lesions. Such information is critical for understanding the magnitude of health effects associated with arsenic exposure throughout the world.
C1 Jackson State Univ, NIH, Ctr Environm Hlth, Mol Toxicol Res Lab,Sch Sci & Technol, Jackson, MS 39217 USA.
   Dept Armed Forces Inst Pathol, Washington, DC USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, NIH, Ctr Environm Hlth, Mol Toxicol Res Lab,Sch Sci & Technol, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA.
RI 张, 楠/B-1010-2010
FU NCRR NIH HHS [1G12RR13459]
NR 182
TC 162
Z9 176
U1 6
U2 55
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD NOV-DEC
PY 2003
VL 31
IS 6
BP 575
EP 588
DI 10.1080/01926230390242007
PG 14
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 737AF
UT WOS:000186205900001
PM 14585726
ER

PT J
AU Vaidya, VS
   Shankar, K
   Lock, EA
   Dixon, D
   Mehendale, HM
AF Vaidya, VS
   Shankar, K
   Lock, EA
   Dixon, D
   Mehendale, HM
TI Molecular mechanisms of renal tissue repair in survival from acute renal
   tubule necrosis: Role of ERK1/2 pathway
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article; Proceedings Paper
CT 42nd Annual Meeting of the Society-of-Toxicology
CY MAR 09-13, 2003
CL SALT LAKE CITY, UTAH
SP Soc Toxicol
DE renal tubular necrosis; cytokines; ERK1/2 pathway; tissue repair; growth
   factors; nephrotoxicity
ID KINASE SIGNAL-TRANSDUCTION; GROWTH-FACTOR RECEPTOR; CELL-SURFACE; MAP
   KINASE; KIDNEY; EXPRESSION; PROTEIN; INJURY; INTERLEUKIN-6; CYTOKINES
AB Our earlier studies with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) showed that prior administration of a low priming dose of 15 mg/kg, IP to mice, given 72 hours before administration of a normally lethal dose of DCVC ( 75 mg/kg, IP) led to renal tubule necrosis, however sustained renal tubule regeneration was observed and these mice recovered from renal failure and survived. The objective of the present study was to investigate the role of extracellular signal-regulated kinase (ERK) pathway in this autoprotection model. Following the priming dose of DCVC, IL-6 protein and mRNA increased markedly as early as 1 hour after dosing, peaking at 3 hours with a 1.5-fold increase in plasma. Immunocytochemistry on kidney sections using specific antibodies against TGF-alpha, HB-EGF, EGFr, IGF-1Rbeta, Grb-2, and phospho-p44/42 MAP kinase (ERK1/2) revealed a significantly higher staining of these molecules 3 to 72 hours after dosing, indicating up regulation of the ERK pathway. Following a lethal dose of DCVC (75 mg/kg) the early increase in these signaling molecules was not sustained, being markedly reduced 24 and 36 hours after dosing, leading to inhibition of S- phase DNA synthesis, cell division and renal tubule repair. In contrast, prior treatment with a low dose of DCVC, followed by a high dose led to a sustained stimulation of the renal ERK pathway, renal tubule regeneration and recovery from acute renal failure. These results suggest that a sustained activation of the ERK1/2 pathway may be a key factor in enabling a continued renal tubule repair and hence protection from the progressive phase of DCVC-induced acute renal tubular necrosis in the mouse.
C1 Univ Louisiana Monroe, Coll Hlth Sci, Sch Pharm, Dept Toxicol, Monroe, LA 71209 USA.
   Syngenta, Cent Toxicol Lab, Macclesfield, Cheshire, England.
   NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA.
RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Hlth Sci, Sch Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall Rm 306, Monroe, LA 71209 USA.
FU NIDDK NIH HHS [DK-61650]
NR 38
TC 25
Z9 28
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD NOV-DEC
PY 2003
VL 31
IS 6
BP 604
EP 618
DI 10.1080/01926230390241945
PG 15
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 737AF
UT WOS:000186205900003
PM 14585728
ER

PT J
AU Long, PH
   Herbert, RA
   Peckham, JC
   Grumbein, SL
   Shackelford, CC
   Abdo, K
AF Long, PH
   Herbert, RA
   Peckham, JC
   Grumbein, SL
   Shackelford, CC
   Abdo, K
TI Morphology of nasal lesions in F344/N rats following chronic inhalation
   exposure to naphthalene vapors
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE naphthalene; rat; olfactory; inhalation; toxicity; carcinogenicity;
   neuroblastoma; adenoma
ID POLYCYCLIC AROMATIC-HYDROCARBONS; RESPIRATORY-TRACT; MICE; TOXICITY;
   CARCINOGENICITY; ACETALDEHYDE; GENOTOXICITY; HAMSTERS; TUMORS; CAVITY
AB Naphthalene (CAS No. 91-20-3) administered by inhalation at concentrations of 10, 30, or 60 ppm for 6 hours per day, 5 days per week for 105 weeks caused nonneoplastic and neoplastic effects in nasal respiratory and olfactory regions of male and female F344/N rats. Non-neoplastic nasal effects were characterized by an increase in the incidence and severity of a complex group of lesions, including atypical hyperplasia, atrophy, chronic inflammation, and hyaline degeneration of olfactory epithelium; hyperplasia, squamous metaplasia, hyaline degeneration, and goblet cell hyperplasia of the respiratory epithelium; and hyperplasia and squamous metaplasia of mucosal glands. Neoplastic effects were characterized by the induction of two types of rare primary nasal tumors, olfactory neuroblastomas and respiratory epithelial adenomas. The incidences of olfactory neuroblastomas in males at 0 ppm, 10 ppm, 30 ppm, and 60 ppm were, respectively, 0%, 0%, 8%, and 6%, whereas in females they were 0%, 4%, 6%, and 24%. The incidences of respiratory epithelial adenomas in males at 0 ppm, 10 ppm, 30 ppm, and 60 ppm were, respectively, 0%, 12%, 17%, and 31% and in females 0%, 0%, 8%, and 4%. The olfactory neuroblastomas and respiratory epithelial adenomas were considered carcinogenic effects related to naphthalene exposure based on their relatively high incidence in exposed rats, their absence in concurrent control rats and NTP historical controls, and their rare spontaneous occurrence in rats of any strain.
C1 Pathol Associates Inc, W Chester, OH 45069 USA.
   NIEHS, Res Triangle Pk, NC 27709 USA.
   Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA.
   Battelle NW Labs, Richland, WA 99352 USA.
RP Long, PH (reprint author), Pathol Associates Inc, 6217 Centre Pk Dr, W Chester, OH 45069 USA.
NR 30
TC 22
Z9 22
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD NOV-DEC
PY 2003
VL 31
IS 6
BP 655
EP 664
DI 10.1080/01926230390242016
PG 10
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 737AF
UT WOS:000186205900009
PM 14585734
ER

PT J
AU Haseman, JK
   Ney, E
   Nyska, A
   Rao, GN
AF Haseman, JK
   Ney, E
   Nyska, A
   Rao, GN
TI Effect of diet and animal care/housing protocols on body weight,
   survival, tumor incidences, and nephropathy severity of F344 rats in
   chronic studies
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE NIH-07 diet; NTP-2000 diet; housing; animal care; body weight; survival;
   F344 rats; tumor incidence; nephropathy; rodent carcinogenicity studies
ID FISCHER-344 RATS; LONG-TERM; CORN-OIL; INCREASED CARCINOGENICITY; RODENT
   CARCINOGENICITY; TOXICOLOGY; MICE; NTP-2000; PROTEIN; GROWTH
AB Diet is an important environmental factor affecting body weight, survival, and age-related diseases of rodents. The NIH-07 open formula diet was the diet used in the National Toxicology Program's (NTPs) rodent carcinogenicity studies from 1980 to 1994. In 1994 the NTP began using a new diet designated the NTP-2000 diet. This paper compares body weight, survival, tumor incidence, and nephropathy severity in untreated control groups of Fischer 344 (F344) rats fed the NTP-2000 or NIH-07 diets, using data from 22 separate 2-year feed and inhalation studies. The feed studies were conducted in 3 different facilities, and all the inhalation studies were conducted in a single facility. During feed studies, rats were group housed in polycarbonate cages and fed diets in powder (mash) form, while in inhalation studies, rats were housed individually in wire mesh cages, and fed diets in pelleted form. Survival was significantly (p < 0.05) higher in groups fed NTP-2000 diet compared to the corresponding groups fed NIH-07 diet, irrespective of sex or housing conditions. Use of the NTP-2000 diet was also associated with a decreased incidence of pituitary gland tumors in both sexes and decreased incidences of adrenal pheochromocytoma and preputial gland tumors in males. The incidence and severity of nephropathy was also decreased in animals receiving the NTP-2000 diet, especially males. The decreased nephropathy severity and the decreased incidence of pituitary gland tumors are likely the major factors contributing to the improved survival of rats receiving the NTP-2000 diet relative to those given the NIH-07 diet. These data also support earlier findings that decreased incidences of adrenal pheochromocytoma are associated with reduced nephropathy severity in male F344 rats. Throughout the two-year study female rats receiving the NTP-2000 diet were significantly (p < 0.05) lighter than those receiving the NIH-07 diet. However, it is uncertain if this difference can be attributed to the NTP-2000 diet, since implementation of this diet by the NTP approximately coincided with changes in the F344 rat production colony that resulted in somewhat lighter animals being provided to the NTP. Controls from inhalation studies and feed studies differed significantly (p < 0.01) in the incidence of a variety of tumors, irrespective of diet. This suggests that differences in animal care and housing protocols may impact tumor incidence in F344 rats, most notably pituitary gland and testis tumors.
C1 NIEHS, Biostat Branch, Environm Dis & Med Program, Res Triangle Pk, NC 27709 USA.
   NIEHS, Lab Expt Pathol, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Haseman, JK (reprint author), NIEHS, Biostat Branch, Environm Dis & Med Program, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA.
NR 40
TC 36
Z9 36
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD NOV-DEC
PY 2003
VL 31
IS 6
BP 674
EP 681
DI 10.1080/01926230390241927
PG 8
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 737AF
UT WOS:000186205900011
PM 14585736
ER

PT J
AU Haseman, JK
AF Haseman, JK
TI Response to Waddell & Rozman
SO TOXICOLOGIC PATHOLOGY
LA English
DT Letter
ID EXPERIMENTS TELLING US; CHEMICAL CARCINOGENESIS; THRESHOLDS
C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Haseman, JK (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 11
TC 2
Z9 2
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD NOV-DEC
PY 2003
VL 31
IS 6
BP 715
EP 716
DI 10.1080/01926230390257975
PG 2
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 737AF
UT WOS:000186205900019
ER

PT J
AU He, B
   Rhodes-Brower, S
   Miller, MR
   Munson, AE
   Germolec, DR
   Walker, VR
   Korach, KS
   Meade, BJ
AF He, B
   Rhodes-Brower, S
   Miller, MR
   Munson, AE
   Germolec, DR
   Walker, VR
   Korach, KS
   Meade, BJ
TI Octamethylcyclotetrasiloxane exhibits estrogenic activity in mice via ER
   alpha
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE octamethylcyclotetrasiloxane; estrogenic activity; uterotrophic assays;
   estrogen receptors; ERKO; ICI 182,780
ID ACTIVATED PROTEIN-KINASE; PURE-ANTIESTROGEN; FISCHER-344 RATS;
   METABOLIZING-ENZYMES; INHALATION EXPOSURE; RECEPTOR; BETA; GENE;
   PHOSPHORYLATION; EXPRESSION
AB Octamethylcyclotetrasiloxane (D4) is a low molecular weight cyclic silicone used in the synthesis of larger silicone polymers and in the formulation of a variety of personal care products. The effects of oral D4 exposure in mice on serum estradiol levels, uterine wet weight, and uterine peroxidase activity were investigated. Additionally, in vitro estrogen receptor binding activity was evaluated. Serum estradiol levels decreased in a dose-dependent manner after exposure to 100 mg/kg to 1000 mg/kg D4. Studies with adrenalectomized animals demonstrated that the decreased serum estradiol levels were not due to elevated serum corticosterone levels. Uterine wet weights in ovariectomized mice were significantly increased in a dose-dependent manner by exposure to 250-1000 mg of D4/kg, but not by exposure to other silicone compounds tested (hexamethylcyclotrisiloxane, decamethylcyclopentasiloxane, decamethyltetrasiloxane, and octaphenyl-cyclotetrasiloxane). Uterine peroxidase activity, a marker for estrogenic activity, was also significantly increased in D4-exposed mice, but not in mice exposed to the other siloxanes. Pretreating mice with the estrogen receptor antagonist ICI 182,780 completely blocked the D4-induced increase in uterine weight, and ovariectomized estrogen receptor-alpha knockout mice showed no increases in uterine weights when orally exposed to D4 or estradiol. In an in vitro estrogen receptor binding assay, D4 showed significant competition with H-3-estradiol for binding to estrogen receptor-alpha, but not estrogen receptor-beta. The data presented here indicate that D4 has weak estrogenic activity, and that these effects are mediated through estrogen receptor-alpha. (C) 2003 Elsevier Inc. All rights reserved.
C1 Off Director, Natl Inst Occupat Safety & Hlth, Morgantown, WV 26505 USA.
   W Virginia Univ, Dept Biochem & Mol Pharmacol, Morgantown, WV 26506 USA.
   Hlth Effects Lab Div, Morgantown, WV 26505 USA.
   NIEHS, Res Triangle Pk, NC 27709 USA.
RP Meade, BJ (reprint author), 1095 Willowdale Rd,MS 4020, Morgantown, WV 26505 USA.
OI Korach, Kenneth/0000-0002-7765-418X
FU NIEHS NIH HHS [Y1-ES-0001-02]
NR 33
TC 38
Z9 47
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD NOV 1
PY 2003
VL 192
IS 3
BP 254
EP 261
DI 10.1016/S0041-008X(03)00282-5
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 739MX
UT WOS:000186352000007
PM 14575643
ER

PT J
AU Lee, JL
   Mukhtar, H
   Bickers, DR
   Kopelovich, L
   Athar, M
AF Lee, JL
   Mukhtar, H
   Bickers, DR
   Kopelovich, L
   Athar, M
TI Cyclooxygenases in the skin: pharmacological and toxicological
   implications
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Review
ID PROSTAGLANDIN-E RECEPTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SYSTEMIC
   IMMUNE SUPPRESSION; POLYUNSATURATED FATTY-ACID; FISH-OIL
   SUPPLEMENTATION; GREEN TEA POLYPHENOLS; KINASE-C-ALPHA; FACTOR-KAPPA-B;
   MOUSE SKIN; HUMAN KERATINOCYTES
AB Cyclooxygenase (COX), a prostaglandin-endoperoxide synthase (PTGS), catalyzes the formation of prostaglandins from arachidonic acid. Prostaglandins are lipid signaling mediators that play a central role in a broad range of diverse physiological and pathophysiological processes, including inflammation, reproduction, nocioception, and gastrointestinal protection. Inhibition of cyclooxygenase activity is the mechanism by which nonsteroidal antiinflammatory drugs (NSAIDS) exert their analgesic, antipyretic, antiinflammatory, and antithrombotic effects. COX is currently believed to exist in three isoforms. In this review, we provide a concise state-of-the-art description of the role of COX in pharmacology and toxicology of skin including its involvement in normal physiology, cutaneous inflammation, nociception, wound healing, and tumorigenesis. COX-dependent pathways influence keratinocyte differentiation, hair follicle development, and hair growth. The critical role of COX-2 in pathophysiology of skin is also addressed. COX-2 mediates inflammatory processes in skin, including inflammatory hyperalgesia and nociception, and administration of specific COX-2 inhibitors reduces edema, vascular permeability, and other markers of cutaneous inflammation. A number of studies in animal models and in humans show that COX-2 inhibitors possess cancer chemopreventive properties. Selective COX-2 inhibitors have a more favorable side-effect profile. Topical formulations of COX-2 inhibitors are being developed as a novel pharmacologic approach for the treatment of COX-2 mediated skin diseases. (C) 2003 Elsevier Inc. All rights reserved.
C1 Columbia Univ, Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA.
   Univ Wisconsin, Sch Med, Madison, WI USA.
   NCI, Div Canc Prevent, Bethesda, MD 20892 USA.
RP Athar, M (reprint author), Columbia Univ, Coll Phys & Surg, Dept Dermatol, 630 W 168th St, New York, NY 10032 USA.
FU NCI NIH HHS [N01-CN-35105, U19 CA 81888, N01-CN-35006-72, CA-10106-01,
   N01-CN-15011-72, N01-CN-15109, R01 CA-97249-01]; NIAMS NIH HHS [P30 AR
   44535]
NR 114
TC 113
Z9 117
U1 2
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD NOV 1
PY 2003
VL 192
IS 3
BP 294
EP 306
DI 10.1016/S0041-008X(03)00301-6
PG 13
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 739MX
UT WOS:000186352000011
PM 14575647
ER

PT J
AU Pomper, GJ
   Rick, ME
   Epstein, JS
   Read, EJ
   Leitman, SE
AF Pomper, GJ
   Rick, ME
   Epstein, JS
   Read, EJ
   Leitman, SE
TI Management of severe VWD with cryoprecipitate collected by repeated
   apheresis of a single dedicated donor
SO TRANSFUSION
LA English
DT Article
ID PLASMA-EXCHANGE DONATION; VON-WILLEBRAND-DISEASE; SEVERE VONWILLEBRAND
   DISEASE; FACTOR-VIII; DDAVP
AB BACKGROUND: Rare and severe forms of VWD are associated with trace or absent VWF. The feasibility of supporting a child with severe VWD from birth through age 12 with cryoprecipitate derived from DDAVP-stimulated plasma exchange of a single dedicated donor is reported.
   STUDY DESIGN AND METHODS: An infant with excessive hemorrhage at circumcision was found to have Type 3 VWD. His father carried an allele with a mutation at the level of VWF mRNA expression but did not have a history of bleeding. Cryoprecipitate was prepared from serial DDAVP-stimulated plasma exchanges of the father
   RESULTS: Repeated plasma-exchange donations were performed to provide all of the VWF needed for his son. An average of 14 cryoprecipitate units was prepared from each donation, and the units contained markedly elevated levels of FVIII:C. The cryoprecipitate was stored for up to 102 months. Components tested after more than 8 years of storage showed 48 to 130 percent of original FVIII:C activity. Ninety-seven percent of the bleeding episodes, such as epistaxis, tongue-biting accidents, and other minor lacerations, were successfully managed with a single 50- to 100-percent replacement dose of FVIII. The patient experienced normal growth and development and is free of any long-term sequelae attributable to his disease.
   CONCLUSIONS: Cryoprecipitate prepared by repeated plasma exchange of a VWD carrier provided excellent hemostatic function, even after storage intervals of more than a year. Plasma exchange of a committed donor was a cost-effective and safe option for long-term management of VWD.
C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
   NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
   NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA.
RP Pomper, GJ (reprint author), Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA.
NR 19
TC 3
Z9 4
U1 0
U2 0
PU AMER ASSOC BLOOD BANKS
PI BETHESDA
PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD NOV
PY 2003
VL 43
IS 11
BP 1514
EP 1521
DI 10.1046/j.1537-2995.2003.00550.x
PG 8
WC Hematology
SC Hematology
GA 737TG
UT WOS:000186247400003
PM 14617308
ER

PT J
AU Leitman, SF
   Browning, JN
   Yau, YU
   Mason, G
   Klein, HG
   Conry-Cantilena, C
   Bolan, CD
AF Leitman, SF
   Browning, JN
   Yau, YU
   Mason, G
   Klein, HG
   Conry-Cantilena, C
   Bolan, CD
TI Hemochromatosis subjects as allogeneic blood donors: a prospective study
SO TRANSFUSION
LA English
DT Article
ID HEREDITARY HEMOCHROMATOSIS; PHLEBOTOMY THERAPY; CLINICAL CONSEQUENCES;
   IRON OVERLOAD; DONATION; HOMOZYGOTES; MANAGEMENT; PROBANDS; MUTATION;
   GENE
AB BACKGROUND: Persons with hemochromatosis constitute a plentiful and willing source of blood for transfusion. A program was established and evaluated for treating persons with hemochromatosis in a donor center and making their blood available for transfusion.
   STUDY DESIGN AND METHODS: Phlebotomy therapy was performed free of charge regardless of whether subjects met criteria for allogeneic donation. A Hb level of 12.5 g per dL was used as the threshold for performing phlebotomy, and decreases in the MCV were used to guide the endpoints of therapy.
   RESULTS: A total of 130 subjects were consecutively enrolled: 74 percent were homozygous for the C282Y mutation in the HFE gene, 76 percent met eligibility criteria for allogeneic donation, and 55 percent were previous blood donors. A median of 20 weekly or biweekly phlebotomies (range, 7-99) were performed before the MCV reached the targeted endpoint of 3 percent below baseline, at which time the ferritin level was less than 30 mug per L and the transferrin saturation was less than 30 percent. The median phlebotomy interval necessary to keep the MCV at this level during maintenance therapy was 10 weeks. No incident seroconversions for agents of transfusion-transmissible disease occurred during 1402 donations. All subjects testing positive for viral agents gave a prior history of deferrable risk. Twenty-seven months after starting the program, hemochromatosis donors were contributing 14 percent of the RBC units collected for allogeneic use.
   CONCLUSIONS: Hemochromatosis subjects can safely and significantly augment the allogeneic blood supply. Provision of phlebotomy therapy unrestricted by considerations of cost or suitability for donation can improve access to care and remove incentives for incomplete risk disclosure.
C1 NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
   Walter Reed Army Inst Res, Silver Spring, MD USA.
RP Leitman, SF (reprint author), NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA.
NR 27
TC 31
Z9 31
U1 0
U2 1
PU AMER ASSOC BLOOD BANKS
PI BETHESDA
PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD NOV
PY 2003
VL 43
IS 11
BP 1538
EP 1544
DI 10.1046/j.1537-2995.2003.00570.x
PG 7
WC Hematology
SC Hematology
GA 737TG
UT WOS:000186247400007
PM 14617312
ER

PT J
AU Provenzano, M
   Lim, JB
   Mocellin, S
   Monsurro, V
   Bettinotti, M
   Marincola, FM
   Stroncek, DF
AF Provenzano, M
   Lim, JB
   Mocellin, S
   Monsurro, V
   Bettinotti, M
   Marincola, FM
   Stroncek, DF
TI The matrix protein pp65(341-350): a peptide that induces ex vivo
   stimulation and in vitro expansion of CMV-specific CD8+ T cells in
   subjects bearing either HLA-A*2402 or A*0101 allele
SO TRANSFUSION
LA English
DT Article
ID HUMAN CYTOMEGALOVIRUS-INFECTION; ALLOGENEIC BONE-MARROW; DENDRITIC
   CELLS; CTL RESPONSE; IDENTIFICATION; EPITOPES; ANTIGEN; BLOOD; PP65;
   LYMPHOCYTES
AB BACKGROUND: The stimulation of PBMNCs with HLA Class I restricted synthetic peptides derived from CMV phosphorylated matrix protein 65 (pp65) evokes CMV-specific cytotoxic T lymphocyte (CTL) activity, a necessary condition for initiating adoptive immunotherapy against CMV-related diseases in immune-compromised patients. It was previously demonstrated that the CMV decamer (10-mer) peptide pp65(341-310), QYDPVAALFF, was able to induce CMV-specific CTLs in HLA-A*2402 CMV-seropositive individuals.
   STUDY DESIGN AND METHOD: We investigated the ability of the peptide pp65(341-350) to reactivate memory CD8+ T cells in CMV-seropositive subjects bearing either the HLA-A24 or A1 allele. CTL responses were measured by IFN-gamma mRNA expression and IFN-gamma protein production as well as cytotoxic activity.
   RESULTS: In this study it was found that peptide pp65(341-350) induced a specific reactivation of memory CD8+ T cells from CMV-seropositive donors expressing either HLA-A*2402 and/or HLA-A*0101. Moreover, a pp65(341-350)-specific selection and expansion using PBMNCs of CMV-seropositive donors bearing both HLA-A*2402 and HLA-A*0101 alleles produced cytotoxic CTLs to both HLA-A24 and A1 peptide-pulsed and autologous CMV-infected target cells.
   CONCLUSION: The results demonstrate that pp65341-350 induced a specific CTL activity at both molecular and protein levels and that the peptide is specifically processed, presented, and recognized by subjects bearing HLA-A*2402 and/or A*0101. These findings suggest that it may be possible to use this single immune dominant peptide to induce and expand CMV-reactive CTLs for the treatment of individuals with both HLA-A24 and A1 types.
C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
   Univ Padua, Dept Oncol & Surg Sci, Surg Branch, Padua, Italy.
RP Provenzano, M (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bldg 10-1C711, Bethesda, MD 20892 USA.
NR 32
TC 11
Z9 12
U1 0
U2 0
PU AMER ASSOC BLOOD BANKS
PI BETHESDA
PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD NOV
PY 2003
VL 43
IS 11
BP 1567
EP 1574
DI 10.1046/j.1537-2995.2003.00564.x
PG 8
WC Hematology
SC Hematology
GA 737TG
UT WOS:000186247400012
PM 14617317
ER

PT J
AU Stratakis, CA
AF Stratakis, CA
TI Genetics of adrenocortical tumors: gatekeepers, landscapers and
   conductors in symphony
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID PROTEIN-KINASE-A; MACRONODULAR ADRENAL-HYPERPLASIA; GASTRIC-INHIBITORY
   POLYPEPTIDE; INDEPENDENT CUSHINGS-SYNDROME; GENOMIC HYBRIDIZATION
   ANALYSIS; MEMBRANE HORMONE-RECEPTORS; ALPHA REGULATORY SUBUNIT; SPOTTY
   SKIN PIGMENTATION; IN-SITU HYBRIDIZATION; CARNEY COMPLEX
AB The genetic and histopathological backgrounds of adrenocortical tumorigenesis remain poorly characterized. In other tissues, there is conclusive evidence that hyperplasia and adenomas precede cancer. In the adrenal, there are few clinical cases of either hyperplasia or adenoma associated with later development of cancer, and there are few biological studies that attempt to characterize this process molecularly. Current research focuses on the early lesions of the adrenal cortex because of their possible molecular link with carcinogenesis, and evidence of their frequent association with atypical forms of Cushing's and Conn's syndromes, obesity, hypertension and/or diabetes. These studies indicate a model for oncogenesis that is the same as that in other tissues. The rarity of adrenal cancer compared to benign lesions could be a clue to unique features of adrenocortical cells. It might also highlight the function of genes that are associated with endocrine tumors in the context of which the concept of gene 'conductors' is introduced here.
C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
NR 82
TC 45
Z9 46
U1 0
U2 2
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD NOV
PY 2003
VL 14
IS 9
BP 404
EP 410
DI 10.1016/j.tem.2003.08.005
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 741TA
UT WOS:000186474300005
PM 14580759
ER

PT J
AU Belyantseva, IA
   Labay, V
   Boger, ET
   Griffith, AJ
   Friedman, TB
AF Belyantseva, IA
   Labay, V
   Boger, ET
   Griffith, AJ
   Friedman, TB
TI Stereocilia: the long and the short of it
SO TRENDS IN MOLECULAR MEDICINE
LA English
DT Article
ID SYNDROME TYPE 1D; HAIR-CELLS; UNCONVENTIONAL MYOSIN; HEARING-LOSS;
   DEAFNESS DFNB3; MUTATIONS; MOUSE; GENE; HARMONIN; PROTEIN
AB Mutations in whirlin, a putative PDZ scaffold protein, have recently been shown to cause deafness and short cochlear hair cell stereocilia in whirler mice and recessive deafness (DFNB31) in humans. Through its PDZ domains, whirlin might organize a group of proteins into a functional complex required for stereocilia elongation. Identifying these protein partners will advance our understanding of the development of stereocilia and their function as mechanosensory organelles indispensable for normal hearing.
C1 Natl Inst Deafness & Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
RP Friedman, TB (reprint author), Natl Inst Deafness & Commun Disorders, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA.
NR 26
TC 14
Z9 14
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4914
J9 TRENDS MOL MED
JI Trends Mol. Med
PD NOV
PY 2003
VL 9
IS 11
BP 458
EP 461
DI 10.1016/j.molmed.2003.09.008
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 747GT
UT WOS:000186797400002
PM 14604820
ER

PT J
AU Ben-Yosef, T
   Friedman, TB
AF Ben-Yosef, T
   Friedman, TB
TI The genetic bases for syndromic and nonsyndromic deafness among Jews
SO TRENDS IN MOLECULAR MEDICINE
LA English
DT Review
ID SYNDROME-TYPE-IIA; ASHKENAZI JEWISH POPULATION; SENSORINEURAL
   HEARING-LOSS; CONNEXIN 26 MUTATIONS; MYOSIN VIIA GENE; SYNDROME-TYPE-I;
   USHER-SYNDROME; RECESSIVE DEAFNESS; ALPORT-SYNDROME; PROTOCADHERIN GENE
AB There are hundreds of different mutated genes associated with hearing loss. However, recent findings indicate that a large proportion of both syndromic and nonsyndromic forms of deafness in some Jewish populations is caused by a small number of founder mutations. This review is focused on genetic disorders such as nonsyndromic deafness, Usher syndrome and Alport syndrome, in which hearing loss is a major part of the phenotype and in which the underlying prevalent founder mutations have been recently identified in different Jewish populations. These and other examples of common mutations within a distinct population allow for sensitive and specific use of genetic testing for carrier screening and diagnosis, and are an impetus for development of therapeutic strategies.
C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA.
FU NIDCD NIH HHS [1 Z01 DC 00039-06]
NR 73
TC 6
Z9 6
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4914
J9 TRENDS MOL MED
JI Trends Mol. Med
PD NOV
PY 2003
VL 9
IS 11
BP 496
EP 502
DI 10.1016/j.molmed.2003.09.004
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 747GT
UT WOS:000186797400010
PM 14604828
ER

PT J
AU Lawrence, JJ
   McBain, CJ
AF Lawrence, JJ
   McBain, CJ
TI Interneuron Diversity series: Containing the detonation - Feedforward
   inhibition in the CA3 hippocampus
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID LONG-TERM POTENTIATION; TARGET-SPECIFIC EXPRESSION; MOSSY FIBER
   SYNAPSES; RAT HIPPOCAMPUS; PYRAMIDAL CELLS; SYNAPTIC-TRANSMISSION;
   DENTATE GYRUS; FOREBRAIN ISCHEMIA; POPULATION EVENTS; RECEPTOR SUBTYPES
AB Feedforward inhibitory circuits are involved both in the suppression of excitability and timing of action potential generation in principal cells. In the CA3 hippocampus, a single mossy fiber from a dentate gyrus granule cell forms giant boutons with multiple release sites, which are capable of detonating CA3 principal cells. By contrast, mossy fiber terminals form a larger number of Lilliputian-sized synapses with few release sites onto local circuit interneurons, with distinct presynaptic and postsynaptic properties. This dichotomy between the two synapse types endows the circuit with exquisite control over pyramidal cell discharge. Under pathological conditions where feedforward inhibition is compromised, focal excitation is no longer contained, rendering the circuit susceptible to hyperexcitability.
C1 NICHD, LCSN, Lab Cellular & Synapt Physiol, Bethesda, MD 20892 USA.
RP McBain, CJ (reprint author), NICHD, LCSN, Lab Cellular & Synapt Physiol, Bldg 49,Room 5A72, Bethesda, MD 20892 USA.
NR 68
TC 137
Z9 139
U1 2
U2 5
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD NOV
PY 2003
VL 26
IS 11
BP 631
EP 640
DI 10.1016/j.tins.2003.09.007
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 741HN
UT WOS:000186452800012
PM 14585604
ER

PT J
AU Holmes, A
   Heilig, M
   Rupniak, NMJ
   Steckler, T
   Griebel, G
AF Holmes, A
   Heilig, M
   Rupniak, NMJ
   Steckler, T
   Griebel, G
TI Neuropeptide systems as novel therapeutic targets for depression and
   anxiety disorders
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID CORTICOTROPIN-RELEASING HORMONE; P NK1 RECEPTOR; PITUITARY-ADRENAL AXIS;
   CENTRAL-NERVOUS-SYSTEM; ANXIOLYTIC-LIKE ACTION; DORSAL RAPHE NUCLEUS;
   ELEVATED PLUS-MAZE; SUBSTANCE-P; Y NPY; IN-VIVO
AB The health burden of stress-related diseases, including depression and anxiety disorders, is rapidly increasing, whereas the range of available pharmacotherapies to treat these disorders is limited and suboptimal with regard to efficacy and tolerability. Recent findings support a major role for neuropeptides in mediating the response to stress and thereby identify neuropeptide systems as potential novel therapeutic targets for the treatment of depression and anxiety disorders. In preclinical models, pharmacological and/or genetic manipulation of substance P, corticotropin-releasing factor (CRF), vasopressin, neuropeptide Y and galanin function alters anxiety- and depression-related responses. Recently, specific and highly potent small-molecule neuropeptide receptor agonists and antagonists have been developed that can readily cross the blood-brain barrier. Clinical assessment of several compounds is currently underway, with antidepressant efficacy confirmed in double-blind, placebo-controlled trials of tachykinin NK1 (substance P) receptor antagonists, and preliminary evidence of antidepressant activity in an open-label trial of a CRF1 receptor antagonist.
C1 NIAAA, Sect Behav Sci & Genet, Bethesda, MD 20892 USA.
   Karolinska Inst, Div Psychiat, NEUROTEC Dept, Stockholm, Sweden.
   Merck Res Labs, W Point, PA 19456 USA.
   Janssen Pharmaceut NV, Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium.
   Dept Psychopharmacol, Bagneux, France.
RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Bethesda, MD 20892 USA.
RI Griebel, Guy/F-8752-2014; 
OI Griebel, Guy/0000-0002-6052-9438; Heilig, Markus/0000-0003-2706-2482
NR 90
TC 279
Z9 288
U1 0
U2 12
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD NOV
PY 2003
VL 24
IS 11
BP 580
EP 588
DI 10.1016/j.tips.2003.09.001
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 746CD
UT WOS:000186728200009
PM 14607081
ER

PT J
AU Zhang, ZJ
   Huckle, J
   Francomano, CA
   Spencer, RGS
AF Zhang, ZJ
   Huckle, J
   Francomano, CA
   Spencer, RGS
TI The effects of pulsed low-intensity ultrasound on chondrocyte viability,
   proliferation, gene expression and matrix production
SO ULTRASOUND IN MEDICINE AND BIOLOGY
LA English
DT Article
DE chondrocyte; ultrasound; gene expression; proliferation; viability
ID CHICK STERNAL CARTILAGE; X COLLAGEN-SYNTHESIS; OSTEOARTHRITIC CARTILAGE;
   ARTICULAR-CARTILAGE; DIFFERENTIATION; CHONDROGENESIS; PROTEIN; CULTURE;
   BONE
AB This study was designed to examine the effects of pulsed low-intensity ultrasound (PLIUS) on chondrocyte viability, proliferation, matrix production and gene expression. Chondrocytes were isolated from the distal part of the sternum of 16-day-old chick embryos and cultured in alginate beads. PLIUS at 2 mW/cm(2) (group PLIUS2) and 30 MW/cm(2) (group PLIUS30) was applied to chondrocytes for a single 20-min treatment. A control group was treated without PLIUS. The viability of chondrocytes was not affected by exposure to PLIUS. PLIUS influenced chondrocyte proliferation in an intensity-dependent manner. By day 7 after application of PLIUS, the gene expression and synthesis of aggrecan was the same as in the controls. At this same time point, the expression and synthesis of type II collagen was not different between the controls and PLIUS30, but was increased in PLIUS2. PLIUS was shown to inhibit the expression of type X collagen. This inhibition of chondrocyte hypertrophy may prove to be significant in the management of cartilage degeneration.
C1 NIA, NIH, Baltimore, MD 21224 USA.
   Smith & Nephew Grp Res Ctr, York, N Yorkshire, England.
RP Spencer, RGS (reprint author), NIA, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
NR 26
TC 91
Z9 106
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-5629
J9 ULTRASOUND MED BIOL
JI Ultrasound Med. Biol.
PD NOV
PY 2003
VL 29
IS 11
BP 1645
EP 1651
DI 10.1016/j.ultrasmedbio.2003.08.011
PG 7
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 748RA
UT WOS:000186873800012
PM 14654159
ER

PT J
AU Hwang, JJ
   Uchio, EM
   Linehan, WM
   Walther, MM
AF Hwang, JJ
   Uchio, EM
   Linehan, WM
   Walther, MM
TI Hereditary kidney cancer
SO UROLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
ID RENAL-CELL-CARCINOMA; TUMOR-SUPPRESSOR GENE; HIPPEL-LINDAU-DISEASE;
   HOGG-DUBE-SYNDROME; TUBEROUS SCLEROSIS COMPLEX; PARENCHYMAL SPARING
   SURGERY; GERMLINE MUTATIONS; MET PROTOONCOGENE; SOMATIC MUTATIONS;
   NATURAL-HISTORY
AB Patients with hereditary renal cancer syndromes may be predisposed to the development of multiple bilateral renal tumors and can face a lifelong risk of tumor recurrence. Understanding of the genetic basis of hereditary syndromes has led to early screening of families at risk and improved disease management. In addition, the identification of molecular pathways in hereditary settings has given insights into tumoriogenesis of sporadic renal cancers.
C1 NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, 9000 Rockville Pike,Bldg 10,Rm 2B47, Bethesda, MD 20892 USA.
NR 78
TC 4
Z9 4
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 0094-0143
J9 UROL CLIN N AM
JI Urol. Clin. N. Am.
PD NOV
PY 2003
VL 30
IS 4
BP 831
EP +
DI 10.1016/S0094-0143(03)00054-5
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA 754FQ
UT WOS:000187292400014
PM 14680318
ER

PT J
AU Hwang, JJ
   Dharmawardana, PG
   Uchio, EM
   Wynberg, J
   Phillips, JL
AF Hwang, JJ
   Dharmawardana, PG
   Uchio, EM
   Wynberg, J
   Phillips, JL
TI Prostate cancer in Klinefelter syndrome during hormonal replacement
   therapy
SO UROLOGY
LA English
DT Article
ID ADENOCARCINOMA; CARCINOMA; MEN
AB Prostate cancer detection is a rare occurrence in patients with Klinefelter syndrome, in whom chronically low circulating androgen levels are common findings. Administration of exogenous testosterone has increasingly been used to, treat young adolescents diagnosed with Klinefelter syndrome and documented androgen deficiency. Although testosterone replacement in adult patients has been associated with prostatic enlargement, it remains unknown whether chronic supplementation of exogenous testosterone to pubescent males with hypogonadism results in early prostate carcinogenesis. We report a first case of prostate cancer in a patient with Klinefelter syndrome who had undergone long-term testosterone replacement therapy since childhood for chronically depressed levels of testosterone. Published by Elsevier Inc.
C1 NCI, UOB, DCT, NIH, Bethesda, MD 20892 USA.
RP Hwang, JJ (reprint author), NCI, UOB, DCT, NIH, Bldg 10,Room 2B47,10 Ctr Dr,MSC 1501, Bethesda, MD 20892 USA.
NR 11
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 0090-4295
J9 UROLOGY
JI Urology
PD NOV
PY 2003
VL 62
IS 5
DI 10.1016/S0090-4295(03)00693-9
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 765EB
UT WOS:000188253200036
ER

PT J
AU Ashcroft, GS
   Mills, SJ
   Flanders, KC
   Lyakh, LA
   Anzano, MA
   Gilliver, SC
   Roberts, AB
AF Ashcroft, GS
   Mills, SJ
   Flanders, KC
   Lyakh, LA
   Anzano, MA
   Gilliver, SC
   Roberts, AB
TI Role of Smad3 in the hormonal modulation of in vivo wound healing
   responses
SO WOUND REPAIR AND REGENERATION
LA English
DT Article
ID GROWTH-FACTOR-BETA; TGF-BETA; INFLAMMATORY RESPONSE; CANCER
AB Smad3 is involved in mediating intracellular signaling by members of the transforming growth factor-beta superfamily and plays a critical role in the cellular proliferation, differentiation, migration, and elaboration of matrix pivotal to cutaneous wound healing. Cross-talk between Smad3 and hormone signaling in vitro has been suggested as an important control mechanism regulating cell activities; however, its relevance in vivo is unknown. Here we report that Smad3 plays a role in androgen-mediated inhibition of wound healing but not in the responses to estrogen modulation in vivo. Both wild-type and Smad3 null female mice exhibited delayed healing following ovariectomy, which could be reversed by estrogen replacement. By contrast, castration accelerated healing in wild-type male mice and was reversible by exogenous androgen treatment. Intriguingly, modulation of androgen levels resulted in no discernible perturbation in the healing response in the Smad3 null mice. Mutant monocytes could be lipopolysaccharide stimulated to produce specific pro-inflammatory agents (macrophage monocyte inhibitory factor) in a fashion similar to wild-type cells, but exhibited a muted response to androgen-mediated stimulation while maintaining a normal response to estrogen-induced macrophage inhibitory factor inhibition. These data suggest that Smad3 plays a role in mediating androgen signaling during the normal wound healing response and implicate Smad3 in the modulation of inflammatory cell activity by androgens.
C1 Univ Manchester, Sch Biol Sci, Div Immunol Microbiol & Dev, Manchester M13 9PT, Lancs, England.
   NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA.
RP Ashcroft, GS (reprint author), Univ Manchester, Sch Biol Sci, Div Immunol Microbiol & Dev, 3-239 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England.
RI Mills, Stuart/L-4889-2014; Gilliver, Stephen/B-3406-2015
OI Mills, Stuart/0000-0002-2462-7081; Gilliver, Stephen/0000-0003-4973-0621
NR 15
TC 30
Z9 33
U1 0
U2 2
PU BLACKWELL PUBLISHING INC
PI MALDEN
PA 350 MAIN ST, MALDEN, MA 02148 USA
SN 1067-1927
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD NOV-DEC
PY 2003
VL 11
IS 6
BP 468
EP 473
DI 10.1046/j.1524-475X.2003.11614.x
PG 6
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA 746ZP
UT WOS:000186779200015
PM 14617288
ER

PT J
AU Singh, G
   Klar, AJS
AF Singh, G
   Klar, AJS
TI DNA sequence of the mat2,3 region of Schizosaccharomyces kambucha shares
   high homology with the corresponding sequence from Sz. pombe
SO YEAST
LA English
DT Article
DE fission yeast; Schizosaccharomyces kambucha; mat2,3 region sequence;
   silencing
ID MATING-TYPE CASSETTE; FISSION YEAST; HETEROCHROMATIN DOMAIN; DAUGHTER
   CELLS; INHERITANCE; DIRECTIONALITY; TRANSPOSITION; BOUNDARIES;
   ASYMMETRY; ELEMENTS
AB To define conserved sequences for mat1 imprinting and silencing of the mat2,3 region of Schizosaccharomyces pombe, we determined the DNA sequence of the cognate region (mat2,3 region) of another fission yeast, Sz. kambucha, a yeast species isolated from Kambucha tea mix. The entire mat2,3 region shows more than 98% identity between the two species. Sequence similarity is even higher (99.3%) for mating-type cassettes; deduced amino acid sequences of three of the four Mat peptides (Pi, Pc and Mi) are identical between the two species, while the fourth (Me) has a single amino acid polymorphism. Comparison of the sequence motif of the imprint site essential for mat1 switching shows that mat-P of Sz. kambucha has a sequence identical to the conserved motif present in Sz. pombe. However, this sequence motif of nine bases differs by one base for mat-M of Sz. kambucha. The sequence of the K region shows about 98% identity between the two species, with the cenH region showing 98.3% homology. Thus, the arrangement of the mat2,3 region in both yeasts is conserved and shows 1-2% nucleotide sequence variation throughout the region. The DNA sequence of the mat2,3 region from Sz. kambucha has been submitted to GenBank under Accession No. AY271822. Copyright (C) 2003 John Wiley Sons, Ltd.
C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
RP Klar, AJS (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA.
NR 31
TC 6
Z9 10
U1 1
U2 1
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0749-503X
J9 YEAST
JI Yeast
PD NOV
PY 2003
VL 20
IS 15
BP 1273
EP 1278
DI 10.1002/yea.1042
PG 6
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Microbiology; Mycology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Microbiology; Mycology
GA 745UF
UT WOS:000186706600005
PM 14618565
ER

PT J
AU Bradley, C
   Craigie, R
AF Bradley, C
   Craigie, R
TI MoMLV reverse transcriptase regulates its own expression
SO CELL
LA English
DT Editorial Material
ID RNA
AB A precise ratio of Gag:Gag-Pol expression is required for assembly of infectious retroviral virions. In this issue of Cell, Orlova et al. show that MoMLV reverse transcriptase binds the translation release factor eRF1, and that this interaction promotes translation readthrough to make Gag-Pol.
C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bradley, C (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 5
TC 0
Z9 1
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 31
PY 2003
VL 115
IS 3
BP 250
EP 251
DI 10.1016/S0092-8674(03)00850-X
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 740RH
UT WOS:000186415000004
PM 14636552
ER

PT J
AU Zhao, GQ
   Zhang, YF
   Hoon, MA
   Chandrashekar, J
   Erlenbach, I
   Ryba, NJP
   Zuker, CS
AF Zhao, GQ
   Zhang, YF
   Hoon, MA
   Chandrashekar, J
   Erlenbach, I
   Ryba, NJP
   Zuker, CS
TI The receptors for mammalian sweet and umami taste
SO CELL
LA English
DT Article
ID METABOTROPIC GLUTAMATE-RECEPTOR; PHOSPHOLIPASE-C; GENE-EXPRESSION;
   CHORDA TYMPANI; BITTER TASTE; RESPONSES; CELLS; MICE; IDENTIFICATION;
   FAMILY
AB Sweet and umami (the taste of monosodium glutamate) are the main attractive taste modalities in humans. T1Rs are candidate mammalian taste receptors that combine to assemble two heteromeric G-protein-coupled receptor complexes: T1R1+3, an umami sensor, and T1R2+3, a sweet receptor. We now report the behavioral and physiological characterization of T1R1, T1R2, and T1R3 knockout mice. We demonstrate that sweet and umami taste are strictly dependent on T1R-receptors, and show that selective elimination of T1R-subunits differentially abolishes detection and perception of these two taste modalities. To examine the basis of sweet tastant recognition and coding, we engineered animals expressing either the human T1R2-receptor (hT1R2), or a modified opioid-receptor (RASSL) in sweet cells. Expression of hT1R2 in mice generates animals with humanized sweet taste preferences, while expression of RASSL drives strong attraction to a synthetic opiate, demonstrating that sweet cells trigger dedicated behavioral outputs, but their tastant selectivity is determined by the nature of the receptors.
C1 Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
   Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA.
   Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
   Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Ryba, NJP (reprint author), Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
NR 40
TC 633
Z9 667
U1 7
U2 79
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
SN 0092-8674
J9 CELL
JI Cell
PD OCT 31
PY 2003
VL 115
IS 3
BP 255
EP 266
DI 10.1016/S0092-8674(03)00844-4
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 740RH
UT WOS:000186415000006
PM 14636554
ER

PT J
AU Rothman, RB
   Baumann, MH
AF Rothman, RB
   Baumann, MH
TI Monoamine transporters and psychostimulant drugs
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE cocaine; monoamine; psychostimulant; amphetamine; dopamine; 5-HT
   (5-hydroxytryptamine, serotonin); DAT (dopamine transporter); SERT
   (serotonin transporter)
ID BIOGENIC-AMINE TRANSPORTERS; RAT NUCLEUS-ACCUMBENS; HIGH-AFFINITY
   BINDING; ANALOG I-125 RTI-55; SEROTONIN-RELEASING AGENTS;
   CENTRAL-NERVOUS-SYSTEM; FREELY MOVING RATS; GUINEA-PIG BRAIN; DOPAMINE
   TRANSPORTER; NEUROTRANSMITTER TRANSPORTERS
AB Most psychostimulants interact with monoamine transport proteins. This paper reviews work our laboratory has conducted to investigate the interaction of psychostimulants with monoamine transporters in order to advance our understanding of how these drugs affect the brain. We review two topics: (1) characterization of multiple binding sites for cocaine-like drugs and (2) an examination of the mechanisms of action of amphetamine-type anorectic agents. We conclude that the brain contains high abundance nonclassical binding sites for cocaine-like drugs that have micromolar affinity for cocaine and that none of the clinically available amphetamine-type appetite suppressants are equipotent substrates for dopamine transporter (DAT) and serotonin transporter (SERT) proteins. Future medications discovery efforts should focus on identifying new compounds which possess the equipotent substrate activity at DAT and SERT, but which lack the adverse effects of stimulants developed decades ago. (C) 2003 Elsevier B.V. All rights reserved.
C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA.
NR 104
TC 243
Z9 248
U1 4
U2 20
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD OCT 31
PY 2003
VL 479
IS 1-3
BP 23
EP 40
DI 10.1016/j.ejphar.2003.08.054
PG 18
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 745NG
UT WOS:000186694300004
PM 14612135
ER

PT J
AU Uhl, GR
   Lin, ZC
AF Uhl, GR
   Lin, ZC
TI The top 20 dopamine transporter mutants: structure-function
   relationships and cocaine actions
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE DAT (dopamine transporter); SERT (serotonin transporter); transmembrane
   domain; mutant; cocaine selective; antagonism
ID PROTEIN-KINASE-C; NUCLEUS-ACCUMBENS; ANALOG RECOGNITION; MICE LACKING;
   EXPRESSION; MECHANISM; MUTATIONS; DOMAINS; ESTERS; PHOSPHORYLATION
AB Our laboratory and others elucidated the primary amino acid sequences of the dopamine transporter (DAT) by cloning its cDNA and genomic sequences more than 12 years ago. Motivations for this work included the ideas that cocaine's interactions with DAT accounted for its rewarding properties and that selective inhibitors of DAT/cocaine interactions might thus provide good anticocaine medications. Such ideas supported interest in the detailed structure-function relationships of cocaine/DAT interactions, and in the construction and characterization of extensive series of site-directed DAT mutants. We can now select the most interesting 20 cocaine-analog selective mutations of the more than 100 single- and multiple amino acid substitution mutations that we have characterized. These mutants selectively reduce the affinities of the mutant DATs for cocaine analogs, but (absolutely or relatively) spare their affinities for dopamine. Several themes relevant to cocaine/DAT interactions emerge from these mutants. First, such mutations are found in a number of different DAT domains. Secondly, many but not all of these mutations lie in groups, near each other and near the same faces of presumably helical DAT transmembrane domains. Third, most are also conserved in the serotonin transporter (SERT), a transporter that is now strongly implicated in cocaine reward based on data from knockout mice. We discuss the results from these "top 20" mutants in light of the strengths and limitations of current DAT models and data from other studies. Taken together, these studies appear to indicate direct or indirect participation of several specific portions of DAT in selective recognition of cocaine analogs. These studies provide a strong basis for redirected studies aimed at producing dopamine- and serotonin-sparing cocaine antagonists that would represent combined DAT/SERT disinhibitors. (C) 2003 Elsevier B.V. All rights reserved.
C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA.
RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA.
NR 48
TC 26
Z9 26
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD OCT 31
PY 2003
VL 479
IS 1-3
BP 71
EP 82
DI 10.1016/j.ejphar.2003.08.058
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 745NG
UT WOS:000186694300008
PM 14612139
ER

PT J
AU Kim, YH
   Lee, JH
   Lim, DS
   Shim, WJ
   Ro, YM
   Park, GH
   Becker, KG
   Cho-Chung, YS
   Kim, MK
AF Kim, YH
   Lee, JH
   Lim, DS
   Shim, WJ
   Ro, YM
   Park, GH
   Becker, KG
   Cho-Chung, YS
   Kim, MK
TI Gene expression profiling of oxidative stress on atrial fibrillation in
   humans
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
DE atrial fibrillation; cDNA microarray; gene expression profile; oxidative
   stress
ID MONOAMINE-OXIDASE; DAMAGE; PEROXYNITRITE; MITOCHONDRIA; INDUCTION;
   PLACENTA; CELLS
AB Atrial Fibrillation (AF) is thought be caused by oxidative stress. Oxidative stress at the cellular level results from many factors, including exposure to alcohol, medications, cold, toxins or radiation. In this study we investigated gene transcriptional profiles on the human myocardial tissues from AF and oxidative stress conditions. Right atrial appendages were obtained from AF patients (n = 26) undergoing the Maze procedure, and from control patients (n = 26) who were in normal sinus rhythm and undergoing coronary artery bypass graft operation. To examine the effects of oxidative stress on AF, we used radioactive complementary DNA (cDNA) microarrays to evaluate changes in the expression of 1,152 known genes. This technology, which monitors thousands of genes simultaneously, gives us a better picture of the interactions between AF and oxidative stress. Total RNAs prepared from the retrieved tissues were used to synthesize P-33-labeled cDNAs by reverse transcription and hybridized to cDNA microarrays. Gene expression profiles showed that 30 genes were upregulated and 25 were downregulated in AF patients compared with control patients. Moreover, comparison rank analysis revealed that the expression of five genes related to reactive oxygen species (ROS)-including flavin containing monooxygenase 1, monoamine oxidase 13, ubiquitin specific protease 8, tyrosinase-related protein 1, and tyrosine 3-monooxygenase-increased by more than 2.0 of the Z-ratio, and two genes related to antioxidantsincluding glutathione peroxidase 1, and heme oxygenase 2-decreased to the Z-ratio levels of less than or equal to -2.0. Apparently, a balanced regulation of pro- and anti-oxidation can be shifted toward pro-oxidation and can result in serious damage similar to that of human AF. Western blotting analysis confirmed the upregulation of tyrosinase-related protein 1 and tyrosine 3-monooxygenase and the downregulation of heme oxygenase 2. These results suggested that the gene expression pattern of myocardial tissues in AF patients can be associated with oxidative stress, resulting in a significant increase in ROS. Thus, the cDNA microarray technique was useful for investigating transcription profiles in AF. It showed that the intracellular mechanism of oxidative stress plays a pivotal role in the pathologic progression of AF and offers novel insight into potential treatment with antioxidants.
C1 Korea Univ, Coll Med, Dept Internal Med, Seoul 136701, South Korea.
   Korea Univ, Coll Med, Dept Biochem, Seoul 136701, South Korea.
   NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA.
   NCI, Basic Res Lab, CCR, Cellular Biochem Sect, Bethesda, MD 20892 USA.
RP Kim, MK (reprint author), Korea Univ, Coll Med, Dept Internal Med, Seoul 136701, South Korea.
OI Becker, Kevin/0000-0002-6794-6656
NR 20
TC 94
Z9 104
U1 0
U2 3
PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
PI SEOUL
PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1226-3613
J9 EXP MOL MED
JI Exp. Mol. Med.
PD OCT 31
PY 2003
VL 35
IS 5
BP 336
EP 349
PG 14
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 748WU
UT WOS:000186884600002
PM 14646586
ER

PT J
AU Storek, J
   Douek, DC
   Keesey, JC
   Boehmer, L
   Storer, B
   Maloney, DG
AF Storek, J
   Douek, DC
   Keesey, JC
   Boehmer, L
   Storer, B
   Maloney, DG
TI Low T cell receptor excision circle levels in patients thymectomized
   25-54 years ago
SO IMMUNOLOGY LETTERS
LA English
DT Letter
ID THYMIC FUNCTION; PERIPHERAL-BLOOD
C1 Univ Washington, FHCRC, Seattle, WA 98109 USA.
   NIH, Bethesda, MD 20892 USA.
   Univ Calif Los Angeles, Los Angeles, CA USA.
RP Storek, J (reprint author), Univ Washington, FHCRC, D1-100,1100 Fariview Ave N, Seattle, WA 98109 USA.
FU NCI NIH HHS [CA18029, CA15704, CA18221]; NHLBI NIH HHS [HL36444]; NIAID
   NIH HHS [AI46108]
NR 8
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD OCT 31
PY 2003
VL 89
IS 2-3
BP 91
EP 92
DI 10.1016/S0165-2478(03)00133-0
PG 2
WC Immunology
SC Immunology
GA 733WG
UT WOS:000186023200001
PM 14556964
ER

PT J
AU Charukamnoetkanok, P
   Brady, JP
   Wawrousek, EF
   Egwuagu, CE
   Zigler, JS
   Vistica, BP
   Whitcup, SM
   Gery, I
AF Charukamnoetkanok, P
   Brady, JP
   Wawrousek, EF
   Egwuagu, CE
   Zigler, JS
   Vistica, BP
   Whitcup, SM
   Gery, I
TI Immunotolerance toward native alpha A-crystallin in knockout mice
   deficient in the functional protein
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE immunotolerance; knockout mice; lens crystallins; self antigens; thymic
   deletion
ID THYMIC EPITHELIAL-CELLS; DOUBLE-TRANSGENIC MICE; NEO-SELF-ANTIGEN;
   B-CRYSTALLIN; IMMUNE-RESPONSES; GENE-EXPRESSION; LENS; TOLERANCE;
   AUTOANTIGENS; DISRUPTION
AB Immune response against self antigens is normally prevented by an elaborate immunotolerance mechanism. A potential problem for recipients of gene therapy is, therefore, an immune response against the newly introduced gene product. To examine this issue we tested the immune response to the native proteins in knockout (KO) mice in which the genes for alphaA- or alphaB-crystallin were disrupted by partial or complete gene deletion, respectively. alphaA- and alphaB-crystallins are two immunologically distinct polypeptides which form the large ( similar to 800 kDa) complex in the lens referred to as alpha-crystallin. When immunized with murine alpha-crystallin, alphaB-crystallin KO mice, in which the corresponding gene was completely deleted, responded well to the absent self antigen. In contrast, alphaA-crystallin KO mice, with the partial gene deletion, resembled wild type (WT) mice in being immunotolerant toward the native crystallin. Although no functional alphaA-crystallin could be detected in the lens of alphaA-crystallin KO mice, mRNA transcript coding for a truncated alphaA-crystallin gene was found in thymi of these mice, suggesting that thymic expression of a residual fragment of the protein is responsible for the tolerance induction. These data suggest that nonfunctional proteins may induce immunotolerance and protect recipients of gene therapy from immunity against the native proteins. (C) 2003 Elsevier B.V. All rights reserved.
C1 NEI, NIH, Bethesda, MD 20892 USA.
   NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
RP Gery, I (reprint author), NEI, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA.
RI Wawrousek, Eric/A-4547-2008
NR 30
TC 2
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD OCT 31
PY 2003
VL 89
IS 2-3
BP 259
EP 265
DI 10.1016/S0165-2478(03)00153-6
PG 7
WC Immunology
SC Immunology
GA 733WG
UT WOS:000186023200024
PM 14556987
ER

PT J
AU Wick, MJ
   Ramos, FJ
   Chen, H
   Quon, MJ
   Dong, LQ
   Liu, F
AF Wick, MJ
   Ramos, FJ
   Chen, H
   Quon, MJ
   Dong, LQ
   Liu, F
TI Mouse 3-phosphoinositide-dependent protein kinase-1 undergoes
   dimerization and trans-phosphorylation in the activation loop
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TYROSINE PHOSPHORYLATION; DOCKING SITE; C-ZETA; PDK1; IDENTIFICATION;
   MECHANISM; POCKET; PKC
AB Activation of mouse 3-phosphoinositide-dependent protein kinase-1 (mPDK1) requires phosphorylation at a conserved serine residue, Ser(244), in the activation loop. However, the mechanism by which mPDK1 is phosphorylated at this site remains unclear. We have found that kinase-defective mPDK1 (mPDK1(KD)), but not a kinase-defective mPDK1 in which Ser(244) was replaced with alanine (mPDK1(KD/S244A)), is significantly phosphorylated in intact cells and is a direct substrate of wild-type mPDK1 fused to the yellow fluorescence protein. Phosphoamino acid analysis and phosphopeptide mapping studies revealed that mPDK1 trans-autophosphorylation occurred mainly on Ser(244). On the other hand, Ser(399) and Thr(516), two recently identified autophosphorylation sites of mPDK1, are phosphorylated primarily through a cis mechanism. In vivo labeling studies revealed that insulin stimulated both mPDK1KD and mPDK1(KD/S244A) phosphorylation in Chinese hamster ovary cells overexpressing the insulin receptor. However, Western blot analysis using a phosphospecific antibody revealed no increase in insulin-stimulated phosphorylation of Ser244 in these cells overexpressing mPDK1. mPDK1 undergoes dimerization in cells and this self-association is enhanced by kinase inactivation. Deletion of the extreme C terminus disrupts mPDK1 dimerization and Ser(244) trans-phosphorylation, suggesting that dimerization is important for mPDK1 transphosphorylation. Taken together, our results show that mPDK1 autophosphorylation occurs at multiple sites through both cis and trans mechanisms and suggest that dimerization and trans-phosphorylation may serve as mechanisms to regulate PDK1 activity in cells.
C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA.
   Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA.
   Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
   NCCAM, Diabet Unit, Clin Invest Lab, NIH, Bethesda, MD 20892 USA.
RP Liu, F (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
RI Quon, Michael/B-1970-2008; 
OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707
FU NIDDK NIH HHS [DK56166]
NR 23
TC 39
Z9 42
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 42913
EP 42919
DI 10.1074/jbc.M304172200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000024
PM 12923190
ER

PT J
AU Yoo, JY
   Ghiassi, M
   Jirmanova, L
   Balliet, AG
   Hoffman, B
   Fornace, AJ
   Liebermann, DA
   Bottinger, EP
   Roberts, AB
AF Yoo, JY
   Ghiassi, M
   Jirmanova, L
   Balliet, AG
   Hoffman, B
   Fornace, AJ
   Liebermann, DA
   Bottinger, EP
   Roberts, AB
TI Transforming growth factor-beta-induced apoptosis is mediated by
   SMad-dependent expression of GADD45b through p38 activation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEPATOMA-CELL LINE; A-INDUCED APOPTOSIS; TGF-BETA; PROTEIN-KINASE;
   SIGNAL-TRANSDUCTION; REGRESSING LIVER; MAP KINASES;
   CULTURED-HEPATOCYTES; POSSIBLE ASSOCIATION; TRANSGENIC MICE
AB Transforming growth factor-beta(TGF-beta)-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. In this report, we identify GADD45b as an effector of TGF-beta-induced apoptosis. GADD45b has been shown to be a positive mediator of apoptosis induced by certain cytokines and oncogenes. We show that Gadd45b is an immediate-early response gene for TGF-beta and that the proximal Gadd45b promoter is activated by TGF-beta through the action of Smad2, Smad3, and Smad4. We show that ectopic expression of GADD45b in AML12 murine hepatocytes is sufficient to activate p38 and to trigger apoptotic cell death, whereas antisense inhibition of Gadd45b expression blocks TGF-beta-dependent p38 activation and apoptosis. Furthermore, we also show that TGF-beta can activate p38 and induce apoptosis in mouse primary hepatocytes from wild-type mice, but not from Gadd45b(-/-) mice. All of these findings suggest that GADD45b participates in TGF-beta-induced apoptosis by acting upstream of p38 activation.
C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA.
   NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA.
   Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA.
   Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA.
RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Rm C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA.
RI Fornace, Albert/A-7407-2008
OI Fornace, Albert/0000-0001-9695-085X
NR 65
TC 150
Z9 160
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43001
EP 43007
DI 10.1074/jbc.M307869200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000035
PM 12933797
ER

PT J
AU Magnifico, A
   Ettenberg, S
   Yang, CH
   Mariano, J
   Tiwari, S
   Fang, SY
   Lipkowitz, S
   Weissman, AM
AF Magnifico, A
   Ettenberg, S
   Yang, CH
   Mariano, J
   Tiwari, S
   Fang, SY
   Lipkowitz, S
   Weissman, AM
TI WW domain HECT E3s target Cbl RING finger E3s for proteasomal
   degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; UBIQUITIN-PROTEIN LIGASE; EPITHELIAL NA+
   CHANNEL; ROUS-SARCOMA VIRUS; C-CBL; DOWN-REGULATION; TYROSINE KINASES;
   IN-VIVO; NEDD4; FAMILY
AB Cbl proteins have RING finger-dependent ubiquitin ligase (E3) activity that is essential for down-regulation of tyrosine kinases. Here we establish that two WW domain HECT E3s, Nedd4 and Itch, bind Cbl proteins and target them for proteasomal degradation. This is dependent on the E3 activity of the HECT E3s but not on that of Cbl. Consistent with these observations, in cells expressing the epidermal growth factor receptor, Nedd4 reverses Cbl-b effects on receptor down-regulation, ubiquitylation, and proximal events in signaling. Cbl-b also targets active Src for degradation in cells, and Nedd4 similarly reverses Cbl-mediated Src degradation. These findings establish that RING finger E3s can be substrates, not only for autoubiquitylation but also for ubiquitylation by HECT E3s and suggest an additional level of regulation for Cbl substrates including protein-tyrosine kinases.
C1 NCI, Regulat Prot Funct Lab, Ctr Canc Res, Frederick, MD 21702 USA.
   NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20817 USA.
RP Weissman, AM (reprint author), NCI, Regulat Prot Funct Lab, Ctr Canc Res, Bldg 560,Rm 22-102, Frederick, MD 21702 USA.
RI Fang, Shengyun/H-3802-2011
NR 59
TC 129
Z9 132
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43169
EP 43177
DI 10.1074/jbc.M308009200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000058
PM 12907674
ER

PT J
AU Bruns, K
   Fossen, T
   Wray, V
   Henklein, P
   Tessmer, U
   Schubert, U
AF Bruns, K
   Fossen, T
   Wray, V
   Henklein, P
   Tessmer, U
   Schubert, U
TI Structural characterization of the HIV-1 Vpr N terminus - Evidence of
   cis/trans-proline isomerism
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL PROTEIN-R; CELL-CYCLE ARREST;
   NUCLEAR-LOCALIZATION SIGNAL; GLUCOCORTICOID-RECEPTOR; SECONDARY
   STRUCTURE; NMR STRUCTURE; PREINTEGRATION COMPLEX; BIOLOGICAL FUNCTIONS;
   CIRCULAR-DICHROISM
AB The 96-residue human immunodeficiency virus (HIV) accessory protein Vpr serves manifold functions in the retroviral life cycle including augmentation of viral replication in non-dividing host cells, induction of G(2) cell cycle arrest, and modulation of HIV-induced apoptosis. Using a combination of dynamic light scattering, circular dichroism, and NMR spectroscopy the N terminus of Vpr is shown to be a unique domain of the molecule that behaves differently from the C-terminal domain in terms of self-association and secondary structure folding. Interestingly, the four highly conserved proline residues in the N terminus are predicted to have a high propensity for cis/trans isomerism. Thus the high resolution structure and folding of a synthetic N-terminal peptide (Vpr(1-40)) and smaller fragments thereof have been investigated. H-1 NMR data indicate Vpr(1-40) possesses helical structure between residues 17-32, and for the first time, this helix, which is bound by proline residues, was observed even in aqueous solution devoid of any detergent supplements. In addition, NMR data revealed that all of the proline residues undergo a cis/trans isomerism to such an extent that similar to40% of all Vpr molecules possess at least one proline in a cis conformation. This phenomenon of cis/trans isomerism, which is unprecedented for HIV-1 Vpr, not only provides an explanation for the molecular heterogeneity observed in the full-length molecule but also indicates that in vivo the folding and function of Vpr should depend on a cis/trans-proline isomerase activity, particularly as two of the proline residues in positions 14 and 35 show considerable amounts of cis isomers. This prediction correlates well with our recent observation (Zander, K., Sherman, M. P., Tessmer, U., Bruns, K., Wray, V., Prechtel, A. T., Schubert, E., Henklein, P., Luban, J., Neidleman, J., Greene, W. C., and Schubert, U. (2003) J. Biol. Chem. 278, 43170-43181) of a functional interaction between the major cellular isomerase cyclophilin A and Vpr, both of which are incorporated into HIV-1 virions.
C1 Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany.
   Gesell Biotechnol Forsch mbH, Dept Biol Struct, D-38124 Braunschweig, Germany.
   Univ Hamburg, Heinrich Pette Inst, D-20251 Hamburg, Germany.
   Univ Bergen, Dept Chem, N-5007 Bergen, Norway.
   Humboldt Univ, Inst Biochem, D-10115 Berlin, Germany.
   NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Schubert, U (reprint author), Univ Erlangen Nurnberg, Inst Clin & Mol Virol, Schlossgarten 4, D-91054 Erlangen, Germany.
FU NIDDK NIH HHS [DK59537-1]
NR 79
TC 45
Z9 45
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43188
EP 43201
DI 10.1074/jbc.M305413200
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000060
PM 12881523
ER

