FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rudek, MA Figg, WD Dyer, V Dahut, W Turner, ML Steinberg, SM Liewehr, DJ Kohler, DR Pluda, JM Reed, E AF Rudek, MA Figg, WD Dyer, V Dahut, W Turner, ML Steinberg, SM Liewehr, DJ Kohler, DR Pluda, JM Reed, E TI Phase I clinical trial of oral COL-3, a matrix metalloproteinase inhibitor, in patients with refractory metastatic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLLAGENASE ACTIVITY; TETRACYCLINES; DOXYCYCLINE; MECHANISM; MINOCYCLINE; PHARMACOKINETICS; PROCOLLAGENASE; ACTIVATION; KINETICS; FLUID AB Purpose: This phase I clinical trial war designed to determine the maximum-tolerated dose and dose-limiting toxicities of the matrix metalloproteinase (MMP) inhibitor COL-3 in patients with refractory solid tumors. Patients and Methods: Thirty-five patients with different cancer types were enrolled. COL-3 doses were escalated from 36 mg/m(2)/d in successive cohorts of at least three patients. Circulating levels of MMP-2, MMP-9, vascular endothelial growth factor, and basic fibroblast growth factor were assessed during treatment. Pharmacokinetic parameters were assessed for single and multiple doses of drug. Results: Cutaneous phototoxicity was dose-limiting at 98 mg/m(2)/d. With the use of prophylactic sunblock, COL-3 was well tolerated at 70 mg/m(2)/d. The dose of 36 mg/m2/d was well tolerated without the use of sunblock. Other toxicities that did not seem to be related to dose or pharmacokinetics included anemia. anorexia, constipation, dizziness, elevated liver function rest results, fever, headache, heartburn, nausea, vomiting, peripheral and central neurotoxicities, fatigue, and three cases of drug-induced lupus. Disease stabilization for periods of 26+ months, 8 months, and 6 months were seen in hemangioendothelioma, Sertoli-Leydig cell tumor, and fibrosarcoma, respectively. There was a potentially statistically significant relationship between changes in plasma MMP-2 levels and cumulative doses of drug when progressive disease patients were compared with those with stable disease or toxicity (P =.042), Conclusion: COL-3 induced disease stabilization in several patients who had a nonepithelial type of malignancy, phototoxicity was dose-limiting. We recommend the dose of 36 mg/m(2)/d for phase II trials, J Clin Oncol 19:584-592. (C) 2001 by American Society of Clinical Oncology. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 41 TC 99 Z9 105 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 15 PY 2001 VL 19 IS 2 BP 584 EP 592 PG 9 WC Oncology SC Oncology GA 394QD UT WOS:000166534000039 PM 11208854 ER PT J AU Sayers, TJ Brooks, AD Ward, JM Hoshino, T Bere, WE Wiegand, GW Kelley, JM Smyth, MJ AF Sayers, TJ Brooks, AD Ward, JM Hoshino, T Bere, WE Wiegand, GW Kelley, JM Smyth, MJ TI The restricted expression of granzyme M in human lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; DELTA T-CELLS; GRANULE-MEDIATED APOPTOSIS; SERINE-PROTEASE; TARGET-CELLS; RAPID INDUCTION; MET-ASE; ACTIVATION; RECEPTOR; CYTOTOXICITY AB We have analyzed the expression of human granzyme M (Gzm M) in various human leukocyte subsets using the specific mAb 4H10, Using FAGS and Western blotting analysis we compared the expression of Gzm M with that of other granzymes (Gzm A and Gzm B) and the lytic protein perforin, Human Gzm M was constitutively highly expressed in NK cells as was perforin and Gzm A. Surprisingly, freshly isolated NK cells had very low (sometimes undetectable) levels of Gzm B. In contrast to Gzm B and perforin, Gzm M was not detected in highly purified CD4(+) and CD8(+) T cells either constitutively or after short term activation in vitro. However, low levels of Gzm M were observed in some T cell clones on prolonged passage in vitro. Gzm M was not detected in highly purified neutrophils, monocytes, or tumor cells of the myelomonocytic lineage. Examination of minor T cell subsets from human peripheral blood showed detectable Gzm M in CD3(+), CD56(+) T cells and gamma delta T cells. A histological staining procedure was developed that demonstrated a granular staining pattern for Gzm M and a cellular distribution similar to that observed by Western blotting. These data indicate that the expression of Gzm M does not always correlate with the lytic activity of cytotoxic cells. However, expression of Gzm M in NK cells, CD3(+), CD56(+) T cells, and gamma delta T cells suggests that this enzyme may play some role in innate immune responses. C1 NCI, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Div Basic Sci,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Austin Res Inst, Cellular Cytotox Lab, Heidelberg, Vic, Australia. RP Sayers, TJ (reprint author), NCI, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Bldg 560,Room 31-30, Frederick, MD 21702 USA. RI Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU NCI NIH HHS [N01-CO-56000] NR 42 TC 75 Z9 79 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2001 VL 166 IS 2 BP 765 EP 771 PG 7 WC Immunology SC Immunology GA 389VP UT WOS:000166259600008 PM 11145648 ER PT J AU Wigginton, JM Park, JW Gruys, ME Young, HA Jorcyk, CL Back, TC Brunda, MJ Strieter, RM Ward, J Green, JE Wiltrout, RH AF Wigginton, JM Park, JW Gruys, ME Young, HA Jorcyk, CL Back, TC Brunda, MJ Strieter, RM Ward, J Green, JE Wiltrout, RH TI Complete regression of established spontaneous mammary carcinoma and the therapeutic prevention of genetically programmed neoplastic transition by IL-12/pulse IL-2: Induction of local T cell infiltration, Fas/Fas ligand gene expression, and mammary epithelial apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; INDUCIBLE PROTEIN-10 IP-10; ANTIGEN-TRANSGENIC MICE; FAS LIGAND; MEDIATED CYTOTOXICITY; STIMULATORY FACTOR; IN-VIVO; ANTITUMOR-ACTIVITY; TUMOR-REGRESSION; GAMMA PRODUCTION AB Using a novel transgenic mouse model of spontaneous mammary carcinoma, we show here that the IL-12/pulse IL-2 combination can induce rapid and complete regression of well-established autochthonous tumor in a setting where the host immune system has been conditioned by the full dynamic process of neoplastic progression and tumorigenesis. Further, this regimen inhibits neovascularization of established mammary tumors, and does so in conjunction with potent local induction of genes encoding the IFN-gamma- and TNF-alpha -inducible antiangiogenic chemokines IFN-inducible protein 10 and monokine induced by IFN-gamma. In contrast to untreated juvenile C3(1)TAg mice in which histologically normal mammary epithelium predictably undergoes progressive hyperplasia, atypical changes, and ultimately transition to overt carcinoma, the current studies also demonstrate a unique preventative therapeutic role for IL-12/pulse IL-2. In juvenile mice, early administration of IL-12/pulse IL-2 markedly limits the expected genetically programmed neoplastic transition within the mammary epithelium and does so in conjunction with enhancement of constitutive Fas and pronounced induction of local Fas ligand gene expression, T cell infiltration, and induction of apoptosis within the mammary epithelium. These events occur in the absence of a durable Ag-specific memory response. Thus, this novel model system demonstrates that the potent therapeutic activity of the IL-12/pulse IL-2 combination rapidly engages potent apoptotic and antiangiogenic mechanisms that remain active during the delivery of IL-12/pulse IL-2. The results also demonstrate that these mechanisms are active against established tumor as well as developing preneoplastic lesions. C1 NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Chemoprevent Lab, Div Basic Sci, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. Hoffmann La Roche Inc, Dept Oncol, Nutley, NJ 07110 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, Div Basic Sci,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Wiltrout, RH (reprint author), NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 67 TC 41 Z9 41 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2001 VL 166 IS 2 BP 1156 EP 1168 PG 13 WC Immunology SC Immunology GA 389VP UT WOS:000166259600057 PM 11145697 ER PT J AU Coe, JE Race, RE Ross, MJ AF Coe, JE Race, RE Ross, MJ TI Serological evidence for an inflammatory response in murine scrapie SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID AMYLOID-P-COMPONENT; C-REACTIVE PROTEIN; HAMSTER FEMALE PROTEIN; ACUTE-PHASE RESPONSE; PLASMA INTERLEUKIN-6; SYRIAN-HAMSTER; MOUSE; PENTRAXIN; MICE; SAP AB Transmissible spongiform encephalopathies (TSEs) are initiated by a novel kind of agent that produces characteristic degenerative changes in the brain without a detectable systemic inflammatory response or serological changes. A murine scrapie model was evaluated for changes in plasma concentration of serum amyloid P component (SAP), a protein that is up-regulated in infected and/or injured mice during the acute phase response (APR). C57BL10 and IRW mice inoculated with scrapie brain developed clinical scrapie 125-150 days later. At this time, concentration of plasma SAP increased in most of them. The SAP level increased greater than or equal to3-fold in >80% of the scrapie-affected C57BL10 mice and IRW male mice. A similar increase was found in <3% of respective nonscrapie control mice. The up-regulation of mouse SAP during clinical scrapie provides evidence for the activation of a systemic APR in TSE, a serological change that may be clinically useful. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Coe, JE (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. NR 31 TC 6 Z9 6 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 JAN 15 PY 2001 VL 183 IS 2 BP 185 EP 191 DI 10.1086/317922 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385DU UT WOS:000165987700002 PM 11120924 ER PT J AU Lee, HS Brown, P Cervenakova, L Garruto, RM Alpers, MP Gajdusek, DC Goldfarb, LG AF Lee, HS Brown, P Cervenakova, L Garruto, RM Alpers, MP Gajdusek, DC Goldfarb, LG TI Increased susceptibility to Kuru of carriers of the PRNP 129 methionine/methionine genotype SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN GENE; VARIANT; NEUROPATHOLOGY; POLYMORPHISM AB Kuru reached epidemic proportions by the mid-twentieth century among the Fore people of New Guinea and disappeared after the abolition of cannibalistic rituals. To determine susceptibility to kuru and its role in the spread and elimination of the epidemic, we analyzed the PRNP gene coding sequences in 5 kuru patients; no germline mutations were found. Analysis of the PRNP 129 methionine (M)/valine (V) polymorphism in 80 patients and 95 unaffected controls demonstrated that the kuru epidemic preferentially affected individuals with the M/M genotype. A higher representation of M/M carriers was observed among the affected young Fore males entering the age of risk, whereas a lower frequency of M/M homozygotes was found among the survivors. M/V and V/V genotypes predisposed to a lower risk of disease development and longer incubation times. These findings are relevant to the current outbreak of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom, because all vCJD patients tested thus far have been M/M carriers. C1 NINDS, Clin Neurogenet Unit, NIH, Bethesda, MD 20892 USA. NINDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Amer Red Cross, JH Holland Lab, Rockville, MD USA. SUNY Binghamton, Dept Anthropol, Binghamton, NY USA. Inst Med Res, Goroka, Papua N Guinea. Inst Alfred Fessard, CNRS, Gif Sur Yvette, France. RP Goldfarb, LG (reprint author), NINDS, Clin Neurogenet Unit, NIH, Bldg 10,Rm 4B37,10 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 93 Z9 96 U1 0 U2 8 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 JAN 15 PY 2001 VL 183 IS 2 BP 192 EP 196 DI 10.1086/317935 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385DU UT WOS:000165987700003 PM 11120925 ER PT J AU Nagai, M Kubota, R Greten, TF Schneck, JP Leist, TP Jacobson, S AF Nagai, M Kubota, R Greten, TF Schneck, JP Leist, TP Jacobson, S TI Increased activated human T cell lymphotropic virus type I (HTLV-I) tax11-19-specific memory and effector CD8(+) cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: Correlation with HTLV-I provirus load SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; SPINAL-CORD LESIONS; CEREBROSPINAL-FLUID; NEUROLOGICAL DISEASE; PERIPHERAL-BLOOD; DIRECT VISUALIZATION; HAM/TSP PATIENTS; TAX; ANTIGEN; PROLIFERATION AB To discern the T cell subtype associated with T cell differentiation, the expression of CD45RA and CD27 was measured from total CD8(high) cells and from human T cell lymphotropic virus type I (HTLV-I) Tax11-19 peptide-specific CD8(+) cells in peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Phenotypically defined memory and/or effector cells (CD45RA(-)CD27(+), CD45RA(+)CD27(-), and CD45RA(-)CD272(-)) were increased in HAM/TSP CD8(+) cells, compared with those of HTLV-I-seronegative healthy control subjects. The percentage of human leukocyte antigen (HLA)-DR-positive cells was also increased in CD8(+) cells of HAM/TSP, compared with those in HLA-DR(+)CD8(+) cells of healthy control subjects. HTLV-I provirus load correlated with the frequency of Tax11-19-specific CD8(+) cells. The high frequency of memory and/or effector type HTLV-I Tax11-19-specific CD8(+) cells suggests that continuous restimulation driven by HTLV-I antigens in vivo may be associated with the pathogenesis of HAM/TSP. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol & Oncol, Baltimore, MD USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Rm 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Greten, Tim/B-3127-2015; Kubota, Ryuji/A-7139-2009 OI Greten, Tim/0000-0002-0806-2535; NR 39 TC 79 Z9 82 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 JAN 15 PY 2001 VL 183 IS 2 BP 197 EP 205 DI 10.1086/317932 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385DU UT WOS:000165987700004 PM 11120926 ER PT J AU Burnett, MS Gaydos, CA Madico, GE Glad, SM Paigen, B Quinn, TC Epstein, SE AF Burnett, MS Gaydos, CA Madico, GE Glad, SM Paigen, B Quinn, TC Epstein, SE TI Atherosclerosis in apoE knockout mice infected with multiple pathogens SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 73rd Scientific Sessions of the American-Heart-Association CY NOV 12-15, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc ID MURINE CYTOMEGALOVIRUS-INFECTION; CHLAMYDIA-PNEUMONIAE INFECTION; TRANSPLANTED MOUSE HEARTS; CORONARY-ARTERY DISEASE; E-DEFICIENT MICE; SMOOTH-MUSCLE CELLS; INTERFERON-GAMMA; APOLIPOPROTEIN-E; RABBIT MODEL; KILLER CELL AB Cytomegalovirus (CMV) and Chlamydia pneumoniae (CP) possibly contribute to atherosclerosis. Murine CMV (MCMV) and CP increase lesion size in apoE knockout mice. In this study, apoE knockout mice were infected with MCMV and CP to determine whether infection with multiple pathogens increases lesion size to a greater extent than either pathogen alone and whether infection with MCMV changes serum cytokine levels in a manner that could increase lesion development. One group of mice received MCMV at 2 weeks of age, followed by 2 doses of CP at 6 and 8 weeks of age. Additional groups received only MCMV or CP. Animals were killed at 16 weeks of age to determine lesion area. Infection with MCMV alone, CP alone, and both MCMV and CP increased lesion size 84% (P <.001), 70% (P <.0001), and 45% (P <.01), respectively. The MCMV-induced increase in circulating levels of interferon- may have contributed to this increase. C1 Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. Johns Hopkins Univ, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Epstein, SE (reprint author), Washington Hosp Ctr, Cardiovasc Res Inst, 110 Irving St NW,Suite 4B-1, Washington, DC 20010 USA. RI Gaydos, Charlotte/E-9937-2010 NR 55 TC 69 Z9 73 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2001 VL 183 IS 2 BP 226 EP 231 DI 10.1086/317938 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385DU UT WOS:000165987700008 PM 11120928 ER PT J AU Rothstein, NM Quinn, TC Madico, G Gaydos, CA Lowenstein, CJ AF Rothstein, NM Quinn, TC Madico, G Gaydos, CA Lowenstein, CJ TI Effect of azithromycin on murine arteriosclerosis exacerbated by Chlamydia pneumoniae SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; CIRCULATING IMMUNE-COMPLEXES; ARTERY DISEASE; RISK FACTOR; RABBIT MODEL; ATHEROSCLEROTIC PLAQUES; CAROTID ATHEROSCLEROSIS; SECONDARY PREVENTION; SEROLOGICAL EVIDENCE AB Chlamydia pneumoniae infection can exacerbate atherosclerosis in animals. To test the hypothesis that antibiotic therapy inhibits the atherogenic effects of C. pneumoniae infection, 10-week-old apolipoprotein E (ApoE) null mice were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin or placebo, and were killed at 20 weeks of age. Infection did not affect the size of the aortic lesion, and antibiotic treatment had no effect. Another group of mice, 12-week-old ApoE mice, were infected with C. pneumoniae or placebo, were treated for 2 weeks after infection with azithromycin or placebo, and were killed at 26 weeks of age. C. pneumoniae infection increased the size of the lesion in infected mice, but azithromycin did not reduce the size of the aortic lesion in infected mice. Therefore, immediate therapy of acute infection may be necessary to prevent the proatherogenic effects of C. pneumoniae infection. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Lowenstein, CJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, 950 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 FU NHLBI NIH HHS [HL-56091, HL-5361, HL-63706] NR 72 TC 53 Z9 57 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 JAN 15 PY 2001 VL 183 IS 2 BP 232 EP 238 DI 10.1086/317941 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385DU UT WOS:000165987700009 PM 11120929 ER PT J AU Jacobson, JM Greenspan, JS Spritzler, J Fox, L Fahey, JL Jackson, JB Chernoff, M Wohl, DA Pulvirenti, JJ Hooton, TM Shikuma, C AF Jacobson, JM Greenspan, JS Spritzler, J Fox, L Fahey, JL Jackson, JB Chernoff, M Wohl, DA Pulvirenti, JJ Hooton, TM Shikuma, C CA Natl Inst Allergy Infect Dis AIDS TI Thalidomide in low intermittent doses does not prevent recurrence of human immunodeficiency virus-associated aphthous ulcers SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INFECTION; PLACEBO AB A multicenter, double- blind, randomized, placebo- controlled study was conducted to determine the safety and efficacy of thalidomide in reduced, intermittent doses for preventing recurrences of oral and esophageal aphthous ulcers in patients with human immunodeficiency virus (HIV) infection. Forty- nine HIV- infected patients whose ulcers previously had healed as a result of thalidomide therapy were randomly assigned to receive either 100 mg of oral thalidomide or placebo 3 times per week for 6 months. Ulcers recurred in 14 (61%) of 23 thalidomide- randomized patients, compared with 11 (42%) of 26 placebo- randomized patients, with no significant difference in the median time to recurrence of ulcers (P = .221). There were no changes in plasma levels of HIV RNA, tumor necrosis factor (TNF)-alpha, and soluble TNF receptor II at the time of ulcer recurrence. Adverse events among patients treated with thalidomide included neutropenia (5 patients), rash (5 patients), and peripheral sensory neuropathy (3 patients). Thalidomide in lower intermittent doses is ineffective at preventing recurrence of aphthous ulcers in HIV- infected persons. C1 Mt Sinai Sch Med, Dept Med, New York, NY USA. Univ Calif San Francisco, Dept Stomatol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Cook Cty Hosp, Div Infect Dis, Chicago, IL 60612 USA. Rush Med Sch, Chicago, IL USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Hawaii, Sch Med, Dept Med, Honolulu, HI 96822 USA. RP Jacobson, JM (reprint author), CUNY, Mt Sinai Med Ctr, 1 Gustave Levy Pl,Box 1009, New York, NY 10029 USA. FU NIAID NIH HHS [AI-38855] NR 10 TC 15 Z9 18 U1 3 U2 3 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 JAN 15 PY 2001 VL 183 IS 2 BP 343 EP 346 DI 10.1086/317928 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385DU UT WOS:000165987700024 PM 11120935 ER PT J AU Tanaka, T Veeranna Ohshima, T Rajan, P Amin, ND Cho, A Sreenath, T Pant, HC Brady, RO Kulkarni, AB AF Tanaka, T Veeranna Ohshima, T Rajan, P Amin, ND Cho, A Sreenath, T Pant, HC Brady, RO Kulkarni, AB TI Neuronal cyclin-dependent kinase 5 activity is critical for survival SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Cdk5; cerebrum; cerebellum; neuron; astrocyte; phosphorylation; neurodegeneration; transgenic mice ID AMYOTROPHIC-LATERAL-SCLEROSIS; DIRECTED PROTEIN-KINASE; REGULATORY SUBUNIT; CDK5 ACTIVATOR; NERVOUS-SYSTEM; MOLECULAR-CLONING; CDC2-LIKE KINASE; TAU-PROTEIN; RAT-BRAIN; P35 AB Cyclin-dependent kinase 5 (Cdk5) null mice exhibit a unique phenotype characterized by perinatal mortality, disrupted cerebral cortical layering attributable to abnormal neuronal migration, lack of cerebellar foliation, and chromatolytic changes of neurons in the brainstem and the spinal cord. Because Cdk5 is expressed in both neurons and astrocytes, it has been unclear whether this phenotype is primarily attributable to defects in neurons or in astrocytes. Herein we report reconstitution of Cdk5 expression in neurons in Cdk5 null mice and its effect on the null phenotype. Unlike the Cdk5 null mice, the reconstituted Cdk5 null mice that express the Cdk5 transgene under the p35 promoter (TgKO mice) were viable and fertile. Because Cdk5 expression is mainly limited to neurons in these mice and rescues the defects in the nervous system of the Cdk5 null phenotype, it clearly demonstrates that Cdk5 activity is necessary for normal development and survival of p35-expressing neurons. C1 Natl Inst Dent & Craniofacial Res, Funct Genom Unit, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Unit, Gene Targeting Facil, NIH, Bldg 30,Room 529, Bethesda, MD 20892 USA. NR 45 TC 65 Z9 67 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 JAN 15 PY 2001 VL 21 IS 2 BP 550 EP 558 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 394WB UT WOS:000166545300021 PM 11160434 ER PT J AU Bichot, NP Thompson, KG Rao, SC Schall, JD AF Bichot, NP Thompson, KG Rao, SC Schall, JD TI Reliability of macaque frontal eye field neurons signaling saccade targets during visual search SO JOURNAL OF NEUROSCIENCE LA English DT Article DE oculomotor; visual cortex; vision; attention; eye movements; selection; model ID SELECTIVE ATTENTION; NEURAL MECHANISMS; CEREBRAL-CORTEX; CORTICAL AREAS; TIME COURSE; RESPONSES; MOTION; MONKEY; INFORMATION; V4 AB Although many studies have explored the neural correlates of visual attention and selection, few have examined the reliability with which neurons represent relevant information. We monitored activity in the frontal eye field (FEF) of monkeys trained to make a saccade to a target defined by the conjunction of color and shape or to a target defined by color differences. The difficulty of conjunction search was manipulated by varying the number of distractors, and the difficulty of feature search was manipulated by varying the similarity in color between target and distractors. The reliability of individual neurons in signaling the target location in correct trials was determined using a neuron-anti-neuron approach within a winner-take-all architecture. On average, approximately seven trials of the activity of single neurons were sufficient to match near-perfect behavioral performance in the easiest search, and similar to 14 trials were sufficient in the most difficult search. We also determined how many neurons recorded separately need to be evaluated within a trial to match behavioral performance. Results were quantitatively similar to those of the single neuron analysis. We also found that signal reliability in the FEF did not change with task demands, and overall, behavioral accuracy across the search tasks was approximated when only six trials or neurons were combined. Furthermore, whether combining trials or neurons, the increase in time of target discrimination corresponded to the increase in mean saccade latency across visual search difficulty levels. Finally, the variance of spike counts in the FEF increased as a function of the mean spike count, and the parameters of this relationship did not change with attentional selection. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Psychol, Vanderbilt Vis Res Ctr, Nashville, TN 37240 USA. RP Bichot, NP (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. FU NEI NIH HHS [R01-EY08890, P30-EY08126, T32-EY07135] NR 44 TC 65 Z9 66 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 JAN 15 PY 2001 VL 21 IS 2 BP 713 EP 725 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 394WB UT WOS:000166545300037 PM 11160450 ER PT J AU Dudek, SM Fields, RD AF Dudek, SM Fields, RD TI Mitogen-activated protein kinase/extracellular signal-regulated kinase activation in somatodendritic compartments: Roles of action potentials, frequency, and mode of calcium entry SO JOURNAL OF NEUROSCIENCE LA English DT Article DE long-term potentiation; hippocampus; ERK; activity-dependent; dendrite; soma; CA1 ID LONG-TERM POTENTIATION; THETA-FREQUENCY; SYNAPTIC STIMULATION; HIPPOCAMPAL-NEURONS; GENE-EXPRESSION; NUCLEAR CALCIUM; MAP KINASE; TRANSCRIPTION; INDUCTION; RECEPTORS AB Mitogen-activated protein kinase (MAPK) has been identified as a potential element in regulating excitability, long-term potentiation (LTP), and gene expression in hippocampal neurons. The objective of the present study was to determine whether the pattern and intensity of synaptic activity could differentially regulate MAPK phosphorylation via selective activation of different modes of calcium influx into CA1 pyramidal neurons. An antibody specific for the phosphorylated (active) form of MAPK was used to stain sections from hippocampal slices, which were first stimulated in vitro. LTP-inducing stimulation [theta-burst (TBS) and 100 Hz] was effective in inducing intense staining in both dendritic and somatic compartments of CA1 neurons. Phosphorylation of MAPK was also induced, however, with stimulation frequencies (3-10 Hz) not typically effective in inducing LTP. Intensity and extent of staining was better correlated with the spread of population spikes across the CA1 subfield than with frequency (above 3 Hz). Experiments using inhibitors of NMDA receptors and voltage-sensitive calcium channels (VSCCs) revealed that, although MAPK is activated after both TBS and 5 Hz stimulation, the relative contribution of calcium through L-type calcium channels differs. Blockade of NMDA receptors alone was sufficient to prevent MAPK phosphorylation in response to 5 Hz stimulation, whereas inhibitors of both NMDA receptors and VSCCs were necessary for inhibition of the TBS-induced staining. We conclude that the intensity and frequency of synaptic input to CA1 hippocampal neurons are critically involved in determining the path by which second-messenger cascades are activated to activate MAPK. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHHD, NIH, Bldg 49,Room 5A38,MSC 4480,49 Convent Dr, Bethesda, MD 20892 USA. EM fields@helix.nih.gov NR 31 TC 60 Z9 60 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 JAN 15 PY 2001 VL 21 IS 2 AR RC122 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 394WB UT WOS:000166545300002 PM 11160456 ER PT J AU Le, YY Gong, WH Tiffany, HL Tumanov, A Nedospasov, S Shen, WP Dunlop, NM Gao, JL Murphy, PM Oppenheim, JJ Wang, JM AF Le, YY Gong, WH Tiffany, HL Tumanov, A Nedospasov, S Shen, WP Dunlop, NM Gao, JL Murphy, PM Oppenheim, JJ Wang, JM TI Amyloid beta(42) activates a G-protein-coupled chemoattractant receptor, FPR-Like-1 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloid beta; receptor; FPRL1; monocytes; chemotaxis; Alzheimer's disease ID ALZHEIMERS-DISEASE; SCAVENGER RECEPTOR; MURINE MICROGLIA; TRANSGENIC MICE; CELL-LINE; KINASE-C; PEPTIDE; MONOCYTES; FIBRILS; GAMMA AB Amyloid beta (A beta) is a major contributor to the pathogenesis of Alzheimer's disease (AD). Although A beta has been reported to be directly neurotoxic, it also causes indirect neuronal damage by activating mononuclear phagocytes (microglia) that accumulate in and around senile plaques. In this study, we show that the 42 amino acid form of beta amyloid peptide, A alpha (42), is a chemotactic agonist for a seven-transmembrane, G-protein-coupled receptor named FPR-Like-1 (FPRL1), which is expressed on human mononuclear phagocytes. Moreover, FPRL1 is expressed at high levels by inflammatory cells infiltrating senile plaques in brain tissues from AD patients. Thus, FPRL1 may mediate inflammation seen in AD and is a potential target for developing therapeutic agents. C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIH, Bethesda, MD 20892 USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-40, Frederick, MD 21702 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 40 TC 152 Z9 158 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 2001 VL 21 IS 2 AR RC123 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 394WB UT WOS:000166545300003 PM 11160457 ER PT J AU Baskin, F Rosenberg, RN Iyer, L Schellenberg, GD Hynan, L Nee, LE AF Baskin, F Rosenberg, RN Iyer, L Schellenberg, GD Hynan, L Nee, LE TI Platelet APP isoform ratios in asymptomatic young adults expressing an AD-related presenilin-1 mutation SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Alzheimer amyloid precursor protein (APP); platelets; presenilin 1 (PS1) ID AMYLOID PROTEIN-PRECURSOR; ALZHEIMERS-DISEASE AB The Alzheimer's disease (AD) related amyloid precursor protein (APP) is stored, cleaved and released similarly from neurons and from platelets. We have reported that the proportion of 120-130 to 110 kDa carboxyl-cleaved APP present in the platelets of AD patients is significantly lower than that of platelets of age-matched controls. This reduced APP isoform ratio, not seen in several other disease groups, is further reduced as the severity of AD increases. Since the neuropathology of AD is believed to begin many years before the onset of cognitive loss, we have also compared platelet APP ratios of four pre-symptomatic young adults carrying a presenilin-1 mutation to seven siblings homozygous for the normal PS-1 gene in an effort to determine whether reduced APP ratios are present before apparent cognitive loss in familial AD. Decreased platelet APP ratios were not seen in any of these subjects at this time. We will continue to monitor these subjects as they near the mean age of AD onset in these families. As the magnitude of the APP ratio reduction is proportional to the severity of cognitive loss in sporadic AD, these cognitively normal incipient AD subjects would not be expected to present significant reductions in this AD severity index at this time. Alternatively, the absence of platelet APP ratio reductions may result from a failure of platelets from familial PS-I AD subjects to manifest altered APPs, as has been reported for PS-2 AD subjects, unlike those of sporadic AD patients. Continued monitoring of cognitive status in our sub-set of controls with AD-like low APP ratios may yet validate the ability of this assay to detect incipient sporadic AD. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA. Univ Washington, Dept Neurol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Texas, SW Med Ctr, Dept Acad Comp Serv, Dallas, TX 75390 USA. NINDS, Family Studies Unit, Bethesda, MD 20892 USA. RP Baskin, F (reprint author), Univ Texas, SW Med Ctr, Dept Neurol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. OI Hynan, Linda/0000-0002-4642-7769 FU NIA NIH HHS [AG-05136, P30AG-12300] NR 22 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JAN 15 PY 2001 VL 183 IS 1 BP 85 EP 88 DI 10.1016/S0022-510X(00)00483-4 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 401VZ UT WOS:000166950500015 PM 11166800 ER PT J AU Smith, GH Chepko, G AF Smith, GH Chepko, G TI Mammary epithelial stem cells SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE epithelial stem cells; asymmetric mitosis; symmetric mitosis; mammary gland; morphogenesis; progenitors ID CENTRAL-NERVOUS-SYSTEM; MYOEPITHELIAL CELLS; HUMAN-BREAST; FUNCTIONAL-DIFFERENTIATION; IN-VITRO; GLAND; PROGENITORS; EXPRESSION; CULTURE; MORPHOGENESIS AB It has recently been shown that the progeny from a single cell may comprise the epithelial population of a fully developed lactating mammary outgrowth in mice. Serial transplantation of epithelial fragments from this clonally derived gland demonstrates that the subsequently generated outgrowths are also comprised of progeny from the original antecedent. All epithelial cell types were found to be present within these clonal normal populations including luminal, myoepithelial, ductal, and lobule-committed epithelial progenitors and fully competent mammary epithelial stem cells. These observations demonstrate the presence of multipotent tissue-specific epithelial stem cells among the parenchyma of the murine mammary gland. Similarly, genetic analysis of contiguous portions of individual human mammary ducts within the same breast indicates their clonal derivation. Here, we discuss the properties, location, division-potential, senescence, and plasticity associated with mammary epithelial stem cells and present the developing evidence for their presence in human breast and their important role in the risk for breast cancer development. Further, we review the present morphologic and genetic evidence for the characterization of specific stem cell markers and lineage-limited progenitor cells in human and rodent mammary epithelium. Published 2001 Wiley-Liss, Inc.(dagger). C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Smith, GH (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bldg 10,room 8B07,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Chepko, Gloria/B-2235-2010 OI Chepko, Gloria/0000-0002-4691-9894 NR 55 TC 137 Z9 149 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD JAN 15 PY 2001 VL 52 IS 2 BP 190 EP 203 DI 10.1002/1097-0029(20010115)52:2<190::AID-JEMT1005>3.0.CO;2-O PG 14 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 395GB UT WOS:000166571100006 PM 11169867 ER PT J AU Huestis, R Cloonan, N Tchavtchitch, M Saul, A AF Huestis, R Cloonan, N Tchavtchitch, M Saul, A TI An algorithm to predict 3 ' intron splice sites in Plasmodium falciparum genomic sequences SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE malaria; Plasmodium falciparum; Plasmodium vivax; exons; introns; splice sites; computer prediction program AB A new algorithm, PfAGSS, for predicting 3' splice sites in Plasmodium falciparum genomic sequences is described. Application of this program to the published P. falciparum chromosome 2 and 3 data suggests that existing programs result in a high error rate in assigning 3' intron boundaries. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Queensland, Australian Ctr Int & Trop Hlth & Nutr, Brisbane, Qld 4072, Australia. Univ Queensland, Queensland Inst Med Res, Brisbane, Qld 4072, Australia. NIAID, LPD, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. RP Huestis, R (reprint author), Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia. RI Cloonan, Nicole/B-5272-2008; Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 16 TC 7 Z9 7 U1 0 U2 0 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 JAN 15 PY 2001 VL 112 IS 1 BP 71 EP 77 DI 10.1016/S0166-6851(00)00347-9 PG 7 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 403GA UT WOS:000167033100008 PM 11166388 ER PT J AU Hoffmann, KF Davis, EM Fischer, ER Wynn, TA AF Hoffmann, KF Davis, EM Fischer, ER Wynn, TA TI The guanine protein coupled receptor rhodopsin is developmentally regulated in the free-living stages of Schistosoma mansoni SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE GPCR; rhodopsin; schistosoma; RT-PCR; EST; parasite; IF ID GROWTH-FACTOR RECEPTOR; GENE-EXPRESSION; RAS HOMOLOG; CLONING; ANTIGEN; IDENTIFICATION; MEMBRANE; DATABASE; MEMBER; FAMILY AB Schistosoma mansoni parasites inhabit three distinct environments including water, intermediate molluscan hosts, and definitive vertebrate hosts. Determining how schistosomes interact with these environments may be one mechanism by which suitable vaccines or novel chemotherapeutic targets will be identified. Towards this end, we describe the identification of a 36-kDa S. mansoni protein that shares extensive sequence similarity to light absorbing rhodopsin guanine protein coupled receptors (GPCRs). This protein, S. mansoni rhodopsin (SmRHO), is the first molecularly characterized GPCR described in schistosomes. Sequence analysis reveals that SmRHO shares extensive phylogenetic conservation among rhodopsins/opsins expressed in water-dwelling invertebrates, possibly indicative of orthology. We demonstrate here that SmRHO is expressed in the free-living light responsive miracidia and cercaria stages and is down-regulated in the adult, vertebrate residing forms. Moreover, we show that SmRHO is localized to sub-tegumental structures found towards the anterior end of cercariae. As SmRHO may be implicated in schistosome photoreception processes, we have begun a search for additional parasite encoded GPCR super-family members, which may be associated with chemoreception, chemotaxis, and olfaction. Identifying and characterizing new GPCRs may uncover hidden aspects of parasite biology useful towards the development of novel intervention strategies. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Bethesda, MD 20892 USA. RP Hoffmann, KF (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. RI Wynn, Thomas/C-2797-2011 NR 44 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JAN 15 PY 2001 VL 112 IS 1 BP 113 EP 123 DI 10.1016/S0166-6851(00)00352-2 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 403GA UT WOS:000167033100012 PM 11166392 ER PT J AU Altschul, SF Bundschuh, R Olsen, R Hwa, T AF Altschul, SF Bundschuh, R Olsen, R Hwa, T TI The estimation of statistical parameters for local alignment score distributions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ACID SUBSTITUTION MATRICES; SEQUENCE ALIGNMENT; SEARCH; IDENTIFICATION; SIMILARITIES; ALGORITHM AB The distribution of optimal local alignment scores of random sequences plays a vital role in evaluating the statistical significance of sequence alignments, These scores can be well described by an extreme-value distribution. The distribution's parameters depend upon the scoring system employed and the random letter frequencies; in general they cannot be derived analytically, but must be estimated by curve fitting. For obtaining accurate parameter estimates, a form of the recently described 'island' method has several advantages. We describe this method in detail, and use it to investigate the functional dependence of these parameters on finite-length edge effects. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA. RP Altschul, SF (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Bundschuh, Ralf/B-9623-2008; Hwa, Terence/J-4012-2013 OI Bundschuh, Ralf/0000-0002-6699-8614; Hwa, Terence/0000-0003-1837-6842 NR 38 TC 108 Z9 109 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 15 PY 2001 VL 29 IS 2 BP 351 EP 361 DI 10.1093/nar/29.2.351 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 394CM UT WOS:000166506500001 PM 11139604 ER PT J AU Lengler, J Krausz, E Tomarev, S Prescott, A Quinlan, RA Graw, J AF Lengler, J Krausz, E Tomarev, S Prescott, A Quinlan, RA Graw, J TI Antagonistic action of Six3 and Prox1 at the gamma-crystallin promoter SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FIBER CELL-DIFFERENTIATION; LENS-SPECIFIC EXPRESSION; HOMEOBOX GENE PROX-1; TRANSCRIPTION FACTOR; EYE DEVELOPMENT; MURINE GAMMA-2-CRYSTALLIN; NUCLEOTIDE-SEQUENCE; REGULATORY ELEMENTS; IN-VITRO; MOUSE AB gamma -Crystallin genes are specifically expressed in the eye lens, Their promoters constitute excellent models to analyse tissue-specific gene expression, We investigated murine Cryge/f promoters of different length in lens epithelial cell lines. The most active fragment extends from position -219 to +37, Computer analysis predicts homeodomain and paired-domain binding sites for all rodent Crygd/e/f core promoters. As examples, we analysed the effects of Prox1 and Six3, which are considered important transcription factors involved in lens development. Because of endogenous Prox1 expression in N/N1003A cells, a weak stimulation of Cryge/f promoter activity was found for PROX1, In contrast, PROX1 stimulated the Crygf promoter 10-fold in CD5A cells without endogenous PROX1, In both cell lines Six3 repressed the Crygf promoter to 10% of its basal activity. Our cell transfection experiments indicated that Cryg expression increases as Six3 expression decreases. Prox1 and Six3 act antagonistically on regulation of the Crygd/e/f promoters, Functional assays using randomly mutated gammaF-crystallin promoter fragments define a Six3-responsive element between -101 and -123 and a Prox1-responsive element between -151 and -174, Since Prox1 and Six3 are present at the beginning of lens development, expression of Crygd/e/f is predicted to remain low at this time. It increases as Six3 expression decreases during ongoing lens development. C1 GSF, Natl Res Ctr Environm & Hlth, Inst Mammalian Genet, D-85764 Neuherberg, Germany. NEI, NIH, Bethesda, MD 20892 USA. Univ Dundee, Inst Med Sci, Dept Biochem, Dundee DD1 4HN, Scotland. RP Graw, J (reprint author), GSF, Natl Res Ctr Environm & Hlth, Inst Mammalian Genet, D-85764 Neuherberg, Germany. RI Graw, Jochen/D-9336-2013; Quinlan, Roy/A-1348-2012; OI Quinlan, Roy/0000-0003-0644-4123; Graw, Jochen/0000-0003-0298-9660 NR 53 TC 40 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 15 PY 2001 VL 29 IS 2 BP 515 EP 526 DI 10.1093/nar/29.2.515 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 394CM UT WOS:000166506500019 PM 11139622 ER PT J AU Boguna, M Masoliver, J Weiss, GH AF Boguna, M Masoliver, J Weiss, GH TI A discrete formulation of the theory of sojourn times in a two-state system SO PHYSICA A LA English DT Article ID MOLECULE FLUORESCENCE SPECTROSCOPY; SINGLE MOLECULES; TEMPERATURE AB Most theoretical analyses of single-molecule spectroscopy (SMS) are formulated in terms of a first-order isomerization process. The mathematical problem to which the analysis reduces requires one to find the probability density for the total residence time in one of the states at a given observation time T. In this paper we develop a slightly more rigorous theory in which account is taken of the discrete pulsing of the laser. It is shown how to pass to the continuum limit. We develop analogous results to analyze experiments in which the quantum yield is less than 1. (C) 2001 Published by Elsevier Science B.V. All rights reserved. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Barcelona, Dept Fis Fonamental, E-08028 Barcelona, Spain. RP Boguna, M (reprint author), NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. RI Boguna, Marian/B-7795-2011; Masoliver, Jaume/F-7198-2016 OI Boguna, Marian/0000-0001-7833-3487; Masoliver, Jaume/0000-0002-5810-879X NR 17 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD JAN 15 PY 2001 VL 289 IS 3-4 BP 307 EP 320 DI 10.1016/S0378-4371(00)00265-X PG 14 WC Physics, Multidisciplinary SC Physics GA 392XM UT WOS:000166437900001 ER PT J AU Masellis, M Basile, VS Meltzer, HY Lieberman, JA Sevy, S Goldman, DA Hamblin, MW Macciardi, FM Kennedy, JL AF Masellis, M Basile, VS Meltzer, HY Lieberman, JA Sevy, S Goldman, DA Hamblin, MW Macciardi, FM Kennedy, JL TI Lack of association between the T -> C 267 serotonin 5-MT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE clozapine response; pharmacogenetic; polymorphism; serotonin receptor ID HALOPERIDOL-INDUCED CATALEPSY; 5-HT2A RECEPTOR; CLINICAL-RESPONSE; TOURETTES-SYNDROME; ALLELIC VARIATION; NO EVIDENCE; RFLP; DISORDERS; EXCLUSION; 8-OH-DPAT AB The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5-HT1A receptors has been suggested to contribute to various aspects of its complex clinical actions. This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine. We employed a pharmacogenetic approach in a group (n=185) of schizophrenia patients that have been clinically well characterized for clozapine response. Polymorphisms in the 5-HT6 (HTR6), 5-MT1A (HTR6) and 5-HT7 (HTR7) receptor genes were genotyped. No evidence for either an allelic or genotypic association of the T-->C 267 HTR6 polymorphism with response to clozapine was found in our sample (allele: chi (2)=0.06, 1 df, P=0.80; genotype: chi (2)=1.21. 2 df, P=0.55), The pro161eu HTR1A polymorphism was not observed in our sample: all individuals genotyped were pro/pro 16 homozygotes, With respect to the pro279leu HTR7 polymorphism, one Caucasian male responder to clozapine was observed to be heterozygous (pro/leu 279 genotype), This individual was clinically similar to the other clozapine responders. Overall, our findings do not support a role for the T-->C 267 polymorphism of the 5-HT6 receptor gene in response to clozapine, although replication is required to confirm this finding. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Toronto, Ctr Addict & Mental Hlth, Clarke Div, Neurogenet Sect, Toronto, ON M5T 1R8, Canada. Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Bronx Vet Adm Med Ctr, Dept Vet Affairs, New York, NY USA. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Univ Washington, VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Kennedy, JL (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Clarke Div, Neurogenet Sect, 100 Coll St, Toronto, ON M5T 1R8, Canada. RI Meltzer, Herbert/E-8131-2013; Macciardi, Fabio/N-3768-2014; Goldman, David/F-9772-2010 OI Macciardi, Fabio/0000-0003-0537-4266; Goldman, David/0000-0002-1724-5405 NR 63 TC 62 Z9 63 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN 15 PY 2001 VL 47 IS 1 BP 49 EP 58 DI 10.1016/S0920-9964(00)00016-5 PG 10 WC Psychiatry SC Psychiatry GA 400CY UT WOS:000166852100005 PM 11163544 ER PT J AU Hunsberger, S Follmann, DA AF Hunsberger, S Follmann, DA TI Testing for treatment and interaction effects in semi-parametric analysis of covariance SO STATISTICS IN MEDICINE LA English DT Article ID LIKELIHOOD-BASED MODELS; REGRESSION FUNCTION AB Semi-parametric regression models assume that the effects of covariates on the mean response are additive. We propose a test of additivity when there is one continuous covariate and a group indicator. At p fixed points, the differences of the within-group kernel estimates of the means are calculated, and the likelihood ratio test that the p differences have a constant mean is formed. The kernel bandwidth and the location of the p fixed points are chosen to give the test good power. Performance of the proposed test is compared with parametric and non-parametric tests of additivity. Published in 2001 by John Wiley & Sons, Ltd. C1 NCI, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD USA. RP Hunsberger, S (reprint author), EPN, Rm 739,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 2001 VL 20 IS 1 BP 1 EP 19 DI 10.1002/1097-0258(20010115)20:1<1::AID-SIM629>3.0.CO;2-0 PG 19 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 395XT UT WOS:000166607100001 PM 11135344 ER PT J AU Wu, MC Albert, PS Wu, BU AF Wu, MC Albert, PS Wu, BU TI Adjusting for drop-out in clinical trials with repeated measures: design and analysis issues SO STATISTICS IN MEDICINE LA English DT Article ID LONGITUDINAL DATA; MODEL AB Recently, Wu and Follmann developed summary measures to adjust for informative drop-out in longitudinal studies where drop-out depends on the underlying true value of the response. In this paper we evaluate these procedures in the common situation where drop-out depends on the observed responses. We also discuss various design and analysis strategies which minimize the bias obtained with this type of drop-out. Of particular interest is the use of multiple measurements of the response at each visit to reduce bias. These strategies are evaluated with a simulation study. The results are highlighted with applications to both a hypertensive and a respiratory disease clinical trial, where multiple measurements of the primary response were made for all participants at each visit. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY 10016 USA. RP Wu, MC (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 18 TC 10 Z9 10 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 2001 VL 20 IS 1 BP 93 EP 108 DI 10.1002/1097-0258(20010115)20:1<93::AID-SIM655>3.3.CO;2-U PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 395XT UT WOS:000166607100007 PM 11135350 ER PT J AU Spiegelman, D Carroll, RJ Kipnis, V AF Spiegelman, D Carroll, RJ Kipnis, V TI Efficient regression calibration for logistic regression in main study/internal validation study designs with an imperfect reference instrument SO STATISTICS IN MEDICINE LA English DT Article ID COVARIATE MEASUREMENT ERROR; FOOD FREQUENCY QUESTIONNAIRE; EXPOSURE MEASUREMENT ERROR; PERSON MEASUREMENT ERROR; FAILURE TIME REGRESSION; CORONARY HEART-DISEASE; ALLOYED GOLD STANDARD; RELATIVE RISK; BREAST-CANCER; DIETARY-FAT AB An extension to the version of the regression calibration estimator proposed by Rosner et al, for logistic and other generalized linear regression models is given for main study/internal validation study designs. This estimator combines the information about the parameter of interest contained in the internal validation study with Rosner et al.'s regression calibration estimate, using a generalized inverse-variance weighted average. It is shown that the validation study selection model can be ignored as long as this model is jointly independent of the outcome and the incompletely observed covariates, conditional, at most, upon the surrogates and other completely observed covariates. In an extensive simulation study designed to follow a complex, multivariate setting in nutritional epidemiology, it is shown that with validation study sizes of 340 or more, this estimator appears to be asymptotically optimal in the sense that it is nearly unbiased and nearly as efficient as a properly specified maximum likelihood estimator. A modification to the regression calibration variance estimator which replaces the standard uncorrected logistic regression coefficient variance with the sandwich estimator to account for the possible misspecification of the logistic regression fit to the surrogate covariates in the main study, was also studied in this same simulation experiment. In this study, the alternative variance formula yielded results virtually identical to the original formula. A version of the proposed estimator is also derived for the case where the reference instrument, available only in the validation study, is imperfect but unbiased at the individual level and contains error that is uncorrelated with other covariates and with error in the surrogate instrument. Replicate measures are obtained in a subset of study participants. In this case it is shown that the validation study selection model can be ignored when sampling into the validation study depends, at most, only upon perfectly measured covariates. Two data sets, a study of fever in relation to occupational exposure to antineoplastics among hospital pharmacists and a study of breast cancer incidence in relation to dietary intakes of alcohol and vitamin A, adjusted for total energy intake, from the Nurses' Health Study, were analysed using these new methods. In these data, because the validation studies contained less than 200 observations and the events of interest were relatively rare, as is typical, the potential improvements offered by this new estimator were not apparent. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. NCI, Biometry Res Grp EPN344, Bethesda, MD 20892 USA. RP Spiegelman, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA57030, CA50597, CA74112]; NIEHS NIH HHS [ES09411, P30-ES09106] NR 51 TC 37 Z9 39 U1 1 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 2001 VL 20 IS 1 BP 139 EP 160 DI 10.1002/1097-0258(20010115)20:1<139::AID-SIM644>3.0.CO;2-K PG 22 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 395XT UT WOS:000166607100010 PM 11135353 ER PT J AU Ojo, AO Meier-Kriesche, HU Hanson, JA Leichtman, A Magee, JC Cibrik, D Wolfe, RA Port, FK Agodoa, L Kaufman, DB Kaplan, B AF Ojo, AO Meier-Kriesche, HU Hanson, JA Leichtman, A Magee, JC Cibrik, D Wolfe, RA Port, FK Agodoa, L Kaufman, DB Kaplan, B TI The impact of simultaneous pancreas-kidney transplantation on long-term patient survival SO TRANSPLANTATION LA English DT Article ID DIABETIC NEPHROPATHY; RENAL-TRANSPLANTATION; ALONE TRANSPLANTS; GLUCOSE CONTROL; RECIPIENTS; MORTALITY; DIALYSIS; MELLITUS; IMMUNOSUPPRESSION; IMPROVEMENT AB Background. Simultaneous pancreas-kidney transplantation (SPK) ameliorates the progression of microvascular diabetic complications but the procedure is associated with excess initial morbidity and an uncertain effect on patient survival when compared with solitary cadaveric or living donor renal transplantation, We evaluated mortality risks associated with SPR, solitary renal transplantation, and dialysis treatment in a national cohort of type 1 diabetics with end-stage nephropathy. Methods. A total of 13,467 adult-type 1 diabetics enrolled on the renal and renal-pancreas transplant waiting list between 10/01/88 and 06/30/97 were followed until 06/30/98. Time-dependent mortality risks and life expectancy were calculated according to the treatment received subsequent to wait-list registration: SPK; cadaveric kidney only (CAD); living donor kidney only (LKD) transplantation; and dialysis [wait-listed, maintenance dialysis treatment (WLD)]. Results. Adjusted 10 year patient survival mas 67% or SPK vs. 65% for LKD recipients (P=0.19) and 46% for CAD recipients (P<0.001), The excess initial mortality normally associated with renal transplantation and the risk of early infectious death was S-fold higher in SPK recipients. The time to achieve equal proportion of survivors as the WLD patients was 170, 95, and 72 days for SPK, CAD, and LKD recipients, respectively (P<0.001), However, the adjusted 5-year morality risk (RR) using WLD as the reference and the expected remaining life years were 0.40, 0.45, and 0.75 and 23.4, 20.9, and 12.6 years for SPK, LKD, and CAD, respectively. There was no survival benefit in SPK recipients greater than or equal to 50 years old (RR=1.38, P=0.81), Conclusions. Among patients with type 1 DM with end-stage nephropathy, SPK transplantation before the age of 50 years was associated with long-term improvement in survival compared to solitary cadaveric renal transplantation or dialysis. C1 Univ Michigan, Med Ctr, Dept Med, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Epidemiol, Ann Arbor, MI 48109 USA. NIDDK, Div Kidney Urol & Digest Dis, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Surg, Chicago, IL 60611 USA. RP Kaplan, B (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, TC 3914,Box 0364, Ann Arbor, MI 48109 USA. FU NIDDK NIH HHS [5 K08 DK02519] NR 44 TC 197 Z9 206 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 JAN 15 PY 2001 VL 71 IS 1 BP 82 EP 90 DI 10.1097/00007890-200101150-00014 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 396LH UT WOS:000166637500014 PM 11211201 ER PT J AU Neal, R Zigler, JS Bettelheim, FA AF Neal, R Zigler, JS Bettelheim, FA TI On the equilibrium between monomeric alpha-lactalbumin and the chaperoning complex of alpha-crystallin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE alpha-crystallin; alpha-lactalbumin; chaperone; equilibrium ID PROTEIN AB In chaperoning dithiothreitol denatured alpha -lactabumin, alpha -crystallin forms a chaperoning complex. In order to study the kinetics of such chaperoning it needs to be established whether the formation of the chaperoning complex is a reversible or irreversible process. The chaperoning reaction was studied by dynamic light scattering as a function of concentration and weight ratio of alpha -lactalbumin/alpha -crystallin. HPLC and subsequent SDS-PAGE gel electrophoresis experiments established that the chaperoning complex formed contains both alpha -crystallin and alpha -lactalbumin. Upon rechromatographing the chaperoning complex, the presence of monomeric alpha -lactalbumin has been demonstrated in addition to the chaperoning complex itself, This and equilibrium dialysis experiments demonstrated conclusively the existence of an equilibrium between monomeric partially denatured alpha -lactalbumin and the chaperoning complex made of alpha -lactalbumin and alpha -crystallin. (C) 2001 Academic Press. C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. Adelphi Univ, Dept Chem, Garden City, NY 11530 USA. RP Bettelheim, FA (reprint author), NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY-12496-01] NR 17 TC 7 Z9 7 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 12 PY 2001 VL 280 IS 1 BP 14 EP 18 DI 10.1006/bbrc.2000.4092 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 392HB UT WOS:000166404700004 PM 11162470 ER PT J AU Hoffmann, HJ Bjerke, T Karawajczyk, M Dahl, R Knepper, MA Nielsen, S AF Hoffmann, HJ Bjerke, T Karawajczyk, M Dahl, R Knepper, MA Nielsen, S TI SNARE proteins are critical for regulated exocytosis of ECP from human eosinophils SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE human; eosinophils; regulated exocytosis; allergy; cell activation; Fc receptors ID INTRACELLULAR VESICLES; GLUT4 TRANSLOCATION; MURINE MACROPHAGES; PITUITARY-CELLS; WATER CHANNELS; MEMBRANE; RECEPTORS; COMPARTMENTS; SECRETION; LEUKOCYTE AB The SNARE hypothesis, describing a protein assembly-disassembly pathway, was recently proposed for the sequential steps of synaptic vesicle docking, activation and fusion, To determine if SNARE proteins are involved in regulated exocytosis in eosinophils, the presence and functional role of SNAREs was examined in human blood eosinophils. Immunoblotting, subcellular fractionation, and immunocytochemistry documented that vesicle-associated mem brane protein-2 (VAMP-2), a vesicle-SNARE, was expressed in human eosinophils. Syntaxin 4 and SNAP-25 were also detected. Sequencing of cloned RT-PCR products amplified from a domain conserved among VAMP isoforms revealed identity only to VAMP-2 but not to VAMP-1 or cellubrevin, Functional experiments revealed that tetanus toxin pretreatment, which cleaved VAMP-S in eosinophils, significantly inhibited both IgE receptor- and phorbol ester-mediated exocytosis of eosinophil cationic protein (ECP) from streptolysin-O-permeabilized eosinophils. Thus, these results strongly suggest a critical role of SNAREs in regulated exocytosis in eosinophils. (C) 2001 Academic Press. C1 Aarhus Univ Hosp, Dept Resp Med, Allergy & Lung Res Lab, DK-8000 Aarhus C, Denmark. Aarhus Univ, Dept Cell Biol, DK-8000 Aarhus, Denmark. Univ Uppsala Hosp, Clin Chem, Dept Med Sci, S-75185 Uppsala, Sweden. NHLBI, NIH, Bethesda, MD 20892 USA. RP Hoffmann, HJ (reprint author), Aarhus Univ Hosp, Dept Resp Med, Allergy & Lung Res Lab, DK-8000 Aarhus C, Denmark. RI Dahl, Ronahl/F-8170-2013 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 29 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 12 PY 2001 VL 280 IS 1 BP 172 EP 176 DI 10.1006/bbrc.2000.4117 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 392HB UT WOS:000166404700029 PM 11162495 ER PT J AU Wilcox, ER Burton, QL Naz, S Riazuddin, S Smith, TN Ploplis, B Belyantseva, I Ben-Yosef, T Liburd, NA Morell, RJ Kachar, B Wu, DK Griffith, AJ Riazuddin, S Friedman, TB AF Wilcox, ER Burton, QL Naz, S Riazuddin, S Smith, TN Ploplis, B Belyantseva, I Ben-Yosef, T Liburd, NA Morell, RJ Kachar, B Wu, DK Griffith, AJ Riazuddin, S Friedman, TB TI Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29 SO CELL LA English DT Article ID INTERCELLULAR-JUNCTIONS; STRIA VASCULARIS; DOWN-SYNDROME; INNER-EAR; PROTEIN; STRANDS; OCCLUDIN; BARRIER; LINKAGE; REGIONS AB Tight junctions in the cochlear duct are thought to compartmentalize endolymph and provide structural support for the auditory neuroepithelium. The claudin family of genes is known to express protein components of tight junctions in other tissues. The essential function of one of these claudins in the inner ear was established by identifying mutations in CLDN14 that cause nonsyndromic recessive deafness DFNB29 in two large consanguineous Pakistani families. In situ hybridization and immunofluorescence studies demonstrated mouse claudin-14 expression in the sensory epithelium of the organ of Corti. C1 NIDCD, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Punjab Univ, Ctr Excellence Mol Biol, Lahore, Pakistan. NIDCD, Sect Sensory Cell Regenerat & Dev, NIH, Rockville, MD 20850 USA. NIDCD, Sect Struct Cell biol, NIH, Rockville, MD 20850 USA. NIDCD, Neurootol Branch, NIH, Rockville, MD 20850 USA. RP Wilcox, ER (reprint author), NIDCD, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. OI Naz, Sadaf/0000-0002-1912-0235; Morell, Robert/0000-0003-1537-7356 NR 66 TC 261 Z9 273 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 12 PY 2001 VL 104 IS 1 BP 165 EP 172 DI 10.1016/S0092-8674(01)00200-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 400QD UT WOS:000166882300016 PM 11163249 ER PT J AU Matsumoto, RR McCracken, KA Pouw, B Miller, J Bowen, WD Williams, W De Costa, BR AF Matsumoto, RR McCracken, KA Pouw, B Miller, J Bowen, WD Williams, W De Costa, BR TI N-alkyl substituted analogs of the sigma receptor ligand BD1008 and traditional sigma receptor ligands affect cocaine-induced convulsions and lethality in mice SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; convulsion; dystonia; lethality; red nucleus; sigma receptor; toxicity ID ANTIPSYCHOTIC-DRUGS; RAT-BRAIN; BINDING; CLONING; SITE; MODULATION; ATTENUATE; TOXICITY; (+)-PENTAZOCINE; CONTRACTIONS AB Cocaine binds to sigma receptors with comparable affinity to its well-established interaction with dopamine transporters. Previous studies have shown BD1008(N-[2-(3.4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine) to have high affinity and selectivity for sigma receptors, and to additionally attenuate the locomotor stimulatory effects of cocaine. Therefore. in the present study, three N-alkyl substituted analogs of BD1008 were characterized in receptor binding and behavioral studies: BD1060 (N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)ethylamine). BD1067 (N-[2-(3,4-dichlorophenyl)ethyl]-N-ethyl-2-(1-pyrrolidinyl)ethylamine), and BD1052 (N-[2-(3,4-dichlorophenyl)ethyl]-N-allyl-2-(1-pyrrolidinyl)ethylamine). Similarly to BD1008, all three analogs exhibited high affinity and selectivity for a receptors. In behavioral studies, BD1008. BD1060 or BD1067 attenuated cocaine-induced convulsions and lethality in Swiss Webster mice. The protective effects appear to be mediated through a receptor antagonism because traditional a receptor antagonists with high to moderate affinity for these receptors also attenuated the behavioral toxicity of cocaine. In contrast, traditional and novel a receptor agonists such as di-o-tolylguanidine and BD1052 worsened the behavioral toxicity of cocaine. To further characterize the actions of the N-alkyl substituted compounds, they were microinjected into the rat red nucleus, a functional assay of a receptor activity, where they produced agonist vs. antagonist actions that were consistent with their effects on cocaine-induced behaviors. Together, the data demonstrate that BD1008, BD1060 or BD1067 can attenuate the behavioral toxicity of cocaine, most likely through functional antagonism of a receptors. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Matsumoto, RR (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, POB 26901, Oklahoma City, OK 73190 USA. FU NIDA NIH HHS [DA11979]; NIMH NIH HHS [MH50564] NR 64 TC 47 Z9 48 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 12 PY 2001 VL 411 IS 3 BP 261 EP 273 DI 10.1016/S0014-2999(00)00917-1 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396UF UT WOS:000166654300007 PM 11164383 ER PT J AU Vonakis, BM Haleem-Smith, H Benjamin, P Metzger, H AF Vonakis, BM Haleem-Smith, H Benjamin, P Metzger, H TI Interaction between the unphosphorylated receptor with high affinity for IgE and Lyn kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-EPSILON-RI; DETERGENT-RESISTANT MEMBRANES; BASOPHILIC LEUKEMIA-CELLS; IMMUNOGLOBULIN-E RECEPTOR; PROTEIN-TYROSINE KINASE; SIGNAL-TRANSDUCTION; T-CELL; BETA-SUBUNIT; MAST-CELLS; ACTIVATION AB Chinese hamster ovary fibroblasts previously transfected with the high affinity receptor for IgE (Fc epsilon RI) were further transfected with the cu subunit of the receptor for interleukin 2 (Tac) or with chimeric constructs in which the cytoplasmic domain of Tac was replaced with the C-terminal cytoplasmic domain of either the beta subunit or the gamma subunit of Fc epsilon RI. Whereas native Tac failed to affect the aggregation-induced phosphorylation of Fc epsilon RI, both chimeric constructs substantially inhibited this reaction. Alternatively, the Fc epsilon RI-bearing fibroblasts were transfected with two chimeric constructs in which the cytoplasmic domain of Tac was replaced with a modified short form of Lyn kinase. The Lyn in both of the chimeric constructs had been mutated to remove the sites that are normally myristoylated and palmitoylated, respectively; one of the constructs had in addition been altered to be catalytically inactive. The catalytically active construct enhanced, and the inactive construct inhibited, aggregation-induced phosphorylation of the receptors. All of the chimeric constructs were largely distributed outside the detergent resistant microdomains, and whereas aggregation caused them to move to the domains in part, their aggregation was neither necessary nor enhanced their effects. These results and others indicate that the receptor and Lyn interact through protein-protein interactions that neither are dependent upon either the posttranslational modification of the kinase with lipid moieties nor result exclusively from their co-localization in specialized membrane domains. C1 NIAMS, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Metzger, H (reprint author), NIAMS, Sect Chem Immunol, Arthrit & Rheumatism Branch, NIH, Bldg 10,Rm 9N-228,10 Ctr Dr,MSC-1820, Bethesda, MD 20892 USA. NR 38 TC 31 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 12 PY 2001 VL 276 IS 2 BP 1041 EP 1050 DI 10.1074/jbc.M003397200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392UL UT WOS:000166430900026 PM 11010962 ER PT J AU Braun, FJ Broad, LM Armstrong, DL Putney, JW AF Braun, FJ Broad, LM Armstrong, DL Putney, JW TI Stable activation of single Ca2+ release-activated Ca2+ channels in divalent cation-free solutions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; JURKAT T-LYMPHOCYTES; STORE DEPLETION; MAST-CELLS; ANTIGEN AB The regulation of store-operated, calcium-selective channels in the plasma membrane of rat basophilic leukemia cells (RBL-2H3 m1), an immortalized mucosal mast cell line, was studied at the single-channel level with the patch clamp technique by removing divalent cations from both sides of the membrane. The activity of the single channels in excised patches could be modulated by Ca2+, Mg2+, and pH. The maximal activation of these channels by divalent cation-free conditions occurred independently of depletion of intracellular Ca2+ stores, whether in excised patches or in whole cell mode. Yet, a number of points of evidence establish these single-channel openings as amplified store-operated channel events. Specifically, (i) the single channels are exquisitely sensitive to inhibition by intracellular Ca2+, and (ii) both the store-operated current and the single-channel openings are completely blocked by the capacitative calcium entry blocker, 2-aminoethoxydiphenyl borane, In addition, in Jurkat T cells single-channel openings with lower open probability have been observed in the whole cell mode with intracellular Mg2+ present (Kerschbaum, H. H., and Cahalan, M. D. (1999) Science 283, 836-839), and in RBL-2H3 m1 cells a current with similar properties is activated by store depletion. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Braun, FJ (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 96 Z9 98 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 12 PY 2001 VL 276 IS 2 BP 1063 EP 1070 DI 10.1074/jbc.M008348200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392UL UT WOS:000166430900029 PM 11042187 ER PT J AU Kliger, Y Gallo, SA Peisajovich, SG Munoz-Barroso, I Avkin, S Blumenthal, R Shai, Y AF Kliger, Y Gallo, SA Peisajovich, SG Munoz-Barroso, I Avkin, S Blumenthal, R Shai, Y TI Mode of action of an antiviral peptide from HIV-1 - Inhibition at a post-lipid mixing stage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; FLUORESCENCE ENERGY-TRANSFER; MEDIATED MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; SIV GP41; TRANSMEMBRANE PROTEIN; CRYSTAL-STRUCTURE; PORE FORMATION; CELL-FUSION AB DP178, a synthetic peptide corresponding to a segment of the transmembrane envelope glycoprotein (gp41) of human immunodeficiency virus, type 1 (HIV-l), is a potent inhibitor of viral infection and virus-mediated cell-cell fusion, Nevertheless, DP178 does not contain gp41 coiled-coil cavity binding residues postulated to be essential for inhibiting HIV-1 entry. We find that DP178 inhibits phospholipid redistribution mediated by the HIV-1 envelope glycoprotein at a concentration 8 times greater than that of solute redistribution (the IC,, values are 43 and 335 nM, respectively), In contrast, C34, a synthetic peptide which overlaps with DP178 but contains the cavity binding residues, did not show this phenomenon (11 and 25 nM, respectively). The ability of DP178 to inhibit membrane fusion at a post-lipid mixing stage correlates with its ability to bind and oligomerize on the surface of membranes. Furthermore, our results are consistent with a model in which DP178 inhibits the formation of gp41 viral hairpin structure at low affinity, whereas C34 inhibits its formation at high affinity: the failure to form the viral hairpin prevents both lipid and solute from redistributing between cells, However, our data also suggest an additional membrane-bound inhibitory site for DP178 in the ectodomain of gp41 within a region immediately adjacent to the membrane-spanning domain. By binding to this higher affinity site, DP178 inhibits the recruitment of several. gp41-membrane complexes, thus inhibiting fusion pore formation. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. NCI, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. RI Peisajovich, Sergio/C-6641-2011; OI Gallo, Stephen/0000-0001-6043-2153 NR 88 TC 125 Z9 128 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 12 PY 2001 VL 276 IS 2 BP 1391 EP 1397 DI 10.1074/jbc.M004113200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392UL UT WOS:000166430900072 PM 11027678 ER PT J AU Wexler, P AF Wexler, P TI Introduction to special issue on digital information and tools SO TOXICOLOGY LA English DT Editorial Material C1 Natl Lib Med, Toxicol & Environm Hlth Informat Program, NIH, Bethesda, MD 20894 USA. RP Wexler, P (reprint author), Natl Lib Med, Toxicol & Environm Hlth Informat Program, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 12 PY 2001 VL 157 IS 1-2 BP 1 EP 2 DI 10.1016/S0300-483X(00)00336-X PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 401CL UT WOS:000166909400001 PM 11164970 ER PT J AU Wexler, P AF Wexler, P TI TOXNET: An evolving web resource for toxicology and environmental health information SO TOXICOLOGY LA English DT Article DE TOXNET; computerized toxicology information; web-based toxicology resources; NLM; TOXLINE; HSDB; toxicology databases ID LIBRARY-OF-MEDICINE; BIBLIOGRAPHIC DATABASES; SUBSTANCES; PROGRAM AB TOXNET, developed by the National Library of Medicine (NLM), is a web-based system of databases providing information on toxicology. hazardous chemicals, and the environment. Databases fall under the general headings of Toxicology Data. Toxicology Literature, Toxic Releases. and Chemical Identification/Nomenclature. Among TOXNET's pre-eminent databases are the Hazardous substances Data Bank (HSDB) and the TOXLINE file of bibliographic references. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Lib Med, Toxicol & Environm Hlth Informat Program, NIH, Bethesda, MD 20894 USA. RP Wexler, P (reprint author), Natl Lib Med, Toxicol & Environm Hlth Informat Program, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 16 TC 25 Z9 25 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 12 PY 2001 VL 157 IS 1-2 BP 3 EP 10 DI 10.1016/S0300-483X(00)00337-1 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 401CL UT WOS:000166909400002 PM 11164971 ER PT J AU Wright, LL AF Wright, LL TI Searching fee and non-fee toxicology information resources: an overview of selected databases SO TOXICOLOGY LA English DT Article DE databases; bibliographic; databases; factual; online systems; toxicology databases ID BIBLIOGRAPHIC DATABASES; ONLINE AB Toxicology profiles organize information by broad subjects, the first of which affirms identity of the agent studied. Studies here show two non-fee databases (ChemFinder and ChemIDplus) verify the identity of compounds with high efficiency (63% and 73% respectively) with the fee-based Chemical Abstracts Registry file serving well to fill data gaps (100%,). Continued searching proceeds using knowledge of structure scope and content to select databases. Valuable sources for information are factual databases that collect data and facts in special subject areas organized in formats available for analysis or use. Some sources representative of factual files are RTECS, CCRIS, HSDB, GENE-TOX and IRIS, Numerous factual databases offer a wealth of reliable information: however. exhaustive searches probe information published in journal articles and/or technical reports with records residing in bibliographic databases such as BIOSIS, EMBASE, MEDLINE, TOXLINE and Web of Science. Listed with descriptions are numerous factual and bibliographic databases supplied by 11 producers. Given the multitude of options and resources. it is often necessary to seek service desk assistance. Questions were posed by telephone and e-mail to service desks at DIALOG, ISI, MEDLARS, Micromedex and STN International. Results of the survey are reported. (C) 2001 Published by Elsevier Science Ireland Ltd. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Wright, LL (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 13 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JAN 12 PY 2001 VL 157 IS 1-2 BP 89 EP 110 DI 10.1016/S0300-483X(00)00361-9 PG 22 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 401CL UT WOS:000166909400008 PM 11164977 ER PT J AU Jas, GS Eaton, WA Hofrichter, J AF Jas, GS Eaton, WA Hofrichter, J TI Effect of viscosity on the kinetics of alpha-helix and beta-hairpin formation SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID FREQUENCY-DEPENDENT FRICTION; ISOMERIZATION DYNAMICS; LANDSCAPE PERSPECTIVE; SOLVENT VISCOSITY; AQUEOUS-SOLUTION; FAST EVENTS; PEPTIDE; SIMULATION; PROTEINS; PATHWAYS AB Nanosecond laser temperature jumps and fluorescence detection were used to measure the effect of viscosity on the kinetics of beta -helix and beta -hairpin formation in peptides containing 21 and 16 amino acids. respectively. The solvent viscosity was changed by adding glucose and sucrose at concentrations that do not significantly alter the equilibrium unfolding curves. Analysis of the temperature dependence at fixed solvent compositions shows that the activation energies are also unaffected, indicating that the slowing of the relaxation rates upon addition of the sugars results entirely from their dynamical effect of increasing the solvent viscosity (eta). The rate of beta -hairpin formation was found to vary nearly as 1/eta, as predicted by Kramers theory in the high friction limit. In contrast, the rate of alpha -helix formation exhibited a fractional viscosity dependence (k = eta (-alpha)) with an exponent alpha approximate to 0.6. The intrinsic activation energy for the elementary kinetic step of rotating a pair of backbone dihedral angles, obtained using a simple statistical mechanical model, is near zero for the beta -hairpin but is similar to5 kcal/mol for the alpha -helix. If a higher barrier frequency can be associated with the larger activation energy, the fractional viscosity dependence for the alpha -helix may result from the fact that motion across the barrier top is faster than the solvent relaxation time. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Eaton, WA (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. NR 44 TC 117 Z9 118 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 11 PY 2001 VL 105 IS 1 BP 261 EP 272 DI 10.1021/jp0022048 PG 12 WC Chemistry, Physical SC Chemistry GA 390XE UT WOS:000166324400038 ER PT J AU Abashkin, YG Erickson, JW Burt, SK AF Abashkin, YG Erickson, JW Burt, SK TI Quantum chemical investigation of enzymatic activity in DNA polymerase beta. A mechanistic study SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID CRYSTAL-STRUCTURE; RNA-POLYMERASE; DENSITY; REPLICATION; HYDROLYSIS; ENERGY; APPROXIMATION; RESOLUTION; BINDING; GTP AB Recent experimental observations support the assumption that all families of polynucleotide polymerases have a universal "two-metal-ion" mechanism of nucleotide addition. This mechanism provides a general picture of the nucleotidyl transfer reaction. However, the detailed reaction pathway is still a matter of debate. We investigated two potential reaction pathways for DNA polymerase beta using density-functional theory. Our model consists of 67 atoms of the polymerase active site and includes all major features thought to be important for catalysis. The first mechanism we investigated involves the formation of a PO3 intermediate. This intermediate is thought to be involved in phosphate reactions in solution and could be accommodated in the polymerase beta active site. However, the barrier to formation of this intermediate is 37.0 kcal/mol, and we do not expect that this mechanism is the one that occurs in the enzyme. The second mechanism that leads to a pentacoordinated intermediate appears to be feasible. This stepwise mechanism has relatively low barriers and, after the nucleophilic attack, every step of the reaction is exothermic. The rate-limiting step of the reaction is the nucleophilic attack, which needs 13 kcal/mol of activation energy. We predict that the barrier of the corresponding transition state, which is ionic, can be further lowered by taking into account electrostatic stabilization coming from the rest of the protein. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Struct Biochem Program, Frederick, MD 21702 USA. RP Abashkin, YG (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Adv Biomed Comp Ctr, POB B, Frederick, MD 21702 USA. NR 25 TC 40 Z9 40 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JAN 11 PY 2001 VL 105 IS 1 BP 287 EP 292 DI 10.1021/jp003629x PG 6 WC Chemistry, Physical SC Chemistry GA 390XE UT WOS:000166324400041 ER PT J AU Inskip, PD Tarone, RE Hatch, EE Wilcosky, TC Shapiro, WR Selker, RG Fine, HA Black, PM Loeffler, JS Linet, MS AF Inskip, PD Tarone, RE Hatch, EE Wilcosky, TC Shapiro, WR Selker, RG Fine, HA Black, PM Loeffler, JS Linet, MS TI Cellular-telephone use and brain tumors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MOBILE COMMUNICATION; EXPOSURE; HEAD; RADIATION; PHONE; RISK; SAR AB Background: Concern has arisen that the use of hand-held cellular telephones might cause brain tumors. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices. Methods: We examined the use of cellular telephones in a case-control study of intracranial tumors of the nervous system conducted between 1994 and 1998. We enrolled 782 patients through hospitals in Phoenix, Arizona; Boston; and Pittsburgh; 489 had histologically confirmed glioma, 197 had meningioma, and 96 had acoustic neuroma. The 799 controls were patients admitted to the same hospitals as the patients with brain tumors for a variety of nonmalignant conditions. Results: As compared with never, or very rarely, having used a cellular telephone, the relative risks associated with a cumulative use of a cellular telephone for more than 100 hours were 0.9 for glioma (95 percent confidence interval, 0.5 to 1.6), 0.7 for meningioma (95 percent confidence interval, 0.3 to 1.7), 1.4 for acoustic neuroma (95 percent confidence interval, 0.6 to 3.5), and 1.0 for all types of tumors combined (95 percent confidence interval, 0.6 to 1.5). There was no evidence that the risks were higher among persons who used cellular telephones for 60 or more minutes per day or regularly for five or more years. Tumors did not occur disproportionately often on the side of head on which the telephone was typically used. Conclusions: These data do not support the hypothesis that the recent use of hand-held cellular telephones causes brain tumors, but they are not sufficient to evaluate the risks among long-term, heavy users and for potentially long induction periods. (N Engl J Med 2001;344:79-86.) Copyright (C) 2001 Massachusetts Medical Society. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Res Triangle Inst, Epidemiol & Med Studies Program, Res Triangle Pk, NC 27709 USA. St Josephs Hosp & Med Ctr, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Inskip, PD (reprint author), Execut Plaza S,Rm 7052,6120 Execut Blvd, Rockville, MD 20852 USA. NR 40 TC 273 Z9 290 U1 11 U2 44 PU MASSACHUSETTS MEDICAL SOC 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 JAN 11 PY 2001 VL 344 IS 2 BP 79 EP 86 DI 10.1056/NEJM200101113440201 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 390DU UT WOS:000166281100001 PM 11150357 ER PT J AU Stark, AR Carlo, WA Tyson, JE Papile, L Wright, LL Shankaran, S Donovan, EF Oh, W Bauer, CR Saha, S Poole, WK Stoll, BJ AF Stark, AR Carlo, WA Tyson, JE Papile, L Wright, LL Shankaran, S Donovan, EF Oh, W Bauer, CR Saha, S Poole, WK Stoll, BJ CA Nat Inst Child Hlth Human Dev Ne TI Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC LUNG-DISEASE; PREVENT BRONCHOPULMONARY DYSPLASIA; RESPIRATORY-DISTRESS SYNDROME; EARLY ADRENAL INSUFFICIENCY; PREMATURE-INFANTS; NECROTIZING ENTEROCOLITIS; CONTROLLED TRIAL; PRETERM INFANTS; PERFORATION; THERAPY AB Background: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. Methods: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. Results: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. Conclusions: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth. (N Engl J Med 2001;344:95-101.) Copyright (C) 2001 Massachusetts Medical Society. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Alabama, Birmingham, AL USA. Univ Texas, Houston, TX USA. Univ New Mexico, Albuquerque, NM 87131 USA. NICHHD, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Univ Miami, Miami, FL 33152 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Emory Univ, Atlanta, GA 30322 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Yale Univ, New Haven, CT USA. Univ Tennessee, Memphis, TN USA. Stanford Univ, Stanford, CA 94305 USA. RP Stark, AR (reprint author), Brigham & Womens Hosp, CWN-6,75 Francis St, Boston, MA 02115 USA. FU NICHD NIH HHS [U10 HD34167, U10 HD34216, U10 HD21373] NR 32 TC 256 Z9 261 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC 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 JAN 11 PY 2001 VL 344 IS 2 BP 95 EP 101 DI 10.1056/NEJM200101113440203 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 390DU UT WOS:000166281100003 PM 11150359 ER PT J AU Childs, R Barrett, AJ Linehan, WM AF Childs, R Barrett, AJ Linehan, WM TI Treatment of renal-cell cancer by transplantation of allogeneic stem cells. Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HUMAN TISSUES; LINDAU C1 NHLBI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 11 PY 2001 VL 344 IS 2 BP 138 EP 138 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 390DU UT WOS:000166281100014 ER PT J AU Zhou, Q Hopp, T Fuqua, SAW Steeg, PS AF Zhou, Q Hopp, T Fuqua, SAW Steeg, PS TI Cyclin D1 in breast premalignancy and early breast cancer: implications for prevention and treatment SO CANCER LETTERS LA English DT Review DE cyclin D; breast cancer; tumorigenesis; cell cycle; apoptosis; Apo-2; radiation; estrogen receptor; atypical ductal hyperplasia; ductal carcinoma in situ ID CARCINOMA IN-SITU; ATYPICAL DUCTAL HYPERPLASIA; SURGICAL-ADJUVANT-BREAST; ENDOTHELIAL GROWTH-FACTOR; TERM FOLLOW-UP; ESTROGEN-RECEPTOR; TRANSCRIPTION FACTOR; GENE AMPLIFICATION; EPITHELIAL-CELLS; RETINOIC ACID C1 NCI, Womens Canc Sect, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, Div Clin Sci,NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 96 TC 25 Z9 25 U1 0 U2 2 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 JAN 10 PY 2001 VL 162 IS 1 BP 3 EP 17 DI 10.1016/S0304-3835(00)00657-1 PG 15 WC Oncology SC Oncology GA 428BA UT WOS:000168440200002 PM 11121857 ER PT J AU Leyton, J Garcia-Marin, LJ Tapia, JA Jensen, RT Moody, TW AF Leyton, J Garcia-Marin, LJ Tapia, JA Jensen, RT Moody, TW TI Bombesin and gastrin releasing peptide increase tyrosine phosphorylation of focal adhesion kinase and paxillin in non-small cell lung cancer cells SO CANCER LETTERS LA English DT Article DE bombesin/gastrin releasing peptide; focal adhesion kinase; non-small cell lung cancer; antisense ID SWISS 3T3 CELLS; GROWTH-FACTORS; RECEPTOR ANTAGONIST; PROTEIN; STIMULATION; ACTIN; PROLIFERATION; NEUROPEPTIDES; CYTOSKELETON; VASOPRESSIN AB The effects of some oncogenes, growth factors and neuropeptides are mediated by tyrosine phosphorylation of focal adhesion kinase (p125(FAK)) and paxillin cytoskeletal proteins. In this study the ability of bombesin/gastrin releasing peptide (BB/GRP) to stimulate tyrosine phosphorylation of p125(FAK) and paxillin in non-small cell lung cancer (NSCLC) H1299 cells was investigated. BB, 100 nM caused increased p125(FAK) and paxillin tyrosine phosphorylation maximally after 1 min. The effect of BB on p125(FAK) and paxillin tyrosine phosphorylation was concentration-dependent being half maximal at 4-8 nM. Also, 100 nM GRP, GRP(14-27) but not GRP(1-16) increased p125(FAK) and paxillin tyrosine phosphorylation indicating that the C-terminal of GRP is essential. BW2258U89, a GRP receptor antagonist, caused a dose-dependent inhibition of BB-stimulated p125(FAK) and paxillin tyrosine phosphorylation with an IC50 value of 3 muM. Cytochalasin D (0.3 muM), which inhibits actin polymerization, reduced the ability of BB to stimulate tyrosine phosphorylation of p125FAK and paxillin. Genistein (50 muM) and H-7 (50 muM), which are kinase inhibitors, reduced the tyrosine phosphorylation of p125(FAK) and paxillin stimulated by BB. Also, treatment of NCI- H1299 cells with FAK antisense resulted in decreased FAK tyrosine kinase activity and proliferation. These results suggest that p125(FAK) is,important enzyme for NSCLC proliferation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Med Branch, Rockville, MD 20850 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Moody, TW (reprint author), NCI, Med Branch, Bldg KWC,Rm 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. RI Garcia-Marin, Luis /L-4680-2014; Tapia, Jose/C-5181-2008 OI Garcia-Marin, Luis /0000-0002-1795-7381; Tapia, Jose/0000-0002-3614-6867 NR 39 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 10 PY 2001 VL 162 IS 1 BP 87 EP 95 DI 10.1016/S0304-3835(00)00639-X PG 9 WC Oncology SC Oncology GA 428BA UT WOS:000168440200011 PM 11121866 ER PT J AU Zhang, MF Fukushima, A Vistica, BP Kim, SJ Hung, L Wawrousek, EF Egwuagu, CE Lee, RS Whitcup, SM Gery, I AF Zhang, MF Fukushima, A Vistica, BP Kim, SJ Hung, L Wawrousek, EF Egwuagu, CE Lee, RS Whitcup, SM Gery, I TI Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1 beta or interferon-gamma SO CELLULAR IMMUNOLOGY LA English DT Article DE transgenic animals; immunotolerance; cytokines; IL-1; IFN-gamma; T-cell help; antibody isotypes; Th subtypes ID T-CELLS; PERIPHERAL TOLERANCE; LOCAL EXPRESSION; TNF-ALPHA; B-CELLS; IMMUNOLOGICAL-TOLERANCE; NOD MICE; INDUCTION; CYTOKINES; LIPOPOLYSACCHARIDE AB Transgenic (Tg) mice expressing hen egg lysozyme (HEL) under the control of the alphaA-crystallin promoter exhibit tolerance to HEL by both their T- and B-cell compartments. Here, we show that double-Tg mice, coexpressing HEL with either interleukin-l beta or interferon (IFN)-gamma, demonstrated unresponsiveness to HEL by their T-cell compartment, but most of them developed antibodies against HEL following a challenge with the antigen. The abrogation of humoral tolerance was more pronounced in the HEL/IL-1 double-Tg mice than in the HEL/IFN-gamma mice. Unlike their controls, double-Tg mice exhibited remarkable levels of variability in their antibody levels. The skewed abrogation of tolerance in the double-Tg mice is proposed to be due to the cytokines' capacity to rescue from clonal deletion small numbers of T cells, which provide help to antibody producing B cells. This notion is supported by the finding that adoptive transfer of small numbers of Th1 or Th2 cells into HEL-Tg mice made possible antibody production similar to that seen in the double-Tg mice. (C) 2001 Academic Press. 