PT J
AU Zander, K
   Sherman, MP
   Tessmer, U
   Bruns, K
   Wray, V
   Prechtel, AT
   Schubert, E
   Henklein, P
   Luban, J
   Neidleman, J
   Greene, WC
   Schubert, U
AF Zander, K
   Sherman, MP
   Tessmer, U
   Bruns, K
   Wray, V
   Prechtel, AT
   Schubert, E
   Henklein, P
   Luban, J
   Neidleman, J
   Greene, WC
   Schubert, U
TI Cyclophilin A interacts with HIV-1 Vpr and is required for its
   functional expression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; REGULATORY PROTEIN VPR; CELL-CYCLE ARREST;
   N-TERMINAL DOMAIN; CYCLOSPORINE-A; TYPE-1 VPR; NMR STRUCTURE; T-CELLS;
   GLUCOCORTICOID-RECEPTOR; VIRAL EXPRESSION
AB Viral protein R (Vpr) of human immunodeficiency virus, type 1 (HIV-1) is the major virion-associated accessory protein that affects a number of biological functions in the retroviral life cycle, including promotion of the transport of the preintegration complex into the nucleus and the induction of G(2) host cell cycle arrest. Our recent investigation of the conformational heterogeneity of the proline residues in the N terminus of Vpr suggested a functional interaction between Vpr and a host peptidylprolyl cis/trans isomerase (PPIase) that might regulate the cis/trans interconversion of the imidic bond within the conserved proline residues of Vpr in vivo. Using surface plasmon resonance spectroscopy, Far Western blot, and pulldown experiments a physical interaction of Vpr with the major host PPIase cyclophilin A (CypA) is now demonstrated. The interaction domain involves the N-terminal region of Vpr including an essential role for proline in position 35. The CypA inhibitor cyclosporin A and non-immunosuppressive PPIase inhibitors such as NIM811 and sanglifehrin A block expression of Vpr without affecting pre- or post-translational events such as transcription, intracellular transport, or virus incorporation of Vpr. Similarly to CypA inhibition, Vpr expression is also reduced in HIV-1 infected CypA(-/-) knock-out T cells. This study thus shows that in addition to the interaction between CypA and HIV-1 capsid occurring during early steps in virus replication, CypA is also important for the de novo synthesis of Vpr and that in the absence of CypA activity, the Vpr-mediated cell cycle arrest is completely lost in HIV-1-infected T cells.
C1 Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-91054 Erlangen, Germany.
   Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-20251 Hamburg, Germany.
   Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94103 USA.
   Gesell Biotechnol Forsch mbH, Dept Mol Struct Res, D-38124 Braunschweig, Germany.
   Humboldt Univ, Inst Biochem, D-10115 Berlin, Germany.
   Columbia Univ, Dept Microbiol, New York, NY 10018 USA.
   Columbia Univ, Dept Med, New York, NY 10018 USA.
   NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Schubert, U (reprint author), Univ Erlangen Nurnberg, Inst Clin & Mol Virol, Schlossgarten 4, D-91054 Erlangen, Germany.
FU NIAID NIH HHS [R01 AI36199, R01 AI036199]; NIDDK NIH HHS [R01
   DK59537-01]
NR 71
TC 64
Z9 68
U1 3
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43202
EP 43213
DI 10.1074/jbc.M305414200
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000061
PM 12881522
ER

PT J
AU Ishima, R
   Torchia, DA
   Lynch, SM
   Gronenborn, AM
   Louis, JM
AF Ishima, R
   Torchia, DA
   Lynch, SM
   Gronenborn, AM
   Louis, JM
TI Solution structure of the mature HIV-1 protease monomer - Insight into
   the tertiary fold and stability of a precursor
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID VIRUS TYPE-1 PROTEASE; GAG-POL POLYPROTEIN; HUMAN-IMMUNODEFICIENCY;
   RETROVIRAL PROTEASES; TRANSFRAME PROTEIN; CRYSTAL-STRUCTURES; SUBSTRATE
   COMPLEX; VIRAL INFECTIVITY; ACTIVE-SITE; NMR
AB We present the first solution structure of the HIV-1 protease monomer spanning the region Phe(1)-Ala(95) (PR1-95). Except for the terminal regions (residues 1-10 and 91-95) that are disordered, the tertiary fold of the remainder of the protease is essentially identical to that of the individual subunit of the dimer. In the monomer, the side chains of buried residues stabilizing the active site interface in the dimer, such as Asp(25), Asp(29), and Arg(87), are now exposed to solvent. The flap dynamics in the monomer are similar to that of the free protease dimer. We also show that the protease domain of an optimized precursor flanked by 56 amino acids of the N-terminal transframe region is predominantly monomeric, exhibiting a tertiary fold that is quite similar to that of PR1-95 structure. This explains the very low catalytic activity observed for the protease prior to its maturation at its N terminus as compared with the mature protease, which is an active stable dimer under identical conditions. Adding as few as 2 amino acids to the N terminus of the mature protease significantly increases its dissociation into monomers. Knowledge of the protease monomer structure and critical features of its dimerization may aid in the screening and design of compounds that target the protease prior to its maturation from the Gag-Pol precursor.
C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   NIDCR, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA.
RP Louis, JM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 411, Bethesda, MD 20892 USA.
EM jmlouis@helix.nih.gov
OI Gronenborn, Angela M/0000-0001-9072-3525
NR 51
TC 59
Z9 61
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43311
EP 43319
DI 10.1074/jbc.M307549200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000074
PM 12933791
ER

PT J
AU Su, CL
   Sztalryd, C
   Contreras, JA
   Holm, C
   Kimmel, AR
   Londos, C
AF Su, CL
   Sztalryd, C
   Contreras, JA
   Holm, C
   Kimmel, AR
   Londos, C
TI Mutational analysis of the hormone-sensitive lipase translocation
   reaction in adipocytes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LIPID STORAGE DROPLETS; PROTEIN-KINASE; IN-VITRO; LIPOLYSIS;
   IDENTIFICATION; PHOSPHORYLATION; EXPRESSION; PURIFICATION; MECHANISM;
   PERILIPIN
AB Lipolysis in adipocytes governs the release of fatty acids for the supply of energy to various tissues of the body. This reaction is mediated by hormone-sensitive lipase (HSL), a cytosolic enzyme, and perilipin, which coats the lipid droplet surface in adipocytes. Both HSL and perilipin are substrates for polyphosphorylation by protein kinase A (PKA), and phosphorylation of perilipin is required to induce HSL to translocate from the cytosol to the surface of the lipid droplet, a critical step in the lipolytic reaction (Sztalryd C., Xu, G., Dorward, H., Tansey, J.T., Contreras, J.A, Kimmel, A. R., and Londos, C. (2003) J. Cell Biol. 161, 1093-1103). In the present paper we demonstrate that phosphorylation at one of the two more recently discovered PKA sites within HSL, serines 659 and 660, is also required to effect the translocation reaction. Translocation does not occur when these serines residues are mutated simultaneously to alanines. Also, mutation of the catalytic Ser-423 eliminates HSL translocation, showing that the inactive enzyme does not migrate to the lipid droplet upon PKA activation. Thus, HSL translocation requires the phosphorylation of both HSL and perilipin.
C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
   Lund Univ, Dept Cell & Mol Biol, Sect Mol Signaling, SE-22184 Lund, Sweden.
RP Londos, C (reprint author), Bldg 50,Rm 3140,MSC-8028, Bethesda, MD 20892 USA.
NR 18
TC 82
Z9 85
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43615
EP 43619
DI 10.1074/jbc.M301809200
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000109
PM 12832420
ER

PT J
AU Baxa, U
   Taylor, KL
   Wall, JS
   Simon, MN
   Cheng, NQ
   Wickner, RB
   Steven, AC
AF Baxa, U
   Taylor, KL
   Wall, JS
   Simon, MN
   Cheng, NQ
   Wickner, RB
   Steven, AC
TI Architecture of Ure2p prion filaments - The N-terminal domains form a
   central core fiber
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSMISSION ELECTRON-MICROSCOPY; YEAST SACCHAROMYCES-CEREVISIAE;
   NUCLEAR-LOCALIZATION; PROTEIN DETERMINANT; PODOSPORA-ANSERINA; MASS
   ANALYSIS; IN-VITRO; SCRAPIE; GENE; ORGANIZATION
AB The [URE3] prion is an inactive, self-propagating, filamentous form of the Ure2 protein, a regulator of nitrogen catabolism in yeast. The N-terminal "prion" domain of Ure2p determines its in vivo prion properties and in vitro amyloid-forming ability. Here we determined the overall structures of Ure2p filaments and related polymers of the prion domain fused to other globular proteins. Protease digestion of 25-nm diameter Ure2p filaments trimmed them to 4-nm filaments, which mass spectrometry showed to be composed of prion domain fragments, primarily residues similar to1-70. Fusion protein filaments with diameters of 14-25 nm were also reduced to 4-nm filaments by proteolysis. The prion domain transforms from the most to the least protease-sensitive part upon filament formation in each case, implying that it undergoes a conformational change. Intact filaments imaged by cryo-electron microscopy or after vanadate staining by scanning transmission electron microscopy (STEM) revealed a central 4-nm core with attached globular appendages. STEM mass per unit length measurements of unstained filaments yielded 1 monomer per 0.45 nm in each case. These observations strongly support a unifying model whereby subunits in Ure2p filaments, as well as in fusion protein filaments, are connected by interactions between their prion domains, which form a 4-nm amyloid filament backbone, surrounded by the corresponding C-terminal moieties.
C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
   NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
   Brookhaven Natl Labs, Dept Biol, Upton, NY 11973 USA.
RP Steven, AC (reprint author), Bldg 50,Rm 1517,50 South Dr,MSC 8025, Bethesda, MD 20892 USA.
NR 46
TC 119
Z9 120
U1 1
U2 12
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43717
EP 43727
DI 10.1074/jbc.M306004200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000121
PM 12917441
ER

PT J
AU Shcherbakova, PV
   Pavlov, YI
   Chilkova, O
   Rogozin, IB
   Johansson, E
   Kunkel, TA
AF Shcherbakova, PV
   Pavlov, YI
   Chilkova, O
   Rogozin, IB
   Johansson, E
   Kunkel, TA
TI Unique error signature of the four-subunit yeast DNA polymerase epsilon
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CELL NUCLEAR ANTIGEN; SACCHAROMYCES-CEREVISIAE; REPLICATION ERRORS;
   MUTATIONAL SPECTRA; ENZYMOLOGICAL CHARACTERIZATION; EXONUCLEASE
   ACTIVITY; ACCESSORY PROTEINS; BASE SUBSTITUTION; CONSERVED REGION;
   CHROMOSOMAL DNA
AB We have purified wild type and exonuclease-deficient four-subunit DNA polymerase epsilon (Pol epsilon) complex from Saccharomyces cerevisiae and analyzed the fidelity of DNA synthesis by the two enzymes. Wild type Pol epsilon synthesizes DNA accurately, generating single-base substitutions and deletions at average error rates of less than or equal to 2 x 10(-5) and less than or equal to 5 x 10(-7), respectively. Pol epsilon lacking 3' --> 5' exonuclease activity is less accurate to a degree suggesting that wild type Pol epsilon proofreads at least 92% of base substitution errors and at least 99% of frameshift errors made by the polymerase. Surprisingly the base substitution fidelity of exonuclease-deficient Pol epsilon is severalfold lower than that of proofreading-deficient forms of other replicative polymerases. Moreover the spectrum of errors shows a feature not seen with other A, B, C, or X family polymerases: a high proportion of transversions resulting from T . dTTP, T . dCTP, and C . dTTP mispairs. This unique error specificity and amino acid sequence alignments suggest that the structure of the polymerase active site of Pol epsilon differs from those of other B family members. We observed both similarities and differences between the spectrum of substitutions generated by proofreading-deficient Pol epsilon in vitro and substitutions occurring in vivo in a yeast strain defective in Pol epsilon proofreading and DNA mismatch repair. We discuss the implications of these findings for the role of Pol epsilon polymerase activity in DNA replication.
C1 NIEHS, Lab Struct Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   Umea Univ, Dept Med Biochem & Biophys, SE-90187 Umea, Sweden.
   Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA.
   Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
RP Kunkel, TA (reprint author), NIEHS, Lab Struct Biol, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 73
TC 69
Z9 69
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 31
PY 2003
VL 278
IS 44
BP 43770
EP 43780
DI 10.1074/jbc.M306893200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736EA
UT WOS:000186157000127
PM 12882968
ER

PT J
AU Ito, Y
   Yang, FQ
   Fitze, P
   Powell, J
   Ide, D
AF Ito, Y
   Yang, FQ
   Fitze, P
   Powell, J
   Ide, D
TI Improved spiral disk assembly for high-speed counter-current
   chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE counter-current chromatography; instrumentation; spiral disk assembly;
   coil planet centrifuge; peptides; proteins
AB The spiral disk for type-J high-speed counter-current chromatography (HSCCC) has been improved by placing short segments of PTFE (tetrafluoroethylene) tubing into the channel at regular intervals. The best results were obtained with a four-channel spiral column using 600 spacers, which significantly improved stationary phase retention and partition efficiency in both n-butanol-acetic acid-water (4:1:5) and poly(ethylene glycol) 1000-dibasic phosphate polymer phase systems. Based on these findings, a "bead-chain spiral disk" was designed and its performance tested with a type-J HSCCC centrifuge. This new column design substantially improved the separation of both dipeptide and protein samples in terms of stationary phase retention and partition efficiency. (C) 2003 Elsevier B.V All rights reserved.
C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA.
   NIH, Machine Instrument Design Fabricat, Bethesda, MD 20892 USA.
   NIMH, NIH, Bethesda, MD 20892 USA.
RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3334, Bethesda, MD 20892 USA.
NR 5
TC 35
Z9 42
U1 4
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD OCT 31
PY 2003
VL 1017
IS 1-2
BP 71
EP 81
DI 10.1016/j.chroma.2003.08.011
PG 11
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 730XZ
UT WOS:000185856600007
PM 14584692
ER

PT J
AU Wei, Y
   Zhang, TY
   Ito, Y
AF Wei, Y
   Zhang, TY
   Ito, Y
TI Preparative separation of rhein from Chinese traditional herb by
   repeated high-speed counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE counter-current chromatography; rheum officinale; preparative
   chromatography; plant materials; pharmaceutical analysis; rhein
ID MODULATED STEPWISE ELUTION
AB High-speed counter-current chromatography (HSCCC) was repeatedly used for isolation and purification of them from Rheum officinale Baill (Dahuang) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3:7:5:5, v/v), which had been selected by analytical (HSCCC). Using two preparative units of the HSCCC centrifuge, about a 500 mg amount of the crude extract was separated, yielding 6.7 mg of them at a high purity of over 97%. (C) 2003 Elsevier B.V All rights reserved.
C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA.
   Beijing Inst New Technol Applicat, Beijing Res Ctr Separat & Purificat Technol Nat P, Beijing 100035, Peoples R China.
RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3334, Bethesda, MD 20892 USA.
NR 8
TC 27
Z9 31
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD OCT 31
PY 2003
VL 1017
IS 1-2
BP 125
EP 130
DI 10.1016/j.chroma.2003.08.015
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 730XZ
UT WOS:000185856600012
PM 14584697
ER

PT J
AU Leipe, DD
   Koonin, EV
   Aravind, L
AF Leipe, DD
   Koonin, EV
   Aravind, L
TI Evolution and classification of P-loop kinases and related proteins
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
DE molecular evolution; LUCA; P-loop kinase
ID TRANSFER-RNA LIGASE; COLI PHOSPHOENOLPYRUVATE CARBOXYKINASE; MULTIPLE
   SEQUENCE ALIGNMENT; NUCLEOTIDE-BINDING SITE; SIMPLEX-VIRUS TYPE-1; SP
   STRAIN PCC6308; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ADENYLATE KINASE;
   MOLECULAR CHARACTERIZATION
AB Sequences and structures of all P-loop-fold proteins were compared with the aim of reconstructing the principal events in the evolution of P-loop-containing kinases. It is shown that kinases and some related proteins comprise a monophyletic assemblage within the P-loop NTPase fold. An evolutionary classification of these proteins was developed using standard phylogenetic methods, analysis of shared sequence and structural signatures, and similarity-based clustering. This analysis resulted in the identification of approximately 40 distinct protein families within the P-loop kinase class. Most of these enzymes phosphorylate nucleosides and nucleotides, as well as sugars, coenzyme precursors, adenosine 5'-phosphosulfate and polynucleotides. In addition, the class includes sulfotransferases, amide bond ligases, pyrimidine and dihydrofolate reductases, and several other families of enzymes that have acquired new catalytic capabilities distinct from the ancestral kinase reaction. Our reconstruction of the early history of the P-loop NTPase fold includes the initial split into the common ancestor of the kinase and the GTPase classes, and the common ancestor of ATPases. This was followed by the divergence of the kinases, which primarily phosphorylated nucleoside monophosphates (NMP), but could have had broader specificity We provide evidence for the presence of at least two to four distinct P-loop kinases, including distinct forms specific for dNMP and rNMP, and related enzymes in the last universal common ancestor of all extant life forms. Subsequent evolution of kinases seems to have been dominated by the emergence of new bacterial and, to a lesser extent, archaeal families. Some of these enzymes retained their kinase activity but evolved new substrate specificities, whereas others acquired new activities, such as sulfate transfer and reduction. Eukaryotes appear to have acquired most of their kinases via horizontal gene transfer from Bacteria, partly from the mitochondrial and chloroplast endosymbionts and partly at later stages of evolution. A distinct superfamily of kinases, which we designated DxTN after its sequence signature, appears to have evolved in selfish replicons, such as bacteriophages, and was subsequently widely recruited by eukaryotes for multiple functions related to nucleic acid processing and general metabolism. In the course of this analysis, several previously undetected groups of predicted kinases were identified, including widespread archaeo-eukaryotic and archaeal families. The results could serve as a framework for systematic experimental characterization of new biochemical and biological functions of kinases. Published by Elsevier Ltd.
C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
NR 180
TC 145
Z9 149
U1 2
U2 22
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 31
PY 2003
VL 333
IS 4
BP 781
EP 815
DI 10.1016/j.jmb.2003.08.040
PG 35
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 736QU
UT WOS:000186185300009
PM 14568537
ER

PT J
AU Collins, FS
   Watson, JD
AF Collins, FS
   Watson, JD
TI Genetic discrimination: Time to act
SO SCIENCE
LA English
DT Editorial Material
C1 NHGRI, NIH, Bethesda, MD 20892 USA.
   NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA.
   Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
NR 4
TC 20
Z9 20
U1 0
U2 8
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 31
PY 2003
VL 302
IS 5646
BP 745
EP 745
DI 10.1126/science.302.5646.745
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 737XQ
UT WOS:000186258000001
PM 14593134
ER

PT J
AU Singleton, AB
   Farrer, M
   Johnson, J
   Singleton, A
   Hague, S
   Kachergus, J
   Hulihan, M
   Peuralinna, T
   Dutra, A
   Nussbaum, R
   Lincoln, S
   Crawley, A
   Hanson, M
   Maraganore, D
   Adler, C
   Cookson, MR
   Muenter, M
   Baptista, M
   Miller, D
   Blancato, J
   Hardy, J
   Gwinn-Hardy, K
AF Singleton, AB
   Farrer, M
   Johnson, J
   Singleton, A
   Hague, S
   Kachergus, J
   Hulihan, M
   Peuralinna, T
   Dutra, A
   Nussbaum, R
   Lincoln, S
   Crawley, A
   Hanson, M
   Maraganore, D
   Adler, C
   Cookson, MR
   Muenter, M
   Baptista, M
   Miller, D
   Blancato, J
   Hardy, J
   Gwinn-Hardy, K
TI alpha-synuclein locus triplication causes Parkinson's disease
SO SCIENCE
LA English
DT Article
C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
   NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
   Mayo Clin, Genet Neurodgenerat Lab, Jacksonville, FL 32224 USA.
   Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA.
   Mayo Clin, Dept Neurol, Scottsdale, AZ 85259 USA.
   Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RI Gwinn, Katrina/C-2508-2009; Johnson, Janel/A-7136-2010; Singleton,
   Andrew/C-3010-2009; Hardy, John/C-2451-2009
NR 5
TC 2162
Z9 2214
U1 21
U2 166
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 31
PY 2003
VL 302
IS 5646
BP 841
EP 841
DI 10.1126/science.1090278
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 737XQ
UT WOS:000186258000041
PM 14593171
ER

PT J
AU Changelian, PS
   Flanagan, ME
   Ball, DJ
   Kent, CR
   Magnuson, KS
   Martin, WH
   Rizzuti, BJ
   Sawyer, PS
   Perry, BD
   Brissette, WH
   McCurdy, SP
   Kudlacz, EM
   Conklyn, MJ
   Elliott, EA
   Koslov, ER
   Fisher, MB
   Strelevitz, TJ
   Yoon, K
   Whipple, DA
   Sun, JM
   Munchhof, MJ
   Doty, JL
   Casavant, JM
   Blumenkopf, TA
   Hines, M
   Brown, MF
   Lillie, BM
   Subramanyam, C
   Shang-Poa, C
   Milici, AJ
   Beckius, GE
   Moyer, JD
   Su, CY
   Woodworth, TG
   Gaweco, AS
   Beals, CR
   Littman, BH
   Fisher, DA
   Smith, JF
   Zagouras, P
   Magna, HA
   Saltarelli, MJ
   Johnson, KS
   Nelms, LF
   Des Etages, SG
   Hayes, LS
   Kawabata, TT
   Finco-Kent, D
   Baker, DL
   Larson, M
   Si, MS
   Paniagua, R
   Higgins, J
   Holm, B
   Reitz, B
   Zhou, YJ
   Morris, RE
   O'Shea, JJ
   Borie, DC
AF Changelian, PS
   Flanagan, ME
   Ball, DJ
   Kent, CR
   Magnuson, KS
   Martin, WH
   Rizzuti, BJ
   Sawyer, PS
   Perry, BD
   Brissette, WH
   McCurdy, SP
   Kudlacz, EM
   Conklyn, MJ
   Elliott, EA
   Koslov, ER
   Fisher, MB
   Strelevitz, TJ
   Yoon, K
   Whipple, DA
   Sun, JM
   Munchhof, MJ
   Doty, JL
   Casavant, JM
   Blumenkopf, TA
   Hines, M
   Brown, MF
   Lillie, BM
   Subramanyam, C
   Shang-Poa, C
   Milici, AJ
   Beckius, GE
   Moyer, JD
   Su, CY
   Woodworth, TG
   Gaweco, AS
   Beals, CR
   Littman, BH
   Fisher, DA
   Smith, JF
   Zagouras, P
   Magna, HA
   Saltarelli, MJ
   Johnson, KS
   Nelms, LF
   Des Etages, SG
   Hayes, LS
   Kawabata, TT
   Finco-Kent, D
   Baker, DL
   Larson, M
   Si, MS
   Paniagua, R
   Higgins, J
   Holm, B
   Reitz, B
   Zhou, YJ
   Morris, RE
   O'Shea, JJ
   Borie, DC
TI Prevention of organ allograft rejection by a specific Janus kinase 3
   inhibitor
SO SCIENCE
LA English
DT Article
ID T-CELL HOMEOSTASIS; TRANSPLANTATION; LEUKEMIA; SURVIVAL; MICE; GENE;
   JAK3
AB Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.
C1 Pfizer Global Res & Dev, Dept Antibacterials & Immunol, Immunol Grp, Groton, CT 06340 USA.
   Pfizer Global Res & Dev, Dept Drug Safety Evaluat, Groton, CT 06340 USA.
   Pfizer Global Res & Dev, Dept Pharmacokinet Dynam & Metab, Groton, CT 06340 USA.
   Pfizer Global Res & Dev, Dept Genom & Proteom Sci, Groton, CT 06340 USA.
   Stanford Univ, Sch Med, Transplantat Immunol Lab, Stanford, CA 94305 USA.
   NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA.
RP Changelian, PS (reprint author), Pfizer Global Res & Dev, Dept Antibacterials & Immunol, Immunol Grp, Groton, CT 06340 USA.
RI Ain, Kenneth/A-5179-2012
OI Ain, Kenneth/0000-0002-2668-934X
NR 24
TC 370
Z9 390
U1 3
U2 30
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 31
PY 2003
VL 302
IS 5646
BP 875
EP 878
DI 10.1126/science.1087061
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 737XQ
UT WOS:000186258000052
PM 14593182
ER

PT J
AU Prisinzano, T
   Hsin, LW
   Folk, JE
   Flippen-Anderson, JL
   George, C
   Jacobson, AE
   Rice, KC
AF Prisinzano, T
   Hsin, LW
   Folk, JE
   Flippen-Anderson, JL
   George, C
   Jacobson, AE
   Rice, KC
TI A concise synthesis of
   (S)-(+)-1-(4-{2-[bis(4-fluorophenyl)methoxy]-ethyl}piperazin-1-yl)-2-phe
   nylpropan-2-ol dimaleate
SO TETRAHEDRON-ASYMMETRY
LA English
DT Article
ID ABUSE THERAPEUTIC AGENTS; DOPAMINE TRANSPORTER AFFINITY; COCAINE-ABUSE;
   RHESUS-MONKEYS; ANALOGS
AB (S)-(+)-1-(4-{2-[Bis-(4-fluorophenyl)methoxy]-ethyl}piperazin-1-yl)-2-phenylpropan-2-ol dimaleate was prepared in several steps from (S)-(+)-atrolactic acid by a process permitting synthesis of multigram quantities. With the information provided by asymmetric synthesis, the X-ray crystal structure was solved. Published by Elsevier Ltd.
C1 NIDDK, Med Chem Lab, Dept Hlth, NIH, Bethesda, MD 20892 USA.
   Human Serv, Bethesda, MD 20892 USA.
   USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA.
RP Rice, KC (reprint author), NIDDK, Med Chem Lab, Dept Hlth, NIH, Bethesda, MD 20892 USA.
RI Prisinzano, Thomas/B-7877-2010; 
OI HSIN, LING-WEI/0000-0001-5018-4491
NR 23
TC 10
Z9 10
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0957-4166
J9 TETRAHEDRON-ASYMMETR
JI Tetrahedron: Asymmetry
PD OCT 31
PY 2003
VL 14
IS 21
BP 3285
EP 3289
DI 10.1016/j.tetasy.2003.05.001
PG 5
WC Chemistry, Inorganic & Nuclear; Chemistry, Organic; Chemistry, Physical
SC Chemistry
GA 739NA
UT WOS:000186352300006
ER

PT J
AU Lohner, R
   Cebral, J
   Soto, O
   Yim, P
   Burgess, JE
AF Lohner, R
   Cebral, J
   Soto, O
   Yim, P
   Burgess, JE
TI Applications of patient-specific CFD in medicine and life sciences
SO INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS
LA English
DT Article
DE hemodynamics; pulmonary flows; CFD; bioengineering
ID NAVIER-STOKES EQUATIONS; FINITE-ELEMENT METHODS; FREE IMPLICIT METHOD;
   UNSTRUCTURED GRIDS; AEROELASTIC COMPUTATIONS; SURFACE RECONSTRUCTION;
   FLOW PROBLEMS; BLOOD-FLOW; ALGORITHMS; MESHES
AB Recent advances in medical image segmentation, grid generation, flow solvers, realistic boundary conditions, fluid-structure interaction, data reduction and visualization arc reviewed with special emphasis on patient-specific flow prediction. At the same time, present shortcomings in each one of these areas are identified. Several examples are given that show that this methodology is maturing rapidly, and may soon find widespread use in medicine. Copyright (C) 2003 John Wiley Sons, Ltd.
C1 George Mason Univ, Sch Computat Sci, Fairfax, VA 22030 USA.
   Natl Inst Hlth, Dept Diagnost Radiol, Bethesda, MD USA.
   Fairfax Hosp, INOVA, Fairfax, VA USA.
RP Lohner, R (reprint author), George Mason Univ, Sch Computat Sci, MS 4C7, Fairfax, VA 22030 USA.
EM rlohner@gmu.edu
NR 52
TC 19
Z9 20
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0271-2091
J9 INT J NUMER METH FL
JI Int. J. Numer. Methods Fluids
PD OCT 30
PY 2003
VL 43
IS 6-7
BP 637
EP 650
DI 10.1002/fld.544
PG 14
WC Computer Science, Interdisciplinary Applications; Mathematics,
   Interdisciplinary Applications; Mechanics; Physics, Fluids & Plasmas
SC Computer Science; Mathematics; Mechanics; Physics
GA 737GG
UT WOS:000186221600002
ER

PT J
AU McCarron, JA
   Pike, VW
AF McCarron, JA
   Pike, VW
TI Synthesis of no-carrier-added [C-11]methanesulfonyl chloride as a new
   labeling agent for PET radiopharmaceutical development
SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
LA English
DT Article
DE carbon-11; labeling agent; PET; [C-11]mesyl chloride;
   [C-11]methanesulfonamide; [C-11]mesylate
ID POSITRON-EMISSION-TOMOGRAPHY; SUBSTITUTION; SULFUR; IODIDE; ETHYL
AB Three methods are described for labeling methanesulfonyl (mesyl) chloride with no-carrier-added (NCA) carbon-11 (t(1/2)=20.4min; beta(+)=99.8%) to provide a new labeling agent of potential value in radiopharmaceutical development for positron emission tomography (PET). Each method uses NCA [C-11]iodomethane, which is readily prepared from cyclotron-produced [C-11]carbon dioxide or [C-11]methane by known procedures. The first method (route 1) consisted of converting [C-11]iodomethane into [C-11]methyllithium and then treatment with sulfuryl chloride. NCA [C-11]mesyl chloride was obtained in 78% decay-corrected radiochemical yield (RCY) from [C-11]iodomethane at 30 min from the end of radionuclide production (ERP). However, co-production of n-butanesulfonyl chloride limited the extent of reaction of this labeling agent with 1,2,3,4-tetrahydroisoquinoline (THIQ). Two new syntheses were devised, based on converting [C-11]iodomethane into [C-11]methanethiol by passage over heated sodium hydrogen sulfide for subsequent treatment with either chlorinated water (route 2) or over heated manganese(IV) oxide and then calcium hypochlorite (route 3). These procedures gave NCA [C-11]mesyl cloride in 77% (route 2) and 28% (route 3) RCYs from [11C]iodomethane at about 20 min from ERP. Crude [11C]mesyl chloride, produced by route 2 or 3, reacted rapidly with THIQ to give the corresponding NCA [11C]methanesulfonamide in 49 or 74% RCY, respectively. Phenol was also converted rapidly with [11C]mesyl cholide into the corresponding [11C]mesylate (>90% RCY). Copyright (C) 2003 John Wiley & Sons, Ltd.
C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, MRC, Cyclotron Unit, London W12 0NN, England.
RP McCarron, JA (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bldg 10,Rm B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mccarroj@intra.nimh.nih.gov
NR 32
TC 3
Z9 3
U1 1
U2 7
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0362-4803
J9 J LABELLED COMPD RAD
JI J. Label. Compd. Radiopharm.
PD OCT 30
PY 2003
VL 46
IS 12
BP 1127
EP 1140
DI 10.1002/jlcr.745
PG 14
WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry,
   Analytical
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 745RW
UT WOS:000186702700004
ER

PT J
AU Liotta, LA
   Ferrari, M
   Petricoin, E
AF Liotta, LA
   Ferrari, M
   Petricoin, E
TI Written in blood
SO NATURE
LA English
DT Article
C1 NCI, Bethesda, MD 20892 USA.
   Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Dept Internal Med, Columbus, OH 43210 USA.
   US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Liotta, LA (reprint author), NCI, 10 Ctr Dr, Bethesda, MD 20892 USA.
NR 5
TC 341
Z9 375
U1 6
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 30
PY 2003
VL 425
IS 6961
BP 905
EP 905
DI 10.1038/425905a
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 737KY
UT WOS:000186230600022
PM 14586448
ER

PT J
AU Gong, SC
   Zheng, C
   Doughty, ML
   Losos, K
   Didkovsky, N
   Schambra, UB
   Nowak, NJ
   Joyner, A
   Leblanc, G
   Hatten, ME
   Heintz, N
AF Gong, SC
   Zheng, C
   Doughty, ML
   Losos, K
   Didkovsky, N
   Schambra, UB
   Nowak, NJ
   Joyner, A
   Leblanc, G
   Hatten, ME
   Heintz, N
TI A gene expression atlas of the central nervous system based on bacterial
   artificial chromosomes
SO NATURE
LA English
DT Article
ID DEVELOPING CEREBRAL-CORTEX; INSITU HYBRIDIZATION; SUPERIOR COLLICULUS;
   ESCHERICHIA-COLI; TRANSGENIC MICE; GOOSECOID-LIKE; AXON GUIDANCE;
   MOUSE-BRAIN; NEURONS; RECEPTORS
AB The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.
C1 Rockefeller Univ, Howard Hughes Med Inst, Mol Biol Lab, New York, NY 10021 USA.
   Rockefeller Univ, Howard Hughes Med Inst, GENSAT Project, New York, NY 10021 USA.
   Rockefeller Univ, Howard Hughes Med Inst, Dev Neurobiol Lab, New York, NY 10021 USA.
   E Tennessee State Univ, Dept Anat & Cell Biol, Johnson City, TN 37614 USA.
   Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
   NYU, Sch Med, Dept Cell Biol, Skirball Inst Biomol Med,Dev Genet Program, New York, NY 10016 USA.
   Howard Hughes Med Inst, New York, NY 10016 USA.
   Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP Heintz, N (reprint author), Rockefeller Univ, Howard Hughes Med Inst, Mol Biol Lab, 1230 York Ave,Box 260, New York, NY 10021 USA.
NR 46
TC 1057
Z9 1072
U1 5
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 30
PY 2003
VL 425
IS 6961
BP 917
EP 925
DI 10.1038/nature02033
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 737KY
UT WOS:000186230600032
PM 14586460
ER

PT J
AU Lee, HC
   Wang, JM
   Swartz, KJ
AF Lee, HC
   Wang, JM
   Swartz, KJ
TI Interaction between extracellular hanatoxin and the resting conformation
   of the voltage-sensor paddle in Kv channels
SO NEURON
LA English
DT Article
ID SHAKER K+ CHANNEL; GATED ION CHANNELS; GATING MODIFIER TOXINS; POTASSIUM
   CHANNEL; ACTIVATION GATE; CHARGE MOVEMENT; HELICAL STRUCTURE; SENSING
   DOMAINS; RECEPTOR-SITE; MOVING PARTS
AB In voltage-activated potassium (Kv) channels, basic residues in S4 enable the voltage-sensing domain to move in response to membrane depolarization and thereby trigger the activation gate to open. In the X-ray structure of the KvAP channel, the S4 helix is located near the intracellular boundary of the membrane where it forms a "voltage-sensor paddle" motif with the S3b helix. It has been proposed that the paddle is lipid-exposed and that it translocates through the membrane as it activates. We studied the interaction of externally applied Hanatoxin with the voltage-sensor paddle in Kv channels and show that the toxin binds tightly even at negative voltages where the paddle is resting and the channel is closed. Moreover, measurements of gating charge movement suggest that Hanatoxin interacts with and stabilizes the resting paddle. These findings point to an extracellular location for the resting conformation of the voltage-sensor paddle and constrain its transmembrane movements during activation.
C1 Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA.
RP Swartz, KJ (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, NIH, Bldg 36,Room 2C19,36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA NS002945-13]
NR 58
TC 91
Z9 96
U1 2
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD OCT 30
PY 2003
VL 40
IS 3
BP 527
EP 536
DI 10.1016/S0896-6273(03)00636-6
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 740AQ
UT WOS:000186379000012
PM 14642277
ER

PT J
AU Weinstein, LS
   Simonds, WF
AF Weinstein, LS
   Simonds, WF
TI HRPT2, a marker of parathyroid cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA.
RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA.
OI Weinstein, Lee/0000-0002-1899-5152
NR 3
TC 26
Z9 27
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 30
PY 2003
VL 349
IS 18
BP 1691
EP 1692
DI 10.1056/NEJMp038159
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 737FJ
UT WOS:000186219500001
PM 14585935
ER

PT J
AU Shattuck, TM
   Valimaki, S
   Obara, T
   Gaz, RD
   Clark, OH
   Shoback, D
   Wierman, ME
   Tojo, K
   Robbins, CM
   Carpten, JD
   Farnebo, LO
   Larsson, C
   Arnold, A
AF Shattuck, TM
   Valimaki, S
   Obara, T
   Gaz, RD
   Clark, OH
   Shoback, D
   Wierman, ME
   Tojo, K
   Robbins, CM
   Carpten, JD
   Farnebo, LO
   Larsson, C
   Arnold, A
TI Somatic and germ-line mutations of the HRPT2 gene in sporadic
   parathyroid carcinoma
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID JAW TUMOR SYNDROME; HEREDITARY HYPERPARATHYROIDISM; SUPPRESSOR GENES;
   RETINOBLASTOMA; DIAGNOSIS; MANAGEMENT; HISTORY; CANCER; BRCA2
AB BACKGROUND:
   We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism -- hyperparathyroidism-jaw tumor (HPT-JT) syndrome -- that carries an increased risk of parathyroid cancer.
   METHODS:
   We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2.
   RESULTS:
   Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations.
   CONCLUSIONS:
   Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant.
C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA.
   Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA.
   Karolinska Hosp, Dept Mol Med, S-10401 Stockholm, Sweden.
   Karolinska Hosp, Dept Surg Sci, S-10401 Stockholm, Sweden.
   Tokyo Womens Med Univ, Dept Endocrine Surg, Sinjuku Ku, Tokyo, Japan.
   Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   Univ Calif San Francisco, Mt Zion Med Ctr, Dept Surg, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Vet Affairs Med Ctr, Endocrine Res Unit, San Francisco, CA 94143 USA.
   Univ Colorado, Vet Affairs Med Ctr, Div Endocrinol, Denver, CO 80202 USA.
   Jikei Univ, Sch Med, Dept Internal Med, Div Diabet & Endocrinol, Tokyo, Japan.
   NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA.
NR 34
TC 266
Z9 278
U1 1
U2 5
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 30
PY 2003
VL 349
IS 18
BP 1722
EP 1729
DI 10.1056/NEJMoa031237
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 737FJ
UT WOS:000186219500006
PM 14585940
ER

PT J
AU Nelson, KB
AF Nelson, KB
TI Can we prevent cerebral palsy?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CESAREAN-SECTION; BIRTH-WEIGHT; RISK-FACTORS; INFANTS; STROKE;
   INTRAPARTUM; DELIVERY; TRENDS
C1 NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA.
RP Nelson, KB (reprint author), NINDS, Neuroepidemiol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 25
TC 103
Z9 108
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 30
PY 2003
VL 349
IS 18
BP 1765
EP 1769
DI 10.1056/NEJMsb035364
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 737FJ
UT WOS:000186219500013
PM 14585946
ER

PT J
AU Allegra, CJ
   Kim, G
   Kirsch, IR
AF Allegra, CJ
   Kim, G
   Kirsch, IR
TI Microsatellite instability in colon cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID ADJUVANT CHEMOTHERAPY; COLORECTAL-CANCER; SURVIVAL; BENEFIT
C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
   Mayo Clin Jacksonville, Jacksonville, FL 32224 USA.
   NCI, Bethesda, MD 20889 USA.
RP Allegra, CJ (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA.
NR 4
TC 6
Z9 6
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 30
PY 2003
VL 349
IS 18
BP 1774
EP 1775
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 737FJ
UT WOS:000186219500024
PM 14585950
ER

PT J
AU Ho, NC
AF Ho, NC
TI Long-term outcomes after successful early defibrillation
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 NIH, Baltimore, MD 21224 USA.
RP Ho, NC (reprint author), NIH, Baltimore, MD 21224 USA.
NR 4
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 30
PY 2003
VL 349
IS 18
BP 1777
EP 1777
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 737FJ
UT WOS:000186219500028
PM 14585952
ER

PT J
AU Lei, SB
   Pelkey, KA
   Topolnik, L
   Congar, P
   Lacaille, JC
   McBain, CJ
AF Lei, SB
   Pelkey, KA
   Topolnik, L
   Congar, P
   Lacaille, JC
   McBain, CJ
TI Depolarization-induced long-term depression at hippocampal mossy
   fiber-CA3 pyramidal neuron synapses
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE LTD; depolarization; L-type Ca2+ channels; glutamate receptor;
   hippocampus; mossy fiber
ID VOLTAGE-GATED CALCIUM; EXCITATORY SYNAPTIC TRANSMISSION;
   DOMAIN-CONTAINING PROTEINS; 2 DISTINCT FORMS; GYRUS IN-VITRO; CA2+
   CHANNELS; AMPA RECEPTORS; NMDA RECEPTORS; DENTATE GYRUS; RAT HIPPOCAMPUS
AB Hippocampal CA3 pyramidal neurons receive two types of excitatory afferent innervation: mossy fibers (MFs) from granule cells of the dentate gyrus and recurrent collateral fibers (CFs) from other CA3 pyramidal neurons. At CF - CA3 pyramidal neuron synapses, membrane depolarization paired with low (0.33 Hz) presynaptic stimulation generated a heterogeneous response that ranged from long-term potentiation (LTP), long-term depression (LTD), to no alteration of synaptic strength. However, the same induction paradigm applied at MF-CA3 pyramidal neuron synapses consistently induced LTD. This novel form of LTD was independent of NMDARs, mGluRs, cannabinoid receptors, opioid receptors, or coincident synaptic activity, but was dependent on postsynaptic Ca2+ elevation through L-type Ca2+ channels and release from inositol 1,4,5-trisphosphate receptor- sensitive intracellular stores. Ca2+ imaging of both proximal and distal CA3 pyramidal neuron dendrites demonstrated that the depolarizing induction paradigm differentially elevated intracellular Ca2+ levels. L-type Ca2+ channel activation was observed only at the most proximal locations where mossy fibers make synapses. Depolarization- induced LTD did not occlude the conventional 1 Hz-induced LTD or vice versa, suggesting independent mechanisms underlie each form of plasticity. The paired-pulse ratio and coefficient of variation of synaptic transmission were unchanged after LTD induction, suggesting that the expression locus of LTD is postsynaptic. Moreover, peak-scaled nonstationary variance analysis indicated that depolarization-induced LTD correlated with a reduction in postsynaptic AMPA receptor numbers without a change in AMPA receptor conductance. Our results suggest that this novel form of LTD is selectively expressed at proximal dendritic locations closely associated with L-type Ca2+ channels.
C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA.
   Univ Montreal, Ctr Rech Sci Neurol, Dept Physiol, Montreal, PQ H3C 3J7, Canada.
RP McBain, CJ (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
RI yu, yan/C-2322-2012
NR 89
TC 40
Z9 43
U1 1
U2 1
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 OCT 29
PY 2003
VL 23
IS 30
BP 9786
EP 9795
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 737PZ
UT WOS:000186242100011
PM 14586006
ER

PT J
AU Wang, YN
   Topol, IA
   Collins, JR
   Burt, SK
AF Wang, YN
   Topol, IA
   Collins, JR
   Burt, SK
TI Theoretical studies on the hydrolysis of mono-phosphate and
   tri-phosphate in gas phase and aqueous solution
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID CORRELATED MOLECULAR CALCULATIONS; PHOSPHATE MONOESTER MONOANIONS;
   CONTINUUM DIELECTRIC THEORY; FREE-ENERGY RELATIONSHIPS; GAUSSIAN-BASIS
   SETS; AB-INITIO; RAS P21; GTPASE REACTION; GENERAL BASE; MODEL
AB Phosphate hydrolysis by GTPases plays an important role as a molecular switch in signal transduction and as an initiator of many other biological processes. Despite the centrality of this ubiquitous reaction, the mechanism is still poorly understood. As a first step to understand the mechanisms of this process, the nonenzymatic hydrolysis of mono-phosphate and tri-phosphate esters were systematically studied in gas phase and aqueous solution using hybrid density functional methods. The dielectric effect of the environment on the energetics of these processes was also explored. Theoretical results show that for mono-phosphate ester, the dissociative pathway is much more favorable than the associative pathway. However, the reaction barriers for the dissociative and associative pathways of tri-phosphate hydrolysis are very close in aqueous solution, though the dissociative pathway is more favorable in the gas phase. High dielectric solvents, such as water, significantly lower the activation barrier of the associative pathway due to the greater solvation energy of the associative transition states than that of the reactant complex. By contrast, the barrier of the dissociative pathway, with respect to the gas phase, is less sensitive to the surrounding dielectric. In the associative hydrolysis pathway of the tri-phosphate ester, negative charge is transferred from the gamma-phosphate to beta-phosphate through the bridging ester oxygen and results in P(gamma)-O bond dissociation. No analogous charge transfer was observed in the dissociative pathway, where P(gamma)-O bond dissociation resulted from proton transfer from the gamma-phosphate to the bridge oxygen. Finally, the active participation of local water molecules can significantly lower the activation energy of the dissociative pathway for both mono-phosphate and tri-phosphate.
C1 NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
RP Burt, SK (reprint author), NCI, Adv Biomed Comp Ctr, POB B, Frederick, MD 21702 USA.
EM burt@ncifcrf.gov
FU NCI NIH HHS [N01 CO 12400]
NR 55
TC 40
Z9 40
U1 0
U2 9
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 OCT 29
PY 2003
VL 125
IS 43
BP 13265
EP 13273
DI 10.1021/ja0279794
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 735PN
UT WOS:000186123900057
PM 14570503
ER

PT J
AU Bektas, M
   Barak, LS
   Jolly, PS
   Liu, H
   Lynch, KR
   Lacana, E
   Suhr, KB
   Milstien, S
   Spiegel, S
AF Bektas, M
   Barak, LS
   Jolly, PS
   Liu, H
   Lynch, KR
   Lacana, E
   Suhr, KB
   Milstien, S
   Spiegel, S
TI The G protein-coupled receptor GPR4 suppresses ERK activation in a
   ligand-independent manner
SO BIOCHEMISTRY
LA English
DT Article
ID MULTIPLE SIGNALING PATHWAYS; GROWTH-FACTOR RECEPTOR; BETA-ARRESTIN;
   SPHINGOSINE 1-PHOSPHATE; KINASE ACTIVATION; BETA(2)-ADRENERGIC RECEPTOR;
   LYSOPHOSPHATIDIC ACID; CA2+ SENSITIZATION; ADENYLATE-CYCLASE; TYPE-2
   RECEPTORS
AB The lysophospholipids, lysophosphatidic acid, sphingosine-1-phosphate, and sphingosylphosphorylcholine (SPC), are bioactive lipid molecules that regulate diverse biological processes. Although the specific G protein-coupled receptors for lysophosphatidic acid and sphingosine-1-phosphate have been well-characterized, much less is known of the SPC receptors. It has been reported that ovarian cancer G protein-coupled receptor 1 (OGR1) is a high affinity receptor for SPC, and its closely related homologue GPR4 is a high affinity receptor for SPC with low affinity for lysophosphatidylcholine (LPC). However, in a functional assay to examine the specificity of ligand binding, we found that neither SPC nor LPC, or other related lysophospholipids, induced internalization of GPR4 from the plasma membrane. In agreement, these lysolipids also did not induce translocation of beta-arrestin2-GFP from the cytosol to the plasma membrane in GPR4 expressing cells. However, when these cells were cotransfected with G protein-coupled receptor kinase 2. in the absence of added ligands, beta-arrestin2-GFP accumulated in cytoplasmic vesicles, reminiscent of vesicular labeling usually observed after agonist stimulation of GPCRs. In addition, neither SPC nor LPC stimulated the binding of GTPgammaS to membranes prepared from GPR4 expressing cells and did not activate ERK1/2. Surprisingly, enforced expression of GPR4 inhibited activation of ERK1/2 induced by several stimuli, including SPC, sphingosine-1-phosphate, and even EGF. Collectively, our results suggest that SPC and LPC are not the ligands for GPR4 and that this receptor may constitutively inhibit ERK1/2 activation.
C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA.
   Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
   Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA.
   US FDA, Immunol Lab, Bethesda, MD 20892 USA.
   Chungnam Natl Univ, Sch Med, Dept Dermatol, Taejon 301040, South Korea.
   NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA.
FU NCI NIH HHS [CA61774]; NHLBI NIH HHS [HL61365]
NR 70
TC 48
Z9 49
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD OCT 28
PY 2003
VL 42
IS 42
BP 12181
EP 12191
DI 10.1021/bi035051y
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 735UX
UT WOS:000186133900007
PM 14567679
ER

PT J
AU Hunter, KW
AF Hunter, KW
TI Allelic diversity in the host genetic background may be an important
   determinant in tumor metastatic dissemination
SO CANCER LETTERS
LA English
DT Review
DE metastasis; cancer; progression; genetics; microarray; gene expression;
   inefficiency; mouse models; modifier; quantitative traits; genetic
   background
ID BREAST-CANCER; SIGNAL-TRANSDUCTION; SECONDARY SITE; INBRED STRAINS;
   MELANOMA-CELLS; COMPLEX-TRAIT; MOUSE; PROGRESSION; EXPRESSION;
   5-AZACYTIDINE
AB Metastasis, the spread and growth of tumors at secondary sites, is an extremely important clinical event, since the majority of cancer mortality is associated with the metastatic tumors rather than the primary tumor. In spite of the importance of metastasis in the clinical setting, the actual process is extremely inefficient. Millions of tumor cells can be shed into the vasculature daily yet few secondary tumors are formed. To successfully colonize a distant site tumor cells must overcome a series of barriers. Failure to complete any single step in the metastatic cascade abrogates the ability to form a secondary lesion. A variety of theories have been proposed to explain the inefficiency of the metastatic process. The most commonly accepted, the progression theory, posits a series of random mutational occurs within a primary tumor to generate a small subpopulation that acquires full metastatic capability. While significant evidence supports this model, recent discoveries demonstrating the ability to predict metastatic propensity from gene expression profiles in bulk tumor tissue are not consistent with only a small subpopulation of cells in the primary tumor acquiring metastatic ability. A second theory of metastatic inefficiency, the transient compartment theory, is more consistent with the microarray data, but does not completely explain observations like metastasis associated loss-of-heterozygosity events. To reconcile the observed results additional variables need to be added to the model of metastatic inefficiency. One possible variable that might explain the discrepancies is genetic background effects. Studies have demonstrated that the genetic background a tumor arises on can have significant affects on the ability of the tumor to metastasize and on gene expression profiles. Thus the observations could be reconciled by combining the theories, with genetic background influencing both metastatic efficiency and predictive gene expression profiles, upon which subsequently occur metastasis-promoting mutational and epigenetic events. If the genetic background is an important determinant of metastatic efficiency it would have significant implications for the clinical prediction and treatment of metastatic disease, as well as for the design of potential prevention strategies. Published by Elsevier Ireland Ltd.
C1 NCI, Lab Populat Genet, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Hunter, KW (reprint author), NCI, Lab Populat Genet, Canc Res Ctr, NIH, Bldg 41,Room D702,41 Lib Dr, Bethesda, MD 20892 USA.
NR 56
TC 30
Z9 32
U1 1
U2 1
PU ELSEVIER SCI IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD OCT 28
PY 2003
VL 200
IS 2
BP 97
EP 105
DI 10.1016/S0304-3835(03)00420-8
PG 9
WC Oncology
SC Oncology
GA 741GM
UT WOS:000186450400001
PM 14568162
ER

PT J
AU Mozzicato, S
   Joshi, BV
   Jacobson, KA
   Liang, BT
AF Mozzicato, S
   Joshi, BV
   Jacobson, KA
   Liang, BT
TI Role of a direct RhoA-Phospholipase D1 interaction in mediating
   adenosine-induced protection from ischemia
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Connecticut, Farmington, CT USA.
   Natl Inst Hlth, Bethesda, MD USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2
BP 1
EP 1
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600065
ER

PT J
AU Wang, W
   Wang, SQ
   Zhu, WZ
   Xiao, RP
   Cheng, HP
AF Wang, W
   Wang, SQ
   Zhu, WZ
   Xiao, RP
   Cheng, HP
TI Long-term b1-adrenergic modulation of cardiac Contractility via
   calmodulin kinase II signaling pathway
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIA, LCS, NIH, Baltimore, MD 21224 USA.
NR 0
TC 17
Z9 17
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3
BP 1
EP 1
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600066
ER

PT J
AU Gladwin, MT
   Cosby, K
   Partovi, K
   Martyr, S
   Reiter, C
   Zalos, G
   Schechter, AN
   Cannon, RO
AF Gladwin, MT
   Cosby, K
   Partovi, K
   Martyr, S
   Reiter, C
   Zalos, G
   Schechter, AN
   Cannon, RO
TI Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilalates the
   human circulation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 98
BP 20
EP 21
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600161
ER

PT J
AU Gonzalez-Navarro, H
   Nong, ZX
   Amar, M
   Freeman, L
   Knapper, C
   Shamburek, R
   Paigen, BJ
   Brewer, BH
   Santamarina-Fojo, S
AF Gonzalez-Navarro, H
   Nong, ZX
   Amar, M
   Freeman, L
   Knapper, C
   Shamburek, R
   Paigen, BJ
   Brewer, BH
   Santamarina-Fojo, S
TI In vivo evidence that the ligand-binding function of hepatic lipase
   modulates the development of atherosclerosis in transgenic mice that
   express the catalytically inactive hepatic lipase
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
   Jackson Labs, Bar Harbor, ME USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 120
BP 25
EP 25
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600182
ER

PT J
AU Lakatta, EG
   Deo, S
   Barlow, M
   Johnson, S
   Caffrey, JL
AF Lakatta, EG
   Deo, S
   Barlow, M
   Johnson, S
   Caffrey, JL
TI Beta adrenergic receptor stimulation induced cardioacceleration in situ
   requires intact ryanodine receptor function of sinoartial nodal cells
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX USA.
   NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 167
BP 35
EP 35
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600229
ER

PT J
AU Tong, HY
   Steenbergen, C
   Koch, WJ
   Murphy, E
AF Tong, HY
   Steenbergen, C
   Koch, WJ
   Murphy, E
TI G beta gamma-dependent signaling pathway in ischemic preconditioning: A
   role for endosomal signaling
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIEHS, Res Triangle Pk, NC 27709 USA.
   Duke Univ, Med Ctr, Durham, NC USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 178
BP 37
EP 37
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600240
ER

PT J
AU Camera, M
   Frigerio, M
   Cattaneo, M
   Abbracchio, M
   Jacobson, KA
   Biglioli, P
   Tremoli, E
AF Camera, M
   Frigerio, M
   Cattaneo, M
   Abbracchio, M
   Jacobson, KA
   Biglioli, P
   Tremoli, E
TI Differential role of P2Y receptors in agonist-induced TF expression by
   platelets
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Milan, Dipartimento Sci Farmacol, Milan, Italy.
   Ctr Cardiol Monzino, Milan, Italy.
   NIH, Bethesda, MD 20892 USA.
   Osped San Paolo, Milan, Italy.
RI Jacobson, Kenneth/A-1530-2009; tremoli, elena/C-1035-2011; Abbracchio,
   Maria Pia/B-9342-2014
OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria
   Pia/0000-0002-7833-3388
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 201
BP 42
EP 42
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600263
ER

PT J
AU Morita, H
AF Morita, H
TI Sarcomere protein gene and cardiac hypertrophy in the general
   population; Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   Boston Univ, Harvard Med Sch, NHLBI Framingham Heart Study, CardioGenom Grp, Boston, MA 02215 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 228
BP 50
EP 50
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600289
ER

PT J
AU Wang, SC
   Chang, HP
AF Wang, SC
   Chang, HP
TI Ca2+sparks exert negative feedback to the Ca2+release units in cardiac
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIA, Baltimore, MD 21224 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 248
BP 54
EP 54
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600309
ER

PT J
AU Spinetti, G
   Wang, M
   Monticone, RE
   Zhang, J
   Di, Z
   Lakatta, EG
AF Spinetti, G
   Wang, M
   Monticone, RE
   Zhang, J
   Di, Z
   Lakatta, EG
TI Age-associated arterial remodeling: Role of MCP-1 and its receptor, CCR2
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 298
BP 64
EP 65
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600359
ER

PT J
AU Spinetti, G
   Wang, MY
   Monticone, RE
   Zhang, J
   Di, Z
   Lakatta, EG
AF Spinetti, G
   Wang, MY
   Monticone, RE
   Zhang, J
   Di, Z
   Lakatta, EG
TI The chemokine, MCP-1, activates metalloproteinase-2 production: A novel
   mechanism for vascular smooth muscle cell invasion
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 299
BP 65
EP 65
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600360
ER

PT J
AU Neufeld, EB
   Stonik, JA
   Demosky, SJ
   Knapper, C
   Remaley, AT
   Santamarina-Fojo, S
   Brewer, HB
AF Neufeld, EB
   Stonik, JA
   Demosky, SJ
   Knapper, C
   Remaley, AT
   Santamarina-Fojo, S
   Brewer, HB
TI ABCA1 expression in Tangier fibroblasts restores ApoA-I mediated
   cholesterol efflux
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 335
BP 72
EP 72
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600396
ER

PT J
AU Seubert, JM
   Gabel, SA
   Yang, BC
   Murphy, E
   Zeldin, DC
AF Seubert, JM
   Gabel, SA
   Yang, BC
   Murphy, E
   Zeldin, DC
TI Enhanced postischemic functional recovery in CYP2J2 Transgenic hearts
   involves mitochondrial K-ATP channels
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 428
BP 91
EP 92
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600489
ER

PT J
AU Ahmet, I
   Lakatta, EG
   Talan, MI
AF Ahmet, I
   Lakatta, EG
   Talan, MI
TI Complimentary effects of chronic Pharmacologic manipulation of
   beta-adrenergic receptor (beta AR) subtype signaling in rodent dilated
   ischemic cardiomyopathy
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 443
BP 95
EP 95
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600504
ER

PT J
AU Fatkin, D
   Nikolova, V
   Leimena, C
   McMahon, A
   Tan, JC
   Chandar, S
   Jogia, D
   Kesteven, S
   Michalicek, J
   Otway, R
   Martin, D
   Stewart, CL
   Rainer, S
   Feneley, MP
AF Fatkin, D
   Nikolova, V
   Leimena, C
   McMahon, A
   Tan, JC
   Chandar, S
   Jogia, D
   Kesteven, S
   Michalicek, J
   Otway, R
   Martin, D
   Stewart, CL
   Rainer, S
   Feneley, MP
TI Nuclear structure and function defects promote dilated cardiomyopathy in
   lamin A/C-deficient mice
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Cardiac Res Inst, Darlinghurst, NSW, Australia.
   NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA.
   St Vincents Hosp, Darlinghurst, NSW 2010, Australia.
RI Kesteven, Scott/I-8008-2015
NR 0
TC 0
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 449
BP 96
EP 96
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600510
ER

PT J
AU Paul, JD
   Powell, TM
   Hill, JM
   Cannon, RO
AF Paul, JD
   Powell, TM
   Hill, JM
   Cannon, RO
TI Cytokine enhancement of endothelial progenitor cell colony-forming
   ability in patients with coronary artery disease
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 496
BP 106
EP 106
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600557
ER

PT J
AU Crook, MF
   Boehm, M
   Olive, M
   Nabel, EG
AF Crook, MF
   Boehm, M
   Olive, M
   Nabel, EG
TI Ets-1 regulates hKIS gene expression - A regulator of vascular smooth
   muscle cell proliferation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 524
BP 111
EP 112
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600585
ER

PT J
AU Keaney, JF
   Massaro, JM
   Larson, MG
   Vasan, RS
   Wilson, PW
   Lipinska, I
   Corey, D
   Sutherland, P
   Vita, JA
   Benjamin, EJ
AF Keaney, JF
   Massaro, JM
   Larson, MG
   Vasan, RS
   Wilson, PW
   Lipinska, I
   Corey, D
   Sutherland, P
   Vita, JA
   Benjamin, EJ
TI Heritability and correlates of sICAM-1 in the Framingham Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Framingham Study, Framingham, MA USA.
   Boston Univ, Sch Med, Boston, MA 02215 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 612
BP 129
EP 130
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600673
ER

PT J
AU Gaussin, V
   Jing, L
   Mishina, Y
   Hanks, MC
   Schneider, MD
   Burch, JB
AF Gaussin, V
   Jing, L
   Mishina, Y
   Hanks, MC
   Schneider, MD
   Burch, JB
TI ALK3-Dependent mechanism regulating atrio-ventricular valve development
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Res Triangle Pk, NC USA.
   Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA.
   Procter & Gamble Pharmaceut, Mason, OH USA.
   Baylor Coll Med, Houston, TX 77030 USA.
   Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 665
BP 141
EP 141
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600726
ER

PT J
AU Oh, H
   Bradfute, SB
   Gallardo, TD
   Nakamura, T
   Chi, X
   Gaussin, V
   Mishina, Y
   Pocius, J
   Michael, LH
   Behringer, RR
   Schwartz, RJ
   Garry, DJ
   Entman, ML
   Schneider, MD
AF Oh, H
   Bradfute, SB
   Gallardo, TD
   Nakamura, T
   Chi, X
   Gaussin, V
   Mishina, Y
   Pocius, J
   Michael, LH
   Behringer, RR
   Schwartz, RJ
   Garry, DJ
   Entman, ML
   Schneider, MD
TI Cardiac progenitor cells from adult myocardium: Differentiation in
   vitro, in utero, and after homing to the infarct border
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Baylor Coll Med, Houston, TX 77030 USA.
   Univ Texas, Dallas, TX 75230 USA.
   Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
   NIEHS, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 683
BP 144
EP 145
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600744
ER

PT J
AU Powell, TM
   Paul, JD
   McCoy, JP
   Cannon, RO
   Hill, JM
AF Powell, TM
   Paul, JD
   McCoy, JP
   Cannon, RO
   Hill, JM
TI Granulocyte colony stimulating factor upregulates CD34 progenitor cells
   with chemokine receptors CXCR4 and CX3CR1 in patients with coronary
   artery disease: Potential for benefit and harm
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 792
BP 168
EP 168
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600853
ER

PT J
AU Feinberg, MW
   Lebedeva, MA
   Haspel, R
   Sen, S
   Gray, S
   Segre, JA
   Miyamoto, T
   Akashi, K
   Jain, MK
AF Feinberg, MW
   Lebedeva, MA
   Haspel, R
   Sen, S
   Gray, S
   Segre, JA
   Miyamoto, T
   Akashi, K
   Jain, MK
TI The Kruppel-like factor KLF4 is a novel regulator of monocytic
   differentiation
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
   NIH, Bethesda, MD 20892 USA.
   Dana Farber Canc Inst, Boston, MA 02115 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 990
BP 209
EP 209
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601050
ER

PT J
AU Pinz, I
   Christians, E
   Wawrousek, E
   Robbins, J
   Benjamin, I
   Ingwall, JS
AF Pinz, I
   Christians, E
   Wawrousek, E
   Robbins, J
   Benjamin, I
   Ingwall, JS
TI Alpha-B-crystallin and HSPB2, two small heat shock proteins, have
   distinct physiological functions in the mouse heart
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
   Univ Texas, SW Med Ctr, Dallas, TX 75230 USA.
   NEI, NIH, Bethesda, MD 20892 USA.
   Childrens Hosp Res Fdn, Cincinnati, OH 45229 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1046
BP 221
EP 221
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601106
ER

PT J
AU Paul, JD
   Powell, TM
   Hill, JM
   Cannon, R
AF Paul, JD
   Powell, TM
   Hill, JM
   Cannon, R
TI Feasibility of ex vivo cytokine expansion of endothelial progenitor
   cells in patients with coronary artery disease
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1051
BP 222
EP 222
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601111
ER

PT J
AU Boehm, M
   True, AC
   Olive, M
   Crook, MF
   San, H
   Qu, X
   Nabel, EG
AF Boehm, M
   True, AC
   Olive, M
   Crook, MF
   San, H
   Qu, X
   Nabel, EG
TI p27(Kip1) directly regulates proliferation, inflammation, and bone
   marrow-derived progenitor cells in vascular remodeling
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1078
BP 227
EP 228
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601138
ER

PT J
AU Freeman, LA
   Wu, J
   Bark, S
   Remaley, TA
   Brewer, BH
   Santamarina-Fojo, S
AF Freeman, LA
   Wu, J
   Bark, S
   Remaley, TA
   Brewer, BH
   Santamarina-Fojo, S
TI Transcriptional analysis of the ABCG5/ABCG8 intergenic promoter
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1099
BP 232
EP 232
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601159
ER

PT J
AU Basso, F
   Amar, MJ
   Vaisman, B
   Joyce, C
   Wu, J
   Brewer, HB
   Santamarina-Fojo, S
AF Basso, F
   Amar, MJ
   Vaisman, B
   Joyce, C
   Wu, J
   Brewer, HB
   Santamarina-Fojo, S
TI Overexpression of ABCG1 lowers plasma HDL-C and enhances biliary
   cholesterol and phospholipid secretion in transgenic mice
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1221
BP 258
EP 259
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601280
ER

PT J
AU Wu, J
   Basso, F
   Shamburek, R
   Amar, M
   Vaisman, B
   Terese, T
   Freeman, L
   Szakacs, G
   Knapper, C
   Paigen, B
   Fruchart-Najib, J
   Brewer, HB
   Santamarina-Fojo, S
AF Wu, J
   Basso, F
   Shamburek, R
   Amar, M
   Vaisman, B
   Terese, T
   Freeman, L
   Szakacs, G
   Knapper, C
   Paigen, B
   Fruchart-Najib, J
   Brewer, HB
   Santamarina-Fojo, S
TI Differential hepatic and intestinal overexpression of human ABCG5 and
   ABCG8 in transgenic mice: Effects on intestinal cholesterol absorption,
   biliary sterol excretion and atherosclerosis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Bethesda, MD 20892 USA.
   NCI, Bethesda, MD 20892 USA.
   Jackson Labs, Bar Harbor, ME USA.
   Inst Pasteur, F-59019 Lille, France.
   NHLBI, Bethesda, MD 20892 USA.
RI Szakacs, Gergely/A-2580-2009
OI Szakacs, Gergely/0000-0002-9311-7827
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1223
BP 259
EP 259
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601282
ER

PT J
AU Mohiddin, SA
   Owens, D
   Tripodi, D
   St Peter, M
   McAreavey, D
   Sachdev, V
   Plehn, J
   Fananapazir, L
AF Mohiddin, SA
   Owens, D
   Tripodi, D
   St Peter, M
   McAreavey, D
   Sachdev, V
   Plehn, J
   Fananapazir, L
TI Predicting clinical outcome in hypertrophic cardiomyopathy associated
   with beta-myosin mutations: A novel strategy based on functional domain
   affected
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1245
BP 263
EP 263
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601304
ER

PT J
AU Mohiddin, SA
   Ahmed, Z
   Griffith, AJ
   Tripodi, D
   Friedman, TB
   Fananapazir, L
   Morell, RJ
AF Mohiddin, SA
   Ahmed, Z
   Griffith, AJ
   Tripodi, D
   Friedman, TB
   Fananapazir, L
   Morell, RJ
TI Novel association of hypertrophic cardiomyopathy, sensorineural
   deafness, and a mutation in an unconventional myosin
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIDCD, Rockville, MD USA.
   NHLBI, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1244
BP 263
EP 263
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601303
ER

PT J
AU McCarthy, J
   Minners, JO
   McLeod, J
   Ping, P
   Sack, MN
AF McCarthy, J
   Minners, JO
   McLeod, J
   Ping, P
   Sack, MN
TI PKC epsilon activation augments cardiac mitochondrial respiratory
   capacity - A putative mechanism in attenuating mitochondrial
   permeability transition
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Cape Town, ZA-7925 Cape Town, South Africa.
   NIH, Bethesda, MD 20892 USA.
   Univ Calif Los Angeles, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1302
BP 275
EP 275
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601360
ER

PT J
AU Lammerding, J
   Schulze, C
   Takahashi, T
   Kozlov, S
   Sullivan, T
   Kamm, RD
   Stewart, CL
   Lee, RT
AF Lammerding, J
   Schulze, C
   Takahashi, T
   Kozlov, S
   Sullivan, T
   Kamm, RD
   Stewart, CL
   Lee, RT
TI Defective nuclear mechanics and mechanotransduction in larnin A/C null
   cells
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 MIT, Biol Engn Div, Cambridge, MA 02139 USA.
   Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
   NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1370
BP 289
EP 289
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601428
ER

PT J
AU Imahashi, K
   Schneider, MD
   Steenbergen, C
   Murphy, E
AF Imahashi, K
   Schneider, MD
   Steenbergen, C
   Murphy, E
TI Transgenic expression of Bcl-2 modulates energy metabolism and prevents
   cytosolic acidification during ischemia and reduces ischemia-reperfusion
   injury
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   Baylor Coll Med, Houston, TX 77030 USA.
   Duke Univ, Med Ctr, Durham, NC USA.
NR 0
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1413
BP 297
EP 297
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601471
ER

PT J
AU Cooper, HA
   Domanski, M
   Rosenberg, Y
   Norman, J
   Scott, J
   Assmann, S
   McKinlay, S
   Hochman, J
   Antman, E
AF Cooper, HA
   Domanski, M
   Rosenberg, Y
   Norman, J
   Scott, J
   Assmann, S
   McKinlay, S
   Hochman, J
   Antman, E
TI Acute ST-segment elevation myocardial infarction in patients with prior
   stroke - An analysis from the MAGIC trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Washington Hosp Ctr, Washington, DC 20010 USA.
   NHLBI, Bethesda, MD 20892 USA.
   New England Res Inst, Watertown, MA 02172 USA.
   NYU, Med Ctr, New York, NY 10016 USA.
   Brigham & Womens Hosp, Boston, MA 02115 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1481
BP 314
EP 314
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601539
ER

PT J
AU Fox, CS
   Evans, JC
   Larson, MG
   Sorlie, PD
   Manolio, TA
   Lloyd-Jones, DM
   Kannel, W
   O'Donnell, CJ
   Levy, D
AF Fox, CS
   Evans, JC
   Larson, MG
   Sorlie, PD
   Manolio, TA
   Lloyd-Jones, DM
   Kannel, W
   O'Donnell, CJ
   Levy, D
TI Death certificate out-of-hospital cardiac death overestimates sudden
   cardiac death
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Framingham Heart Study, Framingham, MA USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   NHLBI, Rockville, MD USA.
   Boston Univ, Sch Med, Boston, MA 02118 USA.
RI Lloyd-Jones, Donald/C-5899-2009
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1501
BP 318
EP 318
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601559
ER

PT J
AU Lee, CD
   Binder, AL
   Swanson, JC
   Zetts, AD
   Davies, CH
AF Lee, CD
   Binder, AL
   Swanson, JC
   Zetts, AD
   Davies, CH
TI Validation of long axis three-dimensional tissue Doppler reconstruction
   imaging in a chronic animal model of segmental left ventricular
   dysfunction
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA.
   NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1581
BP 337
EP 337
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601639
ER

PT J
AU Shin, JH
   Jones, M
   Qin, JX
   Agler, DA
   Greenberg, N
   Oryszak, S
   Saracino, G
   Eto, Y
   Shiota, T
AF Shin, JH
   Jones, M
   Qin, JX
   Agler, DA
   Greenberg, N
   Oryszak, S
   Saracino, G
   Eto, Y
   Shiota, T
TI Automated computer analysis of left ventricular functions using
   real-time three-dimensional echocardiography: A chronic animal study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1584
BP 338
EP 338
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601642
ER

PT J
AU Herzog, CA
   Littrell, K
   Arko, C
   Frederick, P
   Blaney, M
   Eggers, P
AF Herzog, CA
   Littrell, K
   Arko, C
   Frederick, P
   Blaney, M
   Eggers, P
TI The clinical characteristics of dialysis patients with acute myocardial
   infarction (AMI) in the United States: A collaborative project of the
   United States Renal Data System (USRDS)/NIH and the National Registry of
   Myocardial Infarction (NRMI)
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Minneapolis Med Res Fdn Inc, US Renal Data Syst, Cardiovasc SSC, Minneapolis, MN USA.
   Genentech Inc, San Francisco, CA USA.
   Ovat Res Grp, Seattle, WA USA.
   NIH, US Renal Data Syst, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1751
BP 377
EP 377
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601808
ER

PT J
AU Lim, JG
   Shapiro, EP
   Fleg, JL
   Vaidya, D
   Ouyang, P
   Turner, KL
   Dobrosielski, DA
   Bacher, AC
   Stewart, KJ
AF Lim, JG
   Shapiro, EP
   Fleg, JL
   Vaidya, D
   Ouyang, P
   Turner, KL
   Dobrosielski, DA
   Bacher, AC
   Stewart, KJ
TI Gender differences in age related changes in ventricular function and
   vascular stiffness among persons with mild hypertension
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Johns Hopkins Univ, Baltimore, MD 21218 USA.
   NIA, Baltimore, MD 21224 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1830
BP 395
EP 396
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601887
ER

PT J
AU Mohiddin, SA
   Begley, DA
   McAreavey, D
   Fananapazir, L
   Biddle, S
   Tripodi, D
   Plehn, J
   Owens, D
   Agyeman, K
   Norman, JE
   Arai, AE
AF Mohiddin, SA
   Begley, DA
   McAreavey, D
   Fananapazir, L
   Biddle, S
   Tripodi, D
   Plehn, J
   Owens, D
   Agyeman, K
   Norman, JE
   Arai, AE
TI Double-blind placebo-controlled study of inhibition of renin-angiotensin
   system on cardiac mass in human hypertrophic cardiomyopathy
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1842
BP 398
EP 398
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601899
ER

PT J
AU Einhorn, P
   Davis, B
   Piller, L
   deLeon, B
   Simpson, L
   Kostis, J
   Levy, D
   Massie, B
   Nwachuku, C
   Black, H
   Cushman, W
AF Einhorn, P
   Davis, B
   Piller, L
   deLeon, B
   Simpson, L
   Kostis, J
   Levy, D
   Massie, B
   Nwachuku, C
   Black, H
   Cushman, W
CA ALLHAT Collaborative Rsch Grp
TI Review of heart failure events in the antihypertensive and lipid
   lowering treatment to prevent heart attack trial (ALLHAT): ALLHAT heart
   failure validation study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Bethesda, MD 20892 USA.
   Univ Texas, Sch Publ Hlth, Houston, TX USA.
   Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
   NHLBI, Framingham Heart Study, Framingham, MA USA.
   VA Med Ctr, San Francisco, CA USA.
   Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA.
   Memphis VA Med Ctr, Memphis, TN USA.
NR 0
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1847
BP 399
EP 400
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601904
ER

PT J
AU Ingkanisorn, WP
   Kwong, RY
   Rhoads, KL
   Dyke, CK
   Davis, JE
   Syed, MA
   Paterson, I
   Aletras, AH
   Arai, AE
AF Ingkanisorn, WP
   Kwong, RY
   Rhoads, KL
   Dyke, CK
   Davis, JE
   Syed, MA
   Paterson, I
   Aletras, AH
   Arai, AE
TI Diagnostic and prognostic value of adenosine stress MRI in the
   assessment of chest pain in troponin-negative patients
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1860
BP 402
EP 402
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601917
ER

PT J
AU Herzog, CA
   Li, SL
   Eggers, P
AF Herzog, CA
   Li, SL
   Eggers, P
TI A tale of two medicare populations: 30 day mortality after acute
   myocardial infarction has markedly decreased in general medicare
   patients but not dialysis patients from 1986 to 2000
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Minneapolis Med Rsch Fdn, Cardiovasc SSC, US Renal Data Syst, Minneapolis, MN USA.
   NIH, US Renal Data Syst, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1924
BP 417
EP 417
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360601981
ER

PT J
AU Guttman, MA
   Dick, AJ
   Raman, VK
   Lederman, RJ
   McVeigh, ER
AF Guttman, MA
   Dick, AJ
   Raman, VK
   Lederman, RJ
   McVeigh, ER
TI Real-time multi-slice MRI with novel adaptive-orientation projection and
   interactive point marking improves navigation and positioning of
   intravascular devices in swine
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1974
BP 428
EP 428
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602031
ER

PT J
AU Raman, VK
   Karmarkar, P
   Dick, AJ
   Guttman, MA
   Peters, DC
   Thompson, RB
   Pessanha, BS
   De Silva, R
   Atalar, E
   McVeigh, ER
   Lederman, RJ
AF Raman, VK
   Karmarkar, P
   Dick, AJ
   Guttman, MA
   Peters, DC
   Thompson, RB
   Pessanha, BS
   De Silva, R
   Atalar, E
   McVeigh, ER
   Lederman, RJ
TI Magnetic resonance fluoroscopy-guided endovascular repair of abdominal
   aortic aneurysm in swine
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
   Johns Hopkins Sch Med, Baltimore, MD USA.
RI Atalar, Ergin/D-3184-2012
OI Atalar, Ergin/0000-0002-6874-6103
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 1973
BP 428
EP 428
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602030
ER

PT J
AU Chung, MK
   Shemanski, L
   Rosenberg, Y
   Sherman, DG
   Kim, SG
   Kellen, J
   Martin, L
   Wyse, DG
AF Chung, MK
   Shemanski, L
   Rosenberg, Y
   Sherman, DG
   Kim, SG
   Kellen, J
   Martin, L
   Wyse, DG
TI Effect of rate- versus rhythm-control strategies on the functional
   status of patients in the atrial fibrillation follow-up investigation of
   rhythm management (AFFIRM) study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   Axio Rsch, Seattle, WA USA.
   NHLBI, Bethesda, MD 20892 USA.
   Univ Texas, Hlth Sci Ctr, San Antonio, TX USA.
   Montefiore Med Ctr, Bronx, NY 10467 USA.
   Univ Calgary, Calgary, AB, Canada.
   Kaiser Permanente Mid Atlantic Reg, Rockville, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2163
BP 471
EP 472
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602220
ER

PT J
AU Hill, JM
   Paul, JD
   Powell, TM
   McCoy, JP
   Dunbar, CE
   Horne, M
   Csako, G
   Cannon, RO
AF Hill, JM
   Paul, JD
   Powell, TM
   McCoy, JP
   Dunbar, CE
   Horne, M
   Csako, G
   Cannon, RO
TI Efficacy and risk of granulocyte colony stimulating factor
   administration in patients with severe coronary artery disease
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NIH, Bethesda, MD 20892 USA.
NR 0
TC 16
Z9 16
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2189
BP 478
EP 478
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602246
ER

PT J
AU Shizukuda, Y
   Matoba, S
   Mian, OY
   Brenneman, CL
   Birdsall, CW
   Sachdev, V
   Plehn, JF
   Hwang, PM
AF Shizukuda, Y
   Matoba, S
   Mian, OY
   Brenneman, CL
   Birdsall, CW
   Sachdev, V
   Plehn, JF
   Hwang, PM
TI p53 mediates doxorubicin-induced cardiac toxicity in mice
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2281
BP 498
EP 498
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602338
ER

PT J
AU Hoffmann, U
   Bull-Stewart, A
   Achenbach, S
   Ferencik, M
   Brady, TJ
   O'Donnell, C
AF Hoffmann, U
   Bull-Stewart, A
   Achenbach, S
   Ferencik, M
   Brady, TJ
   O'Donnell, C
TI Interscan and Interobserver variability of coronary artery calcium
   measurements in prospectively triggered multislice computed tomography
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
   NHLBI, Framingham Heart Study, Framingham, MA USA.
   Massachusetts Gen Hosp, Div Cardiol, NHLBI, Framingham Heart Study, Boston, MA 02114 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2416
BP 529
EP 529
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602472
ER

PT J
AU Ganesh, SK
   Billings, EM
   Sharma, YK
   Dayhoff, J
   Fales, HM
   Kickler, TS
   Nabel, EG
AF Ganesh, SK
   Billings, EM
   Sharma, YK
   Dayhoff, J
   Fales, HM
   Kickler, TS
   Nabel, EG
TI A novel MALDI-TOF mass spectroscopic proteomic technique for serum
   biomarker assessment in venous thromboembolism
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2553
BP 560
EP 560
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602608
ER

PT J
AU Natori, S
   Lai, SH
   Finn, JP
   Gomes, AS
   Hundley, G
   Lima, JA
   Pearson, G
   Sinha, S
   Olson, J
   Bluemke, DA
AF Natori, S
   Lai, SH
   Finn, JP
   Gomes, AS
   Hundley, G
   Lima, JA
   Pearson, G
   Sinha, S
   Olson, J
   Bluemke, DA
TI Normal values of cardiac parameters in MESA study: Left ventricular
   function and mass by gender, race, and age
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   Northwestern Univ, Sch Med, Chicago, IL USA.
   Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
   Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
   Columbia Univ, New York, NY USA.
   NHLBI, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2586
BP 567
EP 567
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602641
ER

PT J
AU Warshaw, DM
   Alpert, NR
   Brosseau, C
   Tripodi, D
   Mohiddin, SA
   Fananapazir, L
AF Warshaw, DM
   Alpert, NR
   Brosseau, C
   Tripodi, D
   Mohiddin, SA
   Fananapazir, L
TI Homozygous and compound heterozygote mutations of myosin heavy chain
   result in severe hypertrophic cardiomyopathy
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Vermont, Burlington, VT 05405 USA.
   NHLBI, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 2844
BP 626
EP 626
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360602896
ER

PT J
AU Aletras, AH
   Natanzon, A
   Tilak, GS
   Arai, AE
AF Aletras, AH
   Natanzon, A
   Tilak, GS
   Arai, AE
TI Differentiating acute from chronic myocardial infarction with MRI: The
   role of edema and Delayed Hyper-Enhancement in MI size determination
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, LCE, NIH, Bethesda, 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3167
BP 697
EP 697
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603217
ER

PT J
AU Johnson, BD
   Reis, SE
   Sharaf, BL
   Stylianou, M
   Olson, MB
   Gierach, GL
   Shaw, LJ
   Pohost, GM
   Kelsey, SF
   Sopko, G
   Merz, CNB
AF Johnson, BD
   Reis, SE
   Sharaf, BL
   Stylianou, M
   Olson, MB
   Gierach, GL
   Shaw, LJ
   Pohost, GM
   Kelsey, SF
   Sopko, G
   Merz, CNB
TI Anginal symptom presentation and angiographic coronary artery disease in
   black and white women: The National Heart, Lung, and Blood
   Institute-sponsored women's ischemia syndrome evaluation (WISE) study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
   Rhode Isl Hosp, Providence, RI USA.
   NHLBI, Bethesda, MD 20892 USA.
   Atlanta Cardiovasc Rsch Inst, Atlanta, GA USA.
   Univ So Calif, Los Angeles, CA USA.
   Cedars Sinai Med Ctr, Los Angeles, CA USA.
RI Reis, Steven/J-3957-2014; Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3244
BP 716
EP 716
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603294
ER

PT J
AU Olson, MB
   Merz, NB
   Kelsey, SF
   Pepine, CJ
   Sopko, G
   Rogers, WJ
   Mankad, S
   Phankao, C
   Krantz, D
AF Olson, MB
   Merz, NB
   Kelsey, SF
   Pepine, CJ
   Sopko, G
   Rogers, WJ
   Mankad, S
   Phankao, C
   Krantz, D
TI Hostility scores are associated with increased risk of events in women
   undergoing coronary angiography: Results from the NHLBI-sponsored WISE
   study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Pittsburgh, Pittsburgh, PA USA.
   Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   Univ Pittsburgh, Pittsburgh, PA USA.
   Univ Florida, Gainesville, FL USA.
   Natl Heart Lung Blood Inst, Washington, DC USA.
   Univ Alabama, Birmingham, AL 35487 USA.
   Allegheny Gen Hosp, Pittsburgh, PA USA.
   Uniformed Serv Univ Hlth Sci, Washington, DC USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3243
BP 716
EP 716
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603293
ER

PT J
AU Lloyd-Jones, DM
   Nam, BH
   D'Agostino, RB
   Levy, D
   Murabito, JM
   Wang, TJ
   Wilson, PW
   O'Donnell, CJ
AF Lloyd-Jones, DM
   Nam, BH
   D'Agostino, RB
   Levy, D
   Murabito, JM
   Wang, TJ
   Wilson, PW
   O'Donnell, CJ
TI Parental history of cardiovascular disease adds predictive information
   to traditional risk factors and multivariate predicted risk
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Framingham Heart Study, Framingham, MA USA.
RI Lloyd-Jones, Donald/C-5899-2009
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3278
BP 725
EP 726
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603328
ER

PT J
AU Camethon, MR
   Hill, JO
   Loria, CM
   Sidney, S
   Savage, PJ
   Liu, K
AF Camethon, MR
   Hill, JO
   Loria, CM
   Sidney, S
   Savage, PJ
   Liu, K
TI Risk factors for the development of metabolic syndrome: The CARDIA study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Northwestern Univ, Chicago, IL 60611 USA.
   Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Kaiser Permanente, Div Res, Oakland, CA 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3291
BP 728
EP 728
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603340
ER

PT J
AU Barasch, E
   Marino, EK
   Burke, GL
   Newman, AB
   Chaves, PH
   Manolio, TA
   Gottdiener, JS
AF Barasch, E
   Marino, EK
   Burke, GL
   Newman, AB
   Chaves, PH
   Manolio, TA
   Gottdiener, JS
TI Severity and predictive value of mitral annular calcification for
   cardiovascular and total mortality in the elderly. The cardiovascular
   health study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 SUNY Stony Brook, St Francis Hosp, Roslyn, NY USA.
   Univ Washington, CHS Coordinating Ctr, Seattle, WA 98195 USA.
   Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
   Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   Johns Hopkins Univ, Welch Ctr, Baltimore, MD USA.
   NHLBI, NIH, DECA, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3295
BP 729
EP 729
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603344
ER

PT J
AU Fox, CS
   Larson, MG
   Kupka, MJ
   Levy, D
   Clouse, M
   Culleton, B
   O'Donnell, CJ
AF Fox, CS
   Larson, MG
   Kupka, MJ
   Levy, D
   Clouse, M
   Culleton, B
   O'Donnell, CJ
TI Reduced kidney function is associated with subclinical coronary artery
   calcification: The Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI, Framingham Heart Study, Framingham, MA USA.
   Boston Univ, Sch Med, Boston, MA 02118 USA.
   Boston Univ, Dept Math, Boston, MA 02118 USA.
   Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   Univ Calgary, Foothills Hosp, Calgary, AB, Canada.
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3296
BP 730
EP 730
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603345
ER

PT J
AU Cushman, M
   Brown, E
   Tsai, M
   Psaty, B
   Bild, D
   Arnett, D
   Jacobs, D
   Goff, D
   Wong, N
   Kondos, G
AF Cushman, M
   Brown, E
   Tsai, M
   Psaty, B
   Bild, D
   Arnett, D
   Jacobs, D
   Goff, D
   Wong, N
   Kondos, G
TI Associations of novel cardiovascular risk markers with coronary artery
   calcium: the multiethnic study of atherosclerosis
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Vermont, Burlington, VT 05405 USA.
   Univ Washington, Seattle, WA 98195 USA.
   Univ Minnesota, Minneapolis, MN 55455 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Wake Forest Univ, Winston Salem, NC 27109 USA.
   Univ Calif Irvine, Irvine, CA 92717 USA.
   Univ Illinois, Chicago, IL 60680 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3303
BP 731
EP 731
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603352
ER

PT J
AU Nicklas, BJ
   Penninx, BW
   Cesari, M
   Kritchevsky, SB
   Newman, AB
   Kanaya, AM
   Pahor, M
   Ding, JZ
   Harris, TB
AF Nicklas, BJ
   Penninx, BW
   Cesari, M
   Kritchevsky, SB
   Newman, AB
   Kanaya, AM
   Pahor, M
   Ding, JZ
   Harris, TB
TI Relationship of visceral adipose tissue to incident myocardial
   infarction: The health, aging and body composition study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 WFU Hlth Sci, Winston Salem, NC USA.
   Univ Tennessee, Memphis, TN USA.
   Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
   NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA.
RI Cesari, Matteo/A-4649-2008
OI Cesari, Matteo/0000-0002-0348-3664
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3319
BP 734
EP 735
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603368
ER

PT J
AU Wilson, PW
   D'Agostino, RB
   Nam, BH
   Benjamin, EJ
   O'Donnell, CJ
AF Wilson, PW
   D'Agostino, RB
   Nam, BH
   Benjamin, EJ
   O'Donnell, CJ
TI C-reactive protein and CVD risk in Framingham
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Boston Univ, Sch Med, Boston, MA 02118 USA.
   NHLBI, Framingham Heart Study, Framingham, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3380
BP 748
EP 749
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603429
ER

PT J
AU Jenny, NS
   Brown, ER
   Detrano, R
   Folsom, AR
   Herrington, D
   Jacobs, D
   Manolio, TA
   Tracy, RP
AF Jenny, NS
   Brown, ER
   Detrano, R
   Folsom, AR
   Herrington, D
   Jacobs, D
   Manolio, TA
   Tracy, RP
TI Race/ethnic differences in the relationship of inflammatory markers to
   coronary calcium
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Vermont, Burlington, VT USA.
   Univ Washington, Seattle, WA 98195 USA.
   Univ Calif Los Angeles, Res & Educ Inst, Torrance, CA USA.
   Univ Minnesota, Minneapolis, MN USA.
   Wake Forest Univ, Sch Med, Winston Salem, NC USA.
   NHLBI, Bethesda, MD 20892 USA.
RI Brown, Elizabeth/A-8984-2008
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3401
BP 753
EP 753
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603450
ER

PT J
AU Liu, YM
   Berthier-Schaad, Y
   Fallin, DM
   Fink, N
   Tracy, RP
   Klag, MJ
   Smith, MW
   Coresh, J
AF Liu, YM
   Berthier-Schaad, Y
   Fallin, DM
   Fink, N
   Tracy, RP
   Klag, MJ
   Smith, MW
   Coresh, J
TI Interleukin-6 haplotypes, inflammation, and risk of cardiovascular
   disease in a MultiEthnic dialysis cohort
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   Univ Vermont, Burlington, VT USA.
   NCI, Basic Rsch Program, SAIC, Frederick, MD USA.
RI Smith, Michael/B-5341-2012
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3460
BP 766
EP 766
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603509
ER

PT J
AU O'Donnell, CJ
   Yang, Q
   Lochner, A
   Larson, MG
   Kathiresan, S
   Tofler, GH
   Gabriel, SB
AF O'Donnell, CJ
   Yang, Q
   Lochner, A
   Larson, MG
   Kathiresan, S
   Tofler, GH
   Gabriel, SB
TI Associations of haplotypes of fibrinogen beta, alpha and gamma chain
   genes on chromosome 4 with circulating fibrinogen levels in men and
   women
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Massachusetts Gen Hosp, NHLBI Framingham Heart Study, Framingham, MA USA.
   Massachusetts Gen Hosp, Div Cardiol, Framingham, MA USA.
   NHLBI, Framingham Heart Study, Boston, MA USA.
   Boston Univ, Sch Med, Boston, MA 02118 USA.
   MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02142 USA.
   Royal N Shore Hosp, Sydney, NSW, Australia.
RI Yang, Qiong/G-5438-2014
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3479
BP 771
EP 772
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603528
ER

PT J
AU Rinfret, S
   Cohen, DJ
   Lamas, GA
   Fleischmann, KE
   Weinstein, MC
   Orav, J
   Schron, E
   Lee, KL
   Goldman, L
AF Rinfret, S
   Cohen, DJ
   Lamas, GA
   Fleischmann, KE
   Weinstein, MC
   Orav, J
   Schron, E
   Lee, KL
   Goldman, L
TI Cost-effectiveness of dual-chamber versus ventricular pacing from the
   mode selection trial (MOST) in sinus-node dysfunction
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Univ Montreal, Notre Dame Hosp, CHUM, Montreal, PQ H3C 3J7, Canada.
   Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
   Univ Miami, Mt Sinai Med Ctr, Sch Med, Miami Beach, FL 33140 USA.
   Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA.
   Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Boston, MA 02115 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Duke Univ, Clin Res Inst, Durham, NC 27706 USA.
   Duke Univ, Sch Med, Durham, NC 27706 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3499
BP 776
EP 776
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603548
ER

PT J
AU Lloyd-Jones, DM
   Leip, EP
   Larson, MG
   D'Agostino, RB
   Beiser, A
   Wilson, PW
   Wolf, PA
   Levy, D
AF Lloyd-Jones, DM
   Leip, EP
   Larson, MG
   D'Agostino, RB
   Beiser, A
   Wilson, PW
   Wolf, PA
   Levy, D
TI Lifetime risk for atherosclerotic cardiovascular disease by risk factor
   levels at age 50
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 NHLBI Framingham Heart Study, Framingham, MA USA.
RI Lloyd-Jones, Donald/C-5899-2009
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3517
BP 779
EP 780
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603566
ER

PT J
AU Barasch, E
   Marino, EK
   Burke, GL
   Newman, AB
   Chaves, PH
   Manolio, TA
   Gottdiener, JS
AF Barasch, E
   Marino, EK
   Burke, GL
   Newman, AB
   Chaves, PH
   Manolio, TA
   Gottdiener, JS
TI Predictive value of calcification of the fibrous skeleton of the base of
   the heart for incident cardiovascular disease in the elderly. The
   Cardiovascular Health Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 SUNY Stony Brook, St Francis Hosp, Roslyn, NY USA.
   Univ Washington, CHS Coordinating Ctr, Seattle, WA 98195 USA.
   Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
   Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   Johns Hopkins Univ, Welch Ctr, Baltimore, MD USA.
   NHLBI, DECA, NIH, Bethesda, MD 20892 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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3518
BP 780
EP 780
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603567
ER

PT J
AU Hsia, J
   Manson, JE
   Johnson, KC
   Assaf, AR
   Lasser, NL
   Trevisan, M
   Black, HR
   Heckbert, SR
   Detrano, R
   Wong, ND
   Crouse, JR
   Stein, E
   Cushman, M
AF Hsia, J
   Manson, JE
   Johnson, KC
   Assaf, AR
   Lasser, NL
   Trevisan, M
   Black, HR
   Heckbert, SR
   Detrano, R
   Wong, ND
   Crouse, JR
   Stein, E
   Cushman, M
TI Estrogen plus progestin and coronary heart disease risk: Final results
   from the women's health initiative randomized trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 George Washington Univ, Washington, DC USA.
   Brigham & Womens Hosp, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Brown Univ, Sch Med, Providence, RI 02912 USA.
   Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA.
   SUNY Coll Buffalo, Buffalo, NY 14222 USA.
   Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA.
   Univ Washington, Seattle, WA 98195 USA.
   Univ Calif Los Angeles, Harbor Med Ctr, Torrance, CA 90509 USA.
   Inst Educ, Torrance, CA USA.
   Emory Univ, Atlanta, GA 30322 USA.
   Univ Calif Irvine, Irvine, CA USA.
   Wake Forest Univ, Winston Salem, NC 27109 USA.
   Med Res Labs Int, Highland Hts, KY USA.
   Univ Vermont, Burlington, VT 05405 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
MA 3553
BP 787
EP 787
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360603602
ER

PT J
AU Liu, YM
   Berthier-Schaad, Y
   Fallin, DM
   Fink, N
   Tracy, RP
   Klag, MJ
   Smith, MW
   Coresh, J
AF Liu, YM
   Berthier-Schaad, Y
   Fallin, DM
   Fink, N
   Tracy, RP
   Klag, MJ
   Smith, MW
   Coresh, J
TI Interleukin-6 haplotypes, inflammation, and risk of cardiovascular
   disease in a multiethnic dialysis cohort
SO CIRCULATION
LA English
DT Meeting Abstract
CT 76th Annual Scientific Session of the American-Heart-Association
CY NOV 07-12, 2003
CL ORLANDO, FLORIDA
SP Amer Heart Assoc
C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   Univ Vermont, Burlington, VT USA.
   NCI, Basic Res Program, SAIC, Frederick, MD USA.
RI Smith, Michael/B-5341-2012
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 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 28
PY 2003
VL 108
IS 17
SU S
BP T
EP T
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 739RQ
UT WOS:000186360600050
ER

PT J
AU Zhou, MS
   Deng, LW
   Kashanchi, F
   Brady, JN
   Shatkin, AJ
   Kumar, A
AF Zhou, MS
   Deng, LW
   Kashanchi, F
   Brady, JN
   Shatkin, AJ
   Kumar, A
TI The Tat/TAR-dependent phosphorylation of RNA polymerase IIC-terminal
   domain stimulates cotranscriptional capping of HIV-1 mRNA
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID VIRUS TYPE-1 TRANSCRIPTION; ELONGATION; ENZYME; KINASE;
   GUANYLYLTRANSFERASE; RECRUITMENT; PROTEIN; BINDING; REGION; CDK9
AB The HIV type 1 (HIV-1) Tat protein stimulates transcription elongation by recruiting P-TEFb (CDK9/cyclin T1) to the transactivation response (TAR) RNA structure. Tat-induced CDK9 kinase has been shown to phosphorylate Ser-5 of RNA polymerase II (RNAP II) C-terminal domain (CTD). Results presented here demonstrate that Tat-induced Ser-5 phosphorylation of CTD by P-TEFb stimulates the guanylyltransferase activity of human capping enzyme and RNA cap formation. Sequential phosphorylation of CTD by Tat-induced P-TEFb enhances the stimulation of human capping enzyme guanylyltransferase activity and RNA cap formation by transcription factor IIH-mediated CTD phosphorylation. Using an immobilized template assay that permits isolation of transcription complexes, we show that Tat/TAR-dependent phosphorylation of RNAP II CTD stimulates cotranscriptional capping of HIV-1 mRNA. Upon transcriptional induction of latently infected cells, accumulation of capped transcripts occurs along with Ser-5-phosphorylated RNAP II in the promoter proximal region of the HIV-1 genome. Therefore, these observations suggest that Tat/TAR-dependent phosphorylation of RNAP II CTD is crucial not only in promoting transcription elongation but also in stimulating nascent viral RNA capping.
C1 George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
   NCI, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA.
   Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
RP Kumar, A (reprint author), George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
NR 30
TC 46
Z9 47
U1 2
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 28
PY 2003
VL 100
IS 22
BP 12666
EP 12671
DI 10.1073/pnas.1835726100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 738RF
UT WOS:000186301100030
PM 14569024
ER

PT J
AU Gratepanche, S
   Gamain, B
   Smith, JD
   Robinson, BA
   Saul, A
   Miller, LH
AF Gratepanche, S
   Gamain, B
   Smith, JD
   Robinson, BA
   Saul, A
   Miller, LH
TI Induction of crossreactive antibodies against the Plasmodium falciparum
   variant protein
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID CHONDROITIN SULFATE-A; BINDING DOMAIN; CELL-SURFACE; MALARIA; CD36;
   ANTIGEN; PFEMP1; ADHERENCE; IDENTIFICATION; ERYTHROCYTES
AB The variant antigen Plasmodium, falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surface of A falciparum-parasitized erythrocytes (PE), plays a central role in naturally acquired immunity, although antibodies to PfEMP1 are predominantly variant specific. To overcome this major limitation for vaccine development, we immunized mice with three cysteine-rich interdomain 1 (CIDR1) domains of PfEMP1 that have the critical function of binding the PE to CD36 on endothelium and thus preventing spleen-dependent killing of the parasite. The immunizations consisted of different combinations of three CIDR1 encoded by DNA followed by recombinant protein boost. Immunizations with a single variant in a prime-boost regimen induced no or low crossreactivity toward heterologous CIDR1; however, a broad range of crossreactivity was detected in mice that were immunized with all three variants simultaneously. The induced crossreactivity suggests that an anti-PfEMP1 vaccine may be possible.
C1 NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA.
   Seattle Biomed Res Inst, Seattle, WA 98109 USA.
   Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA.
   Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA.
RP Miller, LH (reprint author), NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA.
RI Saul, Allan/I-6968-2013; 
OI Saul, Allan/0000-0003-0665-4091; Gamain, Benoit/0000-0002-8255-2145
NR 21
TC 15
Z9 16
U1 0
U2 0
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 28
PY 2003
VL 100
IS 22
BP 13007
EP 13012
DI 10.1073/pnas.2235588100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 738RF
UT WOS:000186301100090
PM 14569009
ER

PT J
AU Isaacs, EB
   Vargha-Khadem, F
   Watkins, KE
   Lucas, A
   Mishkin, M
   Gadian, DG
AF Isaacs, EB
   Vargha-Khadem, F
   Watkins, KE
   Lucas, A
   Mishkin, M
   Gadian, DG
TI Developmental amnesia and its relationship to degree of hippocampal
   atrophy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID LOW-BIRTH-WEIGHT; COGNITIVE MEMORY; CHILDREN; MONKEYS; INJURY
AB Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8-9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by approximate to20-30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.
C1 NIMH, Bethesda, MD 20892 USA.
   UCL, Inst Child Hlth, London WC1N 1EH, England.
   McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 1S2, Canada.
RP Mishkin, M (reprint author), NIH, Room 1880,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA.
EM mm@ln.nimh.nih.gov
RI Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008; Watkins,
   Kate/A-6559-2012
OI Watkins, Kate/0000-0002-2621-482X; 
NR 20
TC 61
Z9 61
U1 1
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 28
PY 2003
VL 100
IS 22
BP 13060
EP 13063
DI 10.1073/pnas.1233825100
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 738RF
UT WOS:000186301100099
PM 14555756
ER

PT J
AU Snapp, EL
   Hegde, RS
   Francolini, M
   Lombardo, F
   Colombo, S
   Pedrazzini, E
   Borgese, N
   Lippincott-Schwartz, J
AF Snapp, EL
   Hegde, RS
   Francolini, M
   Lombardo, F
   Colombo, S
   Pedrazzini, E
   Borgese, N
   Lippincott-Schwartz, J
TI Formation of stacked ER cisternae by low affinity protein interactions
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
DE endoplasmic reticulum; photobleaching; cytochrome b5; GFP; FRAP
ID CRYSTALLOID ENDOPLASMIC-RETICULUM; RETINAL-PIGMENT EPITHELIUM; HMG-COA
   REDUCTASE; MITOCHONDRIAL OUTER-MEMBRANE; TAIL-ANCHORED PROTEIN; LIVING
   CELLS; CYTOCHROME B(5); NOTOPHTHALMUS-VIRIDESCENS; GOLGI CISTERNAE;
   PLASMA-MEMBRANE
AB The endoplasmic reticulum (ER) can transform from a network of branching tubules into stacked membrane arrays (termed organized smooth ER [OSER]) in response to elevated levels of specific resident proteins, such as cytochrome b(5). Here, we have tagged OSER-inducing proteins with green fluorescent protein (GFP) to study OSER biogenesis and dynamics in living cells. Overexpression of these proteins induced formation of karmellae, whorls, and crystalloid OSER structures. Photobleaching experiments revealed that OSER-inducing proteins were highly mobile within OSER structures and could exchange between OSER structures and surrounding reticular ER. This indicated that binding interactions between proteins on apposing stacked membranes of OSER structures were not of high affinity. Addition of GFP, which undergoes low affinity, antiparallel dimerization, to the cytoplasmic domains of non-OSER-inducing resident ER proteins was sufficient to induce OSER structures when overexpressed, but addition of a nondimerizing GFP variant was not. These results point to a molecular mechanism for OSER biogenesis that involves weak homotypic interactions between cytoplasmic domains of proteins. This mechanism may underlie the formation of other stacked membrane structures within cells.
C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
   CNR, Inst Neurosci, Cellular & Mol Pharmacol Sect, I-20129 Milan, Italy.
   Univ Milan, Dept Med Pharmacol, I-20129 Milan, Italy.
   CNR, Ist Biol & Biotecnol Agr, I-20133 Milan, Italy.
   Univ Catanzaro, Dept Pharmacobiol, I-88021 Catanzaro, Italy.
RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, 18 Lib Dr,Bldg 18T,Rm 101, Bethesda, MD 20892 USA.
OI PEDRAZZINI, EMANUELA/0000-0002-9238-3840; Borgese,
   Nica/0000-0002-7537-3974; Hegde, Ramanujan/0000-0001-8338-852X
NR 52
TC 255
Z9 259
U1 1
U2 16
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 27
PY 2003
VL 163
IS 2
BP 257
EP 269
DI 10.1083/jcb.200306020
PG 13
WC Cell Biology
SC Cell Biology
GA 739EU
UT WOS:000186331100008
PM 14581454
ER

PT J
AU Kwon, YK
   Jang, HJ
   Kole, S
   He, HJ
   Bernier, M
AF Kwon, YK
   Jang, HJ
   Kole, S
   He, HJ
   Bernier, M
TI Role of the pleckstrin homology domain of PLC gamma 1 in its interaction
   with the insulin receptor
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
DE PLC; signal transduction; cultured cells; mass spectrometry
ID GROWTH-FACTOR RECEPTOR; PHOSPHOLIPASE C-GAMMA; FACTOR-I RECEPTOR;
   TYROSINE KINASE; 3T3-L1 ADIPOCYTES; CONFORMATIONAL-CHANGES; SIGNALING
   PATHWAYS; FILAMENTOUS ACTIN; DNA-SYNTHESIS; SH2 DOMAINS
AB A thiol-reactive membrane-associated protein (TRAP) binds covalently to the cytoplasmic domain of the human insulin receptor (IR) beta-subunit when cells are treated with the homobifunctional cross-linker reagent 1,6-bismaleimidohexane. Here, TRAP was found to be phospholipase C gamma1 (PLCgamma1) by mass spectrometry analysis. PLCgamma1 associated with the IR both in cultured cell lines and in a primary culture of rat hepatocytes. Insulin increased PLCgamma1 tyrosine phosphorylation at Tyr-783 and its colocalization with the IR in punctated structures enriched in cortical actin at the dorsal plasma membrane. This association was found to be independent of PLCgamma1 Src homology 2 domains, and instead required the pleckstrin homology (PH)-EF-hand domain. Expression of the PH-EF construct blocked endogenous PLCgamma1 binding to the IR and inhibited insulin-dependent phosphorylation of mitogen-activated protein kinase (MAPK), but not AKT. Silencing PLCgamma1 expression using small interfering RNA markedly reduced insulin-dependent MAPK regulation in HepG2 cells. Conversely, reconstitution of PLCgamma1 in PLCgamma1(-/-) fibroblasts improved MAPK activation by insulin. Our results show that PLCgamma1 is a thiol-reactive protein whose association with the IR could contribute to the activation of MAPK signaling by insulin.
C1 NIA, Gerontol Res Ctr, Diabet Sect, Lab Clin Invest,NIH, Baltimore, MD 21224 USA.
RP Bernier, M (reprint author), NIA, Gerontol Res Ctr, Diabet Sect, Lab Clin Invest,NIH, 5600 Nathan Shock Dr,Box 23, Baltimore, MD 21224 USA.
RI jang, hyeung jin/C-8022-2013; 
OI Bernier, Michel/0000-0002-5948-368X
NR 45
TC 9
Z9 9
U1 0
U2 0
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 27
PY 2003
VL 163
IS 2
BP 375
EP 384
DI 10.1083/jcb.200301131
PG 10
WC Cell Biology
SC Cell Biology
GA 739EU
UT WOS:000186331100018
PM 14568990
ER

PT J
AU Du, J
   Feng, LY
   Zaitsev, E
   Je, HS
   Liu, XW
   Lu, B
AF Du, J
   Feng, LY
   Zaitsev, E
   Je, HS
   Liu, XW
   Lu, B
TI Regulation of TrkB receptor tyrosine kinase and its internalization by
   neuronal activity and Ca2+ influx
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
DE BDNF; endocytosis; calcium influx; hippocampus; activity dependent
ID NERVE GROWTH-FACTOR; DEVELOPING NEUROMUSCULAR SYNAPSES; NEUROTROPHIN
   SIGNAL-TRANSDUCTION; HIPPOCAMPAL-NEURONS; SYMPATHETIC NEURONS;
   RETROGRADE SIGNAL; PLASMA-MEMBRANE; POTENTIATION; ENDOCYTOSIS; CLATHRIN
AB Internalization of the neurotrophin-Trk receptor complex is critical for many aspects of neurotrophin functions. The mechanisms governing the internalization process are unknown. Here, we report that neuronal activity facilitates the internalization of the receptor for brain-derived neurotrophic factor, TrkB, by potentiating its tyrosine kinase activity. Using three independent approaches, we show that electric stimulation of hippocampal neurons markedly enhances TrkB internalization. Electric stimulation also potentiates TrkB tyrosine kinase activity. The activity-dependent enhancement of TrkB internalization and its tyrosine kinase requires Ca2+ influx through N-methyl-D-aspartate receptors and Ca2+ channels. inhibition of internalization had no effect on TrkB kinase, but inhibition of TrkB kinase prevents the modulation of TrkB internalization, suggesting a critical role of the tyrosine kinase in the activity-dependent receptor endocytosis. These results demonstrate an activity and Ca2+-dependent modulation of TrkB tyrosine kinase and its internalization, and they provide new insights into the cell biology of tyrosine kinase receptors.
C1 NICHHD, Sect Neural Dev & Plast, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA.
   NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorder Program, Bethesda, MD 20878 USA.
   Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China.
   George Washington Univ, Grad Program Genet, Washington, DC 20052 USA.
RP Lu, B (reprint author), NICHD, Sect Neural Dev & Plast, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 49,Rm 6A80,49 Convent Dr, Bethesda, MD 20892 USA.
RI Lu, Bai/A-4018-2012; Du, Jing/A-9023-2012; 
OI Je, hyunsoo/0000-0002-2924-5621
NR 41
TC 54
Z9 55
U1 0
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 27
PY 2003
VL 163
IS 2
BP 385
EP 395
DI 10.1083/jcb.200305134
PG 11
WC Cell Biology
SC Cell Biology
GA 739EU
UT WOS:000186331100019
PM 14581459
ER

PT J
AU Sarlis, NJ
   Gourgiotis, L
   Filie, AC
AF Sarlis, NJ
   Gourgiotis, L
   Filie, AC
TI Misclassification of cytologic diagnoses in patients with follicular
   lesions or follicular neoplasms of the thyroid gland - Implications for
   patient care and clinical research - Author reply
SO CANCER CYTOPATHOLOGY
LA English
DT Letter
ID FINE-NEEDLE ASPIRATION; CARCINOMA
C1 Univ Texas, MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA.
   NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
   NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA.
RP Sarlis, NJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, 1515 Holcombe Blvd, Houston, TX 77030 USA.
NR 8
TC 1
Z9 1
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2003
VL 99
IS 5
BP 319
EP 320
DI 10.1002/cncr.11724
PG 2
WC Oncology; Pathology
SC Oncology; Pathology
GA 732VQ
UT WOS:000185966600010
ER

PT J
AU Castle, PE
   Hildesheim, A
   Schiffman, M
   Gaydos, CA
   Cullen, A
   Herrero, R
   Bratti, MC
   Freer, E
AF Castle, PE
   Hildesheim, A
   Schiffman, M
   Gaydos, CA
   Cullen, A
   Herrero, R
   Bratti, MC
   Freer, E
TI Stability of archived liquid-based cytologic specimens
SO CANCER CYTOPATHOLOGY
LA English
DT Letter
ID AMPLICOR CT/NG TESTS; MULTICENTER EVALUATION; CHLAMYDIA-TRACHOMATIS;
   GONORRHOEAE
C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD USA.
   Digene Corp, Gaithersburg, MD USA.
   Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
   Univ Costa Rica, Ctr Invest Estructuras Microscoicas, San Jose, Costa Rica.
RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RI Gaydos, Charlotte/E-9937-2010
NR 6
TC 9
Z9 9
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD OCT 25
PY 2003
VL 99
IS 5
BP 320
EP 322
DI 10.1002/cncr.11723
PG 3
WC Oncology; Pathology
SC Oncology; Pathology
GA 732VQ
UT WOS:000185966600011
PM 14579301
ER

PT J
AU Valtcheva, R
   Stephanova, E
   Jordanova, A
   Pankov, R
   Altankov, G
   Lalchev, Z
AF Valtcheva, R
   Stephanova, E
   Jordanova, A
   Pankov, R
   Altankov, G
   Lalchev, Z
TI Effect of halothane on lung carcinoma cells A 549
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE halothane; cytotoxicity; A 549; pulmonary surfactant
ID VOLATILE GENERAL-ANESTHETICS; IN-VITRO; INHALATION ANESTHETICS;
   GUTTA-PERCHA; II CELLS; HEPATITIS; TUMOR; ACTIVATION; NEURONS; SURGERY
AB The halogenated hydrocarbons, such as halothane, are widely used as anesthetics in clinical practice; however their application is often accompanied with metabolic, cardiovascular and respiratory complications. One of the possible factors for this negative outcome might be the severe toxicity of these agents. In this paper, we investigate in vitro effects of halothane on human lung carcinoma A 549 cells, namely on their cytotoxicity, adhesive properties and metabolic activity.
   The cytotoxicity response of lung carcinoma A 549 cells to halothane was determined by lactate dehydrogenase (LDH) assay (for cytotoxicity), by detachment assay after adhesion to type IV collagen (for cell adhesive properties) and by surface tension measurements of culture medium (for cell metabolic activity).
   Regarding the cytotoxicity, the determined maximal non-toxic concentration of halothane on A549 cells, given here as volume percentages (vol.%) was 0.7 vol.% expressed as aqueous concentration in the culture medium. Direct measurement of the actual halothane concentration in the culture medium showed that 0.7 vol.% corresponds to 1.05 mM and 5.25 aqueous-phase minimum alveolar concentration (MAC). Concentrations equal or higher than 1.4 vol.% (2.1 mM; 10.5 MAC) of halothane provoked complete detachment (cell death), or reduction of initial adhesion to collagen IV in half of the cell population. Surfactant production of A 549 cells, registered up to 48 It after halothane treatment, was inhibited by halothane concentrations as low as 0.6 vol.% (0.9 mM; 4.5 MAC).
   Our results demonstrate that sub toxic halothane concentrations of 0.6 vol.% inhibits surfactant production; concentrations in the range 0.8-1.4 vol.% induce membrane damages and concentrations equal and higher than 1.4 vol.%-cell death of approximately 50% of the cells. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
C1 Univ Sofia, Fac Biol, Dept Cell Biol, Sofia 1164, Bulgaria.
   Bulgarian Acad Sci, Inst Biophys, BU-1113 Sofia, Bulgaria.
   Natl Inst Dent & Cranofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Stephanova, E (reprint author), Univ Sofia, Fac Biol, Dept Cell Biol, St Kliment Ohridski 8 Dragan Tsankov Blv, Sofia 1164, Bulgaria.
RI Lalchev, Zdravko/A-6136-2008; Pankov, Roumen/B-3284-2014
OI Pankov, Roumen/0000-0002-3157-3659
NR 51
TC 11
Z9 13
U1 0
U2 2
PU ELSEVIER SCI IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0009-2797
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD OCT 25
PY 2003
VL 146
IS 2
BP 191
EP 200
DI 10.1016/j.cbi.2003.08.002
PG 10
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA 744KC
UT WOS:000186627200008
PM 14597132
ER

PT J
AU Kaplan, B
   Cojocaru, M
   Unsworth, E
   Knecht, A
   Martin, BM
AF Kaplan, B
   Cojocaru, M
   Unsworth, E
   Knecht, A
   Martin, BM
TI Search for peptidic "middle molecules" in uremic sera: isolation and
   chemical identification of fibrinogen fragments
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
   AND LIFE SCIENCES
LA English
DT Article
DE middle molecules; fibrinogen
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYACRYLAMIDE-GEL ELECTROPHORESIS;
   SODIUM DODECYL-SULFATE; GLYCOPROTEIN-IIB-IIIA; MASS-SPECTROMETRY;
   COMPLEMENT ACTIVATION; BIOLOGICAL-ACTIVITY; AMYLOID PROTEINS;
   RENAL-FAILURE; HEMODIALYSIS
AB According to the "middle molecule" (MM) hypothesis, the uremic solutes ranging from 500 to 5000 Da are insufficiently eliminated by conventional hemodialysis and may act as uremic toxins. However, because of the methodological difficulties of MM purification, their chemical analysis is complicated and the precise structure of these molecules remains obscure. In the present study, a new micro-preparative procedure including SDS electrophoresis and liquid chromatography was applied for isolation of MM peptides from uremic sera. Microsequencing and NISIMS analyses of these peptides showed that most of the identified MM (22 out of 23) represented the N- and C-terminal fragments of the alpha- and beta-chains of fibrinogen. The obtained data provide new information on the precise structure of fibrinogen fragments accumulating in uremic serum as MM. (C) 2003 Elsevier B.V. All rights reserved.
C1 Tel Aviv Univ, Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel.
   Bar Ilan Univ, Dept Chem, Ramat Gan, Israel.
   NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA.
   Chaim Sheba Med Ctr, Dept Nephrol, IL-52621 Tel Hashomer, Israel.
RP Kaplan, B (reprint author), Tel Aviv Univ, Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel.
NR 52
TC 22
Z9 23
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD OCT 25
PY 2003
VL 796
IS 1
BP 141
EP 153
DI 10.1016/j.jchromb.2003.08.008
PG 13
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 732PX
UT WOS:000185955700015
PM 14552825
ER

PT J
AU Lepper, ER
   Swain, SM
   Tan, AR
   Figg, WD
   Sparreboom, A
AF Lepper, ER
   Swain, SM
   Tan, AR
   Figg, WD
   Sparreboom, A
TI Liquid-chromatographic determination of erlotinib (OSI-774), an
   epidermal growth factor receptor tyrosine kinase inhibitor
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
   AND LIFE SCIENCES
LA English
DT Article
DE pharmacokinetics; erlotinib; OSI-774
ID HUMAN PLASMA; MALIGNANCIES; VALIDATION
AB A high-performance liquid-chromatographic (HPLC) assay with UV detection has been developed for the quantitative determination of erlotinib (OSI-774) in human plasma. Quantitative extraction was achieved by a single-solvent extraction involving a mixture of acetonitrile and n-butyl chloride (1:4, v/v). Erlotinib and the internal standard hydrochloride salt (OSI-597) were separated on a column packed with Nova-Pak C18 material and a mobile phase composed of acetonitrile and water, pH 2.0 (60:40, v/v). The column effluent was monitored with dual UV detection at wavelengths of 348 nm (erlotinib) and 383 mn (OSI-597). The calibration graph was linear in the range of 100-4500 ng/ml, with values for accuracy and precision ranging from 87.9 to 96.2% and 2.13 to 5.10%, respectively, for three different sets of quality control samples. The developed method was successfully applied to study the pharmacokinetics of erlotinib in a cancer patient at the recommended daily dose of 150 mg. (C) 2003 Elsevier B.V. All rights reserved.
C1 NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA.
   NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Clin Res Unit, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016
NR 13
TC 33
Z9 34
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD OCT 25
PY 2003
VL 796
IS 1
BP 181
EP 188
DI 10.1016/j.jchromb.2003.08.015
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 732PX
UT WOS:000185955700019
PM 14552829
ER

PT J
AU Donaldson, JG
AF Donaldson, JG
TI Multiple roles for Arf6: Sorting, structuring, and signaling at the
   plasma membrane
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID ADP-RIBOSYLATION FACTOR-6; NUCLEOTIDE-EXCHANGE FACTORS; REGULATED
   EXOCYTOSIS; ACTIN CYTOSKELETON; RECYCLING PATHWAY; CHROMAFFIN CELLS;
   PHOSPHOLIPASE-D; FACTOR ARNO; ACTIVATION; PROTEIN
C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2503, Bethesda, MD 20892 USA.
NR 61
TC 301
Z9 303
U1 4
U2 23
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2003
VL 278
IS 43
BP 41573
EP 41576
DI 10.1074/jbc.R300026200
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 733FP
UT WOS:000185989500001
PM 12912991
ER

PT J
AU Beck, GR
   Knecht, N
AF Beck, GR
   Knecht, N
TI Osteopontin regulation by inorganic phosphate is ERK1/2-, protein kinase
   C-, and proteasome-dependent
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OSTEOBLAST-LIKE CELLS; SMOOTH-MUSCLE-CELLS; FIBROBLAST-GROWTH-FACTOR;
   P-I TRANSPORT; MC3T3-E1 CELLS; EXTRACELLULAR SIGNAL;
   PARATHYROID-HORMONE; GENE-EXPRESSION; DOWN-REGULATION; STIMULATION
AB The generation of inorganic phosphate by alkaline phosphatase during osteoblast differentiation represents an important signaling event, although the molecular and cellular consequences are currently undefined. We have previously described osteopontin as a gene regulated by an increase in inorganic phosphate not only in osteoblasts but also in other cell types. We describe here the identification of specific signaling pathways required for the stimulation of osteopontin expression by inorganic phosphate. We have determined that phosphate selectively activates the extracellular signal-regulated kinase (ERK1/2) signaling pathway but does not activate the other mitogen-activated protein kinase signaling proteins, p38, or the c-Jun N-terminal kinase. In addition, our results suggest that cellular exposure to 10 mM inorganic phosphate causes a biphasic ERK1/2 activation. The second ERK1/2 activation is required for osteopontin regulation, whereas the first is not sufficient. Analysis of common protein kinase families has revealed that phosphate-induced osteopontin expression specifically uses a protein kinase C-dependent signaling pathway. In addition, our results suggest that protein kinase C and ERK1/2 are not part of the same pathway but constitute two distinct pathways. Finally, we have determined that the proteasomal activity is required not only for phosphate-induced expression of osteopontin but also for the induction of osteopontin in response to 12-O-tetradecanoylphorbol 13-acetate and okadaic acid. The data presented here define for the first time the ability of increased inorganic phosphate to stimulate specific signaling pathways resulting in functionally significant changes in gene expression and identify three important signaling pathways in the regulation of osteopontin.
C1 NCI, Ctr Canc Res, Basic Res Lab, Frederick, MD 21702 USA.
RP Beck, GR (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Bldg 576,Rm 110, Frederick, MD 21702 USA.
FU NCI NIH HHS [CA 84573]
NR 61
TC 77
Z9 80
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2003
VL 278
IS 43
BP 41921
EP 41929
DI 10.1074/jbc.M304470200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 733FP
UT WOS:000185989500046
PM 12920127
ER

PT J
AU Yakovleva, L
   Tian, LG
   Sayer, JM
   Kalena, GP
   Kroth, H
   Jerina, DM
   Shuman, S
AF Yakovleva, L
   Tian, LG
   Sayer, JM
   Kalena, GP
   Kroth, H
   Jerina, DM
   Shuman, S
TI Site-specific DNA transesterification by vaccinia topoisomerase -
   Effects of benzo[a]pyrene-dA, 8-oxoguanine, 8-oxoadenine, and
   2-aminopurine modifications
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CODON 61 SEQUENCE; DIOL EPOXIDE; VIRUS TOPOISOMERASE; COVALENT
   CATALYSIS; MINOR-GROOVE; MUTATIONAL ANALYSIS; IB TOPOISOMERASE; DUPLEX
   DNA; ADDUCT; MECHANISM
AB Vaccinia DNA topoisomerase forms a covalent DNA(3'-phosphotyrosyl)-enzyme intermediate at a specific target site 5'-C(+5)C(+4)C(+3)T(+2)T(+1)p down arrow N-1 in duplex DNA. Here we study the effects of base modifications on the rate and extent of single-turnover DNA transesterification. Chiral trans opened C-10 R and S adducts of benzo[a]pyrene (BP) 7,8-diol 9,10-epoxide were introduced at single N-6-deoxyadenosine (dA) positions within the 3'-G(+5)G(+4)G(+3)A(+2)A(+1)T(-1)A(-2) sequence of the nonscissile DNA strand. The R and S BPdA adducts intercalate from the major groove on the 5' and 3' sides of the modified base, respectively, and perturb local base stacking. We found that R and S BPdA modifications at +1A reduced the transesterification rate by a factor of 700-1000 without affecting the yield of the covalent topoisomerase-DNA complex. BPdA modifications at +2A reduced the extent of transesterification and elicited rate decrements of 200- and 7000-fold for the S and R diastereomers, respectively. In contrast, BPdA adducts at the -2 position had no effect on the extent of the reaction and relatively little impact on the rate of cleavage. A more subtle probe of major groove contacts entailed substituting each of the purines of the nonscissile strand with its 8-oxo analog. The +3 oxoG modification slowed transesterification 35-fold, whereas other 8-oxo modifications were benign. 8-Oxo substitutions at the -1 position in the scissile strand slowed single-turnover cleavage by a factor of six but had an even greater slowing effect on religation, which resulted in an increase in the cleavage equilibrium constant. 2-Aminopurine at positions +3, +4, or +5 in the nonscissile strand had no effect on transesterification per se but had synergistic effects when combined with 8-oxoA at position -1 in the scissile strand. These findings illuminate the functional interface of vaccinia topoisomerase with the DNA major groove.
C1 Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA.
   NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Shuman, S (reprint author), Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA.
FU NIAID NIH HHS [AI 053471]; NIGMS NIH HHS [GM 46330]
NR 54
TC 12
Z9 12
U1 2
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2003
VL 278
IS 43
BP 42170
EP 42177
DI 10.1074/jbc.M308079200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 733FP
UT WOS:000185989500075
PM 12909623
ER

PT J
AU Zhou, YX
   Zhao, MR
   Li, D
   Shimazu, K
   Sakata, K
   Deng, CX
   Lu, B
AF Zhou, YX
   Zhao, MR
   Li, D
   Shimazu, K
   Sakata, K
   Deng, CX
   Lu, B
TI Cerebellar deficits and hyperactivity in mice lacking Smad4
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR-BETA; RAT HIPPOCAMPAL-NEURONS; BONE MORPHOGENETIC
   PROTEINS; LONG-TERM POTENTIATION; MAD-RELATED PROTEIN; NERVOUS-SYSTEM;
   TUMOR-SUPPRESSOR; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1;
   SIGNAL-TRANSDUCTION
AB Smad4 is a central mediator of TGF-beta signals, which are known to play essential roles in many biological processes. Using a Cre-loxP approach to overcome early embryonic lethality, we have studied functions of TGFbeta/Smad4 signals in the central nervous system (CNS). No obvious deficits were detected in mice carrying the targeted disruption of Smad4 in the CNS. The overall morphology of the hippocampus appeared normal. There was no change in the proliferation of neuronal precursor cells, nor in several forms of synaptic plasticity. In contrast, deletion of Smad4 resulted in a marked decrease in the number of cerebellar Purkinje cells and parvalbumin-positive interneurons. Accompanied by the abnormality in the cerebellum, mutant mice also exhibited significantly increased vertical activity. Thus, our study reveals an unexpected role for Smad4 in cerebellar development and in the control of motor function.
C1 NIDDK, Mammalian Genet Sect, NIH, Bethesda, MD 20892 USA.
   NICHD, Sect Neural Dev & Plast, NIH, Bethesda, MD 20892 USA.
RP Lu, B (reprint author), NIDDK, Mammalian Genet Sect, NIH, Bethesda, MD 20892 USA.
RI Lu, Bai/A-4018-2012; deng, chuxia/N-6713-2016
NR 70
TC 40
Z9 43
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2003
VL 278
IS 43
BP 42313
EP 42320
DI 10.1074/jbc.M308287200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 733FP
UT WOS:000185989500092
PM 12896967
ER

PT J
AU He, YY
   Huang, JL
   Gentry, JB
   Chignell, CF
AF He, YY
   Huang, JL
   Gentry, JB
   Chignell, CF
TI Epidermal growth factor receptor down-regulation induced by UVA in human
   keratinocytes does not require the receptor kinase activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TYROSINE KINASE; EGF RECEPTOR; C-CBL; MALIGNANT-MELANOMA;
   ULTRAVIOLET-LIGHT; RING FINGER; INTERNALIZATION; UBIQUITINATION;
   ACTIVATION; APOPTOSIS
AB Activation of the epidermal growth factor (EGF) receptor by EGF, its ligand, results in receptor internalization and down-regulation, which requires receptor kinase activity, phosphorylation, and ubiquitination. In contrast, we have found here in human HaCaT keratinocytes that exposure to UVA induces EGF receptor internalization and down-regulation without receptor phosphorylation and ubiquitination. The presence of the receptor kinase activity inhibitor AG1478 increased UVA-induced receptor down-regulation, whereas it inhibited EGF-induced receptor down-regulation. These observations demonstrate that, in contrast to EGF, receptor kinase activity is not required for receptor downregulation by UVA. Concurrent with receptor down-regulation, caspases were activated by UVA exposure. The presence of caspase inhibitors blocked receptor downregulation in a pattern similar to poly(ADP)-ribose polymerase cleavage. Much more receptor down-regulation was observed after UVA exposure in apoptotic detached cells in which caspase is activated completely. These results indicate that UVA-induced receptor downregulation is dependent on caspase activation. Similar to UVA, both UVB and UVC induced receptor downregulation, in which receptor kinase activity is not required, whereas caspase activation is involved. Inhibition of EGF receptor down-regulation increased receptor activation and activation of its downstream survival signaling ERK and AKT after UVA exposure. Preventing the activation of each of these pathways enhanced apoptosis induced by UVA. These findings suggest that EGF receptor down-regulation by UVA may play an important role in the execution of the cell suicide program by attenuating its anti-apoptotic function and thereby preventing cell transformation and tumorigenesis in vivo.
C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
RP He, YY (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 42
TC 38
Z9 44
U1 2
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 24
PY 2003
VL 278
IS 43
BP 42457
EP 42465
DI 10.1074/jbc.M303376200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 733FP
UT WOS:000185989500110
PM 12930839
ER

PT J
AU Minsky, A
   Sharma, AK
   Englander, J
AF Minsky, A
   Sharma, AK
   Englander, J
TI The structure of D-radiodurans - Response
SO SCIENCE
LA English
DT Letter
ID DEINOCOCCUS-RADIODURANS
C1 Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel.
   NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
RP Minsky, A (reprint author), Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel.
NR 6
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 24
PY 2003
VL 302
IS 5645
BP 567
EP 568
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735MV
UT WOS:000186119900023
ER

PT J
AU Merikangas, KR
   Risch, N
AF Merikangas, KR
   Risch, N
TI Genomic priorities and public health
SO SCIENCE
LA English
DT Article
ID GENETIC EPIDEMIOLOGY; ADOLESCENT SMOKING; DIABETES-MELLITUS;
   ALZHEIMER-DISEASE; COMPLEX TRAITS; FAMILY-HISTORY; LIFE-STYLE;
   STRATEGIES; CANCER; RISK
AB Given the continuing difficulty of identifying genes for complex disorders in a robust, replicable manner, and the extensive resources devoted to this effort, it is becoming increasingly important to analyze the relative benefits of genomics research for public health applications and for the understanding of disease pathogenesis. To establish priorities for genetics research, we review and evaluate several characteristics of selected exemplary complex diseases, including phenotypic accuracy, knowledge of specific and nonspecific genetic and environmental risk factors, and population prevalence and impact. We propose that complex diseases with the strongest evidence for genetic etiology, limited ability to modify exposure or risk factors, and high public health impact should have the highest priority for genetics research.
C1 NIMH, Sec Dev Genet Epidemiol, Mood & Anxiety Disorders Progrma, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
   Kaiser Permanente, Div Res, Oakland, CA 94612 USA.
RP Merikangas, KR (reprint author), NIMH, Sec Dev Genet Epidemiol, Mood & Anxiety Disorders Progrma, NIH,Dept Hlth & Human Serv, 15K N Dr,Mail Stop Code 2670, Bethesda, MD 20892 USA.
NR 51
TC 158
Z9 163
U1 0
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 24
PY 2003
VL 302
IS 5645
BP 599
EP 601
DI 10.1126/science.1091468
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735MV
UT WOS:000186119900045
PM 14576422
ER

PT J
AU Wang, RF
   Harada, S
   Mitsuya, H
   Zemlicka, J
AF Wang, RF
   Harada, S
   Mitsuya, H
   Zemlicka, J
TI Inhibition of human immunodeficiency virus reverse transcriptase by
   synadenol triphosphate and its E-isomer
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID METHYLENECYCLOPROPANE NUCLEOSIDE ANALOGS; ANTIVIRAL ACTIVITY; PRODRUGS;
   ACTIVATION; RESISTANT
AB Triphosphate 1c is a potent competitive inhibitor of wild-type HIV-1 reverse transcriptase with K-i close to ddATP. The E-isomer 2c is about 30-times weaker. Triphosphates le and 2c interact with the same active site of reverse transcriptase as ddATP. The extent of inhibition of two mutant forms of reverse transcriptase (RT), RTM184V and RTM184I, with triphosphate 1c was about 5 and 8 times lower than that of wild-type RTwt.
C1 Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Chem,Sch Med, Dev Therapeut Program, Detroit, MI 48201 USA.
   Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan.
   NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Zemlicka, J (reprint author), Wayne State Univ, Barbara Ann Karmanos Canc Inst, Dept Chem,Sch Med, Dev Therapeut Program, Detroit, MI 48201 USA.
EM zemlicka@kci.wayne.edu
FU NCI NIH HHS [CA32779]
NR 15
TC 9
Z9 9
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD OCT 23
PY 2003
VL 46
IS 22
BP 4799
EP 4802
DI 10.1021/jm030048y
PG 4
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 733GG
UT WOS:000185991100020
PM 14561099
ER

PT J
AU Baumgart, T
   Hess, ST
   Webb, WW
AF Baumgart, T
   Hess, ST
   Webb, WW
TI Imaging coexisting fluid domains in biomembrane models coupling
   curvature and line tension
SO NATURE
LA English
DT Article
ID GIANT PHOSPHOLIPID-VESICLES; INTRAMEMBRANE DOMAINS; MEMBRANES; SHAPE;
   FISSION; TRANSITIONS; MONOLAYERS; DYNAMICS
AB Lipid bilayer membranes - ubiquitous in biological systems and closely associated with cell function - exhibit rich shape-transition behaviour, including bud formation(1) and vesicle fission(2). Membranes formed from multiple lipid components can laterally separate into coexisting liquid phases, or domains, with distinct compositions. This process, which may resemble raft formation in cell membranes, has been directly observed in giant unilamellar vesicles(3,4). Detailed theoretical frameworks(5-11) link the elasticity of domains and their boundary properties to the shape adopted by membranes and the formation of particular domain patterns, but it has been difficult to experimentally probe and validate these theories. Here we show that high-resolution fluorescence imaging using two dyes preferentially labelling different fluid phases directly provides a correlation between domain composition and local membrane curvature. Using freely suspended membranes of giant unilamellar vesicles, we are able to optically resolve curvature and line tension interactions of circular, stripe and ring domains. We observe long-range domain ordering in the form of locally parallel stripes and hexagonal arrays of circular domains, curvature-dependent domain sorting, and membrane fission into separate vesicles at domain boundaries. By analysing our observations using available membrane theory, we are able to provide experimental estimates of boundary tension between fluid bilayer domains.
C1 Cornell Univ, Ithaca, NY 14853 USA.
   NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Webb, WW (reprint author), Cornell Univ, Ithaca, NY 14853 USA.
RI Webb, Watt/B-5905-2011
NR 29
TC 909
Z9 929
U1 21
U2 222
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 23
PY 2003
VL 425
IS 6960
BP 821
EP 824
DI 10.1038/nature02013
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735ME
UT WOS:000186118500041
PM 14574408
ER

PT J
AU Zhang, JW
   Niu, C
   Ye, L
   Huang, HY
   He, X
   Tong, WG
   Ross, J
   Haug, J
   Johnson, T
   Feng, JQ
   Harris, S
   Wiedemann, LM
   Mishina, Y
   Li, LH
AF Zhang, JW
   Niu, C
   Ye, L
   Huang, HY
   He, X
   Tong, WG
   Ross, J
   Haug, J
   Johnson, T
   Feng, JQ
   Harris, S
   Wiedemann, LM
   Mishina, Y
   Li, LH
TI Identification of the haematopoietic stem cell niche and control of the
   niche size
SO NATURE
LA English
DT Article
ID BONE MORPHOGENETIC PROTEIN-2; DROSOPHILA-OVARY; IN-VIVO;
   DIFFERENTIATION; OSTEOBLAST; CADHERIN; LINEAGES; PROLIFERATION;
   MESODERM; MARROW
AB Haematopoietic stem cells (HSCs) are a subset of bone marrow cells that are capable of self-renewal and of forming all types of blood cells (multi-potential)(1). However, the HSC 'niche'-the in vivo regulatory microenvironment where HSCs reside-and the mechanisms involved in controlling the number of adult HSCs remain largely unknown. The bone morphogenetic protein (BMP) signal has an essential role in inducing haematopoietic tissue during embryogenesis(2,3). We investigated the roles of the BMP signalling pathway in regulating adult HSC development in vivo by analysing mutant mice with conditional inactivation of BMP receptor type IA (BMPRIA). Here we show that an increase in the number of spindle-shaped N-cadherin(+)CD45(-) osteoblastic (SNO) cells correlates with an increase in the number of HSCs. The long-term HSCs are found attached to SNO cells. Two adherens junction molecules, N-cadherin and beta-catenin, are asymmetrically localized between the SNO cells and the long-term HSCs. We conclude that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of HSCs by regulating niche size.
C1 Stowers Inst Med Res, Kansas City, MO 64110 USA.
   Univ Missouri, Sch Dent, Dept Oral Biol, Kansas City, MO 64108 USA.
   NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA.
   Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA.
RP Li, LH (reprint author), Stowers Inst Med Res, Kansas City, MO 64110 USA.
RI Wiedemann, Leanne/E-3316-2010
NR 31
TC 1722
Z9 1833
U1 21
U2 111
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 23
PY 2003
VL 425
IS 6960
BP 836
EP 841
DI 10.1038/nature02041
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 735ME
UT WOS:000186118500045
PM 14574412
ER

PT J
AU Manolio, T
AF Manolio, T
TI Novel risk markers and clinical practice
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID INFLAMMATION
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP Manolio, T (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 6
TC 120
Z9 128
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 23
PY 2003
VL 349
IS 17
BP 1587
EP 1589
DI 10.1056/NEJMp038136
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 734ZT
UT WOS:000186088400001
PM 14573728
ER