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,Rm 10N112, Bethesda, MD 20892 USA. EM igery@helix.nih.gov RI Wawrousek, Eric/A-4547-2008 NR 24 TC 3 Z9 3 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JAN 10 PY 2001 VL 207 IS 1 BP 6 EP 12 DI 10.1006/cimm.2000.1750 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 405DM UT WOS:000167142600002 PM 11161447 ER PT J AU Song, SU Oh, IS Lee, B Suh, JK Kim, JH Cha, YD Lee, KH Kim, DH AF Song, SU Oh, IS Lee, B Suh, JK Kim, JH Cha, YD Lee, KH Kim, DH TI Identification of a negative Cis-regulatory element and multiple DNA binding proteins that inhibit transcription of the transforming growth factor-beta type II receptor gene SO GENE LA English DT Article DE cytokine receptor; promoter; gene-specific repressor; palindromic sequence ID CHROMOSOMAL LOOP ANCHORAGE; TGF-BETA; COLON-CANCER; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; PROMOTER REGION; CARCINOMA-CELLS; CYCLIN D1; EXPRESSION; MUTATIONS AB Expression of the transforming growth factor-beta type RII receptor (TGF-beta RII) is highly regulated and is a critical determinant of the cellular response to TGF-beta. Previous analysis of the promoter region for the TGF-beta RII gene introduced the possible existence of a negative regulatory element (NRE) upstream adjacent to the core promoter region (Bae et al., 1995. J. Biol. Chem. 270, 29460-29468). We have confirmed the presence of a strong NRE located between base pairs -100 and -67 relative to the transcription start site. Utilizing DNA transfection techniques and a series of synthesized oligonucleotide promoter fragments, we have shown that this NRE is active in a variety of cell lines. Electrophoretic mobility shift assays have revealed the presence of multiple DNA binding proteins specifically interacting with the NRE. At least three distinct protein complexes are variably present depending on the specific cell line examined, and mutational analysis of the NRE has identified a ten-base pair recognition sequence which is shared by all three complexes. This palindromic sequence has not been previously reported and does not share homology with any known transcription factor consensus sequences. When inserted into an E4 Delta heterologous promoter construct, the NRE binding sequence failed to inhibit either basal or activated transcription of the target gene, indicating that the NRE does not act as a general repressor but may specifically operate within the context of the TGF-beta RII core promoter. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Inha Univ, Coll Med, Clin Res Ctr, Inchon 400711, South Korea. NCI, Chemoprevent Lab, NIH, Rockville, MD 20852 USA. RP Lee, KH (reprint author), Inha Univ, Coll Med, Clin Res Ctr, 7-206,3-Ga, Inchon 400711, South Korea. NR 31 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 10 PY 2001 VL 262 IS 1-2 BP 179 EP 187 DI 10.1016/S0378-1119(00)00534-5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 405CW UT WOS:000167140800021 PM 11179682 ER PT J AU Freedman, R Leonard, S Gault, JM Hopkins, J Cloninger, CR Kaufmann, CA Tsuang, MT Farone, SV Malaspina, D Svrakic, DM Sanders, A Gejman, P AF Freedman, R Leonard, S Gault, JM Hopkins, J Cloninger, CR Kaufmann, CA Tsuang, MT Farone, SV Malaspina, D Svrakic, DM Sanders, A Gejman, P TI Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha 7-nicotinic acetylcholine receptor subunit gene (CHRNA7) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE human chromosome pair 15; genetic linkage; nicotinic receptor; polymorphism; schizophrenia ID NO EVIDENCE; TDT AB The transmission/disequilibrium test was used for fine mapping of the linkage of schizophrenia to the chromosome 15q13-14 region, the site of a candidate gene, the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7), in parent-child triads from the NIMH Schizophrenia Genetics Initiative families. This candidate gene was identified from neurobiological studies of deficits in schizophrenics of the inhibitory gating of the P50 auditory evoked potential. The neurobiological deficit was also used as a phenotype for subsequent linkage analysis. In the present study, significant genotype-wise disequilibrium (P < 0.007) was found at D15S165, a polymorphic simple sequence marker physically located within 1 megabase of both CHRNA7 and a partially duplicated, expressed sequence that includes exons 5-10 of CHRNA7, Replication of this result was found in an additional set of families. The results support this region as a chromosomal location involved in the genetic transmission of schizophrenia. Am. J, Med, Genet, (Neuropsychiatr,Genet,) 105: 20-22, 2001, (C) 2001 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. NIMH, Schizophrenia Genet Initiat, Bethesda, MD 20892 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. RP Freedman, R (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat C268 71, 4200 E 9th Ave, Denver, CO 80262 USA. RI Cloninger, Claude/F-5357-2012 OI Cloninger, Claude/0000-0003-3096-4807 FU NIDA NIH HHS [DA09457]; NIMH NIH HHS [MH38321] NR 17 TC 137 Z9 142 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 8 PY 2001 VL 105 IS 1 BP 20 EP 22 DI 10.1002/1096-8628(20010108)105:1<20::AID-AJMG1047>3.3.CO;2-3 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 390GA UT WOS:000166286300006 PM 11424985 ER PT J AU Howard, OMZ Dong, HF Oppenheim, JJ Insaf, S Santhosh, KC Paul, G Cushman, M AF Howard, OMZ Dong, HF Oppenheim, JJ Insaf, S Santhosh, KC Paul, G Cushman, M TI Inhibition of RANTES/CCR1-mediated chemotaxis by cosalane and related compounds SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ANTI-HIV AGENT; CHEMOKINE RECEPTORS; PHARMACOPHORE; INFECTION; POTENCY AB The anti-HIV agent cosalane and several of its analogues inhibited RANTES-induced migration of human monocytes, but they did not inhibit migration induced by MIP1 alpha or MIP1 beta. RANTES-induced migration of single receptor CCR1-HEK transfectants was also inhibited by the cosalanes. Acetylation of the reactive amino groups of RANTES abrogated the inhibitory activity of cosalane. The data suggest that cosalane and its structural analogues may interfere with the RANTES/CCR1 interaction by binding to RANTES. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, SAIC Frederich, Frederick, MD 21702 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [AI 36624] NR 18 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 8 PY 2001 VL 11 IS 1 BP 59 EP 62 DI 10.1016/S0960-894X(00)00601-6 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 384PD UT WOS:000165953300014 PM 11140734 ER PT J AU Nicolaou, KC Namoto, K Li, J Ritzen, A Ulven, T Shoji, M Zaharevitz, D Gussio, R Sackett, DL Ward, RD Hensler, A Fojo, T Giannakakou, P AF Nicolaou, KC Namoto, K Li, J Ritzen, A Ulven, T Shoji, M Zaharevitz, D Gussio, R Sackett, DL Ward, RD Hensler, A Fojo, T Giannakakou, P TI Synthesis and biological evaluation of 12,13-cyclopropyl and 12,13-cyclobutyl epothilones SO CHEMBIOCHEM LA English DT Editorial Material DE antitumor agents; epothilones; natural products; structure-activity relationships; synthesis design ID COUPLING REACTION; PACLITAXEL; CHLORIDE C1 Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. NCI, Target Structure Based Drug Discovery Grp, Informat Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Nicolaou, KC (reprint author), Scripps Res Inst, Dept Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI Giannakakou, Paraskevi/0000-0001-7378-262X; Ulven, Trond/0000-0002-8135-1755 NR 39 TC 24 Z9 25 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD JAN 8 PY 2001 VL 2 IS 1 BP 69 EP 75 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 392EB UT WOS:000166396800009 PM 11828429 ER PT J AU Holaska, JM Black, BE Love, DC Hanover, JA Leszyk, J Paschal, BM AF Holaska, JM Black, BE Love, DC Hanover, JA Leszyk, J Paschal, BM TI Calreticulin is a receptor for nuclear export SO JOURNAL OF CELL BIOLOGY LA English DT Article DE nucleocytoplasmic transport; Ran GTPase; nuclear pore complex; protein export; hormone receptor ID DEPENDENT RNA EXPORT; SACCHAROMYCES-CEREVISIAE; PORE COMPLEX; IN-VITRO; GLUCOCORTICOID RECEPTOR; GUANOSINE TRIPHOSPHATE; TRANSPORT FACTOR; BINDING PROTEIN; IMPORTIN-ALPHA; SIGNAL AB In previous work, we used a permeabilized cell assay that reconstitutes nuclear export of protein kinase inhibitor (PKI) to show that cytosol contains an export activity that is distinct from Crml (Holaska, J.M., and B.M. Paschal, 1995, Proc. Natl. Acad. Sci USA. 95: 14739-14744). Here, we describe the purification and characterization of the activity as calreticulin (CRT), a protein previously ascribed to functions in the lumen of the ER. We show that cells contain both ER and cytosolic pools of CRT. The mechanism of CRT-dependent export of PKI requires a functional nuclear export signal (NES) in PKI and involves formation of an export complex that contains RanGTP. Previous studies linking CRT to downregulation of steroid hormone receptor function led us to examine itspotential role in nuclear export of the glucocorticoid receptor (GR).We found that CRT mediates nuclear export of GR in permeabilized cell, microinjection, and transfection assays. GR export is insensitive to the Crm1 inhibitor leptomycin B in vivo, and it does not rely on a leucine-rich NES. Rather, GR export is facilitated by its DNA-binding domain, which is shown to function as an NES when transplanted to a green fluorescent protein reporter. CRT defines a new export pathway that may regulate the transcriptional activity of steroid hormone receptors. C1 Univ Virginia, Hlth Sci Ctr, Sch Med, Ctr Cell Signaling, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Microbiol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NIH, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Worcester, MA 01545 USA. RP Paschal, BM (reprint author), Univ Virginia, Hlth Sci Ctr, Sch Med, Ctr Cell Signaling, Box 800577 Hlth Syst, Charlottesville, VA 22908 USA. FU NIGMS NIH HHS [GM58639-01, R01 GM058639] NR 59 TC 188 Z9 195 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 8 PY 2001 VL 152 IS 1 BP 127 EP 140 DI 10.1083/jcb.152.1.127 PG 14 WC Cell Biology SC Cell Biology GA 391QR UT WOS:000166367100012 PM 11149926 ER PT J AU Aridor, M Fish, KN Bannykh, S Weissman, J Roberts, TH Lippincott-Schwartz, J Balch, WE AF Aridor, M Fish, KN Bannykh, S Weissman, J Roberts, TH Lippincott-Schwartz, J Balch, WE TI The Sar1 GTPase coordinates biosynthetic cargo selection with endoplasmic reticulum export site assembly SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Sar1; COPII; endoplasmic reticulum; vesicle; cargo export ID TO-GOLGI TRANSPORT; LIVING CELLS; PLASMA-MEMBRANE; VESICULAR TRANSPORT; VESICLE FORMATION; COATED VESICLES; PROTEIN; COPII; ER; COMPARTMENTS AB Cargo selection and export from the endoplasmic reticulum is mediated by the COPII coat machinery that includes the small GTPase Sari and the Sec23/24 and Sec13/31 complexes. We have analyzed the sequential events regulated by purified Sari and COPII coat complexes during synchronized export of cargo from the ER in vitro. We find that activation of Sari alone, in the absence of other cytosolic components, leads to the formation of ER-derived tubular domains that resemble ER transitional elements that initiate cargo selection, These Sari-generated tubulardomains were shown to be transient, functional intermediates in ER to Golgi transport in vitro. By following cargo export in live cells, we show that ER export in vivo is also characterized by the formation of dynamic tubular structures. Our results demonstrate an unanticipated and novel role for Sari in linking cargo selection with ER morphogenesis through the generation of transitional tubular ER export sites. C1 Scripps Res Inst, Dept Cell & Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Inst Childhood & Neglected Dis, La Jolla, CA 92037 USA. NICHHD, Harold L Dorris Neurol Res Ctr, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Balch, WE (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, 3500 Terrace St,BST South 362, Pittsburgh, PA 15251 USA. RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 FU NCI NIH HHS [CA58689]; NIDDK NIH HHS [R01 DK062318]; NIGMS NIH HHS [F32 GM019689, F32 GM019689-01A1, F32 GM019689-02, F32 GM019689-03, GM42336, R01 GM042336] NR 57 TC 182 Z9 186 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 8 PY 2001 VL 152 IS 1 BP 213 EP 229 DI 10.1083/jcb.152.1.213 PG 17 WC Cell Biology SC Cell Biology GA 391QR UT WOS:000166367100018 PM 11149932 ER PT J AU Kuhn, L Coutsoudis, A Moodley, D Trabattoni, D Mngqundaniso, N Shearer, GM Clerici, M Coovadia, HM Stein, Z AF Kuhn, L Coutsoudis, A Moodley, D Trabattoni, D Mngqundaniso, N Shearer, GM Clerici, M Coovadia, HM Stein, Z TI T-helper cell responses to HIV envelope peptides in cord blood: protection against intrapartum and breast-feeding transmission SO AIDS LA English DT Article DE maternal-infant HIV transmission; breast-feeding; T-helper responses; interleukin-2 ID POLYMERASE CHAIN-REACTION; VIRUS TYPE-1 INFECTION; SEROPOSITIVE INDIVIDUALS; INFANT TRANSMISSION; NEONATAL-PERIOD; SOUTH-AFRICA; LYMPHOCYTE; EXPOSURE; FETAL; RECEPTOR AB Background: Acquired HIV-specific cell-mediated immune responses have been observed in exposed-uninfected individuals, and it has been inferred, but not demonstrated, that these responses constitute a part of natural protective immunity to HIV. This inference was tested prospectively in the natural exposure setting of maternal-infant HIV transmission in a predominantly breast-fed population. Methods: Cord blood from infants of HIV-seropositive women in Durban, South Africa, were tested for in vitro reactivity to a cocktail of HIV envelope peptides (Env) using a bioassay measuring interleukin-2 production in a murine cell line. Infants were followed with repeat HIV RNA tests up to 18 months of age to establish which ones acquired HIV-infection. Results: T-helper cell responses to Env were detected in 33 out of 86 (38%) cord blood samples from infants of HIV-seropositive women and in none of nine samples from seronegative women (P = 0.02). Among infants of HIV-seropositive mothers, three out of 33 with T-helper responses to Env were already infected before delivery (HIV RNA positive on the day of birth), two were lost to follow-up, and none of the others (out of 28) were found to be HIV infected on subsequent tests. in comparison, six out of 53 infants unresponsive to Env were infected before delivery, and eight out of 47 (17%) of the others were found to have acquired HIV infection intrapartum or post-partum through breast-feeding (P = 0.02). Conclusions: T-helper cell responses to HIV envelope peptides were detected in more than one-third of newborns of HIV-infected women; no new infections were acquired by these infants at the time of delivery or post-natally through breast-feeding if these T-helper cell responses were detected in cord blood. (C) 2001 Lippincott Williams & Wilkins. C1 Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, Div Epidemiol, New York, NY 10032 USA. Univ Natal, Dept Paediat & Child Hlth, ZA-4001 Durban, South Africa. Univ Milan, Cattedra Immunol, Milan, Italy. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Kuhn, L (reprint author), Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, 630 W 168th St, New York, NY 10032 USA. RI Trabattoni, Daria/G-7424-2012 FU FIC NIH HHS [TW00231]; PHS HHS [36177] NR 50 TC 44 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 5 PY 2001 VL 15 IS 1 BP 1 EP 9 DI 10.1097/00002030-200101050-00003 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 389GQ UT WOS:000166230600007 PM 11192849 ER PT J AU Sereti, I Sarlis, N Arioglu, E Turner, ML Mican, JM AF Sereti, I Sarlis, N Arioglu, E Turner, ML Mican, JM TI Alopecia universalis and Craves' disease in the setting of immune restoration after highly active antiretroviral therapy SO AIDS LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; PATIENT C1 NIAID, Bethesda, MD 20892 USA. NIDDKD, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Sereti, I (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 5 PY 2001 VL 15 IS 1 BP 138 EP 140 DI 10.1097/00002030-200101050-00026 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 389GQ UT WOS:000166230600030 PM 11192862 ER PT J AU Mankani, MH Kuznetsov, SA Fowler, B Kingman, A Robey, PG AF Mankani, MH Kuznetsov, SA Fowler, B Kingman, A Robey, PG TI In vivo bone formation by human bone marrow stromal cells: Effect of carrier particle size and shape SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE bone formation; bone marrow stromal cells; transplantation; hydroxyapatite-tricalcium phosphate ID COLONY-FORMING CELLS; IN-VIVO; STEM-CELLS; OSTEOGENIC CAPACITY; INVIVO; FIBROBLASTS; MICROENVIRONMENT; CERAMICS; INVITRO; SURFACE AB Successful closure of bone defects in patients remains an active area of basic and clinical research. A novel and promising approach is the transplantation of human bone marrow stromal cells (BMSCs), which have been shown to possess a significant osteogenic potential. The extent and quality of bone formation by transplanted human BMSCs strongly depends on the carrier matrix with which cells are transplanted; to date, by hydroxyapatite/tricalcium phosphate (HA/TCP) supports far more osteogenesis than any other matrix tested. In order to further improve the technique of BMSC transplantation, we studied whether commercially available HA/TCP particles, clinically approved as an osteoconductive material and commercially available as particles measuring 0.5-1.0 mm diameter, is an optimum matrix for promoting bone development by BMSCs. HA/TCP and HA particles of varying size were sieved into a variety of size ranges, from <0.044 mm to 1.0-2.0 mm. Transplants were formed by mixing 40 mg aliquots of particles with cultured passaged human BMSCs. They were placed in subcutaneous pockets in immunocompromised Bg-Nu-XID mice and harvested 4 or 10 weeks later. The transplants were examined histologically; the presence of bone within each transplant was evaluated using histomorphometry or blindly scored on a semiquantitative scale. Transplant morphology and the amount of new bone varied in a consistent fashion based on particle size and shape. Transplants incorporating HA/TCP particles of 0.1-0.25 mm size demonstrated the greatest bone formation at both 4 and 10 weeks; larger or smaller particles were associated with less extensive bone formation, while a size of 0.044 mm represented a threshold below which no bone formation could be observed. Flat-sided HA particles measuring 0.1-0.25 mm formed no bone. The differences in bone formation were not attributable to the differences in cell attachment among the groups. Instead, the size and spatial and structural organization of the particles within BMSC transplants appear to determine the extent of bone formation. These findings provide necessary information for the successful clinical application of BMSC transplantation techniques. (C) 2001 John Wiley & Sons, Inc. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Natl Inst Dent & Craniofacial Res, Off Director, NIH, Bethesda, MD USA. RP Mankani, MH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, 1001 Potrero Ave,Ward 3A, San Francisco, CA 94110 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 34 TC 138 Z9 144 U1 2 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JAN 5 PY 2001 VL 72 IS 1 BP 96 EP 107 DI 10.1002/1097-0290(20010105)72:1<96::AID-BIT13>3.0.CO;2-A PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 384YB UT WOS:000165973900013 PM 11084599 ER PT J AU Titus-Ernstoff, L Hatch, EE Hoover, RN Palmer, J Greenberg, ER Ricker, W Kaufman, R Noller, K Herbst, AL Colton, T Hartge, P AF Titus-Ernstoff, L Hatch, EE Hoover, RN Palmer, J Greenberg, ER Ricker, W Kaufman, R Noller, K Herbst, AL Colton, T Hartge, P TI Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy SO BRITISH JOURNAL OF CANCER LA English DT Article DE DES; oestrogens; breast cancer; endometrial cancer; ovarian cancer; cancer ID BREAST-CANCER; FOLLOW-UP; STILBESTROL THERAPY; MOTHERS; ESTROGENS; TRIAL AB From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters, An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence. The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer. (C) 2001 Cancer Research Campaign http://www.bjcancer.com. C1 Dartmouth Coll, Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA. Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Slone Epidemiol Unit, Brookline, MA 02446 USA. Dartmouth Coll, Sch Med, Dept Med, Lebanon, NH 03756 USA. Informat Management Serv, Rockville, MD 20852 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. RP Titus-Ernstoff, L (reprint author), Dartmouth Coll, Sch Med, Dept Community & Family Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA. OI Hatch, Elizabeth/0000-0001-7901-3928 FU NCI NIH HHS [CP50531-21]; NCPDCID CDC HHS [NCI 33011-21] NR 23 TC 51 Z9 51 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 5 PY 2001 VL 84 IS 1 BP 126 EP 133 DI 10.1054/bjoc.2000.1521 PG 8 WC Oncology SC Oncology GA 403BL UT WOS:000167022600024 PM 11139327 ER PT J AU Zieman, SJ Gerstenblith, G Lakatta, EG Rosas, GO Vandegaer, K Ricker, KM Hare, JM AF Zieman, SJ Gerstenblith, G Lakatta, EG Rosas, GO Vandegaer, K Ricker, KM Hare, JM TI Upregulation of the nitric oxide-cGMP pathway in aged myocardium - Physiological response to L-arginine SO CIRCULATION RESEARCH LA English DT Article DE aging; cGMP; nitric oxide synthase; diastole; L-arginine ID CARDIAC MYOCYTES; IN-VIVO; ENDOTHELIAL DYSFUNCTION; DIASTOLIC FUNCTION; HEART-FAILURE; CA2+ CURRENT; SYNTHASE; EXPRESSION; EXERCISE; HUMANS AB Cardiovascular aging is associated with decreased endothelial vasoreactivity and prolonged diastolic relaxation. As diminished NO signaling contributes to age-associated endothelial dysfunction, we tested the hypothesis that impaired NO signaling or bioactivity also contributes to slowed ventricular relaxation with age. Accordingly, we measured myocardial NO synthase (NOS) enzyme activity, protein abundance, and cGMP production in old (22 to 25 months) and young adult (4 to 7 months) male Wistar rats. Both NOS3 protein abundance and calcium-dependent NOS activity were elevated in old compared with young adult hearts (7.2+/-1.1 Versus 4.2+/-0.6 pmol/mg protein, respectively, P=0.03), However, NOS activity and protein abundance were similar in isolated myocytes, indicating that endothelial NOS likely explains the age difference. Cardiac effluent cGMP (enzyme immunoassay) was 4.8-fold higher (1794+/-373 fmol/min per mg heart tissue) in older versus younger hearts (P=0.003). To assess NO pathway responsiveness, we administered the NOS substrate L-arginine (100 mum) to isolated perfused rat hearts. Baseline isovolumic relaxation (7) was prolonged in old (42.9+/-2.5 ms, n=16) versus young hearts (36.0+/-1.9 ms, n=11, P=0.03). L-Arginine decreased tau (P<0.001) and left ventricular end-diastolic pressure in both old and young hearts. Supporting an NO/cGMP-mediating mechanism, the NO donor sodium nitroprusside reduced (maximal effect, -14+/-2%, n=5, P<0.001), and this lusitropic effect was attenuated by the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo- [4,3,-a]quinoxalin-1-one (n=7, P<0.001). Thus, the NO-cGMP pathway is upregulated in the endothelial cells of aged hearts. L-Arginine, the NOS precursor, enhances ventricular relaxation in old and young hearts, indicating that the NOS pathway may be exploited to modulate diastolic function in aged myocardium. C1 Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Hare, JM (reprint author), Johns Hopkins Hosp, Div Cardiol, 600 N Wolfe St,Carnegie 568, Baltimore, MD 21287 USA. FU NHLBI NIH HHS [T32-HL-07227-24]; NIA NIH HHS [AG-98-07] NR 56 TC 30 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JAN 5 PY 2001 VL 88 IS 1 BP 97 EP 102 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 412NZ UT WOS:000167562400018 PM 11139480 ER PT J AU Heidbreder, CA Baumann, MH AF Heidbreder, CA Baumann, MH TI Autoregulation of dopamine synthesis in subregions of the rat nucleus accumbens SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE dopamine synthesis; L-DOPA (L-3,4-dihydroxyphenylalanine) accumulation; nucleus accumbens; (rat) ID MEDIAL PREFRONTAL CORTEX; EXTRACELLULAR DOPAMINE; SHELL SUBTERRITORIES; VENTRAL STRIATUM; REPEATED COCAINE; MESSENGER-RNA; ROSTRAL POLE; CORE; AMPHETAMINE; INCREASES AB The discovery of a core-shell dichotomy within the nucleus accumbens has opened new lines of investigation into the neuronal basis of psychiatric disorders and drug dependence. In the present study, the autoregulation of dopamine synthesis in subdivisions of the rat nucleus accumbens was examined. We measured the accumulation of L-3,4-dihydroxyphenylalanine (DOPA) after the inhibition of aromatic L-amino acid decarboxylase with 3-hydroxylbenzylhydrazine (NSD-1015, 100 mg kg(-1)) as an in vivo index of dopamine synthesis. The effect of the dopamine D-1/D-2 receptor agonist apomorphine (0, 0, 100, 500 mug kg(-1)) and the dopamine D-2/D-3 receptor agonist quinpirole (0, 20, 100, 500 mug kg(-1)) on dopamine synthesis was determined in the dorsolateral core, ventromedial shell, and rostral pole of the nucleus accumbens. DOPA accumulation was also measured in the frontal cortex, olfactory tubercle, and caudate nucleus of the same rats for comparative purposes. The results show that the three sectors of the nucleus accumbens had similar basal levels of DOPA. Both apomorphine and quinpirole produced a decrease in the dopamine synthesis rate in all brain regions examined. In general, the dopamine D-2/D-3 receptor agonist quinpirole produced a significantly greater decrease in DOPA accumulation than the dopamine D-1/D-2 receptor agonist apomorphine. Within the nucleus accumbens, we found no core-shell differences in the agonist-induced suppression of dopamine synthesis, but the rostral pole was less sensitive to the highest dose of both dopamine agonists. These results suggest that differences in dopamine function between the core and shell might not involve region-specific differences in the receptor-mediated autoregulation of dopamine neurotransmission. Moreover, the blunted effect of dopamine agonists in the rostral pole illustrates that this region of the accumbens is functionally distinct, possibly due to a lower dopamine receptor reserve when compared to the core and shell. (C) 2001 Elsevier Science B.V. All rights reserved. C1 SmithKline Beecham Pharmaceut, Neurosci Res, Harlow CM19 5AW, Essex, England. NIDA, IRP NIDA NIH, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Heidbreder, CA (reprint author), SmithKline Beecham Pharmaceut, Neurosci Res, New Frontiers Sci Pk N,Bldg H25,Room 104A, Harlow CM19 5AW, Essex, England. NR 36 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 5 PY 2001 VL 411 IS 1-2 BP 107 EP 113 DI 10.1016/S0014-2999(00)00882-7 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 393VD UT WOS:000166489600013 PM 11137864 ER PT J AU Pise-Masison, CA Mahieux, R Radonovich, M Jiang, H Brady, JN AF Pise-Masison, CA Mahieux, R Radonovich, M Jiang, H Brady, JN TI Human T-lymphotropic virus type I tax protein utilizes distinct pathways for p53 inhibition that are cell type-dependent SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILD-TYPE P53; NF-KAPPA-B; TRANSFORMS RAT FIBROBLASTS; LEUKEMIA-VIRUS; HTLV-I; DNA-DAMAGE; TUMOR-SUPPRESSOR; BINDING-PROTEIN; LYMPHOCYTES; GENE AB p53 plays a pivotal role in transmitting signals from many forms of genotoxic stress to genes and factors that control the cell cycle and apoptosis, We have previously shown that the human T-lymphotropic virus type I Tax protein can inhibit p53 function. Recently we reported that Tax inhibits p53 function in Jurkat cells and mouse embryo fibroblasts through a mechanism involving the nuclear factor kappaB pathway and correlates with phosphorylation on serines 15 and 392 of p53, However, several groups have also observed a mechanism that correlates with p300 binding of Tax. To address this controversy and to determine the mechanism by which Tax inhibits p53 function, we examined the activation functions of Tax required for p53 inhibition. In HeLa and H1299 cells the cAMP-response element-binding protein/activating transcription factor activation function is essential, as demonstrated by the Tax mutants M47 and K88k In addition, expression of exogenous p300 in H1299 cells allows full recovery of p53 transactivation in the presence of Tax. Consistent with p300 being a limiting factor in H1299, Saos-2, and HeLa cells, we found that the level of endogenous p300 is relatively low in these cells compared with Jurkat cells or the human T-lymphotropic virus type I-infected C81 and MT2 cells. Thus our data suggests that Tax utilizes distinct mechanisms to inhibit p53 function that are cell type-dependent. C1 NCI, Basic Res Lab, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Basic Res Lab, Virus Tumor Biol Sect, NIH, Bldg 41-B201, Bethesda, MD 20892 USA. NR 52 TC 46 Z9 46 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 2001 VL 276 IS 1 BP 200 EP 205 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 390DP UT WOS:000166280700029 PM 11036071 ER PT J AU Tokita, K Hocart, SJ Katsuno, T Mantey, SA Coy, DH Jensen, RT AF Tokita, K Hocart, SJ Katsuno, T Mantey, SA Coy, DH Jensen, RT TI Tyrosine 220 in the 5th transmembrane domain of the neuromedin B receptor is critical for the high selectivity of the peptoid antagonist PD168368 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GASTRIN-RELEASING PEPTIDE; SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; MAMMALIAN BOMBESIN RECEPTORS; HUMAN NEUROKININ-1 RECEPTOR; CATION-PI INTERACTIONS; HIGH-AFFINITY; BINDING-SITES; AGONIST-BINDING; ORBITAL ELECTRONEGATIVITY AB Peptoid antagonists are increasingly being described for G; protein-coupled receptors; however, little is known about the molecular basis of their binding, Recently, the peptoid PD168368 was found to be a potent selective neuromedin B receptor (MMBR) antagonist. To investigate the molecular basis for its selectivity for the NMBR over the closely related receptor for gastrin-releasing peptide (GRPR), we used a chimeric receptor approach and a site-directed mutagenesis approach. Mutated receptors were transiently expressed in Balb 3T3. The extracellular domains of the NMBR were not important for the selectivity of PD168368, However, substitution of the 5th upper transmembrane domain (uTM5) of the NMBR by the comparable GRPR domains decreased the affinity Is-fold. When the reverse study was performed by substituting the uTM5 of NMBR into the GRPR, a 9-fold increase in affinity occurred. Each of the 4 amino acids that differed between NMBR and GRPR in the uTM5 region were exchanged, but only the substitution of Phe(220) for Tyr in the NMBR caused a decrease in affinity, When the reverse study was performed to attempt to demonstrate a gain of affinity in the GRPR, the substitution of Tyr(219) for phe caused an increase in affinity. These results suggest that the hydroxyl group of Tyr(220) in uTM5 of NMBR plays a critical role for high selectivity of PD168368 for NMBR over GRPR. Receptor and ligand modeling suggests that the hydroxyl of the Tyr(220) interacts with nitrophenyl group of PD168368 likely primarily by hydrogen bonding; This result shows the selectivity of the peptoid PD168368, similar to that reported for numerous non-peptide analogues with other G protein-coupled receptors, is primarily dependent on interaction with transmembrane amino acids. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA 70112 USA. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 80 TC 23 Z9 23 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 2001 VL 276 IS 1 BP 495 EP 504 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 390DP UT WOS:000166280700067 PM 11013243 ER PT J AU Kumar, A Novoselov, V Celeste, AJ Wolfman, NM ten Dijke, P Kuehn, MR AF Kumar, A Novoselov, V Celeste, AJ Wolfman, NM ten Dijke, P Kuehn, MR TI Nodal signaling uses activin and transforming growth factor-beta receptor-regulated smads SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EARLY MOUSE EMBRYO; LEFT-RIGHT AXIS; TGF-BETA; MESODERM INDUCTION; TARGETED DISRUPTION; HEPG2 CELLS; GENE; EXPRESSION; XENOPUS; ACTIVATION AB Nodal, a member of the transforming growth factor beta (TGF-beta) superfamily, is implicated in many events critical to the early vertebrate embryo, including mesoderm formation, anterior patterning, and left-right axis specification. Here we define the intracellular signaling pathway induced by recombinant nodal protein treatment of P19 embryonal carcinoma cells. Nodal signaling activates pAR3-Lux, a luciferase reporter previously shown to respond specifically to activin and TGF-beta. However, nodal is unable to induce pTlx2-Lux, a reporter specifically responsive to bone morphogenetic proteins. We also demonstrate that nodal induces p(CAGA)(12), a reporter previously shown to be specifically activated by Smad3. Expression of a dominant negative Smad2 significantly reduces the level of luciferase reporter activity induced by nodal treatment. Finally, we show that nodal signaling rapidly leads to the phosphorylation of Smad2. These results provide the first direct biochemical evidence that nodal signaling is mediated by both activin-TGF-beta pathway Smads, Smad2 and Smads. We also show here that the extracellular cripto protein is required for nodal signaling, making it distinct from activin or TGF-beta signaling. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Genet Inst, Cambridge, MA 02140 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. RP Kuehn, MR (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B-36,10 Ctr Dr, Bethesda, MD 20892 USA. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 46 TC 83 Z9 84 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 2001 VL 276 IS 1 BP 656 EP 661 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 390DP UT WOS:000166280700088 PM 11024047 ER PT J AU Zamostiano, R Pinhasov, A Gelber, E Steingart, RA Seroussi, E Giladi, E Bassan, M Wollman, Y Eyre, HJ Mulley, JC Brenneman, DE Gozes, I AF Zamostiano, R Pinhasov, A Gelber, E Steingart, RA Seroussi, E Giladi, E Bassan, M Wollman, Y Eyre, HJ Mulley, JC Brenneman, DE Gozes, I TI Cloning and characterization of the human activity-dependent neuroprotective protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; COMPARATIVE GENOMIC HYBRIDIZATION; BREAST-CANCER; IN-VITRO; RECEPTOR; LOCALIZATION; GROWTH; VIP; IDENTIFICATION; HOMEODOMAIN AB We have recently cloned the mouse activity-dependent neuroprotective protein (ADNP). Here, we disclose the cloning of human ADNP (hADNP) from a fetal brain cDNA library. Comparative sequence analysis of these two ADNP orthologs indicated 90% identity at the mRNA level. Several single nucleotide polymorphic sites were noticed. The deduced protein structure contained nine zinc fingers, a proline-rich region, a nuclear bipartite localization signal, and a homeobox domain profile, suggesting a transcription factor function. Further comparative analysis identified an ADNP paralog (33% identity and 46% similarity), indicating that these genes belong to a novel protein family with a nine-zinc finger motif followed by a homeobox domain. The hADNP gene structure spans similar to 40 kilobases and includes five exons and four introns with alternative splicing of an untranslated second exon. The hADNP gene was mapped to chromosome 20q12-13.2, a region associated with aggressive tumor growth, frequently amplified in many neoplasias, including breast, bladder, ovarian, pancreatic, and colon cancers, hADNP mRNA is abundantly expressed in distinct normal tissues, and high expression levels were encountered in malignant cells. Down-regulation of ADNP by antisense oligodeoxynucleotides up-regulated the tumor suppressor p53 and reduced the viability of intestinal cancer cells by 90%. Thus, ADNP is implicated in maintaining cell survival, perhaps through modulation of p53. C1 Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Agr Res Org, Volcani Ctr, Inst Anim Sci, IL-50250 Bet Dagan, Israel. Tel Aviv Med Ctr, Dept Nephrol, IL-64239 Tel Aviv, Israel. Univ Adelaide, Dept Genet, Adelaide, SA 5006, Australia. NICHD, Dev Neurobiol Lab, Sect Dev & Mol Pharmacol, NIH, Bethesda, MD 20892 USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 41 TC 117 Z9 122 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 2001 VL 276 IS 1 BP 708 EP 714 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 390DP UT WOS:000166280700095 PM 11013255 ER PT J AU Andric, SA Kostic, TS Tomic, M Koshimizu, T Stojilkovic, SS AF Andric, SA Kostic, TS Tomic, M Koshimizu, T Stojilkovic, SS TI Dependence of soluble guanylyl cyclase activity on calcium signaling in pituitary cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-HORMONE SECRETION; NITRIC-OXIDE SYNTHASES; PROTEIN-KINASE-A; CA2+ OSCILLATIONS; INTRACELLULAR CALCIUM; GH(3) CELLS; SELECTIVE-INHIBITION; PROLACTIN-RELEASE; RAT SOMATOTROPHS; MECHANISM AB The role of nitric oxide (NO) in the stimulation of soluble guanylyl cyclase (sGC) is well established, but the mechanism by which the enzyme is inactivated during the prolonged NO stimulation has not been characterized. In this paper we studied the interactions between NO and intracellular Ca2+ in the control of sGC in rat anterior pituitary cells. Experiments were done in cultured cells, which expressed neuronal and endothelial NO synthases, and in cells with elevated NO levels induced by the expression of inducible NO synthase and by the addition of several NO donors. Basal sGC-dependent cGMP production was stimulated by the increase in NO levels in a time-dependent manner. In contrast, depolarization of cells by high K+ and Bay K 8644, an L-type Ca2+ channel agonist, inhibited sGC activity. Depolarization-induced down-regulation of sGC activity was also observed in cells with inhibited cGMP-dependent phosphodiesterases but not in cells bathed in Ca2+ deficient medium. This inhibition was independent from the pattern of Ca2+ signaling (oscillatory versus nonoscillatory) and NO levels, and was determined by averaged concentration of intracellular Ca2+. These results indicate that inactivation of sGC by intracellular Ca2+ serves as a negative feedback to break the stimulatory action of NO on enzyme activity in intact pituitary cells. C1 NICHD, Sect Cellular Signalling, ERRB, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signalling, ERRB, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. RI Tomic, Melanija/C-3371-2016; OI Koshimizu, Taka-aki/0000-0001-5292-7535 NR 47 TC 22 Z9 23 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 2001 VL 276 IS 1 BP 844 EP 849 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 390DP UT WOS:000166280700113 PM 11031255 ER PT J AU Calderara, S Xiang, Y Moss, B AF Calderara, S Xiang, Y Moss, B TI Orthopoxvirus IL-18 binding proteins: Affinities and antagonist activities SO VIROLOGY LA English DT Article ID MOLLUSCUM CONTAGIOSUM; INTERLEUKIN-18; INFECTION; CYTOKINE; POXVIRUS; FAMILY AB The affinities of purified recombinant human IL-18 binding protein (BP) and ectromelia and cowpox virus homologs for human and murine IL-18 were compared by plasmon resonance. The dissociation constants of human IL-18BP were similar for murine and human IL-18. By contrast, the dissociation constants of the viral proteins for murine IL-18 were 12- to 50-fold lower than that for human IL-18. The ectromelia and cowpox virus proteins were biologically active, as judged by their ability to inhibit induction of interferon-gamma by murine and human IL-18. The relative affinities of the orthopoxvirus IL-18BPs are consistent with the rodent host range of the viruses. (C) 2001 Academic Press. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,Room 229,MSC 0445, Bethesda, MD 20892 USA. NR 12 TC 49 Z9 50 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2001 VL 279 IS 1 BP 22 EP 26 DI 10.1006/viro.2000.0689 PG 5 WC Virology SC Virology GA 394GU UT WOS:000166516300003 PM 11145885 ER PT J AU Kumar, A Buch, S Foresman, L Bischofberger, N Lifson, JD Narayan, O AF Kumar, A Buch, S Foresman, L Bischofberger, N Lifson, JD Narayan, O TI Development of virus-specific immune responses in SHIVKU-infected macaques treated with PMPA SO VIROLOGY LA English DT Article; Proceedings Paper CT XIIIth International AIDS Conference CY JUL 09-14, 2000 CL DURBAN, SOUTH AFRICA DE SHIV; in vivo animal models; CTL; antibodies; AIDS; antiretroviral treatment ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTE; ACTIVE ANTIRETROVIRAL THERAPY; VIRAL LOAD; RHESUS MACAQUES; TYPE-1 INFECTION; IN-VIVO; NEUTRALIZING ANTIBODIES; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY AB Therapeutic intervention with highly active antiretroviral therapy (HAART) can lead to the suppression of HIV viremia below the threshold of detection for several years. However, impact of HAART on reconstitution of virus-specific immune responses remains poorly understood. In this study, four macaques were infected with pathogenic SHIVKU. One week postinoculation two of the four animals were treated with PMPA [9-R-(2-phosphophomethoxypropyl)adenine] daily for 83 days. Two other macaques, that did not receive treatment, exhibited explosive virus replication accompanied by a near total loss of CD4(+) T cells and succumbed to AIDS-related complications within 6 months of infection. These animals did not develop any virus-specific immune responses. On the contrary, the animals that received PMPA showed transient loss of CD4(+) T cells that recovered during the treatment period. The virus burden declined below the level of detection that rebounded soon after cessation of PMPAtherapy. The virus replicated productively for several weeks before both animals controlled the productive replication of virus. This control of virus replication was found to be associated with the development of virus-specific neutralizing antibodies, T-helper cells, and CTLs. Although PMPA did not eliminate virus from the animals, it provided them with enough time to mount virus-specific immune responses that eventually controlled the virus replication in the blood, Our results suggest that antiretroviral therapy, ii initiated early during infection, would help the host in mounting virus-specific immune responses that might control productive replication of the virus, (C) 2001 Academic Press. C1 Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. Gilead Sci Inc, Foster City, CA 94404 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Kumar, A (reprint author), Univ Kansas, Med Ctr, Marion Merrell Dow Lab Viral Pathogenesis, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. OI Buch, Shilpa/0000-0002-3103-6685 FU NCRR NIH HHS [RR-06753, RR-13152]; NIAID NIH HHS [AI-29382]; NINDS NIH HHS [NS-32203] NR 73 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2001 VL 279 IS 1 BP 97 EP 108 DI 10.1006/viro.2000.0710 PG 12 WC Virology SC Virology GA 394GU UT WOS:000166516300011 PM 11145893 ER PT J AU Carlson, BA Mushinski, JF Henderson, DW Kwon, SY Crain, PF Lee, BJ Hatfield, DL AF Carlson, BA Mushinski, JF Henderson, DW Kwon, SY Crain, PF Lee, BJ Hatfield, DL TI 1-methylguanosine in place of Y base at position 37 in phenylalanine tRNA is responsible for its shiftiness in retroviral ribosomal frameshifting SO VIROLOGY LA English DT Article DE frameshift site; 1-methylguanosine; phenylalanine tRNA; rabbit reticulocyte lysates; ribosomal frameshifting; shifty tRNAs; tRNA modification; Y base; wybutoxosine base ID TRANSFER-RNA; TRANSLATIONAL SUPPRESSION; MASS-SPECTROMETRY; GENE-EXPRESSION AB Many mammalian retroviruses express their protease and polymerase by ribosomal frameshifting. It was originally proposed that a specialized shifty tRNA promotes the frameshift event. We previously observed that phenylalanine tRNA(Phe) lacking the highly modified wybutoxosine (Y) base on the 3' side of its anticodon stimulated frameshifting, demonstrating that this tRNA is shifty. We now report the shifty tRNA(Phe) contains 1-methylguanosine (m(1)G) in place of Y and that the m(1)G form from rabbit reticulocytes stimulates frameshifting more efficiently than its m(1)G-containing counterpart from mouse neuroblastoma cells. The latter tRNA contains unmodified C and G nucleosides at positions 32 and 34, respectively, while the former tRNA contains the analogous 2'-O-methylated nucleosides at these positions. The data suggest that not only does the loss of a highly modified base from the 3' side of the anticodon render tRNA(Phe) shifty, but the modification status of the entire anticodon loop contributes to the degree of shiftiness. Possible biological consequences of these findings are discussed. (C) 2001 Academic Press. C1 NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Genet Sect, Genet Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Inst Mol Biol & Genet, Genet Mol Lab, Seoul 151742, South Korea. Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA. RP Hatfield, DL (reprint author), NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bldg 37,Room 2D09, Bethesda, MD 20892 USA. EM hatfield@dc37a.nci.nih.gov RI Kwon, So Yeon/M-5625-2014 OI Kwon, So Yeon/0000-0002-8490-9101 FU NIGMS NIH HHS [GM29812] NR 17 TC 26 Z9 26 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 JAN 5 PY 2001 VL 279 IS 1 BP 130 EP 135 DI 10.1006/viro.2000.0692 PG 6 WC Virology SC Virology GA 394GU UT WOS:000166516300014 PM 11145896 ER PT J AU Kumar, A Lifson, JD Li, Z Jia, FL Mukherjee, S Adany, I Liu, ZL Piatak, M Sheffer, D McClure, HM Narayan, O AF Kumar, A Lifson, JD Li, Z Jia, FL Mukherjee, S Adany, I Liu, ZL Piatak, M Sheffer, D McClure, HM Narayan, O TI Sequential immunization of macaques with two differentially attenuated vaccines induced long-term virus-specific immune responses and conferred protection against AIDS caused by heterologous simian human immunodeficiency virus (SHIV89.6P) SO VIROLOGY LA English DT Article; Proceedings Paper CT XIIIth International AIDS Conference CY JUL 09-14, 2000 CL DURBAN, SOUTH AFRICA DE SHIV; in vivo animal models; CTL; antibodies; AIDS ID T-LYMPHOCYTE RESPONSES; NEUTRALIZING ANTIBODY-RESPONSES; PIG-TAILED MACAQUES; RHESUS-MONKEYS; HIV-1 INFECTION; VIRAL LOAD; TYPE-1 INFECTION; CELL; ENVELOPE; CHALLENGE AB Four rhesus macaques were sequentially immunized with live Vaccines Delta vpu Delta nefSHIV-4 (vaccine-l) and Delta vpu SHIVPPC (vaccine-ll). The Vaccine viruses did not replicate productively in the peripheral blood mononuclear cells (PBMCs) of the vaccinated animals. All four animals developed binding antibodies against both the vaccine-I and -II envelope glycoproteins but neutralizing antibodies only against vaccine-I. They developed vaccine virus-specific CTLs that also recognized homologous as well as heterologous pathogenic SHIVs. Thirty weeks after the last immunization, the vaccinated animals and three unvaccinated control animals were challenged iv with a highly virulent heterologous SHIV89.6P. As expected, the three unvaccinated control animals developed large numbers of infectious PBMCs, high plasma viremia, and precipitous loss of CD4(+) T cells. Two controls did not develop any immune response and succumbed to AIDS in about 6 months. The third control animal developed neutralizing antibodies and had a more chronic disease course, but eventually succumbed to AIDS-related complications 81 weeks after inoculation. The four vaccinated animals became infected with challenge virus as indicated by the presence of challenge virus-specific DNA in the PBMCs and RNA in plasma. However, Virus in these animals replicated approximately 200- to 60,000-fold less efficiently than in control animals and eventually, plasma viral RNA became undetectable in three of the four vaccinates. The animals maintained normal CD4(+) T-cell levels throughout the observation period of 85 weeks after a transient drop at Week 3 postchallenge. They also maintained CTL responses throughout the observation period. These studies thus showed that the graded immunization schedule resulted in a safe and highly effective long-lasting immune response that was associated with protection against AIDS by highly pathogenic heterologous SHIV89.6P. (C) 2001 Academic Press. C1 Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Lab Viral Pathogenesis, Kansas City, KS 66160 USA. NCI, Frederick Canc Res & Dev Ctr, Retroviral Pathogenesis Lab, AIDS Vaccine Program,SAIC Frederick, Frederick, MD 21702 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Kumar, A (reprint author), Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Lab Viral Pathogenesis, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. FU NCRR NIH HHS [RR-13152, RR-06753]; NIAID NIH HHS [AI-29382]; NINDS NIH HHS [NS-32203] NR 63 TC 23 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2001 VL 279 IS 1 BP 241 EP 256 DI 10.1006/viro.2000.0695 PG 16 WC Virology SC Virology GA 394GU UT WOS:000166516300024 PM 11145906 ER PT J AU Revaz, V Benyacoub, J Kast, WM Schiller, JT De Grandi, P Nardelli-Haefliger, D AF Revaz, V Benyacoub, J Kast, WM Schiller, JT De Grandi, P Nardelli-Haefliger, D TI Mucosal vaccination with a recombinant Salmonella typhimurium expressing human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) or HPV16VLPs purified from insect cells inhibits the growth of HPV16-expressing tumor cells in mice SO VIROLOGY LA English DT Article DE human papillomavirus; Salmonella typhimurium; mucosal vaccination; anti-tumor immunity ID CYTOTOXIC T-LYMPHOCYTES; NEUTRALIZING ANTIBODIES; SYSTEMIC IMMUNIZATION; NASAL IMMUNIZATION; ANTITUMOR IMMUNITY; DELIVERY SYSTEM; CORE ANTIGEN; STRAINS; INDUCTION; PROTEIN AB Human papillomaviruses, mainly type 16 (HPV16), are responsible for cervical intraepithelial neoplasia, which can lead, in association with other factors, to cervical cancer. Both Salmonella recombinant vaccine strains assembling HPV16 virus-like particles (VLPs) and HPV16 VLPs purified from insect cells are able to induce HPV16 neutralizing antibodies in genital secretions of mice after nasal immunization. Anti-HPV16-specific antibodies in cervical secretions of women may prevent genital infection with HPV16, although this cannot be critically evaluated in the absence of an experimental model for genital papillomavirus infection. Induction of HPV16-specific cell-mediated immunity in the genital mucosa could improve the efficacy of a vaccine and a mucosal route of immunization might be necessary to do so. It has been shown that systemic immunization of mice with purified HPV16 VLPs confers protection against an HPV16-expressing tumor cell challenge through the induction of cytotoxic T-lymphocytes. Using the same C3 tumor model, we show that intranasal immunization of mice with purified HPV16 VLPs in a prophylactic setting also induces anti-tumor immunity. More interestingly, mucosal vaccination of mice with a Salmonella recombinant strain stably expressing HPV16 L1 VLPs also induces anti-tumor immunity in prophylactic as well as in therapeutic settings. Our data suggest that attenuated Salmonella strains expressing chimeric VLPs containing nonstructural viral proteins might be a promising candidate vaccine against cervical cancer by inducing both neutralizing antibodies and cell-mediated immunity, (C) 2001 Academic Press. C1 CHU Vaudois, Dept Gynaecol, CH-1011 Lausanne, Switzerland. Loyola Univ, Cardinal Bernadin Canc Ctr, Canc Immunol Program, Maywood, IL 60153 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Nardelli-Haefliger, D (reprint author), Inst Microbiol, Dept Gynecol, Bugnon 44, CH-1011 Lausanne, Switzerland. OI nardelli-haefliger, denise/0000-0003-1812-9905 FU NCI NIH HHS [P01CA74182, R01CA74397] NR 41 TC 42 Z9 45 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2001 VL 279 IS 1 BP 354 EP 360 DI 10.1006/viro.2000.0717 PG 7 WC Virology SC Virology GA 394GU UT WOS:000166516300034 PM 11145916 ER PT J AU Pastrana, DV Vass, WC Lowy, DR Schiller, JT AF Pastrana, DV Vass, WC Lowy, DR Schiller, JT TI NHPV16VLP vaccine induces human antibodies that neutralize divergent variants of HPV16 SO VIROLOGY LA English DT Article DE neutralization; HPV16; variants; pseudovirions; vaccine; VLP; serotypes; papillomavirus; immunoprophylaxis; clinical trial ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT PAPILLOMAVIRUS; MINOR CAPSID PROTEIN; CERVICAL-CANCER; IN-VITRO; MEDIATED NEUTRALIZATION; WORLDWIDE PERSPECTIVE; BOVINE PAPILLOMAVIRUS; MONOCLONAL-ANTIBODY AB Genital HPV genotypes are generally distinct serotypes, but whether variants within a genotype can represent serologic subtypes is unclear, in this study we used serum from human volunteers vaccinated with HPV16 L1 VLPs from variant 114K, to examine cross-neutralization of variants from each of the five major phylogenetic branches of HPV16. Recombinant Semliki Forest virus-derived pseudovirions for each variant were generated and combined with serum from vaccines, and the mixture was monitored for infectivity in a standard C127 cell focal transformation assay. Sera from all 10 VLP-immunized individuals had neutralizing activity against each of the variant pseudovirions. For each of the sera, variant titers differed by only fourfold or less from the median titer. Therefore, from a Vaccine perspective, HPV16 Variants belong to a single serotype. Vaccination with HPV16 114K L1 VLPs generates antibodies that should confer a similar degree of protection against all known phylogenetic branches of HPV16. (C) 2001 Academic Press. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 36,Room 1D-32, Bethesda, MD 20892 USA. NR 51 TC 70 Z9 77 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2001 VL 279 IS 1 BP 361 EP 369 DI 10.1006/viro.2000.0702 PG 9 WC Virology SC Virology GA 394GU UT WOS:000166516300035 PM 11145917 ER PT J AU Schwartz, RH AF Schwartz, RH TI Immunology - It takes more than two to tango SO NATURE LA English DT Editorial Material ID CELL; STIMULATION; ICOS C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 11 TC 7 Z9 9 U1 0 U2 1 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 4 PY 2001 VL 409 IS 6816 BP 31 EP 32 DI 10.1038/35051202 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 388HT UT WOS:000166175600024 PM 11343098 ER PT J AU Sacks, FM Svetkey, LP Vollmer, WM Appel, LJ Bray, GA Harsha, D Obarzanek, E Conlin, PR Miller, ER Simons-Morton, DG Karanja, N Lin, PH AF Sacks, FM Svetkey, LP Vollmer, WM Appel, LJ Bray, GA Harsha, D Obarzanek, E Conlin, PR Miller, ER Simons-Morton, DG Karanja, N Lin, PH CA DASH-Sodium Collaborative Res Grp TI Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IDIOPATHIC HYPERTENSION; CLINICAL-TRIAL; RESTRICTION; POTASSIUM; PATTERNS; CATECHOLAMINES; POPULATION; REDUCTION; CALCIUM; WHITES AB Background: The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension. Methods: A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order. Results: Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P = 0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension. Conclusions: The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods. (N Engl J Med 2001;344:3-10.) Copyright (C) 2001 Massachusetts Medical Society. C1 Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Duke Univ, Sch Med, Sarah W Stedman Ctr Nutr Studies, Durham, NC USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Sacks, FM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [U01-HL57114, U01-HL57173, U01-HL57190] NR 39 TC 1981 Z9 2066 U1 18 U2 177 PU MASSACHUSETTS MEDICAL SOC 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 JAN 4 PY 2001 VL 344 IS 1 BP 3 EP 10 DI 10.1056/NEJM200101043440101 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 388CT UT WOS:000166160400001 PM 11136953 ER PT J AU Fan, SJ Ma, YX Wang, CG Yuan, RQ Meng, QH Wang, JA Erdos, M Goldberg, ID Webb, P Kushner, PJ Pestell, RG Rosen, EM AF Fan, SJ Ma, YX Wang, CG Yuan, RQ Meng, QH Wang, JA Erdos, M Goldberg, ID Webb, P Kushner, PJ Pestell, RG Rosen, EM TI Role of direct interaction in BRCA1 inhibition of estrogen receptor activity SO ONCOGENE LA English DT Article DE BRCA1; estrogen receptor (ER); breast cancer; activation function-2 (AF-2) ID TRANSCRIPTIONAL ACTIVATION; OVARIAN-CANCER; MUTATIONS; BREAST; PROTEINS; CARRIERS; BINDING AB The BRCA1 gene was previously found to inhibit the transcriptional activity of the estrogen receptor [ER-alpha] in human breast and prostate cancer cell Lines. In this study, we found that breast cancer-associated mutations of BRCA1 abolish or reduce its ability to inhibit ER-alpha activity and that domains within the amino- and carboxyl-termini of the BRCA1 protein are required for the inhibition. BRCA1 inhibition of ER-alpha activity was demonstrated under conditions in which a BRCA1 transgene was transiently or stably over-expressed in cell lines with endogenous wild-type BRCA1 and in a breast cancer cell line that lacks endogenous functional BRCA1 (HCC1937), In addition, BRCA1 blocked the expression of two endogenous estrogen-regulated gene products in human breast cancer cells: pS2 and cathepsin D, The BRCA1 protein was found to associate with ER-alpha in vivo and to bind to ER-alpha in vitro, by an estrogen-independent interaction that mapped to the amino-terminal region of BRCA1 (ca, amino acid 1-300) and the conserved carboxyl-terminal activation function [AF-2] domain of ER-alpha, Furthermore, several truncated BRCA1 proteins containing the amino-terminal ER-alpha binding region blocked the ability of the full-length BRCA1 protein to inhibit ER-alpha activity. Our findings suggest that the amino-terminus of BRCA1 interacts with ER-alpha, while the carboxyl-terminus of BRCA1 may function as a transcriptional repression domain. C1 Albert Einstein Coll Med, Long Isl Jewish Med Ctr, Dept Radiat Oncol, New York, NY 11040 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Duv Human Endocrine Tumor Biol, Bronx, NY 10461 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sch Med, Metab Res Unit, San Francisco, CA 94143 USA. RP Rosen, EM (reprint author), Albert Einstein Coll Med, Long Isl Jewish Med Ctr, Dept Radiat Oncol, Long Isl Campus,270-05 76th Ave, New York, NY 11040 USA. FU NCI NIH HHS [R01-CA70897]; NIEHS NIH HHS [R01-ES09169 , +]; PHS HHS [R01-82599] NR 21 TC 166 Z9 178 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 4 PY 2001 VL 20 IS 1 BP 77 EP 87 DI 10.1038/sj.onc.1204073 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 391NE UT WOS:000166361400009 PM 11244506 ER PT J AU Rowe, PC Calkins, H DeBusk, K McKenzie, R Anand, R Sharma, G Cuccherini, BA Soto, N Hohman, P Snader, S Lucas, KE Wolff, M Straus, SE AF Rowe, PC Calkins, H DeBusk, K McKenzie, R Anand, R Sharma, G Cuccherini, BA Soto, N Hohman, P Snader, S Lucas, KE Wolff, M Straus, SE TI Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ORTHOSTATIC TACHYCARDIA SYNDROME; PLACEBO-CONTROLLED TRIAL; HEAD-UP TILT; ADOLESCENT CHRONIC-FATIGUE; AUTONOMIC NERVOUS-SYSTEM; LOW-DOSE HYDROCORTISONE; VASOVAGAL SYNCOPE; DOUBLE-BLIND; NEUROCARDIOGENIC SYNCOPE; CROSSOVER TRIAL AB Context Patients with chronic fatigue syndrome (CFS) are more likely than healthy persons to develop neurally mediated hypotension (NMH) in response to prolonged orthostatic stress. Objective To examine the efficacy of fludrocortisone acetate as monotherapy for adults with both CFS and NMH. Design Randomized, double-blind, placebo-controlled trial conducted between March 1996 and February 1999. Setting Two tertiary referral centers in the United States. Patients One hundred individuals aged 18 to 50 years who satisfied Centers for Disease Control and Prevention criteria for CFS and had NMH provoked during a 2-stage tilt-table test. Eighty-three subjects had adequate outcome data to assess efficacy. Intervention Subjects were randomly assigned to receive fludrocortisone acetate, titrated to 0.1 mg/d (n=50) or matching placebo (n=50) for 9 weeks, followed by 2 weeks of observation after discontinuation of therapy. Main Outcome Measure Proportion of subjects in each group with at least a 15-point improvement on a 100-point global wellness scale. Results Baseline demographic and illness characteristics between the groups were similar; CFS had been present for at least 3 years in 71%, Using an intention-to-treat analysis, 7 subjects (14%) treated with fludrocortisone experienced at least a 15-point improvement in their wellness scores compared with 5 (10%) among placebo recipients (P=.76). No differences were observed in several other symptom scores or in the proportion with normal follow-up tilt test results at the end of the treatment period. Conclusions In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms, Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. EMMES Corp, Potomac, MD USA. RP Rowe, PC (reprint author), Johns Hopkins Hosp, Brady 212,600 N Wolfe St, Baltimore, MD 21287 USA. FU NCRR NIH HHS [RR00052]; NIAID NIH HHS [AI 39500] NR 46 TC 74 Z9 75 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 3 PY 2001 VL 285 IS 1 BP 52 EP 59 DI 10.1001/jama.285.1.52 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 387GH UT WOS:000166114500024 PM 11150109 ER PT J AU Reis, SE Costantino, JP Wickerham, DL Tan-Chiu, E Wang, JP Kavanah, M AF Reis, SE Costantino, JP Wickerham, DL Tan-Chiu, E Wang, JP Kavanah, M CA Natl Surg Adjuvant Breast Bowel Pr TI Cardiovascular effects of tamoxifen in women with and without heart disease: Breast cancer prevention trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CORONARY-ARTERY ATHEROSCLEROSIS; POSTMENOPAUSAL ESTROGEN THERAPY; ADJUVANT TAMOXIFEN; RANDOMIZED TRIAL; FOLLOW-UP; ESTRADIOL; MORBIDITY; RESPONSES; MONKEYS AB Background: The overall effect of prophylactic tamoxifen in women depends on the balance between the effects of the drug, which include preventing breast cancer and altering cardiovascular risk. In a recent clinical trial, postmenopausal estrogen-progestin therapy was shown to increase the risk of early cardiovascular events among women with a history of coronary heart disease (CHD). The cardiovascular effects of tamoxifen in women with and without CHD are not known.: The National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (BCPT) is the only clinical trial that provides data to assess the cardiovascular effects of tamoxifen in women with and without CHD, Methods: A total of 13 388 women at increased risk for breast cancer were randomly assigned in the BCPT to receive either tamoxifen (20 mg/day) or placebo. Cardiovascular follow-up was available for 13 194 women, 1048 of whom had prior clinical CHD, Fatal and nonfatal myocardial infarction, unstable angina, and severe angina were tabulated (mean follow-up: 49 months). All statistical tests were two-sided. Results: Cardiovascular event rates were not statistically significantly different between women assigned to receive tamoxifen and those assigned to receive placebo, independent of pre-existing CHD, Among women without CHD (6074 on tamoxifen versus 6072 on placebo), risk ratios (95% confidence intervals [CIs]) for tamoxifen users were 1.75 (0.44 to 8.13) for fatal myocardial infarction, 1.11 (0.55 to 2.28) for nonfatal myocardial infarction, 0.69 (0.29 to 1.57) for unstable angina, and 0.83 (0.32 to 2.10) for severe angina. In women with CHD (516 on tamoxifen versus 532 on placebo), risk ratios (95% CIs) for tamoxifen users were 0.00 (0 to 1.58) for fatal myocardial infarction, 1.25 (0.32 to 5.18) for nonfatal myocardial infarction, 2.26 (0.87 to 6.55) for unstable angina, and 1.39 (0.23 to 9.47) for severe angina. There was no evidence that the lack of association between tamoxifen and cardiovascular events was related to an early increase in risk that may have been offset by a late decrease in risk. Conclusion: When used for breast cancer prevention in women with or without heart disease, tamoxifen is not associated with beneficial or adverse cardiovascular effects. C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Boston Med Ctr, Boston, MA USA. RP Reis, SE (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, 200 Lothrop St, Pittsburgh, PA 15213 USA. RI Reis, Steven/J-3957-2014 FU NCI NIH HHS [U10CA37377, U10CA69974] NR 22 TC 83 Z9 86 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 3 PY 2001 VL 93 IS 1 BP 16 EP 21 DI 10.1093/jnci/93.1.16 PG 6 WC Oncology SC Oncology GA 387ME UT WOS:000166125700009 PM 11136837 ER PT J AU Herbert, BS Wright, AC Passons, CM Wright, WE Ali, IU Kopelovich, L Shay, JW AF Herbert, BS Wright, AC Passons, CM Wright, WE Ali, IU Kopelovich, L Shay, JW TI Effects of chemopreventive and antitelomerase agents on the spontaneous immortalization of breast epithelial cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; CATALYTIC SUBUNIT HTERT; LARGE T-ANTIGEN; TELOMERASE ACTIVITY; CANCER-CELLS; RETROVIRAL VECTORS; GROWTH ARREST; GENE-TRANSFER; INHIBITION; EXPRESSION AB Background: Activation of telomerase is an early event in the development of breast and other cancers that may lead to cell immortalization, a critical and rate-limiting step in cancer progression. Breast epithelial cells from women with Li-Fraumeni syndrome (LFS) immortalize spontaneously and reproducibly in culture. We, therefore, tested whether immortalization of these cells could be prevented by treating them with chemopreventive agents and by inhibiting telomerase activity, Methods: Noncancerous, preimmortal breast epithelial cells derived from a patient with LFS were treated for 3 months with nontoxic concentrations of the chemopreventive agents oltipraz, difluoromethylornithine, tamoxifen, and retinoic acid or with two different telomerase inhibitors. The frequency of spontaneous immortalization of LFS-derived cells was estimated by an approach based on fluctuation analyses. Statistical analyses were two-sided. Results: The frequency of spontaneous immortalization events of LFS-derived breast epithelial cells was reduced by long-term treatment with retinoic acid (P<.001) or tamoxifen (P<.05) compared with solvent-treated cells. The frequency of immortalization was also reduced by treating LFS-derived cells with an antitelomerase antisense oligonucleotide (P<.001) or by inducing the cells to express a dominant negative mutant of telomerase (P<.025) compared with cells treated with a control oligonucleotide or with empty vector, respectively. Conclusions: Treatment of preimmortal LFS breast epithelial cells with chemopreventive and antitelomerase agents decreased the frequency of spontaneous immortalization in vitro. These studies validate the application of a new cell culture model system to screen the effects of novel chemopreventive agents by use of cell immortalization as an end point. The results also suggest that the telomerase ribonucleoprotein complex may be an important molecular target for breast cancer prevention. C1 Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Shay, JW (reprint author), Univ Texas, SW Med Ctr, Dept Cell Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. RI Shay, Jerry/F-7878-2011 FU NCI NIH HHS [CN85139, CN85143] NR 48 TC 41 Z9 48 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 3 PY 2001 VL 93 IS 1 BP 39 EP 45 DI 10.1093/jnci/93.1.39 PG 7 WC Oncology SC Oncology GA 387ME UT WOS:000166125700012 PM 11136840 ER PT J AU Stevens, VJ Obarzanek, E Cook, NR Lee, IM Appel, LJ West, DS Milas, NC Mattfeldt-Beman, M Belden, L Bragg, C Millstone, M Raczynski, J Brewer, A Singh, B Cohen, J AF Stevens, VJ Obarzanek, E Cook, NR Lee, IM Appel, LJ West, DS Milas, NC Mattfeldt-Beman, M Belden, L Bragg, C Millstone, M Raczynski, J Brewer, A Singh, B Cohen, J CA Trials Hypertension Prevention Res TI Long-term weight loss and changes in blood pressure: Results of the trials of hypertension prevention, phase II SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; CONTROL PROGRAM; FINAL REPORT; THERAPY; OBESITY; POPULATION; RISK AB Background: Weight loss appears to be an effective method for primary prevention of hypertension. However, the long-term effects of weight loss on blood pressure have not been extensively studied. Objective: To present detailed results from the weight loss arm of Trials of Hypertension Prevention (TOHP) II. Design: Multicenter, randomized clinical trial testing the efficacy of lifestyle interventions for reducing blood pressure over 3 to 4 years, Participants in TOHP II were randomly assigned to one of four groups. This report focuses only on participants assigned to the weight loss (n=595) and usual care control (n=596) groups. Patients: Men and women 30 to 54 years of age who had nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg and were 110% to 165% of their ideal body weight at baseline. Intervention: The weight loss intervention included a 3-year program of group meetings and individual counseling focused on dietary change, physical activity, and social support. Measurements: Weight and blood pressure data were collected every 6 months by staff who were blinded to treatment assignment Results: Mean weight change from baseline in the intervention group was -4.4 kg at 6 months, -2.0 kg at 18 months, and -0.2 kg at 36 months. Mean weight change in the control group at the same time points was 0.1, 0.7, and 1.8 kg, Blood pressure was significantly lower in the intervention group than in the control group at 6, 18, and 36 months. The risk ratio for hypertension in the intervention group was 0.58 (95% CI, 0.36 to 0.94) at 6 months, 0.78 (CI, 0.62 to 1.00) at 18 months, and 0.81 (CI, 0.70 to 0.95) at 36 months. In subgroup analyses, intervention participants who lost at least 4.5 kg at 6 months and maintained this weight reduction for the next 30 months had the greatest reduction in blood pressure and a relative risk for hypertension of 0.35 (a, 0.20 to 0.59). Conclusions: Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss. C1 Kaiser Permanente Ctr Hlth Res, Portland, OR USA. NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. St Louis Univ, Sch Med, St Louis, MO USA. Univ Calif Davis, Sch Med, Davis, CA 95616 USA. Univ Tennessee, Memphis, TN USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. RP Stevens, VJ (reprint author), Kaiser Permanente Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR USA. FU NHLBI NIH HHS [HL37852, HL37907, HL37924] NR 31 TC 430 Z9 451 U1 2 U2 17 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 2 PY 2001 VL 134 IS 1 BP 1 EP 11 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 386CV UT WOS:000166043300001 PM 11187414 ER PT J AU Schechter, CP Dave, HPG Alving, BM AF Schechter, CP Dave, HPG Alving, BM TI Update in hematology SO ANNALS OF INTERNAL MEDICINE LA English DT Review C1 Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Washington, DC USA. NIH, Bethesda, MD 20892 USA. RP Schechter, CP (reprint author), Vet Affairs Med Ctr, 50 Irving St NW,Room 4D-115, Washington, DC 20422 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 2 PY 2001 VL 134 IS 1 BP 38 EP 46 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 386CV UT WOS:000166043300006 ER PT J AU Karibe, A Tobacman, LS Strand, J Butters, C Back, N Bachinski, LL Arai, AE Ortiz, A Roberts, R Homsher, E Fananapazir, L AF Karibe, A Tobacman, LS Strand, J Butters, C Back, N Bachinski, LL Arai, AE Ortiz, A Roberts, R Homsher, E Fananapazir, L TI Hypertrophic cardiomyopathy caused by a novel alpha-tropomyosin mutation (V95A) is associated with mild cardiac phenotype, abnormal calcium binding to troponin, abnormal myosin cycling, and poor prognosis SO CIRCULATION LA English DT Article DE cardiomyopathy; genetics; death, sudden; prognosis ID SKELETAL-MUSCLE CONTRACTION; THIN FILAMENT; CLINICAL-FEATURES; MOLECULAR-BASIS; DISEASE GENE; ACTIN; SUBFRAGMENT-1; MOVEMENT; MODEL; MOTILITY AB Background-We report hypertrophic cardiomyopathy (HCM) in a Spanish-American family caused by a novel alpha -tropomyosin (TPM1) mutation and examine the pathogenesis of the clinical disease by characterizing functional defects in the purified mutant protein. Methods and Results-HCM was linked to the TPM1 gene (logarithm of the odds [LOD] score 3.17). Sequencing and restriction digestion analysis demonstrated a TPM1 mutation V95A that cosegregated with HCM. The mutation has been associated with 13 deaths in 26 affected members (11 sudden deaths and 2 related to heart failure), with a cumulative survival rate of 73+/-10% at the age of 40 years. Left ventricular wall thickness (mean 16+/-6 mm) and disease penetrance (53%) were similar to those for the beta -myosin mutations L908V and G256E previously associated with a benign prognosis. Left ventricular hypertrophy was milder than with the beta -myosin mutation R403Q, but the prognosis was similarly poor. With the use of recombinant tropomyosins, we identified several functional alterations at the protein level. The mutation caused a 40% to 50% increase in calcium affinity in regulated thin filament-myosin subfragment-1 (S1) MgATPase assays, a 20% decrease in MgATPase rates in the presence of saturating calcium, a 5% decrease in unloaded shortening velocity in in vitro motility assays, and no change in cooperative myosin S1 binding to regulated thin filaments. Conclusions-In contrast to other reported TPM1 mutations, V95A-associated HCM exhibits unusual features of mild phenotype but poor prognosis. Both myosin cycling and calcium binding to troponin are abnormal in the presence of the mutant tropomyosin. The genetic diagnosis afforded by this mutation will be valuable in the management of HCM. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fananapazir, L (reprint author), Bldg 10,Room 7B-15,10 Ctr Dr MSC 1650, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-63774]; NIAMS NIH HHS [AR-30988] NR 42 TC 67 Z9 70 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 JAN 2 PY 2001 VL 103 IS 1 BP 65 EP 71 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 390GL UT WOS:000166287300016 PM 11136687 ER PT J AU Requena, JR Chao, CC Levine, RL Stadtman, ER AF Requena, JR Chao, CC Levine, RL Stadtman, ER TI Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VALERIC ACID; DISEASE; SYNTHETASE; INCREASES; MARKER; STRESS; DAMAGE; AGE AB Metal-catalyzed oxidation results in loss of function and structural alteration of proteins. The oxidative process affects a variety of side amino acid groups, some of which are converted to carbonyl compounds. Spectrophotometric measurement of these moieties, after their reaction with 2,4-dinitrophenylhydrazine. is a simple, accurate technique that has been widely used to reveal increased levels of protein carbonyls in aging and disease. We have initiated studies aimed at elucidating the chemical nature of protein carbonyls. Methods based on gas chromatography/mass spectrometry with isotopic dilution were developed for the quantitation of glutamic and aminoadipic semialdehydes after their reduction to hydroxyaminovaleric and hydroxyaminocaproic acids. Analysis of model proteins oxidized in vitro by Cu2+/ascorbate revealed that these two compounds constitute the majority of protein carbonyls generated. Glutamic and aminoadipic semialdehydes were also detected in rat liver proteins, where they constitute approximate to 60% of the total protein carbonyl value. Aminoadipic semialdehyde was also measured in protein extracts from HeLa cells, and its level increased as a consequence of oxidative stress to cell cultures. These results indicate that glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins, and that this reaction is a major route leading to the generation of protein carbonyls in biological samples. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 222,3 Ctr Dr, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 26 TC 269 Z9 277 U1 0 U2 27 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 2 PY 2001 VL 98 IS 1 BP 69 EP 74 DI 10.1073/pnas.011526698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389DD UT WOS:000166222600018 PM 11120890 ER PT J AU Xiao, GH Jeffers, M Bellacosa, A Mitsuuchi, Y Vande Woude, GF Testa, JR AF Xiao, GH Jeffers, M Bellacosa, A Mitsuuchi, Y Vande Woude, GF Testa, JR TI Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR SCATTER FACTOR; MET TYROSINE KINASE; NF-KAPPA-B; CELL-DEATH; MEDIATED APOPTOSIS; RECEPTOR; AKT; PROTOONCOGENE; MIGRATION; MECHANISM AB Hepatocyte growth factor (HGF) is a ligand of the receptor tyrosine kinase encoded by the c-Met protooncogene. HGF/Met signaling has multifunctional effects on various cell types. We sought to determine the role of HGF/Met in apoptosis and identify signal transducers involved in this process. In experiments with human SK-LMS-1 leiomyosarcoma cells, we show that the Akt kinase is activated by HGF in a time- and dose-dependent manner by phosphatidylinositol 3-kinase (PI3-kinase). Akt is also activated by active tumorigenic forms of Met, i,e,, ligand-independent Tpr-Met, a truncated and constitutively dimerized form of Met, and a mutationally activated version of Met corresponding to that found in human hereditary papillary renal carcinoma. In NIH 3T3 cells transfected with wild-type Met, HGF inhibits apoptosis induced by serum starvation and UV irradiation. HGF-induced survival correlates with Akt activity and is inhibited by the specific PI3-kinase inhibitor LY294002, indicating that HGF inhibits cell death through the PI3-kinase/Akt signal transduction pathway. Furthermore, transiently transfected Tpr-Met activates Akt (both Akt1 and Akt2) and protects cells from apoptosis. Mitogen-activated protein kinase (MAPK) also is activated by HGF and rescues cells from apoptosis, although the cytoprotective effect is less marked than for PI3-kinase/Akt. Blocking MAPK with the specific MAPK kinase inhibitor PD098059 impairs the ability of HGF to promote cell survival. Similar results were obtained with NIH 3T3 cells expressing the fusion protein Trk-Met and stimulated with nerve growth factor, the Trk ligand, These results demonstrate that HGF/Met is capable of protecting cells from apoptosis by using both PI3-kinase/Akt and, to a lesser extent, MAPK pathways. C1 Fox Chase Canc Ctr, Human Genet Program, Philadelphia, PA 19111 USA. NCI, Adv Biosci Labs, Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Testa, JR (reprint author), Fox Chase Canc Ctr, Human Genet Program, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA06927, CA77429, P30 CA006927, R01 CA077429] NR 38 TC 268 Z9 273 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 JAN 2 PY 2001 VL 98 IS 1 BP 247 EP 252 DI 10.1073/pnas.011532898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389DD UT WOS:000166222600048 PM 11134526 ER PT J AU Chun, TW Justement, JS Moir, S Hallahan, CW Ehler, LA Liu, SY McLaughlin, M Dybul, M Mican, JM Fauci, AS AF Chun, TW Justement, JS Moir, S Hallahan, CW Ehler, LA Liu, SY McLaughlin, M Dybul, M Mican, JM Fauci, AS TI Suppression of HIV replication in the resting CD4(+) T cell reservoir by autologous CD8(+) T cells: Implications for the development of therapeutic strategies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HIV-1; CD8(+) T cells; soluble factors; latency; HAART ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS REPLICATION; QUANTITATIVE-ANALYSIS; IMMUNE-RESPONSES; LYMPHOCYTES-T; CD4+ CELLS; INFECTION; VIREMIA; IDENTIFICATION; PATHOGENESIS AB CD8(+) T cell-mediated antiviral activity against HIV has been described consistently in infected individuals; however, the role of this activity in controlling replication of HIV in the latently infected, resting CD4(+) T cell reservoir is unclear. By using an ex vivo system, we show that replication of HIV in this viral reservoir is effectively suppressed in coculture by autologous CD8(+) T cells in long-term nonprogressors (LTNPs) and in patients whose viremia was controlled by highly active antiretroviral therapy (HAART), but not in therapy-naive patients who had substantial levels of plasma viremia. This antiviral activity was largely independent of cytotoxic CD8(+) T lymphocytes (CTL). When the role of soluble CD8(+) T cell-derived factors was examined, we found that CC-chemokines played a major role in inhibition of viral replication in the latent viral reservoir in some LTNPs and patients receiving HAART, but not in chronically infected patients who were not receiving antiretroviral therapy. Potent antiviral activity, independent of CC-chemokines, was found mainly in patients in whom HAART was initiated shortly after the acute phase of HIV infection. These results indicate that CD8(+) T cells provide potent suppressive activity against HIV replication in the latent viral reservoir via direct cellular contact in patients who are naturally LTNPs or in those who are treated with HAART. Furthermore, the profound antiviral activity exerted by non-CC-chemokine soluble factors in infected patients who began HAART early in HIV infection suggests that preservation of this HIV-suppressive mechanism by early initiation of therapy may play an important role in the containment of viral replication in infected patients following interruption of therapy. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A32, Bethesda, MD 20892 USA. NR 44 TC 50 Z9 51 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 JAN 2 PY 2001 VL 98 IS 1 BP 253 EP 258 DI 10.1073/pnas.98.1.253 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389DD UT WOS:000166222600049 PM 11136258 ER PT J AU Minter, RM Ferry, MA Rectenwald, JE Bahjat, FR Oberholzer, A Oberholzer, C La Face, D Tsai, V Ahmed, CMI Hutchins, B Copeland, EM Ginsberg, HS Moldawer, LL AF Minter, RM Ferry, MA Rectenwald, JE Bahjat, FR Oberholzer, A Oberholzer, C La Face, D Tsai, V Ahmed, CMI Hutchins, B Copeland, EM Ginsberg, HS Moldawer, LL TI Extended lung expression and increased tissue localization of viral IL-10 with adenoviral gene therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; COLLAGEN-INDUCED ARTHRITIS; IN-VIVO; INTERLEUKIN-10; VECTORS; PROLIFERATION; INFLAMMATION; MONOCYTES; RECEPTOR; HOMOLOGY AB IL-10 is a pleiotropic cytokine that acts as an important regulator of macrophage, T cell, and natural killer cell functions. Human IL-10 (hIL-10) has both stimulatory and inhibitory effects on a wide variety of cell types. Viral IL-10 (vIL-10) possesses only a subset of hIL-10's activities, predominantly its suppression of cytokine synthesis by T helper type 1 clones. In the present report, we evaluated tissue accumulation and biological activity of hIL-10 and vIL-10 in vivo in individual organs by using a first-generation adenoviral (Ad) vector administered intratracheally and intravenously. We report the observation that Ad vectors delivering vIL-10, but not hIL-10, are associated with prolonged expression in the lung (>42 days) when delivered intratracheally. In contrast, there was no prolongation in vIL-10 expression when Ad vectors were intravenously administered, although vIL-10 levels in the tissue, but not serum, were markedly increased relative to hIL-10. Moreover, we report an augmented capacity of expressed vIL-10 versus hIL-10 to suppress the acute inflammatory responses in the lung to intratracheal administration of Ad. These findings confirm fundamental differences in Ad-induced expression of vIL-10 and hIL-10 when administered to the lungs. The results further suggest that Ad vectors expressing vIL-10 may have a role as anti-inflammatory agents in the treatment of acute and chronic lung inflammation. C1 Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. NIAAA, NIH, Rockville, MD 20852 USA. Canji Inc, San Diego, CA 92121 USA. RP Moldawer, LL (reprint author), Univ Florida, Shands Hosp, Coll Med, Dept Surg, Room 6116, Gainesville, FL 32610 USA. FU NHLBI NIH HHS [P50 HL059412, P01 HL059412, P30HL-59412]; NIGMS NIH HHS [T32 GM008721, T32-GM-08721, GM-40586, R37 GM040586, R01 GM040586] NR 30 TC 25 Z9 28 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 2 PY 2001 VL 98 IS 1 BP 277 EP 282 DI 10.1073/pnas.250489297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389DD UT WOS:000166222600053 PM 11134537 ER PT S AU Rhee, S Ritter, TA Shung, KK Wang, H Cao, W AF Rhee, S Ritter, TA Shung, KK Wang, H Cao, W BE Yuhas, DE Schneider, SC TI Materials for acoustic matching in ultrasound transducers SO 2001 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE International Ultrasonic Symposium CY OCT 07-10, 2001 CL ATLANTA, GA SP Ultrason, Ferrelect, & Frequency Control Soc AB Acoustic impedance (Z) and fabrication issues for matching layers in high frequency transducers were identified. Guided by a density/impedance relationship established for various polymers, glasses, ceramics and metals, few monolithic materials with Z in the range of 6 - 9 MRayls were found. Composites of gold- and silver-polymer resulted in the desired impedances, however, with increased attenuation. Issues of microstructural scale, homogeneity and particle size effects were noted including issues of percolation behaviour for conducting composites. Using PiezoCad, the effect of matching layer thickness and impedance variation of a 100 MHz transducer were modeled. C1 Penn State Univ, NIH, Resource Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RP Rhee, S (reprint author), Penn State Univ, NIH, Resource Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RI Cao, Wenwu/F-6091-2012 OI Cao, Wenwu/0000-0002-2447-1486 NR 6 TC 3 Z9 3 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-7177-1 J9 ULTRASON PY 2001 BP 1051 EP 1055 PG 5 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Acoustics; Engineering; Physics GA BU75C UT WOS:000176890800225 ER PT S AU Cannata, JM Ritter, TA Shung, KK AF Cannata, JM Ritter, TA Shung, KK BE Yuhas, DE Schneider, SC TI A 35 MHz linear array for medical imaging SO 2001 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE International Ultrasonic Symposium CY OCT 07-10, 2001 CL ATLANTA, GA SP Ultrason, Ferrelect, & Frequency Control Soc AB This paper discusses the design, fabrication and testing of a 35 MHz linear ultrasonic array. The array features monolithic piezoelectric elements diced out of TRS 600FGHD fine grain high-density ceramic. A lossy urethane doped with gas filled microspheres is used as a kerf-filler to dampen inter-element acoustic propagation and reduce pulse length. The array incorporates a slotted single matching layer made from an unloaded epoxy. This matching layer also contributes to the reduction of pulse length and an increase in sensitivity. Array elements are spaced by a 50 mum pitch and interconnected via a flexible circuit. An 85 Q transmission line coaxial cable is used to electrically match the array elements to the 50 0 system electronics. The final 64-element array design is based on experimental results obtained from several four-element prototype arrays. An average center frequency of 34 MHz with a -6 dB bandwidth of at least 45% per element is achieved with the final prototype array. The maximum combined electrical and acoustical cross-talk for nearest and next nearest elements is less than -29 dB. The average -40 dB pulse length is 105 ns. The simple design and satisfactory performance of this array make it suitable for large-scale production. C1 Penn State Univ, Dept Bioengn, NIH, Resource Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RP Cannata, JM (reprint author), Penn State Univ, Dept Bioengn, NIH, Resource Ctr Med Ultrason Transducer Technol, 205 Hallowell Bldg, University Pk, PA 16802 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-7177-1 J9 ULTRASON PY 2001 BP 1157 EP 1160 PG 4 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Acoustics; Engineering; Physics GA BU75C UT WOS:000176890800248 ER PT S AU Snook, KA Ritter, TA Shrout, TR Shung, KK AF Snook, KA Ritter, TA Shrout, TR Shung, KK BE Yuhas, DE Schneider, SC TI Design of a high frequency annular array for medical ultrasound SO 2001 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE International Ultrasonic Symposium CY OCT 07-10, 2001 CL ATLANTA, GA SP Ultrason, Ferrelect, & Frequency Control Soc AB This paper reports the results of an effort of developing a 50 MHz annular array which incorporates a fine grain lead titanate as the piezoelectric material. The array achieves a better sensitivity than a comparable PVDF annular array and demonstrates low lateral coupling for reduced cross-talk. Using resonance techniques, the lead titanate has been fully characterized. The ceramic shows a clamped permittivity (epsilon(33)(s)/epsilon(0)) equal to 180, a thickness coupling k(t), of 0.49 and a planar coupling, k(p), of 0.08. This material was fabricated into an annular array with an overall diameter of 5 mm and six equal-area elements. Separation of the elements was achieved using laser micromachining. Utilizing the waveforms from one-dimensional modeling, intensity field calculations predicted a maximum -6 dB lateral beamwidth of 160 mum over a six focal-zone region covering a 10 mm depth. Application of a triangular electrical apodization scheme across the elements resulted in a reduction in grating lobe amplitude below -26 dB. C1 Penn State Univ, NIH, Transducer Resource Ctr, University Pk, PA 16802 USA. RP Snook, KA (reprint author), Penn State Univ, NIH, Transducer Resource Ctr, University Pk, PA 16802 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-7177-1 J9 ULTRASON PY 2001 BP 1161 EP 1164 PG 4 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Acoustics; Engineering; Physics GA BU75C UT WOS:000176890800249 ER PT B AU Summers, RM Agcaoili, CML McAuliffe, MJ Dalal, SS Yim, PJ Choyke, PL Walther, MM Linehan, WM AF Summers, RM Agcaoili, CML McAuliffe, MJ Dalal, SS Yim, PJ Choyke, PL Walther, MM Linehan, WM GP IEEE IEEE TI Helical CT of von Hippel-Lindau: Semi-automated segmentation of renal lesions SO 2001 INTERNATIONAL CONFERENCE ON IMAGE PROCESSING, VOL II, PROCEEDINGS LA English DT Proceedings Paper CT International Conference on Image Processing (ICIP 2001) CY OCT 07-10, 2001 CL THESSALONIKI, GREECE SP IEEE Signal Processing Soc, IEEE AB In the setting of von Hippel-Lindau disease, accurate quantitation of kidney lesions is important for genetic research. Unfortunately, fully automated quantitation is difficult because the lesion boundaries are complex. Therefore, we developed a method to semi-automate the quantitation of these renal lesions. We studied helical CT scans of 10 kidneys from 8 patients with von Hippel-Lindau disease. The kidneys were segmented from surrounding structures using an interactive marker-controlled watershed algorithm. Renal lesions (cysts and solid tumors) were identified using thresholding and then characterized by size using mathematical morphology and granulometry. There were 50 cysts and 16 solid lesions. The mean (+/- s.d.) numbers of interior and exterior manually placed contours required to perform a complete watershed segmentation of the kidneys were 2.2 +/- 1.2 and 1.2 +/- 0.6, respectively. The mean difference between the watershed and manual methods of computing renal volume was 13 +/- 8 mL (5 +/- 2% of total renal volume) and is not clinically significant. There was no significant difference between volumes of renal lesions measured manually and using the semi-automated method (p > 0.3). C1 NCI, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. RP NCI, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. EM rms@nih.gov NR 6 TC 5 Z9 5 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-6725-1 PY 2001 BP 293 EP 296 PG 4 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BV16U UT WOS:000178044600075 ER PT B AU Summers, RM Mullick, R Finkelstein, SE Schrump, DS AF Summers, RM Mullick, R Finkelstein, SE Schrump, DS GP IEEE IEEE TI Confocal volume rendering of the thorax SO 2001 INTERNATIONAL CONFERENCE ON IMAGE PROCESSING, VOL II, PROCEEDINGS LA English DT Proceedings Paper CT International Conference on Image Processing (ICIP 2001) CY OCT 07-10, 2001 CL THESSALONIKI, GREECE SP IEEE Signal Processing Soc, IEEE AB Confocal volume rendering is a recently described technique to perform segmentation free rendering. It can be combined with other post-processing techniques to yield images with desirable features such as improved visualization of surface detail and reduced clipping of important anatomy. In this paper, we show the first application (to our knowledge) of confocal volume rendering to imaging of the thorax. We demonstrate how confocal volume rendering can be used to reveal intrathoracic airways and lung masses. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-6725-1 PY 2001 BP 297 EP 299 PG 3 WC Computer Science, Software Engineering; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BV16U UT WOS:000178044600076 ER PT J AU Lavigne, C Yelle, J Sauve, G Thierry, AR AF Lavigne, C Yelle, J Sauve, G Thierry, AR TI Lipid-based delivery of combinations of antisense oligodeoxynucleotides for the in vitro inhibition of HIV-1 replication SO AAPS PHARMSCI LA English DT Article DE antisense; oligonucleotides; HIV; drug delivery ID HUMAN-IMMUNODEFICIENCY-VIRUS; HTLV-III; TYPE-1 RNA; PHOSPHOROTHIOATE; OLIGONUCLEOTIDES; SEQUENCE; PHARMACOKINETICS; COMPLEMENTARY; EXPRESSION; AIDS AB We evaluated a new approach to AIDS therapy by using combinations of oligodeoxynucleotides (ODNs), delivered with a lipid-based carrier system, that target different HN viral genome sites. We identified some of the factors that seem to influence the effectiveness of a combination strategy in cell cultures including ODN concentrations, type of infection (acute vs chronic), backbone modification of the ODN, and the number of sequences. When delivered by the DLS carrier system, some advantages of using a combination of ODNs over treatment with only one ODN could be observed in acute infection assays but not in the chronic infection model. These results suggest that in the acute infection model, the 3 different antisense ODNs in the "cocktail" might block an early step of virus replication by combined inhibitory effects. Various combinations of phosphorothioate-modified (PS) and unmodified oligonucleotides delivered by the DLS system were compared for their antiviral activity in a long-term acute assay using HIV-T (IIIB strain)-infected MOLT-3 cells. The most effective combination had 3 phosphorothioate antisense ODNs: Srev, SDIS, and SPac (>99% inhibition at 100 pM). However, the additive effect determined when using: ODN combinations was rather low, revealing the high; level of nonsequence specificity in HIV-1 cell culture models. Data illustrated the high sequence nonspecific activity of ODNs, especially when comparing activity of antisense ODNs with activity of random control sequence ODNs. The latter exhibited an inhibitory effect similar to that of antisense ODNs under our e;experimental conditions. Nevertheless, we demonstrated that it is possible to achieve high anti-HIV activity by using, in combination picomolar range concentrations of antisense oligonucleotide complexed to a lipid-based carrier system such as the DLS system. without increasing cell toxicity. C1 Medincell Project, F-31240 Lunion, France. Univ Montreal, Fac Med, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. Univ Quebec, Inst Armand Frappier, Laval, PQ H7N 4Z3, Canada. NCI, Tumor Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lavigne, C (reprint author), Medincell Project, 6 Rue des Monts du Vivarais, F-31240 Lunion, France. RI thierry, alain/F-9492-2014 NR 32 TC 5 Z9 5 U1 0 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2001 VL 3 IS 1 AR 7 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 427CG UT WOS:000168386800008 ER PT J AU Makalowski, W AF Makalowski, W TI The human genome structure and organization SO ACTA BIOCHIMICA POLONICA LA English DT Article; Proceedings Paper CT 36th Meeting of the Polish-Biochemical-Society CY 2000 CL POZNAN, POLAND SP Polish Biochem Soc ID DNA-SEQUENCE; HUMAN GENES; CHROMOSOMES; EVOLUTION; NUMBER; JUNK AB Genetic information of human is encoded in two genomes: nuclear and mitochondrial. Both of them reflect molecular evolution of human starting from the beginning of life (about 4.5 billion years ago) until the origin of Homo sapiens species about 100 000 years ago. From this reason human genome contains some features that are common for different groups of organisms and some features that are unique for Homo sapiens. 3.2 X 10(9) base pairs of human nuclear genome are packed into 23 chromosomes of different size. The smallest chromosome - 21st contains 5 X 10(7) base pairs while the biggest one - 1(st) contains 2.63 X 10(8) base pairs. Despite the fact that the nucleotide sequence of all chromosomes is established, the organisation of nuclear genome put still questions: for example: the exact number of genes encoded by the human genome is still unknown giving estimations from 30 to 150 thousand genes. Coding sequences represent a few percent of human nuclear genome. The majority of the genome is represented by repetitive sequences (about 50%) and noncoding unique sequences. This part of the genome is frequently wrongly called "junk DNA". The distribution of genes on chromosomes is irregular, DNA fragments containing low percentage of GC pairs code lower number of genes than the fragments of high percentage of GC pairs. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Makalowski, W (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr,MSC 6510,Bldg 45,Room 6As-47A, Bethesda, MD 20892 USA. EM makalowski@ncbi.nlm.nih.gov RI Makalowski, Wojciech/I-2843-2016 NR 28 TC 23 Z9 25 U1 0 U2 13 PU ACTA BIOCHIMICA POLONICA PI WARSAW PA PASTEURA 3, 02-093 WARSAW, POLAND SN 0001-527X J9 ACTA BIOCHIM POL JI Acta Biochim. Pol. PY 2001 VL 48 IS 3 BP 587 EP 598 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 477PC UT WOS:000171292600001 PM 11833767 ER PT J AU Robles, AI Harris, CC AF Robles, AI Harris, CC TI p53-mediated apoptosis and genomic instability diseases SO ACTA ONCOLOGICA LA English DT Article; Proceedings Paper CT Nobel Conference 2000 CY AUG 19-22, 2000 CL KAROLINSKA INST, STOCKHOLM, SWEDEN HO KAROLINSKA INST ID NUCLEOTIDE EXCISION-REPAIR; CELL-CYCLE CHECKPOINT; LI-FRAUMENI-SYNDROME; WILD-TYPE P53; DNA-REPAIR; XERODERMA-PIGMENTOSUM; WERNER-SYNDROME; SV40-TRANSFORMED CELLS; P53-INDUCED APOPTOSIS; COCKAYNE-SYNDROME AB Mutations in several DExH-containing DNA helicases, including XPD, XPB, WRN, and BLM, are associated with rare familial cancer syndromes characterized by genomic instability and cancer susceptibility. Known cellular activities of these helicases include DNA replication, repair, recombination, and/or transcription. The p53 tumor suppressor is a regulator of cellular responses to stress, and is biochemically involved in the induction of cell-cycle arrest, apoptosis and DNA repair, all of which contribute to maintenance of genomic integrity. Physical and functional interactions of p53 with DExH-containing DNA helicases have been described, We propose that such interactions could be compromised in inherited disorders and contribute to their cancer susceptibility. In particular, the role of DNA helicases in p53-mediated apoptotic pathways is reviewed. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Rm 2C04, Bethesda, MD 20892 USA. NR 63 TC 41 Z9 41 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 2001 VL 40 IS 6 BP 696 EP 701 PG 6 WC Oncology SC Oncology GA 495GM UT WOS:000172331900005 PM 11765063 ER PT J AU Arai, YT Takahashi, H Kameoka, Y Shiino, T Wimalaratne, O Lodmell, DL AF Arai, YT Takahashi, H Kameoka, Y Shiino, T Wimalaratne, O Lodmell, DL TI Characterization of Sri Lanka rabies virus isolates using nucleotide sequence analysis of nucleoprotein gene SO ACTA VIROLOGICA LA English DT Article DE rabies virus; isolates; Sri Lanka; nucleoprotein gene; nucleotide sequence; phylogenetic analysis; RT-PCR ID MOLECULAR EPIDEMIOLOGY; ALIGNMENT; VARIANTS; ONTARIO; PCR AB Thirty-four suspected rabid brain samples from 2 humans, 24 dogs, 4 cats, 2 mongooses, 1 jackal and 1 water buffalo were collected in 1995-1996 in Sri Lanka. Total RNA,vas extracted directly from brain suspensions and examined using a one-step reverse transcription-polymerase chain reaction (RT-PCR) for the rabies virus nucleoprotein (N) gene, Twenty-eight samples were found positive for the virus N gene by RT-PCR and also for the virus antigens by fluorescent antibody (FA) test. Rabies virus isolates obtained from different animal species in different regions of Sri Lanka were genetically homogenous. Sequences of 203 nucleotides (nt)-long RT-PCR products obtained from 16 of 27 samples were found identical. Sequences of 1350 nt of N genes of 14 RT-PCR products were determined. The Sri Lanka isolates under study formed a specific cluster that included also an earlier isolate from India but did not include the known isolates from China, Thailand, Malaysia, Israel, Iran, Oman, Saudi Arabia, Russia, Nepal, Philippines, Japan and from several other countries. These results suggest that one type of rabies virus is circulating among human, dog, cat, mongoose, jackal and water buffalo living near Colombo City and in other five remote regions in Sri Lanka. C1 Natl Inst Infect Dis, Dept Virol 1, Shinjuku Ku, Tokyo 162, Japan. Natl Inst Radiol Sci, Ciba, Japan. Natl Inst Infect Dis, AIDS Res Ctr, Div Genet Resources, Tokyo, Japan. Natl Inst Infect Dis, AIDS Res Ctr, Lab Mol Virol & Epidemiol, Tokyo, Japan. Med Res Inst, Colombo, Sri Lanka. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Arai, YT (reprint author), Natl Inst Infect Dis, Dept Virol 1, Shinjuku Ku, Toyama 1-23-1, Tokyo 162, Japan. NR 26 TC 21 Z9 21 U1 1 U2 2 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57 NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0001-723X J9 ACTA VIROL JI Acta Virol. PY 2001 VL 45 IS 5-6 BP 327 EP 333 PG 7 WC Virology SC Virology GA 553VU UT WOS:000175697600009 PM 12083333 ER PT B AU Long, EO Burshtyn, DN Stebbins, CC Watzl, C AF Long, EO Burshtyn, DN Stebbins, CC Watzl, C BE Cooper, MD Takai, T Ravetch, JV TI How do killer cell Ig-like receptors inhibit natural killer cells? SO ACTIVATING AND INHIBITORY IMMUNOGLOBULIN-LIKE RECEPTORS LA English DT Proceedings Paper CT CREST International Symposium on Immunoglobulin-like Receptors CY SEP 18-19, 2000 CL SENDAI INT CTR, SENDAI, JAPAN SP CREST HO SENDAI INT CTR DE natural killer; inhibitory receptor; adhesion; tyrosine phosphorylation ID LINKED LYMPHOPROLIFERATIVE DISEASE; COMPLEX CLASS-I; CUTTING EDGE; NK CELLS; KINASE ACTIVATION; 2B4; SHP-1; SUBSTRATE AB Several receptors expressed on natural killer (NK) cells provide negative regulation of the NK cell's cytotoxic activity. These inhibitory receptors carry immunoreceptor tyrosine-based inhibition motifs (ITIM) in their cytoplasmic tail that are responsible for the negative signal. ITIM-mediated inhibition of cellular signals has become a common theme in many different cell types that express a receptor with one or more cytoplasmic ITIM. Despite much work on the MHC class I-specific inhibitory receptors expressed by NK cells, the mechanism by which activation signals are blocked is still not well understood. We have chosen to study the inhibition of NK cells by the killer cell Ig-like receptor (KIR) during contact with target cells that express a class I ligand for KIR. Engagement of KIR by HLA-C on the target cell resulted in complete inhibition of the tyrosine phosphorylation of the activation receptor 2B4. In addition, the formation of stable cell-cell conjugates between NK cells and target cells was aborted by KIR binding to HLA-C on the target cells. Therefore, KIR inhibits activation of NK cells at a step as proximal as the phosphorylation of an activation receptor and the adhesion to target cells. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Watzl, Carsten/B-4911-2013; Long, Eric/G-5475-2011 OI Watzl, Carsten/0000-0001-5195-0995; Long, Eric/0000-0002-7793-3728 NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-70297-0 PY 2001 BP 235 EP 241 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BS51Z UT WOS:000170202000029 ER PT J AU Mirsky, AF Duncan, CC AF Mirsky, AF Duncan, CC TI A nosology of disorders of attention SO ADULT ATTENTION DEFICIT DISORDER SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE attention; nosology; sleep; seizure disorders; cerebral structures; neuropsychological tests ID JUVENILE MYOCLONIC EPILEPSY; IDIOPATHIC GENERALIZED EPILEPSY; DEFICIT HYPERACTIVITY DISORDER; CHROMOSOME 6P; SCHIZOPHRENIA; ASSOCIATION; LOCUS; SUSCEPTIBILITY; NARCOLEPSY; CHILDREN AB The trailblazing research on sleep mechanisms and petit mal epilepsy, conducted during the period from 1940 through 1970, illuminated the brain substrate for normal consciousness and attention, as well as their disorders. This research helped inform and structure our neuropsychologically based model of the "elements" of attention. The model has been used to assess attention in the research laboratory and clinic, and has led to a "nosology of disorders of attention," which is presented here in preliminary form. The nosology reviews the possible causes of the symptom(s) of impaired attention, as well as suggesting a blueprint for future research in this area. C1 NIMH, Sect Clin & Expt Neuropsychol, LBC, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Clin Psychophysiol & Psychopharmacol Lab, Dept Psychiat, Bethesda, MD 20814 USA. RP Mirsky, AF (reprint author), NIMH, Sect Clin & Expt Neuropsychol, LBC, NIH, MSC 2615,5415 W Cedar, Bethesda, MD 20892 USA. NR 85 TC 36 Z9 40 U1 2 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 931 BP 17 EP 32 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT11H UT WOS:000172009700002 PM 11462740 ER PT J AU Giedd, JN Blumenthal, J Molloy, E Castellanos, FX AF Giedd, JN Blumenthal, J Molloy, E Castellanos, FX TI Brain imaging of attention deficit/hyperactivity disorder SO ADULT ATTENTION DEFICIT DISORDER SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article DE ADHD; magnetic resonance imaging; child; adolescent; development ID DEFICIT-HYPERACTIVITY DISORDER; CEREBRAL GLUCOSE-METABOLISM; CORPUS-CALLOSUM MORPHOLOGY; BASAL GANGLIA VOLUMES; STIMULANT DRUG-ACTION; AGE-RELATED-CHANGES; MAGNETIC-RESONANCE; QUANTITATIVE MORPHOLOGY; MORPHOMETRIC ANALYSIS; TOURETTES-SYNDROME AB Advances in imaging technology allow unprecedented access to the anatomy and physiology of the living, growing human brain. Anatomical imaging studies of individuals with attention deficit/hyperactivity disorder (ADHD) consistently point to involvement of the frontal lobes, basal ganglia, corpus callosum, and cerebellum. Imaging studies of brain physiology also support involvement of right frontal-basal ganglia circuitry with a powerful modulatory influence from the cerebellum. Although not currently of diagnostic utility, further extension and refinement of these findings may offer hope for greater understanding of the core nature of ADHD and possible subtyping to inform treatment interventions. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 78 TC 201 Z9 203 U1 3 U2 16 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 931 BP 33 EP 49 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT11H UT WOS:000172009700003 PM 11462751 ER PT J AU Moch, H Kononen, J Kallioniemi, OP Sauter, G AF Moch, H Kononen, J Kallioniemi, OP Sauter, G TI Tissue microarrays: What will they bring to molecular and anatomic pathology? SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Article DE tissue chips; tissue microarray; quality control; high throughput analysis; immunohistochemistry; molecular biology ID GENE-EXPRESSION PATTERNS; COMPLEMENTARY-DNA; PROSTATE-CANCER; CDNA MICROARRAY AB The analysis of a large number of tumor tissues with conventional techniques of molecular pathology is tedious and slow. The authors recently developed the tissue microarray technology that makes it possible to sample up to 1000 tumors on one grass slide, which then can be analyzed by fluorescence in situ hybridization, RNA in situ hybridization, or immunohistochemistry. The tissue microarray technology has the potential to significantly accelerate molecular studies that seek associations between molecular changes and clinicopathologic features of the cancer. Examples of potential applications for tissue microarrays include testing and optimization of probes and antibodies, the organization of large tissue repositories, and the facilitation of multicenter studies. Further, tissue microarrays can be used for educational purposes as well as to improve quality control and standardization of staining methods and interpretation. Tissue microarrays have become one of the most promising tools for the molecular and anatomic pathologist and will have many applications in cancer research, as well as in other fields of pathology. This review article gives an overview of current applications of tissue microarrays as well as possible future development of the technology. C1 Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Moch, H (reprint author), Univ Basel, Inst Pathol, Schonbeinstr 40, CH-4003 Basel, Switzerland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 13 TC 106 Z9 143 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD JAN PY 2001 VL 8 IS 1 BP 14 EP 20 DI 10.1097/00125480-200101000-00002 PG 7 WC Pathology SC Pathology GA 387PN UT WOS:000166131100002 PM 11152090 ER PT J AU Pourquier, P Pommier, Y AF Pourquier, P Pommier, Y TI Topoisomerase I-mediated DNA damage SO ADVANCES IN CANCER RESEARCH, VOL 80 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID LARGE T-ANTIGEN; DOUBLE-STRAND BREAKS; PROTEIN-KINASE-C; NUCLEIC-ACID BASES; RNA POLYMERASE-II; EUKARYOTIC TOPOISOMERASE; IONIZING-RADIATION; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; POLY(ADP-RIBOSE) POLYMERASE C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pourquier, P (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 145 TC 160 Z9 162 U1 1 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 2001 VL 80 BP 189 EP 216 DI 10.1016/S0065-230X(01)80016-6 PG 28 WC Oncology SC Oncology GA BQ99C UT WOS:000165289800007 PM 11034544 ER PT J AU Piek, E Roberts, AB AF Piek, E Roberts, AB TI Suppressor and oncogenic roles of transforming growth factor-beta and its signaling pathways in tumorigenesis SO ADVANCES IN CANCER RESEARCH, VOL 83 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID PLASMINOGEN-ACTIVATOR INHIBITOR; HORMONE-RELATED PROTEIN; BREAST-CANCER CELLS; II RECEPTOR GENE; SMAD TRANSCRIPTIONAL COREPRESSOR; MOUSE EPIDERMAL-KERATINOCYTES; INTESTINAL EPITHELIAL-CELLS; VASCULAR ENDOTHELIAL-CELLS; HUMAN COLORECTAL-CANCER; COLON-CARCINOMA CELLS C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Piek, E (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NR 350 TC 78 Z9 83 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 2001 VL 83 BP 1 EP 54 DI 10.1016/S0065-230X(01)83001-3 PG 62 WC Oncology SC Oncology GA BT13D UT WOS:000172043600001 PM 11665716 ER PT S AU Pozsgay, V AF Pozsgay, V BE Horton, D TI Oligosaccharide-protein conjugates as vaccine candidates against bacteria SO ADVANCES IN CARBOHYDRATE CHEMISTRY AND BIOCHEMISTRY, VOL 56 SE Advances in Carbohydrate Chemistry and Biochemistry LA English DT Review ID INFLUENZAE TYPE-B; SHIGELLA-DYSENTERIAE TYPE-1; O-SPECIFIC POLYSACCHARIDE; ARTIFICIAL SALMONELLA VACCINES; CELL-WALL POLYSACCHARIDE; STREPTOCOCCUS GROUP-A; NUCLEAR-MAGNETIC-RESONANCE; SOLID-PHASE SYNTHESIS; BOVINE SERUM-ALBUMIN; INNER-CORE REGION C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, NIH, 6 Ctr Dr,MSC 2720, Bethesda, MD 20892 USA. NR 181 TC 22 Z9 23 U1 2 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2318 BN 0-12-007256-4 J9 ADV CARBOHYD CHEM BI JI Adv. Carbohydr .Chem. Biochem. PY 2001 VL 56 BP 153 EP 199 PG 47 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA BR12E UT WOS:000165696100004 ER PT J AU Gold, B AF Gold, B TI DNA genotyping SO ADVANCES IN CLINICAL CHEMISTRY, VOL 36 SE ADVANCES IN CLINICAL CHEMISTRY LA English DT Review ID TAY-SACHS-DISEASE; GRADIENT GEL-ELECTROPHORESIS; MOLECULAR BEACONS; MULTIPLEX DETECTION; PATIENT SAMPLES; GENOMIC DNA; NEW-ENGLAND; MUTATIONS; GENE; HYBRIDIZATION C1 NCI, Human Genet Sect, Lab genom Divers, Frederick, MD 21702 USA. RP Gold, B (reprint author), NCI, Human Genet Sect, Lab genom Divers, Frederick, MD 21702 USA. NR 86 TC 4 Z9 4 U1 2 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2423 J9 ADV CLIN CHEM PY 2001 VL 36 BP 171 EP 234 DI 10.1016/S0065-2423(01)36028-6 PG 64 WC Medical Laboratory Technology SC Medical Laboratory Technology GA BT07E UT WOS:000171868000005 PM 11605258 ER PT J AU Vihinen, M Arredondo-Vega, FX Casanova, JL Etzioni, A Giliani, S Hammarstrom, L Hershfield, MS Heyworth, PG Hsu, AP Lahdesmaki, A Lappalainen, I Notarangelo, LD Puck, JM Reith, W Roos, D Schumacher, RF Schwarz, K Vezzoni, P Villa, A Valiaho, J Smith, CIE AF Vihinen, M Arredondo-Vega, FX Casanova, JL Etzioni, A Giliani, S Hammarstrom, L Hershfield, MS Heyworth, PG Hsu, AP Lahdesmaki, A Lappalainen, I Notarangelo, LD Puck, JM Reith, W Roos, D Schumacher, RF Schwarz, K Vezzoni, P Villa, A Valiaho, J Smith, CIE TI Primary immunodeficiency mutation databases SO ADVANCES IN GENETICS, VOL 43 SE ADVANCES IN GENETICS INCORPORATING MOLECULAR GENETIC MEDICINE LA English DT Review ID MHC CLASS-II; WISKOTT-ALDRICH-SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; X-LINKED AGAMMAGLOBULINEMIA; INTERFERON-GAMMA-RECEPTOR; HYPER-IGM SYNDROME; ADENOSINE-DEAMINASE DEFICIENCY; LEUKOCYTE ADHESION DEFICIENCY; BARE LYMPHOCYTE SYNDROME; BRUTONS TYROSINE KINASE C1 Tampere Univ, Inst Med Technol, FIN-33014 Tampere, Finland. Tampere Univ Hosp, FIN-33520 Tampere, Finland. Duke Univ, Med Ctr, Dept Med, Div Rheumatol Allergy & Immunol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Hop Necker Enfants Malad, Unite Clin Immunol & Hematol Pediat, F-75015 Paris, France. Hop Necker Enfants Malad, Lab INSERM, U429, F-75015 Paris, France. Rambam Med Ctr, B Rappaport Sch Med, Dept Pediat, IL-31096 Haifa, Israel. Univ Brescia, Dept Pediat, Ist Med Mol Angelo Nocivelli, I-25123 Brescia, Italy. Huddinge Univ Hosp, Karolinska Inst, Div Clin Immunol, S-14186 Huddinge, Sweden. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Dept Biosci, Div Biochem, Helsinki, Finland. Univ Geneva, Sch Med, Dept Genet & Microbiol, CH-1211 Geneva 4, Switzerland. Netherlands Blood Transfus Serv, Cent Lab, Dept Expt Immunohematol, NL-1066 CX Amsterdam, Netherlands. Univ Ulm, Dept Transfus Med, D-7900 Ulm, Germany. CNR, Dept Human Genome & Multifactoral Dis, I-20090 Segrate, Milan, Italy. Huddinge Univ Hosp, Karolinska Inst, Clin Res Ctr, S-14186 Huddinge, Sweden. RP Smith, CIE (reprint author), Tampere Univ, Inst Med Technol, FIN-33014 Tampere, Finland. EM edvard.smith@cbt.ki.se RI Vihinen, Mauno/A-8452-2012; Notarangelo, Luigi/F-9718-2016 OI Vihinen, Mauno/0000-0002-9614-7976; Notarangelo, Luigi/0000-0002-8335-0262 FU NCI NIH HHS [N01-CP-61038]; NIDDK NIH HHS [DK20902]; Telethon [E.0917, E.0668] NR 258 TC 65 Z9 68 U1 0 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 J9 ADV GENET PY 2001 VL 43 BP 103 EP 188 DI 10.1016/S0065-2660(01)43005-7 PG 86 WC Genetics & Heredity SC Genetics & Heredity GA BX61N UT WOS:000185887600004 PM 11037300 ER PT J AU Dougherty, ER Chen, YD AF Dougherty, ER Chen, YD TI Optimal and adaptive design of logical granulometric filters SO ADVANCES IN IMAGING AND ELECTRON PHYSICS, VOL 117 SE ADVANCES IN IMAGING AND ELECTRON PHYSICS LA English DT Review C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. NR 41 TC 4 Z9 4 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1076-5670 J9 ADV IMAG ELECT PHYS PY 2001 VL 117 BP 1 EP 71 DI 10.1016/S1076-5670(01)80111-7 PG 71 WC Physics, Applied SC Physics GA BS64A UT WOS:000170685300001 ER PT J AU Grammer, AC Lipsky, PE AF Grammer, AC Lipsky, PE TI CD40-mediated regulation of immune responses by TRAF-dependent and TRAF-independent signaling mechanisms SO ADVANCES IN IMMUNOLOGY, VOL. 76 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID NF-KAPPA-B; NECROSIS-FACTOR-RECEPTOR; ACTIVATED PROTEIN-KINASE; EPSTEIN-BARR-VIRUS; HYPER-IGM SYNDROME; CD40 LIGAND EXPRESSION; CHRONIC LYMPHOCYTIC-LEUKEMIA; GERMINAL CENTER KINASE; BRUTONS TYROSINE KINASE; HUMAN DENDRITIC CELLS C1 NIAMSD, Intramural Res Program, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Grammer, AC (reprint author), NIAMSD, Intramural Res Program, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NR 567 TC 14 Z9 15 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2001 VL 76 BP 61 EP 178 DI 10.1016/S0065-2776(01)76019-1 PG 118 WC Immunology SC Immunology GA BR16B UT WOS:000165768400002 ER PT J AU Morley, SCP Bierer, BE AF Morley, SCP Bierer, BE TI The actin cytoskeleton, membrane lipid microdomains, and T cell signal transduction SO ADVANCES IN IMMUNOLOGY, VOL 77 SE ADVANCES IN IMMUNOLOGY LA English DT Review ID ALDRICH-SYNDROME PROTEIN; SEVERE COMBINED IMMUNODEFICIENCY; PHOSPHOTYROSINE-BINDING DOMAIN; TRANSMEMBRANE ADAPTER PROTEINS; RECEPTOR ZETA-CHAIN; ANTIGEN-RECEPTOR; TYROSINE KINASES; CYTOCHALASIN-D; F-ACTIN; INTERLEUKIN-2 PRODUCTION C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Div Med Sci, Comm Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Morley, SCP (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 164 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 J9 ADV IMMUNOL JI Adv.Immunol. PY 2001 VL 77 BP 1 EP 43 DI 10.1016/S0065-2776(01)77013-7 PG 43 WC Immunology SC Immunology GA BS01V UT WOS:000168328600001 PM 11293114 ER PT J AU Priola, SA AF Priola, SA TI Prion protein diversity and disease in the transmissible spongiform encephalopathies SO ADVANCES IN PROTEIN CHEMISTRY, VOL 57 SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID SCRAPIE-ASSOCIATED FIBRILS; CREUTZFELDT-JAKOB-DISEASE; PRP KNOCKOUT MICE; ASPARAGINE-LINKED GLYCOSYLATION; GERSTMANN-STRAUSSLER SYNDROME; MOUSE NEUROBLASTOMA-CELLS; TRANSGENIC MICE; CULTURED-CELLS; MINK ENCEPHALOPATHY; SYNTHETIC PEPTIDES C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 165 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2001 VL 57 BP 1 EP 27 PG 27 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BS65Y UT WOS:000170766600001 PM 11447687 ER PT J AU Caughey, B Raymond, GJ Callahan, MA Wong, C Baron, GS Xiong, LW AF Caughey, B Raymond, GJ Callahan, MA Wong, C Baron, GS Xiong, LW TI Interactions and conversions of prion protein isoforms SO ADVANCES IN PROTEIN CHEMISTRY, VOL 57 SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID SCRAPIE-ASSOCIATED FIBRILS; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; MOUSE NEUROBLASTOMA-CELLS; CHRONIC WASTING DISEASE; STRAUSSLER-SCHEINKER DISEASE; CREUTZFELDT-JAKOB DISEASE; IN-VITRO CONVERSION; CONGO-RED; TRANSGENIC MICE; CULTURED-CELLS C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 147 TC 52 Z9 53 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2001 VL 57 BP 139 EP 169 PG 31 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BS65Y UT WOS:000170766600006 PM 11447689 ER PT J AU Wickner, RB Taylor, KL Edskes, HK Maddelein, ML Moriyama, H Roberts, BT AF Wickner, RB Taylor, KL Edskes, HK Maddelein, ML Moriyama, H Roberts, BT TI Yeast prions act as genes composed of self-propagating protein amyloids SO ADVANCES IN PROTEIN CHEMISTRY, VOL 57 SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID FUNGUS PODOSPORA-ANSERINA; SACCHAROMYCES-CEREVISIAE; IN-VITRO; VEGETATIVE INCOMPATIBILITY; SUP35 PROTEIN; SCRAPIE; URE2P; PSI; DETERMINANT; RESISTANT C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RI MADDELEIN, Marie-Lise/G-5395-2010; MORIYAMA, Hiromitsu/F-9256-2013 NR 71 TC 21 Z9 21 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2001 VL 57 BP 313 EP + PG 23 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BS65Y UT WOS:000170766600011 PM 11447695 ER PT J AU Portis, JL AF Portis, JL TI Genetic determinants of neurovirulence of murine oncornaviruses SO ADVANCES IN VIRUS RESEARCH, VOL 56 SE ADVANCES IN VIRUS RESEARCH LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; CELL-SURFACE RECEPTOR; LEUKEMIA-VIRUS-TB; DEHYDROGENASE-ELEVATING VIRUS; INDUCED SPONGIFORM NEURODEGENERATION; ENVELOPE PROTEIN GP120; AMINO-ACID TRANSPORTER; LONG TERMINAL REPEAT; MOTOR NEURON DISEASE; ADULT-MOUSE BRAIN C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Portis, JL (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 157 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2001 VL 56 BP 3 EP 38 DI 10.1016/S0065-3527(01)56003-0 PG 36 WC Virology SC Virology GA BS51U UT WOS:000170186900001 PM 11450304 ER PT S AU Caughey, B Chesebro, B AF Caughey, B Chesebro, B BE Buchmeier, MJ Campball, IL TI Transmissible spongiform encephalopathies and prion protein interconversions SO ADVANCES IN VIRUS RESEARCH, VOL 56: NEUROVIROLOGY: VIRUSES AND THE BRAIN SE Advances in Virus Research LA English DT Review ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE INCUBATION PERIOD; STRAUSSLER-SCHEINKER DISEASE; MICE EXPRESSING HUMAN; CELL-FREE CONVERSION; IN-VITRO CONVERSION; PRP KNOCKOUT MICE; C-TERMINAL DOMAIN; TRANSGENIC MICE; CULTURED-CELLS C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 168 TC 37 Z9 38 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 0-12-039856-7 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2001 VL 56 BP 277 EP 311 DI 10.1016/S0065-3527(01)56031-5 PG 43 WC Virology SC Virology GA BS51U UT WOS:000170186900009 PM 11450303 ER PT J AU Soldan, SS Jacobson, S AF Soldan, SS Jacobson, S TI Role of viruses in etiology and pathogenesis of multiple sclerosis SO ADVANCES IN VIRUS RESEARCH, VOL 56 SE ADVANCES IN VIRUS RESEARCH LA English DT Review ID MYELIN BASIC-PROTEIN; HUMAN HERPESVIRUS-6 INFECTION; CENTRAL-NERVOUS-SYSTEM; T-LYMPHOTROPIC VIRUS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; THEILERS MURINE ENCEPHALOMYELITIS; I-ASSOCIATED MYELOPATHY; TROPICAL SPASTIC PARAPARESIS; POLYMERASE CHAIN-REACTION C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Dept Genet, Washington, DC 20052 USA. RP Soldan, SS (reprint author), NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. NR 211 TC 22 Z9 22 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2001 VL 56 BP 517 EP 555 DI 10.1016/S0065-3527(01)56037-6 PG 39 WC Virology SC Virology GA BS51U UT WOS:000170186900015 PM 11450311 ER PT J AU Guillot, PV Kittles, RA Long, JC Bergen, AW Virkkunen, M Naukarinnen, H Linnoila, M Goldman, D AF Guillot, PV Kittles, RA Long, JC Bergen, AW Virkkunen, M Naukarinnen, H Linnoila, M Goldman, D TI Genetic determinism of aggressive behavior SO AGGRESSIVE BEHAVIOR LA English DT Meeting Abstract C1 NIAAA, Clin Studies Lab, NIH, Rockville, MD 20852 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0096-140X J9 AGGRESSIVE BEHAV JI Aggressive Behav. PY 2001 VL 27 IS 3 BP 175 EP 175 PG 1 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA 428VN UT WOS:000168482500035 ER PT J AU Troisi, A Carosi, M AF Troisi, A Carosi, M TI Effects of aggressive harassment on male copulatory behavior in Japanese macaques SO AGGRESSIVE BEHAVIOR LA English DT Meeting Abstract C1 Univ Roma Tor Vergata, Dept Psychiat, Rome, Italy. NICHHD, Comparat Ethol Lab, Anim Ctr, Poolesville, MD USA. RI Carosi, Monica/C-9683-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0096-140X J9 AGGRESSIVE BEHAV JI Aggressive Behav. PY 2001 VL 27 IS 3 BP 182 EP 182 PG 1 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA 428VN UT WOS:000168482500046 ER PT J AU Knutson, JK Sternberg, K AF Knutson, JK Sternberg, K TI A computer-based data log for describing samples of maltreated children SO AGGRESSIVE BEHAVIOR LA English DT Meeting Abstract C1 Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0096-140X J9 AGGRESSIVE BEHAV JI Aggressive Behav. PY 2001 VL 27 IS 3 BP 194 EP 194 PG 1 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA 428VN UT WOS:000168482500064 ER PT J AU Allende, MC Lane, HC AF Allende, MC Lane, HC TI Cytokine-based therapies for HIV infection SO AIDS LA English DT Article DE HIV; immune-based therapies; cytokines; interleukin-2; vaccines ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; COLONY-STIMULATING FACTOR; BLOOD MONONUCLEAR-CELLS; RANDOMIZED CONTROLLED TRIAL; PHASE-II TRIAL; SUBCUTANEOUS INTERLEUKIN-2; VIRAL LOAD; T-CELLS; INTRAVENOUS INTERLEUKIN-2 C1 NIAID, Clin & Mol Retrovirol Sect, NIH, Bethesda, MD 20892 USA. RP Lane, HC (reprint author), NIAID, Clin & Mol Retrovirol Sect, NIH, Bethesda, MD 20892 USA. NR 61 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 2001 VL 15 SU 5 BP S183 EP S191 DI 10.1097/00002030-200100005-00022 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 504AL UT WOS:000172834100022 PM 11816167 ER PT J AU Schultz, AM Bradac, JA AF Schultz, AM Bradac, JA TI The HIV vaccine pipeline, from preclinical to phase III SO AIDS LA English DT Article DE AIDS vaccine; HIV; vaccine vectors; nucleic acid immunization; HIV protein immunogens ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODY-RESPONSE; IMMUNE-RESPONSES; RHESUS-MONKEYS; ENVELOPE GLYCOPROTEIN; PATHOGENIC SIV; DNA VACCINES; RECOMBINANT; MACAQUES; PROTECTION C1 Int AIDS Vaccine Initiat, New York, NY USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Schultz, AM (reprint author), 1600 E Gude Dr, Rockville, MD 20850 USA. NR 86 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PY 2001 VL 15 SU 5 BP S147 EP S158 DI 10.1097/00002030-200100005-00018 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 504AL UT WOS:000172834100018 PM 11816163 ER PT J AU Saif, MW Greenberg, B AF Saif, MW Greenberg, B TI HIV and thrombosis: A review SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTITHROMBIN-III DEFICIENCY; PROTEIN-S DEFICIENCY; CYTOMEGALO-VIRUS; INFECTION; THROMBOEMBOLISM; PATIENT; DISEASE; AIDS; ABNORMALITIES AB The array of clinicopathologic factors associated with acquired immune deficiency syndrome (AIDS) patients continues to increase and surprise many physicians. The recent literature contains reports of thrombotic episodes occurring in patients with human immunodeficiency virus (HIV) infection. Various abnormalities predisposing to a hypercoagulable state have also been reported in AIDS patients including the presence of antiphospholipid antibodies and the lupus anticoagulant; deficiencies of protein C, protein S, heparin cofactor II, and antithrombin and increased levels of von Willebrand factor, and d-dimers. These abnormalities correlate with the severity of HIV-associated immunosuppression as measured by the CD4 cell counts and with the presence of concurrent infectious or neoplastic diseases. The authors reviewed the medical literature and describe various abnormalities predisposing to a hypercoagulable state in AIDS patients along with the management of such complications. This issue is important because deep venous thrombosis (DVT), pulmonary embolus (PE), or thrombosis at other sites can develop in patients with AIDS who are ambulatory and have no known risk factors for pathologic thrombus formation, providing another challenge in an already difficult clinical situation. This also provides a strong rationale for careful prospective studies focusing on the prevalence and risk factors involved in the development of thromboembolic complications in patients with AIDS. C1 NCI, Med Branch, Natl Naval Med Ctr, NIH, Bethesda, MD 20889 USA. Univ Connecticut, Ctr Hlth, Dept Med, Div Hematol Oncol, Farmington, CT USA. RP Saif, MW (reprint author), NCI, Med Branch, Natl Naval Med Ctr, NIH, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 39 TC 70 Z9 72 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 2001 VL 15 IS 1 BP 15 EP 24 DI 10.1089/108729101460065 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 399EX UT WOS:000166799600003 PM 11177584 ER PT J AU Arnulf, B Villemain, A Nicot, C Charneau, P Kersuall, J Zermati, Y Derkinderen, M Bex, F Bazarbachi, A Hermine, O AF Arnulf, B Villemain, A Nicot, C Charneau, P Kersuall, J Zermati, Y Derkinderen, M Bex, F Bazarbachi, A Hermine, O TI Human T-cell lymphotropic virus oncoprotein Tax represses TGF-b1 signaling in human T-cells via c-jun activation: A potential mechanism of HTLV-1 leukemogenesis. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Hop Necker Enfants Malad, UMR 860, F-75015 Paris, France. NCI, Div Basic Sci, Basic Res Lab, Bethesda, MD 20814 USA. Inst Pasteur, Dept Retrovirus, Paris, France. Free Univ Brussels, Brussels, Belgium. Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S24 EP S24 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300078 ER PT J AU Azimi, N Mariner, J Jacobson, S Waldmann, TA AF Azimi, N Mariner, J Jacobson, S Waldmann, TA TI IL-15 plays an important role in the pathogenesis of HAM/TSP through activation of the T cells and persistence of antigen specific CD8 cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S27 EP S27 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300088 ER PT J AU Bangham, CRM AF Bangham, CRM TI DNA microarray and immunogenetic analysis of HTLV-I infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 St Marys Hosp, ICSM, Wright Fleming Inst, Dept Immunol, London W2 1PG, England. St Marys Hosp, ICSM, Wright Fleming Inst, Dept GU Med & Communicable Dis, London W2 1PG, England. NCI, SAIC Frederick, Ft Detrick, MD 21702 USA. Inst Adv Study, Princeton, NJ 08540 USA. Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England. Kagoshima Univ, Fac Med, Dept Internal Med 3, Kagoshima 8908520, Japan. Kagoshima Univ, Fac Med, Dept Med Informat, Kagoshima 8908520, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S25 EP S25 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300082 ER PT J AU Bihani, T Gravelyn, CS Yannie, PJ Green, JE McDonagh, KT Gitlin, SD AF Bihani, T Gravelyn, CS Yannie, PJ Green, JE McDonagh, KT Gitlin, SD TI Inhibition of HTLV-I-associated disease by a trans-dominant inhibitory Tax(1) mutant SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S29 EP S29 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300098 ER PT J AU Carvalho, EM Porto, AF Bacelar, O Dutra, WO Carvalho, LP Neva, F Gollob, KJ AF Carvalho, EM Porto, AF Bacelar, O Dutra, WO Carvalho, LP Neva, F Gollob, KJ TI Citokine profile and immunomodulation in asymptomatic HTLV-1 infected blood donors SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 UFBA, Hosp Univ Prof Edgard Santos, Serv Imunol, SSA, Salvador, BA, Brazil. UFMG, ICB, Dept Morfol, Belo Horizonte, MG, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S27 EP S27 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300090 ER PT J AU Franchini, G AF Franchini, G TI HTLV and immortalization/transformation: Current concepts and clinical relevance SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract ID VIRUS TYPE-1; INFECTION; STRONGYLOIDIASIS; CARRIERS; CELLS C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S5 EP S5 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300001 ER PT J AU Hague, BF Zhao, TM Liang, W Kindt, TJ AF Hague, BF Zhao, TM Liang, W Kindt, TJ TI Use of envelope mutants to probe the cellular receptor for HTLV-1. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S22 EP S22 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300071 ER PT J AU Haller, K Wu, YL Derow, E Schmitt, I Jeang, KT Grassmann, R AF Haller, K Wu, YL Derow, E Schmitt, I Jeang, KT Grassmann, R TI Physical interaction of HTLV-I tax with cyclin dependent kinase 4 stimulates the phosphorylation of Rb protein SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. Univ Erlangen Nurnberg, Inst Virol, D-8520 Erlangen, Germany. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S6 EP S6 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300005 ER PT J AU Harrod, R Johnson, JM Nacsa, J Fullen, J Hansen, J Karpova, T McNally, J Franchini, G AF Harrod, R Johnson, JM Nacsa, J Fullen, J Hansen, J Karpova, T McNally, J Franchini, G TI Targeted inhibition of p53K320-acetylation and P/CAF HAT functions by HTLV-1 p30(II) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S7 EP S7 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300009 ER PT J AU Heidecker, G Hill, S Lloyd, PA Derse, D AF Heidecker, G Hill, S Lloyd, PA Derse, D TI A novel protein derived from the Pr76gag-pro precursor is necessary for HTLV-I replication. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S57 EP S57 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300202 ER PT J AU Hisada, M Masciotra, V Lal, R Rudolph, D Martin, M Carrington, M Wilks, R Manns, A AF Hisada, M Masciotra, V Lal, R Rudolph, D Martin, M Carrington, M Wilks, R Manns, A TI Chemokine receptor gene polymorphisms and risk of human T-lymphotropic virus type I infection in Jamaica. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Ctr Dis Control & Prevent, HIV Immunol & Diagnost Branch, DASTLR, NCID, Atlanta, GA USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Univ W Indies, Res Inst Trop Med, Epidemiol Res Unit, Kingston 7, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S37 EP S37 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300123 ER PT J AU Hisada, M Maloney, EM Sawada, T Miley, WJ Palmer, P Hanchard, B Biggar, RJ Goedert, JJ Manns, A AF Hisada, M Maloney, EM Sawada, T Miley, WJ Palmer, P Hanchard, B Biggar, RJ Goedert, JJ Manns, A TI Viral markers associated with vertical transmission of human T-Lymphotropic virus type I in Jamaica. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Tsukuba Eisai Res Labs, Tsukuba, Ibaraki, Japan. Sci Applicat Int Corp, HIV Vaccine Program, Frederick, MD USA. Univ W Indies, Kingston 7, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S10 EP S10 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300020 ER PT J AU Iwanaga, Y Jeang, KT AF Iwanaga, Y Jeang, KT TI Increased prevalence in cancer cells of an R to H change in the coding sequence of HTLV-1 Tax binding protein, MAD1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S49 EP S49 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300171 ER PT J AU Jacobson, S AF Jacobson, S TI Immunopathogenesis of HTLV-I associated neurological disease. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S25 EP S25 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300080 ER PT J AU Johnson, JM Nicot, C Fullen, J Ciminale, V Casareto, L Mulloy, JC Jacobson, S Franchini, G AF Johnson, JM Nicot, C Fullen, J Ciminale, V Casareto, L Mulloy, JC Jacobson, S Franchini, G TI A novel mechanism for targeting the MHC-I heavy chain for degradation by the human T-cell leukemia virus-type 1 (HTLV-1) p12(I) protein SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, New York, NY 10021 USA. NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S21 EP S21 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300066 ER PT J AU Jones, KS Ruscetti, FW Sadowski, C Nath, M AF Jones, KS Ruscetti, FW Sadowski, C Nath, M TI Phorbol esters down modulate expression of cell surface protein(s) critical for direct binding of an HTLV-1 SU fusion protein SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Frederick, MD 21701 USA. NCI, IRSP, SAIC Frederick, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S22 EP S22 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300070 ER PT J AU Kasai, T Iha, H Iwanaga, Y Jeang, KT AF Kasai, T Iha, H Iwanaga, Y Jeang, KT TI Prevalent loss of mitotic checkpoint function in HTLV-1 transformed cell lines holds implications for use of vinca alkaloids in treatment of ATLs. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S6 EP S6 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300004 ER PT J AU Kubota, R Furukawa, Y Izumo, S Usuku, K Jacobson, S Osame, M AF Kubota, R Furukawa, Y Izumo, S Usuku, K Jacobson, S Osame, M TI Diversity of HTLV-I-specific CTL and proviral load in patients with HAM SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Kagoshima Univ, Fac Med, Dept Internal Med 3, Kagoshima 890, Japan. Kagoshima Univ, Fac Med, Ctr Chron Viral Dis, Kagoshima 890, Japan. NINDS, NIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S61 EP S61 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300220 ER PT J AU Liang, W Hague, BF Mahana, W Zhao, TM Kindt, TJ AF Liang, W Hague, BF Mahana, W Zhao, TM Kindt, TJ TI HTLV-I cell lines have differences in constitutively activated signaling pathways that can be altered by cytokine exposure SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. LUMAQ IUT GEnie Biol, F-29334 Quimper, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S27 EP S27 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300091 ER PT J AU Mahieux, R Pise-Masison, C Gessain, A Brady, JN Olivier, R Misteli, T Nicot, C AF Mahieux, R Pise-Masison, C Gessain, A Brady, JN Olivier, R Misteli, T Nicot, C TI Arsenic trioxide promotes apoptosis in HTLV-1 and HTLV-2 infected cells by a caspase-3 dependent mechanism SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, F-75724 Paris 15, France. NCI, Basic Res Lab, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Unite Oncol Virale, F-75724 Paris 15, France. NCI, Lab Receptor Biol & Gene Express, Cell Biol & Gene Express Grp, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S24 EP S24 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300079 ER PT J AU Maloney, EM Wilks, R Hisada, M Hanchard, B Cranston, B Jack, N Edwards, J Bartholomew, C Morgan, O Biggar, R Manns, A AF Maloney, EM Wilks, R Hisada, M Hanchard, B Cranston, B Jack, N Edwards, J Bartholomew, C Morgan, O Biggar, R Manns, A TI HTLV-I infection in family members of patients with ATL, TSP and ID: Results from the Jamaica and Trinidad family studies. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ W Indies, Kingston 7, Jamaica. Med Res Fdn Trinidad & Tobago, Port Of Spain, Trinid & Tobago. NR 0 TC 1 Z9 1 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. PY 2001 VL 17 SU 1 BP S38 EP S38 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300127 ER PT J AU Mariner, JM Lantz, V Waldmann, TA Azimi, N AF Mariner, JM Lantz, V Waldmann, TA Azimi, N TI Human T-Cell Lymphotropic Virus Type I (HTLV-I) Tax protein activates IL-15R alpha expression. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Grad Program Genet, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S71 EP S71 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300260 ER PT J AU Miley, WJ Lifson, J Biggar, RJ Jacobson, S Goedert, JJ Whitby, D Hisada, M AF Miley, WJ Lifson, J Biggar, RJ Jacobson, S Goedert, JJ Whitby, D Hisada, M TI HTLV provirus load in HTLV/HIV coinfected subjects is not significantly higher than in HTLV singly infected subjects SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, AIDS Vaccine Program, SAIC, Frederick, MD 21701 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S39 EP S39 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300131 ER PT J AU Morris, JC Janik, JE Turner, M Lee, C Top, L Jaffe, ES Stetler-Stevenson, M Bleesing, JJ Fleisher, T Waldmann, TA AF Morris, JC Janik, JE Turner, M Lee, C Top, L Jaffe, ES Stetler-Stevenson, M Bleesing, JJ Fleisher, T Waldmann, TA TI A phase I/II study of the efficacy and toxicity of humanized anti-tac (HAT, Zenapax (R)) for the treatment of tac-expressing human lymphotropic virus type-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL): Interim results. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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. PY 2001 VL 17 SU 1 BP S29 EP S29 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300097 ER PT J AU Mueller, NE Okayama, A Stuver, SO Hisada, M AF Mueller, NE Okayama, A Stuver, SO Hisada, M TI The blind epidemiologists and the elephant: The natural history of HTLV-1 infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Miyazaki Med Coll, Miyazaki 88916, Japan. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S8 EP S8 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300014 ER PT J AU Nath, M Ruscetti, F Finch, L Sadowski, C Jones, K AF Nath, M Ruscetti, F Finch, L Sadowski, C Jones, K TI Expression of cell surface molecule(s) on cord and adult blood responsible for binding to HTLV-1 envelope SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Basic Res Lab, FCRDC, Frederick, MD USA. SAIC, CSP, Frederick, MD USA. SAIC, IRSP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S56 EP S56 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300201 ER PT J AU Nicot, C Mulloy, JC Ferrari, MG Johnson, JM Fu, K Trovato, R Fullen, J Fukumoto, R Leonard, WJ Franchini, G AF Nicot, C Mulloy, JC Ferrari, MG Johnson, JM Fu, K Trovato, R Fullen, J Fukumoto, R Leonard, WJ Franchini, G TI The increased STAT5 activation induced by the HTLV-1 p12(I) lowers the IL-2 requirement for proliferation of human primary PBMCs SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immuno, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S21 EP S21 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300067 ER PT J AU Pise-Masison, CA Mahieux, R Radonovich, M Guillerm, C Brady, JN AF Pise-Masison, CA Mahieux, R Radonovich, M Guillerm, C Brady, JN TI Pathways leading to tax-mediated p53 inhibition SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, F-75724 Paris 15, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S7 EP S7 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300008 ER PT J AU Porto, AF Braga, S Dutra, WO Gollob, KJ Neva, F Carvalho, EM AF Porto, AF Braga, S Dutra, WO Gollob, KJ Neva, F Carvalho, EM TI Immunological consequences of the co-infection with HTLV-1 and S-stercoralis SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S63 EP S63 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300228 ER PT J AU Puccioni-Sohler, M Chimelli, L Maraon, M Rios, M Bianco, C Goncalves, RR Pimenta, G Jacobson, S AF Puccioni-Sohler, M Chimelli, L Maraon, M Rios, M Bianco, C Goncalves, RR Pimenta, G Jacobson, S TI HTLV-1 infection with acute encephalomyeloradicultis and systemic inflammation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, BR-21941 Rio De Janeiro, Brazil. CSF Lab Rio de Janeiro, Neurolife, Rio De Janeiro, Brazil. New York Blood Ctr, New York, NY 10021 USA. NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S66 EP S66 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300239 ER PT J AU Simpson, RM Zhao, TM Bryant, MA Kindt, TJ AF Simpson, RM Zhao, TM Bryant, MA Kindt, TJ TI Accumulating evidence for epithelial cell infection by HTLV-1 and a possible role in carcinogenesis. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NIAID, Bethesda, MD 20892 USA. NIH, Diagnost Res Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S14 EP S14 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300037 ER PT J AU Waldmann, T Jacobson, S Azimi, N AF Waldmann, T Jacobson, S Azimi, N TI IL-2 and IL-15 play roles in the pathogenesis and persistence of HTLV-1 associated ATL and TSP/HAM: implications for therapy. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S26 EP S26 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300087 ER PT J AU Wilks, R Braham, J LaGrenade, L Hanchard, B Morgan, OSC Miley, WJ Goebel, PB Cranston, B Manns, A AF Wilks, R Braham, J LaGrenade, L Hanchard, B Morgan, OSC Miley, WJ Goebel, PB Cranston, B Manns, A TI HTLV-I associated diseases in three generations of a Jamaican family SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Univ W Indies, Kingston 7, Jamaica. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Sci Applicat Int Corp, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S45 EP S45 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300155 ER PT J AU Yamano, Y Nagai, M Brennan, MG Mora, CA Soldan, SS Tomaru, U Osame, M Jacobson, S AF Yamano, Y Nagai, M Brennan, MG Mora, CA Soldan, SS Tomaru, U Osame, M Jacobson, S TI Real-time quantitative RT-PCR analysis of human T-cell lymphotropic virus type-1 (HTLV-I) tax mRNA: Correlation with HTLV-I proviral DNA load, Tax protein expression, Tax specific CD8+T-cell frequency and disease severity in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD USA. Kagoshima Univ, Fac Med, Dept Internal Med 3, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S25 EP S25 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300081 ER PT J AU Higley, JD AF Higley, JD TI Individual differences in alcohol-induced aggression - A nonhuman-primate model SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE AOD (alcohol or other drug) dependence; Cloninger's typology; aggressive behavior; AODR (AOD related) violence; impulsive behavior; animal model; serotonin; brain function; cerebrospinal fluid; hydroxyindoleacetic acid; child rearing; predictive factor ID CEREBROSPINAL-FLUID MONOAMINE; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; DIMINISHED SOCIAL COMPETENCE; MONKEYS MACACA-MULATTA; LOW CSF 5-HIAA; RHESUS-MONKEYS; INTERINDIVIDUAL DIFFERENCES; ANTISOCIAL PERSONALITY; SEROTONERGIC FUNCTION; GLUCOSE-METABOLISM AB Some people are more likely than others to become aggressive after consuming alcohol. Researchers studying alcohol use and aggression hope to identify individual differences in behavior and biochemistry that exist among subjects who become aggressive following alcohol consumption. Research with nonhuman primates has shown that individual differences in brain chemistry predict impulsivity, aggression, and alcohol-induced aggression. These differences appear to be associated with early rearing experiences and remain stable throughout the individual's life. C1 NIAAA, Bethesda, MD USA. RP Higley, JD (reprint author), NIAAA, Bethesda, MD USA. NR 82 TC 13 Z9 14 U1 2 U2 6 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2001 VL 25 IS 1 BP 12 EP 19 PG 8 WC Substance Abuse SC Substance Abuse GA 456EE UT WOS:000170069500002 PM 11496962 ER PT J AU Martin, SE Bryant, K Fitzgerald, N AF Martin, SE Bryant, K Fitzgerald, N TI Self-reported alcohol use and abuse by arrestees in the 1998 Arrestee Drug Abuse Monitoring program SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE AODR (alcohol or other drug [AOD] related); crime; arrest; offender; AODR violence; self-report; AOD abuse; demographic characteristics; gender differences; ethnic differences; age differences ID VIOLENCE AB Data collected in the Arrestee Drug Abuse Monitoring (ADAM) program on alcohol and other drug use among arrestees provide a valuable opportunity to examine the relationship between alcohol use and violence. The data are used to explore the combined use of alcohol and other drugs among offenders and the relationships between substance use and the offenders' demographic characteristics and offenses. These findings are used to identify changes in the offenders' alcohol and other drug use over time. C1 NIAAA, Bethesda, MD USA. Natl Inst Justice, Washington, DC USA. RP Martin, SE (reprint author), NIAAA, Bethesda, MD USA. NR 15 TC 8 Z9 8 U1 0 U2 1 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2001 VL 25 IS 1 BP 72 EP 79 PG 8 WC Substance Abuse SC Substance Abuse GA 456EE UT WOS:000170069500010 PM 11496970 ER PT J AU Warren, KR Foudin, LL AF Warren, KR Foudin, LL TI Alcohol-related birth defects - The past, present, and future SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE fetal alcohol effects; fetal alcohol syndrome; birth defects; alcohol-related neurodevelopmental disorder; diagnostic criteria; risk factors; AODR (alcohol- or other drug-related) biological markers; targeted prevention; warning label ID PRENATAL ALCOHOL; SCREENING TOOL; UNITED-STATES; WARNING LABEL; CELL-DEATH; FETAL; EXPOSURE; SUSCEPTIBILITY; PHENOTYPE; DIAGNOSIS AB In 1994 Alcohol Health & Research World (now titled Alcohol Research & Health), last devoted a full issue to the topic of fetal alcohol syndrome (FAS) and other alcohol-related birth defects (ARBD). This introductory article provides readers with information on how the field has advanced since then. In addition to tracing the development of the terminology used in the field, it describes the difficulties involved in determining the true prevalence of FAS and ARBD; the mechanisms that may play a role in alcohol-derived fetal injuries; approaches to preventing drinking during pregnancy; and strategies for assisting people who have been born with FAS and ARBD. C1 NIAAA, Off Sci Affairs, Bethesda, MD USA. NIAAA, Div Basic Res, Bethesda, MD USA. RP Warren, KR (reprint author), NIAAA, Off Sci Affairs, Bethesda, MD USA. NR 38 TC 59 Z9 60 U1 1 U2 5 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2001 VL 25 IS 3 BP 153 EP 158 PG 6 WC Substance Abuse SC Substance Abuse GA 516NN UT WOS:000173559500001 PM 11810952 ER PT J AU Handmaker, NS Wilbourne, P AF Handmaker, NS Wilbourne, P TI Motivational interventions in prenatal clinics SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE motivational interviewing; brief intervention; prevention; prenatal care; pregnancy; prenatal alcohol exposure; fetal alcohol syndrome; treatment outcome; health care delivery ID PREGNANT PROBLEM DRINKERS; ALCOHOL-CONSUMPTION; PROGRAM; WOMEN; PREVENTION; DRINKING; ABUSE; TRIAL AB Although the risks associated with pregnancy are well-documented, prevention efforts, for the most part, have not reached women who drink at levels that present the greatest risk. Recent clinical studies and demonstration projects show that interventions by obstetric caregivers can help reduce drinking even among women who consume alcohol at the heaviest levels. Brief interventions and motivational interviewing are two approaches that can be adapted for busy medical offices to provide interventions before, during, and after pregnancies. By combining these interventions with a stepped-care approach, practitioners will be able to intervene to prevent drinking during pregnancy while minimizing costs to the patient and demands for limited clinic resources. C1 NIAAA, Funded Project Motivating Pregnant Drinkers, Rockville, MD 20852 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. RP Handmaker, NS (reprint author), NIAAA, Funded Project Motivating Pregnant Drinkers, Rockville, MD 20852 USA. NR 44 TC 14 Z9 16 U1 1 U2 3 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2001 VL 25 IS 3 BP 219 EP 229 PG 11 WC Substance Abuse SC Substance Abuse GA 516NN UT WOS:000173559500010 PM 11810961 ER PT J AU Sillanaukee, P Strid, N Allen, JP Litten, RZ AF Sillanaukee, P Strid, N Allen, JP Litten, RZ TI Possible reasons why heavy drinking increases carbohydrate-deficient transferrin SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol abuse; CDT; enzymes; mechanisms ID GAMMA-GLUTAMYL-TRANSFERASE; HIGH ALCOHOL-CONSUMPTION; SERUM TRANSFERRIN; GLYCOPROTEIN SYNDROME; DIFFERENTIAL-DIAGNOSIS; LASER DENSITOMETRY; IRON-ABSORPTION; LIVER-DISEASES; SIALIC-ACID; MARKER AB Background: Transferrin is a globular protein synthesized in the liver that is responsible for iron transport in plasma. The structure of the molecule consists of two carbohydrate residues to which six sialic acid moieties can be attached. After periods of chronic, heavy alcohol consumption, carbohydrate-deficient transferrin (CDT) isoforms often increase, which makes CDT a useful marker in screening for alcohol abuse and monitoring progress of alcoholics in treatment. However, the precise mechanism behind CDT increase remains unknown. Methods: A review of the most relevant literature on CDT was conducted with a computer-assisted literature search. Results: During the past several years, a number of studies have explored possible mechanisms that may account for the alcohol-induced increase of CDT. An inhibition of protein synthesis and a general effect of alcohol on protein glycosylation have been reported. Although the exact mechanisms that underlie production of CDT are not yet fully understood, possible bases for the phenomenon are presented in this article. Conclusions: Experimental findings indicate that the ethanol-induced effect on glycoprotein metabolism is a multistep process in which protein transport and changes of enzyme activity may play an important role. C1 Pharmacia & Upjohn Diagnost AB, Alcohol Related Dis, Uppsala, Sweden. Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. NIAAA, Rockville, MD 20852 USA. RP Sillanaukee, P (reprint author), Oy Finnish Immunotechnol Ltd, Lenkkeilijankatu 8, Tampere 33520, Finland. EM Pekka.Sillanaukee@finnish-immunotech.com NR 74 TC 37 Z9 37 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2001 VL 25 IS 1 BP 34 EP 40 PG 7 WC Substance Abuse SC Substance Abuse GA 392WJ UT WOS:000166435300005 PM 11198712 ER PT J AU Hilton, ME Maisto, SA Conigliaro, J McNiel, M Kraemer, K Kelley, ME Conigliaro, R Samet, JH Larson, MJ Savetsky, J Winter, M Sullivan, LM Saitz, R Weisner, C Mertens, J Parthasarathy, S Moore, C Hunkeler, E Hu, TW Selby, J Stout, RL Zywiak, W Rubin, A Zwick, W Shepard, D AF Hilton, ME Maisto, SA Conigliaro, J McNiel, M Kraemer, K Kelley, ME Conigliaro, R Samet, JH Larson, MJ Savetsky, J Winter, M Sullivan, LM Saitz, R Weisner, C Mertens, J Parthasarathy, S Moore, C Hunkeler, E Hu, TW Selby, J Stout, RL Zywiak, W Rubin, A Zwick, W Shepard, D TI Improving alcoholism treatment across the spectrum of services SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE motivational enhancement; detoxification unit; alcohol and drug treatment; case monitoring; health services research ID DRINKERS; ABUSE; INTERVENTIONS; DESIGN AB This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The chair was Michael E. Hilton. The presentations were (1) The effects of brief advice and motivational enhancement on alcohol use and related variables in primary care, by Stephen A. Maisto, Joseph Conigliaro, Melissa McNiel, Kevin Kraemer, Mary E. Kelley, and Rosemarie Conigliaro; (2) Enhanced linkage of alcohol dependent persons to primary medical care: A randomized controlled trial of a multidisciplinary health evaluation in a detoxification unit, by Jeffrey H. Samet, Mary Jo Larson, Jacqueline Savetsky, Michael Winter, Lisa M. Sullivan, and Richard Saitz; (3) Cost-effectiveness of day hospital versus traditional alcohol and drug outpatient treatment in a health maintenance organization: Randomized and self-selected samples, by Constance Weisner, Jennifer Mertens, Sujaya Parthasarathy, Charles Moore, Enid Hunkeler, Teh-Wei Hu, and Joe Selby; and (4) Case monitoring for alcoholics: One year clinical and health cost effects, by Robert L. Stout, William Zywiak, Amy Rubin, William Zwick, Mary Jo Larson, and Don Shepard. C1 Syracuse Univ, Syracuse, NY USA. NIAAA, MEH, Rockville, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. No Calif Kaiser Fdn, Res Inst, Oakland, CA USA. Kaiser Permanente Med Care Program, Sacramento, CA USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Decis Sci Inst, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. Harvard Vangard Hlth Associates, Boston, MA USA. Brandeis Univ, Waltham, MA 02254 USA. RP Hilton, ME (reprint author), NIAAA, Div Clin Prevent Res, 6000 Execut Blvd,Suite 505,MSC 7003, Bethesda, MD 20892 USA. FU NIAAA NIH HHS [R01 AA009907] NR 16 TC 22 Z9 22 U1 3 U2 9 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 JAN PY 2001 VL 25 IS 1 BP 128 EP 135 DI 10.1111/j.1530-0277.2001.tb02137.x PG 8 WC Substance Abuse SC Substance Abuse GA 392WJ UT WOS:000166435300018 PM 11198708 ER PT J AU Cohen, SG Rizzo, PL AF Cohen, SG Rizzo, PL TI Asthma among the famous - A continuing series SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JAN-FEB PY 2001 VL 22 IS 1 BP 49 EP 59 DI 10.2500/108854101778249285 PG 11 WC Allergy SC Allergy GA 405JR UT WOS:000167156700011 PM 11227918 ER PT J AU Exner, DV Sheldon, RS Pinski, SL Kron, J Hallstrom, A AF Exner, DV Sheldon, RS Pinski, SL Kron, J Hallstrom, A CA AVID Investigators TI Do baseline characteristics accurately discriminate between patients likely versus unlikely to benefit from implantable defibrillator therapy? Evaluation of the Canadian Implantable Defibrillator Study implantable cardioverter defibrillatory efficacy score in the Antiarrhythmics Versus Implantable Defibrillators Trial SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; EJECTION FRACTION; HEART-FAILURE; RISK AB Objective Our purpose was to evaluate whether baseline characteristics predictive of implantable cardioverter defibrillator ([CD) efficacy in the Canadian Implantable Defibrillator Study (CIDS) are predictive in the Antiarrhythmics Versus Implantable Defibrillators [AVID) Trial. Background ICD therapy is superior to antiarrhythmic drug use in patients with life-threatening arrhythmias. However, identification of subgroups most likely to benefit from ICD therapy may be useful. Data from CIDS suggest that 3 characteristics (age greater than or equal to 70 years, ejection Fraction [EF] less than or equal to0.35, and New York Heart Association class >II) can be combined to reliably categorize patients as likely (22 characteristics) versus unlikely to benefit (<2 characteristics) from ICD therapy. Methods The utility of the CIDS categorization of ICD efficacy was assessed by Kaplan-Meier analysis and Cox hazards modeling. The accuracy of the CIDS score was formally tested by evaluating for interaction between categorization of benefit and treatment in a Cox model. Results ICD therapy was associated with a significantly lower risk of death in the 320 patients categorized as likely to benefit (relative risk [RR] 0.57, 95% confidence interval [CI] 0.37-0.88, P = .01) and a trend toward a lower risk of death in the 689 patients categorized as unlikely to benefit (RR 0.70, 95% CI 0.48-1.03, P = .07). Categorization of benefit was imperfect, as evidenced by a lack of statistical interaction (P = .5). Although 32 of the 42 deaths prevented by ICD therapy in AVID were in patients categorized as likely to benefit, all 42 of these patients had EF values 0.35. Neither advanced age nor poorer functional class predicted ICD efficacy in AVID. Conclusion of the 3 characteristics identified to predict ICD efficacy in CIDS, only depressed EF predicted ICD efficacy in AVID. Thus physicians faced with limited resources might elect to consider ICD therapy over antiarrhythmic drug use in patients with severely depressed EF values. C1 Univ Calgary, Calgary, AB, Canada. NHLBI, Bethesda, MD 20892 USA. Rush Med Coll, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Washington, Seattle, WA 98195 USA. RP Exner, DV (reprint author), AVID CTC, 1107 NE 45th St,Suite 505, Seattle, WA 98105 USA. RI Sheldon, Robert/N-9939-2015 FU NHLBI NIH HHS [N01 HC-25117] NR 22 TC 22 Z9 23 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2001 VL 141 IS 1 BP 99 EP 104 DI 10.1067/mhj.2001.111768 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 389WR UT WOS:000166262100016 PM 11136493 ER PT J AU White, CW Campeau, L Canner, P Domanski, M Forrester, JS Gobel, FL Herd, JA Hoogwerf, BJ Hunninghake, DB Knatterud, GL LoPresti, F AF White, CW Campeau, L Canner, P Domanski, M Forrester, JS Gobel, FL Herd, JA Hoogwerf, BJ Hunninghake, DB Knatterud, GL LoPresti, F CA Post CABG Investigators TI Lessons from the Post Coronary Artery Bypass Graft study in evaluating and controlling technical variability in angiographic trials SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OFF-LINE; CINEANGIOGRAMS; QUANTITATION; VALIDATION; DIMENSIONS; SYSTEM; ONLINE AB Although many investigators have evaluated the technical variability of quantitative angiographic techniques used to study atherosclerosis regression in native coronary arteries, few have studied the variability inherent in repeated studies of atherosclerotic saphenous vein grafts. This study describes 2 studies performed during the course of the Post Coronary Artery Bypass Graft (CABG) Clinical Trial that were designed to assess the reproducibility of: (1) repeated angiographic views within a short time period; and (2) reproducibility of the total process of quantitative analysis of saphenous vein graft angiograms. Statistical methods are described that provide a more meaningful assessment of the impact of measurement variability in the analytic process versus the variability related to changes induced by pharmacologic interventions. One such method, the increase in standard deviation (SD) among patients (ISDP), showed that repeated angiographic views increased the variability of calculation of lesion minimal diameter by 1.5%, whereas the ISDP for repetition of the entire process of quantitative angiographic readings increased variability 6.4%. These data from the post CABG trial reveal that technical variability is small and has negligible impact on the conclusions of the study. (C) 2001 by Excerpta Medica, Inc. C1 Univ Minnesota, Div Cardiovasc, Minneapolis, MN 55455 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. Univ Montreal, Montreal, PQ, Canada. Maryland Med Res Inst, Baltimore, MD USA. NHLBI, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Minneapolis Heart Inst, Minneapolis, MN USA. Baylor Coll Med, Houston, TX 77030 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP White, CW (reprint author), Univ Minnesota, Div Cardiovasc, Box 508,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2001 VL 87 IS 1 BP 40 EP 43 DI 10.1016/S0002-9149(00)01269-8 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 388EE UT WOS:000166163800008 PM 11137831 ER PT J AU Havlik, RJ Brock, D Lohman, K Haskell, W Snell, P O'Toole, M Ribisl, P Vaitkevicius, P Spurgeon, HA Lakatta, EG Pullen, P AF Havlik, RJ Brock, D Lohman, K Haskell, W Snell, P O'Toole, M Ribisl, P Vaitkevicius, P Spurgeon, HA Lakatta, EG Pullen, P TI High-density lipoprotein cholesterol and vascular stiffness at baseline in the activity counseling trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR RISK; ARTERIAL STIFFNESS; ADULTS AB In a middle-aged patient population, age was associated with stiffer vessels and high-density lipoprotein cholesterol with more elastic vessels. High-density lipoprotein cholesterol may be an indirect indicator of aerobic capacity or of less atherosclerosis, suggesting mechanisms for preserving vascular integrity. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, ACT Coordinating Ctr, Winston Salem, NC USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Texas, SW Med Ctr, Cooper Inst Aerob Res, Dallas, TX USA. St Louis Univ, Sch Med, St Louis, MO USA. Johns Hopkins Univ, Sch Med, Dept Geriatr, Baltimore, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Havlik, RJ (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-45137, N01-HC-45136, N01-HC-45135] NR 9 TC 12 Z9 12 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2001 VL 87 IS 1 BP 104 EP + DI 10.1016/S0002-9149(00)01282-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 388EE UT WOS:000166163800021 PM 11137844 ER PT J AU Zhang, YQ Felson, DT Ellison, RC Kreger, BE Schatzkin, A Dorgan, JF Cupples, LA Levy, D Kiel, DP AF Zhang, YQ Felson, DT Ellison, RC Kreger, BE Schatzkin, A Dorgan, JF Cupples, LA Levy, D Kiel, DP TI Bone mass and the risk of colon cancer among postmenopausal women - The Framingham Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bone density; cohort studies; colorectal neoplasms; estrogens ID HORMONE REPLACEMENT THERAPY; EXOGENOUS FEMALE HORMONES; LARGE-BOWEL-CANCER; COLORECTAL-CANCER; UNITED-STATES; MINERAL DENSITY; REPRODUCTIVE HISTORY; ENDOGENOUS ESTROGEN; ADENOMATOUS POLYPS; PROSPECTIVE COHORT AB Although postmenopausal estrogen use has been associated with a lower risk of colon cancer in women, some studies do not confirm such findings. No known study has examined the effect of cumulative estrogen exposure on colon cancer risk. Bone mass has been proposed as a marker of cumulative exposure to endogenous and exogenous estrogens. By using data on 1,394 Massachusetts women in the Framingham Study who underwent hand radiography in 1967-1970, the authors examined the association between bone mass (from relative areas of the second metacarpal) and colon cancer incidence. Over 27 years of follow-up, 44 incident colon cancer cases occurred. Colon cancer incidence decreased from 2.19 per 1,000 person-years among the women in the lowest age-specific tertile of bone mass to 1.59 and 1.08 among women in the middle and the highest tertiles, respectively. After adjustment for age and other potential confounding factors, the rate ratios of colon cancer were 1.0, 0.7 (95% confidence interval: 0.3, 1.3), and 0.4 (95% confidence interval: 0.2, 0.9) from the lowest to the highest tertile (p for trend = 0.033). No association was found between bone mass and rectal cancer. The findings suggest that women with higher bone mass, perhaps reflecting greater cumulative estrogen exposure, have a decreased risk of colon cancer. C1 Boston Univ, Sch Med, Arthrit Ctr, Boston, MA 02115 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. RP Zhang, YQ (reprint author), Boston Univ, Med Ctr, Room A-203,80 E Concord St, Boston, MA 02115 USA. OI Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38-38]; NIAMS NIH HHS [AR41398, AR 20613] NR 52 TC 22 Z9 24 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 JAN 1 PY 2001 VL 153 IS 1 BP 31 EP 37 DI 10.1093/aje/153.1.31 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 388MX UT WOS:000166185800006 PM 11159144 ER PT J AU Poiesz, BJ Papsidero, LD Ehrlich, G Sherman, M Dube, S Poiesz, M Dillon, K Ruscetti, FW Slamon, D Fang, C Williams, A Duggan, D Glaser, J Gottlieb, A Goldberg, J Ratner, L Phillips, P Han, T Friedman-Kien, A Siegal, F Rai, K Sawitsky, A Sheremata, LWA Dosik, H Cunningham, C Montagna, R AF Poiesz, BJ Papsidero, LD Ehrlich, G Sherman, M Dube, S Poiesz, M Dillon, K Ruscetti, FW Slamon, D Fang, C Williams, A Duggan, D Glaser, J Gottlieb, A Goldberg, J Ratner, L Phillips, P Han, T Friedman-Kien, A Siegal, F Rai, K Sawitsky, A Sheremata, LWA Dosik, H Cunningham, C Montagna, R TI Prevalence of HTLV-I-associated T-cell lymphoma SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE human T-cell leukemia lymphoma; virus types I and II; non-Hodgkin's lymphoma; blood donors; needle stick victims; recipients of blood products ID VIRUS TYPE-I; LEUKEMIA; BLOOD; INFECTION; PATIENT; TAX; LYMPHOCYTOSIS; DISEASE; FLORIDA; PROTEIN AB In order to assess the prevalence rate of HTLV-l-associated T-cell lymphomas and human retrovirus infection in general, approximately 21,000 individuals representing various patient populations, retroviral risk groups, and blood donors were examined for HTLV-I, HTLV-II, HIV-1, or HIV-2 infection using serologic and PCR assays. The prevalence rates among volunteer blood donors were 0.02% and 0% for HTLV and HIV, respectively. Significantly increased HTLV prevalence rates were observed among paid blood donors, African American health care clinic patients, Amerindians, recipients of HTLV-positive cellular blood products, intravenous drug users, sexual contacts and family members of HTLV-positive people, end patients with primary thrombocytosis and other-than-low-grade non-Hodgkin's lymphoma (NHL). Among some of these groups there were significant differences in the prevalence of HTLV-I versus HTLV-II. The eight HTLV-positive NHL patients all had mature, high-grade, CD4(+) T-cell lymphomas with clonally integrated HTLV-I, for a prevalence of 4% among other-than-low-grade NHL patients. Seven of the eight died from their disease within 2 years despite treatment. Interestingly, two groups at risk for HTLV infection, namely needle stick victims and recipients of HTLV-infected and/or pooled plasma products, showed no evidence for infection. Significantly increased HIV-1 prevalence was observed among paid blood donors, African Americans, homosexuals, female prostitutes, hemophiliacs, and other-than-low-grade NHL patients. Only one patient was infected with HIV-2. Of the nine HIV-positive, other-than-low-grade NHL patients, seven HIV-I positives had B-cell lymphomas, one HIV-1 positive had an HTLV-l-positive CD4(+) T-cell lymphoma, and one infected with HIV-2 had a CD4(+) T-cell lymphoma that was HTLV negative. The data indicate that HTLV-I lymphoma, while uncommon, is not necessarily rare among other-than-low-grade NHL cases in the United States and, given its poor prognosis, should probably be studied separately in clinical trials. (C) 2001 Wiley-Liss, Inc. C1 SUNY Hlth Sci Ctr, Dept Med, Syracuse, NY 13210 USA. Cellular Prod Inc, Buffalo, NY USA. Travenol Labs, Hyland Therapeut Div, Duarte, CA USA. NCI, Frederick Canc Res Facil, Lab Biol Response Modifiers, Frederick, MD USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. Richmond Mem Hosp, Staten Isl, NY USA. Washington Univ, Div Hematol & Oncol, St Louis, MO USA. New York State Dept Hlth, Roswell Pk Mem Inst, Buffalo, NY 14263 USA. NYU, Med Ctr, Dept Dermatol, New York, NY 10016 USA. NYU, Med Ctr, Dept Microbiol, New York, NY 10016 USA. Long Isl Jewish Med Ctr, Dept Med, New Hyde Park, NY 11042 USA. SUNY Hlth Sci Ctr, Dept Pediat, Syracuse, NY 13210 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. Interfaith Med Ctr, Dept Med, Brooklyn, NY USA. Innovat Biotechnol Inc, Niagara Falls, NY USA. RP Poiesz, BJ (reprint author), SUNY Hlth Sci Ctr, Dept Med, 750 E Adams St, Syracuse, NY 13210 USA. FU NCI NIH HHS [CA 11028, CA 03927]; NHLBI NIH HHS [NHLBI-67021] NR 32 TC 22 Z9 24 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2001 VL 66 IS 1 BP 32 EP 38 DI 10.1002/1096-8652(200101)66:1<32::AID-AJH1004>3.0.CO;2-3 PG 7 WC Hematology SC Hematology GA 384EK UT WOS:000165929300005 PM 11426489 ER PT J AU Bork, JM Peters, LM Riazuddin, S Bernstein, SL Ahmed, ZM Ness, SL Polomeno, R Ramesh, A Schloss, M Srisailpathy, CRS Wayne, S Bellman, S Desmukh, D Ahmed, Z Khan, SN Kaloustian, VMD Li, XC Lalwani, A Riazuddin, S Bitner-Glindzicz, M Nance, WE Liu, XZ Wistow, G Smith, RJH Griffith, AJ Wilcox, ER Friedman, TB Morell, RJ AF Bork, JM Peters, LM Riazuddin, S Bernstein, SL Ahmed, ZM Ness, SL Polomeno, R Ramesh, A Schloss, M Srisailpathy, CRS Wayne, S Bellman, S Desmukh, D Ahmed, Z Khan, SN Kaloustian, VMD Li, XC Lalwani, A Riazuddin, S Bitner-Glindzicz, M Nance, WE Liu, XZ Wistow, G Smith, RJH Griffith, AJ Wilcox, ER Friedman, TB Morell, RJ TI Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SYNDROME TYPE-I; MYOSIN-VIIA GENE; HEARING IMPAIRMENT; LINKAGE ANALYSIS; MAPS; CHROMOSOME-10; LOCALIZATION; ENCODES; LOCUS; FAT AB Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22. Seven highly consanguineous families segregating nonsyndromic autosomal recessive dearness were analyzed to refine the DFNB12 locus. In a single family, a critical region was defined between D10S1694 and D1OS173 7, similar to0.55 cM apart. Eighteen candidate genes in the region were sequenced. Mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in families with USH1D. Six missense mutations were found in five families with DFNB12, and two nonsense and two frameshift mutations were found in four families with USH1D. A northern blot analysis of CDH23 showed a 9.5-kb transcript expressed primarily in the retina. CDH23 is also expressed in the cochlea, as is demonstrated by polymerase chain reaction amplification from cochlear cDNA. C1 Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Neurootol Branch, NIH, Rockville, MD 20850 USA. Punjab Univ, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. Mt Sinai Med Ctr, Dept Human Genet, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Pediat, New York, NY 10029 USA. McGill Univ, Dept Ophthalmol, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Otolaryngol, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Pediat & Human Genet, Montreal, PQ H3A 2T5, Canada. Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. Univ Madras, Dept Genet, Madras, Tamil Nadu, India. Great Ormond St Hosp Children NHS Trust, Dept Audiol Med, London WC1N 3JH, England. Inst Child Hlth, Unit Clin & Mol Genet, London, England. Rotary Deaf Sch, Ichalkaranji Tilawani, Maharashtra, India. Epstein Labs, Lab Mol Otol, San Francisco, CA USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Morell, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. RI Bitner-Glindzicz, Maria/A-4231-2009; Nasim Khan, Shaheen/F-2135-2015; OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [T32 DC000035, R01 DC002842, R01-DC02530, R01-DC02842, R03 DC004530, R03 DC04530, Z01 DC000039] NR 37 TC 296 Z9 311 U1 1 U2 14 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2001 VL 68 IS 1 BP 26 EP 37 DI 10.1086/316954 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 392FG UT WOS:000166399900003 PM 11090341 ER PT J AU Lichter-Konecki, U Broman, KW Blau, EB Konecki, DS AF Lichter-Konecki, U Broman, KW Blau, EB Konecki, DS TI Genetic and physical mapping of the locus for autosomal dominant renal Fanconi syndrome, on chromosome 15q15.3 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GIRDLE MUSCULAR-DYSTROPHY; FAMILY AB Autosomal dominant renal Fanconi syndrome is a genetic model for the study of proximal renal tubular transport pathology. We were able to map the locus for this disease to human chromosome 15q15.3 by genotyping a central Wisconsin pedigree with 10 affected individuals. After a whole-genome scan with highly polymorphic simple sequence repeat markers, a maximum LOD score of 3.01 was calculated for marker D15SG53 on chromosome 15q15.3. Linkage and haplotype analysis for an additional 24 markers flanking D15SG53 narrowed the interval to similar to3 cM, with the two highest single-point LOD scores observed being 4.44 and 4.68 (for D15S182 and D15S537, respectively). Subsequently, a complete bacterial artificial chromosome contig was constructed, from the High Throughput Genomic Sequence Database, for the region bounded by D15S182 and D15S143. The identification of the gene and gene product altered in autosomal dominant renal Fanconi syndrome will allow the study of the physiology of proximal renaI tubular transport. C1 Marshfield Med Res Fdn, Ctr Med Genet, Marshfield, WI 54449 USA. Marshfield Clin, Div Pediat Nephrol, Marshfield, WI USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. RP Lichter-Konecki, U (reprint author), NHGRI, Med Genet Branch, Bldg 10,Room 3D-55,10 Ctr Dr,MSC 1852, Bethesda, MD 20892 USA. NR 12 TC 14 Z9 14 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2001 VL 68 IS 1 BP 264 EP 268 DI 10.1086/316923 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 392FG UT WOS:000166399900029 PM 11090339 ER PT J AU Crabtree, JS Scacheri, PC Ward, JM Garrett-Beal, L Emmert-Buck, MR Edgemon, KA Chandrasekharappa, SC Marx, SJ Spiegel, AM Collins, FS AF Crabtree, JS Scacheri, PC Ward, JM Garrett-Beal, L Emmert-Buck, MR Edgemon, KA Chandrasekharappa, SC Marx, SJ Spiegel, AM Collins, FS TI A mouse model of MEN1 develops multiple endocrine tumors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2001 VL 68 IS 1 BP 292 EP 293 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 392FG UT WOS:000166399900037 ER PT J AU Ji, BT Silverman, DT Stewart, PA Blair, A Swanson, GM Baris, D Greenberg, RS Hayes, RB Brown, LM Lillemoe, KD Schoenberg, JB Pottern, LM Schwartz, AG Hoover, RN AF Ji, BT Silverman, DT Stewart, PA Blair, A Swanson, GM Baris, D Greenberg, RS Hayes, RB Brown, LM Lillemoe, KD Schoenberg, JB Pottern, LM Schwartz, AG Hoover, RN TI Occupational exposure to pesticides and pancreatic cancer SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE case-control study; job-exposure matrix; occupation; pancreatic cancer; pesticides ID RISK-FACTORS; MANUFACTURING PLANT; UNITED-STATES; MORTALITY; WORKERS; FARMERS; FLORIDA; DEATH; DDT AB Background An increased risk of exposure to pesticides for pancreatic cancer has been suggested in a number of epidemiologic studies. Methods Cases (N = 484), aged 30-79 years, were diagnosed in 1986-1989. Controls (N = 2,095) were a random sample of the general population. Information on usual occupation and potential confounding factors was obtained. A job-exposure matrix (JEM) approach was used to estimate the level of occupational exposure to pesticides. Results A significant trend in risk with increasing exposure level of pesticides was observed, with ORs of 1.3 and 1.4 for low and moderate/high exposure levels, respectively. Excess risks were found for occupational exposure to fungicides (OR = 1.5) and herbicides (OR = 1.6) in the moderate/high level after adjustment for potential confounding factors. An increased risk for insecticide exposure was disappeared after adjustment for fungicide and herbicide exposures. Results of our occupation-based analysis were consistent with those from the JEM-based analysis. Conclusions Our results suggest that pesticides may increase risk of pancreatic cancer and indicate the need for investigations that can evaluate risk by specific chemical exposures. Am. J. Ind. Med. 39:92-99, 2001. Published 2001 Wiley-Liss, Inc.dagger C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. New Jersey State Dept Hlth, Special Epidemiol Program, Trenton, NJ 08625 USA. NHLBI, Womens Hlth Initiat, NIH, Bethesda, MD 20892 USA. Barbara Ann Karmanos Canc Inst, Detroit, MI USA. RP Ji, BT (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Execut Plaza S,Room 8120, Bethesda, MD 20892 USA. NR 44 TC 57 Z9 58 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 2001 VL 39 IS 1 BP 92 EP 99 DI 10.1002/1097-0274(200101)39:1<92::AID-AJIM9>3.0.CO;2-P PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 389LQ UT WOS:000166239700009 PM 11148019 ER PT J AU Fanos, JH Davis, J Puck, JM AF Fanos, JH Davis, J Puck, JM TI Sib understanding of genetics and attitudes toward carrier testing for X-linked severe combined immunodeficiency SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE severe combined immunodeficiency; sibs; carrier status; family dynamics; genetic counseling; genetic testing ID RECEPTOR-GAMMA-CHAIN; HUNTINGTON DISEASE; PRENATAL-DIAGNOSIS; OBLIGATE CARRIERS; TRANSPLANTATION; POPULATION; HEMOPHILIA; CHILDREN AB X-linked severe combined immunodeficiency (XSCID) is the most common genetic form of SCID, a rare disease with profoundly impaired immunity. SCID was previously fatal but now can be treated by bone marrow transplantation. Mapping of XSCID in 1985 and identification of the disease gene, IL2R4 in 1993 made possible patient and carrier diagnosis. We assessed understanding of the genetics of XSCID in adult sibs recruited from families in which a proband had enrolled in our protocols and had attended an XSCID family workshop. Thirty-seven female and three male sibs completed a questionnaire and semistructured interview. Overall knowledge of genetics of XSCID was excellent. An overwhelming majority of participants (93%) believed that daughters should be tested for XSCID carrier status; 89% would prefer to have their own daughter tested prior to age 18 years (M = 9, median = 12), and 34% would test at birth. Moreover, 89% felt they would disclose carrier results to their daughter before adulthood (M = 12 years, median = 12); 51% would tell prior to adolescence. XSCID sibs were optimistic about medical science and assertive in their search for the latest information. Genetic information should be made available to families over time and should include discussion of reproductive risks for sons surviving with XSCID and daughters as they grow up. We recommend that genetic counseling for XSCID include children in age-appropriate discussions and that counselors help parents weigh benefits of early testing and disclosure versus the potential harm of loss of child autonomy. Am. J. Med. Gen. 98:46-56, 2001. Published 2001 Wiley-Liss, Inc.