PT J
AU Boon, K
   Edwards, JB
   Siu, IM
   Olschner, D
   Eberhart, CG
   Marra, MA
   Strausberg, RL
   Riggins, GJ
AF Boon, K
   Edwards, JB
   Siu, IM
   Olschner, D
   Eberhart, CG
   Marra, MA
   Strausberg, RL
   Riggins, GJ
TI Comparison of medulloblastoma and normal neural transcriptomes
   identifies a restricted set of activated genes
SO ONCOGENE
LA English
DT Article
DE medulloblastoma; tumor-associated antigens; SAGE; bioinformatics
ID INDEPENDENT PROGNOSTIC MARKER; CENTRAL-NERVOUS-SYSTEM; PATIENT SURVIVAL;
   GLIOMA-CELLS; IN-VIVO; EXPRESSION; CANCER; CD24; ANTIGEN
AB Over 1.4 million transcript tags expressed in 20 different human medulloblastomas were counted using serial analysis of gene expression. Digital gene expression profiles in the medulloblastoma were compared to multiple regions of the normal human brain, revealing 30 transcripts with high expression in multiple tumors and little or no expression in the normal cerebellum and other adult and pediatric brain regions. Using independent medulloblastoma samples and normal tissue, real-time PCR verified eight of nine selected genes as candidate tumor-associated antigens. Differential protein expression for CD24, prolactin and Topo2A was further confirmed by immunohistochemical analysis using medulloblastoma and normal brain sections and a tissue microarray. The genes highly expressed in the medulloblastoma include PRAME, a cancer-testis antigen and potential targets for immunotherapy.
C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
   Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   BC Canc Agcy, Sequencing Ctr, Vancouver, BC, Canada.
   NCI, Off Canc Genom, Bethesda, MD 20892 USA.
RP Riggins, GJ (reprint author), Mason Lord Ctr Tower,5th Floor,Bhns Hopkins Beyvi, Baltimore, MD 21224 USA.
RI Tang, Macy/B-9798-2014; Marra, Marco/B-5987-2008
FU NCI NIH HHS [U01 CA88128]; PHS HHS [S98-146]
NR 25
TC 48
Z9 52
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 23
PY 2003
VL 22
IS 48
BP 7687
EP 7694
DI 10.1038/sj.onc.1207043
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 735KQ
UT WOS:000186113000017
PM 14576832
ER

PT J
AU Cooley, M
   Bakalov, V
   Bondy, CA
AF Cooley, M
   Bakalov, V
   Bondy, CA
TI Lipid profiles in women with 45,X vs 46,XX primary ovarian failure
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID TURNER-SYNDROME; RISK
C1 NICHHD, NIH, Bethesda, MD 20892 USA.
RP Cooley, M (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA.
NR 7
TC 26
Z9 26
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 22
PY 2003
VL 290
IS 16
BP 2127
EP 2128
DI 10.1001/jama.290.16.2127
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 734CB
UT WOS:000186036700021
PM 14570947
ER

PT J
AU Smith-Bindman, R
   Chu, PW
   Miglioretti, DL
   Sickles, EA
   Blanks, R
   Ballard-Barbash, R
   Bobo, JK
   Lee, NC
   Wallis, NG
   Patnick, J
   Kerlikowske, K
AF Smith-Bindman, R
   Chu, PW
   Miglioretti, DL
   Sickles, EA
   Blanks, R
   Ballard-Barbash, R
   Bobo, JK
   Lee, NC
   Wallis, NG
   Patnick, J
   Kerlikowske, K
TI Comparison of screening mammography in the United States and the United
   Kingdom
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID POSITIVE PREDICTIVE VALUE; BREAST-CANCER; DIAGNOSTIC MAMMOGRAPHY;
   MEDICAL AUDIT; 22 COUNTRIES; FOLLOW-UP; PROGRAM; PERFORMANCE;
   GUIDELINES; WOMEN
AB Context Screening mammography differs between the United States and the United Kingdom; a direct comparison may suggest methods to improve the practice.
   Objective To compare screening mammography performance between the United States and the United Kingdom among similar-aged women.
   Design, Setting, and Participants Women aged 50 years or older were identified who underwent 5.5 million mammograms from January 1, 1996, to December 31, 1999, within 3 large-scale mammography registries or screening programs: the Breast Cancer Surveillance Consortium (BCSC, n=978591) and National Breast and Cervical Cancer Early Detection Program (NBCCEDP, n=613388) in the United States; and the National Health Service Breast Screening Program (NHSBSP, n =3.94 million) in the United Kingdom. A total of 27612 women were diagnosed with breast cancer (invasive or ductal carcinoma in situ) within 12 months of screening among the 3 groups.
   Main Outcome Measures Recall rates (recommendation for further evaluation including diagnostic imaging, ultrasound, clinical examination, or biopsy) and cancer detection rates were calculated for first and subsequent mammograms, and within 5-year age groups.
   Results Recall rates were approximately twice as high in the United States than in the United Kingdom for all age groups; however, cancer rates were similar. Among women aged 50 to 54 years who underwent a first screening mammogram, 14.4% in the BCSC and 12.5% in the NBCCEDP were recalled for further evaluation vs only 7.6% in the NHSBSP. Cancer detection rates per 1000 mammogram screens were 5.8, 5.9, and 6.3, in the BCSC, NBCCEDP, and NHSBSP, respectively. Recall rates were lower for subsequent examinations in all 3 settings but remained twice as high in the United States. A similar percentage of women underwent biopsy in each setting, but rates of percutaneous biopsy were lower and open surgical biopsy higher in the United States. Open surgical biopsies not resulting in a diagnosis of cancer (negative biopsies) were twice as high in the United States than in the United Kingdom. Based on a 10-year period of screening 1000 women aged 50 to 59 years, 477, 433, and 175 women in the BCSC, NBCCEDP, and NHSBSP, respectively, would be recalled; and for women aged 60 to 69 years, 396, 334, and 1 33 women, respectively. The estimated cancer detection rates per 1000 women aged 50 to 59 years were 24.5, 23.8, and 19.4, respectively, and for women aged 60 to 69 years, 31.5, 26.6, and 27.9, respectively.
   Conclusions Recall and negative open surgical biopsy rates are twice as high in US settings than in the United Kingdom but cancer detection rates are similar. Efforts to improve US mammographic screening should target lowering the recall rate without reducing the cancer detection rate.
C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94115 USA.
   Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA.
   Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   Univ London, Inst Canc Res, Canc Screening Evaluat Unit, London WC1E 7HU, England.
   NCI, Appl Res Program, NIH, Bethesda, MD 20892 USA.
   Ctr Dis Control & Prevent, Atlanta, GA USA.
   Natl Hlth Serv Breast Screening Program, Sheffield, S Yorkshire, England.
   Warwickshire Solihull & Coventry Breast Screening, Coventry, W Midlands, England.
RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, Dept Radiol, Mt Zion Campus,1600 Divisadero St, San Francisco, CA 94115 USA.
FU NCI NIH HHS [CA86032, U01CA63740, U01CA86076]
NR 46
TC 204
Z9 207
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 22
PY 2003
VL 290
IS 16
BP 2129
EP 2137
DI 10.1001/jama.290.16.2129
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 734CB
UT WOS:000186036700022
PM 14570948
ER

PT J
AU Vasan, RS
   Sullivan, LM
   D'Agostino, RB
   Roubenoff, R
   Harris, T
   Sawyer, DB
   Levy, D
   Wilson, PWF
AF Vasan, RS
   Sullivan, LM
   D'Agostino, RB
   Roubenoff, R
   Harris, T
   Sawyer, DB
   Levy, D
   Wilson, PWF
TI Serum insulin-like growth factor I and risk for heart failure in elderly
   individuals without a previous myocardial infarction: The Framingham
   Heart Study
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID DILATED CARDIOMYOPATHY; BODY-COMPOSITION; TRANSGENIC MICE; WALL STRESS;
   OLDER WOMEN; HYPERTROPHY; HORMONE; OVEREXPRESSION; DISEASE; EPIDEMIOLOGY
AB Background: several experimental investigations have emphasized the favorable effects of insulin-like growth factor I (IGF-1) on left ventricular remodeling, partly through its antiapoptotic effects. Cross-sectional clinical studies have reported that low serum IGF-I levels in patients with heart failure correlate with cachexia and severity of ventricular dysfunction. it is unclear whether low serum IGF-I is a risk factor for heart failure.
   Objective: To prospectively study the association between serum IGF-I level and the incidence of congestive heart failure.
   Design: Community-based, prospective cohort study.
   Setting: Framingham, Massachusetts.
   Participants: 717 elderly individuals (mean age, 78.4 years; 67% women) who did not have myocardial infarction and congestive heart failure at baseline.
   Measurement: Incidence of a first episode of congestive heart failure on follow-up.
   Results: During follow-up (mean, 5.2 years), 56 participants (35 women) developed congestive heart failure. In multivarlable Cox regression models adjusting for established risk factors at baseline, there was a 27% decrease in risk for heart failure for every 1 standard. deviation increment in log IGF-I. Individuals with serum IGF-I level at or above the median value (140 mug/L) had half the risk for heart failure (hazard ratio, 0.49 [95% Cl, 0.26 to 0.92]) of those with serum IGF-I levels below the median. These comparisons were maintained in analyses adjusting for the occurrence of a myocardial infarction on follow-up.
   Conclusions: In our prospective, community-based investigation, serum IGF-I level was inversely related to the risk for congestive heart failure in elderly people without a previous myocardial infarction. Additional investigations are warranted to confirm these findings.
C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
   Boston Univ, Boston, MA 02215 USA.
   Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   NHLBI, Bethesda, MD 20892 USA.
   NIA, Bethesda, MD 20892 USA.
RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
OI Ramachandran, Vasan/0000-0001-7357-5970
FU NHLBI NIH HHS [1K24 HL04334, N01-HC-25195]; NIA NIH HHS [AG15797]; NIDDK
   NIH HHS [DK02120]
NR 38
TC 162
Z9 167
U1 0
U2 5
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD OCT 21
PY 2003
VL 139
IS 8
BP 642
EP 648
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 734DW
UT WOS:000186040800002
PM 14568852
ER

PT J
AU Wood, MJ
   Andrade, EC
   Storz, G
AF Wood, MJ
   Andrade, EC
   Storz, G
TI The redox domain of the Yap1p transcription factor contains two
   disulfide bonds
SO BIOCHEMISTRY
LA English
DT Article
ID COLI ASPARTATE TRANSCARBAMOYLASE; OXIDATIVE STRESS;
   SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; NUCLEAR EXPORT; YEAST-CELLS;
   ACTIVATION; BINDING; GENE; SWITCH
AB The subcellular localization of the Saccharomyces cerevisiae transcription factor Yap1p is regulated by oxidation and reduction. We purified Yap1p from yeast and characterized its properties in vitro. Electrophoretic mobility shift assays showed that the purified protein can specifically bind the TRX2 target promoter. Yap1p was purified under reducing conditions, but removal of reducing agents resulted in the formation of an oxidized Yap I p species with properties similar to in vivo oxidized Yap I p. MALDI-TOF mass spectrometry analysis revealed that the oxidized form of Yap1p contains two disulfide bonds between C303-C598 and C310-C629. A stable domain of similar to15 kDa was detected upon limited proteolysis of oxidized but not reduced Yap1p. This Yap1p protease resistant domain was purified, and MALDI-TOF mass spectrometry analysis showed that it was comprised of two separate cysteine-containing peptides of Yap1p. These peptides are separated by 250 amino acids and are joined by the C303-C598 and C310-C629 disulfide bonds. Taken together, these data suggest that the domain that controls Yap1p subcellular localization is modular and contains a redox center comprised of four cysteine residues.
C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA.
OI Storz, Gisela/0000-0001-6698-1241
NR 36
TC 45
Z9 46
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD OCT 21
PY 2003
VL 42
IS 41
BP 11982
EP 11991
DI 10.1021/bi035003d
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 733NH
UT WOS:000186007000011
PM 14556629
ER

PT J
AU Rajagopalan, S
   Mohler, ER
   Lederman, RJ
   Mendelsohn, FO
   Saucedo, JF
   Goldman, CK
   Blebea, J
   Macko, J
   Kessler, PD
   Rasmussen, HS
   Annex, BH
AF Rajagopalan, S
   Mohler, ER
   Lederman, RJ
   Mendelsohn, FO
   Saucedo, JF
   Goldman, CK
   Blebea, J
   Macko, J
   Kessler, PD
   Rasmussen, HS
   Annex, BH
TI Regional angiogenesis with vascular endothelial growth factor in
   peripheral arterial disease - A phase II randomized, double-blind,
   controlled study of adenoviral delivery of vascular endothelial growth
   factor 121 in patients with disabling intermittent claudication
SO CIRCULATION
LA English
DT Article
DE peripheral vascular disease; angiogenesis; gene therapy; claudication;
   viruses
ID MEDIATED GENE-TRANSFER; WALKING DISTANCES; VEGF121 CDNA; TRIAL; THERAPY;
   CILOSTAZOL; ISCHEMIA; VECTOR; NEOVASCULARIZATION; MULTICENTER
AB Background -"Therapeutic angiogenesis" seeks to improve perfusion by the growth of new blood vessels. The Regional Angiogenesis with Vascular Endothelial growth factor ( RAVE) trial is the first major randomized study of adenoviral vascular endothelial growth factor ( VEGF) gene transfer for the treatment of peripheral artery disease ( PAD).
   Methods and Results - This phase 2, double-blind, placebo-controlled study was designed to test the efficacy and safety of intramuscular delivery of AdVEGF121, a replication-deficient adenovirus encoding the 121-amino-acid isoform of vascular endothelial growth factor, to the lower extremities of subjects with unilateral PAD. In all, 105 subjects with unilateral exercise-limiting intermittent claudication during 2 qualifying treadmill tests, with peak walking time (PWT) between 1 to 10 minutes, were stratified on the basis of diabetic status and randomized to low-dose (4 x 10(9) PU) AdVEGF121, high-dose (4 x 10(10) PU) AdVEGF121, or placebo, administered as 20 intramuscular injections to the index leg in a single session. The primary efficacy end point, change in PWT (DeltaPWT) at 12 weeks, did not differ between the placebo (1.8 +/- 3.2 minutes), low-dose (1.6 +/- 1.9 minutes), and high-dose (1.5 +/- 3.1 minutes) groups. Secondary measures, including DeltaPWT, ankle-brachial index, claudication onset time, and quality-of-life measures (SF-36 and Walking Impairment Questionnaire), were also similar among groups at 12 and 26 weeks. AdVEGF121 administration was associated with increased peripheral edema.
   Conclusions - A single unilateral intramuscular administration of AdVEGF121 was not associated with improved exercise performance or quality of life in this study. This study does not support local delivery of single-dose VEGF(121) as a treatment strategy in patients with unilateral PAD.
C1 Duke Univ, Dept Med, Div Cardiol, Durham, NC 27705 USA.
   Univ Michigan Hlth Syst, Dept Internal Med, Sect Vasc Med, Div Cardiovasc Med, Ann Arbor, MI USA.
   Univ Penn Hlth Syst, Dept Med, Div Cardiovasc Med, Sect Vasc Med, Philadelphia, PA USA.
   NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA.
   Baptist Med Ctr Princeton, Dept Cardiol, Birmingham, AL USA.
   Univ Oklahoma, Med Ctr, Oklahoma City, OK USA.
   Oschner Clin, New Orleans, LA USA.
   Penn State Univ, Temple Univ, Dept Vasc Surg, Philadelphia, PA USA.
   GenVec Inc, Gaithersburg, MD USA.
   Vet Affairs Med Ctr, Durham, NC USA.
RP Rajagopalan, S (reprint author), Duke Univ, Dept Med, Div Cardiol, Durham, NC 27705 USA.
NR 26
TC 324
Z9 347
U1 2
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 21
PY 2003
VL 108
IS 16
BP 1933
EP 1938
DI 10.1161/01.CIR.0000093398.16124.29
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 734KT
UT WOS:000186055600006
PM 14504183
ER

PT J
AU Sadjadi, A
   Malekzadeh, R
   Derakhshan, MH
   Sepehr, A
   Nouraie, M
   Sotoudeh, M
   Yazdanbod, A
   Shokoohi, B
   Mashayekhi, A
   Arshi, S
   Majidpour, A
   Babaei, M
   Mosavi, A
   Mohagheghi, MMA
   Alimohammadian, M
AF Sadjadi, A
   Malekzadeh, R
   Derakhshan, MH
   Sepehr, A
   Nouraie, M
   Sotoudeh, M
   Yazdanbod, A
   Shokoohi, B
   Mashayekhi, A
   Arshi, S
   Majidpour, A
   Babaei, M
   Mosavi, A
   Mohagheghi, MMA
   Alimohammadian, M
TI Cancer occurrence in Ardabil: Results of a population-based cancer
   registry from Iran
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cancer incidence; Ardabil; Iran
ID ESOPHAGEAL CANCER
AB The provincial health authority reported a high mortality rate from upper GI cancer in the newly established Ardabil Province of northwest Iran. A comprehensive search was undertaken to survey and register all cases of cancer during a 4-year (1996-1999) period among the indigenous population of Ardabil Province, including subjects seeking care in the cities of Tabriz and Tehran. Diagnosis of cancer was based on histopathology in 71.4%, clinical or radiologic findings in 25% and death certificate in 3.6% of cases. A total of 3,455 cancers (mean age 57.1 +/- 17.3 years) was found during the study. Of these, 60% (2,072) were in males. ASRs for all cancers in males and females were 132.0 and 96.3, respectively. The top 5 cancers in males (excluding skin cancer) according to the calculated ASR were stomach (25.4), esophagus (15.4), lung and bronchus (7.9), colon and rectum (7.9) and bladder (7.6); in females, these were stomach (25.42), esophagus (14.4), breast (7.6), colon and rectum (5. 9) and lung and bronchus (3.6). Compared to rates obtained 30 years ago, the incidence of upper GI cancer in this region has increased about 100%, and there is a striking increase in the incidence of gastric cancer with a decline in the esophageal cancer rate. ASRs for gastric cancer in Ardabil were 49.1 for males and 25.4 for females, while for esophageal cancer these were 15.4 and 14.4, respectively. The ASR for cervical cancer was the lowest (0.4) recorded in the world before. Gastric cancer alone constitutes one-third of all cancers in Ardabil, the ASR of which is the highest reported from Iran up to now and one of the highest in the world. (C) 2003 Wiley-Liss, Inc.
C1 Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
   NCI, Ctr Canc Res, Canc Prevent Studies Branch, Bethesda, MD 20892 USA.
   Ardabil Univ Med Sci, Ardabil, Iran.
   Univ Tehran Med Sci, Inst Canc, Tehran, Iran.
   Univ Tehran Med Sci, Sch Publ Hlth, Tehran, Iran.
RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, N Kargar Ave, Tehran, Iran.
EM malek@ams.ac.ir
RI Derakhshan, Mohammad/B-2756-2008; Derakhshan, Mohammad/K-8694-2016; 
OI Malekzadeh, Reza/0000-0003-1043-3814
NR 24
TC 124
Z9 127
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD OCT 20
PY 2003
VL 107
IS 1
BP 113
EP 118
DI 10.1002/ijc.11359
PG 6
WC Oncology
SC Oncology
GA 720CQ
UT WOS:000185244300016
PM 12925965
ER

PT J
AU Lee, WJ
   Baris, D
   Jarvholm, B
   Silverman, DT
   Bergdahl, IA
   Blair, A
AF Lee, WJ
   Baris, D
   Jarvholm, B
   Silverman, DT
   Bergdahl, IA
   Blair, A
TI Multiple myeloma and diesel and other occupational exposures in Swedish
   construction workers
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE construction industry; diesel exhaust; multiple myeloma; occupational
   exposure; Sweden
ID SOCIOECONOMIC-STATUS; UNITED-STATES; RISK-FACTORS; CANCER; SWEDEN;
   WHITES; MORTALITY; EXHAUST; SMOKING; BLACKS
AB We examined the relationships between occupational exposures and the risk of multiple myeloma among male construction workers in Sweden. A total of 446 myeloma subjects were identified among 365,424 male workers followed from 1971 to 1999. Occupational exposure was assessed using a semiquantitative job-exposure matrix, based on a survey carried out by the Construction Industry's Organization for Working Environment, Occupational Safety and Health in Sweden. Rate ratios (RRRs) in the exposed groups relative to the unexposed groups were estimated by Poisson regression. We found an increased risk (RR = 1.3, 95% Cl 1.04-1.71) among construction workers exposed to diesel exhaust. Adjustment for other occupational exposures did not change this estimate (RR = 1.3, 95% Cl 1.00-1.77). However, there was no monotonic increase in risk with estimated level of exposure (RR for low = 1.4, moderate = 1.1, high = 1.4). There was no evidence of increased risk associated with the other occupational exposures among these construction workers, including asbestos, asphalt, cement dust, metal dust, mineral wool, organic solvents, stone dust and wood dust. Occupational exposure to diesel exhaust in the Swedish construction industry may present a small risk of multiple myeloma, but lack of an exposure-response trend tempers our ability to draw clear conclusions. (C) 2003 Wiley-Liss, Inc.
C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
   Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
RP Lee, WJ (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8111, Rockville, MD 20852 USA.
OI Bergdahl, Ingvar/0000-0003-1227-6859
NR 44
TC 25
Z9 26
U1 1
U2 3
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD OCT 20
PY 2003
VL 107
IS 1
BP 134
EP 138
DI 10.1002/ijc.11351
PG 5
WC Oncology
SC Oncology
GA 720CQ
UT WOS:000185244300019
PM 12925968
ER

PT J
AU Kitani, A
   Fuss, I
   Nakamura, K
   Kumaki, F
   Usui, T
   Strober, W
AF Kitani, A
   Fuss, I
   Nakamura, K
   Kumaki, F
   Usui, T
   Strober, W
TI Transforming growth factor (TGF)-beta 1-producing regulatory T cells
   induce Smad-mediated interleukin 10 secretion that facilitates
   coordinated immunoregulatory activity and amelioration of TGF-beta
   1-mediated fibrosis
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
DE Th1 cells; trinitrobenzene sulfonic acid; fibrosis; doxycycline;
   transcription
ID INDUCED LUNG FIBROSIS; TGF-BETA; MAMMALIAN-CELLS; TRANSCRIPTIONAL
   ACTIVATION; EXPERIMENTAL COLITIS; RETROVIRAL VECTOR; IMMUNE-RESPONSES;
   GENE-EXPRESSION; DOWN-REGULATION; ORAL TOLERANCE
AB Interleukin (IL)-10 and transforming growth factor (TGF)-betal are suppressor cytokines that frequently occur together during a regulatory T cell response. Here we used a one gene doxycycline (Dox)-inducible plasmid encoding TGF-beta1 to analyze this association and test its utility. In initial studies, we showed that intranasal administration of this plasmid (along with Dox) led to the appearance of TGF-beta1-producing cells (in spleen and lamina propria) and the almost concomitant appearance of IL-10-producing cells. Moreover, we showed that these cells exert Dox-regulated suppression of the T helper cell (Th) 1-mediated inflammation in trinitrobenzene sulfonic acid colitis. In subsequent in vitro studies using retroviral TGF-beta1 expression, we established that IL-10 production by Th1 cells occurs after exposure to TGF-beta1 from either an endogenous or exogenous source. In addition, using a self-inactivating retrovirus luciferase reporter construct we showed that TGF-beta1 induces Smad4, which then binds to and activates the IL-10 promoter. Furthermore, intranasal TGF-beta1 plasmid administration ameliorates bleomycin-induced fibrosis in wild-type but not IL-10-deficient juice, strongly suggesting that the amelioration is IL-10 dependent and that IL-10 protects mice from TGF-beta1-mediated fibrosis. Taken together, these findings suggest that the induction of IL-10 by TGF-beta1 is not fortuitous, but instead fulfills important requirements of TGF-beta1 function after its secretion by regulatory T cells.
C1 Natl Inst Allergy & Infect Dis, Lab Clin Invest, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA.
   Natl Lung Heart & Blood Inst, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Strober, W (reprint author), Natl Inst Allergy & Infect Dis, Lab Clin Invest, Mucosal Immun Sect, NIH, Bldg 10,Rd 11N238,10 Ctr Dr, Bethesda, MD 20892 USA.
NR 48
TC 159
Z9 172
U1 1
U2 5
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD OCT 20
PY 2003
VL 198
IS 8
BP 1179
EP 1188
DI 10.1084/jem.20030917
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 736CQ
UT WOS:000186153400006
PM 14557415
ER

PT J
AU Ambudkar, SV
   Kimchi-Sarfaty, C
   Sauna, ZE
   Gottesman, MM
AF Ambudkar, SV
   Kimchi-Sarfaty, C
   Sauna, ZE
   Gottesman, MM
TI P-glycoprotein: from genomics to mechanism
SO ONCOGENE
LA English
DT Review
DE ABC transporter; multidrug resistance; P-glycoprotein; drug transport;
   ATP hydrolysis; catalytic cycle; polymorphism
ID ATP-BINDING CASSETTE; CAUSE PSEUDOXANTHOMA ELASTICUM;
   MULTIDRUG-RESISTANCE GENE; ACUTE MYELOID-LEUKEMIA; HUMAN MDR1 GENE;
   FAMILIAL INTRAHEPATIC CHOLESTASIS; CATALYTIC TRANSITION-STATE; HEALTHY
   JAPANESE SUBJECTS; SOUTHWEST-ONCOLOGY-GROUP; VIRUS EXPRESSION SYSTEM
AB Resistance to chemically different natural product anticancer drugs ( multidrug resistance, or MDR) results from decreased drug accumulation, resulting from expression of one or more ATP-dependent efflux pumps. The first of these to be identified was P-glycoprotein (P-gp), the product of the human MDR1 gene, localized to chromosome 7q21. P-gp is a member of the large ATP-binding cassette (ABC) family of proteins. Although its crystallographic 3-D structure is yet to be determined, sequence analysis and comparison to other ABC family members suggest a structure consisting of two transmembrane (TM) domains, each with six TM segments, and two nucleotide-binding domains. In the epithelial cells of the gastrointestinal tract, liver, and kidney, and capillaries of the brain, testes, and ovaries, P-gp acts as a barrier to the uptake of xenobiotics, and promotes their excretion in the bile and urine. Polymorphisms in the MDR1 gene may affect the pharmacokinetics of many commonly used drugs, including anticancer drugs. Substrate recognition of many different drugs occurs within the TM domains in multiple-overlapping binding sites. We have proposed a model for how ATP energizes transfer of substrates from these binding sites on P-gp to the outside of the cell, which accounts for the apparent stoichiometry of two ATPs hydrolysed per molecule of drug transported. Understanding of the biology, genetics, and biochemistry of P-gp promises to improve the treatment of cancer and explain the pharmacokinetics of many commonly used drugs.
C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 1A-09, Bethesda, MD 20892 USA.
RI Ambudkar, Suresh/B-5964-2008
NR 183
TC 629
Z9 669
U1 7
U2 63
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 20
PY 2003
VL 22
IS 47
BP 7468
EP 7485
DI 10.1038/sj.onc.1206948
PG 18
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 735KL
UT WOS:000186112500017
PM 14576852
ER

PT J
AU Fojo, T
   Bates, S
AF Fojo, T
   Bates, S
TI Strategies for reversing drug resistance
SO ONCOGENE
LA English
DT Review
DE ABC transporters; p53; apoptosis; methylation; glutathione
ID P53 GENE-TRANSFER; PHASE-I TRIAL; CELL LUNG-CANCER; MEDIATED
   MULTIDRUG-RESISTANCE; ACUTE MYELOGENOUS LEUKEMIA; ACUTE
   MYELOID-LEUKEMIA; HUMAN TUMOR-CELLS; P-GLYCOPROTEIN; ANTISENSE
   OLIGONUCLEOTIDES; BUTHIONINE SULFOXIMINE
AB Drug resistance, intrinsic or acquired, is a problem for all chemotherapeutic agents. In this review, we examine numerous strategies that have been tested or proposed to reverse drug resistance. Included among these strategies are approaches targeting the apoptosis pathway. Although the process of apoptosis is complex, it provides several potential sites for therapeutic intervention. A variety of targets and approaches are being pursued, including the suppression of proteins inhibiting apoptosis using antisense oligonucleotides (ASOs), and small molecules targeted at proteins that modulate apoptosis. An alternate strategy is based on numerous studies that have documented methylation of critical regions in the genome in human cancers. Consequently, efforts have been directed at re-expressing genes, including genes that affect drug sensitivity, using 5-azacytidine and 2'-deoxy-5-azacytidine (DAC, decitabine) as demethylating agents. While this strategy may be effective as a single modality, success will most likely be achieved if it is used to modulate gene expression in combination with other modalities such as chemotherapy. At a more basic level, attempts have been made to modulate glutathione (GSH) levels. Owing to its reactivity and high intracellular concentrations, GSH has been implicated in resistance to several chemotherapeutic agents. Several approaches designed to deplete intracellular GSH levels have been pursued including the use of buthionine-(S, R)-sulfoxime (BSO), a potent and specific inhibitor of gamma-glutamyl cysteine synthetase (gamma-GCS), the rate-limiting step in the synthesis of GSH, a hammerhead ribozyme against gamma-GCS mRNA to downregulate specifically its levels and targeting cJun expression to reduce GSH levels. Alternate strategies have targeted p53. The frequent occurrence of p53 mutations in human cancer has led to the development of numerous approaches to restore wild-type (wt) p53. The goals of these interventions are to either revert the malignant phenotype or enhance drug sensitivity. The approach most extensively investigated has utilized one of several viral vectors. An alternate approach, the use of small molecules to restore wt function to mutant p53, remains an option. Finally, the conceptually simplest mechanism of resistance is one that reduces intracellular drug accumulation. Such reduction can be effected by a variety of drug efflux pumps, of which the most widely studied is P-glycoprotein (Pgp). The first strategy utilized to inhibit Pgp function relied on the identication of nonchemotherapeutic agents as competitors. Other approaches have included the use of hammerhead ribozymes against the MDR-1 gene and MDR-1-targeted ASOs. Although modulation of drug resistance has not yet been proven to be an effective clinical tool, we have learned an enormous amount about drug resistance. Should we succeed, these pioneering basic and clinical studies will have paved the road for future developments.
C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Fojo, T (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 12C103,9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 141
TC 236
Z9 256
U1 3
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 20
PY 2003
VL 22
IS 47
BP 7512
EP 7523
DI 10.1038/sj.onc.1206951
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 735KL
UT WOS:000186112500020
PM 14576855
ER

PT J
AU Shalev, U
   Robarts, P
   Shaham, Y
   Morales, M
AF Shalev, U
   Robarts, P
   Shaham, Y
   Morales, M
TI Selective induction of c-Fos immunoreactivity in the prelimbic cortex
   during reinstatement of heroin seeking induced by acute food deprivation
   in rats
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE extinction; immunohistochemistry; prefrontal cortex; reinstatement;
   relapse; stress
ID CONDITIONED PLACE PREFERENCE; STRESS-INDUCED REINSTATEMENT;
   COCAINE-INDUCED REINSTATEMENT; NUCLEUS-ACCUMBENS; DRUG-SEEKING; STRIA
   TERMINALIS; INDUCED RELAPSE; BED NUCLEUS; CORTICOSTERONE SECRETION;
   INDUCED SENSITIZATION
AB We previously reported that acute 1-day food deprivation reinstates heroin seeking in rats. The goal of the present study was to begin identifying brain sites potentially involved in this effect. For this purpose, we measured, by immunohistochemistry, the expression of c-Fos following a test for food deprivation-induced reinstatement. Groups of rats (n = 9-10 per group) were trained to lever-press for heroin (0.05-0.1 mg/kg/infusion) or saline for 10 days (9 h/day); each infusion was paired with a cue light. Rats were then given 10 days of extinction during which the heroin and saline syringes were removed. Next, a test for reinstatement was conducted after exposure to 0 (baseline) or 1-day food deprivation. During training, lever pressing for heroin increased over days, while responding for saline infusions paired with the cue light decreased over time. During extinction, responding on the heroin-paired lever decreased over time, while responding on the saline-paired lever remained low. In heroin-trained rats, food deprivation induced a large increase in responding on the lever associated with drug infusions. Surprisingly, food deprivation also modestly increased responding in the saline-trained rats. Food deprivation selectively increased c-Fos immunoreactivity (IR) in the prelimbic cortex of heroin-trained, but not saline-trained, rats (n = 4 per condition). Food deprivation also increased c-Fos IR in both heroin- and saline-trained rats in the basolateral amygdala and the ventrolateral bed nucleus of stria terminalis (BNST), but had no effect on c-Fos expression in the dorsolateral BNST, cingulate cortex, nucleus accumbens, and central amygdala. These results raise the possibility that the prelimbic cortex is involved in food deprivation-induced reinstatement of heroin seeking. Published by Elsevier Science B.V.
C1 NIDA, IRP, DHHS, Behav Neurosci Branch,NIH, Baltimore, MD 21224 USA.
RP Shaham, Y (reprint author), NIDA, IRP, DHHS, Behav Neurosci Branch,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM yshaham@intra.nida.nih.gov
RI shaham, yavin/G-1306-2014
NR 81
TC 20
Z9 20
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD OCT 17
PY 2003
VL 145
IS 1-2
BP 79
EP 88
DI 10.1016/S0166-4328(03)00103-7
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 734TD
UT WOS:000186073300009
PM 14529807
ER

PT J
AU Lang, UE
   Lang, F
   Richter, K
   Vallon, V
   Lipp, HP
   Schnermann, J
   Wolfer, DP
AF Lang, UE
   Lang, F
   Richter, K
   Vallon, V
   Lipp, HP
   Schnermann, J
   Wolfer, DP
TI Emotional instability but intact spatial cognition in adenosine receptor
   1 knock out mice
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE adenosine; adenosine receptor; anxiety; memory; behaviour; mice;
   environment
ID A(1) RECEPTOR; ANXIETY; LACKING; BEHAVIOR; ACTIVATION; ANALOGS; MODEL;
   BRAIN; MAZE; GENE
AB Several lines of evidence point to the involvement of adenosine in the regulation of important central mechanisms such as cognition, arousal, aggression and anxiety. In order to elucidate the involvement of the adenosine A1 receptor (A1AR) in spatial learning and the control of exploratory behaviour, we assessed A1AR knockout mice (A1AR-/-) and their wild-type littermates (A1AR+/+) in a place navigation task in the water maze and in a battery of forced and free exploration tests. In the water maze, A1AR-/- mice showed normal escape latencies and were indistinguishable from controls with respect to measures of spatial performance during both training and probe trial. But despite normal performance they showed increased wall hugging, most prominently after the relocation of the goal platform for reversal training. Quantitative analysis of strategy choices indicated that wall hugging was increased mainly at the expense of chaining and passive floating, whereas the frequency of trials characterised as direct swims or focal searching was normal in A1AR-/- mice. These results indicate intact spatial cognition, but mildly altered emotional reactions to the water maze environment. In line with this interpretation, A1AR-/- mice showed normal levels and patterns of activity, but a mild increase of some measures of anxiety in our battery of forced and free exploration paradigms. These results are in line with findings published using a genetically similar line, but demonstrate that the magnitude of the changes and the range of affected behavioural measures may vary considerably depending on the environmental conditions during testing. (C) 2003 Elsevier Science B.V. All rights reserved.
C1 Free Univ Berlin, Dept Psychiat, D-14050 Berlin, Germany.
   Univ Tubingen, Dept Physiol 1, Tubingen, Germany.
   Univ Tubingen, Dept Pharmacol, Tubingen, Germany.
   Univ Zurich, Inst Anat, Zurich, Switzerland.
   Univ Zurich, Ctr Neurosci, Zurich, Switzerland.
   NIDDK, Bethesda, MD USA.
RP Lang, UE (reprint author), Free Univ Berlin, Dept Psychiat, Eschenallee 3, D-14050 Berlin, Germany.
RI Lang, Undine Emmi/K-5553-2015; Wolfer, David/B-3293-2016
OI Lang, Undine Emmi/0000-0002-3585-6533; Wolfer, David/0000-0002-5957-1401
NR 30
TC 40
Z9 42
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD OCT 17
PY 2003
VL 145
IS 1-2
BP 179
EP 188
DI 10.1016/S0166-4328(03)00108-6
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 734TD
UT WOS:000186073300018
PM 14529816
ER

PT J
AU Long, YQ
   Guo, RB
   Luo, JH
   Yang, DJ
   Roller, PP
AF Long, YQ
   Guo, RB
   Luo, JH
   Yang, DJ
   Roller, PP
TI Potentiating effect of distant sites in non-phosphorylated cyclic
   peptide antagonists of the Grb2-SH2 domain
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE non-phosphorylated Grb2-SH2 antagonist; thioether-bridged cyclic
   peptide; hydrophobic residue; sulfoxide linkage; conformational
   constraint; phage library; global optimization; chemotherapeutic agents;
   intracellular signaling; ErbB2-related cancer
ID PHOSPHATE-CONTAINING LIGANDS; STRUCTURE-BASED DESIGN; CANCER-CELLS; SH3
   DOMAINS; INHIBITION; AFFINITY; BINDING; REQUIREMENTS; PROTEINS; ADAPTER
AB Without the presence of a phosphotyrosyl group, a phage library derived non-phosphorylated cyclic peptide ligand of Grb2-SH2 domain attributed its high affinity and specificity to well-defined and highly favored interactions of its structural elements with the binding pocket of the protein. We have disclosed a significant compensatory role of the Glu(2-) sidechain for the absence of the phosphate functionality on Tyr(0) in the peptide ligand, cyclo(CH2CO-Glu(2-)Leu-Tyr(0)-Glu-Asn-Val-Gly-Met(5+)-Tyr-Cys)-amide (termed G1TE). In this study, we report the importance of hydrophobic residue at the Tyr +5 site in G1TE. Both acidic and basic amino acid substitutes arc disfavored at this position, and replacement of Met with P-tert-butyl-Ala was found to improve the antagonist properties. Besides, the polarity of the cyclization linkage was implicated as important in stabilizing the favored binding conformation. Oxidation of the thioether linkage into sulfoxide facilitated the binding to Grb2-SH2 markedly. Simultaneous modification of the three distant sites within G1TE provided the best agent with an IC50 of 220 nM, which is among the most potent non-phosphorous- and non-phosphotyrosine-mimic containing Grb2-SH2 domain inhibitors yet reported. This potent peptidomimetic provides a novel template for the development of chemotherapeutic agents for the treatment of erbB2-related cancer, Biological assays on G1TE(Gla(2-)) in which the original residue of Glu(2-) was substituted by gamma-carboxyglutamic acid (Gla) indicated that it could inhibit the interaction between activated GF receptor and Grb2 protein in cell homogenates of MDA-MB-453 breast cancer cells at the 2 muM level. More significantly, both G1TE(Gla(2-)) alone and the conjugate of GITE(Gla(2-)) with a peptide carrier can effectively inhibit intracellular association of erbB2 and Grb2 in the same cell lines with IC50 of 50 and 2 muM, respectively. (C) 2003 Elsevier Inc. All rights reserved.
C1 Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China.
   Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
   NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA.
RP Long, YQ (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China.
EM yqlong@mail.shcnc.ac.cn; proll@helix.nih.gov
NR 25
TC 11
Z9 11
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 17
PY 2003
VL 310
IS 2
BP 334
EP 340
DI 10.1016/j.bbrc.2003.09.022
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 731UF
UT WOS:000185904300013
PM 14521914
ER

PT J
AU Shi, ZD
   Lee, K
   Liu, HP
   Zhang, MC
   Roberts, LR
   Worthy, KM
   Fivash, MJ
   Fisher, RJ
   Yang, DJ
   Burke, TR
AF Shi, ZD
   Lee, K
   Liu, HP
   Zhang, MC
   Roberts, LR
   Worthy, KM
   Fivash, MJ
   Fisher, RJ
   Yang, DJ
   Burke, TR
TI A novel macrocyclic tetrapeptide mimetic that exhibits low-picomolar
   Grb2 SH2 domain-binding affinity
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
ID TYROSINE KINASE INHIBITORS; PHOSPHATE-CONTAINING LIGANDS;
   STRUCTURE-BASED DESIGN; HUMAN BREAST-CANCER; GROWTH-FACTOR;
   SIGNAL-TRANSDUCTION; BIOSENSOR ANALYSIS; CELL MOTILITY; POTENT;
   ANTAGONISTS
AB The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that participates in the signaling of numerous oncogenic growth factor receptor protein-tyrosine kinases (PTKs). Presented herein is a 5-methylindolyl-containing macrocyclic tetrapeptide mimetic (5) that binds to Grb2 SH2 domain protein with K-d = 75 pM. This represents the highest affinity yet reported for a synthetic inhibitor against any SH2 domain. In whole cell assays this novel analogue is able to effectively block the association of Grb2 to cognate cytoplasmic erbB-2 at IC50 < 10nM without prodrug derivatization or the addition of carrier peptide motifs. Anti-mitogenic effects against erbB-2-dependent breast cancers are achieved at non-cytotoxic concentrations (IC50 = 0.6 muM). Macrocycle 5 may be representative of a new class of therapeutically relevant Grb2 SH2 domain-directed agents. Published by Elsevier Inc.
C1 NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA.
   Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
   SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA.
RI Fisher, Robert/B-1431-2009; Burke, Terrence/N-2601-2014
FU PHS HHS [N01-C0-12400]
NR 46
TC 29
Z9 30
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 17
PY 2003
VL 310
IS 2
BP 378
EP 383
DI 10.1016/j.bbrc.2003.09.029
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 731UF
UT WOS:000185904300020
PM 14521921
ER

PT J
AU Minn, AH
   Patterson, NB
   Pack, S
   Hoffmann, SC
   Gavrilova, O
   Vinson, C
   Harlan, DM
   Shalev, A
AF Minn, AH
   Patterson, NB
   Pack, S
   Hoffmann, SC
   Gavrilova, O
   Vinson, C
   Harlan, DM
   Shalev, A
TI Resistin is expressed in pancreatic islets
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE resistin; islets; beta cell; human pancreas; insulin resistance
ID ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; INSULIN-RESISTANCE;
   GENE-EXPRESSION; PPAR-GAMMA; WHITE FAT; OBESITY; MICE; GENOTYPE;
   VARIANTS
AB Resistin, a recently described adipocyte factor, is regulated by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists. While resistin has been proposed to mediate insulin resistance in rodents, little is known about human resistin and its expression in pancreatic islets has not been tested. The goal of the present Study was therefore to analyze whether resistin, like PPARgamma, is expressed in islets. Human islets from seven donors were analyzed by quantitative RT-PCR revealing resistin expression in all samples. Immunohistochemistry using a resistin-specific antibody on human pancreatic sections localized resistin protein to the islets. Mouse resistin was also detected in the Min6 beta cell line. Interestingly, we found a 4-fold increase in islet resistin expression in insulin resistant A-ZIP transgenic compared to wild-type mice. Our results demonstrate that resistin is expressed in islets and up-regulated in insulin resistance and thereby shed new light on the role of resistin in mice and humans. (C) 2003 Elsevier Inc. All rights reserved.
C1 Univ Wisconsin, Dept Med, Endocrinol Sect, Madison, WI 53792 USA.
   NIDDK, DHHS, NIH, Bethesda, MD 20889 USA.
   NCI, DHHS, NIH, Bethesda, MD 20889 USA.
RP Shalev, A (reprint author), Univ Wisconsin, Dept Med, Endocrinol Sect, Madison, WI 53792 USA.
NR 31
TC 62
Z9 71
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 17
PY 2003
VL 310
IS 2
BP 641
EP 645
DI 10.1016/j.bbrc.2003.09.061
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 731UF
UT WOS:000185904300058
PM 14521959
ER

PT J
AU Calzada, MJ
   Sipes, JM
   Krutzsch, HC
   Yurchenco, PD
   Annis, DS
   Mosher, DF
   Roberts, DD
AF Calzada, MJ
   Sipes, JM
   Krutzsch, HC
   Yurchenco, PD
   Annis, DS
   Mosher, DF
   Roberts, DD
TI Recognition of the N-terminal modules of thrombospondin-1 and
   thrombospondin-2 by alpha(6)beta(1) integrin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEPARAN-SULFATE PROTEOGLYCANS; VEIN ENDOTHELIAL-CELLS; IN-VITRO;
   ALPHA(3)BETA(1) INTEGRIN; PROMOTES ANGIOGENESIS; SYNTHETIC PEPTIDES;
   TYPE-1 REPEATS; BINDING SITES; TUMOR-GROWTH; CYR61 CCN1
AB In addition to its recognition by alpha(3)beta(1) and alpha(4)beta(1) integrins, the N-terminal pentraxin module of thrombospondin-1 is a ligand for alpha(6)beta(1) integrin. alpha(6)beta(1) integrin mediates adhesion of human microvascular endothelial and HT-1080 fibrosarcoma cells to immobilized thrombospondin-1 and recombinant N-terminal regions of thrombospondin-1 and thrombospondin-2. alpha(6)beta(1) also mediates chemotaxis of microvascular cells to thrombospondin-1 and thrombospondin-2. Using synthetic peptides, LALERKDHSG was identified as an alpha(6)beta(1)-binding sequence in thrombospondin-1. This peptide inhibited alpha(6)beta(1)-dependent cell adhesion to thrombospondin-1, thrombospondin-2, and the E8 fragment of murine laminin-1. The Glu residue in this peptide was required for activity, and the corresponding residue (Glu(90)) in the N-terminal module of thrombospondin-1 was required for its recognition by alpha(6)beta(1), but not by alpha(4)beta(1). alpha(6)beta(1) was also expressed in human umbilical vein endothelial cells; but in these cells, only certain agonists could activate the integrin to recognize thrombospondins. Selective activation of alpha(6)beta(1) integrin in microvascular endothelial cells by the anti-beta(1) antibody TS2/16 therefore accounts for their adhesion responses to thrombospondins and explains the distinct functions of alpha(4)beta(1) and alpha(6)beta(1) integrins as thrombospondin receptors in microvascular and large vessel endothelial cells.
C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pathol & Lab Med, Piscataway, NJ 08854 USA.
   Univ Wisconsin, Dept Med, Madison, WI 53706 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA.
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU NIDDK NIH HHS [R01 DK036425]
NR 55
TC 59
Z9 59
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 40679
EP 40687
DI 10.1074/jbc.M302014200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200032
PM 12909644
ER

PT J
AU Rathore, D
   Hrstka, SCL
   Sacci, JB
   De la Vega, P
   Linhardt, RJ
   Kumar, S
   McCutchan, TF
AF Rathore, D
   Hrstka, SCL
   Sacci, JB
   De la Vega, P
   Linhardt, RJ
   Kumar, S
   McCutchan, TF
TI Molecular mechanism of host specificity in Plasmodium falciparum
   infection - Role of circumsporozoite protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN MALARIA PARASITE; SPOROZOITES; HEPARIN; GENE; THROMBOSPONDIN;
   KNOWLESI; VACCINE; DNA; GLYCOSAMINOGLYCANS; MITOCHONDRIAL
AB Plasmodium falciparum sporozoites invade liver cells in humans and set the stage for malaria infection. Circumsporozoite protein ( CSP), a predominant surface antigen on sporozoite surface, has been associated with the binding and invasion of liver cells by the sporozoites. Although CSP across the Plasmodium genus has homology and conserved structural organization, infection of a non-natural host by a species is rare. We investigated the role of CSP in providing the host specificity in P. falciparum infection. CSP from P. falciparum, P. gallinaceum, P. knowlesi, and P. yoelii species representing human, avian, simian, and rodent malaria species were recombinantly expressed, and the proteins were purified to homogeneity. The recombinant proteins were evaluated for their capacity to bind to human liver cell line HepG2 and to prevent P. falciparum sporozoites from invading these cells. The proteins showed significant differences in the binding and sporozoite invasion inhibition activity. Differences among proteins directly correlate with changes in the binding affinity to the sporozoite receptor on liver cells. P. knowlesi CSP (PkCSP) and P. yoelii CSP (PyCSP) had 4,790- and 17,800-fold lower affinity for heparin in comparison to P. falciparum CSP (PfCSP). We suggest that a difference in the binding affinity for the liver cell receptor is a mechanism involved in maintaining the host specificity by the malaria parasite.
C1 NIAID, Growth & Dev Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
   Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA.
   Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
   Univ Iowa, Dept Nat Prod Chem, Iowa City, IA 52242 USA.
   Univ Iowa, Dept Chem, Iowa City, IA 52242 USA.
   Univ Iowa, Dept Chem & Biochem Engn, Iowa City, IA 52242 USA.
   Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA.
   US FDA, Bacterial & Parasit Dis Sect, Div Emerging TRansfus & Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
RP McCutchan, TF (reprint author), NIAID, Growth & Dev Sect, Lab Malaria & Vector Res, NIH, Rm 126,Bldg 4,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA.
NR 33
TC 32
Z9 35
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 40905
EP 40910
DI 10.1074/jbc.M306250200
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200061
PM 12904297
ER

PT J
AU Chao, C
   Hergenhahn, M
   Kaeser, MD
   Wu, ZQ
   Saito, S
   Iggo, R
   Hollstein, M
   Appella, E
   Xu, Y
AF Chao, C
   Hergenhahn, M
   Kaeser, MD
   Wu, ZQ
   Saito, S
   Iggo, R
   Hollstein, M
   Appella, E
   Xu, Y
TI Cell type- and promoter-specific roles of Ser(18) phosphorylation in
   regulating p53 responses
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DAMAGE-INDUCED PHOSPHORYLATION; DNA-DAMAGE; IN-VIVO; APOPTOSIS; MDM2;
   RECRUITMENT; DEGRADATION; EXPRESSION; SERINE-15; PATHWAYS
AB Phosphorylation of mouse p53 at Ser(18) occurs after DNA damage. To determine the physiological roles of this phosphorylation event in p53-dependent DNA damage responses, a Ser(18) to Ala missense mutation was introduced into the germline of mice. Thymocytes and fibroblasts from the knock-in mice show reduced transactivation of many p53 target genes following DNA damage. p53 protein stabilization and DNA binding are similar in knock-in and wild type mice, but C-terminal acetylation was defective, consistent with a role for Ser(18) in the recruitment of transcriptional co-activators. The apoptotic response of knock-in thymocytes to ionizing radiation is intermediate between that of wild type and p53 null thymocytes. Despite impaired transcriptional and apoptotic responses, the knock-in mice are not prone to spontaneous tumorigenesis. This indicates that neither phosphorylation of p53 on Ser(18) by ATM nor a full transcriptional response is essential to prevent spontaneous tumor formation in mice.
C1 Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
   Deutsch Krebsforschungszentrum, Dept Genet Alterat Carcinogenesis, D-69120 Heidelberg, Germany.
   Swiss Inst Expt Canc Res, Oncogene Grp, CH-1066 Epalinges, Switzerland.
   NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Xu, Y (reprint author), Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, 9500 Gilman Dr, La Jolla, CA 92093 USA.
RI Iggo, Richard/G-3546-2014
FU NCI NIH HHS [CA94254]
NR 30
TC 95
Z9 96
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 41028
EP 41033
DI 10.1074/jbc.M306938200
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200077
PM 12909629
ER

PT J
AU Smith, JL
   Collins, I
   Chandramouli, GVR
   Butscher, WG
   Zaitseva, E
   Freebern, WJ
   Haggerty, CM
   Doseeva, V
   Gardner, K
AF Smith, JL
   Collins, I
   Chandramouli, GVR
   Butscher, WG
   Zaitseva, E
   Freebern, WJ
   Haggerty, CM
   Doseeva, V
   Gardner, K
TI Targeting combinatorial transcriptional complex assembly at specific
   modules within the interleukin-2 promoter by the immunosuppressant
   SB203580
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; ELEMENT-BINDING PROTEIN; T-CELL
   ACTIVATION; P38 MAP KINASE; IL-2 GENE-EXPRESSION; C-REL;
   LYMPHOCYTE-PROLIFERATION; SELECTIVE-INHIBITION; HISTONE DEACETYLASE
AB The proximal promoter sequence of the interleukin-2 (IL-2) gene contains a series of composite sites or modules that controls much of its responsiveness to environmental stimuli. The integrated targeting of these modules is therefore a major mode of regulation. This report describes how multiple functional hierarchies, required for the recruitment of the p300 co-activator to the CD28RE/AP1 (TRE) module of the IL-2 promoter, are selectively disrupted in human T-cells by the immunosuppressive and anti-inflammatory actions of the p38 mitogen-activated protein kinase inhibitor ( MAPK), SB203580. The molecular hierarchies targeted by SB203580 include the combinatorial interaction of NF-kappaB and CREB at the CD28RE/AP1 element coupled with the subsequent dynamic co-assembly and activation of p300. Several aspects of this targeting are linked to the ability of SB203580 to inhibit p38 MAPK-controlled pathways. Together, these results provide the molecular basis through which the combinatorial structure and context of the composite elements of the IL-2 promoter dictates mitogen responsiveness and drug susceptibility that are quantitatively and qualitatively distinct from the isolated action of single consensus sequences and/or transcriptional motifs.
C1 NCI, Ctr Adv Technol, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Gardner, K (reprint author), NCI, Ctr Adv Technol, Lab Receptor Biol & Gene Express, NIH, Rm 134C,8717 Grovemont Circle, Bethesda, MD 20892 USA.
NR 86
TC 18
Z9 18
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 41034
EP 41046
DI 10.1074/jbc.M305615200
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200078
PM 12896977
ER

PT J
AU Driscoll, HC
   Matson, SW
   Sayer, JM
   Kroth, H
   Jerina, DM
   Brosh, RM
AF Driscoll, HC
   Matson, SW
   Sayer, JM
   Kroth, H
   Jerina, DM
   Brosh, RM
TI Inhibition of Werner syndrome helicase activity by benzo[c]phenanthrene
   diol epoxide dA adducts in DNA is both strand- and
   stereoisomer-dependent
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID POLYCYCLIC AROMATIC-HYDROCARBONS; SYNDROME PROTEIN; SYNDROME CELLS;
   ESCHERICHIA-COLI; BIOCHEMICAL-CHARACTERIZATION; HOMOLOGOUS
   RECOMBINATION; SACCHAROMYCES-CEREVISIAE; DEOXYADENOSINE ADDUCTS;
   SUBSTRATE-SPECIFICITY; SOLUTION CONFORMATION
AB Helicases are among the first enzymes to encounter DNA damage during DNA processing within the cell and thus are likely to be targets for the adverse effects of DNA lesions induced by environmental chemicals. Here we examined the effect of cis- and trans-opened 3,4-diol 1,2-epoxide (DE) DNA adducts of benzo[c] phenanthrene (BcPh) at N-6 of adenine on helicase activity. These adducts are derived from the highly tumorigenic (-)( 1R, 2S, 3S, 4R)- DE as well as its less carcinogenic (+)( 1S, 2R, 3R, 4S)-DE enantiomer in both of which the benzylic 4-hydroxyl group and epoxide oxygen are trans. The hydrocarbon portions of these adducts intercalate into DNA on the 3' or the 5' side of the adducted deoxyadenosine for the 1S- and 1R-adducts, respectively. These adducts inhibited the human Werner (WRN) syndrome helicase activity in a strand-specific and stereospecific manner. In the strand along which WRN translocates, cis- opened adducts were significantly more effective inhibitors than trans-opened isomers, indicating that WRN unwinding is sensitive to adduct stereochemistry. WRN helicase activity was also inhibited but to a lesser extent by cis- opened BcPh DE adducts in the displaced strand independent of their direction of intercalation, whereas inhibition by the trans-opened stereoisomers in the displaced strand depended on their orientation, such that only adducts oriented toward the advancing helicase inhibited WRN activity. A BcPh DE adduct positioned in the helicase-translocating strand did not sequester WRN, nor affect the rate of ATP hydrolysis relative to an unadducted control. Although the Bloom (BLM) syndrome helicase was also inhibited by a cis- opened adduct in a strand-specific manner, this helicase was not as severely affected as WRN. Because BcPh DEs form substantial amounts of deoxyadenosine adducts at dA, their adverse effects on helicases could contribute to genetic damage and cell transformation induced by these DEs. Thus, the unwinding activity of RecQ helicases is sensitive to the strand, orientation, and stereochemistry of intercalated polycyclic aromatic hydrocarbon adducts.
C1 NIA, Lab Mol Gerontol, NIH, DHHS, Baltimore, MD 21224 USA.
   Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Program Mol & Cellular Biophys, Chapel Hill, NC 27599 USA.
   NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, DHHS, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
NR 66
TC 13
Z9 13
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 41126
EP 41135
DI 10.1074/jbc.M304798200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200088
PM 12881525
ER

PT J
AU Das, S
   Gerwin, C
   Sheng, ZH
AF Das, S
   Gerwin, C
   Sheng, ZH
TI Syntaphilin binds to dynamin-1 and inhibits dynamin-dependent
   endocytosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CLATHRIN-MEDIATED ENDOCYTOSIS; VESICLE FORMATION; MEMBRANE; RELEASE;
   DOMAIN; AMPHIPHYSIN; EXOCYTOSIS; EXPRESSION; SYNAPSES; CELLS
AB Syntaphilin is a brain-specific syntaxin-binding partner first characterized as an inhibitor of SNARE complex formation and neurotransmitter release. Here we show that syntaphilin also binds to dynamin-1 and through this interaction inhibits dynamin-mediated endocytosis. Immunoprecipitation studies from crosslinked rat synaptosomes demonstrate that an endogenous syntaphilin-dynamin-1 complex exists independently of dynamin-1 binding to amphiphysin. Functionally, syntaphilin expression inhibits transferrin internalization in COS-7 cells. These data reveal that syntaphilin is an inhibitor of both SNARE-based fusion and dynamin-mediated endocytosis.
C1 NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA.
NR 28
TC 9
Z9 9
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 41221
EP 41226
DI 10.1074/jbc.M304851200
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200100
PM 12896979
ER

PT J
AU Tuli, R
   Tuli, S
   Nandi, S
   Huang, XX
   Manner, PA
   Hozack, WJ
   Danielson, KG
   Hall, DJ
   Tuan, RS
AF Tuli, R
   Tuli, S
   Nandi, S
   Huang, XX
   Manner, PA
   Hozack, WJ
   Danielson, KG
   Hall, DJ
   Tuan, RS
TI Transforming growth factor-beta-mediated chondrogenesis of human
   mesenchymal progenitor cells involves N-cadherin and mitogenactivated
   protein kinase and Wnt signaling cross-talk
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN TRABECULAR BONE; HUMAN ADIPOSE-TISSUE; CHICK LIMB BUD; STEM-CELLS;
   IN-VITRO; MORPHOGENETIC PROTEIN-2; GENE-EXPRESSION; ATDC5 CELLS;
   DIFFERENTIATION; MARROW
AB The multilineage differentiation potential of adult tissue-derived mesenchymal progenitor cells (MPCs), such as those from bone marrow and trabecular bone, makes them a useful model to investigate mechanisms regulating tissue development and regeneration, such as cartilage. Treatment with transforming growth factor-beta( TGF-beta) superfamily members is a key requirement for the in vitro chondrogenic differentiation of MPCs. Intracellular signaling cascades, particularly those involving the mitogen-activated protein ( MAP) kinases, p38, ERK-1, and JNK, have been shown to be activated by TGF-betas in promoting cartilage-specific gene expression. MPC chondrogenesis in vitro also requires high cell seeding density, reminiscent of the cellular condensation requirements for embryonic mesenchymal chondrogenesis, suggesting common chondro-regulatory mechanisms. Prompted by recent findings of the crucial role of the cell adhesion protein, N-cadherin, and Wnt signaling in condensation and chondrogenesis, we have examined here their involvement, as well as MAP kinase signaling, in TGF-beta1-induced chondrogenesis of trabecular bone-derived MPCs. Our results showed that TGF-beta1 treatment initiates and maintains chondrogenesis of MPCs through the differential chondro-stimulatory activities of p38, ERK-1, and to a lesser extent, JNK. This regulation of MPC chondrogenic differentiation by the MAP kinases involves the modulation of N-cadherin expression levels, thereby likely controlling condensation-like cell-cell interaction and progression to chondrogenic differentiation, by the sequential up-regulation and progressive down-regulation of N-cadherin. TGF-beta1-mediated MAP kinase activation also controls WNT-7A gene expression and Wnt-mediated signaling through the intracellular beta-catenin-TCF pathway, which likely regulates N-cadherin expression and subsequent N-cadherin-mediated cell-adhesion complexes during the early steps of MPC chondrogenesis.
C1 NIAMS, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA.
   George Washington Univ, Dept Orthopaed Surg, Washington, DC 20037 USA.
RP Tuan, RS (reprint author), NIAMS, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bldg 50,Rm 1503,50 South Dr,MSC 8022, Bethesda, MD 20892 USA.
NR 54
TC 265
Z9 290
U1 4
U2 40
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 41227
EP 41236
DI 10.1074/jbc.M305312200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200101
PM 12893825
ER

PT J
AU Steinert, PM
   Parry, DAD
   Marekov, LN
AF Steinert, PM
   Parry, DAD
   Marekov, LN
TI Trichohyalin mechanically strengthens the hair follicle - Multiple
   cross-bridging roles in the inner root sheath
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CORNIFIED CELL-ENVELOPE; KERATIN INTERMEDIATE-FILAMENTS; EPITHELIAL
   BARRIER FUNCTION; PROLINE-RICH PROTEINS; PEPTIDYLARGININE DEIMINASE;
   STRUCTURAL FEATURES; HUMAN EPIDERMIS; GENE FAMILY; HUMAN SKIN;
   TRANSGLUTAMINASES
AB Trichohyalin is expressed in specialized epithelia that are unusually mechanically strong, such as the inner root sheath cells of the hair follicle. We have previously shown that trichohyalin is sequentially subjected to post-synthetic modifications by peptidylarginine deaminases, which convert many of its arginines to citrullines, and by transglutaminases, which introduce intra- and interprotein chain cross-links. Here we have characterized in detail the proteins to which it becomes crosslinked in vivo in the inner root sheath of the mouse hair follicle. We suggest that it has three principal roles. First, it serves as an interfilamentous matrix protein by becoming cross-linked both to itself and to the head and tail end domains of the inner root sheath keratin intermediate filament chains. A new antibody reveals that arginines of the tail domains of the keratins are modified to citrullines before cross-linking, which clarifies previous studies. Second, trichohyalin serves as a cross-bridging reinforcement protein of the cornified cell envelope of the inner root sheath cells by becoming crosslinked to several known or novel barrier proteins, including involucrin, small proline-rich proteins, repetin, and epiplakin. Third, it coordinates linkage between the keratin filaments and cell envelope to form a seamless continuum. Together, our new data document that trichohyalin is a multi-functional cross-bridging protein that functions in the inner root sheath and perhaps in other specialized epithelial tissues by conferring to and coordinating mechanical strength between their peripheral cell envelope barrier structures and their cytoplasmic keratin filament networks.
C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA.
   Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand.
RP Marekov, LN (reprint author), NIAMS, Skin Biol Lab, NIH, Bldt 50,Rm 1531, Bethesda, MD 20892 USA.
NR 60
TC 60
Z9 61
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 17
PY 2003
VL 278
IS 42
BP 41409
EP 41419
DI 10.1074/jbc.M302037200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 730TX
UT WOS:000185847200121
PM 12853460
ER

PT J
AU Jager, W
   Gehring, E
   Hagenauer, B
   Aust, S
   Senderowicz, A
   Thalhammer, T
AF Jager, W
   Gehring, E
   Hagenauer, B
   Aust, S
   Senderowicz, A
   Thalhammer, T
TI Biliary excretion of flavopiridol and its glucuronides in the isolated
   perfused rat liver: role of multidrug resistance protein 2 (Mrp2)
SO LIFE SCIENCES
LA English
DT Article
DE flavopiridol; metabolism; isolated perfused rat liver; Mrp2; bilirubin
ID DEPENDENT KINASE INHIBITOR; BREAST-CARCINOMA CELLS; ACTIVITY IN-VIVO;
   CONJUGATED HYPERBILIRUBINEMIA; HEPATOBILIARY TRANSPORT; UP-REGULATION;
   MUTANT RATS; METABOLISM; CANCER; APOPTOSIS
AB Flavopiridol (FLAP) is a novel anticancer agent that is extensively glucuronidated in patients. Biliary excretion is the main elimination pathway of FLAP conjugates responsible for enterohepatic recirculation and for the main side effect diarrhea. To investigate the hepatic transport system for FLAP glucuronides, livers of Wistar and Mrp2-deficient TR- rats were perfused with FLAP (30 muM) in a single pass system. Biliary excretion and efflux into perfusate during a 60 min period greatly differ in TR- rats. While cumulative biliary excretion of M1 and M2 was significantly reduced to 4.3% and 5.4% efflux into perfusate was increased by 1.5 and 4.2-fold. This indicates that in control rats, M1 and M2 are almost exclusively eliminated into bile by Mrp2. Cumulative FLAP secretion into bile and perfusate, however, was non-significantly reduced by 36.7% and 43.2% in the mutant rat strain, suggesting that besides Mrp2, other transporters might also be involved in FLAP elimination. FLAP stimulates bile flow up to 24% in control rats, but secretion is nearly absent in TR- rats further supporting an efficient transport of FLAP glucuronides by Mrp2. FLAP (30 muM) also reversibly inhibited the Mrp2-mediated biliary elimination of bilirubin and bromsulphthalein in Wistar rats by 54% and 51%, respectively, indicating a competition with the elimination of Mrp2-specific substrates. In summary, we found that FLAP glucuronides are substrates of Mrp2 effectively inhibiting the biliary excretion of bilirubin. This may explain the increased serum bilirubin levels observed in cancer patients during FLAP therapy. (C) 2003 Elsevier Inc. All rights reserved.
C1 Univ Vienna, Inst Pharmaceut Chem, A-1090 Vienna, Austria.
   Univ Vienna, Dept Pathophysiol, A-1090 Vienna, Austria.
   Natl Inst Dent & Craniofacial Res, Mol Therapeut Unit, Oral & Pharyngeal Canc Branch, Bethesda, MD USA.
RP Jager, W (reprint author), Univ Vienna, Inst Pharmaceut Chem, Althanstr 14, A-1090 Vienna, Austria.
RI Jager, Walter/I-6242-2013
OI Jager, Walter/0000-0002-4970-8179
NR 33
TC 34
Z9 35
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0024-3205
J9 LIFE SCI
JI Life Sci.
PD OCT 17
PY 2003
VL 73
IS 22
BP 2841
EP 2854
DI 10.1016/S0024-3205(03)00699-4
PG 14
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 727BW
UT WOS:000185637000006
PM 14511769
ER

PT J
AU Varmus, H
   Klausner, R
   Zerhouni, E
   Acharya, T
   Daar, AS
   Singer, PA
AF Varmus, H
   Klausner, R
   Zerhouni, E
   Acharya, T
   Daar, AS
   Singer, PA
TI Grand challenges in global health
SO SCIENCE
LA English
DT Editorial Material
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
   NIH, Bethesda, MD 20892 USA.
   BMGF, Global Hlth Program, Seattle, WA 98102 USA.
   Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5G 1L4, Canada.
RP Varmus, H (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
NR 2
TC 134
Z9 137
U1 1
U2 9
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 17
PY 2003
VL 302
IS 5644
BP 398
EP 399
DI 10.1126/science.1091769
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732UD
UT WOS:000185963200025
PM 14563993
ER

PT J
AU Hacein-Bey-Abina, S
   Von Kalle, C
   Schmidt, M
   McCcormack, MP
   Wulffraat, N
   Leboulch, P
   Lim, A
   Osborne, CS
   Pawliuk, R
   Morillon, E
   Sorensen, R
   Forster, A
   Fraser, P
   Cohen, JI
   de Saint Basile, G
   Alexander, I
   Wintergerst, U
   Frebourg, T
   Aurias, A
   Stoppa-Lyonnet, D
   Romana, S
   Radford-Weiss, I
   Gross, F
   Valensi, F
   Delabesse, E
   Macintyre, E
   Sigaux, F
   Soulier, J
   Leiva, LE
   Wissler, M
   Prinz, C
   Rabbitts, TH
   Le Deist, F
   Fischer, A
   Cavazzana-Calvo, M
AF Hacein-Bey-Abina, S
   Von Kalle, C
   Schmidt, M
   McCcormack, MP
   Wulffraat, N
   Leboulch, P
   Lim, A
   Osborne, CS
   Pawliuk, R
   Morillon, E
   Sorensen, R
   Forster, A
   Fraser, P
   Cohen, JI
   de Saint Basile, G
   Alexander, I
   Wintergerst, U
   Frebourg, T
   Aurias, A
   Stoppa-Lyonnet, D
   Romana, S
   Radford-Weiss, I
   Gross, F
   Valensi, F
   Delabesse, E
   Macintyre, E
   Sigaux, F
   Soulier, J
   Leiva, LE
   Wissler, M
   Prinz, C
   Rabbitts, TH
   Le Deist, F
   Fischer, A
   Cavazzana-Calvo, M
TI LMO2-associated clonal T cell proliferation in two patients after gene
   therapy for SCID-X1
SO SCIENCE
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; NONHUMAN-PRIMATES; TRANSGENIC MICE;
   PROTEIN RBTN2; HUMAN GENOME; GAMMA-CHAIN; LEUKEMIA; TRANSLOCATIONS;
   LYMPHOCYTES; DELTA
AB We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gammac) deficiency] in 9 out of 10 patients by retrovirus-mediated gammac gene transfer into autologous CD34 bone marrow cells. However, almost 3 years after gene therapy, uncontrolled exponential clonal proliferation of mature T cells (with gammadelta+ or alphabeta+ T cell receptors) has occurred in the two youngest patients. Both patients' clones showed retrovirus vector integration in proximity to the LMO2 proto-oncogene promoter, leading to aberrant transcription and expression of LMO2. Thus, retrovirus vector insertion can trigger deregulated premalignant cell proliferation with unexpected frequency, most likely driven by retrovirus enhancer activity on the LMO2 gene promoter.
C1 INSERM, U429, F-75743 Paris 15, France.
   Assistance Publ Hop Paris, Dept Biotherapie, F-75743 Paris, France.
   Univ Paris 05, Lab Cytogenet, F-75743 Paris 15, France.
   Univ Paris 05, Lab Cent Hematol, F-75743 Paris 15, France.
   Univ Paris 05, CNRS, Unite Rech Associee 1461, F-75743 Paris 15, France.
   Hop Necker Enfants Malad, Unite Immunol & Hematol Pediat, F-75743 Paris 15, France.
   Univ Freiburg, Inst Mol Med & Cell Res, Freiburg, Germany.
   Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA.
   MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
   Univ Med Ctr Utrecht, Wilhelmina Kinderziekenhuis, Utrecht, Netherlands.
   Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   INSERM, U277, F-75730 Paris, France.
   Babraham Inst, Lab Chromatin & Gene Express, Dev Genet Programme, Cambridge CB2 4AT, England.
   Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70112 USA.
   Childrens Hosp, New Orleans, LA 70112 USA.
   NIAID, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA.
   Childrens Hosp Westmead, Sydney, NSW 2145, Australia.
   Univ & Childrens Hosp, D-80337 Munich, Germany.
   CHU, Serv Genet, F-76183 Rouen, France.
   Fac Med & Pharm, INSERM 9906, Equipe Mixte, F-76183 Rouen, France.
   Inst Curie, INSERM, U434, Paris 15, France.
   Inst Curie, Dept Oncol Genet, Paris 15, France.
   Hop St Louis, INSERM, U462, Paris, France.
RP Fischer, A (reprint author), INSERM, U429, F-75743 Paris 15, France.
RI Fraser, Peter/B-7549-2009; 
OI Fraser, Peter/0000-0002-0041-1227; DELABESSE, Eric/0000-0002-0928-0753
NR 38
TC 2010
Z9 2107
U1 17
U2 166
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 17
PY 2003
VL 302
IS 5644
BP 415
EP 419
DI 10.1126/science.1088547
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732UD
UT WOS:000185963200033
PM 14564000
ER

PT J
AU Xu, JH
   Shen, XH
   Knutson, JR
AF Xu, JH
   Shen, XH
   Knutson, JR
TI Femtosecond fluorescence upconversion study of the rotations of perylene
   and tetracene in hexadecane
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID LIPID BILAYERS; N-ALKANES; RELAXATION DYNAMICS; BOUNDARY-CONDITION;
   ANISOTROPY DECAY; DIFFUSION; SOLVENT; REORIENTATION; FLUOROMETRY;
   TRYPTOPHAN
AB The rotational relaxation of perylene and tetracene in hexadecane has been studied at several temperatures by femtosecond fluorescence upconversion. The initial emission anisotropy values of both D-2h symmetric fluorophores are now found to be very close to the theoretical value of 0.4, and the anisotropy decay observed with subpicosecond time resolution can no longer be described as a biexponential. The traditional in-plane and out-of-plane rotational diffusion time constants of perylene in hexadecane are verified to be linearly dependent on viscosity/temperature. Moreover, a third, ultrafast rotation, empirically fit to a time constant of similar to450 fs for perylene and similar to600 fs for tetracene, has been found. It is independent of temperature and viscosity, and the amplitude ("beta(fast)") explains the previously described "r(0) defect". Since beta(fast) is similar to0.03 for tetracene vs similar to0.05 for perylene, we presently suggest that "in-plane" femtosecond libration of the molecules within a solvent pocket yields the observed anisotropy.
C1 NHLBI, Biophys Chem Lab, Opt Spectroscopy Sect, NIH, Bethesda, MD 20892 USA.
RP Knutson, JR (reprint author), NHLBI, Biophys Chem Lab, Opt Spectroscopy Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 29
TC 18
Z9 18
U1 5
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1089-5639
J9 J PHYS CHEM A
JI J. Phys. Chem. A
PD OCT 16
PY 2003
VL 107
IS 41
BP 8383
EP 8387
DI 10.1021/jp030113f
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 730YH
UT WOS:000185857400003
ER

PT J
AU Caughey, B
   Kocisko, DA
AF Caughey, B
   Kocisko, DA
TI Prion diseases - A nucleic-acid accomplice?
SO NATURE
LA English
DT Editorial Material
ID CELL-FREE FORMATION; PROTEIN; SCRAPIE
C1 NIAID, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Caughey, B (reprint author), NIAID, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA.
NR 12
TC 23
Z9 26
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 16
PY 2003
VL 425
IS 6959
BP 673
EP 674
DI 10.1038/425673a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 732DA
UT WOS:000185924500025
PM 14562085
ER

PT J
AU Wellems, TE
   Miller, LH
AF Wellems, TE
   Miller, LH
TI Two worlds of malaria
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 NIAID, Bethesda, MD 20892 USA.
RP Wellems, TE (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 37
Z9 39
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 16
PY 2003
VL 349
IS 16
BP 1496
EP 1498
DI 10.1056/NEJMp038127
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 731ZM
UT WOS:000185916400002
PM 14561790
ER

PT J
AU Arbuckle, MR
   McClain, MT
   Rubertone, MV
   Scofield, RH
   Dennis, GJ
   James, JA
   Harley, JB
AF Arbuckle, MR
   McClain, MT
   Rubertone, MV
   Scofield, RH
   Dennis, GJ
   James, JA
   Harley, JB
TI Development of autoantibodies before the clinical onset of systemic
   lupus erythematosus
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTI-DNA ANTIBODIES; CONGENITAL HEART-BLOCK; SJOGRENS-SYNDROME; WILCOXON
   TEST; SM; DSDNA; ANTINUCLEAR; MOTHERS; AUTOIMMUNITY; CHILDREN
AB BACKGROUND:
   Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis.
   METHODS:
   The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls.
   RESULTS:
   In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti-double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 percent, anti-nuclear ribonucleoprotein antibodies in 26 percent, and antiphospholipid antibodies in 18 percent. Antinuclear, antiphospholipid antibodies, anti-Ro, and anti-La antibodies were present earlier than anti-Sm and anti-nuclear ribonucleoprotein antibodies (a mean of 3.4 years before the diagnosis vs. 1.2 years, P=0.005). Anti-double-stranded DNA antibodies, with a mean onset 2.2 years before the diagnosis, were found later than antinuclear antibodies (P=0.06) and earlier than anti-nuclear ribonucleoprotein antibodies (P=0.005). For many patients, the earliest available serum sample was positive; therefore, these measures of the average time from the first positive antibody test to the diagnosis are underestimates of the time from the development of antibodies to the diagnosis. Of the 130 initial matched controls, 3.8 percent were positive for one or more autoantibodies.
   CONCLUSIONS:
   Autoantibodies are typically present many years before the diagnosis of SLE. Furthermore, the appearance of autoantibodies in patients with SLE tends to follow a predictable course, with a progressive accumulation of specific autoantibodies before the onset of SLE, while patients are still asymptomatic.
C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA.
   Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
   Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
   Dept Vet Affairs, Oklahoma City, OK USA.
   Walter Reed Army Med Ctr, Dept Rheumatol, Bethesda, MD USA.
   NIAMSD, NIH, Bethesda, MD 20892 USA.
   USA, Ctr Hlth Promot & Prevent Med, Washington, DC 20310 USA.
RP James, JA (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
FU NCRR NIH HHS [RR14467, RR15577]; NIAID NIH HHS [AI24717, AI31584]; NIAMS
   NIH HHS [AR01981, AR42460, AR45084, AR45231, AR48940, AR4904]
NR 32
TC 1083
Z9 1139
U1 12
U2 43
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 16
PY 2003
VL 349
IS 16
BP 1526
EP 1533
DI 10.1056/NEJMoa021933
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 731ZM
UT WOS:000185916400007
PM 14561795
ER

PT J
AU de Silanes, IL
   Fan, JS
   Yang, XL
   Zonderman, AB
   Potapova, O
   Pizer, ES
   Gorospe, M
AF de Silanes, IL
   Fan, JS
   Yang, XL
   Zonderman, AB
   Potapova, O
   Pizer, ES
   Gorospe, M
TI Role of the RNA-binding protein HuR in colon carcinogenesis
SO ONCOGENE
LA English
DT Article
DE HuR; ELAV; colon cancer; mRNA turnover; carcinogenesis
ID FACTOR MESSENGER-RNAS; STABILITY FACTOR; GENE-EXPRESSION; EFFECTS
   MODELS; CDNA ARRAYS; UV-LIGHT; IN-VIVO; CANCER; RICH; STABILIZATION
AB Immunohistochemical analysis of paired tumor and normal tissue specimens revealed that the expression and cytoplasmic abundance of the RNA-binding protein HuR increased with malignancy, particularly in colon carcinomas. Interventions to modulate HuR expression in human RKO colon cancer cells altered gene expression profiles and identified beta-catenin mRNA as a novel HuR target. Subcutaneous injection of HuR-overexpressing RKO cells into nude mice produced signfiicantly larger tumors than those arising from control populations; conversely, RKO cells expressing reduced HuR through small interference RNA- or antisense HuR-based approaches developed significantly more slowly. We propose that HuR-regulated target mRNA expression contributes to colon cancer growth. Our results suggest a pivotal function for HuR in colon carcinogenesis.
C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   SUGEN Inc, Preclin Res & Translat Med, San Francisco, CA 94080 USA.
   Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
RI Lopez de Silanes, Isabel/K-4962-2015; 
OI Lopez de Silanes, Isabel/0000-0001-6762-9792; Zonderman, Alan
   B/0000-0002-6523-4778
NR 36
TC 139
Z9 143
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 16
PY 2003
VL 22
IS 46
BP 7146
EP 7154
DI 10.1038/sj.onc.1206862
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 732PP
UT WOS:000185955000006
ER

PT J
AU Rangel, LBA
   Sherman-Baust, CA
   Wernyj, RP
   Schwartz, DR
   Cho, KR
   Morin, PJ
AF Rangel, LBA
   Sherman-Baust, CA
   Wernyj, RP
   Schwartz, DR
   Cho, KR
   Morin, PJ
TI Characterization of novel human ovarian cancer-specific transcripts
   (HOSTs) identified by serial analysis of gene expression
SO ONCOGENE
LA English
DT Article
DE ovarian cancer; biomarkers; HOST; gene expression; SAGE
ID EPITHELIAL-CELLS; MESSENGER-RNA; TUMOR; OVEREXPRESSION; CARCINOMA;
   STAGE; H19; COTRANSPORTER; CYSTADENOMAS; PATTERNS
AB A better understanding of changes in gene expression during ovarian tumorigenesis and the identification of specific tumor markers may lead to novel strategies for diagnosis and therapy for this disease. Using our serial analysis of gene expression ( SAGE) data, as well as public SAGE databases that contained a total of 137 SAGE libraries representing a wide variety of normal and neoplastic tissues, we identified five novel SAGE tags specifically expressed in ovarian cancer. Database analysis, cloning and, sequencing of the corresponding expressed sequence tags revealed details about these transcripts that we named human ovarian cancer-specific transcripts (HOSTs). HOST1 was found to be identical to the gene encoding ovarian marker CA125 (MUC16). HOST2 is a novel gene containing multiple copies of retroviral-related sequences without an obvious open reading frame. HOST3 encodes the tight-junction protein claudin-16 (CLDN16). HOST4 encodes a poorly characterized proteoglycan link protein (LP), and HOST5 codes for a type II sodium-dependent phosphate transporter (SLC34A2). Except for MUC16, these genes have not previously been shown to be expressed in ovarian or other cancers. Northern blot analysis confirmed that HOST genes are rarely expressed in normal tissues or nonovarian cancers, but are frequently expressed in ovarian cancer-derived cell lines and primary tumors. Moreover, HOST genes are upregulated in all four major subtypes of ovarian cancer compared to cultivated ovarian surface epithelial cells, as concluded by real-time reverse transcription (RT)-PCR using a panel of microdissected ovarian tumors. The sodium-dependent phosphate transporter (HOST5/SLC34A2) expression was associated with increased differentiation in ovarian serous tumors. While the roles of HOSTs in ovarian malignant transformation remain unclear, we propose that HOSTs may represent alternative targets for diagnosis and therapy and of this deadly disease.
C1 NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
   Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
   Univ Fed Rio de Janeiro, Dept Basic & Clin Pharmacol, Rio De Janeiro, Brazil.
   Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA.
RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
NR 37
TC 56
Z9 77
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 16
PY 2003
VL 22
IS 46
BP 7225
EP 7232
DI 10.1038/sj.onc.1207008
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 732PP
UT WOS:000185955000015
PM 14562052
ER

PT J
AU Hjalgrim, LH
   Westergaard, T
   Rostgaard, K
   Schmiegelow, K
   Melbye, M
   Hjalgrim, H
   Engels, EA
AF Hjalgrim, LH
   Westergaard, T
   Rostgaard, K
   Schmiegelow, K
   Melbye, M
   Hjalgrim, H
   Engels, EA
TI Birth weight as a risk factor for childhood leukemia: A meta-analysis of
   18 epidemiologic studies
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE child; leukemia; lymphocytic; acute; meta-analysis; risk factors
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MATERNAL REPRODUCTIVE HISTORY; CHILDRENS
   CANCER GROUP; GROWTH-FACTOR-I; ACUTE LYMPHOCYTIC-LEUKEMIA;
   NON-HODGKINS-LYMPHOMA; AGED 0-4 YEARS; MYELOID-LEUKEMIA; INFANT
   LEUKEMIA; X-RAY
AB Evidence has emerged that childhood leukemia is initiated in utero. High birth weight is one of the few birth-related factors that has been associated with childhood leukemia, albeit not consistently. The authors conducted a meta-analysis of studies of the association between birth weight and childhood leukemia risk. Study-specific odds ratios for leukemia were calculated, using a cutoff at 4,000 g of birth weight. The authors also evaluated whether the association between birth weight and leukemia followed a log-linear dose-response-like pattern. They calculated summary estimates using weighted averages of study-specific odds ratios from dichotomous and trend analyses. Eighteen studies (published between 1962 and 2002) were included, encompassing 10,282 children with leukemia. Children weighing 4,000 g or more at birth were at higher risk of acute lymphoblastic leukemia than children weighing less (odds ratio (OR) = 1.26, 95% confidence interval (CI): 1.17, 1.37). Furthermore, data were consistent with a close-response-like effect (OR = 1.14/1,000-g birth weight increase, 95% CI: 1.08, 1.20). Studies of acute myeloid leukemia indicated a similar increase in risk for children weighing 4,000 g or more at birth (OR = 1.27, 95% CI: 0.73, 2.20) and a close-response-like effect (OR = 1.29/1,000 g, 95% CI: 0.80, 2.06), but results varied across studies. Our findings support a relation between birth weight and childhood acute lymphoblastic leukemia risk and emphasize the need for additional studies of the biologic mechanisms underlying this association.
C1 Statens Serum Inst, Dept Epidemiol Res, Danish Epidemiol Sci Ctr, DK-2300 Copenhagen S, Denmark.
   Copenhagen Univ Hosp, HS Rigshosp, Dept Pediat, Copenhagen, Denmark.
   NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA.
RP Hjalgrim, LH (reprint author), Statens Serum Inst, Dept Epidemiol Res, Danish Epidemiol Sci Ctr, Artillerivej 5, DK-2300 Copenhagen S, Denmark.
OI Rostgaard, Klaus/0000-0001-6220-9414
NR 80
TC 105
Z9 110
U1 0
U2 2
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 OCT 15
PY 2003
VL 158
IS 8
BP 724
EP 735
DI 10.1098/aje/kwg210
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 731QJ
UT WOS:000185897700002
PM 14561661
ER

PT J
AU Saftlas, AF
   Levine, RJ
   Klebanoff, MA
AF Saftlas, AF
   Levine, RJ
   Klebanoff, MA
TI Re: "Abortion, changed paternity, and risk of preeclampsia in
   nulliparous women" - Three authors reply
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
C1 Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA.
   NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
RP Saftlas, AF (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA.
NR 7
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD OCT 15
PY 2003
VL 158
IS 8
BP 825
EP 825
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 731QJ
UT WOS:000185897700015
ER

PT J
AU Roubenoff, R
   Parise, H
   Payette, HA
   Abad, LW
   D'Agostino, R
   Jacques, PF
   Wilson, PWF
   Dinarello, CA
   Harris, TB
AF Roubenoff, R
   Parise, H
   Payette, HA
   Abad, LW
   D'Agostino, R
   Jacques, PF
   Wilson, PWF
   Dinarello, CA
   Harris, TB
TI Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in
   very old community-dwelling men and women: The Framingham Heart Study
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
ID C-REACTIVE PROTEIN; BIOELECTRICAL-IMPEDANCE; CHRONIC INFLAMMATION;
   BODY-MASS; IGF-I; INTERLEUKIN-6; MICE; IL-6; DISABILITY; INCREASE
AB BACKGROUND: Aging is associated with increased production of catabolic cytokines, reduced circulating levels of insulin-like growth factor 1 (IGF-1), and acceleration of sarcopenia (loss of muscle with age). We hypothesized that these factors are independently linked to mortality in community-dwelling older persons.
   METHODS: We examined the relation of all-cause mortality to peripheral blood mononuclear cell production of inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1beta, interleukin 6), serum interleukin 6 and IGF-1, and fat-free mass and clinical status in 525 ambulatory, free-living participants in the Framingham Heart Study.
   RESULTS: Of the 525 subjects (aged 72 to 92 years at baseline), 122 (23%) died during 4 years of follow-up. After adjusting for age, sex, comorbid conditions, smoking, and body mass index, mortality was associated with greater cellular production of TNF-alpha (hazard ratio [HR] = 1.27 per log(10) difference in ng/mL; 95% confidence interval [Cl]: 1.00 to 1.61; P = 0.05) and higher serum interleukin 6 levels (HR = 1.30 per log(10) difference in pg/mL; 95% Cl: 1.04 to 1.63]; P = 0.02), but not with higher serum IGF-1 levels (HR = 0.70 per log,, difference in pg/mL; 95% Cl: 0.49 to 0.99; P = 0.04). In a subset of 398 subjects (55 deaths) in whom change in fat-free mass index during the first 2 years was measured, less loss of fat-free mass and greater IGF-1 levels were associated with reduced mortality during the next 2 years.
   CONCLUSION: Greater levels or production of the catabolic cytokines TNF-alpha and interleukin 6 are associated with increased mortality in community-dwelling elderly adults, whereas IGF- I levels had the opposite effect. (C) 2003 by Excerpta Medica Inc.
C1 Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
   Boston Univ, Sch Med, Biostat Program, Boston, MA 02118 USA.
   Univ Sherbrooke, Res Ctr Aging, Sherbrooke, PQ J1K 2R1, Canada.
   Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
   Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA.
   NIA, Geriatr Epidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Roubenoff, R (reprint author), Millennium Pharmaceut, Dept Mol Med, 75 Sidney St 35-6, Cambridge, MA 02139 USA.
FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [AG-4-0245, AG15797]; NIAID
   NIH HHS [AI-15614]; NIDDK NIH HHS [DK02120]
NR 26
TC 204
Z9 208
U1 2
U2 15
PU EXCERPTA MEDICA INC
PI NEW YORK
PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD OCT 15
PY 2003
VL 115
IS 6
BP 429
EP 435
DI 10.1016/S0002-9343(03)00478-9
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 733AX
UT WOS:000185978700001
PM 14563498
ER

PT J
AU Ferrucci, L
   Guralnik, JM
AF Ferrucci, L
   Guralnik, JM
TI Inflammation, hormones, and body composition at a crossroad
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CHRONIC HEART-FAILURE; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-I; MUSCLE
   STRENGTH; SKELETAL-MUSCLE; OLDER WOMEN; INTERLEUKIN-6; MORTALITY;
   DISABILITY; CYTOKINES
C1 NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21225 USA.
   NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21225 USA.
RP Ferrucci, L (reprint author), NIA, Harbor Hosp, Longitudinal Studies Sect, Clin Res Branch,NIA, 5th Floor,3001 Hanover St, Baltimore, MD 21225 USA.
NR 23
TC 24
Z9 24
U1 0
U2 1
PU EXCERPTA MEDICA INC
PI NEW YORK
PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD OCT 15
PY 2003
VL 115
IS 6
BP 501
EP 502
DI 10.1016/S0002-9343903)00543-6
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 733AX
UT WOS:000185978700012
PM 14563508
ER

PT J
AU Speer, AM
   Willis, MW
   Herscovitch, P
   Daube-Witherspoon, M
   Shelton, JR
   Benson, BE
   Post, RM
   Wassermann, EM
AF Speer, AM
   Willis, MW
   Herscovitch, P
   Daube-Witherspoon, M
   Shelton, JR
   Benson, BE
   Post, RM
   Wassermann, EM
TI Intensity-dependent regional cerebral blood flow during 1-Hz repetitive
   transcranial magnetic stimulation (rTMS) in healthy volunteers studied
   with (H2O)-O-15 positron emission tomography: I. Effects of primary
   motor cortex rTMS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 55th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 11-13, 2000
CL CHICAGO, ILLINOIS
SP Soc Biol Psychiat
DE repetitive transcranial magnetic stimulation; regional cerebral blood
   flow; motor cortex; 1 Hz; intensity-dependent
ID INTRAVENOUS (H2O)-O-15; SENSORIMOTOR CORTEX; FINGER MOVEMENTS; PET;
   ACTIVATION; TMS; CONNECTIVITY; EXCITABILITY; PERFORMANCE; AREA
AB Background: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity.
   Methods: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H 1 2 150 and PET Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically.
   Results: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex.
   Conclusions: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1. (C) 2003 Society of Biological Psychiatry.
C1 Natl Inst Neurol Disorders & Stroke, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
   NIMH, Positron Emiss Tomog Dept, Warren Grant Magnussen Clin Ctr, Bethesda, MD USA.
   NIMH, Biol Psychiat Branch, Bethesda, MD USA.
   Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, NIH, Bethesda, MD USA.
RP Wassermann, EM (reprint author), Natl Inst Neurol Disorders & Stroke, Dept Hlth & Human Serv, NIH, Bldg 10,Rm 5N234, Bethesda, MD 20892 USA.
NR 29
TC 45
Z9 45
U1 0
U2 6
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 OCT 15
PY 2003
VL 54
IS 8
BP 818
EP 825
DI 10.1016/S0002-3223(03)00002-7
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 729BC
UT WOS:000185750100006
ER

PT J
AU Speer, AM
   Willis, MW
   Herscovitch, P
   Daube-Witherspoon, M
   Shelton, JR
   Benson, BE
   Post, RM
   Wassermann, EM
AF Speer, AM
   Willis, MW
   Herscovitch, P
   Daube-Witherspoon, M
   Shelton, JR
   Benson, BE
   Post, RM
   Wassermann, EM
TI Intensity-dependent regional cerebral blood flow during 1-Hz repetitive
   transcranial magnetic stimulation (rTMS) in healthy volunteers studied
   with (H2O)-O-15 positron emission tomography: II. Effects of prefrontal
   cortex rTMS
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 55th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 11-13, 2000
CL CHICAGO, ILLINOIS
SP Soc Biol Psychiat
DE repetitive transcranial magnetic stimulation; regional cerebral blood
   flow; prefrontal cortex; 1-Hz; intensity-dependent
ID SENSORIMOTOR CORTEX; GLUCOSE-METABOLISM; DEPRESSION; TMS; FREQUENCY;
   BRAIN; CONNECTIVITY; REDUCTION; ADULTS; MOOD
AB Background: The changes in brain activity produced by repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) remain unclear. We examined intensity-related changes in brain activity with positron emission tomography (PET) in normal volunteers during rTMS delivered to the left PFC
   Methods: In 10 healthy volunteers, we delivered 1-Hz rTMS at randomized intensities over left PFC with a figure-eight coil. Intensities were 80, 90, 100, 110, and 120% of the right-hand muscle twitch threshold. Regional cerebral blood flow (rCBF) scans were acquired with (H2O)-O-15 PET during rTMS at each intensity.
   Results: Repetitive transcranial magnetic stimulation intensity was inversely correlated with rCBF in the stimulated and contralateral PFC, ipsilateral medial temporal lobe, both parahippocampi, and posterior middle temporal gyri. Positive correlations of rCBF with intensity occurred in ipsilateral anterior cingulate, cerebellum, contralateral insula, primary auditory cortex, and somatosensory face area.
   Conclusions: The intensity-related inverse relationship between 1-Hz rTMS and prefrontal activity appears opposite to that seen with rTMS over the motor cortex in a companion study. Intensity-dependent increases in rCBF were seen in a number of distant cortical and subcortical areas with PFC rTMS, suggesting activation of left anterior cingulate, claustrum, and cerebellum. The regional differences in direction of rTMS effects and the greater activation of distant structures at higher intensities suggest the potential importance of higher-intensity prefrontal rTMS for therapeutic applications in neuropsychiatric patients. (C) 2003 Society of Biological Psychiatry.
C1 Natl Inst Mental Hlth, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
   NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
   Natl Inst Neurol Disorders & Stroke, NIH, Brain Stimulat Unit, Bethesda, MD USA.
RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, 10 Ctr Dr,Rm 3S239, Bethesda, MD 20892 USA.
NR 31
TC 73
Z9 78
U1 0
U2 2
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 OCT 15
PY 2003
VL 54
IS 8
BP 826
EP 832
DI 10.1016/S0006-3223(03)00324-X
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 729BC
UT WOS:000185750100007
PM 14550682
ER

PT J
AU Goedert, JJ
AF Goedert, JJ
TI Multicentric Castleman disease: viral and cellular targets for
   intervention
SO BLOOD
LA English
DT Editorial Material
ID ANTIBODY; LYMPHOMA
C1 NCI, Bethesda, MD 20892 USA.
RP Goedert, JJ (reprint author), NCI, Bethesda, MD 20892 USA.
NR 5
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 OCT 15
PY 2003
VL 102
IS 8
BP 2710
EP 2711
DI 10.1182/blood-2003-08-2635
PG 2
WC Hematology
SC Hematology
GA 731HB
UT WOS:000185877300003
ER

PT J
AU Brenner, S
   Whiting-Theobald, NL
   Linton, GF
   Holmes, KL
   Anderson-Cohen, M
   Kelly, PF
   Vanin, EF
   Pilon, AM
   Bodine, DM
   Horwitz, ME
   Malech, HL
AF Brenner, S
   Whiting-Theobald, NL
   Linton, GF
   Holmes, KL
   Anderson-Cohen, M
   Kelly, PF
   Vanin, EF
   Pilon, AM
   Bodine, DM
   Horwitz, ME
   Malech, HL
TI Concentrated RD114-pseudotyped MFGS-gp91(phox) vector achieves high
   levels of functional correction of the chronic granulomatous disease
   oxidase defect in NOD/SCID/beta 2-microglobulin(-/-) repopulating
   mobilized human peripheral blood CD34(+) cells
SO BLOOD
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; AMINO-ACID TRANSPORTER; MEDIATED
   GENE-TRANSFER; APE LEUKEMIA-VIRUS; BONE-MARROW-CELLS; CORD BLOOD;
   ENDOGENOUS RETROVIRUS; NOD/SCID MICE; IN-VIVO; ENVELOPE PROTEIN
AB In previous studies amphotropic MFGS-gp91(phox) (murine onco-retrovirus vector) was used in a clinical trial of X-linked chronic granulomatous disease (X-CGD) gene therapy to achieve transient correction of oxidase activity in 0.1% of neutrophils. We later showed that transduced CD34(+) peripheral blood stem cells (CD34(+) PBSCs) from this trial transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice resulted in correction of only 2.5% of human neutrophils. However, higher rates of transduction into stem cells are required. in the current study we demonstrate that the same vector (MFGS-gp91(phox)) pseudo-typed with RD114 envelope in a 4-day culture/transduction regimen results in a 7-fold increase in correction of NOD/SCID mouse repopulating X-CGD CD34(+) PB-SCs (14%-22% corrected human neutrophils; human cell engraftment 13%-67%). This increase may result from high expression of receptor for RD114 that we demonstrate on CD34(+)CD38(-) stem cells. Using RD114-MFGS encoding cyan fluorescent protein to allow similar studies of normal CD34(+) PBSCs, we show that progressively higher levels of gene marking of human neutrophils (67%-77%) can be achieved by prolongation of culture/transduction to 6 days, but with lower rates of human cell engraftment. Our data demonstrate the highest reported level of functional correction of any inherited metabolic disorder in human cells in vivo with the NOD/SCID mouse system using onco-retrovirus vector. (C) 2003 by The American Society of Hematology.
C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
   Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA.
   St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, Memphis, TN 38105 USA.
   NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   Tech Univ Dresden, Univ Clin Carl Gustav Carus, Dept Pediat, D-8027 Dresden, Germany.
RP Brenner, S (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 11N112,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA.
EM sbrenner@nih.gov
RI Brenner, Sebastian/D-7456-2013
NR 35
TC 45
Z9 45
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 OCT 15
PY 2003
VL 102
IS 8
BP 2789
EP 2797
DI 10.1182/blood-2002-05-1482
PG 9
WC Hematology
SC Hematology
GA 731HB
UT WOS:000185877300023
PM 12829597
ER

PT J
AU Alugupalli, KR
   Michelson, AD
   Joris, I
   Schwan, TG
   Hodivala-Dilke, K
   Hynes, RO
   Leong, JM
AF Alugupalli, KR
   Michelson, AD
   Joris, I
   Schwan, TG
   Hodivala-Dilke, K
   Hynes, RO
   Leong, JM
TI Spirochete-platelet attachment and thrombocytopenia in murine relapsing
   fever borreliosis
SO BLOOD
LA English
DT Article
ID DISSEMINATED INTRAVASCULAR COAGULATION; TRYPANOSOMA-CRUZI;
   ORNITHODOROS-MOUBATA; ANTIGENIC VARIATION; EPIMASTIGOTE FORMS; TICK;
   MICE; ACTIVATION; INFECTION; MOUSE
AB Thrombocytopenia is common in persons infected with relapsing fever Borreliae. We previously showed that the relapsing fever spirochete Borrelia hermsii binds to and activates human platelets in vitro and that, after platelet activation, high-level spirochete-platelet attachment is mediated by integrin alpha(IIb)beta(3), a receptor that requires platelet activation for full function. Here we established that B hermsii infection of the mouse results in severe thrombocytopenia and a functional defect in hemostasis caused by accelerated platelet loss. Disseminated intravascular coagulation, immune thrombocytopenic purpura, or splenic sequestration did not play a discernible role in this model. Instead, spirochete-platelet complexes were detected in the blood of infected mice, suggesting that platelet attachment by bacteria might result in platelet clearance. Consistent with this, splenomegally and thrombocytopenia temporally correlated with spirochetemia, and the severity of thrombocytopenia directly correlated with the degree of spirochetemia. Activation of platelets and integrin alpha(IIb)beta(3) were apparently not required for bacterium-platelet binding or platelet clearance because the bacterium-bound platelets in the circulation were not activated, and platelet binding and thrombocytopenia during infection Of beta(3)-deficient and wild-type mice were indistinguishable. These findings suggest that thrombocytopenia of relapsing fever is the result of platelet clearance after beta(3)-independent bacterial attachment to circulating platelets. (C) 2003 by The American Society of Hematology.
C1 Univ Massachusetts, Sch Med, Ctr Platelet Funct Studies, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA.
   Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA.
   Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA.
   NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, Hamilton, MT USA.
   MIT, Ctr Canc Res, Cambridge, MA 02139 USA.
   MIT, Dept Biol, Cambridge, MA 02139 USA.
RP Leong, JM (reprint author), Univ Massachusetts, Sch Med, Ctr Platelet Funct Studies, Dept Mol Genet & Microbiol, 55 Lake Ave N, Worcester, MA 01655 USA.
FU NHLBI NIH HHS [P01HL66105]; NIAID NIH HHS [R01-AI 37601]; NIDDK NIH HHS
   [DK 32520]
NR 61
TC 28
Z9 28
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 OCT 15
PY 2003
VL 102
IS 8
BP 2843
EP 2850
DI 10.1182/blood-2003-02-0426
PG 8
WC Hematology
SC Hematology
GA 731HB
UT WOS:000185877300030
PM 12855586
ER

PT J
AU Rezvani, K
   Grube, M
   Brenchley, JM
   Sconocchia, G
   Fujiwara, H
   Price, DA
   Gostick, E
   Yamada, K
   Melenhorst, J
   Childs, R
   Hensel, N
   Douek, DC
   Barrett, AJ
AF Rezvani, K
   Grube, M
   Brenchley, JM
   Sconocchia, G
   Fujiwara, H
   Price, DA
   Gostick, E
   Yamada, K
   Melenhorst, J
   Childs, R
   Hensel, N
   Douek, DC
   Barrett, AJ
TI Functional leukemia-associated antigen-specific memory CD8(+) T cells
   exist in healthy individuals and in patients with chronic myelogenous
   leukemia before and after stem cell transplantation
SO BLOOD
LA English
DT Article
ID WEGENERS-GRANULOMATOSIS; MYELOID-LEUKEMIA; GENE-EXPRESSION; IN-VITRO;
   LYMPHOCYTES; PEPTIDES; PROTEINASE-3; RESPONSES; IMMUNOTHERAPY;
   ANTIBODIES
AB Antigens implicated in the graft-versus-leukemia (GVL) effect in chronic myeloid leukemia (CML) include WT1, PR1, and BCR-ABL. To detect very low frequencies of these antigen-specific CD8(+) T cells, we used quantitative polymerase chain reaction (qPCR) to measure interferon-gamma (IFN-gamma) mRNA production by peptide-pulsed CD8(+) T cells from HLA-A*0201(+) healthy volunteers and from patients with CML before and after allogeneic stem cell transplantation (SCT). Parallel assays using cytomegalovirus (CMV) pp65 tetramers demonstrated the IFN-gamma copy number to be linearly related to the frequency of tetramer-binding T cells, sensitive to frequencies of 1 responding CD8(+) T cell/ 100 000 CD8(+) T cells. Responses to WT1 and PR1 but not BCR-ABL were detected in 10 of 18 healthy donors. Responses to WT1, PR1, or BCR-ABL were observed in 9 of 14 patients with CML before SCT and 5 of 6 after SCT, often to multiple epitopes. Responses were higher in patients with CML compared with healthy donors and highest after SCT. These antigen-specific CD8(+) T cells comprised central memory (CD45RO(+)CD27(+)CD57(-)) and effector memory (CD45RO(-)CD27(-)CD57(+)) T cells. In conclusion, leukemia-reactive CD8(+) T cells derive from memory T cells and occur at low frequencies in healthy individuals and at higher frequencies in patients with CML. The increased response in patients after SCT suggests a quantitative explanation for the greater effect of allogeneic SCT. (Blood. 2003; 102:2892-2900) (C) 2003 by The American Society of Hematology.
C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
   Nuffield Dept Med, Oxford, England.
RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 7C103, Bethesda, MD 20892 USA.
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
NR 44
TC 164
Z9 166
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 OCT 15
PY 2003
VL 102
IS 8
BP 2892
EP 2900
DI 10.1182/blood-2003-01-0150
PG 9
WC Hematology
SC Hematology
GA 731HB
UT WOS:000185877300037
PM 12829610
ER

PT J
AU Saunthararajah, Y
   Nakamura, R
   Wesley, R
   Wang, QJ
   Barrett, AJ
AF Saunthararajah, Y
   Nakamura, R
   Wesley, R
   Wang, QJ
   Barrett, AJ
TI A simple method to predict response to immunosuppressive therapy in
   patients with myelodysplastic syndrome
SO BLOOD
LA English
DT Article
ID APLASTIC-ANEMIA; ANTITHYMOCYTE GLOBULIN; BONE-MARROW; HLA DR2
AB Immunosuppression with antithymocyte globulin (ATG) or cyclosporine (CSA) can be used to treat the cytopenia associated with myelodysplastic syndrome (MDS). Previously, we identified HLA-DR15, younger age, and shorter duration of red cell transfusion dependence as pretreatment variables that correlate significantly with a response. Using these pretreatment variables we have devised a simple method to prospectively identify patients with low or high probabilities of response to immunosuppression. The ability of this system to predict response was confirmed in a separate cohort of 23 patients with MDS treated with immunosuppression. (Blood. 2003;102:3025-3027) (C) 2003 by The American Society of Hematology.
C1 Univ Illinois, MBRB, Chicago, IL 60607 USA.
   NHLBI, Bethesda, MD 20892 USA.
RP Saunthararajah, Y (reprint author), Univ Illinois, MBRB, Rm3150,MC734,900 S Ashland Ave, Chicago, IL 60607 USA.
NR 11
TC 114
Z9 124
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 OCT 15
PY 2003
VL 102
IS 8
BP 3025
EP 3027
DI 10.1182/blood-2002-11-3325
PG 3
WC Hematology
SC Hematology
GA 731HB
UT WOS:000185877300054
PM 12829603
ER

PT J
AU Klion, AD
   Akin, G
   Nutman, TB
AF Klion, AD
   Akin, G
   Nutman, TB
TI Respons: Hypereosinophilic syndrome with elevated serum tryptase is a
   syndrome that differs from systemic mast cell disease with eosinophilia
SO BLOOD
LA English
DT Letter
C1 NIAID, NIH, Bethesda, MD 20892 USA.
RP Klion, AD (reprint author), NIAID, NIH, Bldg 4,Rm 126,9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 4
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 OCT 15
PY 2003
VL 102
IS 8
BP 3074
EP 3074
PG 1
WC Hematology
SC Hematology
GA 731HB
UT WOS:000185877300064
ER

PT J
AU Chokkalingam, AP
   Nyren, O
   Johansson, JE
   Gridley, G
   McLaughlin, JK
   Adami, HO
   Hsing, AW
AF Chokkalingam, AP
   Nyren, O
   Johansson, JE
   Gridley, G
   McLaughlin, JK
   Adami, HO
   Hsing, AW
TI Prostate carcinoma risk subsequent to diagnosis of benign prostatic
   hyperplasia - A population-based cohort study in Sweden
SO CANCER
LA English
DT Article
DE prostate carcinoma; benign prostatic hyperplasia; Sweden; cohort;
   transurethral resection; transvesical adenomectomy; epidemiology
ID BODY-SIZE; GROWTH-FACTORS; SERUM LEVELS; CANCER RISK; INSULIN; LEPTIN;
   CHINA
AB BACKGROUND. Pathologically, benign prostatic hyperplasia (BPH) is not considered a precursor for prostate carcinoma. However, because the two conditions share not only a similar hormonal environment within the prostate but also several common risk factors, it is possible that men with BPH may be at increased risk of prostate carcinoma due to these shared factors.
   METHODS. To elucidate this further, the authors used Swedish nationwide population-based record-linkage data to assess prostate carcinoma risk up to 26 years after the diagnosis of BPH among 86,626 men.
   RESULTS. Overall, relative to the general population, patients with BPH experienced little, if any, excess risk of prostate carcinoma (2% excess incidence after 10 years of follow-up). However, patients with BPH with and without surgical intervention experienced different prostate carcinoma risk patterns. Those undergoing transvesicular adenomectomy had a significant 22% lower incidence and a 23% lower mortality after the first 5 years of follow-up and those undergoing transurethral resection had a significant 10% higher incidence but a 17% lower mortality. In contrast, after the first 5 years, patients with BPH who did not receive surgical intervention experienced significant excesses of both prostate carcinoma incidence (18%) and mortality (77%).
   CONCLUSIONS. The differences in prostate carcinoma incidence and mortality by BPH treatment type suggest that factors related to treatment or health reasons underlying the selection of treatment influence subsequent prostate carcinoma risk. Further studies are needed to confirm the minimal excess risk of prostate carcinoma among BPH patients overall and the possible impact of BPH treatment methods on subsequent prostate carcinoma risk. Published 2003 by the American Cancer Society.
C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   Karolinska Inst, Stockholm, Sweden.
   Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
   Orebro Univ Hosp, Dept Clin Med, Orebro, Sweden.
   Orebro Univ Hosp, Ctr Assessment Med Technol, Orebro, Sweden.
   Int Epidemiol Inst, Rockville, MD USA.
RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, EPS MSC-7234,6120 Execut Blvd Room 7058, Bethesda, MD 20892 USA.
NR 27
TC 31
Z9 34
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 OCT 15
PY 2003
VL 98
IS 8
BP 1727
EP 1734
DI 10.1002/cncr.11710
PG 8
WC Oncology
SC Oncology
GA 730BR
UT WOS:000185809800023
PM 14534890
ER

PT J
AU Carver, LA
   Schnitzer, JE
   Anderson, RGW
   Mohla, S
AF Carver, LA
   Schnitzer, JE
   Anderson, RGW
   Mohla, S
TI Role of caveolae and lipid rafts in cancer: Workshop summary and future
   needs
SO CANCER RESEARCH
LA English
DT Review
ID ONCOGENICALLY TRANSFORMED-CELLS; ANCHORAGE-INDEPENDENT GROWTH;
   VESICULO-VACUOLAR ORGANELLES; INSENSITIVE PROSTATE-CANCER;
   BREAST-CANCER; SURVIVAL/CLONAL GROWTH; CYCLE PROGRESSION; GENE DELIVERY;
   UP-REGULATION; IN-SITU
C1 Sidney Kimmel Canc Ctr, Vasc Biol & Angiogenesis Program, San Diego, CA 92121 USA.
   Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75235 USA.
   NCI, Tumor Biol & Metastasis Branch, Div Canc Biol, NIH, Rockville, MD 20852 USA.
RP Schnitzer, JE (reprint author), Sidney Kimmel Canc Ctr, Vasc Biol & Angiogenesis Program, 10835 Altman Row, San Diego, CA 92121 USA.
NR 39
TC 20
Z9 21
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2003
VL 63
IS 20
BP 6571
EP 6574
PG 4
WC Oncology
SC Oncology
GA 737DJ
UT WOS:000186213800001
PM 14583447
ER

PT J
AU Maccalli, C
   Li, YF
   El-Gamil, M
   Rosenberg, SA
   Robbins, PF
AF Maccalli, C
   Li, YF
   El-Gamil, M
   Rosenberg, SA
   Robbins, PF
TI Identification of a colorectal tumor-associated antigen (COA-1)
   recognized by CD4(+) T lymphocytes
SO CANCER RESEARCH
LA English
DT Article
ID INFILTRATING LYMPHOCYTES; CANCER-PATIENTS; RANDOMIZED TRIAL; CELL
   RESPONSES; HLA-DR; MELANOMA; EXPRESSION; IMMUNOTHERAPY; EPITOPES;
   PEPTIDES
AB Only a limited number of target molecules have been shown to be recognized by colon tumor-reactive T cells, limiting the options for the development of immunotherapies for patients with colon cancer. The current studies were undertaken in an attempt to generate tumor-reactive T cells that could be used to identify and characterize novel colon tumor-associated antigens. Multiple CD4(+) T-cell clones isolated either from tumor-infiltrating lymphocytes or peripheral blood mononuclear cells that were sensitized in vitro with autologous tumor cells from a colon cancer patient, 1869, recognized autologous tumor cells in a class 11 HLA-DR-restricted manner. One of the peripheral blood mononuclear cell clones, clone C111, was used to screen pools of clones that were generated from an autologous colon tumor cell line cDNA library. A cDNA clone that was isolated encoded a protein that was termed colorectal tumor-associated antigen-1 (COA-1). This product was recognized in the context of the two autologous HLA-DRbeta1 alleles, HLA-DRbeta1*0402 and DRbeta1*1301. The nucleotide sequence of the COA-1 transcript was nearly identical to multiple expressed sequence tag sequences that encode variants of Socius, a protein that was found recently to bind to members of the Rod family of GTPases. The COA-1 gene was expressed at relatively comparable levels in colorectal and melanoma tumor cells, EBV-infected B cells, normal B cells, and cultured fibroblast cell lines. However, the gene that was isolated from normal cell types contained a single nucleotide substitution, resulting in an amino acid change near the COOH terminus of the protein. Although the minimal epitope recognized by CD4(+) cells was encoded by sequences that were upstream from this substitution, C111 T cells did not appear to recognize the normal gene product. Therefore, this alteration may either affect the localization or the processing of this gene product, which may at least in part be responsible for the differential recognition of tumor and normal cells.
C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
   Ist Nazl Tumori, Unit Immunotherapy Human Tumors, I-20133 Milan, Italy.
RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z01 SC003811-32]
NR 31
TC 20
Z9 22
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2003
VL 63
IS 20
BP 6735
EP 6743
PG 9
WC Oncology
SC Oncology
GA 737DJ
UT WOS:000186213800022
PM 14583468
ER

PT J
AU Cardones, AR
   Murakami, T
   Hwang, ST
AF Cardones, AR
   Murakami, T
   Hwang, ST
TI CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro
   and in vivo via beta(1) integrin
SO CANCER RESEARCH
LA English
DT Article
ID LYMPH-NODE METASTASIS; CHEMOKINE RECEPTORS; E-SELECTIN; VASCULAR
   ENDOTHELIUM; MELANOMA-CELLS; CANCER-CELLS; EXPRESSION; FLOW;
   INVOLVEMENT; MOLECULE-1
AB The chemokine receptor, CXCR4, is expressed by human melanomas, and its ligand, CXCL12, is frequently produced at sites of melanoma metastasis. Herein, we examine CXCR4-enhanced binding of B16 murine melanoma cells to endothelial cells (ECs) and recombinant adhesion molecules in vitro to determine the role of tumor- and EC-derived adhesion molecules in tumor metastasis. By flow cytometry, unstimulated primary lung ECs showed constitutive expression of vascular cellular adhesion molecule-1 (VCAM-1), whereas skin-derived ECs did not. All B16 cell lines tested showed constitutive expression of alpha(4) and P, integrin chains but showed no expression of beta(2) integrins. CXCR4-B16 arrest on VCAM-1/immunoglobulin-coated plates and tumor necrosis factor a-stimulated ECs under physiological shear stress conditions (1.5 dynes/cm(2)) was rapid, resistant to shear stress of 10 dynes/cm(2), and showed no evidence of rolling before arrest. In vitro, CXCR4-B16 cell binding to ECs was blocked by anti-beta(1) and anti-CXCL12 monoclonal antibodies. In vivo, metastasis of CXCR4-B16 cells to murine lungs was strongly inhibited by anti-CXCL12 and two different anti-P, monoclonal antibodies. Finally, CXCR4-B16 exposed to CXCL12 rapidly increased binding affinity for soluble VCAM-1/immunoglobulin as detected by a flow cytometric assay. Thus, beta(1) integrins play a critical role in CXCR4-mediated B16 tumor cell metastasis in vivo and may be a potential target for inhibition of tumor metastasis, particularly to the lung.
C1 NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Hwang, ST (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10,Room 12N246,10 Ctr Dr, Bethesda, MD 20892 USA.
NR 34
TC 101
Z9 104
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2003
VL 63
IS 20
BP 6751
EP 6757
PG 7
WC Oncology
SC Oncology
GA 737DJ
UT WOS:000186213800024
PM 14583470
ER

PT J
AU Wang, ZN
   Lee, MP
AF Wang, ZN
   Lee, MP
TI Expressed sequence tags: Clean before using. Correspondence re: Z. Wang
   et al., Computational analysis and experimental validation of
   tumor-associated alternative RNA splicing in human cancer. Cancer Res.,
   63 : 655-657, 2003. Reply
SO CANCER RESEARCH
LA English
DT Letter
C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA.
RP Wang, ZN (reprint author), NCI, Lab Populat Genet, Bethesda, MD 20892 USA.
NR 2
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2003
VL 63
IS 20
BP 6996
EP 6997
PG 2
WC Oncology
SC Oncology
GA 737DJ
UT WOS:000186213800057
ER

PT J
AU Potter, M
AF Potter, M
TI In memoriam: Lloyd W. Law (1910-2002) - Obituary
SO CANCER RESEARCH
LA English
DT Biographical-Item
C1 NCI, Genet Lab, Bethesda, MD 20892 USA.
RP Potter, M (reprint author), NCI, Genet Lab, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD OCT 15
PY 2003
VL 63
IS 20
BP 7002
EP 7002
PG 1
WC Oncology
SC Oncology
GA 737DJ
UT WOS:000186213800060
ER

PT J
AU Zorn, KK
   Jazaeri, AA
   Awtrey, CS
   Gardner, GJ
   Mok, SC
   Boyd, J
   Birrer, MJ
AF Zorn, KK
   Jazaeri, AA
   Awtrey, CS
   Gardner, GJ
   Mok, SC
   Boyd, J
   Birrer, MJ
TI Choice of normal ovarian control influences determination of
   differentially expressed genes in ovarian cancer expression profiling
   studies
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MESSENGER-RNA AMPLIFICATION; EPITHELIAL-CELLS; CDNA MICROARRAY;
   IN-VITRO; CARCINOMAS; IDENTIFICATION; TELOMERASE; LINES
AB Purpose: As with many cancers thought to be of epithelial origin, expression profiling studies of ovarian cancer have relied on a variety of sources of normal cells for comparison with tumors, including whole ovary samples (WO), ovarian surface epithelium (OSE) exposed to short-term culture, and immortalized OSE cell lines (IOSE). Our purpose was to assess the impact of the use of different types of normal controls on the determination of gene expression alterations in ovarian cancer studies.
   Experimental Design: We compared the gene expression profiles generated on an 11,000-element cDNA microarray of OSE brushings, whole ovary samples, short-term cultures of normal OSE, SV40 large T antigen-immortalized OSE cell lines, and telomerase-immortalized OSE cell lines. The function of the groups as normal controls was then assessed by separate comparisons of each group to a set of 24 serous ovarian carcinoma samples.
   Results: The normal groups formed robust, distinct clusters in hierarchical clustering and multidimensional scaling. The Pearson correlation coefficient for all combinations of any two of the groups ranged from 0.04 to 0.54, emphasizing the disparity of the groups. In the gene lists produced by comparing each normal group with the ovarian cancer samples, the majority of genes were unique to that normal-cancer comparison, with no gene appearing on all five lists.
   Conclusions: These results suggest that the selection of a normal control to compare with epithelial ovarian cancer samples in microarray studies strongly influences the genes that are identified as differentially expressed and complicates comparison with studies using a different normal control.
C1 NCI, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA.
   NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Rockville, MD 20850 USA.
   Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
   Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
   Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Lab Gynecol Oncol, Boston, MA 02115 USA.
RP Birrer, MJ (reprint author), NCI, Dept Cell & Canc Biol, NIH, 9610 Med Ctr Dr,Room 300, Rockville, MD 20850 USA.
RI Jazaeri, Amir/A-2400-2008; Jazaeri, Amir/I-3458-2015
OI Jazaeri, Amir/0000-0003-4335-4151
FU NCI NIH HHS [U01 CA88175]
NR 32
TC 72
Z9 74
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2003
VL 9
IS 13
BP 4811
EP 4818
PG 8
WC Oncology
SC Oncology
GA 737CW
UT WOS:000186212000020
PM 14581352
ER

PT J
AU Krajewska, M
   Krajewski, S
   Banares, S
   Huang, XS
   Turner, B
   Bubendorf, L
   Kallioniemi, OP
   Shabaik, A
   Vitiello, A
   Peehl, D
   Gao, GJ
   Reed, JC
AF Krajewska, M
   Krajewski, S
   Banares, S
   Huang, XS
   Turner, B
   Bubendorf, L
   Kallioniemi, OP
   Shabaik, A
   Vitiello, A
   Peehl, D
   Gao, GJ
   Reed, JC
TI Elevated expression of inhibitor of apoptosis proteins in prostate
   cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HUMAN OVARIAN-CANCER; X-LINKED INHIBITOR; CELL-DEATH; ENDOTHELIAL-CELLS;
   CASPASE ACTIVITY; DOWN-REGULATION; KAPPA-B; IAP; XIAP; SURVIVIN
AB Purpose: Inhibitor of apoptosis (IAP) family proteins are suppressors of apoptosis that have been implicated in apoptosis resistance in some cancers. Their expression and relevance to the prognosis of prostate cancer were investigated.
   Experimental Design: The expression of four members of the IAP family (cellular inhibitor of apoptosis protein 1, cellular inhibitor of apoptosis protein 2, X chromosome-linked IAP, and survivin) was examined by immunohistochemistry and immunoblotting in human prostate cancers and in prostate tissues from transgenic mice expressing SV40 large T antigen under control of a probasin promoter.
   Results: Tumor-associated elevations in the levels of all four IAP family members were common in prostate cancers of both humans and mice, suggesting concomitant up-regulation of multiple IAP family proteins. Compared with normal prostatic epithelium, increased IAP expression was often evident even in prostatic intraepithelial neoplasia lesions (carcinoma in situ), suggesting that deregulation of IAP expression occurs early in the pathogenesis of prostate cancer. IAP expression did not correlate with Gleason grade or prostate-specific antigen levels.
   Conclusions: The findings demonstrate that tumor-associated elevations in the expression of several IAP family proteins occur as a frequent and early event in the etiology of prostate cancer.
C1 Burnham Inst, La Jolla, CA 92037 USA.
   Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA.
   Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland.
   NCI, Canc Genet Lab, NHGRI, NIH, Bethesda, MD 20892 USA.
   Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA.
   RW Johnson Pharmaceut Res Inst, San Diego, CA 92121 USA.
   Stanford Univ, Dept Urol, Stanford, CA 94305 USA.
   BD Biosci Pharmingen, San Diego, CA 92121 USA.
RP Reed, JC (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
RI Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011;
   Kallioniemi, Olli/H-4738-2012; 
OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi,
   Olli/0000-0002-3231-0332; Shabaik, Ahmed/0000-0003-1987-3453
NR 50
TC 184
Z9 197
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2003
VL 9
IS 13
BP 4914
EP 4925
PG 12
WC Oncology
SC Oncology
GA 737CW
UT WOS:000186212000034
PM 14581366
ER

PT J
AU de Jong, MC
   Scheffer, GL
   Broxterman, HJ
   Hooijberg, JH
   Slootstra, JW
   Meloen, RH
   Kreitman, RJ
   Husain, SR
   Joshi, BH
   Puri, RK
   Scheper, RJ
AF de Jong, MC
   Scheffer, GL
   Broxterman, HJ
   Hooijberg, JH
   Slootstra, JW
   Meloen, RH
   Kreitman, RJ
   Husain, SR
   Joshi, BH
   Puri, RK
   Scheper, RJ
TI Multidrug-resistant tumor cells remain sensitive to a recombinant
   interleukin-4-Pseudomonas exotoxin, except when overexpressing the
   multidrug resistance protein MRP1
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PERMUTED INTERLEUKIN 4-TOXIN; FIBROBLAST-GROWTH-FACTOR; BREAST-CARCINOMA
   CELLS; P-GLYCOPROTEIN; DRUG-RESISTANCE; CANCER-CELLS;
   ANTITUMOR-ACTIVITY; MEMBRANE-VESICLES; ATPASE ACTIVITY; IL-4 RECEPTORS
AB Tumor cells may become resistant to conventional anticancer drugs through the occurrence of transmembrane transporter proteins such as P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), or members of the multidrug resistance-associated protein family (MRP1-MRP5; ABCC1-ABCC5). In this report, we studied whether tumor cells that are cytostatic drug resistant because of overexpression of one of the above mentioned proteins are sensitive to a new anticancer agent, interieukin-4 toxin (IL-4 toxin). IL-4 toxin is a fusion protein composed of circularly permuted IL-4 and a truncated form of Pseadomonas exotoxin (PE) [IL-4(38-37)-PE38KDEL]. Ninety-six-h cytotoxicity assays and 10-day clonogenic assays showed that drug-selected multidrug resistant (MDR) tumor cells that overexpress P-glycoprotein or breast cancer resistance proteins are still sensitive to IL-4 toxin. Also, tumor cells transfected with cDNA for MRP2-5 showed no resistance, or marginal resistance, only to the toxin as compared with the parent cells. In contrast, MRP1-overexpressing cells, both drug selected and MRP1 transfected, are clearly resistant to IL-4 toxin with resistance factors of 4.3 to 8.4. MRP1-overexpressing cells were not resistant to PE itself. IL-4 toxin resistance in MRP1-overexpressing cells could be reversed by the MRP1 inhibitors probenecid or MK571 and were not affected by glutathione depletion by DL-buthionine-S,R-sulfoximine. In a transport assay using plasma membrane vesicles prepared from MRP1-overexpressing cells, IL-4 toxin and IL-4, but not PE, inhibited the translocation of the known MRP1 substrate 17beta-estradiol 17-(beta-D-glucuronide) (E(2)17betaG). These data suggest that MRP1-overexpressing cells are resistant to IL-4 toxin because of extrusion of this agent by MRP1. Still, the results of this study demonstrate that IL-4 toxin effectively kills most MDR tumor cells and, therefore, represents a promising anticancer drug.
C1 Free Univ Amsterdam, Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands.
   Free Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands.
   Free Univ Amsterdam, Med Ctr, Dept Pediat Hematol Oncol, NL-1081 HV Amsterdam, Netherlands.
   ID DLO, Inst Anim Sci & Hlth, Dept Mol Recognit, NL-8200 AB Lelystad, Netherlands.
   NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA.
   US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Scheper, RJ (reprint author), Free Univ Amsterdam, Med Ctr, Dept Pathol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
NR 47
TC 8
Z9 8
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD OCT 15
PY 2003
VL 9
IS 13
BP 5009
EP 5017
PG 9
WC Oncology
SC Oncology
GA 737CW
UT WOS:000186212000044
PM 14581376
ER

PT J
AU Repetto, L
   Tralongo, P
   Zagonel, V
AF Repetto, L
   Tralongo, P
   Zagonel, V
TI Geriatric oncology: Focus on myelodepression - Introduction
SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
LA English
DT Editorial Material
ID CANCER
C1 Natl Canc Inst, Res IST, Div Med Oncol 1, I-16132 Genoa, Italy.
RP Repetto, L (reprint author), Natl Canc Inst, Res IST, Div Med Oncol 1, Largo Rosanna Benzi 10, I-16132 Genoa, Italy.
RI zagonel, vittorina/F-4226-2014
OI zagonel, vittorina/0000-0002-0829-2525
NR 4
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 1040-8428
J9 CRIT REV ONCOL HEMAT
JI Crit. Rev. Oncol./Hematol.
PD OCT 15
PY 2003
VL 48
SU S
BP S1
EP S1
DI 10.1016/j.critrevonc.2003.07.001
PG 1
WC Oncology; Hematology
SC Oncology; Hematology
GA 744XN
UT WOS:000186658300001
ER

PT J
AU Dai, Q
   Zhang, CL
   Wu, YX
   McDonough, H
   Whaley, RA
   Godfrey, V
   Li, HH
   Madamanchi, N
   Xu, W
   Neckers, L
   Cyr, D
   Patterson, C
AF Dai, Q
   Zhang, CL
   Wu, YX
   McDonough, H
   Whaley, RA
   Godfrey, V
   Li, HH
   Madamanchi, N
   Xu, W
   Neckers, L
   Cyr, D
   Patterson, C
TI CHIP activates HSF1 and confers protection against apoptosis and
   cellular stress
SO EMBO JOURNAL
LA English
DT Article
DE apoptosis; chaperone; proteasome; stress response; ubiquitin
ID HEAT-SHOCK FACTOR; MOLECULAR CHAPERONE HSC70; TRANSCRIPTION FACTOR HSF1;
   TARGETED GENE DISRUPTION; E3 UBIQUITIN LIGASE; IN-VIVO; PROTEIN; MICE;
   HSP70; THERMOTOLERANCE
AB Induction of molecular chaperones is the characteristic protective response to environmental stress, and is regulated by a transcriptional program that depends on heat shock factor 1 (HSF1), which is normally under negative regulatory control by molecular chaperones Hsp70 and Hsp90. In metazoan species, the chaperone system also provides protection against apoptosis. We demonstrate that the dual function co-chaperone/ubiquitin ligase CHIP (C-terminus of Hsp70-interacting protein) regulates activation of the stress-chaperone response through induced trimerization and transcriptional activation of HSF1, and is required for protection against stress-induced apoptosis in murine fibroblasts. The consequences of this function are demonstrated by the phenotype of mice lacking CHIP, which develop normally but are temperature-sensitive and develop apoptosis in multiple organs after environmental challenge. CHIP exerts a central and unique role in tuning the response to stress at multiple levels by regulation of protein quality control and transcriptional activation of stress response signaling.
C1 Univ N Carolina, Carolina Cardiovasc Biol Ctr, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA.
   NCI, Ctr Canc Res, Rockville, MD 20852 USA.
RP Patterson, C (reprint author), Univ N Carolina, Carolina Cardiovasc Biol Ctr, Chapel Hill, NC 27599 USA.
RI Zhang, Chunlian/L-1399-2014; 
OI Madamanchi, Nageswara/0000-0003-0590-0908
FU NHLBI NIH HHS [R01 HL065619, HL65619, R37 HL065619]; NIGMS NIH HHS
   [GM56981, GM61728, R01 GM056981, R01 GM061728]
NR 42
TC 190
Z9 199
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0261-4189
J9 EMBO J
JI Embo J.
PD OCT 15
PY 2003
VL 22
IS 20
BP 5446
EP 5458
DI 10.1093/emboj/cdg529
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 733RJ
UT WOS:000186014200012
PM 14532117
ER

PT J
AU Jung, DK
   Bae, GU
   Kim, YK
   Han, SH
   Choi, WS
   Kang, H
   Seo, DW
   Lee, HY
   Cho, EJ
   Lee, HW
   Han, JW
AF Jung, DK
   Bae, GU
   Kim, YK
   Han, SH
   Choi, WS
   Kang, H
   Seo, DW
   Lee, HY
   Cho, EJ
   Lee, HW
   Han, JW
TI Hydrogen peroxide mediates arsenite activation of p70(s6k) and
   extracellular signal-regulated kinase
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE arsenite; H2O2; p70(s6k); extracellular signal-regulated kinase 1/2
ID GROWTH-FACTOR RECEPTOR; P70 S6 KINASE; PROTEIN-KINASE;
   PHOSPHATIDYLINOSITOL 3-KINASE; MAP KINASE; TRANSDUCTION PATHWAY;
   TRANSCRIPTION FACTOR; INSULIN STIMULATION; CELL-PROLIFERATION; TYROSINE
   KINASES
AB To define the mechanism of arsenite-induced tumor promotion, we examined the role of reactive oxygen species (ROS) in the signaling pathways of cells exposed to arsenite. Arsenite treatment resulted in the persistent activation of p70(s6k) and extracellular signal-regulated kinase 1/2 (ERK1/2) which was accompanied by an increase in intracellular ROS production. The predominant produced appeared to be H2O2, because the arsenite-induced increase in dichlorofluorescein (DCF) fluorescence was completely abolished by pretreatment with catalase but not with heat-inactivated catalase. Elimination of H2O2 by catalase or N-acetyl-(L)-Cysteine inhibited the arsenite-induced activation of p70(s6k) and ERK1/2, indicating the possible role of H2O2 in the arsenite activation of the p70(s6k) and the ERK1/2 signaling pathways. A specific inhibitor of p70(s6k), rapamycin, and calcium chelators significantly blocked the activation of p70(s6k) induced by arsenite. While the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 completely abrogated arsenite activation of p70(s6k), ERK1/2 activation by arsenite was not affected by these inhibitors, indicating that H2O2 might act as an upstream molecule of PI3K as well as ERK1/2. Consistent with these results, none of the inhibitors impaired H2O2 production by arsenite. DNA binding activity of AP-1, downstream of ERK1/2, was also inhibited by catalase, N-acetyl-(L)-cysteine, and the MEK inhibitor PD98059, which significantly blocked arsenite activation of ERK1/2. Taken together, these studies provide insight into mechanisms of arsenite-induced tumor promotion and suggest that H2O2 plays a critical role in tumor promotion by arsenite through activation of the ERK1/2 and p70(s6k) signaling pathways. (C) 2003 Elsevier Inc. All rights reserved.
C1 Sungkyunkwan Univ, Coll Pharm, Dept Biochem & Mol Biol, Suwon 440746, South Korea.
   Konkuk Univ, Coll Med, Dept Immunol, Chungcheongbuk Do 380701, South Korea.
   NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA.
   NCI, Extracellular Matrix Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   Konyang Univ, Coll Med, Dept Pharmacol, Nonsan 320711, South Korea.
RP Han, JW (reprint author), Sungkyunkwan Univ, Coll Pharm, Dept Biochem & Mol Biol, Suwon 440746, South Korea.
EM jhhan@skku.ac.kr
OI Seo, Dong-Wan/0000-0003-4971-834X
NR 61
TC 22
Z9 23
U1 2
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD OCT 15
PY 2003
VL 290
IS 1
BP 144
EP 154
DI 10.1016/S0014-4827(03)00320-3
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 728PA
UT WOS:000185724500013
PM 14516795
ER

PT J
AU Wang, YZ
   Ingram, JL
   Walters, DM
   Rice, AB
   Santos, JH
   Van Houten, B
   Bonner, JC
AF Wang, YZ
   Ingram, JL
   Walters, DM
   Rice, AB
   Santos, JH
   Van Houten, B
   Bonner, JC
TI Vanadium-induced STAT-1 activation in lung myofibroblasts requires H2O2
   and p38 map kinase
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE hydrogen peroxide; vanadium; STAT-1; p38 MAP kinase; myofibroblasts;
   free radicals
ID RAT PULMONARY MYOFIBROBLASTS; PROTEIN-TYROSINE PHOSPHATASES;
   GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; HYDROGEN-PEROXIDE; INDUCED
   APOPTOSIS; INTERFERON-ALPHA; TNF-ALPHA; CELLS; EXPRESSION
AB Vanadium compounds present in air pollution particulate matter activate signal transduction pathways in pulmonary cell types leading to pathological outcomes including aberrant cell proliferation, apoptosis, and cytokine expression. Vanadium has been proposed to activate transcription factors via the generation of hydrogen peroxide (H2O2). We investigated the mechanisms through which vanadium pentoxide (V2O5), the major form of vanadium released from the industrial burning of fuel oil, activated the signal transducer and activator of transcription (STAT)-1. V2O5-induced STAT-1 activation was blocked by catalase and N-acetyl-L-cysteine (NAC), suggesting vanadium-induced generation of H2O2. Surprisingly, however, V2O5 did not increase H2O2 levels released by rat lung myofibroblasts into cell culture supernatants. Instead, these quiescent myofibroblasts spontaneously released micromolar concentrations of H2O2 and the addition of V2O5 reduced H2O2 levels in cell culture supernatants within minutes. V2O5 suppressed H2O2 for as long as 24 h. Differences in the temporal activation of STAT-1 and p38 MAPK were observed following V2O5 or H2O2 treatment, and STAT-1 activation by V2O5 or H2O2 was attenuated by an inhibitor of the EGF receptor tyrosine kinase (AG1478) or p38 MAPK (SB203580). The phosphorylation of p38 MAPK by V2O5 was inhibited by NAC and catalase, yet the EGF receptor inhibitor AG1478 had no effect on V2O5-induced p38 MAPK activation. Collectively, our findings support the novel hypothesis that H2O2 spontaneously generated by myofibroblasts fuels vanadium-induced activation of STAT-1. Moreover, p38 MAPK and EGF receptor activation are required for V2O5-induced STAT-1 activation. Published by Elsevier Inc.
C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Bonner, JC (reprint author), NIEHS, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
OI Walters, Dianne/0000-0003-3888-2646
NR 39
TC 19
Z9 21
U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD OCT 15
PY 2003
VL 35
IS 8
BP 845
EP 855
DI 10.1016/S0891-5849(03)00399-X
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 730FC
UT WOS:000185817700002
PM 14556849
ER