(dagger). C1 Calif Pacific Med Ctr, Res Inst, Dept Pediat, San Francisco, CA 94115 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Calif Pacific Med Ctr, Dept Med, San Francisco, CA 94115 USA. Calif Pacific Med Ctr, Dept Psychiat, San Francisco, CA 94115 USA. RP Fanos, JH (reprint author), Calif Pacific Med Ctr, Res Inst, Dept Pediat, 2340 Clay St,5th Floor, San Francisco, CA 94115 USA. NR 37 TC 23 Z9 23 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 1 PY 2001 VL 98 IS 1 BP 46 EP 56 DI 10.1002/1096-8628(20010101)98:1<46::AID-AJMG1008>3.0.CO;2-K PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 388VE UT WOS:000166203100009 PM 11426455 ER PT J AU Fanos, JH Puck, JM AF Fanos, JH Puck, JM TI Family pictures: Growing up with a brother with X-linked severe combined immunodeficiency SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE severe combined immunodeficiency; sibs; mourning; communication; family dynamics; genetic counseling; bone marrow transplantation; bone marrow donor ID RECEPTOR-GAMMA-CHAIN; CARRIER STATUS; TRANSPLANTATION; SIBLINGS; SIBS AB Severe combined immunodeficiency (SCID) is a rare syndrome of profoundly impaired immunity, most often X-linked (XSCID). In past generations male infants with XSCID succumbed to infections during the first year of life, but prompt diagnosis and bone marrow transplantation currently make survival possible for over 80%. This treatment typically requires hospitalization for several months; thus, the burden on the family is considerable. We assessed the psychological impact on sibs of boys with XSCID, Forty adult sibs from families studied by J.M.P. were interviewed by J.H.F., and rating scales developed. The majority expressed distress over prolonged maternal absence during the affected child's hospitalization; 67% believed the mother had unsuccessfully mourned son(s) who died of XSCID. Half of the sibs reported that communication in the family about XSCID had been poor. Families with a spontaneous mutation were significantly more likely to report separation issues (P = 0.05), perhaps due to stronger maternal guilt. Family communication was significantly related to parental mourning (P = 0.001) and to survivor guilt (P = 0.05). Difficulties for daughters included desire to repair the mother's loss of her own child, as well as attempts to undo feelings of being flawed, by heightened wishes to bear a healthy son. In light of these findings we suggest: 1) bone marrow transplantation and the period of isolation places great stress on the family; parents need help balancing needs of well sibs with needs of the affected son; 2) parents need help with mourning the loss of a son so family secrets will not prevail; and 3) sibs, both bone marrow donors and non-donors, face psychological risks and need support. Am. J. Med. Gen. 98:57-63, 2001. Published 2001 Wiley-Liss, Inc.(dagger). C1 Calif Pacific Med Ctr, Res Inst, Dept Pediat, San Francisco, CA 94115 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Calif Pacific Med Ctr, Dept Med, San Francisco, CA 94115 USA. Calif Pacific Med Ctr, Dept Psychiat, San Francisco, CA 94115 USA. RP Fanos, JH (reprint author), Calif Pacific Med Ctr, Res Inst, Dept Pediat, 2340 Clay St,5th Floor, San Francisco, CA 94115 USA. NR 25 TC 18 Z9 18 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 1 PY 2001 VL 98 IS 1 BP 57 EP 63 DI 10.1002/1096-8628(20010101)98:1<57::AID-AJMG1007>3.0.CO;2-J PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 388VE UT WOS:000166203100010 PM 11426456 ER PT J AU Scuteri, A Bos, AJG Zonderman, AB Brant, LJ Lakatta, EG Fleg, JL AF Scuteri, A Bos, AJG Zonderman, AB Brant, LJ Lakatta, EG Fleg, JL TI Is the apoE4 allele an independent predictor of coronary events? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID APOLIPOPROTEIN-E POLYMORPHISM; HEART-DISEASE; ALZHEIMERS-DISEASE; RISK-FACTORS; MEN; ATHEROSCLEROSIS; FREQUENCIES; POPULATION; PROTEIN AB PURPOSE:Although the apolipoprotein E genotype epsilon4 (apoE4) has been associated with high cholesterol levels, whether it is an independent predictor of coronary events is not certain. SUBJECTS AND METHODS: We measured apoE genotypes in 730 participants in the Baltimore Longitudinal Study of Aging (421 men and 309 women, mean [+/- SD] age of 52 +/- 17 years) who were free of preexisting coronary heart disease. A proportional hazards regression model was used to study the association between risk factors and the occurrence of coronary events, defined as angina pectoris, documented myocardial infarction by history or major Q waves on the electrocardiogram (Minnesota Code 1:1 or 1:2), or coronary death, adjusted for other risk factors, including total plasma cholesterol level. RESULTS: The apoE4 allele was observed in 200 subjects (27%), including 183 heterozygotes and 17 homozygotes. Coronary risk factor profiles were similar in those with and without apoE4. Coronary events developed in 104 (14%) of the 730 subjects, including 77 (18%) of the 421 men during a mean follow-up of 20 years and 27 (9%) of the 309 women during a mean follow-up of 13 years. Corollary events occurred significantly more frequently in subjects with apoE4 (n = 40, 20%) than in those without this allele (64, 12%, P < 0.05). In a multivariate model, apoE4 was an independent predictor of coronary events in men (risk ratio [RR]= 2.9, 95% confidence interval [CI]: 1.8 to 4.5, P < 0.0001) but not in women (RR = 0.9, 95% CI: 0.4 to 1.9, P = 0.62). CONCLUSION: The apoE4 genotype is a strong independent risk factor for coronary events in men, but not women. The association does not appear to be mediated by differences in total cholesterol levels. (C) 2001 by Excerpta Medica, Inc. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Res Resource Branch, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Scuteri, A (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 28 TC 52 Z9 58 U1 0 U2 2 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 JAN PY 2001 VL 110 IS 1 BP 28 EP 32 DI 10.1016/S0002-9343(00)00639-2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 391UH UT WOS:000166373800006 PM 11152862 ER PT J AU Yang, QF Mori, I Shan, L Nakamura, M Nakamura, Y Utsunomiya, H Yoshimura, G Suzuma, T Tamaki, T Umemura, T Sakurai, T Kakudo, K AF Yang, QF Mori, I Shan, L Nakamura, M Nakamura, Y Utsunomiya, H Yoshimura, G Suzuma, T Tamaki, T Umemura, T Sakurai, T Kakudo, K TI Biallelic inactivation of retinoic acid receptor beta 2 gene by epigenetic change in breast cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID UP-REGULATION; CELL-LINES; EXPRESSION; CARCINOMA; 5-AZA-2'-DEOXYCYTIDINE; ISOTRETINOIN; SENSITIVITY; PREVENTION; APOPTOSIS; PROMOTER AB A growing body of evidence supports the hypotheses that retinoic acid receptor beta2 (RAR beta2) is a tumor suppressor gene. Although the loss of RAR beta2 expression has been reported in many malignant tumors, including breast cancer, the molecular mechanism is still poorly understood. We hypothesized that loss of RAR beta2 activity could result from multiple factors, including epigenetic modification and loss of heterozygosity (LOH), Using methylation-specific polymerase chain reaction and LOH analysis, we found that biallelic inactivation via epigenetic changes of both maternal and paternal alleles, or epigenetic modification of one allele combined with genetic loss of the remaining allele, could completely suppress RAR beta2 expression in breast cancer. Thus, it is possible that substantial numbers of human cancers arise through suppressor gene silencing via epigenetic mechanisms that inactivate both alleles. Because of this, chromatin-remodeling drugs may provide a novel strategy for cancer prevention and treatment. C1 Wakayama Med Coll, Dept Pathol 2, Wakayama 6410012, Japan. Wakayama Med Coll, Dept Surg, Wakayama 6410012, Japan. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Yang, QF (reprint author), Wakayama Med Coll, Dept Pathol 2, 811-1 Kimiidera, Wakayama 6410012, Japan. RI Nakamura, Yasushi/J-5143-2014 NR 29 TC 51 Z9 55 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2001 VL 158 IS 1 BP 299 EP 303 DI 10.1016/S0002-9440(10)63969-7 PG 5 WC Pathology SC Pathology GA 390XV UT WOS:000166325800034 PM 11141504 ER PT J AU Ward, JM Yoon, M Anver, MR Haines, DC Kudo, G Gonzalez, FJ Kimura, S AF Ward, JM Yoon, M Anver, MR Haines, DC Kudo, G Gonzalez, FJ Kimura, S TI Hyalinosis and Ym1/Ym2 gene expression in the stomach and respiratory tract of 129S4/SvJae and wild-type and CYP1A2-null B6,129 mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FACTOR-ALPHA; CYTOCHROME-P450 1A2; MOUSE CHROMOSOME-9; TRANSGENIC MICE; MESSENGER-RNA; CARCINOGENESIS; TISSUE; DIFFERENTIATION; LOCALIZATION; EPITHELIUM AB The C57BL/6, 129, and B6,129 mouse strains or stocks have been commonly used to generate targeted mutant mice. The pathology of these mice is not well characterized. In studies of these aging mice, we found high incidences of hyalinosis (eosinophilic cytoplasmic change) in the glandular stomach, respiratory tract, bile duct, and gall bladder of B6,129 CYP1A2-null and wild-type mice as well as in both sexes of the background 129S4/SvJae strain The gastric lesions of the glandular stomach were found in 95.7% of female CYP1A2-null mice as well as in 45.7% of female 129S4/SvJae animals. The eosinophilic protein isolated from characteristic hyaline gastric lesions was identified as Ym2, a member of the chitinase family. Immunohistochemistry, using rabbit polyclonal antibodies to oligopeptides derived from the Ym1 sequence, detected focal to diffuse reactivity within both normal and abnormal nasal olfactory and respiratory epithelium, pulmonary alveolar macrophages, bone marrow myeloid cells, and the squamous epithelium of the forestomach and epithelium of the glandular stomach. Alveolar macrophages in acidophilic pneumonia, a major cause of death of aging 129 mice, and in mice with the me mutation also were highly immunoreactive, The possible cause of this protein excess in gastric and other lesions and its possible functions are discussed. C1 NCI, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Div Basic Sci,FCRDC, Frederick, MD 21702 USA. NCI, Vet Pathol Sect, Pathol Histotechnol Lab, SAIC Frederick, Frederick, MD 21702 USA. NCI, Lab Metab, Div Basic Sci, Bethesda, MD 20892 USA. RP Ward, JM (reprint author), NCI, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Div Basic Sci,FCRDC, Fairview 201,POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-5600] NR 50 TC 76 Z9 78 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2001 VL 158 IS 1 BP 323 EP 332 DI 10.1016/S0002-9440(10)63972-7 PG 10 WC Pathology SC Pathology GA 390XV UT WOS:000166325800037 PM 11141507 ER PT J AU Gerald, MS Higley, S Higley, JD AF Gerald, MS Higley, S Higley, JD TI Reproductive performance in captive male rhesus macaques (Macaca mulatta) differing in cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2001 SU 32 BP 69 EP 69 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 408ZX UT WOS:000167358000155 ER PT J AU Kolman, CJ Robin, RW Goldman, D Long, JC AF Kolman, CJ Robin, RW Goldman, D Long, JC TI Allele: phenotype associations in alcohol dependence and alcohol-related disorders. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Univ Florida, Dept Anthropol, Gainesville, FL 32611 USA. NIH, NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2001 SU 32 BP 92 EP 92 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 408ZX UT WOS:000167358000242 ER PT J AU Soltis, J AF Soltis, J TI Why do female primates engage in non-procreative mating with multiple males? SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Natl Inst Hlth, Comparat Ethol Lab, Poolesville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2001 SU 32 BP 140 EP 140 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 408ZX UT WOS:000167358000427 ER PT J AU Stoner, GL Friedlaender, JS Jobes, DV Mgone, CS Yanagihara, R Agostini, HTS AF Stoner, GL Friedlaender, JS Jobes, DV Mgone, CS Yanagihara, R Agostini, HTS TI JC virus genotypes in the Western Pacific. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Temple Univ, Philadelphia, PA 19122 USA. Inst Med Res, Goroka, Papua N Guinea. Univ Hawaii, Honolulu, HI 96822 USA. Univ Freiburg, D-7800 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2001 SU 32 BP 143 EP 143 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 408ZX UT WOS:000167358000438 ER PT J AU Jacobs, ER Zeldin, DC AF Jacobs, ER Zeldin, DC TI The lung HETEs (and EETs) up SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Review DE arachidnoic acid; monooxygenases; eicosanoids; pulmonary arteries; bronchi; bronchospasm; cytochrome P-450; inflammation; hypoxic vasoconstriction; mitogenesis ID ARACHIDONIC-ACID METABOLISM; HYPOXIC PULMONARY VASOCONSTRICTION; EPOXYEICOSATRIENOIC ACIDS; CYSTIC-FIBROSIS; RABBIT LUNG; 20-HYDROXYEICOSATETRAENOIC ACID; CYTOCHROME-P-450 MONOOXYGENASE; FUNCTIONAL-SIGNIFICANCE; EICOSANOID METABOLISM; MOLECULAR-CLONING AB Arachidonic acid metabolites of the cyclooxygenase and lipoxygenase pathways have a variety of important lung functions. Recent observations indicate that cytochrome P-450 (P-450) monooxygenases are also expressed in the lung, localized to specific pulmonary cell types (e.g., epithelium, endothelium, and smooth muscle), and may modulate critical lung functions. This review summarizes recent data on the presence and biological activity of P-450-derived eicosanoids in the pulmonary vasculature and airways, including effects on pulmonary vascular and bronchial smooth muscle tone and airway epithelial ion transport. We hypothesize a number of potential functions of P-450-derived arachidonate metabolites in the lungs such as contribution to hypoxic pulmonary vasoconstriction, regulation of bronchomotor tone, control of the composition of airway lining fluid, and limitation of pulmonary inflammation. Finally, we describe a number of emerging technologies, including congenic and transgenic strains of experimental animals, P-450 isoform-specific inhibitors and inhibitory antibodies, eicosanoid analogs, and vectors for delivery of P-450 cDNAs and antisense oligonucleotides. These tools will facilitate further studies on the contribution of endogenously formed P-450 eicosanoid metabolites to lung function, under both normal and pathological conditions. C1 Med Coll Wisconsin, Dept Physiol & Med, Cardiovasc Res Ctr, Milwaukee, WI 53226 USA. NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Med Coll Wisconsin, Dept Physiol & Med, Cardiovasc Res Ctr, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM ejacobs@mcw.edu NR 115 TC 58 Z9 59 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2001 VL 280 IS 1 BP H1 EP H10 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 384MW UT WOS:000165948500001 PM 11123211 ER PT J AU Tavakoli, S Cowan, MJ Benfield, T Logun, C Shelhamer, JH AF Tavakoli, S Cowan, MJ Benfield, T Logun, C Shelhamer, JH TI Prostaglandin E-2-induced interleukin-6 release by a human airway epithelial cell line SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE cytokines; eicosanoids; lung inflammation ID PLATELET-ACTIVATING-FACTOR; PROTEIN-KINASE-C; EP2 SUBTYPE; ALVEOLAR MACROPHAGES; ARACHIDONIC-ACID; T-CELLS; RECEPTOR; EXPRESSION; GENERATION; CLONING AB Human airway epithelial cell release of interleukin (IL)-6 in response to lipid mediators was studied in an airway cell line (BEAS-2B). Prostaglandin (PG) E-2 (10(-7) M) treatment caused an increase in IL-6 release at 2, 4, 8, and 24 h. IL-6 release into the culture medium at 24 h was 3,396 +/- 306 vs. 1,051 +/- 154 pg/ml (PGE(2)-treated cells vs. control cells). PGE(2) (10(-7) to 10(-10) M) induced a dose-related increase in IL-6 release at 24 h. PGF(2 alpha) (10(-6) M) treatment caused a similar effect to that of PGE(2) (10(-7) M). PGE(2) analogs with relative selectivity for PGE2 receptor subtypes were studied. Sulprostone, a selective agonist for the EP-3 receptor subtype had no effect on IL-6 release. 11-Deoxy-16,16-dimethyl-PGE(2,) an EP-2/4 agonist, and 17-phenyl trinor PGE(2), an agonist selective for the EP-1 > EP-3 receptor subtype (10(-6) to 10(-8) M), caused dose-dependent increases in IL-6 release. 8-Bromo-cAMP treatment resulted in dose-related increases in IL-6 release. RT-PCR of BEAS-2B cell mRNA demonstrated mRNA for EP-1, EP-2, and EP-4 receptors. After PGE(2) treatment, increases in IL-6 mRNA were noted at 4 and 18 h. Therefore, PGE(2) increases airway epithelial cell IL-6 production and release. C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Shelhamer, JH (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10,Rm 7-D-43, Bethesda, MD 20892 USA. NR 40 TC 27 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2001 VL 280 IS 1 BP L127 EP L133 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 385HA UT WOS:000165997000015 PM 11133502 ER PT J AU Patterson-Buckendahl, P Rusnak, M Fukuhara, K Kvetnansky, R AF Patterson-Buckendahl, P Rusnak, M Fukuhara, K Kvetnansky, R TI Repeated immobilization stress reduces rat vertebral bone growth and osteocalcin SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE restraint immobilization; bone mineral; corticosterone ID PARATHYROID-HORMONE; INDUCED HYPOCALCEMIA; SERUM OSTEOCALCIN; IONIZED CALCIUM; MINERAL DENSITY; GLA-PROTEIN; PLASMA; TERM; RADIOIMMUNOASSAY; ADAPTATION AB We previously showed that psychological stressors alter plasma levels of osteocalcin (pOC), a bone-specific mineral binding protein, in ways that differ with the type of stressor. To determine effects of chronic stress, we examined vertebrae, pOC, and corticosterone levels from conscious rats subjected to foot-restraint immobilization (Immo) daily for 1-42 times. After 40-42 Immo, basal pOC was decreased by 25% compared with unstressed rats, and the subsequent rise in pOC during Immo was blunted. Corticosterone was elevated 10-fold during Immo. Immo for seven times did not change vertebral OC concentration, but caused a slight decrease in calcium and phosphorous concentrations in younger rats. Rats Immo for 42 times exhibited reduced body weight, vertebral weight, and vertebral OC concentration but no significant differences in vertebral mineral concentrations. Body fat content was visibly decreased. We do not know the source of or the stimulus for the initial rise in pOC. We conclude that both decreased growth and bone OC concentration are due to repeatedly elevated stress hormones. C1 Rutgers State Univ, Ctr Alcohol Studies, Piscataway, NJ 08854 USA. NINDS, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. RP Patterson-Buckendahl, P (reprint author), Rutgers State Univ, Ctr Alcohol Studies, 607 Allison Rd, Piscataway, NJ 08854 USA. FU NIAAA NIH HHS [R21-AA-12705-01] NR 37 TC 13 Z9 14 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN PY 2001 VL 280 IS 1 BP R79 EP R86 PG 8 WC Physiology SC Physiology GA 384QB UT WOS:000165955400011 PM 11124137 ER PT J AU Frindt, G Masilamani, S Knepper, MA Palmer, LG AF Frindt, G Masilamani, S Knepper, MA Palmer, LG TI Activation of epithelial Na channels during short-term Na deprivation SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cortical collecting tubule; epithelial sodium channel; aldosterone; sodium transport; potassium transport ID CORTICAL COLLECTING TUBULE; POTASSIUM SECRETION; CATION-TRANSPORT; SODIUM-TRANSPORT; RAT; ALDOSTERONE; KIDNEY; DEOXYCORTICOSTERONE; VASOPRESSIN; CELLS AB The role of epithelial Na channels in the response of the kidney to short-term Na deprivation was studied in rats. Animals were fed either a control-Na (3.9 g/kg) or a low-Na (3.8 mg/kg) diet for 15 h. Urinary excretion of Na (mmol/min), measured in conscious animals in metabolic cages, was 0.45 +/- 0.07 in controls and 0.04 +/- 0.01 in Na-deprived animals. Glomerular filtration rate, measured as the clearance of creatinine, was unaffected by the change in diet, suggesting that the reduced Na excretion was the result of increased Na reabsorption. K excretion (mmol/min), increased after the 15-h period of Na deprivation from 0.70 +/- 0.10 to 1.86 +/- 0.19. Thus the decrease in urine Na was compensated for, in terms of electrical charge balance, by an increase in urine K. Plasma aldosterone increased from 0.50 +/- 0.08 to 1.22 +/- 0.22 nM. Principal cells from cortical collecting tubules isolated from the animals were studied by using the patch-clamp technique. Whole cell amiloride-sensitive currents were negligible in the control group (5 +/- 4 pA/cell) but substantial in the Na-deprived group (140 +/- 28 pA/cell). The abundance of the epithelial Na channel subunits, alpha, beta, and gamma in the kidney was estimated by using immunoblots. There was no change in the overall abundance of any of the subunits after the 15-h Na deprivation. However, the apparent molecular mass of a fraction of the gamma -subunits decreased as was previously reported for long-term Na deprivation. Calculations of the rate of Na transport mediated by the Na channels indicated that activation of the channels during short-term Na deprivation could account in large part for the increased Na reabsorption under these conditions. C1 Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Palmer, LG (reprint author), Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, 1300 York Ave, New York, NY 10021 USA. EM lgpalm@med.cornell.edu FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [DK-27847, DK-11489] NR 32 TC 62 Z9 62 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2001 VL 280 IS 1 BP F112 EP F118 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 385JA UT WOS:000165999300013 PM 11133521 ER PT J AU Saavedra, JM Hauser, W Ciuffo, G Egidy, G Hoe, KL Johren, O Sembonmatsu, T Inagami, T Armando, I AF Saavedra, JM Hauser, W Ciuffo, G Egidy, G Hoe, KL Johren, O Sembonmatsu, T Inagami, T Armando, I TI Increased AT(1) receptor expression and mRNA in kidney glomeruli of AT(2) receptor gene-disrupted mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE renin-angiotensin system; angiotensin II receptor types; gene-disrupted models ID ANGIOTENSIN-II RECEPTOR; SPONTANEOUSLY HYPERTENSIVE RATS; TISSUE-SPECIFIC EXPRESSION; IN-SITU HYBRIDIZATION; HUMAN RENAL-CORTEX; TYPE-2 RECEPTOR; QUANTITATIVE AUTORADIOGRAPHY; PRESSURE-NATRIURESIS; BLOOD-PRESSURE; CONSCIOUS RATS AB The proposed feedback between angiotensin II AT(2) and AT(1) receptors prompted us to study AT(1) receptor expression in kidneys of male AT(2) receptor-gene disrupted mice (agtr2 -/y). In wild-type (agtr2 +/y) mice, AT(1) receptor binding and mRNA is abundant in glomeruli, and AT(1) receptor binding is also high in the inner stripe of the outer medulla. AT(2) receptors are scarce, primarily associated to cortical vascular structures. In agtr2 -/y mice, AT(1) receptor binding and mRNA were increased in the kidney glomeruli, and AT(1) receptor binding was higher in the rest of the cortex and outer stripe of the outer medulla, but not in its inner stripe, indicating different cellular regulation. Although AT(2) receptor expression is very low in male agtr2 +/y mice, their gene disruption alters AT(1) receptor expression. AT(1) upregulation alone may explain the AT(2) gene-disrupted mice phenotype such as increased blood pressure, higher sensitivity to angiotensin II, and altered renal function. The indirect AT(1)/AT(2) receptor feedback could have clinical significance because AT(1) antagonists are widely used in medical practice. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Dr MSC 1514,Bldg 10,Rm 2D-57, Bethesda, MD 20892 USA. EM Saavedrj@irp.nimh.nih.gov RI Johren, Olaf/G-6967-2011 NR 49 TC 28 Z9 29 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2001 VL 280 IS 1 BP F71 EP F78 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 385JA UT WOS:000165999300008 PM 11133516 ER PT J AU Karp, BI Garvey, M Jacobsen, LK Frazier, JA Hamburger, SD Bedwell, JS Rapoport, JL AF Karp, BI Garvey, M Jacobsen, LK Frazier, JA Hamburger, SD Bedwell, JS Rapoport, JL TI Abnormal neurologic maturation in adolescents with early-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CHILDHOOD-ONSET; SOFT SIGNS; AUTISTIC-CHILDREN; NEUROLEPTIC-NAIVE; PSYCHOPATHOLOGY; PSYCHIATRY; PSYCHOPHARMACOLOGY; DYSKINESIAS; CLOZAPINE; RELATIVES AB Objective: This study evaluated neurologic functioning in adolescents with schizophrenia with onset of psychosis before age 13. Method: The authors administered a structured neurologic examination to 21 adolescents with early-onset schizophrenia and 27 healthy age- and sex-matched comparison subjects. Results: The adolescents with schizophrenia had a high frequency of neurologic abnormalities. Neurologic signs decreased with age in the healthy comparison subjects but not in the subjects with schizophrenia. Conclusions: The adolescents with schizophrenia had a high burden of neurologic impairment and a pattern of abnormalities similar to that of adults with schizophrenia. The persistence of neurologic signs in the adolescents with schizophrenia, which faded with age in the healthy comparison adolescents, supports earlier evidence of a delay in or failure of normal brain development during adolescence. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Karp, BI (reprint author), NINDS, NIH, 10-5S-209, Bethesda, MD 20892 USA. NR 50 TC 34 Z9 34 U1 4 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2001 VL 158 IS 1 BP 118 EP 122 DI 10.1176/appi.ajp.158.1.118 PG 5 WC Psychiatry SC Psychiatry GA 387ZY UT WOS:000166154000020 PM 11136643 ER PT J AU Pini, S Cassano, GB Dell'Osso, L Amador, XF AF Pini, S Cassano, GB Dell'Osso, L Amador, XF TI Insight into illness in schizophrenia, schizoaffective disorder, and mood disorders with psychotic features SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Deficits in insight have been found in one study to be more common and severe in patients with schizophrenia than in patients with schizoaffective and major depression with and without psychosis but not more severe than they are in patients with bipolar disorder. The goals of this study were to replicate this finding independently and to clarify whether patients with schizophrenia differ from patients with bipolar disorder in a larger study group. Method: Using the Scale to Assess Unawareness of Mental Disorder, the authors evaluated 29 inpatients with schizophrenia, 24 with schizoaffective disorder, and 183 with mood disorders with psychotic features (153 with bipolar disorder and 30 with unipolar depression). Results: Patients with schizophrenia had poorer insight than patients with schizoaffective disorder and patients with psychotic unipolar depression but did not differ from patients with bipolar disorder. Conclusions: The lack of significant differences between patients with schizophrenia and patients with bipolar disorder was not a result of low statistical power. This replication and more detailed examination of diagnostic group differences in insight have clinical, theoretical, and nosological implications. C1 New York State Psychiat Inst, Dept Psychol, Diag & Treatment Res Core, NIMH,Mental Hlth Clin Res Ctr, New York, NY 10032 USA. Univ Pisa, Dept Psychiat, Pisa, Italy. RP Amador, XF (reprint author), New York State Psychiat Inst, Dept Psychol, Diag & Treatment Res Core, NIMH,Mental Hlth Clin Res Ctr, 1051 Riverside Dr,Unit 2, New York, NY 10032 USA. FU NIMH NIH HHS [MH59342] NR 11 TC 112 Z9 117 U1 3 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2001 VL 158 IS 1 BP 122 EP 125 DI 10.1176/appi.ajp.158.1.122 PG 4 WC Psychiatry SC Psychiatry GA 387ZY UT WOS:000166154000021 PM 11136644 ER PT J AU Helfand, TH Lazarus, J Theerman, P AF Helfand, TH Lazarus, J Theerman, P TI Vaincre le cancer ("Defeat Cancer") SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2001 VL 91 IS 1 BP 20 EP 20 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 387GP UT WOS:000166115100005 ER PT J AU Fox, SA Stein, JA Sockloskie, RJ Ory, MG AF Fox, SA Stein, JA Sockloskie, RJ Ory, MG TI Targeted mailed materials and the Medicare beneficiary: Increasing mammogram screening among the elderly SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HEALTH BELIEF MODEL; OLDER WOMEN; BREAST-CANCER; TAILORED MESSAGES; INSURANCE; REIMBURSEMENT; DIFFERENCE; KNOWLEDGE; SETTINGS; PROGRAM AB Objectives. Older women have the highest breast cancer rates but air under-screened relative to their risk. Racial/ethnic minority women especially have low screening rates, often because of financial constraints. In response, Medicare introduced subsidized biennial mammogram benefits in 1991. This study examined the effect on mammography rates of an intervention that informed women about the Medicare bt nt fit. Methods. A list Frame method of subject selection was used to select random samples of eligible women from the Health Care Financing Administration's master beneficiary file. Women were interviewed by telephone in 1991 (N=917) before the targeted mailing and in 1993 (N=922). One control and 2 treatment communities participated. Results. Mammogram use increased significantly among minorities in the treatment groups. Among minorities who received the intervention, Black women were twice as likely (odds ratio=1.97) and Hispanic women were more than twice as likely (odds ratio=2.33) to undergo screening relative to their untreated cohorts. Conclusions. A targeted low-cost mailed intervention can help increase screening rates among elderly minority women. The Health Care Financing Administration should promote its benefits aggressively if it expects to reach its target-elderly beneficiaries. C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. NIA, US Dept HHS, Bethesda, MD 20892 USA. RP Fox, SA (reprint author), RAND Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. FU NCI NIH HHS [1 R01 CA45003]; NIDA NIH HHS [P01-DA01070] NR 37 TC 23 Z9 23 U1 2 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2001 VL 91 IS 1 BP 55 EP 61 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 387GP UT WOS:000166115100014 PM 11189826 ER PT J AU Klesges, LM Pahor, M Shorr, RI Wan, JY Williamson, JD Guralnik, JM AF Klesges, LM Pahor, M Shorr, RI Wan, JY Williamson, JD Guralnik, JM TI Financial difficulty in acquiring food among elderly disabled women: Results from the women's health and aging study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PHYSICAL-DISABILITY; UNITED-STATES; SERUM-ALBUMIN; INSECURITY; MORTALITY; HOUSEHOLDS; DISEASE; HUNGER; LEVEL; RISK AB Objectives. This study described the prevalence and characteristics of financial difficulty acquiring food and its relation to-nutritional biomarkers in older disabled women. Methods. Baseline data were analyzed from the Women's Health and Aging Study, a population-based survey of 1002 Community-dwelling, disabled women 65 years and older from Baltimore, Md. Results. Minority women (49.5%) were-more likely than White women (13.4%) to report financial difficulty acquiring food (odds ratio [OR]=6.2, 95% confidence interval [CI]=4.5, 8.6). Of the women reporting financial difficulty acquiring food only 19.3% received food stamps and fewer than 7% participated in food assistance programs. Women reporting financial difficulty acquiring food had higher levels:of psychologic depression than women not reporting such difficulty. Greater likelihood of financial difficulty acquiring food was associated with poorer quality of life and physical performance among White women and with more medical conditions among minority women. Finally, anemia (hemoglobin< 120 g/L) was associated with financial difficulty acquiring food (age-adjusted OR=2.9, 95% CI=1.9, 4.3). Conclusions. Financial difficulty acquiring food was common, and receipt of nutritional: services was rare, in community-dwelling, older disabled women. Nutrition assistance programs for the elderly should reexamine their effectiveness in preventing nutritional deficits in older disabled women. C1 Univ Tennessee, Dept Prevent Med, Hlth Sci Ctr, Memphis, TN 38163 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Klesges, LM (reprint author), Univ Tennessee, Dept Prevent Med, Hlth Sci Ctr, 66 N Pauline,Suite 633, Memphis, TN 38163 USA. FU NIA NIH HHS [N01-AG-0-2105] NR 32 TC 49 Z9 54 U1 1 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2001 VL 91 IS 1 BP 68 EP 75 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 387GP UT WOS:000166115100016 PM 11189828 ER PT J AU Griffith, KA Sherrill, DL Siegel, EM Manolio, TA Bonekat, HW Enright, PL AF Griffith, KA Sherrill, DL Siegel, EM Manolio, TA Bonekat, HW Enright, PL TI Predictors of loss of lung function in the elderly the cardiovascular health study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; SPIROMETRY REFERENCE VALUES; FORCED EXPIRATORY VOLUME; RESPIRATORY SYMPTOMS; RAPID DECLINE; VENTILATORY FUNCTION; SMOKING-HABITS; BODY-MASS; FEV(1); ADULTS AB Pulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6% female, mean age 73 yr, 87.5% white and 12.5% African-American) with eligible FEV, measures representing 89% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1. C1 Univ Arizona, Coll Med, Resp Sci Ctr, Tucson, AZ 85724 USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Davis, Med Ctr, Davis, CA 95616 USA. RP Sherrill, DL (reprint author), Univ Arizona, Coll Med, Resp Sci Ctr, 1501 N Campbell Ave, Tucson, AZ 85724 USA. FU PHS HHS [N01-87079] NR 43 TC 87 Z9 90 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 2001 VL 163 IS 1 BP 61 EP 68 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 394TV UT WOS:000166540100016 PM 11208627 ER PT J AU Pujols, L Mullol, J Perez, M Roca-Ferrer, J Juan, M Xaubet, A Cidlowski, JA Picado, C AF Pujols, L Mullol, J Perez, M Roca-Ferrer, J Juan, M Xaubet, A Cidlowski, JA Picado, C TI Expression of the human glucocorticoid receptor alpha and beta isoforms in human respiratory epithelial cells and their regulation by dexamethasone SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID MESSENGER-RNA; DOWN-REGULATION; IN-VITRO; MECHANISMS; TRANSCRIPTION; MODULATION; HORMONES; LINES; CDNA AB Two isoforms of the human glucocorticoid receptor (hGR) have been described, hGR alpha and hGR beta. We analyzed the expression and regulation of both hGR isoforms in human respiratory epithelial cells (BEAS-2B, A549, and primary nasal epithelial cells). In BEAS-2B cells, the expression of hGR alpha messenger RNA (mRNA) was much higher than that of hGR beta mRNA, Dexamethasone (DEX) (10(-6) M) downregulated hGR alpha mRNA at 6 and 24 h (55 +/- 8 and 58 +/- 5% of control, respectively; P < 0.01), whereas it decreased hGR mRNA only at 6 h (55 +/- 7% of control; P < 0.01), Downregulation of hGR and hCRS mRNAs occurred even in the presence of cycloheximide, Actinomycin-D studies revealed that DEX enhanced the stabilization of hGR alpha and hGR beta messages, hGR alpha but not hGR beta protein was detected in BEAS-2B, A549, and nasal epithelial cells. After 24 h of incubation, 10(-6) M DEX decreased the expression of hGR alpha protein in BEAS-2B, A549, and nasal epithelial cells (16 +/- 4, 14 +/- 4 and 28 +/- 7% of control, respectively; P < 0.01), These results suggest that in respiratory epithelial cells: (7) hGR is much more expressed than hGR beta at both the mRNA and protein levels; (2) hGR alpha is downregulated by corticosteroids both in cell lines (BEAS-2B, A549) and in nasal primary cells; and (3) transcriptional, post-transcriptional, and post translational mechanisms appear to be involved in the regulation of hGR expression by corticosteroids. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Hosp Germans Trias & Pujol, Dept Immunol, Barcelona, Catalonia, Spain. RP Picado, C (reprint author), Serv Pneumol, Villarroel 170, Barcelona 08036, Spain. RI Pujols, Laura/G-8920-2015 OI Pujols, Laura/0000-0003-3708-5098 NR 34 TC 70 Z9 73 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 2001 VL 24 IS 1 BP 49 EP 57 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 395TF UT WOS:000166596800007 PM 11152650 ER PT J AU Thornbury, JR Ornstein, DK Choyke, PL Langlotz, CP Weinreb, JC AF Thornbury, JR Ornstein, DK Choyke, PL Langlotz, CP Weinreb, JC TI Prostate Cancer: What is the future role for imaging? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Semiannual Meeting of the American-College-of-Radiology-Imaging-Netwark CY OCT, 1999 CL WASHINGTON, D.C. SP Amer Coll Radiol Imaging Network ID RADICAL RETROPUBIC PROSTATECTOMY; PREDICT PATHOLOGICAL STAGE; UNITED-STATES; TRANSRECTAL ULTRASOUND; CAPROMAB PENDETIDE; CLINICAL STAGE; GLEASON SCORE; ANTIGEN; MEN; CARCINOMA C1 Univ N Carolina, Dept Surg, Div Urol, Chapel Hill, NC 27599 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. eDict Syst, Mt Laurel, NJ 08054 USA. RP Thornbury, JR (reprint author), 185 MorganPl, Castle Rock, CO 80104 USA. FU NCI NIH HHS [CA 80098] NR 65 TC 25 Z9 25 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2001 VL 176 IS 1 BP 17 EP 22 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386QX UT WOS:000166074000003 PM 11133530 ER PT J AU de Baere, T Denys, A Wood, BJ Lassau, N Kardache, M Vilgrain, V Menu, Y Roche, A AF de Baere, T Denys, A Wood, BJ Lassau, N Kardache, M Vilgrain, V Menu, Y Roche, A TI Radiofrequency liver ablation: Experimental comparative study of water-cooled versus expandable systems SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SMALL HEPATOCELLULAR-CARCINOMA; TISSUE ABLATION; HEPATIC METASTASES; NEEDLE ELECTRODE; TUMORS; ELECTROCAUTERY; EXPERIENCE; RESECTION; INCREASE; VOLUME AB OBJECTIVE. We evaluate the uniformity and reproducibility of thermal lesion ablation and quantify the volume of tissue destruction and hemorrhage induced with two different commercially available radiofrequency ablation devices. MATERIALS AND METHODS. A four-array anchor expandable needle electrode and a triple-cluster cooled-tip needle electrode were used to induce lesions in three explanted calf livers and in vivo in eight swine livers. The sizes of the radiofrequency-induced lesions were macroscopically evaluated by measuring two perpendicular dimensions immediately after the experiment. Bleeding was evaluated by weighing gauze swabs used to dry the hemorrhage caused by electrode insertions. RESULTS. In explanted liver, the mean diameter of the radiofrequency-induced lesion was 5.3 +/- 0.7 cm for the cooled-tip needle and 3.7 +/- 0.4 cm for the expandable needle (p = 0.042), which correspond to approximate volumes of 65.35 +/- 26.22 cm(3) and 26.67 +/- 9.59 cm(3), respectively (p < 0.002). In vivo, the mean diameter was 3.7 +/- 0.4 cm for the cooled-tip needle and 3 +/- 0.4 cm for the expandable needle (p < 0.0001), which correspond to approximate volumes of 24.18 +/- 7.56 cm(3) and 11.16 +/- 3.65 cm(3), respectively (p < 0.0001). Blood loss attained a median value of 3.5 g for the cooled-tip needle and 2.6 g for the expandable needle; this difference was not statistically significant (p = 0.06). CONCLUSION. The cooled-tip needle induced significantly larger lesions than the expandable needle, but the lesions produced by the expandable needle are more reproducible, uniform, and spheric. The larger size of the lesions produced by the coaled-tip needle may be attributed to the higher maximum power used by the generator and the higher energy deposition, which is due to the cooling of the needle electrode. C1 Inst Gustave Roussy, Serv Radiol Intervent, F-94805 Villejuif, France. Hop Beaujon, Serv Imagerie Med, F-92110 Clichy, France. NIH, Dept Radiol, Bethesda, MD 20892 USA. RP de Baere, T (reprint author), Inst Gustave Roussy, Serv Radiol Intervent, Rue Camille Desmoulins, F-94805 Villejuif, France. NR 25 TC 145 Z9 145 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2001 VL 176 IS 1 BP 187 EP 192 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 386QX UT WOS:000166074000035 PM 11133564 ER PT J AU Moss, J AF Moss, J TI Introduction to symposium: Clinical and molecular insights from uncommon lung diseases SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Editorial Material C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, 10 Ctr Dr,MSC 1590,Bldg 10,Room 6D03, 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 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 1 EP 2 DI 10.1097/00000441-200101000-00001 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400001 PM 11202473 ER PT J AU Cowan, MJ Gladwin, MT Shelhamer, JH AF Cowan, MJ Gladwin, MT Shelhamer, JH TI Disorders of ciliary motility SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Kartagener syndrome; primary ciliary dyskinesia; cilia; bronchiectasis ID IMMOTILE-CILIA; KARTAGENERS-SYNDROME; MUCOCILIARY CLEARANCE; LUNG TRANSPLANTATION; HUMAN SPERMATOZOA; SITUS-INVERSUS; BEAT FREQUENCY; NASAL-MUCOSA; DYSKINESIA; ULTRASTRUCTURE AB Clearance of mucus and other debris from the airways is achieved by 3 main mechanisms: mucociliary activity, coughing, and alveolar clearance. Disorders of ciliary structure or function results in impaired clearance, and result in chronic sinopulmonary disease manifested as chronic sinusitis, otitis media, nasal polyposis, and ultimately bronchiectasis. In addition, situs inversus, dextrocardia, and infertility can be associated with dysfunctional ciliary activity. The term primary ciliary dyskinesia has been proposed for the spectrum of these diseases. The term Kartagener syndrome applies to this syndrome when accompanied by infertility and dextrocardia or situs inversus. The more common types of ciliary dysmotility syndromes are characterized by missing dynein arms, central microtubule pairs, inner sheath, radial spokes, or nexin links. In addition to structural defects within the cilia, disordered ciliary beating and disordered ciliary arrays on epithelial cell surfaces have been described in this syndrome. Treatment includes rigorous lung physiotherapy, prophylactic and organism-specific antibiotics, and immunization against common pulmonary pathogens. Late stages of the disease may require surgical intervention for bronchiectasis or lung transplant for end-stage lung disease. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Cowan, MJ (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,Bldg 10-7D43, Bethesda, MD 20892 USA. NR 61 TC 41 Z9 53 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 3 EP 10 DI 10.1097/00000441-200101000-00002 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400002 PM 11202477 ER PT J AU Nanavaty, U Goldstein, AD Levine, SJ AF Nanavaty, U Goldstein, AD Levine, SJ TI Polymorphisms in candidate asthma genes SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE asthma; candidate genes; genetic polymorphisms ID FC-EPSILON-RI; HUMAN BETA(2)-ADRENERGIC RECEPTOR; IMMUNOGLOBULIN-E RECEPTOR; AFFINITY IGE RECEPTOR; BETA-SUBUNIT; ALPHA-SUBUNIT; ATOPY; ASSOCIATION; EXPRESSION; GENETICS AB The tried of reversible airway obstruction, bronchial hyperresponsiveness, and airway inflammation characterizes asthma. The etiology of asthma is complex and involves the interaction of multiple genetic foci and a variety of environmental factors, such as protein allergens, chemical sensitizers, and viral or bacterial proteins. Candidate asthma genes have been identified that may be linked or associated with the asthmatic phenotype. Potential candidate asthma genes include cytokine genes, receptor genes, transcription factors, immune recognition genes, and genes regulating lipid mediator generation. Although polymorphisms within either the promoter or coding region of individual asthma candidate genes have been identified, the association between these genetic polymorphisms and the asthmatic phenotype remains incompletely defined. Furthermore, genetic polymorphisms mediating the asthmatic phenotype are rarely identified in individual patients. This manuscript reviews several of the specific mutations and polymorphisms that have been identified in candidate asthma genes, such as the high affinity IgE receptor, the beta2-adrenergic receptor, the interleukin-4 promoter and receptor, the tumor necrosis factor gene, and the 5-lipoxygenase promoter. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Crit Care Med Dept, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anesthesiol, Bethesda, MD 20814 USA. RP Levine, SJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, 10 Ctr Dr,Room 6D03, Bethesda, MD 20892 USA. NR 32 TC 25 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 11 EP 16 DI 10.1097/00000441-200101000-00003 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400003 PM 11202474 ER PT J AU Kelly, J Moss, J AF Kelly, J Moss, J TI Lymphangioleiomyomatosis SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE lymphangioleiomyomatosis; lung disease; pneumothorax ID MESENCHYMAL CYSTIC HAMARTOMA; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; TUBEROUS SCLEROSIS; LUNG TRANSPLANTATION; CT FINDINGS; MEDROXYPROGESTERONE-ACETATE; LYMPHANGIOMYOMATOSIS; OOPHORECTOMY; PROGESTERONE; LESIONS AB Lymphangioleiomyomatosis (LAM), a rare disorder of unknown cause that occurs almost exclusively in women of childbearing years, is characterized microscopically by abnormal smooth muscle proliferation in the lung, lymphatics, and mediastinal, abdominal and lower cervical lymph nodes. LAM is associated with progressive dyspnea, recurrent pneumothoraces, chylous effusions, abdominal tumors (angiomyolipoma), and chylous ascites. Because of the predilection of this disease for young women, therapies to date have mainly involved hormonal manipulation. Although the efficacy of these therapies has not been established, the clinical course is more favorable in recent studies compared with earlier reports. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D03,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. EM mossj@fido.nhlbi.nih.gov NR 74 TC 35 Z9 50 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 17 EP 25 DI 10.1097/00000441-200101000-00004 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400004 PM 11202475 ER PT J AU Sneller, MC AF Sneller, MC TI Common variable immunodeficiency SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE common variable immunodeficiency; immunodeficiency syndrome ID B-CELL DIFFERENTIATION; CLASS-III GENES; T-CELL; HYPOGAMMAGLOBULINEMIC PATIENTS; VARIED IMMUNODEFICIENCY; GRANULOMATOUS-DISEASE; IGA DEFICIENCY; IMMUNOGLOBULIN; INTERLEUKIN-2; SUBSET AB Common variable immunodeficiency (CVI) is a heterogeneous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and a variety of immunological abnormalities. In addition to recurrent infections, patients with this syndrome also suffer from an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by a variety of medical specialists. In this review, the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI are discussed. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Sneller, MC (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 11B-13, Bethesda, MD 20892 USA. NR 47 TC 56 Z9 60 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 42 EP 48 DI 10.1097/00000441-200101000-00007 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400007 PM 11202479 ER PT J AU Holland, SM AF Holland, SM TI Nontuberculous mycobacteria SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE interferon gamma; mycobacteria; immunodeficiency; receptors ID COMPLEX LUNG-DISEASE; INTERFERON-GAMMA-RECEPTOR; AVIUM-INTRACELLULARE COMPLEX; HUMAN-IMMUNODEFICIENCY-VIRUS; CALMETTE-GUERIN INFECTION; PULMONARY-DISEASE; NATURAL-RESISTANCE; UNITED-STATES; NRAMP1 GENE; TUBERCULOSIS AB The nontuberculous mycobacteria are for the most part ubiquitous environmental organisms that only rarely cause disease in humans. Therefore, the normal host defense against these organisms must be quite robust, as exposure is universal and disease is rare. The organisms that are most commonly encountered in clinical practice, Mycobacterium avium, M intracellulare, M kansasii, M fortuitum, M abscessus, and M chelonae, are frequently found in water sources and soil.(1) These organisms share significant structural and biochemical similarities with their more pathogenic relative, M tuberculosis (MTB). Because they are of significantly lower pathogenicity than MTB, patients with abnormal susceptibility to these infections should include those with defects that may be identifiable. Study of these patients should lead to determination of the mechanisms underlying resistance to these organisms, which in turn are likely to be highly informative regarding host defense against these infections and their more virulent relative MTB. Furthermore, recognition of host factors that permit infection with nontuberculous mycobacteria in otherwise normal hosts will identify pathways that can be targeted for therapeutic intervention. Thus, the search for genetic and acquired susceptibility to nontuberculous mycobacteria is also a search for susceptibility factors for MTB as well as an opportunity to recognize endogenous pathways that can be exploited therapeutically. C1 NIAID, Host Def Lab, Clin Pathophysiol Sect, Immunopathogenesis Unit,NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Host Def Lab, Clin Pathophysiol Sect, Immunopathogenesis Unit,NIH, Bldg 10 Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 53 TC 35 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 49 EP 55 DI 10.1097/00000441-200101000-00008 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400008 PM 11202480 ER PT J AU Russian, DA Levine, SJ AF Russian, DA Levine, SJ TI Pneumocystis carinii pneumonia in patients without HIV infection SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Pneumocystis carinii; immunosuppressed host; pneumonia; chemoprophylaxis ID RENAL-TRANSPLANT RECIPIENTS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BONE-MARROW TRANSPLANTATION; RISK-FACTORS; WEGENERS GRANULOMATOSIS; LIVER-TRANSPLANTATION; HEART-TRANSPLANTATION; CLINICAL-FEATURES; CYTOMEGALO-VIRUS; BREAST-CANCER AB Pneumocystis carinii is an important, but sporadic, opportunistic pulmonary pathogen in immunosuppressed HIV seronegative persons. Historically, patients at highest risk for P carinii pneumonia are included infants with severe malnutrition, children with primary immunodeficiencies, patients with hematological malignancies, and recipients of solid organ or bone marrow transplants. Recently, solid tumor patients, in particular those receiving high-dose corticosteroids for brain neoplasms, and patients with inflammatory or collagen-vascular disorders, especially patients with Wegener granulomatosis receiving immunosuppressive therapy, have been identified as subgroups at increased risk for P carinii pneumonia. Other factors associated with P carinii pneumonia include the intensity of the immunosuppressive regimen and tapering doses of corticosteroids. Because P carinii pneumonia is associated with significant morbidity and mortality, it is important to identify high-risk patient populations to administer effective chemoprophylactic agents, such as trimethoprimsulfamethoxazole. C1 NHLBI, Warren Grant Magnuson Pulm Crit Care Med Branch, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Warren Grant Magnuson Pulm Crit Care Med Branch, Dept Crit Care Med, NIH, Bldg 10,Room 6003,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 55 TC 48 Z9 60 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 56 EP 65 DI 10.1097/00000441-200101000-00009 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400009 PM 11202481 ER PT J AU Shamburek, RD Brewer, HB Gochuico, BR AF Shamburek, RD Brewer, HB Gochuico, BR TI Erdheim-Chester disease: A rare multisystem histiocytic disorder associated with interstitial lung disease SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE histiocytosis; cholesterol; Erdheim-Chester; interstitial lung disease; non-Langerhans cells ID HERMANSKY-PUDLAK-SYNDROME; PROGRESSIVE CEREBELLAR SYNDROME; BONE; INVOLVEMENT AB Erdheim-Chester disease (ECD) is a rare multisystem histiocytosis syndrome of unknown cause that usually affects adults. Histiocytic infiltration of multiple end organs produces bone pain, xanthelasma and xanthoma, exophthalmos, diabetes insipidus, and interstitial lung disease. Differential diagnosis includes Langerhans cell histiocytosis, metabolic disorders, malignancy, and sarcoidosis. ECD can be diagnosed using a combination of clinical and histopathologic findings. Sites of involvement include lung, bone, skin, retroorbital tissue, central nervous system, pituitary gland, retroperitoneum, and pericardium. Symmetrical long bone pain with associated osteosclerotic lesions, xanthomas around the eyelids, exophthalmos, and/or diabetes insipidus suggest ECD. Approximately 35% of patients have associated lung involvement, characterized by interstitial accumulations of histiocytic cells and fibrosis in a predominantly perilymphangitic and subpleural pattern. This pattern distinguishes ECD from other histiocytic disorders involving the lung. The diagnosis is confirmed by tissue biopsies that contain histiocytes with non-Langerhans cell features. In general, the clinical course of patients with this disease varies, and the prognosis can be poor despite treatment. Clinical trials for treatment of ECD have not been conducted and treatment is based on anecdotal experience. C1 NHLBI, MDB, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Shamburek, RD (reprint author), NHLBI, MDB, NIH, Bldg 10,Room 7N105,10 Ctr Dr,MSC 1666, Bethesda, MD 20892 USA. NR 42 TC 45 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 66 EP 75 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400010 PM 11202482 ER PT J AU Langford, CA AF Langford, CA TI Wegener granulomatosis SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE vasculitis; wegener; granuloma; cyclophosphamide; methotrexate ID CYTOPLASMIC ANTIBODY TITER; SYSTEMIC VASCULITIS; C-ANCA; METHOTREXATE; THERAPY; CYCLOPHOSPHAMIDE; GLOMERULONEPHRITIS; AUTOANTIBODIES; INVOLVEMENT; MAINTENANCE AB Wegener granulomatosis (WG) is a necrotizing, granulomatous vasculitis that has a clinical predilection to involve the upper airways, lungs, and kidneys.' Although the first case was reported by Klinger in 1931, Friedrich Wegener in 1936 characterized the unique clinical and pathological features of this disease that subsequently came to bear his name. Vascular inflammation and occlusion leading to tissue ischemia is a hallmark of WC. Although strong evidence indicates that such blood vessel damage is immunologically mediated, the mechanisms that initiate this process are still largely unknown.(2) To date, there has been no clearly established association with genetic factors, specific infectious agents, or environmental irritants, although speculation has remained that these may play a role in triggering the onset of disease. Until the introduction of therapy with cyclophosphamide (CYC) and glucocorticoids, WG was uniformly fatal. Although drug toxicity and disease relapse remain of concern with this regimen, it has provided us with a successful means of treatment and the opportunity to better understand this disease through long-term patient follow-up. C1 NIAID, Immunol Dis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Langford, CA (reprint author), NIAID, Immunol Dis Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-13, Bethesda, MD 20892 USA. NR 38 TC 28 Z9 28 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 76 EP 82 DI 10.1097/00000441-200101000-00011 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400011 PM 11202483 ER PT J AU Gochuico, BR AF Gochuico, BR TI Potential pathogenesis and clinical aspects of pulmonary fibrosis associated with rheumatoid arthritis SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE pulmonary fibrosis; interstitial lung disease; lung; rheumatoid arthritis; collagen vascular disease ID INTERSTITIAL LUNG-DISEASE; PNEUMOCYSTIS-CARINII PNEUMONIA; ALPHA-1-ANTITRYPSIN DEFICIENCY; BRONCHOALVEOLAR LAVAGE; METHOTREXATE; THERAPY; SUSCEPTIBILITY; ABNORMALITIES; GLUTAMATE-69; PHENOTYPES AB Pulmonary fibrosis is an extra-articular disorder that can occur in association with rheumatoid arthritis. The differential diagnosis of this disorder is similar to that of idiopathic pulmonary fibrosis, but specific entities such as atypical pulmonary infections and drug-induced interstitial lung disease must be considered as causes of pulmonary fibrosis in patients with rheumatoid arthritis. Although the cause of lung fibrosis in persons with rheumatoid arthritis is unknown, factors that can potentially contribute to the pathogenesis of this pulmonary disease include genetic susceptibility, development of an altered immunologic response, and/or aberrant host repair processes. The clinical course of patients with pulmonary fibrosis and rheumatoid arthritis is heterogeneous but is generally insidious, chronic, and progressive. These patients respond unpredictably to available empiric therapeutic agents and, overall, their prognosis is poor; limited data suggests that the median survival time can be less than 4 years. C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. RP Gochuico, BR (reprint author), NHLBI, PCCMB, NIH, Bldg 10,Room 6D03,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. NR 43 TC 8 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2001 VL 321 IS 1 BP 83 EP 88 DI 10.1097/00000441-200101000-00012 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 390YB UT WOS:000166326400012 PM 11202484 ER PT J AU Breman, JG AF Breman, JG TI The ears of the hippopotamus: Manifestations, determinants, and estimates of the malaria burden SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Review ID PLASMODIUM-FALCIPARUM MALARIA; CEREBRAL MALARIA; RURAL MALAWI; GAMBIAN CHILDREN; AFRICAN CHILDREN; BIRTH-WEIGHT; WEST-AFRICA; DESCRIPTIVE EPIDEMIOLOGY; CHLOROQUINE RESISTANCE; PERENNIAL TRANSMISSION AB Malarious patients experience asymptomatic parasitemia; acute febrile illness (with cerebral damage, anemia, respiratory distress, hypoglycemia); chronic debilitation (anemia, malnutrition, nervous system-related sequelae); and complications of pregnancy (anemia, low birth weight, increased infant mortality). These manifestations in patients, communities, and countries reflect intrinsic (human, parasite, mosquito) and extrinsic (environmental, social, behavioral, political, and economic conditions as well as disease-control efforts) determinants. At a minimum, between 700,000 and 2.7 million persons die yearly from malaria, over 75% of them African children. Between 400 and 900 million acute febrile episodes occur yearly in African children under 5 yr of age living in endemic areas. Although about half of these children are parasitemic, all merit consideration of malaria-specific therapy, which is becoming more problematic because of parasite resistance to drugs. These numbers will more than double over the next 20 yr without effective control. Fewer than 20% of these febrile episodes and deaths come to the attention of any formal health system. The relatively few ill patients who have any contact with the health services represent the "ears of the hippopotamus." Greatly intensified research activities and control of the intolerable burden of malaria are mandatory if economic development is to accelerate in Africa. In particular, support should be targeted to understanding and preventing malaria-induced anemia, hypoglycemia, effects on pregnancy, and neurologic and developmental impairment. To decrease and stop transmission of this intolerable scourge, there is an urgent need for malaria vaccines, newer drugs, and better vector control methods as well as the ability to improve current technologies and use them more efficiently. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Bldg 31,Room B2C39,31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. EM jbreman@nih.gov NR 113 TC 589 Z9 609 U1 3 U2 36 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN-FEB PY 2001 VL 64 IS 1-2 BP 1 EP 11 PG 11 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 443WC UT WOS:000169364300005 PM 11425172 ER PT J AU Breman, JG AF Breman, JG TI The intolerable burden of malaria: A new look at the numbers SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material C1 NIH, Fogarty Int Ctr, Multilateral Initiat Malaria, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Multilateral Initiat Malaria, Bethesda, MD 20892 USA. NR 0 TC 13 Z9 13 U1 1 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN-FEB PY 2001 VL 64 IS 1-2 BP I EP I PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 443WC UT WOS:000169364300001 ER PT J AU Breman, JG Egan, A Keusch, GT AF Breman, JG Egan, A Keusch, GT TI Introduction and summary - The intolerable burden of malaria: A new look at the numbers SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material ID PLASMODIUM-FALCIPARUM; CHLOROQUINE; MORTALITY; AFRICA; MORBIDITY; CHILDREN; EFFICACY C1 NIH, Fogarty Int Ctr, Div Int Training & Res, Multilateral Initiat Malaria, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Div Int Training & Res, Multilateral Initiat Malaria, Bldg 31,Room B2C39,31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. NR 24 TC 111 Z9 111 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN-FEB PY 2001 VL 64 IS 1-2 BP IV EP VII PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 443WC UT WOS:000169364300004 PM 11425185 ER PT J AU Murphy, SC Breman, JG AF Murphy, SC Breman, JG TI Gaps in the childhood malaria burden in Africa: Cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEVERE FALCIPARUM-MALARIA; LOW BIRTH-WEIGHT; PLASMODIUM-FALCIPARUM; CLINICAL-DIAGNOSIS; MALAWIAN CHILDREN; RURAL MALAWI; WEST-AFRICA; BLOOD-TRANSFUSIONS; RISK-FACTORS AB Evaluations of the African childhood malaria burden do not fully quantify the contributions of cerebral malaria (CM), CM-associated neurological sequelae, malarial anemia, respiratory distress, hypoglycemia, and pregnancy-related complications. We estimated the impact of these malaria manifestations on members of the African population < 5 years old. Calculations were based on an extensive literature review that used National Library of Medicine search engines, other bibliographic sources, and demographic data. In sub-Saharan Africa, CM annually affects 575,000 children < 5 years of age and 110,000 (similar to 19% case fatality rate [CFR]) die. Childhood survivors of CM experience developmental and behavioral impairments: each year, 9,000-19,000 children (> 2%, of survivors of CM) < 5 years of age in Africa experience neurological complications lasting > 6 months. Severe malarial anemia heavily burdens hospitals with rising admission and CFRs and with treatments that are complicated by limited and sometimes contaminated blood supplies. Severe malarial anemia occurs 1.42-5.66 million rimes annually and kills 190,000-974,000 (> 13% CFR) children ( 5 years of age annually. Respiratory distress, hypoglycemia, and overlapping clinical manifestations cause 1.12-1.99 million cases and > 225,000 (> 18% CFR) additional deaths among African children with malaria. Maternal, placental, or fetal malaria infection during pregnancy adversely affects development and survival of fetuses and newborns through low birth weight (LBW), maternal anemia, and possibly abortion and stillbirth. Between 167,000 and 967,000 cases of malaria-associated LBW occur yearly; malaria-induced LBW kills 62,000-363,000 (> 38% CFR) newborns each year. All the gaps in the burden comprise 0.4-1.7 million deaths annually, > 50% of which are due to severe malarial anemia. These malaria-induced medical problems constitute major clinical, public health, and research challenges in that they may contribute to more than double the mortality than is generally acknowledged. C1 NIH, Fogarty Int Ctr, Div Int Training & Res, Bethesda, MD 20892 USA. Iowa State Univ, Dept Vet Microbiol & Prevent Med, Ames, IA USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Div Int Training & Res, Bldg 31,Room B2C39,31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. NR 93 TC 204 Z9 208 U1 2 U2 8 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN-FEB PY 2001 VL 64 IS 1-2 BP 57 EP 67 PG 11 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 443WC UT WOS:000169364300011 PM 11425178 ER PT J AU Mendis, K Sina, BJ Marchesini, P Carter, R AF Mendis, K Sina, BJ Marchesini, P Carter, R TI The neglected burden of Plasmodium vivax malaria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TUMOR-NECROSIS-FACTOR; PAPUA-NEW-GUINEA; FALCIPARUM-MALARIA; SRI-LANKA; ENDEMIC REGION; EPIDEMIOLOGY; CHLOROQUINE; TRANSMISSION; RESISTANCE; POPULATION AB We estimate that the global burden of malaria due to Plasmodium vivax is similar to 70-80 million cases annually. Probably similar to 10-20% of the world's cases of P. vivax infection occur in Africa, south of the Sahara. In eastern and southern Africa, P. vivax represents around 10% of malaria cases but < 1% of cases in western and central Africa. Outside of African, P. vivax accounts for > 50% of all malaria cases. About 80-90% of P. vivax outside of Africa occurs in the Middle East, Asia, and the Western Pacific, mainly in the most tropical regions, and 10-15% in Central and South America. Because malaria transmission rates are low in most regions where P. vivax is prevalent, the human populations affected achieve little immunity to this parasite; as a result, in these regions, P. vivax infections affect people of all ages. Although the effects of repeated attacks of P. vivax through childhood and adult life are only rarely directly lethal, they can have major deleterious effects on personal well-being, growth, and development, and on the economic performance at the individual, family, community, and national levels. Features of the transmission biology of P. vivax give this species greater resilience than the less robust Plasmodium falciparum,arum in the face of conditions adverse to the transmission of the parasites. Therefore, as control measures become more effective, the residual malaria burden is likely increasingly to become that of P. vivax. C1 World Hlth Org, Roll Back Malaria Project, CH-1211 Geneva 27, Switzerland. NIH, Fogarty Int Ctr, Multilateral Initiat Malaria Sectetariat, Bethesda, MD 20892 USA. Univ Edinburgh, Div Biol Sci, Inst Cell Anim & Populat Biol, Edinburgh EH9 2JR, Midlothian, Scotland. RP Mendis, K (reprint author), World Hlth Org, Roll Back Malaria Project, CH-1211 Geneva 27, Switzerland. NR 74 TC 601 Z9 615 U1 7 U2 37 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JAN-FEB PY 2001 VL 64 IS 1-2 BP 97 EP 106 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 443WC UT WOS:000169364300015 PM 11425182 ER PT J AU Allen, JP Litten, RZ Fertig, JB Sillanaukee, P AF Allen, JP Litten, RZ Fertig, JB Sillanaukee, P TI Carbohydrate-deficient transferrin: An aid to early recognition of alcohol relapse SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID GAMMA-GLUTAMYL-TRANSPEPTIDASE; DEPENDENT PATIENTS; DETECTING RELAPSE; CONSUMPTION; DRINKING; MARKER; SERUM AB Although the primary use of biochemical markers of heavy drinking is to assist in screening Jar alcohol problems, laboratory tests may also ain in early identification of relapse. This report reviews research findings on a new marker, carbohydrate deficient transferrin (CDT), in alcoholics receiving treatment or in follow-up. It also offers recommendations on how CDT may be employed by clinicians monitoring drinking status. C1 NIAAA, Div Clin & Prevent Res, Bethesda, MD 20892 USA. Oy Finnish Immunotechnol Ltd, Tampere, Finland. RP Allen, JP (reprint author), NIAAA, Div Clin & Prevent Res, Willco Bldg,Suite 505,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 20 TC 13 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2001 VL 10 SU S BP 24 EP 28 DI 10.1080/10550490190942498 PG 5 WC Substance Abuse SC Substance Abuse GA 412UN UT WOS:000167572900004 PM 11268818 ER PT J AU Dai, F Kelley, JA Zhang, HP Malinowski, N Kavlick, MF Lietzau, J Welles, L Yarchoan, R Ford, H AF Dai, F Kelley, JA Zhang, HP Malinowski, N Kavlick, MF Lietzau, J Welles, L Yarchoan, R Ford, H TI Fluorometric determination of 2 '-beta-fluoro-2 ',3 '-dideoxyadenosine 5 '-triphosphate, the active metabolite of a new anti-human immunodeficiency virus drug, in human lymphocytes SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE 2 '-beta-fluoro-2 ',3 '-dideoxyadenosine; 2 '-beta-fluoro-2 ',3 '-dideoxyadenosine; 5 '-triphosphate; HPLC; fluorescence; AIDS ID BLOOD MONONUCLEAR-CELLS; PERFORMANCE LIQUID-CHROMATOGRAPHY; ADENINE-NUCLEOTIDES; ZIDOVUDINE TRIPHOSPHATE; THERAPY; HIV; RADIOIMMUNOASSAY; PHOSPHORYLATION; ADENOSINE; INFECTION AB A sensitive precolumn derivatization method has been developed to measure the 5'-triphosphate of 2'-beta -fluoro-2',3'-dideoxyadenosine (F-ddA, lodenosine), a new anti-HIV drug, in human lymphocytes by HPLC using fluorescence detection. Reaction of chloroacetaldehyde with F-ddA triphosphate in extracts from human lymphocytes produces a highly fluorescent etheno adduct. This derivative is then separated and quantitated by reverse-phase paired-ion chromatography. Degradation of natural nucleic acid ribosides, such as ATP, using periodate oxidation simplifies the chromatogram and minimizes interference with detection of the target analyte. This method, modeled using cultured MOLT-4 T-lymphocytes, achieves a linear detector response for peak area measurements over the range 2.5 to 22.5 pmol (50-450 nM using 50 yl sample). Analyte recovery is greater than 90%, and the method achieves a limit of detection and limit of quantitation of 1.4 and 2.5 pmol per HPLC injection (50 mul sample containing cellular extract from 2.5 x 10(6) cells), respectively. Application of this method to measure F-ddATP in peripheral blood mononuclear cells from HIV-infected patients treated with F-ddA at 3.2 mg/kg twice daily for 22 days shows F-ddATP levels which range from 1.5 to 3.5 pmol/10(6) cells. (C) 2001 Academic Press. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Expt Retrovirol Sect, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Ford, H (reprint author), NCI, Med Chem Lab, FCRDC, NIH, Bldg 376,Room 109, Frederick, MD 21702 USA. NR 38 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 2001 VL 288 IS 1 BP 52 EP 61 DI 10.1006/abio.2000.4862 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 390ZC UT WOS:000166328800007 PM 11141306 ER PT J AU Blegen, H Ghadimi, BM Jauho, A Zetterberg, A Eriksson, E Auer, G Ried, T AF Blegen, H Ghadimi, BM Jauho, A Zetterberg, A Eriksson, E Auer, G Ried, T TI Genetic instability promotes the acquisition of chromosomal imbalances in T1b and T1c breast adenocarcinomas SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CANCER MORTALITY; DNA CONTENT; MAMMOGRAPHY; CARCINOMAS; REDUCTION; SURVIVAL; TUMORS; CELLS; P53 AB In order to evaluate biological and genetic properties of early breast carcinomas we analyzed microdissected tissue from 33 primary breast carcinomas stage T1b and T1c with respect to the nuclear DNA content, the expression pattern of Ki-67, cyclin A, p27(KIP1), p53 and p21(WAF1), and chromosomal gains and losses. The results show that T1b carcinomas (6-10 mm, n = 17) were frequently near-diploid (53%) with low proliferative activity and staining patterns of p53 and p21(WAF1) that suggest the presence of wild type protein. The majority (12/16) of the T1c tumors (11-20 mm), however, was aneuploid, and proliferative activity and p53 expression were increased. Larger tumor size correlated with an increasing number of chromosomal copy number changes and in particular with regional amplifications. High level copy number increases (amplifications), however, were found exclusively in the aneuploid tumors, Amplification events correlated with elevated cyclin A and reduced p27 expression, respectively. Our results suggest that the sequential acquisition of genomic imbalances during tumor progression is accelerated in aneuploid tumors, and may contribute to the increased malignancy potential. C1 NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Div Cellular & Mol Anal, SE-17176 Stockholm, Sweden. RP Ried, T (reprint author), NCI, Dept Genet, Div Clin Sci, NIH, Bldg 9,Rm 1N105,9 Mem Dr, Bethesda, MD 20892 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0921-8912 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2001 VL 22 IS 3 BP 123 EP 131 PG 9 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 465BM UT WOS:000170568400003 PM 11455031 ER PT J AU Macville, MVE Van der Laak, JAWM Speel, EJM Katzir, N Garini, Y Soenksen, D McNamara, G de Wilde, PCM Hanselaar, AGJM Hopman, AHN Ried, T AF Macville, MVE Van der Laak, JAWM Speel, EJM Katzir, N Garini, Y Soenksen, D McNamara, G de Wilde, PCM Hanselaar, AGJM Hopman, AHN Ried, T TI Spectral imaging of multi-color chromogenic dyes in pathological specimens SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE spectral imaging; Fourier-transform spectroscopy; multicolor; in situ hybridization; immunocytochemistry; bright-field microscopy; absorption; optical density; pathology ID IN-SITU HYBRIDIZATION; CERVICAL INTRAEPITHELIAL NEOPLASIA; INSITU HYBRIDIZATION; ABNORMALITIES; CYTOGENETICS; ABERRATIONS; DIAGNOSTICS; MICROSCOPY; TUMORS; CELLS AB We have investigated the use of spectral imaging for multicolor analysis of permanent cytochemical dyes and enzyme precipitates on cytopathological specimens. Spectral imaging is based on Fourier-transform spectroscopy and digital imaging. A pixel-by-pixel spectrum-based color classification is presented of single-, double-, and triple-color in situ hybridization for centromeric probes in T24 bladder cancer cells, and immunocytochemical staining of nuclear antigens Ki-67 and TP53 in paraffin-em bedded cervical brush material (AgarCyto). The results demonstrate that spectral imaging unambiguously identities three chromogenic dyes in a single bright-field microscopic specimen. Serial microscopic fields from the same specimen can be analyzed using a spectral reference library. We conclude that spectral imaging of multi-color chromogenic dyes is a reliable and robust method for pixel color recognition and classification. Our data further indicate that the use of spectral imaging (a) may increase the number of parameters studied simultaneously in pathological diagnosis, (b) may provide quantitative data (such as positive labeling indices) more accurately, and (c) may solve segmentation problems currently faced in automated screening of cell- and tissue specimens. C1 Univ Med Ctr St Radboud, Dept Pathol, Lab ISH, NL-6500 HB Nijmegen, Netherlands. NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ Maastricht, Dept Mol Cell Biol, Maastricht, Netherlands. Appl Spectral Imaging, Migdal Haemeq, Israel. Aperio Technol, Carlsbad, CA USA. Childrens Hosp, Res Inst, Los Angeles, CA 90027 USA. RP Macville, MVE (reprint author), Univ Med Ctr St Radboud, Dept Pathol, Lab ISH, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI van der Laak, Jeroen/D-3057-2015 OI van der Laak, Jeroen/0000-0001-7982-0754 NR 26 TC 19 Z9 19 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0921-8912 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2001 VL 22 IS 3 BP 133 EP 142 PG 10 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 465BM UT WOS:000170568400004 PM 11455032 ER PT J AU Heiskanen, M Kononen, J Barlund, M Torhorst, J Sauter, G Kallioniemi, A Kallioniemi, O AF Heiskanen, M Kononen, J Barlund, M Torhorst, J Sauter, G Kallioniemi, A Kallioniemi, O TI CGH, cDNA and tissue microarray analyses implicate FGFR2 amplification in a small subset of breast tumors SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; COMPLEMENTARY-DNA MICROARRAY; CANCER CELL-LINES; MOLECULAR CLASSIFICATION; OVARIAN-CANCER; EXPRESSION; DISCOVERY; ONCOGENE; KINASE; GENES AB Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH). However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small-scale commercially available cDNA and CGH microarray for-mats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical Significance. According to CGH, the SUM-52 breast cancer cell line harbors several high-level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2) gene has been localized. High level amplification of FGFR2 in SUM-52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40-fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue) experiments revealed high-level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Tampere, Inst Med Technol, Canc Genet Lab, Tampere 33521, Finland. Tampere Univ Hosp, Tampere 33521, Finland. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. RP Heiskanen, M (reprint author), Compugen Inc, 9700 Great Seneca Hwy, Rockville, MD 20850 USA. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Anne/0000-0003-3552-8158 NR 29 TC 39 Z9 41 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0921-8912 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2001 VL 22 IS 4 BP 229 EP 234 PG 6 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 495LR UT WOS:000172343100006 PM 11564899 ER PT J AU Yordanov, AT Yamada, K Krishna, MC Mitchell, JB Woller, E Cloninger, M Brechbiel, MW AF Yordanov, AT Yamada, K Krishna, MC Mitchell, JB Woller, E Cloninger, M Brechbiel, MW TI Spin-labeled dendrimers in EPR imaging with low molecular weight nitroxides SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article ID ELECTRON-PARAMAGNETIC-RESONANCE; POLYNITROXYL-ALBUMIN; MURINE TUMOR; LIVING CELLS; REDUCTION C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. RI Yamada, Ken-ichi/E-6318-2012 NR 20 TC 20 Z9 20 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2001 VL 40 IS 14 BP 2690 EP 2692 DI 10.1002/1521-3773(20010716)40:14<2690::AID-ANIE2690>3.0.CO;2-0 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 454TR UT WOS:000169988300030 ER PT J AU Shibata, N Tarui, T Doi, Y Kirk, KL AF Shibata, N Tarui, T Doi, Y Kirk, KL TI Synthesis of fluorogypsetin and fluorobrevianamide E by a novel fluorination - Cyclization of cyclo-L-Trp-L-AAs SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article ID VAR INCURVATA IFO-9228; ENANTIOSELECTIVE FLUORINATION; DEOXYBREVIANAMIDE-E; BREVIANAMIDE-A; ACYL-COA; GYPSETIN; BIOSYNTHESIS; DERIVATIVES; HIMASTATIN; INHIBITOR C1 Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Toyama 9300194, Japan. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shibata, N (reprint author), Toyama Med & Pharmaceut Univ, Fac Pharmaceut Sci, Sugitani 2630, Toyama 9300194, Japan. EM nozshiba@ms.toyama-mpu.ac.jp NR 38 TC 59 Z9 59 U1 0 U2 8 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2001 VL 40 IS 23 BP 4461 EP + DI 10.1002/1521-3773(20011203)40:23<4461::AID-ANIE4461>3.0.CO;2-E PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 500KP UT WOS:000172626600030 ER PT J AU Li, J Jeong, S Esser, L Harran, PG AF Li, J Jeong, S Esser, L Harran, PG TI Total synthesis of nominal diazonamides - Part 1: Convergent preparation of the structure proposed for (-)-diazonamide A SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article ID TYROSINE-DERIVED BENZOFURANONE; ANTITUMOR AGENT DIAZONAMIDE; OXAZOLE FRAGMENT; ZIRCONOCENE; PORTION; MODEL; CORE C1 Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Harran, PG (reprint author), Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. NR 42 TC 125 Z9 127 U1 3 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2001 VL 40 IS 24 BP 4765 EP 4770 DI 10.1002/1521-3773(20011217)40:24<4765::AID-ANIE4765>3.0.CO;2-1 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 506JR UT WOS:000172967200055 ER PT J AU Li, J Burgett, AWG Esser, L Amezcua, C Harran, PG AF Li, J Burgett, AWG Esser, L Amezcua, C Harran, PG TI Total synthesis of nominal diazonamides - Part 2: On the true structure and origin of natural isolates SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE antitumor agents; natural products; photochemistry; rearrangements; total synthesis C1 Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Harran, PG (reprint author), Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. NR 6 TC 123 Z9 124 U1 2 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2001 VL 40 IS 24 BP 4770 EP + DI 10.1002/1521-3773(20011217)40:24<4770::AID-ANIE4770>3.0.CO;2-T PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 506JR UT WOS:000172967200056 ER PT J AU Liang, R Igarashi, H Tsuzuki, T Nakabeppu, Y Sekiguchi, M Kasprzak, KS Shiao, YH AF Liang, R Igarashi, H Tsuzuki, T Nakabeppu, Y Sekiguchi, M Kasprzak, KS Shiao, YH TI Presence of potential nickel-responsive element(s) in the mouse MTH1 promoter SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE nickel; MTH1 gene; promoter; responsive element; gene expression ID OXIDATIVE DNA-DAMAGE; MALE F344 RATS; GENE-EXPRESSION; MAMMALIAN-CELLS; ALU FUNCTION; BASE DAMAGE; Z-FORM; CARCINOGENESIS; NUCLEOTIDE; INDUCTION AB The murine MTH1 gene codes for MTH1, an 8-oxo-2'-deoxyguanosine 5'-triphosphate pyrophospho-hydrolase (8-oxo-dGTPase) which hydrolyzes 8-oxo-dGTP, a promutagenic product of reactive oxygen species' attack on the nucleotide pool. This gene is regulated by oxidative stress. Therefore, we hypothesized that MTH1 expression can be affected by carcinogenic nickel(II), known to induce such stress. Three plasmid constructs, carrying different upstream regions of the mouse MTH1 and the chloramphenicol acetyltransferase (CAT) reporter gene, were transiently transfected into NIH 3T3 cells and the CAT protein was measured in nickel(II) acetate-treated and untreated cells. Nickel concentration-dependent increase of CAT protein level was observed for low Ni(II) concentrations, up to 400 muM NI(II), in cells transfected with pHI103 plasmid (-5969 to +530 of the MTH1 sequence) only. Cells transfected with the pHI104 (-1331 to +530) or pHI108 (-151 to +530) plasmids did not respond to nickel(II) whatsoever. This finding demonstrated that the MTH1 sequence between -5969 and -1331 contained element(s) responsive to nickel(LI) treatment. DNA sequencing revealed the presence of AP-1, NF-kappaB, and ATF-1 binding sites in both the -5969 to -1331 and -1331 to +530 regions. In contrast, two (CA)n repeats (-5642 to -5582 and -2078 to -2031), a family of B2 (-5428 to -5247) and B1 (-4559 to -4420) short interspersed repeated elements, and an (AT)n repeat (-5243 to -5230) were identified only in the -5969 to -1331 sequence. The results suggest that up-regulation of murine MTH1 expression by nickel(II) is controlled by the repeat sequences, potential candidates for nickel-responsive elements. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Kyushu Univ, Med Inst Bioregulat, Dept Biochem, Fukuoka 812, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Med Biophys & Radiat Biol, Fukuoka 812, Japan. Japan Sci & Technol Corp, CREST, Sawara Ku, Fukuoka, Japan. Fukuoka Dent Coll, Dept Biol, Fukuoka, Japan. Fukuoka Dent Coll, Frontier Res Ctr, Fukuoka, Japan. RP Shiao, YH (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205, Frederick, MD 21702 USA. RI Nakabeppu, Yusaku/A-8902-2011 NR 34 TC 3 Z9 3 U1 0 U2 0 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD JAN PY 2001 VL 31 IS 1 BP 91 EP 98 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 395HN UT WOS:000166575100006 PM 11314867 ER PT J AU Lyon, GR AF Lyon, GR TI Acceptance of the Samuel Torrey Orton Award November 2000, Washington, DC SO ANNALS OF DYSLEXIA LA English DT Editorial Material C1 NICHHD, Child Dev & Behav Branch, Bethesda, MD 20892 USA. RP Lyon, GR (reprint author), NICHHD, Child Dev & Behav Branch, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU INT DYSLEXIA ASSOC PI BALTIMORE PA CHESTER BUILDING, STE 382, 8600 LA SALLE RD, BALTIMORE, MD 21286-2044 USA SN 0736-9387 J9 ANN DYSLEXIA JI Ann. Dyslexia PY 2001 VL 51 BP 3 EP 7 PG 5 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 541YY UT WOS:000175015700003 ER PT J AU Chiu, BCH Lynch, CF Cerhan, JR Cantor, KP AF Chiu, BCH Lynch, CF Cerhan, JR Cantor, KP TI Cigarette smoking and risk of bladder, pancreas, kidney, and colorectal cancers in Iowa SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cigarette smoking; neoplasms; bladder; kidney; pancreas; colon; rectum ID RENAL-CELL CARCINOMA; UNITED-STATES; ALCOHOL-CONSUMPTION; URINARY-BLADDER; TOBACCO SMOKING; BLACKS; WHITES; ASSOCIATIONS; OCCUPATION; BEVERAGES AB PURPOSE: Aid-rough there are numerous reports on the effects of cigarette smoking and cancer, they have infrequently compared risks at more than one cancer site after multivariate adjustment. We analyzed data from a population-based case-control study that included five anatomic sites to evaluate the association between cigarette smoking and each cancer site and to rank the associations by site. METHODS: Study respondents included 1452 bladder. 406 kidney, 376 pancreatic, 685 colon, and 655 rectal cancer cases, as well as 2434 population controls. A self-administered questionnaire was used to collect information on cigarette smoking and other potential confounders including occupation, drinking water source, and dietary practices. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), after adjustment for age, total energy intake, and other site- and sex-specifrc confounders. RESULTS: In both sexes, cigarette smoking (ever vs. never) was associated with risk of bladder cancer (OR = 2.5: 95% CI, 2.0-3.1 for males; OR = 2.7; 2.0-3.6 for females) and pancreatic cancer (OR = 1.8; 1.2-2.8 for males; OR = 2.1; 1.4-3.1 for females). Cigarette smoking also increased the risk of kidney cancer among males (OR = 1.8; 1.3-2.7), and to a lesser degree, among females (OR = 1.2; 0.8-1.8). No association was found for colon or rectal cancer in either sex. CONCLUSIONS: Cigarette smoking increased the risk of bladder, kidney, and pancreatic cancer in men and women. The rankings of multivariate-adjusted ORs from highest to lowest were bladder, pancreas, kidney, and colorectum, with little difference between men and women. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Nebraska, Med Ctr, Dept Prevent & Social Med, Omaha, NE 68198 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Bethesda, MD USA. RP Chiu, BCH (reprint author), Univ Nebraska, Med Ctr, Dept Prevent & Social Med, 984350 Nebraska Med Ctr, Omaha, NE 68198 USA. FU NCI NIH HHS [K07 CA01181, N01-CP-51026, N01-CP-85614] NR 44 TC 59 Z9 60 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2001 VL 11 IS 1 BP 28 EP 37 DI 10.1016/S1047-2797(00)00175-7 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 386QU UT WOS:000166073700005 PM 11164117 ER PT J AU Doody, MM Hayes, HM Bilgrad, R AF Doody, MM Hayes, HM Bilgrad, R TI Comparability of National Death Index Plus and standard procedures for determining causes of death in epidemiologic studies SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cause of death; death certificates; epidemiologic methods ID MORTALITY AB PURPOSE: To determine whether causes of death obtained through National Death Index (NDI) Plus are comparable to those obtained by requesting death certificates from start Vital statistics offices and having deaths coded by contractor nosologists. METHODS: The authors compared underlying cause of death codes obtained from NDI Plus with those assigned by contractor nosologists for a sample of 250 known decedents. RESULTS: The underlying cause of death codes differed for 18 (7%) of 249 successful matches. Independent coding by an expert National Center for Health Statistics (NCHS) nosologist trainer revealed that seven of these had an NDI Plus code that matched the code provided by the NCHS nosologist and a contractor nosologist code that did not match the NCHS nosologist code, seven had a contractor nosologist code that matched the NCHS nosologist code and an NDI Plus code that did not match the NCHS nosologist code, and four had both an NDI Plus and a contractor nosologist: code that did not match the NCHS nosologist code. The level of disagreement with the NCHS nosologist and the organ systems involved mere similar fur NDI Plus and the contractor nosologist. CONCLUSIONS: The authors report that NDI Plus provides comparable information within a substantially shorter time period for most states and, for known decedents, at about half the cost of standard procedures. (C) 2000 Elsevier Science me. All rights reserved. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Doody, MM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7088, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-33013] NR 7 TC 58 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2001 VL 11 IS 1 BP 46 EP 50 DI 10.1016/S1047-2797(00)00177-0 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 386QU UT WOS:000166073700007 PM 11164119 ER PT J AU Rotimi, CN Dunston, GM Berg, K Akinsete, O Amoah, A Owusu, S Acheampong, J Boateng, K Oli, J Okafor, G Onyenekwe, B Osotimehin, B Abbiyesuku, F Johnson, T Fasanmade, O Furbert-Harris, P Kittles, R Vekich, M Adegoke, O Bonney, G Collins, F AF Rotimi, CN Dunston, GM Berg, K Akinsete, O Amoah, A Owusu, S Acheampong, J Boateng, K Oli, J Okafor, G Onyenekwe, B Osotimehin, B Abbiyesuku, F Johnson, T Fasanmade, O Furbert-Harris, P Kittles, R Vekich, M Adegoke, O Bonney, G Collins, F TI In search of susceptibility genes for type 2 diabetes in West Africa: The design and results of the first phase of the AADM study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE genes; type 2 diabetes; West Africa; sib-pairs; linkage ID IMPAIRED GLUCOSE-TOLERANCE; PREVALENCE; MELLITUS; LINKAGE; ADULTS; TRAITS; TWINS; PAIRS; POPULATION; AMERICANS AB PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 mi of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Howard Univ, Natl Human Genome Ctr, Coll Med, Div Genet Epidemiol, Washington, DC 20059 USA. NHGRI, NIH, Bethesda, MD USA. Univ Ghana, Sch Med, Dept Med, Accra, Ghana. Univ Sci & Technol, Dept Med, Kumasi, Ghana. Univ Nigeria, Teaching Hosp, Dept Med, Enugu, Nigeria. Univ Ibadan, Coll Hosp, Dept Chem Pathol, Ibadan, Nigeria. Univ Lagos, Coll Med, Endocrine & Metab Unit, Lagos, Nigeria. Loyola Univ, Med Ctr, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. RP Rotimi, CN (reprint author), Howard Univ, Natl Human Genome Ctr, Coll Med, Div Genet Epidemiol, 2216 6th St NW,Suite 205, Washington, DC 20059 USA. FU FIC NIH HHS [3T37TW00041-03S2] NR 36 TC 42 Z9 42 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JAN PY 2001 VL 11 IS 1 BP 51 EP 58 DI 10.1016/S1047-2797(00)00180-0 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 386QU UT WOS:000166073700008 PM 11164120 ER PT J AU Merlo, F AF Merlo, F TI Epidemiological evidence on the carcinogenicity of silica: Factors in scientific judgement SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Letter C1 Natl Canc Inst, I-16132 Genoa, Italy. RP Merlo, F (reprint author), Natl Canc Inst, Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 3 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD JAN PY 2001 VL 45 IS 1 BP 83 EP 83 DI 10.1016/S0003-4878(00)00063-6 PG 1 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 394TF UT WOS:000166538800010 PM 11302110 ER PT J AU Saif, MW Little, RF Hamilton, JM Allegra, CJ Wilson, WH AF Saif, MW Little, RF Hamilton, JM Allegra, CJ Wilson, WH TI Reactivation of chronic hepatitis B infection following intensive chemotherapy and successful treatment with lamivudine: A case report and review of the literature SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; chronic hepatitis B; corticosteroids; fulminant hepatitis; immunosuppression; interferon; lamivudine (3TC); 'rebound effect'; plasma exchange ID BONE-MARROW TRANSPLANTATION; CHRONIC ACTIVE HEPATITIS; FULMINANT-HEPATITIS; VIRUS-INFECTION; IMMUNOSUPPRESSIVE THERAPY; HEMATOLOGIC MALIGNANCIES; PRECORE REGION; WITHDRAWAL; CARRIERS; MUTATIONS AB Background: Hepatitis B virus reactivation has been reported in cancer patients following administration of chemotherapy or immunosuppressive therapy and may result in liver damage of varying degrees of severity. Although treatment is supportive in nature, lamivudine, a nucleoside analogue has been found to suppress HBV replication as evidenced by reports of 13 cases in the medical literature. Patients and methods: We report a patient who achieved a successful outcome with lamivudine following reactivation of HBV during combination chemotherapy for non-Hodgkin's lymphoma, and provide a brief overview of the literature including the 13 published case reports. Results: Lamivudine therapy resulted in clinical improvement as well as in normalization of liver function tests and coagulation profile. Conclusions: Lamivudine has been found to suppress HBV replication manifested both by histology and serum HBV-DNA levels in chronic carriers of HBV who developed reactivation of hepatic disease following chemotherapy. Physicians caring for such patients should be able to recognize this clinical challenge, and lamivudine should be considered. C1 NCI, Med Branch, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Saif, MW (reprint author), NCI, Med Branch, Natl Naval Med Ctr, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 33 TC 18 Z9 19 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2001 VL 12 IS 1 BP 123 EP 129 PG 7 WC Oncology SC Oncology GA 396AV UT WOS:000166614900028 PM 11249039 ER PT J AU Grem, JL Yee, LK Schuler, B Hamilton, JM Chen, AP Chabuk, C Grollman, F Grabenc, M Allegra, CJ Takimoto, CH AF Grem, JL Yee, LK Schuler, B Hamilton, JM Chen, AP Chabuk, C Grollman, F Grabenc, M Allegra, CJ Takimoto, CH TI N-(phosphonacetyl)-L-aspartate and calcium leucovorin modulation of fluorouracil administered by constant rate and circadian pattern of infusion over 72 hours in metastatic gastrointestinal adenocarcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE biochemical modulation; chronomodulation; fluorouracil; gastrointestinal cancer; PALA ID PHASE-I; BIOCHEMICAL MODULATION; COLORECTAL-CANCER; FOLINIC ACID; 5-FLUOROURACIL; COMBINATION; FLUOROPYRIMIDINES; OXALIPLATIN; CARCINOMA; DELIVERY AB Background: We have reported that N-(phosphonacetyl)-L-aspartic acid (PALA) 1266 mg/m(2) can safely be given 24 hours prior to the start of a 72-hour infusion of fluorouracil (FUra) and leucovorin (LV) at doses of 2000 and 500 mg/m(2)/day. Since inhibition of aspartate carbamoyltransferase (ACTase) activity was evident 4 hours post PALA, we wished to evaluate PALA given 1 hour prior to FUra. Further, we studied the toxicity and pharmacokinetics with FUra given by either fixed-or variable-rate infusion. Patients and methods: Twenty-seven patients with gastrointestinal tract adenocarcinomas were treated with PALA 1266 mg/m(2)/15 min followed by a 72-hour infusion of FUra and LV (1750 & 500 mg/m(2)/day) given by fixed- or variable-rate (peak at 4:00 A.M.). Results: Clinical toxicity was similar in two consecutive cycles in 17 patients receiving fixed- and variable-rate infusion at the same FUra dose. Overall, grade 3 stomatitis and hand-foot syndrome occurred in 12% and 4% patients receiving fixed- and in 16% and 10.5% of patients receiving variable-rate infusions. Six of 24 evaluable patients (25%) had a partial response. The profile of FUra plasma levels (Cp) over a 24-hour period during fixed- and variable-rate infusions were strikingly different, but the average Cp and area under the concentration-time curves were comparable. ACTase activity was significantly decreased at 4 and 24 hours after PALA (12% and 18% of baseline; P < 0.001), but enzyme activity had recovered to 40% by 72 hours. Conclusions: This regimen was active and well tolerated with similar toxicities with FUra given by either fixed- or variable rate infusion. PALA 1266 mg/m(2) significantly inhibited ACTase activity for at least 24 hours. C1 Natl Naval Med Res Inst, NCI, Navy Med Branch, Bethesda, MD 20889 USA. Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), Natl Naval Med Res Inst, NCI, Navy Med Branch, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM gremj@mail.nih.gov NR 28 TC 0 Z9 0 U1 0 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2001 VL 12 IS 11 BP 1581 EP 1587 DI 10.1023/A:1013185125186 PG 7 WC Oncology SC Oncology GA 499TJ UT WOS:000172586200019 PM 11822758 ER PT J AU Weiser, TS Ohnmacht, GA Guo, ZS Fischette, MR Chen, GA Hong, JA Nguyen, DM Schrump, DS AF Weiser, TS Ohnmacht, GA Guo, ZS Fischette, MR Chen, GA Hong, JA Nguyen, DM Schrump, DS TI Induction of MAGE-3 expression in lung and esophageal cancer cells SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 2000 CL FT LAUDERDALE, FLORIDA SP Soc Thorac Surg ID CHROMOBACTERIUM-VIOLACEUM NO-968; CYTOTOXIC T-LYMPHOCYTES; BLOOD MONONUCLEAR-CELLS; GENE-EXPRESSION; DNA METHYLATION; TUMOR-ANTIGENS; MELANOMA; LINES; DEMETHYLATION; CONNECTION AB Background. Although MAGE-3 has been detected in approximately 40% of lung and esophageal cancers, expression of this cancer testis antigen appears to be below the threshold for immune recognition in patients with these malignancies. The aim of this study was to determine if the demethylating agent, 5-Aza-2'-deoxycytidine (DAC) and if the histone deacetylase inhibitor Depsipeptide FR901228 (DP) could enhance MAGE-3 expression in lung and esophageal cancer cells. Methods. Eleven lung and esophageal cancer lines and cultured normal human bronchial epithelial (NHBE) cells were exposed to normal media (NM), DAC, DP, or combination DAC/DP at varying concentrations and exposure durations. MAGE-3 expression was evaluated by quantitative RT-PCR (TaqMan) and immunohistochemistry techniques. Trypan blue exclusion techniques were used to examine the proliferation of cancer cells after drug exposure. Results. Relative to untreated controls, MAGE-3 expression was enhanced 32-fold (range 3.9 to 110) by DAC alone (0.1 mu mol/L x 72 h), 2.1-fold (0.4 to 4.2) by DP alone (25 ng/mL x 6h), and 57-fold (4.6 to 209) by sequential DAC/DP exposure. Increased MAGE-3 mRNA copy numbers coincided with enhanced protein levels in these cells. MAGE-3 expression persisted after drug exposure. flow cytometry confirmed the presence of functional HLA class I expression in these cells. Sequential DAC/DP treatment mediated pronounced growth inhibition in cancer cells but not NHBE. Conclusions. Sequential DAC/DP treatment may be a novel strategy to simultaneously augment MAGE-3 expression and induce growth arrest in thoracic malignancies. (Ann Thorac Surg 2001;71:295-302) (C) 2001 by The Society of Thoracic Surgeons. C1 NCI, Thorac Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Bldg 10,Room 2B-07,10 Ctr Dr, Bethesda, MD 20892 USA. NR 37 TC 59 Z9 62 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2001 VL 71 IS 1 BP 295 EP 301 DI 10.1016/S0003-4975(00)02421-8 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 393FB UT WOS:000166457600069 PM 11216765 ER PT J AU Rhee, SG AF Rhee, SG TI Regulation of phosphoinositide-specific phospholipase C SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE phospholipase C-beta; phospholipase-gamma; phospholipase C-delta; phospholipase C-epsilon; phosphoinositides ID GROWTH-FACTOR RECEPTOR; BETA-GAMMA-SUBUNITS; PLECKSTRIN HOMOLOGY DOMAIN; SMOOTH-MUSCLE CELLS; MEDIATED TYROSINE PHOSPHORYLATION; PROTEIN ALPHA-SUBUNITS; BASIC-AMINO-ACIDS; T-CELL; BINDING-SITE; AUTOPHOSPHORYLATION SITES AB Eleven distinct isoforms of phosphoinositide-specific phospholipase C (PLC), which are grouped into four subfamilies (beta, gamma, delta, and epsilon), have been identified in mammals. These isozymes catalyze the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2] to inositol 1,4,5-trisphosphate and diacylglycerol in response to the activation of more than 100 different cell surface receptors. All PLC isoforms contain X and Y domains, which form the catalytic core, as well as various combinations of regulatory domains that are common to many other signaling proteins. These regulatory domains serve to target PLC isozymes to the vicinity of their substrate or activators through protein-protein or protein-lipid interactions. These domains (with their binding partners in parentheses or brackets) include the pleckstrin homology (PH) domain [PtdIns(3)P, beta gamma subunits of G proteins] and the COOH-terminal region including the C2 domain (GTP-bound alpha subunit of G(q)) Of PLC-beta; the PH domain [PtdIns(3,4,5)P-3] and Src homology 2 domain [tyrosine-phosphorylated proteins, PtdIns(3,4,5)P-3] of PLC-gamma; the PH domain [PtdIns(4,5)P-2] and C2 domain (Ca2+) of PLC-delta; and the Pas binding domain (GTP-bound Ras) of PLC-epsilon. The presence of distinct regulatory domains in PLC isoforms renders them susceptible to different modes of activation. Given that the partners that interact with these regulatory domains of PLC isozymes are generated or eliminated in specific regions of the cell in response to changes in receptor status, the activation and deactivation of each PLC isoform are Likely highly regulated processes. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 129 TC 976 Z9 1005 U1 7 U2 52 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 2001 VL 70 BP 281 EP 312 DI 10.1146/annurev.biochem.70.1.281 PG 32 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 455DK UT WOS:000170012100009 PM 11395409 ER PT J AU Guttmacher, AE AF Guttmacher, AE TI Human genetics on the Web SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS LA English DT Review DE Internet; World Wide Web; computers; genomics; medical genetics AB Use of the World Wide Web ("the web") and our knowledge of human genetics are both currently expanding rapidly. By allowing swift, universal, and free access to data, the web has already played an important role in human genetics research. It has also begun to change the way that information is shared in clinical genetics and, to a lesser degree, affect how education in human genetics occurs. There are scores of web sites helpful to those interested in either research or clinical aspects of human genetics. The web and related communication technologies should continue to play increasingly important roles in human genetics. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Guttmacher, AE (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. NR 6 TC 18 Z9 18 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2001 VL 2 BP 213 EP 233 DI 10.1146/annurev.genom.2.1.213 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA 476AQ UT WOS:000171204200010 PM 11701649 ER PT J AU Sacks, D Kamhawi, S AF Sacks, D Kamhawi, S TI Molecular aspects of parasite-vector and vector-host interactions in Leishmaniasis SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE sand flies; vector biology; lipophosphoglycan; saliva ID FLY LUTZOMYIA-LONGIPALPIS; SANDFLY PHLEBOTOMUS-PAPATASI; DIFFERENT DEVELOPMENTAL STAGES; NITRIC-OXIDE PRODUCTION; SALIVARY-GLAND LYSATE; PERITROPHIC MEMBRANE; CUTANEOUS LEISHMANIASIS; SURFACE LIPOPHOSPHOGLYCAN; MAJOR PROMASTIGOTES; BLOODMEAL DIGESTION AB Leishmania-sand fly interactions are reviewed in the context of the potential barriers to the complete development of the parasite that exist within the midgut environment of phlebotomine flies and the molecular adaptations that the parasite has evolved that permit the development of transmissible infections to proceed. Cell surface and secreted phosphoglycans protect the parasite from the proteolytic activities of the blood-fed midgut, mediate attachment to the gut wall in order to maintain infection during excretion of the bloodmeal, and contribute to the formation of a biological plug in the anterior gut that may promote transmission by bite. The importance of vector saliva in modulating the host response to transmitted parasites is also reviewed. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 133 TC 193 Z9 202 U1 2 U2 22 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2001 VL 55 BP 453 EP 483 DI 10.1146/annurev.micro.55.1.453 PG 33 WC Microbiology SC Microbiology GA 485BA UT WOS:000171732600019 PM 11544364 ER PT J AU Koonin, EV Makarova, KS Aravind, L AF Koonin, EV Makarova, KS Aravind, L TI Horizontal gene transfer in prokaryotes: Quantification and classification SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE phylogenetic analysis; gene acquisition; gene displacement; adaptation; orthologs ID TRANSFER-RNA SYNTHETASES; RESTRICTION-MODIFICATION SYSTEMS; GENOME SEQUENCE; BACTERIAL HYPERTHERMOPHILES; DEINOCOCCUS-RADIODURANS; PHYLOGENETIC CLASSIFICATION; EVOLUTIONARY GENOMICS; THERMOTOGA-MARITIMA; CHROMATIN-STRUCTURE; PROTEIN SEQUENCES AB Comparative analysis of bacterial, archaeal, and eukaryotic genomes indicates that a significant fraction of the genes in the prokaryotic genomes have been subject to horizontal transfer, In some cases, the amount and source of horizontal gene transfer can be linked to an organism's lifestyle. For example, bacterial hyperthermophiles seem to have exchanged genes with archaea to a greater extent than other bacteria, whereas transfer of certain classes of eukaryotic genes is most common in parasitic and symbiotic bacteria. Horizontal transfer events can be classified into distinct categories of acquisition of new genes, acquisition of paralogs of existing genes, and xenologous gene displacement whereby a gene is displaced by a horizontally transferred ortholog from another lineage (xenolog). Each of these types of horizontal gene transfer is common among prokaryotes, but their relative contributions differ in different lineages. The fixation and long-term persistence of horizontally transferred genes suggests that they confer a selective advantage on the recipient organism. In most cases, the nature of this advantage remains unclear, but detailed examination of several cases of acquisition of eukaryotic genes by bacteria seems to reveal the evolutionary forces involved. Examples include isoleucyl-tRNA synthetases whose acquisition from eukaryotes by several bacteria is linked to antibiotic resistance, ATP/ADP translocases acquired by intracellular parasitic bacteria, Chlamydia and Rickettsia, apparently from plants, and proteases that may be implicated in chlamydial pathogenesis. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Pathol, Bethesda, MD 20814 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov; makarova@ncbi.nlm.nih.gov; aravind@ncbi.nlm.nih.gov NR 119 TC 592 Z9 627 U1 17 U2 131 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2001 VL 55 BP 709 EP 742 DI 10.1146/annurev.micro.55.1.709 PG 34 WC Microbiology SC Microbiology GA 485BA UT WOS:000171732600027 PM 11544372 ER PT J AU Cumming, BG DeAngelis, GC AF Cumming, BG DeAngelis, GC TI The physiology of stereopsis SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE binocular vision; disparity; striate cortex; extrastriate cortex; depth perception ID CATS VISUAL-CORTEX; RANDOM-DOT STEREOGRAMS; BINOCULAR DEPTH-PERCEPTION; DISPARITY-SELECTIVE NEURONS; MACAQUE STRIATE CORTEX; EXTRASTRIATE AREA MST; RECEPTIVE-FIELD; SIMPLE CELLS; NEURAL MECHANISMS; STEREOSCOPIC VISION AB Binocular disparity provides the visual system with information concerning the three-dimensional layout of the environment. Recent physiological studies in the primary visual cortex provide a successful account of the mechanisms by which single neurons are able to signal disparity. This work also reveals that additional processing is required to make explicit the types of signal required for depth perception (such as the ability to match features correctly between the two monocular images). Some of these signals, such as those encoding relative disparity, are found in extrastriate cortex. Several other lines of evidence also suggest that the link between perception and neuronal activity is stronger in extrastriate cortex (especially MT) than in the primary visual cortex. C1 Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. RP Cumming, BG (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NR 132 TC 211 Z9 214 U1 7 U2 40 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2001 VL 24 BP 203 EP 238 DI 10.1146/annurev.neuro.24.1.203 PG 36 WC Neurosciences SC Neurosciences & Neurology GA 456XY UT WOS:000170109100008 PM 11283310 ER PT J AU Sueyoshi, T Negishi, M AF Sueyoshi, T Negishi, M TI Phenobarbital response elements of cytochrome P450 genes and nuclear receptors SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE gene regulation; signal transduction; nuclear translocation; CAR; induction ID PREGNANE-X-RECEPTOR; CHICKEN CYP2H1 GENE; BARBITURATE-MEDIATED INDUCTION; MOUSE PRIMARY HEPATOCYTES; RAT-LIVER; BACILLUS-MEGATERIUM; TRANSCRIPTIONAL ACTIVATION; INDUCIBLE CYTOCHROME-P-450; 5'-FLANKING REGION; TRANSGENIC MICE AB Phenobarbital (PB) response elements are composed of various nuclear receptor (NR)-binding sites. A 51-bp distal element PB-responsive enhancer module (PBREM) conserved in the PB-inducible CYP2B genes contains two NR-binding direct repeat (DR)-4 motifs. Responding to PB exposure in liver, the NR constitutive active receptor (CAR) translocates to the nucleus, forms a dimer with the retinoid X receptor (RXR), and activates PBREM via binding to DR-4 motifs. For CYP3A genes, a common NR site [DR-3 or everted repeat (ER)-6] is present in proximal promoter regions. In addition, the distal element called the xenobiotic responsive module (XREM) is found in human CYP3A4 genes, which contain both DR-3 and ER-6 motifs. Pregnane X receptor (PXR) could bind to all of these sites and, upon PB induction, a PXR:RXR heterodimer could transactivate XREM. These response elements and NRs are functionally versatile, and capable of responding to distinct but overlapping groups of xenochemicals. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Sueyoshi, T (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 99 TC 275 Z9 284 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2001 VL 41 BP 123 EP 143 DI 10.1146/annurev.pharmtox.41.1.123 PG 23 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 428AR UT WOS:000168439400006 PM 11264453 ER PT J AU Lesko, LJ Atkinson, AJ AF Lesko, LJ Atkinson, AJ TI Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: Criteria, validation, strategies SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE regulatory review; clinical endpoints ID CLINICAL-TRIALS; END-POINTS; GENE; THERAPY; MARKERS; ATHEROSCLEROSIS; HYPERTENSION; PHARMACOLOGY; INTEGRATION; MICROARRAY AB In the future, biomarkers will play an increasingly important role in all phases of drug development, including regulatory review. However, only a few of these biomarkers will become established well enough to serve in regulatory decision making as surrogate endpoints, thereby substituting for traditional clinical endpoints. Even generally accepted surrogate endpoints are unlikely to capture all the therapeutic benefits and potential adverse effects a drug will have in a diverse patient population. Accordingly, combinations of biomarkers probably will be needed to provide a more complete characterization of the spectrum of pharmacologic response. In the future, pharmacogenomic approaches, including those based on differential expression of gene arrays, will provide panels of relevant biomarkers that can be expected to transform the drug development process. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NR 57 TC 236 Z9 242 U1 2 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2001 VL 41 BP 347 EP 366 DI 10.1146/annurev.pharmtox.41.1.347 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 428AR UT WOS:000168439400014 PM 11264461 ER PT J AU Tycko, R AF Tycko, R TI Biomolecular solid state NMR: Advances in structural methodology and applications to peptide and protein fibrils SO ANNUAL REVIEW OF PHYSICAL CHEMISTRY LA English DT Review DE magnetic resonance; structural biology; amyloid ID NUCLEAR-MAGNETIC-RESONANCE; ANGLE-SPINNING NMR; CHEMICAL-SHIFT TENSORS; MULTIPLE-QUANTUM NMR; ECHO DOUBLE-RESONANCE; MORI SILK FIBROIN; PHOTOSYNTHETIC REACTION CENTERS; MOLECULAR TORSIONAL ANGLE; TILTED ROTATING-FRAME; SPIDER DRAGLINE SILK AB Solid state nuclear magnetic resonance (NMR) methods can provide atomic-level structural constraints on peptides and proteins in forms that are not amenable to characterization by other high-resolution structural techniques, owing to insolubility, high molecular weight, noncrystallinity, or other characteristics. Important examples include peptide and protein fibrils and membrane-bound peptides and proteins. Recent advances in solid state NMR methodology aimed at structural problems in biological systems are reviewed. The power of these methods is illustrated by experimental results on amyloid fibrils and other protein fibrils. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 249 TC 89 Z9 89 U1 1 U2 27 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-426X J9 ANNU REV PHYS CHEM JI Annu. Rev. Phys. Chem. PY 2001 VL 52 BP 575 EP 606 DI 10.1146/annurev.physchem.52.1.575 PG 32 WC Chemistry, Physical SC Chemistry GA 441TW UT WOS:000169246500021 PM 11326075 ER PT J AU Butler, AA Le Roith, D AF Butler, AA Le Roith, D TI Control of growth by the somatropic axis: Growth hormone and the insulin-like growth factors have related and independent roles SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE conditional knockouts; somatomedin hypothesis; cell proliferation ID I IGF-I; MESSENGER-RIBONUCLEIC-ACID; RECEPTOR GENE-EXPRESSION; LONGITUDINAL BONE-GROWTH; BINDING-PROTEIN COMPLEX; NEUROPEPTIDE-Y NEURONS; HYPOPHYSECTOMIZED RATS; GH-RECEPTOR; ADIPOSE CONVERSION; LABILE SUBUNIT AB The traditionally accepted theory has been that most of the biological effects of growth hormone (GH) are mediated by circulating (endocrine) insulin-like growth factor-I (IGF-I). This dogma was modified when it was discovered that most tissues express IGF-I that can act via an autocrine/paracrine fashion. In addition, both GH and IGF-I had independent effects on various target tissues. Using tissue-specific gene deletion of IGF-I in the liver, it has been shown that circulating IGF-I is predominantly liver-derived but is not essential for normal postnatal growth. Therefore, it is proposed that non-hepatic tissue-derived IGF-I may be sufficient for growth and development. Thus the original somatomedin hypothesis has undergone further modifications. C1 Oregon Hlth Sci Univ, Vollum Inst Adv Biomed Res, Portland, OR 97201 USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Butler, AA (reprint author), Oregon Hlth Sci Univ, Vollum Inst Adv Biomed Res, Portland, OR 97201 USA. NR 138 TC 194 Z9 206 U1 0 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2001 VL 63 BP 141 EP 164 DI 10.1146/annurev.physiol.63.1.141 PG 24 WC Physiology SC Physiology GA 421PC UT WOS:000168071900008 PM 11181952 ER PT J AU Brown, ML Lipscomb, J Snyder, C AF Brown, ML Lipscomb, J Snyder, C TI The burden of illness of cancer: Economic cost and quality of life SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE QALYs; DALYs; incidence; prevalence; HRQOL ID OF-LIFE; BREAST-CANCER; COLORECTAL-CANCER; CLINICAL ONCOLOGY; PROSTATE-CANCER; HEALTH; DISEASE; CARE; POPULATION; STAGE AB Cancer is a major public health issue and represents a significant burden of disease. In this chapter, we analyze the main measures of burden of disease as relate to cancer. Specifically, we review incidence and mortality, years of Life lost from cancer, and cancer prevalence. We also discuss the economic burden of cancer, including cost of illness, phase-specific and long-term costs, and indirect costs. We then examine the impact of cancer on health-related quality of life as measured in global terms (disability-adjusted life years and quality-adjusted life years) and using evaluation-oriented applications of health-related quality of life scales. Throughout, we note the relative strengths and weaknesses of the various approaches to measuring the burden of cancer as well as the methodologic challenges that persist in burden-of-illness research. We conclude with a discussion of the research agenda to improve our understanding of the burden of cancer and of illness more generally. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Brown, ML (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 42 TC 147 Z9 150 U1 0 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2001 VL 22 BP 91 EP 113 DI 10.1146/annurev.publhealth.22.1.91 PG 23 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 431TZ UT WOS:000168649000008 PM 11274513 ER PT J AU Murata, T Sugatani, T Shimizu, K Manganiello, VC Tagawa, T AF Murata, T Sugatani, T Shimizu, K Manganiello, VC Tagawa, T TI Phosphodiesterase 3 as a potential target for therapy of malignant tumors in the submandibular gland SO ANTI-CANCER DRUGS LA English DT Article DE phosphodiesterase; phosphodiesterase inhibitor; salivary gland tumor ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; CGMP-INHIBITED PHOSPHODIESTERASE; AMP PHOSPHODIESTERASE; MOLECULAR-CLONING; DIFFERENTIAL EXPRESSION; CAMP-PHOSPHODIESTERASE; RAT-LIVER; CELLS; PURIFICATION; LOCALIZATION AB Phosphodiesterase (PDE) 3s have been characterized in human neoplastic submandibular gland intercalated duct HSG cells. There have been no reports on PDE3 in malignant salivary gland cells. PDE3 activity was detected in homogenates of HSG cells. About 75% of PDE3 activity in HSG cells was recovered in supernatant fractions and 25% in particulate fractions. PDE3A and 3B mRNAs were detected by reverse transcription-polymersse chain reaction in RNA from HSG cells. The nucleotide sequences of the fragments were Identical to those of human PDE3A and 3B. The PDE3-specific inhibitor, cilostamide, inhibited the growth of HSG cells. Our results indicate that PDE3s may be important in the growth of HSG cells. PDE3 thus appears to be a potential new target for antiproliferative therapies. [(C) 2001 Lippincott Williams & Wilkins.]. C1 Mie Univ, Fac Med, Dept Oral & Maxillofacial Surg, Tsu, Mie 5148507, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Murata, T (reprint author), Mie Univ, Fac Med, Dept Oral & Maxillofacial Surg, 2-174 Edobashi, Tsu, Mie 5148507, Japan. NR 33 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JAN PY 2001 VL 12 IS 1 BP 79 EP 83 DI 10.1097/00001813-200101000-00011 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 398KR UT WOS:000166756100011 PM 11272291 ER PT J AU Sullivan, NJ AF Sullivan, NJ TI Antibody-mediated enhancement of viral disease SO ANTIBODIES IN VIRAL INFECTION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; DENGUE HEMORRHAGIC-FEVER; HIV-1 INFECTION INVITRO; T-CELL LINE; DEPENDENT ENHANCEMENT; MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; ENHANCING ANTIBODIES; MONOCYTIC CELLS; HIV-1-INFECTED INDIVIDUALS C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Sullivan, NJ (reprint author), NIH, Vaccine Res Ctr, Bldg 40,Room 4614B,40 Convent Dr, Bethesda, MD 20892 USA. NR 128 TC 58 Z9 59 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2001 VL 260 BP 145 EP 169 PG 25 WC Immunology; Microbiology SC Immunology; Microbiology GA BU12M UT WOS:000175080600008 PM 11443872 ER PT J AU Yang, QF Shan, L Segawa, N Nakamura, M Nakamura, Y Mori, I Sakurai, T Kakudo, K AF Yang, QF Shan, L Segawa, N Nakamura, M Nakamura, Y Mori, I Sakurai, T Kakudo, K TI Novel polymorphisms in prostate specific antigen gene and its association with prostate cancer SO ANTICANCER RESEARCH LA English DT Article DE prostate cancer; prostate-specific antigen gene; polymorphism; risk factor; progression ID EXPRESSION; RECEPTORS; PROTEASE AB Prostate-specific antigen (PSA) is now used widely for the diagnosis and monitoring of patients with prostate cancer. The PSA gene is a target of the androgen receptor (AR) which interacts with androgen response elements (AREs) in the PSA gene promoter. Recently, we identified two novel polymorphisms ir I the PSA promoter ARE2 legion in breast cancer: Wt! hypothesized that some genetic variations might also exist in the AREs of prostate cancer, and that feature might correlate with cancer development and/or progression. To test this hypothesis, three AREs of the PSA gene promoter were characterized for 47 prostate cancer cases and 105 controls from the Japanese population. We demonstrated the presence of two polymorphisms at positions -252 (G or A) and -205 (A or AA), which were the same as those we have found in breast cancel: Interestingly, the -252 A was linked with the presence of -205 AA, and the -252 C was always linked with the presence of -205 A. Therefore, only A-AA and G-A (-252-205) alleles were present in the Japanese population. The proportion of patients who were either heterozygotes or homozygotes for the A-AA allele was not significantly different from that observed among 105 individuals without cancer (p=0.726). However, comparing with c-A allele homozygotes, prostate cancer patients carrying at least I A-AA alleles tended to exhibit high serum PSA levels (p=0.0002), poor differentiation (p=0.0149) and advanced clinical stage (p=0.0077). These results suggest that the novel polymorphisms identified in the PSA gene promoter may affect transcriptional activity of the PSA gene, and ai? excess of PSA production may enhance rapid progression of prostate cancer. C1 Wakayama Med Coll, Dept Pathol 2, Wakayama 6410012, Japan. Osaka Med Coll, Dept Urol, Takatsuki, Osaka 5698686, Japan. Wakayama Med Coll, Affiliated Kihoku Hosp, Dept Surg, Katsuragi 6497113, Japan. NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Yang, QF (reprint author), Wakayama Med Coll, Dept Pathol 2, 811-1 Kimiidera, Wakayama 6410012, Japan. NR 19 TC 19 Z9 19 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 2001 VL 21 IS 1A BP 197 EP 200 PG 4 WC Oncology SC Oncology GA 418DP UT WOS:000167875900026 PM 11299734 ER PT J AU Furman, PA Jeffrey, J Keifer, LL Feng, JY Anderson, KS Borroto-Esoda, K Hill, E Copeland, WC Chu, CK Sommadossi, JP Liberman, I Schinazi, RF Painter, GR AF Furman, PA Jeffrey, J Keifer, LL Feng, JY Anderson, KS Borroto-Esoda, K Hill, E Copeland, WC Chu, CK Sommadossi, JP Liberman, I Schinazi, RF Painter, GR TI Mechanism of action of 1-beta-D-2,6-diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-beta-D-dioxolane guanosine SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DNA-POLYMERASE-GAMMA; NUCLEOSIDE ANALOGS; PHARMACOKINETICS; GUANINE; MONKEYS AB (-)-beta -D-2,6-Diaminopurine dioxolane (DAPD), is a nucleoside reverse transcriptase (RT) inhibitor with activity against human immunodeficiency virus type 1 (HIV-1). DAPD, which nas designed as a water-soluble prodrug, is deaminated by adenosine deaminase to give (-)-beta -D-dioxolane guanine (DXG). By using calf adenosine deaminase a K-m value of 15 +/- 0.7 muM was determined for DAPD, which was similar to the K-m value for adenosine. However, the k(cat) for DAPD was 540-fold slower than the k(cat) for adenosine. In CEM cells and peripheral blood mononuclear cells exposed to DAPD or DXG, only the 5'-triphosphate of DXG (DXG-TP) was detected. DXG-TP is a potent alternative substrate inhibitor of HIV-1 RT. Rapid transient kinetic studies show the efficiency of incorporation for DXG-TP to be lower than that measured for the natural substrate, 2'-deoxyguanosine 5'-triphosphate. DXG-TP is a weak inhibitor of human DNA polymerases alpha and beta. Against the large subunit of human DNA polymerase gamma a K-i value of 4.3 +/- 0.4 muM was determined for DXG-TP. DXG showed little or no cytotoxicity and no mitochondrial toxicity at the concentrations tested. C1 Triangle Pharmaceut, Durham, NC 27707 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA. Univ Alabama, Dept Clin Pharmacol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Liver, Birmingham, AL 35294 USA. Emory Univ, Sch Med, Dept Pediat, Decatur, GA 30322 USA. Vet Affairs Med Ctr, Decatur, GA 30033 USA. RP Furman, PA (reprint author), Triangle Pharmaceut, 4 Univ Pl,4611 Univ Dr, Durham, NC 27707 USA. RI Schinazi, Raymond/B-6777-2017 FU NIAID NIH HHS [AI25899, AI40775, R01 AI025899, R37 AI025899]; NIGMS NIH HHS [GM49551, R01 GM049551] NR 16 TC 58 Z9 62 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2001 VL 45 IS 1 BP 158 EP 165 DI 10.1128/AAC.45.1.158-165.2001 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 384NV UT WOS:000165952500023 PM 11120959 ER PT J AU Ashby, J Spearow, J vom Saal, F Sheehan, D Newbold, R AF Ashby, J Spearow, J vom Saal, F Sheehan, D Newbold, R TI Reassessment of models used to test xenobiotics for oestrogenic potency is overdue - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S300 EP S301 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500062 ER PT J AU Ashby, J Moller, H Thonneau, P Skakkebaek, N Huff, J Grumbach, M AF Ashby, J Moller, H Thonneau, P Skakkebaek, N Huff, J Grumbach, M TI Trends in incidence of testicular cancer and prostate cancer in Denmark - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RI grumbach, melvin/A-9836-2008 NR 1 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S36 EP S36 PG 1 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500009 ER PT J AU Brock, J Huff, J Leffers, H Hossaini, A Newbold, R AF Brock, J Huff, J Leffers, H Hossaini, A Newbold, R TI The role of environmental factors in the pathogenesis of breast cancer - Discussion SO APMIS LA English DT Editorial Material ID ORGANOCHLORINE EXPOSURE C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S94 EP S94 PG 1 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500021 ER PT J AU Fink-Gremmels, J Jensen, T Sasco, A Partsch, CJ Huff, J Joffe, M Toppari, J McLachlan, J Sheehan, D AF Fink-Gremmels, J Jensen, T Sasco, A Partsch, CJ Huff, J Joffe, M Toppari, J McLachlan, J Sheehan, D TI Trends in breast cancerr - General discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S112 EP S113 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500024 ER PT J AU Foster, P Gray, LE Sheehan, D Bro-Rasmussen, F Brock, J Risbridger, G Ashby, J Swan, S van den Akker, E Kogevinas, M Meyer, P Francis, E Newbold, R AF Foster, P Gray, LE Sheehan, D Bro-Rasmussen, F Brock, J Risbridger, G Ashby, J Swan, S van den Akker, E Kogevinas, M Meyer, P Francis, E Newbold, R TI General discussion - New OECD guidelines for animal toxicity: Are they adequate? SO APMIS LA English DT Editorial Material C1 CIIT, Res Triangle Pk, NC 27709 USA. US EPA, Washington, DC 20460 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Foster, P (reprint author), CIIT, Res Triangle Pk, NC 27709 USA. RI Risbridger, Gail/B-8655-2008; Bro, Rasmus/A-7898-2008; Kogevinas, Manolis/C-3918-2017 OI Risbridger, Gail/0000-0003-3089-4028; Bro, Rasmus/0000-0002-7641-4854; NR 0 TC 0 Z9 0 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S332 EP S335 PG 4 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500068 ER PT J AU Grandjean, P Guillette, L Matthiessen, P Part, P Bourguignon, P Bro-Rasmussen, F Russo, J Jegou, B Skakkebaek, N Brock, J Joffe, M Bustos-Obregon, E Olea, N Soto, A Thonneau, P Boersma, R Swan, S Bonefeld-Jorgensen, E Huff, J Kogevinas, M AF Grandjean, P Guillette, L Matthiessen, P Part, P Bourguignon, P Bro-Rasmussen, F Russo, J Jegou, B Skakkebaek, N Brock, J Joffe, M Bustos-Obregon, E Olea, N Soto, A Thonneau, P Boersma, R Swan, S Bonefeld-Jorgensen, E Huff, J Kogevinas, M TI General discussion: Effects of hormone disrupters in man and wildlife SO APMIS LA English DT Editorial Material ID PESTICIDES C1 Commiss European Communities, Ispra, Italy. CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RI Olea, Nicolas/H-3198-2014; Bro, Rasmus/A-7898-2008; Bonefeld-Jorgensen, Eva Cecilie/A-1682-2015; Jegou, Bernard/I-4742-2015; Kogevinas, Manolis/C-3918-2017 OI Olea, Nicolas/0000-0002-8938-3743; Bro, Rasmus/0000-0002-7641-4854; NR 4 TC 0 Z9 0 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S254 EP S260 PG 7 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500053 ER PT J AU Joffe, M Chiumello, G Thonneau, P Andersson, AM Myers, P Toppari, J Huff, J Keizer-Schrama, SD Kulin, H Daxenberger, A Bourguignon, JP AF Joffe, M Chiumello, G Thonneau, P Andersson, AM Myers, P Toppari, J Huff, J Keizer-Schrama, SD Kulin, H Daxenberger, A Bourguignon, JP TI Accidental gynecomastia in children - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S207 EP S209 PG 3 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500044 ER PT J AU Jorgensen, N Swan, S Toppari, J Kogevinas, M Swan, S Lee, P Jouannet, P Moller, H Joffe, M Guo, S Newbold, R Partsch, CJ Grumbach, M Wang, C Gies, A Ritzen, M Sharpe, R McLachlan, J Hughes, I AF Jorgensen, N Swan, S Toppari, J Kogevinas, M Swan, S Lee, P Jouannet, P Moller, H Joffe, M Guo, S Newbold, R Partsch, CJ Grumbach, M Wang, C Gies, A Ritzen, M Sharpe, R McLachlan, J Hughes, I TI Trends in male reproductive disorders - General discussion SO APMIS LA English DT Editorial Material ID RETE TESTIS; DIETHYLSTILBESTROL; CRYPTORCHIDISM; INSL3; TEMPERATURE; LESIONS; SEMEN C1 NIEHS, Res Triangle Pk, NC 27709 USA. RI grumbach, melvin/A-9836-2008; Kogevinas, Manolis/C-3918-2017 NR 18 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S74 EP S79 PG 6 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500018 ER PT J AU Korner, W Veeramachaneni, R Kogevinas, M Swan, S Bourguignon, JP Huff, J AF Korner, W Veeramachaneni, R Kogevinas, M Swan, S Bourguignon, JP Huff, J TI Long-term effects on male reproduction of early exposure to common chemical contaminants in drinking water - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RI Kogevinas, Manolis/C-3918-2017 NR 5 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S328 EP S329 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500066 ER PT J AU Legros, JJ Boersma, R Brock, J Toppari, J Korner, W Huff, J Skakkebaek, N AF Legros, JJ Boersma, R Brock, J Toppari, J Korner, W Huff, J Skakkebaek, N TI Environmental exposure to polychlorinated biphenyls (PCBs) and dioxins - Consequences for longterm neurological and cognitive development of the child. A Review - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S252 EP S253 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500052 ER PT J AU McLachlan, JA Newbold, RR Burow, ME Li, SF AF McLachlan, JA Newbold, RR Burow, ME Li, SF TI From malformations to molecular mechanisms in the male: three decades of research on endocrine disrupters SO APMIS LA English DT Article; Proceedings Paper CT International Workshop on Hormones and Endocrine Disrupters in Food and Water: Possible Effects on Human Health CY MAY 27-30, 2000 CL RIGS HOSP, COPENHAGEN, DENMARK HO RIGS HOSP DE malformations; male, estrogens; reproductive system; molecular mechanisms ID DIETHYLSTILBESTROL EXPOSURE INUTERO; MOUSE SEMINAL-VESICLE; PRENATAL EXPOSURE; MALE-MICE; LACTOTRANSFERRIN GENE; GENITAL-TRACT; EXPRESSION; CRYPTORCHIDISM; ADENOCARCINOMA; ABNORMALITIES AB For three decades, we have known that estrogens alter the development of the mammalian reproductive system in predictable ways. In mice exposed prenatally to diethylstilbestrol (DES) or other estrogens, the male offspring exhibit structural malformations including cryptorchidism, epididymal cysts and retained Mullerian ducts. The estrogen-associated alterations in the genital tract phenotype can be usefully considered as a model called Developmental Estrogenization Syndrome. While estrogen treatment during critical periods of morphogenesis of the male reproductive system has been associated with these changes, the mechanisms at the molecular level are still being discovered. Parallel findings on the hormones involved in Mullerian duct regression and testicular descent have helped guide research on the mechanisms of developmental estrogenization of the male. Cellular localization of molecular signals associated with key steps in genital tract development, use of mice with gene disruption, and knowledge of the mechanisms underlying persistent changes in gene expression are beginning to provide a blue print for both the physiological role and pathological effects of estrogens in reproductive tract development. Since many of the same biological principles underlie genital tract morphogenesis in mammals, one may expect some of the same changes in males of other species exposed to estrogen during the appropriate developmental periods. C1 Tulane Univ, Ctr Bioenvironm Res, Environm Endocrinol Lab, New Orleans, LA 70112 USA. Xavier Univ, Ctr Bioenvironm Res, Environm Endocrinol Lab, New Orleans, LA 70112 USA. Tulane Univ, Hlth Sci Ctr, Dept Pharmacol, New Orleans, LA 70118 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP McLachlan, JA (reprint author), Tulane Univ, Ctr Bioenvironm Res, Environm Endocrinol Lab, New Orleans, LA 70112 USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S1 EP S10 PG 10 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500002 ER PT J AU Meyer, H Swan, S McLachlan, J Swan, S Soto, A Callard, G Brandi, M Newbold, R AF Meyer, H Swan, S McLachlan, J Swan, S Soto, A Callard, G Brandi, M Newbold, R TI Intrauterine exposure to diethylstilbestrol: Long-term effects in humans - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S221 EP S222 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500046 ER PT J AU Myers, P Sorensen, T Moller, H Jensen, T Sippel, W Guo, SM Skakkebaek, N Huff, J Lynge, E AF Myers, P Sorensen, T Moller, H Jensen, T Sippel, W Guo, SM Skakkebaek, N Huff, J Lynge, E TI Causes of juvenile obesity: Clues from epidemiology - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S171 EP S173 PG 3 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500036 ER PT J AU Newbold, RR AF Newbold, RR TI Effects of developmental exposure to diethylstilbestrol (DES) in rodents: clues for other environmental estrogens SO APMIS LA English DT Article DE cancer; diethylstilbestrol; environmental estrogens; estrogen receptor; transgenerational carcinogenesis ID PRENATAL EXPOSURE; UTERINE ADENOCARCINOMA; MOUSE UTERUS; IN-UTERO; MICE; EXPRESSION; TUMORS; DESCENDANTS; FERTILITY; LESIONS AB The synthetic estrogen diethylstilbestrol (DES) is a potent perinatal endocrine disrupter. In humans and experimental animal models, exposure to DES during critical periods of differentiation permanently alters estrogen target tissues subsequently resulting in structural, functional, and long-term abnormalities including neoplasia in reproductive tract tissues. Using the developmentally exposed rodent model, multiple mechanisms have been identified that play a role in DES-induced toxic effects. Although DES is a potent estrogen, it can be used as a model compound to predict the effects of other environmental estrogens. It was, therefore, of particular interest that very low doses of DES were found to adversely affect fertility and increase tumor incidence. These effects were seen at environmentally relevant estrogen dose levels. Not surprising, new studies verify that DES effects are not unique; when other environmental chemicals with estrogenic activity were tested in the experimental rodent model, developmental exposure was shown to result in an increased incidence of neoplasia, including uterine adenocarcinoma, similar to that shown following DES exposure. Finally, a growing number of reports suggest that some adverse effects can be passed on to subsequent generations, although the mechanisms involved in these transgenerational events remain unknown. These data point out the possibility that environmental estrogens and other endocrine disrupting compounds are indeed valid suspects in the alarming rise in adverse reproductive health consequences in human and wildlife populations. C1 NIEHS, Dev Endocrinol Sect, Toxicol Lab, Environm Toxicol Program,Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol Sect, Toxicol Lab, Environm Toxicol Program,Div Intramural Res, Mail Drop E4-02, Res Triangle Pk, NC 27709 USA. EM newbold1@niehs.nih.gov NR 50 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S261 EP S270 PG 10 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500054 ER PT J AU Pescovitz, O Vollmer, G Korach, K Soto, A Labrie, F Leffers, H Huff, J AF Pescovitz, O Vollmer, G Korach, K Soto, A Labrie, F Leffers, H Huff, J TI Phytoestrogens and carcinogenesis - differential effects of genistein in experimental models of normal and malignant rat endometrium - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S517 EP S518 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500098 ER PT J AU Schonfelder, G Newbold, R Ashby, J Russo, J Huff, J AF Schonfelder, G Newbold, R Ashby, J Russo, J Huff, J TI Effects of developmental exposure to diethylstilbestrol (DES) in rodents: clues for other environmental estrogens - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC USA. Zeneca, Macclesfield, Cheshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S270 EP S271 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500055 ER PT J AU Skakkebaek, N Sheehan, D Ritzen, M Grumbach, M Swan, S Kogevinas, M Gray, E AF Skakkebaek, N Sheehan, D Ritzen, M Grumbach, M Swan, S Kogevinas, M Gray, E TI Threshold analysis of selected dose-response data for endocrine active chemicals - Discussion SO APMIS LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. US EPA, Washington, DC 20460 USA. RI Kogevinas, Manolis/C-3918-2017 NR 0 TC 0 Z9 0 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S539 EP S539 PG 1 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500101 ER PT J AU Thayer, KA Ruhlen, RL Howdeshell, KL Buchanan, DL Cooke, PS Preziosi, D Welshons, WV Haseman, J vom Saal, FS AF Thayer, KA Ruhlen, RL Howdeshell, KL Buchanan, DL Cooke, PS Preziosi, D Welshons, WV Haseman, J vom Saal, FS TI Altered prostate growth and daily sperm production in male mice exposed prenatally to subclinical doses of 17 alpha-ethinyl oestradiol SO APMIS LA English DT Article DE endocrine disruption; fetus; oral contraceptive; prostate; testes ID ETHINYL ESTRADIOL; DIETHYLSTILBESTROL DES; SEX-HORMONES; ORAL-CONTRACEPTIVES; REPRODUCTIVE-ORGANS; CELL HYPERPLASIA; SERTOLI CELLS; TESTIS SIZE; HUMAN-SERUM; ADULT-RATS AB Approximately 2 million women in the USA and Europe continue taking oral contraceptives each year during undetected pregnancy due primarily to non-compliance and also to individual variation in sensitivity to hormones in the contraceptives. Prenatal exposure to oral contraceptives containing 17 alpha -ethinyl oestradiol (EE) has generally not been associated with an increased incidence of externally observable malformations at birth. The purpose of this study was to assess effects on reproductive organs in adult male mice that had been exposed during gestation day 0 through 17 (equivalent to gestation week 16 in humans) to clinically relevant (similar to0.5 mug/kg/day) and lower doses of EE. Doses used in this study ranged from 0.002 to 2 mug/kg/day. By 5 months of age, prostate weight was significantly (P < 0.05) higher than controls in most treatment groups of EE (0.02-2 g/kg). Prostatic androgen receptor populations were significantly elevated only in the 0.02 mug/kg group, suggesting different mechanisms for the increase in prostate weight at different doses. Daily sperm production (DSP) and DSP per gramme of testis were reduced in all treatment groups during adolescence, but not later in adulthood. These findings are consistent with prior studies showing that prenatal exposure of mice to very low doses of a number of oestrogenic chemicals can alter the adult male reproductive system without causing gross external malformations. C1 Univ Missouri, Dept Biol Sci, Columbia, MO USA. Univ Missouri, Dept Vet Biomed Sci, Columbia, MO USA. Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Thayer, KA (reprint author), Wildlife & Contaminant World Wildlife Fund, 1250 24th St NW, Washington, DC 20037 USA. EM kristina.thayer@wwfus.org NR 62 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S278 EP S286 PG 9 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500058 ER PT J AU Vollmer, G Korach, K Skakkebaek, N McLachlan, J Mengarda, F AF Vollmer, G Korach, K Skakkebaek, N McLachlan, J Mengarda, F TI Studying endocrine disrupter action and toxicology in ER knock-out mice - Discussion SO APMIS LA English DT Editorial Material ID ESTROGEN C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S491 EP S492 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500092 ER PT J AU Zimmerman, BE Kubicek, GJ Cessna, JT Plascjak, PS Eckelman, WC AF Zimmerman, BE Kubicek, GJ Cessna, JT Plascjak, PS Eckelman, WC TI Radioassays and experimental evaluation of dose calibrator settings for F-18 SO APPLIED RADIATION AND ISOTOPES LA English DT Article ID STANDARDIZATION; EFFICIENCY AB The positron emitter F-18 continues to be one of the most important imaging radionuclides in diagnostic nuclear medicine. Assays of radiopharmaceuticals containing this nuclide are often performed in the clinic using commercial reentrant ionization chambers, or "dose calibrators". Meaningful quantitative clinical studies require accurate knowledge of the injected activity which requires proper calibration of these instruments. Radioassays were performed at thr: National Institute of Standards and Technology (NIST) on a solution of F-18 produced at the National Institutes of Health (NIH) using 4 pi beta liquid scintillation (fS) counting with H-3-standard efficiency tracing. Cocktails containing water fractions of approximately 0.9 and 9% (both as saline) were used. The massic activity values were measured to be 2.52 +/- 0.06 and 2.50 +/- 0.03 MBq g(-1), respectively, for the 0.9 and 9% water cocktails as of the reference time. The uncertainties on the activity measurements are expanded (k = 2) uncertainties. The largest uncertainty component was found to be the repeatability on a single LS source, with the cocktails containing 0.9% water fraction exhibiting a larger variability by nearly a factor of two. Reproducibility between LS cocktails with the same water Traction was also found to be a large uncertainty component, but with a value less than half that due to measurement repeatability. Radionuclidic impurities consisted of V-48 and Sc-46, at levels of 0.11 +/- 0.08% (expanded uncertainties) and approximately 2 x 10(-3)% (upper limit) relative to the activity of the F-18, as Of the reference time. Dose calibrator dial settings for measuring solutions of]SF were experimentally determined for Capintec CRC-12 and CRC-35R dose calibrators in three measurement geometries: a 5-ml standard NIST ampoule (two ampoules measured), a 12-ml plastic syringe containing 9 mi of solution and a 10-ml Mallinckrodt molded dose vial filled with 5 mi of solution. The experimental dial settings land the corresponding expanded uncertainties) for these geometries were found to be 477 +/- 7, 474 +/- 6, 482 +/- 6 and 463 +/- 7 for the two ampoules, the syringe and the dose vial, respectively, in the CRC-12, The dial settings determined for the CRC-35R were 472 +/- 7, 470 +/- 7, 464 +/- 6 and 456 +/- 6 for the two ampoules, the syringe, and the dose vial, respectively. The uncertainties in the dial settings are expanded uncertainties. Comparisons between the empirically determined.. dial settings and the manufacturer's recommended setting of "439" indicate that use of the manufacturer's setting overestimates the activity by between 3 and 6%, depending upon the geometry used. Published by Elsevier Science Ltd. C1 Natl Inst Stand & Technol, Phys Lab, Gaithersburg, MD 20899 USA. NIH, PET Dept, Bethesda, MD 20892 USA. RP Zimmerman, BE (reprint author), Natl Inst Stand & Technol, Phys Lab, Gaithersburg, MD 20899 USA. NR 16 TC 14 Z9 14 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD JAN PY 2001 VL 54 IS 1 BP 113 EP 122 DI 10.1016/S0969-8043(99)00260-2 PG 10 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 379LM UT WOS:000165643600015 PM 11144241 ER PT J AU Knepper, MA Nielsen, S Chou, CL AF Knepper, MA Nielsen, S Chou, CL TI Physiological roles of aquaporins in the kidney SO AQUAPORINS SE CURRENT TOPICS IN MEMBRANES LA English DT Review ID MEDULLARY COLLECTING DUCT; INTEGRAL MEMBRANE-PROTEIN; REGULATED WATER CHANNEL; SYNAPTOSOME-ASSOCIATED PROTEIN; VASOPRESSIN V-2 RECEPTOR; THICK ASCENDING LIMB; RAT-KIDNEY; PROXIMAL TUBULE; ANTIDIURETIC-HORMONE; DESCENDING-LIMB C1 NHLBI, NIH, Bethesda, MD 20892 USA. Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. RP Knepper, MA (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 144 TC 1 Z9 1 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 J9 CURR TOP MEMBR PY 2001 VL 51 BP 121 EP 153 DI 10.1016/S1063-5823(01)51005-4 PG 33 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BS01U UT WOS:000168327600003 ER PT J AU Nielsen, S Kwon, TH Nager, H Knepper, MA Marples, D Frokiaer, J AF Nielsen, S Kwon, TH Nager, H Knepper, MA Marples, D Frokiaer, J TI Pathophysiology of renal aquaporins SO AQUAPORINS SE CURRENT TOPICS IN MEMBRANES LA English DT Review ID WATER CHANNEL EXPRESSION; NEPHROGENIC DIABETES-INSIPIDUS; VASOPRESSIN-INDUCED ANTIDIURESIS; INDUCED NEPHROTIC SYNDROME; MEDULLARY COLLECTING DUCT; INDUCED DOWN-REGULATION; THICK ASCENDING LIMB; RAT-KIDNEY MEDULLA; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING C1 Aarhus Univ, Dept Cell Biol, DK-8000 Aarhus, Denmark. Dongguk Univ, Kyungju, South Korea. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. RP Nielsen, S (reprint author), Aarhus Univ, Dept Cell Biol, DK-8000 Aarhus, Denmark. NR 107 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 J9 CURR TOP MEMBR PY 2001 VL 51 BP 155 EP 183 DI 10.1016/S1063-5823(01)51006-6 PG 29 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BS01U UT WOS:000168327600004 ER PT J AU Leist, TP Gobbini, MI Frank, JA McFarland, HF AF Leist, TP Gobbini, MI Frank, JA McFarland, HF TI Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID SPIN-ECHO; MRI; SERIAL; BRAIN; TOMOGRAPHY AB Objective: To examine the relation between the frequency of enhancing magnetic resonance imaging lesions and their characteristics of enhancement and atrophy in patients with early relapsing multiple sclerosis. Design: Analysis of number of enhancing lesions, ventricular volumes and diameters, and lesion characteristics on monthly magnetic resonance imaging scans during natural history follow-up. Setting: A clinical research institution. Patients: Sixteen patients with confirmed early relapsing multiple sclerosis. Main Outcome Measure: Cerebral atrophy as measured by ventricular enlargement. Results: Numbers of enhancing lesions correlated well with an increase of ventricular size. This correlation was strongest for patients with a high proportion of concentric ring-enhancing lesions with central contrast pallor. Conclusions: Inflammatory events, especially those within lesions with associated blood-brain barrier breakdown, affect the ensuing loss of brain parenchyma. Patients with a high proportion of lesions with central contrast pallor, which is likely associated with more extensive tissue damage, have a higher rate of atrophic changes. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Leist, TP (reprint author), NINDS, Neuroimmunol Branch, NIH, 900 Rockville Pike,Bldg 10,Room 5B16, Bethesda, MD 20892 USA. NR 20 TC 37 Z9 37 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2001 VL 58 IS 1 BP 57 EP 60 DI 10.1001/archneur.58.1.57 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 392KT UT WOS:000166410800007 PM 11176937 ER PT J AU Gilbert, JM Feng, N Patton, JT Greenberg, HB AF Gilbert, JM Feng, N Patton, JT Greenberg, HB TI Rotavirus assembly - interaction of surface protein VP7 with middle layer protein VP6 SO ARCHIVES OF VIROLOGY LA English DT Article ID SEQUENCE-ANALYSIS; RHESUS ROTAVIRUS; RNA-POLYMERASE; MONOCLONAL-ANTIBODIES; NEUTRALIZING EPITOPES; BIOCHEMICAL-EVIDENCE; CAPSID PROTEIN; VIRUS; LOCALIZATION; EXPRESSION AB The interaction between the rotavirus proteins viral protein G (VP6) and VP7 was examined in several exogenous protein expression systems. These proteins associated in the absence of other rotaviral proteins as demonstrated by a coimmunoprecipitation assay. Deletion analysis of VP7 indicated that truncations of either the mature amino or carboxyl terminus disrupted the proper folding of the protein and were not able to coimmunoprecipitate VP6. Truncation analysis of VP6 indicated that trimerization of VP6 was necessary, but not sufficient, for VP7 binding. MAb mapping and coimmunoprecipitation interference assays indicate that the VP6 amino acid residues between 271 and 342 are required for VP7 interaction. The interaction of VP6 and VP7 was also examined by the assembly of soluble VP7 onto baculovirus-expressed virus-like particles containing VP2 and VP6. Abrogation of this binding by preincubation of the particles with VPG MAbs mapped to this same domain of VP6, validated our coimmunoprecipitation results. VP6 IEA MAbs that have been shown to be protective in vivo, but not a nonprotective IEA MAb, can interfere with VP7 binding to VP6. This suggests that these IgA MAbs may protect against rotavirus infection by blocking rotavirus assembly. C1 Stanford Univ, Sch Med, Div Gastroenterol, Palo Alto, CA 94304 USA. Palo Alto VA Hlth Care Syst, Dept Microbiol & Immunol, Palo Alto, CA USA. NIAID, Bethesda, MD 20892 USA. RP Greenberg, HB (reprint author), 3401 Miranda Ave,MC 154C Bldg 101, Palo Alto, CA USA. RI Patton, John/P-1390-2014 FU NIAID NIH HHS [R37AI21632]; NIDDK NIH HHS [DK07056, DK38707] NR 39 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 2001 VL 146 IS 6 BP 1155 EP 1171 DI 10.1007/s007050170112 PG 17 WC Virology SC Virology GA 448AW UT WOS:000169605500008 PM 11504422 ER PT J AU Jobes, DV Friedlaender, JS Mgone, CS Agostini, HT Koki, G Yanagihara, R Ng, TCN Chima, SC Ryschkewitsch, CF Stoner, GL AF Jobes, DV Friedlaender, JS Mgone, CS Agostini, HT Koki, G Yanagihara, R Ng, TCN Chima, SC Ryschkewitsch, CF Stoner, GL TI New JC virus (JCV) genotypes from Papua New Guinea and Micronesia (Type 8 and Type 2E) and evolutionary analysis of 32 complete JCV genomes SO ARCHIVES OF VIROLOGY LA English DT Article ID HUMAN POLYOMAVIRUS JC; AFRICAN-AMERICANS; SEQUENCE-ANALYSIS; DNA-SEQUENCE; REARRANGEMENTS; INDIVIDUALS; SUBTYPES; VARIANTS; REFLECT; CLONING AB The JC virus (JCV) is a ubiquitous human polyomavirus that frequently resides in the kidneys of healthy individuals and is excreted in the urine of a large percentage of the population. Geographic-specific JCV variants, isolated from urine and from brain of progressive multifocal leukoencephalopathy (PML) patients, have been grouped into seven distinct genotypes based on whole genome analysis and by individual polymorphic nucleotides (typing sites) in the VP I coding region. Mutations in the archetypal regulatory region, sometimes consisting of deletions and/or duplications, are also useful taxonomic characters for further characterizing and subdividing genotypes. Investigation of JCV variation in Papua New Guinea (PNG) revealed three distinct variants called PNG-1, PNG-2, and PNG-3. These variants exhibited consistent coding region and regulatory region mutations. Evolutionary analysis of 32 complete JCV genomes including six new viral genomes from the western Pacific suggests that the new PNG JCV variants are closely associated with the broad group of Type 2 strains of JCV found throughout Asia, forming a monophyletic group with the Northeast Asian strains (Type 2A). Within the Type 2 clade, however, the PNG JCV variants cluster as two distinct groups and are therefore described here as new JCV genotypes designated Type 2E and Type 8. C1 NINCDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Temple Univ, Dept Anthropol, Philadelphia, PA 19122 USA. Papua New Guinea Inst Med Res, Goroka, Papua N Guinea. Univ Freiburg, Dept Ophthalmol, Freiburg, Germany. Univ Hawaii Manoa, Pacific Biomed Res Ctr, Honolulu, HI 96822 USA. RP Stoner, GL (reprint author), NINCDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-27, Bethesda, MD 20892 USA. RI Chima, Sylvester Chidi/N-5564-2013 NR 26 TC 42 Z9 43 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 2001 VL 146 IS 11 BP 2097 EP 2113 DI 10.1007/s007050170023 PG 17 WC Virology SC Virology GA 495JC UT WOS:000172336200004 PM 11765914 ER PT J AU Ablan, S Rawat, SS Blumenthal, R Puri, A AF Ablan, S Rawat, SS Blumenthal, R Puri, A TI Entry of influenza virus into a glycosphingolipid-deficient mouse skin fibroblast cell line SO ARCHIVES OF VIROLOGY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; SIALIC-ACID; MEMBRANE-FUSION; BIOLOGICAL-MEMBRANES; PLASMA-MEMBRANE; HEMAGGLUTININ; RECEPTOR; GANGLIOSIDES; INFECTION; BINDING AB A glycosphingolipid (GSL)-deficient mouse skin fibroblast mutant cell line (GM95) was tested for its susceptibility to influenza virus infection and/or fusion. Octadecyl rhodamine labeled influenza virus fused at 37 degreesC and low pH with GM95 cells at similar rates and extents as with the parental cell lines which did bear glycosphingolipids. Influenza virus infected the GM95 cells at the same level as the parental cell lines. The infection and fusion was blocked when the cell lines were pre-treated with neuramindase. We conclude that influenza virus uses mainly sialoglycoproteins and that gangliosides are not essential for influenza virus fusion and infection. C1 NCI, LECB, CCR, NIH, Frederick, MD 21702 USA. RP Puri, A (reprint author), NCI, LECB, CCR, NIH, POB B,Bldg 469,Rm 211,Miller Dr, Frederick, MD 21702 USA. NR 34 TC 15 Z9 15 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 2001 VL 146 IS 11 BP 2227 EP 2238 DI 10.1007/s007050170033 PG 12 WC Virology SC Virology GA 495JC UT WOS:000172336200014 PM 11765924 ER PT J AU Makrigiannis, AP Anderson, SK AF Makrigiannis, AP Anderson, SK TI The murine Ly49 family: Form and function SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE NK cells; MHC class I; receptors; signal transduction; Ly49; gene family ID NATURAL-KILLER-CELLS; HISTOCOMPATIBILITY COMPLEX-MOLECULES; NK CELLS; RECEPTOR REPERTOIRE; LY-49; EXPRESSION; GENES; RECOGNITION; PHOSPHORYLATION; CYTOTOXICITY AB The activity of natural killer (NK) cells is regulated by surface receptors that recognize class I MHC. Murine NK cells express a large family of lectin-related receptors (Ly49s) to perform this function, while human NK cells utilize a separate group of proteins containing Ig-related domains (KIRs). Although these receptor families are not structurally related, the Ly49 family appears to be the functional equivalent of human KIRs, since it uses similar signal transduction pathways for either activation or inhibition of NK cell function. Therefore, lessons learned from the study of the murine MHC class I receptor system may be relevant to human NK function. This review summarizes the current state of knowledge of the Ly49 family. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Div Basic Sci,Lab Exp Immunol, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, 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-56000] NR 33 TC 5 Z9 5 U1 0 U2 0 PU INST IMMUNOLOGY & EXPERIMENTAL THERAPY PI WROCLAW PA POLISH ACADEMY OF SCIENCES CZERSKA 12, 53-114 WROCLAW, POLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PY 2001 VL 49 IS 1 BP 47 EP 50 PG 4 WC Immunology SC Immunology GA 462EL UT WOS:000170407700007 PM 11266090 ER PT B AU Waalkes, MP Keefer, LK Diwan, LA AF Waalkes, MP Keefer, LK Diwan, LA BE Chappell, WR Abernathy, CO Calderon, RL TI Induction of proliferative lesions of the uterus, testes and liver in Swiss mice given repeated injections of sodium arsenate SO ARSENIC EXPOSURE AND HEALTH EFFECTS IV LA English DT Proceedings Paper CT 4th International Conference on Arsenic Exposure and Health Effects CY JUN 18-22, 2000 CL SAN DIEGO, CA SP Univ Colorado, US EPA, Electr Power Res Inst, Int Council Met Environm, Kennecott Corp, UNICEF DE arsenic; uterus; testes; liver; proliferative lesions; mice ID HUMAN BREAST-CANCER; ENVIRONMENTAL ESTROGENS; DIMETHYLARSINIC ACID; ENDOMETRIAL CANCER; DIETHYLSTILBESTROL; RECEPTOR; TUMORS; CARCINOGENESIS; ADENOCARCINOMA; REPLACEMENT AB Inorganic arsenic (As) is a human carcinogen but has not been unequivocally proven carcinogenic in rodents. For instance, one older study indicates that repeated i.v. injections of sodium arsenate might induce lymphomas in Swiss mice (58%, incidence; Osswald and Goerttler, 1971), but it was considered inadequate for critical evaluation of carcinogenic potential largely because of issues in experimental design. Therefore, we studied repeated i.v. sodium arsenate injection and neoplastic response in male and female Swiss mice. Groups (n = 25) of mice received sodium arsenate (0.5 mg/kg, i.v.) or saline (control) once/week for 20 weeks and were observed for a total of 96 weeks when the study ended. Differences in survival and body weights were unremarkable. In females, arsenate induced marked increases in the incidence and severity of cystic hyperplasia of the uterus compared to controls. Arsenate also was associated with a rare adenocarcinoma of the uterus. Hyperplastic uterine epithelium from arsenate-exposed animals showed strong positive immunostaining for the proliferating cell nuclear antigen. There was also an upregulation of estrogen receptor immunoreactive protein in the early lesions of uterine luminal and glandular hyperplasia but a progressive decrease in its expression was seen in the severe hyperplastic or neoplastic epithelium. Arsenate-induced uterine hyperplastic lesions also showed a strong upregulation of cyclin D1, an estrogen-associated gene product essential for progression through the G1 phase of the cell cycle. In other tissues, arsenate increased testicular interstitial cell hyperplasia incidence and severity over control but without affecting the incidence of tubular degeneration. Arsenate also induced increases in hepatic proliferative lesions (foci of alteration + neoplasia), but only in females. Significant skin changes (incidence of hyperkeratotic lesions) also occurred in arsenate treated females. Thus, repeated arsenate exposure, though not outright tumorigenic in the present study, was associated with proliferative, preneoplastic lesions of the uterus, testes, and liver. Estrogen treatment has been associated with proliferative lesions and tumors of the uterus, female liver and testes in other studies, supporting a hypothesis that arsenate might somehow act through an estrogenic mode of action. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 42 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-08-044067-3 PY 2001 BP 255 EP 264 PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA BV09P UT WOS:000177816200023 ER PT B AU Tasca, RJ AF Tasca, RJ BE Gardner, DK Lane, M TI The cell biology of preimplantation development SO ART AND THE HUMAN BLASTOCYST SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT International Symposium on ART and the Human Blastocyst CY MAR 30-APR 02, 2000 CL DANA POINT, CA SP Serono Symposia USA, Inc ID AMINO-ACID-TRANSPORT; MOUSE EMBRYOS; GENE-EXPRESSION; GROWTH-FACTOR; CULTURE; BLASTOCYSTS; ACTIVATION; ATPASE; VIABILITY; CHANNELS C1 NIH, NICHHD, Bethesda, MD 20892 USA. RP Tasca, RJ (reprint author), NIH, NICHHD, Bldg 10, Bethesda, MD 20892 USA. NR 38 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95245-4 J9 SERONO SYMP PY 2001 BP 51 EP 60 PG 10 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA BT34Z UT WOS:000172715700005 ER PT J AU Reboul, P Pelletier, JP Tardif, G Benderdour, M Ranger, P Bottaro, DP Martel-Pelletier, J AF Reboul, P Pelletier, JP Tardif, G Benderdour, M Ranger, P Bottaro, DP Martel-Pelletier, J TI Hepatocyte growth factor induction of collagenase 3 production in human osteoarthritic cartilage - Involvement of the stress-activated protein kinase/c-Jun N-terminal kinase pathway and a sensitive p38 mitogen-activated protein kinase inhibitor cascade SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FACTOR SCATTER FACTOR; RECEPTOR TYROSINE KINASE; GRB2 BINDING-SITE; C-MET RECEPTOR; PROTEOGLYCAN SYNTHESIS; ARTICULAR-CARTILAGE; HUMAN CHONDROCYTES; OXIDATIVE STRESS; CELL MOTILITY; MAP KINASE AB Objective. Osteoarthritis (OA) involves both a decreased reparative process and an increased degradative phenomenon. Several cytokines and growth factors are known to facilitate the repair of articular cartilage defects, The hepatocyte growth factor (HGF) present in OA cartilage is suggested to be involved in the cartilage repair process as well as in matrix remodeling and chondrocyte migration, leading to partial reconstruction of articular cartilage. Since cell migration is often correlated with metalloprotease activity, the effect of HGF on collagenase 3 production was studied because of its possible implication in OA cartilage remodeling. Methods. We examined HGF-stimulated collagenase 3 production in human OA chondrocytes by Western and Northern blotting, Furthermore, we explored the intracellular signaling pathways through which HGF induced collagenase 3 production. Results, This study showed that HGF stimulated collagenase 3 production in human OA chondrocytes at the transcriptional level, and this induction was mediated by activation of the stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) pathway, but not the p38 mitogen-activated protein kinase (MAPK). The p44/42 MAPKs were also phosphorylated and the use of their specific inhibitor (PD 98059) did not affect HGF-induced collagenase 3 production in OA chondrocytes. Induced collagenase 3 production via the SAPK/JNK pathway was mediated, at least in part, by the TRE site in the promoter, and in the activator protein 1 complex, c-Jun, JunD, and Fra-1 were activated. Surprisingly, further experiments revealed that the specific p38 MAPK inhibitor SE 202190 also inhibited collagenase 3 production early in the HGF-induced process. The 50% inhibitory concentration was as low as 50 nM, which is unlikely to be related to p38 MAPK inhibition (which is usually in the muM range), suggesting the involvement of another kinase sensitive to SE 202190. Conclusion. This is the first study to show that HGF has the ability to induce both the expression and synthesis of collagenase 3 in OA chondrocytes. The effect is mediated by kinase cascades involving SAPK/JNK and another, unidentified kinase. This study provides novel information implicating a role for HGF in the pathophysiology of OA through its effect on the production of collagenase 3, which is an enzyme that is possibly involved in OA cartilage remodeling. C1 Ctr Hosp Univ Montreal, Hop Notre Dame, Unite Rech Arthrose, Montreal, PQ H2L 4M1, Canada. Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. NCI, Bethesda, MD 20892 USA. RP Reboul, P (reprint author), Ctr Hosp Univ Montreal, Hop Notre Dame, Unite Rech Arthrose, 1560 Rue Sherbrooke Est, Montreal, PQ H2L 4M1, Canada. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 61 TC 36 Z9 37 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2001 VL 44 IS 1 BP 73 EP 84 DI 10.1002/1529-0131(200101)44:1<73::AID-ANR11>3.0.CO;2-E PG 12 WC Rheumatology SC Rheumatology GA 396VX UT WOS:000166659100011 PM 11212179 ER PT J AU Hayashida, K Nanki, T Girschick, H Yavuz, S Ochi, T Lipsky, PE AF Hayashida, K Nanki, T Girschick, H Yavuz, S Ochi, T Lipsky, PE TI Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP-1 and IL-8 SO ARTHRITIS RESEARCH LA English DT Review DE chemokine; monocyte; rheumatoid arthritis ID CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTORS; CHEMOTACTIC CYTOKINE; T-CELLS; B-CELLS; EXPRESSION; MACROPHAGE; RANTES; ANTAGONIST; APOPTOSIS AB Macrophages that accumulate in the synovium of rheumatoid arthritis patients play an important role in the pathogenesis of this inflammatory disease. However, the mechanism by which macrophages are attracted into the inflamed synovium and accumulate there has not been completely delineated. The results of this study show that rheumatoid arthritis synovial stromal cells produce the chemokines monocyte chemotactic protein-1 and IL-8, and these have the capacity to attract peripheral monocytes. These results suggest that one of the mechanisms by which macrophages accumulate in the inflamed synovium is by responding to the chemokines produced locally. C1 Univ Texas, SW Med Ctr, Dallas, TX USA. Osaka Univ, Sch Med, Osaka, Japan. RP Lipsky, PE (reprint author), NIAMSD, 9000 Rockville Pike,Bldg 10,Room 9N 228, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR-39169] NR 26 TC 72 Z9 77 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-9913 J9 ARTHRITIS RES JI Arthritis Res. PY 2001 VL 3 IS 2 BP 118 EP 126 DI 10.1186/ar149 PG 9 WC Rheumatology SC Rheumatology GA 409TH UT WOS:000167401400007 PM 11178119 ER PT J AU Dorner, T Kaschner, S Hansen, A Pruss, A Lipsky, PE AF Dorner, T Kaschner, S Hansen, A Pruss, A Lipsky, PE TI Perturbations in the impact of mutational activity on V lambda genes in systemic lupus erythematosus SO ARTHRITIS RESEARCH LA English DT Review DE autoimmunity; B cells; SLE; somatic hypermutation; V genes ID HEAVY-CHAIN GENES; SOMATIC HYPERMUTATION; IMMUNOGLOBULIN GENES; SUBSEQUENT SELECTION; SJOGRENS-SYNDROME; RGYW MOTIFS; DNA STRANDS; REPERTOIRE; REARRANGEMENTS; AUTOANTIBODIES AB To assess the impact of somatic hypermutation and selective influences on the V lambda light chain repertoire in systemic lupus erythematosus (SLE), the frequency and pattern of mutations were analyzed in individual CID19(+) B cells from a patient with previously undiagnosed SLE. The mutational frequency of nonproductive and productive rearrangements in the SLE patient was greater (3.1 x 10(-2) vs 3.4 x 10(-2), respectively) than that in normal B cells (1.2 x 10(-2) vs 2.0 x 10(-2), both P < 0.001). The frequencies of mutated rearrangements in both the nonproductive and productive repertoires were significantly higher in the patient with SLE than in normal subjects. Notably, there were no differences in the ratio of replacement to silent (R/S) mutations in the productive and nonproductive repertoires of the SLE patient, whereas the R/S ratio in the framework regions of productive rearrangements of normal subjects was reduced, consistent with active elimination of replacement mutations in this region. The pattern of mutations was abnormal in the SLE patient, with a significant increase in the frequency of G mutations in both the productive and nonproductive repertoires. As in normal subjects, however, mutations were found frequently in specific nucleotide motifs, the RGYW/WRCY sequences, accounting for 34% (nonproductive) and 46% (productive) of all mutations. These data are most consistent with the conclusion that in this SLE patient, the mutational activity was markedly greater than in normal subjects and exhibited some abnormal features. In addition, there was decreased subsequent positive or negative selection of mutations. The enhanced and abnormal mutational activity along with disturbances in selection may play a role in the emergence of autoreactivity in this patient with SLE. C1 Univ Hosp Charite, Dept Med, D-10098 Berlin, Germany. Univ Hosp Charite, Inst Transfus Med, D-10098 Berlin, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Univ Hosp Charite, Dept Med, Schumannstr 20-21, D-10098 Berlin, Germany. NR 34 TC 13 Z9 13 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-9913 J9 ARTHRITIS RES JI Arthritis Res. PY 2001 VL 3 IS 6 BP 368 EP 374 DI 10.1186/ar329 PG 7 WC Rheumatology SC Rheumatology GA 493RT UT WOS:000172237800006 PM 11714391 ER PT J AU Grigolo, B Lisignoli, G Piacentini, A Fiorini, M Roseti, L Major, EO Duca, M Pavesio, A Facchini, A AF Grigolo, B. Lisignoli, G. Piacentini, A. Fiorini, M. Roseti, L. Major, E. O. Duca, M. Pavesio, A. Facchini, A. TI Evidence for re-differentiation of human chondrocytes seeded on a hyaluronan derivative scaffold SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract C1 Ist Ortoped Rizzoli, Lab Immunol & Genet, Bologna, Italy. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Fidia Adv Biopolymers, Abano Terme, Italy. RI Grigolo, Brunella/J-5417-2016 OI Grigolo, Brunella/0000-0002-3990-6745 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2001 VL 3 SU 1 MA P7 PG 1 WC Rheumatology SC Rheumatology GA V31MO UT WOS:000208887900008 ER PT J AU O'Shea, JJ AF O'Shea, J. J. TI Cytokine signalling: new insights and new opportunities for therapeutic intervention? SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract C1 [O'Shea, J. J.] NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2001 VL 3 SU A MA L18 PG 1 WC Rheumatology SC Rheumatology GA V31MP UT WOS:000208888000132 ER PT J AU Abugo, OO Balagopalakrishna, C Rifkind, JM Rudolph, AS Hess, JR Macdonald, VW AF Abugo, OO Balagopalakrishna, C Rifkind, JM Rudolph, AS Hess, JR Macdonald, VW TI Direct measurements of hemoglobin interactions with liposomes using EPR spectroscopy SO ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article ID OXIDATION; DELIVERY; PROTEIN; PEROXIDATION; RABBIT AB Electron paramagnetic resonance (EPR) spectroscopy was used to compare the rates of autoxidation at 37 degreesC of acellular and liposome-encapsulated hemoglobin (LEH) crosslinked between alpha chains with bis (3,5-dibromosalicyl) fumarate (alpha alpha Hb). This method avoids the difficulties inherent in using conventional ultraviolet-visible (UV-vis) spectroscopy caused by the high turbidity of liposome suspensions. Rate constants of 0.039/h and 0.065/h were obtained for the alpha alpha Hb and LEH samples, respectively. Similar oxidation measurements with alpha alpha Hb using UV-vis spectroscopy gave a rate constant comparable to that obtained with EPR spectroscopy. Indirect measurement of the oxidation kinetics of LEH utilizing extraction of aaHb with chloroform from partially oxidized LEH samples was unreliable because the amount of extractable hemoglobin was inversely proportional to the degree of oxidation. EPR measurements showed a shift in the g value and substantial enhancement in the intensity of the bis-histidine low-spin B complex for the encapsulated hemoglobin, indicating a perturbation of this low-spin complex. We suggest that lipid-associated perturbations are responsible for the enhancement of the oxidation observed with the LEH samples compared to the unencapsulated material. C1 Walter Reed Army Inst Res, Blood Res Dept, Silver Spring, MD 20910 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Def Adv Res Projects Agcy, Def Sci Off, Arlington, VA 22203 USA. RP Macdonald, VW (reprint author), Walter Reed Army Inst Res, Blood Res Dept, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1073-1199 J9 ARTIF CELL BLOOD SUB JI Artif. Cells Blood Substit. Immobil. Biotechnol. PY 2001 VL 29 IS 1 BP 5 EP 18 DI 10.1081/BIO-100001252 PG 14 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials Science, Biomaterials SC Biotechnology & Applied Microbiology; Engineering; Materials Science GA 407HV UT WOS:000167266900002 PM 11280684 ER PT J AU Alayash, AI AF Alayash, AI TI Oxidative mechanisms of hemoglobin-based blood substitutes SO ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article DE hemoglobin; blood substitutes; oxidative stress ID CROSS-LINKED HEMOGLOBIN; HYDROGEN-PEROXIDE; POLYOXYETHYLENE CONJUGATE; FERRYL INTERMEDIATE; HEME DEGRADATION; MYOGLOBIN; FERRYLHEMOGLOBIN; GENE; OXYHEMOGLOBIN; AUTOXIDATION AB Chemically or genetically altered cell-free hemoglobin (Hb) has been developed as an oxygen carrying therapeutic. Site-directed modifications are introduced and serve to stabilize the protein molecules in a tetrameric and/or a polymeric functional form. Direct cytotoxic effects associated with cell-free Hb have been ascribed to redox reactions (involving either I or 2 electron steps) between the heme group and peroxides. These interactions are the basis of the pseudoperoxidase activity of Hb and can be cytotoxic when reactive species are formed at relatively high concentrations during inflammation and typically lead to cell death. Peroxides relevant to biological systems include hydrogen peroxide (H2O2), lipid hydroperoxides (LOOH), and peroxynitrite (ONOO-). Reactions between Hb and peroxides form the ferryl oxidation state of the protein, analogous to compounds I and II formed in the catalytic cycle of many peroxidase enzymes. This higher oxidation state of the protein is a potent oxidant capable of promoting oxidative damage to most classes of biological molecules. Further complications are thought to arise through the disruption of key signaling pathways resulting from alteration of or destruction of important physiological mediators. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH Campus,Bldg 29,Rm 112, Bethesda, MD 20892 USA. NR 40 TC 18 Z9 19 U1 1 U2 7 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1073-1199 J9 ARTIF CELL BLOOD SUB JI Artif. Cells Blood Substit. Immobil. Biotechnol. PY 2001 VL 29 IS 6 BP 415 EP 425 DI 10.1081/BIO-100108547 PG 11 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials Science, Biomaterials SC Biotechnology & Applied Microbiology; Engineering; Materials Science GA 509JX UT WOS:000173145600001 PM 11795628 ER PT S AU Wilbur, WJ Kim, W AF Wilbur, WJ Kim, W BE Aversa, E Manley, C TI Flexible phrase based query handling algorithms SO ASIST 2001: PROCEEDINGS OF THE 64TH ASIST ANNUAL MEETING, VOL 38, 2001 SE PROCEEDINGS OF THE ASIST ANNUAL MEETING LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the American-Society-Information-Science-and-Technology CY NOV 03-08, 2001 CL WASHINGTON, D.C. SP Amer Soc Informat Sci Technol AB Flexibility in query handling can be important if one types a search engine query that is misspelled, contains terms not in the database, or requires knowledge of a controlled vocabulary. To obtain such flexibility one must relate phrases to other phrases. Experience suggests that documents are best related to each other based on the individual words they contain. Attempts to break the words in documents down into three letter pieces or tri-grams degrade performance because with many words, tri-gram matches are frequent between unrelated words. However, phrases may be looked at as very small documents and we have found that the ambiguity that arises from longer documents essentially disappears with reasonably short phrases. This has led us to treat a phrase like a document and the tri-grams that make up the words of that phrase like the words of the document. With some minor up-weighting of the first tri-gram of each word and the first letter of each word, one may apply relatively standard vector retrieval methods to obtain a very useful flexible method of phrase matching. Here we present results of experiments that suggest the optimal form of similarity functions that are applicable to the task of phrase based retrieval to find either synonymous or closely related phrases. C1 Natl Lib Med, Bethesda, MD USA. RP Wilbur, WJ (reprint author), Natl Lib Med, Bethesda, MD USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 USA SN 0044-7870 BN 1-57387-138-9 J9 P ASIST ANNU PY 2001 VL 38 BP 438 EP 449 PG 12 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BU37V UT WOS:000175838000041 ER PT S AU Hodge, G Cotter, G Finch, W Frierson, E Molholm, K Shepanek, R Smith, K Warnick, W Carroll, B AF Hodge, G Cotter, G Finch, W Frierson, E Molholm, K Shepanek, R Smith, K Warnick, W Carroll, B BE Aversa, E Manley, C TI The Science.gov Alliance: Developing an interagency portal for science and technology SO ASIST 2001: PROCEEDINGS OF THE 64TH ASIST ANNUAL MEETING, VOL 38, 2001 SE PROCEEDINGS OF THE ASIST ANNUAL MEETING LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the American-Society-Information-Science-and-Technology CY NOV 03-08, 2001 CL WASHINGTON, D.C. SP Amer Soc Informat Sci Technol C1 CENDI, Havertown, PA USA. Natl Biol Informat Infrastruct, Reston, VA USA. Natl Tech Informat Serv, Springfield, VA USA. Natl Agr Lib, Beltsville, MD USA. Def Tech Informat Ctr, Ft Belvoir, VA USA. US EPA, Washington, DC 20460 USA. Natl Lib Med, Bethesda, MD USA. US DOE, Germantown, MD USA. CENDI, Oak Ridge, TN USA. RP Hodge, G (reprint author), CENDI, Havertown, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 USA SN 0044-7870 BN 1-57387-138-9 J9 P ASIST ANNU PY 2001 VL 38 BP 611 EP 611 PG 1 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BU37V UT WOS:000175838000085 ER PT S AU Aronson, A Elkin, P AF Aronson, A Elkin, P BE Aversa, E Manley, C TI Automated concept based medical indexing SO ASIST 2001: PROCEEDINGS OF THE 64TH ASIST ANNUAL MEETING, VOL 38, 2001 SE PROCEEDINGS OF THE ASIST ANNUAL MEETING LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the American-Society-Information-Science-and-Technology CY NOV 03-08, 2001 CL WASHINGTON, D.C. SP Amer Soc Informat Sci Technol C1 Natl Lib Med, Bethesda, MD USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Aronson, A (reprint author), Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 USA SN 0044-7870 BN 1-57387-138-9 J9 P ASIST ANNU PY 2001 VL 38 BP 636 EP 636 PG 1 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BU37V UT WOS:000175838000095 ER PT J AU Krause, RM AF Krause, RM TI Microbes and emerging infections: the compulsion to become something new SO ASM NEWS LA English DT Article C1 NIH, Lab Human Bacterial Pathogenesis, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD JAN PY 2001 VL 67 IS 1 BP 15 EP 20 PG 6 WC Microbiology SC Microbiology GA 390QE UT WOS:000166307200010 ER PT J AU Fauci, AS AF Fauci, AS TI A half-century of NIAID research SO ASM NEWS LA English DT Article C1 NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD JAN PY 2001 VL 67 IS 1 BP 16 EP 16 PG 1 WC Microbiology SC Microbiology GA 390QE UT WOS:000166307200011 ER PT J AU Shrager, RI AF Shrager, RI TI On a three-term variant of the Lomb periodogram SO ASTROPHYSICS AND SPACE SCIENCE LA English DT Article ID SPACED DATA; SEARCH AB Interdependence of trigonometric terms with the constant term in the current two-term form of the Lomb periodogram leads to cases where the maximum computed power does not correspond to the dominant frequency in the data, i.e., the dominant frequency is misidentified. This happens even in noiseless cases with only one frequency present. A three-term form of the Lomb periodogram is considered as a way of correcting the problem. Another difference between the two- and three-term forms is their behavior in poorly-determined cases, particularly at or near the Nyquist frequency (or its integer multiples) for equally spaced data, The two-term form will return reasonable-looking positive (and possibly significant) values, whereas the three-term form will return zeros. Arguments for and against these results will be given. C1 NIH, Phys Sci Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Shrager, RI (reprint author), NIH, Phys Sci Lab, Div Comp Res & Technol, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 9 Z9 9 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0004-640X J9 ASTROPHYS SPACE SCI JI Astrophys. Space Sci. PY 2001 VL 277 IS 4 BP 519 EP 530 DI 10.1023/A:1013832330141 PG 12 WC Astronomy & Astrophysics SC Astronomy & Astrophysics GA 503PA UT WOS:000172805800001 ER PT J AU McNamara, JR Shah, PK Nakajima, K Cupples, LA Wilson, PWF Ordovas, JM Schaefer, EJ AF McNamara, JR Shah, PK Nakajima, K Cupples, LA Wilson, PWF Ordovas, JM Schaefer, EJ TI Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study SO ATHEROSCLEROSIS LA English DT Article DE lipoproteins; very low density lipoproteins; chylomicrons; triglycerides; apolipoprotein B; cardiovascular disease ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; TRIGLYCERIDE-RICH LIPOPROTEINS; APOLIPOPROTEIN-A-I; COMMERCIAL IMMUNOTURBIDIMETRIC ASSAY; SUDDEN CARDIAC DEATH; IMMUNOSEPARATION METHOD; REFERENCE INTERVALS; HDL-CHOLESTEROL; BLOOD-PLASMA AB Remnants of triglyceride-rich lipoproteins (TRL) of both intestinal and liver origin are considered to be atherogenic, but separation of remnant lipoproteins from other TRL is difficult. An assay has been developed that allows immunoseparation of remnant-like particles (RLP) and measurement of cholesterol (RLP-C) and triglyceride (RLP-TG). We measured RLP-C and RLP-TG in fast plasma samples obtained from 1567 women participating in cycle 4 of the Framingham heart study (FHS). When values from 83 women with cardiovascular disease (CVD) were compared with the values from 1484 women without disease, concentrations in women with CVD were found to be significantly higher for both RLP-C (0.215 +/- 0.102 vs. 0.186 +/- 0.162 mmol/l; + 15.6%; P < 0.0001) and RLP-TG (0.319 0.352 vs. 0.251 +/- 0.716 mmol/l; +27.0%; P < 0.0002). Logistic regression analysis revealed that RLP-C was significantly associated with prevalent CVD in women (P < 0.002) after adjustment with other major risk factors. In conclusion, we have documented that RLP-C is an independent risk factor for CVD in women, and provides significantly more information than do triglycerides. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 New England Med Ctr, Lipid Res Lab, Div Endocrinol Diabet Metab & Mol Med, Boston, MA 02111 USA. Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA USA. Otsuka Amer Pharmaceut Inc, Rockville, MD USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. RP McNamara, JR (reprint author), New England Med Ctr, Lipid Res Lab, Div Endocrinol Diabet Metab & Mol Med, 750 Washington St,Box 216, Boston, MA 02111 USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [N01-HC-38038] NR 62 TC 177 Z9 180 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2001 VL 154 IS 1 BP 229 EP 236 DI 10.1016/S0021-9150(00)00484-6 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 387GZ UT WOS:000166116000028 PM 11137104 ER PT J AU Roberts, K Powell, MB AF Roberts, K Powell, MB TI The effect of repeated experience on children's suggestibility across two question types SO AUSTRALIAN JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD 20892 USA. Deakin Univ, Geelong, Vic 3217, Australia. EM Kr63q@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AUSTRALIAN PSYCHOLOGICAL SOC PI CARLTON PA 1 GRATTAN STREET, CARLTON, VICTORIA 3053, AUSTRALIA SN 0004-9530 J9 AUST J PSYCHOL JI Aust. J. Psychol. PY 2001 VL 53 SU S BP 28 EP 28 PG 1 WC Psychology, Multidisciplinary SC Psychology GA V42OE UT WOS:000202876000130 ER PT B AU Walters, JR Bergstrom, DA Molnar, LR Freeman, LE Ruskin, DN AF Walters, JR Bergstrom, DA Molnar, LR Freeman, LE Ruskin, DN BE KultasIlinsky, K Ilinsky, IA TI Effects of dopamine receptor stimulation on basal ganglia activity SO BASAL GANGLIA AND THALAMUS IN HEALTH AND MOVEMENT DISORDERS LA English DT Proceedings Paper CT International Workshop on Basal Ganglia and Thalamus in Health and Movement Disorders CY MAY 29-31, 2000 CL MOSCOW, RUSSIA SP Eli Lilly, Allergan, Solvay, Medtronic, SmithKline Beecham, Integrated Surg Syst, BrainLab, Radionies, FHC ID GLOBUS-PALLIDUS NEURONS; LEVODOPA-INDUCED DYSKINESIAS; SUBTHALAMIC NUCLEUS NEURONS; MPTP-INDUCED PARKINSONISM; NIGRA PARS RETICULATA; RAT STRIATAL NEURONS; SUBSTANTIA-NIGRA; IN-VIVO; MULTISECOND OSCILLATIONS; FIRING RATE C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Walters, JR (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10 Room 5C103,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 103 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46543-4 PY 2001 BP 135 EP 150 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA BS24H UT WOS:000169154400011 ER PT B AU Hallett, M AF Hallett, M BE KultasIlinsky, K Ilinsky, IA TI Plasticity and basal ganglia disorders SO BASAL GANGLIA AND THALAMUS IN HEALTH AND MOVEMENT DISORDERS LA English DT Proceedings Paper CT International Workshop on Basal Ganglia and Thalamus in Health and Movement Disorders CY MAY 29-31, 2000 CL MOSCOW, RUSSIA SP Eli Lilly, Allergan, Solvay, Medtronic, SmithKline Beecham, Integrated Surg Syst, BrainLab, Radionies, FHC ID TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY SOMATOSENSORY CORTEX; REPETITIVE STRAIN INJURY; INDUCED MOVEMENT THERAPY; MOTOR CORTEX; FOCAL DYSTONIA; CORTICAL REORGANIZATION; ADULT MONKEYS; STROKE; HAND C1 NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. NR 53 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46543-4 PY 2001 BP 197 EP 204 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA BS24H UT WOS:000169154400016 ER PT S AU Cassell, OCS Morrison, WA Messina, A Penington, AJ Thompson, EW Stevens, GW Perera, JM Kleinman, HK Hurley, JV Romeo, R Knight, KR AF Cassell, OCS Morrison, WA Messina, A Penington, AJ Thompson, EW Stevens, GW Perera, JM Kleinman, HK Hurley, JV Romeo, R Knight, KR BE Hunkeler, D Cherrington, A Prokop, A Rajotte, R TI The influence of extracellular matrix on the generation of vascularized, engineered, transplantable tissue SO BIOARTIFICIAL ORGANS III: TISSUE SOURCING, IMMUNOISOLATION, AND CLINICAL TRIALS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Bioartificial Organs III - Tissue Sourcing, Immunoisoloation, and Clinical Trials CY OCT 07-11, 2000 CL DAVOS, SWITZERLAND SP Bellevue Asset Management, European Community Cost 840 Encapsulat Network, Fonds Natl Suisse, Inotech Encapsulat AG, Juvenile Diabetes Fdn Int, NIH, Natl Sci Fdn, Nisco Engn, Novartis Pharmaceut Canada Inc, Pronova Biomed, United Engn Fdn DE tissue engineering; extracellular matrix; angiogenesis; chamber model; fibrin; Matrigel; poly-D,L-lactic-co-glycolic acid (PLGA) ID BASEMENT-MEMBRANE; GROWTH-FACTOR; FIBRIN GLUE; ANGIOGENESIS; POLYMER; CELL; CARTILAGE; MUSCLE; LOOP AB In a recently described model for tissue engineering, an arteriovenous loop comprising the femoral artery and vein with interposed vein graft is fabricated in the groin of an adult male rat, placed inside a polycarbonate chamber, and incubated subcutaneously. New vascularized granulation tissue will generate on this loop for up to 12 weeks. In the study described in this paper three different extracellular matrices were investigated for their ability to accelerate the amount of tissue generated compared with a no-matrix control. Poly-D,L-lactic-co-glycolic acid (PLGA) produced the maximal weight of new tissue and vascularization and this peaked at two weeks, but regressed by four weeks. Matrigel was next best. It peaked at four weeks but by eight weeks it also had regressed. Fibrin (20 and 80 mg/ml), by contrast, did not integrate with the generating vascularized tissue and produced less weight and volume of tissue than controls without matrix. The limiting factors to growth appear to be the chamber size and the capacity of the neotissue to integrate with the matrix. Once the sides of the chamber are reached or tissue fails to integrate, encapsulation and regression follow. The intrinsic position of the blood supply within the neotissue has many advantages for tissue and organ engineering, such as ability to seed the construct with stem cells and microsurgically transfer new tissue to another site within the individual. In conclusion, this study has found that PLGA and Matrigel are the best matrices for the rapid growth of new vascularized tissue suitable for replantation or transplantation. C1 Univ Melbourne, Bernard OBrien Inst Microsurg, St Vincents Hosp, Fitzroy, Vic 3065, Australia. Univ Melbourne, Dept Surg, St Vincents Hosp, Fitzroy, Vic 3065, Australia. Univ Melbourne, Dept Chem Engn, Parkville, Vic 3010, Australia. Natl Inst Dent & Craniofacial Res, Cell Biol Sect, NIH, Bethesda, MD USA. RP Knight, KR (reprint author), Univ Melbourne, Bernard OBrien Inst Microsurg, St Vincents Hosp, 42 Fitzroy St, Fitzroy, Vic 3065, Australia. RI Thompson, Erik/A-1425-2009; OI Thompson, Erik/0000-0002-9723-4924; Stevens, Geoffrey/0000-0002-5788-4682 NR 31 TC 83 Z9 86 U1 1 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-342-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 944 BP 429 EP 442 PG 14 WC Engineering, Biomedical; Multidisciplinary Sciences; Transplantation SC Engineering; Science & Technology - Other Topics; Transplantation GA BT69D UT WOS:000173774500036 PM 11797691 ER PT J AU Choi, YH Ekholm, D Krall, J Ahmad, F Degerman, E Manganiello, VC Movsesian, MA AF Choi, YH Ekholm, D Krall, J Ahmad, F Degerman, E Manganiello, VC Movsesian, MA TI Identification of a novel isoform of the cyclic-nucleotide phosphodiesterase PDE3A expressed in vascular smooth-muscle myocytes SO BIOCHEMICAL JOURNAL LA English DT Article DE intracellular signalling; protein phosphorylation; second messengers; vasodilation ID INHIBITED CAMP-PHOSPHODIESTERASE; RNA POLYMERASE-II; SARCOPLASMIC-RETICULUM; MOLECULAR-CLONING; GENE; PROMOTER; CELLS; LOCALIZATION; PROTEIN; HORMONE AB We have identified a new cyclic-nucleotide phosphodiesterase isoform, PDE3A, and cloned its cDNA from cultured aortic myocytes. The nucleotide sequence of its coding region is similar to that of the previously cloned myocardial isoform except for the absence of the initial 300-400 nt that are present in the latter, as confirmed by reverse-transcriptase-mediated PCR, 5' rapid amplification of cDNA ends and a ribonuclease protection assay. Expression in Spodoptera frugiperda (Sf9) cells yields a protein with catalytic activity and inhibitor sensitivity typical of the PDE3 family. The recombinant protein's molecular mass of approx. 131 kDa is compatible with translation from an ATG sequence corresponding to nt 436-438 of the myocardial PDE3A coding region, Antibodies against residues 424-460 (nt 1270-1380) and 1125-1141 (nt 3373-3423) of the myocardial isoform react with an approx. 118 kDa band in Western blots of homogenates of human aortic myocytes, whereas antibodies against residues 29-42 (nt 85-126) do not react with any bands in these homogenates. Our results suggest that a vascular smooth-muscle isoform ('PDE3A2') is a product of the same gene as the longer myocardial ('PDE3A1') and the shorter placental ('PDE3A3') isoforms and is generated pre-translationally in a manner that results in the absence of the 145 N-tenninal amino acids of PDE3A1. C1 VA Salt Lake City Hlth Care Syst, Res Serv, Salt Lake City, UT 84148 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Univ Lund, Sect Mol Signalling, Dept Cell & Mol Biol, S-22100 Lund, Sweden. Univ Utah, Hlth Sci Ctr, Dept Internal Med Cardiol, Salt Lake City, UT 84132 USA. Univ Utah, Hlth Sci Ctr, Dept Pharmacol, Salt Lake City, UT 84132 USA. RP Movsesian, MA (reprint author), VA Salt Lake City Hlth Care Syst, Res Serv, 500 Foothill Blvd, Salt Lake City, UT 84148 USA. FU NCI NIH HHS [5P30CA42014] NR 53 TC 34 Z9 34 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 1 PY 2001 VL 353 BP 41 EP 50 PN 1 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392AE UT WOS:000166387800005 PM 11115397 ER PT J AU Rosenfeldt, HM Hobson, JP Milstien, S Spiegel, S AF Rosenfeldt, HM Hobson, JP Milstien, S Spiegel, S TI The sphingosine-I-phosphate receptor EDG-I is essential for platelet-derived growth factor-induced cell motility SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Colloquium on Enzymes that Regulate Lipid Metabolism in Cell Signalling CY JUL 11-13, 2001 CL DUBLIN, IRELAND SP GlaxoSmithKlin, Yamanouchi, Novartis AstraZeneca, Merck, Pfizer, Serono Pharmaceut DE angiogenesis; transactivation; vascular maturation; chemotaxis ID PDGF-B; SPHINGOSINE-1-PHOSPHATE; PROLIFERATION; 1-PHOSPHATE; MICE AB EDG-1, encoded by the endothelial differentiation gene-1, is a heterotrimeric guanine nucleotide binding protein-coupled receptor (GPCR) for sphingosine-1-phosphate (SPP) that has been shown to stimulate angiogenesis and cell migration in cultured endothelial cells. Unexpectedly, EDG-1 knockout embryos had a normal blood vessel network, vasculogenesis and angiogenesis, but died in utero owing to massive haemorrhaging as a result of failure of smooth muscle cells and pericytes to migrate around the circumference and reinforce endothelial tubes [Liu, Wada, Yamashita, Mi, Deng, Hobson, Rosenfeldt, Nava, Chae, Lee, et al. (2000) J. Clin. Invest. 106, 951-961]. This vascular maturation defect is similar to the phenotype of mice homozygous for disrupted alleles of plate] et-derived growth factor B-subunit homodimer (PDGF-BB) or its receptor PDGFR-beta. We found that fibroblasts from EDG-1 null embryos did not migrate toward PDGF or SPP, and inhibition of motility correlated with defective activation of the small guanosine triphosphatase Rac, which is required for lamellipodia formation and directional locomotion [Hobson, Rosenfeldt, Barak, Olivera, Poulton, Caron, Milstien, and Spiegel (2001) Science 291, 1800-1803]. Moreover, we showed that PDGF-directed cell migration requires both sphingosine kinase activation and expression of EDG-1, suggesting a functional link between PDGF signalling and EDG-1. Indeed, treatment of wild-type cells with PDGF transactivated. EDG-1 as determined by translocation of beta -arrestin and phosphorylation of EDG-1. These findings reveal a new paradigm for receptor cross-communication in which activation of a G-PCR by a receptor tyrosine kinase is critical for cell motility. Our observations might also clarify the role of EDG-1 in vascular maturation and angiogenesis. C1 Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NR 14 TC 34 Z9 35 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PY 2001 VL 29 BP 836 EP 839 DI 10.1042/0300-5127:0290836 PN 6 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499FP UT WOS:000172560600038 PM 11709084 ER PT J AU Czar, MJ Debnath, J Schaeffer, EM Lewis, CM Schwartzberg, PL AF Czar, MJ Debnath, J Schaeffer, EM Lewis, CM Schwartzberg, PL TI Biochemical and genetic analyses of the Tec kinases Itk and Rlk/Txk SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Colloquium on Signal Transduction During Innate and Adaptive Immunity CY JUL 11-13, 2001 CL DUBLIN, IRELAND SP GlaxoSmithKline, Yamanouchi, Novartis, AstraAeneca, Merck, Serono Pharmaceut DE phosphatidylinositol 3-kinase; RAFTs; T lymphocytes; tyrosine kinase ID SRC FAMILY KINASES; TYROSINE KINASE; ACTIVATION; SELECTION; CELLS; RLK; TXK AB The Tee kinases have been implicated as important components of signalling pathways downstream of lymphocyte antigen receptors. Activation of these kinases requires two steps: (i) phosphorylation by Src family kinases and (ii) plasma membrane localization, which is mediated by interaction between the pleckstrin homology (PH) domains of Tee kinases and the products of phosphoinositide-3 kinase (PI-3K). Itk and Rlk/Txk are Tee kinases expressed in T-lymphocytes. Despite similarity to other Tee kinases, Rlk/Txk lacks a PH domain and instead possesses a palmitoylated cysteine-string motif. We have found that both Rlk/Txk and Itk are phosphorylated in response to T-cell receptor stimulation and can be activated by phosphorylation by Sire family kinases. However, consistent with its lack of PH domain, Rlk/Txk is phosphorylated independent of PI-3K activity. Furthermore, we demonstrated that like Itk, Rlk/Txk is associated with lipid RAFTs (detergent-insoluble, cholesterol-rich regions of the membrane), but unlike Itk, Rlk/Txk's RAFT association is independent of PI-3K activity. Despite these differences, Rlk/Txk partially compensates for loss of Itk in gene-targeted animals, suggesting overlapping functions for these kinases. C1 NHGRI, NIH, Bethesda, MD 20814 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, Bethesda, MD 20814 USA. NR 20 TC 13 Z9 14 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PY 2001 VL 29 BP 863 EP 867 DI 10.1042/BST0290863 PN 6 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499FP UT WOS:000172560600043 PM 11709089 ER PT J AU Otten, PA London, RE Levy, LA AF Otten, PA London, RE Levy, LA TI A new approach to the synthesis of APTRA indicators SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CYTOSOLIC-FREE MAGNESIUM; CONVOLUTED TUBULE CELLS; FLUORESCENT INDICATOR; MG2+ UPTAKE; INTRACELLULAR MAGNESIUM; ION CONCENTRATION; NEURONS; CA2+; NMR AB We have devised a general synthesis of Mg2+ indicators which is based on the aminophenol triacetic acid (APTRA) structure. The key step is a palladium-catalyzed coupling reaction of a precursor of the APTRA ligand with a fluorescent group. This strategy resulted in new ratioable fluorescent APTRA indicators and the finding that the fluorescence response of these indicators is different for Mg2+ and Ca2+ in some cases. We believe that this represents a generally useful approach for combining fluorophore and chelator functionalities. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Levy, LA (reprint author), NIEHS, Struct Biol Lab, POB 12233,MR-01, Res Triangle Pk, NC 27709 USA. FU NCRR NIH HHS [P41RR0954] NR 27 TC 11 Z9 12 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 2001 VL 12 IS 1 BP 76 EP 83 DI 10.1021/bc000069w PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 393YF UT WOS:000166496700010 PM 11170369 ER PT J AU Kobayashi, H Sato, N Kawamoto, S Saga, T Hiraga, A Haque, TL Ishimori, T Konishi, J Togashi, K Brechbiel, MW AF Kobayashi, H Sato, N Kawamoto, S Saga, T Hiraga, A Haque, TL Ishimori, T Konishi, J Togashi, K Brechbiel, MW TI Comparison of the macromolecular MR contrast agents with ethylenediamine-core versus ammonia-core generation-6 polyamidoamine dendrimer SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; GD-DTPA; ANGIOGRAPHY; FLEXIBILITY; MEDIA AB Two novel macromolecular MRI contrast agents based upon generation-6 polyamidoamine dendrimers (G6) of presumed similar molecular size, but of different molecular weight, were compared in terms of their blood retention, tissue distribution, and renal excretion. Two G6s with either ammonia core (G6A) or with ethylenediamine core (G6E), which possessed 192 and 256 exterior primary amino groups, respectively, were used. These dendrimers were reacted with 2-(p-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid (1B4M). The G6-IB4M conjugates were reacted with Gd-153 for studying biodistribution and blood clearance or Gd(III) for the MRI study. 3D-micro-MR angiography of the mice were taken with injection of 0.033 mmol of Gd/kg of G6A-(1B4M-Gd)(192) or G6E-(1B4M-Gd)(256) using a 1.5-T superconductive MRI unit. Although numerous fine vessels of similar to 100 mum diameter were visualized on subtracted 3D-MR-angiography with both G6A-(1B4M-Gd)(192) and G6E-(1B4M-Gd)(256), Gd-153-labeled saturated G6E-(1B4M)(256) remained in the blood significantly more than Gd-153-labeled saturated G6A-(1B4M)(192) at later than 15 min postinjection (p < 0.01). In addition, G6E-(IB4M-Gd)(256) visualized these finer vessels longer than G6A-(1B4M-Gd)(192). The G6A-(1B4M-Gd)(192) showed higher signal intensity in the kidney on the dynamic MR images and brighter kidney images than G6E-(1B4M-Gd)(256). In conclusion, the G6A-(1B4M-Gd)(192) was observed to go through glomerular filtration more efficiently than G6E-(1B4M-Gd)(256) resulting faster clearance from the blood and higher renal accumulation, even though both of G6-1B4M conjugates have almost similar molecular size and same chemical structure. In terms of the ability of intravascular contrast agents, G6E-(1B4M-Gd)(256) was better due to more Gd(III) atoms per molecule and longer retention in the circulation than G6A-(1B4M-Gd)(192). C1 Hitachi Med Co, Dept Diagnost & Intervent Imagiol, Kyoto 6068507, Japan. Hitachi Med Co, Dept Nucl Med & Diagnost Imaging, Kyoto 6068507, Japan. Kyoto Univ, Dept Radiol, Kyoto 6068507, Japan. Otsu Municipal Hosp, Dept Radiol, Otsu, Shiga 5200804, Japan. NCI, Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Hitachi Med Co, Dept Diagnost & Intervent Imagiol, Kyoto 6068507, Japan. NR 17 TC 71 Z9 74 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 2001 VL 12 IS 1 BP 100 EP 107 DI 10.1021/bc000075s PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 393YF UT WOS:000166496700013 PM 11170372 ER PT J AU Ying, H Zeng, G Black, KL AF Ying, H Zeng, G Black, KL TI Innovative cancer vaccine strategies based on the identification of tumour-associated antigens SO BIODRUGS LA English DT Review ID CYTOTOXIC T-LYMPHOCYTES; PULSED DENDRITIC CELLS; HLA-DR MOLECULES; IMMUNE-RESPONSE; ANTITUMOR IMMUNITY; IN-VIVO; MELANOMA PATIENTS; GENE-EXPRESSION; DNA VACCINATION; PROSTATE-CANCER AB The identification of tumour-associated antigens has opened up new approaches to cancer immunotherapy. While past research focused on CD8+ cytotoxic T-cell responses, accumulating evidence suggests that CD4+ T cells also play an important role in orchestrating the host immune response against cancer. In this article, we summarise new strategies for the identification of major histocompatibility complex (MHC) class II-associated tumour antigens and discuss the importance of engaging both CD4+ and CD8+ T cells in cancer immunotherapy. The cloning of MHC class I- or class II-associated antigens has made it possible to develop synthetic and recombinant cancer vaccines that express specific tumour antigens. There are three major types of synthetic and recombinant cancer vaccines: recombinant viral and bacterial vaccines; naked DNA or RNA vaccines; and recombinant protein and peptide vaccines. In this article, we also discuss a new generation of recombinant cancer vaccines, 'self-replicating' DNA and RNA vaccines. Studies on the mechanisms of 'self-replicating' nucleic acid vaccines revealed that the enhanced immunogenicity was not due to an enhanced antigen expression, suggesting that the quantitative difference may not be as important as the qualitative difference in antigen presentation. The presence of the RNA replicase in the 'self-replicating' nucleic acid vaccines mimics alphavirus infection, which triggers the innate antiviral pathways of the host cells. Studies on how viral and cellular modulators of the innate antiviral pathways affect vaccine function should provide molecular insights crucial to future vaccine design. C1 Cedars Sinai Med Ctr, Maxine Dunitz Neurosurg Inst, Los Angeles, CA 90048 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Ying, H (reprint author), Cedars Sinai Med Ctr, Maxine Dunitz Neurosurg Inst, 8631 W 3rd St,Suite 800E, Los Angeles, CA 90048 USA. NR 83 TC 6 Z9 7 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2001 VL 15 IS 12 BP 819 EP 831 DI 10.2165/00063030-200115120-00004 PG 13 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 521VF UT WOS:000173861500004 PM 11784213 ER PT J AU Levine, M Wang, YH Katz, A Eck, P Kwon, O Chen, SL Lee, JH Padayatty, SJ AF Levine, M Wang, YH Katz, A Eck, P Kwon, O Chen, SL Lee, JH Padayatty, SJ TI Ideal vitamin C intake SO BIOFACTORS LA English DT Article ID ASCORBIC-ACID; VOLUNTEERS; DEPLETION; REPLETION C1 NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bldg 10 Room 4D52,MSC 1372, Bethesda, MD 20892 USA. RI Chen, Shenglin/B-4049-2010; Padayatty, Sebastian/A-8581-2012; OI Padayatty, Sebastian/0000-0001-8758-3170; Eck, Peter/0000-0003-2371-9774 NR 5 TC 3 Z9 4 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 2001 VL 15 IS 2-4 BP 71 EP 74 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 535BX UT WOS:000174626300003 PM 12016328 ER PT J AU Berry, MJ Tujebajeva, RM Copeland, PR Xu, XM Carlson, BA Martin, GW Low, SC Mansell, JB Grundner-Culemann, E Harney, JW Driscoll, DM Hatfield, DL AF Berry, MJ Tujebajeva, RM Copeland, PR Xu, XM Carlson, BA Martin, GW Low, SC Mansell, JB Grundner-Culemann, E Harney, JW Driscoll, DM Hatfield, DL TI Selenocysteine incorporation directed from the 3'UTR: Characterization of eukaryotic EFsec and mechanistic implications SO BIOFACTORS LA English DT Article; Proceedings Paper CT 7th International Symposium on Selenium in Biology and Medicine (Selenium 2000) CY OCT 01-05, 2000 CL VENICE, ITALY DE selenoprotein; biosynthesis; eukarya; archaea; selenoprotein hierarchy; SBP2; EFSec ID SELENOPROTEIN MESSENGER-RNAS; GLUTATHIONE-PEROXIDASE; RAT-LIVER; ELONGATION-FACTOR; DIETARY SELENIUM; SECIS ELEMENTS; INSERTION; TRANSLATION; EXPRESSION; SENSITIVITY AB The mechanism of selenocysteine incorporation in eukaryotes has been assumed for almost a decade to be inherently different from that in prokaryotes. due to differences in the architecture of selenoprotein mRNAs in the two kingdoms. After extensive efforts in a number of laboratories spanning the same time frame, some of the essential differences between these mechanisms are finally being revealed, through identification of the factors catalyzing cotranslational selenocysteine insertion in eukaryotes, A single factor in prokaryotes recognizes both the selenoprotein mRNA, via sequences in the coding region, and the unique selenocysteyl-tRNA, via both its secondary structure and amino acid. The correponding functions in eukaryotes are conferred by two distinct but interacting factors, one recognizing the mRNA, via structures in the 3' untranslated region, and the second recognizing the tRNA, Now, with these factors in hand, crucial questions about the mechanistic details and efficiency of this intriguing process can begin to be addressed. C1 Brigham & Womens Hosp, Dept Med, Div Thyroid, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44195 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Berry, MJ (reprint author), Harvard Inst Med, Thyroid Div, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM berry@rascal.med.harvard.edu NR 24 TC 37 Z9 39 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 2001 VL 14 IS 1-4 BP 17 EP 24 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 480RC UT WOS:000171474900004 PM 11568436 ER PT J AU Lacourciere, GM Stadtman, TC AF Lacourciere, GM Stadtman, TC TI Utilization of selenocysteine as a source of selenium for selenophosphate biosynthesis SO BIOFACTORS LA English DT Article; Proceedings Paper CT 7th International Symposium on Selenium in Biology and Medicine (Selenium 2000) CY OCT 01-05, 2000 CL VENICE, ITALY DE selenophosphate synthetase; cysteine desulfurase; selenocysteine lyase; NifS-like proteins; selenophosphate biosynthesis ID IN-VITRO BIOSYNTHESIS; COLI TRANSFER-RNA; FE-S CLUSTER; ESCHERICHIA-COLI; CYSTEINE DESULFURASE; GENE CLONING; NIFS; ENZYME; LYASE; 4-THIOURIDINE AB Selenophosphate synthetase (SPS), the selD gene product from Escherichia coli, catalyzes the biosynthesis of monoselenophosphate from selenide and ATP. Characterization of selenophosphate synthetase revealed the determined K-m value for selenide is far above the optimal concentration needed for growth and approached levels which are toxic, Selenocysteine lyase enzymes, which decompose selenocysteine to elemental selenium (Se-o) and alanine, were considered as candidates for the control of free selenium levels in vivo. The ability of a lyase protein to generate Se-o in the proximity of SPS maybe an attractive solution to selenium toxicity as well as the high K-m value for selenide. Recently, three E. coli NifS-like proteins, CsdB, CSD, and IscS, were characterized. All three proteins exhibit lyase activity, on L-cysteine and L-selenocysteine and produce sulfane sulfur, S-o, or Se-o respectively. Each lyase can effectively mobilize Seo from L-selenocysteine for selenophosphate biosynthesis. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Lacourciere, GM (reprint author), NHLBI, Biochem Lab, NIH, 50 South Dr,Room 2126, Bethesda, MD 20892 USA. NR 22 TC 16 Z9 16 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 2001 VL 14 IS 1-4 BP 69 EP 74 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 480RC UT WOS:000171474900010 PM 11568442 ER PT S AU Shippenberg, TS Chefer, VI Zapata, A Heidbreder, CA AF Shippenberg, TS Chefer, VI Zapata, A Heidbreder, CA BE QuinonesJenab, V TI Modulation of the behavioral and neurochemical effects of psychostimulants by kappa-opioid receptor systems SO BIOLOGICAL BASIS OF COCAINE ADDICTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Seminar on Frontiers in Drug Abuse Research: Molecular and Cellular Adaptations to Cocaine CY 2000 CL NEW YORK, NEW YORK SP Natl Inst Hlth, City Univ New York, Grad Ctr & Biopsychol Doc Program DE amphetamine; cocaine; dopamine; dynorphin; glutamate; microdialysis ID RAT NUCLEUS-ACCUMBENS; MEDIAL PREFRONTAL CORTEX; MESSENGER-RNA EXPRESSION; EXCITATORY AMINO-ACIDS; PROTEIN-KINASE-C; EXTRACELLULAR DOPAMINE; VENTRAL STRIATUM; AMPHETAMINE PSYCHOSIS; INDUCED SENSITIZATION; PEPTIDE DYNORPHIN AB The repeated, intermittent use of cocaine and other drugs of abuse produces profound and often long-lasting alterations in behavior and brain chemistry. It has been suggested that these consequences of drug use play a critical role in drug craving and relapse to addiction. This article reviews the effects of psychostimulant administration on dopaminergic and excitatory amino acid neurotransmission in brain regions comprising the brain's motive circuit and provides evidence that the activation of endogenous kappa -opioid receptor systems in these regions opposes the behavioral and neurochemical consequences of repeated drug use. The role of this opioid system in mediating alterations in mood and affect that occur during abstinence from repeated psychostimulant use are also discussed. C1 NIDA, Intramural Res Program, Integrat Neurosci Unit, Baltimore, MD 21224 USA. RP Shippenberg, TS (reprint author), NIDA, Intramural Res Program, Integrat Neurosci Unit, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 99 TC 77 Z9 77 U1 2 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-302-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 937 BP 50 EP 73 PG 24 WC Substance Abuse; Multidisciplinary Sciences SC Substance Abuse; Science & Technology - Other Topics GA BT11P UT WOS:000172010800003 PM 11458540 ER PT S AU Thayer, JF Faith, ML AF Thayer, JF Faith, ML BE Zatorre, RJ Peretz, I TI A dynamic systems model of musically induced emotions - Physiological and self-report evidence SO BIOLOGICAL FOUNDATIONS OF MUSIC SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Biological Foundations of Music CY MAY 20-22, 2000 CL ROCKEFELLER UNIV, NEW YORK, NEW YORK SP Charles A Dana Fdn, David & Lucile Packard Fdn HO ROCKEFELLER UNIV DE musically induced emotions; emotions, musically induced C1 NIA, NIH, Baltimore, MD 21224 USA. RP Thayer, JF (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 6 TC 9 Z9 10 U1 1 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-306-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 930 BP 452 EP 456 PG 5 WC Multidisciplinary Sciences; Psychology SC Science & Technology - Other Topics; Psychology GA BT11G UT WOS:000172009400048 PM 11458866 ER PT J AU Bertolino, A Callicott, JH Mattay, VS Weidenhammer, KM Rakow, R Egan, MF Weinberger, DR AF Bertolino, A Callicott, JH Mattay, VS Weidenhammer, KM Rakow, R Egan, MF Weinberger, DR TI The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; dorsolateral prefrontal cortex; N-acetylaspartate; typical antipsychotics; atypical antipsychotics ID MAGNETIC-RESONANCE SPECTROSCOPY; CHRONIC HALOPERIDOL TREATMENT; POSITRON-EMISSION-TOMOGRAPHY; PREFRONTAL CORTEX; RAT FOREBRAIN; ATYPICAL NEUROLEPTICS; HIPPOCAMPAL-FORMATION; CHEMICAL PATHOLOGY; ACETYL ASPARTATE; DENDRITIC SPINES AB Background: The specific intracellular effects of antipsychotic drugs are largely unknown, Studies in animals have suggested that antipsychotics modify the expression of various intraneuronal proteins, but no analogous in vivo data in humans are available. The; objective of the present study was to assess whether antipsychotics modify N-acetylaspartate tan intraneuronal marker of neuronal functional integrity) measures in brains of patients with schizophrenia. Methods: We used proton magnetic resonance spectroscopic imaging to study 23 patients with schizophrenia (DSM-IV diagnosis) using a within-subject design. Patients were studied twice: once while on a stable regimen of antipsychotic drug treatment (for at least 4 weeks) and once while off medication for at least 2 weeks. Several cortical and subcortical regions were assessed, including the dorsolateral prefrontal cortex and the hippocampal area. Results: Analysis of variance showed that, while on antipsychotics, patients had significantly higher N-acetylaspartate measures in the dorsolateral prefrontal cortex (p =.002). No other region showed any significant effect of treatment. Conclusions: These results indicate that antipsychotic drugs increase N-acetylaspartate measures selectively in the dorsolateral prefrontal cortices of patients with schizophrenia, suggesting that these drugs modify in a regionally specific manner the function of a population of cortical neurons. N-Acetylaspartate measures may provide a useful tool to further investigate the effects of antipsychotics at the intracellular level. Biol Psychiatry 2001;49:39-46 (C) 2001 Society of Biological Psychiatry. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Programs, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Programs, NIH, 10 Ctr Dr,Room 4S235 MSC 1379, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380 NR 66 TC 118 Z9 125 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2001 VL 49 IS 1 BP 39 EP 46 DI 10.1016/S0006-3223(00)00997-5 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 394YZ UT WOS:000166553100005 PM 11163778 ER PT S AU Conney, AH Chang, RL Cui, XX Schiltz, M Yagi, H Jerina, DM Wei, SJC AF Conney, AH Chang, RL Cui, XX Schiltz, M Yagi, H Jerina, DM Wei, SJC BE Dansette, PM Snyder, R Delaforge, M Gibson, GG Greim, H Jollow, DJ Monks, TJ Sipes, IG TI Dose-dependent differences in the profile of mutations induced by carcinogenic (R,S,S,R) bay- and fjord-region diol epoxides of polycyclic aromatic hydrocarbons SO BIOLOGICAL REACTIVE INTERMEDIATES VI: CHEMICAL AND BIOLOGICAL MECHANISMS IN SUSCEPTIBILITY TO AND PREVENTION OF ENVIRONMENTAL DISEASES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Biological Reactive Intermediates CY JUL 16-20, 2000 CL UNIV RENE DESCARTES, PARIS, FRANCE SP CNRS, European Commiss, US EPA, Natl Inst Environm Hlth Sci HO UNIV RENE DESCARTES ID GUANINE PHOSPHORIBOSYLTRANSFERASE GENE; HAMSTER V-79 CELLS; RAS PROTOONCOGENE; BENZOPYRENE; ADDUCTS; REPAIR; DNA; TUMORS; V-H1; LINES AB Chinese hamster V79 cells were exposed to a high or low concentration of the highly carcinogenic (R,S,S,R) or the less active (S,R,R,S) bay- or fjord-region diol epoxides of benzo[a]pyrene, benzo[c]phenanthrene or dibenz[c,h]acridine. Independent 8-azaguanine-resistant clones were isolated, and base substitutions at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus were determined. For the three (R,S,S,R) diol epoxides studied, the proportion of mutations at AT base pairs increased as the concentration of diol epoxide decreased. Concentration-dependent differences in the mutational profile were not observed, however, for the three (S,R,R,S) diol epoxides. In studies, with V-H1 cells (a DNA repair deficient variant of V79 cells), a concentration-dependent difference in the profile of mutations for the (R,S,S,R) diol epoxide of benzo[a]pyrene was not observed. These results suggest that concentration-dependent differences in the mutational profile are dependent on an intact DNA repair system. In additional studies, we initiated mouse skin with a high or low dose of benzo[a]pyrene and promoted the mice for 26 weeks with 12-O-tetradecanoylphorbol-13-acetate. Papillomas were examined for mutations in the c-Ha-ras proto-oncogene. Dose-dependent differences in the profile of c-Ha-ras mutations in the tumors were observed. In summary, (i) dose-dependent differences in mutational profiles at the hprt locus were observed in Chinese hamster V79 cells treated with several highly mutagenic and carcinogenic (R,SS,R) bay- or fjord-region diol epoxides but not with their less active (S,R,R,S) diol epoxide enantiomers, (ii) a dose-dependent difference in the mutational profile was not observed for the (R,S,S,R) diol epoxide of benzo[a]pyrene in a DNA-repair defective V79 cell line, and (iii) a dose-dependent difference in the mutational profile in the c-Ha-ras proto-oncogene was observed in tumors from mice treated with a high or low dose of benzo[a]pyrene. C1 Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, Piscataway, NJ 08854 USA. NIDDKD, Bioorgan Chem Lab, Sect Oxidat Mechanisms, NIH, Bethesda, MD 20892 USA. RP Conney, AH (reprint author), Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. FU NCI NIH HHS [CA-49756] NR 24 TC 8 Z9 9 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46659-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2001 VL 500 BP 697 EP 707 PG 11 WC Medicine, Research & Experimental; Toxicology SC Research & Experimental Medicine; Toxicology GA BT47A UT WOS:000173071900102 PM 11765016 ER PT J AU Kummar, S Ishii, A Yang, HK Venzon, DJ Kim, SJ Gress, RE AF Kummar, S Ishii, A Yang, HK Venzon, DJ Kim, SJ Gress, RE TI Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-beta 1 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE graft-versus-tumor; breast cancer; TGF-beta 1 ID STEM-CELL TRANSPLANTATION; METASTATIC BREAST-CANCER; NATURAL-KILLER-CELLS; T-LYMPHOCYTE CLONES; FACTOR-BETA; HOST DISEASE; INFILTRATING LYMPHOCYTES; MYELOID-LEUKEMIA; REDUCES TUMORIGENICITY; EXPRESSION AB Although graft-versus-leukemia effects in allogeneic bone marrow transplantation (alloBMT) are well documented, graft-versus-tumor (GVT) effects are poorly defined. To investigate the latter, we established a murine model of breast cancer using TS/A, a transforming growth factor (TGF)-beta1-secreting breast cancer cell line of BALB/c origin. In the setting of disparate (parent into F1) alloBMT, no appreciable GVT was identified. To assess whether TGF-beta1 secreted by the tumor might inhibit the antitumor response, TGF-beta1 antisense vector was transfected into the TS/A breast cancer cell line. Mice were inoculated with either TGF-betaL antisense transfected or the mock transfected cell line and underwent syngeneic or alloBMT, No evidence of GVT was appreciated for the mock-transfected breast cancer cell line as assessed by an absence of a statistically significant difference in survival between syngeneic and alloBMT groups. However, there was a highly statistically significant survival difference between allogeneic versus syngeneic bone marrow transplantation groups inoculated with the TGF-beta1 antisense-transfected cell line (P = .00001) as well as when comparing the survival of mice that received alloBMT for TGF-beta1 antisense-transfected tumor versus mock-transfected tumor (P = .0008). These data suggest that (1) GVT exists against the antisense-transfected breast cancer cells in this experimental model and (2) TGF-betaI may be involved in suppressing antitumor responses in the setting of alloBMT for breast cancer. C1 NCI, Expt Immunol Branch, DBS, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Gress, RE (reprint author), NCI, Expt Immunol Branch, DBS, NIH, Bldg 10,Rm 4B14,10 Ctr Dr,MSC 1360, Bethesda, MD 20892 USA. RI Yang, Han-Kwang/J-2767-2012 NR 39 TC 7 Z9 7 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 1 BP 25 EP 30 DI 10.1053/bbmt.2001.v7.pm11215695 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 399YF UT WOS:000166841300004 PM 11215695 ER PT J AU Hixon, JA Blazar, BR Anver, MR Wiltrout, RH Murphy, WJ AF Hixon, JA Blazar, BR Anver, MR Wiltrout, RH Murphy, WJ TI Antibodies to CD40 induce a lethal cytokine cascade after syngeneic bone marrow transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE antibodies; transplantation; cytokines; in vivo animal models ID VERSUS-HOST DISEASE; FACTOR RECEPTOR; LIGAND; STIMULATION; CELLS; ACTIVATION; LYMPHOMA; GROWTH; EXPRESSION; INHIBITION AB CD40 stimulation, by either antibody or ligand, has been shown to inhibit the growth of a variety of neoplastic cells, both in vivo and in vitro. In this study, we assessed the effects of CD40 stimulation using a murine agonistic CD40 monoclonal antibody (MoAb) (FGK115) or a soluble recombinant murine CD40 ligand (srmCD40L) in both lethally irradiated and nonirradiated BALB/c mice. Toxicity after CD40 stimulation was not observed in nonirradiated animals receiving up to 100 mug of the agonist anti-CD40 MoAb. However, as little as 10 mug of the agonistic anti-CD40 MoAb induced acute toxicity resulting in 100% morbidity of lethally irradiated animals by 4 days after irradiation. Histological evaluation of animals receiving anti-CD40 MoAb revealed severe intestinal lesions with disruption of the villi, goblet cell depletion, and crypt hyperplasia of the small intestine, colon, and cecum. Delaying the administration of anti-CD40 MoAb or reducing the amount of irradiation given resulted in increased survival and less severe lesions. Analysis of serum cytokine levels in lethally irradiated mice receiving agonistic anti-CD40 showed a marked increase of interferon (IFN)-gamma. Lethally irradiated IFN-gamma knockout mice given the agonistic anti-CD40 MoAb demonstrated significant increases in survival and minimal gut lesions compared with wild-type mice receiving the same regimen, suggesting that IFN-gamma plays a major role in this toxic reaction. These results indicate that CD40 stimulation using agonistic antibodies following lethal irradiation leads to a fatal, cytokine-induced disease affecting the intestine. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Pathol Histotechnol Lab, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Minnesota, Ctr Canc, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN USA. RP Murphy, WJ (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 567,Room 210, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NHLBI NIH HHS [R01 HL63452]; NIAID NIH HHS [R01 AI34495] NR 20 TC 22 Z9 22 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 3 BP 136 EP 143 DI 10.1053/bbmt.2001.v7.pm11302547 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 416UA UT WOS:000167797500002 PM 11302547 ER PT J AU Antin, JH Childs, R Filipovich, AH Giralt, S Mackinnon, S Spitzer, T Weisdorf, D AF Antin, JH Childs, R Filipovich, AH Giralt, S Mackinnon, S Spitzer, T Weisdorf, D TI Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: Recommendations from a Workshop at the 2001 Tandem Meetings SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE lymphohematopoietic chimerism; allogeneic transplantation; restriction fragment length polymorphism ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; CHRONIC MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; APLASTIC-ANEMIA; MYELOABLATIVE THERAPY; CYTOGENETIC ANALYSIS; VARIABLE NUMBER; REPEAT-MARKERS AB Approaches to the measurement of lymphohematopoietic chimerism. have evolved from laboratory research to important clinical tools. However, there has been no logical, consistent, and uniform set of recommendations for the measurement of chimerism in clinical transplantation. The National Marrow Donor Program and the International Bone Marrow Transplant Registry (IBMTR) sponsored a workshop to discuss the use of chimerism, analysis after allogeneic transplantation. The workshop was organized in an effort to make reasonable recommendations regarding laboratory techniques, the types of specimens to be studied, and the frequency of analysis. The panel recommended the following guidelines: 1. Chimerism. analysis should use sensitive, informative techniques. At present, short tandem repeats (STR) or variable number tandem repeats (VNTR) analysis is the approach most likely to give reproducible informative data. 2. Peripheral blood cells are generally more useful than bone marrow cells for chimerism analysis. 3. Lineage-specific chimerism. should be considered the assay of choice in the setting of nonmyeloablative and reduced-intensity conditioning. 4. The use of T-cell depletion, nonmyeloablative or reduced-intensity conditioning, or novel graft-versus-host disease (GVHD) prophylactic regimens warrants chimerism. analysis at 1, 3, 6, and 12 months, because interventions such as donor lymphocyte infusions may depend on chimerism status. 5. In nonmyeloablative transplantation, the early patterns of chimerism. may predict either GVHD or graft loss. Therefore, more frequent (every 2-4 weeks) peripheral blood analysis may be warranted. 6. For nonmalignant disorders, chimerism. generally should be measured 1, 2, and 3 months after transplantation. Interventions to enhance donor engraftment must be considered on a disease-specific basis in relation to concurrent GVHD and, ultimately, clinical rationale. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. UCL, London, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jantin@partners.org RI Mackinnon, Stephen/C-5559-2008 NR 39 TC 159 Z9 181 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PY 2001 VL 7 IS 9 BP 473 EP 485 DI 10.1053/bbmt.2001.v7.pm11669214 PG 13 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 480EN UT WOS:000171449200001 PM 11669214 ER PT J AU Hager, GL McNally, JG Muller, WG Elbi, C Lim, C Baumann, CT Fletcher, TM AF Hager, GL McNally, JG Muller, WG Elbi, C Lim, C Baumann, CT Fletcher, TM TI Ligand-regulated steroid receptor trafficking in living cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NCI, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 82 EP 82 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900003 ER PT J AU Sapiro, R Murray, JM Zhang, M Blanchette-Mackie, EJ Strauss, JF AF Sapiro, R Murray, JM Zhang, M Blanchette-Mackie, EJ Strauss, JF TI Sperm antigen 6 (Spag 6) binds to microtubules, induces bundling and increases stability. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Ctr Res Reprod & Women Hlth, Philadelphia, PA 19104 USA. Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. NIDDK, NIH, Lipid Cell & Biol Sect, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 106 EP 106 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900057 ER PT J AU Goto, M Eddy, EM AF Goto, M Eddy, EM TI Testis-specific WDAP1 protein is a possible regulator of p55CDC. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 143 EP 143 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900149 ER PT J AU Winterhager, E Korach, K Hewitt, S Gruemmer, R AF Winterhager, E Korach, K Hewitt, S Gruemmer, R TI Different regulation pathways of the Cx26 gene during preimplantation versus embryo recognition. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Univ Essen Gesamthsch, Sch Med, Dept Anat, Essen, Germany. NIH, Res Triangle Pk, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2001 VL 64 SU 1 BP 200 EP 200 PG 1 WC Reproductive Biology SC Reproductive Biology GA 447KR UT WOS:000169570900291 ER PT S AU Bezrukov, SM Kish, LB AF Bezrukov, SM Kish, LB BE Kish, LB TI How much power does neural signal propagation need? SO BIOMEMS AND SMART NANOSTRUCTURES SE Proceedings of SPIE LA English DT Proceedings Paper CT Symposium on BioMEMS and Smart Nanostructures CY DEC 17-19, 2001 CL ADELAIDE, AUSTRALIA SP SPIE, USAF, Off Sci Res, Asian Off Aerosp Res & Dev, Adelaide Univ, Ctr Biomed Engn, Def Sci & Technol Org, S Australia, Dept Ind & Trade DE neuron; ion channel; energy dissipation; information transfer ID STOCHASTIC RESONANCE; ION CHANNELS; NOISE; NEURONS; WHITE AB Two well known, biologically inspired non-dynamical models of stochastic resonance, the threshold-crossing model and the fluctuating rate model are analyzed in terms of channel information capacity and dissipation of energy necessary for small-signal transduction. Using analogies to spike propagation in neurons we postulate the average output pulse rate as a measure of dissipation. The dissipation increases monotonically with the input noise. We find that for small dissipation both models give an asymptotically linear dependence of the channel information capacity on dissipation. In both models the channel information capacity, as a function of dissipation, has a maximum at input noise amplitude that is different from that in the standard signal-to-noise ration vs. input noise plot. Though a direct comparison is not straight forward, for small signals the threshold model gives appreciably higher density of information per dissipation than the exponential fluctuating rate model. We show that a formal introduction of cooperativity in the rate fluctuating model permits us to imitate the response function of the threshold model and to enhance performance. This finding may have direct relevance to real neural spike generation where, due to a strong positive feedback, the ion channel currents are adding up in a synchronized way. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4320-4 J9 PROC SPIE PY 2001 VL 4590 BP 1 EP 5 DI 10.1117/12.454600 PG 5 WC Engineering, Multidisciplinary; Materials Science, Multidisciplinary; Imaging Science & Photographic Technology SC Engineering; Materials Science; Imaging Science & Photographic Technology GA BU25E UT WOS:000175475300001 ER PT J AU Bura, E Gastwirth, JL AF Bura, E Gastwirth, JL TI The binary regression quantile plot: Assessing the importance of predictors in binary regression visually SO BIOMETRICAL JOURNAL LA English DT Article DE binary response; logistic regression; explanatory power; quantile plot ID GOODNESS; RISK; FIT AB We present a graphical measure of assessing the explanatory power of regression models with a binary response. The binary regression quantile plot and an area defined by it are used for the visual comparison and ordering of nested binary response regression models. The plot shows how well various models explain the data. Two data sets are analyzed and the area representing the fit of a model is shown to agree with the usual likelihood ratio test. C1 George Washington Univ, Dept Stat, Washington, DC 20052 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 27 TC 24 Z9 24 U1 1 U2 6 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2001 VL 43 IS 1 BP 5 EP 21 DI 10.1002/1521-4036(200102)43:1<5::AID-BIMJ5>3.0.CO;2-6 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 407GE UT WOS:000167263200002 ER PT B AU Hussain, SP Harris, CC AF Hussain, SP Harris, CC BE Butterworth, FM Gunatilaka, A Gonsebatt, ME TI p53 mutation load - A molecular linkage to carcinogen exposure and cancer SO BIOMONITORS AND BIOMARKERS AS INDICATORS OF ENVIRONMENTAL CHANGE 2: A HANDBOOK SE ENVIRONMENTAL SCIENCE RESEARCH LA English DT Proceedings Paper CT Symposium on Biomonitors and Biomarkers as Indicators of Environmental Change 2 CY MAY 19-22, 1998 CL MCMASTER UNIV, HAMILTON, CANADA HO MCMASTER UNIV ID TUMOR-SUPPRESSOR GENE; TATA-BINDING PROTEIN; WILD-TYPE P53; BRONCHIAL EPITHELIAL-CELLS; HEPATITIS-B VIRUS; SKIN-CANCER; TRANSCRIPTIONAL ACTIVATION; HEPATOCELLULAR CARCINOMAS; INDUCED MUTAGENESIS; SV40-TRANSFORMED CELLS C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Hussain, SP (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 82 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46387-3 J9 ENVIR SCI R PY 2001 VL 56 BP 333 EP 346 PG 14 WC Biotechnology & Applied Microbiology; Environmental Sciences SC Biotechnology & Applied Microbiology; Environmental Sciences & Ecology GA BR72T UT WOS:000167336000018 ER PT J AU Lee, J Lee, J Kim, J Kim, SY Chun, MW Cho, HW Hwang, SW Oh, U Park, YH Marquez, VE Beheshti, M Szabo, T Blumberg, PM AF Lee, J Lee, J Kim, J Kim, SY Chun, MW Cho, HW Hwang, SW Oh, U Park, YH Marquez, VE Beheshti, M Szabo, T Blumberg, PM TI N-(3-acyloxy-2-benzylpropyl)-N '-(4-hydroxy-3-methoxybenzyl) thiourea derivatives as potent vanilloid receptor agonists and analgesics SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ROOT GANGLION NEURONS; CAPSAICIN RECEPTOR; RESINIFERATOXIN ANALOGS; RESINIFERONOL; LIGANDS; ESTERS; STIMULATION; NOCICEPTORS; ANTAGONIST; DISCOVERY AB A series of N-(3-acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl)thioura derivatives were investigated as vanilloid receptor ligands in an effort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin, which includes the C-20-homovanillic moiety, the C-3-carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-inflammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with K-i values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also reflected by an excellent analgesic profile in animal tests with ED50 values of 0.5 mug/kg for 23 and 1.0 mug/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show significant anti-inflammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Med Chem Lab, Kwanak Ku, Seoul 151742, South Korea. Seoul Natl Univ, Coll Pharm, CRI, Sensory Res Grp,Kwanak Ku, Seoul 151742, South Korea. Pacific R&D Ctr, Yougin Si 449900, Kyounggi Do, South Korea. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Med Chem Lab, Kwanak Ku, Shinlim Dong, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr OI Lee, Jiyoun/0000-0003-3819-5889 NR 33 TC 48 Z9 50 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN PY 2001 VL 9 IS 1 BP 19 EP 32 DI 10.1016/S0968-0896(00)00216-9 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 391GP UT WOS:000166348500003 PM 11197340 ER PT J AU Mukerji, I Augustyn, KE Wojtuszewski, K Hawkins, ME AF Mukerji, I Augustyn, KE Wojtuszewski, K Hawkins, ME TI A-tract DNA probed by fluorescence spectroscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Wesleyan Univ, Middletown, CT 06459 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 47 BP 10A EP 11A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200048 ER PT J AU Rios, E Gonzalez, A Shirokova, N Kirsch, W Rengifo, J Stern, M Cheng, HP Brum, G Pizarro, G AF Rios, E Gonzalez, A Shirokova, N Kirsch, W Rengifo, J Stern, M Cheng, HP Brum, G Pizarro, G TI The significance of calcium sparks in excitation-contraction coupling. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. NIA, Baltimore, MD 21224 USA. U Republ, Montevideo, Uruguay. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 50 BP 13A EP 13A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200058 ER PT J AU Cornwall, MC Poitry, S Tsacopoulos, M Wiggert, B Crouch, R AF Cornwall, MC Poitry, S Tsacopoulos, M Wiggert, B Crouch, R TI Retinol fluorescence in bleached salamander rod and cone photoreceptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Geneva, CH-1211 Geneva 4, Switzerland. NEI, NIH, Bethesda, MD USA. Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 82 BP 19A EP 19A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200090 ER PT J AU Carroll, SL Herrera, AH Horowits, R AF Carroll, SL Herrera, AH Horowits, R TI Differential effects of N-RAP domains on myofibril assembly in cultured chick cardiomyocytes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 106 BP 25A EP 25A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200115 ER PT J AU Bryant, SH AF Bryant, SH TI A conserved domain database SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 141 BP 32A EP 33A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200150 ER PT J AU Gawrisch, K AF Gawrisch, K TI Properties of polyunsaturated lipid membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 136 BP 32A EP 32A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200145 ER PT J AU Froehlich, JP Albers, RW AF Froehlich, JP Albers, RW TI Stoichiometry of the phosphorylated intermediates in native pig kidney Na,K-ATPase. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NINDS, Bethesda, MD 20892 USA. NIH, NIA, Bethesda, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 165 BP 38A EP 38A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200174 ER PT J AU Misra, S Beach, BM Hurley, JH AF Misra, S Beach, BM Hurley, JH TI Structure of the Tom1 VHS domain, a protein-protein and potential protein-membrane interaction module SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 256 BP 57A EP 58A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200265 ER PT J AU Bradrick, TD Harvey, JJ Knutson, JR Boggy, G Gunia, K Woodard, S Khozeimeh, N Lee, SP Han, MK AF Bradrick, TD Harvey, JJ Knutson, JR Boggy, G Gunia, K Woodard, S Khozeimeh, N Lee, SP Han, MK TI Steady-state and time-resolved fluorescence spectroscopy of labeled cysteine mutants of HIV-1 integrase. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 277 BP 62A EP 62A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200286 ER PT J AU Sinz, A Wang, K AF Sinz, A Wang, K TI Mapping protein interfaces between nebulin and calmodulin: The application of a fluorogenic cross-linker and mass spectrometry. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, LPB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 412 BP 92A EP 92A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200421 ER PT J AU Bertram, R Sherman, A Goforth, PB Zhang, M Satin, LS AF Bertram, R Sherman, A Goforth, PB Zhang, M Satin, LS TI Unmasking endoplasmic reticulum calcium dynamics in pancreatic beta cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Florida State Univ, Tallahassee, FL 32306 USA. NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 456 BP 101A EP 101A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200465 ER PT J AU Cui, CH Glasser, C Mayer, M AF Cui, CH Glasser, C Mayer, M TI Functional properties of a prokaryotic glutamate receptor SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. RI Mayer, Mark/H-5500-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 488 BP 108A EP 108A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200497 ER PT J AU Betanzos, M Chiang, CS Guy, HR Sukharev, S AF Betanzos, M Chiang, CS Guy, HR Sukharev, S TI The open conformation of a mechanosensitive channel studied by disulfide trapping SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, College Pk, MD 20742 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 495 BP 110A EP 110A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200504 ER PT J AU Chiang, CS Gray, P Betanzos, M Guy, HR Sukharev, S AF Chiang, CS Gray, P Betanzos, M Guy, HR Sukharev, S TI On the role of the S1-M1 linker in the gating mechanism of the large mechanosensitive channel MscL. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, College Pk, MD 20742 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 496 BP 110A EP 110A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200505 ER PT J AU Chen, Y Yunker, AMR Sundarraj, S Brown, KA Copeland, TD Brown, RW Sharp, AH McEnery, MW AF Chen, Y Yunker, AMR Sundarraj, S Brown, KA Copeland, TD Brown, RW Sharp, AH McEnery, MW TI Expression and immunofluorescent localization of voltage-dependent calcium channel (VDCC) subtypes in a differentiating human neurotypic cell line SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Phys, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Physio & Bioph, Cleveland, OH 44106 USA. NCI, ABL, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 525 BP 116A EP 117A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200534 ER PT J AU McEnery, MW Copeland, TD Vance, CL Sundarraj, S AF McEnery, MW Copeland, TD Vance, CL Sundarraj, S TI Differential expression of voltage-dependent calcium channel gamma isoforms (gamma-2, -3, and -4) in developing brain SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Physiol & Biophys & Neurosci, Cleveland, OH 44106 USA. NCI, ABL, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 521 BP 116A EP 116A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200530 ER PT J AU Sharp, AH Ikusika, O Sundarraj, S Fletcher, CF Copeland, NG Jenkins, NA Copeland, TD McEnery, MW AF Sharp, AH Ikusika, O Sundarraj, S Fletcher, CF Copeland, NG Jenkins, NA Copeland, TD McEnery, MW TI Altered expression and localization of calcium channel subunits in alpha1A knock-out mice. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 524 BP 116A EP 116A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200533 ER PT J AU Speelman, B Brooks, BR Post, CB AF Speelman, B Brooks, BR Post, CB TI Molecular dynamics simulations of human rhinovirus and an antiviral compound SO BIOPHYSICAL JOURNAL LA English DT Article ID SYMMETRY BOUNDARY-CONDITIONS; ACID-BINDING PROTEIN; COMMON COLD VIRUS; CONFORMATIONAL CHANGE; ANGSTROM RESOLUTION; POLIOVIRUS; DRUG; VIRIONS; PICORNAVIRUSES; TEMPERATURE AB The human rhinovirus 14 (HRV14) protomer, with or without the antiviral compound WIN 52084s, was simulated using molecular dynamics and rotational symmetry boundary conditions to model the effect of the entire icosahedral capsid. The protein asymmetrical unit, comprising four capsid proteins (VP1, VP2, VP3, and VP4) and two calcium ions, was solvated both on the exterior and the interior to fill the inside of the capsid. The stability of the simulations of this large system (similar to 800 residues and 6,650 water molecules) is comparable to more conventional globular protein simulations. The influence of the antiviral compound on compressibility and positional fluctuations is reported. The compressibility, estimated from the density fluctuations in the region of the binding pocket, was found to be greater with WIN 52084s bound than without the drug, substantiating previous computations on reduced viral systems. An increase in compressibility correlates with an entropically more favorable system. In contrast to the increase in density fluctuations and compressibility, the positional fluctuations decreased dramatically for the external loops of VPI and the N-terminus of VP3 when WIN 52084s is bound. Most of these VPI and VP3 loops are found near the fivefold axis, a region whose mobility was not considered in reduced systems, but can be observed with this simulation of the full viral protomer. Altered loop flexibility is consistent with changes in proteolytic sensitivity observed experimentally. Moreover, decreased flexibility in these intraprotomeric loops is noteworthy since the externalization of VP4, part of VP1, and RNA during the uncoating process is thought to involve areas near the fivefold axis. Both the decrease in positional fluctuations at the fivefold axis and the increase in compressibility near the WIN pocket are discussed in relationship to the antiviral activity of stabilizing the virus against uncoating. C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NHLBI, Computat Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Post, CB (reprint author), Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. FU NIAID NIH HHS [AI39639]; NIGMS NIH HHS [K04-GM00661] NR 44 TC 33 Z9 33 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 BP 121 EP 129 PG 9 WC Biophysics SC Biophysics GA 396QH UT WOS:000166647700009 PM 11159387 ER PT J AU Lagostena, L Kachar, B Mammano, F AF Lagostena, L Kachar, B Mammano, F TI Intercellular communication in supporting cells of the organ of Corti: Frequency dependence and modulation by intracellular calcium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Int Sch Adv Studies, Biophys Sector, I-34014 Trieste, Italy. Int Sch Adv Studies, Ist Nazl Fis Mat, I-34014 Trieste, Italy. NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 556 BP 123A EP 123A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200565 ER PT J AU Nestorovich, EM Winterhalter, M Bezrukov, SM AF Nestorovich, EM Winterhalter, M Bezrukov, SM TI Ampicillin translocation through OmpF studied on a single channel level SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NICHD, Bethesda, MD 20892 USA. CNRS, IPBS, F-31077 Toulouse, France. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 576 BP 128A EP 128A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200585 ER PT J AU Aguilella, VM Bezrukov, SM AF Aguilella, VM Bezrukov, SM TI Lipid charge effects in alamethicin-induced conductance SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Jaume 1, Castellon 12080, Spain. NICHD, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RI Aguilella, Vicente/B-7592-2008 OI Aguilella, Vicente/0000-0002-2420-2649 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 594 BP 132A EP 132A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200603 ER PT J AU Malev, VV Schagina, LV Takemoto, JY Nestorovich, EM Bezrukov, SM AF Malev, VV Schagina, LV Takemoto, JY Nestorovich, EM Bezrukov, SM TI Gating and conductance of syringomycin E channels as manifestations of an asymmetrical channel structure SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 St Petersburg State Univ, St Petersburg 198904, Russia. Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. Utah State Univ, Logan, UT 84322 USA. NIH, Bethesda, MD 20892 USA. RI Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 NR 0 TC 1 Z9 1 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 597 BP 132A EP 132A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200606 ER PT J AU Basanez, G Shinnar, AE Zimmerberg, J AF Basanez, G Shinnar, AE Zimmerberg, J TI Pore formation by hagfish intestinal antimicrobial peptides SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Columbia Univ Barnard Coll, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 603 BP 133A EP 134A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200612 ER PT J AU Coorssen, JR Zimmerberg, J Blank, PS AF Coorssen, JR Zimmerberg, J Blank, PS TI Kinetics of homotypic cortical vesicle fusion. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Calgary, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 62713 BP 141A EP 141A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200648 ER PT J AU Chik, JK Rau, DC Parsegian, VA AF Chik, JK Rau, DC Parsegian, VA TI Exponentially varying concentration of solutes near the surface of hydroxypropylcellulose. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 629 BP 142A EP 142A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200651 ER PT J AU Hansen, PL Podgornik, R Parsegian, VA AF Hansen, PL Podgornik, R Parsegian, VA TI Osmotic properties of DNA: Critical evaluation of counterion condensation theory SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 632 BP 142A EP 143A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200654 ER PT J AU Harms, GS Blab, GA Lommerse, PHM Cognet, L Kahr, H Gamsjaeger, R Soldatov, N Romanin, C Spaink, HP Schmidt, T AF Harms, GS Blab, GA Lommerse, PHM Cognet, L Kahr, H Gamsjaeger, R Soldatov, N Romanin, C Spaink, HP Schmidt, T TI The aggregation of individual eYFP-labeled human cardiac L-type Ca2+ channels in living cell membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Leiden Univ, Ctr Biopharmaceut Sci, NL-2300 RA Leiden, Netherlands. Univ Linz, A-4040 Linz, Austria. NIH, Baltimore, MD 21224 USA. RI Romanin, Christoph/D-5399-2009; Blab, Gerhard/D-2275-2011 OI Romanin, Christoph/0000-0003-3756-4136; NR 0 TC 5 Z9 5 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 655.16 BP 150A EP 150A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200693 ER PT J AU Harms, GS Cognet, L Lommerse, PHM Blab, GA Snaar-Jagalska, E Romanin, C Soldatov, N Spaink, HP Schmidt, T AF Harms, GS Cognet, L Lommerse, PHM Blab, GA Snaar-Jagalska, E Romanin, C Soldatov, N Spaink, HP Schmidt, T TI Autofluorescent-proteins in single-molecule research: Applications to live cell imaging microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Leiden Univ, NL-2300 RA Leiden, Netherlands. Univ Linz, A-4040 Linz, Austria. NIH, Baltimore, MD 21224 USA. RI Romanin, Christoph/D-5399-2009; Blab, Gerhard/D-2275-2011 OI Romanin, Christoph/0000-0003-3756-4136; NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 655.19 BP 151A EP 151A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200696 ER PT J AU Iwasa, KH AF Iwasa, KH TI Outer hair cell motility as two-state piezoelectricity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 6555 BP 157A EP 158A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200727 ER PT J AU Rios, E Shirokova, N Kirsch, WG Pizarro, G Stern, MD Cheng, H Gonzalez, A AF Rios, E Shirokova, N Kirsch, WG Pizarro, G Stern, MD Cheng, H Gonzalez, A TI A preferred amplitude of calcium sparks in skeletal muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID UNDERLYING CA2+ SPARKS; RETICULUM LUMENAL CA2+; SARCOPLASMIC-RETICULUM; CARDIAC-MUSCLE; ELEMENTARY EVENTS; RELEASE CHANNEL; MYOCYTES; CELLS; MODEL; INACTIVATION AB In skeletal and cardiac muscle, calcium release from the sarcoplasmic reticulum, leading to contraction, often results in calcium sparks. Because sparks are recorded by confocal microscopy in line-scanning mode, their measured amplitude depends on their true amplitude and the position of the spark relative to the scanned line. We present a method to derive from measured amplitude histograms the actual distribution of spark amplitudes. The method worked well when tested on simulated distributions of experimental sparks. Applied to massive numbers of sparks imaged in frog skeletal muscle under voltage clamp in reference conditions, the method yielded either a decaying amplitude distribution (6 cells) or one with a central mode (5 cells). Caffeine at 0.5 or 1 mM reversibly enhanced this mode (5 cells) or induced its appearance (4 cells). The occurrence of a mode in the amplitude distribution was highly correlated with the presence of a mode in the distribution of spark rise times or in the joint distribution of rise times and spatial widths. If sparks were produced by individual Markovian release channels evolving reversibly, they should not have a preferred rise time or amplitude. Channel groups, instead, could cooperate allosterically or through their calcium sensitivity, and give rise to a stereotyped amplitude in their collective spark. C1 Rush Univ, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. Fac Med, Dept Biofis, Montevideo, Uruguay. Fac Ciencias, Montevideo, Uruguay. NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. RP Rios, E (reprint author), Rush Univ, Dept Physiol & Mol Biophys, 1750 W Harrison St,Suite 1279 JS, Chicago, IL 60612 USA. NR 37 TC 31 Z9 33 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 BP 169 EP 183 PG 15 WC Biophysics SC Biophysics GA 396QH UT WOS:000166647700015 PM 11159393 ER PT J AU Keskin, O Bahar, I Covell, D Atilgan, AR Durell, S Jernigan, RL AF Keskin, O Bahar, I Covell, D Atilgan, AR Durell, S Jernigan, RL TI Large functional motions of proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NCI, SAIC, Frederick, MD 21701 USA. Bogazici Univ, TR-80815 Bebek, Turkey. NIH, NCI, MSC 5677, Bethesda, MD 20892 USA. RI Atilgan, Ali Rana/A-7805-2011; Jernigan, Robert/A-5421-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 661 BP 173A EP 173A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200793 ER PT J AU Ma, BY Nussinov, R AF Ma, BY Nussinov, R TI Peptide b-sheet complex: Insight into amyloid formation via MD simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 668 BP 174A EP 174A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200800 ER PT J AU Koenig, BW Mitchell, DC Kontaxis, G Louis, JM Litman, BJ Bax, A AF Koenig, BW Mitchell, DC Kontaxis, G Louis, JM Litman, BJ Bax, A TI Structure and orientation of a transducin peptide fragment in the rhodopsin bound state obtained from residual dipolar couplings. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Forschungszentrum Julich, D-52425 Julich, Germany. NIAAA, LMBB, NIH, Rockville, MD 20852 USA. NIDDK, LCP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 698 BP 181A EP 181A PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200830 ER PT J AU Hackos, DH Swartz, KJ AF Hackos, DH Swartz, KJ TI Disrupting the cytoplasmic gate in the shaker K+ channel with mutations in S6 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 705 BP 182A EP 183A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200837 ER PT J AU Polozova, A Litman, BJ AF Polozova, A Litman, BJ TI Role of lipid headgroup type in formation of microdomains around rhodopsin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NIAAA, Rockville, MD 20852 USA. RI Polozova, Alla/C-2395-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 716 BP 185A EP 185A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200848 ER PT J AU Lapidus, LJ Eaton, WA Hofricheter, J AF Lapidus, LJ Eaton, WA Hofricheter, J TI Measuring the rate of intramolecular contact formation in polypeptides SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 721 BP 186A EP 186A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200853 ER PT J AU Li-Smerin, YY Swartz, KJ Swartz, KJ AF Li-Smerin, YY Swartz, KJ Swartz, KJ TI Helical structure of the C-terminus of S3 and its contribution to the gating modifier toxin receptor in voltage-gated ion channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINCDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 746 BP 192A EP 192A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200879 ER PT J AU Ishikawa, T Beuron, F Kessel, M Wickner, S Maurizi, MR Steven, AC AF Ishikawa, T Beuron, F Kessel, M Wickner, S Maurizi, MR Steven, AC TI Binding and translocation of protein substrates by ClpAp protease. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 755 BP 194A EP 194A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200888 ER PT J AU Veigel, C Wang, F Bartoo, ML Hammer, JA Sellers, JA Molloy, JE AF Veigel, C Wang, F Bartoo, ML Hammer, JA Sellers, JA Molloy, JE TI Mechanical properties of single myosin V molecules SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ York, York YO10 5DD, N Yorkshire, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 781 BP 199A EP 200A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200914 ER PT J AU Soler-Llavina, GJ Swartz, KJ AF Soler-Llavina, GJ Swartz, KJ TI Energetic interactions between voltage-sensing and pore domains in the Shaker K+ channel. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 861 BP 217A EP 217A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692200994 ER PT J AU Basanez, G Zhang, J Chau, BN Maksaev, G Frolov, V Li, HL Yuan, JY Hardwick, JM Zimmerberg, J AF Basanez, G Zhang, J Chau, BN Maksaev, G Frolov, V Li, HL Yuan, JY Hardwick, JM Zimmerberg, J TI Proapoptotic proteins form large pores in pure lipid bilayers in a membrane curvature-dependent manner SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Publ Hlth, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Baltimore, MD 21205 USA. AN Frumkin Electrochem Inst, Moscow 117071, Russia. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 958 BP 238A EP 238A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201091 ER PT J AU Rostovtseva, TK Komarov, AG Colombini, M Bezrukov, SM AF Rostovtseva, TK Komarov, AG Colombini, M Bezrukov, SM TI Specificity of nucleotide permeation through VDAC channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, College Pk, MD 20742 USA. NIH, Bethesda, MD 20892 USA. RI Colombini, Marco/A-1540-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 963 BP 239A EP 239A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201096 ER PT J AU Nossal, R Skupsky, R AF Nossal, R Skupsky, R TI Analysis of cyclic metabolic pathways for phosphoinositide synthesis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1019 BP 251A EP 251A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201152 ER PT J AU Tomic, M Zivadinovic, D Stojilkovic, SS AF Tomic, M Zivadinovic, D Stojilkovic, SS TI Endothelin and somatostatin receptor coupling to G(I) signaling pathway in pituitary cells. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1016 BP 251A EP 251A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201149 ER PT J AU Niu, SL Mitchell, DC Litman, BJ AF Niu, SL Mitchell, DC Litman, BJ TI Cholesterol modulates the G-protein coupled signal transduction SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1027 BP 253A EP 253A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201160 ER PT J AU Lewis, MK Adhikari, B VanVliet, JJ Chen, V Bass, AH Wang, K AF Lewis, MK Adhikari, B VanVliet, JJ Chen, V Bass, AH Wang, K TI Examination of Midshipman sonic muscle architecture using confocal immunofluorescence microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1084 BP 265A EP 266A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201216 ER PT J AU Lewis, MK Jia, YW Wang, K AF Lewis, MK Jia, YW Wang, K TI Single molecule fluorescence microscopy of giant muscle proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1080 BP 265A EP 265A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201212 ER PT J AU Gu, J Xu, SG Yu, LPC AF Gu, J Xu, SG Yu, LPC TI The most likely structure of the weakly attached cross-bridges in AMATP state SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1092 BP 267A EP 267A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201223 ER PT J AU Xu, SG Gu, J Melvin, G Yu, LPC AF Xu, SG Gu, J Melvin, G Yu, LPC TI Evidence that the conformation of the actomyosin complex with bound ADP.P-I (the AMADP.P-I state) differs from that in the AMATP state. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1091 BP 267A EP 267A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201222 ER PT J AU Ma, K Kan, LS Wang, K AF Ma, K Kan, LS Wang, K TI Polyproline II helix is a key structural motif of the elastic PEVK segment of titin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NIAMS, LPB, Bethesda, MD 20892 USA. Acad Sinica, Inst Chem, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1099 BP 269A EP 269A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201231 ER PT J AU Adhikari, BB Wang, K AF Adhikari, BB Wang, K TI Inhibition of calcium activation of isometric tension, stiffness and ATPase by S100 in rabbit psoas muscle fibers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1105 BP 270A EP 270A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201237 ER PT J AU Voloshchuk, N Hawkins, ME Davenport, L AF Voloshchuk, N Hawkins, ME Davenport, L TI HIV-1 integrase binding to model nucleotide substrates SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 CUNY Brooklyn Coll, Brooklyn, NY 11210 USA. CUNY, Grad Sch, Univ Ctr, Brooklyn, NY 11210 USA. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1218 BP 294A EP 294A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201350 ER PT J AU Gonzalez, M Weiler, S Ferretti, J Ginsburg, A AF Gonzalez, M Weiler, S Ferretti, J Ginsburg, A TI The VND/NK-2 homeodomain: Thermodynamics of unfolding and DNA binding in relation to free and DNA-bound wild-type and mutant protein structure. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1221 BP 295A EP 295A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201353 ER PT J AU Borken, CM Riener, C Gruber, HJ Schindler, H Smith-Gill, SJ Hinterdorfer, P AF Borken, CM Riener, C Gruber, HJ Schindler, H Smith-Gill, SJ Hinterdorfer, P TI Simultaneous topography and recognition imaging with dynamic force microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Linz, A-4040 Linz, Austria. NCI, NIH, Frederick, MD 21702 USA. RI Hinterdorfer, Peter/C-4235-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1259 BP 303A EP 303A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201391 ER PT J AU Dimitriadis, EK Horkay, F Maresca, J Chadwick, RS AF Dimitriadis, EK Horkay, F Maresca, J Chadwick, RS TI Determination of elastic moduli of soft, thin samples using the atomic force microscope SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, LIMB, Bethesda, MD USA. NIDCD, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1260 BP 303A EP 304A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201392 ER PT J AU Tokumasu, F Jin, AJ Dvorak, JA AF Tokumasu, F Jin, AJ Dvorak, JA TI Atomic force microscopy studies of membrane structure and transformation thermodynamics SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1263 BP 304A EP 304A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201620 ER PT J AU Wallqvist, A Rabow, A Covell, D AF Wallqvist, A Rabow, A Covell, D TI Computational tools for mining structural and functional genomic databases SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1329 BP 318A EP 318A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201460 ER PT J AU Heymann, JB AF Heymann, JB TI Bsoft: An integrated rational approach to software development for structural biology SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Heymann, Bernard/F-6825-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1345 BP 322A EP + PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201476 ER PT J AU Yan, B Chen, YD AF Yan, B Chen, YD TI Molecular dynamics stimulations of nucleotide-dependent kinesin in solution. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1366 BP 326A EP 326A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201497 ER PT J AU Mayer, ML Gouaux, E AF Mayer, ML Gouaux, E TI Structural analysis of the ligand binding domain of GluR0. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, Bethesda, MD 20892 USA. Columbia Univ, New York, NY 10032 USA. RI Mayer, Mark/H-5500-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1404 BP 335A EP 335A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201536 ER PT J AU Kullman, L Winterhalter, M Bezrukov, SM AF Kullman, L Winterhalter, M Bezrukov, SM TI Static and dynamic disorder in protein folding of single maltoporin channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NICHD, LPSB, Bethesda, MD USA. Biozentrum, Basel, Switzerland. CNRS, IPBS, Toulouse, France. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1426 BP 340A EP 340A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201558 ER PT J AU Burgess, S Walker, M Schmitz, S Wang, F Sellers, JR Knight, PJ Trinick, J AF Burgess, S Walker, M Schmitz, S Wang, F Sellers, JR Knight, PJ Trinick, J TI Direct visualisation of gross conformational changes in the heads of myosin V between different nucleotide states. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1430 BP 341A EP 341A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201562 ER PT J AU Guy, HR Durell, SR Sukharev, S AF Guy, HR Durell, SR Sukharev, S TI Structural models of the MscL gating mechanism SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1450 BP 346A EP 346A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201582 ER PT J AU Shen, XH Knutson, JR AF Shen, XH Knutson, JR TI Femtosecond emission anisotropy decay studies of perylene SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1509 BP 360A EP 360A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201643 ER PT J AU Milne, JLS Rosenthal, PB Perham, RN Subramaniam, S Henderson, R AF Milne, JLS Rosenthal, PB Perham, RN Subramaniam, S Henderson, R TI Structural analysis of the pyruvate dehydrogenase complex from B. stearothermophilus SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. MRC, Cambridge CB2 2QH, England. Univ Cambridge, Cambridge CB2 1GA, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1557 BP 370A EP 371A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201691 ER PT J AU Heymann, JAW Sarker, R Hirai, T Milne, JLS Malone, P Subramaniam, S AF Heymann, JAW Sarker, R Hirai, T Milne, JLS Malone, P Subramaniam, S TI Reconstitution and two dimensional crystallization of OxlT, the oxalate transporter from Oxalobacter formigenes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Sch, Baltimore, MD 21205 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RI Hirai, Teruhisa/G-2105-2015 OI Hirai, Teruhisa/0000-0002-2114-8149 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1559 BP 371A EP 371A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201693 ER PT J AU Zhang, PJ Beatty, AL Milne, J Subramaniam, S AF Zhang, PJ Beatty, AL Milne, J Subramaniam, S TI Automated data collection with a Tecnai 12 electron microscope for applications in structural biology SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1565 BP 372A EP 372A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201699 ER PT J AU Rengifo, J Kirschl, WG Rios, E Stern, MD Gonzalez, A AF Rengifo, J Kirschl, WG Rios, E Stern, MD Gonzalez, A TI Fast inactivation of Ca release in muscle. Voltage-dependent aspects. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1581 BP 375A EP 376A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201715 ER PT J AU Rengifo, J Riosl, E Stern, MD Gonzalez, A AF Rengifo, J Riosl, E Stern, MD Gonzalez, A TI Thermodynamic irreversibility of Ca release gating in muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Rush Univ, Chicago, IL 60612 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1582 BP 376A EP 376A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201716 ER PT J AU Robinson, RC Friedman, FK Smith, SV AF Robinson, RC Friedman, FK Smith, SV TI Unique conformational ensembles of different human cytochromes P450 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. RI Friedman, Fred/D-4208-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1704 BP 403A EP 404A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201836 ER PT J AU Anfinrud, PA Roberts, JA Smirnov, AV AF Anfinrud, PA Roberts, JA Smirnov, AV TI Ultrafast photoinduced dynamics in protein crystals: Examining the influence of the crystal lattice SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1713 BP 405A EP 405A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201845 ER PT J AU Deprez, E Tauc, P Leh, H Mouscadet, JF Auclair, C Hawkins, ME Brochon, JC AF Deprez, E Tauc, P Leh, H Mouscadet, JF Auclair, C Hawkins, ME Brochon, JC TI Investigation of the oligomeric states of HIV-1 integrase-oligonucleotide complexes by time-resolved fluorescence anisotropy. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 ENS Cachan, F-94235 Cachan, France. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1737 BP 411A EP 411A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201869 ER PT J AU Watts, NR Cheng, NQ Steven, A Wingfield, P Vethanayagam, J Sackett, D AF Watts, NR Cheng, NQ Steven, A Wingfield, P Vethanayagam, J Sackett, D TI Interactions of HIV-1 Rev with tubulin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1742 BP 412A EP 412A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201874 ER PT J AU Boukari, H Sackett, D Chernomordik, V Nossal, RJ AF Boukari, H Sackett, D Chernomordik, V Nossal, RJ TI Ultra-small-angle X-ray scattering from drug-induced tubulin ring polymers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1751 BP 413A EP 414A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201883 ER PT J AU Chizmadzhev, YA Kuzmin, P Zimmerberg, J Cohen, F AF Chizmadzhev, YA Kuzmin, P Zimmerberg, J Cohen, F TI A pathway of membrane fusion through low energy intermediates SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 AN Frumkin Electrochem Inst, Moscow, Russia. NIH, Bethesda, MD 20892 USA. Rush Med Coll, Chicago, IL 60612 USA. RI Chizmadzhev, Yuri/L-1984-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1762 BP 416A EP 416A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201894 ER PT J AU Zhukovsky, M Markovic, I Leikina, E Bailey, A Chernomordik, LV AF Zhukovsky, M Markovic, I Leikina, E Bailey, A Chernomordik, LV TI Effects of the target membrane and pH on the evolution of the fusion intermediates formed by influenza hemagglutinin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1765 BP 416A EP 417A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201897 ER PT J AU Bentz, J Mittal, A Leikina, E Chernomordik, LV AF Bentz, J Mittal, A Leikina, E Chernomordik, LV TI Kinetics of RBC fusion with influenza hemagglutinin-expressing cells as a function of technique. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Drexel Univ, Philadelphia, PA 19104 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RI Mittal, Aditya/E-3087-2010 OI Mittal, Aditya/0000-0002-4030-0951 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1770 BP 417A EP 418A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201902 ER PT J AU Territo, PR French, SA Balaban, RS AF Territo, PR French, SA Balaban, RS TI Rapid kinetics of matrix calcium in porcine heart mitochondria: Role of uniport dependent and independent pathways. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1830 BP 431A EP 431A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201963 ER PT J AU Territo, PR French, SA Evans, FJ Balaban, RS AF Territo, PR French, SA Evans, FJ Balaban, RS TI Rapid kinetics of NADH and mVO(2) in heart mitochondria: Evidence for non-equilibrium kinetic control of oxidative phosphorylation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1835 BP 432A EP 432A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201968 ER PT J AU Ursos, LMB Dzekunov, SM Fidock, DA Nomura, T Cooper, R Ferdig, MT Wellems, TE Roepe, PD AF Ursos, LMB Dzekunov, SM Fidock, DA Nomura, T Cooper, R Ferdig, MT Wellems, TE Roepe, PD TI Acidification of the digestive vacuole in P-falciparum malarial parasites is linked to chloroquine resistance. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC 20057 USA. NIAID, NIH, Bethesda, MD 20892 USA. RI Ferdig, Michael/C-6627-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1843 BP 433A EP 434A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201976 ER PT J AU Clay, JR AF Clay, JR TI "Trapping" of organic blockers by voltage-gated K+ channels. Is a trap door mechanism for activation necessary? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1848 BP 435A EP 435A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692201981 ER PT J AU Romanin, C Gamsjager, R Kahr, H Schaufler, D Carlson, O Rotte, M Abernethy, DR Soldatov, NM AF Romanin, C Gamsjager, R Kahr, H Schaufler, D Carlson, O Rotte, M Abernethy, DR Soldatov, NM TI Ca2+-dependent two-site modulation of L-type Ca2+ channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Linz, A-4040 Linz, Austria. NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1907 BP 448A EP 448A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202040 ER PT J AU Guia, A Stern, MD Lakatta, EG Josephson, IR AF Guia, A Stern, MD Lakatta, EG Josephson, IR TI Calcium concentration-dependence of cardiac unitary L-type calcium channel conductance SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1910 BP 449A EP 449A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202043 ER PT J AU Sukhareva, M Smith, S Barker, J AF Sukhareva, M Smith, S Barker, J TI Conformational and pharmacological characterization of ryanodine receptors in embryonic hippocampal neurons. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 1929 BP 453A EP 453A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202062 ER PT J AU Hawkins, ME Balis, FM AF Hawkins, ME Balis, FM TI Detection of positive PCR products using fluorescent pteridine nucleoside analogs as hybridization probes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2067 BP 484A EP 484A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202200 ER PT J AU Tolstorkov, MY Ivanov, VI Minchenkova, LE Krylov, DY Jernigan, RL Zhurkin, VB AF Tolstorkov, MY Ivanov, VI Minchenkova, LE Krylov, DY Jernigan, RL Zhurkin, VB TI Trimeric model for the B <-> A transition in DNA SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2069 BP 484A EP 484A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202202 ER PT J AU Hansen, PL Rau, DC Podgornik, R Parsegian, VA AF Hansen, PL Rau, DC Podgornik, R Parsegian, VA TI Hydration and double layer forces: Delineation by ion counting SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2087 BP 488A EP 488A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202220 ER PT J AU Markovic, I Zhukovsky, M Leikina, E Zimmerberg, J Chernomordik, LV AF Markovic, I Zhukovsky, M Leikina, E Zimmerberg, J Chernomordik, LV TI Activation potential and structural stability of influenza virus hemagglutinin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2109 BP 493A EP 493A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202242 ER PT J AU Smaili, SS Kowaltowski, AJ Russell, JT Fiskum, G AF Smaili, SS Kowaltowski, AJ Russell, JT Fiskum, G TI Elevation of resting mitochondrial membrane potential by cyclosporin A, BAPTA-AM and Bcl-2. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Fed Sao Paulo, BR-04044020 Sao Paulo, Brazil. Univ Sao Paulo, Sao Paulo, Brazil. NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. RI Kowaltowski, Alicia/H-8698-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2137 BP 499A EP 499A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202270 ER PT J AU Zorov, DB Juhaszova, M Fishbein, KW Sollott, SJ AF Zorov, DB Juhaszova, M Fishbein, KW Sollott, SJ TI Mechanisms of "reactive oxygen species (ROS)-induced ROS release" during induction of the mitochondrial permeability transition (MPT) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, IRP, Bethesda, MD 21224 USA. Moscow State Univ, Moscow, Russia. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2139 BP 500A EP 500A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202272 ER PT J AU Atilgan, AR Durell, SR Jernigan, RL Demirel, MC Keskin, O Bahar, I AF Atilgan, AR Durell, SR Jernigan, RL Demirel, MC Keskin, O Bahar, I TI Anisotropy of fluctuation dynamics of proteins with an elastic network model SO BIOPHYSICAL JOURNAL LA English DT Article ID RETINOL-BINDING PROTEIN; PRINCIPAL COMPONENT ANALYSIS; MOLECULAR-DYNAMICS; VIBRATIONAL DYNAMICS; CONCERTED MOTIONS; SINGLE-PARAMETER; FOLDED PROTEINS; DOMAIN MOTIONS; ANHARMONICITY; CONFORMATIONS AB Fluctuations about the native conformation of proteins have proven to be suitably reproduced with a simple elastic network model, which has shown excellent agreement with a number of different properties for a wide variety of proteins. This scalar model simply investigates the magnitudes of motion of individual residues in the structure. To use the elastic model approach further for developing the details of protein mechanisms, it becomes essential to expand this model to include the added details of the directions of individual residue fluctuations. In this paper a new tool is presented for this purpose and applied to the retinol-binding protein, which indicates enhanced flexibility in the region of entry to the ligand binding site and for the portion of the protein binding to its carrier protein. C1 Bogazici Univ, Sch Engn, TR-80815 Bebek, Istanbul, Turkey. Bogazici Univ, Ctr Polymer Res, TR-80815 Bebek, Istanbul, Turkey. TUBITAK, Adv Polymer Mat Res Ctr, TR-80815 Bebek, Istanbul, Turkey. NCI, MSS, LECB, DBS,NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, NIH, Frederick, MD 20892 USA. RP Jernigan, RL (reprint author), NCI, MSS, LECB, DBS,NIH, Rm B-116,Bldg 12B, Bethesda, MD 20892 USA. RI Atilgan, Ali Rana/A-7805-2011; Demirel, Melik/E-4495-2010; Jernigan, Robert/A-5421-2012; Demirel, Melik/E-3775-2016 NR 49 TC 840 Z9 859 U1 7 U2 71 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 BP 505 EP 515 PG 11 WC Biophysics SC Biophysics GA 396QH UT WOS:000166647700043 PM 11159421 ER PT J AU Wang, SQ Song, LS Lakatta, EG Cheng, HP AF Wang, SQ Song, LS Lakatta, EG Cheng, HP TI Visualization of calcium influx through single L-type channels in heart cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2174 BP 507A EP 507A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202307 ER PT J AU Durell, SR Guy, HR AF Durell, SR Guy, HR TI Similarities and differences among sequences of K+ channels and their descendents. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2188 BP 510A EP 511A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202321 ER PT J AU Chen, YD Yan, B AF Chen, YD Yan, B TI How are the movements of the kinesin and the bead corelated in a motility assay? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2201 BP 513A EP 513A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202334 ER PT J AU Nizza, DT Brown, CA Feller, SE Gawrisch, K AF Nizza, DT Brown, CA Feller, SE Gawrisch, K TI NMR measurements and MD simulations of ethanol-membrane interaction SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Rockville, MD 20852 USA. Wabash Coll, Crawfordsville, IN 47933 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2323 BP 516A EP 516A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202348 ER PT J AU Nizza, DT Gawrisch, K AF Nizza, DT Gawrisch, K TI A layer model of ethanol partitioning into biological membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2333 BP 518A EP 518A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202358 ER PT J AU Gawrisch, K Feller, SE Eldho, NV Safley, AM AF Gawrisch, K Feller, SE Eldho, NV Safley, AM TI Conformation and flexibility of the polyunsaturated docosahexaenoic acid chain SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. Wabash Coll, Crawfordsville, IN 47933 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2343 BP 520A EP 520A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202367 ER PT J AU Binder, H Gawrisch, K AF Binder, H Gawrisch, K TI A novel fluid lamellar phase of docosahexaenoyl phosphocholine SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Leipzig, D-7010 Leipzig, Germany. NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2359 BP 523A EP 524A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202383 ER PT J AU Teague, WE Fuller, NL Rand, RP Gawrisch, K Sternin, E AF Teague, WE Fuller, NL Rand, RP Gawrisch, K Sternin, E TI Influence of polyunsaturation on membrane curvature elasticity for 1-steroyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Rockville, MD 20852 USA. Brock Univ, St Catharines, ON L2S 3A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2358 BP 523A EP 523A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202382 ER PT J AU Eldho, NV Gawrisch, K AF Eldho, NV Gawrisch, K TI Docosahexaenoic vs docosapentaenoic acid - The difference that the loss of a single double bond makes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2364 BP 524A EP 525A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202388 ER PT J AU Hayakawa, E Mitchell, DC Litman, BJ AF Hayakawa, E Mitchell, DC Litman, BJ TI The relationship between membrane curvature stress and phospholipid acyl chain packing free volume SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2399 BP 532A EP 532A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202423 ER PT J AU Polozov, IV Sternin, E Litman, BJ Gawrisch, K AF Polozov, IV Sternin, E Litman, BJ Gawrisch, K TI Rhodopsin effects on the organization of lipid bilayers - Deuterium NMR studies SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. Brock Univ, St Catharines, ON L2S 3A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2419 BP 536A EP 537A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202443 ER PT J AU Epand, RF Chernomordik, LV Yip, CM LeDuc, DL Shin, YK Epand, RM AF Epand, RF Chernomordik, LV Yip, CM LeDuc, DL Shin, YK Epand, RM TI Self-assembly of influenza hemagglutinin: Studies of ectodomain aggegation by in situ atomic force microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 McMaster Univ, Hamilton, ON L8N 3Z5, Canada. NIH, NICHD, Bethesda, MD 20892 USA. Univ Toronto, Inst Biomat, Toronto, ON M5S 3G9, Canada. Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2422 BP 537A EP 537A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202446 ER PT J AU Mitchell, DC Niu, SL Litman, BJ AF Mitchell, DC Niu, SL Litman, BJ TI Rate of G protein-receptor coupling varies with cholesterol content in ros disk membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2448 BP 543A EP 543A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202472 ER PT J AU Tolstorukov, MY Jernigan, RL Zhurkin, VB AF Tolstorukov, MY Jernigan, RL Zhurkin, VB TI Minor groove interactions in the protein-DNA complexes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2566 BP 568A EP 568A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202589 ER PT J AU Sidorova, N Rau, D AF Sidorova, N Rau, D TI Kinetic approach to the removing water from EcoRI-noncognate DNA complexes with osmotic stress. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2572 BP 569A EP 569A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202595 ER PT J AU Chen, LF Wang, F Meng, HP Sellers, JR AF Chen, LF Wang, F Meng, HP Sellers, JR TI Characterization of recombinant myosin X SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2588 BP 573A EP 573A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202611 ER PT J AU Wei, QZ Adelstein, RS AF Wei, QZ Adelstein, RS TI Using a dominant active mutant of Rho-A (L63Rho-A) to study myosin II filament formation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2605 BP 576A EP 576A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202628 ER PT J AU Combs, CA Balaban, RS AF Combs, CA Balaban, RS TI Electrical pacing increases dehydrogenase activity in unloaded cardiac myocytes as measured by ED-FRAP. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2653 BP 587A EP 587A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202676 ER PT J AU Bogdanov, K Vinogradova, T Lakatta, E AF Bogdanov, K Vinogradova, T Lakatta, E TI Coupling of pre action potential localized calcium transients to Na-Ca exchanger is required for spontaneous beating of sinoatrial node cell. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2740 BP 607A EP 607A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202763 ER PT J AU Colegrove, SL Hongpaisan, J Andrews, SB Friel, DD AF Colegrove, SL Hongpaisan, J Andrews, SB Friel, DD TI Dissection and characterization of ER Ca2+uptake and release fluxes in sympathetic neurons SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. NINDS, Neurobiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2754 BP 610A EP 610A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202777 ER PT J AU Gaal, M Pammer, P Kepplinger, KJF Gamsjager, R Kahr, H Groschner, K Soldatov, NM Romanin, C AF Gaal, M Pammer, P Kepplinger, KJF Gamsjager, R Kahr, H Groschner, K Soldatov, NM Romanin, C TI The effect of mutant calmodulin on single L-type Ca2+ channel currents SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Linz, A-4040 Linz, Austria. Graz Univ, A-8010 Graz, Austria. NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2794 BP 619A EP 619A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202817 ER PT J AU Kahr, H Gamsjager, R Kepplinger, KJF Groschner, K Soldatov, NM Romanin, C AF Kahr, H Gamsjager, R Kepplinger, KJF Groschner, K Soldatov, NM Romanin, C TI Use of fluorescent calmodulins to study Ca2+-dependent inactivation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Univ Linz, A-4040 Linz, Austria. Graz Univ, A-8010 Graz, Austria. NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2795 BP 619A EP 619A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202818 ER PT J AU Shi, CZ Blatt, A Kobrinsky, E Soldatov, NM AF Shi, CZ Blatt, A Kobrinsky, E Soldatov, NM TI Molecular determinants of Ca2+ channel deactivation and voltage-dependence of availability. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2796 BP 619A EP 620A PN 2 PG 2 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202819 ER PT J AU Josephson, IR Guia, A Lakatta, EG Stern, MD AF Josephson, IR Guia, A Lakatta, EG Stern, MD TI Voltage- and ion-dependent modulation of inactivation and facilitation of single L-type cardiac Ca channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2001 VL 80 IS 1 MA 2802 BP 621A EP 621A PN 2 PG 1 WC Biophysics SC Biophysics GA 397JH UT WOS:000166692202825 ER PT J AU Burke, TR Yao, ZJ Liu, DG Voigt, J Gao, Y AF Burke, TR Yao, ZJ Liu, DG Voigt, J Gao, Y TI Phosphoryltyrosyl mimetics in the design of peptide-based signal transduction inhibitors SO BIOPOLYMERS LA English DT Article DE protein-tyrosine kinase; protein-tyrosine phosphatase; SH2 domain; signal transduction inhibitor; phosphotyrosyl mimetic ID PROTEIN-TYROSINE KINASE; SH2 DOMAIN BINDING; CONTAINING PHOSPHOTYROSYL MIMETICS; PHOSPHATE-CONTAINING LIGANDS; SOLID-PHASE SYNTHESIS; DRUG-DISCOVERY; CRYSTAL-STRUCTURE; SUBSTRATE-SPECIFICITY; POTENT INHIBITION; INSULIN-RECEPTOR AB The central roles played by protein-tyrosine kinase (PTK)-dependent signal transduction in normal cellular regulation and homeostasis have made inappropriate or aberrant functions of certain of these pathways contributing factors to a variety of diseases, including several cancers. For this reason, development of PTK signaling inhibitors has evolved into an important approach toward new therapeutics. Since in these pathways phosphotyrosyl (pTyr) residues provide unique and defining functions either by their creation under the catalysis of PTKs, their recognition and binding by protein modules such as SH2 and phosphotyrosyl binding (PTB) domains, or their destruction by protein-tyrosine phosphatases, pTyr mimetics provide useful general starting points for inhibitor design. Important considerations in the development of such pTyr mimetics include enzymatic stability (particularly toward PTPs), high affinity recognition by target pTyr binding proteins, and good cellular bioavailability. Although small molecule, nonpeptide inhibitors may be ultimate objectives of inhibitor development, peptides frequently serve as display platforms for pTyr mimetics, which afford useful and conceptually straightforward starting paints in the development process. Reported herein is a limited overview of pTyr mimetic development as it relates to peptide-based agents. Of particular interest are recent findings that highlight potential limitations of peptides as display platforms for the identification of small molecule lends. One conclusion that results from this work is that while peptide-based approaches toward small molecule inhibitor design are often intellectually satisfying fr-om a structure-based perspective, extrapolation of negative findings to small molecule, nonpeptide contexts should be undertaken with extreme caution. (C) 2001 John Wiley & Sons, Inc.* C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Bldg 376,Boyles St,POB B, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 83 TC 70 Z9 72 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2001 VL 60 IS 1 BP 32 EP 44 DI 10.1002/1097-0282(2001)60:1<32::AID-BIP1002>3.0.CO;2-I PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 442RT UT WOS:000169299300003 PM 11376431 ER PT J AU Hopley, R Zimmer, A AF Hopley, R Zimmer, A TI MouseBank: A database application for managing transgenic mouse breeding programs SO BIOTECHNIQUES LA English DT Article C1 NIMH, NIH, Bethesda, MD 20892 USA. Univ Bonn, D-5300 Bonn, Germany. RP Hopley, R (reprint author), NIMH, NIH, 36 Convent Dr,MSC 4094, Bethesda, MD 20892 USA. RI Zimmer, Andreas/B-8357-2009 NR 0 TC 7 Z9 7 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2001 VL 30 IS 1 BP 130 EP 132 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392GW UT WOS:000166404200019 PM 11196303 ER PT J AU Woods, WG Neudorf, S Gold, S Sanders, J Buckley, JD Barnard, DR Dusenbery, K DeSwarte, J Arthur, DC Lange, BJ Kobrinsky, NL AF Woods, WG Neudorf, S Gold, S Sanders, J Buckley, JD Barnard, DR Dusenbery, K DeSwarte, J Arthur, DC Lange, BJ Kobrinsky, NL TI A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission: a report from the Children's Cancer Group SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; HIGH-DOSE CYTARABINE; POSTREMISSION CHEMOTHERAPY; INTENSIVE CHEMOTHERAPY; CHILDHOOD; INDUCTION; THERAPY; INTENSIFICATION; MELPHALAN AB Intensive, myelosuppressive therapy is necessary to maximize outcomes for patients with acute myeloid leukemia (AML), A comparison was made of 3 aggressive postremission approaches for children and adolescents with AML in a randomized trial, CCG-2891,A total of 652 children and adolescents with AML who achieved remission on 2 induction regimens using identical drugs end doses (standard and intensive timing) were eligible for allocation to allogeneic bone marrow transplantation (BMT) based on matched related donor status (n = 181) or randomization to autologous BMT (n = 177) or to aggressive high-dose cytarabine-based chemotherapy (n = 179). Only 115 patients (18%) refused to participate in the postremission phase of this study. Overall compliance with the 3 allocated regimens was 90%, At 8 years actuarial, 54% +/- 4%(95% confidence interval) of all remission patients remain alive. Survival by assigned regimen ("intent to treat") is as follows: allogeneic BMT, 60% +/- 9%; autologous BMT, 48% +/- 8%; and chemotherapy, 53% +/- 8%, Survival in the allogeneic BMT group is significantly superior to autologous BMT (P = .002) and chemotherapy (P = .05); differences between chemotherapy and autologous BMT are not significant (P = .21). No potential confounding factors affected results. Patients receiving intensive-timing induction therapy had superior long-term survival irrespective of postremission regimen received (allogeneic BMT, 70% +/- 9%; autologous BMT, 54% +/- 9%; chemotherapy, 57% +/- 10%), Allogeneic BMT remains the treatment of choice for children and adolescents with AML in remission, when a matched related donor is available. For all others, there is no advantage to autologous BMT; hence, aggressive nonablative chemotherapy should be used. (C) 2001 by The American Society of Hematology. C1 S Carolina Canc Ctr, Columbia, SC USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Univ N Carolina, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. IWK Grace Hlth Ctr, Halifax, NS, Canada. Univ Minnesota, Minneapolis, MN USA. Long Beach Mem Med Ctr, Long Beach, CA USA. NCI, Bethesda, MD 20892 USA. Riger Maris Canc Ctr, Fargo, ND USA. RP Woods, WG (reprint author), Childrens Canc Grp, POB 60012, Arcadia, CA 91066 USA. NR 24 TC 228 Z9 248 U1 1 U2 6 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 JAN 1 PY 2001 VL 97 IS 1 BP 56 EP 62 DI 10.1182/blood.V97.1.56 PG 7 WC Hematology SC Hematology GA 388JL UT WOS:000166177300006 PM 11133742 ER PT J AU Tiberghien, P Ferrand, C Lioure, B Milpied, N Angonin, R Deconinck, E Certoux, JM Robinet, E Saas, P Petracca, B Juttner, C Reynolds, CW Longo, DL Herve, P Cahn, JY AF Tiberghien, P Ferrand, C Lioure, B Milpied, N Angonin, R Deconinck, E Certoux, JM Robinet, E Saas, P Petracca, B Juttner, C Reynolds, CW Longo, DL Herve, P Cahn, JY TI Administration of herpes simplex-thymidine kinase-expressing donor T cells with a T-cell-depleted allogeneic marrow graft SO BLOOD LA English DT Article ID VERSUS-LEUKEMIA; IN-VIVO; PERIPHERAL-BLOOD; LYMPHOPROLIFERATIVE DISORDERS; TRANSPLANT RECIPIENTS; GENE-THERAPY; LYMPHOCYTES; PROPHYLAXIS; RISK; CYCLOSPORINE AB Administration of donor T cells expressing the herpes simplex-thymidine kinase (HS-tk) with a hematopoietic stem cell (HSC) transplantation could allow, if graft-versus-host disease (GVHD) was to occur, a selective in vivo depletion of these T cells by the use of ganciclovir (GCV), The study evaluates the feasibility of such an approach. Escalating numbers of donor HS-tk-expressing CD3(+) gene-modified cells (GMCs) are infused with a T-cell-depleted bone marrow transplantation (BMT), Twelve patients with hematological malignancies received 2 x 10(5)(n = 5), 6 x 10(5) (n = 5), or 20 x 10(5) (n = 2) donor CD3(+) GMCs/kg with a BMT from a human leukocyte antigen (HLA)-identical sibling. No acute toxicity was associated with GMC administration, An early increase of circulating GMCs followed by a progressive decrease and long-lasting circulation of GMCs was documented, GCV treatment resulted in significant rapid decrease in circulating GMCs, Three patients developed acute GVHD, with a grade of at least II, while one patient developed chronic GVHD. Treatment with GCV alone was associated with a complete remission (CR) in 2 patients with acute GVHD, while the addition of glucocorticoids was necessary to achieve a CR in the last case. Long-lasting CR occurred with GCV treatment in the patient with chronic GVHD. Unfortunately, Epstein-Barr virus-lymphoproliferative disease occurred in 3 patients. Overall, the administration of low numbers of HS-tk-expressing T cells early following an HLA-identical BMT is associated with no acute toxicity, persistent circulation of the GMCs, and GCV-sensitive GVHD, Such findings open the way to the infusion of higher numbers of gene-modified donor T cells to enhance post-BMT immune competence while pre serving GCV-sensitive alloreactivity. (C) 2001 by The American Society of Hematology. C1 Etab Francais Sang, F-25000 Besancon, France. CHU Besancon, Serv Hematol, F-25030 Besancon, France. CHU Strasbourg, Serv Hematol, F-67000 Strasbourg, France. GTI Systemix Novartis, Palo Alto, CA USA. NCI, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD USA. NIA, NIH, Baltimore, MD 21224 USA. RP Tiberghien, P (reprint author), Etab Francais Sang, 1 Bvd Fleming, F-25000 Besancon, France. RI SAAS, Philippe/M-3550-2015 NR 50 TC 190 Z9 201 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 JAN 1 PY 2001 VL 97 IS 1 BP 63 EP 72 DI 10.1182/blood.V97.1.63 PG 10 WC Hematology SC Hematology GA 388JL UT WOS:000166177300007 PM 11133743 ER PT J AU Sporri, B Kovanen, PE Sasaki, A Yoshimura, A Leonard, WJ AF Sporri, B Kovanen, PE Sasaki, A Yoshimura, A Leonard, WJ TI JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling SO BLOOD LA English DT Article ID RECEPTOR-BETA-CHAIN; JAK-3 JANUS KINASE; SOCS-BOX MOTIF; GAMMA-CHAIN; TYROSINE PHOSPHORYLATION; SH2-CONTAINING PROTEIN; CYTOPLASMIC DOMAINS; NEGATIVE REGULATORS; GENE-EXPRESSION; DEFICIENT MICE C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Kurume Univ, Inst Life Sci, Kurume, Fukuoka 830, Japan. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RI Yoshimura, Akihiko/K-5515-2013 NR 55 TC 75 Z9 83 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 JAN 1 PY 2001 VL 97 IS 1 BP 221 EP 226 DI 10.1182/blood.V97.1.221 PG 6 WC Hematology SC Hematology GA 388JL UT WOS:000166177300028 PM 11133764 ER PT J AU Jeyakumar, M Norflus, F Tifft, CJ Cortina-Borja, M Butters, TD Proia, RL Perry, VH Dwek, RA Platt, FM AF Jeyakumar, M Norflus, F Tifft, CJ Cortina-Borja, M Butters, TD Proia, RL Perry, VH Dwek, RA Platt, FM TI Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation SO BLOOD LA English DT Article ID LYSOSOMAL STORAGE DISEASES; N-BUTYLDEOXYNOJIRIMYCIN; GLYCOLIPID BIOSYNTHESIS; TAY-SACHS; INHIBITOR AB Sandhoff disease is a lysosomal storage disorder characterized by G(M2) ganglioside accumulation in the central nervous system (CNS) and periphery. It results from mutations in the HEXB gene, causing a deficiency in beta -hexosaminidase. Bone marrow transplantation (BMT), which augments enzyme levels, and substrate deprivation (using the glycosphingolipid biosynthesis inhibitor N-butyldeoxynojirimycin [NB-DNJ]) independently have been shown to extend life expectancy in a mouse model of Sandhoff disease. The efficacy of combining these 2 therapies was evaluated, Sandhoff disease mice treated with BMT and NB-DNJ survived significantly longer than those treated with BMT or NB-DNJ alone. When the mice were subdivided into 2 groups on the basis of their donor bone marrow-derived CNS enzyme levels, the high enzyme group exhibited a greater degree of synergy (25%) than the group as a whole (13%). Combination therapy may therefore be the strategy of choice for treating the infantile onset disease variants, (C) 2001 by The American Society of Hematology. C1 Univ Oxford, Dept Biochem, Glycobiol Inst, Oxford OX1 3QU, England. Univ Southampton, Sch Biol Sci, Southampton, Hants, England. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Platt, FM (reprint author), Univ Oxford, Dept Biochem, Glycobiol Inst, S Parks Rd, Oxford OX1 3QU, England. RI Platt, Frances/G-1004-2010; Proia, Richard/A-7908-2012; Cortina Borja, Mario/A-3847-2009 NR 15 TC 86 Z9 93 U1 1 U2 3 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 JAN 1 PY 2001 VL 97 IS 1 BP 327 EP 329 DI 10.1182/blood.V97.1.327 PG 3 WC Hematology SC Hematology GA 388JL UT WOS:000166177300043 PM 11133779 ER PT J AU Sloand, E Kim, S Maciejewski, J Young, N AF Sloand, E Kim, S Maciejewski, J Young, N TI Pharmacologic concentrations of granulocyte-colony stimulating factor affect cytokine expression by lymphocytes SO BLOOD LA English DT Letter C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Sloand, E (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 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 JAN 1 PY 2001 VL 97 IS 1 BP 334 EP 335 PG 2 WC Hematology SC Hematology GA 388JL UT WOS:000166177300047 ER PT J AU Abraham, EH Sterling, KM Kim, RJ Salikhova, AY Huffman, HB Crockett, MA Johnston, N Parker, HW Boyle, WE Hartov, A Demidenko, E Efird, J Kahn, J Grubman, SA Jefferson, DM Robson, SC Thakar, JH Lorico, A Rappa, G Sartorelli, AC Okunieff, P AF Abraham, EH Sterling, KM Kim, RJ Salikhova, AY Huffman, HB Crockett, MA Johnston, N Parker, HW Boyle, WE Hartov, A Demidenko, E Efird, J Kahn, J Grubman, SA Jefferson, DM Robson, SC Thakar, JH Lorico, A Rappa, G Sartorelli, AC Okunieff, P TI Erythrocyte membrane ATP binding cassette (ABC) proteins: MRP1 and CFTR as well as CD39 (ecto-apyrase) involved in RBC ATP transport and elevated blood plasma ATP of cystic fibrosis SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE erythrocyte; ATP (adenosine triphosphate); CFTR (cystic fibrosis transmembrane conductance regulator); MRP1 (multidrug resistance-associated; protein); MDR (multidrug resistance protein); Pgp (P-glycoprotein); CD39; apyrase; ATP transporter; plasma ATP ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CONJUGATE EXPORT PUMP; P-GLYCOPROTEIN; INCREASED SENSITIVITY; CHLORIDE CHANNELS; GENE LEADS; MULTIDRUG; GLUTATHIONE; MICE; RELEASE AB In addition to the better-known roles of the erythrocyte in the transport of oxygen and carbon dioxide, the concept that the red blood cell is involved in the transport and release of ATP has been evolving (J. Luthje, Blut 59, 367, 1989; G. R. Bergfeld and T. Forrester, Cardiovasc. Res. 26, 40, 1992; M. L. Ellsworth et al., Am. J. Physiol. 269, H2155, 1995; R. S. Sprague et al., Am. J. Physiol. 275, H1726, 1998). Membrane proteins involved in the release of ATP from erythrocytes now appear to include members of the ATP binding cassette (ABC) family (C. F. Higgins, Annu. Rev. Cell Biol. 8, 67, 1992; C. F. Higgins, Cell 82, 693, 1995). In addition to defining physiologically the presence of ABC proteins in RBCs, accumulating gel electrophoretic evidence suggests that the cystic fibrosis transmembrane conductance regulator (CE;TR) and the multidrug resistance-associated protein (MRP1), respectively, constitute significant proteins in the red blood cell membrane. As such, this finding makes the mature erythrocyte compartment a major mammalian repository of these important ABC proteins. Because of its relative structural simplicity and ready accessibility, the erythrocyte offers an ideal system to explore details of the physiological functions of ABC proteins. Moreover, the presence of different ABC proteins in a single membrane implies that interaction among these proteins and with other membrane proteins may be the norm and not the exception in terms of modulation of their functions, (C) 2001 Academic Press. C1 Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. Dartmouth Med Sch, Dept Pediat, Hanover, NH 03755 USA. Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Med Sch, Epidemiol & Biostat Sect, Hanover, NH 03755 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dev Therapeut Program, New Haven, CT 06520 USA. Univ Rochester, Ctr Canc, Dept Radiat Oncol, Rochester, NY 14642 USA. RP Abraham, EH (reprint author), Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. EM edward.h.abraham@dartmouth.edu NR 70 TC 45 Z9 46 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 1079-9796 EI 1096-0961 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JAN PY 2001 VL 27 IS 1 BP 165 EP 180 DI 10.1006/bcmd.2000.0357 PG 16 WC Hematology SC Hematology GA 415TG UT WOS:000167738300022 PM 11358378 ER PT J AU Abraham, EH Shrivastav, B Salikhova, AY Sterling, KM Johnston, N Guidotti, G Scala, S Litman, T Chan, KC Arceci, RJ Steiglitz, K Herscher, L Okunieff, P AF Abraham, EH Shrivastav, B Salikhova, AY Sterling, KM Johnston, N Guidotti, G Scala, S Litman, T Chan, KC Arceci, RJ Steiglitz, K Herscher, L Okunieff, P TI Cellular and biophysical evidence for interactions between adenosine triphosphate and P-glycoprotein substrates: functional implications for adenosine triphosphate/drug cotransport in P-glycoprotein overexpressing tumor cells and in P-glycoprotein low-level expressing erythrocytes SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE erythrocyte; RBC; ATP (adenosine triphosphate); MDR (multidrug resistance protein); Pgp (P-glycoprotein); CD39; apyrase; ATP transporter; cotransport; plasma ATP; Pgp drug substrates; doxorubicin; adriamycin; verapamil; colchicine; electrophoresis; capillary electrophoresis; knockout mice; Taxol; camptothecin; stoichiometry of coupling; ABC proteins ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CAPILLARY-ZONE-ELECTROPHORESIS; MULTIDRUG-RESISTANCE; ATP CHANNEL; DOXORUBICIN ADRIAMYCIN; DRUG-RESISTANCE; TRANSPORT; ASSOCIATION; MECHANISM; CFTR AB P-glycoprotein is involved with the removal of drugs, most of them cations, from the plasma membrane and cytoplasm. Pgp is also associated with movement of ATP, an anion, from the cytoplasm to the extracellular space. The central question of this study is whether drug and ATP transport associated with the expression of Pgp are in any way coupled. We have measured the stoichiometry of transport coupling between drug and ATP release. The drug and ATP transport that is inhibitable by the sulfonylurea compound, glyburide (P. E. Golstein, A. Boom, J. van Geffel, P. Jacobs, B. Masereel, and R. Beauwens, Pfluger's Arch. 437, 652, 1999), permits determination of the transport coupling ratio, which is close to 1:1. In view of this result, we asked whether ATP interacts directly with Pgp substrates. We show by measuring the movement of Pgp substrates in electric fields that ATP and drug movement are coupled. The results are compatible with the view that substrates for Pgp efflux are driven by the movement of ATP through electrostatic interaction and effective ATP-drug complex formation with net anionic character. This mechanism not only pertains to drug efflux from tumor cells overexpressing Pgp, but also provides a framework for understanding the role of erythrocytes in drug resistance. The erythrocyte consists of a membrane surrounding a millimolar pool of ATP. Mammalian RBCs have no nucleus or DNA drug/toxin targets. From the perspective of drug/ATP complex formation, the RBC serves as an important electrochemical sink for toxins. The presence in the erythrocyte membrane of approximately 100 Pgp copies per RBC provides a mechanism for eventual toxin clearance. The RBC transport of toxins permits their removal from sensitive structures and ultimate clearance from the organism via the liver and/or kidneys. (C) 2001 Academic Press. C1 Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. NCI, Div Clin Sci, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Radiat Oncol Branch, Bethesda, MD 20892 USA. Harvard Univ, Dept Biochem & Mol Biol, Cambridge, MA 02138 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Analyt Chem Lab, SAIC Frederick, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. Univ Rochester, Ctr Canc, Dept Radiat Oncol, Rochester, NY 14642 USA. RP Abraham, EH (reprint author), Dartmouth Med Sch, Dept Med, Hanover, NH 03755 USA. RI Scala, Stefania/K-1380-2016 OI Scala, Stefania/0000-0001-9524-2616 NR 68 TC 18 Z9 19 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JAN PY 2001 VL 27 IS 1 BP 181 EP 200 DI 10.1006/bcmd.2000.0373 PG 20 WC Hematology SC Hematology GA 415TG UT WOS:000167738300023 PM 11358379 ER PT J AU Hori, M Xiang, S Qi, CF Chattopadhyay, SK Fredrickson, TN Hartley, JW Kovalchuk, AL Bornkamm, GW Janz, S Copeland, NG Jenkins, NA Ward, JM Morse, HC AF Hori, M Xiang, S Qi, CF Chattopadhyay, SK Fredrickson, TN Hartley, JW Kovalchuk, AL Bornkamm, GW Janz, S Copeland, NG Jenkins, NA Ward, JM Morse, HC TI Non-Hodgkin lymphomas of mice SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE BCL6; Burkitt lymphoma; mouse lymphoma; MYC; non-Hodgkin lymphoma ID SOMATIC HYPERMUTATION; TRANSGENIC MICE; CELL LYMPHOMA; C-MYC; LEUKEMIA; PATHWAY; BCL-6; MUTATION; FEATURES; STRAINS AB Studies of lymphoid neoplasms occurring in normal or genetically engineered mice have revealed parallels and differences to non-Hodgkin lymphomas (NHL) of humans. Some mouse lymphomas have strong histologic similarities to the human NHL subsets including precursor B- and T-cell lymphoblastic, small lymphocytic, splenic marginal zone, and diffuse large-cell B-cell lymphomas (DLCL); whether molecular parallels also exist is under study. Others mouse types such as sIg(+) lymphoblastic B-cell lymphoma have no histologic equivalent in human NHL even though they share molecular deregulation of BCL6 with human DLCL. Finally, Burkitt lymphoma does not appear to occur naturally in mice, but it can be induced with appropriately engineered transgenes. C1 NIAID, LIP, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Genet Lab, Off Lab Anim Sci, NIH, Bethesda, MD 20892 USA. GSF Forschungszentrum Umwelt & Gesundheit, Inst Klin Mol Biol & Tummorgenet, Munich, Germany. NCI, Mouse Canc Genet Program, Off Lab Anim Sci, NIH, Bethesda, MD 20892 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, NIH, Bethesda, MD 20892 USA. RP Morse, HC (reprint author), NIAID, LIP, NIH, 7 Ctr Dr,Room 7-304,MSC 0760, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 26 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JAN PY 2001 VL 27 IS 1 BP 217 EP 222 DI 10.1006/bcmd.2000.0375 PG 6 WC Hematology SC Hematology GA 415TG UT WOS:000167738300026 PM 11358382 ER PT J AU Star, R AF Star, R TI Design issues for clinical trials in acute renal failure SO BLOOD PURIFICATION LA English DT Article; Proceedings Paper CT International Conference on Dilysis II CY JAN 13-14, 2000 CL TARPON SPRINGS, FLORIDA C1 NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Star, R (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bldg 31,Room 9A35,31 Ctr Dr MSC 2560, Bethesda, MD 20892 USA. NR 13 TC 14 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-5068 J9 BLOOD PURIFICAT JI Blood Purif. PY 2001 VL 19 IS 2 BP 233 EP 237 DI 10.1159/000046947 PG 5 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA 390BR UT WOS:000166274700018 PM 11150816 ER PT J AU Savinova, OV Sugiyama, F Martin, JE Tomarev, SI Paigen, BJ Smith, RS John, SWM AF Savinova, Olga V. Sugiyama, Fumihiro Martin, Janice E. Tomarev, Stanislav I. Paigen, Beverly J. Smith, Richard S. John, Simon W. M. TI Intraocular pressure in genetically distinct mice: an update and strain survey SO BMC GENETICS LA English DT Article AB Background: Little is known about genetic factors affecting intraocular pressure (IOP) in mice and other mammals. The purpose of this study was to determine the IOPs of genetically distinct mouse strains, assess the effects of factors such as age, sex and time of day on IOP in specific strain backgrounds, and to assess the effects of specific candidate gene mutations on IOP. Results: Based on over 30 studied mouse strains, average IOP ranges from approximately 10 to 20 mmHg. Gender does not typically affect IOP and aging results in an IOP decrease in some strains. Most tested strains exhibit a diurnal rhythm with IOP being the highest during the dark period of the day. Homozygosity for a null allele of the carbonic anhydrase II gene (Car2 (n)) does not alter IOP while homozygosity for a mutation in the leptin receptor gene (Lepr (db)) that causes obesity and diabetes results in increased IOP. Albino C57BL/6J mice homozygous for a tyrosinase mutation (Tyr (c-2J)) have higher IOPs than their pigmented counterparts. Conclusions: Genetically distinct mouse strains housed in the same environment have a broad range of IOPs. These IOP differences are likely due to interstrain genetic differences that create a powerful resource for studying the regulation of IOP. Age, time of day, obesity and diabetes have effects on mouse IOP similar to those in humans and other species. Mutations in two of the assessed candidate genes (Lepr and Tyr) result in increased IOP. These studies demonstrate that mice are a practical and powerful experimental system to study the genetics of IOP regulation and disease processes that raise IOP to harmful levels. C1 [Savinova, Olga V.; Martin, Janice E.; Paigen, Beverly J.; Smith, Richard S.; John, Simon W. M.] Jackson Lab, Bar Harbor, ME 04609 USA. [Sugiyama, Fumihiro] Univ Tsukuba, Lab Anim Resource Ctr, Tsukuba, Ibaraki 305, Japan. [Martin, Janice E.; Smith, Richard S.; John, Simon W. M.] Jackson Lab, Howard Hughes Med Inst, Bar Harbor, ME 04609 USA. [Tomarev, Stanislav I.] NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. [John, Simon W. M.] Tufts Univ, Dept Ophthalmol, Sch Med, Boston, MA 02155 USA. RP John, SWM (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM ovs@jax.org; bunbun@sakura.cc.tsukuba.ac.jp; jemartin@jax.org; tomarev@intra.nei.nih.gov; bjp@jax.org; rss@jax.org; swmj@jax.org FU AHAF [97437, G1999023]; NIH [EY11721, HL55001]; Howard Hughes Medical Institute; [CA34196] FX We thank Norma Buckley, Felicia Farley and Jennifer Smith for their assistance with data entry, references, and figures. We also thank Jane Barker for the Car2 mice, Marianna Mertts for her help with analysis of Myoc alleles, and members of the John laboratory, Tatyana Golovkina, Edward Leiter and Timothy O'Brien for critical reading of the manuscript. Supported in part by AHAF 97437 and G1999023, NIH EY11721 and HL55001. Core services were subsidized by grant CA34196. Major funding was provided by the Howard Hughes Medical Institute. SWMJ is an Assistant Investigator of The Howard Hughes Medical Institute. NR 81 TC 104 Z9 109 U1 2 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PY 2001 VL 2 AR 12 DI 10.1186/1471-2156-2-12 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA V31UU UT WOS:000208909300012 PM 11532192 ER PT J AU Irwin, DE Weatherby, LB Huang, WY Rosenberg, DM Cook, SF Walker, AM AF Irwin, DE Weatherby, LB Huang, WY Rosenberg, DM Cook, SF Walker, AM TI Impact of patient characteristics on the risk of influenza/ILI-related complications SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID COST-EFFECTIVENESS; ELDERLY PERSONS; VACCINATION; EPIDEMICS AB Background: We sought to quantify the impact of patient characteristics on complications and health care costs associated with influenza and influenza-like illness (ILI) in a nonelderly population. Methods: Patients with medical reimbursement claims for influenza in the 1996-1997 season were identified from the automated database of a large private New England Insurer (NEI). Influenza care during the 21-day follow-up period was characterized according to age, gender, vaccine status, co-morbidities, prior influenza/ILI episodes, treatments, and recent health care costs and related diagnoses. Results: There were 6,241 patients. Approximately 20% had preexisting chronic lung disease. Overall, 23% had health care services for possible complications, among which respiratory diagnoses were the most common (13%). Two percent of the influenza/ILI episodes involved hospitalization, with a median stay of five days. Factors most strongly predictive of hospitalizations and complications were preexisting malignancy ( hospitalizations OR = 3.7 and complications OR = 2.4), chronic heart disease (OR = 3.2 and OR = 1.8), diabetes (OR = 2.2 and OR = 1.7) and recent illnesses that would have counted as complications had they occurred during an influenza/ILI episode ( hospitalizations OR = 3.2 and complications OR = 1.5). The same factors affected influenza-related costs and total costs of care as dramatically as they affected complication rates. Conclusions: Influenza/ILI-related costs are driven by the characteristics that predict complications of influenza. Patients with chronic illness and those with recent acute respiratory events are the most likely to experience complications and hospitalizations. C1 Ingenix Pharmaceut Serv, Div Epidemiol, Newton Lower Falls, MA 02162 USA. GlaxoSmithKline, Worldwide Epidemiol, Res Triangle Pk, NC USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. GlaxoSmithKline, Worldwide Epidemiol, Greenford, Middx, England. RP Walker, AM (reprint author), Ingenix Pharmaceut Serv, Div Epidemiol, Newton Lower Falls, MA 02162 USA. NR 18 TC 27 Z9 27 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PY 2001 VL 1 AR 8 DI 10.1186/1472-6963-1-8 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 623WV UT WOS:000179726600008 PM 11580874 ER PT J AU Weinrich, M Boser, KI McCall, D Bishop, V AF Weinrich, M Boser, KI McCall, D Bishop, V TI Training agrammatic subjects on passive sentences: Implications for syntactic deficit theories SO BRAIN AND LANGUAGE LA English DT Article DE aphasia; stroke; syntax; agrammatism ID VERB RETRIEVAL; BRAIN POTENTIALS; WORKING-MEMORY; BROCA APHASIA; COMPREHENSION; LANGUAGE; TENSE; REPRESENTATION; DISSOCIATION; MORPHOLOGY AB We trained two subjects with chronic agrammatic aphasia on production of passive sentences using a computerized, iconic-based communication system. After training, one of the subjects demonstrated significant improvements in his abilities to comprehend and verbally produce English passive voiced sentences, including sentences with conjoined subjects and objects. These results suggest that agrammatism does not represent a fixed syntactic deficit. (C) 2001 Academic Press. C1 NICHHD, Natl Ctr Med Rehabil Res, NIH, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. RP Weinrich, M (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, Bldg 6100,Room 2A-03,6100 Execut Blvd, Rockville, MD 20852 USA. NR 50 TC 10 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD JAN PY 2001 VL 76 IS 1 BP 45 EP 61 DI 10.1006/brln.2000.2421 PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 401QY UT WOS:000166940800004 PM 11161354 ER PT J AU Perry, T Hodges, H Gray, JA AF Perry, T Hodges, H Gray, JA TI Behavioural, histological and immunocytochemical consequences following 192 IgG-saporin immunolesions of the basal forebrain cholinergic system SO BRAIN RESEARCH BULLETIN LA English DT Article DE immunotoxin; cholinergic system; memory; basal forebrain ID RADIAL MAZE PERFORMANCE; SELECTIVE IMMUNOTOXIC LESIONS; INDUCED EXCITOTOXIC LESIONS; CEREBELLAR PURKINJE-CELLS; GROWTH-FACTOR RECEPTOR; ACID-INDUCED LESIONS; MEDIAL SEPTAL AREA; RICH NEURAL GRAFTS; NUCLEUS BASALIS; ALZHEIMERS-DISEASE AB Use of the selective immunotoxin; 192 IgG-saporin, is helping to elucidate the role of the cholinergic system in cognition by overcoming the problems of interpretation associated with the use of non-specific lesioning agents. In separate studies, we have compared the long- and short-term effects of single site and combined saporin lesions of the nucleus basalis magnocellularis and medial septal area, on spatial learning and memory in radial arm and water maze tasks. At If months, only rats with combined lesions showed deficits in both radial and water maze tasks, although terminal cholinergic deafferentation was substantial and extensive tissue loss was seen at the injection sites in both single and combined lesions. However, the extensive tissue loss with long-term lesions suggested that behavioural deficits were not solely attributable to cholinergic deafferentation. In contrast, when rats with combined lesions were tested 5 months after lesioning, no deficits were apparent, although there was almost complete loss of choline acetyltransferase- and nerve growth factor receptor-immunoreactivity in the basal forebrain with no tissue damage at the injection sites. This study supports existing literature that selective loss of cholinergic neurons in the basal forebrain does not produce behavioural impairments in standard tasks of learning and memory, but deficits are apparent when damage is non-selective as occurs late after lesioning, confounding interpretation of behavioural data. It further highlights potential problems with this immunotoxin in long-term studies. (C) 2001 Elsevier Science Inc. C1 Kings Coll London, Dept Psychol, Inst Psychiat, London WC2R 2LS, England. RP NIA, Neurosci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM perryt@grc.nia.nih.gov NR 78 TC 44 Z9 47 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 EI 1873-2747 J9 BRAIN RES BULL JI Brain Res. Bull. PD JAN 1 PY 2001 VL 54 IS 1 BP 29 EP 48 DI 10.1016/S0361-9230(00)00413-5 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 408LZ UT WOS:000167328800005 PM 11226712 ER PT J AU Gardner, K Liu, ET AF Gardner, K Liu, ET TI BRCA1 function in T lymphocytes: a cellular specificity of a different kind SO BREAST CANCER RESEARCH LA English DT Review DE BRCA1; breast cancer; DNA repair; lymphocytes; tumor suppressor ID MUTATION; CELLS AB Recent work by Mak et al demonstrates that mice carrying a T-cell-specific disruption of the brca1 gene display markedly impaired T-lymphocyte development and proliferation in the absence of any increased tendency for the formation of tumors. Interestingly, the extent of these defects was found to be highly dependent on cellular context. Contrasting the rather broad tissue expression pattern of brca1 against its exquisitely selective etiologic role in cancers of the breast and ovary, many of us are left to ponder - where is the specificity? C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Div Clin Sci, NIH, Ctr Adv Technol, Gaithersburg, MD USA. RP Liu, ET (reprint author), NCI, Div Clin Sci, NIH, Bldg 31,Rm 3A11,31 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2001 VL 3 IS 1 BP 11 EP 13 DI 10.1186/bcr263 PG 3 WC Oncology SC Oncology GA 408TT UT WOS:000167344300004 PM 11250741 ER PT J AU Zujewski, J Vaughn-Cooke, A Flanders, KC Eckhaus, MA Lubet, RA Wakefield, LM AF Zujewski, J Vaughn-Cooke, A Flanders, KC Eckhaus, MA Lubet, RA Wakefield, LM TI Transforming growth factors-beta are not good biomarkers of chemopreventive efficacy in a preclinical breast cancer model system SO BREAST CANCER RESEARCH LA English DT Review DE antiestrogens; breast cancer; chemoprevention; retinoid; transforming growth factor-beta s ID TGF-BETA; 9-CIS-RETINOIC ACID; MAMMARY-CARCINOMA; RANDOMIZED TRIAL; RETINOIC ACID; IN-VIVO; TAMOXIFEN; CELLS; RAT; PROGRESSION AB Using a carcinogen-initiated rat model of mammary tumorigenesis, we tested the hypothesis that transforming growth factor (TGF)-betas are useful biomarkers of chemopreventive efficacy in the breast. The chemopreventive agents tested were tamoxifen and the retinoids 9-cis-retinoic acid (9cRA) and N-(4-hydroxyphenyl) retinamide (4-HPR), because both antiestrogens and retinoids have previously been shown to upregulate TGF-betas in vitro. Despite demonstrable chemopreventive efficacy in this model, none of these agents, alone or in combination, had any significant impact on the expression of TGF-betas in the mammary ductal epithelium or periductal stroma as determined by immunohistochemistry. These data suggest that TGF-betas are not likely to be useful biomarkers of chemopreventive efficacy in a clinical setting. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Off Director, Bethesda, MD 20892 USA. NCI, Div Canc Res, NIH, Bethesda, MD 20892 USA. RP Wakefield, LM (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, NCI Bldg 41,Rm C629,41 Lib Dr MSC 5055, Bethesda, MD 20892 USA. NR 50 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2001 VL 3 IS 1 BP 66 EP 75 DI 10.1186/bcr273 PG 10 WC Oncology SC Oncology GA 408TT UT WOS:000167344300013 PM 11250748 ER PT J AU Yang, QF Yoshimura, G Sakurai, T Nakamura, M Nakamura, Y Shan, L Suzuma, T Tamaki, T Umemura, T Mori, I Kakudo, K AF Yang, QF Yoshimura, G Sakurai, T Nakamura, M Nakamura, Y Shan, L Suzuma, T Tamaki, T Umemura, T Mori, I Kakudo, K TI Allelic loss of chromosome 3p24 correlates with tumor progression rather than with retinoic acid receptor beta 2 expression in breast carcinoma SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; chromosome 3p24; loss of heterozygosity; retinoic acid receptor beta 2 ID MAMMARY EPITHELIAL-CELLS; LUNG-CANCER CELLS; UP-REGULATION; IN-VITRO; ESOPHAGEAL CANCER; GROWTH ARREST; GENE; HETEROZYGOSITY; LOCALIZATION; LINES AB A tumor suppressor gene, retinoic acid receptor (RAR) beta2, has been mapped to chromosome 3p24, a region where loss of heterozygosity (LOH) has been observed commonly in carcinomas of various tumor tissues. RAR beta2 expression is reduced or lost in many malignant tumors including breast cancer, however, whether LOH accounts for the loss of expression of RAR beta2 in breast cancer is unknown. We, therefore, assessed LOH on chromosome band 3p24 to correlate it with RAR beta2 expression and other established prognostic parameters in 52 breast carcinomas. Based on three microsatellites, D3S 1283, D3S 1293 and D3S 1286, all of the tumors were informative, of these, 12 (23%) exhibited LOH. RAR beta2 expression was lost in 42% (19/45) of these samples. We found that LOH on chromosome band 3p24 was not correlated with loss of RAR beta2, but correlated with higher histological grade, p53-positivity, and loss of estrogen and progesterone receptors. Our findings suggest that LOH of the RAR beta2 gene does not account for the frequent loss of RAR beta2 expression in breast cancer but the genomic structural alteration at or close to the RAR beta2 gene locus are likely to be associated with tumor progression and/or loss of hormonal dependency. C1 Wakayama Med Univ, Sch Med, Dept Pathol 2, Wakayama 6410012, Japan. Wakayama Med Univ, Sch Med, Affiliated Kihoku Hosp, Dept Surg, Wakayama 6410012, Japan. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Shandong Univ, Qilu Hosp, Dept Surg, Jinan 250100, Peoples R China. RP Yang, QF (reprint author), Wakayama Med Univ, Sch Med, Dept Pathol 2, 811-1 Kimiidera, Wakayama 6410012, Japan. RI Nakamura, Yasushi/J-5143-2014 NR 43 TC 10 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 70 IS 1 BP 39 EP 45 DI 10.1023/A:1012574305832 PG 7 WC Oncology SC Oncology GA 488NG UT WOS:000171942100005 PM 11767003 ER PT J AU Azorsa, DO Cunliffe, HE Meltzer, PS AF Azorsa, DO Cunliffe, HE Meltzer, PS TI Association of steroid receptor coactivator AIB1 with estrogen receptor-alpha in breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE AIB1; breast cancer; estrogen receptor; transcriptional coactivators ID TRANSCRIPTIONAL COACTIVATOR; HISTONE ACETYLTRANSFERASE; NUCLEAR RECEPTORS; MONOCLONAL-ANTIBODIES; OVARIAN-CANCER; IN-VIVO; ACTIVATION; SRC-1; AMPLIFICATION; GROWTH AB The steroid receptor coactivator AIB1 (amplified in breast cancer-1) is a transcriptional coactivator which has been found to be amplified in breast cancer. We have now investigated the role of the AIB1 protein in breast cancer cell lines. Although detectable levels of AIB1 were present in most cell lines, high levels of AIB1 expression were observed only in the ER-positive cell lines MCF-7 and BT-474 by western blot analysis. Newly developed monoclonal antibodies (mAbs) were used in several assays to show an association between AIB1 and estrogen receptor-alpha (ER). AIB1 and ER co-localized to the nucleus of ER positive cell lines as shown by immunofluorescence microscopy, and a functional association of native AIB1 and ER in MCF-7 nuclear extracts was shown by EMSA. Recombinant ER also recruited AIB1 protein from nuclear extracts, shown by EMSA and by precipitation of ER-complex proteins bound to a biotinylated-ERE DNA target. Additionally, anti-AIB1 mAbs were able to immunoprecipitate ER from nuclear extracts of chemically cross-linked cells but not from uncross-linked cells. Both immunoprecipitation and oligonucleotide precipitation studies demonstrated the presence of p300 and CBP as part of the ER transcriptional complex. These results suggest that AIB1 and ER do associate physically in ER-positive breast cancer cell lines. We propose that in AIB1 amplified breast cancers, a heightened AIB1/ER association may play a crucial role in the progression of these tumors. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 49 Room 4A10,49 Convent Dr, Bethesda, MD 20892 USA. NR 49 TC 21 Z9 21 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 70 IS 2 BP 89 EP 101 DI 10.1023/A:1012972808558 PG 13 WC Oncology SC Oncology GA 495ML UT WOS:000172344900002 PM 11768608 ER PT J AU Knott, KK McGinley, JN Lubet, RA Steele, VE Thompson, HJ AF Knott, KK McGinley, JN Lubet, RA Steele, VE Thompson, HJ TI Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE 1-methyl-1-nitrosourea; estrogen receptor; hormone dependence; image analysis; immunohistochemistry; ovariectomy; progesterone receptor; rapid emergence model; vorozole ID BREAST-CANCER; CARCINOGENESIS; TAMOXIFEN; INDUCTION; R-83842; LESIONS; MODEL AB Vorozole, a nonsteroidal aromatase inhibitor, impedes the post-initiation stage of chemically induced mammary carcinogenesis. While various aspects of vorozole's effects on mammary carcinoma development have been investigated, little attention has been directed to determining the estrogen receptor (ER) and progesterone receptor (PR) content of mammary carcinomas that arise despite vorozole treatment. Female Sprague-Dawley rats were given an i.p. injection of 50 mg MNU/kg body weight at 21 days of age and placed on diet supplemented with 0 or 3 mg vorozole/kg, which had no effect on mammary tumor development. Histologically confirmed carcinomas were evaluated for ER and PR by immunohistochemistry. In the control group, 78.8% of carcinomas were ER positive with an ER content ranging from 13.8 to 40.0%, similar to ER content of mammary ductal epithelial cells from non-carcinogen treated animals. PR content ranged from 4.4 to 45.2% and also was similar to levels of PR observed in ductal epithelial cells. ER was not correlated with PR in mammary carcinomas (r = 0.05, p > 0.80), whereas there was a significant correlation in ductal epithelium (r = 0.86, p = 0.006). In vorozole-treated rats, no ER negative carcinomas were observed and overall ER expression by vorozole was elevated (p < 0.03). All carcinomas from vorozole-treated rats expressed PR (2.5-60.2%) and correlation between ER and PR content was numerically greater in carcinomas from vorozole-treated animals (r = 0.42, p = 0.09). These data, which are considered hypothesis generating, provide evidence that low doses of vorozole in the diet select for mammary carcinomas with an increased ER positive phenotype. C1 AMC Canc Res Ctr, Ctr Nutr Prevent Dis, Denver, CO 80214 USA. NCI, Chemoprevent Branch, NIH, Washington, DC USA. RP Knott, KK (reprint author), AMC Canc Res Ctr, Ctr Nutr Prevent Dis, 1600 Pierce St, Denver, CO 80214 USA. RI Thompson, Henry/K-7242-2012 OI Thompson, Henry/0000-0002-3730-9322 FU NCPDCID CDC HHS [NCI-CN-75011-72] NR 31 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 70 IS 3 BP 171 EP 183 DI 10.1023/A:1013051107535 PG 13 WC Oncology SC Oncology GA 497GZ UT WOS:000172448200002 PM 11804181 ER PT J AU Benz, CC Hilakivi-Clarke, L Conzen, S Dorn, RV Fleming, GF Grant, K Greene, G Hellman, S Henderson, C Hoover, R Hryniuk, W Jeffrey, S Lippman, M Lung, J Mitchell, M Pike, M AF Benz, CC Hilakivi-Clarke, L Conzen, S Dorn, RV Fleming, GF Grant, K Greene, G Hellman, S Henderson, C Hoover, R Hryniuk, W Jeffrey, S Lippman, M Lung, J Mitchell, M Pike, M TI Expedition inspiration consensus 2001 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article C1 Buck Inst Agr Res, Novato, CA 94945 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Mt States Tumor Inst, Boise, ID USA. Calif Pacific Med Ctr, San Francisco, CA USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, Rockville, MD USA. Karmanos Canc Inst, Detroit, MI USA. Stanford Univ, Stanford, CA 94305 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ So Calif, Los Angeles, CA USA. RP Benz, CC (reprint author), Buck Inst Agr Res, 8001 Redwood Blvd, Novato, CA 94945 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 70 IS 3 BP 213 EP 219 DI 10.1023/A:1013033107304 PG 7 WC Oncology SC Oncology GA 497GZ UT WOS:000172448200006 PM 11804185 ER PT J AU Kerner, JF Mandelblatt, JS Silliman, RA Lynch, JJ Senie, R Cohen, C Hwang, YT AF Kerner, JF Mandelblatt, JS Silliman, RA Lynch, JJ Senie, R Cohen, C Hwang, YT CA OPTIONS Res Team TI Screening mammography and breast cancer treatment patterns in older women SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; elderly; mammography; treatment options ID LATE-STAGE DIAGNOSIS; CERVICAL-CANCER; SOCIAL-CLASS; CARCINOMA; AGE; IMPACT; CARE; PATIENT; HEALTH AB Objective. To examine the impact of mammography screening on treatment options received by a cohort of older breast cancer patients. Setting and population. We studied 718 newly diagnosed breast cancer patients, 67 years and over, diagnosed with TNM Stage I and II disease between 1995 and 1997 at 29 hospitals in five regions. Methods. Data were collected from patients, surgeons, and medical records. A breast cancer diagnosis was considered to have been by screening mammography if so reported by both patient and medical records. Bivariate and logistic regression were used to identify predictors of a women having her cancer detected by screening mammography and the relationships between mode of detection, stage of disease at diagnosis, and local treatment. Results. Women with high school or greater education were 1.75 times (95%, CI 1.11-2.75) more likely to have their cancers diagnosed by screening mammography than women who had not completed high school, controlling for other factors. Screening found earlier stage disease: 96% of women with mammographically diagnosed cancer had T1 lesions, compared to 81% of women diagnosed by other means (p = 0.001). Women with mammography detected lesions were more likely to have ductal cancer, and to be referred to radiation oncologists more than women diagnosed by other means. Controlling for stage and histology, screening remained associated with a higher likelihood of receiving breast conserving surgery (BCS) with radiation (RT) (OR 1.56, 95%, CI 1.10-2.22) than other local therapies. Conclusions. Beyond the impact on stage, ductal cancers were more likely to be diagnosed by screening. Mammographically detected lesions were associated with referrals to radiation oncologists and higher rates of BCS and RT. Research is needed to explain the residual independent effects of mammography screening on breast cancer treatment. C1 NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD USA. Georgetown Univ, Dept Oncol, Washington, DC USA. Georgetown Univ, Inst Hlth Care Res & Policy, Washington, DC USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY USA. RP Mandelblatt, JS (reprint author), Vincent T Lombardi Canc Res Ctr, 2233 Wisconsin Ave NW,Suite 40, Washington, DC 20007 USA. FU NCI NIH HHS [R01 CA72908]; PHS HHS [508395] NR 26 TC 9 Z9 9 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 1 BP 81 EP 91 DI 10.1023/A:1012457703106 PG 11 WC Oncology SC Oncology GA 486DA UT WOS:000171802100009 PM 11759831 ER PT J AU Smith, RE Bryant, J DeCillis, A Anderson, S AF Smith, RE Bryant, J DeCillis, A Anderson, S TI Acute myeloid leukemia and myelodysplastic syndrome following doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the NSABP experience. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 NSABP, Pittsburgh, PA USA. Bristol Myers Squibb Co, New York, NY 10154 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 2 BP 209 EP 209 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800003 ER PT J CA NSABP TI The effect on primary tumor response of adding sequential Taxotere to Adriamycin and cyclophosphamide: preliminary results from NSABP Protocol B-27. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 NSABP, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 5 BP 210 EP 210 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800006 ER PT J AU Lubet, RA You, M Ruchon, Y End, D Wouters, W Christov, K Grubbs, CG AF Lubet, RA You, M Ruchon, Y End, D Wouters, W Christov, K Grubbs, CG TI Therapeutic and chemopreventive effects of R115777, a farnesyl transferase inhibitor (FTI), on methylnitrosourea (MNU)-induced rat mammary cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Ohio State Univ, DCP, NCI, Columbus, OH 43210 USA. Univ Illinois, Janssen Res Fdn, Chicago, IL USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 30 BP 216 EP 216 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800030 ER PT J AU Fabian, CJ Anderson, J Chamberlain, C Kimler, BF Mayo, MS O'Shaughnessy, JA Lynch, HT Johnson, KA AF Fabian, CJ Anderson, J Chamberlain, C Kimler, BF Mayo, MS O'Shaughnessy, JA Lynch, HT Johnson, KA TI Change in serum dehydroepiandrosterone, testosterone, insulin-like growth factor-1, and osteocalcin levels with the third generation selective estrogen receptor modulator arzoxifene (LY353381 center dot HCI). SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. US Oncol Inc, Dallas, TX USA. Creighton Univ, Omaha, NE 68178 USA. NCI, Bethesda, MD 20892 USA. RI Mayo, Matthew/E-3774-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 134 BP 225 EP 225 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800065 ER PT J AU Vogel, VG Costantino, JP Wickerham, DL Cronin, WM Wolmark, N AF Vogel, VG Costantino, JP Wickerham, DL Cronin, WM Wolmark, N TI The study of Tamoxifen and Raloxifene: preliminary enrollment data from a randomized breast cancer risk reduction trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 135 BP 225 EP 225 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800066 ER PT J AU Habel, LA Dignam, JJ Land, S Salane, M Bhat, A AF Habel, LA Dignam, JJ Land, S Salane, M Bhat, A TI Mammographic density and breast cancer after ductal carcinoma in situ. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Univ Chicago, Ctr Canc Res, Chicago, IL 60637 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Pittsburgh, NSABP, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 255 BP 250 EP 250 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800166 ER PT J AU Fehm, T Clifford, E Beitsch, P Saboorian, H Uhr, J Morrison, L Rao, C Heselmeyer-Haddad, K Ried, T AF Fehm, T Clifford, E Beitsch, P Saboorian, H Uhr, J Morrison, L Rao, C Heselmeyer-Haddad, K Ried, T TI Aneuploidy of epithelial cells in blood of breast cancer patients. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Immunicon, Huntingdon Valley, PA USA. Vysis, Downers Grove, IL USA. Univ Texas, SW Med Sch, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 308 BP 258 EP 258 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800199 ER PT J AU Dignam, JJ Johnson, KA Xu, L Rockette, HE AF Dignam, JJ Johnson, KA Xu, L Rockette, HE TI Relationship of body mass index to outcomes after lymph node-negative, estrogen receptor positive breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Chicago, Ctr Canc Res, Chicago, IL 60637 USA. NSABP, Pittsburgh, PA USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 310 BP 259 EP 259 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800201 ER PT J AU Anderson, WF Chatterjee, N Hill, D AF Anderson, WF Chatterjee, N Hill, D TI The impact of estrogen receptor status in the Surveillance, Epidemiology, and End Results database. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 414 BP 280 EP 280 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800284 ER PT J AU Overmoyer, B Robertson, K Persons, M Shenk, R Lewin, J Jesberger, J Ziats, N Tserng, K Hoppel, C Hartman, P Wasman, J Abdul-Karim, F Newton, E Cooper, B Connell, C Pluda, J McCrae, K Remick, S AF Overmoyer, B Robertson, K Persons, M Shenk, R Lewin, J Jesberger, J Ziats, N Tserng, K Hoppel, C Hartman, P Wasman, J Abdul-Karim, F Newton, E Cooper, B Connell, C Pluda, J McCrae, K Remick, S TI A phase I pharmacokinetic and pharmacodynamic study of SU5416 and Adriamycin in inflammatory breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 69 IS 3 MA 432 BP 284 EP 284 PG 1 WC Oncology SC Oncology GA 495MK UT WOS:000172344800301 ER PT J AU Bianco, C Wechselberger, C Ebert, A Khan, NI Sun, YP Salomon, DS AF Bianco, C Wechselberger, C Ebert, A Khan, NI Sun, YP Salomon, DS TI Identification of Cripto-1 in human milk SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Cripto-1; human milk; mammary epithelial cells ID EPIDERMAL GROWTH-FACTOR; MAMMARY EPITHELIAL-CELLS; HUMAN BREAST-MILK; ONE-EYED PINHEAD; TYROSINE PHOSPHORYLATION; PROTEIN; AMPHIREGULIN; EXPRESSION; RECEPTOR; GENE AB Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related peptide that plays an important role in normal mammary gland development. CR-1 is expressed in the growing terminal end buds in the virgin mouse mammary gland and its expression increases during pregnancy and lactation. Furthermore, CR-1 is involved in the early stages of mouse mammary tumorigenesis and in the pathogenesis of human breast cancer. Since CR-1 is expressed in the mouse mammary gland at high levels during pregnancy and lactation, we have evaluated whether this protein is present in human milk. In the present study we demonstrate that a 28 kDa immunoreactive CR-1 protein is present in 24 human milk samples as assessed by western blot analysis and that by enzyme-linked immunosorbent assay the concentration of CR-1 ranges between 62 and 118 ng/ml. In addition, CR-1 that had been purified from human milk is able to stimulate the phosphorylation of mitogen activated protein kinase in nontransformed NMuMG mouse mammary epithelial cells. These results suggest that CR-1 in human milk may be important in regulating mammary gland development during pregnancy and lactation. C1 NCI, Tumor Growth Factor Sect, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. Free Univ Berlin, Dept Obstet & Gynecol, D-1000 Berlin, Germany. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Lab Tumor Immunol & Biol, NIH, Bldg 10 Room 5B39,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 20 Z9 20 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2001 VL 66 IS 1 BP 1 EP 7 DI 10.1023/A:1010648923432 PG 7 WC Oncology SC Oncology GA 421GM UT WOS:000168056700001 PM 11368405 ER PT J AU Tejera, AM Alonso, DF Gomez, DE Olivero, OA AF Tejera, AM Alonso, DF Gomez, DE Olivero, OA TI Chronic in vitro exposure to 3 '-azido-2 ', 3 '-dideoxythymidine induces senescence and apoptosis and reduces tumorigenicity of metastatic mouse mammary tumor cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE apoptosis; AZT; breast cancer; senescence; telomerase ID REVERSE-TRANSCRIPTASE INHIBITORS; COLORECTAL-CANCER PATIENTS; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE AZT; TELOMERASE ACTIVITY; MICE; 3'-AZIDO-3'-DEOXYTHYMIDINE; LEUCOVORIN AB Normal cells in culture divide a certain amount of times and undergo a process termed replicative senescence. Telomere loss is thought to control entry into senescence. Activation of telomerase in tumors bypasses cellular senescence and is thus a requirement for tumor progression. We reported previously the preferential incorporation of 3 ' -azido-2 ', 3 ' -dideoxythymidine (AZT) in telomeric sequences of immortalized cells in culture. In this work, we have investigated the effects of chronic in vitro AZT exposure on F3II mouse mammary carcinoma cells. We demonstrate, for the first time, that AZT-treated tumor cells have a reduced tumorigenicity in syngeneic BALB/c mice. Tumor incidence was reduced and survival was prolonged in animals inoculated with AZT-treated cells when comparing with control counterparts. The number and size of spontaneous metastases were also decreased in animals inoculated with AZT-treated cells. In addition, we present evidence of morphological and biochemical signs of senescence, as shown by the staining for senescence associated beta -galactosidase activity, and induction of programmed cell death, as demonstrated by an increase of caspase-3 activity, in tumor cells exposed to AZT. These data indicate that chronic exposure of mammary carcinoma cells to AZT may be sufficient to induce a senescent phenotype and to reduce tumorigenicity. C1 Univ Nacl Quilmes, Dept Ciencia & Tecnol, Oncol Mol Lab, Buenos Aires, DF, Argentina. Natl Canc Inst, Lab Cellular Carcinogenesis & Tumor Promot, Bethesda, MD USA. RP Gomez, DE (reprint author), Univ Nacl Quilmes, Dept Ciencia & Tecnol, Oncol Mol Lab, R Saenz Pena 180,Bernal B1876BXD, Buenos Aires, DF, Argentina. OI Gomez, Daniel E/0000-0002-8629-0787 NR 22 TC 27 Z9 31 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2001 VL 65 IS 2 BP 93 EP 99 DI 10.1023/A:1006477730934 PG 7 WC Oncology SC Oncology GA 414WN UT WOS:000167689300001 PM 11261835 ER PT J AU Rivera, CE Villagra, J Riordan, M Williams, S Lindstrom, KJ Rick, ME AF Rivera, CE Villagra, J Riordan, M Williams, S Lindstrom, KJ Rick, ME TI Identification of a new mutation in platelet glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Bernard-Soulier syndrome; GPIX; mutation; bleeding; thombocytopenia AB We describe a new mutation in glycoprotein IX (GPIX) in a patient with Bernard-Soulier syndrome (BSS). Sequencing of GPIX revealed a homozygous (T -->C) transition at nucleotide 1717 (GenBank/HUMGPIX/M80478), resulting in a Cys(8) (TGT)--> Arg (CGT) replacement in the mature peptide. DNA restriction enzyme analysis using BsaAI revealed that the patient was homozygous and that his parents were heterozygous for the defect. This mutation disrupts a putative disulphide bond between the Cys(8) and Cys(12) that would alter the secondary structure of GPIX and which probably accounts for the absence of the GPIb/IX/V complex from the platelet surface in this patient. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bethesda, MD 20892 USA. RP Rivera, CE (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Hematol Serv, Bldg 10,Rm 2C390,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 21 Z9 23 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2001 VL 112 IS 1 BP 105 EP 108 DI 10.1046/j.1365-2141.2001.02529.x PG 4 WC Hematology SC Hematology GA 402EW UT WOS:000166973900018 PM 11167791 ER PT J AU Melenhorst, JJ Sorbara, L Kirby, M Hensel, NF Barrett, AJ AF Melenhorst, JJ Sorbara, L Kirby, M Hensel, NF Barrett, AJ TI Large granular lymphocyte leukaemia is characterized by a clonal T-cell receptor rearrangement in both memory and effector CD8(+) lymphocyte populations SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE LGL leukaemia; memory; immunophenotyping; TCR rearrangement; CD57 ID RHEUMATOID-ARTHRITIS; EXPRESSION; LEUKEMIA; EXPANSIONS; GENES AB Large granular lymphocyte (LGL) leukaemia is a disease with increased numbers of circulating granular lymphocytes and an increased percentage of clonally rearranged CD8(+)CD57(+) cells. To determine whether LGL cells are also found in other lymphocyte subsets, CD8(+) cells from 10 LGL patients were sorted into CD57(+) and CD57(-) fractions and analysed for clonality using a T-cell receptor gamma (TCR gamma) polymerase chain reaction (PCR). In nine patients, a clonal TCR rearrangement was identified in the CD8(+)CD57(+) cells, and in one patient, the TCR rearrangement was oligoclonal in the CD8(+)CD57(+) fraction. In eight out of nine of the clonally rearranged patients, the same band was also present in the CD8(+)CD57(-) fraction. To define the relationship between CD57(-) and CD57(+) LGL populations, CD8(+)CD57(-) and CD8(+)CD57(+) cells were sorted from five patients and cultured in the presence of anti-CD3 plus CD28 antibodies. The CD57(+) cells died of apoptosis before d 7, while the CD57(-) cells proliferated and differentiated into CD57(+) cells. Clonal analysis identified the same band in both cultured subpopulations and in the uncultured CD8(+) cells. Immunophenotypical analysis showed that CD8(+)CD57(-) cells expressed memory cell markers, while the CD8(+)CD57(+) cells exhibited effector characteristics. These results suggest that LGL disease originates in a CD57(-) memory T-cell compartment that continually generates CD57(+) (effector cell) progeny. C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Melenhorst, JJ (reprint author), NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 15 TC 28 Z9 28 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2001 VL 112 IS 1 BP 189 EP 194 DI 10.1046/j.1365-2141.2001.02509.x PG 6 WC Hematology SC Hematology GA 402EW UT WOS:000166973900029 PM 11167801 ER PT J AU Saunthararajah, Y Molldrem, JJ Rivera, M Williams, A Stetler-Stevenson, M Sorbara, L Young, NS Barrett, JA AF Saunthararajah, Y Molldrem, JJ Rivera, M Williams, A Stetler-Stevenson, M Sorbara, L Young, NS Barrett, JA TI Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: clinical and pathophysiological features SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE T-cell large granular lymphocytic disease; myelodysplastic syndrome; immunosuppression; cyclosporin; anti-thymocyte globulin ID BONE-MARROW; ANTITHYMOCYTE GLOBULIN; CYCLOSPORINE THERAPY; MEDIATED INHIBITION; CLONALITY; LEUKEMIA; NEUTROPENIA; RESPONSES; ANEMIA AB Myelodysplastic syndrome (MDS) and T-cell large granular lymphocytic disease (T-LGL) are bone marrow failure disorders. Successful use of immunosuppressive agents to treat cytopenia in MDS and LGL suggests a common pathophysiology for the two conditions. Of 100 patients with initial diagnoses of either MDS or T-LGL referred to the National Institutes of Health for immunosuppressive treatment of cytopenia, nine had characteristics of both T-LGL and MDS (T-LGL/MDS). Fifteen patients with T-LGL received cyclosporin (CSA) (10 responses). Eight out of nine patients with T-LGL/MDS received CSA (two responses) and one patient received ATG (one response). Of 76 patients with MDS, eight received CSA (one response) and 68 received ATG (21 responses). The response to immunosuppression was significantly lower in patients with T-LGL/MDS and MDS than in patients with T-LGL disease alone (28% vs. 66%, P = 0.01). The proportion of T-helper cells and T-suppressor cells with an activated phenotype (HLA-DR+) was increased in patients with T-LGL, T-LGL/MDS and MDS, but the increase in activated T-suppressor cells in patients with T-LGL/MDS was not statistically significant. Autoreactive T cells may suppress haematopoiesis and contribute to the cytopenia in T-LGL and some patients with MDS, leading to T-LGL/MDS. The lower response rate of MDS or T-LGL/MDS to immunosuppression, compared with T-LGL alone, may reflect the older age and intrinsic stem cell abnormalities in MDS and T-LGL/MDS patients. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Anat Pathol, NIH, Bethesda, MD 20892 USA. RP Saunthararajah, Y (reprint author), Dept Med, Sect Hematol Oncol MC734, Room 3150 MBRB,900 S Ashland Ave, Chicago, IL 60607 USA. NR 32 TC 59 Z9 61 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2001 VL 112 IS 1 BP 195 EP 200 DI 10.1046/j.1365-2141.2001.02561.x PG 6 WC Hematology SC Hematology GA 402EW UT WOS:000166973900030 PM 11167802 ER PT J AU Lindsay, R Bennett, PH AF Lindsay, R Bennett, PH TI Type 2 diabetes, the thrifty phenotype - an overview SO BRITISH MEDICAL BULLETIN LA English DT Review ID LOW-BIRTH-WEIGHT; INSULIN-RECEPTOR SUBSTRATE-1; PIMA INDIAN WOMEN; GLUCOSE-TOLERANCE; OBESITY; MELLITUS; ASSOCIATION; HYPOTHESIS; YOUNG; RESISTANCE C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. RP Bennett, PH (reprint author), NIDDKD, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. NR 45 TC 22 Z9 23 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-1420 J9 BRIT MED BULL JI Br. Med. Bull. PY 2001 VL 60 BP 21 EP 32 DI 10.1093/bmb/60.1.21 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 518DM UT WOS:000173651400003 PM 11809616 ER PT J AU Lenfant, C AF Lenfant, C TI Can we prevent cardiovascular diseases in low- and middle-income countries? SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article DE cardiovascular diseases/prevention and control/drug therapy; myocardial ischemia/mortality; risk factors; primary prevention; developing countries ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; CHOLESTEROL LEVELS; CONTROLLED TRIALS; MEN; MORTALITY; METAANALYSIS; DIETARY; TRENDS; WOMEN AB Ischaemic heart disease, the largest cause of death worldwide, is rapidly becoming a major threat in low- and middle-income countries. Experience in a variety of populations has demonstrated that lowering certain risk factors, such as hypertension and hypercholesterolaemia, reduces illness and deaths from cardiovascular diseases. A dual approach is recommended: screening and intervening in cases of relatively high risk, while fostering population-wide preventive activities. This is both feasible and affordable. Now is the time to make such efforts. C1 NHLBI, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 23 Z9 27 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2001 VL 79 IS 10 BP 980 EP 982 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 485DT UT WOS:000171738800011 PM 11693981 ER PT J AU Quinn, TC AF Quinn, TC TI AIDS in Africa: a retrospective SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; ZAIRE; INFECTION; VIRUS; UGANDA C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, Ross Res Bldg 1159,720 Rutland Ave, Baltimore, MD 21205 USA. NR 23 TC 4 Z9 4 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2001 VL 79 IS 12 BP 1156 EP 1158 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 509ZU UT WOS:000173184900015 PM 11799449 ER PT J AU Quinn, TC Mann, JM Curran, JW Piot, P AF Quinn, TC Mann, JM Curran, JW Piot, P TI AIDS in Africa: An epidemiologic paradigm SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Review ID ACQUIRED IMMUNODEFICIENCY SYNDROME; VIRUS TYPE-III; T-LYMPHOTROPIC RETROVIRUS; IMMUNE-DEFICIENCY SYNDROME; LYMPHADENOPATHY-ASSOCIATED VIRUS; ENDEMIC KAPOSIS SARCOMA; HEALTH-CARE WORKERS; HTLV-III; NATURAL-HISTORY; OPPORTUNISTIC INFECTIONS AB Cases of the acquired immune deficiency syndrome (AIDS) have been reported in countries throughout the world. Initial surveillance studies in Central Africa suggest an annual incidence of AIDS of 550 to 1000 cases per million adults. The male to female ratio of cases is 1:1, with age- and sex-specific rates greater in females less than 30 years of age and greater in males over age 40. Clinically, AIDS in Africans is often characterized by a diarrhea-wasting syndrome, opportunistic infections, such as tuberculosis, cryptococcosis, and cryptosporidiosis, or disseminated Kaposi's sarcoma. From 1 to 18% of healthy blood donors and pregnant women and as many as 27 to 88% of female prostitutes have antibodies to human immunodeficiency virus (HIV). The present annual incidence of infection is approximately 0.75% among the general population of Central and East Africa. The disease is transmitted predominately by heterosexual activity, parenteral exposure to blood transfusions and unsterilized needles, and perinatally from infected mothers to their newborns, and will continue to spread rapidly where economic and cultural factors favor these modes of transmission. Prevention and control of HIV infection through educational programs and blood bank screening should be an immediate public health priority for all African countries. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. WHO, Control Program AIDS, CH-1211 Geneva, Switzerland. Ctr Dis Control, Ctr Infect Dis, AIDS Program, Atlanta, GA 30333 USA. Inst Trop Med, Dept Microbiol, B-2000 Antwerp, Belgium. RP Quinn, TC (reprint author), Johns Hopkins Univ Hosp, Blalock 111,600 N Wolfe St, Baltimore, MD 21205 USA. NR 163 TC 5 Z9 5 U1 0 U2 1 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2001 VL 79 IS 12 BP 1159 EP 1167 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 509ZU UT WOS:000173184900016 PM 11799437 ER PT J AU Collins, FS Mansoura, MK AF Collins, FS Mansoura, MK TI The human genome project: Revealing the shared inheritance of all humankind SO CANCER LA English DT Article; Proceedings Paper CT 7th Bieannial Symposium on Minorities - The Medically Underseved and Cancer CY FEB 09-13, 2000 CL WASHINGTON, D.C. DE hereditary component; human genome; medical ethics; social issues ID AFRICAN-AMERICANS; GENETIC-VARIATION; HEALTH-CARE; INFORMATION; CHROMOSOME; TUSKEGEE; LOCUS AB The information derived form the Human Genome Project, and international effort to decode the information embedded in the human genome, will revolutionize the practice of medicine in the 21st century by providing the tools to determine the hereditary component of virtually all diseases. This will lead to improved approaches to predict increased risk, provide early detection, and promote more effective treatment strategies. To be ultimately successful, the improvements in research and health care mst reach everyone. This success will depend on participation from a broad spectrum of the population, such as scientists, clinicians, research participants, and active discussant, in deliberations of ethics and public policy. The Human Genome project has helped to inform us about how remarkably similar all human beings are - 99.9 percent at the DNA level. Those who wish to draw precise racial boundaries around certain groups will not be able to use science as a legitimate justification. However, studying the 0.1 percent of human genetic variations, particularly the distribution of single nucleotide polymorphisms, between affected and nonaffected individuals will significantly inform biomedical researchers about the genetic contributions to complex diseases such as cancer, diabetes, and mental illness. We must all work together to ensure that the risks of such research are considered carefully and that the medical benefits are made available to all. Cancer 2001;91;221-225. (C) 2001 American Cancer Society. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. NR 20 TC 40 Z9 44 U1 2 U2 10 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2001 VL 91 IS 1 SU S BP 221 EP 225 DI 10.1002/1097-0142(20010101)91:1+<221::AID-CNCR8>3.0.CO;2-9 PG 5 WC Oncology SC Oncology GA 432DE UT WOS:000168675400006 PM 11148583 ER PT J AU Shavers, VL Lynch, CF Burmeister, LF AF Shavers, VL Lynch, CF Burmeister, LF TI Factors that influence African-Americans' willingness to participate in medical research studies SO CANCER LA English DT Article; Proceedings Paper CT 7th Bieannial Symposium on Minorities - The Medically Underseved and Cancer CY FEB 09-13, 2000 CL WASHINGTON, D.C. ID CANCER CLINICAL-TRIALS; MINORITY; INFECTION; WOMEN; BLACK; AIDS AB BACKGROUND. The underrepresentation of African-Americans among medical research participants is receiving considerable attention because of recent government mandates for the inclusion of all racial/ethnic groups in human subject research. Therefore, there is a need to determine factors that influence minority enrollment in medical research studies. METHODS. Between 1998-1999, 91 African-American residents of the Detroit Primary Metropolitan Statistical Area participated in a mail and telephone survey designed to examine impediments to participation in medical research studies. Chi-square tests and multiple logistic regression analyses were used to examine the association between race, issues related to trust in medical researchers, and the willingness to participate in medical research studies. RESULTS. African-American respondents were somewhat less willing to participate if they attributed high importance to the race of the physician when seeking routine medical care, believed that minorities or the poor bear most of the risks of medical research, and, most especially, their knowledge of the Tuskegee Study resulted in less trust in medical researchers. CONCLUSIONS. These data reiterate the need for medical researchers to build trusting relations with African-Americans and to conduct research in an ethical manner. This includes maximizing benefits, reducing risks, and assuring distributive justice to all medical research study participants. Cancer 2001;91:233-6. (C) 2001 American Cancer Society. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. RP Shavers, VL (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, EPN-4005, Bethesda, MD 20892 USA. FU AHRQ HHS [R03 HS09597-01]; NCI NIH HHS [T 32 CA09314-19, 1 F31 CA 72125-01A1] NR 22 TC 94 Z9 94 U1 2 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2001 VL 91 IS 1 SU S BP 233 EP 236 DI 10.1002/1097-0142(20010101)91:1+<233::AID-CNCR10>3.0.CO;2-8 PG 4 WC Oncology SC Oncology GA 432DE UT WOS:000168675400008 PM 11148585 ER PT J AU Sausville, EA AF Sausville, EA TI The challenge of pathway and environment-mediated drug resistance SO CANCER AND METASTASIS REVIEWS LA English DT Review DE drug resistance; growth factor signal transduction; angiogenesis; metastasis ID IN-VIVO; EXPRESSION; CANCER; CELLS; GLYCOPROTEIN; AGENTS AB New insights into cancer biology have allowed the definition of pathways critical to the success of the cancer cell. These include enhanced activity of positive regulators of cell proliferation, including oncogenes, and loss of tumor suppressor gene function; inactivation of cell death or enhancement of survival functions; activation of telomerase, and enhanced ability of tumor cells to invade and reorganize host stroma. It follows then that these pathways may also mediate drug resistance, in a way that is fundamentally different from classically defined mechanisms for drug resistance which focus on altered handling of the drug or the drug's target by the resistant tumor cell. It is expected that resistance will occur that is predicated on altered pathway predominance in a tumor and altered tumor microenvironment. Cases which exemplify this possibility are presented, including up-regulation of angiogenesis-related regulators in relation to inhibition of EGF-related proliferative and angiogenesis-promoting functions. The implications of this thinking in relation to development of combination regimens targeting distinct pathways are considered. C1 NCI, Dev Therapeut Program, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, 6130 Execut Blvd,Rm 8018, Rockville, MD 20852 USA. NR 28 TC 19 Z9 20 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PY 2001 VL 20 IS 1-2 SI SI BP 117 EP 122 DI 10.1023/A:1013127605407 PG 6 WC Oncology SC Oncology GA 513LM UT WOS:000173380100016 PM 11831639 ER PT J AU McMaster, ML Goldstein, AM Bromley, CM Ishibe, N Parry, DM AF McMaster, ML Goldstein, AM Bromley, CM Ishibe, N Parry, DM TI Chordoma: incidence and survival patterns in the United States, 1973-1995 SO CANCER CAUSES & CONTROL LA English DT Article DE bone neoplasms; chordoma; epidemiology; SEER ID MALIGNANT FIBROUS HISTIOCYTOMA; PROTON RADIATION-THERAPY; LOW-GRADE CHONDROSARCOMA; SKULL BASE; SACRAL CHORDOMA; DEDIFFERENTIATED CHORDOMA; SACROCOCCYGEAL CHORDOMA; DIFFERENTIAL-DIAGNOSIS; CYTOGENETIC ANALYSIS; CHONDROID CHORDOMA AB Background: Chordoma, a rare tumor arising from notochordal remnants, has been described to date only by single-institution case series or small population-based surveys. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, 1973-1995, to calculate age-adjusted incidence and survival rates for 400 cases of microscopically confirmed chordoma and to derive information regarding case distribution and risk of second cancer. Results: The age-adjusted chordoma incidence rate (IR) of 0.08 per 100,000 was age-dependent, more common in males (IR 0.10) than females (IR 0.06) and rare among patients aged < 40 years and blacks. Within the axial skeleton 32% of cases were cranial, 32.8% spinal and 29.2% sacral. Young age (< 26 years; p = 0.0001) and female sex (p = 0.037) were associated with greater likelihood of cranial presentation. There was no overall increased risk for second primary cancers after chordoma. Median survival was 6.29 years; 5- and 10-year relative survival rates were 67.6% and 39.9%, respectively. Comparison with other bone sarcomas revealed racial disparities in incidence for the two developmental tumors, chordoma and Ewing's sarcoma. Conclusions: This study provides new data regarding incidence and survival patterns of chordoma in the US. Additional epidemiologic studies are required to elucidate the genetic and environmental determinants underlying this rare, distinctive neoplasm. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP McMaster, ML (reprint author), Execut Plaza S,Room 7010,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. NR 63 TC 296 Z9 331 U1 0 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2001 VL 12 IS 1 BP 1 EP 11 DI 10.1023/A:1008947301735 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 393EE UT WOS:000166455600001 PM 11227920 ER PT J AU Wolk, A Gridley, G Svensson, M Nyren, O McLaughlin, JK Fraumeni, JF Adami, HO AF Wolk, A Gridley, G Svensson, M Nyren, O McLaughlin, JK Fraumeni, JF Adami, HO TI A prospective study of obesity and cancer risk (Sweden) SO CANCER CAUSES & CONTROL LA English DT Article DE cohort; neoplasms; obesity ID BODY-MASS INDEX; POPULATION-BASED COHORT; RENAL-CELL CANCER; PHYSICAL-ACTIVITY; ENDOMETRIAL CANCER; PROSTATE-CANCER; DIABETES-MELLITUS; PANCREATIC-CANCER; BREAST-CANCER; COLORECTAL-CANCER AB Objective: We evaluated the relation between obesity and the risks for various forms of cancer. Methods: In a population-based cohort of 28,129 hospital patients (8165 men, 19,964 women) with any discharge diagnosis of obesity (9557 only diagnosis, 5266 primary, 13,306 secondary) during 1965-1993, cancer incidence was ascertained through 1993 by record linkage to the nationwide Swedish Cancer Registry. Cancer risk was estimated using the standardized incidence ratio (SIR, with 95% confidence interval), which is the ratio of the observed number of cancers to that expected. Results: Overall, a 33% excess incidence of cancer was seen in obese persons, 25% in men and 37% in women. Significant risk elevations were observed for cancers of the small intestine (SIR = 2.8; 95% CI 1.6-4.5), colon (1.3; 1.1-1.5), gallbladder (1.6; 1.1-2.3), pancreas (1.5; 1.1-1.9), larynx (2.1; 1.1-3.5), renal parenchyma (2.3; 1.8-2.8), bladder (1.2; 1.0-1.6), cervix uteri (1.4; 1.1-1.9), endometrium (2.9; 2.5-3.4), ovary (1.2; 1.1-1.5), brain (1.5; 1.2-1.9), and connective tissue (1.9; 1.1-3.0), and for lymphomas (1.4; 1.0-1.7), with higher risk observed for Hodgkin's disease only in men (3.3; 1.4-6.5) and for non-Hodgkin's lymphoma only in women (1.6; 1.2-2.1). The association of obesity with risk of breast, prostate and pancreas cancers was modified by age. Conclusions: Obesity is associated with more forms of cancer than previously reported. C1 Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Epidemiol Inst Ltd, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Wolk, A (reprint author), Karolinska Inst, Dept Med Epidemiol, Box 281, SE-17177 Stockholm, Sweden. FU NCI NIH HHS [N01-CP-85636] NR 79 TC 375 Z9 383 U1 2 U2 20 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2001 VL 12 IS 1 BP 13 EP 21 DI 10.1023/A:1008995217664 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 393EE UT WOS:000166455600002 PM 11227921 ER PT J AU Matikainen, MP Pukkala, E Schleutker, J Tammela, TLJ Koivisto, P Sankila, R Kallioniemi, OP AF Matikainen, MP Pukkala, E Schleutker, J Tammela, TLJ Koivisto, P Sankila, R Kallioniemi, OP TI Relatives of prostate cancer patients have an increased risk of prostate and stomach cancers: a population-based, cancer registry study in Finland SO CANCER CAUSES & CONTROL LA English DT Article DE cancer risk; prostatic neoplasms; registry-based study; relatives ID FAMILIAL GASTRIC-CANCER; ANDROGEN RECEPTOR GENE; BREAST-CANCER; E-CADHERIN; SUSCEPTIBILITY LOCUS; DOMINANT INHERITANCE; CHROMOSOME 13Q12-13; HISTORY; MEN; MUTATIONS AB Objective: Five to ten percent of prostate cancers may be caused by inherited genetic defects. In order to explore the nature of inherited cancer risks in the genetically homogeneous Finnish population, we investigated the incidence of prostate cancer and other cancers in first-degree relatives of prostate cancer patients by linking the population-based parish records on relatives with the Finnish Cancer Registry (FCR) data. Methods: The study population was composed of first-degree relatives of two groups of prostate cancer patients diagnosed in Finland during 1988-1993: (1) all early-onset (less than or equal to 60years) patients (n=557) from the entire country, (2) a sample (n=989) of prostate cancer patients diagnosed at an age of > 60 years. A total of 11,427 first-degree relatives were identified through parish records, and their cancer incidence was determined based on a total of 299,970 person-years. Standardized incidence ratios (SIR) were calculated based on expected cancer rates in the general population. Results: The SIR of prostate cancer was increased in both Cohort 1 (2.5, 95% CI 1.9-3.2) and Cohort 2 (1.7, 95% CI 1.4-2.1). The risk of prostate cancer was high for relatives of patients diagnosed at an early age, and then leveled off for patients in the median age of prostate cancer diagnosis (70-79 years). However, the prostate cancer risk for relatives of patients diagnosed greater than or equal to 80years was again statistically significantly elevated (SIR 1.8, 95% CI 1.3-2.6), suggesting a contribution of genetic factors to prostate cancer also at a late age of onset. Gastric cancer was the only other cancer type with a significantly elevated risk among the relatives. Increased risk of gastric cancer was seen only in male relatives of prostate cancer patients diagnosed at an early age, with the highest risk detected for the male relatives of prostate cancer patients diagnosed at an age of 55 years or less (SIR 5.0, 95% CI 2.8-8.2). Conclusions: Our population-based study indicates that hereditary factors may play an important role in the development of prostate cancer among the relatives of men diagnosed both at younger and older ages. This finding is relevant in the context of our observations that HPCX (hereditary prostate cancer susceptibility locus on Xq27-28) linkage in Finland is found exclusively among families with late age of onset. The association of gastric cancer with prostate cancer has not been reported previously, and may reflect the effects of a novel predisposition locus, which increases the risk to both of these common tumor types. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Surg, Div Urol, FIN-33101 Tampere, Finland. Seinajoki Cent Hosp, Dept Surg, Seinajoki, Finland. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Int Agcy Res Canc, Unit Descript Epidemiol, F-69372 Lyon, France. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Matikainen, MP (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, POB 607, FIN-33101 Tampere, Finland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NHGRI NIH HHS [N01-HG-55389] NR 48 TC 33 Z9 33 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PY 2001 VL 12 IS 3 BP 223 EP 230 DI 10.1023/A:1011283123610 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 426BW UT WOS:000168330700004 PM 11405327 ER PT J AU Cronin, KA Krebs-Smith, SM Feuer, EJ Troiano, RP Ballard-Barbash, R AF Cronin, KA Krebs-Smith, SM Feuer, EJ Troiano, RP Ballard-Barbash, R TI Evaluating the impact of population changes in diet, physical activity, and weight status on population risk for colon cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE body mass index; cancer incidence; diet; physical activity ID COLORECTAL-CANCER; ALCOHOL-CONSUMPTION; US; OVERWEIGHT; PREVALENCE; OBESITY AB Objective: To estimate the effects of observed population-level changes in risk factors on population risk and incidence of disease. Methods: Trends in a set of risk factors for colon cancer (vegetable intake, red meat intake, alcohol consumption, physical activity levels, and weight status) were modeled for the US adult population over the years 1975-1995 and combined with relative risk estimates from epidemiologic studies and a probability distribution for the induction period to estimate the percentage change in incidence rates from 1985 to 1995 due to the five risk factors. A sensitivity analysis was performed to account for imprecision related to estimates of trends in behavior and epidemiologic risk. Results: Increased vegetable intake and decreased intakes of red meat and alcohol reduced risk, while reduced physical activity and increased body mass index increased risk for colon cancer. When all five factors were considered together, change in the average population relative risk was small and the risk factors accounted for little of the recently observed decline in incidence. Conclusions: Although these factors have the potential to greatly affect risk of colon cancer and incidence rates, little of that potential was realized since adverse trends neutralized what progress had been made in the areas of vegetables, red meat, and alcohol consumption. C1 NCI, Stat Res & Applicat Branch, Bethesda, MD 20892 USA. NCI, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Cronin, KA (reprint author), NCI, Stat Res & Applicat Branch, Bethesda, MD 20892 USA. OI Troiano, Richard/0000-0002-6807-989X NR 31 TC 16 Z9 16 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PY 2001 VL 12 IS 4 BP 305 EP 316 DI 10.1023/A:1011244700531 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 441AL UT WOS:000169208800003 PM 11456226 ER PT J AU Weinstein, SJ Ziegler, RG Selhub, J Fears, TR Strickler, HD Brinton, LA Hamman, RF Levine, RS Mallin, K Stolley, PD AF Weinstein, SJ Ziegler, RG Selhub, J Fears, TR Strickler, HD Brinton, LA Hamman, RF Levine, RS Mallin, K Stolley, PD TI Elevated serum homocysteine levels and increased risk of invasive cervical cancer in US women SO CANCER CAUSES & CONTROL LA English DT Article DE cervix neoplasms; homocysteine; nutrition ID UNITED-STATES; FOLIC-ACID; HUMAN PAPILLOMAVIRUS; INTRAEPITHELIAL NEOPLASIA; FOLATE-DEFICIENCY; INTEGRATION SITES; VITAMIN STATUS; PLASMA FOLATE; FRAGILE SITES; WHITE WOMEN AB Objectives: To explore the relationship between serum homocysteine, a sensitive biomarker for folate inadequacy and problems in one-carbon metabolism, and invasive cervical cancer. Methods: A large case-control study was conducted in five US areas with up to two community controls, obtained by random-digit dialing, individually matched to each case. Cervical cancer risk factors were assessed through at-home interview. Blood was drawn at least 6 months after completion of cancer treatment from 51% and 68% of interviewed cases and controls. Serum homocysteine was measured by high-performance liquid chromatography, and exposure to human papillomavirus (HPV) type 16, the most prevalent oncogenic type, was assessed using an enzyme-linked immunosorbent assay. Cases with advanced cancer and/or receiving chemotherapy were excluded, leaving 183 cases and 540 controls. Results: Invasive cervical cancer risk was substantially elevated for women in the upper three homocysteine quartiles (>6.31 mu mol/L); multivariate-adjusted odds ratios ranged from 2.4 to 3.2 (all 95% CIs excluded 1.0). A trend was apparent and significant (p = 0.01). When cases were compared with HPV-16 seropositive controls only, odds ratios were comparable. Conclusions: Serum homocysteine was strongly and significantly predictive of invasive cervical cancer risk. This association could reflect folate, B-12 and/or B-6 inadequacy, or genetic polymorphisms affecting one-carbon metabolism. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Univ Colorado, Sch Med, Dept Prevent Med & Biometr, Denver, CO USA. Meharry Med Coll, Sch Med Occupat & Prevent Med, Nashville, TN 37208 USA. Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Ziegler, RG (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7246, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 50 TC 33 Z9 36 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PY 2001 VL 12 IS 4 BP 317 EP 324 DI 10.1023/A:1011290103779 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 441AL UT WOS:000169208800004 PM 11456227 ER PT J AU Hisada, M van den Berg, BJ Strickler, HD Christianson, RE Wright, WE Waters, DJ Rabkin, CS AF Hisada, M van den Berg, BJ Strickler, HD Christianson, RE Wright, WE Waters, DJ Rabkin, CS TI Prospective study of antibody to human papilloma virus type 16 and risk of cervical, endometrial, and ovarian cancers (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE female cancers; HPV-16; serology ID INTRAEPITHELIAL NEOPLASIA; SERUM ANTIBODIES; PROSTATE-CANCER; FOLLOW-UP; IN-SITU; HPV DNA; INFECTION; SMOKING; CARCINOMA; WOMEN AB Objective: Human papilloma virus (HPV) is frequently detectable in cancers of the cervix, vagina, and vulva, but its role in endometrial and ovarian cancers is less certain. This analysis aimed to examine the association of presence of HPV type 16 (HPV-16) antibodies with subsequent risk of cervical, endometrial, and ovarian cancers. Methods: In a prospective study enrolling over 15,000 pregnant women, pre-cancer sera from women who developed cervical (n = 83), endometrial (n = 34), and ovarian (n = 35) cancers were compared with sera from 172 control women frequency-matched by age group and race. Results: HPV-16 seropositivity (OR = 2.0, 95% CI 1.0-3.4) was associated with cervical cancer, with the association more prominent for cancers occurring within 10 years of serum sampling (OR = 2.3, 95% CI 1.0-5.3) than cancers occurring later (OR = 1.6, 95% CI 0.75-3.6). Overall, the associations between HPV-16 seropositivity and endometrial (OR = 1.6, 95% CI 0.64-3.8) and ovarian cancers (OR = 1.1, 95% CI 0.43-2.8) were not significant, although the odds ratios for those cancers occurring within 20 years after serum sampling were similar to that for cervical cancer (OR = 2.2 for both). Conclusions: Our results confirm that HPV-16 infection precedes the development of cervical cancer. Predictability of HPV-16 seropositivity for risk of other female cancers warrants further investigation. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Calif Dept Hlth Serv, Canc Surveillance Sec, Sacramento, CA USA. NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Rabkin, CS (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8010, Rockville, MD USA. FU NICHD NIH HHS [N01-HD-9103134] NR 44 TC 16 Z9 18 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PY 2001 VL 12 IS 4 BP 335 EP 341 DI 10.1023/A:1011236803257 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 441AL UT WOS:000169208800006 PM 11456229 ER PT J AU Boffetta, P Dosemeci, M Gridley, G Bath, H Moradi, T Silverman, D AF Boffetta, P Dosemeci, M Gridley, G Bath, H Moradi, T Silverman, D TI Occupational exposure to diesel engine emissions and risk of cancer in Swedish men and women SO CANCER CAUSES & CONTROL LA English DT Article DE diesel engine emissions; epidemiology; neoplasms ID LUNG-CANCER; BLADDER-CANCER; RAILWAY WORKERS; CASE-REFERENT; EXHAUST; MORTALITY; ALCOHOL; TOBACCO; MATRIX; MALES AB Objective: To investigate the risk of cancer among workers exposed to diesel emissions in a large record-linkage study from Sweden. Methods: The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971-1989, by occupation and industry of employment as reported in the 1960 and 1970 censuses. After excluding farmers, we classified job and industry titles according to estimated probability and intensity of exposure to diesel emissions. Exposed men in the 1960 census contributed over 7,400,000 person-years, and exposed women contributed over 240,000. We compared them to the remainder of the employed population, using indirect standardization and multivariate Poisson regression analysis. Results: Men exposed in the 1960 census experienced an increased risk of lung cancer: the relative risks (RRs) were 0.95 (95% confidence interval [CI] 0.9-1.0), 1.1 (1.1-1.2) and 1.3 (1.3-1.4) for low, medium, and high intensity of exposure. Corresponding results for probability of exposure were 1.1 (1.0-1.1), 0.9 (0.86-0.94) and 1.2 (1.1-1.2). The risk was higher for squamous cell carcinoma of the lung than for other histological types. Results in women were not suggestive of an effect (RR in the category of medium or high intensity of exposure 1.1, 95% CI 0.6-1.8). A small but significant increase in risk of cancers of the stomach (SIR 1.06), pancreas (SIR 1.05), larynx (SIR 1.09), and the kidney (SIR 1.06) was present among men exposed to diesel emissions, without a clear trend according to either probability or intensity of exposure. The SIR among women was non-significantly increased for stomach, pancreatic, and laryngeal cancers, but not for kidney cancer. Furthermore, a significantly increased risk of oral/pharyngeal (SIR 1.64) and cervical (SIR 1.48) cancers was present among women, with a suggestion of a dose-response relationship. There was no increased risk of bladder cancer in either gender. Conclusions: The results of this study provide evidence of a positive exposure-response relationship between exposure to diesel emissions and lung cancer risk among men. The positive results for other neoplasms, such as stomach, pancreatic, oral/pharyngeal, and cervical cancers, cannot be attributed to diesel exposure, but they deserve attention in future investigations. C1 Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69008 Lyon, France. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. IMS, Silver Spring, MD USA. RP Boffetta, P (reprint author), Int Agcy Res Canc, Unit Environm Canc Epidemiol, 150 Cours Albert Thomas, F-69008 Lyon, France. NR 30 TC 60 Z9 60 U1 2 U2 11 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PY 2001 VL 12 IS 4 BP 365 EP 374 DI 10.1023/A:1011262105972 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 441AL UT WOS:000169208800010 PM 11456233 ER PT J AU Bosetti, C Kolonel, L Negri, E Ron, E Franceschi, S Maso, LD Galanti, MR Mark, SD Preston-Martin, S McTiernan, A Land, C Jin, F Wingren, G Hallquist, A Glattre, E Lund, E Levi, F Linos, D Vecchia, CL AF Bosetti, C Kolonel, L Negri, E Ron, E Franceschi, S Maso, LD Galanti, MR Mark, SD Preston-Martin, S McTiernan, A Land, C Jin, F Wingren, G Hallquist, A Glattre, E Lund, E Levi, F Linos, D Vecchia, CL TI A pooled analysis of case-control studies of thyroid cancer. VI. Fish and shellfish consumption SO CANCER CAUSES & CONTROL LA English DT Article DE case-control studies; diet; fish; pooled analysis; thyroid cancer ID HISTORY; WOMEN; RISK; DISEASE; DIET; PAPILLARY AB Objective: To better understand the role of fish and shellfish on thyroid cancer risk, we systematically re-analyzed the original data from 13 case-control studies conducted in the US, Japan, China, and Europe. Methods: A total of 2497 cases (2023 women, 474 men) and 4337 controls (3268 women, 1069 men) were considered. Odds ratio (OR) and corresponding 95% confidence interval (CI) were estimated for each study by logistic regression models, conditioned on age and sex, and adjusted for history of goiter, thyroid nodules or adenomas, and radiation. Combined ORs were computed as the weighted average of the estimates from each study. Results: The ORs for the highest level of total fish consumption (three or more times per week) as compared to the lowest one (less than once per week) was above unity in Hawaii, Connecticut, Japan, Norway, Tromso, and Vaud. Conversely, the ORs for the studies in Los Angeles, Shanghai, southeastern Sweden, Uppsala, northern Sweden, northern Italy, and Athens were below one. The pattern of risk for salt water fish and shellfish was not substantially different from that of total fish. Fish was not associated with thyroid cancer risk in all studies combined (OR=0.99, 95% CI 0.85-1.2 for moderate, and OR=0.88, 95% CI 0.71-1.1 for high total fish consumption), but there was a suggestion of a protective effect in endemic goiter areas (OR=0.65, 95% CI 0.48-0.88). Conclusion: This combined analysis indicates that relatively elevated fish consumption does not appreciably increase thyroid cancer risk, and may have a favorable influence in areas where iodine deficiency is, or was, common. C1 Mario Negri Inst Pharmacol Res, Lab Gen Epidemiol, I-20157 Milan, Italy. Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Univ Hosp, Dept Canc Epidemiol, SE-57185 Uppsala, Sweden. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Radiat Effects Res Fdn, Hiroshima 732, Japan. Shanghai Canc Inst, Shanghai, Peoples R China. Linkoping Univ, Fac Hlth Sci, Dept Hlth & Environm, Div Environm & Occupat Med, SE-58185 Linkoping, Sweden. Karolinska Inst, Dept Oncol, SE-11235 Stockholm, Sweden. Stockholms Sujkhem, SE-11235 Stockholm, Sweden. Canc Registry Norway, NO-3010 Oslo, Norway. Univ Tromso, Inst Community Med, NO-9037 Tromso, Norway. Inst Univ Med Sociale & Prevent, Registre Vaudois Tumeurs, CH-1011 Lausanne, Switzerland. Inst Prevent Med, GR-14561 Kifissia, Greece. Univ Milan, Ist Stat Med & Biometria, I-20133 Milan, Italy. RP Negri, E (reprint author), Mario Negri Inst Pharmacol Res, Lab Gen Epidemiol, Via Eritrea 62, I-20157 Milan, Italy. RI Negri, Eva/B-7244-2013 OI Negri, Eva/0000-0001-9712-8526 NR 28 TC 37 Z9 41 U1 2 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PY 2001 VL 12 IS 4 BP 375 EP 382 DI 10.1023/A:1011267123398 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 441AL UT WOS:000169208800011 PM 11456234 ER PT J AU Fox, E Murphy, RF McCully, CL Adamson, PC AF Fox, E Murphy, RF McCully, CL Adamson, PC TI Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE pharmacokinetics; CNS malignancies; hypericin ID PROTEIN-KINASE-C; PSEUDOHYPERICIN AB Hypericin, a polycyclic aromatic dianthroquinone, is a natural pigment derived from the plant Hypericum perforatum (St John's Wort). The compound has been synthesized and shown to inhibit the growth of malignant glioma cell lines in vitro via inhibition of protein kinase C. Oral hypericin has entered clinical trials in adults with recurrent malignant glioma. Purpose: The present study was performed to characterize the plasma pharmacokinetics (PK) and cerebrospinal fluid (CSF) penetration of hypericin in nonhuman primates. Methods: Hypericin was administered as an intravenous bolus dose of 2 mg/kg (n = 3) or 5 mg/kg (n = 1). Plasma and CSF (ventricular or lumbar) were sampled Frier to administration and at frequent intervals for up to 50 h after administration of the drug. Hypericin concentrations in plasma and CSI; were determined using a specific reverse-phase HPLC assay. Results: Mean peak plasma concentration of hypericin following the 2 mg/kg dose was 142 +/- 45 muM. Elimination of hypericin from plasma was biexponential, with an average alpha half-life of 2.8 +/- 0.3 h and average terminal half-life of 26 +/- 14 h. Conclusions: The 2 mg/kg dose in the nonhuman primate was sufficient to maintain plasma concentrations above 10 muM (the in vitro concentration required for growth inhibition of human glioma cell lines) for up to 12 h. No hypericin was detected in the CSF of any animal (lower limit of detection 0.1 muM); the CSF penetration is therefore less than 1%. A severe dose-limiting photosensitivity skin rash was seen at the 5 mg/kg dose level. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Fox, E (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 18 TC 32 Z9 33 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2001 VL 47 IS 1 BP 41 EP 44 DI 10.1007/s002800000188 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 401EX UT WOS:000166915300008 PM 11221960 ER PT J AU Ewesuedo, RB Wilson, LR Friedman, HS Moschel, RC Dolan, ME AF Ewesuedo, RB Wilson, LR Friedman, HS Moschel, RC Dolan, ME TI Inactivation of O-6-alkylguanine-DNA alkyltransferase by 8-substituted O-6-benzylguanine analogs in mice SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE alkyltransferase; O-6-benzylguanine; mice; pharmacokinetic; O-6-benzyl-8-oxoguanine ID MALIGNANT GLIOMA; TUMOR XENOGRAFTS; DNA-REPAIR; DERIVATIVES; METABOLISM; DEPLETION; PROTEIN; PHARMACOKINETICS; INHIBITION; SURVIVAL AB Purpose: The purpose of this study was to determine the usefulness of various 8-substituted O-6-benzylguanine (BG) analogs as modulators of the DNA repair protein, O-6-alkylguanine-DNA alkyltransferase (AGT). More specifically, the degree of inactivation of AGT in mouse brain, liver, kidney and tumor by O-6-benzyl-8-oxoguanine (8-oxoBG), 8-aza-O(6-)benzylguanine (8-azaBG), O-6-benzyl-8-bromoguanine (8-bromoBG) and O-6-benzyl-8-trifluoromethylguanine (8-tfmBG) was compared to inactivation by BC, a modulator in phase II clinical trials. BG is converted rapidly to 8-oxoBG in rodents, monkeys and humans. It was reasoned that 8-substituted analogs of BG would exhibit different pharmacological properties compared to BG which could influence tissue bioavailability and, thus, the extent of ACT inactivation in vivo. We compared the tissue distribution of these agents and AGT activity following administration of the 8-substituted analogs. Materials and methods: At various time points up to 24 h after i.p. administration of the BG analogs, tissues (i.e. brain, liver, kidney), A549 lung tumor xenografts (i.p.) or D456 brain tumor xenografts (i.c.) were harvested from athymic nude mice for AGT analysis. AGT activity was quantified in tissue extracts using a biochemical assay with [H-3]methylated DNA as a substrate. In addition, concentrations of BG and 8-oxoBG were determined by HPLC with fluorescence detection in mouse tissues following administration of drug. Results: Each of the 8-substituted analogs of BG demonstrated variable AGT inactivation capabilities that were comparable to or better than those of BG especially in kidney and brain tissues. There was a more pronounced depletion of AGT inactivation in brain and D456 brain tumor xenografts following administration of BG compared to 8-oxoBG that could be explained by a much greater concentration of ACT-inactivating drug (BG plus the metabolite 8-oxoBG for mice treated with BG Versus 8-oxoBG for mice treated with 8-oxoBG) present in these tissues. The AUCs for brain, kidney and liver were 3.2, 6.9 and 11.8 times greater for BG than for 8-oxoBG. Conclusions: 8-substituted analogs of BG possess unique ACT-inactivation profiles in vivo that are different from that of BG. The AGT-inhibitory activities of BG and its major metabolite, 8-oxoBG, are related to tissue disposition of both drugs. C1 Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Comm Clin Pharmacol, Dept Pediat, Sect Pediat Hematol Oncol, Chicago, IL 60637 USA. Duke Univ, Dept Pediat & Pathol, Durham, NC 27710 USA. NCI, Frederick Canc Res & Dev Ctr, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. RP Dolan, ME (reprint author), Univ Chicago, Hematol Oncol Sect, 5841 S Maryland Ave,Box MC2115, Chicago, IL 60637 USA. FU NCI NIH HHS [CA57725] NR 26 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2001 VL 47 IS 1 BP 63 EP 69 DI 10.1007/s002800000202 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 401EX UT WOS:000166915300012 PM 11221964 ER PT J AU Cohen, LA Zhao, ZL Pittman, B Aliaga, C Lubet, R AF Cohen, LA Zhao, ZL Pittman, B Aliaga, C Lubet, R TI Feeding thiol-containing compounds, derived from vegetables, fails to inhibit N-methylnitrosourea-induced mammary tumorigenesis SO CANCER DETECTION AND PREVENTION LA English DT Article DE dietary thiols; chemoprevention; mammary tumor; NMU ID METHYL METHANE THIOSULFONATE; MALE F344 RATS; 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOL-3-THIONE OLTIPRAZ; CARCINOGENESIS; CHEMOPREVENTION; ENZYMES; AZOXYMETHANE; GLUTATHIONE; METABOLISM; CANCER AB Various thiol-containing compounds have been shown to inhibit chemically-induced tumors in animal models. Two thiol-containing compounds derived from vegetables. namely 1,2 dithiol-3-thione (DTT) and S-methylmethane thiolsulfonate (MMTS), were tested for their chemopreventive activity in the N-methylnitrosourea (NMU)-induced rat mammary tumor model. Each compound was incorporated into the grain-based Teklad 7001 diet and fed to the rats one week prior to initiation with NMU until termination 18 weeks post NMU. DTT was fed at 166 and 500 ppm and MMTS at 200 and 800 ppm. Neither compound exerted a significant inhibitory effect on any index of tumor development including incidence, total turner, tumor multiplicity, volume or latency. Serum levels of DTT assessed at termination in the 500 ppm DTT group ranged from 10-30 mug/ml. MMTS was undetectable in serum from either MMTS-fed group. The results of this study, using the direct acting carcinogen, NMU, suggest that the chemopreventive effect of thiol-containing compounds may be confined to animal models using carcinogens that require host activation. C1 Amer Hlth Fdn, Valhalla, NY 10595 USA. NCI, Chemoprevent Branch, NCI, Bethesda, MD 20892 USA. RP Cohen, LA (reprint author), Amer Hlth Fdn, 1 Dana Rd, Valhalla, NY 10595 USA. FU NCI NIH HHS [P30-CA17613]; NCPDCID CDC HHS [NCI-CN-55163] NR 39 TC 1 Z9 1 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2001 VL 25 IS 3 BP 254 EP 261 PG 8 WC Oncology SC Oncology GA 442LE UT WOS:000169286600005 PM 11425267 ER PT J AU Thigpen, JE Locklear, J Haseman, JK Saunders, H Grant, MF Forsythe, DB AF Thigpen, JE Locklear, J Haseman, JK Saunders, H Grant, MF Forsythe, DB TI Effects of the dietary phytoestrogens daidzein and genistein on the incidence of vulvar carcinomas in 129/J mice SO CANCER DETECTION AND PREVENTION LA English DT Article DE vulvar carcinomas; dietary phytoestrogens; daidzein; genistein; rodent diets ID ESTROGENIC ACTIVITY; RODENT DIETS; MOUSE BIOASSAY; BREAST-CANCER; ISOFLAVONES; CARCINOGENESIS; FORMULA AB The objective of this study was to determine the effect of dietary phytoestrogens on the incidence of spontaneous vulvar carcinomas in 129/J mice using three natural ingredient diets and two purified diets containing predetermined levels of daidzein and genistein. Eighty weanling female mice without clinical evidence of vulvar carcinomas were randomly assigned 16 per diet to each of 5 test diets. Mice were clinically examined for vulvar masses weekly for 3 months and at monthly intervals thereafter. Vulvar carcinomas in representative groups of mice were confirmed using routine histological procedures. The incidence of vulvar carcinomas increased sharply in mice on ail test diets during the first 2 months with minor changes during the remainder of the study, Within one month, the incidence of vulvar carcinomas in mice fed the AIN-76A modified soy protein diet was significantly (P < .05) increased over those of mice fed the AIN-76A modified casein diet, the #5K96, or the # 5058 diet. At three months, the incidence of vulvar carcinomas in mice fed the soy protein diet was significantly (P < .05) increased over those of mice fed the NIH-31 diet or the PMI #5K96 diet. There was a marginally significant (P < .10) correlation between the total daidzein and genistein levels in the five test diets and the incidence of vulvar carcinomas in mice as determined by clinical examination. We concluded that dietary levels of daidzein and genistein were associated with an increase in the incidence of vulvar carcinomas in mice and that the 129/J mouse may provide an animal model for studying the development of vulvar carcinomas. C1 NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Thigpen, JE (reprint author), NIEHS, Comparat Med Branch, POB 12233,Mail Drop C1-06, Res Triangle Pk, NC 27709 USA. NR 36 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2001 VL 25 IS 6 BP 527 EP 532 PG 6 WC Oncology SC Oncology GA 507YQ UT WOS:000173059400004 PM 12132873 ER PT J AU Chow, HHS Cai, Y Alberts, DS Hakim, I Dorr, R Shahi, F Crowell, JA Yang, CS Hara, Y AF Chow, HHS Cai, Y Alberts, DS Hakim, I Dorr, R Shahi, F Crowell, JA Yang, CS Hara, Y TI Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER AB Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its principal active components include epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin gallate, of which EGCG is the most abundant and possesses the most potent antioxidative activity. We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E (decaffeinated green tea catechin mixture). Twenty healthy subjects (five subjects/dose level) were randomly assigned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG content). All subjects were randomly crossed-over to receive the two catechin formulations at the same dose level. Blood and urine samples were collected for up to 24 h after oral administration of the study medication. Tea catechin concentrations in plasma and urine samples were determined using highperformance liquid chromatography with the coulometric electrode array detection system, After EGCG versus Polyphenon E administration, the mean area under the plasma concentration-time curves (AUC) of unchanged EGCG were 22.5 versus 21.9, 35.4 versus 52.2, 101.9 versus 79.7, and 167.1 versus 161.4 min.mug/ml at the 200-, 400-, 600-, and 800-mg dose levels, respectively, EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration. High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine samples after Polyphenon E administration, There were no significant differences in the pharmacokinetic characteristics of EGCG between the two study medications. The AUC and maximum plasma concentration (C-max) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose. The AUC and C-max of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses. We conclude that the two catechin Formulations resulted in similar plasma EGCG levels. EGC and EC were present in the body after the Polyphenon E administration; however, they were present predominantly in conjugated forms. The systemic availability of EGCG increased at higher doses, possibly due to saturable presystemic elimination of orally administered green tea polyphenols. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Rutgers State Univ, Coll Pharm, Piscataway, NJ 08854 USA. Mitsui Norin Co Ltd, Shizuoka 42601, Japan. RP Chow, HHS (reprint author), Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. FU NCI NIH HHS [N01-CN-85179] NR 12 TC 275 Z9 284 U1 0 U2 19 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2001 VL 10 IS 1 BP 53 EP 58 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 396TA UT WOS:000166651600008 PM 11205489 ER PT J AU Woodson, K Mason, J Choi, SW Hartman, T Tangrea, J Virtamo, J Taylor, PR Albanes, D AF Woodson, K Mason, J Choi, SW Hartman, T Tangrea, J Virtamo, J Taylor, PR Albanes, D TI Hypomethylation of p53 in peripheral blood DNA is associated with the development of lung cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOLATE/METHYL-DEFICIENT RATS; TUMOR-SUPPRESSOR GENE; NESTED CASE-CONTROL; COLORECTAL-CANCER; METHYL-DEFICIENT; S-ADENOSYLHOMOCYSTEINE; FOLATE-DEFICIENCY; ALPHA-TOCOPHEROL; BETA-CAROTENE; STRAND BREAKS AB Alterations in DNA methylation have been associated with cancers at almost all tumor sites and represent one of the most consistent changes in neoplastic cells. The underlying etiological mechanisms for alteration of DNA methylation patterns are not understood, but experimental studies in animals suggest potential environmental and genetic influences. The purpose of this study was to investigate whether DNA hypomethylation in peripheral blood DNA (potentially representing status at the lung) was associated with increased risk for the development of lung cancer. We evaluated genome-wide and p53 gene-specific hypomethylation in 100 lung cancer cases and controls selected from a large clinical trial of male smokers, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Genome-wide methylation status was assessed using the in vitro methyl acceptance capacity assay and p53 gene-specific methylation status using the HgaII quantitative PCR assay. Hypomethylation was evaluated as a risk factor using multivariate conditional logistic regression analyses. Genome-wide methylation status was unrelated to lung cancer risk; the odds ratio was 1.25 and the 95% confidence interval was 0.48-3.21 for those in the highest versus lowest quartile of hypomethylation status. Hypomethylation of the p53 gene in exons 5-8, the hypermutable region, was associated with a 2-fold increased risk for lung cancer (odds ratio, 2.20; 95% confidence interval, 1.04-4.65), whereas there was no risk increase for hypomethylation at exons 2-4, a region of the gene not known for its mutability or functional significance in cancer. Our results indicate that hypomethylation status within exons 5-8 of p53 from peripheral lymphocyte DNA may be a relevant predictor of lung cancer among male smokers. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Tufts Univ, USDA, Boston, MA 02111 USA. Natl Publ Hlth Inst, SF-00300 Helsinki, Finland. RP Woodson, K (reprint author), NCI, Canc Prevent Studies Branch, Div Clin Sci, 6006 Execut Blvd,MSC 7058, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 40 TC 43 Z9 47 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2001 VL 10 IS 1 BP 69 EP 74 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 396TA UT WOS:000166651600011 PM 11205492 ER PT J AU Shibata, MA Yoshidome, K Shibata, E Jorcyk, CL Green, JE AF Shibata, MA Yoshidome, K Shibata, E Jorcyk, CL Green, JE TI Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21 SO CANCER GENE THERAPY LA English DT Article DE cell cycle; p21; mammary cancer; transgenic mice; gene therapy ID LARGE-TUMOR-ANTIGEN; BREAST-CANCER; CELL-CYCLE; TRANSGENIC MICE; KINASE-ACTIVITY; P53 PROTEIN; IN-VIVO; APOPTOSIS; OVEREXPRESSION; ARREST AB Mammary carcinomas that develop in C3(1)/SV40 T-antigen (TAg) transgenic mice have lost the p53-mediated induction of p21, leading to increased cellular proliferation and significant elevations of cyclins and Cdks. To test whether p21 could serve as a target for anticancer therapy for this mammary cancer model, a retroviral delivery system for the inducible expression of p21 was developed. We demonstrate that overexpression of p21 in C3(1)/TAg mammary tumor cells using the retroviral inducible p21 expression system results in increased apoptosis, reduced cell proliferation in vitro and reduced tumor growth in vivo associated with reduced expression of cyclins D1 and E, and Cdks 2, 4, and 6. Reciprocal changes in the expression of p21 and p27(Kip1), another cell-cycle regulator, were also observed. Because reduced p21 expression occurs frequently in human breast cancer, restoration of the Cdk inhibitor p21 by gene therapy approaches may provide a method for inhibiting mammary tumor progression. C1 NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Osaka Med Coll, Dept Anat & Biol, Takatsuki, Osaka 5698686, Japan. Boise State Univ, Dept Biol, Boise, ID 83725 USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 39 TC 48 Z9 49 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2001 VL 8 IS 1 BP 23 EP 35 PG 13 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 400NZ UT WOS:000166879400004 PM 11219490 ER PT J AU Ryan, MH Abrams, SI AF Ryan, MH Abrams, SI TI Characterization of CD8(+) cytotoxic T lymphocyte/tumor cell interactions reflecting recognition of an endogenously expressed murine wild-type p53 determinant SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE mouse; CTL; tumor immunity; peptides ID MUTANT; PEPTIDES; EPITOPE; THERAPY; INDUCTION; VACCINES; TUMORS; INVIVO; VIRUS; CTL AB p53 mutations are frequently found in human cancers and are often associated with the overexpression of wild-type (WT) protein or peptide sequences, supporting the notion that WT p53 epitopes may serve as potential targets for tumor immunotherapy. We have developed a cytotoxic T lymphocyte (CTL)/p53 tumor-associated antigen (TAA) model, based on immune recognition of a WT p53 determinant. WT p53-peptide-specific, major histocompatibility complex (MHC) class-I-restricted CTL were produced from immunocompetent C57BL/6 (H-2(b)) mice after immunization with a previously defined WT p53 peptide (P53(232-240)). Epitope-specific CTL were then employed to identify syngeneic tumor cell populations expressing that antigenic determinant. Two syngeneic tumor cell lines, MC38 colon carcinoma and MC57G fibrosarcoma, were demonstrated to express the endogenous WT p53(232-240) determinant naturally, as defined by CD8(+) CTL recognition. Cold-target inhibition assays confirmed that CTL-mediated lysis was due to immune recognition of the p53232-240 peptide epitope. The p53(232-240)-specific CTL line did not lyse syngeneic normal cells (i.e., mitogen-activated splenocytes) in the absence of exogenous peptide, suggesting that the WT-p53-specific CTL could distinguish between tumor cells expressing self-TAA and normal host cells. We have demonstrated, for the first time, that the adoptive transfer of WT-p53-specific CTL to mice with established pulmonary metastasis resulted in antitumor activity in vivo. The ability to generate MHC-class-I-restricted CD8(+) CTL lines specific for a non-mutated p53 determinant from normal, immunocompetent mice, which display antitumor activity both in vitro and in vivo (by adoptive transfer), may have implications for the immunotherapy of certain p53-expressing malignancies. C1 NCI, Tumor Immunol & Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, Div Basic Sci, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. NR 24 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2001 VL 49 IS 11 BP 603 EP 612 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 393TM UT WOS:000166485800004 ER PT J AU Phillips, J Smith, ED AF Phillips, J Smith, ED TI Breast cancer control and African American women: A review SO CANCER INVESTIGATION LA English DT Article DE African American women; breast cancer ID RACIAL-DIFFERENCES; STAGE; MAMMOGRAPHY; SURVIVAL C1 Natl Inst Nursing Res, Bethesda, MD 20892 USA. Univ Illinois, Coll Nursing, Chicago, IL USA. RP Phillips, J (reprint author), Natl Inst Nursing Res, 45 Ctr Dr MSC-6300, Bethesda, MD 20892 USA. NR 27 TC 9 Z9 9 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 3 BP 273 EP 280 DI 10.1081/CNV-100102555 PG 8 WC Oncology SC Oncology GA 453ME UT WOS:000169919000008 PM 11338885 ER PT J AU Ishibe, N Freedman, AN AF Ishibe, N Freedman, AN TI Understanding the interaction between environmental exposures and molecular events in colorectal carcinogenesis SO CANCER INVESTIGATION LA English DT Review DE colorectal cancer; gene-environment interactions; review ID S-TRANSFERASE M1; FAMILIAL ADENOMATOUS POLYPOSIS; METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; BUTYRATE-INDUCED APOPTOSIS; KINASE INHIBITOR P27; ABERRANT CRYPT FOCI; BREAST-CANCER CELLS; N-NITROSO COMPOUNDS; DCC GENE-PRODUCT; K-RAS GENE C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD 20892 USA. RP Ishibe, N (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7236, Rockville, MD 20892 USA. NR 186 TC 8 Z9 9 U1 0 U2 3 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 5 BP 524 EP 539 DI 10.1081/CNV-100103850 PG 16 WC Oncology SC Oncology GA 453MG UT WOS:000169919200008 PM 11458819 ER PT J AU Gurney, JG Smith, MA Olshan, AF Hecht, SS Kasum, CM AF Gurney, JG Smith, MA Olshan, AF Hecht, SS Kasum, CM TI Clues to the etiology of childhood brain cancer: N-nitroso compounds, polyomaviruses, and other factors of interest SO CANCER INVESTIGATION LA English DT Review DE BK virus; brain neoplasms; central nervous system neoplasms; child; epidemiology; folates; JC virus; nitrosamides; nitrosamines; nitrosoureas; pesticides; risk factors; SV40 virus; vitamins ID LARGE-T-ANTIGEN; JC VIRUS-DNA; CHOROID-PLEXUS TUMORS; NEURAL-TUBE DEFECTS; BK VIRUS; METHYLENETETRAHYDROFOLATE REDUCTASE; MOLECULAR-BIOLOGY; HUMAN PAPOVAVIRUS; TRANSGENIC MICE; EPIDEMIOLOGIC EVIDENCE C1 Univ Minnesota, Div Pediat Epidemiol, Dept Pediat, Minneapolis, MN 55454 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55454 USA. Univ Minnesota, Dept Epidemiol, Minneapolis, MN 55454 USA. NCI, Div Canc Treatment Diag, Bethesda, MD 20892 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Gurney, JG (reprint author), Univ Minnesota, Div Pediat Epidemiol, Dept Pediat, 420 Delaware St SE,Mayo Mail Code 712, Minneapolis, MN 55454 USA. OI Hecht, Stephen/0000-0001-7228-1356 NR 130 TC 18 Z9 19 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 6 BP 630 EP 640 DI 10.1081/CNV-100104291 PG 11 WC Oncology SC Oncology GA 454LT UT WOS:000169974600008 PM 11486706 ER PT J AU McGlynn, KA AF McGlynn, KA TI Environmental and host factors in testicular germ cell tumors SO CANCER INVESTIGATION LA English DT Review ID RISK-FACTORS; UNITED-STATES; TESTIS CANCER; PHYSICAL-ACTIVITY; MULTICENTER EXPERIENCE; REPRODUCTIVE HORMONES; DOWNS-SYNDROME; MEN; CRYPTORCHIDISM; GENE C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20893 USA. RP McGlynn, KA (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, EPS-7060,6120 Execut Blvd, Bethesda, MD 20893 USA. NR 120 TC 37 Z9 37 U1 3 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2001 VL 19 IS 8 BP 842 EP 853 DI 10.1081/CNV-100107746 PG 12 WC Oncology SC Oncology GA 498QY UT WOS:000172523000011 PM 11768038 ER PT J AU Wang, E Marincola, FM AF Wang, E Marincola, FM TI cDNA arrays and the enigma of melanoma immune responsiveness SO CANCER JOURNAL LA English DT Article DE functional genomics; immunotherapy; tumor escape; tumor immunology; tumor tolerance ID GENE-EXPRESSION PATTERNS; METASTATIC MELANOMA; TRANSCRIPTIONAL PROGRAM; PERIPHERAL-BLOOD; NATURAL-HISTORY; HUMAN CANCER; BLACK-HOLES; CELL-CYCLE; IN-VIVO; TUMOR AB Melanoma is a cancer characterized by predisposition to natural and induced immune rejection. The occurrence of this phenomenon, however, remains sporadic and capricious while there is no clear understanding of the chain of events responsible. With the progression of the understanding of the molecular immunology of melanoma during the last decade, several theories suggesting immune tolerance (inadequate immune response) and/or immune escape (adaptation of cancer cells to a vigorous immune pressure) as possible modulators of melanoma growth have emerged. As the number of these hypotheses, mostly based on molecular or pre-clinical models, has increased exponentially, the relevance of each individual one has been conversely decreasing leaving the observer without confidence that a theory likely to explain this phenomenon can be soon formulated. In this review, we will discuss a direct approach whereby new theories might be identified by direct observation of human phenomena as they occur by depiction of molecular portraits of melanoma lesions using global transcript analysis. C1 NCI, Surg Branch, Div Clin Sci, Ctr Clin,NIH, Bethesda, MD 20892 USA. NCI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP NCI, Surg Branch, Div Clin Sci, Ctr Clin,NIH, Bethesda, MD 20892 USA. NR 60 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JAN-FEB PY 2001 VL 7 IS 1 BP 16 EP 23 PG 8 WC Oncology SC Oncology GA 406LV UT WOS:000167218400003 PM 11269643 ER PT J AU Gillespie, JW Ahram, M Best, CJM Swalwell, JI Krizman, DB Petricoin, EF Liotta, LA Emmert-Buck, MR AF Gillespie, JW Ahram, M Best, CJM Swalwell, JI Krizman, DB Petricoin, EF Liotta, LA Emmert-Buck, MR TI The role of tissue microdissection in cancer research SO CANCER JOURNAL LA English DT Article DE tissue microdissection; molecular pathology; gene expression; proteomics ID LASER CAPTURE MICRODISSECTION; DENSITY OLIGONUCLEOTIDE ARRAYS; POLYMERASE CHAIN-REACTION; GENE-EXPRESSION PATTERNS; ALLELIC LOSS; MEN1 GENE; CHROMOSOME 8P12-21; PROTEOMIC ANALYSIS; MOLECULAR ANALYSIS; PROSTATE-CANCER AB Tissue microdissection is a laboratory method that is used to procure specific cells or cell populations from a histology slide under direct microscopic visualization. The recovered cells can be studied with a variety of DNA, messenger RNA, and protein analysis methods, including new high-throughput gene expression and proteomics technologies. This approach is permitting investigators to comprehensively examine the molecular anatomy of cells in tissue sections for the first time. This article reviews the development and evolution of tissue microdissection techniques, summarizes examples of research studies, and discusses related challenges that the research community must address. Additional information and complete laboratory protocols are available on a website at http://cgap-mf.nih.gov/. C1 NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Room 2A33,Bldg 10, Bethesda, MD 20892 USA. NR 46 TC 40 Z9 44 U1 1 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD JAN-FEB PY 2001 VL 7 IS 1 BP 32 EP 39 PG 8 WC Oncology SC Oncology GA 406LV UT WOS:000167218400005 PM 11269646 ER PT J AU Schaefer, C Grouse, L Buetow, K Strausberg, RL AF Schaefer, C Grouse, L Buetow, K Strausberg, RL TI A new cancer genome anatomy project web resource for the community SO CANCER JOURNAL LA English DT Article DE genomics; cancer; gene discovery; expressed sequence tags; SAGE; single nucleotide polymorphisms; molecular cytogenetics; chromosome aberrations; bioinformatics; bacterial artificial chromosomes ID GENE-EXPRESSION; DISCOVERY; PROSTATE AB The National Cancer Institute's Cancer Genome Anatomy Project (CGAP) is developing publicly accessible information, technology, and material resources that provide a platform for the interface of cancer research and genomics. CGAP's efforts have focused toward (1) building and annotating catalogues of genes expressed during cancer development, (2) identifying polymorphisms in those genes, and (3) developing resources for the molecular characterization of cancer-related chromosomal aberrations. To date, CGAP has produced more than 1,000,000 expressed sequence tags, approximately 3,300,000 serial analysis of gene expression tags, and identified more than 10,000 human gene-based single-nucleotide polymorphisms. To enhance access to these datasets by the research community, a new Cancer Genome Project web site (http://cgap.nci.nih.gov/) is being introduced. The web site includes genomic data for humans and mice, including transcript sequence, gene expression patterns, single-nucleotide polymorphisms, clone resources, and cytogenetic information. Descriptions of the methods and reagents used in deriving the CGAP datasets are also provided. An extensive suite of informatics tools facilitates queries and analysis of the CGAP data by the community. One of the newest features of the CGAP web site is an electronic version of the Mitelman Database of Chromosome Aberrations in Cancer. C1 NCI, Canc Genom Off, Bethesda, MD 20892 USA. NCI, Ctr Bioinformat, Bethesda, MD 20892 USA. RP Strausberg, RL (reprint author), NCI, Canc Genom Off, 31 Ctr Dr,Room 11A03, Bethesda, MD 20892 USA. NR 13 TC 22 Z9 23 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD JAN-FEB PY 2001 VL 7 IS 1 BP 52 EP 60 PG 9 WC Oncology SC Oncology GA 406LV UT WOS:000167218400007 PM 11269648 ER PT J AU Bichsel, VE Liotta, LA Petricoin, EF AF Bichsel, VE Liotta, LA Petricoin, EF TI Cancer proteomics: From biomarker discovery to signal pathway profiling SO CANCER JOURNAL LA English DT Article DE proteomics; cancer; microdissection; signaling; pharmacoproteomics ID LASER CAPTURE MICRODISSECTION; POLYACRYLAMIDE-GEL ELECTROPHORESIS; TRANSITIONAL-CELL CARCINOMAS; PROSTATE-SPECIFIC ANTIGEN; GENE-EXPRESSION PATTERNS; MAMMARY EPITHELIAL-CELLS; ACID-BINDING PROTEIN; LOW-FEMTOMOLE LEVEL; MASS-SPECTROMETRY; IN-VITRO AB In the post-genomic era of science, the field of proteomics promises the discovery of new molecular targets for therapy, biomarkers for early detection, and new endpoints for therapeutic efficacy and toxicity. Patient-specific targeted therapeutics with reduced toxicity and increased efficacy, the ultimate goal for rational drug development, can only be achieved if direct analyses of the tissue cells in the actual human malignancy are analyzed. To that end, technologies such as Laser Capture Microdissection (LCM), is providing unparalleled access to the purified diseased human cells directly from tissue specimens. However, limited availability of patient material is a challenge towards the development of new highly sensitive proteomic methodologies. Two-dimensional gel electrophoresis (2D-PAGE), still the mainstay of most proteomic analysis of disease, is being complemented, and in some instances replaced by new exciting approaches to multiparametric protein characterization. The use of rapid, high throughput mass spectrometric-based fingerprints of peptides and proteins may prove to be Valuable for new molecular classification of human tumors and disease stages. Coupled with LCM, high-density protein arrays, antibody arrays, and small molecular arrays, could have a substantial impact on proteomic profiling of human malignancies. Finally, detailed real-time knowledge about the states of intracellular signaling circuitry and pathways in the normal and malignant cells before, during and after thera py will yield invaluable information about mechanism of action and efficacy of existing and novel therapeutics for the treatment of human cancer. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Bethesda, MD 20892 USA. NR 82 TC 104 Z9 118 U1 0 U2 5 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD JAN-FEB PY 2001 VL 7 IS 1 BP 69 EP 78 PG 10 WC Oncology SC Oncology GA 406LV UT WOS:000167218400009 PM 11269650 ER PT S AU Umar, A Viner, JL Hawk, ET AF Umar, A Viner, JL Hawk, ET BE Osborne, MP TI The future of colon cancer prevention SO CANCER PREVENTION: MOLECULAR MECHANISMS TO CLINICAL APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th Strang International Cancer Prevention Conference CY NOV 10-11, 2000 CL STRANG CANC PREVENT CTR, NEW YORK, NEW YORK SP Int Soc Canc Chemoprevent, Amer Hlth Fdn, Cornell Univ, Weill Med Coll, Janssen Pharmaceut, Merck, Pharmacia HO STRANG CANC PREVENT CTR DE colorectal cancer (CRC) prevention; cyclooxygenase; COX-1/2; hyperplasia; dysplasia; aberrant crypt foci; adenomas; carcinoma; nonsteroidal anti-inflammatory drugs (NSAID); Celecoxib; difluoromethylornithine (DFMO); colonoscopy; sigmoidoscopy; microarray expression profiling; high-resolution chromoendoscopy; optical reflectance spectroscopy; optical coherence tomography; proteomics ID OPTICAL COHERENCE TOMOGRAPHY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FECAL-OCCULT-BLOOD; FAMILIAL ADENOMATOUS POLYPOSIS; LASER CAPTURE MICRODISSECTION; ABERRANT CRYPT FOCI; COLORECTAL-CANCER; ALPHA-DIFLUOROMETHYLORNITHINE; CYCLOOXYGENASE-2 INHIBITOR; ORNITHINE DECARBOXYLASE AB Chemoprevention science is in flux owing to rapid advances in postgenomic technology. We have witnessed enormous advances in the areas of early detection and molecular profiling of colorectal carcinogenesis; however, unique interpretive and technologic challenges persist. Neoplastic hallmarks must be iteratively tested and validated as markers of risk, targets for intervention, and/or markers of response in order to expedite the development of preventive interventions. In this review, we highlight several of the technologies that are revolutionizing our understanding of carcinogenesis and our approach to colorectal cancer prevention. C1 NCI, EPN, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA. RP Hawk, ET (reprint author), NCI, EPN, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 142 TC 26 Z9 26 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-350-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 952 BP 88 EP 108 PG 21 WC Oncology; Multidisciplinary Sciences SC Oncology; Science & Technology - Other Topics GA BT69J UT WOS:000173778200008 PM 11795446 ER PT S AU Brawley, OW Barnes, S Parnes, H AF Brawley, OW Barnes, S Parnes, H BE Osborne, MP TI The future of prostate cancer prevention SO CANCER PREVENTION: MOLECULAR MECHANISMS TO CLINICAL APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th Strang International Cancer Prevention Conference CY NOV 10-11, 2000 CL STRANG CANC PREVENT CTR, NEW YORK, NEW YORK SP Int Soc Canc Chemoprevent, Amer Hlth Fdn, Cornell Univ, Weill Med Coll, Janssen Pharmaceut, Merck, Pharmacia HO STRANG CANC PREVENT CTR DE prostate; prostate cancer; chemoprevention; clinical trials; 5-alpha-reductase inhibitor; vitamin A; vitamin D; vitamin E; selenium; alpha-tocopherol ID 5-ALPHA-REDUCTASE INHIBITOR; ALPHA-TOCOPHEROL; CONTROLLED TRIAL; BETA-CAROTENE; VITAMIN-D; FINASTERIDE; CHEMOPREVENTION; CARCINOMA; SELENIUM; GROWTH AB The dramatic international variation in prostate cancer mortality rates suggest an environmental influence. This combined with a building understanding of the genetic mechanisms of carcinogenesis encourages a search for ways to prevent it. Androgenic stimulation over a period of time has been suggested a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. Decreasing androgenic stimulation of the prostate with 5-alpha-reductase inhibitors such as finasteride has been shown to decrease prostate size and may prevent prostate cancer. A large, long-term clinical trial is underway using finasteride to determine if it can prevent prostate cancer. Results are expected in 2004. Epidemiologic and laboratory studies also suggest that high selenium and vitamin E intake lowers risk of prostate cancer. Recent serendipitous findings of two randomized clinical trials support the hypothesis that selenium and vitamin administration will decrease prostate cancer risk. A study to assess these compounds is beginning. Other promising, but less developed, interventions in chemoprevention of prostate cancer include vitamin D supplementation and diet modification. All will need to be rigorously evaluated before they can be advocated for prostate cancer prevention. C1 NCI, Off Director, Rockville, MD 20852 USA. NCI, Div Canc Prevent, Rockville, MD 20852 USA. RP Brawley, OW (reprint author), Emory Univ, Sch Med, Winship Canc Inst, 1365 Clifton Rd, Atlanta, GA 30322 USA. NR 45 TC 37 Z9 37 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-350-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 952 BP 145 EP 152 PG 8 WC Oncology; Multidisciplinary Sciences SC Oncology; Science & Technology - Other Topics GA BT69J UT WOS:000173778200013 PM 11795434 ER PT S AU Katdare, M Kopelovich, L Telang, N AF Katdare, M Kopelovich, L Telang, N BE Osborne, MP TI Chemopreventive agents inhibit aberrant proliferation of the aneuploid phenotype in a colon epithelial cell line established from Apc 1638N [+/-] mouse SO CANCER PREVENTION: MOLECULAR MECHANISMS TO CLINICAL APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th Strang International Cancer Prevention Conference CY NOV 10-11, 2000 CL STRANG CANC PREVENT CTR, NEW YORK, NEW YORK SP Int Soc Canc Chemoprevent, Amer Hlth Fdn, Cornell Univ, Weill Med Coll, Janssen Pharmaceut, Merck, Pharmacia HO STRANG CANC PREVENT CTR DE adenomatous polyposis coli (APC); colon epithelial cells; carcinogenic transformation; chemoprevention ID MIN MOUSE; INDUCTION; APOPTOSIS; PHYTOCHEMICALS; TRANSFORMATION; TUMORIGENESIS; EXPRESSION AB Loss of function of the adenomatous polyposis coli (APC) tumor suppressor gene predisposes for familial adenomatous polyposis (FAP) syndrome. The Ape gene knockout mice exhibit accelerated intestinal carcino-gensis modifiable by diverse pharmacological agents. Present experiments utilized the Ape[+/-] 1638N COL colon epithelial cell line (origin: histologically normal colon) as the model. Retinoid receptor modulator 9-cis-retinoic acid (9-cis-RA), ornithine decarboxylase inhibitor difluoromethyl ornithine (DFMO), and nonselective cyclooxygenase inhibitor sulindac (SUL) represented the chemopreventive test compounds. Population doubling, cell cycle progression, and anchorage-independent growth provided mechanistic end points for chemopreventive efficacy. Treatment of 1638N COL cells with 9-cis-RA, DFMO and SUL produced a dose-dependent cytostatic growth arrest by decreasing the number of population doublings and altering aneuploid G(0)/G(1):S+G(2)/M ratio. The clonally expanded 1638N-Cl-1 cells selected for anchorage-independent growth exhibited decreased anchorage-independent colony formation in response to treatment with the three test compounds. Susceptibility of preneoplastic 1638N COL cells to mechanistically distinct chemopreventive agents validates a unique epithelial cell culture model for FAP syndrome, and facilitates investigations on Apc regulated colon carcinogenesis and cancer Prevention. C1 Strang Canc Prevent Ctr, Chemoprevent Res Lab, New York, NY 10021 USA. NCI, Chemoprevent Branch, Bethesda, MD 20852 USA. RP Telang, N (reprint author), Rockefeller Univ, Strang Canc Res Lab, 1230 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [N01-CN-85141, P01-CA-29502-S1] NR 15 TC 4 Z9 4 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-350-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 952 BP 169 EP 174 PG 6 WC Oncology; Multidisciplinary Sciences SC Oncology; Science & Technology - Other Topics GA BT69J UT WOS:000173778200016 PM 11795437 ER PT J AU Pourquier, P Waltman, JL Urasaki, Y Loktionova, NA Pegg, AE Nitiss, JL Pommier, Y AF Pourquier, P Waltman, JL Urasaki, Y Loktionova, NA Pegg, AE Nitiss, JL Pommier, Y TI Topoisomerase I-mediated cytotoxicity of N-methyl-N '-nitro-N-nitrosoguanidine: Trapping of topoisomerase I by the O-6-methylguanine SO CANCER RESEARCH LA English DT Article ID DNA CLEAVABLE COMPLEXES; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CAMPTOTHECIN DERIVATIVES; PHOSPHODIESTER BOND; TRANSGENIC MICE; CELLS; ENZYME; SITE; CHEMOTHERAPY; REPLICATION AB Alkylating agents such as N methyl-N'-nitro-N-nitrosoguanidine (MNNG) are known to covalently link alkyl groups at the position 6 of guanines (O6hMG) in DNA. O-6-alkylguanine-DNA alkyltransferase (AGT) specifically removes the methyl group of the O6MG. Using purified human topoisomerase I (Top1), we found an 8-10-fold enhancement of Top1 cleavage complexes when O6MG is incorporated in oligonucleotides at the +1 position relative to a unique Top1 cleavage site. Top1 poisoning by O6MG is attributable to a decrease of the Top1-mediated DNA religation as well as an increase in the enzyme cleavage step. Increased cleavage is probably linked to a change in the hydrogen bonding pattern, such as in the ease of the 8-oxoguanine, whereas inhibition of religation could be attributed to altered base pairing, such as abasic sites or base mismatches, because incorporation of a 6-thioguanine did not affect Top1 activity. Top1-DNA covalent complexes are also induced in MNNG-treated CHO cells constitutively lacking the AGT enzyme. Conversely, no increase could be detected in CHO cells transfected with the wild-type human AGT. Moreover, we show that yeasts overexpressing the human Top1 are more sensitive to MNNG, whereas knock-out Top1 strain cells display some resistance to the drug. Altogether, these results suggest a role for Top1 poisoning by alkylated bases in the antiproliferative activity of alkylating agents as well as in the DNA lesions resulting from endogenous and carcinogenic DNA modifications. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E28, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Nitiss, John/E-9974-2010; OI Nitiss, John/0000-0002-1013-4972 FU NCI NIH HHS [CA21765, CA52814] NR 53 TC 71 Z9 76 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2001 VL 61 IS 1 BP 53 EP 58 PG 6 WC Oncology SC Oncology GA 392WR UT WOS:000166436000013 PM 11196197 ER PT J AU Kass, E Panicali, DL Mazzara, G Schlom, J Greiner, JW AF Kass, E Panicali, DL Mazzara, G Schlom, J Greiner, JW TI Granulocyte/macrophage-colony stimulating factor produced by recombinant avian poxviruses enriches the regional lymph nodes with antigen-presenting cells and acts as an immunoadjuvant SO CANCER RESEARCH LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; EPIDERMAL LANGERHANS CELLS; FACTOR RHGM-CSF; DENDRITIC CELLS; FOWLPOX VIRUS; MONOCLONAL-ANTIBODIES; RABIES GLYCOPROTEIN; IMMUNE-RESPONSES; CANCER VACCINES; TRANSGENIC MICE AB Recombinant avian poxviruses [fowlpox and canarypox (ALVAC)], restricted for replication in nonarian cell substrates and expressing granulocyte/macrophage-colony stimulating factor (avipox-GM-CSF), were evaluated for their ability to enrich an immunization site with antigen-presenting cells (APCs) and, in turn, function as biological vaccine adjuvants. Avipox-GM-CSF administered as a single s.c. injection significantly enhanced the percentage and absolute number of APCs in the regional lymph nodes that drain the injection site. Both the magnitude and duration of the cellular and phenotypic increases within the lymph nodes induced by the avipox-GM-CSF viruses were significantly (P < 0.05) greater than those measured in mice treated with four daily injections of recombinant GM-CSF protein. Temporal studies revealed that the APC enrichment of regional lymph nodes was sustained for 21-28 days after injection of the recombinant avipox virus expressing GM-CSF and, moreover, three injections of the recombinant virus could be given without any appreciable loss of in vivo bioactivity. Mice expressing human carcinoembryonic antigen (CEA) as a transgene (CEA.Tg) developed CEA-specific humoral and cell-mediated immunity after being immunized with avipox-CEA. The coadministration of recombinant avipox viruses expressing CEA and GM-CSF significantly enhanced CEA-specific host immunity with an accompanying immunotherapeutic response in tumor-bearing CEA.Tg mice. The optimal use of avipox-GM-CSF, in terms of dose and dose schedule, especially when used with different immunogens, remains to be determined. Nonetheless, the present findings demonstrate: (a) the effective delivery of GM-CSF to an immunization site using a recombinant avian poxvirus; (b) the compatibility of delivering an antigen and GMCSF in replication-defective viruses to enhance antigen-specific immunity; and (c) the combined use of recombinant avipox viruses expressing CEA and GM-CSF to generate antitumor immunity directed at a self tumor antigen. C1 NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Therion Biol Corp, Cambridge, MA 02142 USA. RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. NR 43 TC 102 Z9 104 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 JAN 1 PY 2001 VL 61 IS 1 BP 206 EP 214 PG 9 WC Oncology SC Oncology GA 392WR UT WOS:000166436000035 PM 11196163 ER PT J AU Olshan, AF Weissler, MC Watson, MA Bell, DA AF Olshan, AF Weissler, MC Watson, MA Bell, DA TI Risk of head and neck cancer and the alcohol dehydrogenase 3 genotype SO CARCINOGENESIS LA English DT Article ID ALCOHOL-DEHYDROGENASE-3 GENOTYPE; GENETIC-POLYMORPHISM; PHARYNGEAL CANCERS; ORAL CAVITY; ACETALDEHYDE; EXPRESSION; ADH AB Squamous cell carcinoma of the head and neck (SCCHN), including the oral cavity, pharynx and larynx, is an excellent tumor model to evaluate gene-environment interactions, including alcohol and alcohol-metabolizing enzymes such as alcohol dehydrogenase (ADH). We conducted a hospital-based case-control study including 182 cases with newly diagnosed SCCHN and 202 controls with non-neoplastic conditions of the head and neck that required surgery. The joint effects of lifetime alcohol use and the presence of the ADH3 'rapid' allele (ADH3*1) was evaluated in relation to the risk of SCCHN. Logistic regression was used to estimate the interaction between alcohol use and ADH3 genotype with adjustment for tobacco use, age, sex and race. The interaction was evaluated on both the multiplicative and additive scales. The risk of SCCHN was increased nearly 6-fold with consumption of 40 or more alcoholic beverages per week [odds ratio (OR) = 5.9; 95% confidence interval (CI) = 2.0-17.7; adjusted for age, sex, race and years of tobacco use]. We did not find any increase in risk for ADH3*1 homozygotes (OR = 0.9; CI = 0.4-1.9) or heterozygotes(OR = 0.8; CI = 0.4-1.7) relative to ADH3*2 homozygotes, There was no suggestion of an interaction between any alcohol use variable and the ADH3*1 genotype, For example, the interaction term, including the continuous variable average number of drinks per week and the ADH3 genotypes, was non-significant (P = 0.22). The study does not indicate an important role for the ADH3 *1 polymorphism in SCCHN, but larger numbers are needed to more precisely estimate the interaction, if any, with ADH3. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Surg, Div ENT Head & Neck Surg, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC USA. RP Olshan, AF (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, CP 7400, Chapel Hill, NC 27599 USA. NR 23 TC 50 Z9 50 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2001 VL 22 IS 1 BP 57 EP 61 DI 10.1093/carcin/22.1.57 PG 5 WC Oncology SC Oncology GA 396BW UT WOS:000166617300009 PM 11159741 ER PT J AU Fischer, SM Lee, M Lubet, RA AF Fischer, SM Lee, M Lubet, RA TI Difluoromethylornithine is effective as both a preventive and therapeutic agent against the development of UV carcinogenesis in SKH hairless mice SO CARCINOGENESIS LA English DT Article ID MOUSE SKIN CARCINOGENESIS; ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; POLYAMINE BIOSYNTHESIS; IRREVERSIBLE INHIBITOR; TUMOR PROMOTION; EPIDERMAL PROLIFERATION; COLON CANCER; DNA-DAMAGE; PHASE-II AB Targeting specific events associated with tumor development represents a rational approach to chemoprevention as well as therapeutic intervention. In this study the ability of difluoromethylornithine (DFMO) to inhibit UV-induced skin carcinogenesis when administered before or after the appearance of tumors was examined. SKH hairless mice were irradiated 3 times per week with 90 mJ/cm(2); this dose was increased by 10% weekly to a maximum of 175 mJ/cm(2). Mice supplied 0.4% DFMO in the drinking water continuously throughout the experiment had an average of 2.0 tumors/mouse (72% incidence) at 30 weeks while controls had an average of 8.2 tumors/mouse (100% incidence). DFMO started after 12 weeks of UV, a time prior to tumor appearance, yielded 3.6 tumors and 100% incidence at 30 weeks. Starting DFMO at 22 weeks, when an average of 2.5 tumors were present, caused regression of tumors for several weeks, followed by a slight rebound. The final tumor number at 30 weeks was 3.0 (96% incidence). Thus, DFMO has strong chemopreventive efficacy, as well as therapeutic activity, against UV-induced skin tumors. Histological and proliferative markers support this conclusion. C1 Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, Smithville, TX 78957 USA. NIH, Div Canc Prevent & Control, Bethesda, MD 20852 USA. RP Fischer, SM (reprint author), Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, POB 389,Park Rd 1C, Smithville, TX 78957 USA. FU NCI NIH HHS [CN-85145, CA-16672]; NIEHS NIH HHS [P30 ES07784] NR 42 TC 25 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2001 VL 22 IS 1 BP 83 EP 88 DI 10.1093/carcin/22.1.83 PG 6 WC Oncology SC Oncology GA 396BW UT WOS:000166617300013 PM 11159745 ER PT J AU Hulla, JE French, JE Dunnick, JK AF Hulla, JE French, JE Dunnick, JK TI Chromosome 11 allelotypes reflect a mechanism of chemical carcinogenesis in heterozygous p53-deficient mice SO CARCINOGENESIS LA English DT Article ID DNA DOUBLE-STRAND; MICRONUCLEATED ERYTHROCYTES; MITOTIC RECOMBINATION; P53; PHENOLPHTHALEIN; GENE; TUMORIGENESIS; TUMORS; MOUSE; DEFICIENT AB Mice heterozygous for a null p53 allele were administered three well-characterized carcinogens to learn more about mechanisms of carcinogenesis and to evaluate the p53-deficient mouse as a tool for identifying potential human carcinogens. Benzene-induced sarcomas, p-cresidine-induced bladder carcinomas and phenolphthalein-induced thymic lymphomas were allelotyped at the Trp53 locus and chromosome 11 simple sequence length polymorphic (SSLP) loci. Loss of Trp53 and loss of one copy of chromosome 11 occurred in each of 10 lymphomas examined and each of the eight sarcomas examined. Loss of Trp53 and loss of heterozygosity (LOH) at SSLP loci were sporadic in the bladder carcinomas. However, LOH was detected at two or more SSLP loci in six of the eight bladder tumors examined. Loss of one complete copy of chromosome 11 was implicated in three of the bladder tumors where LOH occurred at seven or more widely dispersed SSLP loci. Loss of one copy of chromosome 11 likely occurred through a p53-mediated selection process since Trp53 is located on mouse chromosome 11 and only one copy harbored a functional gene. The data suggest that loss occurred through a mechanism common among the three tumor types. Allelotype patterns of the maternal chromosome 11 were inconsistent with those expected from a nullizygous C57BL/6-Trp53 (N4)x inbred C57BL/6 cross which was reported for production of the mice under investigation. However, comparison with individual control tissues still allowed deduction of maternal chromosome loss. If the breeding protocols were carried out as described, the unexpected allelotype patterns observed in histologically normal tissues might be due to mitotic homologous recombination during embryogenesis. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ N Dakota, Sch Med, Grand Forks, ND 58202 USA. RP Hulla, JE (reprint author), NIEHS, NIH, 111 TW Alexander Dr,Box 12233,F1-05, Res Triangle Pk, NC 27709 USA. NR 40 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2001 VL 22 IS 1 BP 89 EP 98 DI 10.1093/carcin/22.1.89 PG 10 WC Oncology SC Oncology GA 396BW UT WOS:000166617300014 PM 11159746 ER PT J AU French, JE Lacks, GD Trempus, C Dunnick, JK Foley, J Mahler, J Tice, RR Tennant, RW AF French, JE Lacks, GD Trempus, C Dunnick, JK Foley, J Mahler, J Tice, RR Tennant, RW TI Loss of heterozygosity frequency at the Trp53 locus in p53-deficient (+/-) mouse tumors is carcinogen- and tissue-dependent SO CARCINOGENESIS LA English DT Article ID CELL-CYCLE CHECKPOINT; DNA DOUBLE-STRAND; P53 WILD-TYPE; INDUCED TUMORIGENESIS; V(D)J RECOMBINATION; TRANSGENE TARGET; LUNG-TUMORS; MICE; MUTATIONS; CANCER AB Mutagenic carcinogens rapidly induced tumors in the p53 haploinsufficient mouse. Heterozygous p53-deficient (+/-) mice were exposed to different mutagenic carcinogens to determine whether p53 loss of heterozygosity (LOH) was carcinogen- and tissue-dependent. For 26 weeks, C57BL/6 (N5) p53-deficient (+/-) male or female mice were exposed to p-cresidine, benzene or phenolphthalein, Tumors were examined first for loss of the wild-type p53 allele, p-cresidine induced p53 LOH in three of 13 bladder tumors, whereas hepatocellular tumors showed p53 LOH in carcinomas (2/2), but not in adenomas (0/3). Benzene induced p53 LOH in 13 of 16 tumors examined. Finally, phenolphthalein induced p53 LOH in all tumors analyzed (21/21), Analysis of the p-cresidine-induced bladder tumors by cold single-strand conformation polymorphism (SSCP) analysis of exon 4-9 amplicons failed to demonstrate polymorphisms associated with mutations in tumors that retained the p53 wild-type allele, p-cresidine induced a dose-related increase in lacI mutations in bladder DNA. In summary, these data demonstrate that loss of the wildtype allele occurred frequently in thymic lymphomas and sarcomas, but less frequently in carcinomas of the urinary bladder. In the bladder carcinomas other mechanisms may be operational. These might include (i) other mechanisms of p53 inactivation, (ii) inactivating mutations occurring outside exons 4-9 or (iii) p53 haploinsufficiency creating a condition that favors other critical genetic events which drive bladder carcinogenesis, as evidenced by the significant decrease in tumor latency. Understanding the mechanisms of p53 LOH and chemical carcinogenesis in this genetically altered model could lead to better models for prospective identification and understanding of potential human carcinogens and the role of the p53 tumor suppressor gene in different pathways of chemical carcinogenesis. C1 Lab Environm Mutagenesis & Carcinogenesis, Res Triangle Pk, NC 27709 USA. Integrated Syst Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP French, JE (reprint author), Lab Environm Mutagenesis & Carcinogenesis, Res Triangle Pk, NC 27709 USA. NR 56 TC 42 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2001 VL 22 IS 1 BP 99 EP 106 DI 10.1093/carcin/22.1.99 PG 8 WC Oncology SC Oncology GA 396BW UT WOS:000166617300015 PM 11159747 ER PT J AU Miller, AC Mog, S McKinney, L Luo, L Allen, J Xu, JQ Page, N AF Miller, AC Mog, S McKinney, L Luo, L Allen, J Xu, JQ Page, N TI Neoplastic transformation of human osteoblast cells to the tumorigenic phenotype by heavy metal-tungsten alloy particles: induction of genotoxic effects SO CARCINOGENESIS LA English DT Article ID MOUSE EMBRYO CELLS; FISSION-SPECTRUM NEUTRONS; HUMAN OSTEOSARCOMA CELLS; NICKEL CARCINOGENESIS; MOLECULAR MECHANISMS; EPITHELIAL-CELLS; COBALT METAL; MACROPHAGES; EXPOSURE; URANIUM AB Heavy metal-tungsten alloys (HMTAs) are dense heavy metal composite materials used primarily in military applications. HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%) and either cobalt (2-4%) or iron (2-4%) particles. Like the heavy metal depleted uranium (DU), the use of HMTAs in military munitions could result in their internalization in humans. Limited data exist, however, regarding the long-term health effects of internalized HMTAs in humans. We used an immortalized, nontumorigenic, human osteoblast-like cell line (HOS) to study the tumorigenic transforming potential of reconstituted mixtures of tungsten, nickel and cobalt (rWNiCo) and tungsten, nickel and iron (rWNiFe), We report the ability of rWNiCo and rWNiFe to transform immortalized HOS cells to the tumorigenic phenotype, These HMTA transformants are characterized by anchorage-independent growth, tumor formation in nude mice and high level expression of the K-ras oncogene, Cellular exposure to rWNiCo and rWNiFe resulted in 8.90 +/- 0.93- and 9.50 +/- 0.91-fold increases in transformation frequency, respectively, compared with the frequency in untreated cells. In comparison, an equivalent dose of crystalline NiS resulted in a 7.7 +/- 0.73-fold increase in transformation frequency. The inert metal tantalum oxide did not enhance HOS transformation frequency above untreated levels. The mechanism by which rWNiCo and rWNiFe induce cell transformation in vitro appears to involve, at least partially, direct damage to the genetic material, manifested as increased DNA breakage or chromosomal aberrations (i.e. micronuclei). This is the first report showing that HMTA mixtures of W, Ni and Co or Fe cause human cell transformation to the neoplastic phenotype, While additional studies are needed to determine if protracted HMTA exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized HMTAs exposure may be comparable with the risk from other biologically reactive and insoluble carcinogenic heavy metal compounds (e.g. nickel subsulfide and nickel oxide). C1 Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, Bethesda, MD 20889 USA. Armed Forces Radiobiol Res Inst, Dept Vet Sci, Bethesda, MD 20889 USA. NCI, Mol Oncol Branch, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. RP Page, N (reprint author), Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 47 TC 61 Z9 65 U1 4 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2001 VL 22 IS 1 BP 115 EP 125 DI 10.1093/carcin/22.1.115 PG 11 WC Oncology SC Oncology GA 396BW UT WOS:000166617300017 PM 11159749 ER PT J AU Kamitani, H Taniura, S Ikawa, H Watanabe, T Kelavkar, U Eling, TE AF Kamitani, H Taniura, S Ikawa, H Watanabe, T Kelavkar, U Eling, TE TI Expression of 15-lipoxygenase-1 is regulated by histone acetylation in human colorectal carcinoma SO CARCINOGENESIS LA English DT Article ID WAF1/CIP1 GENE PROMOTER; CELL-DIFFERENTIATION; EPITHELIAL-CELLS; SODIUM-BUTYRATE; MESSENGER-RNA; SP1 SITES; DEACETYLASE; INHIBITION; APOPTOSIS; CANCER AB 15-Lipoxygenase-1 (15-LO-1) is expressed at higher levels in human colorectal tumors compared with normal tissue. 15-LO-1 is expressed in cultured human colorectal cells, but only after treatment with sodium butyrate (NaBT), which also stimulates apoptosis and cell differentiation. We examined the regulation of 15-LO-1 in human tissue and the colorectal carcinoma cell lines Caco-2 and SW-480 by treatment with histone deacetylase (HDAC) inhibitors: NaBT, trichostatin A (TSA) and HC toxin, Northern and western analysis showed that expression of 15-LO-1 was up-regulated by these HDAC inhibitors. Furthermore, HDAC inhibitors stimulated promoter activity of the 15-LO-1 gene similar to 12- to 21-fold using the -331/-23 region of the 15-LO-1 promoter, as measured with a luciferase-15-LO-1 promoter-reporter system, suggesting that 15-LO-1 is regulated at the transcriptional level by HDAC inhibitors. Histone proteins in colorectal cells were acetylated after treatment with HDAC inhibitors. Histone acetylation was also measured in human colorectal tissue and a correlation was observed between increased histone acetylation and 15-LO-1 expression. Thus, regulation of 15-LO-1 expression in colorectal tissues appears to occur by a novel and new mechanism associated with histone acetylation. Moreover, these results suggest that 15-LO-1 is a marker that reflects histone acetylation in colorectal carcinoma. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Tottori Univ, Sch Med, Div Neurosurg, Inst Neurol Sci, Yonago, Tottori 6830805, Japan. Emory Univ, Div Renal, Atlanta, GA 30322 USA. Emory Univ, Glomerulonephritis Ctr, Atlanta, GA 30322 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 33 TC 43 Z9 43 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2001 VL 22 IS 1 BP 187 EP 191 DI 10.1093/carcin/22.1.187 PG 5 WC Oncology SC Oncology GA 396BW UT WOS:000166617300026 PM 11159758 ER PT S AU Johnson, WE Eizirik, E Lento, GM AF Johnson, WE Eizirik, E Lento, GM BE Gittleman, JL Funk, SM Macdonald, DW Wayne, RK TI The control, exploitation, and conservation of carnivores SO CARNIVORE CONSERVATION SE CONSERVATION BIOLOGY SERIES LA English DT Proceedings Paper CT Meeting on Carnivore Conservation CY NOV 20-21, 1998 CL ZOOL SOC LONDON, LONDON, ENGLAND HO ZOOL SOC LONDON C1 NCI, Lab Genom Diversit, Frederick, MD 21702 USA. RP Johnson, WE (reprint author), NCI, Lab Genom Diversit, Frederick, MD 21702 USA. RI Eizirik, Eduardo/K-8034-2012 OI Eizirik, Eduardo/0000-0002-9658-0999 NR 0 TC 15 Z9 15 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND SN 1363-3090 BN 0-521-66232-X J9 CONSERV BIOL SER PY 2001 VL 5 BP 196 EP 219 PG 24 WC Biodiversity Conservation; Zoology SC Biodiversity & Conservation; Zoology GA BS76S UT WOS:000171058900010 ER PT S AU Johnson, WE Eizirik, E Roelke-Parker, M O'Brien, SJ AF Johnson, WE Eizirik, E Roelke-Parker, M O'Brien, SJ BE Gittleman, JL Funk, SM Macdonald, DW Wayne, RK TI Applications of genetic concepts and molecular methods to carnivore conservation SO CARNIVORE CONSERVATION SE CONSERVATION BIOLOGY SERIES LA English DT Proceedings Paper CT Meeting on Carnivore Conservation CY NOV 20-21, 1998 CL ZOOL SOC LONDON, LONDON, ENGLAND HO ZOOL SOC LONDON C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Johnson, WE (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. RI Eizirik, Eduardo/K-8034-2012 OI Eizirik, Eduardo/0000-0002-9658-0999 NR 0 TC 13 Z9 14 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND SN 1363-3090 BN 0-521-66232-X J9 CONSERV BIOL SER PY 2001 VL 5 BP 335 EP 358 PG 24 WC Biodiversity Conservation; Zoology SC Biodiversity & Conservation; Zoology GA BS76S UT WOS:000171058900015 ER PT S AU Clarke, L Bucholz, RD Fuchs, H Kikinis, R Robb, RA Shahidi, R Vannier, MW AF Clarke, L Bucholz, RD Fuchs, H Kikinis, R Robb, RA Shahidi, R Vannier, MW BE Lemke, HU Vannier, MW Inamura, K Farman, AG Doi, K TI White Paper: Challenges and opportunities in computer-assisted interventions SO CARS 2001: COMPUTER ASSISTED RADIOLOGY AND SURGERY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 15th International Congress and Exhibition on Computer Assisted Radiology and Surgery CY JUN 27-30, 2001 CL BERLIN, GERMANY SP Amer Acad Oral & Maxillofacial Radiol, Bulgarian Assoc Radiol, British Inst Radiol, Czech Radiol Soc, Deutsch Gesell Biomed Tech eV, DRG, European Soc Engn & Med, Gesell Informatik, GMDS, Int Assoc Dento Maxillo Facial Radiol, IEEE, Informat Processing Med Imaging, Japanese Coll Radiol, Japan Radiol Soc, Japanese Soc Oral & Maxillofacial Radiol, Nederlandse Vereniging Radiol, ORG, Royal Coll Radiologists, Soc Francaise Radiol Med, Schweizer Gesell Med Radiol, Assoc Italiana Radiol Med, Chinese Soc Comp Assisted Radiol, SPIE, Slovak Radiol Soc, Techn Univ Berlin, World Acad Biomed Technologies C1 NIH, Bethesda, MD 20892 USA. RP Clarke, L (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50866-X J9 INT CONGR SER PY 2001 VL 1230 BP 198 EP 203 PG 6 WC Computer Science, Interdisciplinary Applications; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA BT72A UT WOS:000173844800034 ER EF