PT J
AU Romashko, J
   Horowitz, S
   Franek, WR
   Palaia, T
   Miller, EJ
   Lin, AN
   Birrer, MJ
   Scott, W
   Mantell, LL
AF Romashko, J
   Horowitz, S
   Franek, WR
   Palaia, T
   Miller, EJ
   Lin, AN
   Birrer, MJ
   Scott, W
   Mantell, LL
TI MAPK pathways mediate hyperoxia-induced oncotic cell death in lung
   epithelial cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE hyperoxia; oncosis; MAPK; apoptosis; AP-1; JNK; p38; oxidative; free
   radicals
ID FACTOR-KAPPA-B; C-JUN; OXYGEN-TOXICITY; ANTIOXIDANT VITAMINS; ACTIVATION
   DOMAIN; INDUCED APOPTOSIS; OXIDANT INJURY; DNA-DAMAGE; HA-RAS; PROTECTS
AB Cell injury and cell death of pulmonary epithelium plays an important role in the pathogenesis of acute lung injury in animals exposed to prolonged hyperoxia. The aim of this study was to decipher the molecular mechanisms modulating cell death induced by hyperoxia in lung epithelium. Cell death is thought to be either apoptotic, with shrinking phenotypes and activated caspases, or oncotic, with swelling organelles. Exposure to 95% O-2 (hyperoxia) induced cell death of MLE-12 cells with cellular as well as nuclear swelling, cytosolic vacuolation, and loss of mitochondrial structure and enzyme function. Neither elevated caspase-3 activity nor phosphatidylserine translocation were detected, suggesting that in hyperoxia, MLE-12 cells die via oncosis rather than apoptosis. In addition, hyperoxia triggered a sustained activation of the transcription factor AP-1, as well as mitogen-activated protein kinase (MAPK) family members p38 and JNK. Importantly, survival of MLE-12 cells in hyperoxia was significantly enhanced when either AP-1, p38, or JNK activation was inhibited by either specific inhibitors or dominant negative DNA constructs, indicating that in lung epithelial cells hyperoxia induces a program-driven oncosis, involving AP-1, JNK, and p38 MAPK. Interestingly, hydrogen peroxide-induced oxidative apoptosis of MLE-12 cells, with a shrinking nuclear morphology and activated caspase-3 activity, is also mediated by AP-1, JNK, and p38. Therefore, our data indicate that although they have divergent downstream events, oxidative oncosis and apoptosis share upstream JNK/p38 and AP-1 pathways, which could be used as potential targets for reducing hyperoxic inflammatory lung injury. (C) 2003 Elsevier Inc.
C1 NYU, Sch Med, Royal N Shore Hosp, Dept Surg, Manhasset, NY USA.
   SUNY Stony Brook, Winthrop Univ Hosp, Sch Med, Dept Cardiovasc Thorac Surg, Mineola, NY 11501 USA.
   SUNY Stony Brook, Winthrop Univ Hosp, Sch Med, Dept Med, Mineola, NY 11501 USA.
   Miami Childrens Hosp, Inst Res, Miami, FL USA.
   Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA.
   NCI, Rockville, MD USA.
RP Mantell, LL (reprint author), NYU, Sch Med, N Shore Long Isl Jewish Hlth Syst, N Shore Long Isl Jewish Res Inst, 350 Community Dr, Manhasset, NY 11030 USA.
NR 67
TC 55
Z9 63
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD OCT 15
PY 2003
VL 35
IS 8
BP 978
EP 993
DI 10.1016/S0891-5849(03)00494-5
PG 16
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 730FC
UT WOS:000185817700015
PM 14556862
ER

PT J
AU Kessler, RC
   Demler, O
   Jin, R
   Walters, EE
   Berglund, P
   Koretz, D
   Merikangas, KR
   Rush, AJ
   Wang, PS
AF Kessler, RC
   Demler, O
   Jin, R
   Walters, EE
   Berglund, P
   Koretz, D
   Merikangas, KR
   Rush, AJ
   Wang, PS
TI Treatment of depression by mental health specialists and primary care
   physicians - Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
   Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
   NIH, Div Mental Disorders, Rockville, MD USA.
   NIH, Intramural Res Program, Rockville, MD USA.
   Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
NR 3
TC 0
Z9 0
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 15
PY 2003
VL 290
IS 15
BP 1992
EP 1993
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 732CX
UT WOS:000185924200013
ER

PT J
AU Herce, DH
   Darden, T
   Sagui, C
AF Herce, DH
   Darden, T
   Sagui, C
TI Calculation of ionic charging free energies in simulation systems with
   atomic charges, dipoles, and quadrupoles
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID PARTICLE-MESH EWALD; ELECTROSTATIC POTENTIAL TRUNCATION;
   MOLECULAR-DYNAMICS SIMULATIONS; PERIODIC BOUNDARY-CONDITIONS; AB-INITIO;
   AQUEOUS-SOLUTIONS; WATER-MOLECULES; BROMIDE ION; SOLVATION; HYDRATION
AB The ionic charging free energy is a very sensitive probe for the treatment of electrostatics in any given simulation setting. In this work, we present methods to compute the ionic charging free energy in systems characterized by atomic charges and higher-order multipoles, mainly dipoles and quadrupoles. The results of these methods for periodic boundary conditions and for spherical clusters are then compared. For the treatment of spherical clusters, we introduce a generalization of Gauss' law that links the microscopic variables to the measurable macroscopic electrostatics via a work function. (C) 2003 American Institute of Physics.
C1 N Carolina State Univ, Dept Phys, Raleigh, NC 27606 USA.
   NIEHS, Res Triangle Pk, NC 27709 USA.
RP Herce, DH (reprint author), N Carolina State Univ, Dept Phys, Raleigh, NC 27606 USA.
NR 45
TC 18
Z9 18
U1 0
U2 1
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
   MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD OCT 15
PY 2003
VL 119
IS 15
BP 7621
EP 7632
DI 10.1063/1.1609191
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 728EK
UT WOS:000185703100002
ER

PT J
AU Bishop, MR
AF Bishop, MR
TI The graft-versus-lymphoma effect: Fact, fiction, or opportunity?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID BONE-MARROW-TRANSPLANTATION; HOST DISEASE; LEUKEMIA; PCR
C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NR 11
TC 12
Z9 12
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 15
PY 2003
VL 21
IS 20
BP 3713
EP 3715
DI 10.1200/JCO.2003.05.984
PG 3
WC Oncology
SC Oncology
GA 731VH
UT WOS:000185906800002
PM 12963698
ER

PT J
AU Tomita, S
   Jiang, HB
   Ueno, T
   Takagi, S
   Tohi, K
   Maekawa, S
   Miyatake, A
   Furukawa, A
   Gonzalez, FJ
   Takeda, J
   Ichikawa, Y
   Takahama, Y
AF Tomita, S
   Jiang, HB
   Ueno, T
   Takagi, S
   Tohi, K
   Maekawa, S
   Miyatake, A
   Furukawa, A
   Gonzalez, FJ
   Takeda, J
   Ichikawa, Y
   Takahama, Y
TI T cell-specific disruption of arylhydrocarbon receptor nuclear
   translocator (Arnt) gene causes resistance to
   2,3,7,8-tetrachlorodibenzo-p-dioxin-induced thymic involution
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ARYL-HYDROCARBON RECEPTOR; TISSUE-SPECIFIC EXPRESSION; MESSENGER-RNA
   EXPRESSION; AH DIOXIN RECEPTOR; MICE LACKING; IN-VIVO; (TCDD)-INDUCED
   IMMUNOTOXICITY; TRANSCRIPTION FACTOR; ANCHORED PROTEINS; DEFICIENT MICE
AB The arylhydrocarbon receptor nuclear translocator (ARNT) is a member of the basic helix-loop-helix, PER-ARNT-SIM family of heterodimeric transcription factors, and serves as a dimerization partner for arylhydrocarbon receptor (AHR) and hypoxia-inducible factor-1alpha. To assess the function of ARNT in T cells, we disrupted the Arnt gene specifically in T cells of mice by conditional gene targeting using T cell-specific p56(lck)-Cre (Lck-Cre) transgenic Arnt-floxed mice. Thus generated, T cell-specific Arnt-disrupted mice (Lck-Cre;Arnt(flox/Delta) transgenic mice) exhibited complete loss of the expression of ARNT protein only in T cells, and were viable and appeared normal. The Arnt-disrupted T cells in the thymus were phenotypically and histologically normal. The Arnt-deficient T cells in the spleen were capable of responding to TCR stimulation in vitro. However, unlike normal mice in which exposure to the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an AHR ligand, resulted in thymic involution, the thymus of Lck-Cre;Arnt(flox/Delta) mice were resistant to TCDD treatment in vivo. In contrast, benzo(a)pyrene, another AHR ligand, still caused thymic involution in Lck-Cre;Arnt(flox/Delta) mice. Finally, fetal thymus organ culture using Lck-Cre;Arnt(flox/Delta) and K5-Cre;Arnt(flox/Delta) (epithelial cell-specific Arnt-disrupted mice) showed that thymocytes rather than thymic epithelial cells are predominantly responsible for TCDD-induced thymic atrophy. Our results indicate that ARNT in T lineage cells is essential for TCDD-mediated thymic involution.
C1 Univ Tokushima, Div Expt Immunol, Inst Genome Res, Tokushima 7708503, Japan.
   Kagawa Med Univ, Dept Biochem, Kagawa, Japan.
   Univ Tokushima, Dept Immune Syst Dev, Inst Phys & Chem Res, Res Ctr Allergy & Immunol, Tokushima 7708503, Japan.
   Osaka Univ, Grad Sch Med, Dept Plast Surg, Osaka, Japan.
   Osaka Univ, Dept Social Environm Med, Grad Sch Med, Osaka, Japan.
   NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Tomita, S (reprint author), Univ Tokushima, Div Expt Immunol, Inst Genome Res, 3-18-15 Kuramoto, Tokushima 7708503, Japan.
RI Takahama, Yousuke/A-5863-2010
NR 57
TC 33
Z9 35
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 OCT 15
PY 2003
VL 171
IS 8
BP 4113
EP 4120
PG 8
WC Immunology
SC Immunology
GA 731CC
UT WOS:000185866100027
PM 14530333
ER

PT J
AU Liu, KB
   McDuffie, E
   Abrams, SI
AF Liu, KB
   McDuffie, E
   Abrams, SI
TI Exposure of human primary colon carcinoma cells to anti-Fas interaction
   influences the emergence of pre-existing Fas-resistant metastatic
   subpopulations
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FLICE-INHIBITORY PROTEIN; LIGAND INTERACTIONS; IMMUNE ESCAPE; MEDIATED
   APOPTOSIS; COLORECTAL-CANCER; INTERFERON-GAMMA; TUMOR ESCAPE;
   EXPRESSION; LINES; DEATH
AB Fas, an important death receptor-mediated signaling pathway, has. been shown to be down-regulated during human colon tumorigenesis; however, how alterations in Fas expression influence the metastatic process remains unresolved. In mouse models, loss of Fas function was found to be both necessary and sufficient for tumor progression. In this study, we investigated the link between functional Fas status and malignant phenotype using a matched pair of naturally occurring primary (Fas-sensitive) and metastatic (Fas-resistant) human colon carcinoma cell lines in both in vitro and in vivo (xenograft) settings. Metastatic sublines were produced in vitro from the primary tumor cell line by functional elimination of Fas-responsive cells. Conversely, sublines derived from the primary tumor in vivo at distal metastatic sites were Fas-resistant. In contrast, simply disrupting the Fas pathway by molecular-based strategies in the Fas-sensitive primary tumor failed to achieve the same metastatic outcome. Interestingly, both in vitro- and in vivo-produced sublines resembled the naturally occurring metastatic population, based on functional and morphologic studies and genome-scale gene expression profiling. Overall, using this human colon carcinoma model, we: 1) showed that loss of Fas function was linked to, but alone was insufficient for, acquisition of a detectable metastatic phenotype; 2) demonstrated that metastatic subpopulations pre-existed within the heterogeneous primary tumor, and that anti-Fas interactions served as a selective pressure for their outgrowth; and 3) identified a large set of differentially expressed genes distinguishing the primary from metastatic malignant phenotypes. Thus, Fas-based interactions may represent a novel mechanism for the biologic or immunologic selection of certain types of Fas-resistant neoplastic clones with enhanced metastatic ability.
C1 NCI, Lab Tumor Immunol & Biol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Abrams, SI (reprint author), NCI, Lab Tumor Immunol & Biol, Canc Res Ctr, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA.
OI Liu, Kebin/0000-0003-1965-7240
NR 51
TC 25
Z9 26
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 OCT 15
PY 2003
VL 171
IS 8
BP 4164
EP 4174
PG 11
WC Immunology
SC Immunology
GA 731CC
UT WOS:000185866100033
PM 14530339
ER

PT J
AU Mason, LH
   Willette-Brown, J
   Anderson, SK
   Alvord, WG
   Klabansky, RL
   Young, HA
   Ortaldo, JR
AF Mason, LH
   Willette-Brown, J
   Anderson, SK
   Alvord, WG
   Klabansky, RL
   Young, HA
   Ortaldo, JR
TI Receptor glycosylation regulates Ly-49 binding to MHC class I
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; INHIBITORY RECEPTOR; NK CELLS;
   SIGNAL-TRANSDUCTION; MOLECULES; LIGAND; RECOGNITION; H-2D(D); FAMILY;
   DOMAINS
AB Murine NK cells express the Ly-49 family of class I MHC-binding receptors that control their ability to lyse tumor or virally infected host target cells. X-ray crystallography studies have identified two predominant contact sites (sites 1 and 2) that are involved in the binding of the inhibitory receptor, Ly-49A, to H-2D(d). Ly-49G2 (inhibitory) and Ly-49D (activating) are highly homologous to Ly-49A and also recognize H-2D(d). However, the binding of Ly-49D and G(2) to H-2D(d) is of lower affinity than Ly-49A. All Ly-49s contain N-glycosylation motifs; however, the importance of receptor glycosylation in Ly-49-class I interactions has not been determined. Ly-49D and G(2) contain a glycosylation motif (NTT (221-223)), absent in Ly-49A, adjacent to one of the proposed binding sites for H-2D(d) (site 2). The presence of a complex carbohydrate group at this critical site could interfere with class I binding. In this study, we are able to demonstrate for the first time that Ly-49D binds H-2D(d) in the presence of mouse beta(2)-microglobulin. We also demonstrate that glycosylation of the NTT (221-23) motif of Ly-49D inteferes with, recognition of H-2D(d). Alteration of the Ly-49D-NTT (221-23) motif to abolish glycosylation at this site resulted in enhanced H-2D(d) binding and receptor activation. Furthermore, glycosylation of Ly-49G2 at NTT (221-23) also reduces receptor binding to H-2D(d) tetramers. Therefore, the addition of complex carbohydrates to the Ly-49 family of receptors may represent a mechanism by which NK cells regulate affinity for host class I ligands.
C1 NCI, Expt Immunol Lab, Div Basic Sci, NIH, Frederick, MD 21702 USA.
   Sci Applicat Int Corp Frederick, Basic Res Program, Frederick, MD 21702 USA.
   NCI, Data Management Serv, Frederick, MD 21702 USA.
RP Mason, LH (reprint author), NCI, Expt Immunol Lab, Div Basic Sci, NIH, Bldg 560,Room 31-93, Frederick, MD 21702 USA.
RI Anderson, Stephen/B-1727-2012
OI Anderson, Stephen/0000-0002-7856-4266
FU NCI NIH HHS [N01-CO-12400]
NR 34
TC 15
Z9 15
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 OCT 15
PY 2003
VL 171
IS 8
BP 4235
EP 4242
PG 8
WC Immunology
SC Immunology
GA 731CC
UT WOS:000185866100041
PM 14530347
ER

PT J
AU Lore, K
   Betts, MR
   Brenchley, JM
   Kuruppu, J
   Khojasteh, S
   Perfetto, S
   Roederer, M
   Seder, RA
   Koup, RA
AF Lore, K
   Betts, MR
   Brenchley, JM
   Kuruppu, J
   Khojasteh, S
   Perfetto, S
   Roederer, M
   Seder, RA
   Koup, RA
TI Toll-like receptor ligands modulate dendritic cells to augment
   cytomegalovirus- and HIV-1-specific T cell responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INTERFERON-PRODUCING CELLS; IMMUNE-RESPONSE; CPG OLIGODEOXYNUCLEOTIDES;
   HIV-1 INFECTION; EXPRESSION; SUBSETS; VIRUS; IMMUNODEFICIENCY;
   ADJUVANTS; INDUCTION
AB Optimal Ag targeting and activation of APCs, especially dendritic cells (DCs), are important in vaccine development. In this study, we report the effects of different Toll-like receptor (TLR)-binding compounds to enhance immune responses induced by human APCs, including CD123(+) plasmacytoid DCs (PDCs), CD11c(+) myeloid DCs (MDCs), monocytes, and B cells. PDCs, which express TLR7 and TLR9, responded to imidazoquinolines (imiquimod and R-848) and to CpG oligodeoxynucleotides stimulation, resulting in enhancement in expression of costimulatory molecules and induction of IFN-alpha and IL-12p70. In contrast, MDCs, which express TLR3, TLR4, and TLR7, responded to poly(I:C), LPS, and imidazoquinolines with phenotypic maturation and high production of IL-12 p70 without producing detectable IFN-alpha. Optimally TLR ligand-stimulated PDCs or MDCs exposed to CMV or HIV-1 Ags enhanced autologous CMV- and HIV-1-specific memory T cell responses as measured by effector cytokine production compared with TLR ligand-activated monocytes and B cells or unstimulated PDCs and MDCs. Together, these data show that targeting specific DC subsets using TLR ligands can enhance their ability to activate virus-specific T cells, providing information for the rational design of TLR ligands as adjuvants for vaccines or immune modulating therapy.
C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Lore, K (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40 Room 3612B, Bethesda, MD 20892 USA.
RI Roederer, Mario/G-1887-2011
NR 39
TC 204
Z9 213
U1 2
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2003
VL 171
IS 8
BP 4320
EP 4328
PG 9
WC Immunology
SC Immunology
GA 731CC
UT WOS:000185866100051
PM 14530357
ER

PT J
AU Atasoy, U
   Curry, SL
   de Silanes, IL
   Shyu, AB
   Casolaro, V
   Gorospe, M
   Stellato, C
AF Atasoy, U
   Curry, SL
   de Silanes, IL
   Shyu, AB
   Casolaro, V
   Gorospe, M
   Stellato, C
TI Regulation of eotaxin gene expression by TNF-alpha and IL-4 through mRNA
   stabilization: Involvement of the RNA-binding protein HuR
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; AU-RICH ELEMENTS; T-CELL-ACTIVATION;
   ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; MAMMALIAN-CELLS; IN-VIVO;
   RIBONUCLEOPROTEIN COMPLEXES; AIRWAY HYPERRESPONSIVENESS; DIFFERENTIAL
   REGULATION
AB During inflammatory responses, a major posttranscriptional regulation of early response and inflammatory gene expression occurs through modulation of mRNA turnover. We report that two potent inducers of the CC chemokine eotaxin, TNF-alpha and IL-4, regulate its production in airway epithelial cells by increasing eotaxin mRNA stability. In experiments using the transcriptional inhibitor actinomycin D, eotaxin mRNA half-life was significantly prolonged by cell stimulation with TNF-alpha or IL-4, with the combination of the two cytokines being the most effective in extending the mRNA half-life. Involvement of the eotaxin 3' untranslated region in the mRNA-stabilizing effect was tested by transient transfection of a construct expressing a chimeric transcript carrying a serum-inducible beta-globin reporter linked to the eotaxin 3' untranslated region. The half-life of the chimeric mRNA was markedly increased in cells stimulated with TNF-alpha and IL-4. Evidence that the mRNA-stabilizing protein HuR participated in the cytokine effect was obtained: first, HuR presence in the cytoplasm, believed to be required for HuR-mediated mRNA stabilization, increased in both transformed (BEAS-2B cell line) and primary bronchial epithelial cells following treatment with TNF-alpha and IL-4. Second, endogenous eotaxin mRNA was found to bind to HuR in vivo, as detected by immunoprecipitation of HuR-containing messenger ribonucleoprotein complexes followed by real-time RT-PCR analysis; such association increased after cell treatment with TNF-alpha and IL-4. Third, overexpression of HuR in BEAS-2B cells significantly increased the expression of eotaxin mRNA and protein. Our findings implicate mRNA stabilization in the cytokine-mediated increase in eotaxin expression and strongly suggest a role for HuR in this effect.
C1 Johns Hopkins Univ, Div Clin Immunol & Allergy, Baltimore, MD 21224 USA.
   Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
   NIA, NIH, Baltimore, MD 21224 USA.
   Univ Texas, Hlth Sci Ctr, Sch Med, Houston, TX 77030 USA.
RP Stellato, C (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle,Room 1A 12A, Baltimore, MD 21224 USA.
RI Casolaro, Vincenzo/E-9144-2010; Stellato, Cristiana/P-3001-2015
OI Casolaro, Vincenzo/0000-0001-9810-0488; Stellato,
   Cristiana/0000-0002-1294-8355
FU NIAID NIH HHS [AI44242-01A2, AI 46451-03]
NR 74
TC 81
Z9 83
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 15
PY 2003
VL 171
IS 8
BP 4369
EP 4378
PG 10
WC Immunology
SC Immunology
GA 731CC
UT WOS:000185866100056
PM 14530362
ER

PT J
AU Gieffers, J
   Durling, L
   Ouellette, SP
   Rupp, J
   Maass, M
   Byrne, GI
   Caldwell, HD
   Belland, RJ
AF Gieffers, J
   Durling, L
   Ouellette, SP
   Rupp, J
   Maass, M
   Byrne, GI
   Caldwell, HD
   Belland, RJ
TI Genotypic differences in the Chlamydia pneumoniae tyrP locus related to
   vascular tropism and pathogenicity
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; ENDOVASCULAR PRESENCE; GENOME SEQUENCES; HUMAN
   MONOCYTES; KAPPA-B; INFECTION; ATHEROSCLEROSIS; MODEL; TRACHOMATIS;
   EXPRESSION
AB Chlamydia pneumoniae is an obligate intracellular pathogen that causes respiratory infections and has been associated with cardiovascular disease. We compared respiratory and cardiovascular isolates to find genetic differences associated with pathogenicity. A polymorphic region encoding a tyrosine/tryptophan permease was found to differ between disease isolates. Respiratory strains contained multiple copies of the tyrP gene, and vascular strains contained a single copy. Single-nucleotide polymorphism analysis revealed the duplication to be a phylogenetically old event. Gene amplification was associated with higher mRNA levels and higher uptake of the substrate tyrosine, indicating an amino-acid transport-related phenotype associated with the tyrP genotype. Vascular strains, despite their reduced ability to transport tyrosine, do not appear to have a reduced growth rate in vitro. We hypothesize that the important difference between strains of vascular and respiratory origin may lie in the increased tendency of vascular strains to elicit persistent infection that is triggered by amino-acid starvation.
C1 Med Univ Lubeck, Inst Med Microbiol & Hyg, Lubeck, Germany.
   Univ Tennessee, Dept Mol Sci, Memphis, TN USA.
   NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT USA.
RP Gieffers, J (reprint author), Univ Lubeck, Inst Med Microbiol & Hyg, Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM jens.gieffers@hygiene.ukl.mu-luebeck.de
RI Rupp, Jan/C-8794-2011
FU NHLBI NIH HHS [HL 71735, R01 HL071735]; NIAID NIH HHS [AI-42790, R01
   AI042790]
NR 25
TC 29
Z9 31
U1 0
U2 0
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 OCT 15
PY 2003
VL 188
IS 8
BP 1085
EP 1093
DI 10.1086/378692
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 730VD
UT WOS:000185850100001
PM 14551876
ER

PT J
AU Ma, X
   Reich, RA
   Gonzalez, O
   Pan, X
   Fothergill, AK
   Starke, JR
   Teeter, LD
   Musser, JM
   Graviss, EA
AF Ma, X
   Reich, RA
   Gonzalez, O
   Pan, X
   Fothergill, AK
   Starke, JR
   Teeter, LD
   Musser, JM
   Graviss, EA
TI No evidence for association between the polymorphism in the 3 '
   untranslated region of interleukin-12B and human susceptibility to
   tuberculosis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID LINKAGE DISEQUILIBRIUM; IL12B; GENE; DISEASE
AB Interleukin (IL)-12 plays a pivotal role in cell-mediated immunity to Mycobacterium tuberculosis infection. We tested the association between a biallelic single-nucleotide polymorphism in the 3' untranslated region (UTR) of IL-12B and human susceptibility to tuberculosis (TB), in a population-based case-control study of adult patients with TB from 2 ethnicities, African American and white, and in a family-based transmission/disequilibrium study of 60 informative families with at least 1 pediatric patient with TB and 1 heterozygous parent. Our results suggest that IL-12B 3' UTR has no effect or has a negligible effect on human susceptibility to TB.
C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
   NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Graviss, EA (reprint author), Baylor Coll Med, Dept Pathol 209E, 1 Baylor Plaza, Houston, TX 77030 USA.
FU NIAID NIH HHS [AI-41168]; PHS HHS [N01-A0-02738]
NR 13
TC 27
Z9 30
U1 0
U2 0
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 OCT 15
PY 2003
VL 188
IS 8
BP 1116
EP 1118
DI 10.1086/378674
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 730VD
UT WOS:000185850100005
PM 14551880
ER

PT J
AU Edghill-Smith, Y
   Venzon, D
   Karpova, T
   McNally, J
   Nacsa, J
   Tsai, WP
   Tryniszewska, E
   Moniuszko, M
   Manischewitz, J
   King, LR
   Snodgrass, SJ
   Parrish, J
   Markham, P
   Sowers, M
   Martin, D
   Lewis, MG
   Berzofsky, JA
   Belyakov, IM
   Moss, B
   Tartaglia, J
   Bray, M
   Hirsch, V
   Golding, H
   Franchini, G
AF Edghill-Smith, Y
   Venzon, D
   Karpova, T
   McNally, J
   Nacsa, J
   Tsai, WP
   Tryniszewska, E
   Moniuszko, M
   Manischewitz, J
   King, LR
   Snodgrass, SJ
   Parrish, J
   Markham, P
   Sowers, M
   Martin, D
   Lewis, MG
   Berzofsky, JA
   Belyakov, IM
   Moss, B
   Tartaglia, J
   Bray, M
   Hirsch, V
   Golding, H
   Franchini, G
TI Modeling a safer smallpox vaccination regimen, for human
   immunodeficiency virus type 1-infected patients, in immunocompromised
   Macaques
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID VACCINIA VIRUS; INFECTION; AIDS; RECOMBINANT; THERAPY; COMPLICATIONS;
   PROTECTION; EXPRESSION; CHALLENGE; SIVMAC251
AB We have modeled smallpox vaccination with Dryvax (Wyeth) in rhesus macaques that had depletion of CD4(+) T cells induced by infection with simian immunodeficiency virus or simian/human immunodeficiency virus. Smallpox vaccination induced significantly larger skin lesions in immunocompromised macaques than in healthy macaques. Unexpectedly, "progressive vaccinia" was infrequent. Vaccination of immunocompromised macaques with the genetically-engineered, replication-deficient poxvirus NYVAC, before or after retrovirus infection, was safe and lessened the severity of Dryvax-induced skin lesions. Neutralizing antibodies to vaccinia were induced by NYVAC, even in macaques with severe CD4(+) T cell depletion, and their titers inversely correlated with the time to complete resolution of the skin lesions. Together, these results provide the proof of concept, in macaque models that mirror human immunodeficiency virus type 1 infection, that a prime-boost approach with a highly attenuated poxvirus followed by Dryvax increases the safety of smallpox vaccination, and they highlight the importance of neutralizing antibodies in protection against virulent poxvirus.
C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA.
   NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
   NCI, Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
   NCI, Metab Branch, Bethesda, MD 20892 USA.
   US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA.
   NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
   NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA.
   NIAID, Mol Microbiol Lab, Rockville, MD USA.
   NIAID, Bioqual, Rockville, MD USA.
   Adv BioSci Labs, Kensington, NSW, Australia.
   So Res Inst, Frederick, MD USA.
   Med Acad Bialystok, Dept Pediat 3, Bialystok, Waszyngtona, Poland.
   Aventis Pasteur, Toronto, ON, Canada.
RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA.
RI Venzon, David/B-3078-2008
FU NIAID NIH HHS [N01-AI-15451]
NR 31
TC 23
Z9 24
U1 0
U2 0
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 OCT 15
PY 2003
VL 188
IS 8
BP 1181
EP 1191
DI 10.1086/378518
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 730VD
UT WOS:000185850100014
PM 14551889
ER

PT J
AU Ikemoto, S
AF Ikemoto, S
TI Involvement of the olfactory tubercle in cocaine reward: Intracranial
   self-administration studies
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE reinforcement; conditioned place preference; nucleus accumbens shell;
   core; ventral pallidum; dorsal striatum; procaine; dopamine D-1 and D-2
   receptor antagonists; SCH 23390; raclopride
ID MEDIAL PREFRONTAL CORTEX; CONDITIONED PLACE PREFERENCE;
   BRAIN-STIMULATION REWARD; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS;
   6-HYDROXYDOPAMINE LESIONS; D-AMPHETAMINE; LOCAL-ANESTHETICS; DOPAMINE
   TRANSPORTER; INVIVO MICRODIALYSIS
AB Cocaine has multiple actions and multiple sites of action in the brain. Evidence from pharmacological studies indicates that it is the ability of cocaine to block dopamine uptake and elevate extracellular dopamine concentrations, and thus increase dopaminergic receptor activation, that makes cocaine rewarding. Lesion studies have implicated the nucleus accumbens (the dorsal portion of the "ventral striatum") as the probable site of the rewarding action of the drug. However, the drug is only marginally self-administered into this site. We now report that cocaine (60 or 200 mM in 75 nl/infusion) is readily self-administered into the olfactory tubercle, the most ventral portion of the ventral striatum. Cocaine (200 mM) was self-administered marginally into the accumbens shell but not into the core, dorsal striatum, or ventral pallidum. In addition, cocaine injections (200 mM in 300 nl) into the tubercle but not the shell or ventral pallidum induced conditioned place preference. Rewarding effects of cocaine in the tubercle were blocked by coadministration of dopamine D-1 or D-2 antagonists (1 mM SCH 23390 or 3 mM raclopride) and were not mimicked by injections of the local anesthetic procaine (800 mM). In conclusion, the tubercle plays a critical role in mediating rewarding action of cocaine.
C1 NIDA, Behav Neurosci Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA.
RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
OI Ikemoto, Satoshi/0000-0002-0732-7386
NR 56
TC 116
Z9 117
U1 1
U2 3
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 OCT 15
PY 2003
VL 23
IS 28
BP 9305
EP 9311
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 732LT
UT WOS:000185948100005
PM 14561857
ER

PT J
AU Sans, N
   Vissel, B
   Petralia, RS
   Wang, YX
   Chang, K
   Royle, GA
   Wang, CY
   O'Gorman, S
   Heinemann, SF
   Wenthold, RJ
AF Sans, N
   Vissel, B
   Petralia, RS
   Wang, YX
   Chang, K
   Royle, GA
   Wang, CY
   O'Gorman, S
   Heinemann, SF
   Wenthold, RJ
TI Aberrant formation of glutamate receptor complexes in hippocampal
   neurons of mice lacking the GluR2 AMPA receptor subunit
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE AMPA receptors; assembly; GluR2 knock-out mouse; hippocampus; glutamate
   receptors; immunoprecipitation
ID RAT HIPPOCAMPUS; MESSENGER-RNAS; STOICHIOMETRY; INTERNEURONS;
   TRAFFICKING; EXPRESSION; PROTEINS; CHANNEL; LTP
AB The number and type of receptors present at the postsynaptic membrane determine the response to the neurotransmitter released from the presynaptic terminal. Because most neurons receive multiple and distinct synaptic inputs and contain several different subtypes of receptors stimulated by the same neurotransmitter, the assembly and trafficking of receptors in neurons is a complex process involving many levels of regulation. To investigate the mechanism that neurons use to regulate the assembly of receptor subunits, we studied a GluR2 knock-out mouse. GluR2 is a critical subunit that controls calcium permeability of AMPA receptors and is present in most native AMPA receptors. Our data indicate that in the absence of GluR2, aberrant receptor complexes composed of GluR1 and GluR3 are formed in the hippocampus, and that there is an increased number of homomeric GluR1 and GluR3 receptors. We also show that these homomeric and heteromeric receptors are less efficiently expressed at the synapse. Our results show that GluR2 plays a critical role in controlling the assembly of AMPA receptors, and that the assembly of subunits may reflect the affinity of one subunit for another or the stability of intermediates in the assembly process. Therefore, GluR1 may have a greater preference for GluR2 than it does for GluR3.
C1 Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
   Salk Inst Biol Studies, La Jolla, CA 92037 USA.
   Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia.
RP Sans, N (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bldg 50,Room 4146, Bethesda, MD 20892 USA.
FU PHS HHS [188819]
NR 27
TC 85
Z9 87
U1 0
U2 1
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 OCT 15
PY 2003
VL 23
IS 28
BP 9367
EP 9373
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 732LT
UT WOS:000185948100012
PM 14561864
ER

PT J
AU Montcouquiol, M
   Kelley, MW
AF Montcouquiol, M
   Kelley, MW
TI Planar and vertical signals control cellular differentiation and
   Patterning in the mammalian cochlea
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cochlea; mesenchyme; development; hair cell; inner ear; epithelium
ID EAR HAIR-CELLS; MOUSE INNER-EAR; FATE DETERMINATION; OTIC PLACODE;
   INDUCTION; MATH1; MICE; MATURATION; EXPRESSION; DEAFNESS
AB The sensory epithelium of the mammalian cochlea is composed of a regular mosaic of sensory hair cells and nonsensory supporting cells. During development, differentiation occurs in a gradient that progresses along the axis of the cochlea from base to apex. To begin to identify some of the factors that regulate this developmental process, the potential roles of planar and vertical signals were examined during early stages of cochlear development. We demonstrate roles for both underlying mesenchymal cells and adjacent epithelial cells in the differentiation and patterning of the sensory epithelium, and in particular in the development of mechanosensory hair cells. As development proceeds, the requirements for both planar and vertical signals decrease, and development of the sensory epithelium becomes essentially independent from these cues. Finally, we demonstrate that the temporal gradient of cellular differentiation is not dependent on planar signals within the developing sensory epithelium.
C1 Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA.
RP Montcouquiol, M (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, 5 Res Court, Rockville, MD 20850 USA.
NR 42
TC 75
Z9 81
U1 0
U2 0
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 OCT 15
PY 2003
VL 23
IS 28
BP 9469
EP 9478
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 732LT
UT WOS:000185948100025
PM 14561877
ER

PT J
AU Klein, JP
   Tendi, EA
   Dib-Hajj, SD
   Fields, RD
   Waxman, SG
AF Klein, JP
   Tendi, EA
   Dib-Hajj, SD
   Fields, RD
   Waxman, SG
TI Patterned electrical activity modulates sodium channel expression in
   sensory neurons
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE stimulation; ion channel; activity-dependent plasticity; pain
ID ROOT GANGLION NEURONS; ACTIVITY-DEPENDENT RELEASE; NERVE GROWTH-FACTOR;
   RAT MUSCLE-CELLS; DRG NEURONS; NEUROPATHIC PAIN; GENE-EXPRESSION;
   IN-VIVO; NEUROTROPHIC FACTOR; CARDIAC MYOCYTES
AB Peripheral nerve injury induces changes in the level of gene expression for sodium channels Nav1.3, Nav1.8, and Nav1.9 within dorsal root ganglion (DRG) neurons, which may contribute to the development of hyperexcitability, ectopic neuronal discharge, and neuropathic pain. The mechanism of this change in sodium channel expression is unclear. Decreased availability of neurotrophic factors following axotomy contributes to these changes in gene transcription, but the question of whether changes in intrinsic neuronal activity levels alone can trigger changes in the expression of these sodium channels has not been addressed. We examined the effect of electrical stimulation on the expression of Nav1.3, Nav1.8, and Nav1.9 by using cultured embryonic mouse sensory neurons under conditions in which nerve growth factor (NGF) was not limiting. Expression of Nav1.3 was not significantly changed following stimulation. In contrast, we observed activity-dependent down-regulation of Nav1.8 and Nav1.9 mRNA and protein levels after stimulation, as demonstrated by quantitative polymerase chain reaction and immunocytochemistry. These results show that a change in neuronal activity can alter the expression of sodium channel genes in a subtype-specific manner, via a mechanism independent of NGF withdrawal. (C) 2003 Wiley-Liss, Inc.
C1 Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA.
   Yale Univ, Sch Med, PVA EPVA Ctr Neurosci & Regenerat Res, New Haven, CT 06510 USA.
   VA Connecticut Healthcare Syst, Rehabil Res Ctr, West Haven, CT USA.
   NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD USA.
RP Waxman, SG (reprint author), Yale Univ, Sch Med, Dept Neurol, 333 Cedar St,LCI 707, New Haven, CT 06510 USA.
NR 60
TC 34
Z9 37
U1 1
U2 4
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD OCT 15
PY 2003
VL 74
IS 2
BP 192
EP 198
DI 10.1002/jnr.10768
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 728AK
UT WOS:000185692900003
PM 14515348
ER

PT J
AU Woo, SH
   Soldatov, NM
   Morad, M
AF Woo, SH
   Soldatov, NM
   Morad, M
TI Modulation of Ca2+ signalling in rat atrial myocytes: possible role of
   the alpha(1C) carboxyl terminal
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID VENTRICULAR MYOCYTES; RYANODINE RECEPTORS; CARDIAC MYOCYTES;
   CALCIUM-RELEASE; CA2+-INDUCED INACTIVATION; DIHYDROPYRIDINE RECEPTOR;
   SARCOPLASMIC-RETICULUM; HEART-MUSCLE; CHANNEL; CONTRACTION
AB Ca2+ influx through L-type Ca(v)1.2 (alpha(1C)) Ca2+ channels is a critical step in the activation of cardiac ryanodine receptors (RyRs) and release of Ca2+ via Ca2+-induced Ca2+ release(CICR). The released Ca2+, in turn, is the dominant determinant of inactivation of the Ca2+ current (I-Ca) and termination of release. Although Ca2+ cross-signalling is mediated by high Ca2+ fluxes in the microdomains of alpha(1C)-RyR complexes, I-Ca-gated Ca2+ cross-signalling is surprisingly resistant to intracellular Ca2+ buffering and has steeply voltage-dependent gain, inconsistent with a strict CICR mechanism, suggesting the existence of additional regulatory step(s). To explore the possible regulatory role of the carboxyl (C)-terminal tail of alpha(1C) in modulating Ca2+ signalling, we tested the effects of introducing two alpha(1C) C-terminal peptides, LA (1571-1599) and K (1617-1636) on the central alpha(1C)-unassociated Ca2+-release sites of atrial myocytes, using rapid (240 Hz) two-dimensional confocal Ca2+ imaging. The frequency of spontaneously activating central sparks increased by approximately fourfold on dialysing LA- but not K-peptide into myocytes voltage-clamped at -80 mV. The rate but not the magnitude of caffeine (10 mm)-triggered central Ca2+ release was significantly accelerated by LA- but not K-peptide. Individual Ca2+ spark size and flux were larger in LA- but not in K-peptide-dialysed myocytes. Although LA-peptide did not change the amplitude or inactivation kinetics of I-Ca, LA-peptide did strongly enhance the central Ca2+ transients triggered by I-Ca at -30 mV (small I-Ca) but not at +20 mV (large I-Ca). In contrast, K-peptide had no effect on either I-Ca or the local Ca2+ transients. LA-peptide with a deleted calmodulin-binding region (LM1-peptide) had no significant effects on the central spark frequency but suppressed spontaneous spark frequency in the periphery. Our results indicate that the calmodulin-binding LA motif of the alpha(1C) C-terminal tail may sensitize the RyRs, thereby increasing their open probability and providing for both the voltage-dependence of CICR and the higher frequency of spark occurrence in the periphery of atrial myocytes where the native alpha(1C)-RyR complexes are intact.
C1 Georgetown Univ, Ctr Med, Dept Pharmacol, Washington, DC 20057 USA.
   NIA, NIH, Baltimore, MD 21224 USA.
RP Morad, M (reprint author), Georgetown Univ, Ctr Med, Dept Pharmacol, 3900 Reservoir Rd NW, Washington, DC 20057 USA.
NR 40
TC 24
Z9 24
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD OCT 15
PY 2003
VL 552
IS 2
BP 437
EP 447
DI 10.1113/jphysiol.2003.048330
PG 11
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 739DY
UT WOS:000186328100011
PM 14561827
ER

PT J
AU Engels, EA
   Katki, HA
   Rosenberg, PS
   Frisch, M
AF Engels, EA
   Katki, HA
   Rosenberg, PS
   Frisch, M
TI Re: Cancer incidence in Denmark following exposure to poliovirus vaccine
   contaminated with simian virus 40 - Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD 20892 USA.
   Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, Copenhagen, Denmark.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, 6120 Execut Blvd,EPS 8010, Rockville, MD 20892 USA.
RI Katki, Hormuzd/B-4003-2015; Frisch, Morten/E-9206-2016
OI Frisch, Morten/0000-0002-3864-8860
NR 5
TC 0
Z9 0
U1 0
U2 0
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 OCT 15
PY 2003
VL 95
IS 20
BP 1553
EP 1555
DI 10.1093/jnci/djg086
PG 3
WC Oncology
SC Oncology
GA 732BQ
UT WOS:000185921300021
ER

PT J
AU Leitzmann, MF
   Giovannucci, EL
AF Leitzmann, MF
   Giovannucci, EL
TI Re: Zinc supplement use and risk of prostate cancer - Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID CADMIUM
C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Leitzmann, MF (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS-MSC 7232, Bethesda, MD 20892 USA.
NR 6
TC 0
Z9 1
U1 0
U2 0
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 OCT 15
PY 2003
VL 95
IS 20
BP 1556
EP 1557
DI 10.1093/jnci/djg089
PG 2
WC Oncology
SC Oncology
GA 732BQ
UT WOS:000185921300024
ER

PT J
AU Dagdug, L
   Weiss, GH
AF Dagdug, L
   Weiss, GH
TI Absorptive effects on a parameter used to characterize the region of
   tissue visited by photons in continuous wave measurements
SO OPTICS COMMUNICATIONS
LA English
DT Article
DE optical imaging; photon trajectories
ID ANISOTROPIC RANDOM-WALKS; SCALING RELATIONSHIPS
AB It has been shown that many aspects of photon trajectories in tissue are well described by a lattice random walk model. We take advantage of this to characterize the region interrogated by photons in experiments designed to estimate internal optical parameters from light intensity re-emitted on the interface between tissue and the exterior in continuous-wave measurements. The parameter chosen to characterize the investigated region is the expected number of distinct sites visited by a photon that survives to reach the surface at a specific point. (C) 2003 Elsevier B.V. All rights reserved.
C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Weiss, GH (reprint author), NIH, Ctr Informat Technol, Bldg 12a,Room 2007, Bethesda, MD 20892 USA.
NR 15
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0030-4018
J9 OPT COMMUN
JI Opt. Commun.
PD OCT 15
PY 2003
VL 226
IS 1-6
BP 149
EP 154
DI 10.1016/j.optcom.2003.08.018
PG 6
WC Optics
SC Optics
GA 738QE
UT WOS:000186298700017
ER

PT J
AU Berger, VW
   Ivanova, A
   Knoll, MD
AF Berger, VW
   Ivanova, A
   Knoll, MD
TI Minimizing predictability while retaining balance through the use of
   less restrictive randomization procedures
SO STATISTICS IN MEDICINE
LA English
DT Article
DE allocation concealment; baseline imbalance; chronological bias; clinical
   trials; confounding; randomized block procedure; restricted
   randomization; selection bias
ID CLINICAL-TRIALS; SELECTION BIAS; ALLOCATION
AB The interpretation of between-group comparisons is facilitated by the creation of treatment groups that are similar to each other in baseline composition. To prevent treatment effects from being confounded with time effects, most trials use restricted randomization to force balance. An unintended consequence of these restrictions is that they create patterns that allow for the prediction of future treatment allocations, and hence selection bias, especially in unmasked trials. In fact, the more restrictive the allocation procedure, the greater the potential for selection bias. It was decided, in the context of a recent clinical trial comparing two dosing schedules of paclitaxel and carboplatin for advanced stage IIIB/IV nonsmall-cell lung cancer, that the randomized block procedure could not simultaneously protect sufficiently against both selection and chronological bias. In this paper we detail our development of the maximal procedure. The maximal procedure takes as input the extent of chronological bias allowed by the randomized block procedure, then matches it, but does so with fewer restrictions. This feature makes the maximal procedure more resistant to selection bias than the randomized block procedure is. Published in 2003 by John Wiley Sons, Ltd.
C1 NCI, EPN, Bethesda, MD 20892 USA.
   Univ Maryland, Dept Math & Stat, Baltimore, MD 21250 USA.
   Univ N Carolina, Dept Biostat, Chapel Hill, NC 27514 USA.
   Northwestern Univ, Chicago, IL 60611 USA.
RP Berger, VW (reprint author), NCI, EPN, Suite 3131,6130 Execut Blvd,MSC-7354, Bethesda, MD 20892 USA.
NR 26
TC 87
Z9 87
U1 1
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD OCT 15
PY 2003
VL 22
IS 19
BP 3017
EP 3028
DI 10.1002/sim.1538
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Medicine, Research &
   Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
   Occupational Health; Medical Informatics; Research & Experimental
   Medicine; Mathematics
GA 723VF
UT WOS:000185451700003
PM 12973784
ER

PT J
AU Chan, PC
   Haseman, JK
   Prejean, JD
   Nyska, A
AF Chan, PC
   Haseman, JK
   Prejean, JD
   Nyska, A
TI Toxicity and carcinogenicity of riddelline in rats and mice
SO TOXICOLOGY LETTERS
LA English
DT Article
DE carcinogenicity; riddellime; rats; mice; hemangiosarcoma; arteritis
ID UNSCHEDULED DNA-SYNTHESIS; PYRROLIZIDINE ALKALOID SENECIONINE;
   PETASITES-JAPONICUS MAXIM; ENDOTHELIAL GROWTH-FACTOR; S-PHASE SYNTHESIS;
   ADDUCT FORMATION; INVIVO TREATMENT; HEPATIC-TUMORS; LIVER; CELLS
AB These investigations of riddelliine analyzed potential carcinogenesis and the utility of the female-rat/male-mouse design in bioassays and dose-response. Groups of 50 Fischer rats and B6C3F1 mice were gavage-administered riddelliine 5 days per week for 105 weeks. The dose levels for male rats were 0 or 1.0 mg/kg body weight; female rats 0, 0.01, 0.033 0.1 0.33, or 1.0 mg/kg; male mice 0, 0.1, 0.3, or 1.0, 3.0 mg/kg; and female mice 0 or 3.0 mg/kg. The dose groups were purposely designed to evaluate the dose-response relationship only in female rats and male mice. In rats, liver hemangiosarcoma, hepatocellular adenoma, and mononuclear cell leukemia were significantly increased in the 1.0 mg/kg male and female dose groups. Non-neoplastic lesions occurred in the liver and kidney of male and female rats. In mice, hemangiosarcomas increased significantly in the liver of males in the 3.0 mg/kg dose group. Alveolar/bronchiolar neoplasms in the 3.0 mg/kg dose group of female mice were significantly increased. Hepatocellular neoplasms were significantly decreased in the 1.0 mg/kg dose group of male and 3.0 mg/kg dose groups of male and female mice. Nonneoplastic lesions occurred in the liver and kidney of male and female, and lung and arteries of female mice. These studies demonstrate toxicity and carcinogenicity of riddelliine in rats and mice, and a dose-response relationship in female rats and male mice under the experimental conditions employed. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
C1 NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
   NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
   So Res Inst, Birmingham, AL 35255 USA.
   NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA.
RP Chan, PC (reprint author), NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
NR 52
TC 36
Z9 36
U1 0
U2 1
PU ELSEVIER SCI IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD OCT 15
PY 2003
VL 144
IS 3
BP 295
EP 311
DI 10.1016/S0378-4274(03)00240-6
PG 17
WC Toxicology
SC Toxicology
GA 726BV
UT WOS:000185579000003
PM 12927348
ER

PT J
AU Li, CX
   Liu, J
   Waalkes, MP
   Jaeschke, H
AF Li, CX
   Liu, J
   Waalkes, MP
   Jaeschke, H
TI Gene array analysis of the hepatic response to endotoxin in glutathione
   peroxidase-deficient mice
SO TOXICOLOGY LETTERS
LA English
DT Article
DE endotoxin; Gpx1-/- mice; gene expression; gene array; real-time RT-PCR
ID PARENCHYMAL-CELL APOPTOSIS; MESSENGER-RNA EXPRESSION; KAPPA-B
   ACTIVATION; OXIDATIVE STRESS; SELENIUM DEFICIENCY; LIPID-PEROXIDATION;
   LIVER NECROSIS; UP-REGULATION; REAL-TIME; IN-VIVO
AB Glutathione peroxiclase-1 (Gpx1) is a major defense enzyme against peroxides. Gpx1-deficient mice (Gpx1 -/-) are more susceptible than wild-type (WT) mice to neutrophil-induced oxidant stress and liver injury produced by 700 mg/kg galactosamine and 10 mug/kg endotoxin (Gal/ET). However, it is unclear if Gal/ET modulates redox-sensitive genes in Gpx1 -/- mice before the injury. Hepatic RNA was isolated 1.5 and 6 It after Gal/ET administration and subjected to gene expression analysis using Clontech customer-designed mouse toxicology array (600-gene). Gal/ET induced a significant increase in the expression of genes encoding inflammatory response, oxidative stress, growth arrest and responses to DNA damage and/or its repair. In general, more marked alterations were seen in Gpx1 -/- as compared with WT mice, supporting the role of Gpx1 in cellular defense against oxidant stress to cope with aberrant gene expression. However, comparison with previous functional studies indicated that not all changes of gene expression are relevant for the pathophysiology. Thus, only a combination of gene array analysis with functional studies allows valid conclusions regarding mechanisms of cell injury. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
C1 Univ Arizona, Coll Med, Liver Res Inst, Tucson, AZ 85724 USA.
   NIEHS, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, Res Triangle Pk, NC 27709 USA.
RP Jaeschke, H (reprint author), Univ Arizona, Coll Med, Liver Res Inst, AHSC 24136,1501 N Campbell Ave, Tucson, AZ 85724 USA.
FU NIAAA NIH HHS [AA12916]
NR 33
TC 7
Z9 8
U1 0
U2 1
PU ELSEVIER SCI IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD OCT 15
PY 2003
VL 144
IS 3
BP 397
EP 406
DI 10.1016/S0378-4274(03)00258-3
PG 10
WC Toxicology
SC Toxicology
GA 726BV
UT WOS:000185579000011
PM 12927356
ER

PT J
AU Arbab, AS
   Bashaw, LA
   Miller, BR
   Jordan, EK
   Bulte, JWM
   Frank, JA
AF Arbab, AS
   Bashaw, LA
   Miller, BR
   Jordan, EK
   Bulte, JWM
   Frank, JA
TI Intracytoplasmic tagging of cells with ferumoxides and transfection
   agent for cellular magnetic reisonance imaging after cell
   transplantation: Methods and techniques
SO TRANSPLANTATION
LA English
DT Article
ID SUPERPARAMAGNETIC IRON-OXIDE; MESENCHYMAL STEM-CELLS; IN-VIVO TRACKING;
   RESONANCE TRACKING; CONTRAST AGENTS; DELIVERY; NANOPARTICLES;
   DENDRIMERS; METABOLISM; MIGRATION
AB Background. Superparamagnetic iron oxides (SPIO) are being us ad to label cells for in vivo monitoring by magnetic resonance imaging (MRI). The purpose of this study if; to present protocols using SPIO and a polycationic transfection agent for magnetic labeling of cells as a basis for cellular MRI.
   Methods. Various concentrations of ferumoxides (FE)-poly-L-lysine (PLL) complexes were used to magnetically label cells. Iron incorporation into cells along with c all viability and short- and long-term toxicity were evaluated.
   Results. Rapidly growing cell suspension and adherent cells were effectively labeled by means of endocytosis into endosomes at low concentrations of FE (25 mug/mL media) and PLL (0.75 mug/mL media). Hematopoietic stem cells and lymphocytes required higher concentrations of PLL (1.5 mug/mL) in serum-free media during initial FE-PLL complex formation before labeling the cells: in culture. Total iron concentration in cells depended on the cell type, concentration of FE-PLL complexes in media, cellular density, and incubation time. Iron concentrations after overnight incubation with given FE at 25 mug/ml, media resulted in, for example, T cells being labeled with 1 to 3 pg/cell of intracytoplasmic endosomal iron and 15 to 20 pg/cell of intracytoplasmic iron in mesenchymal stem cells compared with 0.01 to 0.1 pg/cell for unlabeled cells. Protocols developed for this study demonstrated no adverse effect on the cell viability, functional capacity, or toxicity.
   Conclusion: This technique can be used to label cells for in vivo MRI tracking of stem cells and lymphocytes. FE at a concentration of 25 to 50 mug/ml, with a ratio of SPIO to PLL of 1:0.03 to 1:0.06 would be sufficient to label cells for cellular MRI.
C1 NIH, Lab Diagnost Radiol Res, Expt Neuroimaging Sect, Bethesda, MD 20892 USA.
   Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
RP Arbab, AS (reprint author), NIH, Lab Diagnost Radiol Res, Expt Neuroimaging Sect, Bldg 10,Room B1N256, Bethesda, MD 20892 USA.
RI Bulte, Jeff/A-3240-2008; Miller, Bradley/G-7426-2014
OI Bulte, Jeff/0000-0003-1202-1610; 
NR 27
TC 177
Z9 222
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD OCT 15
PY 2003
VL 76
IS 7
BP 1123
EP 1130
DI 10.1097/01.TP.0000089237.39220.83
PG 8
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 733QY
UT WOS:000186013200021
PM 14557764
ER

PT J
AU Creevy, KE
   Bauer, TR
   Tuschong, LM
   Embree, LJ
   Silverstone, AM
   Bacher, JD
   Romines, C
   Garnier, J
   Thomas, ML
   Colenda, L
   Hickstein, DD
AF Creevy, KE
   Bauer, TR
   Tuschong, LM
   Embree, LJ
   Silverstone, AM
   Bacher, JD
   Romines, C
   Garnier, J
   Thomas, ML
   Colenda, L
   Hickstein, DD
TI Mixed chimeric hematopoietic stem cell transplant reverses the disease
   phenotype in canine leukocyte adhesion deficiency
SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
LA English
DT Article
DE adhesion; BMT; CLAD; dog; integrins; LAD
ID MARROW TRANSPLANTATION; P150,95 GLYCOPROTEINS; MONOCLONAL-ANTIBODIES;
   WHITE SETTERS; IRISH RED; DOG; LFA-1; INFECTIONS; MUTATION; MAC-1
AB The genetic disease canine leukocyte adhesion deficiency (CLAD) is characterized by recurrent, severe bacterial infections, typically culminating in death by 6 months of age. CLAD is due to a mutation in the leukocyte integrin CD 18 subunit, which prevents surface expression of the CD11/CD18 leukocyte integrin complex. We demonstrate that stable mixed donor:host hematopoietic chimerism, achieved by a non-myeloablative bone marrow transplant from a histocompatible littermate, reverses the disease phenotype in CLAD. Donor chimerism following the transplant was demonstrated both by flow cytometric detection of donor-derived CD18-positive leukocytes in the peripheral blood of the recipient, and by the demonstration of donor-derived DNA microsatellite repeats in the peripheral blood leukocytes of the recipient. These results indicate that mixed hematopoietic chimerism reverses the clinical phenotype in CLAD and represents a potential therapeutic approach for the human disease leukocyte adhesion deficiency. Published by Elsevier B.V.
C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   NIH, Off Res Serv, Vet Resource Program, Bethesda, MD 20892 USA.
RP Hickstein, DD (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Rm 12C-116,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
NR 20
TC 19
Z9 22
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2427
J9 VET IMMUNOL IMMUNOP
JI Vet. Immunol. Immunopathol.
PD OCT 15
PY 2003
VL 95
IS 3-4
BP 113
EP 121
DI 10.1016/S0165-2427(03)00108-9
PG 9
WC Immunology; Veterinary Sciences
SC Immunology; Veterinary Sciences
GA 725EL
UT WOS:000185530600003
PM 12963272
ER

PT J
AU Cutler, JA
   Thom, T
AF Cutler, JA
   Thom, T
TI Trends in stroke mortality
SO CIRCULATION
LA English
DT Letter
C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Cutler, JA (reprint author), NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD OCT 14
PY 2003
VL 108
IS 15
BP E108
EP E108
DI 10.1161/01.CIR.0000093723.57673.9F
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 731WH
UT WOS:000185909100003
PM 14557347
ER

PT J
AU Berthet, C
   Aleem, E
   Coppola, V
   Tessarollo, L
   Kaldis, P
AF Berthet, C
   Aleem, E
   Coppola, V
   Tessarollo, L
   Kaldis, P
TI Cdk2 knockout mice are viable
SO CURRENT BIOLOGY
LA English
DT Article
ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; DNA-REPLICATION; RETINOBLASTOMA
   PROTEIN; CENTROSOME DUPLICATION; P27(KIP1); PHOSPHORYLATION; LACKING;
   GENE; PROLIFERATION
AB Background: Cyclin-dependent kinases (Cdks) and their cyclin regulatory subunits control cell growth and division. Cdk2/cyclin E complexes are thought to be required because they phosphorylate the retinoblastoma protein and drive cells through the G1/S transition into the S phase of the cell cycle. In addition, Cdk2 associates with cyclin A, which itself is essential for cell proliferation during early embryonic development.
   Results: In order to study the functions of Cdk2 in vivo, we generated Cdk2 knockout mice. Surprisingly, these mice are viable, and therefore Cdk2 is not an essential gene in the mouse. However, Cdk2 is required for germ cell development; both male and female Cdk2(-/-) mice are sterile. Immunoprecipitates of cyclin E1 complexes from Cdk2(-/-) spleen extracts displayed no activity toward histone H1. Cyclin A2 complexes were active in primary mouse embryonic fibroblasts (MEFs), embryo extracts and in spleen extracts from young animals. In contrast, there was little cyclin A2 kinase activity in immortalized MEFs and spleen extracts from adult animals. Cdk2(-/-) MEFs proliferate but enter delayed into S phase. Ectopic expression of Cdk2 in Cdk2(-/-) MEFs rescued the delayed entry into S phase.
   Conclusions: Although Cdk2 is not an essential gene in the mouse, it is required for germ cell development and meiosis. Loss of Cdk2 affects the timing of S phase, suggesting that Cdk2 is involved in regulating progression through the mitotic cell cycle.
C1 NCI, Regulat Cell Growth Lab, Frederick, MD 21702 USA.
   NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
RP Kaldis, P (reprint author), NCI, Regulat Cell Growth Lab, Bldg 560,1050 Boyles St, Frederick, MD 21702 USA.
RI Coppola, Vincenzo/E-2917-2011; Kaldis, Philipp/G-2714-2010; 
OI Coppola, Vincenzo/0000-0001-6163-1779; Kaldis,
   Philipp/0000-0002-7247-7591; Aleem, Eiman/0000-0002-9215-8213
NR 57
TC 428
Z9 440
U1 2
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD OCT 14
PY 2003
VL 13
IS 20
BP 1775
EP 1785
DI 10.1016/j.cub.2003.09.024
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 732LH
UT WOS:000185946500018
PM 14561402
ER

PT J
AU Voller, B
   Sycha, T
   Gustorff, B
   Schmetterer, L
   Lehr, S
   Eichler, HG
   Auff, E
   Schnider, P
AF Voller, B
   Sycha, T
   Gustorff, B
   Schmetterer, L
   Lehr, S
   Eichler, HG
   Auff, E
   Schnider, P
TI A randomized, double-blind, placebo controlled study on analgesic
   effects of botulinum toxin A
SO NEUROLOGY
LA English
DT Article
ID SPASMODIC TORTICOLLIS; EXPERIMENTAL PAIN; HYPERALGESIA; INJECTIONS;
   MECHANISMS; NEURONS; NOCICEPTION; STIMULATION; CAPSAICIN
AB Objective: Botulinum toxin type A (BTXA) is used to treat neurologic disorders associated with increased muscle tone. Its use is often associated with pain relief. Methods: A possible direct analgesic effect of BTXA on C and Adelta fibers was studied on 16 healthy volunteers receiving 30 U BTXA into one forearm and pure saline into the other. To exclude the secondary effect due to muscular tone reduction, BTXA was injected intradermally. Thermal sensory testing of heat pain (threshold and tolerance) and neuroselective current sensory testing of current pain threshold/tolerance were performed at baseline and 3, 14, and 28 days after treatment. Thereafter, on day 28, capsaicin was administered simultaneously into both forearms to evaluate a possible peripheral effect and central effect on pain processing and on the axon reflex flare. Results: The authors observed no significant difference in any of the perception outcome measures between BTXA and placebo pretreated areas. Flare areas as a result of the release of neuropeptides after capsaicin application showed no differences. Conclusions: The results suggest that pain reduction after BTXA treatment is mediated through its effect on muscle tone rather than a direct analgesic effect.
C1 Univ Vienna, Dept Clin Pharmacol, A-1010 Vienna, Austria.
   Univ Vienna, Dept Neurol, A-1010 Vienna, Austria.
   Univ Vienna, Dept Anesthesiol & Gen Intens Care B, A-1010 Vienna, Austria.
   Univ Vienna, Inst Med Phys, A-1010 Vienna, Austria.
   Univ Vienna, Inst Med Stat, A-1010 Vienna, Austria.
RP Voller, B (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA.
OI Voller, Bernhard/0000-0001-5809-874X
NR 33
TC 68
Z9 72
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 14
PY 2003
VL 61
IS 7
BP 940
EP 944
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 731XH
UT WOS:000185911400014
PM 14557564
ER

PT J
AU Eerola, J
   Hernandez, D
   Launes, J
   Hellstrom, O
   Hague, S
   Gulick, C
   Johnson, J
   Peuralinna, T
   Hardy, J
   Tienari, PJ
   Singleton, AB
AF Eerola, J
   Hernandez, D
   Launes, J
   Hellstrom, O
   Hague, S
   Gulick, C
   Johnson, J
   Peuralinna, T
   Hardy, J
   Tienari, PJ
   Singleton, AB
TI Assessment of a DJ-1 (PARK7) polymorphism in Finnish PD
SO NEUROLOGY
LA English
DT Article
ID PARKINSONS-DISEASE; EARLY-ONSET; FAMILIAL AGGREGATION; PROMOTER
AB Mutations in DJ-1 are a cause of autosomal recessive parkinsonism. Polymorphism of genes implicated in hereditary forms of parkinsonism may be a predisposing factor in sporadic Parkinson's disease (PD). The authors analyzed whether a polymorphism (g. 168_ 185del) within exon 1 of DJ-1 contributes to the risk of sporadic PD in a Finnish case-control series. This gene does not play a major role in the genetic predisposition to PD in this population.
C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
   Univ Helsinki, Neurosci Programme, Biomedicum, Helsinki, Finland.
   Seinajoki Cent Hosp, Dept Neurol, Seinajoki, Finland.
RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10 Room 6C103,9000 Rockville Pike, Bethesda, MD 20892 USA.
RI Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009; Tienari,
   Pentti/A-4893-2012; Hardy, John/C-2451-2009; 
OI Launes, Jyrki/0000-0002-3477-398X
NR 8
TC 23
Z9 27
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD OCT 14
PY 2003
VL 61
IS 7
BP 1000
EP 1002
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 731XH
UT WOS:000185911400030
PM 14557580
ER

PT J
AU Rein, A
AF Rein, A
TI Genetic footprinting of a retroviral Gag gene suggests an important role
   in virus replication
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Editorial Material
ID MURINE LEUKEMIA-VIRUS; EARLY EVENTS; PROTEIN; CORE; CELLS; DNA; DOMAINS;
   MUTANTS
C1 NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Rein, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA.
NR 24
TC 1
Z9 1
U1 0
U2 0
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2003
VL 100
IS 21
BP 11929
EP 11930
DI 10.1073/pnas.2135539100
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 733WU
UT WOS:000186024300002
PM 14530396
ER

PT J
AU Sadqi, M
   Lapidus, LJ
   Munoz, V
AF Sadqi, M
   Lapidus, LJ
   Munoz, V
TI How fast is protein hydrophobic collapse?
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID ENERGY LANDSCAPE; FOLDING KINETICS; DENATURED STATE; DIFFUSION;
   DYNAMICS; PATHWAYS; DOMAIN; SPECTROSCOPY; PERSPECTIVE; SIMULATION
AB One of the most recurring questions in protein folding refers to the interplay between formation of secondary structure and hydrophobic collapse. In contrast with secondary structure, it is hard to isolate hydrophobic collapse from other folding events. We have directly measured the dynamics of protein hydrophobic collapse in the absence of competing processes. Collapse was triggered with laser-induced temperature jumps in the acid-denatured form of a simple protein and monitored by fluorescence resonance energy transfer between probes placed at the protein ends. The relaxation time for hydrophobic collapse is only approximate to60 ns at 305 K, even faster than secondary structure formation. At higher temperatures, as the protein becomes increasingly compact by a stronger hydrophobic force, we observe a slowdown of the dynamics of collapse. This dynamic hydrophobic effect is a high-temperature analogue of the dynamic glass transition predicted by theory. Our results indicate that in physiological conditions many proteins will initiate folding by collapsing to an unstructured globule. Local motions will presumably drive the following search for native structure in the collapsed globule.
C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
   Univ Maryland, Ctr Biomol Struct & Org, College Pk, MD 20742 USA.
   NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Munoz, V (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
NR 44
TC 140
Z9 140
U1 2
U2 22
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2003
VL 100
IS 21
BP 12117
EP 12122
DI 10.1073/pnas.2033863100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 733WU
UT WOS:000186024300036
PM 14530404
ER

PT J
AU Kyng, KJ
   May, A
   Kolvraa, S
   Bohr, VA
AF Kyng, KJ
   May, A
   Kolvraa, S
   Bohr, VA
TI Gene expression profiling in Werner syndrome closely resembles that of
   normal aging
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID REPLICATIVE SENESCENCE; CALORIC RESTRICTION; OXIDATIVE STRESS; SYNDROME
   PROTEIN; DNA-REPAIR; TRANSCRIPTION; RNA; HELICASE; PRODUCT; MICE
AB Werner syndrome (WS) is a premature aging disorder, displaying defects in DNA replication, recombination, repair, and transcription. It has been hypothesized that several WS phenotypes are secondary consequences of aberrant gene expression and that a transcription defect may be crucial to the development of the syndrome. We used cDNA microarrays to characterize the expression of 6,912 genes and ESTs across a panel of 15 primary human fibroblast cell lines derived from young donors, old donors, and WS patients. Of the analyzed genes, 6.3% displayed significant differences in expression when either WS or old donor cells were compared with young donor cells. This result demonstrates that the WS transcription defect is specific to certain genes. Transcription alterations in WS were strikingly similar to those in normal aging: 91% of annotated genes displayed similar expression changes in WS and in normal aging, 3% were unique to WS, and 6% were unique to normal aging. We propose that a defect in the transcription of the genes as identified in this study could produce many of the complex clinical features of WS. The remarkable similarity between WS and normal aging suggests that WS causes the acceleration of a normal aging mechanism. This finding supports the use of WS as an aging model and implies that the transcription alterations common to WS and normal aging represent general events in the aging process.
C1 NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, Baltimore, MD 21224 USA.
   Aarhus Univ, Dept Human Genet, DK-8000 Aarhus C, Denmark.
RP Bohr, VA (reprint author), NIA, Gerontol Res Ctr, Mol Genet Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
OI Kyng, Kasper Jacobsen/0000-0001-7940-1656
NR 40
TC 105
Z9 108
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2003
VL 100
IS 21
BP 12259
EP 12264
DI 10.1073/pnas.2130723100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 733WU
UT WOS:000186024300060
PM 14527998
ER

PT J
AU Lohning, M
   Richter, A
   Stamm, T
   Hu-Li, J
   Assenmacher, M
   Paul, WE
   Radbruch, A
AF Lohning, M
   Richter, A
   Stamm, T
   Hu-Li, J
   Assenmacher, M
   Paul, WE
   Radbruch, A
TI Establishment of memory for IL-10 expression in developing T helper 2
   cells requires repetitive IL-4 costimulation and does not impair
   proliferation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID T-HELPER LYMPHOCYTES; IFN-GAMMA; IN-VIVO; INTERFERON-GAMMA;
   INTERLEUKIN-10; ANTIGEN; DIFFERENTIATION; GENE; ACTIVATION; INDUCTION
AB T helper (Th) lymphocytes can develop memory for the expression of particular cytokines, like IL-4 or IL-10, in that reexpression of those cytokines is independent of the original costimulatory signal IL-4 and depends only on T cell receptor stimulation. Here, we show that in the course of Th2 cell differentiation in vitro, IL-4 memory is established during primary activation of naive Th cells, whereas the establishment of IL-10 memory requires repetitive stimulation of the Th cell with IL-4 and T cell receptor. Likewise, established IL-10 memory, maintained in the absence of further IL-4 signals, was observed in individual IL-10-producing cells generated from in vivo antigen-experienced CD62L(low) Th cells and isolated by using the newly developed cytometric cytokine secretion assay for IL-10. In naive Th cells undergoing primary activation, the induction of both IL-4 and IL-10 memory requires DNA synthesis, but reexpression of the cytokine genes can occur throughout cell cycle. In in vitro polarized Th2 cell populations, Th cells with IL-4 or IL-10 memory do not differ in proliferative behavior. Populations of Th cells isolated from polarized Th2 cultures according to expression of IL-4 or IL-10 also do not differ in proliferative behavior. Their proliferation mainly depends on IL-2. Thus, effector memory Th lymphocytes with memory for IL-4 or IL-10 expression are not intrinsically impaired in their proliferative potential and can play an essential role in reactive immunological memory and its regulation.
C1 Deutsch Rheumaforschungzentrum, D-10117 Berlin, Germany.
   Miltenyi Biotec, D-51429 Bergisch Gladbach, Germany.
   NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Lohning, M (reprint author), Deutsch Rheumaforschungzentrum, Schumannstr 21-22, D-10117 Berlin, Germany.
NR 39
TC 24
Z9 24
U1 0
U2 0
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2003
VL 100
IS 21
BP 12307
EP 12312
DI 10.1073/pnas.2035254100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 733WU
UT WOS:000186024300068
PM 14514890
ER

PT J
AU Oh, H
   Bradfute, SB
   Gallardo, TD
   Nakamura, T
   Gaussin, V
   Mishina, Y
   Pocius, J
   Michael, LH
   Behringer, RR
   Garry, DJ
   Entman, ML
   Schneider, MD
AF Oh, H
   Bradfute, SB
   Gallardo, TD
   Nakamura, T
   Gaussin, V
   Mishina, Y
   Pocius, J
   Michael, LH
   Behringer, RR
   Garry, DJ
   Entman, ML
   Schneider, MD
TI Cardiac progenitor cells from adult myocardium: Homing, differentiation,
   and fusion after infarction
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW CELLS; SIDE POPULATION CELLS;
   IN-VIVO; SKELETAL-MUSCLE; TRANSPLANTATION; CARDIOMYOCYTES; MYOCYTES;
   REGENERATION; EXPRESSION
AB Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure. Whether cardiac progenitors exist in adult myocardium itself is unanswered, as is the question whether undifferentiated cardiac precursor cells merely fuse with preexisting myocytes. Here we report the existence of adult heart-derived cardiac progenitor cells expressing stem cell antigen-1. Initially, the cells express neither cardiac structural genes nor Nkx2.5 but differentiate in vitro in response to 5'-azacytidine, in part depending on Bmpr1a, a receptor for bone morphogenetic proteins. Given intravenously after ischemia/reperfusion, cardiac stem cell antigen 1 cells home to injured myocardium. By using a Cre/Lox donor/ recipient pair (alphaMHC-Cre/R26R), differentiation was shown to occur roughly equally, with and without fusion to host cells.
C1 Baylor Coll Med, Ctr Cardiovasc Dev, Houston, TX 77030 USA.
   Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
   Baylor Coll Med, Debakey Heart Ctr, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Physiol & Mol Biophys, Houston, TX 77030 USA.
   Univ Texas, SW Med Ctr, Dept Med, Dallas, TX 75390 USA.
   Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA.
   NIEHS, Res Triangle Pk, NC 27709 USA.
   Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Schneider, MD (reprint author), Baylor Coll Med, Ctr Cardiovasc Dev, Houston, TX 77030 USA.
OI Schneider, Michael/0000-0001-9645-1938
NR 37
TC 1066
Z9 1138
U1 7
U2 41
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2003
VL 100
IS 21
BP 12313
EP 12318
DI 10.1073/pnas.2132126100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 733WU
UT WOS:000186024300069
PM 14530411
ER

PT J
AU Khan, QA
   Kohlhagen, G
   Marshall, R
   Austin, CA
   Kalena, GP
   Kroth, H
   Sayer, JM
   Jerina, DM
   Pommier, Y
AF Khan, QA
   Kohlhagen, G
   Marshall, R
   Austin, CA
   Kalena, GP
   Kroth, H
   Sayer, JM
   Jerina, DM
   Pommier, Y
TI Position-specific trapping of topoisomerase II by benzo[a]pyrene diol
   epoxide adducts: Implications for interactions with intercalating
   anticancer agents
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID DNA CLEAVAGE COMPLEXES; DEOXYGUANOSINE ADDUCTS; MINOR-GROOVE; MECHANISM;
   SEQUENCE; DRUGS; ENZYME; BENZO<A>PYRENE; DUPLEX; SITES
AB DNA topoisomerase II (Top2) is the target of some of the most effective anticancer DNA intercalators. To determine the effect of intercalating ligands at defined positions relative to a known DNA cleavage site for human Top2alpha, we synthesized oligodeoxynucleotides containing single trans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide (DE) deoxyadenosine (dA) adducts of known absolute configuration, placed at specific positions in a duplex sequence containing staggered Top2 cleavage sites on both strands. Because the orientations of the intercalated hydrocarbon are known from NMR solution structures of duplex oligonucleotides containing these dA adducts, a detailed analysis of the relationship between the position of intercalation and trapping of Top2 is possible. Our findings demonstrate that (i) Top2 cleavage complexes are trapped by intercalation of the hydrocarbon at either of the staggered cleavage sites or immediately adjacent to the base pairs flanking the cleavage sites within the stagger; (ii) both concerted and nonconcerted cleavage by both subunits of a Top2 homodimer were detected depending on the position of the benzo[a]pyrene DE dA adduct; and (iii) intercalation immediately outside of the staggered Top2 cleavage site, and to a lesser extent in the middle of the stagger, prevents Top2 from cleaving DNA at this site, consistent with the effect of some intercalators as suppressors of Top2-mediated DNA cleavage. These results identify specific binding sites for intercalators that result in trapping of Top2. Such poisoning of Top2 by bulky polycyclic aromatic hydrocarbon DE adducts constitutes a potential mechanism for their carcinogenic activity.
C1 NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
   NIDDKD, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Univ Newcastle Upon Tyne, Sch Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
RP Pommier, Y (reprint author), NCI, Ctr Canc Res, Mol Pharmacol Lab, Bldg 37,Room 5068, Bethesda, MD 20892 USA.
NR 45
TC 29
Z9 32
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 14
PY 2003
VL 100
IS 21
BP 12498
EP 12503
DI 10.1073/pnas.2032456100
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 733WU
UT WOS:000186024300100
PM 14523238
ER

PT J
AU Fernandez-Capetillo, O
   Liebe, B
   Scherthan, H
   Nussenzweig, A
AF Fernandez-Capetillo, O
   Liebe, B
   Scherthan, H
   Nussenzweig, A
TI H2AX regulates meiotic telomere clustering
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
DE DNA repair; genomic instability; meiosis; ATM; spermatocyte
ID HISTONE H2AX; GENOMIC INSTABILITY; LENGTH DYNAMICS; MOUSE; ATM; MICE;
   PROPHASE; RECOMBINATION; INACTIVATION; DYSFUNCTION
AB T he histone H2A variant H2AX is phosphorylated in response to DNA double-strand breaks originating from diverse origins, including dysfunctional telomeres. Here, we show that normal mitotic telomere maintenance does not require H2AX. Moreover, H2AX is dispensable for the chromosome fusions arising from either critically shortened or deprotected telomeres. However, H2AX has an essential role in controlling the proper topological distribution of telomeres during meiotic prophase 1. Our results suggest that H2AX is a downstream effector of the ataxia telangiectasia-mutated kinase in controlling telomere movement during meiosis.
C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
   Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Fernandez-Capetillo, Oscar/H-3508-2015
OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885
NR 36
TC 37
Z9 39
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 13
PY 2003
VL 163
IS 1
BP 15
EP 20
DI 10.1083/jcb.200305124
PG 6
WC Cell Biology
SC Cell Biology
GA 732QJ
UT WOS:000185956800001
PM 14530383
ER

PT J
AU Sigurdson, AJ
   Jones, IM
AF Sigurdson, AJ
   Jones, IM
TI Second cancers after radiotherapy: any evidence for radiation-induced
   genomic instability?
SO ONCOGENE
LA English
DT Article
DE second primary cancer; radiation therapy; genomic instability;
   chromosomal instability; review
ID DNA-REPAIR GENES; THERAPY-RELATED LEUKEMIA; HODGKINS-DISEASE;
   IONIZING-RADIATION; LUNG-CANCER; P53 MUTATIONS; SOLID TUMORS;
   MICROSATELLITE INSTABILITY; CHROMOSOMAL-ABERRATIONS; MARROW
   TRANSPLANTATION
AB Do second primary cancers in humans arise from radiation-induced somatic genomic instability after radiotherapy for the first malignancy? The amount of truly pertinent human information on this issue is sparse, leading to the conclusion that we cannot confirm or refute that instability induction by radiation is involved. However, the in vitro findings of radiation-induced genomic instability through bystander effects or increased mutation rates in cell progeny of apparently normal but irradiated cells are provocative and their transferability to human in vivo biology deserves further investigation. We describe possible animal and human studies to stimulate ideas, but the collaborative commitment of multiple large institutions to tumor tissue procurement and retrieval will be essential. In addition, detecting the temporal progression of genomic instability and identifying the salient genetic events as being radiation-induced will be pivotal. Execution of some of the studies suggested is not possible now, but applying next-generation methods could bring the concepts to fruition. As nearly one in 10 cancer diagnoses are second (or higher) malignancies, it is important to understand the contribution of radiotherapy to second cancer induction and pursue well-coordinated efforts to determine the role of induced genomic instability.
C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
   Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94551 USA.
RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7092,MSC 7238, Bethesda, MD 20892 USA.
NR 61
TC 34
Z9 36
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 13
PY 2003
VL 22
IS 45
BP 7018
EP 7027
DI 10.1038/sj.onc.1206989
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 731UB
UT WOS:000185903900006
PM 14557806
ER

PT J
AU Karev, GP
   Wolf, YI
   Koonin, EV
AF Karev, GP
   Wolf, YI
   Koonin, EV
TI Simple stochastic birth and death models of genome evolution: was there
   enough time for us to evolve?
SO BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT International Conference in Bioinformatics
CY NOV 13-16, 2003
CL ATLANTA, GEORGIA
ID PROTEIN-INTERACTION NETWORKS; FAMILY; UNIVERSE; GENES
AB Motivation: The distributions of many genome-associated quantities, including the membership of paralogous gene families can be approximated with power laws. We are interested in developing mathematical models of genome evolution that adequately account for the shape of these distributions and describe the evolutionary dynamics of their formation.
   Results: We show that simple stochastic models of genome evolution lead to power-law asymptotics of protein domain family size distribution. These models, called Birth, Death and Innovation Models (BDIM), represent a special class of balanced birth-and-death processes, in which domain duplication and deletion rates are asymptotically equal up to the second order. The simplest, linear BDIM shows an excellent fit to the observed distributions of domain family size in diverse prokaryotic and eukaryotic genomes. However, the stochastic version of the linear BDIM explored here predicts that the actual size of large paralogous families is reached on an unrealistically long timescale. We show that introduction of non-linearity, which might be interpreted as interaction of a particular order between individual family members, allows the model to achieve genome evolution rates that are much better compatible with the current estimates of the rates of individual duplication/loss events.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
NR 31
TC 36
Z9 37
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD OCT 12
PY 2003
VL 19
IS 15
BP 1889
EP 1900
DI 10.1093/bioinformatics/btg351
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 736PJ
UT WOS:000186179000005
PM 14555621
ER

PT J
AU Zhao, YD
   Pinilla, C
   Valmori, D
   Martin, R
   Simon, R
AF Zhao, YD
   Pinilla, C
   Valmori, D
   Martin, R
   Simon, R
TI Application of support vector machines for T-cell epitopes prediction
SO BIOINFORMATICS
LA English
DT Article
ID ARTIFICIAL NEURAL-NETWORK; BINDING PEPTIDES; CLASS-I; ANTIGENIC PEPTIDE;
   PROTEIN ANTIGENS; EXPRESSION DATA; AMINO-ACIDS; CLASSIFICATION;
   SEQUENCES; MATRICES
AB Motivation: The T-cell receptor, a major histocompatibility complex (MHC) molecule, and a bound antigenic peptide, play major roles in the process of anti gen-specific T-cell activation. T-cell recognition was long considered exquisitely specific. Recent data also indicate that it is highly flexible, and one receptor may recognize thousands of different pepticles. Deciphering the patterns of pepticles that elicit a MHC restricted T-cell response is critical for vaccine development.
   Results: For the first time we develop a support vector machine (SVM) for T-cell epitope prediction with an MHC type I restricted T-cell clone. Using cross-validation, we demonstrate that SVMs can be trained on relatively small data sets to provide prediction more accurate than those based on previously published methods or on MHC binding.
C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.
   Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA.
   CHU Vaudois, Ludwig Inst Canc Res, Div Clin Oncoimmunol, CH-1011 Lausanne, Switzerland.
   Natl Inst Neurol Disorder & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.
RI Valmori, Danila/K-2439-2015
NR 40
TC 95
Z9 102
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD OCT 12
PY 2003
VL 19
IS 15
BP 1978
EP 1984
DI 10.1093/bioinformatics/btg255
PG 7
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 736PJ
UT WOS:000186179000016
PM 14555632
ER

PT J
AU Taha, TE
   Kumwenda, NI
   Gibbons, A
   Broadhead, RL
   Fiscus, S
   Lema, V
   Liomba, G
   Nkhoma, C
   Miotti, PG
   Hoover, DR
AF Taha, TE
   Kumwenda, NI
   Gibbons, A
   Broadhead, RL
   Fiscus, S
   Lema, V
   Liomba, G
   Nkhoma, C
   Miotti, PG
   Hoover, DR
TI Short postexposure prophylaxis in newborn babies to reduce
   mother-to-child transmission of HIV-1: NVAZ randomised clinical trial
SO LANCET
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL PROPHYLAXIS; VERTICAL
   TRANSMISSION; ORAL ZIDOVUDINE; COTE-DIVOIRE; DOUBLE-BLIND; NEVIRAPINE;
   EFFICACY; AFRICA; INTRAPARTUM
AB Background In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone.
   Methods We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6-8 weeks. Primary outcome was HIV infection in babies at 6-8 weeks in those not infected at birth. Analysis was by intention to treat.
   Findings The overall rate of mother-to-child transmission at 6-8 weeks was 15.3% in 484 babies who received nevirapine and zidovudine and 20.9% in 468 babies who received nevirapine only (p=0.03). At 6-8 weeks, in babies who were HIV negative at birth, 34 (7-7%) babies who had nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were infected (p=0.03 -a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups.
   Interpretation Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.
C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
   Univ Malawi, Coll Med, Blantyre, Malawi.
   Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA.
   Johns Hopkins Univ, Blantyre, Malawi.
   Coll Med, Blantyre, Malawi.
   Minist Hlth Res Project, Blantyre, Malawi.
   NIH, Off AIDS Res, Bethesda, MD 20892 USA.
   Rutgers State Univ, Dept Stat, Piscataway, NJ USA.
   Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA.
RP Taha, TE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E7138, Baltimore, MD 21205 USA.
FU FIC NIH HHS [5R03TW01199]
NR 21
TC 129
Z9 133
U1 0
U2 2
PU LANCET LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0140-6736
J9 LANCET
JI Lancet
PD OCT 11
PY 2003
VL 362
IS 9391
BP 1171
EP 1177
DI 10.1016/S0140-6736(03)14538-2
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 732CW
UT WOS:000185924100007
PM 14568737
ER

PT J
AU Hayes, DM
   Braud, S
   Hurtado, DE
   McCallum, J
   Standley, S
   Isaac, JTR
   Roche, KW
AF Hayes, DM
   Braud, S
   Hurtado, DE
   McCallum, J
   Standley, S
   Isaac, JTR
   Roche, KW
TI Trafficking and surface expression of the glutamate receptor subunit,
   KA2
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
ID ER RETENTION SIGNAL; PRESYNAPTIC KAINATE RECEPTORS;
   ENDOPLASMIC-RETICULUM; SYNAPTIC-TRANSMISSION; NMDA; PLASTICITY;
   HIPPOCAMPUS; AMPA; DETERMINANTS; ACTIVATION
AB Kainate receptors are a class of ionotropic glutamate receptors that are widely expressed in the mammalian brain, yet little is known about their physiological role or the mechanisms by which they are regulated. Kainate receptors are composed of multiple subunits (GluR5-7; KA1-2), which can combine to form homomeric or heteromeric channels. While the kainate receptor subunit KA2 can combine with GluR5-7 to form heteromeric channels, it does not form functional homomeric channels when expressed alone. In an attempt to identify the molecular mechanisms for this, we have characterized the trafficking and surface expression of KA2. We find that KA2 alone does not traffic to the plasma membrane and is retained in the endoplasmic reticulum (ER). In contrast, co-expression with GluR6 disrupts ER-retention of KA2 and allows plasma membrane expression. Using a chimeric reporter protein we have identified an ER-retention motif within the KA2 cytosolic domain. Recent studies have identified a consensus ER-retention motif (RRR) that is contained within both the NMDA receptor NR1 subunit and K+ channels. While KA2 contains a similar stretch of amino acids within its C-terminus (RRRRR), unlike the NR1 motif, disruption of this motif with alternating glutamic acid residues does not disrupt ER-retention of KA2, suggesting a unique mechanism regulating KA2 surface expression. Published by Elsevier Inc.
C1 NINDS, Receptor Biol Unit, NIH, Bethesda, MD 20892 USA.
   Univ Bristol, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England.
   Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Roche, KW (reprint author), NINDS, Receptor Biol Unit, NIH, Bethesda, MD 20892 USA.
OI Roche, Katherine/0000-0001-7282-6539
NR 32
TC 17
Z9 17
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 10
PY 2003
VL 310
IS 1
BP 8
EP 13
DI 10.1016/j.bbrc.2003.08.115
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 730MX
UT WOS:000185835500002
PM 14511640
ER

PT J
AU Burnett, JC
   Schmidt, JJ
   Stafford, RG
   Panchal, RG
   Nguyen, TL
   Hermone, AR
   Vennerstrom, JL
   McGrath, CF
   Lane, DJ
   Sausville, EA
   Zaharevitz, DW
   Gussio, R
   Bavari, S
AF Burnett, JC
   Schmidt, JJ
   Stafford, RG
   Panchal, RG
   Nguyen, TL
   Hermone, AR
   Vennerstrom, JL
   McGrath, CF
   Lane, DJ
   Sausville, EA
   Zaharevitz, DW
   Gussio, R
   Bavari, S
TI Novel small molecule inhibitors of botulinum neurotoxin A
   metalloprotease activity
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE bioterrorism; botulinum neurotoxin; drug discovery; high-throughput
   screen; inhibitors; molecular modeling; pharmacophore; three-dimensional
   database search; metalloprotease
ID SEROTYPE-A; ANCISTROCLADUS-KORUPENSIS; NEUROTRANSMITTER RELEASE;
   PROTEOLYTIC ACTIVITY; TOXIN; VAMP/SYNAPTOBREVIN; MICHELLAMINES;
   BISQUINOLINES; ANTAGONISTS; MANAGEMENT
AB Botulinum neurotoxins (BoNTs) are among the most lethal biological substances to have been weaponized and are listed as biodefense category A agents. Currently, no small molecule (non-peptidic) therapeutics exist to counter this threat; hence, identifying and developing compounds that inhibit BoNTs is a high priority. In the present study, a high-throughput assay was used to identify small molecules that inhibit the metalloprotease activity of BoNT serotype A light chain (BoNT/A LC). All inhibitors were further verified using a HPLC-based assay. Conformational analyses of these compounds, in conjunction with molecular docking studies, were used to predict structural features that contribute to inhibitor binding and potency. Based on these results, a common pharmacophore for BoNT/A LC inhibitors is proposed. This is the first study to report small molecules (non-peptidics) that inhibit BoNT/A LC metalloprotease activity in the low muM range. (C) 2003 Elsevier Inc. All rights reserved.
C1 NCI, Dev Therapeut Program, Frederick, MD 21702 USA.
   USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
   Univ Nebraska, Med Ctr, Coll Pharm, Omaha, NE 68198 USA.
RP Gussio, R (reprint author), NCI, Dev Therapeut Program, Frederick, MD 21702 USA.
NR 34
TC 67
Z9 70
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 10
PY 2003
VL 310
IS 1
BP 84
EP 93
DI 10.1016/j.bbrc.2003.08.112
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 730MX
UT WOS:000185835500014
PM 14511652
ER

PT J
AU Nahm, DH
   Tkaczyk, C
   Fukuishi, N
   Colucci-Guyon, E
   Gilfillan, AM
   Metcalfe, DD
AF Nahm, DH
   Tkaczyk, C
   Fukuishi, N
   Colucci-Guyon, E
   Gilfillan, AM
   Metcalfe, DD
TI Identification of Fyn-binding proteins in MC/9 mast cells using mass
   spectrometry
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Fyn; mast cell; signaling; protein; mass spectrometry
ID TYROSINE PHOSPHORYLATION; UP-REGULATION; SH3 DOMAIN; ACTIVATION; RI;
   KINASE; DEGRANULATION; PROTEOMICS; RECEPTOR
AB Fyn is a Src kinase known to have an essential role in mast cell degranulation induced following aggregation of the high affinity IgE-receptor. Although Fyn possesses SH2 and SH3 protein binding domains, the molecules that interact with Fyn have not been characterized in mast cells. We thus analyzed Fyn-binding proteins in MC/9 mast cells to explore the Fyn-mediated signaling pathway. On mass spectrometric analysis of proteins binding to the SH2 and SH3 domains of Fyn, we identified six proteins that bind to Fyn including vimentin, pyruvate kinase, p62 ras-GAP associated phosphoprotein, SLP-76, HS-1, and FYB. Among these proteins, vimentin and pyruvate kinase have not been shown to bind to Fyn. After IgE-receptor mediated stimulation, binding of vimentin to Fyn was increased; and this interaction was via binding to the SH2, but not the SH3, domain of Fyn. Mast cells from vimentin-deficient mice showed enhanced mediator release and tyrosine phosphorylation of intracellular proteins including NTAL and LAT. The observation that vimentin and pyruvate kinase bind to Fyn provides additional insight into Fyn-mediated signaling pathways, and suggests a critical role for Fyn in mast cell degranulation in interacting with both cytosolic and structural proteins. Published by Elsevier Inc.
C1 NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA.
   Inst Curie, Sect Rech, Lab Dynam Cytosquelette & Membrane, CNRS,UMR 144, F-75248 Paris 05, France.
RP Gilfillan, AM (reprint author), NIAID, NIH, Lab Allerg Dis, Bldg 10,Room 11C206,10 Ctr Dr, Bethesda, MD 20892 USA.
NR 27
TC 11
Z9 11
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD OCT 10
PY 2003
VL 310
IS 1
BP 202
EP 208
DI 10.1016/j.bbrc.2003.08.132
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 730MX
UT WOS:000185835500033
PM 14511671
ER

PT J
AU Makarova, KS
   Koonin, EV
AF Makarova, KS
   Koonin, EV
TI Filling a gap in the central metabolism of archaea: prediction of a
   novel aconitase by comparative-genomic analysis
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Article
DE aconitase; swiveling domain; superfamily; operon; non-orthologous gene
   displacement
ID CITRIC-ACID CYCLE; EVOLUTIONARY INFORMATION; PROTEIN SEQUENCES;
   DATABASE; SULFUR; ASSIMILATION; GENERATION; MECHANISM; PHYLOGENY;
   PATHWAY
AB Aconitase. an essential enzyme of the tricarboxylic acid cycle (TCA), so far has been identified only in a minority of archaeal genomes. This enzyme belongs to the aconitase A family, which is represented in most bacteria and eukaryotes. Using iterative sequence database search, we linked two previously uncharacterized protein families (COG1679 and COG1786), respectively, to the three Fe-S-cluster-associated aconitase domains and the swiveling domain, the four domains that are present in all known aconitase families. The respective genes are often found in one predicted operon and, moreover, are fused in several species, suggesting a functional and physical interaction. We predict that these proteins together comprise a previously undetected, distinct aconitase family, which we designated aconitase X. Aconitase X is encoded in the genomes of many archaea and some proteobacteria. Among archaea, the pattern of aconitase X occurrence complements that of aconitase A such that together the two enzymes account for aconitase activity in all archaea. Phylogenetic analysis indicates that aconitase X is likely to be the ancestral archaeal form, with non-orthologous displacement in some of the archaea apparently brought about by horizontal transfer of the gene for bacterial aconitase A. The prediction of aconitase X completes the TCA cycle for Methanothermobacter thermoautotrophicus and Archaeoglobus fulgidus and suggests that most archaea have a full TCA cycle. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Makarova, KS (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
NR 32
TC 19
Z9 19
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1097
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD OCT 10
PY 2003
VL 227
IS 1
BP 17
EP 23
DI 10.1016/S0378-1097(03)00596-2
PG 7
WC Microbiology
SC Microbiology
GA 733TH
UT WOS:000186016400003
PM 14568143
ER

PT J
AU Newcomer, LM
   Newcomb, PA
   Trentham-Dietz, A
   Longnecker, MP
   Greenberg, R
AF Newcomer, LM
   Newcomb, PA
   Trentham-Dietz, A
   Longnecker, MP
   Greenberg, R
TI Oral contraceptive use and risk of breast cancer by histologic type
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE breast neoplasms; carcinoma; lobular carcinoma; infiltrating duct; oral
   contraceptives; histology
ID HORMONE REPLACEMENT THERAPY; UNITED-STATES; CARCINOMA; AGREEMENT; WOMEN;
   HISTORIES
AB We examined the association between oral contraceptive use and risk of specific breast cancer histopathologies in a large, multi-center, population-based, case-control study. Women younger than age 75 with a new diagnosis of invasive breast cancer were identified from 4 statewide tumor registries. We compared women with lobular (n = 493) and ductal carcinoma (n = 5,5 10) to randomly selected controls (n = 9,311). Odds ratios (OR) and 95% confidence intervals (Cl) for each histologic type were estimated using polytomous logistic regression, adjusted for other breast cancer risk factors. Current oral contraceptive use was associated with increased risk of lobular carcinoma (OR = 2.6, 95%CI = 1.0-7.1) and there was a significant trend (p = 0.017) of increased risk with more recent use. Oral contraceptive use was not clearly associated with ductal carcinoma (OR = 1.2, 9S%CI = 0.8-1.9). These results suggest that the association between oral contraceptive use and risk of breast cancer may vary by histologic type. (C) 2003 Wiley-Liss, Inc.
C1 Fred Hutchinson Canc Res Ctr, Dept Epidemiol, Seattle, WA 98109 USA.
   Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA.
   NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
   Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA.
RP Newcomer, LM (reprint author), Fred Hutchinson Canc Res Ctr, Dept Epidemiol, 1100 Fairview Ave N,MP-474,POB 19024, Seattle, WA 98109 USA.
OI Longnecker, Matthew/0000-0001-6073-5322
FU NCI NIH HHS [CA47305, CA47147]
NR 23
TC 28
Z9 28
U1 1
U2 3
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD OCT 10
PY 2003
VL 106
IS 6
BP 961
EP 964
DI 10.1002/ijc.11307
PG 4
WC Oncology
SC Oncology
GA 717JW
UT WOS:000185086200021
PM 12918077
ER

PT J
AU Ishaq, M
   DeGray, G
   Natarajan, V
AF Ishaq, M
   DeGray, G
   Natarajan, V
TI Protein kinase C0 modulates nuclear receptor-corepressor interaction
   during T cell activation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID KAPPA-B ACTIVATION; THYROID-HORMONE RECEPTORS; SMALL INTERFERING RNAS;
   RETINOID-X-RECEPTOR; PKC-THETA; MAMMALIAN-CELLS; IL-2 PROMOTER;
   LYMPHOCYTES; CALCINEURIN; TCR
AB Transcriptional repression by nuclear receptor corepressors plays a critical role in T cell development. However, the role of these corepressors in T cell activation is poorly understood. We report that T cell activation silenced transcription driven by nuclear receptors retinoic acid receptor, retinoid X receptor, and thyroid hormone receptor and induced silencing mediator of retinoic acid and thyroid hormone receptors (SMRT)-receptor interaction. Whereas the expression of a dominant active mutant of protein kinase Ctheta (PKCtheta) induced strong SMRT-receptor interaction in the absence of T cell activation, a dominant negative mutant of PKCtheta decreased the interaction. Loss of PKCtheta expression by induction of "RNA interference" resulted in the attenuation of basal and activation-induced SMRT-receptor interaction. We suggest that T cell activation silences nuclear receptor-dependent transactivation in part through PKCtheta-dependent enhancement of SMRT-receptor interaction.
C1 NCI, Mol Cell Biol Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA.
RP Ishaq, M (reprint author), NCI, Mol Cell Biol Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA.
FU NCI NIH HHS [N0-CO12400]
NR 47
TC 13
Z9 15
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 10
PY 2003
VL 278
IS 41
BP 39296
EP 39302
DI 10.1074/jbc.M302767200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 728JJ
UT WOS:000185713800006
PM 12890684
ER

PT J
AU Liu, MF
   Gupte, G
   Roy, S
   Bandwar, RP
   Patel, SS
   Garges, S
AF Liu, MF
   Gupte, G
   Roy, S
   Bandwar, RP
   Patel, SS
   Garges, S
TI Kinetics of transcription initiation at lacP1 - Multiple roles of cyclic
   AMP receptor protein
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID OPEN COMPLEX-FORMATION; RNA-POLYMERASE; PROMOTER DNA; BASE;
   FLUORESCENCE; ACTIVATION; MECHANISM; CAMP; 2-AMINOPURINE; DYNAMICS
AB The cyclic AMP receptor protein (CRP) acts as a transcription activator at many promoters of Escherichia coli. We have examined the kinetics of open complex formation at the lacP1 promoter using tryptophan fluorescence of RNA polymerase and DNA fragments with 2-aminopurine substituted at specific positions. Apart from the closed complex formation and promoter clearance, we were able to detect three steps. The first step after the closed complex formation leads to a rapid increase of 2-aminopurine fluorescence. This was followed by another rapid step in which quenching of tryptophan fluorescence of RNA polymerase was observed. The slowest step detected by 2-aminopurine fluorescence increase is assigned to the final open complex formation. We have found that CRP not only enhances RNA polymerase binding at the promoter, but also enhances the slowest isomerization step by about 2-fold. Furthermore, potassium permanganate probing shows that the conformation of the open complex in the presence of CRP appears qualitatively and quantitatively different from that in the absence of CRP, suggesting that contact with RNA polymerase is maintained throughout the transcription initiation.
C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   Bose Inst, Dept Biophys, Kolkata 700054, W Bengal, India.
   Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA.
RP Liu, MF (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5138, Bethesda, MD 20892 USA.
EM liumo@pop.nci.nih.gov
FU NIGMS NIH HHS [GM51966]
NR 25
TC 11
Z9 11
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 10
PY 2003
VL 278
IS 41
BP 39755
EP 39761
DI 10.1074/jbc.M305995200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 728JJ
UT WOS:000185713800061
PM 12881519
ER

PT J
AU Liang, W
   Austin, S
   Hoang, Q
   Fishman, PH
AF Liang, W
   Austin, S
   Hoang, Q
   Fishman, PH
TI Resistance of the human beta(1)-adrenergic receptor to agonist-mediated
   down-regulation - Role of the C terminus in determining beta-subtype
   degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; HUMAN BETA-2-ADRENERGIC RECEPTOR;
   BETA(2)-ADRENERGIC RECEPTOR; ADRENERGIC-RECEPTOR; CARDIAC MYOCYTES;
   BETA-1-ADRENERGIC RECEPTOR; DIFFERENTIAL REGULATION; ACTIVATED
   RECEPTOR-1; HEART-FAILURE; RAT-HEART
AB Prolonged agonist stimulation results in down-regulation of most G protein-coupled receptors. When we exposed baby hamster kidney cells stably expressing the human beta(1)-adrenergic receptor (beta(1)AR) to agonist over a 24-h period, we instead observed an increase of similar to30% in both beta(1)AR binding activity and immune-detected receptors. In contrast, beta(2)AR expressed in these cells exhibited a decrease of greater than or equal to50%. We determined that the basal turnover rates of the two subtypes were similar (t1/2 similar to 7 h) and that agonist stimulation increased beta(2)AR but not beta(1)AR turnover. Blocking receptor trafficking to lysosomes with bafilomycin A(1) had no effect on basal turnover of either subtype but blocked agonist-stimulated beta(2)AR turnover. As beta(1)AR mRNA levels increased in agonist-stimulated cells, beta(1)AR up-regulation appeared to result from increased synthesis with no change in degradation. To explore the basis for the subtype differences, we expressed chimeras in which the C termini had been exchanged. Each chimera responded to persistent agonist stimulation based on the source of its C-tail; beta(1)AR with a beta(2)AR C-tail underwent down-regulation, and beta(2)AR with a beta(1)AR C-tail underwent up-regulation. The C-tails had a corresponding effect on agonist-stimulated receptor phosphorylation and internalization with the order being beta(2)AR > beta(1)AR with beta(2)AR C-tail > beta(2)AR with a beta(1)AR C-tail > beta(1)AR. As internalization may be a prerequisite for down-regulation, we addressed this possibility by co-expressing each subtype with arrestin-2. Although beta(1)AR internalization was increased to that of beta(2)AR, down-regulation still did not occur. Instead, beta(1)AR accumulated inside the cells. We conclude that in unstimulated cells, both subtypes appear to be turned over by the same mechanism. Upon agonist stimulation, both subtypes are internalized, and beta(2)AR but not beta(1)AR undergoes lysosomal degradation, the fate of each subtype being regulated by determinants in its C-tail.
C1 NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
RP Fishman, PH (reprint author), NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bldg 49,Rm 2A28,49 Convent Dr,MSC4440, Bethesda, MD 20892 USA.
NR 58
TC 21
Z9 22
U1 1
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 10
PY 2003
VL 278
IS 41
BP 39773
EP 39781
DI 10.1074/jbc.M304482200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 728JJ
UT WOS:000185713800063
PM 12888573
ER

PT J
AU Sobol, RW
   Kartalou, M
   Almeida, KH
   Joyce, DF
   Engelward, BP
   Horton, JK
   Prasad, R
   Samson, LD
   Wilson, SH
AF Sobol, RW
   Kartalou, M
   Almeida, KH
   Joyce, DF
   Engelward, BP
   Horton, JK
   Prasad, R
   Samson, LD
   Wilson, SH
TI Base excision repair intermediates induce p53-independent cytotoxic and
   genotoxic responses
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DNA-POLYMERASE-BETA; MISMATCH REPAIR; PHOSPHATE LYASE; MICE DEFICIENT;
   N-GLYCOSYLASE; MOUSE CELLS; DAMAGE; P53; PROTEIN; GENES
AB DNA alkylation damage is primarily repaired by the base excision repair (BER) machinery in mammalian cells. In repair of the N-alkylated purine base lesion, for example, alkyl adenine DNA glycosylase (Aag) recognizes and removes the base, and DNA polymerase beta (beta-pol) contributes the gap tailoring and DNA synthesis steps. It is the loss of beta-pol-mediated 5'-deoxyribose phosphate removal that renders mouse fibroblasts alkylation-hypersensitive. Here we report that the hypersensitivity of beta-pol-deficient cells after methyl methanesulfonate-induced alkylation damage is wholly dependent upon glycosylase-mediated initiation of repair, indicating that alkylated base lesions themselves are tolerated in these cells and demonstrate that beta-pol protects against accumulation of toxic BER intermediates. Further, we find that these intermediates are initially tolerated in vivo by a second repair pathway, homologous recombination, inducing an increase in sister chromatid exchange events. If left unresolved, these BER intermediates trigger a rapid block in DNA synthesis and cytotoxicity. Surprisingly, both the cytotoxic and genotoxic signals are independent of both the p53 response and mismatch DNA repair pathways, demonstrating that p53 is not required for a functional BER pathway, that the observed damage response is not part of the p53 response network, and that the BER intermediate-induced cytotoxic and genotoxic effects are distinct from the mechanism engaged in response to mismatch repair signaling. These studies demonstrate that, although base damage is repaired by the BER pathway, incomplete BER intermediates are shuttled into the homologous recombination pathway, suggesting possible coordination between BER and the recombination machinery.
C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   MIT, Biol Engn Div, Cambridge, MA 02139 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RI Sobol, Robert/E-4125-2013
OI Sobol, Robert/0000-0001-7385-3563
FU NCI NIH HHS [CA79287, CA55042, CA84740, CA92584, P01 CA092584, R01
   CA055042, R01 CA079827, R21 CA084740]; NIEHS NIH HHS [5 T32 ES07020,
   ES02109, P30 ES002109]
NR 49
TC 120
Z9 125
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 10
PY 2003
VL 278
IS 41
BP 39951
EP 39959
DI 10.1074/jbc.M306592200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 728JJ
UT WOS:000185713800083
PM 12882965
ER

PT J
AU Liu, H
   Toman, RE
   Goparaju, SK
   Maceyka, M
   Nava, VE
   Sankala, H
   Payne, SG
   Bektas, M
   Ishii, I
   Chun, J
   Milstien, S
   Spiegel, S
AF Liu, H
   Toman, RE
   Goparaju, SK
   Maceyka, M
   Nava, VE
   Sankala, H
   Payne, SG
   Bektas, M
   Ishii, I
   Chun, J
   Milstien, S
   Spiegel, S
TI Sphingosine kinase type 2 is a putative BH3-only protein that induces
   apoptosis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LONG-CHAIN BASES; BCL-X-L; CELL-MIGRATION; FUNCTIONAL-CHARACTERIZATION;
   SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; COUPLED RECEPTOR;
   CYTOCHROME-C; BH3 DOMAINS; 1-PHOSPHATE
AB There are two isoforms of sphingosine kinase (SphK) that catalyze the formation of sphingosine 1-phosphate, a potent sphingolipid mediator. Whereas SphK1 stimulates growth and survival, here we show that SphK2 enhanced apoptosis in diverse cell types and also suppressed cellular proliferation. Apoptosis was preceded by cytochrome c release and activation of caspase-3. SphK2-induced apoptosis was independent of activation of sphingosine 1-phosphate receptors. Sequence analysis revealed that SphK2 contains a 9-amino acid motif similar to that present in BH3-only proteins, a proapoptotic subgroup of the Bcl-2 family. As with other BH3-only proteins, co-immunoprecipitation demonstrated that SphK2 interacted with Bcl-x(L). Moreover, site-directed mutation of Leu-219, the conserved leucine residue present in all BH3 domains, markedly suppressed SphK2-induced apoptosis. Hence, the apoptotic effect of SphK2 might be because of its putative BH3 domain.
C1 Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA.
   Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20007 USA.
   Georgetown Univ, Med Ctr, Dept Biochem, Washington, DC 20007 USA.
   NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
   Natl Inst Neurosci, Dept Mol Genet, Tokyo 1878502, Japan.
   Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA.
RI Maceyka, Michael/B-9277-2008; Goparaju, Sravan/H-3422-2011; 
OI Ishii, Isao/0000-0002-5367-205X
FU NCI NIH HHS [CA61774]; NIMH NIH HHS [MH01723]
NR 47
TC 207
Z9 214
U1 0
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 10
PY 2003
VL 278
IS 41
BP 40330
EP 40336
DI 10.1074/jbc.M304455200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 728JJ
UT WOS:000185713800126
PM 12835323
ER

PT J
AU Byeon, IJL
   Louis, JM
   Gronenborn, AM
AF Byeon, IJL
   Louis, JM
   Gronenborn, AM
TI A protein contortionist: Core mutations of GB1 that induce dimerization
   and domain swapping
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE GB1; core mutants; NMR structure; domain-swapping; oligomerization
ID IMMUNOGLOBULIN-BINDING DOMAIN; LIQUID-CRYSTALLINE PHASE; SIDE-CHAIN;
   CYANOVIRIN-N; NMR-SPECTRA; J-COUPLINGS; RESTRAINTS; STABILITY;
   COMPLEXES; RESIDUES
AB Immunoglobulin-binding domain B1 of streptococcal protein G (GB1), a small (56 residues), stable, single-domain protein, is one of the most extensively used model systems in the area of protein folding and design. Recently, NMR and X-ray structures of a quintuple GB1 core mutant (L5V/A26F/F30V/Y33F/A34F) that showed an unexpected, intertwined tetrameric architecture were determined. Here, we report the NMR structure of another mutant, derived from the tetramer by reverting the single amino acid position F26 back to the wild-type sequence A26. The structure reveals a domain-swapped dimer that involves exchange of the second beta-hairpin. The resulting overall structure comprises an eight-stranded beta-sheet whose concave side is covered by two alpha helices. The dimer dissociates into a partially folded, monomeric species with a dissociation constant of 93(+/-10) muM. Published by Elsevier Ltd.
C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Gronenborn, AM (reprint author), NIDDKD, Phys Chem Lab, NIH, Bldg 5,Room 130, Bethesda, MD 20892 USA.
NR 37
TC 53
Z9 53
U1 1
U2 10
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD OCT 10
PY 2003
VL 333
IS 1
BP 141
EP 152
DI 10.1016/S0022.2836(03)00928-8
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 729VA
UT WOS:000185794700011
PM 14516749
ER

PT J
AU Sappol, M
AF Sappol, M
TI The anatomical mission to Burma
SO SCIENCE
LA English
DT Editorial Material
C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA.
RP Sappol, M (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA.
NR 6
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 10
PY 2003
VL 302
IS 5643
BP 232
EP 233
DI 10.1126/science.1086308
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 730HT
UT WOS:000185825900022
PM 14551420
ER

PT J
AU Biacchesi, S
   Skiadopoulos, MH
   Boivin, G
   Hanson, CT
   Murphy, BR
   Collins, PL
   Buchholz, UJ
AF Biacchesi, S
   Skiadopoulos, MH
   Boivin, G
   Hanson, CT
   Murphy, BR
   Collins, PL
   Buchholz, UJ
TI Genetic diversity between human metapneumovirus subgroups
SO VIROLOGY
LA English
DT Article
DE metapneumovirus; subgroup; genomic sequence
ID RESPIRATORY SYNCYTIAL VIRUS; G-GLYCOPROTEIN; ANTIGENIC RELATEDNESS;
   SEQUENCE CONSERVATION; N-PROTEINS; M2 GENE; RNA; TRANSCRIPTION;
   PNEUMOVIRUS; INFECTIONS
AB Complete consensus nucleotide sequences were determined for human metapneumovirus (HMPV) isolates CAN97-83 and CAN98-75, representing the two proposed genotypes or genetic subgroups of HMPV. The overall level of genome nucleotide sequence identity and aggregate proteome amino acid sequence identity between the two HMPV subgroups were 80 and 90%, respectively, similar to the respective values of 81 and 88% between the two antigenic subgroups of human respiratory syncytial virus (HRSV). The diversity between HMPV subgroups was greatest for the SH and G proteins (59 and 37% identity, respectively), which were even more divergent than their HRSV counterparts (72 and 55% cross-subgroup identity, respectively). It is reasonable to anticipate that the two genetic subgroups of HMPV represent antigenic subgroups approximately comparable to those of HRSV. (C) 2003 Elsevier Inc. All rights reserved.
C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
   Ctr Hosp Univ Quebec, St Foy, PQ G1V 4G2, Canada.
   Univ Laval, St Foy, PQ G1V 4G2, Canada.
RP Buchholz, UJ (reprint author), Bldg 50,Room 6507,50 S Dr MSC, Bethesda, MD 20892 USA.
RI Biacchesi, Stephane/A-6924-2010
NR 29
TC 157
Z9 184
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 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 10
PY 2003
VL 315
IS 1
BP 1
EP 9
DI 10.1016/S0042-6822(03)00528-2
PG 9
WC Virology
SC Virology
GA 739YE
UT WOS:000186373700001
PM 14592754
ER

PT J
AU Xiang, SH
   Wang, LP
   Abreu, M
   Huang, CC
   Kwong, PD
   Rosenberg, E
   Robinson, JE
   Sodroski, J
AF Xiang, SH
   Wang, LP
   Abreu, M
   Huang, CC
   Kwong, PD
   Rosenberg, E
   Robinson, JE
   Sodroski, J
TI Epitope mapping and characterization of a novel CD4-induced human
   monoclonal antibody capable of neutralizing primary HIV-1 strains
SO VIROLOGY
LA English
DT Article
DE human immunodeficiency virus (HIV-1); primary HIV-1 isolates;
   CD4-induced (CD4i) antibodies; neutralizing antibodies; epitope mapping;
   human monoclonal antibody E51; structured treatment interruption (STI);
   soluble CD4 (sCD4); envelope glycoprotein (gp120)
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; CD4
   BINDING-SITE; PASSIVE IMMUNOTHERAPY; SYNERGISTIC NEUTRALIZATION;
   TYROSINE SULFATION; RECEPTOR-BINDING; TYPE-1; INFECTION; CCR5
AB Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the beta19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies. (C) 2003 Elsevier Inc. All rights reserved.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Div Aids, Boston, MA 02115 USA.
   Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70012 USA.
RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Jimmy Fund Bldg,Room 824, Boston, MA 02115 USA.
FU NIAID NIH HHS [AI28691, AI31783, AI39420, AI24755, AI41851]
NR 68
TC 58
Z9 60
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 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 10
PY 2003
VL 315
IS 1
BP 124
EP 134
DI 10.1016/S0042-6822(03)00521-X
PG 11
WC Virology
SC Virology
GA 739YE
UT WOS:000186373700012
PM 14592765
ER

PT J
AU Villanueva, RA
   Campbell, S
   Roth, MJ
AF Villanueva, RA
   Campbell, S
   Roth, MJ
TI Molecular analysis of a recombinant M-MuLV/RaLV retrovirus
SO VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; CELL-SURFACE RECEPTORS; REVERSE-TRANSCRIPTASE;
   ENDOGENOUS RETROVIRUS; ENVELOPE PROTEIN; TRANSMEMBRANE PROTEIN;
   INTEGRATION SITE; RNA DIMERIZATION; MATRIX PROTEIN; PATCH REPAIR
AB A replication-competent retrovirus was isolated from Rat1 cells after stable transfection of a defective Moloney murine leukemia virus (M-MuLV) provirus bearing mutations in two conserved cysteines of the TM protein. Immunoprecipitation of the viral proteins indicated the infectious virus is not related to M-MuLV. Electron microscopy of budding virions revealed a mammalian type C virus. The host range of the virus is limited to rat cells. N-terminal sequence analysis of the capsid-associated protein identified the virus to be related to rat leukemia virus (RaLV). Analysis of the cloned sequences indicated a recombinant provirus with a genetic organization in which the leader region and open reading frames of the endogenous RaLV are flanked by identical M-MuLV LTRs at both ends. These results highlight the effects of exogenous viral infection on endogenous viruses. (C) 2003 Elsevier Inc. All rights reserved.
C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA.
   NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Roth, MJ (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, 675 Hoes Lane, Piscataway, NJ 08854 USA.
FU NCI NIH HHS [R01 CA49932]
NR 62
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD OCT 10
PY 2003
VL 315
IS 1
BP 195
EP 208
DI 10.1016/S0042-6822(03)00518-X
PG 14
WC Virology
SC Virology
GA 739YE
UT WOS:000186373700018
PM 14592771
ER

PT J
AU Fortini, ME
AF Fortini, ME
TI Double trouble for neurons
SO NATURE
LA English
DT Editorial Material
ID ALZHEIMERS-DISEASE; GAMMA-SECRETASE; CADHERIN; PRESENILINS; CLEAVAGE;
   BIOLOGY; NOTCH; BETA
C1 NCI, Lab Prot Dynam & Signalling, Frederick, MD 21702 USA.
RP Fortini, ME (reprint author), NCI, Lab Prot Dynam & Signalling, 1050 Boyles St, Frederick, MD 21702 USA.
NR 11
TC 7
Z9 8
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 9
PY 2003
VL 425
IS 6958
BP 565
EP 566
DI 10.1038/425565a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729XU
UT WOS:000185801000019
PM 14534567
ER

PT J
AU Derynck, R
   Zhang, YE
AF Derynck, R
   Zhang, YE
TI Smad-dependent and Smad-independent pathways in TGF-beta family
   signalling
SO NATURE
LA English
DT Review
ID GROWTH-FACTOR-BETA; ACTIVATED PROTEIN-KINASE; EPITHELIAL-CELL
   PLASTICITY; ANAPHASE-PROMOTING COMPLEX; CDK INHIBITOR P15(INK4B);
   UBIQUITIN LIGASE COMPLEX; TRANSCRIPTIONAL ACTIVATION; MESENCHYMAL
   TRANSDIFFERENTIATION; ADIPOCYTE DIFFERENTIATION; RECEPTOR
   INTERNALIZATION
AB Transforming growth factor-beta (TGF-beta) proteins regulate cell function, and have key roles in development and carcinogenesis. The intracellular effectors of TGF-beta signalling, the Smad proteins, are activated by receptors and translocate into the nucleus, where they regulate transcription. Although this pathway is inherently simple, combinatorial interactions in the heteromeric receptor and Smad complexes, receptor-interacting and Smad-interacting proteins, and cooperation with sequence-specific transcription factors allow substantial versatility and diversification of TGF-beta family responses. Other signalling pathways further regulate Smad activation and function. In addition, TGF-beta receptors activate Smad-independent pathways that not only regulate Smad signalling, but also allow Smad-independent TGF-beta responses.
C1 Univ Calif San Francisco, Dept Growth & Dev, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Cell Biol Program, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Program Dev Biol, San Francisco, CA 94143 USA.
   NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Derynck, R (reprint author), Univ Calif San Francisco, Dept Growth & Dev, San Francisco, CA 94143 USA.
RI Zhang, Ying/G-3657-2015; Tang, Amy/L-3226-2016
OI Zhang, Ying/0000-0003-2753-7601; Tang, Amy/0000-0002-5772-2878
NR 101
TC 2593
Z9 2816
U1 24
U2 203
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD OCT 9
PY 2003
VL 425
IS 6958
BP 577
EP 584
DI 10.1038/nature02006
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 729XU
UT WOS:000185801000027
PM 14534577
ER

PT J
AU Harris, JP
   Weisman, MH
   Derebery, JM
   Espeland, MA
   Gantz, BJ
   Gulya, AJ
   Hammerschlag, PE
   Hannley, M
   Hughes, GB
   Moscicki, R
   Nelson, RA
   Niparko, JK
   Rauch, SD
   Telian, SA
   Brookhouser, PE
AF Harris, JP
   Weisman, MH
   Derebery, JM
   Espeland, MA
   Gantz, BJ
   Gulya, AJ
   Hammerschlag, PE
   Hannley, M
   Hughes, GB
   Moscicki, R
   Nelson, RA
   Niparko, JK
   Rauch, SD
   Telian, SA
   Brookhouser, PE
TI Treatment of corticosteroid-responsive autoimmune inner ear disease with
   methotrexate - A randomized controlled trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RHEUMATOID-ARTHRITIS; INFLIXIMAB; EFFICACY; THERAPY
AB Context A number of therapies have been proposed for the long-term management of corticosteroid-responsive, rapidly progressive, bilateral sensorineural hearing loss (autoimmune inner ear disease [AIED]). Methotrexate has emerged as the benchmark agent but has not been rigorously evaluated for hearing improvement in patients with AIED.
   Objective To assess the efficacy of long-term methotrexate in maintaining hearing improvements achieved with glucocorticoid (prednisone) therapy in patients with AIED.
   Design, Setting, and Participants A randomized, double-blind, placebo-controlled trial conducted from February 3, 1998, to November 5, 2001, of 67 patients with rapidly progressive, bilateral sensorineural hearing loss at 10 tertiary care centers in the United States.
   Intervention Randomization to either oral methotrexate (15 to 20 mg/wk; n=33) or placebo (n=34), in combination with an 18-week prednisone taper. Follow-up examinations, including audiometric evaluation, were performed at 4, 8,12, 24, 36, 48, and 52 weeks, or until hearing loss was documented.
   Main Outcome Measure Maintenance of hearing improvement achieved from prednisone treatment.
   Results Sixty-seven patients (57.8%) enrolled in the prednisone challenge experienced hearing improvement. Twenty-five patients (37%) experienced hearing improvements in both ears. Of the individuals who reached study end points, 24 (80%) of 30 end points were because of measured hearing loss in the methotrexate group and 29 (93.5%) of 31 end points were because of measured hearing loss in the placebo group (P=.15). Methotrexate was no more effective than placebo in maintaining the hearing improvement achieved with prednisone treatment (hazard ratio, 1.31 95% confidence, interval, 0.79-2.17; P=30).
   Conclusion Methotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy in patients with AIED.
C1 Univ Calif San Diego, Div Otolaryngol Head & Neck Surg, San Diego, CA 92103 USA.
   Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA.
   House Ear Res Inst, Los Angeles, CA USA.
   Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
   Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA.
   Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
   NYU, Dept Otolaryngol Head & Neck Surg, New York, NY USA.
   Amer Acad Otolaryngol Head & Neck Surg, Res Dev, Alexandria, VA USA.
   Cleveland Clin, Cleveland, OH 44106 USA.
   Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA.
   Johns Hopkins Univ, Dept Otolaryngol, Baltimore, MD USA.
   Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
   Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA.
   Boys Town Natl Res Hosp, Omaha, NE 68131 USA.
RP Harris, JP (reprint author), Univ Calif San Diego, Div Otolaryngol Head & Neck Surg, 200 W Arbor Dr,Mail Code 8895, San Diego, CA 92103 USA.
FU NIDCD NIH HHS [5 U01 DC03209]
NR 29
TC 76
Z9 82
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD OCT 8
PY 2003
VL 290
IS 14
BP 1875
EP 1883
DI 10.1001/jama.290.14.1875
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 729CB
UT WOS:000185752600028
PM 14532316
ER

PT J
AU Berezhkovskii, AM
   Zitserman, VY
   Shvartsman, SY
AF Berezhkovskii, AM
   Zitserman, VY
   Shvartsman, SY
TI Effective diffusivity in periodic porous materials
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID FACILITATED MEMBRANE-TRANSPORT; KINETICS; SYSTEMS; RELEASE; CHANNEL
AB Diffusion of a solute in a periodic porous solid is analyzed. An expression for the effective diffusion coefficient is derived for a solute diffusing in a porous medium formed by a simple cubic lattice of spherical cavities connected by narrow tubes. This expression shows how the effective diffusion coefficient depends on microgeometry of the porous material. Generalizations to nonspherical cavities, other lattices, and nonequal diffusion coefficients in the cavities and in the tubes are discussed. (C) 2003 American Institute of Physics.
C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
   Russian Acad Sci, Inst High Temp, Thermophys Ctr, Moscow 127412, Russia.
   Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA.
   Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   Karpov Inst Phys Chem, Moscow 103064, Russia.
RP Berezhkovskii, AM (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
NR 14
TC 34
Z9 34
U1 0
U2 3
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
   MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD OCT 8
PY 2003
VL 119
IS 14
BP 6991
EP 6993
DI 10.1063/1.1615758
PG 3
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 726AT
UT WOS:000185575700001
ER

PT J
AU Khiroug, L
   Giniatullin, R
   Klein, RC
   Fayuk, D
   Yakel, JL
AF Khiroug, L
   Giniatullin, R
   Klein, RC
   Fayuk, D
   Yakel, JL
TI Functional mapping and Ca2+ regulation of nicotinic acetylcholine
   receptor channels in rat hippocampal CA1 neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE nicotinic; acetylcholine; hippocampus; interneuron; patch clamp; channel
ID EXCITATORY SYNAPTIC TRANSMISSION; LONG-TERM POTENTIATION; CHROMAFFIN
   CELLS; PYRAMIDAL NEURONS; ACH RECEPTORS; MOLECULAR CHARACTERIZATION;
   INTRACELLULAR CALCIUM; STRATUM-RADIATUM; BETA-2 SUBUNITS; ALPHA-7
   SUBUNIT
AB Diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including fast-desensitizing alpha7-containing receptors thought to be Ca2+-permeable, are expressed in the CNS, where they appear to regulate cognitive processing and synaptic plasticity. To understand the physiological role of nAChRs in regulating neuronal excitability, it is important to know the distribution of functional receptors along the surface of neurons, whether they can increase [Ca2+](i), and/or are regulated by Ca2+. We mapped the distribution of receptors on the membrane of rat hippocampal CA1 stratum radiatum interneurons and pyramidal cells in acute slices by recording nAChR-mediated currents elicited by local UV laser-based photolysis of caged carbachol in patch-clamped neurons. The local application (similar to7 mum patches) allowed mapping of functional nAChRs along the soma and dendritic tree, whereas the fast uncaging minimized the effects of desensitization of alpha7-containing nAChRs and allowed us to measure the kinetics of responses. The alpha7-containing nAChRs were the predominant subtype on interneurons, and were located primarily at perisomatic sites (<70 &mu;m from the soma; in contrast to the more uniform distribution of glutamate receptors); no currents were detectable on pyramidal neurons. The activation of nAChRs increased [Ca2+](i), indicating that these native receptors in acute slices are significantly Ca2+-permeable, consistent with previous observations made with recombinant receptors. In addition, they exhibited strong desensitization, the rate of recovery from which was controlled by [Ca2+](i). Our results demonstrate the strategic location and Ca2+ regulation of &alpha;7-containing nAChRs, which may contribute to understanding their involvement in hippocampal plasticity.
C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Lab Signal Transduct, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
NR 59
TC 90
Z9 91
U1 0
U2 2
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 OCT 8
PY 2003
VL 23
IS 27
BP 9024
EP 9031
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 730GZ
UT WOS:000185822200003
PM 14534236
ER

PT J
AU Sano, H
   Yasoshima, Y
   Matsushita, N
   Kaneko, T
   Kohno, K
   Pastan, I
   Kobayashi, K
AF Sano, H
   Yasoshima, Y
   Matsushita, N
   Kaneko, T
   Kohno, K
   Pastan, I
   Kobayashi, K
TI Conditional ablation of striatal neuronal types containing dopamine D2
   receptor disturbs coordination of basal ganglia function
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE motor control; dopamine; dopamine D2 receptor; striatum; medium spiny
   neuron; immunotoxin-mediated cell targeting
ID MESSENGER-RNA EXPRESSION; SPINY PROJECTION NEURONS; HIGH-LEVEL
   EXPRESSION; RAT STRIATUM; TRANSGENIC MICE; SUBTHALAMIC NUCLEUS; OPIOID
   RECEPTOR; GLOBUS-PALLIDUS; FOS EXPRESSION; C-FOS
AB Dopamine (DA) exerts synaptic organization of basal ganglia circuitry through a variety of neuronal populations in the striatum. We performed conditional ablation of striatal neuronal types containing DAD2 receptor (D2R) by using immunotoxin- mediated cell targeting. Mutant mice were generated that express thehumaninterleukin-2 receptor alpha-subunit under the control of the D2R gene. Intrastriatal immunotoxin treatment of the mutants eliminated the majority of the striatopallidal medium spiny neurons and cholinergic interneurons. The elimination of these neurons caused hyperactivity of spontaneous movement and reduced motor activation in response to DA stimulation. The elimination also induced upregulation of GAD gene expression in the globus pallidus (GP) and downregulation of cytochrome oxidase activity in the subthalamic nucleus (STN), whereas it attenuated DA-induced expression of the immediate-early genes (IEGs) in the striatonigral neurons. In addition, chemical lesion of cholinergic interneurons did not alter spontaneous movement but caused a moderate enhancement in DA-induced motor activation. This enhancement of the behavior was accompanied by an increase in the IEG expression in the striatonigral neurons. These data suggest that ablation of the striatopallidal neurons causes spontaneous hyperactivity through modulation of the GP and STN activity and that the ablation leads to the reduction in DA-induced behavior at least partly through attenuation of the striatonigral activity as opposed to the influence of cholinergic cell lesion. We propose a possible model in which the striatopallidal neurons dually regulate motor behavior dependent on the state of DA transmission through coordination of the basal ganglia circuitry.
C1 Fukushima Med Univ Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan.
   Nara Inst Sci & Technol, Res & Educ Ctr Genet Informat, Ikoma 6300101, Japan.
   Kyoto Univ, Grad Sch Med, Dept Morphol Brain Sci, Kyoto 6068501, Japan.
   NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, K (reprint author), Fukushima Med Univ Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan.
NR 53
TC 44
Z9 48
U1 0
U2 3
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 OCT 8
PY 2003
VL 23
IS 27
BP 9078
EP 9088
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 730GZ
UT WOS:000185822200008
PM 14534241
ER

PT J
AU Blackwell, KT
   Czubayko, U
   Plenz, D
AF Blackwell, KT
   Czubayko, U
   Plenz, D
TI Quantitative estimate of synaptic inputs to striatal neurons during up
   and down states in vitro
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE striatum; up state; down state; spiny projection neuron; fast spiking
   interneuron; population statistics; synaptic inputs; organotypic culture
ID MEMBRANE-POTENTIAL FLUCTUATIONS; PARVALBUMIN-IMMUNOREACTIVE NEURONS;
   SPINY PROJECTION NEURONS; RAT NEOSTRIATUM; GABAERGIC INTERNEURONS;
   NIGROSTRIATAL PATHWAY; NEURAL DYNAMICS; CORTICAL INPUT; CORTEX; CULTURES
AB Up states are prolonged membrane potential depolarizations critical for synaptic integration and action potential generation in cortical and striatal neurons. They commonly result from numerous concurrent synaptic inputs, whereas neurons reside in a down state when synaptic inputs are few. By quantifying the composition, frequency, and amplitude of synaptic inputs for both states, we provide important constraints for state transitions in striatal network dynamics.
   Up and down states occur naturally in cortex - striatum - substantia nigra cocultures, which were used as an in vitro model in the present study. Spontaneous synaptic inputs during down states were extracted automatically in spiny projection neurons and fast spiking interneurons of the striatum using a newly developed computer algorithm. Consistent with a heterogeneous population of synaptic inputs, PSPs and PSCs showed no correlation in amplitude and rise time and occurred at relatively low frequencies of 10 - 40 Hz during the down state. The number of synaptic inputs during up states, estimated from the up-state charge and the unitary charge of down-state PSCs, was 217 +/- 44. Given the average up-state duration of 284 +/- 34 msec, synaptic input frequency was similar to 800 Hz during up-states for both neuronal types. Many down-state events reversed at the chloride reversal potential and were blocked by GABA(A) antagonists. The high correlation between up- and down-state reversal potential suggests that despite these drastic changes in synaptic input frequency, the ratio of inhibitory to excitatory currents is similar during both states.
C1 George Mason Univ, Krasnow Inst Adv Studies, Fairfax, VA 22030 USA.
   George Mason Univ, Sch Computat Sci, Fairfax, VA 22030 USA.
   NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Bethesda, MD 20892 USA.
RP Blackwell, KT (reprint author), George Mason Univ, Krasnow Inst Adv Studies, Mail Stop 2A1,Rockfish Creek Lane, Fairfax, VA 22030 USA.
FU NIMH NIH HHS [K21 MH001141, K21-MH01141]
NR 48
TC 46
Z9 48
U1 0
U2 3
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 OCT 8
PY 2003
VL 23
IS 27
BP 9123
EP 9132
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 730GZ
UT WOS:000185822200013
PM 14534246
ER

PT J
AU Emanuel, EJ
AF Emanuel, EJ
TI The lessons of SARS
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID PHYSICIANS; AIDS
AB Given the low mortality and morbidity of the severe acute respiratory syndrome (SARS) compared with other public health scourges, is the attention devoted to it misdirected? The SARS experience has provided at least 4 enduring lessons. First, by providing a test of the capacity of each part of the public health system, from national to local and hospital responses, it has better prepared the world for the anticipated and much-feared next real pandemic. Second, SARS has reemphasized that from housing, sexual practices, and slaughtering techniques to health care capacity, the situation in other, especially developing, countries affects us. Global cooperation is necessary not only for justice but to ensure our own health. Third, despite trends toward commercialization, easier lives, and self-centered individualism, the response of health care professionals to SARS reaffirmed dedication to caring for the sick even at great personal risks as the core ethical principle of medicine. Finally, SARS also emphasized the importance of the duty of health care administrators and senior physicians to rapidly institute procedures to maximize the safety of frontline physicians and nurses. These lessons will be valuable far beyond the SARS episode.
C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA.
RP Emanuel, EJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bldg 10,1C118, Bethesda, MD 20892 USA.
NR 19
TC 29
Z9 29
U1 0
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD OCT 7
PY 2003
VL 139
IS 7
BP 589
EP 591
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 729AP
UT WOS:000185748800007
PM 14530230
ER

PT J
AU Plo, I
   Liao, ZY
   Barcelo, JM
   Kohlhagen, G
   Caldecott, KW
   Weinfeld, M
   Pommier, Y
AF Plo, I
   Liao, ZY
   Barcelo, JM
   Kohlhagen, G
   Caldecott, KW
   Weinfeld, M
   Pommier, Y
TI Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the
   repair of topoisomerase I-mediated DNA lesions
SO DNA REPAIR
LA English
DT Article
DE camptothecin; topoisomerase I; XRCC1; transcription-mediated damage;
   replication-mediated DSB
ID STRAND-BREAK REPAIR; POLYMERASE-BETA; LIGASE-III; CLEAVABLE COMPLEXES;
   COVALENT COMPLEXES; MAMMALIAN-CELLS; POLY(ADP-RIBOSE) POLYMERASE;
   REPLICATION FORKS; MOLECULAR-CLONING; DRUG CAMPTOTHECIN
AB DNA topoisomerase I (Top 1) is converted into a cellular poison by camptothecin (CPT) and various endogenous and exogenous DNA lesions. In this study, we used X-ray repair complementation group 1 (XRCC1)-deficient and XRCC1-complemented EM9 cells to investigate the mechanism by which XRCC1 affects the cellular responses to Top I cleavage complexes induced by CPT. XRCC1 complementation enhanced survival to CPT-induced DNA lesions produced independently of DNA replication. CPT-induced comparable levels of Top I cleavage complexes (single-strand break (SSB) and DNA-protein cross-links (DPC) in both XRCC1-deficient and XRCC1-complemented cells. However, XRCC1-complemented cells repaired Top 1-induced DNA breaks faster than XRCC1-deficient cells, and exhibited enhanced tyrosyl DNA phosphodiesterase (Tdp1) and polynucleotide kinase phosphatase (PNKP) activities. XRCC1 immunoprecipitates contained Tdp1 polypeptide, and both Tdp1 and PNKP activities, indicating a functional connection between the XRCC1 single-strand break repair pathway and the repair of Top 1 covalent complexes by Tdp1 and PNKP. (C) 2003 Elsevier B.V. All rights reserved.
C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
   Univ Sussex, Brighton BN1 9RR, E Sussex, England.
   Univ Alberta, Edmonton, AB T6G 1Z2, Canada.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Building 37,Room 5068, Bethesda, MD 20892 USA.
NR 77
TC 132
Z9 134
U1 1
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD OCT 7
PY 2003
VL 2
IS 10
BP 1087
EP 1100
DI 10.1016/S1568-7864(03)00116-2
PG 14
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 727CC
UT WOS:000185637700002
PM 13679147
ER

PT J
AU Hawse, J
   Hejtmancik, J
   Huang, QL
   Sheets, N
   Hosack, D
   Lempicki, R
   Horwitz, J
   Kantorow, M
AF Hawse, J
   Hejtmancik, J
   Huang, QL
   Sheets, N
   Hosack, D
   Lempicki, R
   Horwitz, J
   Kantorow, M
TI Identification and functional clustering of global gene expression
   differences between human age-related cataract and clear lenses
SO MOLECULAR VISION
LA English
DT Article
ID ANTERIOR POLAR CATARACTS; NUCLEAR-PORE COMPLEX; ALPHA-B-CRYSTALLIN;
   EPITHELIAL-CELLS; NONSENSE MUTATION; PROLYL ISOMERASES; HOMOLOGOUS
   DOMAIN; DEFICIENCY LEADS; NA+/H+ EXCHANGE; IN-VITRO
AB Purpose: Age-related cataract is a multi-factorial disease with a poorly understood etiology. Numerous studies provide evidence that the human eye lens has evolved specific regulatory and protective systems to ameliorate lens damage associated with cataract. Other studies suggest that the presence of cataract is associated with the altered expression of specific genes including metallothionein IIa, osteonectin, transglutaminase 2, betaig-h3, multiple ribosomal proteins, ADAM9, and protein phosphatase 2A. Here, we sought to identify further gene expression changes that are associated with cataract and to cluster the identified genes into specific biological pathways.
   Methods: Oligonucleotide microarray hybridization was used to analyze the full complement of gene expression differences between lens epithelia isolated from human age-related cataract relative to clear lenses. The expression levels of a subset of the identified genes were further evaluated by semi-quantitative RT-PCR. The identified genes were functionally clustered into specific categories and the probability of over-representation of each category was determined using the computer program EASE.
   Results: 412 transcripts were observed to be increased and 919 transcripts were observed to be decreased by 2 fold or more in lens epithelia isolated from age-related cataract relative to clear lenses. Of these, 74 were increased and 241 were decreased at the 5 fold level or greater. Seventeen genes selected for further confirmation exhibited similar trends in expression when examined by RT-PCR using both the original and separately prepared clear and cataract RNA populations. Functional clustering of the identified genes using the EASE bioinformatics software package revealed that, among others, transcripts increased in cataract are associated with transcriptional control, chromosomal organization, ionic and cytoplasmic transport, and extracellular matrix components while transcripts decreased in cataract are associated with protein synthesis, defense against oxidative stress, heat-shock/chaperone activity, structural components of the lens, and cell cycle control.
   Conclusions: These data suggest that cataract is associated with multiple previously identified and novel changes in lens epithelial gene expression and they point to numerous pathways likely to play important roles in lens protection, maintenance, and age-related cataract.
C1 Florida Atlantic Univ, Boca Raton, FL 33431 USA.
   W Virginia Univ, Dept Biol, Morgantown, WV 26506 USA.
   NIH, OGVFB, Bethesda, MD 20892 USA.
   Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
   SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, Frederick, MD USA.
RP Kantorow, M (reprint author), Florida Atlantic Univ, 777 Glades Rd,POB 3091, Boca Raton, FL 33431 USA.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
FU NEI NIH HHS [EY03897, EY13022, R01 EY003897, R01 EY013022, R01
   EY013022-04, R37 EY003897]
NR 70
TC 48
Z9 52
U1 0
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 7
PY 2003
VL 9
IS 63-66
BP 515
EP 537
PG 23
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 731QX
UT WOS:000185898900003
PM 14551530
ER

PT J
AU Storer, RD
   French, JE
   Donehower, LA
   Gulezian, D
   Mitsumori, K
   Recio, L
   Schiestl, RH
   Sistare, FD
   Tamaoki, N
   Usui, T
   van Steeg, H
AF Storer, RD
   French, JE
   Donehower, LA
   Gulezian, D
   Mitsumori, K
   Recio, L
   Schiestl, RH
   Sistare, FD
   Tamaoki, N
   Usui, T
   van Steeg, H
CA IWGT Working Grp
TI Transgenic tumor models for carcinogen identification: the heterozygous
   Trp53-deficient and RasH2 mouse lines
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article; Proceedings Paper
CT International Workshop on Genotoxicity Testing
CY JUN 28-29, 2002
CL PLYMOUTH, ENGLAND
DE carcinogen; genetically altered mouse model; rodent
ID INDUCE INTRACHROMOSOMAL RECOMBINATION; SHORT-TERM CARCINOGENICITY; EYED
   UNSTABLE MUTATION; P53-DEFICIENT MICE; THYMIC LYMPHOMAS; TG.AC MOUSE;
   NONRESPONDER PHENOTYPE; KNOCKOUT MICE; MESSENGER-RNA; XPA
AB Genetically altered mouse models (GAMM) for human cancers have been critical to the investigation and characterization of oncogene and tumor suppressor gene expression and function and the associated cancer phenotype. Similarly, several of the mouse models with defined genetic alterations have shown promise for identification of potential human carcinogens and investigation of mechanisms of carcinogen-gene interactions and tumorigenesis. In particular, both the B6.129N5-Trp53 mouse, heterozygous for a p53 null allele, and the CB6F(1)-RasH2 mouse, hemizygous for the human H-ras transgene, have been extensively investigated. Using 26-week exposure protocols at or approaching the maximum tolerated dose, the summary results to date indicate the potential for GAMM to identify and, possibly, classify chemicals of potential risk to humans using short-term carcinogenicity experiments. This IWGT session focused on: (1) the development of recommendations for genetic/molecular characterization required in animals, tissues, and tumors before and after treatment for identification of presumptive human carcinogens based on the current state of knowledge, (2) identification of data gaps in our current state of knowledge, and (3) development of recommendations for research strategies for further development of our knowledge base of these particular models. By optimization of protocols and identification of significant outcomes and responses to chemical exposure in appropriate short-term mechanism-based genetically altered rodent models, strategies for prevention and intervention may be developed and employed to the benefit of public health. Published by Elsevier B.V.
C1 Merck Res Labs, Dept Genet & Cellular Toxicol, W Point, PA 19486 USA.
   NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
   Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   Tacon Farms Inc, Germantown, NY 12526 USA.
   Tokyo Univ Agr & Technol, Fac Agr, Tokyo 1838509, Japan.
   Merck Res Labs, Dept Genet & Cellular Toxicol, W Point, PA 19486 USA.
   Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol Environm Hlth & Radiat Oncol, Los Angeles, CA 90024 USA.
   Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
   US FDA, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA.
   Cent Inst Expt Anim, Kawasaki, Kanagawa 2160001, Japan.
   Natl Inst Publ Hlth & Environm, RIVM, Lab Toxicol Pathol & Genet, Bilthoven, Netherlands.
RP Storer, RD (reprint author), Merck Res Labs, Dept Genet & Cellular Toxicol, WP45-311, W Point, PA 19486 USA.
OI MITSUMORI, KUNITOSHI/0000-0002-0754-572X
NR 52
TC 4
Z9 4
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD OCT 7
PY 2003
VL 540
IS 2
BP 165
EP 176
DI 10.1016/j.mrgentox.2003.07.006
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 733PX
UT WOS:000186010800006
PM 14550500
ER

PT J
AU Krajewski, K
   Long, YQ
   Marchand, C
   Pommier, Y
   Koller, PP
AF Krajewski, K
   Long, YQ
   Marchand, C
   Pommier, Y
   Koller, PP
TI Design and synthesis of dimeric HIV-1 integrase inhibitory peptides
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
ID SOLID-PHASE
AB Dimers of known HIV-1 integrase inhibitory hexapeptide H-His-Cys-Lys-Phe-Trp-Trp-NH2 containing different lengths of cross linkers in the place of cysteine residue, were designed, and synthesized. The inhibitory potency of these dimeric peptides is consistently higher than the lead hexapeptide. The dimeric peptide with djenkolic acid linker exhibited IC50 values of 5.3 and 6.5 muM, for 3'-end processing and strand transfer, respectively. (C) 2003 Elsevier Ltd. All rights reserved.
C1 NCI Frederick, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA.
   Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China.
   NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA.
   Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland.
RP Koller, PP (reprint author), NCI Frederick, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA.
RI Marchand, Christophe/D-8559-2016
NR 14
TC 26
Z9 29
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD OCT 6
PY 2003
VL 13
IS 19
BP 3203
EP 3205
DI 10.1016/S0960-894X(03)00679-6
PG 3
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 721NM
UT WOS:000185322500016
PM 12951093
ER

PT J
AU Wang, SS
   Schiffman, M
   Shields, TS
   Herrero, R
   Hildesheim, A
   Bratti, MC
   Sherman, ME
   Rodriguez, AC
   Castle, PE
   Morales, J
   Alfaro, M
   Wright, T
   Chen, S
   Clayman, B
   Burk, RD
   Viscidi, RP
AF Wang, SS
   Schiffman, M
   Shields, TS
   Herrero, R
   Hildesheim, A
   Bratti, MC
   Sherman, ME
   Rodriguez, AC
   Castle, PE
   Morales, J
   Alfaro, M
   Wright, T
   Chen, S
   Clayman, B
   Burk, RD
   Viscidi, RP
TI Seroprevalence of human papillomavirus-16,-18,-31, and -45 in a
   population-based cohort of 10 000 women in Costa Rica
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE HPV; seroprevalence; cervical cancer; predictors
ID VIRUS-LIKE PARTICLES; CERVICAL INTRAEPITHELIAL NEOPLASIA;
   LINKED-IMMUNOSORBENT-ASSAY; SERUM ANTIBODIES; HPV DNA; SEXUAL-BEHAVIOR;
   NEGATIVE WOMEN; UNITED-STATES; RISK FACTOR; TYPE-16
AB Human papillomavirus (HPV) seroprevalence and determinants of seropositivity were assessed in a 10 049-woman population-based cohort in Guanacaste, Costa Rica. Serologic responses based on VLP-based ELISA were obtained from the plasma collected at study enrollment in 1993/1994 for HPV-16 (n = 9949), HPV-18 (n = 9928), HPV-31 (n = 9932), and HPV-45 (n = 3019). Seropositivity was defined as five standard deviations above the mean optical density obtained for studied virgins (n = 573). HPV-16, -18, -31, and -45 seroprevalence was 15, 15, 16, and 11%, respectively. Of women DNA-positive for HPV-16, -18, -31, or -45, seropositivity was 45, 34, 51, and 28%, respectively. Peak HPV seroprevalence occurred a decade after DNA prevalence; lifetime number of sexual partners was the key determinant of seropositivity independent of DNA status and age. DNA- and sero-positive women showed the highest risk for concurrent CIN3/cancer, followed by DNA- positive, sero-negative women.
C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   FUCODOCSA, Proyecto Epidemiol Guanacaste, Costa Rica 12531007, Mexico.
   Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA.
   Informat Management Serv Inc, Silver Spring, MD 20904 USA.
   Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21205 USA.
   Albert Einstein Coll Med, Bronx, NY 10461 USA.
RP Wang, SS (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA.
FU NCI NIH HHS [R01 CA078527, N01CP21081, R01CA78527]; PHS HHS [N01PP31061]
NR 36
TC 79
Z9 83
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD OCT 6
PY 2003
VL 89
IS 7
BP 1248
EP 1254
DI 10.1038/sj.bjc.6601272
PG 7
WC Oncology
SC Oncology
GA 729XC
UT WOS:000185799500021
PM 14520455
ER

PT J
AU Grandjean, I
   Duban, L
   Bonney, EA
   Corcuff, E
   Di Santo, JP
   Matzinger, P
   Lantz, O
AF Grandjean, I
   Duban, L
   Bonney, EA
   Corcuff, E
   Di Santo, JP
   Matzinger, P
   Lantz, O
TI Are major histocompatibility complex molecules involved in the survival
   of naive CD4(+) T cells?
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
DE T cell; naive; MHC; homeostasis
ID MHC CLASS-II; LYMPHOPENIA-INDUCED PROLIFERATION; HOMEOSTATIC
   PROLIFERATION; THYMIC SELECTION; ALPHA-BETA; POSITIVE SELECTION;
   DENDRITIC CELLS; GAMMA-CHAIN; LIFE-SPAN; MEMORY
AB yThe exact role of major histocompatibility complex (MHC) molecules in the peripheral survival of naive T cells is controversial, as some studies have suggested that they are critically required whereas others have suggested that they are not. Here we controlled for some of the features that differed among the earlier studies, and analyzed both the survival and expansion of naive CD4(+) T cells transferred into MHC syngeneic, allogeneic, or MHC negative environments. We found that naive T cells transferred into MHC negative or allogeneic environments often fail to survive because of rejection and/or competition by natural killer (NK) cells, rather than failure to recognize a particular MHC allele. In the absence of NK cells, naive CD4(+) T cells survived equally well regardless of the MHC type of the host. There was, however, an MHC requirement for extensive space-induced "homeostatic" expansion. Although the first few divisions occurred in the absence of MHC molecules, the cells did not continue to divide or transit to a CD44(hi) phenotype. Surprisingly, this MHC requirement could be satisfied by alleles other than the restricting haplotype. Therefore, space-induced expansion and survival are two different phenomena displaying different MHC requirements. Memory CD4(+) T cells, whose survival and expansion showed no requirements for MHC molecules at all, dampened the space-induced expansion of naive cells, showing that the two populations are not independent in their requirements for peripheral niches.
C1 Inst Curie, Immunol Lab, F-75005 Paris, France.
   Inst Curie, U520, INSERM, F-75005 Paris, France.
   NIAID, Ghost Lab, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
   Univ Vermont, Coll Med, Dept Obstet & Gynecol, Burlington, VT 05405 USA.
   Inst Pasteur, EMI 0101, INSERM, Unite Cytokines & Dev Lymphoide, F-75015 Paris, France.
RP Lantz, O (reprint author), Inst Curie, Immunol Lab, 26 Rue Ulm, F-75005 Paris, France.
RI Lantz, Olivier/J-4960-2012; Di Santo, James/M-4298-2014
OI Lantz, Olivier/0000-0003-3161-7719; Di Santo, James/0000-0002-7146-1862
NR 64
TC 60
Z9 61
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD OCT 6
PY 2003
VL 198
IS 7
BP 1089
EP 1102
DI 10.1084/jem.20030963
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 730ZQ
UT WOS:000185860400011
PM 14517277
ER

PT J
AU Singh, NJ
   Schwartz, RH
AF Singh, NJ
   Schwartz, RH
TI The strength of persistent antigenic stimulation modulates adaptive
   tolerance in peripheral CD4(+) T cells
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
DE tuning; adaptation; CD69; f-actin; anergy
ID IN-VIVO; SIGNAL INTEGRATION; IMMUNE-SYSTEM; SELF; ACTIVATION;
   FLEXIBILITY; REACTIVITY; SELECTION; SENSITIVITY; REPERTOIRE
AB The quantitative adaptation of receptor thresholds allows cells to tailor their responses to changes in ambient ligand concentration in many biological systems. Such a cell-intrinsic calibration of T cell receptor (TCR) sensitivity could be involved in regulating responses to autoantigens, but this has never been demonstrated for peripheral T cells. We examined the ability of monoclonal naive T cells to modulate their responsiveness differentially after exposure to fourfold different levels of persistent antigen stimulation in vivo. T cells expanded and entered a tolerant state with different kinetics in response to the two levels of stimulation, but eventually adjusted to a similar slow rate of turnover. In vivo restimulation revealed a greater impairment in the proliferative ability of T cells resident in a higher antigen presentation environment. We also observed subtle differences in TCR signaling and in vitro cytokine production consistent with differential adaptation. Unexpectedly, the system failed to similarly compensate to the persistent stimulus in vivo at the level of CD69 expression and actin polymerization. This greater responsiveness of T cells residing in a host with a lower level of antigen presentation allows us to demonstrate for the first time an intrinsic tuning process in mature T lymphocytes, albeit one more complex than current theories predict.
C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Room 111,4 Ctr Dr MSC-0420, Bethesda, MD 20892 USA.
NR 30
TC 67
Z9 67
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD OCT 6
PY 2003
VL 198
IS 7
BP 1107
EP 1117
DI 10.1084/jem.20030913
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 730ZQ
UT WOS:000185860400013
PM 14530379
ER

PT J
AU de Jong, FA
   Mathijssen, RHJ
   de Bruijn, P
   Loos, WJ
   Verweij, J
   Sparreboom, A
AF de Jong, FA
   Mathijssen, RHJ
   de Bruijn, P
   Loos, WJ
   Verweij, J
   Sparreboom, A
TI Determination of irinotecan (CPT-11) and SN-38 in human whole blood and
   red blood cells by liquid chromatography with fluorescence detection
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
   AND LIFE SCIENCES
LA English
DT Article
DE irinotecan; SN-38; CPT-11
ID CAMPTOTHECIN; PHARMACOKINETICS; ERYTHROCYTES; SEPARATION; METABOLITE;
   TOPOTECAN; ALBUMIN; PLASMA
AB An analytical method was developed for the anticancer agent irinotecan (CPT-11) and its main metabolite SN-38 in human whole blood and in red blood cells (RBCs). Sample pretreatment involved deproteinization of whole blood or plasma-diluted RBCs isolated by MESED instruments, with a mixture of aqueous perchloric acid and methanol (1:1, v/v). Separation was carried out using isocratic elution on a Hypersil ODS stationary phase. with detection at excitation and emission wavelengths of 355 and 515 nm, respectively. The lower limit of quantitation (LLQ) in blood was established at 5.00 ng/ml for both compounds, with values for within-run precision (WRP) and between-run precision (BRP) of less than 10%. The method is currently being applied to investigate the blood distribution of CPT-11 and SN-38 in cancer patients. (C) 2003 Elsevier B.V. All rights reserved.
C1 Erasmus MC Univ, Med Ctr Rotterdam, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands.
RP Sparreboom, A (reprint author), NCI, Med Oncol Clin Res Unit, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011
NR 16
TC 30
Z9 30
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD OCT 5
PY 2003
VL 795
IS 2
BP 383
EP 388
DI 10.1016/S1570-0232(03)00574-9
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 730GA
UT WOS:000185819800025
PM 14522044
ER

PT J
AU Kovacs, M
   Wang, F
   Hu, AH
   Zhang, Y
   Sellers, JR
AF Kovacs, M
   Wang, F
   Hu, AH
   Zhang, Y
   Sellers, JR
TI Functional divergence of human cytoplasmic myosin II - Kinetic
   characterization of the non-muscle IIA isoform
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DEPENDENT ADENOSINE-TRIPHOSPHATASE; SKELETAL-MUSCLE MYOSIN; HEAVY-CHAIN;
   DIFFERENTIAL LOCALIZATION; ACTOMYOSIN SUBFRAGMENT-1; FLUORESCENT-PROBE;
   NEURITE OUTGROWTH; SMOOTH-MUSCLE; RELEASE STEPS; LIGHT-CHAINS
AB Cytoplasmic (or non-muscle) myosin II isoforms are widely expressed molecular motors playing essential cellular roles in cytokinesis and cortical tension maintenance. Two of the three human non-muscle myosin II isoforms (IIA and IIB) have been investigated at the protein level. Transient kinetics of non-muscle myosin IIB showed that this motor has a very high actomyosin ADP affinity and slow ADP release. Here we report the kinetic characterization of the non-muscle myosin IIA isoform. Similar to non-muscle myosin IIB, non-muscle myosin IIA shows high ADP affinity and little enhancement of the ADP release rate by actin. The ADP release rate constant, however, is more than an order of magnitude higher than the steady-state ATPase rate. This implies that non-muscle myosin IIA spends only a small fraction of its ATPase cycle time in strongly actin-bound states, which is in contrast to non-muscle myosin IIB. Non-muscle myosin II isoforms thus appear to have distinct enzymatic properties that may be of importance in carrying out their cellular functions.
C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202, Bethesda, MD 20892 USA.
RI Kovacs, Mihaly/A-6841-2011
NR 46
TC 120
Z9 122
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 38132
EP 38140
DI 10.1074/jbc.M305453200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100007
PM 12847096
ER

PT J
AU Webster, JM
   Tiwari, S
   Weissman, AM
   Wojcikiewicz, RJH
AF Webster, JM
   Tiwari, S
   Weissman, AM
   Wojcikiewicz, RJH
TI Inositol 1,4,5-trisphosphate receptor ubiquitination is mediated by
   mammalian Ubc7, a component of the endoplasmic reticulum-associated
   degradation pathway, and is inhibited by chelation of intracellular Zn2+
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ER-ASSOCIATED DEGRADATION; SH-SY5Y NEUROBLASTOMA-CELLS; MOTILITY
   FACTOR-RECEPTOR; INDUCED DOWN-REGULATION; ALZHEIMERS-DISEASE; PROTEASOME
   PATHWAY; CHOLINESTERASE-INHIBITORS; PROTEIN TRANSLOCATION;
   LIGAND-BINDING; CA2+
AB In response to activation of certain cell surface receptors, inositol 1,4,5-trisphosphate receptors (InsP(3)Rs), which are located in the endoplasmic reticulum, can be rapidly ubiquitinated and then degraded by the proteasome. Ubiquitination is mediated by the concerted action of ubiquitin-conjugating enzymes (Ubcs or E2s) and ubiquitin-protein ligases (E3s). In the present study we have examined the enzymology of ubiquitination of endogenous InsP(3)Rs in muscarinic agonist-stimulated SH-SY5Y human neuroblastoma cells, focusing our attention on two mammalian E2s, MmUbc6 and MmUbc7, that have been implicated in endoplasmic reticulum-associated degradation (ERAD) and are homologous to the yeast ERAD E2s, Ubc6p and Ubc7p. Analysis of SH-SY5Y cells stably expressing these enzymes and their dominant-negative mutants revealed that MmUbc7 mediates InsP(3)R ubiquitination and down-regulation, but that MmUbc6 does not. These data indicate that InsP(3)Rs are processed by a component of the ERAD pathway and suggest that MmUbc7 may be employed selectively to ubiquitinate proteins, like InsP(3)Rs, that are subject to regulated ERAD. Additional studies showed that the Zn2+ chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine blocked InsP(3)R ubiquitination, suggesting that a RING finger domain- containing E3 is also involved in this process. Finally, muscarinic agonist-induced InsP(3)R ubiquitination was seen in rat brain slices, indicating that the results obtained from SH-SY5Y cells reflect a physiological process.
C1 SUNY Upstate Med Univ, Dept Pharmacol, Syracuse, NY 13210 USA.
   NCI, Regulat Prot Funct Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Wojcikiewicz, RJH (reprint author), SUNY Upstate Med Univ, Dept Pharmacol, 750 E Adams St, Syracuse, NY 13210 USA.
FU NIDDK NIH HHS [5R01DK49194]
NR 67
TC 40
Z9 42
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 38238
EP 38246
DI 10.1074/jbc.M305600200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100020
PM 12869571
ER

PT J
AU Harada, J
   Kokura, K
   Kanei-Ishii, C
   Nomura, T
   Khan, MM
   Kim, Y
   Ishii, S
AF Harada, J
   Kokura, K
   Kanei-Ishii, C
   Nomura, T
   Khan, MM
   Kim, Y
   Ishii, S
TI Requirement of the co-repressor homeodomain-interacting protein kinase 2
   for Ski-mediated inhibition of bone morphogenetic protein-induced
   transcriptional activation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSFORMING-GROWTH-FACTOR; HISTONE DEACETYLASE COMPLEX; TGF-BETA
   RECEPTOR; THYROID-HORMONE RECEPTOR; N-COR; COREPRESSOR COMPLEX;
   SIGNALING PATHWAYS; TUMOR-SUPPRESSOR; SMAD PROTEINS; MAD PROTEINS
AB Multiple co-repressors such as N-CoR/SMRT, mSin3, and the c-ski proto-oncogene product (c-Ski) mediate the transcriptional repression induced by Mad and the thyroid hormone receptor by recruiting the histone deacetylase complex. c-Ski also binds directly to Smad proteins, which are transcriptional activators in the transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP) signaling pathways, and inhibits TGF-beta/BMP-induced transcriptional activation. However, it remains unknown whether other co-repressor(s) are also involved with Ski in the negative regulation of the TGF-beta/BMP signaling pathways. Here, we report that the co-repressor homeodomain-interacting protein kinase 2 (HIPK2) directly binds to both c-Ski and Smad1. HIPK2 efficiently inhibited Smad1/4-induced transcription from the Smad site-containing promoter. A dominant negative form of HIPK2, in which the ATP binding motif in the kinase domain and the putative phosphorylation sites were mutated, enhanced Smad1/4-dependent transcription and the BMP-induced expression of alkaline phosphatase. Furthermore, the c-Ski-induced inhibition of the Smad1/4-dependent transcription was suppressed by a dominant negative form of HIPK2. The HIPK2 co-repressor activity may be regulated by an un-characterized HIPK2 kinase. These results indicate that HIPK2, together with c-Ski, plays an important role in the negative regulation of BMP-induced transcriptional activation.
C1 RIKEN, Tsukuba Inst, Mol Genet Lab, Tsukuba, Ibaraki 3050074, Japan.
   NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Ishii, S (reprint author), RIKEN, Tsukuba Inst, Mol Genet Lab, 3-1-1 Koyadai, Tsukuba, Ibaraki 3050074, Japan.
RI Ishii, Shunsuke/A-5271-2016
NR 60
TC 43
Z9 47
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 38998
EP 39005
DI 10.1074/jbc.M307112200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100111
PM 12874272
ER

PT J
AU Ying, SX
   Hussain, ZJ
   Zhang, YE
AF Ying, SX
   Hussain, ZJ
   Zhang, YE
TI Smurf1 facilitates myogenic differentiation and antagonizes the bone
   morphogenetic protein-2-induced osteoblast conversion by targeting Smad5
   for degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSFORMING-GROWTH-FACTOR; TGF-BETA RECEPTOR; E3 UBIQUITIN LIGASE;
   SIGNAL-TRANSDUCTION; C2C12 MYOBLASTS; I RECEPTORS; CELL-LINE;
   EXPRESSION; MUSCLE; SUPERFAMILY
AB Controlled proteolysis mediated by Smad ubiquitination regulatory factors (Smurfs) plays a crucial role in modulating cellular responses to signaling of the transforming growth factor-beta (TGF-beta) superfamily. However, it is not clear what influences the selectivity of Smurfs in the individual signaling pathway, nor is it clear the biological function of Smurfs in vivo. Using a mouse C2C12 myoblast cell differentiation system, which is subject to control by both TGF-beta and bone morphogenetic protein (BMP), here we examine the role of Smurf1 in myogenic differentiation. We show that increased expression of Smurf1 promotes myogenic differentiation of C2C12 cells and blocks the BMP-induced osteogenic conversion but has no effect on the TGF-beta-induced differentiation arrest. Consistent with an inhibitory role in the BMP signaling pathway, the elevated Smurf1 markedly reduces the level of endogenous Smad5, whereas it leaves unaltered that of Smad2, Smad3, and Smad7, which are components of the TGF-beta pathway. Adding back Smad5 from a different source to the Smurf1-overexpressing cells restores the BMP-mediated osteoblast conversion. Finally, by depletion of the endogenous Smurf1 through small interfering RNA-mediated RNA interference, we demonstrate that Smurf1 is required for the myogenic differentiation of C2C12 cells and plays an important regulatory role in the BMP-2-mediated osteoblast conversion.
C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 1C27, Bethesda, MD 20892 USA.
RI Zhang, Ying/G-3657-2015
OI Zhang, Ying/0000-0003-2753-7601
FU Intramural NIH HHS [Z01 BC010419-08, ZIA BC011168-01]
NR 37
TC 51
Z9 57
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 39029
EP 39036
DI 10.1074/jbc.M301193200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100115
PM 12871975
ER

PT J
AU Hwang, S
   Tamilarasu, N
   Kibler, K
   Cao, H
   Ali, A
   Ping, YH
   Jeang, KT
   Rana, TM
AF Hwang, S
   Tamilarasu, N
   Kibler, K
   Cao, H
   Ali, A
   Ping, YH
   Jeang, KT
   Rana, TM
TI Discovery of a small molecule Tat-trans-activation-responsive RNA
   antagonist that potently inhibits human immunodeficiency virus-1
   replication
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LONG TERMINAL REPEAT; CELLULAR PROTEIN-KINASE; HIV-1 TAR; P-TEFB;
   TRANSCRIPTION-ELONGATION; IN-VITRO; GENE-EXPRESSION; TYPE-1 TAT; CYCLIN
   T1; RECOGNITION
AB Antiretroviral therapy to treat AIDS uses molecules that target the reverse transcriptase and protease enzymes of human immunodeficiency virus, type 1 (HIV-1). A major problem associated with these treatments, however, is the emergence of drug-resistant strains. Thus, there is a compelling need to find drugs against other viral targets. One such target is the interaction between Tat, an HIV-1 regulatory protein essential for viral replication, and trans-activation-responsive (TAR) RNA. Here we describe the design and synthesis of an encoded combinatorial library containing 39,304 unnatural small molecules. Using a rapid high through-put screening technology, we identified 59 compounds. Structure-activity relationship studies led to the synthesis of 19 compounds that bind TAR RNA with high affinities. In the presence of a representative Tat-TAR inhibitor (5 muM TR87), we observed potent and sustained suppression of HIV replication in cultured cells over 24 days. The same concentration of this inhibitor did not exhibit any toxicity in cell cultures or in mice. TR87 was also shown to specifically disrupt Tat-TAR binding in vitro and inhibit Tat-mediated transcriptional activation in vitro and in vivo, providing a strong correlation between its activities and inhibition of HIV-1 replication. These results provide a structural scaffold for further development of new drugs, alone or in combination with other drugs, for treatment of HIV-1-infected individuals. Our results also suggest a general strategy for discovering pharmacophores targeting RNA structures that are essential in progression of other infectious, inflammatory, and genetic diseases.
C1 Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Chem Biol Program, Worcester, MA 01605 USA.
   NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Chem Biol Program, 364 Plantat St, Worcester, MA 01605 USA.
EM tariq.rana@umassmed.edu
RI Jeang, Kuan-Teh/A-2424-2008
FU NIAID NIH HHS [AI45466, AI41404]
NR 49
TC 60
Z9 63
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 39092
EP 39103
DI 10.1074/jbc.M301749200
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100123
PM 12857725
ER

PT J
AU Bose, S
   French, S
   Evans, FJ
   Joubert, F
   Balaban, RS
AF Bose, S
   French, S
   Evans, FJ
   Joubert, F
   Balaban, RS
TI Metabolic network control of oxidative phosphorylation - Multiple roles
   of inorganic phosphate
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CREATINE-KINASE; MITOCHONDRIAL RESPIRATION; MATHEMATICAL-MODEL;
   OXYGEN-CONSUMPTION; ENERGY-METABOLISM; ISOLATED HEART; RABBIT HEARTS;
   DEHYDROGENASE; HEMOGLOBIN; TRANSPORT
AB Phosphate (P-i) is a putative cytosolic signaling molecule in the regulation of oxidative phosphorylation. Here, by using a multiparameter monitoring system, we show that P-i controls oxidative phosphorylation in a balanced fashion, modulating both the generation of useful potential energy and the formation of ATP by F1F0-ATPase in heart and skeletal muscle mitochondria. In these studies the effect of P-i was determined on the mitochondria [NADH], NADH generating capacity, matrix pH, membrane potential, oxygen consumption, and cytochrome reduction level. P-i enhanced NADH generation and was obligatory for electron flow under uncoupled conditions. P-i oxidized cytochrome b (cyto-b) and reduced cytochrome c (cyto-c), potentially improving the coupling between the NADH free energy and the proton motive force. The apparent limitation in reducing equivalent flow between cyto-b and cyto-c in the absence of P-i was confirmed in the intact heart by using optical spectroscopic techniques under conditions with low cytosolic [P-i]. These results demonstrate that P-i signaling results in the balanced modulation of oxidative phosphorylation, by influencing both DeltaG(H+) generation and ATP production, which may contribute to the energy metabolism homeostasis observed in intact systems.
C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bldg 10,Rm BID-161, Bethesda, MD 20892 USA.
RI Balaban, Robert/A-7459-2009
OI Balaban, Robert/0000-0003-4086-0948
NR 48
TC 120
Z9 120
U1 1
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 39155
EP 39165
DI 10.1074/jbc.M306409200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100129
PM 12871940
ER

PT J
AU Bortner, CD
   Cidlowski, JA
AF Bortner, CD
   Cidlowski, JA
TI Uncoupling cell shrinkage from apoptosis reveals that Na+ influx is
   required for volume loss during programmed cell death
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CASPASE ACTIVATION; NEURONAL APOPTOSIS; K+ CHANNELS; POTASSIUM; EFFLUX;
   MECHANISMS; DEGRADATION; LYMPHOCYTES; THYMOCYTES; INHIBITION
AB Cell shrinkage, or the loss of cell volume, is a ubiquitous characteristic of programmed cell death that is observed in all examples of apoptosis, independent of the death stimulus. This decrease in cell volume occurs in synchrony with other classical features of apoptosis. The molecular basis for cell shrinkage during apoptosis involves fluxes of intracellular ions including K+, Na+, and Cl-. Here we show for the first time that these ion fluxes, but not cell shrinkage, are necessary for apoptosis. Using sodium-substituted medium during anti-Fas treatment of Jurkat cells, we observed cellular swelling, a property normally associated with necrosis, in contrast to the typical cell shrinkage. Surprisingly, these swollen cells displayed all of the other classical features of apoptosis, including chromatin condensation, externalization of phosphatidylserine, caspase activity, poly(ADP)-ribose polymerase cleavage, and internucleosomal DNA degradation. These swollen cells had a marked decrease in intracellular potassium, and subsequent inhibition of this potassium loss completely blocked apoptosis. Reintroduction of sodium ions in cell cultures reversed this cellular swelling, resulting in a dramatic loss of cell volume and the characteristic apoptotic morphology. Additionally, inhibition of sodium influx using a sodium channel blocker saxitoxin completely prevented the onset of anti-Fas-induced apoptosis in Jurkat cells. These findings suggest that sodium influx can control not only changes in cell size but also the activation of apoptosis, whereas potassium ion loss controls the progression of the cell death process. Therefore cell shrinkage can be separated from other features of apoptosis.
C1 NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
NR 39
TC 110
Z9 114
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 39176
EP 39184
DI 10.1074/jbc.M303516200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100131
PM 12821680
ER

PT J
AU Czipri, M
   Otto, JM
   Cs-Szabo, G
   Kamath, RV
   Vermes, C
   Firneisz, G
   Kolman, KJ
   Watanabe, H
   Li, YF
   Roughley, PJ
   Yamada, Y
   Olsen, BR
   Glant, TT
AF Czipri, M
   Otto, JM
   Cs-Szabo, G
   Kamath, RV
   Vermes, C
   Firneisz, G
   Kolman, KJ
   Watanabe, H
   Li, YF
   Roughley, PJ
   Yamada, Y
   Olsen, BR
   Glant, TT
TI Genetic rescue of chondrodysplasia and the perinatal lethal effect of
   cartilage link protein deficiency
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN ARTICULAR-CARTILAGE; N-TERMINAL PEPTIDE; TUMOR-NECROSIS-FACTOR;
   AMINO-ACID-SEQUENCES; HYALURONIC-ACID; MESSENGER-RNA; CHROMOSOMAL
   LOCALIZATION; CDNA CLONES; SULFATE PROTEOGLYCAN; RAT CHONDROSARCOMA
AB The targeted disruption of cartilage link protein gene (Crtl1) in homozygous mice resulted in a severe chondrodysplasia and perinatal lethality. This raised the question of whether the abnormalities seen in Crtl1 null mice are all caused by the absence of link protein in cartilage or whether the deficiency of the protein in other tissues and organs contributed to the phenotype. To address this question we have generated transgenic mice overexpressing cartilage link protein under the control of a cartilage-specific promoter, and then these transgenic mice were used for a genetic rescue of abnormalities in Crtl1 null mice. While the overexpression of cartilage link protein resulted in no abnormal phenotype, the cartilage-specific transgene expression of link protein could completely prevent the perinatal mortality of link protein-deficient mice and, depending on the level of the link protein expression, rescue skeletal abnormalities. Although link protein was originally isolated from cartilage, we found and determined Crtl1 transcripts and corresponding proteins in every organ tested from mouse embryos to aging animals. We also identified three additional members of the link protein family, all co-localized with hyaluronic acid-binding proteoglycans in the mouse genome. The ubiquitous presence of link protein suggests a general and systemic function of link protein in the organization of extracellular matrix in a number of tissues, possibly interacting with other proteoglycans, such as versican, brevican, and neurocan.
C1 Rush Univ, Rush Presbyterian St Lukes Med Ctr, Dept Biochem, Sect Biochem & Mol Biol, Chicago, IL 60612 USA.
   Rush Univ, Rush Presbyterian St Lukes Med Ctr, Dept Orthoped Surg, Sect Biochem & Mol Biol, Chicago, IL 60612 USA.
   Aichi Med Univ, Inst Mol Sci Med, Aichi 4801195, Japan.
   Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   Shriners Hosp Crippled Children, Genet Unit, Montreal, PQ H3G 1A6, Canada.
   McGill Univ, Dept Surg, Montreal, PQ H3G 1A6, Canada.
   NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20982 USA.
RP Glant, TT (reprint author), Rush Univ, Rush Presbyterian St Lukes Med Ctr, Dept Biochem, Sect Biochem & Mol Biol, 1653 W Congress Pkwy, Chicago, IL 60612 USA.
FU NIAMS NIH HHS [AR40310, AR47135]
NR 63
TC 26
Z9 28
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 3
PY 2003
VL 278
IS 40
BP 39214
EP 39223
DI 10.1074/jbc.M303329200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 726AM
UT WOS:000185575100136
PM 12732630
ER

PT J
AU Zerhouni, E
AF Zerhouni, E
TI The NIH roadmap
SO SCIENCE
LA English
DT Editorial Material
C1 NIH, Bethesda, MD 20892 USA.
RP Zerhouni, E (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 537
Z9 579
U1 1
U2 23
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD OCT 3
PY 2003
VL 302
IS 5642
BP 63
EP +
DI 10.1126/science.1091867
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 727UD
UT WOS:000185678500030
PM 14526066
ER

PT J
AU Court, DL
   Swaminathan, S
   Yu, DG
   Wilson, H
   Baker, T
   Bubunenko, M
   Sawitzke, J
   Sharan, SK
AF Court, DL
   Swaminathan, S
   Yu, DG
   Wilson, H
   Baker, T
   Bubunenko, M
   Sawitzke, J
   Sharan, SK
TI Mini-lambda: a tractable system for chromosome and BAC engineering
SO GENE
LA English
DT Article
DE recombineering; red recombination; oligo-recombination; BAC engineering;
   MAMA-PCR
ID BACTERIAL ARTIFICIAL CHROMOSOMES; ESCHERICHIA-COLI; DNA FRAGMENTS;
   RECOMBINATION; CLONING; OLIGONUCLEOTIDES; VECTOR; GENE
AB The bacteriophage lambda (lambda) recombination system Red has been used for engineering large DNA fragments cloned into P1 and bacterial artificial chromosomes (BAC or PAC) vectors. So far, this recombination system has been utilized by transferring the BAC or PAC clones into bacterial cells that harbor a defective lambda prophage. Here we describe the generation of a mini-lambda DNA that can provide the Red recombination functions and can be easily introduced by electroporation into any E. coli strain, including the DH10B-carrying BACs or PACs. The mini-lambda DNA integrates into the bacterial chromosome as a defective prophage. In addition, since it retains attachment sites, it can be excised out to cure the cells of the phage DNA. We describe here the use of the mini-lambda recombination system for BAC modification by introducing a selectable marker into the vector sequence of a BAC clone. In addition, using the mini-lambda, we create a single missense mutation in the human BRCA2 gene cloned in a BAC without the use of any selectable marker. The ability to generate recombinants very efficiently demonstrates the usefulness of the mini-h as a very simple mobile system for in vivo genome engineering by homologous recombination, a process named recombineering. (C) 2003 Elsevier B.V. All rights reserved.
C1 NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, FCRDC, Frederick, MD 21702 USA.
   NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Court, DL (reprint author), NCI, Mol Control & Genet Sect, Gene Regulat & Chromosome Biol Lab, FCRDC, Bldg 539,Room 243,POB B, Frederick, MD 21702 USA.
NR 16
TC 74
Z9 77
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD OCT 2
PY 2003
VL 315
BP 63
EP 69
DI 10.1016/S0378-1119(03)00728-5
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 737HU
UT WOS:000186225000007
PM 14557065
ER

PT J
AU Choi, MS
   Anderson, MA
   Zhang, ZJ
   Zimonjic, DB
   Popescu, N
   Mukherjee, AB
AF Choi, MS
   Anderson, MA
   Zhang, ZJ
   Zimonjic, DB
   Popescu, N
   Mukherjee, AB
TI Neutral ceramidase gene: role in regulating ceramide-induced apoptosis
SO GENE
LA English
DT Article
DE neutral/alkaline ceramidase; ceramide; apoptosis; gastrointentinal
ID MOLECULAR-CLONING; INTESTINAL-TRACT; SPHINGOMYELIN; PURIFICATION;
   DISEASE; KIDNEY; STRESS
AB The sphingolipid, ceramide, is a natural dietary constituent and a potent mediator of apoptosis. If left undegraded, it may induce apoptosis and cause disruption of cellular integrity. A potential mechanism to prevent ceramide-induced apoptosis in various organs may involve ceramidases that facilitate the degradation of ceramide. In this study, we first isolated and characterized the murine neutral ceramidase (N-CDase) gene, mapped its chromosomal location and determined its developmental and organ-specific expression. Then we used cultured mesangial cells as our in vitro model and mouse gastrointestinal (GI) tract as the in vivo model to determine the effects of an inhibitor of N-CDase, D-erythro-MAPP, to delineate whether N-CDase plays a role in preventing ceramide-induced apoptosis. Our results show that: (i) the structure of the murine neutral ceramidase gene is virtually identical to that of the human gene; (ii) it is localized on chromosome 19 at bands C2-C3 that is syntenic to human chromosome 10q24-26; (iii) N-CDase expression is developmentally regulated and it is expressed at high levels in cultured mesangial cells and in specific regions of the mouse small intestine; (iv) inhibition of N-CDase by D-erythro-MAPP leads to increased ceramide levels and consequent apoptosis in cultured mesangial cells; (v) mice treated with D-erythro-MAPP alone also caused apoptosis in the small intestine; and (vi) mice treated with D-erythro-MAPP prior to feeding C2 ceramide manifest markedly elevated levels of apoptosis in the GI tract raising the possibility that neutral ceramidase plays a detoxifying role against inadvertent stimulation of ceramide-induced apoptosis in organs that come in contact with this sphingolipid. We propose that N-CDase is an essential component of an innate detoxifying mechanism to prevent ceramide-induced apoptosis. (C) 2003 Elsevier B.V. All rights reserved.
C1 NICHHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA.
   NCI, NIH, Bethesda, MD 20892 USA.
RP Mukherjee, AB (reprint author), NICHHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Room 9S241,Bldg 10, Bethesda, MD 20892 USA.
EM mukherja@exchange.nih.gov
NR 34
TC 28
Z9 30
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
EI 1879-0038
J9 GENE
JI Gene
PD OCT 2
PY 2003
VL 315
BP 113
EP 122
DI 10.1016/S0378-1119(03)00721-2
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 737HU
UT WOS:000186225000013
PM 14557071
ER

PT J
AU Lanh, MN
   Bay, PV
   Ho, VA
   Thanh, TC
   Lin, FYC
   Bryla, DA
   Chu, CY
   Schiloach, J
   Robbins, JB
   Schneerson, R
   Szu, SC
AF Lanh, MN
   Bay, PV
   Ho, VA
   Thanh, TC
   Lin, FYC
   Bryla, DA
   Chu, CY
   Schiloach, J
   Robbins, JB
   Schneerson, R
   Szu, SC
TI Persistent efficacy of Vi conjugate vaccine against typhoid fever in
   young children
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID VIETNAM
C1 Dong Thap Prov Hosp, Cao Lanh, Vietnam.
   Inst Pasteur, Ho Chi Minh City, Vietnam.
   NIH, Bethesda, MD 20892 USA.
RP Lanh, MN (reprint author), Dong Thap Prov Hosp, Cao Lanh, Vietnam.
EM szus@mail.nih.gov
NR 5
TC 13
Z9 14
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 2
PY 2003
VL 349
IS 14
BP 1390
EP 1391
DI 10.1056/NEJM200310023491423
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 727EM
UT WOS:000185644000033
ER

PT J
AU George, A
   Morse, HC
   Justice, MJ
AF George, A
   Morse, HC
   Justice, MJ
TI The homeobox gene Hex induces T-cell-derived lymphomas when
   overexpressed in hematopoietic precursor cells
SO ONCOGENE
LA English
DT Article
DE Hex; retroviral transduction; T-cell lymphoma
ID LEUKEMIC HEMATOPOIESIS; EXPRESSION; DIFFERENTIATION; MOUSE; PROTEIN;
   MICE; PRH; TRANSFORMATION; ACTIVATION; ZEBRAFISH
AB Proviral insertions at the viral insertion site Lvis1 occur frequently in B- and T-cell leukemias and lymphomas in AKXD mice and activate two nearby genes, the divergent homeobox gene Hex and the kinesin-related spindle protein gene Eg5. To determine whether Hex misexpression results in the altered differentiation or neoplastic transformation of hematopoietic lineages, we have transplanted mice with bone marrow cells transduced with retrovirus containing the Hex coding region. High levels of Hex expression in hematopoietic precursor cells inhibit contribution to mature blood cell lineages by these precursors. Hex bone marrow transplant recipient mice also develop hematologic neoplasms that appear to originate in the bone marrow. The tumors have clonal rearrangements of the TCR locus, are Thy1(+), and are CD4(+)CD8(+), CD4(-)CD8(-), or mixed, indicating tumor origin from a precursor T-cell population. Tumors in transplant mice contain clonal and transcriptionally active Hex proviral insertions, demonstrating a causal role for Hex misexpression in the onset of these neoplasms. Our results demonstrate that Hex can act as a T lineage oncogene when misexpressed in hematopoietic precursor cells.
C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   Baylor Coll Med, MD PhD Program, Houston, TX 77030 USA.
   NIAID, Immunopathol Lab, NIH, Rockville, MD USA.
RP Justice, MJ (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA.
OI Morse, Herbert/0000-0002-9331-3705
FU NCI NIH HHS [CA63229]
NR 37
TC 34
Z9 34
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 2
PY 2003
VL 22
IS 43
BP 6764
EP 6773
DI 10.1038/sj.onc.1206822
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 729XA
UT WOS:000185799300011
PM 14555989
ER

PT J
AU Hornstein, I
   Mortin, MA
   Katzav, S
AF Hornstein, I
   Mortin, MA
   Katzav, S
TI DroVav, the Drosophila melanogaster homologue of the mammalian Vav
   proteins, serves as a signal transducer protein in the Rac and DER
   pathways
SO ONCOGENE
LA English
DT Article
DE Vav; Rac; cytoskeleton; RNAi; Drosophila
ID T-CELL-RECEPTOR; NUCLEOTIDE EXCHANGE FACTOR; EMBRYONIC VENTRAL ECTODERM;
   DOUBLE-STRANDED-RNA; EGF RECEPTOR; CYTOSKELETAL REORGANIZATION;
   PROTOONCOGENE PRODUCT; GDP/GTP EXCHANGE; TYROSINE KINASES; FEEDBACK LOOP
AB Mammalian Vav signal transducer proteins couple receptor tyrosine kinase signals to the activation of the Rho/Rac GTPases, leading to cell differentiation and/or proliferation. The unique and complex structure of mammalian Vav proteins is preserved in the Drosophila melanogaster homologue, DroVav. We demonstrate that DroVav functions as a guanine-nucleotide exchange factor (GEF) for DRac. Drosophila cells overexpressing wildtype (wt) DroVav exhibited a normal morphology. However, overexpression of a truncated DroVav mutant ( that functions as an oncogene when expressed in NIH3T3 cells) results in striking changes in the actin cytoskeleton, resembling those usually visible following Rac activation. Dominant-negative DRac abrogated these morphological changes, suggesting that the effect of the truncated DroVav mutant is mediated by activation of DRac. In Drosophila cells, we find that stimulation of the Drosophila EGF receptor (DER) increases tyrosine phosphorylation of DroVav, which in turn associates with tyrosine-phosphorylated DER. In addition, the following results imply that DroVav participates in downstream DER signalling, such as ERK phosphorylation: ( a) overexpression of DroVav induces ERK phosphorylation; and (b) 'knockout' of DroVav by RNA interference blocks ERK phosphorylation induced by DER stimulation. Unlike mammalian Vav proteins, DroVav was not found to induce Jnk phosphorylation under the experimental circumstances tested in fly cells. The se results establish the role of DroVav as a signal transducer that participates in receptor tyrosine kinase pathways and functions as a GEF for the small RhoGTPase, DRac.
C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Hubert H Humphrey Ctr Expt Med & Canc Res, IL-91120 Jerusalem, Israel.
   NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Katzav, S (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Hubert H Humphrey Ctr Expt Med & Canc Res, IL-91120 Jerusalem, Israel.
RI Mortin, Mark/B-4251-2008
NR 75
TC 13
Z9 13
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 2
PY 2003
VL 22
IS 43
BP 6774
EP 6784
DI 10.1038/sj.onc.1207027
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 729XA
UT WOS:000185799300012
PM 14555990
ER

PT J
AU Chevallier, C
   Richardson, AD
   Edler, MC
   Hamel, E
   Harper, MK
   Ireland, CM
AF Chevallier, C
   Richardson, AD
   Edler, MC
   Hamel, E
   Harper, MK
   Ireland, CM
TI A new cytotoxic and tubulin-interactive milnamide derivative from a
   marine sponge Cymbastela sp.
SO ORGANIC LETTERS
LA English
DT Article
ID HEMIASTERLIN; PEPTIDES; TRIPEPTIDE
AB The crude methanol extract of a marine sponge Cymbastela sp. collected in Papua New Guinea was selected for chemical investigation due to its significant cytotoxicity. Fractionation of the extract led to the isolation of jaspamide (1), hemiasterlin (2), milnamide A (3), and a new metabolite, milnamide D (4). The structure was solved by interpretation of NMR and mass spectra data. The cytotoxic and antitubulin activities of milinamide D (4) were evaluated.
C1 Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA.
   NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Screening Technol Branch,NIH, Ft Detrick, MD 21702 USA.
RP Ireland, CM (reprint author), Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA.
EM cireland@pharm.utah.edu
RI Richardson, Adam/B-5157-2008
FU NCI NIH HHS [5 P30 CA 42014, CA 36622]; NCRR NIH HHS [1 S10RR06262]
NR 10
TC 28
Z9 30
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1523-7060
J9 ORG LETT
JI Org. Lett.
PD OCT 2
PY 2003
VL 5
IS 20
BP 3737
EP 3739
DI 10.1021/ol035476c
PG 3
WC Chemistry, Organic
SC Chemistry
GA 725WN
UT WOS:000185565500050
PM 14507218
ER

PT J
AU Yang, YS
   Guccione, S
   Bednarski, MD
AF Yang, YS
   Guccione, S
   Bednarski, MD
TI Comparing genomic and histologic correlations to radiographic changes in
   tumors: A murine SCCVII model study
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE contrast-enhanced magnetic resonance imaging (MRI); functional genomics;
   microarray analysis; animal tumor model; histologic analysis
ID ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; ANGIOGENESIS
   IN-VITRO; GENE-EXPRESSION; MACROPHAGE METALLOELASTASE; MOLECULAR
   CLASSIFICATION; EXTRACELLULAR-MATRIX; MAGNETIC-RESONANCE; CANCER;
   INTERLEUKIN-1
AB Rationale and Objectives. To investigate the correlation between the temporal changes in T1- and T2-weighted contrast-enhanced magnetic resonance imaging (MRI), histologic evaluation, and genomic analysis using oligonucleotide microarrays in a murine squamous cell carcinoma tumor models.
   Materials and Methods. The squamous cell carcinoma (SCC VII) cell line was used to initiate subcutaneous tumors in mice. This mouse model has been used as a model for human head and neck carcinomas. Animals were imaged using contrast enhanced MRI (CE-MRI). Different stages of tumor growth were defined based on changes in the T1- and T2-weighted MRI patterns. The contrast enhancing (CE) and nonenhancing (NE) regions of the tumors were marked and biopsied for oligonucleotide microarray and histologic analysis. Tumors with no differential contrast enhancement were used as controls.
   Results. Distinct temporal stages of tumor progression can be defined using both T1- and T2-weighted CE-MRI and microarray analysis. The early stage tumors show a homogeneous contrast enhancement pattern in the T1- and T2-weighted images with no significant differential gene expression from the center and periphery of the tumor. The more advanced tumors that show discrete regions of contrast enhancement in the post-contrast T1-weighted MRIs and tissues from the CE and NE regions show distinctly differential gene expression profiles. Histologic analysis (hematoxylin-eosin stain) showed that the samples obtained from the periphery and center of the early stage tumors and the CE and NE regions from these more advanced tumors were similar. The gene expression profiles of late-stage tumors that showed changes in T2-weighted MRI signal intensity were consistent with tissue degradation in the NE region, which also showed characteristic signs of tissue necrosis in histologic analysis.
   Conclusion. These results show that temporal changes in T1- and T2-weighted CE-MRI are related to distinct gene expression profiles, and histologic analysis may not be sufficient to detect these detailed changes. As tumors progress, discrete regions of post-contrast T1 enhancement are identified; these regions have distinct gene expression patterns despite similar histologic features. In late-stage tumors, regions of T2 signal changes are observed which correspond with tissue necrosis.
C1 Stanford Univ, Sch Med, Dept Radiol, MRS Res Ctr, Stanford, CA 94305 USA.
   NIH, Ctr Clin, Radiol & Imaging Sci Program, Bethesda, MD 20892 USA.
RP Bednarski, MD (reprint author), Stanford Univ, Sch Med, Dept Radiol, MRS Res Ctr, Stanford, CA 94305 USA.
FU NCI NIH HHS [CA86312-0, T32 CA09696]; NCRR NIH HHS [P41 RR09784]
NR 54
TC 15
Z9 15
U1 0
U2 0
PU ASSOC UNIV RADIOLOGISTS
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD OCT
PY 2003
VL 10
IS 10
BP 1165
EP 1175
DI 10.1016/S1076-6332(03)00327-1
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 732KR
UT WOS:000185944700011
PM 14587635
ER

PT J
AU Perbandt, M
   Tsai, IH
   Fuchs, A
   Banumathi, S
   Rajashankar, KR
   Georgieva, D
   Kalkura, N
   Singh, TP
   Genov, N
   Betzel, C
AF Perbandt, M
   Tsai, IH
   Fuchs, A
   Banumathi, S
   Rajashankar, KR
   Georgieva, D
   Kalkura, N
   Singh, TP
   Genov, N
   Betzel, C
TI Structure of the heterodimeric neurotoxic complex viperotoxin F
   (RV-4/RV-7) from the venom of Vipera russelli formosensis at 1.9
   angstrom resolution
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID SECRETORY PHOSPHOLIPASE A(2); X-RAY-DIFFRACTION; SNAKE-VENOM;
   AMMODYTES-AMMODYTES; PISCIVORUS PISCIVORUS; ANTICOAGULANT; PROTEIN;
   PURIFICATION; ASSOCIATION; INHIBITION
AB The presynaptic viperotoxin F is the major lethal component of the venom of Vipera russelli formosensis ( Taiwan viper). It is a heterodimer of two highly homologous (65% identity) but oppositely charged subunits: a basic and neurotoxic PLA(2) (RV-4) and an acidic non-toxic component with a very low enzymatic activity (RV-7). The crystal structure of the complex has been determined by molecular replacement and refined to 1.9 Angstrom resolution and an R factor of 22.3% with four RV-4/RV-7 complexes in the asymmetric unit, which do not exhibit any local point-group symmetry. The complex formation decreases the accessible surface area of the two subunits by similar to 1425 Angstrom(2). Both PLA(2)s are predicted to have very low, if any, anticoagulant activity. The structure of viperotoxin F is compared with that of the heterodimeric neurotoxin vipoxin from the venom of another viper, V. ammodytes meridionalis. The structural basis for the differences between the pharmacological activities of the two toxins is discussed. The neutralization of the negative charge of the major ligand for Ca2+, Asp49, by intersubunit salt bridges is probably a common mechanism of self-stabilization of heterodimeric Viperinae snake-venom neurotoxins in the absence of bound calcium.
C1 Univ Hamburg, Hosp Eppendorf, Inst Biochem & Mol Biol 1, DESY, D-22603 Hamburg, Germany.
   Acad Sinica, Inst Biol Chem, Taipei, Taiwan.
   NCI, Frederick & Brookhaven Natl Lab, Upton, NY 11973 USA.
   All India Inst Med Sci, Dept Biophys, New Delhi 110029, India.
   Bulgarian Acad Sci, Inst Organ Chem, BU-1113 Sofia, Bulgaria.
RP Betzel, C (reprint author), Univ Hamburg, Hosp Eppendorf, Inst Biochem & Mol Biol 1, DESY, Bldg 22A,Notkestr 85, D-22603 Hamburg, Germany.
NR 37
TC 13
Z9 15
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 OCT
PY 2003
VL 59
BP 1679
EP 1687
DI 10.1107/S0907444903014987
PN 10
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 723VA
UT WOS:000185451200001
PM 14501106
ER

PT J
AU Frank, S
   Karbowski, M
   Gaume, B
   Leitner, WW
   Bergmann, ES
   Smith, CL
   Youle, RJ
AF Frank, S
   Karbowski, M
   Gaume, B
   Leitner, WW
   Bergmann, ES
   Smith, CL
   Youle, RJ
TI Bax and Mfn2: New players in the regulation of mitochondrial fission
   during apoptosis
SO ACTA NEUROPATHOLOGICA
LA English
DT Meeting Abstract
CT 48th Annual Meeting of the
   German-Society-for-Neuropathology-and-Neuroanatomy
CY OCT 08-11, 2003
CL BERLIN, GERMANY
SP German Soc Neuropathol & Neuroanat
C1 NINDS, NIH, Bethesda, MD 20892 USA.
   NCI, NIH, Bethesda, MD 20892 USA.
   Univ Bonn, Dept Neuropathol, D-5300 Bonn, Germany.
RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011
OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner,
   Wolfgang/0000-0003-3125-5922
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD OCT
PY 2003
VL 106
IS 4
BP 394
EP 394
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 726LN
UT WOS:000185600700041
ER

PT J
AU Kim, KS
   Shin, JH
   Baek, SJ
   Yoon, JH
AF Kim, KS
   Shin, JH
   Baek, SJ
   Yoon, JH
TI Expression of non-steroidal anti-inflammatory drug-activated gene-1 in
   human nasal mucosa and cultured nasal epithelial cells: A preliminary
   investigation
SO ACTA OTO-LARYNGOLOGICA
LA English
DT Article
DE differentiation; human nasal mucosa; localization; non-steroidal
   anti-inflammatory drug-activated gene-1; normal human nasal epithelial
   cells
ID TGF-BETA SUPERFAMILY; MORPHOGENETIC PROTEIN; MEMBER; DIFFERENTIATION;
   PLACENTA
AB Objective-Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a recently discovered transforming growth factor-beta superfamily cytokine. The localization and functions of NAG-1 have not been thoroughly studied. The aims of this study were to investigate its expression and localization in human nasal mucosa and also the change in NAG-1 expression as a function of mucociliary and squamous differentiation.
   Material and Methods-Anterior and middle portions of human inferior turbinate were used and immunohistochemical studies were performed using NAG-1 antibody. Passage-2 normal human nasal epithelial (NHNE) cell culture was performed for 14 days using the air-liquid interface method and the cells were divided into retinoic acid (RA)-sufficient and -deficient groups. Each group of cells was stained with hematoxylin-eosin to study the degree of differentiation. Western blot analysis for NAG-1 expression was performed in each group after 0, 7 and 14 days.
   Results-NAG-1 expression in mucociliated epithelium was noted in ciliated cells and serous acini, but was not found in goblet cells or mucous acini. In squamous epithelium, NAG-1 expression was weaker than that in mucociliated epithelium. In RA-sufficient culture, NHNE cells were differentiated into ciliated epithelium, but in RA-deficient culture, keratinizing squamous epithelium was noted. Western blot analysis showed that NAG-1 expression was significantly higher in RA-sufficient than -deficient culture (three-fold difference) and this expression was time-dependent.
   Conclusions-NAG-1 may be involved in differentiation and apoptotic processes of nasal epithelial cells. However, it is still unclear whether NAG-1 is an inducer or a byproduct of differentiation or apoptosis. The role of NAG-1 protein remains to be solved.
C1 Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul 120752, South Korea.
   Yonsei Univ, Coll Med, Brian Korea Project Med Sci 21, Seoul, South Korea.
   NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Yoon, JH (reprint author), Yonsei Univ, Coll Med, Dept Otorhinolaryngol, 134 Shinchon Dong, Seoul 120752, South Korea.
RI Yoon, Joo-Heon/E-5781-2016; 
OI Baek, Seung/0000-0001-7866-7778; Yoon, Joo-Heon/0000-0003-2404-7156
NR 13
TC 4
Z9 4
U1 0
U2 0
PU TAYLOR & FRANCIS AS
PI OSLO
PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY
SN 0001-6489
J9 ACTA OTO-LARYNGOL
JI Acta Oto-Laryngol.
PD OCT
PY 2003
VL 123
IS 7
BP 857
EP 861
DI 10.1080/00016480310000584
PG 5
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 718GR
UT WOS:000185137200011
PM 14575402
ER

PT J
AU Kinter, A
   Moorthy, A
   Jackson, R
   Fauci, AS
AF Kinter, A
   Moorthy, A
   Jackson, R
   Fauci, AS
TI Productive HIV infection of resting CD41 T cells: Role of lymphoid
   tissue microenvironment and effect of immunomodulating agents
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; IN-VIVO;
   MYCOPHENOLIC-ACID; LATENT RESERVOIR; GENE-EXPRESSION; HOST FACTORS;
   REPLICATION; LYMPHOCYTES; PATHOGENESIS
AB The ability of resting CD4(+) T cells to support HIV replication is relevant to understanding how the reservoir of HIV-1-infected resting CD4(+) T cells is generated, maintained and, hopefully, how it might be reduced or eliminated. We have utilized a tonsillar histoculture system to demonstrate that HIV, particularly X4 strains, can productively infect phenotypically resting CD4(+) T cells in vitro and that this event is largely dependent on the lymphoid tissue microenvironment. Highly purified CD4(+) tonsillar T cells that lack expression of both cell surface and nuclear antigens characteristic of classic T cell activation produce X4 HIV-1 mRNA, p24, and infectious virus while maintaining a resting phenotype when cultured in a tonsillar tissue microenvironment; in contrast, comparable purified resting CD4(+) tonsillar T cells that have been exposed to X4 HIV do not support HIV replication when cultured in the absence of a lymphoid tissue microenvironment. HIV production from phenotypically resting CD4(+) T cells is dramatically inhibited by anti-proinflammatory cytokine agents or immunosuppressive cytokines, but is only modestly suppressed by an inhibitor of the cell cycle. The ability of resting CD4(+) T cells to support HIV replication in the microenvironment of the lymphoid tissue has implications in the pathogenesis of HIV disease and may provide an additional avenue for therapeutic intervention.
C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Kinter, A (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A33,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA.
NR 64
TC 34
Z9 35
U1 0
U2 2
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2003
VL 19
IS 10
BP 847
EP 856
DI 10.1089/088922203322493012
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 736MT
UT WOS:000186175100002
PM 14585216
ER

PT J
AU Buge, SL
   Ma, HL
   Amara, RR
   Wyatt, LS
   Earl, PL
   Villinger, F
   Montefiori, DC
   Staprans, SI
   Xu, Y
   Carter, E
   O'Neil, SP
   Herndon, JG
   Hill, E
   Moss, B
   Robinson, HL
   McNicholl, JM
AF Buge, SL
   Ma, HL
   Amara, RR
   Wyatt, LS
   Earl, PL
   Villinger, F
   Montefiori, DC
   Staprans, SI
   Xu, Y
   Carter, E
   O'Neil, SP
   Herndon, JG
   Hill, E
   Moss, B
   Robinson, HL
   McNicholl, JM
TI Gp120-alum boosting of a Gag-Pol-Env DNA/MVA AIDS vaccine: Poorer
   control of a pathogenic viral challenge
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RHESUS MACAQUES; NEUTRALIZING ANTIBODY;
   SIV INFECTION; HIV-INFECTION; ANKARA; REPLICATION; TYPE-1; RESPONSES;
   CELL
AB Envelope protein immunogens may improve DNA or live-vectored HIV vaccines by complementing antiviral cellular responses with Env antibodies. We tested this concept by administering two immunizations of alum-adjuvanted HIV-1 89.6 gp120 to macaques being primed at weeks 0 and 8 with SHIV 89.6 Gag-Pol-Env DNA and boosted at week 24 with SHIV-89.6 Gag-Pol-Env recombinant modified vaccinia Ankara (MVA). Three hundred micrograms of gp120 was delivered with the second DNA prime and the MVA booster. Eight months after vaccination, all animals were challenged intrarectally with the related, yet serologically distinct, SHIV-89.6P. The gp120 immunizations raised binding, but not neutralizing antibody for the challenge virus, and allowed testing of whether gp120 vaccines that fail to raise neutralizing antibody can improve protection. Following the second gp120 immunization, the plus-gp120 group showed >10 times higher levels of binding antibody than the minus-gp120 group. These levels fell and were overall similar in both groups at the time of challenge. Following the second challenge, both groups had similar temporal patterns and heights of binding and neutralizing antibodies. However, the plus-gp120 group had less consistent control of viremia and higher levels of plasma viral RNA for the first year postchallenge. Assays for complement-dependent enhancing antibody revealed a trend toward higher levels of activity in the plus-gp120 group. This trend did not reach significance in our animal groups of 8. We conclude that gp120 inoculations that fail to raise neutralizing antibody do not improve the efficacy of Gag- Pol-Env DNA/MVA vaccines.
C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA 30333 USA.
   Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA.
   NIAID, NIH, Bethesda, MD 20892 USA.
   Emory Univ, Sch Med, Atlanta, GA 30322 USA.
   Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
   Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA.
RP McNicholl, JM (reprint author), CDC, Div AIDS STD & TB Lab Res, NICD, MS A25,1600 Clifton Rd NE, Atlanta, GA 30333 USA.
FU NCRR NIH HHS [P51 RR 000165]; NIAID NIH HHS [AI 85343, P01 AI 43045];
   NIDA NIH HHS [5P30 DA 12121]
NR 37
TC 23
Z9 23
U1 0
U2 0
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD OCT
PY 2003
VL 19
IS 10
BP 891
EP 900
DI 10.1089/088922203322493067
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 736MT
UT WOS:000186175100007
PM 14585221
ER

PT J
AU Allen, JP
   Litten, RZ
AF Allen, JP
   Litten, RZ
TI Recommendations on use of biomarkers in alcoholism treatment trials
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article; Proceedings Paper
CT Conference on Measuring Alcohol Treatment Efficacy
CY DEC, 2001
CL BETHESDA, MARYLAND
DE biomarkers; biochemical measures; treatment outcome measures; research
   design
ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; CONSUMPTION; DRINKING; UTILITY;
   MARKERS
AB Background: Biochemical markers of heavy drinking are playing increasingly prominent roles in alcohol treatment efficacy studies, especially in those designed to evaluate medications. Among these roles are serving as inclusion or exclusion criteria for research participants, corroboration of self-report of drinking status, assessment of the safety of the agent being evaluated, and determination of treatment outcome.
   Methods: Recent alcohol medication development trials that included biomarker information were reviewed and critiqued from the perspectives of how biomarker measures were used and how findings on them were reported.
   Results: Although generally the application of biomarkers as inclusion criteria is not recommended, they may aid in exclusion of potential subjects (e.g., elevated liver function measures in trials of agents that could result in liver damage). Biomarkers are most commonly used as indicators of outcome, usually serving as secondary outcome variables. The relationship of outcome findings on biomarker and self-report measures is positive, but only moderate. As used to date, biomarkers of drinking tend to be less sensitive than well-standardized and properly administered self-report measures. Nevertheless, they do provide a useful, unique source of information on drinking status.
   Conclusions: The contribution of biomarkers to alcoholism clinical research would be enhanced if certain design strategies were incorporated into their application and if critical information were included in the research publication. This article offers a series of recommendations to improve on their use in a research context.
C1 NIAAA, Vienna, VA USA.
   NIAAA, Rockville, MD 20852 USA.
RP Allen, JP (reprint author), 2009 Carriage Court, Vienna, VA 22181 USA.
NR 10
TC 20
Z9 20
U1 0
U2 0
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 OCT
PY 2003
VL 27
IS 10
BP 1667
EP 1670
DI 10.1097/01.ALC.0000091224.78880.47
PG 4
WC Substance Abuse
SC Substance Abuse
GA 733JW
UT WOS:000185998000018
PM 14574239
ER

PT J
AU Pawliczak, R
   Shelhamer, JH
AF Pawliczak, R
   Shelhamer, JH
TI Application of functional genomics in allergy and clinical immunology
SO ALLERGY
LA English
DT Article
ID CYTOSOLIC PHOSPHOLIPASE A(2); EXPRESSION MICROARRAY DATA;
   GENE-EXPRESSION; OLIGONUCLEOTIDE ARRAYS; WIDE SEARCH; T-CELLS; ASTHMA;
   IDENTIFICATION; PHOSPHORYLATION; SCLERODERMA
C1 Med Univ Lodz, Dept Allergy & Clin Immunol, PL-92213 Lodz, Poland.
   NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
RP Pawliczak, R (reprint author), Med Univ Lodz, Dept Allergy & Clin Immunol, 251 Pomorska Str,Bldg C5,Rm 46, PL-92213 Lodz, Poland.
RI Pawliczak, Rafal/S-9649-2016
NR 42
TC 8
Z9 10
U1 1
U2 1
PU BLACKWELL MUNKSGAARD
PI COPENHAGEN
PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK
SN 0105-4538
J9 ALLERGY
JI Allergy
PD OCT
PY 2003
VL 58
IS 10
BP 973
EP 980
DI 10.1034/j.1398-9995.2003.00283.x
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 723RQ
UT WOS:000185445700002
PM 14510713
ER

EF