FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chan, WC Alizadeh, A Eisen, M Davis, RE Ma, C Sabet, H Tran, T Powell, JI Yang, L Greiner, TC Weisenburger, DD Armitage, JO Marti, GE Moores, T Hudson, J Lossos, I Warnke, R Levy, R Botstein, D Brown, PO Staudt, LM AF Chan, WC Alizadeh, A Eisen, M Davis, RE Ma, C Sabet, H Tran, T Powell, JI Yang, L Greiner, TC Weisenburger, DD Armitage, JO Marti, GE Moores, T Hudson, J Lossos, I Warnke, R Levy, R Botstein, D Brown, PO Staudt, LM TI Gene expression in large B-cell lymphoma using cDNA microarray technology. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Dept Microbiol, Omaha, NE 68105 USA. Univ Nebraska, Med Ctr, Dept Med, Omaha, NE 68105 USA. Natl Canc Inst, Metab Branch, Div Clin Sci, NIH, Bethesda, MD USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Stanford Univ, Sch Med, Stanford, CA USA. NIH, CIT, CBEL, Bioinformat & Mol Anal Sect, Bethesda, MD USA. US FDA, CBER, Bethesda, MD USA. Res Genet, Huntsville, AL USA. Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE 68105 USA. RI Alizadeh, Arash Ash/C-5594-2009 OI Alizadeh, Arash Ash/0000-0002-5153-5625 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3087 BP 698A EP 698A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303136 ER PT J AU Munshi, NC Desikan, RK Siegal, D Jagganath, S Vesole, D Terry, J Sternas, L Reynolds, C Barlogie, B Kwak, L AF Munshi, NC Desikan, RK Siegal, D Jagganath, S Vesole, D Terry, J Sternas, L Reynolds, C Barlogie, B Kwak, L TI Preliminary report of clinical efficacy of patient (pt) specific vaccination using purified idiotype protein in myeloma. SO BLOOD LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. NCI, Dept Expt Transplantat & Immunol, Bethesda, MD USA. SAIC, Frederick, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3112 BP 704A EP 704A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303161 ER PT J AU Childs, R Contentin, N Clave, E Bahceci, E Chernoff, A Linehan, M Epperson, D Jayasekera, D Eniafe, R Young, NS Barrett, AJ AF Childs, R Contentin, N Clave, E Bahceci, E Chernoff, A Linehan, M Epperson, D Jayasekera, D Eniafe, R Young, NS Barrett, AJ TI Sustained regression of metastatic renal cell carcinoma (RCC) following nonmyeloablative allogeneic peripheral blood stem cell transplantation: A new application of allogeneic immunotherapy. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3137 BP 710A EP 710A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303186 ER PT J AU Horwitz, ME Barrett, AJ Childs, R Miller, JA Leitman, SF Read, EJ Carter, CS Linton, GF Malech, HL AF Horwitz, ME Barrett, AJ Childs, R Miller, JA Leitman, SF Read, EJ Carter, CS Linton, GF Malech, HL TI Nonmyeloablative, T-cell depleted allogeneic peripheral blood stem cell (PBSC) transplantation for patients with chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Bethesda, MD USA. NHLBI, Bethesda, MD USA. Natl Inst Hlth, Dept Transfus Med, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3136 BP 710A EP 710A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303185 ER PT J AU Kreitman, RJ Wilson, WH Robbins, D Margulies, I Stetler-Stevenson, M Waldmann, TA Pastan, I AF Kreitman, RJ Wilson, WH Robbins, D Margulies, I Stetler-Stevenson, M Waldmann, TA Pastan, I TI Responses in refractory hairy cell leukemia to a recombinant immunotoxin SO BLOOD LA English DT Article ID PHASE-I TRIAL; A-CHAIN IMMUNOTOXIN; CHRONIC LYMPHOCYTIC-LEUKEMIA; FUSION TOXIN DAB486IL-2; PSEUDOMONAS-EXOTOXIN; MONOCLONAL-ANTIBODY; INTERLEUKIN-2 RECEPTOR; DIPHTHERIA-TOXIN; HEMATOLOGIC MALIGNANCIES; ANTI-B4-BLOCKED RICIN AB We report major responses in 4 of 4 patients with hairy cell leukemia (HCL) who have recently been treated on a phase I trial with the recombinant immunotoxin LMB-2, The immunotoxin, designed to target CD25(+) malignancies, is composed of the Fv portion of the anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of Pseudomonas exotoxin A, and has previously been called anti-Tac(Fv)-PE38, All 4 HCL patients were resistant to standard and salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and interferon alpha, and all patients responded to LMB-2 after a single cycle, One patient treated with 2 cycles had a complete remission (CR), with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR after treatment with CdA, minimal residual disease was detectable by flow cytometry of the bone marrow aspirate. This patient has not relapsed after 11 months. Three other patients had 98% to 99.8% reductions in malignant circulating cells. These results represent a proof of principal that targeted therapy with recombinant Fv-containing proteins can be clinically useful. LMB-2 may be an effective new therapy for patients with chemotherapy-resistant CD25+ HCL, This is a US government work. There are no restrictions on its use. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Clin Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37-4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 58 TC 109 Z9 117 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 BP 3340 EP 3348 PG 9 WC Hematology SC Hematology GA 254NG UT WOS:000083618600008 PM 10552943 ER PT J AU Miller, CP Liu, ZY Noguchi, CT Wojchowski, DM AF Miller, CP Liu, ZY Noguchi, CT Wojchowski, DM TI A minimal cytoplasmic subdomain of the erythropoietin receptor mediates erythroid and megakaryocytic cell development SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; TYROSINE PHOSPHORYLATION; FETAL LIVER; TRANSGENIC MICE; DEFICIENT MICE; SHC PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CYTOKINE-RECEPTOR; BONE-MARROW; BFU-E AB Signals provided by the erythropoietin (Epo) receptor are essential for the development of red blood cells, and at least 15 distinct signaling factors are now known to assemble within activated Epo receptor complexes. Despite this intriguing complexity, recent investigations in cell lines and retrovirally transduced murine fetal liver cells suggest that most of these factors and signals may be functionally nonessential. To test this hypothesis in erythroid progenitor cells derived from adult tissues, a truncated Epo receptor chimera (EE372) was expressed in transgenic mice using a GATA-1 gene-derived vector, and its capacity to support colony-forming unit-erythroid proliferation and development was analyzed. Expression at physiological levels was confirmed in erythroid progenitor cells expanded ex vivo, and this EE372 chimera was observed to support mitogenesis and red blood cell development at wild-type efficiencies both independently and in synergy with c-Kit. In addition, the activity of this minimal chimera in supporting megakaryocyte development was tested and, remarkably, was observed to approximate that of the endogenous receptor for thrombopoietin. Thus, the box 1 and 2 cytoplasmic subdomains of the Epo receptor, together with a tyrosine 343 site (each retained within EE372), appear to provide all of the signals necessary for the development of committed progenitor cells within both the erythroid and megakaryocytic lineages. (C) 1999 by The American Society of Hematology. C1 Penn State Univ, Genet Program, University Pk, PA 16802 USA. Penn State Univ, Program Cell & Dev Biol, University Pk, PA 16802 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. RP Wojchowski, DM (reprint author), Penn State Univ, Genet Program, 115 Henning Bldg, University Pk, PA 16802 USA. FU NIDDK NIH HHS [DK40242] NR 54 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 BP 3381 EP 3387 PG 7 WC Hematology SC Hematology GA 254NG UT WOS:000083618600012 PM 10552947 ER PT J AU de Bruin, M Miyake, K Litman, T Robey, R Bates, SE AF de Bruin, M Miyake, K Litman, T Robey, R Bates, SE TI Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR SO CANCER LETTERS LA English DT Article DE GF120918; P-glycoprotein; multidrug resistance; MXR; mitoxantrone ID MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; DRUG-SENSITIVITY; PROTEIN MRP; INHIBITOR GG918; CANCER-CELLS; GENE; OVEREXPRESSION; ACCUMULATION; CALCEIN AB The emergence of several newly identified members of the ABC transporter family has necessitated the development of antagonists that are able to inhibit more than one transporter. We assessed the ability of the chemosensitizer GF120918 to function as a multispecific antagonist using cytotoxicity assays, rhodamine and calcein efflux assays, and confocal microscopy in cell lines expressing different multidrug resistance transporters. At a concentration of 1 mu M in cytotoxicity assays, GF120918 was able to sensitize both S1-B1-20, a subline expressing P-glycoprotein (Pgp), and S1-M1-80, a subline expressing a newly identified mitoxantrone transporter, MXR, GF120918 was ineffective in sensitizing MRP-overexpressing MCF-7 VP-16 cells to etoposide as determined by cytotoxicity studies. In how cytometry experiments, rhodamine 123 efflux in S1-B1-20 cells was decreased at GF120918 concentrations as low as 25-50 nM, with 250 nM giving complete inhibition of rhodamine efflux. Complete inhibition of rhodamine efflux in mitoxantrone-resistant S1-M1-80 cells required 10 mu M. Examination of intracellular mitoxantrone accumulation by confocal microscopy confirmed higher levels of mitoxantrone in S1-B1-20 and S1-M1-80 cells when incubated in the presence of GF120918 than when incubated with mitoxantrone alone. Thus, GF120918 appears to fit the paradigm of a multispecific blocker and is able to block rhodamine and mitoxantrone efflux by the newly identified mitoxantrone transporter. Further studies of this compound should be pursued to determine its feasibility for use in the clinic. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Dev Therapeut Dept, Med Branch, Div Clin Sci,NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 29 TC 210 Z9 212 U1 2 U2 8 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 NOV 15 PY 1999 VL 146 IS 2 BP 117 EP 126 DI 10.1016/S0304-3835(99)00182-2 PG 10 WC Oncology SC Oncology GA 256WB UT WOS:000083748500001 PM 10656616 ER PT J AU Lemmer, ER Gelderblom, WCA Shephard, EG Abel, S Seymour, BL Cruse, JP Kirsch, RE Marasas, WFO Hall, PDM AF Lemmer, ER Gelderblom, WCA Shephard, EG Abel, S Seymour, BL Cruse, JP Kirsch, RE Marasas, WFO Hall, PDM TI The effects of dietary iron overload on fumonisin B(1)-induced cancer promotion in the rat liver SO CANCER LETTERS LA English DT Article DE fumonisin B(1); iron overload; rat liver; hepatic lipid peroxidation; cancer initiation and promotion ID OXIDATIVE DNA-DAMAGE; HEPATOCELLULAR-CARCINOMA; FUSARIUM-MONILIFORME; CELL-PROLIFERATION; LIPID-PEROXIDATION; ESOPHAGEAL CANCER; RISK FACTOR; B-1; MYCOTOXINS; CORN AB The present study was performed to determine whether excess hepatic iron modulates the cancer-initiating and promoting properties of FB(1). Thirty-eight male F344 rats were divided into four dietary treatment groups: (i) control diet (AIN, n = 8); (ii) FB(1) 250 mg/kg diet (FB(1), n = 10); (iii) 1-2% carbonyl iron (CI, n = 10); or (iv) FB(1) plus iron loading (FB(1)/CI, n = 10) for 5 weeks (2 x 2 factorial design). Hepatic iron concentrations in iron-loaded animals at 5 weeks were 444 +/- 56 (CI) and 479 +/- 80 mu mol/g dry weight (FB(1)/CI) (mean +/- SEM). AU the FB(1)-fed rats, in the presence or absence of CI, developed a toxic hepatitis with a 4-fold rise in serum alanine transaminase (ALT) levels. FB(1) appeared to augment iron-induced hepatic lipid peroxidation, as measured by the generation of thiobarbituric acid reacting substances (TBARS) in liver homogenates (P < 0.0001). Morphometric analysis showed that FB(1) caused a significantly greater mean +/- SEM number of 'enzyme-altered' foci and nodules per cm(2) (5.34 +/- 1.42 vs. 1.50 +/- 0.52, P < 0.05), as well as a greater area (4b) of liver occupied by foci and nodules (0.33 +/- 0.12% vs. 0.05 +/- 0.03%, P < 0.001), compared with FB(1)/CI. The addition of FB(1) to dietary iron loading caused a shift in distribution of iron from hepatocytes to Kupffer cells, probably due to phagocytosis of necrotic iron-loaded hepatocytes. In conclusion, (i) FB(1) appears to cause toxicity in the liver independently from effects on lipid peroxidation; (ii) FB(1) has a potentiating effect on iron-induced lipid peroxidation; and (iii) dietary iron loading appears to protect against the cancer promoting properties of FB(1), possibly due to a stimulatory effect of iron on hepatocyte regeneration. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Cape Town, MRC UCT Liver Res Ctr, ZA-7925 Cape Town, South Africa. Programme Mycotoxins & Expt Carcinogenesis, Tygerberg, South Africa. Univ Cape Town, Dept Anat Pathol, ZA-7925 Cape Town, South Africa. Flinders Univ S Australia, Flinders Med Ctr, Dept Anat Pathol, Flinders, Australia. RP Lemmer, ER (reprint author), NCI, Expt Carcinogenesis Lab, Bldg 37,Rm 3C25, Bethesda, MD 20892 USA. EM eric_lemmer@nih.gov NR 45 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 15 PY 1999 VL 146 IS 2 BP 207 EP 215 DI 10.1016/S0304-3835(99)00274-8 PG 9 WC Oncology SC Oncology GA 256WB UT WOS:000083748500013 PM 10656628 ER PT J AU Qin, LX Tang, ZY Sham, JST Ma, ZC Ye, SL Zhou, XD Wu, ZQ Trent, JM Guan, XY AF Qin, LX Tang, ZY Sham, JST Ma, ZC Ye, SL Zhou, XD Wu, ZQ Trent, JM Guan, XY TI The association of chromosome 8p deletion and tumor metastasis in human hepatocellular carcinoma SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; GENETIC ALTERATIONS; BREAST-CANCER; ABNORMALITIES; LOCALIZATION; PATTERN; LOSSES AB To understand the genetic mechanisms underlying the progression of hepatocellular carcinoma (HCC) metastasis, differences of genomic alterations between 10 pairs of primary HCC tumors and their matched metastatic lesions were analyzed by comparative genomic hybridization. Several chromosomal alterations including loss of 8p, 4q, 17p, and 19p, gain of 5p and high-level amplification of 1q12-q22 were detected in two or more cases. The most significant finding is the loss of 8p which was detected in 8 metastatic tumors but only in 3 corresponding primary tumors (P = 0.03), This result suggests that the deletion of chromosome 8p might contribute to the development of HCC metastasis, Another interesting result is the detection of a minimum high-level amplification region at 1q12-q22 in HCC, This result provides a candidate amplification region in HCC for further study to identify amplified oncogenes related to the development or progression of HCC, Finally, this study provides a practicable model to detect specific genetic alterations related to the tumor metastasis through comparing the primary tumor and its corresponding metastatic lesion using comparative genomic hybridization technique. C1 Univ Hong Kong, Queen Mary Hosp, Dept Clin Oncol, Hong Kong, Peoples R China. Shanghai Med Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200032, Peoples R China. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. RP Guan, XY (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Clin Oncol, Room 118,Professorial Block,Pokfulam Rd, Hong Kong, Peoples R China. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 23 TC 92 Z9 114 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1999 VL 59 IS 22 BP 5662 EP 5665 PG 4 WC Oncology SC Oncology GA 258RQ UT WOS:000083853300005 PM 10582679 ER PT J AU Pasche, B Kolachana, P Nafa, K Satagopan, J Chen, YG Lo, RS Brener, D Yang, D Kirstein, L Oddoux, C Ostrer, H Vineis, P Varesco, L Jhanwar, S Luzzatto, L Massague, J Offit, K AF Pasche, B Kolachana, P Nafa, K Satagopan, J Chen, YG Lo, RS Brener, D Yang, D Kirstein, L Oddoux, C Ostrer, H Vineis, P Varesco, L Jhanwar, S Luzzatto, L Massague, J Offit, K TI T beta R-I(6A) is a candidate tumor susceptibility allele SO CANCER RESEARCH LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; FACTOR-BETA RECEPTOR; COLON-CARCINOMA CELLS; TGF-BETA; II RECEPTOR; MICROSATELLITE INSTABILITY; SUPPRESSOR GENE; BREAST-CANCER; DPC4 GENE; MUTATION AB We have previously described a type I transforming growth factor (TGF)-beta receptor (T beta R-I) polymorphic allele, T beta R-I(6A), that has a deletion of three alanines from a nine-alanine stretch. We observed a higher than expected number of T beta R-I(6A) homozygotes among tumor and nontumor DNA from patients with a diagnosis of cancer. To test the hypothesis that T beta R-I(6A) homozygosity is associated with cancer, we performed a case-central study in patients with a diagnosis of cancer and matched healthy individuals with no history of cancer and who were identical in their gender and their geographical and ethnic background to determine the relative germ-line frequencies of this allele. We round nine T beta R-I(6A) homozygotes among 851 patients with canter. In comparison, there were no T beta R-I(6A) homozygotes among 735 healthy volunteers (P < 0.01). We also observed an excess of T beta R-E(6A) heterozygotes in cancer cases compared to controls (14.6% versus 10.6%; P = 0.02, Fisher's exact test). A subset analysis revealed that 4 of 112 patients with colorectal cancer were T beta R-I(6A) homozygotes (P < 0.01). Using mink lung epithelial cell lines devoid of T beta R-I, we established stably transfected T beta R-I and T beta R-I(6A) cell lines. We found that, compared to T beta R-I, T beta R-I(6A) was impaired as a mediator of TGF-beta antiproliferative signals, We conclude that T beta R-I(6A) acts as a tumor susceptibility allele that may contribute to the development of cancer, especially colon cancer, by means of reduced TGF-beta-mediated growth inhibition. C1 Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Human Genet, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. NYU, Med Ctr, Dept Pediat, Human Genet Program, New York, NY 10016 USA. Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA. Univ Turin, Dipartimento Sci Biomed & Oncol Umana, Canc Epidemiol Unit, I-10126 Turin, Italy. CPO Piemonte, I-10126 Turin, Italy. Natl Canc Inst, Expt Oncol Lab, I-16132 Genoa, Italy. RP Massague, J (reprint author), Mem Sloan Kettering Canc Ctr, Cell Biol Program, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [CA43610, K12 CA01712-04, CA08748] NR 31 TC 123 Z9 132 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1999 VL 59 IS 22 BP 5678 EP 5682 PG 5 WC Oncology SC Oncology GA 258RQ UT WOS:000083853300009 PM 10582683 ER PT J AU Lombardi, DP Geradts, J Foley, JF Chiao, C Lamb, PW Barrett, JC AF Lombardi, DP Geradts, J Foley, JF Chiao, C Lamb, PW Barrett, JC TI Loss of KAI1 expression in the progression of colorectal cancer SO CANCER RESEARCH LA English DT Article ID METASTASIS SUPPRESSOR GENE; LYMPH-NODE; KAI1/CD82 EXPRESSION; MISMATCH REPAIR; CELL-LINES; TRANSMEMBRANE-4 SUPERFAMILY; MICROSATELLITE INSTABILITY; ADENOMATOUS POLYPOSIS; DECREASED EXPRESSION; SYNCYTIUM FORMATION AB The transmembrane 4 superfamily member KAL1 (CD82) has been shown to inhibit pulmonary metastases in experimental metastasis models of prostate cancer and melanoma, KAI1 expression is decreased in the progression of common solid epithelial tumors of adulthood, including lung, prostate, breast, esophageal, gastric, pancreatic, and bladder cancers. The purpose of our study was to investigate KAI1 expression in the progression of human colorectal cancer. We first analyzed 20 colorectal cancer cell lines by immunoblot techniques. KAI1 was expressed heterogeneously, with the tumor cell Lines having a more complex degree of glycosylation compared with that of the normal colonic tissue. KAI1 was highly expressed in the primary SW480 colon cancer cell line but was down-regulated 15-fold in the matched metastatic SW620 cell line. We also investigated KAI1 protein expression by immunohistochemistry in tissues from 84 patients with colorectal cancer. Each tissue section was assigned a KAI1 mean score (KMS) from 0 to 300 based on the product of the percentage of cells that stained for KAI1 and the intensity of the stain (1, 2, or 3). In 84 patients with colorectal cancer, KAI1 was expressed at high levels in normal colonic mucosa (KMS 226) but was expressed at lower levels in the primary tumors (KMS 65; P < 0.0001), In a subset of 12 patients with stage TV metastatic disease, we observed a progressive down-regulation of KAtI1, from the normal adjacent colonic mucosa (KMS 193) to the primary tumor (KMS 72; P = 0.0001) to the liver metastasis (KMS 25; tumor compared with metastasis, P = 0.0135). We found no correlation between toss of KAI1 expression and stage of disease. In 10 patients, we also noted loss of KAI1 expression in the transition from normal colonic mucosa (KR IS 237) to adenoma (KMS 174) to carcinoma (KMS 62; P < 0.0167 for all three comparisons). We conclude that the down-regulation of KAI1 occurs early in the progression of colorectal cancer. C1 Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Pathol & Bacteriol, Oxford OX3 9DU, England. RP Barrett, JC (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, POB 12233,MD C2-15, Res Triangle Pk, NC 27709 USA. FU NCRR NIH HHS [3 M01 RR00046-38S2] NR 61 TC 119 Z9 135 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1999 VL 59 IS 22 BP 5724 EP 5731 PG 8 WC Oncology SC Oncology GA 258RQ UT WOS:000083853300017 PM 10582691 ER PT J AU Hodge, JW Sabzevari, H Yafal, AG Gritz, L Lorenz, MGO Schlom, J AF Hodge, JW Sabzevari, H Yafal, AG Gritz, L Lorenz, MGO Schlom, J TI A triad of costimulatory molecules synergize to amplify T-cell activation SO CANCER RESEARCH LA English DT Article ID RECOMBINANT VACCINIA VIRUS; TUMOR-IMMUNITY; ANTITUMOR IMMUNITY; ICAM-1; LYMPHOCYTES; CD4(+); LFA-3; B7-1; EXPRESSION; NAIVE AB The activation of a T cell has been shown to require two signals via molecules present on professional antigen-presenting cells: signal 1, via a peptide/MHC complex; and signal, via a costimulatory molecule. Here, the role of three costimulatory molecules in the activation of T cells was examined. Poxvirus (vaccinia and avipox) vectors ere used because of their ability to efficiently express multiple genes. Murine cells provided with signal 1 and infected with either recombinant vaccinia or avipox vectors containing a TRIad of COstimulatory Molecules (B7-1/ICAM-1/LFA-3, designated TRICOM) induced the activation of T cells to a far greater extent than cells infected with any one or two costimulatory molecules. Despite this T-cell "hyperstimulation" using TRICOM vectors, no evidence of apoptosis above that seen using the B7-1 vector was observed. Results using the TRICOm vectors were most dramatic under conditions of either low levels of first signal or low stimulator cell:l-cell ratios. Experiments using a four-gene construct also showed that TRICOm recombinants can enhance antigen-specific T-cell responses in vivo. These studies thus demonstrate for the first time the ability of vectors to introduce three costimulatory molecules into cells, thereby activating both CD4(+) and CD8(+) T-cell populations to levels greater than those achieved with the use of only one or two costimulatory molecules. This new threshold of T-cell activation has broad implications in vaccine design and development. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Therion Biol Corp, Cambridge, MA 02142 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Room 8B07, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 30 TC 208 Z9 212 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1999 VL 59 IS 22 BP 5800 EP 5807 PG 8 WC Oncology SC Oncology GA 258RQ UT WOS:000083853300028 PM 10582702 ER PT J AU Chadwick, BP Gill, S Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Slaugenhaupt, SA AF Chadwick, BP Gill, S Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Slaugenhaupt, SA TI Cloning, genomic organization and expression of a putative human transmembrane protein related to the Caenorhabditis elegans M01F1.4 gene SO GENE LA English DT Article DE 9q31; Ashkenazi Jewish; neuropathy; peripheral nervous system; recessive ID FAMILIAL DYSAUTONOMIA; EXON AMPLIFICATION; CHROMOSOME; STRATEGY AB A novel human transcript CG-2 (C9ORF5), was isolated from the familial dysautonomia candidate region on 9q31 using a combination of cDNA selection and exon trapping. CG-2 was detected as a relatively abundant 8 kb transcript in all adult and fetal tissues with the exception of adult thymus, Genomic analysis of CG-2 identified 18 exons that span more than 110 kb, The gene encodes a 911-amino-acid protein with a predicted molecular weight of 101 kDa and a hypothetical pI of 9.03. Sequence analysis of CG-2 indicates that it is likely to encode a transmembrane protein. Here, we assess CG-2 as a candidate for familial dysautonomia, (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Unit Dev Mol Biol & Genet Engn, IL-91120 Jerusalem, Israel. NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Slaugenhaupt, SA (reprint author), HIM Bldg Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Brownstein, Michael/B-8609-2009; Pinkett, Heather/M-9235-2014 FU NINDS NIH HHS [NS36326] NR 17 TC 5 Z9 6 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 NOV 15 PY 1999 VL 240 IS 1 BP 67 EP 73 DI 10.1016/S0378-1119(99)00432-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 258RR UT WOS:000083853400007 PM 10564813 ER PT J AU Kirschner, LS Taymans, SE Pack, S Pak, E Pike, BL Chandrasekharappa, SC Zhuang, ZP Stratakis, CA AF Kirschner, LS Taymans, SE Pack, S Pak, E Pike, BL Chandrasekharappa, SC Zhuang, ZP Stratakis, CA TI Genomic mapping of chromosomal region 2p15-p21 (D2S378-D2S391): Integration of Genemap'98 within a framework of yeast and bacterial artificial chromosomes SO GENOMICS LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Endocrine-Society CY JUN 23-27, 1998 CL NEW ORLEANS, LOUISIANA SP Endocrine Soc ID NONPOLYPOSIS COLORECTAL-CANCER; LUTEINIZING-HORMONE RECEPTOR; RADIATION HYBRID MAP; COPY NUMBER CHANGES; MALATTIA LEVENTINESE; DNA-REPAIR; GENE; HYBRIDIZATION; MUTATION; LOCALIZATION AB The region of chromosome 2 encompassed by the polymorphic markers D2S378 (centromeric) and D2S391 (telomeric) spans an approximately 10-cM distance in cytogenetic bands 2p15-p21. This area is frequently involved in cytogenetic alterations in human cancers. It also harbors the genes for several genetic disorders, including Type I hereditary nonpolyposis colorectal cancer (HNPCC), familial male precocious puberty (FMPP), Carney complex (CNC), Doyne's honeycomb retinal dystrophy (DHRD), and one form of familial dyslexia (DYX-3). Only a handful of known genes have been mapped to 2p16. These include MSH2, which is responsible for HNPCC, FSHR, the gene responsible for FMPP, EFEMP-1, the gene mutated in DHRD, GTBP, a DNA repair gene, and SPTBN1, nonerythryocytic beta-spectrin. The genes for CNC and DYX-3 remain unknown, due to lack of a contig of this region and its underrepresentation in the existing maps. This report presents a yeast- and bacterial-artificial chromosome (YAC and BAG, respectively) resource for the construction of a sequence-ready map of 2p15-p21 between the markers D2S378 and D2S391 at the centromeric and telomeric ends, respectively. The recently published Genemap'98 lists 146 expressed sequence tags (ESTs) in this region; we have used our YAC-BAC map to place each of these ESTs within a framework of 40 known and 3 newly cloned polymorphic markers and 37 new sequence-tagged sites. This map provides an integration of genetic, radiation hy-brid, and physical mapping information for the region corresponding to cytogenetic bands 2p15-p21 and is expected to facilitate the identification of disease genes from the area, (C) 1999 Academic Press. C1 NICHD, Unit Genet & Endocrinol, DEB, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Kirschner, LS (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 51 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1999 VL 62 IS 1 BP 21 EP 33 DI 10.1006/geno.1999.5957 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 264KB UT WOS:000084178800003 PM 10585764 ER PT J AU Lorenzi, MV Castagnino, P Aaronson, DC Lieb, DC Lee, CC Keck, CL Popescu, NC Miki, T AF Lorenzi, MV Castagnino, P Aaronson, DC Lieb, DC Lee, CC Keck, CL Popescu, NC Miki, T TI Human FRAG1 encodes a novel membrane-spanning protein that localizes to chromosome 11p15.5, a region of frequent loss of heterozygosity in cancer SO GENOMICS LA English DT Article ID BECKWITH-WIEDEMANN SYNDROME; HUMAN GENOME; GENE; GROWTH; RECEPTOR; CLONING; FUSION; TRANSLOCATION; REARRANGEMENT; ACTIVATION AB We have previously identified a chromosomal rearrangement between fibroblast growth factor receptor 2 (FGFR2) and a novel gene, FRAGI, in a rodent model of osteosarcoma. To assess the potential role of FRAGI in disease further, we have isolated cDNA and genomic clones of human FRAGI. Sequence analysis of the cDNA revealed the presence of an insertion not contained in the original FRAG1 sequence. This insertion in human FRAGI encoded a region highly homologous to and immediately following the first 55 amino acids of the protein, indicating the presence of a repetitive domain within FRAG1;1, designated the FRAG1 homology (FH) domain. Analysis of FRAG1 gene structure revealed that the FH domains were encoded by tandem duplicated exons. Database searches identified several transmembrane proteins displaying homology to the FH domain of FRAG1. In addition, hydropathy analysis predicted FRAGI to encode an integral membrane protein with multiple membrane-spanning segments. FRAGI mRNA was ubiquitously expressed in human adult tissues and several tumor cell lines at varying levels of abundance. Human FRAGI was mapped by fluorescence in situ hybridization and radiation hybrid analysis to chromosome 11 at band p15.5, a region implicated in Beckwith-Wiedemann syndrome and a region of frequent loss of heterozygosity in multiple tumor types. These results suggest that FRAGI may be a useful candidate gene for genetic disorders associated with alterations at 11p15.5. (C) 1999 Academic Press. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Lorenzi, MV (reprint author), AstraZeneca Pharmaceut, POB 15437,1800 Concord Pike,CRDL127, Wilmington, DE 19850 USA. NR 35 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 15 PY 1999 VL 62 IS 1 BP 59 EP 66 DI 10.1006/geno.1999.5980 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 264KB UT WOS:000084178800007 PM 10585768 ER PT J AU Toth, ZE Gallatz, K Fodor, M Palkovits, M AF Toth, ZE Gallatz, K Fodor, M Palkovits, M TI Decussations of the descending paraventricular pathways to the brainstem and spinal cord autonomic centers SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE double immunohistochemistry; Phaseolus vulgaris-leucoagglutinin; nucleus of the solitary tract; rat; ventrolateral medulla ID ROSTRAL VENTROLATERAL MEDULLA; PHASEOLUS-VULGARIS-LEUKOAGGLUTININ; SYMPATHETIC PREGANGLIONIC NEURONS; HYPOTHALAMIC NUCLEUS; BARRINGTONS NUCLEUS; RAT-BRAIN; PROJECTIONS; ORGANIZATION; CONNECTIONS; SYSTEM AB Decussations of descending fibers of the hypothalamic paraventricular nucleus (PVN) were investigated by using Phaseolus vulgaris-leucoagglutinin (PHA-L) in intact and brainstem-operated rats. Fibers descend ipsilaterally along the brainstem and spinal cord and decussate at four levels: 1) Supramamillary decussations (SM). PVN fibers reach this area through the lateral hypothalamus and along the third ventricle in the dorsal hypothalamus. In the posterior hypothalamus some fibers crossover in the SM and terminate in the supramamillary region bilaterally. 2) Pontine tegmentum. PVN fibers run in the lateral part of the tegmentum arching to the basis of the pens. Some fibers crossover under the fourth ventricle, The locus ceruleus and the Barrington's nucleus receive bilateral innervation with ipsilateral dominance. 3) Commissural part of the nucleus of the solitary tract (NTS). The major crossover of PVN fibers is found here. The decussated fibers form a dense network: here, and loop rostralward to innervate the entire NTS, A midsagittal knife-cut through the NTS eliminated paraventricular-fibers on the contralateral side. Synaptic contacts between PHA-L-labeled boutons and tyrozine hydroxilase-positive neurons were verified in the NTS. The caudal ventrolateral medulla also receives bilateral innervation. 4) Lamina X of the thoracic spinal cord. Paraventricular fibers enter the lateral funiculus ipsilaterally and innervate the intermediolateral cell column (IML). Some fibers cross the midline ventral and dorsal to the central canal running to the contralateral IML, at the level of the decussation. Our results demonstrated that paraventricular projections form a continuous descending pathway on their side of origin, and provide crossover fibers which may terminate segmentally without forming long tracts after crossover. (C) 1999 Wiley-Liss, Inc. C1 Semmelweis Univ Med, Sch Med, Neuromorphol Lab, Budapest, Hungary. RP Toth, ZE (reprint author), NIMH, Genet Sect, NIH, Bldg 36-3D06, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 43 TC 51 Z9 52 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 15 PY 1999 VL 414 IS 2 BP 255 EP 266 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 246WY UT WOS:000083188900008 PM 10516595 ER PT J AU Diaw, L Siwarski, D Coleman, A Kim, J Jones, GM Dighiero, G Huppi, K AF Diaw, L Siwarski, D Coleman, A Kim, J Jones, GM Dighiero, G Huppi, K TI Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE V(D)J rearrangement; plasmacytoma; allelic exclusion; polyreactivity; V gene usage ID B-CELL DIFFERENTIATION; HEAVY-CHAIN; LYMPHOMA SHOWS; NATURAL AUTOANTIBODIES; FEEDBACK INHIBITION; ANTIBODY DIVERSITY; ALLELIC EXCLUSION; BURKITTS-LYMPHOMA; ANTIGEN RECEPTORS; MULTIPLE-MYELOMA AB The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructo-furanans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (V-L) and heavy (V-H) variable region genes to express a characteristic monoclonal antibody. In this study, we have examined by enzyme-linked immunosorbent assay five antibodies secreted by silicone-induced mouse plasmacytomas using a broader panel of antigens including actin, myosin, tubulin, single-stranded DNA, and double-stranded DNA. We have determined the Ig heavy and light chain V gene usage in these same plasmacytomas at the DNA and RNA level. Our studies reveal: (a) antibodies secreted by plasmacytomas bind to different antigens in a manner similar to that observed for natural autoantibodies; (b) the expressed Ig heavy genes are restricted in V gene usage to the V-H-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both kappa and lambda light chain genes. These results suggest that plasmacytomas use a restricted population of B cells that may still be undergoing rearrangement, thereby bypassing the allelic exclusion normally associated with expression of antibody genes. C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Lab Immunohematol & Immunopathol, F-75724 Paris 15, France. RP Huppi, K (reprint author), NCI, Genet Lab, NIH, Bldg 37,Rm 2B-21, Bethesda, MD 20892 USA. NR 67 TC 15 Z9 16 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 15 PY 1999 VL 190 IS 10 BP 1405 EP 1415 DI 10.1084/jem.190.10.1405 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 256GY UT WOS:000083718600006 PM 10562316 ER PT J AU Sommers, CL Rabin, RL Grinberg, A Tsay, HC Farber, J Love, PE AF Sommers, CL Rabin, RL Grinberg, A Tsay, HC Farber, J Love, PE TI A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE transgenic mice; signal transduction; T cell receptors; phospholipase C; T cells ID X-LINKED AGAMMAGLOBULINEMIA; PLECKSTRIN HOMOLOGY DOMAIN; ANTIGEN RECEPTOR; NEGATIVE SELECTION; TRANSGENIC MICE; PREDOMINANT EXPRESSION; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; SRC FAMILY; ZETA-CHAIN AB Recent data indicate that several members of the Tec family of protein tyrosine kinases function in antigen receptor signal transduction. Txk, a Tec family protein tyrosine kinase, is expressed in both immature and mature T cells and in mast cells. By overexpressing Txk in T cells throughout development, ne found that Txk specifically augments the phospholipase C (PLC)-gamma 1-mediated calcium signal transduction pathway upon T cell antigen receptor (-TCR) engagement. Although Txk is structurally different from inducible T cell kinase (Itk), another Tec family member expressed in T cells, expression of the Txk transgene could partially rescue defects in positive selection and signaling in itk(-/-) mice. Conversely, in the itk(+/+) (wild-type) background, overexpression of Txk inhibited positive selection of TCR transgenic thymocytes, presumably due to induction of cell death. These results identify a role for Txk in TCR signal transduction, T cell development, and selection and suggest that the Tec family kinases Itk and Txk perform analogous functions. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Sommers, CL (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bldg 6B,Rm 2B-210,6 Ctr Dr,MSC 2780, Bethesda, MD 20892 USA. NR 56 TC 45 Z9 46 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 15 PY 1999 VL 190 IS 10 BP 1427 EP 1438 DI 10.1084/jem.190.10.1427 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 256GY UT WOS:000083718600008 PM 10562318 ER PT J AU Bosselut, R Zhang, WG Ashe, JM Kopacz, JL Samelson, LE Singer, A AF Bosselut, R Zhang, WG Ashe, JM Kopacz, JL Samelson, LE Singer, A TI Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cell receptor; development; signaling; thymus; phosphorylation ID PROTEIN-TYROSINE KINASE; IMMATURE CD4+CD8+ THYMOCYTES; CYTOPLASMIC DOMAINS; ACTIVATION; PHOSPHORYLATION; P56LCK; ZAP-70; CHAIN; TCR; EXPRESSION AB Linker for activation of T cells (LAT) is an adaptor protein whose tyrosine phosphorylation is critical for transduction of the T cell receptor (TCR) signal. LAT phosphorylation is accomplished by the protein tyrosine kinase ZAP-70, but it is not at all clear how LAT (which is not associated with the TCR) encounters ZAP-70 (which is bound to the TCR). Here we show that LAT associates with surface CD4 and CD8 coreceptors and that its association is promoted by the same coreceptor cysteine motif that mediates Lck binding. In Get, LAT competes with Lck for binding to individual coreceptor molecules but differs from Lck in its preferential association with CD8 rather than CD4 ill CD4(+)CD8(+) thymocytes. Importantly, as a consequence of LAT association with surface coreceptors, coengagement of the TCR with surface coreceptors induces LAT phosphorylation and the specific recruitment of downstream signaling mediators to coreceptor-associated LAT molecules. These results point to a new function for CD-F and CD8 coreceptors in TCR signal transduction, namely to promote LAT phosphorylation by ZAP-70 by recruiting LAT to major histocompatibility complex-engaged TCR complexes. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA. NR 44 TC 89 Z9 89 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 15 PY 1999 VL 190 IS 10 BP 1517 EP 1525 DI 10.1084/jem.190.10.1517 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 256GY UT WOS:000083718600015 PM 10562325 ER PT J AU Ortaldo, JR Winkler-Pickett, R Willette-Brown, J Wange, RL Anderson, SK Palumbo, GJ Mason, LH McVicar, DW AF Ortaldo, JR Winkler-Pickett, R Willette-Brown, J Wange, RL Anderson, SK Palumbo, GJ Mason, LH McVicar, DW TI Structure/function relationship of activating Ly-49D and inhibitory Ly-49G2 NK receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CLASS-I MOLECULES; TYROSINE KINASE; SIGNAL-TRANSDUCTION; T-CELLS; FAMILY; CYTOTOXICITY; PHOSPHATASE; RECOGNITION; SHP-1 AB Murine NK cells express Ly-49 family receptors capable of either inhibiting or activating lytic function. The overlapping patterns of expression of the various receptors have complicated their precise biochemical characterization. Here we describe the use of the Jurkat T cell line as the model for the study of Ly-49s. We demonstrate that Ly-49D is capable of delivering activation signals to Jurkat T cells even in the absence of the recently described Ly-49D-associated chain, DAP-12, Ly-49D signaling in Jurkat leads to tyrosine phosphorylation of TCR zeta and requires Syk/Zap70 family kinases and arginine 54 of Ly-49D, suggesting that Ly-49D signals via association with TCR zeta. Coexpression studies in 293-T cells confirmed the ability of Ly-49D to associate with TCR zeta. In addition, we have used this model to study the functional interactions between an inhibitory Ly-49 (Ly-49G2) and an activating Ly-49 (Ly-49D). Ly-49G2 blocks activation mediated by Ly-49D in an immunoreceptor tyrosine-based inhibitory motif (ITIM)-dependent manner. In contrast, Ly-49G2 was incapable of inhibiting activation by the TCR even though human killer cell inhibitory receptor (KIR) (KIR3DL2(GL183)) effectively inhibits TCR, Both the ability of Ly-49G2 to block Ly-49D activation and the failure of Ly-49G2 to inhibit TCR signaling were confirmed in primary murine NK cells and NK/T cells, respectively. These data demonstrate the dominant effects of the inhibitory receptors over those that activate and suggest an inability of the Ly-49 type II inhibitory receptors to efficiently inhibit type I transmembrane receptor signaling in T cells and NK cells. C1 NCI, Intrammural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Ortaldo, JR (reprint author), NCI, Intrammural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; FU NCI NIH HHS [N01-CO-56000] NR 33 TC 33 Z9 33 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 NOV 15 PY 1999 VL 163 IS 10 BP 5269 EP 5277 PG 9 WC Immunology SC Immunology GA 254XB UT WOS:000083638400014 PM 10553049 ER PT J AU Yamada, N Katz, SI AF Yamada, N Katz, SI TI Generation of mature dendritic cells from a CD14(+) cell line (XS52) by IL-4, TNF-alpha, IL-1 beta, and agonistic anti-CD40 monoclonal antibody SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; LANGERHANS CELLS; MURINE EPIDERMIS; BLOOD MONOCYTES; UP-REGULATION; FACTOR-I; T-CELLS; ANTIGEN; EXPRESSION; SKIN AB We established a model system to generate mature dendritic cells (DC) from a GM-CSP-dependent cell line, XS52, which had been isolated from the epidermis of newborn BALB/c mice. Screening of various soluble factors revealed that IL-4 induces phenotypic maturation of XS52 (as evaluated by enhanced expression of class II, CD40, CD80, CD86, CD11c, and loss of expression of CD14) in a time-dependent manner. The addition of TNF-alpha, IL-1 beta, and agonistic anti-CD40 mAb further enhanced expression of these maturation markers. Consistent with their phenotypic maturation, these cells (termed XS-DC) exhibited potent Ag-presenting capacity to both naive and primed T cells. In addition, injection of hapten-conjugated XS-DC induced contact hypersensitivity in vivo, suggesting their potential as tools for vaccination. Expression of CD14 by the starting cell population, the requirement for GM-CSF and IL-4, and the relatively long culture period are the common characteristics shared between our cells and human monocyte-derived DC, whose analogues in mice have not been identified. Because large numbers of skin-associated mature DC devoid of other cell lineages are easily obtained, this model system may facilitate the study of molecular events associated,vith maturation of DC and the use of DC for immunization. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238, Bethesda, MD 20892 USA. NR 33 TC 27 Z9 28 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 NOV 15 PY 1999 VL 163 IS 10 BP 5331 EP 5337 PG 7 WC Immunology SC Immunology GA 254XB UT WOS:000083638400021 PM 10553056 ER PT J AU Anderson, HA Bergstralh, DT Kawamura, T Blauvelt, A Roche, PA AF Anderson, HA Bergstralh, DT Kawamura, T Blauvelt, A Roche, PA TI Phosphorylation of the invariant chain by protein kinase C regulates MHC class II trafficking to antigen-processing compartments SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOUSE DENDRITIC CELLS; ENDOPLASMIC-RETICULUM; DEVELOPMENTAL REGULATION; TRANSPORT-PROPERTIES; SURFACE EXPRESSION; PEPTIDE COMPLEXES; IN-VIVO; MOLECULES; RECEPTOR; ASSOCIATION AB The invariant chain (Ii) plays a critical role in the transport of newly synthesized class II molecules to endosomal Ag-processing compartments. Of the two major isoforms of human Ii, only Ii-p35 is phosphorylated in vivo, and inhibiting Ii phosphorylation inhibits the trafficking of newly synthesized class II molecules to Ag-processing compartments. We now report that a member of the protein kinase C family of serine/threonine kinases is responsible for the constitutive phosphorylation of 50% of the total cellular pool of Ii-p35 in a wide variety of APCs, including B lymphocytes, PBMC, immature dendritic cells, and mature dendritic cells, Stimulation of protein kinase C activity in APCs significantly enhanced the kinetics of degradation of class II-associated Ii in Ag-processing compartments and the binding of antigenic peptides to these class II molecules, In cells expressing an Ii-phosphorylation mutant, trafficking of class II molecules to endosomes was impaired and Ii proteolysis was inhibited, demonstrating a direct effect of Ii phosphorylation on MHC class II trafficking, These results demonstrate that phosphorylation of Ii in APCs alters the kinetics of trafficking of newly synthesized class II molecules to lysosomal Ag-processing compartments. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 49 TC 45 Z9 45 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1999 VL 163 IS 10 BP 5435 EP 5443 PG 9 WC Immunology SC Immunology GA 254XB UT WOS:000083638400034 PM 10553069 ER PT J AU Deng, XL Ladenheim, B Tsao, LI Cadet, JL AF Deng, XL Ladenheim, B Tsao, LI Cadet, JL TI Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE methamphetamine; neurotoxicity; c-fos mutant; glial fibrillary acidic protein; DNA fragmentation; cell death; apoptosis ID DISMUTASE TRANSGENIC MICE; FIBRILLARY ACIDIC PROTEIN; POSITRON-EMISSION-TOMOGRAPHY; DNA-BINDING ACTIVITY; S-TRANSFERASE GENE; OXIDATIVE STRESS; DOPAMINERGIC NEUROTOXICITY; FREE-RADICALS; MOUSE-BRAIN; RAT-BRAIN AB Methamphetamine neurotoxicity has been demonstrated in rodents and nonhuman primates. These neurotoxic effects may be associated with mechanisms involved in oxidative stress and the activation of immediate early genes (IEG). It is not clear, however, whether these IEG responses are involved in a methamphetamine-induced toxic cascade or in protective mechanisms against the deleterious effects of the drug. As a first step toward clarifying this issue further, the present study was thus undertaken to assess the toxic effects of methamphetamine in heterozygous and homozygous c-fos knock-out as well as wild-type mice. Administration of methamphetamine caused significant reduction in [I-125] RTI-121-labeled dopamine uptake sites, dopamine transporter protein, and tyrosine hydroxylase-like immunohistochemistry in the striata of wild-type mice. These decreases were significantly exacerbated in heterozygous and homozygous c-fos knock-out mice, with the homozygous showing greater loss of striatal dopaminergic markers. Moreover, in comparison with wild-type animals, both genotypes of c-fos knock-out mice showed more DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTPnick-end-labeled nondopaminergic cells in their cortices and striata. In contrast, wild-type mice treated with methamphetamine demonstrated a greater number of glial fibrillary acidic protein-positive cells than did c-fos knock-out mice. These data suggest that c-fos induction in response to toxic doses of methamphetamine might be involved in protective mechanisms against this drug-induced neurotoxicity. C1 NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 85 TC 82 Z9 84 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1999 VL 19 IS 22 BP 10107 EP 10115 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 254JG UT WOS:000083607700046 PM 10559418 ER PT J AU Chen, Y Hertz, L AF Chen, Y Hertz, L TI Noradrenaline effects on pyruvate decarboxylation: Correlation with calcium signaling SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE astrocyte; adrenergic agonist; free intracellular calcium; mitochondria; pyruvate metabolism ID RAT-HEART MITOCHONDRIA; PRIMARY CULTURES; ENERGY-METABOLISM; RUTHENIUM RED; DEHYDROGENASE ACTIVITY; INTRAMITOCHONDRIAL CA2+; GLIAL-CELLS; ASTROCYTES; RECEPTORS; NEURONS AB Noradrenaline effects on the rate of metabolism of pyruvate to acetyl coenzyme A, catalyzed by the pyruvate dehydrogenase complex, was measured in primary cultures of mouse astrocytes as rate of production of labeled CO2 from 1-[C-14]pyruvate in the absence of competing glucose in the medium. The subtype specificity of a noradrenaline-stimulated increase in rate of CO2 formation was identical to that for noradrenaline-induced increase in free intracellular calcium ([Ca2+](i)), suggesting a causal relationship between these two phenomena, The noradrenaline-induced stimulation of pyruvate decarboxylation was abolished in the presence of 10 mM magnesium chloride in the medium, combined with the omission of calcium, a procedure known to prevent an increased [Ca2+] in the cytosol from raising intramitochondrial [Ca2+]. Thus, the stimulation of metabolic flux through the reaction catalyzed by the pyruvate dehydrogenase complex appears to result from an increase in intramitochondrial [Ca2+] ions in astrocytes, Such a mechanism for stimulation of the same enzyme has been convincingly demonstrated in other cell types, primarily heart muscle and hepatic cells, but it has not previously been demonstrated in any cell type from the central nervous system. J. Neurosci. Res, 58:599-606, 1999. (C) 1999 Wiley-Liss, Inc. C1 Univ Saskatchewan, Dept Pharmacol, Saskatoon, SK S7N 0W0, Canada. RP Chen, Y (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Rm 4A03,36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 44 TC 23 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 15 PY 1999 VL 58 IS 4 BP 599 EP 606 DI 10.1002/(SICI)1097-4547(19991115)58:4<599::AID-JNR13>3.0.CO;2-W PG 8 WC Neurosciences SC Neurosciences & Neurology GA 253XK UT WOS:000083582100013 PM 10533052 ER PT J AU Zhu, JH Quyyumi, AA Norman, JE Csako, G Epstein, SE AF Zhu, JH Quyyumi, AA Norman, JE Csako, G Epstein, SE TI Cytomegalovirus in the pathogenesis of atherosclerosis - The role of inflammation as reflected by elevated C-reactive protein levels SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; RISK FACTOR; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; INFECTION AB OBJECTIVES We hypothesized that cytomegalovirus ( infection: 1) stimulates an inflammatory response, reflected by elevated C-reactive protein (CRP) levels, and 2) predisposes to coronary artery disease (CAD), in part, through CMV-induced inflammation. BACKGROUND Although some studies show an association between CMV and atherosclerosis, others do not. We believed that CMV exerted an atherogenic effect by inducing inflammation, and the disparate results may derive partly from individual variability in the capacity to control CMV inflammatory activity. METHODS Blood samples were tested for CMV seropositivity and CRP levels from 238 individuals being evaluated for CAD by coronary angiography. RESULTS An elevated CRP level (>0.5 mg/dl) was a significant CAD determinant even after adjustment for traditional CAD risk factors (odds ratio [OR] = 2.4; p = 0.02). Moreover, CMV seropositivity was significantly associated with increased CRP levels ip = 0.04 after adjustment for CAD risk factors), suggesting that CMV could evoke subclinical inflammatory response. However, considerable host variation existed in this response to CMV. When adjusted for CAD risk factors, the OR for CAD were 1.3 in the subgroup with CMV seropositivity alone (p = 0.7), 2.3 in the subgroup with elevated CRP levels alone (p = 0.2), and 4.3 in the subgroup with combined CMV seropositivity and elevated CRP levels (p = 0.01). CONCLUSIONS Our results suggest that 1) CMV elicits a subclinical inflammatory response, but only in certain individuals, and 2) individuals with an inflammatory response appear susceptible to the atherogenic effects of CMV whereas those without appear resistant. These results may partly explain the disparate results of studies attempting to relate CMV to atherogenesis. (C) 1999 by the American College of Cardiology. C1 Washington Hosp Ctr, Cardiovasc Res Fdn, Washington, DC 20010 USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Epstein, SE (reprint author), Washington Hosp Ctr, Cardiovasc Res Fdn, Suite 4B-1,110 Irving St NW, Washington, DC 20010 USA. NR 20 TC 113 Z9 121 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 15 PY 1999 VL 34 IS 6 BP 1738 EP 1743 DI 10.1016/S0735-1097(99)00410-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 257JG UT WOS:000083778300014 PM 10577564 ER PT J AU Terenzi, F deVeer, MJ Ying, H Restifo, NP Williams, BRG Silverman, RH AF Terenzi, F deVeer, MJ Ying, H Restifo, NP Williams, BRG Silverman, RH TI The antiviral enzymes PKR and RNase L suppress gene expression from viral and non-viral based vectors SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; INTERFERON-TREATED CELLS; INITIATION FACTOR-II; MESSENGER-RNA; TRANSLATIONAL CONTROL; ACTIVATION; VIRUS; TRANSFECTION; RESPONSES; BINDING AB Expression of transfected genes is shown to be suppressed by two intracellular enzymes, RNase L and protein kinase PKR, which function in interferon-treated cells to restrict viral replication, RNase L-/- or PKR-/- murine embryonic fibroblasts produced enhanced levels of protein from transfected genes compared with wild-type cells, Increased expression of exogenous genes in RNase L-/- cells correlated with elevated levels of mRNA and thus appeared to be due to enhanced mRNA stability. Plasmid encoding adenovirus VA RNAs was able to further enhance accumulation of the exogenous gene transcript and protein, even in cells lacking PKR, In contrast to the increased expression of transfected genes in cells lacking RNase L or PKR, expression of endogenous host genes was unaffected by the absence of these enzymes. In addition, a dominant-negative PKR mutant improved expression from a conventional plasmid vector and from a Semliki Forest virus derived, self-replicating vector. These results indicate that viral infections and transfections produce similar stress responses in mammalian cells and suggest strategies for selectively increasing expression of exogenous genes. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Silverman, RH (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, NB40,9500 Euclid Ave, Cleveland, OH 44195 USA. RI Restifo, Nicholas/A-5713-2008; Williams, Bryan/A-5021-2009; OI Williams, Bryan/0000-0002-4969-1151; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [CA 44059]; NIAID NIH HHS [AI34039] NR 29 TC 40 Z9 40 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 1999 VL 27 IS 22 BP 4369 EP 4375 DI 10.1093/nar/27.22.4369 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 259PG UT WOS:000083901800009 PM 10536144 ER PT J AU Balajee, AS Dianova, I Bohr, VA AF Balajee, AS Dianova, I Bohr, VA TI Oxidative damage-induced PCNA complex formation is efficient in xeroderma pigmentosum group A but reduced in Cockayne syndrome group B cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; NUCLEAR ANTIGEN PCNA; INDUCED DNA DAMAGE; POLYMERASE-DELTA; IONIZING-RADIATION; AUXILIARY PROTEINS; REPLICATION; FIBROBLASTS; CYCLIN; INHIBITOR AB Proliferating cell nuclear antigen (PCNA), a processivity factor for DNA polymerases delta and epsilon, is essential for both DNA replication and repair. PCNA is required in the resynthesis step of nucleotide excision repair (NER). After UV irradiation, PCNA translocates into an insoluble protein complex, most likely associated with the nuclear matrix. It has not previously been investigated in vivo whether PCNA complex formation also takes place after oxidative stress. in this study, we have examined the involvement of PCNA in the repair of oxidative DNA damage. PCNA complex formation was studied in normal human cells after treatment with hydrogen peroxide, which generates a variety of oxidative DNA lesions. PCNA was detected by two assays, immunofluorescence and western blot analyses. We observed that PCNA redistributes from a soluble to a DNA-bound form during the repair of oxidative DNA damage. PCNA complex formation was analyzed in two human natural mutant cell lines defective in DNA repair: xeroderma pigmentosum group A (XP-A) and Cockayne syndrome group B (CS-B). XP-A cells are defective in overall genome NER while CS-B cells are defective only in the preferential repair of active genes. Immunofluorescent detection of PCNA complex formation was similar in normal and XP-A cells, but was reduced in CS-B cells. Consistent with this observation, western blot analysis in CS-B cells showed a reduction in the ratio of PCNA relocated as compared to normal and XP-A cells. The efficient PCNA complex formation observed in XP-A cells following oxidative damage suggests that formation of PCNA-dependent repair foci may not require the XPA gene product. The reduced PCNA complex formation observed in CS-B cells suggests that these cells are defective in the processing of oxidative DNA damage. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 43 TC 34 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 1999 VL 27 IS 22 BP 4476 EP 4482 DI 10.1093/nar/27.22.4476 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 259PG UT WOS:000083901800023 PM 10536158 ER PT J AU Diwan, BA Riggs, CW Logsdon, D Haines, DC Olivero, OA Rice, JM Yuspa, SH Poirier, MC Anderson, LM AF Diwan, BA Riggs, CW Logsdon, D Haines, DC Olivero, OA Rice, JM Yuspa, SH Poirier, MC Anderson, LM TI Multiorgan transplacental and neonatal carcinogenicity of 3 '-azido-3 '-deoxythymidine in mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE carcinogenesis; transplacental; perinatal; AZT; fetus; mice ID IMMUNODEFICIENCY-VIRUS TYPE-1; FETAL MOUSE SUSCEPTIBILITY; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE AZT; N-NITROSODIETHYLAMINE; LIVER CARCINOGENESIS; ZIDOVUDINE TREATMENT; BARBITURIC-ACID; TUMOR-INCIDENCE; ADULT MICE; LIFE-SPAN AB The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is used successfully for reduction of perinatal viral transmission. However toxic side effects including carcinogenesis are possible. To test this, pregnant CD-1 Swiss mice were given 25.0 or 12.5 mg AZT on gestation days 12-18. Previously we reported an increase in lung, liver, and female reproductive system tumors in offspring euthanized at 1 year (Olivero et al., J. Natl. Cancer Inst. 89, 1602-1608, 1997). Findings for all remaining offspring up to 2 years old are reported here. AZT effects were most prominent in female offspring, with a significant threefold increase in lung tumors, a reduction in lymphoblastic and follicle center cell lymphomas, and a significant increase in histiocytic sarcomas (0 in controls, 3% after low-dose AZT, and 8% after high-dose AZT, p = 0.022). Dose-dependent incidences of mammary gland, ovarian, and seminal vesicle tumors were low but significant: 0/106 controls, 3/105 low-dose, and 8/105 high-dose mice presented one of these neoplasms (p = 0.0025). Incidences of females showing any clearly AZT-related neoplasm, in lung, liver, ovary, or mammary gland or histiocytic sarcoma, in the second year, were 12/32 after the low dose and 14/27 after the high dose vs 3/23 controls (p = 0.0045). Also, the sensitivity of neonatal mice was assessed by administration of 25, 50, 100, or 200 mg/kg AZT on postnatal days 1 through 8. The effects at 2 years were similar to those seen after transplacental exposure, with significant increases in lung, liver, and mammary tumors in females. The results confirm that AZT is a moderately effective perinatal carcinogen in mice, targeting several tissue types. C1 Data Management Serv Inc, Intramural Res Support Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Lab Anim Sci Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Pathol Histotechnol Lab, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. RP Diwan, BA (reprint author), Data Management Serv Inc, Intramural Res Support Program, Frederick, MD 21702 USA. FU NCI NIH HHS [N01CO56000] NR 70 TC 56 Z9 56 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 1999 VL 161 IS 1 BP 82 EP 99 DI 10.1006/taap.1999.8782 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 259PT UT WOS:000083902800009 PM 10558926 ER PT J AU Morgan, RA Blaese, RM AF Morgan, RA Blaese, RM TI Gene therapy: lessons learnt from the past decade SO BRITISH MEDICAL JOURNAL LA English DT Article ID ADENOASSOCIATED VIRUS; TRANSDUCTION; LYMPHOCYTES; VECTOR; CELLS AB If is more than a decade since the first approved clinical trial to put genes into the tells of human beings was initiated, In that first trial, investigators at the US National Institutes of Health used a modified mouse leukaemia virus to insert a DNA marker into lymphocytes being used to treat cancer(1). A year later, a similar viral technique was used as treatment for two gills who had severe combined immunodeficiency with mutant adenosine deaminase,(2) Ten years and more than 3000 patients later, it is appropriate to ask, "Where are we now?" C1 NIH, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. Kimeragen Inc, Newtown, PA 18940 USA. RP Morgan, RA (reprint author), NIH, Clin Gene Therapy Branch, Bldg 10, Bethesda, MD 20892 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD NOV 13 PY 1999 VL 319 IS 7220 BP 1310 EP U85 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 257MZ UT WOS:000083786900030 PM 10559061 ER PT J AU Orenstein, JM Feinberg, M Yoder, C Schrager, L Mican, JM Schwartzentruber, DJ Davey, RT Walker, RE Falloon, J Kovacs, JA Miller, KD Fox, C Metcalf, JA Masur, H Polis, MA AF Orenstein, JM Feinberg, M Yoder, C Schrager, L Mican, JM Schwartzentruber, DJ Davey, RT Walker, RE Falloon, J Kovacs, JA Miller, KD Fox, C Metcalf, JA Masur, H Polis, MA TI Lymph node architecture preceding and following 6 months of potent antiviral therapy: follicular hyperplasia persists in parallel with p24 antigen restoration after involution and CD4 cell depletion in an AIDS patient SO AIDS LA English DT Article DE AIDS; highly active antiretroviral therapy; HIV; immunohistochemistry; in-situ hybridization; lymph nodes; p24; transmission electron microscopy ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTION; VIRAL-LOAD; VIRUS-REPLICATION; PLASMA; TISSUE; RNA; DISEASE; BLOOD; IMMUNOPATHOGENESIS AB Objectives: To evaluate changes in architecture, viral RNA, and viral protein over 6 months in lymph nodes from retroviral-naive HIV-infected persons before and after commencing highly active antiretroviral therapy (HAART). Methods: Nine antiretroviral-naive HIV-infected persons had lymph nodes excised at baseline and at 2 and 6-8 months after beginning a four-drug combination regimen containing zidovudine, lamivudine, nevirapine, and indinavir. Two patients had AIDS. Lymph nodes were examined by immunohistochemical staining for Gag p24 HIV, CD3, CD21, CD20, HAM 56, and Ki67 antigens and by in-situ hybridization (ISH) for HIV RNA and H3-histone RNA. Results: Eight of nine baseline lymph nodes showed follicular hyperplasia and germinal center and paracortical mononuclear cell activation. At 2 months, the lymph nodes from seven patients, including the AIDS patients, showed more follicular hyperplasia and activation than their baseline specimens but with decreased mononuclear cell activation. By 6 months, seven lymph nodes were less hyperplastic and activated than their corresponding 2 month specimens. Combined ISH/immunohistochemical staining of baseline lymph nodes revealed productively infected T (CD3) and B (CD20) cells and macrophages (HAM56+). HIV RNA-positive mononuclear cells were infrequent at 2 months, and rare at 6 months. HIV RNA was still associated with follicular dendritic cells (FDC) at 2 months, but not at 6 months. HIV p24-positive antigen in germinal centers persisted through all 6, and the one 8 month specimens. The baseline lymph nodes from one of the AIDS patients was involuted and T cell depleted, whereas the follow-up lymph nodes were hyperplastic with normal T cell levels. Conclusion: Follicular hyperplasia and cell activation, possibly caused by persistent viral protein in germinal centers, may help explain why HIV viremia rebounds so rapidly after the interruption of HAART. Restoration of architecture may follow the treatment of patients with AIDS who initially had involuted and CD4 cell-depleted lymph nodes. (C) 1999 Lippincott Williams & Wilkins. C1 George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. Emory Univ, Sch Med, Atlanta, GA USA. Mol Histol Inc, Gaithersburg, MD USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Orenstein, JM (reprint author), George Washington Univ, Med Ctr, Dept Pathol, Ross 502,2300 Eye St NW, Washington, DC 20037 USA. OI Polis, Michael/0000-0002-9151-2268 NR 31 TC 53 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 12 PY 1999 VL 13 IS 16 BP 2219 EP 2229 DI 10.1097/00002030-199911120-00004 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 252PF UT WOS:000083510700004 PM 10563707 ER PT J AU Brambilla, D Reichelderfer, PS Bremer, JW Shapiro, DE Hershow, RC Katzenstein, DA Hammer, SM Jackson, B Collier, AC Sperling, RS Fowler, MG Coombs, RW AF Brambilla, D Reichelderfer, PS Bremer, JW Shapiro, DE Hershow, RC Katzenstein, DA Hammer, SM Jackson, B Collier, AC Sperling, RS Fowler, MG Coombs, RW CA Adult & Pediat AIDS Clinical Trial Women Infant Transmission Study C Virology Quality Assurance Program TI The contribution of assay variation and biological variation to the total variability of plasma HIV-1 RNA measurements SO AIDS LA English DT Article; Proceedings Paper CT 12th International Conference on AIDS CY JUN-JUL -, 1998 CL GENEVA, SWITZERLAND DE clinical trials; HIV diagnostic tests; viral load ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 CELL COUNTS; VIRAL LOAD; ZIDOVUDINE TREATMENT; CUBIC MILLIMETER; INFECTED ADULTS; TRANSMISSION; THERAPY; QUANTIFICATION; MARKERS AB Objectives: To assess the specific contributions of assay variation and biological variation to the total variation of plasma HIV-1 RNA measured by the Roche Monitor assay and the extent to which batch assays reduced both assay variability and total variability compared with real-time determinations. Design: A retrospective analysis of data obtained from three trials conducted by the Adult and Pediatric AIDS Clinical Trials Groups (ATCG), the Women and Infants Transmission Study (WITS) and the NIAID-sponsored Virology Quality Assurance Program. Methods: Within-subject variation was assessed from stored, serially collected plasma samples from 663 subjects enrolled in the ACTG and WITS studies. Interassay and intra-assay variation were estimated from two of the clinical trials and 22 laboratories that participated in a quality assurance program and were used to estimate the effect of real-time testing on total variation. Results: The total variation (standard deviation) from a random effects model was 0.26 log(10) RNA copies/ml. The estimated interassay variation was 0.08 log(10) and intra-assay variation was 0.12 log(10) RNA copies/ml. Biological variation accounted for 56-80% of total variation. The effect of real-time testing compared with batch testing was minimal. Conclusion: Our estimates of total within-subject HIV-1 RNA variation support the current recommendation to obtain at least two specimens, preferably obtained less than 2 weeks apart, for viral RNA measurement before starting therapy. The major contribution of biological variation to the total variation supports the use of real-time HIV-1 RNA assays, provided that consistent specimen collection procedures are followed and acceptable assay proficiency is maintained. (C) 1999 Lippincott Williams & Wilkins. C1 New England Res Inst, Watertown, MA 02472 USA. NICHHD, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Univ Illinois, Coll Med, Chicago, IL USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Deaconess Med Ctr, Boston, MA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Mt Sinai Sch Med, New York, NY USA. NIAID, Bethesda, MD 20892 USA. RP Brambilla, D (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. FU NIAID NIH HHS [AI-27664, N0-AI-35172, UO1-AI-4110] NR 29 TC 62 Z9 63 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 NOV 12 PY 1999 VL 13 IS 16 BP 2269 EP 2279 DI 10.1097/00002030-199911120-00009 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 252PF UT WOS:000083510700009 PM 10563712 ER PT J AU Kim, L Liu, JC Kimmel, AR AF Kim, L Liu, JC Kimmel, AR TI The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate specification SO CELL LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; PROTEIN-KINASES; DICTYOSTELIUM-DISCOIDEUM; AXIS SPECIFICATION; RECEPTOR; XENOPUS; PHOSPHORYLATION; IDENTIFICATION; DIFFERENTIATION; CLASSIFICATION AB Inhibition of GSK3 by 7-TM Wnt/wg receptor signaling is critical for specifying embryonic cell fate patterns. In Dictyostelium, the 7-TM cAMP receptors regulate GSK3 by parallel, antagonistic pathways to establish a developmental body plan. We describe here a novel tyrosine kinase, ZAK1, downstream of 7-TM cAMP receptor signaling that is required for GSK3 activation during development, zak1-nulls have reduced GSK3 activity and are defective in GSK3-regulated developmental pathways. Moreover, recombinant ZAK1 phosphorylates and activates GSK3 in vitro. We propose that ZAK1 is a positive regulator of GSK3 activity required for cell pattern formation in Dictyostelium and speculate that similar mechanisms exist to antagonize Wnt/wg signaling for metazoan cell fate specification. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kimmel, AR (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 38 TC 124 Z9 128 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 12 PY 1999 VL 99 IS 4 BP 399 EP 408 DI 10.1016/S0092-8674(00)81526-3 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 256CX UT WOS:000083709300007 PM 10571182 ER PT J AU Wang, YX Neamati, N Jacob, J Palmer, I Stahl, SJ Kaufman, JD Huang, PL Huang, PL Winslow, HE Pommier, Y Wingfield, PT Lee-Huang, S Bax, A Torchia, DA AF Wang, YX Neamati, N Jacob, J Palmer, I Stahl, SJ Kaufman, JD Huang, PL Huang, PL Winslow, HE Pommier, Y Wingfield, PT Lee-Huang, S Bax, A Torchia, DA TI Solution structure of anti-HIV-1 and anti-tumor protein MAP30: Structural insights into its multiple functions SO CELL LA English DT Article ID RIBOSOME-INACTIVATING PROTEINS; POKEWEED ANTIVIRAL PROTEIN; ADENOSINE GLYCOSIDASE ACTIVITY; RICIN A-CHAIN; CRYSTAL-STRUCTURE; STAPHYLOCOCCAL NUCLEASE; BACKBONE DYNAMICS; STRANDED-DNA; J-COUPLINGS; NMR AB We present the solution structure of MAP30, a plant protein with anti-HIV and anti-tumor activities. Structural analysis and subsequent biochemical assays lead to several novel discoveries. First, MAP30 acts like a DNA glycosylase/apurinic (ap) lyase, an additional activity distinct from its known RNA N-glycosidase activity toward the 28S rRNA. Glycosylase/ap lyase activity explains MAP30's apparent inhibition of the HIV-1 integrase, MAP30's ability to irreversibly relax supercoiled DNA, and may be an alternative cytotoxic pathway that contributes to MAP30's anti-HIV/anti-tumor activities. Second, two distinct, but contiguous, subsites are responsible for MAP30's glycosylase/ap lyase activity. Third, Mn2+ and Zn2+ interact with negatively charged surfaces next to the catalytic sites, facilitating DNA substrate binding instead of directly participating in catalysis. C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Mol Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. Amer BioSci, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Lee-Huang, S (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R01 AI-31343] NR 63 TC 56 Z9 68 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 12 PY 1999 VL 99 IS 4 BP 433 EP 442 DI 10.1016/S0092-8674(00)81529-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 256CX UT WOS:000083709300010 PM 10571185 ER PT J AU Jin, F Devesa, SS Chow, WH Zheng, W Ji, BT Fraumeni, JF Gao, YT AF Jin, F Devesa, SS Chow, WH Zheng, W Ji, BT Fraumeni, JF Gao, YT TI Cancer incidence trends in urban Shanghai, 1972-1994: An update SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ENDOMETRIAL CANCER; PROSTATE-CANCER; CHINA; HEALTH; BREAST; HYPERTENSION; PREVALENCE AB Incidence rates for a number of cancers in urban Shanghai, China, have been changing markedly. Herein we update the trends using population-based data from the Shanghai Cancer Registry for 1972-1994. During 1993-1994, cancers of the lung, stomach, and liver were the 3 leading forms among men, with age-adjusted (world standard) incidence rates of 50.9, 39.2, and 26.5 per 100,000 person-years, respectively, followed by cancers of the colon (12.4) and esophagus (10.0). Among women, cancers of the breast (27.5), stomach (19.1), and lung (17.7) were the most common tumors, followed by cancers of the colon (11.3) and liver (9.4). Over the 23-year period, the rate for all cancers combined, excluding nonmelanoma skin cancer, decreased from 247.5 to 215.2 among men and from 173.6 to 154.0 among women. However, trends for individual forms of cancer varied considerably. Rates doubled for cancers of the colon and biliary tract in both sexes, and they increased substantially for cancers of the brain and nervous system, kidney, pancreas, prostate, corpus uteri, female breast, and ovary, and for non-Hodgkin's lymphoma. Rates for cancers of the lung and rectum changed little. Rates declined by at least one-half for cancers of the esophagus and cervix, with notable decreases also for cancers of the stomach and liver. Some of these trends may reflect variations in diagnostic or screening practices, although changes in lifestyle and other environmental exposures are likely to play important roles. Further epidemiologic research in China is needed to identify risk factors influencing the cancer incidence trends. Int. J. Cancer 83:435-440, 1999. (C) 1999 Wiley-Liss, Inc. C1 Shanghai Canc Inst, Shanghai 200032, Peoples R China. NCI, Bethesda, MD 20892 USA. Univ S Carolina, Sch Publ Hlth, Columbia, SC 29208 USA. Univ S Carolina, Ctr Canc, Columbia, SC 29208 USA. RP Devesa, SS (reprint author), Shanghai Canc Inst, 2200 Xie Tu Rd, Shanghai 200032, Peoples R China. NR 25 TC 134 Z9 153 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 12 PY 1999 VL 83 IS 4 BP 435 EP 440 DI 10.1002/(SICI)1097-0215(19991112)83:4<435::AID-IJC1>3.0.CO;2-J PG 6 WC Oncology SC Oncology GA 247KM UT WOS:000083220000001 PM 10508476 ER PT J AU Fernandes, A Hamburger, AW Gerwin, BI AF Fernandes, A Hamburger, AW Gerwin, BI TI Erbb-2 kinase is required for constitutive STAT 3 activation in malignant human lung epithelial cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SINGLE-CHAIN ANTIBODY; FACTOR RECEPTOR; CARCINOMA-CELLS; BREAST-CANCER; EXPRESSION; TRANSFORMATION; OVEREXPRESSION; INHIBITION; GENE AB Overexpression of the growth factor receptor ErbB-2/Her2/Neu has been implicated in the development of non-small-cell lung cancer. We have reported that the transformation of human lung epithelial cells by c-erbB-2 also requires an active ErbB-1 (EGF receptor) and the autocrine production of its ligand, TGF-alpha. In this report, we demonstrate that STAT 3 is constitutively activated in these cells by the TGF-alpha-stimulated qErbB-1/-2 heterodimer complex. STAT 3 activation was confirmed by mobility shift assays and nuclear localization. ErbB-1 was required, but not sufficient for the TGF-alpha-induced activation of STATs, Inhibition of ErbB-2 kinase activity by tyrphostin AC825 prevented the constitutive activation of STAT 3 in the TGF-alpha-producing, ErbB-1 expressing cell line. Our results demonstrate a requirement for ErbB-2 kinase activity to establish constitutive STAT 3 activation resulting from an autocrine ErbB-1/ TGF-alpha loop. Int. J. Cancer 83:564-570, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. RP Gerwin, BI (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. FU NCI NIH HHS [F33CA63763] NR 31 TC 108 Z9 113 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 12 PY 1999 VL 83 IS 4 BP 564 EP 570 DI 10.1002/(SICI)1097-0215(19991112)83:4<564::AID-IJC20>3.0.CO;2-Q PG 7 WC Oncology SC Oncology GA 247KM UT WOS:000083220000020 PM 10508495 ER PT J AU Broad, LM Armstrong, DL Putney, JW AF Broad, LM Armstrong, DL Putney, JW TI Role of the inositol 1,4,5-trisphosphate receptor in Ca2+ feedback inhibition of calcium release-activated calcium current (I-crac) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT MAST-CELLS; STORE DEPLETION; ENTRY; TRISPHOSPHATE; CHANNELS; INFLUX; DISSOCIATION; THAPSIGARGIN; INACTIVATION; INSP(3) AB We examined the activation and regulation of calcium release-activated calcium current (I-crac) in RBL-1 cells in response to various Ca2+ store-depleting agents. With [Ca2+](i) strongly buffered to 100 nM, I-crac was activated by ionomycin, thapsigargin, inositol 1,4,5-trisphosphate (IP,), and two metabolically stable IP3 receptor agonists, adenophostin A and L-alpha-glycerophospho-D-myoinositol-4,5-bisphosphate (GPIP(2)). With minimal [Ca2+](i) buffering, with [Ca2+](i) free to fluctuate I-crac was activated by ionomycin, thapsigargin, and by the potent IP3 receptor agonist, adenophostin A, but not by GPIP(2) or IP3 itself. Likewise, when [Ca2+](i) was strongly buffered to 500 nM, ionomycin, thapsigargin, and adenophostin A did and GPIP(2) and IP3 did not activate detectable I-crac. However, with minimal [Ca2+](i) buffering, or with [Ca2+](i) buffered to 500 nM, GPIP(2) was able to fully activate detectable I-crac if uptake of Ca2+ intracellular stores was first inhibited. Our findings suggest that when IP3 activates the IP3 receptor, the resulting influx of Ca2+ quickly inactivates the receptor, and Ca2+ is re-accumulated at sites that regulate I-crac. Adenophostin A, by virtue of its high receptor affinity, is resistant to this inactivation, Comparison of thapsigargin-releasabIe Ca2+ pools following activation by different IP3 receptor agonists indicates that the critical regulatory pool of Ca2+ may be very small in comparison to the total IP3-sensitive component of the endoplasmic reticulum, These findings reveal new and important roles for IP3 receptors located on discrete IP3-sensitive Ca2+ pools in calcium feedback regulation of I-crac and capacitative calcium entry. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Broad, LM (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 34 TC 61 Z9 61 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 NOV 12 PY 1999 VL 274 IS 46 BP 32881 EP 32888 DI 10.1074/jbc.274.46.32881 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254QE UT WOS:000083623000052 PM 10551852 ER PT J AU Lewis, DA Bebenek, K Beard, WA Wilson, SH Kunkel, TA AF Lewis, DA Bebenek, K Beard, WA Wilson, SH Kunkel, TA TI Uniquely altered DNA replication fidelity conferred by an amino acid change in the nucleotide binding pocket of human immunodeficiency virus type 1 reverse transcriptase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MISPAIR EXTENSION KINETICS; SITE-DIRECTED MUTAGENESIS; ESCHERICHIA-COLI; POLYMERASE-BETA; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; HIV-1; MECHANISM; MUTANT; RNA AB Arginine 72 in human immunodeficiency virus type I reverse transcriptase (RT), a highly conserved residue among retroviral polymerases and telomerases, forms part of the binding pocket for the nascent base pair. me show here that replacement of Arg(72) by alanine strongly alters fidelity in a highly unusual manner. R72A reverse transcriptase is a frameshift and base substitution anti-mutator polymerase whose increased fidelity results both from increased nucleotide selectivity and from a decreased ability to extend mismatched primer termini. Thus, Arg(72)-substrate interactions in wild-type human immunodeficiency virus type I RT can stabilize incorrect nucleotides allowing misinsertion and promoting extension of mismatched and perhaps misaligned template-primers. In contrast to the higher fidelity at most sites, R72A RT is highly error-prone for misincorporations opposite template T in the sequence context: 5'-C (T) under bar GG. Surprisingly this results mostly from a 1200-fold increase in the apparent K-m for correct dAMP incorporation. Thus, Arg(72) interactions with substrate are critical for the stability of the correct T.dAMP base pair when the 5'-C (T) under bar GG sequence is present in the binding pocket for the nascent base pair. Collectively, the data show that a mutant polymerase may yield higher than normal average replication fidelity, yet paradoxically place specific sequences at very high risk of mutation. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 52 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 12 PY 1999 VL 274 IS 46 BP 32924 EP 32930 DI 10.1074/jbc.274.46.32924 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254QE UT WOS:000083623000058 PM 10551858 ER PT J AU Meighan-Mantha, RL Hsu, DKW Guo, Y Brown, SAN Feng, SLY Peifley, KA Alberts, GF Copeland, NG Gilbert, DJ Jenkins, NA Richards, CM Winkles, JA AF Meighan-Mantha, RL Hsu, DKW Guo, Y Brown, SAN Feng, SLY Peifley, KA Alberts, GF Copeland, NG Gilbert, DJ Jenkins, NA Richards, CM Winkles, JA TI The mitogen-inducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-I; NIH 3T3 CELLS; SITE-DIRECTED MUTAGENESIS; MESSENGER-RNA EXPRESSION; SIGNAL-TRANSDUCTION; MOUSE FIBROBLASTS; CYCLE PROGRESSION; ALDOSE REDUCTASE; LIGAND-BINDING; INTEGRIN AB The binding of polypeptide growth factors to their appropriate cell surface transmembrane receptors triggers numerous biochemical responses, including the transcriptional. activation of specific genes. We have used a differential display approach to identify fibroblast growth factor-1-inducible genes in murine NIH 3T3 cells. Here, we report that the fibroblast growth factorinducible-14 (Fn14) gene is a growth factor-regulated, immediate-early response gene expressed in a developmental stage- and adult tissue-specific manner in vivo. This gene, located on mouse chromosome 17, is predicted to encode an 129-amino acid type Ia membrane protein with no significant sequence similarity to any known protein. me have used two experimental approaches, direct fluorescence microscopy and immunoprecipitation analysis of biotinylated cell surface proteins, to demonstrate that Fn14 is located on the plasma membrane. To examine the biological consequences of constitutive Fn14 expression, we isolated NIH 3T3 cell lines expressing variable levels of epitope-tagged Fn14 and analyzed their phenotypic properties in vitro. These experiments revealed that Fn14 expression decreased cellular adhesion to the extracellular matrix proteins fibronectin and vitronectin and also reduced serum-stimulated cell growth and migration. These results indicate that Fn14 is a novel plasma membrane-spanning molecule that may play a role in cell-matrix interactions. C1 Amer Red Cross, Holland Lab, Dept Vasc Biol, Rockville, MD 20855 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Inst Biomed Sci, Washington, DC 20037 USA. RP Amer Red Cross, Holland Lab, Dept Vasc Biol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM winkles@usa.redcross.org FU NHLBI NIH HHS [HL-39727, R01 HL039727] NR 61 TC 155 Z9 165 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 12 PY 1999 VL 274 IS 46 BP 33166 EP 33176 DI 10.1074/jbc.274.46.33166 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254QE UT WOS:000083623000089 PM 10551889 ER PT J AU Nawrocki, JP Chu, RA Pannell, LK Bai, YW AF Nawrocki, JP Chu, RA Pannell, LK Bai, YW TI Intermolecular aggregations are responsible for the slow kinetics observed in the folding of cytochrome c at neutral pH SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein folding; protein folding pathway; H-2/H exchange pulse-labeling; intermolecular aggregation; cytochrome c ID HYDROGEN-EXCHANGE; MASS-SPECTROMETRY; MOLTEN GLOBULE; INTERMEDIATE; LYSOZYME; PATHWAY; MECHANISM; STATE; STEP; NMR AB Folding of equine cytochrome c at a low protein concentration (26 mu M) eliminated a slow kinetic phase (time constant three seconds) that was observed in the previous hydrogen exchange pulse-labeling experiments at pH 6.2 and 10 degrees C. It was demonstrated that this slow folding phase was caused by intermolecular aggregations. Because heterogeneous kinetics is a very general feature in the folding of proteins characterized by pulsed hydrogen exchange coupled with two-dimensional NMR, our experimental results suggest aggregations might also be responsible for the complex folding kinetics of other proteins. This is possible since these experiments were performed at relatively high protein concentrations. (C) 1999 Academic Press. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8,Room B2A23, Bethesda, MD 20892 USA. NR 28 TC 20 Z9 20 U1 0 U2 7 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 12 PY 1999 VL 293 IS 5 BP 991 EP 995 DI 10.1006/jmbi.1999.3226 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 257TT UT WOS:000083798400001 PM 10547279 ER PT J AU Kumar, S Nussinov, R AF Kumar, S Nussinov, R TI Salt bridge stability in monomeric proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE stability; salt bridge; electrostatics; geometry; hierarchical folding ID ELECTROSTATIC INTERACTIONS; STATISTICAL-ANALYSIS; BINDING; INTERFACES; ENERGIES; COMPLEX; MODELS; PHASE; SITE AB Here, we present the results of continuum electrostatic calculations on a dataset of 222 non-equivalent salt bridges derived from 36 non-homologous high-resolution monomeric protein crystal structures. Most of the salt bridges in our dataset are stabilizing, regardless of whether they are buried or exposed, isolated or networked, hydrogen bonded or non-hydrogen bonded. One-third of the salt bridges in our dataset are buried in the protein core, with the remainder exposed to the solvent. The difference in the dielectric properties of water versus the hydrophobic protein interior cost buried salt bridges large desolvation penalties. However, the electrostatic interactions both between the salt-bridging side-chains, and between the salt bridges and charges in their protein surroundings, are also stronger in the interior, due to the absence of solvent screening. Even large desolvation penalties for burying salt bridges are frequently more than compensated for, primarily by the electrostatic interactions between the salt-bridging side-chains. In networked salt bridges both types of electrostatic interactions, those between the salt-bridging side-chains, and those between the salt bridge and its protein environment, are of similar magnitudes. In particular, a major finding of this work is that salt bridge geometry is a critical factor in determining salt bridge stability. Salt bridges with favorable geometrical positioning of the interacting side-chain charged groups are likely to be stabilizing anywhere in the protein structure. We further find that most of the salt bridges are formed between residues that are relatively near each other in the sequence. (C) 1999 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Lab Expt & Computat Biol, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick Lab Expt & Computat Biol, Intramural Res Support Program, Bldg 469,Rm 151, Frederick, MD 21702 USA. OI Kumar, Sandeep/0000-0003-2840-6398 FU NCI NIH HHS [N01-CO-56000] NR 45 TC 271 Z9 273 U1 2 U2 24 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 12 PY 1999 VL 293 IS 5 BP 1241 EP 1255 DI 10.1006/jmbi.1999.3218 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 257TT UT WOS:000083798400020 PM 10547298 ER PT J AU Mima, T Simpkins, N Oluwatimilehin, T Hallett, M AF Mima, T Simpkins, N Oluwatimilehin, T Hallett, M TI Force level modulates human cortical oscillatory activities SO NEUROSCIENCE LETTERS LA English DT Article DE coherence; force coding; electroencephalography power spectra; piper rhythm; mu rhythm; gamma band ID MOTOR CORTEX; ELECTROPHYSIOLOGICAL CORRELATE; SYNCHRONIZATION ERS; AREAS; TASK AB We studied the relationship between cortical and muscular oscillatory activities and muscular force level during a tonic contraction task using electroencephalography (EEG). Within the weak to moderate force level, the normalized power in the alpha band in the contralateral sensorimotor areas was inversely linearly correlated with the force. Cortical-muscular coherence was observed in the beta band and its magnitude was not affected by the force. In contrast, during strong contractions, EEG power in the gamma band increased and was partly correlated with the Piper rhythm in the electromyogram. Our results show that the multiple oscillatory activities in the cortex are correlated with the force level in different ways. Cortical gamma band oscillation may reflect both focused attention and the efferent drive to the muscle during very strong tonic contraction. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NIH, Human Motor Control Sect, Med Neurol Branch, NINCDS, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NIH, Human Motor Control Sect, Med Neurol Branch, NINCDS, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. OI Mima, Tatsuya/0000-0001-7783-1599; Mima, Tatsuya/0000-0001-7787-4855 NR 19 TC 77 Z9 78 U1 1 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 12 PY 1999 VL 275 IS 2 BP 77 EP 80 DI 10.1016/S0304-3940(99)00734-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA 254TN UT WOS:000083628400002 PM 10568503 ER PT J AU Su, XZ Ferdig, MT Huang, YM Huynh, CQ Liu, A You, JT Wootton, JC Wellems, TE AF Su, XZ Ferdig, MT Huang, YM Huynh, CQ Liu, A You, JT Wootton, JC Wellems, TE TI A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum SO SCIENCE LA English DT Article ID CROSS; RESISTANCE; SEQUENCE AB Genetic investigations of malaria require a genome-wide, high-resolution Linkage map of Plasmodium falciparum. A genetic cross was used to construct such a map from 901 markers that fall into 14 inferred Linkage groups corresponding to the 14 nuclear chromosomes. Meiotic crossover activity in the genome proved high (17 kilobases per centimorgan) and notably uniform over chromosome length. Gene conversion events and spontaneous microsatellite length changes were evident in the inheritance data. The markers, map, and recombination parameters are facilitating genome sequence assembly, Localization of determinants for such traits as virulence and drug resistance, and genetic studies of parasite field populations. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Guangxi Inst Parasit Dis Control, Nanning, Guangxi, Peoples R China. Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wellems, TE (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RI Ferdig, Michael/C-6627-2016; OI Su, Xinzhuan/0000-0003-3246-3248 NR 18 TC 251 Z9 256 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 12 PY 1999 VL 286 IS 5443 BP 1351 EP 1353 DI 10.1126/science.286.5443.1351 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255NF UT WOS:000083675500040 PM 10558988 ER PT J AU Fletcher, TM Trevino, A Woynarowski, JM AF Fletcher, TM Trevino, A Woynarowski, JM TI Enzymatic activity of endogenous telomerase associated with intact nuclei from human leukemia CEM cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TETRAHYMENA TELOMERASE; CHROMATIN STRUCTURE; 30-NM FIBER; DNA; PROTEIN; END; IMMORTALITY; MECHANISMS; ACTIVATION; INHIBITION AB Telomerase, a telomere-specific DNA polymerase and novel target for chemotherapeutic intervention, is found in many types of cancers. Telomerase activity is typically assayed using an exogenous primer and cellular extracts as the source of enzyme, Since the nuclear organization might affect telomerase function, we developed a system in which telomerase in intact nuclei catalyzes primer extension. Telomerase activity in isotonically isolated nuclei from human CEM cells shows low processivity (addition of up to four TTAGGG repeats), In contrast, telomerase activity which leaks into a 500 g postnuclear supernatant and the activity in a CHAPS extract are highly processive. The nucleotide inhibitor, 7-deaza-dGTP, seems to be more inhibitory against the nuclei-associated enzyme compared to telomerase from cytoplasmic extracts. However, 7-deaza-dATP and ddGTP are less inhibitory against nuclei-associated telomerase. The results suggest that the association of telomerase with the nuclear chromatin affects telomerase activity. Examination of telomerase activity in a more natural nuclear environment may shed new light on the telomerase function and provide a useful system for the evaluation of new telomerase inhibitors. (C) 1999 Academic Press. C1 Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78245 USA. RP Fletcher, TM (reprint author), NCI, NIH, Div Basic Sci, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA9408, CA71969] NR 49 TC 6 Z9 6 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 NOV 11 PY 1999 VL 265 IS 1 BP 51 EP 56 DI 10.1006/bbrc.1999.1626 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 256JB UT WOS:000083721200009 PM 10548489 ER PT J AU Reddy, ST Tiano, HF Langenbach, R Morham, SG Herschman, HR AF Reddy, ST Tiano, HF Langenbach, R Morham, SG Herschman, HR TI Genetic evidence for distinct roles of COX-1 and COX-2 in the immediate and delayed phases of prostaglandin synthesis in mast cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SWISS 3T3 CELLS; ENDOPEROXIDE SYNTHASE-2; PHOSPHOLIPASE A(2); D-2 GENERATION; H SYNTHASE-1; EXPRESSION; ACTIVATION; MOUSE; CYCLOOXYGENASE; MACROPHAGES AB Activation of mast cells by aggregation of their high-affinity IgE receptors stimulates prostaglandin (PG) D-2 synthesis and secretion. An immediate phase of PGD(2) synthesis, complete within 30 min, is followed by a delayed, second phase of PGD(2) production that reaches a maximum 4 to 8 h after activation. Activation of mast cells from COX-2 (-/-) mice stimulates the release of PGD(2) during the first 30 min, whereas activation of mast cells from COX-1 (-/-) mice does not generate any PGD(2) in the first 2 h. On the other hand, COX-2 (-/-) cells do not participate in delayed phase of PGD(2) synthesis, white COX-1 (-/-) cells secrete low levels of PGD(2) between 2 and 4 h after activation. These data demonstrate that (i) the first phase of PG synthesis is COX-1 dependent and (ii) the second, delayed phase of PG synthesis is dependent on activation-induced synthesis and activity of COX-2. (C) 1999 Academic Press. C1 Univ Calif Los Angeles, Mol Biol Inst 341, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Biol Chem, Los Angeles, CA 90024 USA. NIEHS, Lab Expt Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Myriad Genet Inc, Salt Lake City, UT USA. RP Herschman, HR (reprint author), Univ Calif Los Angeles, Mol Biol Inst 341, Ctr Hlth Sci, 611 Charles Young Dr E, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [AI34567] NR 24 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 11 PY 1999 VL 265 IS 1 BP 205 EP 210 DI 10.1006/bbrc.1999.1658 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 256JB UT WOS:000083721200035 PM 10548515 ER PT J AU Dickert, N Grady, C AF Dickert, N Grady, C TI What's the price of a research subject? Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Dickert, N (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 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 NOV 11 PY 1999 VL 341 IS 20 BP 1552 EP 1552 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 254RK UT WOS:000083625800024 ER PT J AU Blagosklonny, MV An, WG Melillo, G Nguyen, P Trepel, JB Neckers, LM AF Blagosklonny, MV An, WG Melillo, G Nguyen, P Trepel, JB Neckers, LM TI Regulation of BRCA1 by protein degradation SO ONCOGENE LA English DT Article DE BRCA1; protein degradation; proteasome; acidic proteases; cathepsin; calpain ID SUSCEPTIBILITY GENE-PRODUCT; BREAST-CANCER CELLS; NUCLEAR EXPORT; P53 PROTEIN; TRANSCRIPTIONAL ACTIVATION; PROTEOLYTIC CLEAVAGE; MUTATED P53; DNA-DAMAGE; IN-VIVO; EXPRESSION AB BRCA1, a tumor suppressor protein implicated in hereditary forms of breast and ovarian cancer, is transcriptionally regulated in a proliferation-dependent manner. In this study, we demonstrate a substantial role for proteolysis in regulating the BRCA1 steady-state protein level in several cell lines. N-acetyl-leu-leu-norleucinal (ALLN), an inhibitor of the proteasome, calpain, and cathepsins, caused BRCA1 protein to accumulate in the nucleus of several human breast, prostate, and melanoma cell lines which express low or undetectable basal levels of BRCA1 protein, but not in cells with high basal expression of BRCA1. Protease inhibition did not increase BRCA1 synthesis, nor change its mRNA level, but it dramatically prolonged the protein's half-life. In contrast to ALLN, lactacystin and PS341, two specific proteasome inhibitors, as well as calpastatin peptide and PD150606, two selective calpain inhibitors, had no effect on BRCA1 stability, whereas ALLM, an effective calpain and cathepsin inhibitor but weak proteasome inhibitor, did stimulate accumulation of BRCA1. Moreover, three inhibitors of acidic cysteine proteases, chloroquine, ammonium chloride and bafilomycin, were as effective as ALLN. These results demonstrate that degradation by a cathepsin-like protease in fine balance with BRCA1 transcription is responsible for maintaining the low steady-state level of BRCA1 protein seen in many cancer cells. C1 NCI, Med Branch, Dept Therapeut, NIH, Rockville, MD 20850 USA. NCI, Dept Cell & Canc Biol, Med Branch, NIH, Bethesda, MD 20892 USA. RP Neckers, LM (reprint author), NCI, Med Branch, Dept Therapeut, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 54 TC 50 Z9 51 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 11 PY 1999 VL 18 IS 47 BP 6460 EP 6468 DI 10.1038/sj.onc.1203068 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 256CW UT WOS:000083709200008 PM 10597248 ER PT J AU Li, WQ Zhang, JC Flechner, L Hyun, T Yam, A Franke, TF Pierce, JH AF Li, WQ Zhang, JC Flechner, L Hyun, T Yam, A Franke, TF Pierce, JH TI Protein kinase C-alpha overexpression stimulates Akt activity and suppresses apoptosis induced by interleukin 3 withdrawal SO ONCOGENE LA English DT Article DE apoptosis; Akt/protein kinase B; protein; kinase C-alpha ID MYC-INDUCED APOPTOSIS; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEOLYTIC ACTIVATION; MOLECULAR-CLONING; LEUKEMIA-CELLS; BETA-II; DELTA; FAMILY; TARGET AB To investigate the role of protein kinase C (PKC) in apoptotic signaling induced by cytokine withdrawal, we expressed PKC-alpha, -delta and -epsilon individually in the 32D myeloid progenitor cells. The parental and PKC-delta- and PKC-epsilon- transfected 32D cells underwent apoptosis within 24 h in the absence of interleukin 3. In contrast, expression of PKC-alpha inhibited the onset of apoptosis as determined by genomic DNA fragmentation and flow cytometric analysis. Correlating with the inhibition of apoptosis, PKC-alpha transfectants exhibited increased activity of the endogenous Akt serine/threonine kinase. Furthermore, PKC-alpha, but not PKC-delta or -epsilon, specifically activated overexpressed Akt. PKC-alpha-induced Akt activity was partially dependent on phosphoinositol 3' kinase (PI 3'K) since a PI 3'K inhibitor was able to suppress PKC-alpha-induced Akt activation. Both basal and interleukin 3-stimulated phosphorylation of Akt on serine 473 was enhanced in the PKC-alpha and Akt contransfectants. Coexpression of wild type Akt and PKC-alpha resulted in greater suppression of apoptosis than PKC-alpha expression alone. Together, our results demonstrate that suppression of apoptosis by PKC-alpha correlates with its ability of activating endogenous Akt. Furthermore, activation of overexpressed Akt by PKC-alpha is consistent with their synergistic effect on suppressing apoptosis, providing the strong evidence of cross talk between Akt and PKC-alpha. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. RP Li, WQ (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Stem Cell Res Lab, 3970 Reservoir Rd NW,NRB W309, Washington, DC 20007 USA. NR 45 TC 85 Z9 86 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 11 PY 1999 VL 18 IS 47 BP 6564 EP 6572 DI 10.1038/sj.onc.1203065 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 256CW UT WOS:000083709200020 PM 10597260 ER PT J AU Somasundaram, K MacLachlan, TK Burns, TF Sgagias, M Cowan, KH Weber, BL El-Deiry, WS AF Somasundaram, K MacLachlan, TK Burns, TF Sgagias, M Cowan, KH Weber, BL El-Deiry, WS TI BRCA1 signals ARF-dependent stabilization and coactivation of p53 SO ONCOGENE LA English DT Article DE p53; BRCA1; p14(ARF) ID CELL-CYCLE CONTROL; TUMOR-SUPPRESSOR; OVARIAN-CANCER; TRANSCRIPTIONAL ACTIVATION; GENE BRCA1; DNA-DAMAGE; BREAST; EXPRESSION; APOPTOSIS; ARREST AB The hereditary breast and ovarian tumor suppressor BRCA1 can activate p53-dependent gene expression. We show here that BRCA1 increases p53 protein levels through a post-transcriptional mechanism. BRCA1-stabilized p53 has increased sequence-specific DNA-binding and transcriptional activity, BRCA1 does not stabilize p53 in p14(ARF)-deficient cells. A deletion mutant of BRCA1 which inhibits p53-dependent transcription confers resistance to topoisomerase II-targeted chemotherapy, Our results suggest that BRCA1 may trigger the p53 pathway through two potentially separate mechanisms: accumulation of p53 through a direct or indirect induction of p14(ARF) as well as direct transcriptional coactivation of p53, BRCA1 may also enhance chemosensitivity and repair of DNA damage through binding to and coactivation of p53. C1 Univ Penn, Sch Med, Lab Mol Oncol & Cell Cycle Regulat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med & Genet, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Canc, Philadelphia, PA 19104 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP El-Deiry, WS (reprint author), Univ Penn, Sch Med, Lab Mol Oncol & Cell Cycle Regulat, CRB 437A,415 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA7641701] NR 40 TC 53 Z9 54 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 11 PY 1999 VL 18 IS 47 BP 6605 EP 6614 DI 10.1038/sj.onc.1203284 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 256CW UT WOS:000083709200025 PM 10597265 ER PT J AU Donovan, DM Miner, LL Perry, MP Revay, RS Sharpe, LG Przedborski, S Kostic, V Philpot, RM Kirstein, CL Rothman, RB Schindler, CW Uhl, GR AF Donovan, DM Miner, LL Perry, MP Revay, RS Sharpe, LG Przedborski, S Kostic, V Philpot, RM Kirstein, CL Rothman, RB Schindler, CW Uhl, GR TI Cocaine reward and MPTP toxicity: alteration by regional variant dopamine transporter overexpression SO MOLECULAR BRAIN RESEARCH LA English DT Article DE cocaine; dopamine transporter; transgenic mice; conditioned place preference; drug reward; MPTP ID PARKINSONISM-INDUCING NEUROTOXIN; TYROSINE-HYDROXYLASE; TRANSGENIC MICE; UPTAKE SITES; RAT-BRAIN; DISEASE; RECEPTOR; BINDING; SEROTONIN; EXPRESSION AB Polygenic factors play important roles in animal models of substance abuse and susceptibility to dopaminergic neurodegeneration. Genetic factors are also likely to contribute to the etiology of human drug abuse disorders, and may alter human vulnerabilities to Parkinsonian neurodegeneration. The dopamine transporter (DAT; SLC6A3) is densely expressed by the dopaminergic midbrain neurons that play central roles in drug reward and is believed to be a primary site of action for cocaine reward. This transporter is necessary for the action of selective dopaminergic neurotoxins, and is uniquely expressed on neurons that are the primary targets of Parkinsonian neurodegeneration. To study possible influences of variant DAT expression on these processes, we have constructed transgenic mice (THDAT) in which tyrosine hydroxylase (TH) promoter sequences drive expression of a rat DAT cDNA variant, increase striatal DAT expression by 20-30%, and provide modest alterations in striatal levels of dopamine and its metabolites. THDAT mice habituate more rapidly to a novel environment than wildtype Littermates. These animals display enhanced reward conferred by cocaine, as measured by conditioned place preference. However, locomotor responses to cocaine administration are similar to those of wildtype mice, except at high cocaine doses. THDAT mice display more than 50% greater losses of dopaminergic neurons following a course of MPTP treatment than do wildtype control mice. These results document a model for allelic variation at a gene locus that can exert significant effects in murine models of human substance abuse vulnerability and dopaminergic neurodegeneration. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Clin Psychopharmacol Branches, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21224 USA. Columbia Univ, Dept Neurol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Univ S Florida, Coll Arts & Sci, Dept Psychol, Tampa, FL 33620 USA. RP Donovan, DM (reprint author), Ctr Gerontol Res, Transgen & Knockout Facil, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Philpot, Rex/I-8904-2012; OI Philpot, Rex/0000-0001-9107-3034 NR 63 TC 67 Z9 67 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 10 PY 1999 VL 73 IS 1-2 BP 37 EP 49 DI 10.1016/S0169-328X(99)00235-1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 259TZ UT WOS:000083911200005 ER PT J AU Scortegagna, M Galdzicki, Z Rapoport, SI Hanbauer, I AF Scortegagna, M Galdzicki, Z Rapoport, SI Hanbauer, I TI Activator protein-1 DNA binding activation by hydrogen peroxide in neuronal and astrocytic primary cultures of trisomy-16 and diploid mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE trisomy-16 mouse; Down's syndrome; astrocyte; embryonic primary culture; activator protein-1; c-jun; hydrogen peroxide ID ANTIOXIDANT RESPONSE ELEMENT; DOWNS-SYNDROME; HIPPOCAMPAL-NEURONS; TRANSCRIPTION FACTORS; SUPEROXIDE-DISMUTASE; MOUSE; GENE; BRAIN; MODEL; METALLOTHIONEIN AB The effect of H2O2 on DNA binding activity of activator protein-1 (AP-1) was studied by electrophoretic mobility shift assay (EMSA) in cortical primary cultures of trisomy-16 mice and their diploid littermates. Exposure to 10 mu M H2O2 for 15 min elicited a greater and earlier occurring increase of AP-1 DNA binding in neuronal primary cultures of trisomy-16 mice than of diploid mice. When astrocyte-rich primary cultures were exposed to 10 mu M H2O2 a two-fold increase of AP-1 DNA binding activity was found in trisomy-16 and diploid mice. Supershift EMSA analysis revealed that c-jun was a component of AP-1 in neuronal and glial cultures of diploid and trisomic mice. A 15-min exposure to 10 mu M H2O2 increased c-jun mRNA in cortical neuronal cultures by six-fold, compared with a two-fold increase in cultured astrocytes. The results documented that H2O2-elicited activation of AP-1 DNA binding in trisomy-16 primary cultures is transcriptionally regulated. Since oxidative stress also activates various stress-inducible protein kinases that may phosphorylate AP-1 dimers, the increase of AP-1 DNA binding may, in part, be triggered by phosphorylation. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Hanbauer, I (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N312, Bethesda, MD 20892 USA. NR 32 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 10 PY 1999 VL 73 IS 1-2 BP 144 EP 150 DI 10.1016/S0169-328X(99)00257-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 259TZ UT WOS:000083911200017 ER PT J AU Rudick, RA Fisher, E Lee, JC Simon, J Jacobs, L AF Rudick, RA Fisher, E Lee, JC Simon, J Jacobs, L CA Multiple Sclerosis Collaborative R TI Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS SO NEUROLOGY LA English DT Article DE MS; MRI; brain atrophy; interferon beta ID MULTIPLE-SCLEROSIS; MAGNETIC-RESONANCE; DISEASE PROGRESSION; MRI; DISABILITY; LESIONS; CORD AB Background: Episodic inflammation in the CNS during the early stages of MS results in progressive disability years later, presumably due to myelin and axonal injury. MRI demonstrates ongoing disease activity during the early disease stage, even in some patients who are stable clinically. The optimal MRI measure for the destructive pathologic process is uncertain, however. Methods: In this post-hoc study, MRI scans were analyzed from patients with relapsing MS participating in a placebo-controlled trial of interferon beta-1a The brain parenchymal fraction, defined as the ratio of brain parenchymal volume to the total volume within the brain surface contour, was used to measure whole brain atrophy. The relationship between disease features and brain atrophy and effect of interferon beta-1a were determined. Results: MS patients had significant brain atrophy that worsened during each of 2 years of observation. In many patients, brain atrophy worsened without clinical disease activity. Baseline clinical and MRI abnormalities were not strongly related to the rate of brain atrophy during the subsequent 2 years. Treatment with interferon beta-1a resulted in a reduction in brain atrophy progression during the second year of the clinical trial. Conclusions: Patients with relapsing-remitting MS have measurable amounts of whole brain atrophy that worsens yearly, in most cases without clinical manifestations. The brain parenchymal fraction is a marker for destructive pathologic processes ongoing in relapsing MS patients, and appears useful in demonstrating treatment effects in controlled clinical trials. C1 Cleveland Clin Fdn, Mellen Ctr, Area U100, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol MRI, Denver, CO USA. Buffalo Gen Hosp, Dept Neurol, MSCRG Data Management & Stat Ctr, Buffalo, NY 14203 USA. Buffalo Gen Hosp, Div Dev & Behav Neurosci, Buffalo, NY 14203 USA. Phys Imaging Ctr Western New York, New York, NY USA. Roswell Pk Canc Inst, Dept Microbiol, Buffalo, NY 14263 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Prevent & Social Med, Buffalo, NY 14260 USA. Cleveland Clin Fdn, Dept Diagnost Radiol, Cleveland, OH 44195 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol MRI, Denver, CO USA. Good Samaritan Hosp & Med Ctr, Dept Neurol, Portland, OR 97209 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Good Samaritan Hosp & Med Ctr, Dept Radiol, Portland, OR 97209 USA. Walter Reed Army Med Ctr, Dept Neurol, Washington, DC 20307 USA. Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. NINDS, Cognit Neurosci Unit, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. RP Rudick, RA (reprint author), Cleveland Clin Fdn, Mellen Ctr, Area U100, Dept Neurol, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU PHS HHS [R01-26321] NR 22 TC 504 Z9 508 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 10 PY 1999 VL 53 IS 8 BP 1698 EP 1704 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 253MX UT WOS:000083561300018 PM 10563615 ER PT J AU Mottaghy, FM Hungs, M Brugmann, M Sparing, R Boroojerdi, B Foltys, H Huber, W Topper, R AF Mottaghy, FM Hungs, M Brugmann, M Sparing, R Boroojerdi, B Foltys, H Huber, W Topper, R TI Facilitation of picture naming after repetitive transcranial magnetic stimulation SO NEUROLOGY LA English DT Article DE repetitive transcranial magnetic stimulation; speech-related areas; reaction time; linguistic ID DORSOLATERAL PREFRONTAL CORTEX; VISUAL-PERCEPTION; OCCIPITAL CORTEX; MOTOR CORTEX; DEPRESSION; SUPPRESSION; INDUCTION; SAFETY; SPEECH; PARAMETERS AB Objective: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on picture naming. Background: Previous studies have shown that; rTMS disrupts ongoing speech processes when delivered over frontal or parietal areas of the dominant hemisphere. Methods: In 15 healthy right-handed male individuals, rTMS trains of 20 Hz with a duration of 2 seconds and an intensity of 55% of maximum stimulator output were delivered either to Wernicke's area, to the right-hemisphere homologue of Wernicke's area, to Broca's area, or to the primary visual cortex. Twenty black-and-white line drawings, which the individuals had to name as quickly as possible, were shown immediately after the completion of rTMS and again 2 minutes later. Results: Immediately after the end of a train over Wernicke's area a shortening of naming latency was observed compared with naming without rTMS (p < 0.001). No significant effects on picture naming were observed 2 minutes later or at any time after stimulation of the right-hemisphere homologues of Wernicke's area, Broca's area, or the visual cortex. Conclusion: Repetitive transcranial magnetic stimulation over Wernicke's area leads to a brief facilitation of picture naming by shortening linguistic processing time. C1 Forschungszentrum Julich, Res Ctr, Dept Nucl Med, D-52426 Julich, Germany. Univ Hosp, RWTH, Dept Neurol, Aachen, Germany. Univ Hosp, RWTH, Dept Neurolinguist, Aachen, Germany. NINDS, Human Cort Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Mottaghy, FM (reprint author), Forschungszentrum Julich, Res Ctr, Dept Nucl Med, D-52426 Julich, Germany. OI Hungs, Marcel/0000-0003-2200-5972 NR 39 TC 96 Z9 97 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 10 PY 1999 VL 53 IS 8 BP 1806 EP 1812 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 253MX UT WOS:000083561300035 PM 10563632 ER PT J AU Patton, JT Chnaiderman, J Spencer, E AF Patton, JT Chnaiderman, J Spencer, E TI Open reading frame in rotavirus mRNA specifically promotes synthesis of double-stranded RNA: Template size also affects replication efficiency SO VIROLOGY LA English DT Article ID MESSENGER-RNA; GUANYLYLTRANSFERASE ACTIVITY; GENOME REARRANGEMENTS; BOVINE ROTAVIRUS; PROTEIN; POLYMERASE; IDENTIFICATION; STABILITY; PARTICLES; REQUIRES AB The 11 rotavirus mRNAs are capped, but not polyadenylated, have a high AU content, and serve as templates for the synthesis of double-stranded (ds)RNA. Earlier studies using a cell-free replication system showed that the 5'- and 3'-untranslated regions (UTRs) of the mRNAs have cis-acting signals that promote minus-strand synthesis. To identify additional factors that affect RNA replication, chimeric RNAs were made that consisted of portions of the gene 8 mRNA of SA11 rotavirus and of the gene for green fluorescent protein (gfp) or for the N protein of respiratory syncytial virus. Analysis of the chimeras in the cell-free replication system under noncompetitive conditions showed that the open reading frame (ORF) of viral mRNAs contains information that specifically promotes minus-strand synthesis. Results were also obtained indicating that a high AU content may increase the replication efficiency of RNAs and that, in general, an inverse correlation exists between replication efficiency and the length of the RNA template. Replication assays performed under competitive conditions showed that nonviral RNAs can interfere significantly with the replication of viral mRNAs, mostly likely by sequestering nonspecific RNA-binding proteins that are of limited concentration in the replication system and that are essential for dsRNA synthesis. In summary, rotavirus dsRNA synthesis is affected by many factors including cis-acting replication signals located in the 5'-UTR, 3'-UTR, and ORF of the mRNA as well as the size and possibly the AU content of the mRNA. (C) 1999 Academic Press. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Santiago Chile, Fac Quim & Biol, Dept Ciencias Biol, Virol Lab, Santiago, Chile. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 34 TC 16 Z9 16 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 NOV 10 PY 1999 VL 264 IS 1 BP 167 EP 180 DI 10.1006/viro.1999.9989 PG 14 WC Virology SC Virology GA 255MU UT WOS:000083673300019 PM 10544142 ER PT J AU Lambert, J Bergeron, D Kozak, CA Rassart, E AF Lambert, J Bergeron, D Kozak, CA Rassart, E TI Identification of a common site of provirus integration in radiation leukemia virus-induced T-cell lymphomas in mice SO VIROLOGY LA English DT Article ID INSERTIONAL MUTAGENESIS; VIRAL INTEGRATION; C57BL-KA MICE; C-MYC; MURINE; ACTIVATION; ONCOGENE; REGION; GENE; PROGRESSION AB The BL/VL3 Kaplan radiation leukemia virus (RadLV-VL3) is a nondefective retrovirus that induces T cell lymphomas in several strains of mice. By using DNA probes derived from RadLV/VL3 provirus-flanking sequences cloned from the BL/VL3 cell line, we identified a DNA region rearranged in 5 of 19 tumors analysed (25%). All proviruses were integrated in the same 5'-to-3' orientation in a small DNA region called Kis1 (Kaplan integration site 1). This region was localized on distal mouse chromosome 2 in a region not previously identified as important to lymphomagenesis. The cells rearranged at the Kis1 locus represent a clonal subpopulation of the clonal tumor masses examined, indicating a probable role of Kis1 in tumor progression. (C) 1999 Academic Press. C1 Univ Quebec, Dept Sci Biol, Mol Biol Lab, Montreal, PQ H3C 3P8, Canada. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Rassart, E (reprint author), Univ Quebec, Dept Sci Biol, Mol Biol Lab, Montreal, PQ H3C 3P8, Canada. NR 35 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 1999 VL 264 IS 1 BP 181 EP 186 DI 10.1006/viro.1999.9992 PG 6 WC Virology SC Virology GA 255MU UT WOS:000083673300020 PM 10544143 ER PT J AU Zhou, HJ Casas-Finet, JR Coats, RH Kaufman, JD Stahl, SJ Wingfield, PT Rubin, JS Bottaro, DP Byrd, RA AF Zhou, HJ Casas-Finet, JR Coats, RH Kaufman, JD Stahl, SJ Wingfield, PT Rubin, JS Bottaro, DP Byrd, RA TI Identification and dynamics of a heparin-binding site in hepatocyte growth factor SO BIOCHEMISTRY LA English DT Article ID FACTOR SCATTER FACTOR; BACKBONE DYNAMICS; SOLUTION CONFORMATION; SUCROSE OCTASULFATE; MITOGENIC ACTIVITY; MOLECULAR-CLONING; RECEPTOR-BINDING; ESCHERICHIA-COLI; RAT HEPATOCYTES; FACTOR ISOFORMS AB Hepatocyte growth factor (HGF) is a heparin-binding. multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. Heparin or closely related heparan sulfate has profound effects on: HGF signaling. A heparin-binding site in the N-terminal (N) domain of HGF was proposed on the basis of the clustering of surface positive charges [Zhou, H., Mazzulla, M. J., Kaufman, J. D., Stahl, S. J., Wingfield, P. T., Rubin, J. S., Bottaro, D. P., and Byrd, R. A. (1998) Structure 6, 109-116]. In the present study, we confirmed this binding site in a heparin titration experiment monitored by nuclear magnetic resonance spectroscopy, and we estimated the apparent dissociation constant (Kd) Of the heparin-protein complex by NMR and fluorescence techniques. The primary heparin-binding site is composed of Lys60, Lys62, and Arg73, with additional contributions from the adjacent Arg76, Lys78, and N-terminal basic residues. The Kd Of binding is in the micromolar range. A heparin disaccharide analogue, sucrose octasulfate, binds with similar affinity to the N domain and to a naturally occurring HGF isoform, NK1, at nearly the same region as in heparin binding. N-15 relaxation data indicate structural flexibility on a microsecond-to-millisecond time scale around the primary binding site in the N domain. This flexibility appears to be dramatically reduced by ligand binding. On the basis of the NK1 crystal structure, we propose a model in which heparin binds to the two primary binding-sites and the N-terminal regions of the N domains and stabilizes an NK1 dimer. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol NMR Sect, Frederick, MD 21702 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIAMSD, Prot Express Lab, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Byrd, RA (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol NMR Sect, Frederick, MD 21702 USA. RI Bottaro, Donald/F-8550-2010; Byrd, R. Andrew/F-8042-2015 OI Bottaro, Donald/0000-0002-5057-5334; Byrd, R. Andrew/0000-0003-3625-4232 NR 46 TC 40 Z9 40 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 9 PY 1999 VL 38 IS 45 BP 14793 EP 14802 DI 10.1021/bi9908641 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256LE UT WOS:000083726100008 PM 10555961 ER PT J AU Singh, SK Guo, FS Maurizi, MR AF Singh, SK Guo, FS Maurizi, MR TI ClpA and ClpP remain associated during multiple rounds of ATP-dependent protein degradation by ClpAP protease SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; REGULATORY PARTICLE; CHAPERONE AB The Escherichia coli ClpA and ClpP proteins form a complex, ClpAP, that catalyzes ATP-dependent degradation of proteins. Formation of stable ClpA hexamers and stable ClpAP complexes requires binding of ATP or nonhydrolyzable ATP analogues to ClpA. To understand the order of events during substrate binding, unfolding, and degradation by ClpAP, it is essential to know the oligomeric state of the enzyme during multiple catalytic cycles. Using inactive forms of ClpA or ClpP as traps for dissociated species, we measured the rates of dissociation of ClpA hexamers or ClpAP complexes. When ATP was saturating, the rate constant for dissociation of ClpA hexamers was 0.032 min(-1) (t1/2 of 22 min) at 37 degrees C, and dissociation of ClpP from the ClpAP complexes occurred with a rate constant of 0.092 min(-1) (t1/2 of 7.5 min). Because the k(cat) for casein degradation is similar to 10 min(-1), these results indicate that tens of molecules of casein can be turned over by the ClpAP complex before significant dissociation occurs. Mutations in the N-terminal ATP binding site led to faster rates of ClpA and ClpAP dissociation, whereas mutations in the C-terminal ATP binding site, which cause significant decreases in ATPase activity, led to lower rates of dissociation of ClpA and ClpAP complexes. Dissociation rates for wild-type and first domain mutants of ClpA were faster at low nucleotide concentrations. The t1/2 for dissociation of ClpAP complexes in the presence of nonhydrolyzable analogues was greater than or equal to 30 min. Thus, ATP binding stabilizes the oligomeric state of ClpA, and cycles of ATP hydrolysis affect the dynamics of oligomer interaction. However, since the k(cat) for ATP hydrolysis is similar to 140 min(-1), ClpA and the ClpAP complex remain associated during hundreds of rounds of ATP hydrolysis. Our results indicate that the ClpAP complex is the functional form of the protease and as such engages in multiple rounds of interaction with substrate proteins, degradation, and release of peptide products without dissociation. C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, Bldg 37,Room 1B09, Bethesda, MD 20892 USA. NR 26 TC 48 Z9 48 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 9 PY 1999 VL 38 IS 45 BP 14906 EP 14915 DI 10.1021/bi991615f PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256LE UT WOS:000083726100020 PM 10555973 ER PT J AU Benedict, PE Benedict, MB Su, TP Bolling, SF AF Benedict, PE Benedict, MB Su, TP Bolling, SF TI Opiate drugs and delta-receptor-mediated myocardial protection SO CIRCULATION LA English DT Article DE cardioplegia; cardiopulmonary bypass; drugs; hibernation; receptors ID HIBERNATION INDUCTION TRIGGERS; OPIOID RECEPTORS; CARDIAC MYOCYTES; RAT-HEART; PRESERVATION; ANTAGONIST; MONKEY; CA2+ AB Background - Hypothermic myocardial arrest is necessary to complete most cardiac surgery, which limits the success of such operations. Similarly, cold, inhospitable environments limit the survival of warm-blooded animals. Animals have successfully adapted to this challenge through hibernation. Hibernation is an energy-conserving state, now known to be governed by cyclical variation in endogenous opiate compounds. It may also be induced in nonhibernators via hibernating animal serum factors or delta-opiate peptides. Furthermore, hibernation-induction triggers extend organ preservation in many models. This study examined whether opiate drugs with an affinity for the delta-opiate receptor confer similar protection. Methods and Results - Isolated hearts harvested from New Zealand White rabbits were treated with either cardioplegia alone or delta-opiate drugs (fentanyl, morphine, buprenorphine, pentazocine) followed by 2 hours of 34 degrees C ischemia. Hearts were then reperfused, and functional and metabolic indices of treated groups were compared with untreated controls. Isovolumic developed pressure, coronary flow, and oxygen consumption were compared as a percent of preischemia versus 45 minutes after reflow. Developed pressure and oxygen consumption were better preserved in the morphine, buprenorphine, and pentazocine groups when compared with cardioplegia alone. Conclusions - Drugs with delta-opiate activity confer myocardial protection, which is additive to cardioplegia. Use of delta-opiate drugs in this context may have important clinical implications. C1 Univ Michigan Hlth Syst, Univ Hosp, Dept Anesthesiol, Ann Arbor, MI 48109 USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. Natl Inst Hlth, Bethesda, MD USA. RP Benedict, PE (reprint author), Univ Michigan Hlth Syst, Univ Hosp, Dept Anesthesiol, 1500 E Med Ctr Dr,1G323 Box 0048, Ann Arbor, MI 48109 USA. NR 33 TC 48 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 9 PY 1999 VL 100 IS 19 SU S BP 357 EP 360 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 254HE UT WOS:000083605200060 ER PT J AU Blum, A AF Blum, A TI Inflammatory response in unstable angina SO CIRCULATION LA English DT Letter C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Blum, A (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 9 PY 1999 VL 100 IS 19 BP E97 EP E97 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 253WE UT WOS:000083579300003 PM 10556235 ER PT J AU Goldgur, Y Craigie, R Cohen, GH Fujiwara, T Yoshinaga, T Fujishita, T Sugimoto, H Endo, T Murai, H Davies, DR AF Goldgur, Y Craigie, R Cohen, GH Fujiwara, T Yoshinaga, T Fujishita, T Sugimoto, H Endo, T Murai, H Davies, DR TI Structure of the HIV-1 integrase catalytic domain complexed with an inhibitor: A platform for antiviral drug design SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-BINDING; ACTIVE-SITE; IDENTIFICATION; SIMILARITY; PROTEIN AB HIV integrase, the enzyme that inserts the viral DNA into the host chromosome, has no mammalian counterpart, making it an attractive target for antiviral drug design. As one of the three enzymes produced by HIV, it can be expected that inhibitors of this enzyme will complement the therapeutic use of HIV protease and reverse transcriptase inhibitors, We have determined the structure of a complex of the HIV-1 integrase core domain with a novel inhibitor, 5CITEP, 1-(5-chloroindol-3-yl)-3-hydroxy-3-(2H-tetrazole-5-yl)-pro-penone, to 2.1-Angstrom resolution. The inhibitor binds centrally in the active site of the integrase and makes a number of close contacts with the protein. Only minor changes in the protein accompany inhibitor binding. This inhibitor complex will provide a platform for structure-based design of an additional class of inhibitors for antiviral therapy. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Shionogi & Co Ltd, Discovery Res Labs, Fukushima Ku, Osaka 5530002, Japan. RP Davies, DR (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 338, Bethesda, MD 20892 USA. EM david.davies@nih.gov NR 20 TC 412 Z9 432 U1 0 U2 13 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 NOV 9 PY 1999 VL 96 IS 23 BP 13040 EP 13043 DI 10.1073/pnas.96.23.13040 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255BJ UT WOS:000083649400014 PM 10557269 ER PT J AU Simbulan-Rosenthal, CM Haddad, BR Rosenthal, DS Weaver, Z Coleman, A Luo, RB Young, HM Wang, ZQ Ried, T Smulson, ME AF Simbulan-Rosenthal, CM Haddad, BR Rosenthal, DS Weaver, Z Coleman, A Luo, RB Young, HM Wang, ZQ Ried, T Smulson, ME TI Chromosomal aberrations in PARP(-/-) mice: Genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTISENSE RNA EXPRESSION; DNA-DAMAGE; GENE AMPLIFICATION; MAMMALIAN-CELLS; P53 PROTEIN; HYBRIDIZATION; APOPTOSIS; CANCER; REPAIR; ACTIVATION AB Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP(-/-) mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP(-/-) mice and immortalized PARP(-/-) fibroblasts, Neither the chromosomal gains nor the tetraploid population were apparent in PARP(-/-) cells stably transfected with PARP cDNA [PARP(-/-)(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP(-/-) cells, p53 expression was partially restored in PARP(-/-)(+PARP) cells. Loss Of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP(-/-) mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene ion was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency. C1 Georgetown Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Inst Mol & Human Genet, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Sch Med, Dept Gynecol, Washington, DC 20007 USA. Int Agcy Res Canc, F-69372 Lyon, France. NCI, NIH, Bethesda, MD 20892 USA. RP Smulson, ME (reprint author), Georgetown Univ, Sch Med, Dept Biochem & Mol Biol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. EM smulson@bc.georgetown.edu FU NCI NIH HHS [CA25344, 1PO1 CA74175, P01 CA074175] NR 54 TC 95 Z9 98 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 9 PY 1999 VL 96 IS 23 BP 13191 EP 13196 DI 10.1073/pnas.96.23.13191 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255BJ UT WOS:000083649400041 PM 10557296 ER PT J AU Khan, J Bittner, ML Saal, LH Teichmann, U Azorsa, DO Gooden, GC Pavan, WJ Trent, JM Meltzer, PS AF Khan, J Bittner, ML Saal, LH Teichmann, U Azorsa, DO Gooden, GC Pavan, WJ Trent, JM Meltzer, PS TI cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-II; ALVEOLAR RHABDOMYOSARCOMA; EXPRESSION PATTERNS; DOMAIN GENE; PAX3; PROTEIN; MUSCLE; CLONING; SLUG; DIFFERENTIATION AB Alveolar rhabdomyosarcoma is an aggressive pediatric cancer of striated muscle characterized in 60 % of cases by a t(2;13)(q35;q14). This results in the fusion of PAX3, a developmental transcription factor required for limb myogenesis, with FKHR, a member of the forkhead family of transcription factors. The resultant PAX3-FKHR gene possesses transforming properties; however, the effects of this chimeric oncogene on gene expression are largely unknown. To investigate the actions of these transcription factors, both Pax3 and PAX3-FKHR were introduced into NIH 3T3 cells, and the resultant gene expression changes were analyzed with a murine cDNA microarray containing 2,225 elements. We found that PAX3-FKHR but not PAX3 activated a myogenic transcription program including the induction of transcription factors MyoD, Myogenin, Six1, and Slug as well as a battery of genes involved in several aspects of muscle function. Notable among this group were the growth factor gene lgf2 and its binding protein Igfbp5. Relevance of this model was suggested by verification that three of these genes (IGFBP5, HSIX1, and Slug) were also expressed in alveolar rhabdomyosarcoma cell lines. This study utilizes cDNA microarrays to elucidate the pattern of gene expression induced by an oncogenic transcription factor and demonstrates the profound myogenic properties of PAX3-FKHR in NIH 3T3 cells. C1 Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bldg 49,Room 4A10,49 Convent Dr, Bethesda, MD 20892 USA. EM pmeltzer@nhgri.nih.gov RI Saal, Lao/A-2919-2011; Khan, Javed/P-9157-2014 OI Saal, Lao/0000-0002-0815-1896; Khan, Javed/0000-0002-5858-0488 NR 42 TC 237 Z9 245 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 NOV 9 PY 1999 VL 96 IS 23 BP 13264 EP 13269 DI 10.1073/pnas.96.23.13264 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255BJ UT WOS:000083649400054 PM 10557309 ER PT J AU Resnick, HE Valsania, P Phillips, CL AF Resnick, HE Valsania, P Phillips, CL TI Diabetes mellitus and nontraumatic lower extremity amputation in black and white Americans - The national health and nutrition examination survey epidemiologic follow-up study, 1971-1992 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BODY-FAT DISTRIBUTION; VASCULAR-DISEASE; POPULATION; MORTALITY; INSULIN; COHORT; NIDDM; RISK AB Background: The comparative long-term risk of nontraumatic lower extremity amputation (LEA) in black and white Americans, 2 groups with strikingly different rates of diabetes mellitus, is not known. Objective: To examine the 20-year incidence of LEA in relation to race and diabetes mellitus. Methods: The 14407 subjects in the National Health and Nutrition Examination Sun ey Epidemiologic Follow-up Study were observed prospectively between 1971 and 1992. Prevalent diabetes mellitus was ascertained at the baseline examination, and incident diabetes mellitus, during follow-up. Lower extremity amputation was ascertained from hospital discharge records. Cox regression analysis was used to estimate associations between race, diabetes mellitus, and risk of first LEA. Results: During the study period, 158 LEAs occurred among 108 subjects. While black subjects constituted 15.2% of the cohort, they represented 27.8% of the subjects with amputation (P =.002). The 20-year age adjusted rate ratio of first LEAs for black subjects-white subjects was 2.14. Regression analyses confirmed the importance of diabetes mellitus as a key LEA risk factor. The association between prevalent diabetes mellitus and LEA risk was substantially higher (relative risk [RR], 7.19; 95% confidence interval [CI], 4.61-11.22) than that for incident diabetes mellitus (RR, 3.15 [CI, 1.84-5.37]), highlighting the importance of diabetes mellitus duration on LEA risk. While preliminary analyses adjusted for age and diabetes indicated a significant association between race and LEA risk (RR, 1.93 [95% CI, 1.26-2.96]), the effect of race diminished (RR, 1.49 [95% CI, 0.95-2.34]) following adjustment for education, hypertension, and smoking. Conclusions: Although black subjects experienced higher age- and diabetes mellitus-adjusted rates of amputation than their white counterparts, a combination of social and environmental factors may account for the apparent ethnic difference. More research into nonbiological factors associated with LEK may reduce the occurrence of these procedures in both black and white individuals. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Micigan Peer Review Org, Ctr Hlth Outcomes & Evaluat, Plymouth, MI USA. RP Resnick, HE (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. NR 34 TC 72 Z9 73 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 8 PY 1999 VL 159 IS 20 BP 2470 EP 2475 DI 10.1001/archinte.159.20.2470 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 252YX UT WOS:000083530800013 PM 10665896 ER PT J AU Quan, N Mhlanga, JDM Whiteside, MB McCop, AN Kristensson, K Herkenham, M AF Quan, N Mhlanga, JDM Whiteside, MB McCop, AN Kristensson, K Herkenham, M TI Chronic overexpression of proinflammatory cytokines and histopathology in the brains of rats infected with Trypanosoma brucei SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE interleukin-1; tamer necrosis factor; neurotoxicity; parasite infection; glial acidic fibrillary protein; nuclear factor kappa B ID CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1-BETA MESSENGER-RNA; NITRIC-OXIDE SYNTHASE; TRANSGENIC MICE; KAPPA-B; AFRICAN TRYPANOSOMES; DISEASE PROGRESSION; ALZHEIMERS-DISEASE; SLEEPING SICKNESS AB Overproduction of proinflammatory cytokines in the brains of transgenic animals causes brain pathology. To investigate the relationship between brain cytokines and pathology in the brains of animals with adult-onset, pathophysiologically induced brain cytokine expression, we studied rats infected with the parasite Trypanosoma brucei. Several weeks after infection, in situ hybridization histochemistry showed a pattern of chronic overexpression of the mRNAs for proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha in the brains of the animals. Similar spatiotemporal inductions of mRNAs for inhibitory factor kappa B alpha and interleukin-1 beta converting enzyme were found and quantified. The mRNAs for inducible nitric oxide synthase and interleukin-1 receptor antagonist were highly localized to the choroid plexus, which showed evidence of structural abnormalities associated with the parasites' presence there. The mRNAs for interleukin-6, interferon-gamma, and inducible cyclooxygenase showed restricted induction patterns. Another set; of animals was processed for degeneration-induced silver staining, TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) staining, glial fibrillary acidic protein (GFAP) immunohistochemistry, and several other histological markers. Apoptosis of scattered small cells and degeneration of certain nerve fibers was found in patterns spatially related to the cytokine mRNA patterns and to cerebrospinal fluid diffusion pathways. Furthermore, striking cytoarchitectonically defined clusters of degenerating non-neuronal cells, probably astrocytes, were found. The results reveal chronic overexpression of potentially cytotoxic cytokines in the brain and selective histopathology patterns in this natural disease model. (C) Published 1999 Wiley-Liss, Inc. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Room 2D15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 57 TC 57 Z9 58 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 8 PY 1999 VL 414 IS 1 BP 114 EP 130 DI 10.1002/(SICI)1096-9861(19991108)414:1<114::AID-CNE9>3.0.CO;2-G PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 242HV UT WOS:000082935200009 PM 10494082 ER PT J AU Nussbaum, RL AF Nussbaum, RL TI Hot papers - Parkinson's disease - Mutation in the alpha-synuclein gene identified in families with Parkinson's disease by M.H. Polymeropoulos, C. Lavedan, E. Leroy, S.E. Ide, A. Dehejia, A. Dutra, B. Pike, H. Root, J. Rubenstein, R. Boyer, E.S. Stenroos, S. Chandrasekharappa, A. Athanassiadou, T. Papapetropoulos, W.G. Johnson, A.M. Lazzarini, R.C. Duvoisin, G. Di Iorio, L.I. Golbe, R.L. Nussbaum - Comments SO SCIENTIST LA English DT Editorial Material AB Robert L. Nussbaum of the National Human Genome Research Institute discusses genetics in Parkinson's disease. C1 Natl Human Genome Res Inst, Genetic Dis Res Branch, Bethesda, MD USA. RP Nussbaum, RL (reprint author), Natl Human Genome Res Inst, Genetic Dis Res Branch, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 2 U2 5 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 8 PY 1999 VL 13 IS 22 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 253GE UT WOS:000083547800015 ER PT J AU Schneider, TD AF Schneider, TD TI Measuring molecular information SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Letter ID SEQUENCE LOGOS; CHANNEL CAPACITY; BINDING-SITES; DNA; MACHINES; ENERGY; DISPLAY C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Schneider, TD (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, POB B, Frederick, MD 21702 USA. OI Schneider, Thomas/0000-0002-9841-1531 NR 29 TC 24 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD NOV 7 PY 1999 VL 201 IS 1 BP 87 EP 92 DI 10.1006/jtbi.1999.1012 PG 6 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 252RV UT WOS:000083516800008 PM 10534438 ER PT J AU Han, JY Je, GH Kim, IH Rodgers, GP AF Han, JY Je, GH Kim, IH Rodgers, GP TI Culture of fetal erythroid cells from maternal blood using a two-phase liquid system SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter C1 Dong A Univ, Coll Med, Dept Clin Pathol, Pusan, South Korea. Dong A Univ, Coll Med, Dept Obstet & Gynecol, Pusan, South Korea. Dong A Univ, Coll Med, Dept Biochem, Pusan, South Korea. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. RP Han, JY (reprint author), Dong A Univ, Coll Med, Dept Clin Pathol, Pusan, South Korea. NR 9 TC 6 Z9 6 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 5 PY 1999 VL 87 IS 1 BP 84 EP 85 DI 10.1002/(SICI)1096-8628(19991105)87:1<84::AID-AJMG18>3.0.CO;2-S PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 252EW UT WOS:000083490000018 PM 10528255 ER PT J AU Daruwala, R Song, J Koh, WS Rumsey, SC Levine, M AF Daruwala, R Song, J Koh, WS Rumsey, SC Levine, M TI Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2 SO FEBS LETTERS LA English DT Article DE vitamin C; ascorbate; transport; hSVCT1; hSVCT2 ID DEHYDROASCORBIC ACID; ASCORBIC-ACID; PROTEIN; IDENTIFICATION; VOLUNTEERS; EXPRESSION; REDUCTASE; GENE AB Two sodium-dependent vitamin C transporters, hSVCT1 and hSVCT2, were cloned from a human kidney cDNA library. hSVCT1 had a 1797 bp open reading frame encoding a 598 amino acid polypeptide. The 1953 bp open reading frame of hSVCT2 encoded a 650 amino acid polypeptide. Using a Xenopus laevis oocyte expression system, both transporters were functionally expressed. BS Eadie-Hofstee transformation the apparent K-m of hSVCT1 for ascorbate was 252.0 mu M and of hSVCT2 for ascorbate was 21.3 mu M. Both transporters were sodium-dependent and did not transport dehydroascorbic acid. Incubation of oocytes expressing either transporter with phorbol 12-myristate 13-acetate (PMA) inhibited ascorbate transport activity. Availability of the human transporter clones may facilitate new strategies for determining vitamin C intake. (C) 1999 Federation of European Biochemical Societies. C1 NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, NIH, Bldg 10,Rm 4D52,MSC 1372, Bethesda, MD 20892 USA. NR 19 TC 170 Z9 178 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 5 PY 1999 VL 460 IS 3 BP 480 EP 484 DI 10.1016/S0014-5793(99)01393-9 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 255HM UT WOS:000083663500018 PM 10556521 ER PT J AU Jernigan, RL Demirel, MC Bahar, I AF Jernigan, RL Demirel, MC Bahar, I TI Relating structure to function through the dominant slow modes of motion of DNA topoisomerase II SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Article DE topoisomerase; Gaussian network model; DNA binding proteins; slow modes of motion ID VIBRATIONAL DYNAMICS; RESIDUE POTENTIALS; GLOBULAR-PROTEINS; FOLDED PROTEINS; FLUCTUATIONS; LYSOZYME; MACROMOLECULES; SIMULATIONS; MECHANISM; NETWORKS AB Type II DNA topoisomerases are enzymes capable of transporting one DNA duplex through another by performing a cycle of DNA cleavage, transport, and religation, coupled to ATP binding and hydrolysis. Here, we considered a coarse-grained model of the structure and investigated the motions within two structures, DNA topoisomerase II and DNA gyrase A. The coarse graining with only one point per residue means that motions in such large proteins can be thoroughly investigated. The overall motions are reflected in the crystallographic temperature factors, which are reproduced by the model. Also, with this approach, we can view the slowest, most cooperative, modes of motion, corresponding to the largest-scale correlated motions in the protein. These motions are nearly identical in the two proteins and are likely related to individual steps in the enzyme's complex mechanism of activity. (C) 1999 John Wiley & Sons, Inc.*. C1 NCI, Div Basic Sci, Lab Expt & Computat Biol, Mol Struct Sect,NIH, Bethesda, MD 20892 USA. Bogazici Univ, Dept Chem Engn, Istanbul, Turkey. Bogazici Univ, Polymer Res Ctr, Istanbul, Turkey. TUBITAK, Adv Polymer Mat Res Ctr, TR-80815 Istanbul, Turkey. RP Jernigan, RL (reprint author), NCI, Div Basic Sci, Lab Expt & Computat Biol, Mol Struct Sect,NIH, Bethesda, MD 20892 USA. RI Demirel, Melik/E-4495-2010; Jernigan, Robert/A-5421-2012; Demirel, Melik/E-3775-2016 NR 28 TC 30 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7608 J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD NOV 5 PY 1999 VL 75 IS 3 BP 301 EP 312 DI 10.1002/(SICI)1097-461X(1999)75:3<301::AID-QUA19>3.3.CO;2-S PG 12 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA 247BR UT WOS:000083201200017 ER PT J AU Choi, KS Eom, YW Kang, Y Ha, MJ Rhee, H Yoon, JW Kim, SJ AF Choi, KS Eom, YW Kang, Y Ha, MJ Rhee, H Yoon, JW Kim, SJ TI Cdc2 and Cdk2 kinase activated by transforming growth factor-beta 1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASES; BETA-INDUCED APOPTOSIS; TGF-BETA; EPITHELIAL-CELLS; GENE-PRODUCT; C-MYC; DIFFERENTIAL REGULATION; TRANSGENIC MICE; INHIBITS GROWTH; MAMMALIAN-CELLS AB The signaling pathway leading to TGF-beta 1-induced apoptosis was investigated using a TGF-beta 1-sensitive hepatoma cell line, FaO. Cell cycle analysis demonstrated that the accumulation of apoptotic cells was pre ceded by a progressive decrease of the cell, population in the G(1) phase concomitant with a slight increase of the cell population in the G(2)/M phase in response to TGB-beta 1. TGF-beta 1 induced a transient increase in the expression of Cdc2, cyclin A, cyclin B, and cyclin D1 at an early phase of apoptosis. During TGF-beta 1-induced apoptosis, the transient increase in cyclin-dependent kinase (Cdk) activities coincides with a dramatic increase in the hyperphosphorylated forms of RE. Treatment with roscovitine or olomoucine, inhibitors of Cdc2 and Cdk2, blocked TGF-beta 1-induced apoptosis by inhibiting RE phosphorylation. Overexpression of Bcl-2 or adenovirus E1B 19K suppressed TGF-beta 1-induced apoptosis by blocking the induction of Cdc2 mRNA and the subsequent activation of Cdc2 kinase, whereas activation of Cdk2 was not affected, suggesting that Cdc2 plays a more critical role in TGF-beta 1-induced apoptosis. in conclusion, we present the evidence that Cdc2 and Cdk2 kinase activity transiently induced by TGF-beta 1 phosphorylates RE as a physiological target in FaO cells and that RE hyperphosphorylation may trigger abrupt cell cycle progression, leading to irreversible cell death. C1 Ajou Univ, Sch Med, Inst Med Sci, Lab Endocrinol,Paldal Gu, Suwon 442749, South Korea. Ajou Univ, Sch Med, Inst Med Sci, Lab Med Genet,Paldal Gu, Suwon 442749, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Univ Calgary, Fac Med,Julia McFarlane Diabet Res Ctr, Dept Microbiol & Infect Dis, Lab Viral & Immunopathogeneis Diabet, Calgary, AB T2N 4N1, Canada. RP Choi, KS (reprint author), Ajou Univ, Sch Med, Inst Med Sci, Lab Endocrinol,Paldal Gu, 5 Wonchon Dong, Suwon 442749, South Korea. NR 76 TC 70 Z9 74 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 NOV 5 PY 1999 VL 274 IS 45 BP 31775 EP 31783 DI 10.1074/jbc.274.45.31775 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100007 PM 10542199 ER PT J AU Weng, BY Thompson, WC Kim, HJ Levine, RL Moss, J AF Weng, BY Thompson, WC Kim, HJ Levine, RL Moss, J TI Modification of the ADP-ribosyltransferase and NAD glycohydrolase activities of a mammalian transferase (ADP-ribosyltransferase 5) by auto-ADP-ribosylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; LYMPHOCYTE ALLOANTIGEN RT6.1; SKELETAL-MUSCLE CELLS; CYTOTOXIC T-CELLS; MOLECULAR CHARACTERIZATION; BACTERIAL TOXINS; NITRIC-OXIDE; EXPRESSION; SURFACE; PROTEIN AB Mono-ADP-ribosylation, a post-translational modification in which the ADP-ribose moiety of NAD is transferred to an acceptor protein, is catalyzed by a family of amino acid-specific ADP-ribosyltransferases. ADP-ribosyltransferase 5 (ARTS), a murine transferase originally isolated from Yac-1 lymphoma cells, differed in properties from previously identified eukaryotic transferases in that it exhibited significant NAD glycohydrolase (NADase) activity. To investigate the mechanism of regulation of transferase and NADase activities, ARTS was synthesized as a FLAG fusion protein in Escherichia coli, Agmatine was used as the ADP-ribose acceptor to quantify transferase activity. ARTS was found to be primarily an NADase at 10 mu M NAD, whereas at higher NAD concentrations (1 mM), after some delay, transferase activity increased, whereas NADase activity fell. This change in catalytic activity was correlated with auto-ADP-ribosylation and occurred in a time- and NAD concentration-dependent manner. Based on the change in mobility of auto-ADP-ribosylated ARTS by SDS-poly acrylamide gel electrophoresis, the modification appeared to be stoichiometric and resulted in the addition of at least two ADP-ribose moieties, Auto-ADP-ribosylated ARTE isolated after incubation with NAD was primarily a transferase. These findings suggest that auto-ADP-ribosylation of ARTS was stoichiometric, resulted in at least two modifications and converted ARTS from an NADase to a transferase, and could be one mechanism for regulating enzyme activity. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Weng, BY (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,10 Ctr Dr,MSC 1434,Rm 5N307, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 39 TC 18 Z9 19 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 NOV 5 PY 1999 VL 274 IS 45 BP 31797 EP 31803 DI 10.1074/jbc.274.45.31797 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100010 PM 10542202 ER PT J AU Delerive, P De Bosscher, K Besnard, S Vanden Berghe, W Peters, JM Gonzalez, FJ Fruchart, JC Tedgui, A Haegeman, G Staels, B AF Delerive, P De Bosscher, K Besnard, S Vanden Berghe, W Peters, JM Gonzalez, FJ Fruchart, JC Tedgui, A Haegeman, G Staels, B TI Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappa B and AP-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CORONARY-ARTERY DISEASE; CBP-INDUCED STIMULATION; CREB-BINDING PROTEIN; GLUCOCORTICOID RECEPTOR; C-JUN; NUCLEAR FACTOR; PPAR-GAMMA; LIPOPROTEIN METABOLISM; FUNCTIONAL ANTAGONISM; ANDROGEN RECEPTOR AB Interleukin-6 (IL-6) is a pleiotropic cytokine, whose plasma levels are elevated in inflammatory diseases such as atherosclerosis. We have previously reported that peroxisome proliferator-activated receptor alpha (PPAR alpha) Ligands (fibrates) lower elevated plasma concentrations of IL-6 in patients with atherosclerosis and inhibit IL-1-stimulated IL-6 secretion by human aortic smooth muscle cells (SMC). Here, we show that aortic explants isolated from PPAR alpha-null mice display an exacerbated response to inflammatory stimuli, such as li popolysaccharide (LPS), as demonstrated by increased IL-6 secretion. Furthermore, fibrate treatment represses IL-6 mRNA levels in LPS-stimulated aortas of PPAR alpha wild-type, but not of PPAR alpha-null mice, demonstrating a role for PPAR alpha in this fibrate action. in human aortic SMC, fibrates inhibit IL-1-induced IL-6 gene expression. Furthermore, activation of PPAR alpha represses both c-Jun- and p65-induced transcription of the human IL-6 promoter. Transcriptional interference between PPAR alpha and both c-Jun and p65 occurs reciprocally, since c-Jun and p65 also inhibit PPAR alpha-mediated activation of a PPAR response element-driven promoter. This transcriptional interference occurs independent of the promoter context as demonstrated by cotransfection experiments using PPAR alpha, p65, and c-Jun Gal4 chimeras. Overexpression of the transcriptional coactivator cAMP-responsive element-binding protein-binding protein (CBP) does not relieve PPAR alpha-mediated transcriptional repression of p65 and c-Jun, Finally, glutathione S-transferase pull-down experiments demonstrate that PPAR alpha physically interacts with c-dun, p65, and CBP. Altogether these data indicate that fibrates inhibit the vascular inflammatory response via PPAR alpha by interfering with the NF-kappa B and AP-1 transactivation capacity involving direct protein-protein interaction with p65 and c-Jun. C1 Inst Pasteur, Dept Atherosclerose, U325 INSERM, F-59019 Lille, France. Univ Lille 2, Fac Pharm, F-59000 Lille, France. State Univ Ghent, Mol Biol Lab, B-9000 Ghent, Belgium. VIB, B-9000 Ghent, Belgium. INSERM U141, F-75745 Paris 10, France. NCI, Dept Mol Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Staels, B (reprint author), Inst Pasteur, Dept Atherosclerose, U325 INSERM, 1 Rue Pr Calmette, F-59019 Lille, France. RI Peters, Jeffrey/D-8847-2011; Staels, Bart/N-9497-2016 OI Staels, Bart/0000-0002-3784-1503 NR 61 TC 724 Z9 751 U1 1 U2 23 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 NOV 5 PY 1999 VL 274 IS 45 BP 32048 EP 32054 DI 10.1074/jbc.274.45.32048 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100045 PM 10542237 ER PT J AU Zeremski, M Hill, JE Kwek, SSS Grigorian, IA Gurova, KV Garkavtsev, IV Diatchenko, L Koonin, EV Gudkov, AV AF Zeremski, M Hill, JE Kwek, SSS Grigorian, IA Gurova, KV Garkavtsev, IV Diatchenko, L Koonin, EV Gudkov, AV TI Structure and regulation of the mouse ing1 gene - Three alternative transcripts encode two PHD finger proteins that have opposite effects on p53 function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CANDIDATE TUMOR-SUPPRESSOR; REGION; MDM2; DEGRADATION; FIBROBLASTS; PROMOTES; RNA AB The human ING1 gene encodes nuclear protein p33(,)(ING1) CII previously shown to cooperate with p53 in cell growth control (Garkavtsev, I., Grigorian, I. A., Ossovskaya, V. S., Chernov, M. V., Chumakov, P, M., and Gudkov, A. V, (1998) Nature 391, 295-298), p33(ING1) belongs to a small family of proteins from human, mouse, and yeast of approximately the same size that show significant similarity to one another within the C-terminaI PHD finger domain and also contain an additional N-terminal region with subtle but reliably detectable sequence conservation Mouse ing1 is transcribed from three differently regulated promoters localized within a 4-kilobase pair region of genomic DNA The resulting transcripts share a long common region encoded by a common exon and differ in their 5'-exon sequences. Two transcripts are translated into the same protein of 185 amino acids, the mouse equivalent of the human p33(ING1), while the third transcript encodes a longer protein that has 94 additional N-terminal amino acids. Overexpression of the longer protein interferes with the accumulation of p53 protein and activation of p53-responsive promoters after DNA damage. Between the two products of ing1, only the longer one forms a complex with p53 detectable by immunoprecipitation, These results indicate that a single gene, ing1, encodes both p53-suppressing and p53-activating proteins that are regulated by alternative promoters. C1 Univ Illinois, Coll Med, Dept Mol Genet, Chicago, IL 60607 USA. CLONTECH Labs Inc, Palo Alto, CA 94303 USA. Genome Therapeut Corp, Dept Funct Gen, Waltham, MA 02154 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Gudkov, AV (reprint author), Univ Illinois, Coll Med, Dept Mol Genet, M-C 669,900 S Ashland Ave, Chicago, IL 60607 USA. FU NCI NIH HHS [CA75179, CA60730] NR 31 TC 58 Z9 61 U1 1 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 NOV 5 PY 1999 VL 274 IS 45 BP 32172 EP 32181 DI 10.1074/jbc.274.45.32172 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100062 PM 10542254 ER PT J AU Lu, JF O'Hara, EB Trieselmann, BA Romano, PR Dever, TE AF Lu, JF O'Hara, EB Trieselmann, BA Romano, PR Dever, TE TI The interferon-induced double-stranded RNA-activated protein kinase PKR will phosphorylate serine, threonine, or tyrosine at residue 51 in eukaryotic initiation factor 2 alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EIF-2-ALPHA KINASE; TRANSLATIONAL CONTROL; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; DEPENDENT KINASE; INSULIN-RECEPTOR; YEAST; GCN2; GENE; FACTOR-2-ALPHA AB The family of eukaryotic initiation factor 2 alpha (eIF2 alpha) protein kinases plays an important role in regulating cellular protein synthesis under stress conditions. The mammalian kinases PKR and HRI and the yeast kinase GCN2 specifically phosphorylate Ser-51 on the a subunit of the translation initiation factor eIF2, By using an in vivo assay in yeast, the substrate specificity of these three eIF2 alpha kinases was examined by substituting Ser-51 in eIF2 alpha with Thr or Tyr. In yeast, phosphorylation of eIF2 inhibits general translation but derepresses translation of the GCN4 mRNA. All three kinases phosphorylated Thr in place of Ser-51 and were able to regulate general and GCN4-specific translation. In addition, both PHR and HRI were found to phosphorylate eIF2 alpha-S51Y and stimulate GCN4 expression. Isoelectric focusing analysis of eIF2 alpha followed by detection using anti-eIF2 alpha and anti-phosphotyrosine-specific antibodies demonstrated that PKR and HRI phosphorylated eIF2 alpha-S51Y on Tyr in vivo. These results provide new insights into the substrate recognition properties of the eIF2 alpha kinases, and they are intriguing considering the potential for alternate substrates for PKR in cellular signaling and growth control pathways. C1 NICHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Dever, TE (reprint author), NICHD, Lab Eukaryot Gene Regulat, NIH, Bldg 6A,Rm B1A-02,6 Ctr Dr,MSC 2716, Bethesda, MD 20892 USA. NR 36 TC 38 Z9 40 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 NOV 5 PY 1999 VL 274 IS 45 BP 32198 EP 32203 DI 10.1074/jbc.274.45.32198 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100065 PM 10542257 ER PT J AU Jimenez-Asensio, J Colvis, CM Kowalak, JA Duglas-Tabor, Y Datiles, MB Moroni, M Mura, U Rao, CM Balasubramanian, D Janjani, A Garland, D AF Jimenez-Asensio, J Colvis, CM Kowalak, JA Duglas-Tabor, Y Datiles, MB Moroni, M Mura, U Rao, CM Balasubramanian, D Janjani, A Garland, D TI An atypical form of alpha B-crystallin is present in high concentration in some human cataractous lenses - Identification and characterization of aberrant N- and C-terminal processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEINS; CHAPERONE-LIKE ACTIVITY; BOVINE LENS; 2-DIMENSIONAL ELECTROPHORESIS; PHOSPHORYLATION SITES; MOLECULAR CHAPERONE; MASS-SPECTROMETRY; STRESS PROTEINS; A-CRYSTALLIN; AMINO-ACID AB Two unique polypeptides, 22.4 and 16.4 kDa, were prominent in some human cataracts. Both proteins mere identified as modified forms of the small heat shock protein, alpha B-crystallin. The concentration of total alpha B-crystallin in most of these cataracts was significantly increased. The 22.4-kDa protein was subsequently designated as alpha B-g. Mass spectrometric analyses of tryptic and Asp-N digests showed alpha B-g is alpha B-crystallin minus the C-terminal lysine. alpha B-g constituted 10-90% of the total alpha B-crystallin in these cataracts and was preferentially phosphorylated over the typical form of alpha B-crystallin. Human alpha B-g and alpha B-crystallin were cloned and expressed in Escherichia coli. The differences in electrophoretic mobility and the large difference in native pI values suggest some structural differences exist. The chaperone-like activity of recombinant human alpha B-g was comparable to that of recombinant human alpha B-crystallin in preventing the aggregation of lactalbumin induced by dithiothreitol, The mechanism involved in generating alpha B-g is not known, but a premature termination of the alpha B-crystallin gene was ruled out by sequencing the polymerase chain reaction products of the last exon for the alpha B-crystallin gene from lenses containing alpha B-g. The 16.4-kDa protein was an N-terminally truncated fragment of alpha B-g. The high concentration of alpha B-crystallin in these cataracts is the first observation of this kind in human lenses. C1 NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Pisa, I-56100 Pisa, Italy. Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India. Ctr Cellular & Mol Biol, Hyderabad 500034, Andhra Pradesh, India. LV Prasad Eye Inst, Hyderabad 500034, Andhra Pradesh, India. RP Garland, D (reprint author), NEI, Lab Mechanisms Ocular Dis, NIH, Bldg 6,Rm 235, Bethesda, MD 20892 USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 58 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1999 VL 274 IS 45 BP 32287 EP 32294 DI 10.1074/jbc.274.45.32287 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100076 PM 10542268 ER PT J AU Ryder, KM Benjamin, EJ AF Ryder, KM Benjamin, EJ TI Epidemiology and significance of atrial fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 71st Scientific Session of the American-Heart-Association Meeting CY NOV 08-12, 1998 CL DALLAS, TEXAS SP Amer Heart Assoc ID ACUTE MYOCARDIAL-INFARCTION; RISK-FACTORS; GENERAL-PRACTICE; HEART-FAILURE; FOLLOW-UP; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; PROGNOSTIC-SIGNIFICANCE; ELDERLY PATIENTS; OLDER PERSONS; STROKE AB Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting an estimated 2.2 million adults in the United States, The median age of people with AF is 75, and it affects 8.8% of the US population >80 years of age. Prevalence data from other countries are presented. Direct comparisons are limited by study design, but rough comparisons suggest that the prevalence of AF in Europe is similar to the prevalence in the United States, whereas the prevalence in Asia may be lower, The limited comparative data underscore our lack of understanding of AF risk factors and complications in racial subgroups and in developing countries, AF increases stroke risk 5-fold. The clinical features that predict higher risk of stroke in AF are prior stroke, hypertension, advancing age, diabetes, and congestive heart failure, Predicting which patients with atrial fibrillation are at the highest risk of stroke remains a challenge, Echocardiographic findings have been investigated to assist in the risk stratification of patients with AF. Despite evidence from clinical trials that anticoagulation with warfarin reduces stroke incidence and even mortality, anticoagulation remains underutilised, especially in the elderly. Improvement in the rate of anticoagulation in patients with AF at risk of stroke can be expected to decrease the complications and mortality of AF, (C)1999 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, NIH, Farmington, MA 01702 USA. Univ Tennessee, Sch Med, Dept Internal Med, Memphis, TN USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Farmington, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [5-R01-NS-17950] NR 69 TC 105 Z9 108 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 4 PY 1999 VL 84 IS 9A SI SI BP 131R EP 138R PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 253EV UT WOS:000083544400020 PM 10568672 ER PT J AU Carroll, FI Bai, X Dehghani, A Mascarella, SW Williams, W Bowen, WD AF Carroll, FI Bai, X Dehghani, A Mascarella, SW Williams, W Bowen, WD TI Asymmetric synthesis of 9-alkyl-2-benzyl-6 7-benzomorphans: Characterization as novel sigma receptor ligands SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID H-3 (+)-PENTAZOCINE; RAT-BRAIN; BINDING; SITE; AFFINITY; CLONING; NAPHTHALENES; INHIBITION; EXPRESSION; ADDITIONS AB A convenient enantioselective synthesis of (1R,5R,9R)- and (1S,5S,9S)-9-alkyl-2-benzyl-6,7-benzomorphans (2a-c) which starts with naphthaldehyde is described. These compounds were designed to gain additional information on the structure-a binding relationship of the 6,7-benzomorphan class of a ligands. In contrast to pentazocine and most 6,7-benzomorphans, the (1R,5R,9R)-isomers of 2a-c showed greater affinity for the al receptor than the (1S,5S,9S)isomers. Despite reversal of enantioselectivity at the ax sites, moderate affinity and enantioselectivity at the sigma(2) sites [greater affinity for (1R,5R,9R)-isomers than (1S,5S,9S)-isomers] were maintained. A comparison of the binding affinities of 2a-e to the more conformationally flexible trans-2-alkyl-1-benzaminoethyl-1,2-dihydronaphthalenes (10a-c) suggested that the relatively rigid structure of 2a-c played an important part in their al binding properties. These compounds, particularly (1R,5R,SR)-2-benzyl-9-methyl-6,7-benzomorphan [(-)-2a], which has a Ki value of 0.96 nM, will be useful in further characterization of the al receptor. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Carroll, FI (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIDA NIH HHS [DA05721] NR 41 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 4 PY 1999 VL 42 IS 22 BP 4621 EP 4629 DI 10.1021/jm990169r PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 252TX UT WOS:000083519300014 PM 10579824 ER PT J AU Langenberg, AGM Corey, L Ashley, RL Leong, WP Straus, SE AF Langenberg, AGM Corey, L Ashley, RL Leong, WP Straus, SE CA Chiron HSV Vaccine Study Grp TI A prospective study of new infections with herpes simplex virus type 1 and type 2 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POLYMERASE CHAIN-REACTION; GENITAL HERPES; ENZYME-IMMUNOASSAY; ANTIBODIES; WOMEN; PREVALENCE; IMMUNOBLOT; MENINGITIS; LESIONS; ASSAY AB Background Herpes simplex virus (HSV) infections are endemic, but the clinical characteristics of newly acquired HSV type 1 (HSV-1) and HSV type 2 (HSV-2) infections in adults have not been rigorously defined. Methods We monitored 2393 sexually active HSV-2-seronegative persons for clinical and serologic evidence of new HSV infection. Of the participants, 1508 were seropositive for HSV-1 and 885 were seronegative. Charts were reviewed in a blinded manner for classification of those with genitourinary or oropharyngeal symptoms. Charts were also reviewed for all 174 persons with HSV seroconversion. Results The rates of new HSV-1 and HSV-2 infections were 1.6 and 5.1 cases per 100 person-years, respectively. Of the 155 new HSV-2 infections, 57 (37 percent) were symptomatic, 47 of which (82 percent) were correctly diagnosed at presentation. Among the 74 patients given a clinical diagnosis of genital HSV-2 infection during the study, 60 were given a correct diagnosis and 14 were given an incorrect diagnosis, for a ratio of true positive results to false positive results of 4:1. Among the 98 persons with asymptomatic HSV-2 seroconversion, 15 percent had genital lesions at some time during follow-up. Women were more likely than men to acquire HSV-2 (P<0.01) and to have symptomatic infection. Previous HSV-1 infection did not reduce the rate of HSV-2 infection, but it did increase the likelihood of asymptomatic seroconversion, as compared with symptomatic seroconversion, by a factor of 2.6 (P<0.001). Of the 19 new HSV-1 infections, 12 were symptomatic. The rates of symptomatic genital HSV-1 infection and oropharyngeal HSV-1 infection were the same (0.5 case per 100 person-years). Conclusions Nearly 40 percent of newly acquired HSV-2 infections and nearly two thirds of new HSV-1 infections are symptomatic. Among sexually active adults, new genital HSV-1 infections are as common as new oropharyngeal HSV-1 infections. (N Engl J Med 1999;341:1432-8.) (C)1999, Massachusetts Medical Society. C1 Chiron Corp, Emeryville, CA 94608 USA. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. RP Corey, L (reprint author), 1100 Fairview Ave N,D3-100, Seattle, WA 98109 USA. NR 30 TC 279 Z9 283 U1 1 U2 8 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 NOV 4 PY 1999 VL 341 IS 19 BP 1432 EP 1438 DI 10.1056/NEJM199911043411904 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 251XR UT WOS:000083472100004 PM 10547406 ER PT J AU Abernethy, DR Schwartz, JB AF Abernethy, DR Schwartz, JB TI Calcium-antagonist drugs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SMOOTH-MUSCLE CELLS; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; VENTRICULAR RATE CONTROL; CORONARY-ARTERY DISEASE; CHANNEL BLOCKERS; CONTROLLED TRIAL; ANGIOTENSIN-II; MEDIATED VASOCONSTRICTION; CARDIOVASCULAR EVENTS C1 Georgetown Univ, Med Ctr, Div Clin Pharmacol, Washington, DC 20007 USA. Northwestern Univ, Med Ctr, Div Clin Pharmacol & Geriatr, Chicago, IL 60611 USA. RP Abernethy, DR (reprint author), NIA, Clin Invest Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIA NIH HHS [AG-00768-02, AG-08226-08]; NIGMS NIH HHS [GM-08386-09] NR 103 TC 222 Z9 231 U1 0 U2 8 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 NOV 4 PY 1999 VL 341 IS 19 BP 1447 EP 1457 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 251XR UT WOS:000083472100007 PM 10547409 ER PT J AU Henderson, DK AF Henderson, DK TI Postexposure prophylaxis for occupational exposure to HIV - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 1999 VL 282 IS 17 BP 1624 EP 1624 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 250BD UT WOS:000083368400023 ER PT J AU Whitcup, SM Fortin, E Lindblad, AS Griffiths, P Metcalf, JA Robinson, MR Manischewitz, J Baird, B Perry, C Kidd, IM Vrabec, T Davey, RT Falloon, J Walker, RE Kovacs, JA Lane, HC Nussenblatt, RB Smith, J Masur, H Polis, MA AF Whitcup, SM Fortin, E Lindblad, AS Griffiths, P Metcalf, JA Robinson, MR Manischewitz, J Baird, B Perry, C Kidd, IM Vrabec, T Davey, RT Falloon, J Walker, RE Kovacs, JA Lane, HC Nussenblatt, RB Smith, J Masur, H Polis, MA TI Discontinuation of anticytomegalovirus therapy in patients with HIV infection and cytomegalovirus retinitis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMBINATION ANTIRETROVIRAL THERAPY; IMMUNE-DEFICIENCY-SYNDROME; RELEASE GANCICLOVIR IMPLANT; POLYMERASE CHAIN-REACTION; MAINTENANCE THERAPY; AIDS; DISEASE; VIRUS; TRIAL AB Context Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. Objective To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. Design Prospective nonrandomized interventional trial performed from July 1997 to August 1999. Setting Clinical Center of the National Institutes of Health, Bethesda, Md. Patients Fourteen patients with stable CMV retinitis and HIV infection and CD4(+) cell counts higher than 0.15 x 10(9)/L and being treated with systemic anti-CMV medications and HAART. Interventions Discontinuation of specific anti-CMV therapy. Main Outcome Measures Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function; quality of life, morbidity, and mortality. Results Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications, Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. Conclusions Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4(+) cell counts and who were taking HAART, The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression. C1 NEI, Clin Branch, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. EMMES Corp, Potomac, MD USA. US FDA, CBER, Lab Virol Retrovirol, Rockville, MD 20857 USA. Royal Free Hosp, Sch Med, Dept Virol, London, England. Wills Eye Hosp, Dept Ophthalmol, Philadelphia, PA USA. RP Whitcup, SM (reprint author), NEI, Clin Branch, NIH, 10 10S221,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 FU NIAID NIH HHS [1R01AI41687] NR 28 TC 107 Z9 114 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 1999 VL 282 IS 17 BP 1633 EP 1637 DI 10.1001/jama.282.17.1633 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 250BD UT WOS:000083368400028 PM 10553789 ER PT J AU Tamura, M Gu, JG Tran, H Yamada, KM AF Tamura, M Gu, JG Tran, H Yamada, KM TI PTEN gene and integrin signaling in cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID FOCAL ADHESION KINASE; MEDIATED CELL-ADHESION; TUMOR-SUPPRESSOR PTEN; ACTIVATED PROTEIN-KINASE; SRC FAMILY KINASES; TYROSINE PHOSPHORYLATION; PROSTATE-CANCER; EXTRACELLULAR-MATRIX; MAP KINASE; PHOSPHATIDYLINOSITOL 3-KINASE AB Integrins are major adhesion- and signaling-receptor proteins that mediate cell migration and invasion, They also trigger a variety of signal transduction pathways and regulate cytoskeletal organization, specific gene expression, growth control, and apoptosis (programmed cell death). Consequently, integrins are thought to play important roles in embryonic development and in the biology of cancers. The functions of integrins can be negatively regulated by the recently discovered tumor suppressor PTEN, a protein with homology to protein tyrosine phosphatases and tensin, The PTEN gene is mutated in a wide range of human cancers. PTEN inhibits cell migration and invasion by directly dephosphorylating two key tyrosine-phosphorylated proteins, thereby antagonizing interactions of integrins with the extracellular matrix and integrin-triggered signaling pathways. Other studies demonstrate important roles for PTEN in dephosphorylating a key signal transduction lipid. In the absence of PTEN, this lipid signal transduction pathway can protect tumor cells from apoptosis, Thus, PTEN appears to be a unique tumor suppressor-with both lipid phosphatase and protein tyrosine phosphatase activities-that negatively regulates cell interactions with the extracellular matrix and that maintains cell sensitivity to apoptosis, e.g., after loss of cell contact with the extracellular matrix. The complex signal transduction pathways regulated by PTEN are described in this review. PTEN and the signaling pathways it regulates may provide novel targets for potential therapy. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD USA. RP Yamada, KM (reprint author), NIH, Bldg 30,Rm 421,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 163 TC 131 Z9 145 U1 1 U2 4 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 NOV 3 PY 1999 VL 91 IS 21 BP 1820 EP 1828 DI 10.1093/jnci/91.21.1820 PG 9 WC Oncology SC Oncology GA 252FK UT WOS:000083491300013 PM 10547389 ER PT J AU Gail, MH Costantino, JP Bryant, J Croyle, R Freedman, L Helzlsouer, K Vogel, V AF Gail, MH Costantino, JP Bryant, J Croyle, R Freedman, L Helzlsouer, K Vogel, V TI Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL-ADJUVANT-BREAST; RECEPTOR-NEGATIVE TUMORS; OVARIAN-CANCER; PULMONARY-EMBOLISM; ENDOMETRIAL CANCER; MEDICAL PROGRESS; RANDOMIZED TRIAL; BRCA1 MUTATIONS; FAMILY HISTORY; HIP FRACTURE AB Background: In response to findings from the Breast Cancer Prevention Trial that tamoxifen treatment produced a 49% reduction in the risk of invasive breast cancer in a population of women at elevated risk, the National Cancer Institute sponsored a workshop on July 7 and 8, 1998, to develop information to assist in counseling and in weighing the risks and benefits of tamoxifen, Our study was undertaken to develop tools to identify women for whom the benefits outweigh the risks, Methods: Information was reviewed on the incidence of invasive breast cancer and of in situ lesions, as well as on several other health outcomes, in the absence of tamoxifen treatment. Data on the effects of tamoxifen on these outcomes were also reviewed, and methods were developed to compare the risks and benefits of tamoxifen, Results: The risks and benefits of tamoxifen depend on age and race, as well as on a woman's specific risk factors for breast cancer, In particular, the absolute risks from tamoxifen of endometrial cancer, stroke, pulmonary embolism, and deep vein thrombosis increase with age, and these absolute risks differ between white and black women, as does the protective effect of tamoxifen on fractures. Tables and aids are developed to describe the risks and benefits of tamoxifen and to identify classes of women for whom the benefits outweigh the risks. Conclusions: Tamoxifen is most beneficial for younger women with an elevated risk of breast cancer. The quantitative analyses presented can assist health care providers and women in weighing the risks and benefits of tamoxifen for reducing breast cancer risk. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Bar Illan Univ, Ramat Gan, Israel. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Pittsburgh, Inst Canc, Magee Womens Hosp, Pittsburgh, PA 15260 USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, EPS-8032, Bethesda, MD 20892 USA. NR 85 TC 427 Z9 429 U1 0 U2 12 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 NOV 3 PY 1999 VL 91 IS 21 BP 1829 EP 1846 DI 10.1093/jnci/91.21.1829 PG 18 WC Oncology SC Oncology GA 252FK UT WOS:000083491300014 PM 10547390 ER PT J AU Veronesi, U De Palo, G Marubini, E Costa, A Formelli, F Mariani, L Decensi, A Camerini, T Del Turco, MR Di Mauro, MG Muraca, MG Del Vecchio, M Pinto, C D'Aiuto, G Boni, C Campa, T Magni, A Miceli, R Perloff, M Malone, WF Sporn, MB AF Veronesi, U De Palo, G Marubini, E Costa, A Formelli, F Mariani, L Decensi, A Camerini, T Del Turco, MR Di Mauro, MG Muraca, MG Del Vecchio, M Pinto, C D'Aiuto, G Boni, C Campa, T Magni, A Miceli, R Perloff, M Malone, WF Sporn, MB TI Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SYNTHETIC RETINOID FENRETINIDE; GROWTH-FACTOR-I; REGRESSION-MODEL; OVARIAN-CANCER; CELL-LINES; CHEMOPREVENTION; RISK; TAMOXIFEN; THERAPY; BRCA1 AB Background: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies, We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. Methods: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence mere determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. Results: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P = .642) or ipsilateral breast cancer (P = .177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes = .045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0.92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1.89), There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. Conclusions: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed. C1 Ist Europeo Oncol, I-20141 Milan, Italy. Ist Nazl Tumori, I-20133 Milan, Italy. Univ Milan, Ist Stat Med & Biometria, I-20122 Milan, Italy. Ctr Prevenz Oncol, Florence, Italy. Ist Oncol F Addarii, Bologna, Italy. Ist Nazl Tumori, Naples, Italy. Osped Santa Maria Maggiore, Reggio Emilia, Italy. NCI, Chemoprevent Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Dartmouth Med Sch, Hanover, NH USA. RP Costa, A (reprint author), Ist Europeo Oncol, Via Ripamonti 435, I-20141 Milan, Italy. RI Miceli, Rosalba/C-1215-2017; Mariani, Luigi/C-2580-2017 OI Miceli, Rosalba/0000-0003-0954-375X; Mariani, Luigi/0000-0001-6208-4084 FU NCI NIH HHS [CA38567, CA72286] NR 50 TC 316 Z9 326 U1 1 U2 4 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 NOV 3 PY 1999 VL 91 IS 21 BP 1847 EP 1856 DI 10.1093/jnci/91.21.1847 PG 10 WC Oncology SC Oncology GA 252FK UT WOS:000083491300015 PM 10547391 ER PT J AU Fisher, B Costantino, JP AF Fisher, B Costantino, JP TI Tamoxifen for prevention of breast cancer: Report of the national surgical adjuvant breast and bowel project P-1 study - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Ctr Biostat, Div Stat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Costantino, JP (reprint author), Ctr Biostat, Div Stat, Natl Surg Adjuvant Breast & Bowel Project, 230 McKee Pl,Suite 403, Pittsburgh, PA 15213 USA. NR 1 TC 5 Z9 5 U1 1 U2 5 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 NOV 3 PY 1999 VL 91 IS 21 BP 1891 EP 1892 PG 2 WC Oncology SC Oncology GA 252FK UT WOS:000083491300023 ER PT J AU Ursin, G London, S AF Ursin, G London, S TI Urinary 2-hydroxyestrone/16 alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Ursin, G (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,MS 44,Suite 4407, Los Angeles, CA 90089 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 3 PY 1999 VL 91 IS 21 BP 1893 EP 1894 PG 2 WC Oncology SC Oncology GA 252FK UT WOS:000083491300026 ER PT J AU Zack, DJ Dean, M Molday, RS Nathans, J Redmond, TM Stone, EM Swaroop, A Valle, D Weber, BHF AF Zack, DJ Dean, M Molday, RS Nathans, J Redmond, TM Stone, EM Swaroop, A Valle, D Weber, BHF TI What can we learn about age-related macular degeneration from other retinal diseases? SO MOLECULAR VISION LA English DT Article ID CONE-ROD DYSTROPHY; RECESSIVE RETINITIS-PIGMENTOSA; SORSBYS FUNDUS DYSTROPHY; TISSUE INHIBITOR; GYRATE ATROPHY; HOMEOBOX GENE; METALLOPROTEINASES-3 TIMP3; STARGARDT-DISEASE; PHOTORECEPTOR PERIPHERIN/RDS; CONGENITAL AMAUROSIS AB Over the last 10 years there has been an explosion of new information about the genetics of retinal disease. Over 104 genetic loci have been mapped and more than 45 disease causing genes have been identified (see RetNet). The biology of some of these genes is beginning to be understood and animal models that express some of these mutated human genes have been developed. It is likely that the increasing knowledge derived from these studies will have implications for understanding the genetics and pathogenesis of age related macular degeneration (AMD). Selected aspects of the genetics and biology of photoreceptor degeneration are presented, including the role of ABCR in Stargardt disease and its possible relationship to AMD, the role of rom-1, rds-peripherin, and CRX in various forms of photoreceptor degeneration, and the development and initial characterization of mice carrying targeted deletions of the OAT, TIMP-3, and RPE65 genes. The relevance and limitations of these studies for helping to understand AMD are discussed. C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. NEI, LRCMB, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Bioctr, Inst Human Genet, D-97074 Wuerzburg, Germany. RP Zack, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, 600 N Wolfe St,809 Maumenee, Baltimore, MD 21287 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 47 TC 1 Z9 1 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 3 PY 1999 VL 5 IS 24-35 BP U37 EP U43 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 260ER UT WOS:000083937000007 ER PT J AU Askling, J Sorensen, P Ekbom, A Frisch, M Melbye, M Glimelius, B Hjalgrim, H AF Askling, J Sorensen, P Ekbom, A Frisch, M Melbye, M Glimelius, B Hjalgrim, H TI Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer? SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE carcinoma, squamous cell; lymphoma, non-Hodgkin; colonic neoplasms; prostatic neoplasms; lung neoplasms; breast neoplasms ID CYTOKINE DYSREGULATION; CARCINOMA; RISK; LYMPHOMA AB Background: Nonmelanoma skin cancer is associated with increased occurrence of subsequent cancer and death from cancer, but it is not known whether a history of skin cancer is associated with poor prognosis after a second diagnosis of cancer. Objective: To determine whether history of squamous-cell skin cancer is a marker of poor prognosis in patients with cancer. Design: Population-based cohort study. Setting: Sweden, 1958 to 1996. Patients: All patients in the Swedish Cancer Registry with or without a first diagnosis of squamous-cell skin cancer and a subsequent or first diagnosis of non-Hodgkin lymphoma (including chronic lymphocytic leukemia) or cancer of the colon, breast, prostate, or lung. Measurements: Relative risk (RR) for death determined by using Cox proportional hazards regression analysis. Results: Patients with a history of squamous-cell skin cancer had a significantly greater risk for death than those with no such history after receiving a diagnosis of non-Hodgkin lymphoma (RR, 1.33). colon cancer (RR, 1.24), breast cancer (RR, 1.19), or prostate cancer (RR, 1.17). Patients with lung cancer and a history of squamous-cell skin cancer who survived for 1 year after diagnosis of lung cancer also had an increased risk for death (RR, 1.29). Conclusion: Patients with a registered history of squamous-cell skin cancer have a poor prognosis after diagnosis of subsequent cancer and warrant careful medical attention. C1 Karolinska Inst, Dept Med Epidemiol, S-17177 Stockholm, Sweden. State Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark. Harvard Sch Publ Hlth, Boston, MA USA. NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. Univ Uppsala Hosp, Uppsala, Sweden. RP Askling, J (reprint author), Karolinska Inst, Dept Med Epidemiol, Box 281, S-17177 Stockholm, Sweden. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 26 TC 18 Z9 18 U1 0 U2 1 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 NOV 2 PY 1999 VL 131 IS 9 BP 655 EP + PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 251LB UT WOS:000083446200003 PM 10577327 ER PT J AU Mu, Y Kamada, H Kodaira, H Sato, K Tsutsumi, Y Maeda, M Kawasaki, K Nomizu, M Yamada, Y Mayumi, T AF Mu, Y Kamada, H Kodaira, H Sato, K Tsutsumi, Y Maeda, M Kawasaki, K Nomizu, M Yamada, Y Mayumi, T TI Bioconjugation of laminin-related peptide YIGSR with polyvinyl pyrrolidone increases its antimetastatic effect due to a longer plasma half-life SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE peptide modification; YIGSR; polyvinyl pyrrolidone; plasma half-life; stability; antimetastasis ID EXPERIMENTAL METASTASIS FORMATION; NECROSIS-FACTOR-ALPHA; POLYETHYLENE-GLYCOL; BASEMENT-MEMBRANE; AMINO-ACIDS; TUMOR; FIBRONECTIN; POTENCY; CELLS AB Polyvinyl pyrrolidone (PVP) which can be radically synthesized and have a long blood residency was used to modify the laminin-related peptide YIGSR, and its inhibitory effect on experimental lung metastasis of B16-BL6 melanoma cells was examined. The antimetastatic effect of PVP-conjugated MG;SR (PVP-YIGSR) was more than 100-fold greater than that of native YIGSR. When injected intravenously, PVP-YIGSR showed more than a 15-fold longer plasma half-life relative to native YIGSR. In addition, the stability of YIGSR in plasma was increased by conjugation with PVP. These findings suggest that PVP is a useful polymeric modifier for increasing the antimetastatic activity of YIGSR. (C) 1999 Academic Press. C1 Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, Suita, Osaka 5650871, Japan. Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6510871, Japan. NIDR, Mol Biol Sect, NIH, Bethesda, MD 20892 USA. RP Mayumi, T (reprint author), Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan. NR 21 TC 20 Z9 21 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 NOV 2 PY 1999 VL 264 IS 3 BP 763 EP 767 DI 10.1006/bbrc.1999.1567 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 255JR UT WOS:000083666200027 PM 10544005 ER PT J AU Liu, XF Essand, M Vasmatzis, G Lee, B Pastan, I AF Liu, XF Essand, M Vasmatzis, G Lee, B Pastan, I TI Identification of three new alternate human kallikrein 2 transcripts: Evidence of long transcript and alternative splicing SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE EST; kallikrein; alternative splicing; hKLK2 gene ID HUMAN-GLANDULAR-KALLIKREIN; PROSTATE-SPECIFIC ANTIGEN; CANCER; GENE; EXPRESSION; MARKER; HK2 AB In a search for prostate-specific genes in the human expressed sequence tag (EST) database, we identified a seemingly unique EST cluster C81. Experimental data linked C81 to the human hKLK2 gene that encodes a prostate specific serine protease-human glandular kallikrein (hK2). We uncovered a full-length hKLK2 cDNA corresponding to a 3.0 kb hKLK2 mRNA by PCR and sequence analysis. The 3.0 kb transcript accounts for about 25% of the hKLK2 transcripts as compared to the previously known 1.5 kb transcript. We also identified a third spliced form of the hKLK2 gene produced by alternative splicing between intron III and exon 4. This spliced form was detected in normal prostate, prostate cancer and the prostate adenocarcinoma cell line LNCaP. The identification of long hKLK2 transcript and an alternative spliced form of the hKLK2 gene indicates that regulation of the gene is complex. (C) 1999 Academic Press. C1 NIH, Mol Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NIH, Mol Biol Lab, Div Basic Sci, Bldg 37,Room 4E16, Bethesda, MD 20892 USA. NR 22 TC 24 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 2 PY 1999 VL 264 IS 3 BP 833 EP 839 DI 10.1006/bbrc.1999.1595 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 255JR UT WOS:000083666200039 PM 10544017 ER PT J AU Alrefai, RH Beecham, EJ Bohr, VA Gearhart, PJ AF Alrefai, RH Beecham, EJ Bohr, VA Gearhart, PJ TI Less repair of pyrimidine dimers and single-strand breaks in genes by Scid cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DEPENDENT PROTEIN-KINASE; NUCLEOTIDE EXCISION-REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; V(D)J RECOMBINATION; DNA-REPAIR; CATALYTIC SUBUNIT; MUTANT-CELLS; MICE CAUSES; GROUP-C; MUTATION AB Severe combined immunodeficient (Scid) mice have a mutation in the catalytic subunit of the DNA binding protein kinase that is involved in repair of double-strand breaks in DNA, To determine if the protein also influences repair of single-strand breaks, we examined the ability of Scid cells to repair lesions introduced by ultraviolet light and gamma-ray irradiation. DNA repair was measured both in total genomic DNA and in specific genes from murine Scid and wildtype fibroblast cell lines. The removal of pyrimidine dimers and repair of strand breaks in genes was measured using quantitative Southern blot analyses. After ultraviolet irradiation, there was no significant difference in the repair of photoproducts in bulk DNA between Scid and wildtype cells, as measured by cellular survival and unscheduled DNA synthesis. However, deficient repair was evident in genes, where Scid cells had 25-50% less repair in the c-myc and dihydrofolate reductase genes. After gamma-irradiation, Scid fibroblasts had 20-35% less repair of DNA breaks in immunoglobulin kappa and heavy constant genes than wildtype cells. The data suggest that intact DNA-PK enzyme is needed for the efficient operation of cellular repair of pyrimidine dimers and single-strand breaks in genes, as well as in its established role in rejoining double-strand breaks. (C) 1999 Academic Press. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Harvard Inst Med, Biotherapeut Dev Lab, Div Hematol Oncol, Boston, MA 02115 USA. RP Gearhart, PJ (reprint author), NIA, Mol Genet Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 2 PY 1999 VL 264 IS 3 BP 878 EP 882 DI 10.1006/bbrc.1999.1608 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 255JR UT WOS:000083666200046 PM 10544024 ER PT J AU Long, YQ Yao, ZJ Voigt, JH Lung, FDT Luo, JH Burke, TR King, CR Yang, DJ Roller, PP AF Long, YQ Yao, ZJ Voigt, JH Lung, FDT Luo, JH Burke, TR King, CR Yang, DJ Roller, PP TI Structural requirements for Tyr in the consensus sequence Y-E-N of a novel nonphosphorylated inhibitor to the Grb2-SH2 domain SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SH2 DOMAIN; DRUG DESIGN; BINDING; PHOSPHOTYROSINE; RECEPTOR; SPECIFICITY; MECHANISMS; PEPTIDES; TARGETS; LIGANDS AB The phage library derived, nonphosphorylated and thioether-cyclized peptide, termed G1TE, cyclo(CH2CO-Glu(1)-Leu-Tyr(3)-Glu-Asn-Val-Gly-Met-Tyr-Cys(10))-amide, represents a new structural motif that binds to the Grb2-SH2 domain in a pTyr-independent manner, with an IC50 of 20 mu M. The retention of binding affinity is very sensitive with respect to peptide ring-size alterations and Ala mutations. We demonstrated previously that the Glu(1) side chain and its closely related analogs partially compensate for the absence of the phosphate functionality on Tyr(3), and, based on molecular modeling, these acidic side-chains complex with the Arg67 and Arg86 sidechains of the protein in the binding cavity. In this study we judiciously altered and incorporated various natural and unnatural amino acids as Tyr replacements within the -YEN- motif, and me demonstrate the functional importance and structural requirement of Tyr(3) for effective binding of this novel non-phosphorylated ligand to the Grb2-SH2 domain. The phenyl side-chain moiety and a polar functional group with specific orientation in position Y-3 of the peptide are particularly required. Using SPR binding assays, a submicromolar inhibitor (IC 0.70 mu M) was obtained when Glu(1) was replaced with alpha-aminoadipate and Tyr(3) was replaced with 4-carboxymethyl-Phe, providing peptide 14, G1TE(Adi(1), cmPhe(3)). Peptide 14 also inhibited Grb2/p185(erbB-2) protein association in cell homogenates of erb-2-overexpressing MDA-MA-453 cancer cells at near one micromolar concentrations, (C) 1999 Academic Press. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Roller, PP (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Room 5C02,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 29 TC 25 Z9 26 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 NOV 2 PY 1999 VL 264 IS 3 BP 902 EP 908 DI 10.1006/bbrc.1999.1599 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 255JR UT WOS:000083666200050 PM 10544028 ER PT J AU Zlotnick, A Johnson, JM Wingfield, PW Stahl, SJ Endres, D AF Zlotnick, A Johnson, JM Wingfield, PW Stahl, SJ Endres, D TI A theoretical model successfully identifies features of hepatitis B virus capsid assembly SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; CORE ANTIGEN; ELECTRON CRYOMICROSCOPY; PROTEIN COMPLEXES; DNA-SYNTHESIS; C-TERMINUS; RNA; MICROSCOPY; PRECURSORS; PARTICLES AB The capsids of most spherical viruses are icosahedral, an arrangement of multiples of 60 subunits, Though it is a salient point in the life cycle of any virus, the physical chemistry of virus capsid assembly is poorly understood. We have developed general models of capsid assembly that describe the process in terms of a cascade of low order association reactions. The models predict sigmoidal assembly kinetics, where intermediates approach a low steady state concentration for the greater part of the reaction. Features of the overall reaction can be identified on the basis of the concentration dependence of assembly. In simulations, and on the basis of our understanding of the models, we find that nucleus size and the order of subsequent "elongation" reactions are reflected in the concentration dependence of the extent of the reaction and the rate of the fast phase, respectively. The reaction kinetics deduced for our models of virus assembly can be related to the assembly of any "spherical" polymer. Using light scattering and size exclusion chromatography, we observed polymerization of assembly domain dimers of hepatitis B virus (HBV) capsid protein. Empty capsids assemble at a rate that is a function of protein concentration and ionic strength. The kinetics of capsid formation were sigmoidal, where the rate of the fast phase had second-power concentration dependence. The extent of assembly had third-power concentration dependence. Simulations based on the models recapitulated the concentration dependences observed for HBV capsid assembly. These results strongly suggest that in vitro HBV assembly is nucleated by a trimer of dimers and proceeds by the addition of individual dimeric subunits. On the basis of this mechanism, we suggest that HBV capsid assembly could be an important target for antiviral therapeutics. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Cent Oklahoma, Dept Math & Stat, Edmond, OK 73074 USA. RP Zlotnick, A (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, POB 26901 BRC 464, Oklahoma City, OK 73190 USA. NR 34 TC 184 Z9 186 U1 1 U2 37 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 2 PY 1999 VL 38 IS 44 BP 14644 EP 14652 DI 10.1021/bi991611a PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 255JF UT WOS:000083665200025 PM 10545189 ER PT J AU Pandey, SK Theberge, JF Bernier, M Srivastava, AK AF Pandey, SK Theberge, JF Bernier, M Srivastava, AK TI Phosphatidylinositol 3-kinase requirement in activation of the ras/C-raf-1/MEK/ERK and p70(s6k) signaling cascade by the insulinomimetic agent vanadyl sulfate SO BIOCHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; EPIDERMAL GROWTH-FACTOR; PROTEIN MAP KINASES; RAT ADIPOCYTES; DIABETES-MELLITUS; INSULIN ACTION; PHOSPHOINOSITIDE 3-KINASE; TYROSINE PHOSPHORYLATION; MEK KINASE; WORTMANNIN AB The mechanisms by which inorganic salts of the trace element vanadium mediate their insulinomimetic effects are not clearly understood and were investigated. We have shown previously that vanadium salts activate mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase activities (PI3-K) via a pathway that does not involve the insulin receptor (IR) tyrosine kinase function [Pandey, S. K., Anand-Srivastava, M. B., and Srivastava, A. K. (1998) Biochemistry 37, 7006-7014]. Herein, we have examined a possible role of PI3-K in the vanadyl sulfate (VS)-mediated increase in the level of ras-MAPK activation as well as the contribution of signaling components upstream to MAPK in this VS response. Treatment of IR-overexpressing cells with VS resulted in an increased level of tyrosine phosphorylation of p44(mapk) (ERK-1) and p42(mapk) (ERK-2) along with stimulation of MAPK, MAPK kinase (MEK), and C-raf-1 activities, and ras activation. Preincubation with wortmannin and LY294002, two structurally and mechanistically different inhibitors of PI3-K, blocked the VS-mediated increase in MAPK activity and phosphorylation of ERK-1 and ERK-2. Furthermore, wortmannin inhibited activation of ras, C-raf-1, and MEK in response to VS. The addition of a farnesyltransferase inhibitor, B581, to cells reduced the level of MAPK activation as well as ERK-1 and ERK-2 phosphorylation stimulated by VS. Finally, VS increased PI3-K activity in ras immunoprecipitates. A VS-mediated increase in p70(s6k) activity was also found to be inhibited by wortmannin, Taken together, these results demonstrate that the insulinomimetic effects of VS may be mediated, in part, by PI3-K-dependent stimulation of the ras-MAPK and p70(s6k) pathways. C1 Univ Montreal, Ctr Hosp Univ Montreal, Res Ctr, Montreal, PQ H2W 1T8, Canada. Univ Montreal, Dept Med, Montreal, PQ H2W 1T8, Canada. Univ Montreal, Dept Physiol, Montreal, PQ H2W 1T8, Canada. NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Srivastava, AK (reprint author), Univ Montreal, Ctr Hosp Univ Montreal, Res Ctr, Campus Hotel Dieu,3840 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM Srivasta@ere.umontreal.ca OI Bernier, Michel/0000-0002-5948-368X NR 67 TC 71 Z9 72 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 2 PY 1999 VL 38 IS 44 BP 14667 EP 14675 DI 10.1021/bi9911886 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 255JF UT WOS:000083665200028 PM 10545192 ER PT J AU Scuteri, A Bos, AJG Brandt, LJ Zonderman, AB Fleg, JL AF Scuteri, A Bos, AJG Brandt, LJ Zonderman, AB Fleg, JL TI Apoe4 allele is an independent predictor of coronary events in asymptomatic volunteers SO CIRCULATION LA English DT Meeting Abstract C1 NIA, LCS, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 20 BP 4 EP 4 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100021 ER PT J AU Young, LT Lee, JE Jacobson, KA Liang, BT AF Young, LT Lee, JE Jacobson, KA Liang, BT TI Human adenosine A(3) receptor signals via phospholipase D to induce cardiac myocyte protection SO CIRCULATION LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NIDDK, NIH, Bethesda, MD USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 26 BP 5 EP 6 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100027 ER PT J AU Merz, CNB Chan, P Kenkre, T Bittner, V Braunstein, G Hodgson, TK Lewis, J Sharaf, BL Berga, S Johnson, DB Sopko, G AF Merz, CNB Chan, P Kenkre, T Bittner, V Braunstein, G Hodgson, TK Lewis, J Sharaf, BL Berga, S Johnson, DB Sopko, G TI Reproductive history and CAD in women: The NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Univ Florida, Gainesville, FL USA. Brown Univ, Providence, RI 02912 USA. NHLBI, Bethesda, MD 20892 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 144 BP 29 EP 29 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100145 ER PT J AU Merz, CNB Johnson, DB Braunstein, G Pepine, CJ Jordan, RL Reis, SE Paul-Labrador, M Sopko, G Kelsey, SF AF Merz, CNB Johnson, DB Braunstein, G Pepine, CJ Jordan, RL Reis, SE Paul-Labrador, M Sopko, G Kelsey, SF TI Phytoestrogen levels mediate lipoproteins in women independent of estrogen level: The NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Florida, Gainesville, FL USA. NHLBI, Bethesda, MD 20892 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 146 BP 29 EP 29 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100147 ER PT J AU Vasan, RS Larson, MG Evans, JC O'Donnell, CJ Levy, D AF Vasan, RS Larson, MG Evans, JC O'Donnell, CJ Levy, D TI High normal blood pressure and risk of cardiovascular disease: The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 171 BP 34 EP 34 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100172 ER PT J AU Lloyd-Jones, DM Evans, JC O'Donnell, CJ Roccella, EJ Levy, D AF Lloyd-Jones, DM Evans, JC O'Donnell, CJ Roccella, EJ Levy, D TI Rates of hypertension control based on systolic versus diastolic blood pressure level SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Natl High Blood Pressure Educ Program, Bethesda, MD 20892 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 175 BP 35 EP 35 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100176 ER PT J AU Chase, MB Amar, MJ Shamburek, RD Lambert, GC Knapper, CL Allen, DT Santamarina-Fojo, S Brewer, HB AF Chase, MB Amar, MJ Shamburek, RD Lambert, GC Knapper, CL Allen, DT Santamarina-Fojo, S Brewer, HB TI Adenovirus-mediated expression of scavenger receptor type a class I (SR-BI) corrects the reverse cholesterol transport defect associated with LCAT transgenic mouse HDL SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 185 BP 37 EP 37 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100186 ER PT J AU Akyurek, LM Yang, ZY Aoki, K San, H Nabel, GJ Parmacek, MS Nabel, EG AF Akyurek, LM Yang, ZY Aoki, K San, H Nabel, GJ Parmacek, MS Nabel, EG TI SM22 alpha promoter targets gene expression to vascular smooth muscle cells in vitro and in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 237 BP 47 EP 47 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100238 ER PT J AU Toma, C Rosas, GO Fraites, TJ Jones, DC Guo, J Judge, DP Weiss, JL Plotz, P Raben, N Byrne, BJ Kessler, PD AF Toma, C Rosas, GO Fraites, TJ Jones, DC Guo, J Judge, DP Weiss, JL Plotz, P Raben, N Byrne, BJ Kessler, PD TI Systemic enzymatic and functional correction in a mouse model of the cardioskeletal myopathy, Pompe's disease SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Florida, Gainesville, FL USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 238 BP 47 EP 47 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100239 ER PT J AU Li, SY Margulies, KB Cheng, HP Houser, SR AF Li, SY Margulies, KB Cheng, HP Houser, SR TI Calcium current and calcium transients are depressed in failing human ventricular myocytes and recover in patients supported with left ventricular assist devices SO CIRCULATION LA English DT Meeting Abstract C1 Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 308 BP 60 EP 61 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100309 ER PT J AU Wang, S Song, LS Boheler, ER Wang, SQ Xiao, RP Lakatta, EG Shou, WL Cheng, HP AF Wang, S Song, LS Boheler, ER Wang, SQ Xiao, RP Lakatta, EG Shou, WL Cheng, HP TI Alterations of Ca2+ signaling in FKBP12-deficient mouse cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 307 BP 60 EP 60 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100308 ER PT J AU Angkeow, P Deshpande, SS Ozaki, M Saharkhiz-Langroodi, A Finkel, T Irani, K AF Angkeow, P Deshpande, SS Ozaki, M Saharkhiz-Langroodi, A Finkel, T Irani, K TI Overexpression of APE/REF-1 suppresses hypoxia-reoxygenation-induced apoptosis in human vascular endothelial cells SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. RI Ozaki, Michitaka/A-4549-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 328 BP 64 EP 64 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100329 ER PT J AU Chesley, A Ohtani, S Asai, T Lundberg, M Xiao, RP Lakatta, EG Crow, M AF Chesley, A Ohtani, S Asai, T Lundberg, M Xiao, RP Lakatta, EG Crow, M TI A pertussis toxin-sensitive signaling pathway linked to beta 2-adrenergic receptor stimulation blocks apoptosis in hypoxic neonatal cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 327 BP 64 EP 64 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100328 ER PT J AU Lim, HW Begley, DA Molkentin, JD Fananapazir, L AF Lim, HW Begley, DA Molkentin, JD Fananapazir, L TI Elevated activated calcineurin levels in patients with familiar hypertrophic cardiomyopathy caused by sarcomeric gene missense mutations SO CIRCULATION LA English DT Meeting Abstract C1 Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 397 BP 77 EP 77 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100398 ER PT J AU Mohiddin, SA Begley, DA Tripodi, D Fananapazir, L AF Mohiddin, SA Begley, DA Tripodi, D Fananapazir, L TI Myocardial bridging in children with hypertrophic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 395 BP 77 EP 77 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100396 ER PT J AU Hees, PS Shapiro, EP Harman, SM Cottrell, E Stewart, KJ Livengood, S Christmas, C Muenzer, T Pabst, K Sorkin, JD Blackman, MR AF Hees, PS Shapiro, EP Harman, SM Cottrell, E Stewart, KJ Livengood, S Christmas, C Muenzer, T Pabst, K Sorkin, JD Blackman, MR TI Growth hormone administration to healthy elderly individuals increases cardiac endurance without effects on cardiac structure or function at rest SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 407 BP 79 EP 79 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100408 ER PT J AU Hees, PS Fleg, JL Vaitkevicius, PV Reiersen, P Bosley, SL Shapiro, EP AF Hees, PS Fleg, JL Vaitkevicius, PV Reiersen, P Bosley, SL Shapiro, EP TI Is race a determinant of age-related changes in LV mass in normotensive subjects? SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 406 BP 79 EP 79 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100407 ER PT J AU Taylor, HA Jones, D Sempos, CT Thom, TJ Harrington, AM Fletcher, BW Mehrotra, BD Coll, T Wyatt, SB Davis, CE AF Taylor, HA Jones, D Sempos, CT Thom, TJ Harrington, AM Fletcher, BW Mehrotra, BD Coll, T Wyatt, SB Davis, CE TI Rising levels of cardiovascular mortality in a special population: Trends among African Americans in Mississippi SO CIRCULATION LA English DT Meeting Abstract C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Off Res Minor Hlth, Bethesda, MD USA. NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. Jackson State Univ, Jackson, MS 39217 USA. Tougaloo Coll, Jackson, MS USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 526 BP 102 EP 102 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100526 ER PT J AU Okin, PM Howard, BV Kors, JA van Herpen, G Crow, RS Fabsitz, RR AF Okin, PM Howard, BV Kors, JA van Herpen, G Crow, RS Fabsitz, RR TI Computerized ST depression analysis improves prediction of cardiovascular morbidity and mortality in American Indians: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Mednt Res Inst, Washington, DC USA. Erasmus Univ, Rotterdam, Netherlands. Univ Minnesota, Minneapolis, MN USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 535 BP 104 EP 104 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100535 ER PT J AU Scuteri, A Vaitkevicius, PV Bos, AJG Fleg, JL AF Scuteri, A Vaitkevicius, PV Bos, AJG Fleg, JL TI Estrogens but not progestins reduce age-associated increase in arterial stiffness and blood pressure in post-menopausal women SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NIA, LCS, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 539 BP 105 EP 105 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100539 ER PT J AU Kauser, K daCunha, V Milstein, S Katusic, ZS Rubanyi, GM AF Kauser, K daCunha, V Milstein, S Katusic, ZS Rubanyi, GM TI Endothelial dysfunction is associated with elevated biopterin production in the aorta of old apolipoprotein E-deficient mouse SO CIRCULATION LA English DT Meeting Abstract C1 Berlex BioScis, Richmond, CA USA. NIMH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 586 BP 114 EP 114 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100586 ER PT J AU Fleg, JL O'Connor, FC Clulow, J Cosgriff, R Gerstenblith, G AF Fleg, JL O'Connor, FC Clulow, J Cosgriff, R Gerstenblith, G TI Cardiovascular adaptations at rest and during maximal aerobic exercise in middle aged female endurance athletes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 728 BP 140 EP 140 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100728 ER PT J AU Correia, LC Lakatta, EG O'Connor, FC Clulow, J Townsend, S Schulman, SP Gerstenblith, G Fleg, JL AF Correia, LC Lakatta, EG O'Connor, FC Clulow, J Townsend, S Schulman, SP Gerstenblith, G Fleg, JL TI Attenuated cardiovascular response to prolonged submaximal cycle exercise in healthy older SO CIRCULATION LA English DT Meeting Abstract C1 Inst Procardiaco, Salvador, Brazil. NIH, GRC, LCS, Baltimore, MD USA. Johns Hopkins, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 732 BP 141 EP 141 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100732 ER PT J AU Fleg, JL Gerstenblith, G O'Connor, FC Becker, LC Clulow, J Schulman, SP Lakatta, EG AF Fleg, JL Gerstenblith, G O'Connor, FC Becker, LC Clulow, J Schulman, SP Lakatta, EG TI Longitudinal changes in cardiovascular performance during maximal upright cycle exercise in healthy men SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIA, Baltimore, MD 21224 USA. Johns Hopkins, Baltimore, MD USA. NIH, GRC, LCS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 731 BP 141 EP 141 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100731 ER PT J AU Roman, MJ Fishman, DP Lee, ET Marion, S Fabsitz, RR AF Roman, MJ Fishman, DP Lee, ET Marion, S Fabsitz, RR TI Anti-hypertensive therapy may not reverse arterial hypertrophy: The strong heart study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Oklahoma, Sch Publ Hlth Serv, Oklahoma City, OK USA. Aberdeen Area Tribal Chairmans Hlth Board, Rapid City, SD USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 918 BP 176 EP 176 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100917 ER PT J AU Scuteri, A Chen, CH Spurgeon, HA Lakatta, EG AF Scuteri, A Chen, CH Spurgeon, HA Lakatta, EG TI Conduit arterial structural and functional correlates in untreated persons with elevated blood pressure SO CIRCULATION LA English DT Meeting Abstract C1 NIA, LCS, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 916 BP 176 EP 176 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100915 ER PT J AU Domanski, MJ Norman, J Mitchell, G Exner, DV Pfeffer, MA AF Domanski, MJ Norman, J Mitchell, G Exner, DV Pfeffer, MA TI Risk stratification by pulse pressure of "normotensives" in the multiple risk factor intervention trial: Potential treatment implications SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 938 BP 180 EP 180 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100937 ER PT J AU Hunt, KJ Folsom, AR Chambless, LE Evans, GW Sharrett, AR Tegeler, CH Brown, CA Heiss, G AF Hunt, KJ Folsom, AR Chambless, LE Evans, GW Sharrett, AR Tegeler, CH Brown, CA Heiss, G TI Mineralized carotid atherosclerosis on B-mode ultrasound predicts ischemic stroke: The atherosclerosis risk in communities (ARIC) study SO CIRCULATION LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Univ Minnesota, Minneapolis, MN USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. NHLBI, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 945 BP 181 EP 182 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100944 ER PT J AU Sharaf, BL Pepine, CJ Reis, SE Reichek, N Rogers, WJ Sopko, G Holubkov, R Miele, NJ Kerensky, R AF Sharaf, BL Pepine, CJ Reis, SE Reichek, N Rogers, WJ Sopko, G Holubkov, R Miele, NJ Kerensky, R TI A detailed angiographic analysis of women presenting with suspected ischemic chest pain: Pilot phase data from the NHLBI women's Ischemia syndrome evaluation (WISE) study angiographic core laboratory SO CIRCULATION LA English DT Meeting Abstract C1 Rhode Isl Hosp, Providence, RI USA. Univ Florida, Gainesville, FL 32611 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Alabama, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 954 BP 185 EP 185 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100953 ER PT J AU Wang, S Kuschel, M Sollott, S Xiao, RP Crow, M Lakatta, EG AF Wang, S Kuschel, M Sollott, S Xiao, RP Crow, M Lakatta, EG TI Constitutively active calmodulin kinase II in rat ventricular myocytes reduces the myofilament Ca2+ response and accelerates relaxation SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 990 BP 192 EP 192 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100989 ER PT J AU Palmiter, KA Alpert, NR Fananapazir, L Warshaw, DM AF Palmiter, KA Alpert, NR Fananapazir, L Warshaw, DM TI Single cardiac myosin molecules from familial hypertrophic cardiomyopathy patients exhibit enhanced mechanical performance in the laser trap assay SO CIRCULATION LA English DT Meeting Abstract C1 Univ Vermont, Burlington, VT USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 NOV 2 PY 1999 VL 100 IS 18 SU S MA 999 BP 193 EP 194 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100998 ER PT J AU Taheri, H Fananapazir, L Meacham, D Begley, DA Rettmann, D Tripodi, D Arai, AE AF Taheri, H Fananapazir, L Meacham, D Begley, DA Rettmann, D Tripodi, D Arai, AE TI Spiral hypertrophic cardiomyopathy: A new variant SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Rettmann, Dan/G-5265-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1003 BP 194 EP 194 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101002 ER PT J AU Devereux, RB Jones, EC Lee, ET Fabsitz, RR Welty, TK AF Devereux, RB Jones, EC Lee, ET Fabsitz, RR Welty, TK TI Prevalence and correlates of mitral value prolapse in a general population sample: The strong heart study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, New York, NY USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. NHLBI, Bethesda, MD 20892 USA. Aberdeen Area Tribal Chairmans Hlth Board, Rapid City, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1100 BP 212 EP 212 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101099 ER PT J AU Williams, K Hodgin, J Smithies, O Korach, K AF Williams, K Hodgin, J Smithies, O Korach, K TI The relative role of ER-alpha and ER-beta in modulating the effects of estradiol and genistein on constrictor and dilator responses of arteries SO CIRCULATION LA English DT Meeting Abstract C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ N Carolina, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1135 BP 219 EP 219 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101134 ER PT J AU London, JF Epstein, FH Fananapazir, L Agyeman, KO Begley, DA Arai, AE AF London, JF Epstein, FH Fananapazir, L Agyeman, KO Begley, DA Arai, AE TI MRI stress perfusion detects subendocardial ischemia in hypertrophic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1166 BP 225 EP 225 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101165 ER PT J AU Epstein, FH Taylor, JL Goncalves, L London, JF Balaban, RS Arai, AE AF Epstein, FH Taylor, JL Goncalves, L London, JF Balaban, RS Arai, AE TI Miorosphere validation of high-resolution whole-heart first-pass MRI SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1174 BP 226 EP 226 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101173 ER PT J AU Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Hennekens, CH AF Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Hennekens, CH TI Pulse pressure predicts mortality in the elderly SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NIA, Bethesda, MD 20892 USA. E Boston Neighborhood Hlth Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1195 BP 230 EP 230 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101194 ER PT J AU Taylor, HA Brown, A Burchfield, C Clemons, T Arnett, DK Skelton, T Garrison, R Jones, D AF Taylor, HA Brown, A Burchfield, C Clemons, T Arnett, DK Skelton, T Garrison, R Jones, D TI Pulse pressure: Potent predictor of coronary disease risk in a biracial cohort of normo- and hypertensives SO CIRCULATION LA English DT Meeting Abstract C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NHLBI Field Site, Jackson, MS USA. Univ Minnesota, Minneapolis, MN USA. Jackson State Univ, Jackson, MS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1194 BP 230 EP 230 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101193 ER PT J AU Haider, AW Wilson, PWF Larson, MG O'Donnell, CJ Wolf, PA D'Agostino, RB Michelson, EL Levy, D AF Haider, AW Wilson, PWF Larson, MG O'Donnell, CJ Wolf, PA D'Agostino, RB Michelson, EL Levy, D TI Association of H pylori, C pneumoniae and Cytomegalovirus seropositivity with cardiovascular disease in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI Framingham Heart Study, Framingham, MA USA. Astra Pharm, Wayne, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1203 BP 232 EP 232 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101202 ER PT J AU Xu, D Finkel, T AF Xu, D Finkel, T TI Homocysteine induces endothelial cell senescence SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1216 BP 234 EP 234 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101215 ER PT J AU Bosworth-Farrell, SA Schron, E Yao, Q Powell, J Collura, R Jenkins, L Kandrac, J Nelson, L AF Bosworth-Farrell, SA Schron, E Yao, Q Powell, J Collura, R Jenkins, L Kandrac, J Nelson, L CA AVID Investigators TI Spousal quality of life in the antiarrhythmics versus implantable defibrillators (AVID) trial SO CIRCULATION LA English DT Meeting Abstract C1 Maine Med Ctr, Portland, ME 04102 USA. NHLBI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Midwest Heart Res Fdn, Lombard, IL USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1319 BP 254 EP 254 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101318 ER PT J AU Lambert, GC Amar, MJA Shamburek, RD Hoyt, RF Madj, Z Fruchart-Najib, J Brewer, BH Santamarina-Fojo, S AF Lambert, GC Amar, MJA Shamburek, RD Hoyt, RF Madj, Z Fruchart-Najib, J Brewer, BH Santamarina-Fojo, S TI Hepatic lipase deficiency decreases the selective uptake of HDL-cholesteryl esters in vivo SO CIRCULATION LA English DT Meeting Abstract C1 NIH, NHLBI, Bethesda, MD 20892 USA. Inst Pasteur, F-59019 Lille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1322 BP 254 EP 254 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101321 ER PT J AU Sullivan, DM Wehr, NB Fergusson, MM Levine, RL Finkel, T AF Sullivan, DM Wehr, NB Fergusson, MM Levine, RL Finkel, T TI A novel method for the in situ identification of redox sensitive proteins: evidence for a reactive cysteine in annexin II. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1364 BP 262 EP 262 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101363 ER PT J AU Tobacman, LS Back, N Butters, C Karibe, A Strand, J Fananapazir, L Homsher, E AF Tobacman, LS Back, N Butters, C Karibe, A Strand, J Fananapazir, L Homsher, E TI A novel alpha-tropomyosin mutation associated with a malignant form of hypertrophic cardiomyopathy causes increased thin filament calcium affinity and altered myosin cycling SO CIRCULATION LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA 52242 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Baylor Coll Med, Houston, TX 77030 USA. NHLBI, FRCP, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1438 BP 276 EP 276 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101437 ER PT J AU Feng, DL Lindpaintner, K Larson, MG O'Donnell, CJ Lipinska, I Sutherland, PA D'Agostino, RB Tofler, GH AF Feng, DL Lindpaintner, K Larson, MG O'Donnell, CJ Lipinska, I Sutherland, PA D'Agostino, RB Tofler, GH TI Platelet GPIIIa PlA2 polymorphism, fibrinogen levels and platelet aggregability: The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BI Deaconess Med Ctr, IPCD, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Royal N Shore Hosp, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1715 BP 327 EP 327 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101713 ER PT J AU Blum, A Schenke, WH Hathaway, L Mincemoyer, R Cannon, RO AF Blum, A Schenke, WH Hathaway, L Mincemoyer, R Cannon, RO TI Effects of estrogen and raloxifene on markers of vascular inflammation in postmenopausal women SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1740 BP 332 EP 332 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101738 ER PT J AU Zanger, D Blum, A Hathaway, L Mincemoyer, R Panza, JA Schenke, WH Cannon, RO AF Zanger, D Blum, A Hathaway, L Mincemoyer, R Panza, JA Schenke, WH Cannon, RO TI Vascular effects of estrogen therapy in postmenopausal women with coronary artery disease on conventional medical management SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1741 BP 332 EP 332 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101739 ER PT J AU Boehm, M Richards, M Nabel, GJ Nabel, EG AF Boehm, M Richards, M Nabel, GJ Nabel, EG TI Identification of hKIS as a nuclear kinase that phosphorylates and inactivates the cyclin-dependent kinase inhibitor p27(Kipt) SO CIRCULATION LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1752 BP 334 EP 334 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101750 ER PT J AU Jarai, Z Wagner, JA Lake, KD Martin, BR Zimmer, A Kunos, G AF Jarai, Z Wagner, JA Lake, KD Martin, BR Zimmer, A Kunos, G TI Non-psychoactive cannabinoid causes hypotension in rodents by a novel mechanism SO CIRCULATION LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. RI Zimmer, Andreas/B-8357-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1782 BP 340 EP 340 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101780 ER PT J AU Forbes, RA Steenbergen, C Murphy, E AF Forbes, RA Steenbergen, C Murphy, E TI The protective effect of diazoxide is blocked by antioxidants SO CIRCULATION LA English DT Meeting Abstract C1 Natl Inst Environm Hlth Scis, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Durham, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1795 BP 342 EP 342 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101793 ER PT J AU Irvine, T Jones, M Sachdev, V Stetten, GD Castelluci, JB Szwarc, R Ritscher, DE Panza, JA AF Irvine, T Jones, M Sachdev, V Stetten, GD Castelluci, JB Szwarc, R Ritscher, DE Panza, JA TI Determination of right ventricular diastolic and systolic cavity volumes and stroke volumes by real-time 3D ultrasound: Validation studies using endocardial crystal array 3D maps, conductance catheters and electromagnetic flow meters SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NHLBI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC USA. Biometr, Las Vegas, NV USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1872 BP 356 EP 357 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101870 ER PT J AU Sachdev, V Agyeman, KO Magno, PM Laurienzo, JM Freidlin, RZ Arai, AE Panza, JA AF Sachdev, V Agyeman, KO Magno, PM Laurienzo, JM Freidlin, RZ Arai, AE Panza, JA TI Left ventricular mess measurements in cardiac patients using contrast-enhanced real-time three-dimensional echocardiography SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1871 BP 356 EP 356 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101869 ER PT J AU Rusk, RA Li, XN Mori, Y Jones, M Sachdev, V Kenny, A AF Rusk, RA Li, XN Mori, Y Jones, M Sachdev, V Kenny, A TI Directly quantifying transmitral stroke volume with digital four-dimensional Doppler: A preliminary in vivo comparison to electromagnetic flowmeter SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. ATL Ultrasound, Bothell, WA USA. NHLBI, LAMS, Bethesda, MD 20892 USA. Freeman Rd Hosp, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1875 BP 357 EP 357 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101873 ER PT J AU Bauer, FJ Marwaha, VR Zetts, AD Panza, JA AF Bauer, FJ Marwaha, VR Zetts, AD Panza, JA TI Non-invasive assessment of left ventricular chamber stiffness with real-time 3D echocardiography: Comparison with an invasive method in an animal study SO CIRCULATION LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1878 BP 358 EP 358 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101876 ER PT J AU Exner, DV Lancaster, SE Pinski, SL Graham-Renfroe, E Wyse, DG Coromilas, J Follmann, D Gold, MR Beckman, KJ Karagounis, L Hallstrom, A AF Exner, DV Lancaster, SE Pinski, SL Graham-Renfroe, E Wyse, DG Coromilas, J Follmann, D Gold, MR Beckman, KJ Karagounis, L Hallstrom, A TI Electrical storm is an independent risk factor for early death: The antiarrhythmics versus implantable defibrillators (AVID) trial SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Calgary, Calgary, AB, Canada. Columbia Univ, New York, NY USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Oklahoma, Oklahoma City, OK USA. Univ Utah, Salt Lake City, UT USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1921 BP 366 EP 366 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101919 ER PT J AU McAnulty, JH Hallstrom, A Wilkoff, BI Follmann, D Shih, T Carlson, M Powell, J AF McAnulty, JH Hallstrom, A Wilkoff, BI Follmann, D Shih, T Carlson, M Powell, J CA AVID Investigators TI The law arrhythmia frequency sextile: A subgroup that doesn't need an implanted defibrillator SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Washington, Seattle, WA 98195 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Houston, TX USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1926 BP 367 EP 367 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101924 ER PT J AU Steinberg, JS Vloka, ME Qing, Y Schron, E Dorian, P Powell, J AF Steinberg, JS Vloka, ME Qing, Y Schron, E Dorian, P Powell, J CA AVID Investigators TI Relationship of baseline quality of life scores to long-term survival in the antiarrhythmics versus implantable defibrillators (AVID) trial SO CIRCULATION LA English DT Meeting Abstract C1 St Lukes Roosevelt Hosp, New York, NY 10025 USA. Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1925 BP 367 EP 367 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101923 ER PT J AU Mori, YH Rusk, RA Li, XN Jones, M Irvine, T Sachdev, V Sahn, DJ AF Mori, YH Rusk, RA Li, XN Jones, M Irvine, T Sachdev, V Sahn, DJ TI Quantifying pulmonary regurgitant now with dynamic 3D digital Doppler compared with electromagnetic flowmeters: An in vivo study in a chronic animal model SO CIRCULATION LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. ATL Ultrasound, Bothell, WA USA. NHLBI, LAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2067 BP 394 EP 394 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102065 ER PT J AU Amar, MJ Vaisman, BL Koch, CA Paiz, JA Meyn, SM Fruchart-Najib, J Majd, Z Paigen, B Brewer, HB Santamarina-Fojo, S AF Amar, MJ Vaisman, BL Koch, CA Paiz, JA Meyn, SM Fruchart-Najib, J Majd, Z Paigen, B Brewer, HB Santamarina-Fojo, S TI Expression of murine LCAT in transgenic mice; Evaluation of the role of LCAT cholesteryl ester-fatty acid specificity in the development of atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Inst Pasteur, F-59019 Lille, France. Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2106 BP 401 EP 401 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102104 ER PT J AU Shamburek, RD Hoeg, JM Duverger, N Houbebine, LM Hoyt, RF Wood, DO Santamarina-Fojo, S Brewer, HB AF Shamburek, RD Hoeg, JM Duverger, N Houbebine, LM Hoyt, RF Wood, DO Santamarina-Fojo, S Brewer, HB TI Transgenic rabbits expressing both human ApoA-I and LCAT have a protective lipoprotein profile with increased HDL and enhanced LDL catabolism SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. RPR Gencell, Lille, France. INRA, Jouy En Josas, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2112 BP 402 EP 402 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102110 ER PT J AU Speir, EE Takeda, K Yu, ZX Ferrans, VJ Cannon, RO AF Speir, EE Takeda, K Yu, ZX Ferrans, VJ Cannon, RO TI Regulation of nuclear factor-kappa B-dependent genes by the estrogen receptor in human coronary smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2142 BP 408 EP 408 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102140 ER PT J AU Freedman, JE Pezzullo, JC Abernethy, DR Jordan, RE Frederick, B Mascelli, MA AF Freedman, JE Pezzullo, JC Abernethy, DR Jordan, RE Frederick, B Mascelli, MA TI Pharmocodynamic profile of acute readministration of abciximab SO CIRCULATION LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIA, Baltimore, MD 21224 USA. Centocor, Malvern, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2270 BP 431 EP 431 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102267 ER PT J AU Blum, A Hathaway, L Mincemoyer, R Schenke, WH Csako, G O Cannon, R AF Blum, A Hathaway, L Mincemoyer, R Schenke, WH Csako, G O Cannon, R TI Hormonal and lipoprotein effects of selective estrogen receptor modulator therapy in hypercholesterolemic men SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2468 BP 469 EP 469 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102465 ER PT J AU O'Donnell, CJ Silbershatz, H D'Agostino, RB Haider, AW Polak, JF Levy, D Wilson, PWF AF O'Donnell, CJ Silbershatz, H D'Agostino, RB Haider, AW Polak, JF Levy, D Wilson, PWF TI Relationship of C-reactive protein to carotid stenosis and intimal medial thickness in the framingham heart study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2513 BP 477 EP 477 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102509 ER PT J AU Akyurek, LM Aoki, K Yang, ZY San, H Richards, M Nabel, GJ Nabel, EG AF Akyurek, LM Aoki, K Yang, ZY San, H Richards, M Nabel, GJ Nabel, EG TI Modified thymidine kinase vector enhances prodrug cytotoxicity SO CIRCULATION LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2539 BP 482 EP 482 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102535 ER PT J AU Halcox, JPJ Narayanan, S Mincemoyer, R Panza, JA Waclaviv, M Quyyumi, AA AF Halcox, JPJ Narayanan, S Mincemoyer, R Panza, JA Waclaviv, M Quyyumi, AA TI Hyperkalemia inhibits endothelium-dependent hyperpolarization in the normal human forearm circulation SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2559 BP 486 EP 486 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102555 ER PT J AU Zhou, YY Zhu, WZ Zhang, SJ Wang, DG Chruscinski, A Kolbilka, BK Lakatta, EG Xiao, RP AF Zhou, YY Zhu, WZ Zhang, SJ Wang, DG Chruscinski, A Kolbilka, BK Lakatta, EG Xiao, RP TI Ligand-independent constitutive activation of beta(2)- but not beta(1)-adrenoceptors overexpressed in beta(1)beta(2)-adrenoceptor double knockout mouse myocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2566 BP 487 EP 487 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102562 ER PT J AU Xiao, RP Cheng, HP Zhou, YY Wang, DG Lefkowitz, RJ Zhang, SJ Koch, WJ Lakatta, EG AF Xiao, RP Cheng, HP Zhou, YY Wang, DG Lefkowitz, RJ Zhang, SJ Koch, WJ Lakatta, EG TI Muscarinic stimulation rescues beta(1)-adrenoceptors from desensitization induced by constitutively active beta(2)-adrenoceptors in cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2571 BP 488 EP 488 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102567 ER PT J AU Cross, HR Murphy, E Bolli, R Ping, PP Steenbergen, C AF Cross, HR Murphy, E Bolli, R Ping, PP Steenbergen, C TI Overexpression of PKC epsilon protects the ischemic heart, without attenuating ischemic H+ production SO CIRCULATION LA English DT Meeting Abstract C1 Univ Louisville, Louisville, KY 40292 USA. NIEHS, RTP, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 3 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2586 BP 490 EP 491 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102582 ER PT J AU Cross, HR Steenbergen, C Lefkowitz, RJ Murphy, E AF Cross, HR Steenbergen, C Lefkowitz, RJ Murphy, E TI Expression of a beta ARK-1 inhibitor increases myocardial contractility without increasing susceptibility to ischemic injury SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2598 BP 493 EP 493 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102594 ER PT J AU Jaffer, FA O'Donnell, CJ Chan, SK Kissinger, KV Levy, D Manning, WJ AF Jaffer, FA O'Donnell, CJ Chan, SK Kissinger, KV Levy, D Manning, WJ TI A new MRI index of aortic atherosclerotic burden in a healthy population SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Beth Israel Daconess Med Ctr, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2745 BP 521 EP 521 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102741 ER PT J AU Cohen, JD Grandits, G Cutler, JA Neaton, JD Kuller, LH Stamler, J AF Cohen, JD Grandits, G Cutler, JA Neaton, JD Kuller, LH Stamler, J TI Dietary sodium intake and mortality: MRFIT follow-un study results SO CIRCULATION LA English DT Meeting Abstract C1 St Louis Univ, St Louis, MO 63103 USA. Univ Minnesota, Minneapolis, MN USA. NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2758 BP 524 EP 524 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102754 ER PT J AU Lipshultz, SE Easley, KA Orav, JE Kaplan, S Bricker, JT Lal, WW Moodie, DS Sopko, G Colan, SD AF Lipshultz, SE Easley, KA Orav, JE Kaplan, S Bricker, JT Lal, WW Moodie, DS Sopko, G Colan, SD TI Cardiac dysfunction and mortality in HIV-infected children: The prospective (PCHIV)-C-2-H-2 multicenter study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Rochester, Rochester, NY USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Mt Sinai Sch Med, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2795 BP 531 EP 531 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102791 ER PT J AU Kilborn, MJ Karasik, PE Fisher, SG Domanski, MJ Singh, SN Fletcher, RD AF Kilborn, MJ Karasik, PE Fisher, SG Domanski, MJ Singh, SN Fletcher, RD TI Anticoagulation in patients with congestive heart failure: Evidence for lack of mortality benefit. SO CIRCULATION LA English DT Meeting Abstract C1 Washington VA Med Ctr, Washington, DC USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Washington Vet Affairs Med Ctr, Washington, DC USA. VA Cooperat Studies Program, Hines, IL USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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 NOV 2 PY 1999 VL 100 IS 18 SU S MA 2831 BP 537 EP 537 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102827 ER PT J AU Prasad, A Halcox, JPJ Zalos, G Mincemoyer, R Quyyumi, AA AF Prasad, A Halcox, JPJ Zalos, G Mincemoyer, R Quyyumi, AA TI Coronary epicardial endothelium-dependent vasodilation improves with angiotensin AT-1 receptor inhibition SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2891 BP 549 EP 549 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102887 ER PT J AU Takeda, K Yu, ZX Qian, SJ Uren, D Chin, TK Adelstein, RS Ferrans, VJ AF Takeda, K Yu, ZX Qian, SJ Uren, D Chin, TK Adelstein, RS Ferrans, VJ TI Nonmuscle myosin heavy chain II-B is localized to the Z lines and intercalated discs of cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. E Tennessee State Univ, Johnson City, TN 37614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2956 BP 561 EP 561 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102952 ER PT J AU Korzick, DH Holiman, DA Boluyt, MO Laughlin, MH AF Korzick, DH Holiman, DA Boluyt, MO Laughlin, MH TI Impaired alpha(1)-adrenergic signaling in aged rat heart is mediated by PKC alpha, PKC epsilon and selective PKC binding protein (RACK) deficiency SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Univ Missouri, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2988 BP 567 EP 567 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102984 ER PT J AU Bauer, FJ Shiota, T Qin, JX Tsujino, H Travaglini, A Marwaha, VR Zetts, AD Panza, JA Thomas, JD AF Bauer, FJ Shiota, T Qin, JX Tsujino, H Travaglini, A Marwaha, VR Zetts, AD Panza, JA Thomas, JD TI Change in left atrial function during acute coronary occlusion: A pressure-volume loop analysis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, LAMS, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3018 BP 572 EP 572 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103014 ER PT J AU Mirza, ZA Hees, PS Bosley, SL Reyerson, P Livengood, S Weiss, JL Fleg, JL Shapiro, EP AF Mirza, ZA Hees, PS Bosley, SL Reyerson, P Livengood, S Weiss, JL Fleg, JL Shapiro, EP TI Increasing dobutamine hose augments relaxation but fails to improve filling in normal humans SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3037 BP 576 EP 576 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103033 ER PT J AU Cooper, HA Exner, DV Domanski, MJ AF Cooper, HA Exner, DV Domanski, MJ TI Moderate alcohol consumption and outcomes in patients with left ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3053 BP 579 EP 579 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103049 ER PT J AU Zhu, J Quyyumi, AA Norman, JE Epstein, SE AF Zhu, J Quyyumi, AA Norman, JE Epstein, SE TI The potential causal role of infection in hypertension SO CIRCULATION LA English DT Meeting Abstract C1 CV Res Fdn, Washington, DC USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3198 BP 607 EP 607 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103194 ER PT J AU Olson, TM Doan, TP Kishimoto, NY Whitby, FG Fananapazir, L AF Olson, TM Doan, TP Kishimoto, NY Whitby, FG Fananapazir, L TI Hypertrophic and dilated cardiomyopathy are caused by mutations in the cardiac actin gene SO CIRCULATION LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT 84112 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3256 BP 617 EP 618 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103252 ER PT J AU Karibe, A Bachinski, LL Arai, AE Tripodi, D Roberts, R Fananapazir, L AF Karibe, A Bachinski, LL Arai, AE Tripodi, D Roberts, R Fananapazir, L TI Familial hypertrophic cardiomyopathy caused by a novel alpha-tropomyosin mutation (Val(95)Ala) is associated with mild cardiac hypertrophy but a high incidence of sudden death SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3263 BP 619 EP 619 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103259 ER PT J AU Exner, DV Dries, DL Cooper, HA Domanski, MJ AF Exner, DV Dries, DL Cooper, HA Domanski, MJ TI Smoking is associated with an increased risk of sudden death in patients with non-ischemic left ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3454 BP 655 EP 655 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103450 ER PT J AU Roman, MJ Howard, BV Fabsitz, RR Lee, ET Marion, S Fishman, DP AF Roman, MJ Howard, BV Fabsitz, RR Lee, ET Marion, S Fishman, DP TI Carotid atherosclerosis is independently predicted by absolute blood pressure but not pulse pressure: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Welll Med Coll, New York, NY USA. Mednt Res Inst, Washington, DC USA. NHLBI, Bethesda, MD 20892 USA. Univ Oklahoma, Sch Publ Hlth Serv, Oklahoma City, OK USA. Aberdeen Area Tribal Chairmans Hlth Board, Rapid City, SD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3557 BP 675 EP 675 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103552 ER PT J AU Sutton-Tyrrell, K Havlik, RJ Newman, AB Pahor, M Spurgeon, HA Vaitkevicius, PV AF Sutton-Tyrrell, K Havlik, RJ Newman, AB Pahor, M Spurgeon, HA Vaitkevicius, PV TI Aortic stiffness is positively associated with ethnicity, visceral adiposity and other correlates of insulin resistance SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3561 BP 676 EP 676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103556 ER PT J AU Wong, ML Xie, B Beatini, N Marathe, S Johns, A Hirsch, E Williams, KJ Licinio, J Tabas, I AF Wong, ML Xie, B Beatini, N Marathe, S Johns, A Hirsch, E Williams, KJ Licinio, J Tabas, I TI Secretory sphingomyelinase (S-SMase), an atherogenic enzyme, is stimulated by IL1 beta and TNF alpha in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. NIH, Bethesda, MD 20892 USA. Berlex Bioscis, Richmond, CA USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3664 BP 695 EP 695 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103658 ER PT J AU Karas, RH Hodgins, J Kwoun, M Krege, J Aronovitz, M Mackey, W Gustafsson, JA Korach, K Smithies, O AF Karas, RH Hodgins, J Kwoun, M Krege, J Aronovitz, M Mackey, W Gustafsson, JA Korach, K Smithies, O TI Estrogen inhibits the vascular injury response in estrogen receptor beta-deficient mice SO CIRCULATION LA English DT Meeting Abstract C1 New England Med Ctr, Boston, MA 02111 USA. Natl Inst Environm Hlth Scis, Res Triangle Pk, NC USA. Tufts Univ, New England Med Ctr Hosp, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3708 BP 703 EP 703 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103702 ER PT J AU Duckers, HJ Yet, SF San, H Lee, ME Nabel, EG Nabel, GJ AF Duckers, HJ Yet, SF San, H Lee, ME Nabel, EG Nabel, GJ TI Heme oxygenase 1 regulates smooth muscle cell proliferation by induction of cell cycle arrest SO CIRCULATION LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3729 BP 707 EP 707 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103723 ER PT J AU Knatterud, GL White, C Campeau, L Domanski, MJ Geller, N Forman, S Forrester, J Gobel, F Herd, A Hoogwerf, BJ Hunninghake, D Rosenberg, Y AF Knatterud, GL White, C Campeau, L Domanski, MJ Geller, N Forman, S Forrester, J Gobel, F Herd, A Hoogwerf, BJ Hunninghake, D Rosenberg, Y TI Angiographic changes in saphenous vein grafts are predictive of clinical outcomes SO CIRCULATION LA English DT Meeting Abstract C1 Maryland Med Res Inst, Baltimore, MD USA. Univ Minnesota, Minneapolis, MN USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. 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 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3757 BP 712 EP 712 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103750 ER PT J AU Territo, PR French, SA Balaban, RS AF Territo, PR French, SA Balaban, RS TI Calcium activation of oxidative phosphorylation: Changes in ATP synthesis rate with clamped NADH redox state SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3760 BP 712 EP 712 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103753 ER PT J AU Territo, PR French, SA Balaban, RS AF Territo, PR French, SA Balaban, RS TI Calcium activation of oxidative phosphorylation: Rapid kinetics of mVO(2), NADH and light scattering SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3761 BP 712 EP 713 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103754 ER PT J AU McNamara, DM Holubkov, R Wang, JJ Palmer, A Merz, CNB Sharaf, BL Pepine, CJ Reichek, N Sopko, G Rels, SE AF McNamara, DM Holubkov, R Wang, JJ Palmer, A Merz, CNB Sharaf, BL Pepine, CJ Reichek, N Sopko, G Rels, SE TI The eNOS Asp(294) variant is hot associated with atherosclerosis or endothelial dysfunction in women; Results from the NHLBI WISE study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Rhode Isl Hosp, Providence, RI USA. Univ Florida, Gainesville, FL USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NHLBI, NIH, DHVD, CDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3794 BP 718 EP 719 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103786 ER PT J AU Couture, P Otvos, JD Cupples, LA Wilson, PWF Schaefer, EJ Ordovas, JM AF Couture, P Otvos, JD Cupples, LA Wilson, PWF Schaefer, EJ Ordovas, JM TI Association of the A-278C polymorphism in the cholesterol 7 alpha-hydroxylase gene with variations in plasma low-density lipoprotein cholesterol levels in the framingham offspring study SO CIRCULATION LA English DT Meeting Abstract C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. N Carolina State Univ, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3908 BP 740 EP 740 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103900 ER PT J AU Russo, G Cupples, LA Otvos, JD Wilson, PWF Kelleher, AL Schaefer, EJ Ordovas, JM AF Russo, G Cupples, LA Otvos, JD Wilson, PWF Kelleher, AL Schaefer, EJ Ordovas, JM TI The s2 allele at the APOC3 gene locus is associated with lipid profiles that are atherogenic but that differ by gender SO CIRCULATION LA English DT Meeting Abstract C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Boston, MA 02215 USA. N Carolina State Univ, Raleigh, NC 27695 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3906 BP 740 EP 740 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103898 ER PT J AU Kuschel, M Zhou, YY Kuramochi, T Lakatta, EG Xiao, RP AF Kuschel, M Zhou, YY Kuramochi, T Lakatta, EG Xiao, RP TI Frequency-dependent Thr(17)PLB phosphorylation is independent of Ser(16)PLB phosphorylation in rat ventricular myocytes SO CIRCULATION LA English DT Meeting Abstract C1 LCS, GRC, NIA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4029 BP 763 EP 763 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104021 ER PT J AU Fedorova, OV Lakatta, EG Bagrov, AY AF Fedorova, OV Lakatta, EG Bagrov, AY TI Endogenous sodium pump ligands, myocardial Na/K ATPase and left ventricular remodeling in hypertensive dahl rats SO CIRCULATION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4044 BP 766 EP 766 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104036 ER PT J AU Cross, HR Steenbergen, C Murphy, E AF Cross, HR Steenbergen, C Murphy, E TI Phospholamban knock-out (PLB-K0) mice exhibit increased susceptibility to myocardial ischemic injury: A gender-specific effect SO CIRCULATION LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4050 BP 767 EP 767 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104042 ER PT J AU Wang, NP Verna, L Hardy, S Zhu, Y Ma, KS Birrer, MJ Stemerman, MB AF Wang, NP Verna, L Hardy, S Zhu, Y Ma, KS Birrer, MJ Stemerman, MB TI c-Jun triggers apoptosis in human vascular endothelial cells SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calif Riverside, Riverside, CA 92521 USA. Chiron Corp, Emeryville, CA 94608 USA. NIH, Rockville, MD USA. RI Wang, Nanping/G-1818-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4084 BP 773 EP 773 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104076 ER PT J AU Benjamin, EJ Larson, MG Vasan, RS Wolf, PA D'Agostino, RB Silbershatz, H Evans, JC Kannel, WB Murabito, JM Levy, D AF Benjamin, EJ Larson, MG Vasan, RS Wolf, PA D'Agostino, RB Silbershatz, H Evans, JC Kannel, WB Murabito, JM Levy, D TI The joint influences of atrial fibrillation and heart failure on mortality: The Framingham Study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4187 BP 793 EP 793 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104179 ER PT J AU Talbot, LA Metter, EJ Morrell, CH Fleg, JL AF Talbot, LA Metter, EJ Morrell, CH Fleg, JL TI Physical activity, cardiorespiratory fitness and the risk of coronary events in healthy men SO CIRCULATION LA English DT Meeting Abstract C1 Loyola Coll, Baltimore, MD 21210 USA. Johns Hopkins Univ, Baltimore, MD USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4197 BP 795 EP 795 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104189 ER PT J AU Shachter, NS Ramakrishnan, R Stohl, S Holleran, S Bray, MS Park, E Chambless, LE Sharrett, R Boerwinkle, E AF Shachter, NS Ramakrishnan, R Stohl, S Holleran, S Bray, MS Park, E Chambless, LE Sharrett, R Boerwinkle, E TI The Hpa I RFLP of apoC-I predicts plasma triglyceride levels in African-Americans: The ARIC study SO CIRCULATION LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. Univ Texas, Houston, TX USA. Univ N Carolina, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4334 BP 821 EP 821 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104325 ER PT J AU Palmieri, V de Simone, G Roman, MJ Celentano, AJ Lee, ET Welty, TK Fabsitz, RR Tracy, RP Robbins, DS Howard, BV AF Palmieri, V de Simone, G Roman, MJ Celentano, AJ Lee, ET Welty, TK Fabsitz, RR Tracy, RP Robbins, DS Howard, BV TI Relation of fibrinogen to left ventricular mass and systolic function: The strong heart study SO CIRCULATION LA English DT Meeting Abstract C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Naples Federico II, Naples, Italy. Univ Oklahoma, Sch Publ Hlth Serv, Oklahoma City, OK USA. Aberdeen Area Tribal Chairmans Hlth Board, Rapid City, SD USA. NHLBI, Bethesda, DC USA. Univ Vermont, Burlington, VT USA. Mednt Res Inst, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4555 BP 863 EP 863 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104545 ER PT J AU Izzo, MR Holubkov, R Cropcho, L Virji, MA Merz, CNB Pepine, CJ Reichek, N Sopko, G Sharaf, BL Rickens, CR Reis, SE AF Izzo, MR Holubkov, R Cropcho, L Virji, MA Merz, CNB Pepine, CJ Reichek, N Sopko, G Sharaf, BL Rickens, CR Reis, SE TI Homocysteine levels are not associated with coronary artery disease or endothelial dysfunction in women: Results from the NHLBI WISE study SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Florida, Gainesville, FL USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NHLBI, Bethesda, MD 20892 USA. Rhode Isl Hosp, Providence, RI USA. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4587 BP 869 EP 869 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104577 ER PT J AU Koh, KK Blum, A Hathaway, L Mincemoyer, R Csako, G Waclawiw, MA Panza, JA Cannon, RO AF Koh, KK Blum, A Hathaway, L Mincemoyer, R Csako, G Waclawiw, MA Panza, JA Cannon, RO TI Vascular effects of estrogen and vitamin E therapies in postmenopausal women SO CIRCULATION LA English DT Article DE atherosclerosis; endothelium; antioxidants; cell adhesion molecules; fibrinolysis ID LOW-DENSITY-LIPOPROTEIN; CELL-ADHESION MOLECULE-1; CORONARY-ARTERY DISEASE; CHOLESTEROL-FED RABBITS; ENDOTHELIAL-CELLS; NITRIC-OXIDE; E-SELECTIN; ALPHA-TOCOPHEROL; HUMAN ATHEROSCLEROSIS; EXPRESSION AB Background-Estrogen and vitamin E therapies have been suggested to reduce cardiovascular risk, but comparison of the vascular effects of these therapies to determine mechanisms of potential benefit has not been performed in postmenopausal women. Methods and Results-In a double-blind, 3-period crossover study, We randomly assigned 28 healthy postmenopausal women to conjugated equine estrogens (CE) 0.625 mg/d, vitamin: E 800 IU/d, and their combination, with measurements made before and after each 6-week treatment period. The ratio: of LDL to HDL cholesterol and lipoprotein(a) decreased on therapies including CE but increased on vitamin E alone (P < 0.001 and P = 0.002, respectively, by ANOVA). Brachial artery flow-mediated dilation improved on all therapies (all P < 0.001 versus pretreatment values) and to a similar degree (P = 0.267 by ANOVA). No therapy improved the dilator response to nitroglycerin. CE lowered serum levels of cell adhesion molecules E-selectin, ICAM-1, and VCAM-1 (all P < 0.05 versus pretreatment values). Vitamin E had no: significant effect on levels of these markers of inflammation (P < 0.001 by ANOVA for E-selectin). CE alone or Combined with vitamin E but not vitamin E alone lowered or showed a trend for lowering plasma levels of plasminogen activator inhibitor type-1 (P = 0.069 by ANOVA). Conclusions-Estrogen and vitamin E therapies similarly improved arterial endothelium-dependent vasodilator responsiveness consistent with increased nitric oxide in healthy postmenopausal women, despite divergent effects on atherogenic lipoproteins. However, only estrogen reduced markers of vascular disease. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Ctr Clin, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr,MSC-1650, Bethesda, MD 20892 USA. NR 49 TC 82 Z9 86 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 NOV 2 PY 1999 VL 100 IS 18 BP 1851 EP 1857 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250XT UT WOS:000083416100003 PM 10545428 ER PT J AU Bidgood, WD D'Orsi, CJ Greenes, RA Huang, HK Jost, RG Langlotz, CP Schilling, RB Sickles, EA Staab, EV AF Bidgood, WD D'Orsi, CJ Greenes, RA Huang, HK Jost, RG Langlotz, CP Schilling, RB Sickles, EA Staab, EV TI Report of the Joint Working Group on Telemammography/Teleradiology and Information Management - March 15-17, 1999 Washington, DC - Abstracts SO ACADEMIC RADIOLOGY LA English DT Article ID TELERADIOLOGY C1 Univ Oklahoma, Ctr Telemed, Norman, OK 73019 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Massachusetts, Amherst, MA 01003 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mallinckrodt Inst Radiol, St Louis, MO USA. NCI, Bethesda, MD 20892 USA. RP Bidgood, WD (reprint author), Univ Oklahoma, Ctr Telemed, Norman, OK 73019 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 1999 VL 6 SU 7 BP S303 EP S324 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296QH UT WOS:000086034900001 ER PT J AU Liao, W Tang, M Li, JJ Leo, LM Cao, Y AF Liao, W Tang, M Li, JJ Leo, LM Cao, Y TI Epstein-Barr virus encoded latent membrane protein 1 increases expression of immunoglobulin kappa light chain through NF kappa B in a nasopharyngeal carcinoma cell line SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA Chinese DT Article DE EBV encoded LMP1; NF kappa B; Ig kappa; nasopharyngeal carcinoma AB NF kappa B activity analysis was performed with pNF kappa B-luc reporter plasmid. Expression of NF kappa B in nuclear and expression of Ig kappa in intact cells were analyzed by Western blot to identify whether Epstein-Barr virus encoded latent membrane protein 1 (LMP1) increases the expression of immunoglobulin kappa light chain through NF kappa B signal transduction pathway in nasopharyngeal carcinoma. Results showed that LMP1 could increase NF kappa B activity and promote the accumulation of NF kappa B p65 in nucleus, and LMP1 also increased Ig kappa expression. In addition, phosphorothioate oligonucleotides to antisense NF kappa B p65 and p50 inhibited the Ig kappa expression. These imply that LMP1 can regulate Ig kappa expression via NF kappa B signal transduction pathway in nasopharyngeal carcinoma. C1 Hunan Med Univ, Canc Res Inst, Changsha 410078, Peoples R China. NCI, Gene Regulat Sect, Frederick, MD USA. NCI, DNA Recombinant Lab, Frederick, MD USA. NR 12 TC 10 Z9 10 U1 0 U2 0 PU SHANGHAI INST BIOCHEMISTRY, ACADEMIA SINICA PI SHANGHAI PA 320 YUE-YANG ROAD, SHANGHAI 20031, PEOPLES R CHINA SN 0582-9879 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophys. Sin. PD NOV PY 1999 VL 31 IS 6 BP 659 EP 663 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 258BE UT WOS:000083817500009 ER PT J AU Mauceri, A Fasulo, S Ainis, L Licata, A Lauriano, ER Martinez, A Mayer, B Zaccone, G AF Mauceri, A Fasulo, S Ainis, L Licata, A Lauriano, ER Martinez, A Mayer, B Zaccone, G TI Neuronal nitric oxide synthase (nNOS) expression in th epithelial neuroendocrine cell system and nerve fibers in the gill of the catfish, Heteropneustes fossilis SO ACTA HISTOCHEMICA LA English DT Article DE neuronal nitric oxide synthase; immunocytochemistry; epithelial neuroendocrine cells; nerve fibers; gill; catfish; Heteropneustes fossilis ID SALMO-GAIRDNERI; FISH GILL; RESPIRATORY-TRACT; NADPH-DIAPHORASE; CHANNEL CATFISH; TELEOST GILL; IMMUNOREACTIVITY; INNERVATION; LOCALIZATION; STOMACH AB We studied immunohistochemically the localization of neuronal nitric oxide synthase (nNOS) in gills of an Indian catfish species, Heteropneustes fossilis. It is shown that most of the epithelial neuroendocrine cells that are present in gill filaments and lamellae stained positively. Go-localization of nNOS and endothelin was also shown in neuroendocrine cells. A dense plexus of nNOS-containing nerve fibers was present beneath the gill epithelium, associated with efferent filament arteries and the basal side of neuroendocrine cells. nNOS immunopositive neurons were not found in gill areas. nNOS immunopositive neuroendocrine cells appeared to differ from neuroepithelial cells in gills Of various teleost species, which are considered as oxygen-sensitive receptors and are present in the distal halves of gill filaments. Other types of neuroendocrine cells have been identified previously in other areas of gills using antibodies to serotonin and endothelin peptides. These: cell types are likely to be involved in chemical regulation of the physiology of gill cells. In relation to the function of the other cell types, our data on nNOS localization suggest that NO is a wide-spread transmitter in the gill of the Indian catfish. C1 Univ Messina, Fac Sci, Dept Anim Biol & Marine Ecol, Sect Cell & Evolut Biol, I-98166 Messina, Italy. NCI, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. Karl Franzens Univ Graz, Inst Pharmakol & Toxikol, A-8010 Graz, Austria. RP Mauceri, A (reprint author), Univ Messina, Fac Sci, Dept Anim Biol & Marine Ecol, Sect Cell & Evolut Biol, Salita Sperone 31, I-98166 Messina, Italy. RI Mayer, Bernd/B-9391-2008; Martinez, Alfredo/A-3077-2013; Fasulo, Salvatore/J-8861-2016; OI Martinez, Alfredo/0000-0003-4882-4044; Fasulo, Salvatore/0000-0001-8316-6791; MAUCERI, Angela Rita/0000-0002-3136-1103 NR 38 TC 38 Z9 40 U1 0 U2 2 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX NO.100 537, D-07705 JENA, GERMANY SN 0065-1281 J9 ACTA HISTOCHEM JI Acta Histochem. PD NOV PY 1999 VL 101 IS 4 BP 437 EP 448 PG 12 WC Cell Biology SC Cell Biology GA 268WG UT WOS:000084440300007 PM 10611932 ER PT J AU Cohen, SG AF Cohen, SG TI Commentary on future allergy practice article SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Editorial Material C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 4 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 NOV-DEC PY 1999 VL 20 IS 6 BP 393 EP 393 DI 10.2500/108854199778251753 PG 1 WC Allergy SC Allergy GA 266DR UT WOS:000084285800010 PM 10681163 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Editorial Material C1 NIAAA, Rockville, MD 20852 USA. RP Cohen, SG (reprint author), NIAAA, Rockville, MD 20852 USA. NR 8 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 NOV-DEC PY 1999 VL 20 IS 6 BP 395 EP 402 DI 10.2500/108854199778251843 PG 8 WC Allergy SC Allergy GA 266DR UT WOS:000084285800012 PM 10624497 ER PT J AU Quinn, TC Gaydos, CA AF Quinn, TC Gaydos, CA TI In vitro infection and pathogenesis of Chlamydia pneumoniae in endovascular cells SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT International Symposium on Infection and Atherosclerosis CY DEC 06-09, 1998 CL ANNECY LE VIEUX, FRANCE SP Merieux Fdn, French Natl Inst Hlth & Sci Res ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; RABBIT MODEL; RISK FACTOR; ATHEROSCLEROSIS; MACROPHAGES; TWAR AB The strength of the epidemiologic and clinical associations of Chlamydia pneumoniae with atherosclerosis can be increased by the demonstration that C pneumoniae can initiate and sustain growth in human vascular cells as well as in animal models. To investigate the biological basis for the dissemination and proliferation of this organism in vascular cells, the in vitro growth of C pneumoniae was studied in 2 macrophage cell lines, peripheral blood monocyte (PBMC)-derived macrophages, human bronchoalveolar lavage (BAL) macrophages, several endothelial cell lines, and aortic artery smooth muscle cells. Five of 5 strains of C pneumoniae were capable of 3 passages in human U-937 macrophages and in murine RAW 246.7 macrophages. Titers were suppressed in both macrophage types with each passage as compared with growth in HEp-2 cells. Both human BAL macrophages and PBMC-derived macrophages were able to inhibit C pneumoniae after 96 hours' growth. Eleven C pneumoniae strains were capable of replicating in normal human aortic artery-derived endothelial cells, umbilical vein-derived endothelial cells, and pulmonary artery endothelial cells. Infection in human aortic artery smooth muscle cells was also established For 13 strains of C pneumoniae. C pneumoniae was also capable of growing in endothelial cells derived from human cadaver coronary artery endothelial cells (CAEC). U-937 human macrophages that were infected with C pneumoniae were capable of transmitting the infection to CAEC when they were brought inta contact with the endothelial cells by centrifugation, rocking overnight, and direct layering overnight, with and without using artificial laboratory tissue culture enhancements, such as centrifugation of the inoculum and cycloheximide in the growth media. The in vitro ability of C pneumoniae to maintain infections in macrophages, endothelial cells, and aortic smooth muscle cells may provide support for the hypothesis that C pneumoniae can infect such cells, which when followed by an immune response may contribute to atheroma formation in vivo. Stimulation of cytokine responses by infection with C pneumoniae has indicated that this organism is capable of interacting with the immune system. In vitro infection by C pneumoniae of U-937 macrophages stimulated the production of IL-1 beta, IFN-gamma, and TNF-a in tissue culture. Human CAEC that are infected with C pneumoniae produce more IL-8 compared with those inoculated with killed C pneumoniae or negative control cells, indicating a chemokine response to infection that may play a role in recruitment of inflammatory cells to sites of infection in vascular cells. When IFN-gamma was used to up regulate HEp-2 and U-937 cells before infection by C pneumoniae, inhibition of a lytic growth cycle occurred in a dose related response. However, removal of the IFN-gamma after 24 to 48 hours' exposure allowed subsequent productive growth in the cells, perhaps indicating the prior induction of a persistent infection. More studies are needed to study the complex relationship between lytic infection and persistence, the ability of C pneumoniae to affect the immune response of vascular cells, and the potential for C pneumoniae to influence the initiation of or progression of atheromatous lesions. C1 NIAID, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Quinn, TC (reprint author), Ross 1159,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 27 TC 30 Z9 30 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 NOV PY 1999 VL 138 IS 5 SU S BP S507 EP S511 DI 10.1016/S0002-8703(99)70287-5 PN 2 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 252NL UT WOS:000083507500023 PM 10539860 ER PT J AU Lloyd-Jones, DM Camargo, CA Giugliano, RP Walsh, CR O'Donnell, CJ AF Lloyd-Jones, DM Camargo, CA Giugliano, RP Walsh, CR O'Donnell, CJ TI Characteristics and prognosis of patients with suspected acute myocardial infarction and elevated MB relative index but normal total creatine kinase SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; SERUM TROPONIN-T; UNSTABLE ANGINA; CK-MB; RISK; ISOENZYME; INJURY; DEATH; EVOLUTION; DIAGNOSIS AB "MB Leak" patients who develop an elevated MB rela tive index with a normal total creatine kinase (CK) level are not as well characterized as those who have diagnostic enzyme elevations in the setting of ST elevation (up arrow) or non-ST up arrow acute myocardial infarction (AMI). During a 1-year period, we studied all patients hospitalized in an urban academic hospital with suspected AMI who developed an elevated MB relative index within 24 hours of presentation. OF 595 patients, 44% had MB Leak, 34% had non-ST up arrow AMI and 22% had ST up arrow AMI. patients with MB Leak and non-ST up arrow AMI were significantly older than those with ST up arrow AMI (mean ages 69, 71, and 63 years, respectively; p <0.001), and were more likely to have previous AMI (55%, 46%, 12%; p, <0.001) or past coronary revascularization (40%, 19%, 12%; p <0.001). The in-hospital death rate of patients with MB Leak was half that of patients with non-ST up arrow AMI or ST up arrow AMI (6%, 12%, 12%; p = 0.03). By 1 year after presentation, the death rate of patients with MB Leak (17%) was intermediate between that of non-ST up arrow AMI (24%) and ST up arrow AMI (14%). Within the MB Leak group, those with elevated absolute CK-MB levels were at highest risk. In a multivariable model using MB Leak as the referent, the relative risks for 1 year death were 1.4 (95% confidence interval, 0.9 to 2.2) for patients with non-ST up arrow AM and 1.7(0.8 to 3.4) for patients with ST up arrow AMI. patients with MB Leak are at high risk for cardiovascular events in the hospital and for death by 1 year. Therefore, they may benefit from early aggressive therapy and risk stratification. These results suggest that CK-MB should be measured in all patients with suspected AMI, regardless of their total CK level. (C) 1999 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Lloyd-Jones, DM (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL-03533, HL-07575] NR 26 TC 11 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1999 VL 84 IS 9 BP 957 EP 962 DI 10.1016/S0002-9149(99)00480-4 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 252BB UT WOS:000083479900001 PM 10569646 ER PT J AU Wellman, NS Scarbrough, FE Ziegler, RG Lyle, B AF Wellman, NS Scarbrough, FE Ziegler, RG Lyle, B TI Do we facilitate the scientific process and the development of dietary guidance when findings from single studies are publicized? An American Society for Nutritional Sciences Controversy Session Report SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 97 Conference CY APR 06-10, 1997 CL NEW ORLEANS, LOUISIANA DE dietary guidance; publicity; science journalism; communicating research; media; nutrition AB This American Society for Nutritional Sciences Controversy Session presented at the 1997 Experimental Biology meeting considered whether publicity of findings from single studies facilitates or hampers the scientific process and the development of scientifically sound dietary guidance. Ln a 1995 survey, 78% of primary household shoppers believed it "very likely" or "somewhat likely" that in the next 5 y experts would have a completely different idea about which foods were healthy and which were not. This skepticism is fueled by the media's emphasis on reporting new and often controversial findings about food and nutrition. Media efforts are reinforced by the fact that some scientific journals regularly publicize newly published research findings. As a consequence, journalists frequently mediate scientific debate in a public forum-debate that previously was conducted among knowledgeable peers. Tight deadlines often make it difficult for reporters to thoroughly investigate findings publicized in press releases. Headlines can make results from single studies appear important, even when results are inconclusive. Finally, scientists and public policymakers have limited opportunity for making timely comments in response to an issue reported in the media. Nevertheless, the public has a right to be informed about health-related research findings to help them make decisions about their diets, The media are a valuable resource for educating the public and maintaining public interest in the importance of diet in overall health status. Nutrition scientists should be more involved in helping the media accurately convey diet and health messages. C1 Florida Int Univ, Dept Nutr & Dietet, Natl Policy & Resource Ctr Nutr & Aging, Miami, FL 33199 USA. USDA, Food Safety & Inspect Serv, Washington, DC 20250 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Kraft Gen Foods Inc, Dept Nutr, Glenview, IL 60025 USA. RP Wellman, NS (reprint author), Florida Int Univ, Dept Nutr & Dietet, Natl Policy & Resource Ctr Nutr & Aging, OE 200, Miami, FL 33199 USA. NR 21 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1999 VL 70 IS 5 BP 802 EP 805 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249WL UT WOS:000083356200005 PM 10539738 ER PT J AU Gautier, JF Chen, KW Uecker, A Bandy, D Frost, J Salbe, AD Pratley, RE Lawson, M Ravussin, E Reiman, EM Tataranni, PA AF Gautier, JF Chen, KW Uecker, A Bandy, D Frost, J Salbe, AD Pratley, RE Lawson, M Ravussin, E Reiman, EM Tataranni, PA TI Regions of the human brain affected during a liquid-meal taste perception in the fasting state: a positron emission tomography study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE taste; positron emission tomography; PET; human brain; cortex; thalamus; cingulate gyrus; caudate; cerebral blood flow; men ID EMOTION; FOOD; STIMULATION AB Background: The sensation of taste provides reinforcement for eating and is of possible relevance to the clinical problem of obesity. Objective: Positron emission tomography (PET) was used to explore regions of the brain that were preferentially affected during the taste perception of a liquid meal by 11 right-handed, lean men in the fasting state. Design: After subjects had fasted for 36 h, 2 measurements of regional cerebral blood flow (rCBF) obtained immediately after subjects retained and swallowed 2 mt of a flavored liquid meal (the taste condition) were compared with 2 measurements of rCBF obtained immediately after subjects retained and swallowed 2 mt of water (the baseline condition). Results: Compared with the baseline condition, taste was associated with increased rCBF (P < 0.005) in the left dorsolateral prefrontal cortex and superior temporal gyrus; the right ventrolateral prefrontal cortex, supramarginal gyrus, and anterior thalamus; and bilaterally in the hippocampal formation, posterior cingulate, midbrain, occipital cortex, and cerebellum. Taste was also associated with decreased rCBF (P < 0.005) in the right dorsolateral prefrontal cortex, superior temporal gyrus, and supplementary motor area, and bilaterally in the medial prefrontal cortex and inferior parietal lobule. Conclusions: This exploratory study provides additional evidence that the temporal cortex, thalamus, cingulate cortex, caudate, and hippocampal formation are preferentially affected by taste stimulation. The asymmetric pattern of activity in the dorsolateral prefrontal cortex and superior temporal gyrus may contribute to the taste perception of a liquid meal perceived as pleasant. Additional studies are required to determine how these regions are affected in patients with obesity or anorexia. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Good Samaritan Reg Med Ctr, Positron Emiss Tomog Ctr, Phoenix, AZ USA. Univ Arizona, Dept Psychiat, Tucson, AZ 85721 USA. RP Tataranni, PA (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 NR 16 TC 46 Z9 49 U1 3 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1999 VL 70 IS 5 BP 806 EP 810 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249WL UT WOS:000083356200006 PM 10539739 ER PT J AU Stabler, SP Allen, RH Fried, LP Pahor, M Kittner, SJ Penninx, BWJH Guralnik, JM AF Stabler, SP Allen, RH Fried, LP Pahor, M Kittner, SJ Penninx, BWJH Guralnik, JM TI Racial differences in prevalence of cobalamin and folate deficiencies in disabled elderly women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE race; methylmalonic acid; homocysteine; cobalamin; folate; women; elderly; multivitamin use ID CHROMATOGRAPHY MASS-SPECTROMETRY; URINARY METHYLMALONIC ACID; CORONARY HEART-DISEASE; PLASMA HOMOCYSTEINE; VITAMIN-B12 DEFICIENCY; PERNICIOUS-ANEMIA; SERUM; DIAGNOSIS; PEOPLE; ASSAY AB Background: Many previous investigations of cobalamin and folate status were performed in white populations. Objective: Our objective was to determine whether there are racial differences in the prevalence of cobalamin and folate deficiency. Design: The study was a cross-sectional comparison of baseline serum cobalamin, folate, methylmalonic acid (MMA), total homocysteine (tHcy), and creatinine concentrations, complete blood count, and vitamin supplementation in 550 white and 212 African American subjects from a cohort of physically disabled older women. Results: The mean (ISD) serum MMA concentration was significantly higher in whites than in African Americans: 284 +/- 229 compared with 218 +/- 158 nmol/L (P = 0.0001), tHcy concentration was higher in African Americans than in whites: 12.4 +/- 7.0 compared with 10.9 +/- 4.6 mu mol/L (P = 0.001). Serum cobalamin was lower in whites (P = 0.0002). Cobalamin deficiency (serum cobalamin <258 mu mol/L and MMA >271 nmol/L) was more frequent in the white women (19% compared with 8%; P < 0.0003). Folate deficiency (serum folate <11.4 nmol/L, tHcy >13.9 mu mol/L, and MMA <271 nmol/L) was more prevalent in African Americans than in whites (5% compared with 2%; P = 0.01). Multivitamin use was associated with lower tHcy but not with MMA concentrations. Regression models showed that age >85 y, African American race, serum creatinine >90 mu mol/L, and high MMA concentration were all significantly correlated with higher tHcy, Creatinine > 90 mu mol/L, white race, and folate concentration were positively associated with MMA concentration. Conclusions: Cobalamin deficiency with elevated serum MMA concentration is more prevalent in elderly white than in African American women and elevated serum tHcy and folate deficiency are more prevalent in elderly African American than in white women. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Div Hematol, Denver, CO 80220 USA. Johns Hopkins Med Inst, Dept Med, Div Geriatr, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Div Geriatr, Baltimore, MD 21205 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Stabler, SP (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Div Hematol, 4200 E 9th Ave,Box B-170, Denver, CO 80220 USA. FU NIA NIH HHS [N01-AG-1-2112, AG-09834] NR 44 TC 53 Z9 53 U1 1 U2 4 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 1999 VL 70 IS 5 BP 911 EP 919 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 249WL UT WOS:000083356200021 PM 10539754 ER PT J AU Ellison, RC Myers, RH Zhang, YQ Djousse, L Knox, S Williams, RR Province, MA AF Ellison, RC Myers, RH Zhang, YQ Djousse, L Knox, S Williams, RR Province, MA CA NHLBI Family Heart Study Investiga TI Effects of similarities in lifestyle habits on familial aggregation of high density lipoprotein and low density lipoprotein cholesterol - The NHLBI Family Heart Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cholesterol; coronary disease; genetics; medical; risk factors ID FOOD FREQUENCY QUESTIONNAIRE; ENZYMATIC DETERMINATION; NUTRIENT INTAKE; DISEASE; LIPIDS; DIET; ENERGY; REPRODUCIBILITY; TRIGLYCERIDES; HERITABILITY AB It is generally assumed that familial aggregation of lipids relates to both genetic and shared environmental factors. To determine the degree to which familiar similarities in lifestyle habits explain familial aggregation of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol, the authors analyzed 1994-1996 data from 2,284 US adult participants in the National Heart, Lung, and Blood Institute Family Heart Study For men and women, respectively, HDL cholesterol correlated with alcohol consumption (r = 0.27, p < 0.001; r = 0.21, p < 0.001), exercise (r = 0.06, p = 0.05; r = 0.10, p = 0.002), and smoking (r = -0.09, p = 0.005; r = -0.13, p < 0.001). There was strong familial aggregation of HDL cholesterol (parent-child, r = 0.32; sibling-sibling, r = 0.29), but less than 10% was explained by lifestyle habits. For LDL cholesterol, weak correlations were found for intake of total fat (r = 0.06, p = 0.07) and fruits/vegetables (r = -0.09, p = 0.005) among men and for smoking (r = 0.10, p = 0.002) among women. LDL cholesterol correlated strongly among family members (parent-child, r = 0.24; sibling-sibling, r = 0.31), but essentially none of this aggregation related to the lifestyle factors studied. This study suggests that lifestyle factors have little effect on the familial aggregation of HDL and LDL cholesterol. C1 Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Dept Internal Med, Cardiovasc Genet Res Clin, Salt Lake City, UT USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. RP Ellison, RC (reprint author), Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU NHLBI NIH HHS [N01-HC-25104, N01-HC-25105, N01-HC-25106] NR 33 TC 21 Z9 21 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1999 VL 150 IS 9 BP 910 EP 918 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 251VX UT WOS:000083468000003 PM 10547136 ER PT J AU Biggar, RJ Wohlfahrt, J Westergaard, T Melbye, M AF Biggar, RJ Wohlfahrt, J Westergaard, T Melbye, M TI Sex ratios, family size, and birth order SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth order; family characteristics; infant; reproduction; sex distribution; sex ratio ID MALE/FEMALE RATIO; DENMARK AB In many countries, the male:female ratio at birth has varied significantly over the past century, but the reasons for these changes have been unclear. The authors observed a close parallel between decreasing family size and declining male:female sex ratio in Denmark from 1960 to 1994. To explain this finding, they examined the sex ratio and birth order of 1,403,021 children born to 700,030 couples. Overall, 51.2% of the first births were male. However, families with boys were significantly more likely than expected to have another boy (biologic heterogeneity). By the fourth birth to families with three prior boys, 52.4% were male. The increase varied directly with the number of prior boys (p for trend = 0.0007). Furthermore, couples with boys were more likely to continue to have children. In summary, the authors found that the declining male:female ratio in Denmark and probably other European populations is mainly attributable to three effects: declining family size, biologic heterogeneity, and child sex preference. Why families with boys are more likely to have additional boys is unknown. C1 State Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, Copenhagen, Denmark. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Biggar, RJ (reprint author), State Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, Copenhagen, Denmark. NR 13 TC 39 Z9 43 U1 0 U2 7 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1999 VL 150 IS 9 BP 957 EP 962 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 251VX UT WOS:000083468000008 PM 10547141 ER PT J AU Sorkin, JD Muller, DC Andres, R AF Sorkin, JD Muller, DC Andres, R TI Longitudinal change in height of men and women: Implications for interpretation of the body mass index - The Baltimore Longitudinal Study of Aging SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE age factors; body height; body mass index; longitudinal studies ID WEIGHT AB Age differences in height derived from cross-sectional studies can be the result of differential secular influences among the age cohorts. To determine the magnitude of height loss that accompanies aging, longitudinal studies are required. The authors studied 2,084 men and women aged 17-94 years enrolled from 1958 to 1993 in the Baltimore Longitudinal Study of Aging, Baltimore, Maryland. On average, men's height was measured nine times during 15 years and women's height five times during 9 years. The rate of decrease in height was greater for women than for men. For both sexes, height loss began at about age 30 years and accelerated with increasing age. Cumulative height loss from age 30 to 70 years averaged about 3 cm for men and 5 cm for women; by age 80 years, it increased to 5 cm for men and 8 cm for women. This degree of height loss would account for an "artifactual" increase in body mass index of approximately 0.7 kg/m(2) for men and 1.6 kg/m(2) for women by age 70 years that increases to 1.4 and 2.6 kg/m(2), respectively, by age 80 years. True height loss with aging must be taken into account when height (or indexes based on height) is used in physiologic or clinical studies. C1 NIA, Clin Invest Lab, Intramural Res Program, Ctr Gerontol Res, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Baltimore Vet Affairs Med Ctr, Div Gerontol, Baltimore, MD 21201 USA. RP Sorkin, JD (reprint author), NIA, Clin Invest Lab, Intramural Res Program, Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 11 TC 152 Z9 157 U1 0 U2 8 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1999 VL 150 IS 9 BP 969 EP 977 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 251VX UT WOS:000083468000010 PM 10547143 ER PT J AU Haynie, DL Beck, KH Crump, AD Shattuck, T Simons-Morton, B AF Haynie, DL Beck, KH Crump, AD Shattuck, T Simons-Morton, B TI Parenting strategies regarding teen behavior: Parent and teen perceptions SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article ID ADOLESCENT DRINKING; INVOLVEMENT; SMOKING AB Objective: To examine parents' awareness of their adolescents' alcohol-related behavior and compare parent and teen perceptions of parent strategies to manage teen behavior. Methods: Four hundred twenty-eight parents and their adolescents were recruited via random digit dialing for telephone interviews. Results: Parents underestimated their adolescents' alcohol-related behavior. Although most parents reported appropriate parenting strategies, they relied primarily on passive strategies to supervise teen behavior. Conclusion: Parents employed a limited repertoire of strategies to manage teen behavior. Parent education programs should foster proactive parenting by broadening parents' repertoire of strategies to monitor and manage their teens' behavior. C1 NICHD, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Hlth Educ, College Pk, MD 20742 USA. RP Haynie, DL (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, NIH, Bldg 6100,Room 7B05,9000 Rockvile Pike MSC 7510, Bethesda, MD 20892 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 24 TC 11 Z9 11 U1 1 U2 3 PU PNG PUBLICATIONS PI STAR CITY PA PO BOX 4593, STAR CITY, WV 26504-4593 USA SN 1087-3244 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD NOV-DEC PY 1999 VL 23 IS 6 BP 403 EP 414 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 259VH UT WOS:000083914300001 ER PT J AU Millat, G Marcais, C Rafi, MA Yamamoto, T Morris, JA Pentchev, PG Ohno, K Wenger, DA Vanier, MT AF Millat, G Marcais, C Rafi, MA Yamamoto, T Morris, JA Pentchev, PG Ohno, K Wenger, DA Vanier, MT TI Niemann-Pick C1 disease: The I1061T substitutions a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NIEMANN-PICK-DISEASE; CHOLESTEROL ESTERIFICATION; C-DISEASE; HETEROGENEITY AB Niemann-Pick type C (NPC) disease is an autosomal recessive lipid-storage disorder usually characterized by hepatosplenomegaly and severe progressive neurological dysfunction, resulting from mutations affecting either the NPC1 gene (in 95% of the patients) or the yet-to-be-identified NPC2 gene. Our initial study of 25 patients with NPC1 identified a T-3182-->C transition that leads to an I1061T substitution in three patients. The mutation, located in exon 21, affects a putative transmembrane domain of the protein. PCR-based tests with genomic DNA were used to survey 115 unrelated patients from around the world with all known clinical and biochemical phenotypes of the disease. The I1061T allele constituted 33 (14.3%) of the 230 disease-causing alleles and was never found in controls (>200 alleles). The mutation was particularly frequent in patients with NPC from Western Europe, especially France (11/62 alleles) and the United Kingdom (9/32 alleles), and in Hispanic patients whose roots were in the Upper Rio Grande valley of the United States. The I1061T mutation originated in Europe and the high frequency in northern Rio Grande Hispanics results from a founder effect. All seven unrelated patients who were homozygous for the mutation and their seven affected siblings had a juvenile-onset neurological disease and severe alterations of intracellular LDL-cholesterol processing. The mutation was not found (0/40 alleles) in patients with the severe infantile neurological form of the disease. Testing for this mutation therefore has important implications for genetic counseling of families affected by NPC. C1 Ctr Hosp Lyon Sud, Lab Fdn Gillet Merieux, F-69495 Pierre Benite, France. Lyon Sud Sch Med, INSERM, U189, Oullins, France. Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurol, Philadelphia, PA 19107 USA. Tottori Univ, Fac Med, Ctr Gene Res, Yonago, Tottori 683, Japan. Tottori Univ, Fac Med, Dept Neurobiol, Yonago, Tottori 683, Japan. NINDS, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. RP Vanier, MT (reprint author), Ctr Hosp Lyon Sud, Lab Fdn Gillet Merieux, Batiment 3B, F-69495 Pierre Benite, France. NR 24 TC 83 Z9 89 U1 3 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1999 VL 65 IS 5 BP 1321 EP 1329 DI 10.1086/302626 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 252YZ UT WOS:000083531000013 PM 10521297 ER PT J AU Drayna, D Kilshaw, J Kelly, J AF Drayna, D Kilshaw, J Kelly, J TI The sex ratio in familial persistent stuttering SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Hollins Commun Res Inst, Roanoke, VA USA. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA. FU PHS HHS [ZO1-00046-01] NR 10 TC 17 Z9 22 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1999 VL 65 IS 5 BP 1473 EP 1475 DI 10.1086/302625 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 252YZ UT WOS:000083531000034 PM 10521318 ER PT J AU Oriji, GK Keiser, HR AF Oriji, GK Keiser, HR TI Nitric oxide in cyclosporine A-induced hypertension: Role of protein kinase C SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE cyclosporine A; L-arginine; endothelin; acetylcholine; nitrate/nitrite; guanosine 3 ', 5 '-cyclic monophosphate; rats; protein kinase C; aortic rings ID SMOOTH-MUSCLE CELLS; TREATED RATS; L-ARGININE; TRANSPLANT RECIPIENTS; VASCULAR RELAXATION; ENDOTHELIAL-CELLS; RESPONSES; TOXICITY; DYSFUNCTION; ARTERIES AB Chronic treatment with cyclosporine A (CsA), an immunosuppressive agent, causes hypertension. The effect of CsA on vascular responses was determined in Sprague-Dawley rats and isolated rat aortic rings. Male rats weighing 250 to 300 g were given either CsA (25 mg/kg/day) in olive oil or vehicle by intraperitoneal injection for 7 days. Cyclosporine A administration produced a 42% increase (P < .001) in mean arterial pressure (MAP), which reached a plateau after 3 days. Conversely, the level of both nitrate/nitrite (NO2/NO3), metabolites of nitric oxide (NO), and 3', 5' cyclic guanosine monophosphate (cGMP), which mediates NO action, decreased by 50% (P < .001) and 35% (P < .001), respectively, in the urine. Thoracic aortic rings from rats treated with CsA, and precontracted with endothelin (10(-9) mol/L), showed a 35% increase (P < .001) in tension, whereas acetylcholine-induced (Ach; 10(-9) mol/L) endothelium-dependent relaxation was inhibited 65% (P < .001) compared with untreated rats. This response was similar to that of aortic rings, denuded of endothelium, from untreated rats in which Ach-induced relaxation was completely abolished (P < .001). Ach-induced formation of both NO2/NO3 and cGMP by both denuded and CsA-treated aortic rings was inhibited 95% (P < .001) and 65% P < .001), respectively, compared with intact aortic rings. The effects of CsA were reversed both in vivo and in vitro by pretreatment with L-arginine (L-Arg; 10 mg/kg/day intraperitoneally), the precursor of NO. There were no changes in MAP and tension in rats treated with L-Arg alone. In addition, in the aorta of rats that were treated intraperitoneally with CsA for 7 days, CsA significantly activated protein kinase C (PKC) translocation and decreased NO2/NO3 production. This suggest that PKC mediates, in part, CsA-induced hypertension. In summary, CsA activates PKC, which inhibits endothelial NO formation, with resulting increases in MAP and tension, and this inhibition can be overcome by L-Arg administration. (C) 1999 American Journal of Hypertension, Ltd. C1 William Paterson Univ, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Oriji, GK (reprint author), William Paterson Univ, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NR 29 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 1999 VL 12 IS 11 BP 1091 EP 1097 DI 10.1016/S0895-7061(99)00089-8 PN 1 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 258VL UT WOS:000083859900006 PM 10604485 ER PT J AU Hanson, JA Hulbert-Shearon, TE Ojo, AO Port, FK Wolfe, RA Agodoa, LYC Daugirdas, JT AF Hanson, JA Hulbert-Shearon, TE Ojo, AO Port, FK Wolfe, RA Agodoa, LYC Daugirdas, JT TI Prescription of twice-weekly hemodialysis in the MSA SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE end stage renal disease (ESRD); dialysis dose; hemodialysis schedule; ESRD survival ID MORTALITY; DURATION; DISEASE; TIME AB Background/Aims: The purpose of this study was to investigate the frequency and characteristics of two hemodialysis sessions/week, to identify factors which influence or predict this prescription, and to examine the outcomes of patients receiving hemodialysis two times/week as compared to the more common treatment of three times/week. Methods: Data from a national sample of 15,067 adult hemodialysis patients were utilized to compare twice-weekly with thrice-weekly therapy by logistic regression. Results: Patients treated less than one year were more likely to be treated twice-weekly (6.1%) than patients on dialysis for one year or more (2.7%) (AOR = 1.49, p = 0.002). Treatment schedules also varied significantly by geographic region. Factors predictive of twice-weekly hemodialysis (p < 0.05) were older age, Caucasian race, female gender, higher serum albumin, lower serum creatinine levels, and lower body mass index. A higher estimated renal function at the start of ESRD was also predictive of a twice-weekly schedule among incident patients (AOR = 1.05, p = 0.05). In addition, Cox-adjusted survival analysis indicated a lower mortality risk (RR = 0.76, p = 0.02) for twice-weekly hemodialysis compared to thrice-weekly among prevalent patients. For incident patients, however, the results were not significant when adjusted for GFR at ESRD onset (RR = 0.85, p = 0.31). Conclusion: Geographic differences in prescribed treatment remained unexplained by measured characteristics. The survival advantage associated with twice-weekly hemodialysis is likely to be related to patient selection and greater residual renal function. Copyright (C) 1999 S. Karger AG, Basel. C1 Univ Michigan, Kidney Epidemiol & Cost Ctr, Ann Arbor, MI 48103 USA. US Renal Data Syst Coordinating Ctr, Ann Arbor, MI USA. Westside VAMC, Chicago, IL USA. NIDDKD, Bethesda, MD 20892 USA. RP Port, FK (reprint author), Univ Michigan, Kidney Epidemiol & Cost Ctr, 315 W Huron St,Suite 240, Ann Arbor, MI 48103 USA. NR 25 TC 32 Z9 34 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PD NOV-DEC PY 1999 VL 19 IS 6 BP 625 EP 633 DI 10.1159/000013533 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 262TX UT WOS:000084083500001 PM 10592355 ER PT J AU McFarland, HF AF McFarland, HF TI Correlation between MR and clinical findings of disease activity in multiple sclerosis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP McFarland, HF (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 5 TC 10 Z9 11 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1999 VL 20 IS 10 BP 1777 EP 1778 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 259HB UT WOS:000083887500003 PM 10588096 ER PT J AU Post, MJD Yiannoutsos, C Simpson, D Booss, J Clifford, DB Cohen, B McArthur, JC Hall, CD AF Post, MJD Yiannoutsos, C Simpson, D Booss, J Clifford, DB Cohen, B McArthur, JC Hall, CD CA AIDS Clin Trials Grp 243 Team TI Progressive multifocal leukoencephalopathy in AIDS: Are there any MR findings useful to patient management and predictive of patient survival? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Neuroradiology CY MAY 18, 1998 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Neuroradiol ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; STEREOTAXIC BRAIN BIOPSY; SPIN-ECHO MR; JC VIRUS; CEREBROSPINAL-FLUID; PATHOLOGICAL CORRELATION; PROLONGED SURVIVAL; IMMUNE-DEFICIENCY; INFECTED PATIENTS AB BACKGROUND AND PURPOSE: While MR findings in progressive multifocal leukoencephalopathy (PML) have been described previously, usually in retrospective studies with limited sample size, what has not been well addressed is whether any are predictive of longer survival, Our participation in a large prospective clinical trial of AIDS patients with biopsy-proved PML and MR correlation allowed us to test our hypothesis that certain MR features could be found favorable to patient survival. METHODS: The patient cohort derived from a randomized multicenter clinical trial of cytosine arabinoside for PML. Pretreatment T1- and T2-weighted noncontrast images (n = 48) and T1-weighted contrast-enhanced images (n = 45) of 48 HIV-positive patients with a PML tissue diagnosis as well as the follow-up images in 15 patients were reviewed to determine signal abnormalities, lesion location and size, and the presence or absence of mass effect, contrast enhancement, and atrophy, and to ascertain the frequency of these findings, A statistical analysis was performed to determine if any MR abnormalities, either at baseline or at follow-up, were predictive of patient survival. RESULTS: No MR abnormalities either on univariate or multivariate analysis significantly correlated with patient survival, with the exception of mass effect, which was significantly associated with shorter survival. The mass effect, however, always minimal, was infrequent (five of 48), More severe degrees of cortical atrophy and ventricular dilatation, lesion location and size, and other MR variables were not predictive of outcome. CONCLUSION: Except for mass effect, we found no MR findings predictive of the risk of death in patients with PML. The mass effect, however, was so infrequent and minimal that it was not a useful MR prognostic sign. C1 NIH, Bethesda, MD 20892 USA. NIAID, Adult AIDS Clin Trials Grp, Bethesda, MD 20892 USA. RP Post, MJD (reprint author), Univ Miami, Sch Med, Dept Radiol R 308, MRI Ctr, 1115 NW 14th St, Miami, FL 33136 USA. FU NCRR NIH HHS [RR00036-37]; NINDS NIH HHS [1 PO1 NS3228]; PHS HHS [A1-25868] NR 89 TC 92 Z9 97 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 1999 VL 20 IS 10 BP 1896 EP 1906 PG 11 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 259HB UT WOS:000083887500023 PM 10588116 ER PT J AU Maymon, E Ghezzi, F Edwin, SS Mazor, M Yoon, BH Gomez, R Romero, R AF Maymon, E Ghezzi, F Edwin, SS Mazor, M Yoon, BH Gomez, R Romero, R TI The tumor necrosis factor alpha and its soluble receptor profile in term and preterm parturition SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-for-Maternal-Fetal Medicine CY JAN 18-23, 1999 CL SAN FRANCISCO, CALIFORNIA SP Soc Maternal Fetal Med DE infection; parturition; preterm labor; soluble receptors; tumor necrosis factor alpha ID AMNIOTIC-FLUID; TNF RECEPTORS; LABOR; EXPRESSION; INFECTION; PLACENTA; WOMEN; P55 AB OBJECTIVE: The common terminal pathway of parturition describes the anatomic, biochemical, endocrine, and clinical events present in the fetus and mother in both term and preterm labor. Labor at term is thought to result from physiologic activation of this pathway, whereas preterm labor is the result of pathologic activating events. The purpose of this study was to determine whether physiologic and pathologic activation could be discerned by the analysis of a cytokine-receptor signaling system. Tumor necrosis factor alpha and its soluble receptors were used as probes because of their pivotal role in the regulation of several processes activated during parturition. Soluble receptors are thought to buffer the biologic and potentially deleterious effects of tumor necrosis factor alpha in pathologic conditions. STUDY DESIGN: The in vivo concentrations of tumor necrosis factor alpha and its soluble receptors were studied in patients in term labor and preterm labor. Amniotic fluid was retrieved from 175 women and tumor necrosis factor alpha, tumor necrosis factor receptor 1, and tumor necrosis factor receptor 2 concentrations were measured by highly sensitive immunoassays. Patients were classified in the following groups: (1) term labor (n = 29), (2) term not in labor (n = 29), (3) preterm labor leading to term delivery (n = 34), (4) preterm labor without infection resulting in preterm delivery (n = 34), (5) preterm labor with intra-amniotic infection (n = 23), and (6) second trimester (n = 26). RESULTS: Tumor necrosis factor alpha and tumor necrosis factor receptor 1 concentrations decreased with advanced gestational age (r = -0.51 and r = -0.7; P < .01 for each). (1) Patients in Spontaneous term labor had a higher median concentration of tumor necrosis factor alpha than those at term not in labor (median; 6.4 pg/mL; range, 2.4->500 pg/mL vs median, 4.1 pg/mL; range, 1.1-22.7 pg/mL; P < .01) but had lower concentrations of tumor necrosis factor receptor 1 (median, 3.2 ng/mL; range, 1.3-9.1 ng/mL vs median, 4.2 ng/mL; range, 1.6-8.3; P < .001) and tumor necrosis factor receptor 2 (median, 5.5 ng/mL; range, 0.73-12.8 ng/mL vs median, 6.8 ng/mL; range, 2.9-12.9 ng/mL; P < .01). (2) In contrast, patients with preterm labor leading to preterm delivery had higher concentrations of tumor necrosis factor alpha (median, 12.3 pg/mL; range, 1.5->500 pg/mL vs median, 4.8 pg/mL; range, 1-60.9 pg/mL; P < .01), tumor necrosis factor receptor 1 (median, 8.8 ng/mL; range, 2.5-38 ng/mL vs median, 6.2 ng/mL; range, 1.4-28 ng/mL; P < .05), and tumor necrosis factor receptor 2 (median, 8.5 ng/mL; range, 3.5-45.4 ng/mL vs median, 6.1 ng/mL; range, 1.99-14.1 ng/mL; P < .01) than patients with preterm labor who delivered at term. (3) Microbial invasion of the amniotic cavity was associated with dramatic increases in the concentrations of tumor necrosis factor alpha (median, 93.5 pg/mL; range, 1.2->500 pg/mL) and its soluble receptors tumor necrosis factor receptor 1 (median, 8.8 ng/mL; range, 2.1-36.7 ng/mL) and tumor necrosis factor receptor 2 (median, 11.8 ng/mL; range, 3.4-46.3 ng/mL), concentrations that were significantly higher than in those with preterm labor who delivered at term and those who delivered preterm but were nor infected. CONCLUSION: The tumor necrosis factor alpha and tumor necrosis factor alpha soluble receptor profiles are different in term and preterm parturition. Our observations provide support for the thesis that preterm parturition is a pathologic condition. Increased tumor necrosis factor alpha soluble receptor concentrations may attenuate the deleterious effects of the excess of tumor necrosis factor alpha found in pathologic labor. C1 Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept Obstet & Gynecol,NICHHD, Detroit, MI 48201 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Ben Gurion Univ Negev, Dept Obstet & Gynecol, Soroka Hosp, IL-84105 Beer Sheva, Israel. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Maymon, E (reprint author), Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept Obstet & Gynecol,NICHHD, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011; OI Ghezzi, Fabio/0000-0003-3949-5410 NR 25 TC 102 Z9 104 U1 0 U2 9 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1999 VL 181 IS 5 BP 1142 EP 1148 DI 10.1016/S0002-9378(99)70097-9 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 256RH UT WOS:000083739000020 PM 10561634 ER PT J AU Gulya, AJ AF Gulya, AJ TI The NIDCD's clinical trials cooperative groups: A brief overview SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article AB The National Institute on Deafness and Other Communication Disorders (NIDCD) embarked on the establishment of two clinical trials cooperative groups in October 1996 in response to a scientific research need. It intended that the clinical trials cooperative groups (CTCGs) design and implement clinical trial protocols capable of addressing the efficacy of therapeutic interventions for diseases and disorders of human communication. Most commonly, owing to the substantial number of patients required, the trials are expected to involve multiple study sites, with each study site adhering to a uniform study protocol, standardized treatment regimens, and prescribed data collection procedures. A complex administrative structure is required to coordinate the activities of the CTCGs and to assure compliance with a myriad of government regulations. Similarly, participating study sites must meet stringent requirements including leadership by an individual experienced in clinical trials. There is a relative dearth of experienced clinical trialists dedicated to research in human communication. This article details the complexities involved in the conduct of multicenter clinical trials and the NIDCD's efforts to promote clinical trials activities and to develop clinical trials training opportunities. C1 Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. RP Gulya, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1999 VL 20 IS 6 BP 705 EP 708 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 392UT UT WOS:000166431500001 PM 10565711 ER PT J AU Kim, CJ Matsuo, T Lee, KH Thiele, CJ AF Kim, CJ Matsuo, T Lee, KH Thiele, CJ TI Up-regulation of insulin-like growth factor-II expression is a feature of trkA but not trkB activation in SH-SY5Y neuroblastoma cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NEUROTROPHIC FACTOR; SYMPATHETIC NEURONS; INDUCED APOPTOSIS; IGF2 EXPRESSION; FACTOR RECEPTOR; NERVOUS-SYSTEM; MESSENGER-RNA; NEURAL CREST; IN-VIVO; DIFFERENTIATION AB The types of neurotrophin receptors that are expressed in neuroblastomas have different prognostic implications; trkA is a marker of good prognosis, whereas trkB expression is associated with poor prognosis. This suggests that either the signaling that is mediated via these receptors modulates the biological features of neuroblastoma cells differently, or that distinct lineages of sympathoadrenal precursors have been transformed. In this report, we evaluate the biological effects after activation of trkA or trkB by their major ligands in SH-SY5Y human neuroblastoma cells. Both trkA and trkB induce differentiation, inhibit growth, and promote the survival of cells under conditions of nutrient deprivation. However, the up-regulation of insulin-like growth factor-II (IGF-II) expression is a predominant feature of trkA. activation by nerve growth factor (NGF). The growth inhibition induced by blocking the insulin-like growth factor-I receptor suggests that IGF-II is a component of the effector mechanism of trkA activation by NGF in trkA-transfected cells. Although trkA and trkB expression is associated with different prognoses in neuroblastoma, our study indicates that the effects mediated by these receptors in vivo may be quite similar for certain subsets of neuroblastomas. C1 Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea. NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Samsung Med Ctr, Dept Nucl Med, Seoul, South Korea. RP Kim, CJ (reprint author), Seoul Natl Univ, Coll Med, Dept Pathol, 28 Yongon Dong, Seoul 110799, South Korea. EM cjkim@plaza.snu.ac.kr RI Lee, Kyun Han/C-9648-2011; Seoul National University, Pathology/B-6702-2012 NR 45 TC 34 Z9 37 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1999 VL 155 IS 5 BP 1661 EP 1670 DI 10.1016/S0002-9440(10)65481-8 PG 10 WC Pathology SC Pathology GA 253ZT UT WOS:000083587600031 PM 10550322 ER PT J AU Smith, DG Malhi, RS Eshleman, J Lorenz, JG Kaestle, FA AF Smith, DG Malhi, RS Eshleman, J Lorenz, JG Kaestle, FA TI Distribution of mtDNA haplogroup X among Native North Americans SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE restriction analysis; DNA sequencing; HVSI; recent admixture; founding matriline ID MITOCHONDRIAL-DNA ANALYSIS; NEW-WORLD; CONTROL REGION; EUROPEAN POPULATIONS; SEQUENCE DIVERSITY; ANCIENT DNA; ORIGIN; LINEAGES; SINGLE; MIGRATIONS AB Mitochondrial DNA (mtDNA) samples of 70 Native Americans, most of whom had been found not to belong to any of the four common Native American haplogroups (A, B, C, and D), were analyzed for the presence of Dde I site losses at np 1715 and np 10394. These two mutations are characteristic of haplogroup X which might be of European origin. The first hypervariable segment (HVSI) of the non-coding control region (CR) of mtDNA of a representative selection of samples exhibiting these mutations was sequenced to confirm their assignment to haplogroup X, Thirty-two of the samples exhibited the restriction site losses characteristic of haplogroup X and, when sequenced, a representative selection (n = 11) of these exhibited the CR mutations commonly associated with haplogroup X, C --> T transitions at np 16278 and 16223, in addition to as many as three other HVSI mutations. The wide distribution of this haplogroup throughout North America, and its prehistoric presence there, are consistent with its being a fifth founding haplogroup exhibited by about 3% of modern Native Americans. Its markedly nonrandom distribution with high frequency in certain regions, as for the other four major mtDNA haplogroups, should facilitate establishing ancestor/descendant relationships between modern and prehistoric groups of Native Americans. The low frequency of haplogroups other than A, B, C, D, and X among the samples studied suggests a paucity of both recent non-Native American maternal admixture in alleged fullblood Native Americans and mutations at the restriction sites that characterize the five haplogroups as well as the absence of additional (undiscovered) founding haplogroups. (C) 1999 Wiley-Liss, Inc. C1 Univ Calif Davis, Dept Anthropol, Davis, CA 95616 USA. Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. NIAA, DCIBR, LNG, NIH, Rockville, MD 20851 USA. Yale Univ, Dept Anthropol, New Haven, CT 06511 USA. RP Smith, DG (reprint author), Univ Calif Davis, Dept Anthropol, Davis, CA 95616 USA. FU NCRR NIH HHS [RR00169, RR05090] NR 58 TC 74 Z9 76 U1 1 U2 10 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. PD NOV PY 1999 VL 110 IS 3 BP 271 EP 284 DI 10.1002/(SICI)1096-8644(199911)110:3<271::AID-AJPA2>3.0.CO;2-C PG 14 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 249AR UT WOS:000083310200002 PM 10516561 ER PT J AU Coon, SL Zarazaga, LA Malpaux, B Ravault, JP Bodin, L Voisin, P Weller, JL Klein, DC Chemineau, P AF Coon, SL Zarazaga, LA Malpaux, B Ravault, JP Bodin, L Voisin, P Weller, JL Klein, DC Chemineau, P TI Genetic variability in plasma melatonin in sheep is due to pineal weight, not to variations in enzyme activities SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE pineal gland; arylalkylamine N-acetyltransferase; hydroxyindole O-methyltransferase ID N-ACETYLTRANSFERASE; SEROTONIN; RHYTHM; GLAND; EWE AB This study was conducted to determine the origin of the high variability in the mean nocturnal plasma melatonin concentration (MC) in sheep. Two extreme groups of 25 lambs each [flow (L) and high (H)] were obtained by calculating their genetic value on the basis of the MC of their parents. The MC of lambs was significantly higher in the H group than in the L group (L: 189.7 +/- 24.4 vs. H: 344.1 +/- 33.0 pg/ml, P < 0.001). Within each group, 13 lambs were slaughtered during the day (D) and 12 lambs during the night (N). Pineal weight was significantly higher in the H group than in the L group (L: 83.5 +/- 6.7 vs. H: 119.1 +/- 9.2 mg, P < 0.01) but did not differ between D and N. The amount of melatonin released in vitro per milligram of pineal gland, the arylalkylamine N-acetyltransferase (AANAT) activity, the AANAT protein content, and the level of AANAT mRNA differed significantly between D and N but not with genetic group. Hydroxyindole O-methyltransferase activity did not differ significantly between D and N or between genetic groups. Therefore, the genetic difference in MC between the two groups of lambs was attributed to a difference in pineal size, not in enzymatic activity of the pinealocytes. C1 NIH, Sect Neuroendocrinol, Dev Biol Lab, Bethesda, MD 20892 USA. INRA, PRMD, CNRS URA 1291, F-37380 Nouzilly, France. INRA, Stn Ameliorat Genet Animaux, F-31326 Castanet Tolosan, France. Fac Sci Neurobiol & Neuroendocrinol Cellulaire, CNRS UMR 1869, F-86002 Poitiers, France. RP Chemineau, P (reprint author), INRA, PRMD, CNRS URA 1291, F-37380 Nouzilly, France. EM Philippe.Chemineau@tours.inra.fr RI Zarazaga, Luis/L-6107-2014 NR 18 TC 32 Z9 32 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 1999 VL 277 IS 5 BP E792 EP E797 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 254EJ UT WOS:000083598700003 PM 10567004 ER PT J AU Hong, DH Petrovics, G Anderson, WB Forstner, J Forstner, G AF Hong, DH Petrovics, G Anderson, WB Forstner, J Forstner, G TI Induction of mucin gene expression in human colonic cell lines by PMA is dependent on PKC-epsilon SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE protein kinase C; signal transduction; phorbol 12-myristate 13-acetate ID PROTEIN-KINASE-C; POLYMERASE CHAIN-REACTION; HUMAN INTESTINAL MUCIN; EPITHELIAL-CELLS; SECRETION; RAT; CLONING; REGION; CDNA; DIFFERENTIATION AB Treatment of HT-29 cells with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), induces MUC2 expression. To investigate the role of PKC in regulating mucin genes in intestinal cells, we examined the regulation of MUC1, MUC2, MUC5AC, MUC5B, and MUC6 expression in two human mucin-producing colonic cell lines, T84 and HT29/A1. T84 and HT29/A1 cells (at 80-90% confluency) were exposed to 100 nM PMA for 0, 3, and 6 h. Twofold or greater increases in mRNA levels for MUC2 and MUC5AC were observed in both cell lines during this time period, whereas the levels of MUC1, MUC5B, and MUC6 mRNAs were only marginally affected. These results indicated that PKC differentially regulates mucin gene expression and that it may be responsible for altered mucin expression. Our previous results suggested that the Ca2+-independent PKC-epsilon isoform appeared to mediate PMA-regulated mucin exocytosis in these cell lines. To determine if PKC-epsilon was also involved in MUC2/MUC5AC gene induction, HT29/A1 cells were stably transfected with either a wild-type PKC-epsilon or a dominant-negative ATP-binding mutant of PKC-epsilon (PKC-epsilon K437R). Overexpression of the dominant-negative PKC-epsilon K437R blocked induction of both mucin genes, whereas PMA-induced mucin gene expression was not prevented by overexpression of wild-type PKC-epsilon. PMA-dependent MUC2 mucin secretion was also blocked in cells overexpressing the dominant-negative PKC-epsilon K437R. On the basis of these observations, PKC-epsilon appears to mediate the expression of two major gastrointestinal mucins in response to PMA as well as PMA-regulated mucin exocytosis. C1 Univ Toronto, Hosp Sick Children, Div Gastroenterol, Res Inst,Dept Paediat, Toronto, ON M5G 1X8, Canada. Univ Toronto, Hosp Sick Children, Div Gastroenterol, Res Inst,Dept Biochem, Toronto, ON M5G 1X8, Canada. NCI, Cellular Oncol Lab, Signal Transduct Sect, NIH, Bethesda, MD 20892 USA. RP Forstner, G (reprint author), Univ Toronto, Hosp Sick Children, Div Gastroenterol, Res Inst,Dept Paediat, 555 Univ Ave,Rm 3423, Toronto, ON M5G 1X8, Canada. NR 40 TC 45 Z9 48 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1999 VL 277 IS 5 BP G1041 EP G1047 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 257YN UT WOS:000083810500016 PM 10564110 ER PT J AU Nussbacher, A Gerstenblith, G O'Connor, FC Becker, LC Kass, DA Schulman, SP Fleg, JL Lakatta, EG AF Nussbacher, A Gerstenblith, G O'Connor, FC Becker, LC Kass, DA Schulman, SP Fleg, JL Lakatta, EG TI Hemodynamic effects of unloading the old heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE aging; myocardial function; preload; afterload; exercise hemodynamics ID VENTRICULAR EJECTION FRACTION; PULSE-WAVE VELOCITY; ADVANCING AGE; ARTERIAL; EXERCISE; NITROGLYCERIN; PRESSURE; VOLUME; LOAD; IMPEDANCE AB A reduction in upright exercise capacity with aging in healthy individuals is accompanied by acute left ventricular (LV) dilatation and impaired LV ejection. To determine whether acute vasodilator administration would improve LV ejection during exercise, sodium nitroprusside (NP) was administered to 16 healthy subjects, ages 64-84 yr, who had been screened for the absence of coronary heart disease by prior exercise thallium scintigraphy. Infusion of NP (0.3- 1.0 mu g.kg(-1).min(-1)), titrated to reduce the resting mean arterial pressure 10% (and eliminate the late augmentation of carotid arterial pressure), increased LV ejection fraction (EF) compared with placebo during upright, maximal graded cycle exercise at all work rates and permitted an equivalent stroke volume and stroke work from a smaller end-diastolic volume. The maximum increase in exercise EF in older subjects during NP infusion was equal to that in healthy, younger (22-39 yr) control subjects. The maximum cycle work rate and cardiac index were unchanged compared with placebo. Thus combined preload and afterload reduction with NP in older individuals improves overall LV ejection phase function: exercise LV stroke work is reduced, EF is increased, and stroke volume is maintained in the setting of a reduced ventricular size. These findings suggest that at least some of the age-associated decline in cardiac function during maximal aerobic exercise may be secondary to adverse loading conditions. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Cardiol, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), Gerontol Res Ctr, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 34 TC 28 Z9 29 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 1999 VL 277 IS 5 BP H1863 EP H1871 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 254EH UT WOS:000083598600026 PM 10564141 ER PT J AU Traynor, TR Smart, A Briggs, JP Schnermann, J AF Traynor, TR Smart, A Briggs, JP Schnermann, J TI Inhibition of macula densa-stimulated renin secretion by pharmacological blockade of cyclooxygenase-2 SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE kidney; rabbit; NS-398; valerylsalicylate; isolated perfused juxtaglomerular apparatus ID NITRIC-OXIDE SYNTHASE; PROSTAGLANDIN SYNTHESIS; RAT-KIDNEY; PROSTACYCLIN RECEPTOR; MESANGIAL CELLS; MESSENGER-RNA; RELEASE; EXPRESSION; LOCALIZATION; RABBIT AB Previous results from our laboratory have shown that in the isolated perfused juxtaglomerular apparatus, nonselective inhibitors of cyclooxygenase (COX) activity prevent the stimulation of renin secretion by a reduction in luminal NaCl concentration at the macula densa. The present studies were performed to examine which COX isoform is involved in NaCl-dependent renin secretion. In the absence of COX inhibitors, a reduction in luminal NaCl (from Na 141/Cl 120 mM to Na 26/Cl 7 mM) caused an increase in renin secretion rate from 4.5 +/- 1.8 to 26.1 +/- 7.4 nGU/min (P < 0.01, n = 19). The presence of the COX-1 inhibitor valerylsalicylate (500 mu M) in lumen and bath did not affect the stimulation of renin secretion by a reduction in luminal NaCl concentration (5 +/- 1.8 nGU/min at high NaCl, and 30.5 +/- 9.4 nGU/min at low NaCl; P < 0.01, n = 8). In contrast, the specific COX-2 inhibitor NS-398 (50 mu M) in lumen and bath abolished the stimulating effect of low luminal NaCl (12.8 +/- 3.9 nGU/min at high NaCl, and 10.7 +/- 3.1 nGU/min at low NaCl; NS, n = 15). The finding that COX-2 is critically involved in macula densa control of renin secretion indicates that the COX-2-expressing epithelial cells in the tubuloglomerular contact area are a likely source of prostaglandins participating in the signaling pathway between the macula densa and renin-producing granular cells. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Physiol, Ann Arbor, MI 48109 USA. RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Rm 4D51,10 Ctr Dr MSC 1370, Bethesda, MD 20892 USA. EM JurgenS@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK NIH HHS [DK-37448, DK-39255, DK-40042] NR 46 TC 95 Z9 99 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 NOV PY 1999 VL 277 IS 5 BP F706 EP F710 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 258BN UT WOS:000083818300005 PM 10564233 ER PT J AU Humphreys, BL Ruffin, AB Cahn, MA Rambo, N AF Humphreys, BL Ruffin, AB Cahn, MA Rambo, N TI Powerful connections for public health: The National Library of Medicine and the National Network of Libraries of Medicine SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material AB As incorporated in Healthy People 2010 objectives, data and information systems and a skilled workforce are 2 of the-critical components of the public health infrastructure. The National Library of Medicine (NLM) and the National Network of Libraries of Medicine (NN/LM) are important resources for improving Internet access and providing related training to the public health workforce and to those in training for public health careers. The NLM and the NN/LM have joined forces with the Centers for Disease Control and Prevention, the Health Resources and Services Administration, the Association of State and Territorial Health Officials, the National Association of County and City Health Officials, and the Public Health Foundation. The goal of this collaboration is to improve electronic resources useful in public health practice and increase awareness of them, to train public health professionals to use electronic information services, and to help public health agencies obtain the equipment and Internet connections needed to use these services effectively. The databases, outreach programs, and connection grants available to public health professionals from the NLM, and the training and ongoing support available from the NN/LM for accessing these programs and services, are described. C1 Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, Bethesda, MD 20894 USA. Natl Network Lib Med, Bethesda, MD USA. RP Cahn, MA (reprint author), Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, 8600 Rockville Pike,Bldg 38A,Room 4S410,MS 20, Bethesda, MD 20894 USA. OI Rambo, Neil/0000-0003-2376-5121 NR 5 TC 3 Z9 3 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1999 VL 89 IS 11 BP 1633 EP 1636 DI 10.2105/AJPH.89.11.1633 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 250ML UT WOS:000083392100004 PM 10553380 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI The relation of wages to the public health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1999 VL 89 IS 11 BP 1641 EP 1644 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 250ML UT WOS:000083392100006 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI Public health at the crossroads SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. NR 4 TC 0 Z9 1 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1999 VL 89 IS 11 BP 1645 EP 1648 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 250ML UT WOS:000083392100007 ER PT J AU Allaire, SH LaValley, MP Evans, SR O'Connor, GT Kelly-Hayes, M Meenan, RF Levy, D Felson, DT AF Allaire, SH LaValley, MP Evans, SR O'Connor, GT Kelly-Hayes, M Meenan, RF Levy, D Felson, DT TI Evidence for decline in disability and improved health among persons aged 55 to 70 years: The Framingham Heart Study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FUNCTIONAL LIMITATIONS; CARDIOVASCULAR-DISEASE; MENOPAUSAL STATUS; OLDER AMERICANS; RISK-FACTORS; TRENDS; SELF; MORTALITY; LIFE; INTERVIEWER AB Objectives. This study detected secular change in disability and health among persons aged 55 to 70 years, the life period when increases in disability and morbidity begin and retirement occurs. Methods. Cross-sectional comparisons were completed with data from similarly aged members of the original (n = 1760) and offspring (n = 1688) cohorts of the Framingham Heart Study, which represent 2 generations. Analyses were conducted by gender and on chronic disease subgroups by logistic regression. Results. There was substantially less disability in the offspring cohort than in the original cohort. Thirty-six percent of offspring men were disabled vs 52% of original cohort men (P =.001); among women, these proportions were 54% vs 72% (P =.001). Fewer offspring perceived their health as fair or poor and fewer had chronic diseases. Offspring were more physically active and less likely to smoke or consume high amounts of alcohol, but their average weight was greater. The secular decline in disability was strongly evident among individuals with chronic diseases. Conclusions. Our findings depict a secular change toward a less disabled and globally healthier population in the period of life when retirement occurs. C1 Boston Univ, Multipurpose Arthrit & Musculoskeletal Dis Ctr, Boston, MA 02118 USA. Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Allaire, SH (reprint author), Boston Univ, Multipurpose Arthrit & Musculoskeletal Dis Ctr, 715 Albany St,A203, Boston, MA 02118 USA. OI O'Connor, George/0000-0002-6476-3926 FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [AR20613] NR 40 TC 53 Z9 53 U1 2 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 1999 VL 89 IS 11 BP 1678 EP 1683 DI 10.2105/AJPH.89.11.1678 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 250ML UT WOS:000083392100012 PM 10553388 ER PT J AU Liu, HJ Cho, BY Strong, R Krull, IS Cohen, S Chan, KC Issaq, HJ AF Liu, HJ Cho, BY Strong, R Krull, IS Cohen, S Chan, KC Issaq, HJ TI Derivatization of peptides and small proteins for improved identification and detection in capillary zone electrophoresis (CZE) SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT Measurement for the Next Millennium - International Symposium Celebrating the 3rd Millennium CY APR 14-16, 1999 CL EGMOND AAN ZEE, NETHERLANDS DE peptide and protein tagging; HPCE; MALDI-TOFMS; CZE-LIF; derivatizations ID PERFORMANCE LIQUID-CHROMATOGRAPHY; INDUCED FLUORESCENCE DETECTION; HORMONE RELEASING-FACTOR; AMINO-ACIDS; 6-AMINOQUINOLYL-N-HYDROXYSUCCINIMIDYL CARBAMATE; MASS-SPECTROMETRY; GROWTH-HORMONE; COMBINATORIAL LIBRARIES; REAGENT; 6-AMINOQUINOLINE AB Peptides and small proteins, of limited molecular weight (MW) can be derivatized with a 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (6-AQC) reagent, leading to a single capillary zone electrophoresis (CZE) peak, suggestive of a completely tagged product. The number of tags per molecule was demonstrated by matrix assisted, laser desorption, time-of-flight mass spectrometry (MALDI-TOFMS) studies. In CZE, these species have greatly improved plate count and peak shape, improved (lowered) detectabilities, and in general, improved identification properties in the CZE mode in high performance capillary electrophoresis (HPCE). The formation of what appears to be a single, homogeneously tagged product is a function of how the derivatizations are performed. Once these conditions are optimized, virtually all peptides and small proteins tested (limited MW) can form single, fully tagged products, with the desirable CZE properties. These derivatization approaches thus lead to products that perform and are detected much better in CZE than their precursors (native, untagged peptides). The determined plate counts for these tagged peptides were as high as 6 million plates/m, which was very reproducible, and 59-12,000 times higher than the untagged (native) molecules. The peak symmetry was also improved greatly. The limit of detection (LOD) of some tested 6-AQC tagged peptides were nine to 209 times improved (lower) with ultraviolet (UV) absorption detection, again as compared with that for the native species. The LOD could be further lowered via laser induced fluorescence (LIF) detection in CZE, especially when acetonitrile (ACN) containing buffers were used. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Northeastern Univ, Dept Chem, Boston, MA 02115 USA. Waters Corp, Biotechnol Appl Lab, Milford, MA 01757 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Krull, IS (reprint author), Northeastern Univ, Dept Chem, 102 Hurtig Bldg,360 Huntington Ave, Boston, MA 02115 USA. NR 71 TC 25 Z9 26 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD NOV PY 1999 VL 400 SI SI BP 181 EP 209 DI 10.1016/S0003-2670(99)00615-7 PG 29 WC Chemistry, Analytical SC Chemistry GA 264VT UT WOS:000084204200017 ER PT J AU Kasper, JD Shapiro, S Guralnik, JM Bandeeen-Roche, KJ Fried, LP AF Kasper, JD Shapiro, S Guralnik, JM Bandeeen-Roche, KJ Fried, LP TI Designing a community study of moderately to severely disabled older women: The Women's Health and Aging Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE elderly; methods; disability; functional status; women ID FUNCTIONAL STATUS; INSTRUMENTAL ACTIVITIES; DISABILITY; ADULTS; DISEASE AB PURPOSE: This paper reports on the design of a community-based study focusing on the effects of prevalent and incident disease and other modifying influences, on changes in functioning among moderately and severely disabled elderly women over a 3-year period [the Women's Health and Aging Study (WHAS)]. METHODS: An approach to conceptualizing and assessing disability which captured functional difficulty across a broad range of activities and tasks was developed, tested on existing national data, and used, in the form of a brief screening instrument, to identify moderately to severely disabled elderly women in a large community sample representative of women 65 and older. Women meeting study criteria were recruited for a baseline interview, a 3-hour in-home clinical exam, as well as follow-up interviews and physical performance tests at 6-month intervals for three years. RESULTS: Prevalence of moderate to severe disability among the screened population proved similar to rat expected from analysis of national data (about one-third). The screening interview response rate was 78%, and 71% of women eligible by disability criteria participated. Only women completing both the baseline interview and clinical exam were counted as respondents. Analysis of characteristics of participants and nonparticipants indicated no selection bias related to levels of disability. However, education, race, and age were associated with participation. Women with some college education, black women, and younger women were more likely To participate. CONCLUSIONS: The approach used to identify and recruit moderately to severely disabled elderly women in the WHAS is both feasible and applicable to other community-based research where inclusion of elderly people with moderate to severe disability across several areas of functioning is an objective. Other aspects of study design, such as use of proxy respondents, mill also affect recruitment of individuals with impaired functioning into epidemiologic studies. Ann Epidemiol 1999;9:498-507, (C) 1999 Elsevier Science Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. RP Kasper, JD (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Hlth Policy & Management, 624 N Broadway, Baltimore, MD 21205 USA. FU NIA NIH HHS [N01-AG-1-2112] NR 36 TC 69 Z9 69 U1 6 U2 7 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 NOV PY 1999 VL 9 IS 8 BP 498 EP 507 DI 10.1016/S1047-2797(99)00026-5 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 250HD UT WOS:000083382200006 PM 10549883 ER PT J AU Papa, SM Desimone, R Fiorani, M Oldfield, EH AF Papa, SM Desimone, R Fiorani, M Oldfield, EH TI Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias SO ANNALS OF NEUROLOGY LA English DT Article ID PRIMATE SUBTHALAMIC NUCLEUS; ADVANCED PARKINSONS-DISEASE; BASAL GANGLIA; NEURONAL-ACTIVITY; MOTOR FUNCTION; GPI PALLIDOTOMY; L-DOPA; MOVEMENT; MONKEYS; LESIONS AB The functional status of the globus pallidus internal segment (GPi) plays a key role in mediating the effects of antiparkinsonian drugs. During long-term levodopa therapy, patients develop abnormal movements, dyskinesias, the pathophysiological basis of which is poorly understood. We recorded single cells in the GPi of parkinsonian monkeys continuously through the "off" and "on" states, and 10 to 15 minutes later during "on with or without dyskinesias," depending on two doses of levodopa. The transition from the "off" to the "on" state was characterized by a decrease (most cells), no change, or an increase in firing rate of individual cells. During dyskinesias, firing rates declined profoundly in almost all cells, with decrements as low as 97% in individual cells. These changes occurred only when dyskinesias mere present. The difference in GPi activity between "on" and "on with dyskinesias" suggests that normal motor function in Parkinson's disease critically depends on fine tuning of the basal ganglia output. Dyskinesias result from an imbalanced low GPi discharge, a circumstance that may be susceptible to development of new therapeutic approaches. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Papa, SM (reprint author), Emory Univ, Dept Neurol, 6000 WMRB, Atlanta, GA 30322 USA. NR 30 TC 108 Z9 110 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1999 VL 46 IS 5 BP 732 EP 738 DI 10.1002/1531-8249(199911)46:5<732::AID-ANA8>3.0.CO;2-Q PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 252JH UT WOS:000083498000008 PM 10553990 ER PT J AU Theodore, WH Gaillard, WD AF Theodore, WH Gaillard, WD TI Association between hippocampal volume and epilepsy duration SO ANNALS OF NEUROLOGY LA English DT Letter ID SEIZURES C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 6 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1999 VL 46 IS 5 BP 800 EP 800 DI 10.1002/1531-8249(199911)46:5<800::AID-ANA21>3.0.CO;2-I PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 252JH UT WOS:000083498000021 PM 10554003 ER PT J AU Sausville, EA Feigal, E AF Sausville, EA Feigal, E TI Evolving approaches to cancer drug discovery and development at the National Cancer Institute, USA SO ANNALS OF ONCOLOGY LA English DT Article DE drug discovery; early clinical trials ID TUMOR RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, Div Canc Treatment & Diag, NIH, Execut Plaza N,Suite 843,6130 Execut Blvd, Rockville, MD 20852 USA. NR 6 TC 28 Z9 29 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 1999 VL 10 IS 11 BP 1287 EP 1291 DI 10.1023/A:1008333901925 PG 5 WC Oncology SC Oncology GA 278FZ UT WOS:000084979300008 PM 10631454 ER PT J AU Kass, ES Salman, S AF Kass, ES Salman, S TI Imaging case study of the month - Developmental changes in the antrum of child with chronic maxillary atelectasis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID SINUS HYPOPLASIA C1 NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kass, ES (reprint author), NIH, Bldg 10,Room 8B07,10 Ctr Dr MSC 1750, Bethesda, MD 20892 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 1999 VL 108 IS 11 BP 1091 EP 1094 PN 1 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 256LB UT WOS:000083725800012 PM 10579238 ER PT J AU Wang, XW AF Wang, XW TI Role of p53 and apoptosis in carcinogenesis SO ANTICANCER RESEARCH LA English DT Review DE apoptosis; programmed cell death; carcinogenesis; tumor suppressor gene; p53 ID WILD-TYPE P53; PROGRAMMED CELL-DEATH; NF-KAPPA-B; DNA-BINDING FUNCTION; TUMOR-SUPPRESSOR PROTEIN; DRUG-INDUCED APOPTOSIS; VIRUS HBX PROTEIN; X-GENE PRODUCT; TRANSCRIPTIONAL ACTIVATION; P53-MEDIATED APOPTOSIS AB Carcinogenesis is a process that converts normal cells from controllable to uncontrollable growth. Coordinate regulation of the rates of cell proliferation and cell death is an important determinant in maintenance of homeostasis. Loss of control of this balance is central to the development of cancer: This loss may be due to genetic alteration in either growth promoting genes resulting in constitutive activation or negative growth regulating genes such as tumor suppressor genes. Recent advances in studying the molecular mechanisms related to the etiology of cancel have provided further understanding of these pathways. Earlier studies have been primarily concerned with cell proliferation resulting from activation of oncogenes. However, many recent studies have focused on the induction of cell death. The recognition of the importance of apoptosis, a distinct mode of cell death, in maintenance of genomic stability was further prompted by studying the mechanism of the tumor suppressor gene product p53, as well as many other oncogenes and tumor suppressor genes. For example, many oncogenes appeal to act as potent inducers of apoptosis through activation of p53 dependent apoptosis pathways. Therefore, one possible mechanism for tumor suppression involves activation of apoptosis pathways in cells at risk of neoplastic transformation. These studies have provided extensive knowledge of the signal transduction pathways in response to genotoxic stress and promoted mechanistic research related to the apoptosis pathways. These studies also provide a perfect explanation that p53 is a key element in maintaining genomic stability and loss of the p53 function is a common event during carcinogenesis. This chapter will mainly focus on the role of apoptosis in carcinogenesis. In particular, I will summarize recent studies related to the mechanisms of p53 and its role in this process. C1 NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Div Basic Sci, NIH, Bldg 37,Rm 2C05,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 199 TC 47 Z9 49 U1 0 U2 3 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 NOV-DEC PY 1999 VL 19 IS 6A BP 4759 EP 4771 PG 13 WC Oncology SC Oncology GA 284EE UT WOS:000085317100011 PM 10697590 ER PT J AU Mirochnick, M Cooper, E McIntosh, K Xu, J Lindsey, J Jacobus, D Mofenson, L Sullivan, JL Dankner, W Frenkel, LM Nachman, S Wara, DW Johnson, D Bonagura, VR Rathore, MH Cunningham, CK McNamara, J AF Mirochnick, M Cooper, E McIntosh, K Xu, J Lindsey, J Jacobus, D Mofenson, L Sullivan, JL Dankner, W Frenkel, LM Nachman, S Wara, DW Johnson, D Bonagura, VR Rathore, MH Cunningham, CK McNamara, J TI Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PREVENTION AB Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0.3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age. C1 Boston Med Ctr, Boston, MA 02118 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Jacobus Pharmaceut Co Inc, Princeton, NJ USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. SUNY Stony Brook, Hlth Sci Ctr, Stony Brook, NY 11794 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Chicago, Childrens Hosp, Chicago, IL 60637 USA. Long Isl Jewish Med Ctr, Schneider Childrens Hosp, New Hyde Park, NY 11042 USA. SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. RP Mirochnick, M (reprint author), Boston Med Ctr, Matern 6,1 Boston Med Ctr Pl, Boston, MA 02118 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 19 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 1999 VL 43 IS 11 BP 2586 EP 2591 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 251KR UT WOS:000083445300002 PM 10543733 ER PT J AU Fujiwara, M Kodama, EN Okamoto, M Tokuhisa, K Ide, T Hanasaki, Y Katsuura, K Takayama, H Aimi, N Mitsuya, H Shigeta, S Konno, K Yokota, T Baba, M AF Fujiwara, M Kodama, EN Okamoto, M Tokuhisa, K Ide, T Hanasaki, Y Katsuura, K Takayama, H Aimi, N Mitsuya, H Shigeta, S Konno, K Yokota, T Baba, M TI Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217 SO ANTIVIRAL CHEMISTRY & CHEMOTHERAPY LA English DT Article DE thiadiazole; NNRTI; resistance ID HIGHLY POTENT; NONNUCLEOSIDE INHIBITORS; SELECTIVE-INHIBITION; COMBINATION THERAPY; HIV-1 REPLICATION; IN-VITRO; DERIVATIVES; MUTATIONS; SERIES; NEVIRAPINE AB The non-nucleoside reverse transcriptase (RT) inhibitor RD4-2217 is a thiadiazole derivative that has proved to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in vitro. In this study we examined genotypic and phenotypic characteristics of RD4-2217-resistant mutants that have been obtained by serial passage of HIV-1 in MT-4 cells in the presence of increasing concentrations (0.05, 0.25, 1 and 10 mu M) of the compound. The strains obtained, IIIB/2217RE/0.05 and IIIB/2217RE/0.25, were two- and 15-fold resistant to RD4-2217, respectively, whereas IIIB/2217RE/1 and IIIB/2217RE/10 displayed 161- and >238-fold resistance, respectively. Both IIIB/2217RE/1 and IIIB/2217RE/10 had two amino acid substitutions, V1891 and T2401, in the Furthermore, RD4-2217 did not inhibit the replication of an HIV-1 molecular clone, which had the same mutation, at concentrations up to 10 mu M, indicating that the V1891 plus T2401 mutation confers high-level resistance to RD4-2217. Interestingly, the replicability of IIIB/2217RE/1 and IIIB/2217RE/10 appeared to be lower than that of wild-type IIIB in MT-4 cells, suggesting that the plus T2401 mutation may impair the enzymatic activity of HIV-1 RT. C1 Rat Drug Design Labs, Tokyo 1748612, Japan. Fukushima Med Univ, Sch Med, Dept Microbiol, Fukushima 9601295, Japan. Tokyo Res Labs, Kanagawa 2521123, Japan. Chiba Univ, Fac Pharmaceut Sci, Chiba 2630022, Japan. NCI, Med Branch, Expt Retrovirol Sect, Bethesda, MD 20892 USA. Kagoshima Univ, Fac Med, Ctr Chron Viral Dis, Kagoshima 8908520, Japan. RP Fujiwara, M (reprint author), Glaxo Wellcome, Tsukuba Res Labs, 43 Wadai, Tsukuba, Ibaraki 3004247, Japan. RI Kodama, Eiichi /C-4032-2009; Baba, Masanori/G-3867-2011; Takayama, Hiromitsu/H-6829-2015 OI Kodama, Eiichi /0000-0002-6622-2752; NR 27 TC 9 Z9 10 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 0956-3202 J9 ANTIVIR CHEM CHEMOTH JI Antivir. Chem. Chemother. PD NOV PY 1999 VL 10 IS 6 BP 315 EP 320 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology GA 260YZ UT WOS:000083982200002 PM 10628806 ER PT J AU Sugumaran, M Duggaraju, P Jayachandran, E Kirk, KL AF Sugumaran, M Duggaraju, P Jayachandran, E Kirk, KL TI Formation of a new quinone methide intermediate during the oxidative transformation of 3,4-dihydroxyphenylacetic acids: Implication for eumelanin biosynthesis SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE mechanism of melanogenesis; quinone isomerization; quinone methide formation; homoprotocatechuate oxidation ID 3,4-DIHYDROXYMANDELIC ACID; TYROSINASE; DECARBOXYLATION AB Oxidation of dopa and dopamine requires a net removal six electrons to produce indolequinones, the monomeric precursors of eumelanin pigment. On the other hand, their 6-fluoroderivatives suffer only four-electron oxidation to yield the same products (M. E, Rice, B, Mogaddam, C, R, Creveling, and R. L. Kirk, Anal. Chem, 59, 1534-1536, 1987). Taking advantage of this novel fluorochemistry, we reexamined the oxidative mechanism of 3,4-dihydroxyphenylacetic acid and 6-fluoro-3,4-dihydroxyphenylacetic acid to throw more light on the nature of reactive intermediates formed during the reaction, Enzymatic or chemical oxidation of 3,4-dihydroxyphenylacetic acid generated the transient o-quinone which exhibited rapid intramolecular cyclization and side chain modification to produce 2,5,6-trihydrobenzofuran and 3,4-dihydroxymandelic acid, respectively. However, when 6-fluoro-3,4-dihydroxyphenylacetic acid was oxidized either by tyrosinase or by sodium periodate, the resultant quinone uniquely exhibited only cyclization coupled with loss of fluoride ion. This clean reaction allowed us to establish the structures of the transient reactive intermediates, Two interconvertable isomeric forms of the product were isolated and characterized from the reaction mixture. If the oxidation was carried out in water, a yellow quinolactone accumulated in the reaction mixture. This compound was instantaneously converted to a purple quinone methide upon addition of a trace amount of sodium phosphate. Passage through a C,, HPLC column caused the reverse transformation, The structures of these products were established by semiempirical molecular orbital calculations and NMR spectrometry, comparison of the oxidation mechanisms of melanin precursors, dopa and dopamine, with that of 3,4-dihydroxyphenylacetic acids reveals that a similar quinone methide intermediate is likely to be formed during eumelanin biosynthesis. (C) 1999 Academic Press. C1 Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Sugumaran, M (reprint author), Univ Massachusetts, Dept Biol, Boston, MA 02125 USA. FU NIAID NIH HHS [R01-AI-14753] NR 14 TC 17 Z9 18 U1 0 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1999 VL 371 IS 1 BP 98 EP 106 DI 10.1006/abbi.1999.1420 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 255DM UT WOS:000083654300013 PM 10525294 ER PT J AU Ruvinov, SB Thompson, J Sackett, DL Ginsburg, A AF Ruvinov, SB Thompson, J Sackett, DL Ginsburg, A TI Tetrameric N-5-(L-1-carboxyethyl)-L-ornithine synthase: Guanidine center dot HCl-induced unfolding and a low temperature requirement for refolding SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE N-5-(L-1-carboxyethyl)ornithine synthase; guanidine center dot HCl denaturation : inactivation; tetramer dissociation; protein unfolding/refolding; GroEL; chaperonin-60 ID DODECAMERIC GLUTAMINE-SYNTHETASE; ESCHERICHIA-COLI; TAILSPIKE PROTEIN; CRYSTAL-STRUCTURE; AGGREGATION; DEHYDROGENASE; DISSOCIATION; CHAPERONINS; CHLORIDE; IRREVERSIBILITY AB Guanidine . HCl (GdnHCl)-induced unfolding of tetrameric N-5-(L-1-carboxyethyl)-L-ornithine synthase (CEOS; 141,300 M-r) from Lactococcus lactis at pH 7.2 and 25 degrees C occurred in several phases, The enzyme was inactivated at similar to 1 M GdnHCl, A time-, temperature-, and concentration-dependent formation of soluble protein aggregates occurred at 0.5-1.5 M GdnHCl due to an increased exposure of apolar surfaces. A transition from tetramer to unfolded monomer was observed between 2 and 3.5 M GdnHCl (without observable dimer or trimer intermediates), as evidenced by tyrosyl and tryptophanyl fluorescence changes, sulfhydryl group exposure, loss of secondary structure, size-exclusion chromatography, and sedimentation equilibrium data. GdnHCl-induced dissociation and unfolding of tetrameric CEOS was concerted, and yields of reactivated CEOS by dilution from 5 M GdnHCl were improved when unfolding took place on ice rather than at 25 degrees C, Refolding and reconstitution of the enzyme were optimal at less than or equal to 15 degrees C and yields of active tetramer increased as the concentration of unfolded subunits decreased. Refolding of unfolded subunits and active tetramer assembly upon 100-fold dilution from 5 M GdnHCl at 0 degrees C also was increased two- or fourfold (to 44 or 28% reactivation for 0.08 or 0.28 mu M subunit, respectively) when incubated at 15 degrees C, pH 7.2, for 4 h with the Escherichia coli molecular chaperonin GroEL, ATP, MgCl2, and KCl. (C) 1999 Academic Press. C1 NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIDR, Microbial & Biochem Genet Unit, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res & Dev, DTP, NIH, Bethesda, MD 20892 USA. RP Ginsburg, A (reprint author), NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bldg 3,Room 208, Bethesda, MD 20892 USA. EM ginsbura@fido.nhlbi.nih.gov NR 38 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1999 VL 371 IS 1 BP 115 EP 123 DI 10.1006/abbi.1999.1429 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 255DM UT WOS:000083654300015 PM 10525296 ER PT J AU Chu, KC Tarone, RE Brawley, OW AF Chu, KC Tarone, RE Brawley, OW TI Breast cancer trends of black women compared with white women SO ARCHIVES OF FAMILY MEDICINE LA English DT Article ID BIRTH COHORT PATTERNS; RACIAL-DIFFERENCES; UNITED-STATES; PROGESTERONE RECEPTORS; AFRICAN-AMERICAN; MORTALITY-RATES; MAMMOGRAPHY USE; SURVIVAL; RACE; CARCINOMA AB Objective: To investigate why breast cancer mortality rates have decreased in the 1990s for white women but not for black women. Design: Racial differences in breast cancer incidence, survival, and mortality rates were examined using regression methods and age-period-cohort models. Setting: United States breast cancer mortality rates from 1970 through 1995, breast cancer incidence rates from 1980 through 1995, and 3-year survival rates from 1980 through 1993. The incidence and survival data are from the Surveillance, Epidemiology, and End Results Program, representing 11% of the US population, of the National Cancer Institute, Bethesda, Md. Results: For both white and black women aged 30 to 39 years, breast cancer mortality rates began decreasing in 1987. For white women aged 40 to 79 years, breast cancer mortality rates declined after 1989, and for black women aged 40 to 69 years, mortality rates ceased increasing in the middle to late 1980s. Birth cohort trends were similar by race, but calendar period trends and survival rates differed. Conclusions: Declines in mortality rates in women younger than 40 years reflect a favorable birth cohort trend for women born after 1948 and likely reflect changes in risk factors. The increased early detection of breast cancer by mammography and improvements in breast cancer treatment appear to be contributing to the improving mortality trends in older women, although black women appear to have benefited less than white women from early detection and treatment advances. In addition, substantial increases in survival rates for white women with regional disease have contributed to their declining mortality rates and likely reflect an increasing use of beneficial adjuvant therapy. C1 NCI, Off Special Populat Res, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Etiol & Genet, Bethesda, MD 20892 USA. RP Chu, KC (reprint author), NCI, Off Special Populat Res, Bldg Execut Plaza S,Room 320,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 53 TC 66 Z9 66 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD NOV-DEC PY 1999 VL 8 IS 6 BP 521 EP 528 DI 10.1001/archfami.8.6.521 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 257GZ UT WOS:000083775300013 PM 10575392 ER PT J AU Grewal, RP Karkera, JD Grewal, RK Detera-Wadleigh, SD AF Grewal, RP Karkera, JD Grewal, RK Detera-Wadleigh, SD TI Mutation analysis of oculopharyngeal muscular dystrophy in Hispanic American families SO ARCHIVES OF NEUROLOGY LA English DT Article ID CHROMOSOME 14Q11.2-Q13 AB Background: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant muscular dystrophy characterized by progressive ptosis, swallowing difficulties, and proximal limb weakness. Recently, the genetic basis of this disease has been characterized by mutations in the PABP2 gene that involve short expansions of the trinucleotide repeat GCG. Objectives: To independently confirm the presence and study the meiotic stability of the GCG expansion mutations in a distinct ethnic population with OPMD. Settings: Hospital and university research laboratories in los Angeles, Calif. Subjects and Methods: Three unrelated families of Hispanic American descent were identified in whom OPMD was transmitted in an autosomal dominant pattern. All of these families can trace affected ancestors to the southwestern United States or to the bordering states of Mexico. In these families, 14 persons with OPMD were identified and studied. Results: Our results confirm that in these families, expansion mutations characterized by a gain of 3 GCG repeats in the wild-type allele result in an abnormal nucleotide length of 9 GCG repeats in the PABP2 gene. In these families, these mutations are associated with the OPMD phenotype. The identical repeat mutation ([GCG](9)) is found in all affected members of these unrelated families and shows relative meiotic stability. Conclusions: These results support and extend our study of haplotype analysis and suggest that a founder effect may have occurred for OPMD in this Hispanic American population. C1 Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA USA. Kaiser Permanente Med Ctr, Dept Ophthalmol, W Los Angeles, CA USA. NIMH, Unit Gene Mapping & Express, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Grewal, RP (reprint author), JFK Med Ctr, New Jersey Neurosci Inst, 65 James St, Edison, NJ 08818 USA. FU NIA NIH HHS [K12AG00521] NR 12 TC 12 Z9 13 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 NOV PY 1999 VL 56 IS 11 BP 1378 EP 1381 DI 10.1001/archneur.56.11.1378 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 253KG UT WOS:000083555300011 PM 10555658 ER PT J AU Metman, LV Del Dotto, P LePoole, K Konitsiotis, S Fang, J Chase, TN AF Metman, LV Del Dotto, P LePoole, K Konitsiotis, S Fang, J Chase, TN TI Amantadine for levodopa-induced dyskinesias - A 1-year follow-up study SO ARCHIVES OF NEUROLOGY LA English DT Article ID PARKINSONS-DISEASE; MOTOR FLUCTUATIONS; BLOCKADE AB Background: In a recent acute study, amantadine was found to have antidyskinetic effect against levodopa-induced motor complications in patients with Parkinson disease. The longevity of this effect was not addressed but is of interest in light of the controversy in the literature regarding the duration of amantadine's well-established antiparkinsonian action. Objective: To determine the duration of the antidyskinetic effect of amantadine in advanced Parkinson disease. Design: One year after completion of an acute, double-blind, placebo-controlled, crossover study, patients returned for re-evaluation of motor symptoms and dyskinesias using a nonrandomized, double-blind, placebo-controlled follow-up paradigm. Setting: National Institutes of Health Clinical Center. Patients: Seventeen of the original 18 patients with advanced Parkinson disease complicated by dyskinesias and motor fluctuations participated in this study; 1 was lost to follow-up. Thirteen of the 17 individuals had remained on amantadine therapy for the entire year. Interventions: Ten days prior to the follow-up assessment, amantadine was replaced with identical capsules containing either amantadine or placebo. Main Outcome Measures: Parkinsonian symptoms and dyskinesia severity were scored using standard rating scales, while subjects received steady-state intravenous levodopa infusions at the same rate as I year earlier. Results: One year after initiation of amantadine cotherapy, its antidyskinetic effect was similar in magnitude (56% reduction in dyskinesia compared with 60% 1 year earlier). Motor complications occurring with the patients' regular oral levodopa regimen also remained improved according to the Unified Parkinson's Disease Rating Scale (UPDRS-IV). Conclusion: The beneficial effects of amantadine on motor response complications are maintained for at least 1 year after treatment initiation. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Chase, TN (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C104,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 13 TC 131 Z9 132 U1 1 U2 2 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 NOV PY 1999 VL 56 IS 11 BP 1383 EP 1386 DI 10.1001/archneur.56.11.1383 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 253KG UT WOS:000083555300012 PM 10555659 ER PT J AU Sobel, ME AF Sobel, ME TI Ethical issues in molecular pathology - Paradigms in flux SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT XXXIV Conference of the College-of-American-Pathologists on Molecular Pathology: Role in Improving Patient Outcome CY FEB 26-28, 1999 CL BETHESDA, MARYLAND SP Coll Amer Pathologists ID INFORMED CONSENT; SAMPLES AB Recent advances in molecular pathology and molecular genetics have created new concerns about the use of human biologic materials in research. Since researchers now have the ability to extract and amplify DNA from minuscule archived samples, virtually any human tissue sample can potentially become the template for a test that provides information that may relate to the inherited genes of an individual. Researchers using human biologic materials should follow the 3 basic principles that have been defined for all ethical human subjects research: respect for persons, beneficence, and justice. Institutional Review Boards are responsible for providing review of the risks and benefits of research proposals to safeguard the rights and welfare of human subjects. Currently, there is considerable debate concerning the role of informed consent procedures and the Institutional Review Board oversight process in situations when researchers use human biologic materials that have been anonymized or coded. In 1999, the National Bioethics Advisory Commission is expected to make recommendations to President Clinton and the National Science and Technology Council that are expected to clarify the balance between respect for personal autonomy and the societal need to pursue biomedical research to improve the health and welfare of all individuals. C1 NCI, Mol Pathol Sect, Pathol Lab, Bethesda, MD 20892 USA. RP Sobel, ME (reprint author), NCI, Mol Pathol Sect, Pathol Lab, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 10 TC 7 Z9 8 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 1999 VL 123 IS 11 BP 1076 EP 1078 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 253YD UT WOS:000083584000021 PM 10539912 ER PT J AU Tornwall, ME Virtamo, J Haukka, JK Aro, A Albanes, D Huttunen, JK AF Tornwall, ME Virtamo, J Haukka, JK Aro, A Albanes, D Huttunen, JK TI The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial SO ATHEROSCLEROSIS LA English DT Article DE intermittent claudication; alpha-tocopherol; beta-carotene; supplementation; smoking ID PERIPHERAL ARTERIAL-DISEASE; POPULATION; CHOLESTEROL; PREVALENCE; LDL AB We evaluated the effect of long-term supplementation with vitamin E (alpha-tocopherol) and beta-carotene on occurrence of claudication symptoms and risk for peripheral vascular surgery among men with intermittent claudication. Subjects, 50-69-year old male smokers, were participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who reported intermittent claudication through a structured questionnaire (Rose) at study entry (n = 1484). They were randomly assigned to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo, in a 2 x 2 design. During follow-up, claudication was evaluated by repeating use of the questionnaire once a year. Information on peripheral vascular surgery came from the National Hospital Discharge Register. We observed no effect of alpha-tocopherol and beta-carotene supplementation on claudication during a mean follow-up of 3.7 years. A slightly increased risk (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.05-2.44) for vascular surgery was observed among beta-carotene supplemented men compared to those who did not receive beta-carotene. Alpha-tocopherol supplementation had no effect. In conclusion, long-term supplementation with alpha-tocopherol and beta-carotene showed no beneficial effect on symptoms and progression of intermittent claudication. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Publ Hlth Inst, Dept Nutr, ATBC Study, SF-00300 Helsinki, Finland. NCI, Bethesda, MD 20892 USA. RP Tornwall, ME (reprint author), Natl Publ Hlth Inst, Dept Nutr, ATBC Study, Mannerheimintie 166, SF-00300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 25 TC 20 Z9 20 U1 0 U2 0 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 NOV PY 1999 VL 147 IS 1 BP 193 EP 197 DI 10.1016/S0021-9150(99)00176-8 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 252UD UT WOS:000083519900024 PM 10525141 ER PT J AU Ferrara, CM Cushman, SW AF Ferrara, CM Cushman, SW TI GLUT4 trafficking in insulin-stimulated rat adipose cells: evidence that heterotrimeric GTP-binding proteins regulate the fusion of docked GLUT4-containing vesicles SO BIOCHEMICAL JOURNAL LA English DT Article DE adenosine; exocytosis; G-proteins; isopreterenol; membrane fusion ID GLUCOSE-TRANSPORT ACTIVITY; PLASMA-MEMBRANE; SUBCELLULAR TRAFFICKING; SKELETAL-MUSCLE; TRANSLOCATION; ADENOSINE; PHOSPHORYLATION; ISOPROTERENOL; PHOTOLABEL; MODULATION AB Agents that activate the G-protein G(i) (e.g. adenosine) increase, and agents that activate G(s) [e.g. isoprenaline (isoproterenol)] decrease, steady-state insulin-stimulated glucose transport activity and cell-surface GLUT4 in isolated rat adipose cells without changing plasma membrane GLUT4 content. Here pile leave further examined the effects of R(s)G(s) and R(i)G(i) ligands (in which R-s and R-i are G(s)- and G(i)-coupled receptors respectively) on insulin-stimulated cell-surface GLUT4 and the kinetics of GLUT4 trafficking in these same cells. Rat adipose cells were preincubated for 2 min with or without isoprenaline (200 nM) and adenosine deaminase (1 unit/ml), to stimulate G(s) and decrease the stimulation of G(i) respectively, followed by 0-20 min with insulin (670 nM). Treatment with isoprenaline and adenosine deaminase decreased insulin-stimulated glucose transport activity by 58%. Treatment with isoprenaline and adenosine deaminase also resulted in similar decreases in insulin-stimulated cell-surface GLUT4 as assessed by both bis-mannose photolabelling of the substrate-binding site and biotinylation of the extracellular carbohydrate moiety when evaluated under similar experimental conditions. After stimulation with insulin in the absence of G(s) and the presence of G(i) agents, a distinct sequence of plasma membrane events took place, starting with an increase in immunodetectable GLUT4, then an increase in the accessibility of GLUT4 to bis-mannose photolabel, and finally an increase in glucose transport activity. Pretreatment with isoprenaline and adenosine deaminase before stimulation with insulin did not affect the time course of the increase in immunodetectable GLUT4 in the plasma membrane, but did delay both the increase in accessibility of GLUT4 to photolabel and the increase in glucose transport activity. These results suggest that R(s)G(s) and R(i)G(i) modulate insulin-stimulated glucose transport by influencing the extent to which GLUT4 is associated with occluded vesicles attached to the plasma membrane during exocytosis, perhaps by regulating the fusion process through which the GLUT4 in docked vesicles becomes exposed on the cell surface. C1 NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Ferrara, CM (reprint author), Univ Maryland, Vet Adm Med Ctr, 10 N Greene St,GRECC, Baltimore, MD 21201 USA. NR 21 TC 25 Z9 27 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 1999 VL 343 BP 571 EP 577 DI 10.1042/0264-6021:3430571 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 255JC UT WOS:000083664900009 PM 10527935 ER PT J AU Wojda, U Goldsmith, P Miller, JL AF Wojda, U Goldsmith, P Miller, JL TI Surface membrane biotinylation efficiently mediates the endocytosis of avidin bioconjugates into nucleated cells SO BIOCONJUGATE CHEMISTRY LA English DT Article ID TARGETED GENE DELIVERY; GPI-ANCHORED PROTEINS; IN-VITRO; LIVING CELLS; RECEPTOR; ERYTHROCYTES; POLYETHYLENIMINE; VIVO; TRANSFERRIN; HEPATOCYTES AB Here we demonstrate that biotin covalently attached to cell surface obligates existing receptors to endocytose avidin bioconjugates into nucleated cells. Incubation of fluorescein-labeled avidin with biotinylated cell lines resulted in uniform and rapid surface attachment and endocytosis compared with no detectable association of the avidin-conjugated dye with unbiotinylated cells. Uptake was detected within minutes with efficiencies approaching 100% in cell Lines and freshly obtained peripheral blood mononuclear cells. After 24 h, avidin was barely detectable on the surface of the nucleated cells. In marked contrast, fluorescent avidin remained exclusively on the external membrane of erythrocytes after 24 h. To investigate biotin mediated endocytosis for the delivery of DNA, we prepared polyethylenimine-avidin (PEI-avidin) conjugates. Surface biotinylation significantly increased the transfection efficiencies of PEI-avidin condensed plasmid DNA coding green fluorescent protein (GFP) to the level of transferrin-receptor targeted gene delivery (15-20% GFP positive cells in culture after 48 h). The increase in transfection efficiency was blocked by the addition of free avidin or biotin to the culture medium. Biotin covalently bound to cell surface membrane proteins efficiently mediates the entry of avidin bioconjugates into nucleated cells. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, Bldg 10,Room 9N308,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Wojda, Urszula/M-6079-2015 OI Wojda, Urszula/0000-0002-4525-2004 NR 35 TC 22 Z9 24 U1 1 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 NOV-DEC PY 1999 VL 10 IS 6 BP 1044 EP 1050 DI 10.1021/bc990059z PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 260VN UT WOS:000083974300016 PM 10563774 ER PT J AU Brambila, E Munoz-Sanchez, JL Albores, A Waalkes, M AF Brambila, E Munoz-Sanchez, JL Albores, A Waalkes, M TI Early effects of surgery on zinc and metallothionein levels in female rats SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE zinc; metallothionein; metallothionein isoforms; inflammation; experimental surgery ID GENE-EXPRESSION; INTERLEUKIN-6; SERUM; METABOLISM; INDUCTION; LIVER; HEPATOCYTES; THIONEIN; CULTURES; ENZYMES AB Time-response effects of experimental surgery on zinc (Zn) and metallothionein (MT) homeostasis were investigated in female rats up to 24 h. Hepatic Zn content increased at 20 and 24 h postsurgery, whereas serum Zn levels decreased. Hepatic MT increased significantly by 9 h postsurgery and peaked at up to twofold of control at 12 h after surgery. Following the peak at 12 h, hepatic MT content decreased with time but did not reach control levels at the end of this study. When MT isoforms were evaluated, MT-II levels were elevated to the highest extent by 12 h after surgery, whereas MT-I levels started to decrease after 3 h postsurgery but then increased by 20 h. The early increases in MT content are probably mediated by nonmetallic mediators released during the postsurgical inflammatory process, favoring the plasma/tissue mobilization of Zn. This process might be part of the overall mechanisms occurring in the inflammation. C1 Univ Autonoma Puebla, Fac Ciencias Quim, Lab Invest Quim Clin, Puebla 72570, Mexico. IPN, Escuela Nacl Cs Biol, Dept Bioquim, Mexico City 07738, DF, Mexico. IPN, CINVESTAV, Secc Toxicol Ambiental, Mexico City 07738, DF, Mexico. NIEHS, NCI, Res Triangle Pk, NC 27709 USA. RP Brambila, E (reprint author), Univ Autonoma Puebla, Fac Ciencias Quim, Lab Invest Quim Clin, Puebla 72570, Mexico. NR 35 TC 4 Z9 4 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD NOV PY 1999 VL 70 IS 2 BP 173 EP 182 DI 10.1007/BF02783858 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 246RN UT WOS:000083178500007 PM 10535526 ER PT J AU Chappell, LL Rogers, BE Khazaeli, MB Mayo, MS Buchsbaum, DJ Brechbiel, MW AF Chappell, LL Rogers, BE Khazaeli, MB Mayo, MS Buchsbaum, DJ Brechbiel, MW TI Improved synthesis of the bifunctional chelating agent 1,4,7,10-tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N ',N '',N '''-tris(acetic acid)cyclododecane (PA-DOTA) SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE DOTA; lutetium-177; radioimmono-conjugate; biodistribution ID MACROCYCLIC POLYAMINO CARBOXYLATES; MONOCLONAL-ANTIBODY; LANTHANIDE COMPLEXES; IN-VIVO; BIODISTRIBUTION; RADIOIMMUNOTHERAPY; DISSOCIATION; LIGANDS; STABILITY; XENOGRAFT AB A concise synthesis of the bifunctional chelating agent 1,4,7,10-tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)N',N ",N'''-tris(acetic acid)cyclododecane (PA-DOTA) is reported. Difficulties involving the production of partially alkylated products and their removal have been addressed and obviated. After the purl nitro form of PA-DOTA was obtained, conversion to the isothiocyanato form PA-DOTA (1, conjugation to HuCC49 and HuCC49 Delta CH2 monoclonal antibodies was achieved. Subsequent radiolabeling with (LU)-L-177 was performed, demonstrating a useful bifunctional chelating agent suitable for clinical radio-immnunotherapy applications. (C) 1999 Published by Elsevier Science Ltd. All rights reserved. C1 NCI, Radioimmune & Inorgran Chem Sect, DCS, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgran Chem Sect, DCS, NIH, Bethesda, MD 20892 USA. RI Mayo, Matthew/E-3774-2015 FU NCI NIH HHS [5P30CA13148-27] NR 30 TC 34 Z9 34 U1 1 U2 8 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 NOV PY 1999 VL 7 IS 11 BP 2313 EP 2320 DI 10.1016/S0968-0896(99)00171-6 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 263YP UT WOS:000084153100006 PM 10632041 ER PT J AU Andurkar, SV Stables, JP Kohn, H AF Andurkar, SV Stables, JP Kohn, H TI The anticonvulsant activities of N-benzyl 3-methoxypropionamides SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE anticonvulsants; amino acids and derivatives; peptoids; sudstituents effects ID DERIVATIVES AB We recently reported that the ED(50) value for (R,S)-2,3-dimethoxypropionamide (1) in the maximal electroshock (MES)induced seizure test in mice was 30 mg/kg (Choi, D.; Stables, J.P., Kohn, H. Bioorg. Med. Chem. 1996, 4, 2105). This value is comparable to that observed for phenobarbital (ED(50) = 22 mg/kg). Compound 1 is structurally similar to a class of MES-selective anticonvulsant agents, termed functionalized amino acids (2), that were developed in our laboratory. The distinguishing feature of 2 is the differential activities observed for enantiomers. In this study, we asked whether comparable differences in activities were observed in the MES-induced seizure test for (R)- and (S)-1. We developed stereospecific syntheses for these enantiomers and showed that both compounds exhibit nearly equal anticonvulsant activity in mice (ip) (MES ED(50) = 79-111 mg/kg). The surprisingly high ED(50) values for (R)- and (S)-1 required our redetermining the ED(50) value for (R,S)-1. We revised this value to 79 mg/kg. A limited structure-activity relationship study for 1 was conducted. Special attention was given to the C(2) methoxy unit in 1. We found that replacement of this moiety led to only modest differences in the MES activities upon ip administration to mice. Significantly we observed an enhancement in the anticonvulsant activity for (R,S)-N-benzyl 2-hydroxy-3-methoxypropionamide ((R,S)-6) upon oral administration to rats ((R,S)-6: mice tip) ED(50) > 100, < 300 mg/kg; rat (oral) ED(50) = 62 mg/kg), The activities of 3-methoxypropionamides, functionalized amino acids, and related compounds are discussed. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Houston, Dept Chem, Houston, TX 77204 USA. NINDS, Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Kohn, H (reprint author), Univ Houston, Dept Chem, Univ Pk, Houston, TX 77204 USA. EM harold_kohn@unc.edu NR 22 TC 27 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV PY 1999 VL 7 IS 11 BP 2381 EP 2389 DI 10.1016/S0968-0896(99)00186-8 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 263YP UT WOS:000084153100012 PM 10632047 ER PT J AU Foster, JE Nicholson, JM Butcher, R Stables, JP Edafiogho, IO Goodwin, AM Henson, MC Smith, CA Scott, KR AF Foster, JE Nicholson, JM Butcher, R Stables, JP Edafiogho, IO Goodwin, AM Henson, MC Smith, CA Scott, KR TI Synthesis, characterization and anticonvulsant activity of enaminones. Part 6: Synthesis of substituted vinylic benzamides as potential anticonvulsants SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE anticonvulsants; NMR; X-ray crystal structures; molecular modeling/mechanics ID ACIDS AB A comparison of enaminones from various unsubstituted and p-substituted benzamides to the analogous benzylamines has been undertaken with the aim of elucidating the essential structural parameters necessary for anticonvulsant activity. Initial studies on methyl 4-N-(benzylamino)-6-methyl-2-oxocyclohex-3-en-1-oate, 3a, 3-N-(benzylamino)cyclohex-2-en-1-one, 3p, and 5,5-dimethyl-3-N-(benzylamino)-cyclohex-2-en-1-one, 3r indicated that benzylamines possessed significant anti-maximal electroshock seizure (MES) activity. Evaluation of the analogous benzamides revealed significant differences in anticonvulsant activity, these differences were most probably related to the differences in their three-dimensional structures. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Howard Univ, Coll Pharm Nursing & Allied Hlth Sci, Dept Pharmaceut Sci, Washington, DC 20059 USA. Howard Univ, Grad Sch Arts & Sci, Dept Chem, Washington, DC 20059 USA. NINDS, Div Convuls Dev & Neuromuscular Disorders, Epilepsy Branch, Bethesda, MD 20892 USA. RP Scott, KR (reprint author), Howard Univ, Coll Pharm Nursing & Allied Hlth Sci, Dept Pharmaceut Sci, Washington, DC 20059 USA. FU NIGMS NIH HHS [GM08244-06] NR 34 TC 82 Z9 84 U1 0 U2 2 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 NOV PY 1999 VL 7 IS 11 BP 2415 EP 2425 DI 10.1016/S0968-0896(99)00185-6 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 263YP UT WOS:000084153100016 PM 10632051 ER PT J AU Ikeda, H Abushanab, E Marquez, VE AF Ikeda, H Abushanab, E Marquez, VE TI The assembly of beta-methylene-TAD, a metabolically stable analogue of the antitumor agent TAD, by the stepwise esterification of monodeprotected methylenebis(phosphonate) benzyl esters under Mitsunobu conditions SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID MECHANISM; 2-BETA-D-RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE; TIAZOFURIN AB Synthesis of the metabolically stable analogue of thiazole-4-carboxamide adenine dinucleotide (beta-methylene-TAD) was achieved via the sequential monodeprotection of tetrabenzyl methylenebis(phosphonate) after two rounds of Mitsunobu esterifications with the corresponding nucleoside components, tiazofurin and adenosine. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 12 TC 13 Z9 13 U1 1 U2 6 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 NOV 1 PY 1999 VL 9 IS 21 BP 3069 EP 3074 DI 10.1016/S0960-894X(99)00544-2 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 253NH UT WOS:000083562300002 PM 10560727 ER PT J AU Xu, S Gu, J Rhodes, T Belknap, B Rosenbaum, G Offer, G White, H Yu, LC AF Xu, S Gu, J Rhodes, T Belknap, B Rosenbaum, G Offer, G White, H Yu, LC TI The M center dot ADP center dot P-i state is required for helical order in the thick filaments of skeletal muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID RABBIT PSOAS MUSCLE; X-RAY-DIFFRACTION; MYOSIN MOTOR DOMAIN; RELAXED FIBER STIFFNESS; SPIN-LABELED MYOSIN; PARALLEL INHIBITION; STRUCTURAL-CHANGES; FORCE GENERATION; ATP HYDROLYSIS; IONIC-STRENGTH AB The thick filaments of mammalian and avian skeletal muscle fibers are disordered at low temperature, but become increasingly ordered into an helical structure as the temperature is raised. Wray and colleagues (Schlichting, I.,and J. Wray. 1986. J. Muscle Res. Cell Motil. 7:79; Wray, J., R. S. Goody, and K. Holmes. 1986, Adv. Exp. Med. Biol. 226:49-59) interpreted the transition as reflecting a coupling between nucleotide state and global conformation with M . ATP (disordered) being favored at 0 degrees C and M . ADP . P-i (ordered) at 20 degrees C. However, hitherto this has been limited to a qualitative correlation and the biochemical state of the myosin heads required to obtain the helical array has not been unequivocally identified. In the present study we have critically tested whether the helical arrangement of the myosin heads requires the M . ADP . P-i state. X-ray diffraction patterns were recorded from skinned rabbit psoas muscle fiber bundles stretched to non-overlap to avoid complications due to interaction with actin, The effect of temperature on the intensities of the myosin based layer lines and on the phosphate burst of myosin hydrolyzing ATP in solution were examined under closely matched conditions, The results showed that the fraction of myosin mass in the helix closely followed that of the fraction of myosin in the M . ADP . P-i state. Similar results were found by using a series of nucleoside triphosphates, including CTP and GTP, In addition, fibers treated by N-phenylmaleimide (Barnett, V. A., A. Ehrlich, and M, Schoenberg. 1992, Biophys. J 61:358-367) so that the myosin was exclusively in the M ATP state revealed no helical order. Diffraction patterns from muscle fibers in nucleotide-free and in ADP-containing solutions did not show helical structure. All these confirmed that in the presence of nucleotides, the M . NDP . P-i state is required for helical order. We also found that the spacing of the third meridional refection of the thick filament is linked to the helical order. The spacing in the ordered M . NDP . P-i state is 143.4 Angstrom, but in the disordered state, it is 144.2 Angstrom. This may be explained by the different interference functions for the myosin heads and the thick filament backbone. C1 NIAMSD, NIH, Phys Biol Lab, Bethesda, MD 20892 USA. Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23501 USA. Argonne Natl Lab, Chicago, IL USA. Univ Bristol, Dept Vet Clin Sci, Bristol, Avon, England. RP Yu, LC (reprint author), NIAMSD, NIH, Phys Biol Lab, Bldg 6,Room 408, Bethesda, MD 20892 USA. NR 71 TC 39 Z9 39 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 NOV PY 1999 VL 77 IS 5 BP 2665 EP 2676 DI 10.1016/S0006-3495(99)77101-8 PG 12 WC Biophysics SC Biophysics GA 253KC UT WOS:000083554900031 PM 10545367 ER PT J AU Brenner, B Kraft, T Yu, LC Chalovich, JM AF Brenner, B Kraft, T Yu, LC Chalovich, JM TI Thin filament activation probed by fluorescence of N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole-l abeled troponin I incorporated into skinned fibers of rabbit psoas muscle SO BIOPHYSICAL JOURNAL LA English DT Article ID MYOSIN MOTOR DOMAIN; DICTYOSTELIUM-DISCOIDEUM MYOSIN; X-RAY STRUCTURE; SKELETAL-MUSCLE; ACTOMYOSIN ATPASE; FORCE GENERATION; ADENOSINE 5'-TRIPHOSPHATE; PARALLEL INHIBITION; TROPOMYOSIN COMPLEX; COOPERATIVE BINDING AB A method is described for the exchange of native troponin of single rabbit psoas muscle fibers for externally applied troponin complexes without detectable impairment of functional properties of the skinned fibers. This approach is used to exchange native troponin for rabbit skeletal troponin with a fluorescent label (N-((2-(iodoacetoxy)ethyl)-N-methyl) amino-7-nitrobenz-2-oxa-1,3-diazole, IANBD) on Cys(133) of the troponin I subunit. IANBD-labeled troponin I has previously been used in solution studies as an indicator for the state of activation of reconstituted actin filaments (Trybus and Taylor, 1980, Proc. Natl Acad. Sci. USA. 77:7209-7213). In the skinned fibers, the fluorescence of this probe is unaffected when cross-bridges in their weak binding states attach to actin filaments but decreases either upon the addition of Ca2+ or when cross-bridges in their strong binding states attach to actin. Maximum reduction is observed when Ca2+ is raised to saturating concentrations. Additional attachment of cross-bridges in strong binding states gives no further reduction of fluorescence. Attachment of cross-bridges in strong binding states alone (low Ca2+ concentration) gives only about half of the maximum reduction seen with the addition of calcium. This illustrates that fluorescence of IANBD-labeled troponin I can be used to evaluate thin filament activation, as previously introduced for solution studies. In addition, at nonsaturating Ca2+ concen; trations IANBD fluorescence can be used for straightforward classification of states of the myosin head as weak binding (nonactivating) and strong binding (activating), irrespective of ionic strength or other experimental conditions. Furthermore, the approach presented here not only can be used as a means of exchanging native skeletal troponin and its subunits for a variety of fluorescently labeled or mutant troponin subunits, but also allows the exchange of native skeletal troponin for cardiac troponin. C1 Hannover Med Sch, Dept Mol & Cell Physiol, D-30623 Hannover, Germany. NIH, Phys Biol Lab, Bethesda, MD 20892 USA. E Carolina Univ, Sch Med, Dept Biochem, Greenville, NC 27858 USA. RP Brenner, B (reprint author), Hannover Med Sch, Dept Mol & Cell Physiol, D-30623 Hannover, Germany. FU NIAMS NIH HHS [R01 AR044504, R01 AR044504-03, 1R01AR44504] NR 64 TC 32 Z9 32 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 NOV PY 1999 VL 77 IS 5 BP 2677 EP 2691 DI 10.1016/S0006-3495(99)77102-X PG 15 WC Biophysics SC Biophysics GA 253KC UT WOS:000083554900032 PM 10545368 ER PT J AU Lo, M Bloom, ML Imada, K Berg, M Bollenbacher, JM Bloom, ET Kelsall, BL Leonard, WJ AF Lo, M Bloom, ML Imada, K Berg, M Bollenbacher, JM Bloom, ET Kelsall, BL Leonard, WJ TI Restoration of lymphoid populations in a murine model of X-linked severe combined immunodeficiency by a gene-therapy approach SO BLOOD LA English DT Article ID RECEPTOR-GAMMA-CHAIN; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW TRANSPLANTATION; IL-2 RECEPTOR; BETA-CHAIN; IMMUNE RECONSTITUTION; FUNCTIONAL COMPONENT; MICE LACKING; EXPRESSION; JAK3 AB X-linked severe combined immunodeficiency (XSCID) is a life-threatening syndrome in which both cellular and humoral immunity are profoundly compromised. This disease results from mutations in the IL2RG gene, which encodes the common cytokine receptor gamma chain, gamma(c). Previously, we generated gamma(c)-deficient mice as a murine model of XSCID. We have now used lethally irradiated gamma(c)-deficient mice to evaluate a gene therapeutic approach for treatment of this disease. Transfer of the human gamma(c) gene to repopulating hematopoietic stem cells using an ecotropic retrovirus resulted in an increase in T cells, B cells, natural killer (NK) cells, and intestinal intraepithelial lymphocytes, as well as normalization of the CD4:CD8 T-cell ratio and of serum Ig levels. In addition, the restored cells could proliferate in response to interleukin-2 (IL-2). Thus, our results provide added support that gene therapy is a feasible therapeutic strategy for XSCID. Moreover, because we used a vector directing expression of human gamma(c) to correct a defect in gamma(c)-deficient mice, these data also indicate that human gamma(c) can cooperate with the distinctive cytokine receptor chains such as IL-2R beta and IL-7R alpha to mediate responses to murine cytokines in vivo. This is a US government work. There are no restrictions on its use. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N252, Bethesda, MD 20892 USA. NR 40 TC 62 Z9 63 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1999 VL 94 IS 9 BP 3027 EP 3036 PG 10 WC Hematology SC Hematology GA 249UG UT WOS:000083351200012 PM 10556186 ER PT J AU Verbeek, W Lekstrom-Himes, J Park, DJ Dang, PMC Vuong, PT Kawano, S Babior, BM Xanthopoulos, K Koeffler, HP AF Verbeek, W Lekstrom-Himes, J Park, DJ Dang, PMC Vuong, PT Kawano, S Babior, BM Xanthopoulos, K Koeffler, HP TI Myeloid transcription factor C/EBP epsilon is involved in the positive regulation of lactoferrin gene expression in neutrophils SO BLOOD LA English DT Article ID CCAAT DISPLACEMENT PROTEIN; GRANULE PROTEIN; MOUSE HOMOLOG; NADPH OXIDASE; BINDING; RECEPTOR; PROMOTER; CLONING; CELLS; DNA AB Targeted mutation of the myeloid transcription factor C/EBP epsilon in mice results in gram-negative septic death at 3 to 5 months of age. This study defines the underlying molecular defects in their terminal granulocytic differentiation. The mRNA for the precursor protein of the cathelin-related antimicrobial peptides was almost completely absent in the bone marrow cells of C/EBP epsilon-/- mice. This finding may help explain their susceptibility to gram-negative sepsis, because both are bacteriocidal peptides with potent activity against gram-negative bacteria. Superoxide production was found to be reduced in both granulocytes and monocytes of C/EBP epsilon-/- mice, While gp91 phox protein levels were normal, p47phox protein levels were considerably reduced in C/EBP epsilon-/- granulocytes/monocytes, possibly limiting the assembly of the NADPH oxidase, In addition, expression of mRNA of the secondary and tertiary granule proteins, lactoferrin and gelatinase, were not detected, and levels of neutrophil collagenase mRNA were reduced in bone marrow cells of the knock-out mice. The murine lactoferrin promoter has a putative C/EBP site close to the transcription start site. C/EBP epsilon bound to this site in electromobility shift assay studies and mutation of this site abrogated binding to it. A mutation in the C/EBP site reduced the activity of the promoter by 35%, Furthermore, overexpression of C/EBP epsilon in U937 cells increased the activity of the wild-type lactoferrin promoter by 3-fold. In summary, our data implicate C/EBP epsilon as a critical factor of host antimicrobial defense and suggests that it has a direct role as a positive regulator of expression of lactoferrin in vivo. (C) 1999 by The American Society of Hematology. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Burns & Allen Res Inst,Dept Med,Div Hematol Oncol, Los Angeles, CA 90048 USA. NIH, Clin Gene Therapy Branch, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Expt Med, Div Biochem, La Jolla, CA USA. Aurora Biosci Inc, San Diego, CA USA. RP Koeffler, HP (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Burns & Allen Res Inst,Dept Med,Div Hematol Oncol, Davis Res Bldg,Room D 5066,8700 Beverly Blvd, Los Angeles, CA 90048 USA. NR 46 TC 69 Z9 70 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1999 VL 94 IS 9 BP 3141 EP 3150 PG 10 WC Hematology SC Hematology GA 249UG UT WOS:000083351200027 PM 10556201 ER PT J AU Meyron-Holtz, EG Vaisman, B Cabantchik, ZI Fibach, E Rouault, TA Hershko, C Konijn, AM AF Meyron-Holtz, EG Vaisman, B Cabantchik, ZI Fibach, E Rouault, TA Hershko, C Konijn, AM TI Regulation of intracellular iron metabolism in human erythroid precursors by internalized extracellular ferritin SO BLOOD LA English DT Article ID ELEMENT-BINDING-PROTEIN; LIQUID CULTURE; MESSENGER-RNA; CELLS; POOL; ISOFERRITINS; TRANSFERRIN; PROGENITORS; DEGRADATION AB Human erythroid precursors grown in culture possess membrane receptors that bind and internalize acid isoferritin. These receptors are regulated by the iron status of the cell, implying that ferritin iron uptake may represent a normal physiologic pathway. The present studies describe the fate of internalized ferritin, the mechanisms involved in the release of its iron, and the recognition of this iron by the cell. Normal human erythroid precursors were grown in a 2-phase liquid culture that supports the proliferation, differentiation, and maturation of erythroid precursors. At the stage of polychromatic normoblasts, cells were briefly incubated with Fe-59- and/or I-125-labeled acid isoferritin and chased. The I-125-labeled ferritin protein was rapidly degraded and only 50% of the label remained in intact ferritin protein after 3 to 4 hours. In parallel, Fe-59 decreased in ferritin and increased in hemoglobin. Extracellular holoferritin uptake elevated the cellular labile iron pool (LIP) and reduced iron regulatory protein (IRP) activity; this was inhibited by leupeptin or chloroquine. Extracellular apoferritin taken up by the cell functioned as an iron scavenger: it decreased the level of cellular tip and increased IRP activity. We suggest that the iron from extracellular is metabolized in a similar fashion by developing erythroid cells as is intracellular ferritin. Following its uptake, extracellular ferritin iron is released by proteolytic degradation of the protein shell in an acid compartment, The released iron induces an increase in the cellular LIP and participates in heme synthesis and in intracellular iron regulatory pathways. (C) 1999 by The American Society of Hematology. C1 Hebrew Univ Jerusalem, Fac Med, Dept Human Nutr & Metab, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Fac Med, Dept Hematol, Jerusalem, Israel. Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. Shaare Zedek Med Ctr, Dept Med, IL-91000 Jerusalem, Israel. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Konijn, AM (reprint author), Hebrew Univ Jerusalem, Fac Med, Dept Human Nutr & Metab, POB 12272, IL-91120 Jerusalem, Israel. RI Meyron-Holtz, Esther/B-5991-2013 NR 33 TC 37 Z9 38 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1999 VL 94 IS 9 BP 3205 EP 3211 PG 7 WC Hematology SC Hematology GA 249UG UT WOS:000083351200035 PM 10556209 ER PT J AU Childs, R Clave, E Contentin, N Jayasekera, D Hensel, N Leitman, S Read, EJ Carter, C Bahceci, E Young, NS Barrett, AJ AF Childs, R Clave, E Contentin, N Jayasekera, D Hensel, N Leitman, S Read, EJ Carter, C Bahceci, E Young, NS Barrett, AJ TI Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: Full donor T-cell chimerism precedes alloimmune responses SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; POLYMERASE CHAIN-REACTION; THERAPY; DNA AB Nonmyeloablative allogeneic stem cell transplantation has recently been explored as a safer alternative to conventional high-dose transplant regimens. Although a high incidence of mixed chimerism after nonmyeloablative procedures has been reported, the exact kinetics of engrafting donor cells in specific cellular lineages has yet to be defined. We investigated lineage-specific chimerism in 15 patients receiving an allogeneic peripheral blood stem cell (PBSC) transplant from an HLA-identical (n = 14) or a 5/6 antigen-matched sibling donor after a preparative regimen of cyclophosphamide and fludarabine. Donor chimerism was assessed weekly in T lymphocytes and myeloid cells by polymerase chain reaction (PCR) of minisatellite regions. Eight patients survived between 121 to 409 days after transplant. Ten of 14 patients surviving more than 30 days (71.4%) had delayed disease regression consistent with a graft-versus-malignancy (GVM) effect. One patient rejected the transplant with subsequent recovery of autologous hematopoiesis. Hematological recovery was rapid (median, 11 days to greater than or equal to 500 neutrophils/mu L) and was initially predominantly recipient In origin. Donor myeloid chimerism gradually supplanted recipient hematopoiesis and became fully donor in all survivors by 200 days after transplantation. In contrast, T-cell engraftment was more rapid, with full chimerism in 7 patients by day 30 and in 6 further patients by day 200 after cyclosporine withdrawal and donor lymphocyte infusion. Full donor T-cell engraftment preceded donor myeloid engraftment, acute graft-versus-host disease, and disease regression, consistent with a requirement for 100% donor T-cell chimerism for full expression of the alloresponse. These results emphasize the importance of lineage-specific chimerism analysis to successfully manipulate engraftment after nonmyeloablative allogeneic PBSC transplantation. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 24 TC 433 Z9 450 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1999 VL 94 IS 9 BP 3234 EP 3241 PG 8 WC Hematology SC Hematology GA 249UG UT WOS:000083351200038 PM 10556212 ER PT J AU Dimitrov, M Granetz, J Peterson, M Hollnagel, C Alexander, G Grafman, J AF Dimitrov, M Granetz, J Peterson, M Hollnagel, C Alexander, G Grafman, J TI Associative learning impairments in patients with frontal lobe damage SO BRAIN AND COGNITION LA English DT Article ID AUTOMATIC MEMORY PROCESSES; TEMPORAL-ORDER; PREFRONTAL CORTEX; FRONTOTEMPORAL DEMENTIA; RECOGNITION MEMORY; PARKINSONS-DISEASE; LESIONS; DEFICITS; INTERFERENCE; BRAIN AB The performance of 18 frontal lobe lesion (FL) and 10 frontal lobe dementia (FLD) patients on an associative memory test was compared with the performance of their matched normal controls. The FL group was severely impaired on cued and free recall and was moderately impaired on a recognition condition. Left FL patients performed the poorest on the cued and free recall conditions. The no patients were moderately impaired on the free recall condition only but there was a subgroup of no patients with additional left temporal atrophy who appeared severely impaired on both cued and free recall. These findings indicate that both left frontal and temporal lobe damage can impair associative learning and that this impairment is more strikingly seen with free rather than cued recall. (C) 1999 Academic Press. C1 NINDS, Cognit Neurosci Sect, NIH, MNB, Bethesda, MD 20892 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, MNB, Bldg 10,Room 5C205,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM jgr@box-j.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 70 TC 20 Z9 20 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD NOV PY 1999 VL 41 IS 2 BP 213 EP 230 DI 10.1006/brcg.1999.1121 PG 18 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 254CZ UT WOS:000083595500005 PM 10590820 ER PT J AU Rumsey, JM Horwitz, B Donohue, BC Nace, KL Maisog, JM Andreason, P AF Rumsey, JM Horwitz, B Donohue, BC Nace, KL Maisog, JM Andreason, P TI A functional lesion in developmental dyslexia: Left angular gyral blood flow predicts severity SO BRAIN AND LANGUAGE LA English DT Article DE dyslexia; angular gyrus; reading; regional cerebral blood flow; positron emission tomography ID READING-DISABILITY; WORD RECOGNITION; BRAIN ACTIVITY; CORTEX; CONNECTIVITY; SUBTYPES; MRI; MEN AB Functional imaging studies have shown reduced regional cerebral blood flow (rCBF) in temporal and inferior parietal regions in dyslexia. To relate such abnormalities to the severity of dyslexia, correlations between reading skill and rCBF during a series of reading tasks and visual fixation were mapped for 17 right-handed dyslexic men, ages 18-40, and 14 matched controls. These correlations uniquely identified the left angular gyrus as the most probable site of a functional lesion in dyslexia: Here, higher rCBF was associated with better reading skill in controls (p < .01), but with worse reading skill in dyslexia (p < .01). This suggests that greater reliance on this region normally facilitates reading, but impairs reading in dyslexia. Thus, developmental dyslexia may share a common localization with alexia. (C) 1999 Academic Press. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Psychol & Psychopathol Lab, Bethesda, MD 20892 USA. US FDA, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Rumsey, JM (reprint author), NIMH, Clin Neurosci Branch, Ctr Neurosci, 6001 Execut Blvd,MSC 9639, Bethesda, MD 20892 USA. EM jrumsey@box-j.nih.gov NR 49 TC 68 Z9 69 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD NOV PY 1999 VL 70 IS 2 BP 187 EP 204 DI 10.1006/brln.1999.2158 PG 18 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 257ER UT WOS:000083770000002 PM 10550226 ER PT J AU Burke, RE AF Burke, RE TI The significance of supraspinal control of reflex actions SO BRAIN RESEARCH BULLETIN LA English DT Article C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Burke, RE (reprint author), NINDS, Neural Control Lab, NIH, Bldg 49,Rm 3A50, Bethesda, MD 20892 USA. NR 3 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 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV-DEC PY 1999 VL 50 IS 5-6 BP 325 EP 325 DI 10.1016/S0361-9230(99)00150-1 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 310CK UT WOS:000086808800013 PM 10643419 ER PT J AU O'Donovan, MJ AF O'Donovan, MJ TI Noise analysis at the neuromuscular junction SO BRAIN RESEARCH BULLETIN LA English DT Article C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP O'Donovan, MJ (reprint author), NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RI o'donovan, michael/A-2357-2015 OI o'donovan, michael/0000-0003-2487-7547 NR 2 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV-DEC PY 1999 VL 50 IS 5-6 BP 329 EP 329 DI 10.1016/S0361-9230(99)00148-3 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 310CK UT WOS:000086808800015 PM 10643421 ER PT J AU Herkenham, M AF Herkenham, M TI Extrasynaptic receptors and parasynaptic communication in the brain SO BRAIN RESEARCH BULLETIN LA English DT Article ID LOCALIZATION; NEURONS; VIEW C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Rm 2D-15,36 Convent Dr,MSC 4070, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 8 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV-DEC PY 1999 VL 50 IS 5-6 BP 351 EP 352 DI 10.1016/S0361-9230(99)00101-X PG 2 WC Neurosciences SC Neurosciences & Neurology GA 310CK UT WOS:000086808800026 PM 10643432 ER PT J AU Kety, SS AF Kety, SS TI Circulation and metabolism of the human brain SO BRAIN RESEARCH BULLETIN LA English DT Article C1 NIH, Bethesda, MD 20892 USA. RP Kety, SS (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV-DEC PY 1999 VL 50 IS 5-6 BP 415 EP 416 DI 10.1016/S0361-9230(99)00171-9 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 310CK UT WOS:000086808800055 PM 10643461 ER PT J AU Pietrini, P Furey, ML Guazzelli, M AF Pietrini, P Furey, ML Guazzelli, M TI In vivo biochemistry of the brain in understanding human cognition and emotions: Towards a molecular psychology SO BRAIN RESEARCH BULLETIN LA English DT Article C1 Univ Pisa, Sch Med, Inst Med Chem & Biochem, Dept Human & Environm Sci, I-56100 Pisa, Italy. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Pisa, Sch Med, Dept Psychiat Pharmacol Neurobiol & Biotechnol, I-56100 Pisa, Italy. RP Pietrini, P (reprint author), Univ Pisa, Sch Med, Inst Med Chem & Biochem, Dept Human & Environm Sci, Via Roma 55, I-56100 Pisa, Italy. RI Furey, Maura/H-5273-2013 NR 6 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV-DEC PY 1999 VL 50 IS 5-6 BP 417 EP 418 DI 10.1016/S0361-9230(99)00172-0 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 310CK UT WOS:000086808800056 PM 10643462 ER PT J AU Ablashi, D Chatlynne, L Cooper, H Thomas, D Yadav, M Norhanom, AW Chandana, AK Churdboonchart, V Kulpradist, SAR Patnaik, M Liegmann, K Masood, R Reitz, M Cleghorn, F Manns, A Levine, PH Rabkin, C Biggar, R Jensen, F Gill, P Jack, N Edwards, J Whitman, J Boshoff, C AF Ablashi, D Chatlynne, L Cooper, H Thomas, D Yadav, M Norhanom, AW Chandana, AK Churdboonchart, V Kulpradist, SAR Patnaik, M Liegmann, K Masood, R Reitz, M Cleghorn, F Manns, A Levine, PH Rabkin, C Biggar, R Jensen, F Gill, P Jack, N Edwards, J Whitman, J Boshoff, C TI Seroprevalence of human herpesvirus-8 (HHV-8) in countries of Southeast Asia compared to the USA, the Caribbean and Africa SO BRITISH JOURNAL OF CANCER LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; SEXUAL TRANSMISSION; BLOOD-DONORS; HUMAN-HERPESVIRUS-8; ANTIBODIES; INFECTION; ANTIGENS; LYMPHOMA; KS AB Seroprevalence of HHV-8 has been studied in Malaysia, India, Sri Lanka, Thailand, Trinidad, Jamaica and the USA, in both healthy individuals and those infected with HIV. Seroprevalence was found to be low in these countries in both the healthy and the HIV-infected populations. This correlates with the fact that hardly any AIDS-related Kaposi's sarcoma has been reported in these countries, in contrast, the African countries of Ghana, Uganda and Zambia showed high seroprevalences in bath healthy and HIV-infected populations. This suggests that human herpes virus-8 (HHV-8) may be either a recently introduced virus or one that has extremely low infectivity. Nasopharyngeal and oral carcinoma patients from Malaysia, Hong Kong and Sri Lanka who have very high EBV titres show that only 3/82 (3.7%) have antibody to HHV-8, demonstrating that there is little, ii any, cross-reactivity between antibodies to these two gamma viruses. (C) 1999 Cancer Research Campaign. C1 Adv Biotechnol Inc, Columbia, MD 21046 USA. Univ Malaya, Pusat Asasi Sains, Kuala Lumpur 50603, Malaysia. Mahidol Univ, Dept Pathol, Bangkok 10400, Thailand. Specialty Labs Inc, Santa Monica, CA 90404 USA. Univ So Calif, Sch Med, Div Hematol, Los Angeles, CA 90033 USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20852 USA. George Washington Univ, Sch Med, Dept Epidemiol, Washington, DC 20037 USA. Immune Response Corp, Carlsbad, CA 92008 USA. Med Res Fdn Trinidad & Tobago, Port Of Spain, Trinid & Tobago. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. RP Ablashi, D (reprint author), Adv Biotechnol Inc, 9108 Guilford Rd, Columbia, MD 21046 USA. RI ABDUL WAHAB, NORHANOM/B-5207-2010 NR 30 TC 90 Z9 94 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV PY 1999 VL 81 IS 5 BP 893 EP 897 DI 10.1038/sj.bjc.6690782 PG 5 WC Oncology SC Oncology GA 250LH UT WOS:000083389500024 PM 10555764 ER PT J AU Steinbuch, M Weinberg, CR Buckley, JD Robison, LL Sandler, DP AF Steinbuch, M Weinberg, CR Buckley, JD Robison, LL Sandler, DP TI Indoor residential radon exposure and risk of childhood acute myeloid leukaemia SO BRITISH JOURNAL OF CANCER LA English DT Article DE radon; childhood; acute myeloid leukaemia; epidemiology ID CANCER-STUDY-GROUP; LUNG-CANCER; LEUKEMIA; CHILDREN; MINERS; ASSOCIATION; LYMPHOCYTES; FREQUENCY; RADIATION; PARENTS AB Exposure to radon has been identified as a risk factor for lung cancer in uranium miners, but evidence of adverse health effects due to indoor radon exposure is inconsistent. Ecological studies have suggested a correlation between indoor radon levels and leukaemia incidence. We evaluated the risk associated with indoor residential radon exposure within a larger interview-based case-control study of risk factors for childhood acute myeloid leukaemia (AML). A total of 173 cases and 254 controls met the eligibility criteria, and information was collected through telephone interviews with parents and analysis of alpha-track radon detectors placed in the home for a period of 1 year. No association was observed between radon exposure and risk of AML, with adjusted odds ratios of 1.2 (95% confidence interval (CI) 0.7-1.8) for 37-100 Bq m(-3) and 1.1 (95% Cl 0.6-2.0) for > 100 Bq m(-3) compared with < 37 Bq m(-3). Although there was an inverse association between radon level and AML risk among children < 2 years at diagnosis, among children greater than or equal to 2 years, AML risk was increased among those with higher radon exposure. The observed association after age 2 is most likely due to chance. Overall, there was no association between residential radon and risk of childhood AML. (C) 1999 Cancer Research Campaign. C1 Univ Minnesota, Div Epidemiol & Clin Res, Minneapolis, MN 55455 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Norris Cotton Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Steinbuch, M (reprint author), Childrens Canc Grp, POB 60012, Arcadia, CA 91066 USA. OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [CA49450] NR 37 TC 32 Z9 36 U1 1 U2 3 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 NOV PY 1999 VL 81 IS 5 BP 900 EP 906 DI 10.1038/sj.bjc.6690784 PG 7 WC Oncology SC Oncology GA 250LH UT WOS:000083389500026 PM 10555766 ER PT J AU Egan, CA Taylor, TB Meyer, LJ Petersen, MJ Zone, JJ AF Egan, CA Taylor, TB Meyer, LJ Petersen, MJ Zone, JJ TI IgA1 is the major IgA subclass in cutaneous blood vessels in Henoch-Schonlein purpura SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE Henoch-Schonlein purpura; IgA; skin; vasculitis ID NEPHRITIS; GLYCOSYLATION; NEPHROPATHY; DEPOSITION; CHILDREN; SERUM AB Henoch-Schonlein purpura (HSP) is characterized by palpable purpura predominantly involving the lower extremities. On direct immunofluorescence IgA can be seen deposited in the blood vessel walls of the superficial dermis. The subclass distribution of antibodies to this IgA was studied in the biopsies of 28 patients with HSP by direct immunofluorescence using anti-IgA1 and anti-IgA2 specific monoclonal antibodies. All 28 patients' biopsies demonstrated deposition of IgA1 while only one patient: had IgA2 deposition. Positive and negative controls stained appropriately. This demonstrates that IgA1 is the dominant IgA subclass found in the skin in Henoch-Schonlein purpura. C1 Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84132 USA. Vet Affairs Med Ctr, Dermatol Sect, Med Serv, Salt Lake City, UT USA. Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Salt Lake City, UT USA. RP Egan, CA (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01DK50678-01A1] NR 21 TC 17 Z9 18 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 1999 VL 141 IS 5 BP 859 EP 862 DI 10.1046/j.1365-2133.1999.03159.x PG 4 WC Dermatology SC Dermatology GA 265BC UT WOS:000084218100013 PM 10583167 ER PT J AU Childs, R Epperson, D Bahceci, E Clave, E Barrett, J AF Childs, R Epperson, D Bahceci, E Clave, E Barrett, J TI Molecular remission of chronic myeloid leukaemia following a non-myeloablative allogeneic peripheral blood stem cell transplant: in vivo and in vitro evidence for a graft-versus-leukaemia effect SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic myeloid leukaemia; graft-versus-leukaemia effect; cyclophosphamide; fludarabine ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC PHASE; PROGENITORS; THERAPY AB Two patients with chronic myeloid leukaemia (CML) received a non-myeloablative preparative regimen of cyclophosphamide and fludarabine, followed by an unmanipulated, G-CSF-mobilized, peripheral blood stem cell transplant from an HLA-identical sibling. Chimaerism, evaluated in myeloid and T-lymphoid lineages by PCR of minisatellite variable regions, showed day 14 post-transplant haemopoietic recovery to be 90% autologous in both patients. On day 30 the bone marrow showed only 1/20 and 2/18 donor metaphases. By day 100 post transplant both had 100% donor myeloid and lymphoid lineages as assessed by karyotype and minisatellite chimaerism analysis. They subsequently became RT-PCR negative for BCR-ABL. Both survive 7 and 14 months post transplant in molecular remission of CML. In one, donor T cells, stimulated with pre-transplant CML cells, induced 30-50% inhibition of pre-transplant leukaemic CFU-GM, but did not inhibit CFU-GM in the day 60 marrow (46% Ph-negative recipient, 54% donor), These results show that a non-myeloablative allotransplant can induce molecular remissions of CML through a graft-versus-leukaemia effect. C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bldg 10,Room 7C103,10 Ctr Dr,MSC 1652, Bethesda, MD 20892 USA. NR 19 TC 37 Z9 37 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 NOV PY 1999 VL 107 IS 2 BP 396 EP 400 DI 10.1046/j.1365-2141.1999.01706.x PG 5 WC Hematology SC Hematology GA 256AV UT WOS:000083703200029 PM 10583233 ER PT J AU Daly, SF Molloy, AM Mills, JL Lee, YJ Conley, M Kirke, PN Weir, DG Scott, JM AF Daly, SF Molloy, AM Mills, JL Lee, YJ Conley, M Kirke, PN Weir, DG Scott, JM TI The influence of 5,10 methylenetetrahydrofolate reductase genotypes on enzyme activity in placental tissue SO BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID NEURAL-TUBE DEFECTS; FOLATE INTAKE; RISK FACTOR; MUTATION; DISEASE AB Objective To study the effects of heterozygosity and homozygosity for the C677T mutation of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene on the activity of this enzyme in placental tissue from pregnancies not affected by neural tube defect. Design Placental tissue was genotyped for the C677T variants of MTHFR. Total enzyme activity and residual activity after heating to 46 degrees C for 5 minutes was then measured. Setting A teaching hospital. Sample Placental samples (n = 200), one from each of 200 uncomplicated term deliveries. Main outcome measures Total and residual enzyme activity for MTHFR. Results Placentae heterozygous for the C677T mutation of the MTHFR gene had significantly lower total enzyme activity than those without the mutation; the lowest activity occurred in homozygotes for the mutation. The same pattern was seen in relation to enzyme activity after heating. Conclusion This study demonstrates that reduced enzyme activity is associated with the C677T variant of MTHFR in placental tissue. This is an important metabolic step in folic acid metabolism and pro-(sic). C1 Coombe Womens Hosp, Royal Coll Surg Ireland, Dublin 8, Ireland. Trinity Coll, Dept Clin Med, Dublin, Ireland. NICHD, Epidemiol Branch, NIH, Bethesda, MD USA. NICHD, Branch Stat, NIH, Bethesda, MD USA. Hlth Res Board, Dublin, Ireland. Trinity Coll, Dept Biochem, Dublin, Ireland. RP Daly, SF (reprint author), Coombe Womens Hosp, Royal Coll Surg Ireland, Dublin 8, Ireland. NR 12 TC 11 Z9 12 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0306-5456 J9 BRIT J OBSTET GYNAEC JI Br. J. Obstet. Gynaecol. PD NOV PY 1999 VL 106 IS 11 BP 1214 EP 1218 DI 10.1111/j.1471-0528.1999.tb08151.x PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 252ZD UT WOS:000083531400020 PM 10549970 ER PT J AU Velez, G Whitcup, SM AF Velez, G Whitcup, SM TI New developments in sustained release drug delivery for the treatment of intraocular disease SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID BLOOD-OCULAR BARRIERS; CYTOMEGALO-VIRUS RETINITIS; INTRAVITREAL GANCICLOVIR; EXPERIMENTAL UVEITIS; CYCLOSPORIN-A; THERAPY; AIDS; SERUM; MANAGEMENT; TOXICITY C1 NEI, NIH, Bethesda, MD 20892 USA. RP Velez, G (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N112, Bethesda, MD 20892 USA. NR 55 TC 40 Z9 42 U1 0 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD NOV PY 1999 VL 83 IS 11 BP 1225 EP 1229 DI 10.1136/bjo.83.11.1225 PG 5 WC Ophthalmology SC Ophthalmology GA 252YY UT WOS:000083530900011 PM 10535845 ER PT J AU Mirsalis, JC Schindler-Horvat, J Hill, JR Tomaszewski, JE Donohue, SJ Tyson, CA AF Mirsalis, JC Schindler-Horvat, J Hill, JR Tomaszewski, JE Donohue, SJ Tyson, CA TI Toxicity of dolastatin 10 in mice, rats and dogs and its clinical relevance SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE preclinical toxicology; cancer chemotherapy; myelotoxicity; dolastatin 10 ID LYMPHOMA CELL-LINES; PHASE-I; INFUSION; INHIBITION; TUBULIN; BINDING; AGENTS; CANCER; TAXOL; TRIAL AB Purpose: Dolastatin 10 (DOL 10), an oligopeptide isolated from the sea hare Dolabella auricularia, has been shown to be a highly potent cytotoxic agent in a variety of human tumor cell lines. The purpose of this study was to conduct preclinical toxicity evaluations to determine the target organ(s) of toxicity and its reversibility, the dose-limiting toxicity and the maximum tolerated dose (MTD), and to use this information for arriving at a safe starting dose and dose schedule for phase I clinical trails. Methods: DOL10 was administered as a single intravenous bolus dose to CD2F1 mice, Fischer-344 rats and beagle dogs. Endpoints evaluated included clinical observations, body weights, hematology, serum clinical chemistry, and microscopic pathology of tissues. Results: The MTD (i.e. the highest dose that did not cause lethality but produced substantial toxicity) was approximately 1350 mu g/m(2) body surface area (450 mu g/kg) in mice, 450 mu g/m2 (75 mu g/kg) in rats and less than or equal to 400 mu g/m(2) (less than or equal to 20 mu g/kg) in dogs. Adverse signs were observed at doses greater than or equal to 1350 mu g/m(2) in mice, greater than or equal to 150 mu g/m(2) in rats and greater than or equal to 400 mu g/m(2) in dogs. Decreased weight gain or actual weight loss was observed at doses greater than or equal to 1350 mu g/m(2) in mice, greater than or equal to 600 mu g/m(2) in rats and greater than or equal to 450 mu g/m(2) in dogs. In all three species, the primary target organ of toxicity was the bone marrow, as indicated by decreases in the numbers of erythroid cells, myeloid cells, and megakaryocytes in the femoral bone marrow and by decreased white blood cell (WBC) and reticulocyte counts in peripheral blood. Marked neutropenia (i.e. >50% decrease compared to control animal or baseline values) was the principal effect on WBCs and occurred within a week of dosing. A mild anemia was evident I week after administering the drug to rats and dogs. The hematologic effects were transient and reversed by study termination. Other lesions at the MTD levels were cellular depletion and necrosis in lymphoid organs (rats and dogs), marked depletion of extramedullary hematopoietic cellular elements in the spleen (rats), thymic atrophy (mice and dogs), and minimal cellular necrosis in the ileum (rats). More extensive and severe pathology was observed in animals sacrificed in a moribund condition or found dead. Conclusions: Myelotoxicity was dose-limiting in all three species with mice being the least sensitive. In a phase I clinical trial, granulocytopenia was dose-limiting. Moreover, the MTD of DOL10 for rats and dogs is comparable to the human MTD. Therefore, the results from the preclinical toxicology studies correctly predicted a safe starting dose, the dose-limiting toxicity, and the MTD in humans. C1 SRI Int, Toxicol Lab, Menlo Park, CA 94025 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Bethesda, MD 20892 USA. RP Mirsalis, JC (reprint author), SRI Int, Toxicol Lab, 333 Ravenswood Ave, Menlo Park, CA 94025 USA. FU NCI NIH HHS [N01-CM-37837] NR 20 TC 24 Z9 24 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 NOV PY 1999 VL 44 IS 5 BP 395 EP 402 DI 10.1007/s002800050995 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 241WG UT WOS:000082906400007 PM 10501913 ER PT J AU Hiatt, RA Rimer, BK AF Hiatt, RA Rimer, BK TI A new strategy for cancer control research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID BEHAVIORAL-RESEARCH CONTRIBUTIONS; ENVIRONMENTAL TOBACCO-SMOKE; HEALTH-CARE SYSTEM; BREAST-CANCER; SCREENING MAMMOGRAPHY; UNITED-STATES; PUBLIC-HEALTH; PREVENTION; METAANALYSIS; US C1 Natl Canc Inst, US Dept Hlth & Human Serv,Publ Hlth Serv, NIH, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. RP Hiatt, RA (reprint author), Natl Canc Inst, US Dept Hlth & Human Serv,Publ Hlth Serv, NIH, Div Canc Control & Populat Sci, Execut Plaza N,Suite 243,6130 Execut Blvd, Rockville, MD 20852 USA. NR 69 TC 100 Z9 105 U1 3 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 NOV PY 1999 VL 8 IS 11 BP 957 EP 964 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 255QU UT WOS:000083682300002 PM 10566549 ER PT J AU Woodson, K Stewart, C Barrett, M Bhat, NK Virtamo, J Taylor, PR Albanes, D AF Woodson, K Stewart, C Barrett, M Bhat, NK Virtamo, J Taylor, PR Albanes, D TI Effect of vitamin intervention on the relationship between GSTM1, smoking, and lung cancer risk among male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; TRANS-STILBENE OXIDE; ALPHA-TOCOPHEROL; JAPANESE POPULATION; CYTOGENETIC DAMAGE; BETA-CAROTENE; NULL GENOTYPE; DNA ADDUCTS; SUSCEPTIBILITY; MU AB The GSTM1 (glutathione S-transferase mu-l) null genotype is suspected of increasing an individual's susceptibility to tobacco smoke carcinogens because of impaired carcinogen detoxification, We were interested in whether there were differences in lung cancer susceptibility to smoking within the GSTM1 genotypes and the impact of antioxidant supplementation on this. For this purpose, we conducted a nested lung cancer case-control study and evaluated the role of GSTM1 within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. GSTM1 genotype status was determined for 319 cases and 333 controls using a PCR-based approach, GSTM1 was evaluated as an independent risk factor and as an effect modifier of smoking using logistic regression analyses. The GSTM1 null genotype itself was unrelated to risk of lung cancer, odds ratio (OR) = 1.09 and 95% confidence interval (CI), 0.79-1.50, but it may have modified the effect of smoking. There was a suggestion for a stronger association between years of smoking and lung cancer among the GSTM1 null genotype, but the differences between GSTM1 null and present genotypes were not statistically significant (P = 0.12), Furthermore, the smoking association was strongest among those with the GSTM1 null genotype not receiving a-tocopherol supplementation, whereas among those receiving alpha-tocopherol, there was no modification by GSTM1 on the association between smoking duration and lung cancer risk. beta-Carotene supplementation did not modify the relationship between GSTM1, smoking years, and lung cancer risk. In conclusion, GSTM1 is not associated with lung cancer risk in male smokers but may confer a higher susceptibility to cumulative tobacco exposure. This association may be attenuated by alpha-tocopherol but not by beta-carotene supplementation. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Recombinant DNA Lab, Frederick, MD 21702 USA. Informat Management Serv Inc, Silver Spring, MD 20904 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 33 TC 27 Z9 27 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 1999 VL 8 IS 11 BP 965 EP 970 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 255QU UT WOS:000083682300003 PM 10566550 ER PT J AU Schroeder, JR Saah, AJ Hoover, DR Margolick, JB Ambinder, RF Martinez-Maza, O Breen, EC Jacobson, LP Variakojis, D Rowe, DT Armenian, HK AF Schroeder, JR Saah, AJ Hoover, DR Margolick, JB Ambinder, RF Martinez-Maza, O Breen, EC Jacobson, LP Variakojis, D Rowe, DT Armenian, HK TI Serum soluble CD23 level correlates with subsequent development of AIDS-related non-Hodgkin's lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; CLINICAL IMPLICATIONS AB The cytokine soluble CD23 (sCD23) has been shown to act as a B cell growth factor and to be elevated in serum prior to development of AIDS-related non-Hodgkin's lymphoma (AIDS NHL), To further characterize the elevation of serum sCD23 in AIDS NRL patients and investigate its potential as a diagnostic test, a matched case-control study of AIDS NHL (n = 101) was nested within the Multicenter AIDS Cohort Study. Serum sCD23 was measured in cases' and controls' serum specimens at three different time periods (0-6, 6-12, and 12-18 months) and CD4+ thresholds (0-99, 100-199, and 200-299 cells/mu l) prior to the case's NHL diagnosis. Changes in serum sCD23 over time were examined in AIDS NHL cases relative to controls, and t tests were performed to determine whether cases' serum sCD23 exceeded that of controls at each time period and CD4+ threshold. Overall, cases' median serum sCD23 levels were approximately double those of controls. Serum sCD23 concentration was positively correlated with lymphocyte counts for both cases and controls. The difference in cases' and controls' serum sCD23 levels became greater as AIDS NHL diagnosis date approached: in the 18 months preceding the case's NHL diagnosis, serum sCD23 was stable in cases but dropped in controls. Although this difference was statistically significant (P < 0.05), it was not clinically significant. It is unlikely that serum sCD23 would make a useful test for AIDS NHL because the magnitude of the difference between cases and controls was small and there was no change in serum sCD23 in cases that would indicate disease. C1 Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. Rutgers State Univ, Dept Stat, New Brunswick, NJ 08901 USA. Rutgers State Univ, Inst Aging Hlth & Hlth Care Policy, New Brunswick, NJ 08901 USA. Univ Calif Los Angeles, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Northwestern Univ, Dept Pathol, Evanston, IL 60208 USA. Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. RP Schroeder, JR (reprint author), NIDA, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Martinez-Maza, Otoniel/B-2667-2009 OI Martinez-Maza, Otoniel/0000-0003-1364-0675 FU NCRR NIH HHS [5-M01-RR-00052]; NIAID NIH HHS [U01-AI-35042, U01-AI-35043] NR 23 TC 24 Z9 24 U1 0 U2 0 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 NOV PY 1999 VL 8 IS 11 BP 979 EP 984 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 255QU UT WOS:000083682300005 PM 10566552 ER PT J AU O'Connell, AC Baccaglini, L Fox, PC O'Connell, BC Kenshalo, D Oweisy, H Hoque, ATMS Sun, D Herscher, LL Braddon, VR Delporte, C Baum, BJ AF O'Connell, AC Baccaglini, L Fox, PC O'Connell, BC Kenshalo, D Oweisy, H Hoque, ATMS Sun, D Herscher, LL Braddon, VR Delporte, C Baum, BJ TI Safety and efficacy of adenovirus-mediated transfer of the human aquaporin-1 cDNA to irradiated parotid glands of non-human primates SO CANCER GENE THERAPY LA English DT Article DE salivary gland; radiation damage; adenoviral-mediated gene transfer; aquaporin-1; non-human primates ID RAT SALIVARY-GLANDS; NONHUMAN-PRIMATES; RHESUS-MONKEY; CFTR GENE; LUNG; CELLS; RADIOSENSITIVITY; RADIOTHERAPY; VECTORS AB This study evaluated the safety and efficacy of a single administration of a recombinant adenovirus encoding human aquaporin-1 (AdhAQP1) to the parotid glands of adult rhesus monkeys. In anticipation of possible clinical use of this virus to correct irradiation damage to salivary glands, AdhAQP1 was administered (at either 2 x 10(9) or 1 x 10(8) plaque-forming units/gland) intraductally to irradiated glands and to their contralateral nonirradiated glands. Radiation (single dose, 10 Gy) significantly reduced salivary flow in exposed glands. Virus administration resulted in gene transfer to irradiated and nonirradiated glands and was without untoward local (salivary) or systemic (sera chemistry, complete blood count) effects in all animals. However, the effect of AdhAQP1 administration varied and did not result in a consistent positive effect on salivary flow rates for all animals under these experimental conditions. We conclude that a single adenoviral-mediated gene transfer to primate salivary glands is well-tolerated, although its functional utility in enhancing fluid secretion from irradiated parotid glands is inconsistent. C1 NCI, Gene Therapy & Therapeut Branch, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NCI, Pain & Neurosensory Mech Branch, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NCI, Gene Therapy & Therapeut Branch, Natl Inst Dent & Craniofacial Res, NIH, Room 1N113,MSC-1190, Bethesda, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983; O'Connell, Brian/0000-0003-4529-7664 NR 35 TC 27 Z9 28 U1 1 U2 1 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 BP 505 EP 513 DI 10.1038/sj.cgt.7700078 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 264DC UT WOS:000084164200003 PM 10608347 ER PT J AU Kim, M Katayose, Y Li, Q Rakkar, AN Li, Z Hwang, SG Katayose, D Trepel, J Cowan, KH Seth, P AF Kim, M Katayose, Y Li, Q Rakkar, AN Li, Z Hwang, SG Katayose, D Trepel, J Cowan, KH Seth, P TI Cancer gene therapy with a recombinant adenovirus expressing a Von Hippel-Lindau tumor suppressor gene SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Human Gene Therapy Res Inst, Des Moines, IA USA. NCI, NIH, Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 SU S MA O4 BP S1 EP S2 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 265JR UT WOS:000084240100005 ER PT J AU Makower, D Rozenblit, A Edelman, M Augenlicht, L Kaufman, H Haynes, H Zwiebel, J Wadler, S AF Makower, D Rozenblit, A Edelman, M Augenlicht, L Kaufman, H Haynes, H Zwiebel, J Wadler, S TI Phase IIB trial of ONYX-015 therapy in hepatobiliary tumors SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Radiol, Bronx, NY 10467 USA. Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Pathol, Bronx, NY 10467 USA. Natl Canc Inst, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 SU S MA PD61 BP S16 EP S16 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 265JR UT WOS:000084240100060 ER PT J AU Nishimura, MI Clay, TM Custer, MC Yu, DC Rosenberg, SA AF Nishimura, MI Clay, TM Custer, MC Yu, DC Rosenberg, SA TI Retroviral-mediated transfer of tumor antigen-reactive T-cell receptor genes to peripheral blood lymphocytes confers antitumor reactivity SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Natl Canc Inst, Surg Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 SU S MA O99 BP S27 EP S27 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 265JR UT WOS:000084240100098 ER PT J AU Lutchman, M Pack, S Kim, AC Azim, A Emmert-Buck, M van Huffel, C Zhuang, ZP Chishti, AH AF Lutchman, M Pack, S Kim, AC Azim, A Emmert-Buck, M van Huffel, C Zhuang, ZP Chishti, AH TI Loss of heterozygosity on 8p in prostate cancer implicates a role for dematin in tumor progression SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID HUMAN ERYTHROID DEMATIN; CELL-LINES; GENE; PTEN; DELETION; IDENTIFICATION; HYBRIDIZATION; MUTATIONS; CLONING; PROTEIN AB Dematin is a cytoskeletal protein that bundles actin filaments in a phosphorylation-dependent manner. The primary structure of dematin is organized into an N-terminal core domain of unknown function and a C-terminal domain that is homologous to the "headpiece" domain of villin. We have previously localized the dematin gene on human chromosome 8p21.1, a region distal to the ankyrin locus for hereditary spherocytosis. Radiation hybrid mapping now places dematin between D8S258 and D8S137, two microsatellite markers frequently deleted in prostate cancer. The 8p21.1 region is also deleted in prostate, breast, colon, and bladder cancers, suggesting the presence of a tumor suppressor gene(s). Using laser-capture microdissection technique and fluorescence in situ hybridization (FISH), we demonstrate loss of heterozygosity (LOH) of the dematin gene in a majority of chromosomal region 8p21-linked prostate tumors. One allele of dematin was also deleted in the established prostate adenocarcinoma cell line PC-3, which displays a classic oncogenic phenotype. Overexpression of wild-type dematin in PC-3 cells resulted in the restoration of a more polarized, epithelial-like phenotype. Conversely, the heterologous expression of dominant negative mutants of dematin perturbed normal cell morphology of NIH 3T3 fibroblasts. These results suggest a biological function of dematin in the regulation of cell shape, with implications in the pathobiology of prostate tumorigenesis. (C) Elsevier Science Inc., 1999. All rights reserved. C1 Tufts Univ, Sch Med, St Elizabeths Med Ctr, Sect Hematol Oncol Res, Boston, MA 02135 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Millenium Pharmaceut Inc, Cambridge, MA USA. RP Chishti, AH (reprint author), Tufts Univ, Sch Med, St Elizabeths Med Ctr, Sect Hematol Oncol Res, ACH4,736 Cambridge St, Boston, MA 02135 USA. RI Pack, Svetlana/C-2020-2014 FU NHLBI NIH HHS [HL51445] NR 22 TC 28 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD NOV PY 1999 VL 115 IS 1 BP 65 EP 69 DI 10.1016/S0165-4608(99)00081-3 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 253PG UT WOS:000083564500012 PM 10565303 ER PT J AU Lal, A Lash, AE Altschul, SF Velculescu, V Zhang, L McLendon, RE Marra, MA Prange, C Morin, PJ Polyak, K Papadopoulos, N Vogelstein, B Kinzler, KW Strausberg, RL Riggins, GJ AF Lal, A Lash, AE Altschul, SF Velculescu, V Zhang, L McLendon, RE Marra, MA Prange, C Morin, PJ Polyak, K Papadopoulos, N Vogelstein, B Kinzler, KW Strausberg, RL Riggins, GJ TI A public database for gene expression in human cancers SO CANCER RESEARCH LA English DT Article ID P53-INDUCED APOPTOSIS; SERIAL ANALYSIS; GLIOBLASTOMA; PROGRESSION; PROFILES; CELLS; TUMOR AB A public database, SAGEmap, was created as a component of the Cancer Genome Anatomy Project to provide a central location for depositing, retrieving, and analyzing human gene expression data. This database uses serial analysis of gene expression to quantify transcript levels in both malignant and normal human tissues. By accessing SAGEmap (http://www.ncbi.nlm.nih.gov/SAGE) the user can compare transcript populations between any of the posted libraries. As an initial demonstration of the database's utility, gene expression in human glioblastomas was compared with that of normal brain white matter. Of the 47,174 unique transcripts expressed in these two tissues, 471 (1.0%) were differentially expressed by more than 5-fold (P < 0.001). Classification of these genes revealed functions consistent with the biological properties of glioblastomas, in particular: angiogenesis, transcription, and cell cycle related genes. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. Washington Univ, Genome Sequencing Ctr, St Louis, MO 63108 USA. Univ Calif Lawrence Livermore Natl Lab, IMAGE Consortium, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. NIA, Gerontol Res Ctr, Biol Chem Lab, Baltimore, MD 21224 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. NCI, Off Director, Canc Genome Anat Project, Bethesda, MD 20892 USA. RP Riggins, GJ (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3156, Durham, NC 27710 USA. RI Papadopoulos, Nickolas/K-7272-2012; Marra, Marco/B-5987-2008; OI Lash, Alex/0000-0003-3787-1590 NR 20 TC 322 Z9 338 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1999 VL 59 IS 21 BP 5403 EP 5407 PG 5 WC Oncology SC Oncology GA 252KG UT WOS:000083500200002 PM 10554005 ER PT J AU Melillo, G Sausville, EA Cloud, K Lahusen, T Varesio, L Senderowicz, AM AF Melillo, G Sausville, EA Cloud, K Lahusen, T Varesio, L Senderowicz, AM TI Flavopiridol, a protein kinase inhibitor, down-regulates hypoxic induction of vascular endothelial growth factor expression in human monocytes SO CANCER RESEARCH LA English DT Article ID INDUCIBLE FACTOR-I; FACTOR MESSENGER-RNA; CELLS; APOPTOSIS; PATHWAY; STABILIZATION; ACTIVATION; ELEMENT; THERAPY AB We have investigated the effects of flavopiridol, a novel protein kinase inhibitor that is selective for cyclin-dependent kinases, on hypoxia-induced vascular endothelial growth factor (VEGF) expression in human monocytes, We found that hypoxia induces a time-dependent increase of VEGF mRNA expression and protein levels in human monocytes, Flavopiridol showed a minimal effect on the constitutive levels of VEGF mRNA but completely blocked hypoxia-induced VEGF mRNA and protein expression. The inhibitory effects of flavopiridol on VEGF mRNA induction also occurred in the presence of cycloheximide. The transcriptional activation of either a VEGF promoter-luciferase construct or a hypoxia-inducible factor 1 reporter plasmid was not affected by addition of flavopiridol in transient transfection experiments. In contrast, actinomycin D experiments demonstrated that flavopiridol dramatically decreased VEGF mRNA stability. These data provide the first evidence that flavopiridol can affect gene expression by altering mRNA stability. We propose that flavopiridol may interfere with one or more signaling events, leading to hypoxia-induced, protein kinase-modulated, RNA protein binding activity. An important clinical implication of our results is that flavopiridol, presently under investigation in clinical trials, might have antiangiogenic as well as direct antiproliferative effects. C1 NCI, Clin Trials Unit, Dev Therapeut Program, NIH, Bethesda, MD 20892 USA. Ist Giannina Gaslini, Mol Biol Lab, I-16157 Genoa, Italy. RP Melillo, G (reprint author), NCI, DTP Tumor Hypoxia Program, Frederick Canc Res & Dev Ctr, Bldg 432,Room 218, Ft Detrick, MD 21702 USA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 22 TC 123 Z9 126 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1999 VL 59 IS 21 BP 5433 EP 5437 PG 5 WC Oncology SC Oncology GA 252KG UT WOS:000083500200009 PM 10554012 ER PT J AU Ashburner, BP Shackelford, RE Baldwin, AS Paules, RS AF Ashburner, BP Shackelford, RE Baldwin, AS Paules, RS TI Lack of involvement of ataxia telangiectasia mutated (ATM) in regulation of nuclear factor-kappa B (NF-kappa B) in human diploid fibroblasts SO CANCER RESEARCH LA English DT Article ID DOSE IONIZING-RADIATION; SIGNALING PATHWAY; ACTIVATION; PHOSPHORYLATION; APOPTOSIS; CELLS; INDUCTION; KINASE; ALPHA; GENE AB It has been suggested that the cellular response to exposure to ionizing radiation involves activation of the transcription Factor nuclear factor-kappa B (NF-kappa B) and that this response is defective in cells from individuals with ataxia telangiectasia (AT), In one study, it was found that SV40 large T-transformed cells derived from a patient null for the AT mutated (ATM) gene exhibited constitutive activation of NP-kappa B and that in those cells, inhibition of NF-kappa B by expression of a modified form of I kappa B alpha led to correction of the radiosensitivity associated with the AT phenotype [M, Jung ed at, Science (Washington DC), 268: 1691-1621, 1995]. From those data, it was suggested that NF-kappa B played a role in the AT phenotype, We show here that normal diploid cells derived from AT patients do not exhibit constitutive activation of NF-kappa B, Furthermore, we provide data that the transformation process associated with SV40 large T antigen expression in AT-/- cells leads to aberrant cellular responses. Our studies highlight the importance of using diploid, nontransformed AT-/- cells for in vitro studies relevant to the AT phenotype whenever possible. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. RP Paules, RS (reprint author), NIEHS, 111 Alexander Dr,Mail Drop F1-05,POB 12233, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [CA72771] NR 23 TC 17 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1999 VL 59 IS 21 BP 5456 EP 5460 PG 5 WC Oncology SC Oncology GA 252KG UT WOS:000083500200014 PM 10554017 ER PT J AU Pack, SD Zbar, B Pak, E Ault, DO Humphrey, JS Pham, T Hurley, K Weil, RJ Park, WS Kuzmin, I Stolle, C Glenn, G Liotta, LA Lerman, MI Klausner, RD Linehan, WM Zhuang, ZP AF Pack, SD Zbar, B Pak, E Ault, DO Humphrey, JS Pham, T Hurley, K Weil, RJ Park, WS Kuzmin, I Stolle, C Glenn, G Liotta, LA Lerman, MI Klausner, RD Linehan, WM Zhuang, ZP TI Constitutional von Hippel-Lindau (VHL) gene deletions detected in VHL families by fluorescence in situ hybridization SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; FIELD GEL-ELECTROPHORESIS; GERMLINE MUTATIONS; DISEASE; IDENTIFICATION; DIAGNOSIS AB von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited cancer syndrome predisposing to a variety of tumor types that include retinal hemangioblastomas, hemangioblastomas of the central nervous system, renal cell carcinomas, pancreatic cysts and tumors, pheochromocytomas, endolymphatic sac tumors, and epididymal cystadenomas [W. M. Linehan et al, J. Am. Med. Assoc., 273: 564-570, 1995; E, A. Maher and W. G. Kaelin, Jr., Medicine (Baltimore), 76: 381-391, 1997; W. M. Linehan and R. D. Klausner, In: B. Vogelstein and K. Kinzler (eds.), The Genetic Basis of Human Cancer, pp. 455-473, McGraw-Hill, 1998]. The VHL gene was localized to chromosome 3p25-26 and cloned [F. Latif et al, Science (Washington DC), 260: 1317-1320, 1993]. Germline mutations in the VHL gene have been detected in the majority of VHL kindreds. The reported frequency of detection of VHL germline mutations has varied from 39 to 80% (J. M. Whaley et at, Am. J, Hum. Genet., 55: 1092-1102, 1994; Clinical Research Group for Japan, Hum. Mel. GEnet,, 4: 2233-2237, 1995; F. Chen et at, Hum. Mutat., 5: 66-75, 1995; E. R. Maher et at, J. Med. Genet., 33: 328-332, 1996; B. Zbar, Cancer Surv., 25: 219-232, 1995). Recently a quantitative Southern blotting procedure was found to improve this frequency (C. Stolle et al., Hum. Mutat., 12: 417-423, 1998). In the present study, we report the use of fluorescence in situ hybridization (FISH) as a method to detect and characterize VHL germline deletions. We reexamined a group of VHL patients shown previously by single-strand conformation and sequencing. analysis not to harbor point mutations in the VHL locus. We found constitutional deletions in 29 of 30 VHL patients In this group using cosmid and PI probes that cover the VHL locus. We then tested six phenotypically normal offspring from four of these VHL families: two were found to carry the deletion and the other four were deletion-free. In addition, germline mosaicism of the VHL gene was identified in one family. In sum, FISH was found to be a simple and reliable method to detect VHL germline deletions and practically useful in cases where other methods of screening have failed to detect a VHL gene abnormality. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Off Director, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Dept Pathol, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Genet Diagnost Lab, Philadelphia, PA 19104 USA. RP Pak, E (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [N01-CO-56000] NR 21 TC 45 Z9 45 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1999 VL 59 IS 21 BP 5560 EP 5564 PG 5 WC Oncology SC Oncology GA 252KG UT WOS:000083500200032 PM 10554035 ER PT J AU Hsi, LC Angerman-Stewart, J Eling, TE AF Hsi, LC Angerman-Stewart, J Eling, TE TI Introduction of full-length APC modulates cyclooxygenase-2 expression in HT-29 human colorectal carcinoma cells at the translational level SO CARCINOGENESIS LA English DT Article ID HUMAN COLON-CANCER; BETA-CATENIN; GENE-PRODUCT; PROSTAGLANDINS; SYNTHASE-2; ADHESION; PROTEIN; TUMORIGENESIS; ASSOCIATION; ACTIVATION AB Mutation of the adenomatous polyposis coli (APC) gene is associated with the earliest stages of colorectal tumorigenesis and appears to be responsible for the hereditary condition familial adenomatous polyposis (FAP), Evidence indicates that cyclooxygenase-2 (COX-2) is induced and at elevated levels in human colorectal cancers and in the polyps of mouse FAP models. We have used HT-29 cells, a human colorectal carcinoma cell line with a mutant carboxy-truncated APC gene, in which intact APC gene has been introduced under the control of an inducible promoter, These HT-29-APC cells provide a suitable model system to examine how COX-2 expression becomes dysregulated after loss of APC function, Induction of full-length APC causes the HT-29-APC cells to undergo apoptosis, However, differentiation, as measured by alkaline phosphatase activity, is not induced upon expression of full-length APC, Full-length APC protein has been shown to bind the intracellular protein beta-catenin and, as a result, the Lef/Tcf transcription factors are down-regulated, Analysis of APC immunoprecipitates demonstrate a time-dependent increase of beta-catenin interacting with full-length APC, Thus, the Lef/Tcf signaling pathway is intact at this point in these cells. Furthermore, upon expression of full-length APC, COX-2 protein expression is down-regulated while COX-2 mRNA levels remain the same. These data indicate that APC plays a role, either directly or indirectly, in the translational regulation of COX-2, Treatment of the HT-29-APC cells with sodium butyrate, an inducer of apoptosis, does not alter COX-2 protein expression. Thus, COX-2 down-regulation appears to be APC specific and not just due to apoptotic induction. APC appears to uniquely regulate COX-2 expression. The mechanism by which COX-2 protein expression is down-regulated in the HT-29-APC cells is under investigation. C1 NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 51 Z9 52 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1999 VL 20 IS 11 BP 2045 EP 2049 DI 10.1093/carcin/20.11.2045 PG 5 WC Oncology SC Oncology GA 257UM UT WOS:000083800400002 PM 10545404 ER PT J AU Lazarous, DF Shou, M Stiber, JA Hodge, E Thirumurti, V Goncalves, L Unger, EF AF Lazarous, DF Shou, M Stiber, JA Hodge, E Thirumurti, V Goncalves, L Unger, EF TI Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis SO CARDIOVASCULAR RESEARCH LA English DT Article DE collateral circulation; coronary circulation; gene therapy; growth factors; ischemia ID ENDOTHELIAL GROWTH-FACTOR; IN-VIVO; BLOOD-FLOW; THERAPEUTIC ANGIOGENESIS; RABBIT MODEL; HEPARIN; VECTORS; HYPOXIA; LIMB; INJECTION AB Objective: Angiogenic peptides like VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) have entered clinical trials for coronary artery disease. Attempts are being made to devise clinically relevant means of delivery and to effect site-specific delivery of these peptides to the cardiac tissue, in order to limit systemic side-effects. We characterized the response of the pericardium to delivery of a replication-deficient adenovirus carrying the cDNA for AdCMV.VEGF(165), and assessed the effect of pericardial VEGF(165) on myocardial collateral development in a canine model of progressive coronary occlusion. Methods: Ameroid constrictors were placed on the proximal left circumflex coronary artery of mongrel dogs. Ten days later, 6x10(9) pfu AdCMV.VEGF(165) (n=9, AdRSV.beta-gal (n=9), or saline (n=7) were injected through an indwelling pericardial catheter. Transfection efficiency was assessed by X-gal staining. Pericardial and serum VEGF levels were measured serially by ELISA. Maximal myocardial collateral perfusion was quantified with radiolabeled or fluorescent microspheres 28 days after treatment. Results: In AdRSV.beta-gal-treated dogs, there was extensive beta-gal staining in the pericardium and epicardium, with minimal beta-gal staining in the mid-myocardium and endocardium. Pericardial delivery of AdCMV.VEGF(165) resulted in sustained (8-14 day) pericardial transgene expression, with VEGF levels peaking 3 days after infection (>200 ng/ml) and decreasing; thereafter. There was no detectable increase in serum VEGF levels. Maximal collateral perfusion, a principal correlate of collateral development and angiogenesis, was equivalent in all groups. Conclusion: Adenoviral-mediated gene transfer is capable of inducing sustained VEGF(165) expression in the pericardium; however, locally targeted pericardial VEGF delivery failed to improve myocardial collateral perfusion in this model. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NHLBI, Expt Physiol & Pharmacol Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Lazarous, DF (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, Johns Hopkins Bayview Med Ctr, A1 E,4940 Eastern Ave, Baltimore, MD 21224 USA. OI Goncalves, Lino/0000-0001-9255-3064 NR 37 TC 72 Z9 80 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV PY 1999 VL 44 IS 2 BP 294 EP 302 DI 10.1016/S0008-6363(99)00203-5 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 253FW UT WOS:000083546700010 PM 10690306 ER PT J AU Liu, DM Lin, SZ Wang, SD Wu, MY Wang, Y AF Liu, DM Lin, SZ Wang, SD Wu, MY Wang, Y TI Xenografting human T2 sympathetic ganglion from hyperhidrotic patients provides short-term restoration of catecholaminergic functions in hemiparkinsonian athymic rats SO CELL TRANSPLANTATION LA English DT Article DE sympathetic ganglion; Parkinson's disease; transplantation; hyperhidrosis; athymic rats ID VENTRAL MESENCEPHALIC GRAFTS; SUPERIOR CERVICAL-GANGLION; NERVE GROWTH-FACTOR; NEURONS IN-VIVO; NEUROTROPHIC FACTOR; PALMAR HYPERHIDROSIS; DOPAMINE NEURONS; AUTOLOGOUS TRANSPLANTATION; PARKINSONS-DISEASE; INDUCED INJURY AB Previous studies have suggested that allografting peripheral sympathetic ganglia, such as superior cervical ganglia, partially relieves clinical or behavioral deficits in parkinsonian patients and animals. However, removal of these ganglia can cause Horner's syndrome, which limits the utilization of this approach. Hyperhidrosis, a disease of excessive sweating, is commonly seen in young Orientals. Treatment of hyperhidrosis often involves surgical removal of the second thoracic sympathetic ganglia (T2G), which contain catecholaminergic neurons. The purpose of our study was to investigate behavioral responses and tyrosine hydroxylase (TH) immunoreactivity in hemiparkinsonian rats at different time points after transplantation of human T2G from hyperhidrotic patients. Athymic Fisher 344 rats were injected unilaterally with 6-hydroxydopamine into the medial forebrain bundle to destroy the nigrostriatal dopaminergic (DA) pathway. The effectiveness of lesions was tested by measuring methamphetamine (MA)-induced rotations. These unilaterally lesioned rats were later transplanted with T2G or T2 fiber tract (T2F) obtained from adult hyperhidrotic patients. Animals grafted with T2G showed a reduction in MA-induced rotation by 2 weeks; however, rotation returned to the pregrafting levels by 3 months. Animals receiving T2F grafts did not show any reduction of rotation over a 3-month period. Animals were later sacrificed for TH immunostaining at different time points. Tyrosine hydroxylase-positive [TH(+)] cell bodies and fibers were found in the lesioned striatum 2-4 weeks after T2G grafting, suggesting the survival of transplant. Two to 3 months after grafting, TH(+) fibers were still found in almost all the recipients. However, TH(+) cell bodies were found in only three of seven rats studied. Animals receiving T2F grafting did not show any TH immunoreactivity in the lesioned striatum over the 3-month period. These data indicate that T2G transplants from adult hyperhidrotic patients can survive and provide transient normalization of the motor behavior in the hemiparkinsonian athymic rats. Because of the short-term improvement in behavior after grafting, the use of T2G in human trials should be cautious at the present time. Further laboratory research is required. C1 Natl Inst Drug Abuse, IRP, Baltimore, MD 21224 USA. Natl Def Med Ctr, TriServ Gen Hosp, Taipei, Taiwan. RP Wang, Y (reprint author), Natl Inst Drug Abuse, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 2 Z9 2 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD NOV-DEC PY 1999 VL 8 IS 6 BP 583 EP 591 PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 285DH UT WOS:000085374000004 PM 10701487 ER PT J AU Benathan, M Virador, V Furumura, M Kobayashi, N Panizzon, RG Hearing, VJ AF Benathan, M Virador, V Furumura, M Kobayashi, N Panizzon, RG Hearing, VJ TI Co-regulation of melanin precursors and tyrosinase in human pigment cells: Roles of cysteine and glutathione SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 8th Meeting of the European-Society-for-Pigment-CellResearch CY SEP 23-26, 1998 CL PRAGUE, CZECH REPUBLIC SP European Soc Pigment Cell Res DE melanocytes; melanoma cells; cysteine; glutathione; DOPA; 5-S-cysteinyldopa; tyrosinase; tyrosinase-related protein 1; eumelanin; pheomelanin ID 5-S-CYSTEINYLDOPA FORMATION; INTRACELLULAR THIOLS; CULTURED MELANOCYTES; INHIBITION; MELANOGENESIS; COPPER; DOPA AB Glutathione (GSH) and cysteine (CysH) have both been implicated in the biogenesis of the pheomelanin precursor 5-S-cysteinyldopa (5-S-CD), However, recent studies have shown that only CysH is transported across the membrane of isolated melanosomes, and that the positive regulation of CysH in pigment cells leads to an increased production of 5-S-CD, In the present study, the question was examined as to whether melanin precursors and tyrosinase could be coregulated by cellular thiols, To address this issue, the levels of CysH and GSH were varied in normal melanocytes and melanoma cells using buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis, Treatment with 50-100 mu M BSO decreased GSH levels to less than 10% of control, and increased CysH levels between two- and five-fold in both cell types. Concomitant with this, an increase in the ratio of 5-S-CD to DOPA and a decrease in the pigment content of the cells were observed. The decrease in cell pigmentation was associated with strong decreases in tyrosine hydroxylase activity and C-14-melanin production. Only melanoma cells showed a modified tyrosinase isozyme pattern on Western immunoblots in response to BSO, while the mRNA expression of tyrosinase and TRP-1 were unchanged in both cell types. These results suggest that the balance between CysH and GSH, which is partly determined by the rate of utilization of CysH for GSH biosynthesis, regulates not only the levels of 5-S-CD and DOPA but also the melanogenic activity of pigment cells. Since DOPA functions as a cofactor in the monophenolase reaction of tyrosinase, it is proposed that the ratio of S-CD to DOPA may be an important factor in the regulation of tyrosinase activity in situ. C1 CHU Vaudois, Dept Dermatol, DHURDV, CH-1011 Lausanne, Switzerland. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Benathan, M (reprint author), CHU Vaudois, Dept Dermatol, DHURDV, CH-1011 Lausanne, Switzerland. NR 31 TC 12 Z9 12 U1 0 U2 5 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD NOV PY 1999 VL 45 IS 7 BP 981 EP 990 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273ZP UT WOS:000084739500012 PM 10644002 ER PT J AU Matsunaga, J Sinha, D Solano, F Santis, C Wistow, G Hearing, V AF Matsunaga, J Sinha, D Solano, F Santis, C Wistow, G Hearing, V TI Macrophage migration inhibitory factor (MIF) - Its role in catecholamine metabolism SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 8th Meeting of the European-Society-for-Pigment-CellResearch CY SEP 23-26, 1998 CL PRAGUE, CZECH REPUBLIC SP European Soc Pigment Cell Res DE dopamine; cytotoxicity; apoptosis; neuromelanin ID DOPAMINE INDUCES APOPTOSIS; D-DOPACHROME TAUTOMERASE; PARKINSONS-DISEASE; CELL-DEATH; CLONING; MECHANISM; NEURONS; GENE AB Macrophage migration inhibitory factor (MIF) was originally identified several decades ago as a lymphokine-derived protein that inhibited monocyte migration. Recently, it has been reported that MIF has D-dopachrome tautomerase, phenylpyruvate tautomerase and thiol protein oxidoreductase activities, although the physiological significance of those activities is not yet clear. Here we show that MIF is able to catalyze the conversion of dopaminechrome and norepinephrinechrome, toxic quinone products of the neurotransmitters dopamine and norepinephrine, respectively, to indole derivatives that may serve as precursors to neuromelanin. Since MIF is highly expressed in human brain, these observations raise the possibility that MIF participates in a detoxification pathway for catecholamine products and could therefore have an important role for neural tissues. The potential role of MIF in the formation of neuromelanin from catecholamines is also an extremely interesting possibility. C1 NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NEI, Mol Struct & Funct Sect, NIH, Bethesda, MD 20892 USA. Univ Murcia, Sch Med, Dept Biochem & Mol Biol B, E-30071 Murcia, Spain. RP Hearing, V (reprint author), NIH, Cell Biol Lab, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. RI Solano, Francisco/G-5001-2013 OI Solano, Francisco/0000-0001-9612-761X NR 20 TC 23 Z9 24 U1 0 U2 0 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD NOV PY 1999 VL 45 IS 7 BP 1035 EP 1040 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273ZP UT WOS:000084739500017 PM 10644007 ER PT J AU Sumner, SCJ Fennell, TR Moore, TA Chanas, B Gonzalez, F Ghanayem, BI AF Sumner, SCJ Fennell, TR Moore, TA Chanas, B Gonzalez, F Ghanayem, BI TI Role of cytochrome P450 2E1 in the metabolism of acrylamide and acrylonitrile in mice SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; URINARY METABOLITES; 2-CYANOETHYLENE OXIDE; CYANOETHYLENE OXIDE; RATS; DNA; PHARMACOKINETICS; POLYMORPHISMS; MECHANISMS; OXIDATION AB Acrylonitrile (AN) and acrylamide (AM) are commonly used in the synthesis of plastics and polymers. In rodents, AM and AN are metabolized to the epoxides glycidamide and cyano-ethylene oxide, respectively. The aim of this study was to determine the role of cytochrome P450 in the metabolism of AM and AN in vivo. Wild-type (WT) mice, WT mice pretreated with aminobenzotriazole (ABT, 50 mg/kg ip, 2 h pre-exposure), and mice devoid of cytochrome P450 2E1 (P450 2E1-null) were treated with 50 mg/kg [C-13]AIM po. WT mice and P450 2E1-null mice were treated with 2.5 or 10 mg/kg [C-13]AN po. Urine was collected for 24 h, and metabolites were characterized using C-13 NMR. WT mice excreted metabolites derived from the epoxides and from direct GSH conjugation with AM or AN. Only metabolites derived from direct GSH conjugation with AM or AN were observed in the urine from ABT-pretreated WT mice and P450 2E1-null mice. On the basis of evaluation of urinary metabolites at these doses, these data suggest that P450 2E1 is possibly the only cytochrome P450 enzyme involved in the metabolism of AM and AN in mice, that inhibiting total P450 activity does not result in new pathways of non-P450 metabolism of AM, and that mice devoid of P450 2E1 do not excrete metabolites of AM or AN that would be produced by oxidation by other cytochrome P450s. P450 2E1-null mice may be an appropriate model for the investigation of the role of oxidative metabolism in the toxicity or carcinogenicity of these compounds. C1 Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NCI, Bethesda, MD 20892 USA. RP Sumner, SCJ (reprint author), Chem Ind Inst Toxicol, 6 Davis Dr,POB 12137, Res Triangle Pk, NC 27709 USA. RI Fennell, Tim/D-9936-2013 NR 37 TC 197 Z9 203 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 1999 VL 12 IS 11 BP 1110 EP 1116 DI 10.1021/tx990040k PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 257HR UT WOS:000083776900010 PM 10563837 ER PT J AU Fan, SJ Duba, DE O'Connor, PM AF Fan, SJ Duba, DE O'Connor, PM TI Cellular effects of olomoucine in human lymphoma cells differing in p53 function SO CHEMOTHERAPY LA English DT Article DE olomoucine; p53; cyclin E/Cdk2; cyclin B1/Cdc2; Burkitt's lymphoma and lymphoblastoid cells cell cycle; chemosensitivity ID CYCLIN-DEPENDENT KINASES; INHIBITOR OLOMOUCINE; CANCER CELLS; APOPTOSIS; SURVIVAL; GENE; PHOSPHORYLATION; OVEREXPRESSION; ROSCOVITINE; DISRUPTION AB Olomoucine, a purine derivative, inhibits multiple cyclin-dependent kinases that play important roles in regulating the G1/S and G2/M transitions of the cell cycle. In this study we investigated the cellular effects of olomoucine in two human Burkitt's lymphoma cell lines, WMN (containing wild-type p53) and CA46 (containing mutant p53), and found that in consistency with its ability to block the activity of cyclin E/Cdk2 and cyclin B1/Cdc2 kinases, olomoucine caused cell cycle arrest at both G1/S and G2/S boundaries. Moreover, cell cycle arrest occurred equally well in these two cell lines bearing different p53 gene status, suggesting that p53 was not responsible for the cell cycle arrest by olomoucine. A similar p53-independent fashion was also observed in the cytotoxic potency and apoptosis induction of olomoucine, in contrast to ionizing radiation which caused more cytotoxic activity and apoptosis in the WMN cell line bearing wild-type p53 compared with CA46 cells bearing mutant p53. Such p53-independent cytotoxicity of olomoucine was also confirmed in other human Burkitt's lymphoma and lymphoid cell lines containing wild-type and mutant p53. Therefore, our results give an impetus to continued research into olomoucine that might be a very useful chemotherapeutic strategy in the treatment of patients with mutant p53 tumors, at least in lymphoma patients. Copyright (C) 1999 S. Karger AG, Basel. C1 Long Isl Jewish Med Ctr, Dept Radiat Oncol, New Hyde Park, NY 10042 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Fan, SJ (reprint author), Long Isl Jewish Med Ctr, Dept Radiat Oncol, 270-05,76th Ave, New Hyde Park, NY 10042 USA. NR 30 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 J9 CHEMOTHERAPY JI Chemotherapy PD NOV-DEC PY 1999 VL 45 IS 6 BP 437 EP 445 DI 10.1159/000007237 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 257BT UT WOS:000083762300006 PM 10567774 ER PT J AU Roessler, E Muenke, M AF Roessler, E Muenke, M TI The molecular genetics of holoprosencephaly: a model of brain development for the next century SO CHILDS NERVOUS SYSTEM LA English DT Article; Proceedings Paper CT World Conference on Pediatric Neurosurgery, 2000 AD CY NOV 27-DEC 04, 1999 CL MARTINIQUE DE holoprosencephaly; sonic hedgehog; SIX3; ZIC2 ID SONIC-HEDGEHOG GENE; RETINOIC ACID; CRITICAL REGION; MOUSE EMBRYOS; EXPRESSION; MUTATIONS; DROSOPHILA; ORGANIZER; DISORDERS; POLARITY AB The recent identification of some of the human holoprosencephaly,genes is beginning to elucidate the intricate developmental programs that pattern normal and abnormal brain development, Here we present some of these advances in the context of our present understanding and conclude with some speculations regarding the direction for future investigations. We are living in a tremendously exciting time in medicine with the rapid application of molecular genetic approaches to the understanding of human disease. It is the purpose of this review to stress the underlying principals of our approach at a level that can be readily appreciated by colleagues who themselves are experts in brain anatomy but not necessarily the molecular genetics of brain development. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Genet & Neurol, Philadelphia, PA 19104 USA. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, Bldg 10,10C101, Bethesda, MD 20892 USA. NR 47 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0256-7040 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD NOV PY 1999 VL 15 IS 11-12 BP 646 EP 651 DI 10.1007/s003810050453 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 258WM UT WOS:000083862700005 PM 10603005 ER PT J AU Muller, S Stanyon, R O'Brien, PCM Ferguson-Smith, MA Plesker, R Wienberg, J AF Muller, S Stanyon, R O'Brien, PCM Ferguson-Smith, MA Plesker, R Wienberg, J TI Defining the ancestral karyotype of all primates by multidirectional chromosome painting between tree shrews, lemurs and humans SO CHROMOSOMA LA English DT Article ID INSITU SUPPRESSION HYBRIDIZATION; IN-SITU HYBRIDIZATION; ZOO-FISH ANALYSIS; REARRANGEMENTS; FLUORESCENCE; HOMOLOGIES; SEGMENTS AB We used multidirectional chromosome painting with probes derived by bivariate flourescence-activated flow sol ting of chromosomes from human, black lemur (Eulemur macaco macaco) and tree shrew (Tupaia belangeri, order Scandentia) to better define the karyological relationship of tree shrews and primates. An assumed close relationship between tree shrews and primates also assists in the reconstruction of the ancestral primate karyotype taking the tree shrew as an "out-group" species. The results indicate that T. belangeri has a highly derived karyotype. Tandem fusions or fissions of chromosomal segments seem to be the predominant mechanism in the evolution of this tree shrew karyotype. The 22 human autosomal painting probes delineated 40 different segments, which is in the range found in most mammals analyzed by chromosome painting up to now. There were no reciprocal translocations that would distinguish the karyotype of the tree shrew from an assumed primitive primate karyotype. This karyotype would have included the chromosomal forms la, Ib, 2a, 2b, 3/21, 4-11, 12a/22a, 12b/22b, 13, 14/15, 16a, 16b, 17, 18, 19a, 19b, 20 and X and Y and had a diploid chromosome number of 2n = 50. Of these forms, chromosomes la, Ib, 4, 8, 12a/22a, and 12b/22b may be common derived characters that would link the tree shrew with primates. To define the exact phylogenetic relationships of the tree shrews and the genomic rearrangements that gave rise to the primates and eventually to humans further chromosome painting in Rodentia, Lagomorpha, Dermoptera and Chiroptera is needed, but many of the landmarks of genomic evolution are now known. C1 Univ Munich, Inst Anthropol & Human Genet, D-8000 Munich, Germany. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. NCI, Lab Gen Divers, Frederick, MD 21702 USA. Paul Ehrlich Inst, Frankfurt, Germany. RP Wienberg, J (reprint author), Univ Munich, Inst Anthropol & Human Genet, D-8000 Munich, Germany. OI Stanyon, Roscoe/0000-0002-7229-1092 NR 35 TC 83 Z9 86 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD NOV PY 1999 VL 108 IS 6 BP 393 EP 400 DI 10.1007/s004120050391 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 258JZ UT WOS:000083837200007 PM 10591999 ER PT J AU Takahashi, H Iwata, T Kitagawa, Y Takahashi, RH Sato, Y Wakabayashi, H Takashima, M Kido, H Nagashima, K Kenney, K Gibbs, CJ Kurata, T AF Takahashi, H Iwata, T Kitagawa, Y Takahashi, RH Sato, Y Wakabayashi, H Takashima, M Kido, H Nagashima, K Kenney, K Gibbs, CJ Kurata, T TI Increased levels of epsilon and gamma isoforms of 14-3-3 proteins in cerebrospinal fluid in patients with Creutzfeldt-Jakob disease SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID SPONGIFORM ENCEPHALOPATHIES; DIAGNOSIS; VARIANT; MARKER AB We established four hybridoma cell lines producing monoclonal antibodies (MAbs) against 14-3-3 proteins. Immunoblot analysis revealed that epsilon and gamma isoforms were specifically increased in premortem cerebrospinal fluid samples from patients with sporadic Creutzfeldt-Jakob disease. Furthermore, dot immunoblot analysis shelved that MAbs were more specific for native antigen than polyclonal antibodies were. C1 Natl Inst Infect Dis, Dept Pathol, Shinjuku Ku, Tokyo 1628640, Japan. Univ Tokushima, Inst Enzyme Res, Div Enzyme Chem, Tokushima 770, Japan. Hokkaido Univ, Sch Med, Lab Mol & Cellular Pathol, Sapporo, Hokkaido 060, Japan. CREST, JST, Sapporo, Hokkaido, Japan. Natl Inst Neurol Disorders & Stroke, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD USA. RP Takahashi, H (reprint author), Natl Inst Infect Dis, Dept Pathol, Shinjuku Ku, Toyama 1-23-1, Tokyo 1628640, Japan. NR 12 TC 20 Z9 21 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 1999 VL 6 IS 6 BP 983 EP 985 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 254RF UT WOS:000083625400037 PM 10548598 ER PT J AU Bates, SE AF Bates, SE TI Drug resistance: Still on the learning curve SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID MDR1 GENE-EXPRESSION; MULTIDRUG-RESISTANCE; BINDING-PROTEIN; PHASE-I; ACTIVATION; PROMOTER; YB-1; INVOLVEMENT; MODULATORS; INDUCTION C1 NCI, Med Branch, Bethesda, MD 20814 USA. RP Bates, SE (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 11 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 IS 11 BP 3346 EP 3348 PG 3 WC Oncology SC Oncology GA 258RP UT WOS:000083853200002 PM 10589742 ER PT J AU Chaudhry, A Carrasquillo, JA Avis, IL Shuke, N Reynolds, JC Bartholomew, R Larson, SM Cuttitta, F Johnson, BE Mulshine, JL AF Chaudhry, A Carrasquillo, JA Avis, IL Shuke, N Reynolds, JC Bartholomew, R Larson, SM Cuttitta, F Johnson, BE Mulshine, JL TI Phase I and imaging trial of a monoclonal antibody directed against gastrin-releasing peptide in patients with lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SMALL-CELL-CARCINOMA; BOMBESIN; GROWTH; T101; RADIOIMMUNODETECTION; CHEMOTHERAPY; EXPRESSION; CISPLATIN; LYMPHOMA; THERAPY AB Small cell lung cancer (SCLC) cells express and secrete bombesin-like peptides (BLP) that can activate specific receptors that stimulate the growth of these cells. A murine monoclonal antibody, 2A11, which binds to the BLP, gastrin-releasing peptide with high affinity, has been reported to decrease the growth of SCLC cells in vitro and in athymic nude mice. A Phase I trial in lung cancer patients was performed using multiple doses of 2A11, Thirteen patients with lung cancer received 12 doses of 2A11 antibody three times a week for 4 weeks at one of four dose levels. Serum samples were obtained prior to initiation and before each dose of 2A11 antibody therapy for measurement of 2A11 antibody levels and determination of serum human antimouse antibody levels. A pilot imaging evaluation using (111)In conjugated 2A11 monoclonal antibody was also performed in the same patients to aid in the study of pharmacokinetics and biodistribution. No toxic reactions were observed, and none of the patients developed detectable human antimouse antibody; however, no objective antitumor responses were observed. The mean trough serum 2A11 levels in patients increased with increasing dose level: 0.26 +/- 0.2 mu g/ml, 6.7 +/- 6 mu g/ml, 71.5 +/- 60 mu g/ml, 248 +/- 184 mu g/ml for dose levels 1 mg/m(2), 10 mg/m(2), 100 mg/m(2), and 250 mg/m(2), respectively, At each dose level, sustained detectable serum levels of the monoclonal antibody were achieved. Tumor uptake was noted in 11 of 12 patients who were injected with (111)In conjugated 2A11, Because no dose-limiting clinical toxicity was observed, a mathematical model was used to define the recommended Phase II dose of 250 mg/m(2). This trial established that repeated doses of monoclonal antibody 2A11 could be given safely to patients, and sustained levels could be achieved for a 1-week schedule. Further evaluation of the antitumor effects of 2A11 is warranted. C1 NCI, Intervent Sect, Dept Cell & Canc Biol, Med Branch,Div Clin Sci,Clin Ctr,NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. Hybritech Inc, San Diego, CA 92121 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Dept Cell & Canc Biol, Med Branch,Div Clin Sci,Clin Ctr,NIH, Room 12N226, Bethesda, MD 20892 USA. EM mulshinej@bprb.nci.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 47 TC 47 Z9 47 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 IS 11 BP 3385 EP 3393 PG 9 WC Oncology SC Oncology GA 258RP UT WOS:000083853200009 PM 10589749 ER PT J AU Hu, N Roth, MJ Emmert-Buck, MR Tang, ZZ Polymeropolous, M Wang, QH Goldstein, AM Han, XY Dawsey, SM Ding, T Giffen, C Taylor, PR AF Hu, N Roth, MJ Emmert-Buck, MR Tang, ZZ Polymeropolous, M Wang, QH Goldstein, AM Han, XY Dawsey, SM Ding, T Giffen, C Taylor, PR TI Allelic loss in esophageal squamous cell carcinoma patients with and without family history of upper gastrointestinal tract cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; LASER CAPTURE MICRODISSECTION; SHANXI-PROVINCE; CHINA; HETEROZYGOSITY; ADENOCARCINOMA; IDENTIFICATION; ALLELOTYPE; SEQUENCE; 11P15 AB Chromosomal regions with frequent allelic loss may point to major susceptibility genes that will assist in understanding molecular events involved in esophageal carcinogenesis. Esophageal squamous cell carcinoma samples and blood from 46 patients, including 23 patients with and 23 patients without a family history of upper gastrointestinal dancer, were screened using laser microdissected DNA and tested for Loss of heterozygosity (LOH) at 18 marker loci representing 14 chromosomal regions (on 2q, 3p, 4p, 4p, 5q, 6q, 8p, 9p, 9q, lip, 13q, 14q, 15q, and 17p) identified in an earlier genome-wide scan to have frequent LOH, Clinical/pathological and lifestyle risk factor data were also collected, For all 46 tumors combined, the lowest frequency LOH for any of the 18 markers was 37%, and 8 markers showed LOH in greater than or equal to 75% of informative tumors, One marker (D13S894 on 13q) showed greater LOH in patients with a positive family history (93% versus 50%; P = 0.04), whereas two markers (D6S1027 on 6q and D9S910 on 9q) had significantly more LOH in patients with metastasis, and one marker (D4S2361 on 4p) showed significantly higher LOH in patients with a lower pathological tumor grade. No relation was seen between LOH and lifestyle risk factors. This study confirms the previously observed high frequency LOH for these 14 chromosomal regions, including a locus on 13q where LOH is more common in patients with a family history of upper gastrointestinal cancer than in those without such history, suggesting that a gene in this area may be involved in genetic susceptibility to esophageal cancer. C1 NCI, Bethesda, MD 20892 USA. Shanxi Canc Hosp & Inst, Taiyuan 030013, Shanxi, Peoples R China. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Taylor, PR (reprint author), NCI, Room 321,6006 Execut Blvd, Bethesda, MD 20892 USA. NR 27 TC 53 Z9 60 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 IS 11 BP 3476 EP 3482 PG 7 WC Oncology SC Oncology GA 258RP UT WOS:000083853200021 PM 10589761 ER PT J AU Koivisto, PA Schleutker, J Helin, H Ehren-van Eekelen, C Kallioniemi, OP Trapman, J AF Koivisto, PA Schleutker, J Helin, H Ehren-van Eekelen, C Kallioniemi, OP Trapman, J TI Androgen receptor gene alterations and chromosomal gains and losses in prostate carcinomas appearing during finasteride treatment for benign prostatic hyperplasia SO CLINICAL CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; THERAPY FAILURE; CANCER; AMPLIFICATION; PROGRESSION AB Finasteride is commonly used for the treatment of benign prostatic hyperplasia and has been suggested to prevent prostate cancer development. To gain insight to the molecular effects of finasteride on prostate cancer development, me studied six prostate cancers diagnosed during finasteride treatment for benign prostatic hyperplasia. Comparative genomic hybridization detected genetic alterations in four tumors (1-5 changes/tumor). Xq gains and 6q losses were the most common alterations. The recurrent Xq gains motivated us to study the involvement of the androgen receptor (AR) gene. One tumor with Xq gain had a 3-fold amplification of the AR gene, suggesting that tumor development in finasteride-treated patients may require increased AR copy number and expression, as has previously been shown. for prostate cancers recurring during hormonal therapy. Furthermore, in another tumor, an Arg726Leu mutation of the AR gene was found, This mutation was also present in the germ-line DNA of the patient. Arg726Leu mutation has previously been reported to affect the trans-activational properties of the AR, In summary, prostate cancers developing during finasteride therapy may have distinct biological properties, such as a low number of chromosomal alterations and frequent involvement of the AR gene. Further studies are needed to explore the role of germ-line AR mutations in these patients. C1 Tampere Univ Hosp, Canc Genet Lab, FIN-33521 Tampere, Finland. Tampere Univ Hosp, Dept Clin Chem, FIN-33521 Tampere, Finland. Tampere Univ Hosp, Dept Pathol, FIN-33521 Tampere, Finland. NIH, Natl Ctr Human Genome Res, Canc Genet Lab, Bethesda, MD 20892 USA. Erasmus Univ, Dept Pathol, NL-3000 DR Rotterdam, Netherlands. RP Koivisto, PA (reprint author), Tampere Univ Hosp, Canc Genet Lab, POB 2000, FIN-33521 Tampere, Finland. EM blpako@uta.fi 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 21 TC 28 Z9 29 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 IS 11 BP 3578 EP 3582 PG 5 WC Oncology SC Oncology GA 258RP UT WOS:000083853200034 PM 10589774 ER PT J AU Kokkinakis, DM Moschel, RC Pegg, AE Schold, SC AF Kokkinakis, DM Moschel, RC Pegg, AE Schold, SC TI Eradication of human medulloblastoma tumor xenografts with a combination of O-6-benzyl-2 '-deoxyguanosine and 1,3-bis(2-chloroethyl)-1-nitrosoureal SO CLINICAL CANCER RESEARCH LA English DT Article ID O-6-METHYLGUANINE-DNA METHYLTRANSFERASE ACTIVITY; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; DNA METHYLTRANSFERASE; ALKYLATING-AGENTS; CROSS-LINKING; O-6-BENZYLGUANINE; DEPLETION; CHLOROETHYLNITROSOUREA; METABOLISM; CELLS AB O-6-Benzyl-2'-deoxyguanosine (dBG), a water-soluble inhibitor of O-6-methylguanine-DNA methyltransferase (MGMT), potentiates the efficacy of 1,3-bis(2-chloroethyl)I-nitrosourea (BCNU) against MGMT-positive, BCNU-resistant Daoy human medulloblastoma tumor xenografts in athymic mice (S. C. Schold et at, Cancer Res., 56: 2076-2081, 1996), Such potentiation was comparable to that observed ed for O-6-benzylguanine, the prototype MGMT inhibitor that is currently undergoing clinical trials, In this study, we optimized the therapeutic effect of the dBG and BCNU combination against brain tumor xenografts without inducing substantial toxicity in the host by adjusting the doses of both compounds. dBG was escalated from 133 mg/m(2) to 200 and 300 mg/m(2), whereas corresponding doses of BCNU were reduced from 25 mg/m(2) to 17 and 11 mg/m(2), respectively. The growth delays of 30.2, 38.4, and 22.3 days, respectively, observed for the above regimens suggest that the optimal drug combination is not achieved with maximum doses of dBG, In fact, the highest doses of dBG (300 mg/m(2)) contributed to more frequent BCNU-related toxicities, despite the reduced BCNU dosage, and a reduction of the therapeutic effect. Toxicity was related to the depletion of MGMT activity in the gut of host mice and was manifested by edema, inflammation, and hemorrhage in the bowel wall by subsequent BCNU administration. With additional dosage adjustments, we found that tumor suppression of >90 days without toxicity was observed at 200 mg/m(2) dB6 and 23 mg/m(2) BCNU, At these doses, tumors were eradicated (regressed to an undetectable size for >90 days) in 8 of 12 animals. Thus, dBG is the first of the MGMT inhibitors to show a curative effect in combination with BCNU against a human central nervous system turner xenograft in athymic mice. C1 Univ Texas, SW Med Ctr, Dept Neurosurg, Dallas, TX 75235 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA. Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. RP Kokkinakis, DM (reprint author), Univ Texas, SW Med Ctr, Dept Neurosurg, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NCI NIH HHS [CA 57725, CA78561] NR 37 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 IS 11 BP 3676 EP 3681 PG 6 WC Oncology SC Oncology GA 258RP UT WOS:000083853200046 PM 10589786 ER PT J AU Dowlati, A Majka, S Hopper, C Ingalls, S Spiro, T Gerson, S Ivy, P Willson, JKV Sedransk, N Remick, SC AF Dowlati, A Majka, S Hopper, C Ingalls, S Spiro, T Gerson, S Ivy, P Willson, JKV Sedransk, N Remick, SC TI The activity and pharmacokinetics of rebeccamycin analog (NSC 655649) in cancer of the biliary tract during a phase I trial. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Case Western Reserve Univ, Ireland Canc Ctr, Dev Therapeut Program, Cleveland, OH 44106 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 4 BP 3729S EP 3729S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700005 ER PT J AU Gabrielsen, B Carroll, K Lovoy, E Marquis, S Stackhouse, T Twomey, P Maurey, K Sybert, K AF Gabrielsen, B Carroll, K Lovoy, E Marquis, S Stackhouse, T Twomey, P Maurey, K Sybert, K TI National Cancer Institute: Connections with commercial partners for technology development. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Technol Dev & Commercializat Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 46 BP 3739S EP 3739S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700047 ER PT J AU Becker, KF Mages, J Handschuh, G Kremmer, E Wang, QC Pastan, I Hofler, H AF Becker, KF Mages, J Handschuh, G Kremmer, E Wang, QC Pastan, I Hofler, H TI Mutant E-cadherin as basis for cancer specific immunotoxins. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Pathol, D-85764 Neuherberg, Germany. GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Mol Immunol, D-85764 Neuherberg, Germany. NCI, NIH, Mol Biol Lab, Bethesda, MD 20892 USA. Tech Univ Munich, Klinikum Rechts Isar, Inst Pathol, D-81675 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 87 BP 3747S EP 3747S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700088 ER PT J AU Dowlati, A Robertson, K Ksenich, P Jacobberger, J Whitacre, C Schnur, G Cooper, B Spiro, T Lazarus, H Gerson, S Murgo, A Sedransk, N Remick, SC AF Dowlati, A Robertson, K Ksenich, P Jacobberger, J Whitacre, C Schnur, G Cooper, B Spiro, T Lazarus, H Gerson, S Murgo, A Sedransk, N Remick, SC TI Phase I trial of combination bryostatin-1 and vincristine in B-cell malignancies. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Case Western Reserve Univ, Ireland Canc Ctr, Dev Therapeut Program, Cleveland, OH 44106 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 113 BP 3752S EP 3753S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700114 ER PT J AU Kubo, A Nakagawa, K Varma, RK Conrad, NK Cheng, JQ Lee, WC Testa, JR Johnson, BE Kaye, FJ Kelley, MJ AF Kubo, A Nakagawa, K Varma, RK Conrad, NK Cheng, JQ Lee, WC Testa, JR Johnson, BE Kaye, FJ Kelley, MJ TI The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin dependent kinase (CDK) 4. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. NCI, MB & DTP, Bethesda, MD 20892 USA. RI kaye, frederic/E-2437-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 128 BP 3755S EP 3756S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700129 ER PT J AU Newell, DR Arris, CE Boyle, FT Calvert, AH Curtin, NJ Dewsbury, P Endicott, JA Garman, EF Gibson, AE Golding, BT Griffin, RJ Johnson, LN Lawrie, A Noble, MEM Sausville, EA Schultz, R AF Newell, DR Arris, CE Boyle, FT Calvert, AH Curtin, NJ Dewsbury, P Endicott, JA Garman, EF Gibson, AE Golding, BT Griffin, RJ Johnson, LN Lawrie, A Noble, MEM Sausville, EA Schultz, R TI Antiproliferative cyclin dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Oxford, Oxford OX1 2JD, England. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 124 BP 3755S EP 3755S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700125 ER PT J AU Giannakakou, P Sackett, DL Ward, Y Blagosklonny, M Fojo, T AF Giannakakou, P Sackett, DL Ward, Y Blagosklonny, M Fojo, T TI P53 is associated with cytoplasmic and spindle microtubules and requires functional microtubules for nuclear accumulation. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Med Branch, Bethesda, MD 20892 USA. NIDDK, Lab Integrat & Med Biophys, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 134 BP 3757S EP 3757S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700135 ER PT J AU Zaremba, S Siccardi, A Paganelli, G Schlom, J AF Zaremba, S Siccardi, A Paganelli, G Schlom, J TI Peptide-MHC monomers bound to tumor cell surfaces via an antibody-avidin bridge can mediate tumor killing by peptide-specific CTL. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Ist Sci San Raffaele, Milan, Italy. European Inst Oncol, Milan, Italy. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 164 BP 3763S EP 3763S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700165 ER PT J AU Lin, K Mikovits, JA Shoemaker, RH Sausville, EA Ricciardi, RP AF Lin, K Mikovits, JA Shoemaker, RH Sausville, EA Ricciardi, RP TI The DNA polymerase/processivity factor complex of Kaposi's sarcoma-associated herpesvirus: a novel target for high-through-put drug screening. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. NCI, SAIC Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 172 BP 3764S EP 3764S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700172 ER PT J AU Tang, NM Morrison, D Leung, DW Bonham, L Hollenback, DM Finney, RE AF Tang, NM Morrison, D Leung, DW Bonham, L Hollenback, DM Finney, RE TI Generation of phosphatidic acid by lysophosphatidic acid acyl transferase-beta is implicated in tumorigenesis, loss of "contact inhibition," reduced actin filaments, and activation of Raf-1 kinase. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Cell Therapeut Inc, Seattle, WA 98119 USA. Frederick Canc Res Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 171 BP 3764S EP 3764S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700171 ER PT J AU Pizer, ES Thupari, J Han, WF Pinn, ML Chrest, FJ Townsend, CA Kuhajda, FP AF Pizer, ES Thupari, J Han, WF Pinn, ML Chrest, FJ Townsend, CA Kuhajda, FP TI Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty acid synthase inhibition in human breast cancer cells and xenografts. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 188 BP 3767S EP 3767S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700187 ER PT J AU Makower, D Rozenblit, A Edelman, M Augenlicht, L Kaufman, H Haynes, H Zwiebel, J Wadler, S AF Makower, D Rozenblit, A Edelman, M Augenlicht, L Kaufman, H Haynes, H Zwiebel, J Wadler, S TI Efficacy of p53-directed ONYX-015 therapy in hepatobiliary tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, IDB, Bethesda, MD 20892 USA. Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY USA. Albert Einstein Canc Ctr, Dept Radiol, Bronx, NY USA. Albert Einstein Canc Ctr, Dept Pathol, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 211 BP 3772S EP 3772S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700210 ER PT J AU Myers, TG Holbeck, SL Bell, P Rubinstein, L Monks, A Drake, JC Sausville, EA AF Myers, TG Holbeck, SL Bell, P Rubinstein, L Monks, A Drake, JC Sausville, EA TI Exploring putative molecular determinants of cytotoxicity and antiproliferative effects in the NCI anticancer drug screen using pattern analysis tools. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Dev Therapeut Program, DCTD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 233 BP 3776S EP 3776S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700232 ER PT J AU Fletcher, TM Halliday, SM Ptak, RG Ward, PA Shoemaker, RH Mikovits, JA Sausville, EA Lin, K Ricciardi, RP Buckeit, RW AF Fletcher, TM Halliday, SM Ptak, RG Ward, PA Shoemaker, RH Mikovits, JA Sausville, EA Lin, K Ricciardi, RP Buckeit, RW TI A mammalian two-hybrid system for high throughput screening of inhibitors of the interaction between human herpesvirus 8 (HHV-8) polymerase and HHV-8 processivity factor. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Dev Therapeut Program, DCTD, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. So Res Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 250 BP 3779S EP 3779S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700249 ER PT J AU Ozbun, LL Jakowlew, SB AF Ozbun, LL Jakowlew, SB TI A novel transforming growth factor-beta 1-regulated gene in lung cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Med Branch, Dept Cell & Canc Biol, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 248 BP 3779S EP 3779S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700247 ER PT J AU Gussio, R Zaharevitz, DW McGrath, CF Pattabiraman, N Kellogg, GE Schultz, C Link, A Kunick, C Leost, M Meijer, L Sausville, EA AF Gussio, R Zaharevitz, DW McGrath, CF Pattabiraman, N Kellogg, GE Schultz, C Link, A Kunick, C Leost, M Meijer, L Sausville, EA TI Optimization of the paullone molecular scaffold for cyclin-dependent kinase inhibition: a structure-based, three-dimensional, quantitative structure activity relationship (3D QSAR) approach. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DTP, DCTD, Frederick, MD 21701 USA. Univ Hamburg, Inst Pharm, Hamburg, Germany. CNRS, Biol Stn, Roscoff, France. RI Kellogg, Glen/A-8008-2011; Link, Andreas/H-5067-2013 OI Link, Andreas/0000-0003-1262-6636 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 254 BP 3780S EP 3780S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700253 ER PT J AU McGrath, CF Pattabiraman, N Gussio, R Zaharevitz, DW Sausville, EA AF McGrath, CF Pattabiraman, N Gussio, R Zaharevitz, DW Sausville, EA TI Homology models for CDK1 and CDK1/cyclin B SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Adv Biol Comp Ctr, Frederick, MD USA. NCI, DTP, DCTD, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 255 BP 3780S EP 3781S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700254 ER PT J AU Shiotsu, Y An, GW Shulte, TW Neckers, LM Soga, S Murakata, C Tamaoki, T Inoue, K Akinaga, S AF Shiotsu, Y An, GW Shulte, TW Neckers, LM Soga, S Murakata, C Tamaoki, T Inoue, K Akinaga, S TI Novel oxime derivatives of radicicol induces erythroid differentiation associated with preferential G1 phase accumulation against chronic myelogenous leukemia cells through destabilization of bcr-abl with hsp90 complex. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Labs, Nagaizumi, Shizuoka 4118731, Japan. NCI, Clin Pharmacol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 291 BP 3787S EP 3787S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700290 ER PT J AU Beerheide, W Bernard, HU Tan, YJ Ganesan, A Rice, WG Ting, AE AF Beerheide, W Bernard, HU Tan, YJ Ganesan, A Rice, WG Ting, AE TI Novel screens for potential drugs against cervical cancer identify zinc ejecting inhibitors of the HPV-16 E6 oncoprotein. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore. NCI, Lab Antiviral Drug Mechanisms, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. RI Ganesan, A/F-6698-2011; ASTAR, IMCB/E-2320-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 294 BP 3788S EP 3788S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700293 ER PT J AU Blagosklonny, MV Dixon, SC Figg, WD AF Blagosklonny, MV Dixon, SC Figg, WD TI Selective loss of response to activators or inhibitors of PKC in prostate cancer cells: p2l/cyclin D1 balance. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 359 BP 3801S EP 3802S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700358 ER PT J AU Brognard, J Clark, A Oppoliner, A Dennis, P AF Brognard, J Clark, A Oppoliner, A Dennis, P TI Constitutive kinase activity and survival of non-small cell lung cancer cells: new molecular determinants of therapeutic resistance in lung cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Dept Dev Therapeut, Med Branch, NIH, Bethesda, MD 20889 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 355 BP 3801S EP 3801S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700354 ER PT J AU Marcu, MG Schulte, TW Neckers, LM AF Marcu, MG Schulte, TW Neckers, LM TI Localization of the novobiocin binding site on heat shock protein 90 (Hsp90) to the carboxyl terminal dimerization domain: Implications for alternative inhibition of Hsp90 activity. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Dept Cell & Canc Biol, Med Branch, NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 363 BP 3802S EP 3802S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700362 ER PT J AU Munster, PN Zheng, FZF Srethapakdi, M Sausville, E Rosen, N AF Munster, PN Zheng, FZF Srethapakdi, M Sausville, E Rosen, N TI Induction of differentiation and apoptosis in human breast cancer cell lines by modified geldanamycin derivatives (17-AAG). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 364 BP 3802S EP 3803S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700363 ER PT J AU Wigginton, JM Back, TC Gieselhart, L Wiltrout, TA Sayers, T McCormick, K Wiltrout, RH AF Wigginton, JM Back, TC Gieselhart, L Wiltrout, TA Sayers, T McCormick, K Wiltrout, RH TI IL-12/pulse IL-2 induces endothelial injury, inhibits tumor neovascularization, and induces complete tumor regression via mechanisms dependent on CD8(+) T cells and FAS-L. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DCS, POB, Bethesda, MD 20892 USA. NCI, IRSP, SAIC, LEI,DBS, Frederick, MD 21701 USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 379 BP 3805S EP 3805S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700378 ER PT J AU Wigginton, JM Wiltrout, TA Smith, J Back, TC Wiltrout, RH AF Wigginton, JM Wiltrout, TA Smith, J Back, TC Wiltrout, RH TI The antitumor activity of II-18/II-2: mechanisms accounting for the induction of complete tumor regression. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, IRSP, SAIC, LEI,DBS, Frederick, MD 21701 USA. NCI, POB DCS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 381 BP 3806S EP 3806S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700380 ER PT J AU Burger, AM McGown, A Kelland, L Fiebig, HH Harter, M Sausville, EA AF Burger, AM McGown, A Kelland, L Fiebig, HH Harter, M Sausville, EA TI Antivascular effects and antitumor activity of NSC 643314 in vitro and in vivo. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Paterson Inst Canc Res, Manchester M20 9BX, Lancs, England. Tumor Biol Ctr, Freiburg, Germany. Canc Res Inst, Sutton, Surrey, England. Bayer AG, D-5600 Wuppertal, Germany. NCI, DTP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 403 BP 3810S EP 3810S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700402 ER PT J AU Fortier, AH Fogler, WE Tomaszewski, JE DuVall, M Schweikart, KM Covey, JM Paciotti, GF Ruiz, A Sim, BKL AF Fortier, AH Fogler, WE Tomaszewski, JE DuVall, M Schweikart, KM Covey, JM Paciotti, GF Ruiz, A Sim, BKL TI Recombinant human Endostatin (TM) in Cynomolgus monkeys produces no toxicological effects following i.v. administration for 28 consecutive days. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 EntreMed Inc, Rockville, MD USA. NCI, Toxicol & Pharmacol Branch, DTP, Bethesda, MD 20892 USA. Covance Labs, Vienna, VA USA. Cytimmune Sci Inc, College Pk, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 417 BP 3813S EP 3813S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700416 ER PT J AU Tzung, SP Kim, KM Basanez, G Zimmerberg, J Zhang, KYJ Hockenbery, DM AF Tzung, SP Kim, KM Basanez, G Zimmerberg, J Zhang, KYJ Hockenbery, DM TI Antimycin a mimics a BH3 domain-containing peptide and selectively induces apoptosis in cell lines overexpressing Bcl-x(L). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98109 USA. NICHD, NIH, Bethesda, MD 20892 USA. RI Zhang, Kam/B-3552-2012 OI Zhang, Kam/0000-0002-9282-8045 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 429 BP 3815S EP 3816S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700428 ER PT J AU Christov, K Shilkaitis, A Green, A Grubbs, C Kelloff, G Lubet, R AF Christov, K Shilkaitis, A Green, A Grubbs, C Kelloff, G Lubet, R TI Kinetics of tamoxifen-induced cell death in rat mammary tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Inst Chemoprevent, Birmingham, AL USA. Univ Illinois, Dept Surg Oncol, Chicago, IL USA. NCI, Div Chemoprevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 433 BP 3816S EP 3816S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700432 ER PT J AU Chan, KK Jiang, C Zheng, HH Chiu, MH Covey, JM AF Chan, KK Jiang, C Zheng, HH Chiu, MH Covey, JM TI Pharmacokinetics of S(-)XK469 (NSC 698216) in CD1F2 mice and Fischer 344 rats. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 546 BP 3839S EP 3839S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700543 ER PT J AU Kang, MH Li, ZY Chan, KK Sandor, V Bakke, S Tucker, E Balcerak, S Bender, J Peng, L Fojo, T Figg, WD Bates, SE AF Kang, MH Li, ZY Chan, KK Sandor, V Bakke, S Tucker, E Balcerak, S Bender, J Peng, L Fojo, T Figg, WD Bates, SE TI A preliminary pharmacokinetic evaluation of intravenous FR901228 (Depsipeptide) given over 4 hours. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 553 BP 3841S EP 3841S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700550 ER PT J AU Alvarez-Salas, LM DiPaolo, JA AF Alvarez-Salas, LM DiPaolo, JA TI Antisense oligodeoxynucleotides targeting the human papilloma-virus type 16 (HPV-16) E6 gene inhibits proliferation of cervical carcinoma cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIP, Ctr Res & Adv Studies, Dept Mol Biol, Lab Gene Therapy, Mexico City 07300, DF, Mexico. NCI, DBS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 587 BP 3848S EP 3848S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700584 ER PT J AU Takebayashi, Y Urasaki, Y Pourquier, P Zimonjic, DB Popescu, NC Pommier, Y AF Takebayashi, Y Urasaki, Y Pourquier, P Zimonjic, DB Popescu, NC Pommier, Y TI Multidrug resistance induced by DNA minor groove alkylation of Ecteinascidin 743 (Et743). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 602 BP 3851S EP 3851S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700598 ER PT J AU Urasaki, Y Takebayashi, Y Pourquier, P Kohlhagen, G Chatterjee, D Pantazis, P Pommier, Y AF Urasaki, Y Takebayashi, Y Pourquier, P Kohlhagen, G Chatterjee, D Pantazis, P Pommier, Y TI Mechanism of camptothecin resistance in human prostate carcinoma cell lines. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Brown Univ, Dept MCB, Providence, RI 02912 USA. NCI, Mol Pharmacol Lab, DBS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 623 BP 3855S EP 3855S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700618 ER PT J AU Bai, R Ewell, J Nguyen, N Brossi, A Hamel, E AF Bai, R Ewell, J Nguyen, N Brossi, A Hamel, E TI Mapping the binding site of the A ring of colchicine on beta-tubulin: the covalent reactions of 2-chloroacetyl-2-demethylthiocolchicine (2CTC) and 3-chloroacetyl-3-demethylthiocolchicine (3CTC) with cysteine residues 239 and 354. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIDDK, Struct Biol Lab, Bethesda, MD USA. US FDA, Fac Biotechnol Resources, Bethesda, MD 20014 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 630 BP 3856S EP 3856S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700625 ER PT J AU Verdier-Pinard, P Wang, Z Mohanakrishnan, AK Cushman, M Hamel, E AF Verdier-Pinard, P Wang, Z Mohanakrishnan, AK Cushman, M Hamel, E TI Steroid derivatives interacting with tubulin: from colchicine-like to paclitaxel-like effects on tubulin polymerization. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, Urbana, IL 61801 USA. NCI, Lab Drug Discovery Res & Dev, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 631 BP 3856S EP 3856S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700626 ER PT J AU Santha, E Medina, JC Shan, B Baichwal, V Ladd, A Frankmoelle, WP Poruchynsky, MS Chou, TC Jean, JC Timmermans, PBMWM Beckmann, H AF Santha, E Medina, JC Shan, B Baichwal, V Ladd, A Frankmoelle, WP Poruchynsky, MS Chou, TC Jean, JC Timmermans, PBMWM Beckmann, H TI Cytotoxicity and antitumor efficacy of T138067, a novel microtubule disrupter, against MDR-positive tumor cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. Tularik Inc, S San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 637 BP 3857S EP 3857S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700632 ER PT J AU Blagosklonny, MV Robey, R Bates, S Fojo, T AF Blagosklonny, MV Robey, R Bates, S Fojo, T TI DNA damage-induced p21(WAF1/CIP1) abrogates cell death caused by microtubule-active drugs but does not affect killing of checkpoint-deficient cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 641 BP 3858S EP 3858S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700636 ER PT J AU Durso, NA Sackett, DL Bai, R Gamble, WO Cardellina, JH Hamel, E AF Durso, NA Sackett, DL Bai, R Gamble, WO Cardellina, JH Hamel, E TI Biochemical and cytotoxic comparisons of the sponge-derived natural product hemiasterlin, an antimitotic tripeptide, with other cytotoxic compounds. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 643 BP 3858S EP 3858S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700638 ER PT J AU Gussio, R Giannakakou, P Nogales, E Downing, KH Zaharevitz, D Sackett, D Nicolaou, KC Fojo, T AF Gussio, R Giannakakou, P Nogales, E Downing, KH Zaharevitz, D Sackett, D Nicolaou, KC Fojo, T TI A common pharmacophore for microtubule-stabilizing agents: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. NIDDK, Lab Integrat & Med Biophys, NIH, Bethesda, MD USA. NCI, Informat Technol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 640 BP 3858S EP 3858S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700635 ER PT J AU Pourquier, P Takebayashi, Y Kohlhagen, G Gioffre, C Pommier, Y AF Pourquier, P Takebayashi, Y Kohlhagen, G Gioffre, C Pommier, Y TI Poisoning of topoisomerase I by 1-beta-D arabinofuranosylcytosine. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 660 BP 3861S EP 3861S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700655 ER PT J AU Pommier, Y Kohlhagen, G Strumberg, D Jarayaman, M Cushman, M AF Pommier, Y Kohlhagen, G Strumberg, D Jarayaman, M Cushman, M TI Novel non-camptothecin topoisomerase I poisons: the indenoisoquinolines. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, DBS, NIH, Bethesda, MD 20892 USA. Purdue Univ, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 663 BP 3862S EP 3862S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700658 ER PT J AU Pourquier, P Loktionova, NA Pegg, AE Pommier, Y AF Pourquier, P Loktionova, NA Pegg, AE Pommier, Y TI Effects of the O6-methylguanine on topoisomerase I activity in vitro and in MNNG-treated cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cell & Mol Physiol, Hershey, PA 17033 USA. NCI, Mol Pharmacol Lab, DBS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 661 BP 3862S EP 3862S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700656 ER PT J AU Dirk, S Nitiss, JL Dong, JW Nicklaus, MC Kohn, KW Heddle, JG Maxwell, A Pommier, Y AF Dirk, S Nitiss, JL Dong, JW Nicklaus, MC Kohn, KW Heddle, JG Maxwell, A Pommier, Y TI The third alpha-helix of the CAP homology domain of type II topoisomerases is critical for DNA cleavage site recognition and quinolone-action. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, DBS, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. RI Nitiss, John/E-9974-2010; Nicklaus, Marc/N-4183-2014; Heddle, Jonathan/H-4586-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 670 BP 3863S EP 3863S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700665 ER PT J AU Lubet, RA Hu, L Wang, YA Kelloff, GJ You, M AF Lubet, RA Hu, L Wang, YA Kelloff, GJ You, M TI Altered gene expression in MNU-induced rat mammary tumors following long term exposure to vorozole or dehydroepiandrosterone. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 676 BP 3864S EP 3865S PG 2 WC Oncology SC Oncology GA 260JL UT WOS:000083945700671 ER PT J AU Zhang, Z Lantry, LE Wang, Y Wiseman, RW Lubet, RA You, M AF Zhang, Z Lantry, LE Wang, Y Wiseman, RW Lubet, RA You, M TI Organ-specific effect of a germline p53 mutation on chemical carcinogenesis in mice: a new mouse model for cancer therapy and prevention. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Chemoprevent Drug Dev Grp, Bethesda, MD 20892 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S MA 693 BP 3868S EP 3868S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700687 ER PT J AU Pastan, L Vasmatzis, G Essand, M Olsson, P Liu, XF Iavarone, C Ailey, B Duray, P Bera, T Lee, B AF Pastan, L Vasmatzis, G Essand, M Olsson, P Liu, XF Iavarone, C Ailey, B Duray, P Bera, T Lee, B TI Discovery of new targets for prostate cancer immunotherapy by EST database analysis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 SU S BP 3869S EP 3869S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700691 ER PT J AU de Lacerda, L Carvalho, JAR Stannard, B Werner, H Boguszewski, MCS Sandrini, R Malozowski, SN LeRoith, D Underwood, LE AF de Lacerda, L Carvalho, JAR Stannard, B Werner, H Boguszewski, MCS Sandrini, R Malozowski, SN LeRoith, D Underwood, LE TI In vitro and in vivo responses to short-term recombinant human insulin-like growth factor-1 (IGF-1) in a severely growth-retarded girl with ring chromosome 15 and deletion of a single allele for the type 1 IGF receptor gene SO CLINICAL ENDOCRINOLOGY LA English DT Article ID FACTOR-BINDING PROTEIN-2; HORMONE INSENSITIVITY SYNDROME; DISTAL LONG ARM; FACTOR-I; POSTNATAL-GROWTH; LARON SYNDROME; SECRETION; IDENTIFICATION; FIBROBLASTS; EXPRESSION AB OBJECTIVES Patients with single allele defects in the gene encoding the type 1 IGF receptor have been reported to have growth failure, but fibroblasts from affected patients have not exhibited insensitivity to the effects of IGF-I in vitro. The in vitro and in vivo responses to short-term recombinant human IGF-I (rhIGF-I) in a severely growth-retarded girl with ring chromosome 15 and deletion of a single allele for the type 1 IGF receptor gene have been investigated. DESIGN AND PATIENT The child exhibited prenatal and severe post-natal growth failure, and delayed psychomotor development. Southern blotting revealed a 50% reduction in IGF-I receptor DNA, and in an RNase protection assay (RPA), a quantitatively similar reduction in steady-state mRNA for type 1 IGF receptor. rhIGF-I was administered in graded doses of 40, 60 and 80 mu g/kg twice daily by subcutaneous injection for periods of 2-2.5 days each. RESULTS During rhIGF-I treatment, mean urinary nitrogen excretion was unchanged and urinary calcium rose to 60% greater than in the pre-treatment period, rhIGF-I injections produced only a modest decrease in indices of GH secretion, assessed by frequent (every 20 min) sampling over periods of 12 h. There was no significant difference between the mean GH concentrations during rhIGF-I treatment (5.32+/-6.2mU/I) compared with that before rhIGF-I treatment (8.46+/-10.2 mU/I). Mean IGFBP-3-values were increased (4.5 mg/l before vs. 5.4 mg/l during rhIGF-I). TSH values after injection of TRH were not significantly reduced by IGF-I (mean of all values, 18.6 mU/I vs. 15.5 mU/I during rhIGF-I treatment). In vitro binding of radiolabelled IGF-I to the patient's fibroblasts was less than that bound by control fibroblasts (patient, 0.69% binding by 248000 cells, vs. 1 41% binding by 260000 fibroblasts from an age-matched control). However, the patient's fibroblasts exhibited a growth response in vitro to the addition of IGF-I in a fashion similar to that of control fibroblasts. CONCLUSIONS These studies show evidence in each of the indices examined of in vivo resistance to IGF-I and suggest that the growth retardation observed in such patients may be the direct result of the absence of one of the alleles encoding the type 1 IGF receptor. C1 Univ Fed Parana, Dept Paediat, BR-80060000 Curitiba, Parana, Brazil. NIDDK, Diabet Branch, NIH, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. Univ N Carolina, Dept Paediat, Chapel Hill, NC 27515 USA. RP de Lacerda, L (reprint author), Univ Fed Parana, Hosp Clin, Paediat Endocrine Unit, Rua Padre Camargo 250, BR-80060900 Curitiba, Parana, Brazil. EM lacerda@hc.ufpr.br RI Carvalho, Julienne/G-5043-2013 OI Carvalho, Julienne/0000-0002-6263-344X NR 40 TC 26 Z9 27 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD NOV PY 1999 VL 51 IS 5 BP 541 EP 550 DI 10.1046/j.1365-2265.1999.00799.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257JB UT WOS:000083777800003 PM 10594514 ER PT J AU Whitcup, SM Chan, CC Kozhich, AT Magone, MT AF Whitcup, SM Chan, CC Kozhich, AT Magone, MT TI Blocking ICAM-1 (CD54) and LFA-1 (CD11a) inhibits experimental allergic conjunctivitis SO CLINICAL IMMUNOLOGY LA English DT Article DE ICAM-1; LFA-1; conjunctiva; allergy; intercellular adhesion molecules; mast cell; ragweed; treatment ID INTERCELLULAR-ADHESION MOLECULE-1; ENDOTOXIN-INDUCED UVEITIS; HUMAN MAST-CELLS; MONOCLONAL-ANTIBODIES; ELAM-1 EXPRESSION; EPITHELIAL-CELLS; EOSINOPHILS; ANTIGEN; DEGRANULATION; AGGREGATION AB Cell adhesion molecules are critical for the homing and migration of leukocytes into inflamed tissues. We investigated the role of ICAM-1 and LFA-1 in a previously described experimental model of ragweed (Rw)induced allergic conjunctivitis, SWR/J mice were treated intraperitoneally 6 and 1 h prior to topical challenge with Rw with injections of anti-ICAM-1 monoclonal antibody (mAb), anti-LFA-l mAb, both anti-ICAM-1 and anti-LFA-mAbs, or rat IgG. Blocking ICAM-1 or LFA-1 reduced the clinical signs of allergic conjunctivitis. Treatment with anti-ICAM-1 or anti-LFA-1 mAbs also significantly inhibited cellular infiltration into the conjunctiva. The greatest inhibitory effect was achieved with the combination of antibodies against both cell adhesion molecules. Since antibodies against ICAM-1 and LFA-1 significantly inhibit the development of the clinical and histologic signs of allergic conjunctivitis, they may be useful for treating patients with ocular allergy. C1 NIH, NEI, Bethesda, MD 20892 USA. RP Whitcup, SM (reprint author), NIH, NEI, Bldg 10, Bethesda, MD 20892 USA. NR 31 TC 32 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 1999 VL 93 IS 2 BP 107 EP 113 DI 10.1006/clim.1999.4775 PG 7 WC Immunology SC Immunology GA 255GV UT WOS:000083661900002 PM 10527686 ER PT J AU Boellaard, JW Brown, P Tateishi, J AF Boellaard, JW Brown, P Tateishi, J TI Gerstmann-Straussler-Scheinker disease - The dilemma of molecular and clinical correlations SO CLINICAL NEUROPATHOLOGY LA English DT Review DE Gerstmann-Straussler-Scheinker disease; GSSD; cerebellar ataxia; prion diseases; transmissible spongiform encephalopathy ID PRION PROTEIN GENE; CREUTZFELDT-JAKOB-DISEASE; NEUROFIBRILLARY TANGLES; AMYLOID PLAQUES; ALZHEIMERS-DISEASE; SPONGIFORM ENCEPHALOPATHY; CEREBRAL AMYLOIDOSIS; CODON-105 MUTATION; PRESENILE-DEMENTIA; REPEAT INSERTION AB Gerstmann-Straussler-Scheinker disease (GSSD) is a hereditary as well as transmissible human prion disease, restricted to families carrying point mutations of the PRPN gene on chromosome 20. To date 7 different causative mutations have been found. In this review the results of molecular biology with regard to the clinical course are discussed. As the findings of the disorder an very variable, the clinical picture and the neuropathology are extensively reported. An attempt has been made to define the disease, and filter out atypical non-GSSD cases. Finally, a comprehensive bibliography and tabulation of cases reported in the Western and Japanese literature are provided. C1 Univ Tubingen, Inst Hirnforsch, D-72076 Tubingen, Germany. NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. Geriatr Hlth Fac, Brain Res Lab, Fukuoka, Japan. RP Boellaard, JW (reprint author), Univ Tubingen, Inst Hirnforsch, D-72076 Tubingen, Germany. NR 105 TC 10 Z9 11 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0722-5091 J9 CLIN NEUROPATHOL JI Clin. Neuropathol. PD NOV-DEC PY 1999 VL 18 IS 6 BP 271 EP 285 PG 15 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 254LC UT WOS:000083611900001 PM 10580553 ER PT J AU Mima, T Hallett, M AF Mima, T Hallett, M TI Electroencephalographic analysis of cortico-muscular coherence: reference effect, volume conduction and generator mechanism SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE coherence; current source density; EEG, EMG ID VISUAL-CORTEX; MOTOR CORTEX; EEG; SCALP; AREAS; TASK; SYNCHRONIZATION; ELECTROMYOGRAMS; OSCILLATIONS; PERFORMANCE AB Objective: To measure the synchrony between cortical and muscle oscillatory activities, the coherence estimate between EEG and EMG was computed. Methods: The multichannel electroencephalogram (EEG) and electromyogram (EMG) of the right abductor pollicis brevis muscle were recorded in 5 normal volunteers. Various types of EEG derivation methods were systematically compared to establish a standard method to study cortico-muscular coupling. Results: The use of a reference-free EEG derivation (current source density) greatly improved cortico-muscular coherence. In all subjects, EEGs over the left sensorimotor cortex were coherent with EMG (mean peak frequency: 18.7 Hz, mean highest coherence: 0.124). The time lag from cortex to muscle in 14-50 Hz was 14.3 ms. EEG source derivation revealed that both radial and tangential generators in the precentral cortex might contribute to this phenomenon. In the EEG signals using common average reference, an artifactual coherence peak over the medial frontal area was observed, which might largely be explained by Volume conduction from the primary sensorimotor cortex. Conclusions: We conclude that the current source density or its approximation is preferable to estimate the cortico-muscular coherence and that the interpretation of such coherence using referenced EEGs should be taken with care. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, 10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. OI Mima, Tatsuya/0000-0001-7783-1599; Mima, Tatsuya/0000-0001-7787-4855 NR 26 TC 116 Z9 117 U1 1 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 1999 VL 110 IS 11 BP 1892 EP 1899 DI 10.1016/S1388-2457(99)00238-2 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 248RJ UT WOS:000083288900007 PM 10576484 ER PT J AU Avila, NA Doppman, JL Walther, MM Keiser, HR AF Avila, NA Doppman, JL Walther, MM Keiser, HR TI Synchronous multicentric extraadrenal phaeochromocytoma: Implications for management SO CLINICAL RADIOLOGY LA English DT Article ID EXTRA-ADRENAL PHEOCHROMOCYTOMA; URINARY-BLADDER C1 Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, NIH, Bldg 10,Room 1C660,10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD NOV PY 1999 VL 54 IS 11 BP 772 EP 774 DI 10.1016/S0009-9260(99)91182-0 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 255TW UT WOS:000083687100010 PM 10580770 ER PT J AU Walsh, PJ Handel-Fernandez, ME Vincek, V AF Walsh, PJ Handel-Fernandez, ME Vincek, V TI Characterization and sequencing of glutamine synthetase cDNA from liver of the ureotelic gulf toadfish (Opsanus beta) SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE glutamine synthetase; liver; gulf toadfish; Opsanus beta; ornithine-urea cycle; ureagenesis ID NITROGEN-METABOLISM; SQUALUS-ACANTHIAS; UREA SYNTHESIS; MITOCHONDRIAL; CYCLE; AMPHIPHILICITY; EVOLUTION; ISOZYMES; ENZYMES; BRAIN AB The hepatic enzyme, glutamine synthetase (GSase) is a pivotal protein in the regulation of urea synthesis in fish. The sequence of the DNA encoding for GSase from liver of the ureotelic gulf toadfish (Opsanus beta) was analyzed through a suite of molecular techniques (including cDNA cloning, RACE PCR, and genomic PCR). An open reading frame (ORF) was identified in the cDNA sequence which codes for a protein of 394 amino acids with high identity (86%) to dogfish shark GSase. In the course of generating a suitable probe, a partial sequence was also obtained for horned shark GSase which also had high identity with the dogfish shark gene (93%). Like the dogfish shark GSase, the toadfish gene has two methionine translation initiation sites; the downstream site apparently codes for a cytoplasmic isozyme, while the upstream site adds an N-terminal peptide leader sequence of 23 amino acids to the 'cytoplasmic' protein. This leader sequence has characteristics consistent with a mitochondrial targeting peptide, including a cleavage recognition motif (Arg-X-Phe) and the apparent ability to form an amphiphathic helix. Northern analysis revealed that there is a single predominant transcript of similar to 2 kb in size. These results are consistent with the interpretation that in the gulf toadfish GSase cytoplasmic and mitochondrial isozymes are coded for by a single gene and mRNA transcript which is differentially translated at either initiation site. These results are discussed in the context of prior results for enzyme kinetic characteristics and urea synthesis/excretion physiology. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, Miami, FL 33149 USA. Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33136 USA. RP Walsh, PJ (reprint author), Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. NR 32 TC 15 Z9 15 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD NOV PY 1999 VL 124 IS 3 BP 251 EP 259 DI 10.1016/S0305-0491(99)00105-4 PG 9 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 254RA UT WOS:000083624900004 PM 10631802 ER PT J AU Gordon, T Keel, J Hardin, TA Rosenthal, NE AF Gordon, T Keel, J Hardin, TA Rosenthal, NE TI Seasonal mood change and neuroticism: The same construct? SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; 5-FACTOR MODEL; PERSONALITY; POLYMORPHISM AB The personality trait of neuroticism has been found to be associated with a polymorphism in the regulatory region of the serotonin (5-HT) transporter gene (5-HTTLPR). This same genetic polymorphism has also been associated with seasonal changes in mood and behavior, or seasonality. The purpose of the current study was to determine whether seasonality and neuroticism are actually the same construct given that they are both associated with the same genetic polymorphism. We administered the Seasonal Pattern Assessment Questionnaire (SPAQ), which measures the severity of seasonality, and the Revised MEO Personality Inventory (NEO-PI-R), which measures the severity of neuroticism, to 45 subjects diagnosed with seasonal affective disorder (SAD), SAD is a clinical expression of seasonality in which patients develop a major depressive disorder in the winter that remits in the summer and can be treated with light therapy. No significant correlation was found between neuroticism and seasonality. We conclude that seasonality and neuroticism are not the same construct, even though the 5-HTTLPR polymorphism is a genetic risk factor for each. Copyright (C) 1999 by W.B. Saunders Company. C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. NIMH, Adult OCD Res Unit, Bethesda, MD 20892 USA. RP Gordon, T (reprint author), NIMH, Sect Biol Rhythms, 10 Ctr Dr,Bldg 10,Room 3S-231, Bethesda, MD 20892 USA. NR 16 TC 12 Z9 12 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 1999 VL 40 IS 6 BP 415 EP 417 DI 10.1016/S0010-440X(99)90083-4 PG 3 WC Psychiatry SC Psychiatry GA 258AE UT WOS:000083815200002 PM 10579371 ER PT J AU DePetrillo, PB Speers, D Ruttimann, UE AF DePetrillo, PB Speers, D Ruttimann, UE TI Determining the Hurst exponent of fractal time series and its application to electrocardiographic analysis SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE heart; nonlinear dynamics; fractals; electrocardiography; software ID HEART-RATE-VARIABILITY AB An alternative regression-based method for estimating the Hurst coefficient of a fractal time series is proposed. A formal mathematical description of the methodology is presented. The geometric relationship of the algorithm to the family of self-similar fractal curves is outlined. The computational structure of the algorithm is optimal for generation of real-time estimates of H. We show that the method can be applied to biologically-derived time series such as the cardiac interbeat interval and we obtain estimates of H from several diverse electrocardiographic data sets. (C) 1999 Published by Elsevier Science Ltd. All rights reserved. C1 Unit Clin & Biol Res, Sect Clin Sci, Clin Studies Lab, Bethesda, MD USA. Thomson Labs, Intelligent Syst, Rockville, MD USA. NIAAA, Sect Brain Electrophysiol & Imaging, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP DePetrillo, PB (reprint author), Unit Clin & Biol Res, Sect Clin Sci, Clin Studies Lab, Bethesda, MD USA. NR 14 TC 31 Z9 32 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD NOV PY 1999 VL 29 IS 6 BP 393 EP 406 DI 10.1016/S0010-4825(99)00018-9 PG 14 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 261TR UT WOS:000084025800003 PM 10591173 ER PT J AU Floyd, JA Falahee, ML Fhobir, RH AF Floyd, JA Falahee, ML Fhobir, RH TI The use of the arcs software system to store and examine sleep research results SO COMPUTERS IN NURSING LA English DT Article DE evidence-based practice; meta-analysis; research dissemination; sleep promotion AB Ready access to research results is essential if nurses are to keep current with the scientific knowledge available to guide practice. Sigma Theta Tau international has supported the development of a software system that facilitates ongoing storage of information from research reports and tan be used to gain online access to continually updated databases of research results called "knowledgebases." One such experimental knowledgebase, the Sleep Promotion Knowledgebase, includes studies of correlates of poor sleep in adults as well as sleep interventions and outcomes. The authors describe the creation of the Sleep Promotion Knowledgebase using arcs BUILDER to store information about research reports and the scientific findings they contain. The use of are; MAPPER to examine sleep promotion interventions also is described, me strengths and limitations of the software system are identified, and the potential uses of arcs to disseminate sleep research results are discussed. C1 Natl Inst Nursing Res, Bethesda, MD 20892 USA. RP Floyd, JA (reprint author), 5557 Cass Ave, Detroit, MI 48202 USA. NR 18 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-8593 J9 COMPUT NURS JI Comput. Nurs. PD NOV-DEC PY 1999 VL 17 IS 6 BP 259 EP 268 PG 10 GA 262VM UT WOS:000084088400010 PM 10609400 ER PT J AU Gozes, I Fridkin, M Hill, JM Brenneman, DE AF Gozes, I Fridkin, M Hill, JM Brenneman, DE TI Pharmaceutical VIP: Prospects and problems SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID VASOACTIVE-INTESTINAL-PEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; CENTRAL-NERVOUS-SYSTEM; DIFFERENTIAL SIGNAL-TRANSDUCTION; NONINVASIVE IMPOTENCE TREATMENT; TERMINAL EXTRACELLULAR DOMAIN; ALLERGIC CONTACT-DERMATITIS; MESSENGER-RIBONUCLEIC-ACID; SITE-DIRECTED MUTAGENESIS; LUNG-CANCER GROWTH AB Recently, multiple receptors for vasoactive intestinal peptide (VIP) have been molecularly cloned and our understanding of VIP chemistry and mechanisms of action has been broadened. The following review outlines the physiological effects of the hormone from growth regulation, reproduction, bronchodilation, vasodilation and immune interactions to neurotrophism. VIP-based drug design and non-invasive innovative delivery modes are discussed with emphasis on tumor diagnosis and treatment, impotence treatment and neuroprotection. C1 Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, IL-76100 Rehovot, Israel. NICHD, Sect Dev & Mol Pharamcol, LDN, NIH, Bethesda, MD 20892 USA. RP Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. EM igozes@post.tau.ac.il NR 188 TC 74 Z9 77 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PD NOV PY 1999 VL 6 IS 11 BP 1019 EP 1034 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 245DW UT WOS:000083091800003 PM 10519911 ER PT J AU Park, M Krause, MW AF Park, M Krause, MW TI Regulation of postembryonic G(1) cell cycle progression in Caenorhabditis elegans by a cyclin D/CDK-like complex SO DEVELOPMENT LA English DT Article DE Caenorhabditis elegans; cell cycle; cyclin D; CDK; cyd-1; cdk-4 ID C-ELEGANS; PROTEIN-KINASES; DROSOPHILA EMBRYOGENESIS; DEVELOPMENTAL CONTROL; DEPENDENT KINASES; PHASE PROGRESSION; CDK INHIBITORS; FAMILY; EXPRESSION; TRANSITION AB In many organisms, initiation and progression through the G(1) phase of the cell cycle requires the activity of G(1)-specific cyclins (cyclin D and cyclin E) and their associated cyclin-dependent kinases (CDK2, CDK4, CDK6), We show here that the Caenorhabditis elegans genes cyd-1 and cdk-4, encoding proteins similar to cyclin D and its cognate cyclin-dependent kinases, respectively, are necessary for proper division of postembryonic blast cells. Animals deficient for cyd-1 and/or cdk-4 activity have behavioral and developmental defects that result from the inability of the postembryonic blast cells to escape G(1) cell cycle arrest, Moreover, ectopic expression of cyd-1 and cdk-4 in transgenic animals is sufficient to activate a S-phase reporter gene. We observe no embryonic defects associated with depletion of either of these two gene products, suggesting that their essential functions are restricted to postembryonic development; We propose that the cyd-1 and cdk-4 gene products are an integral part of the developmental control of larval cell proliferation through the regulation of G(1) progression. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Krause, MW (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room B1-04, Bethesda, MD 20892 USA. OI Krause, Michael/0000-0001-6127-3940 NR 73 TC 67 Z9 71 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1999 VL 126 IS 21 BP 4849 EP 4860 PG 12 WC Developmental Biology SC Developmental Biology GA 259EM UT WOS:000083881600016 PM 10518501 ER PT J AU Amano, O Bringas, P Takahasi, I Takahashi, I Takahashi, K Yamane, A Chai, Y Nuckolls, GH Shum, L Slavkin, HC AF Amano, O Bringas, P Takahasi, I Takahashi, I Takahashi, K Yamane, A Chai, Y Nuckolls, GH Shum, L Slavkin, HC TI Nerve growth factor (NGF) supports tooth morphogenesis in mouse first branchial arch explants SO DEVELOPMENTAL DYNAMICS LA English DT Article DE first branchial arch; odontogenesis; tooth bud; chondrogenesis; cartilage; myogenesis; tongue; epidermal growth factor (EGF); nerve growth factor (NGF); Pax9; in vitro; DiI-labeling; morphometry; whole-mount in situ hybridization; polymerase chain reaction (PCR) ID NEURAL-CREST CELLS; MESSENGER-RNA EXPRESSION; NEUROTROPHIC FACTORS; MOLAR TOOTH; MANDIBULAR MORPHOGENESIS; RECEPTOR EXPRESSION; MULTIPLE FUNCTIONS; EMBRYONIC-TISSUES; GENE-EXPRESSION; FACTOR BINDING AB Posterior midbrain and anteorior hindbrain neuroectoderm transdifferentiate into cranial neural crest cells (CNCC), emigrate from the neural folds, and become crest-derived ectomesenchyme within the mandibular and maxillary processes. To investigate the growth factor requirement specific for the initiation of tooth morphogenesis, we designed studies to test whether nerve growth factor (NGF) can support odontogenesis in a first branchial arch (FBA) explant culture system. FBA explants containing neural-fold tissues before CNCC emigration and the anlagen of the FBA were microdissected from embryonic day 8 (E8) mouse embryos, and cultured for 8 days in medium supplemented with 10% fetal calf serum only, or serum-containing medium further supplemented with either NGF or epidermal growth factor (EGF) at three different concentrations: 50, 100, or 200 ng/ml. Morphological, morphometric, and total protein analyses indicated that growth and development in all groups were comparable. Meckel's cartilage and tongue formation were also observed in all groups. However, odontogenesis was only detected in explants cultured in the presence of exogenous NGF. NGF-supplemented cultures were permissive for bud stage (50 ng/ml) as well as cap stage of tooth morphogenesis (100 and 200 ng/ml), Morphometric analyses of the volume of tooth organs showed a significant dose-dependent increase in tooth volume as the concentration of NGF increased. Whole-mount in situ hybridization and semiquantitative reverse transcription-polymerase chain reaction for Pax9, a molecular marker of dental mesenchyme, further supported and confirmed the morphological data of the specificity and dose dependency of NGF on odontogenesis. We conclude that (1) E8 FBA explants contain premigratory CNCC that are capable of emigration, proliferation, and differentiation in vitro; (2) serum-supplemented medium is permissive for CNCC differentiation into tongue myoblasts and chondrocytes in FBA explants; and (3) NGF controls CNCC cell fate specification and differentiation into tooth organs. Dev Dyn 1999;216:299-310. Published 1999 Wiley-Liss, Inc.dagger C1 NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90089 USA. Kanazawa Univ, Sch Med, Dept Anat, Kanazawa, Ishikawa 920, Japan. RP Slavkin, HC (reprint author), NIAMSD, Craniofacial Dev Sect, NIH, Bldg 6,Room 324,MSC2745,6 Ctr Dr, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR-41114]; NIDCR NIH HHS [DE-09165] NR 94 TC 19 Z9 19 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 1999 VL 216 IS 3 BP 299 EP 310 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 250KL UT WOS:000083387500008 PM 10590481 ER PT J AU Sasagasako, N Ohno, M Quarles, RH AF Sasagasako, N Ohno, M Quarles, RH TI Evidence for regulation of myelin protein synthesis by contact between adjacent Schwann cell plasma membranes SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE cell-cell interactions; gene expression; myelination; myelin-associated glycoprotein; plasma membrane; PO glycoprotein; Schwann cells ID ADRENAL CHROMAFFIN CELLS; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; CULTURE DENSITY; N-CAM; GLYCOPROTEIN; PROLIFERATION; INDUCTION; PHENOTYPE; RECEPTOR AB The spontaneously immortalized S16 Schwann cell line expresses higher levels of myelin-associated glycoprotein (MAG) and PO glycoprotein and their messenger RNAs when grown at high density than at low density [Sasagasako et al: J Neurochem 1996;66:1432-1439]. This up-regulation of myelin protein expression at high density is not associated with decreased cellular proliferation and may be caused by direct cell-to-cell contact. To investigate the hypothesis that increased mRNA levels for myelin proteins are caused by contact between Schwann cells, sparse S16 cell cultures were treated for 48 h with plasma-membrane-enriched fractions isolated from dense S16 cells. The treatment had no effect on the proliferation of the cells, but MAG and PO mRNAs were elevated 2- and 1.3-fold, respectively, in comparison to untreated cells. These effects on levels of myelin protein mRNAs were eliminated by pretreatment of the membrane fraction with heat or trypsin and were not caused by plasma membrane fractions from NIH 3T3 cells. These data support the hypothesis that homotypic contact between Schwann cells up-regulates expression of myelin proteins and suggest the possibility of autotypic contact-mediated regulation of myelinogenesis by adjacent spiraled membranes of individual Schwann cells. Copyright (C) 2000 S. Karger AG, Basel . C1 NINDS, Myelin & Brain Dev Sect, Lab Mol & Cellular Neurobiol, NIH, Bethesda, MD 20892 USA. RP Quarles, RH (reprint author), NINDS, Myelin & Brain Dev Sect, Lab Mol & Cellular Neurobiol, NIH, Bldg 49,Rm 2A28,49 Convent Dr,MSC 4440, Bethesda, MD 20892 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD NOV-DEC PY 1999 VL 21 IS 6 BP 417 EP 422 DI 10.1159/000017409 PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 279ZD UT WOS:000085076000002 PM 10640860 ER PT J AU Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, CA Burchinal, M Caldwell, B Campbell, SB Clarke-Stewart, A Cox, M Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M AF Appelbaum, M Batten, DA Belsky, J Booth, C Bradley, R Brownell, CA Burchinal, M Caldwell, B Campbell, SB Clarke-Stewart, A Cox, M Friedman, SL Hirsh-Pasek, K Huston, A Jaeger, E Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M CA NICHD Early Child Care Res Network TI Child care and mother-child interaction in the first 3 years of life SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID MATERNAL EMPLOYMENT; EARLY INTERVENTION; BEHAVIOR PROBLEMS; ATTACHMENT; QUALITY; INFANTS; FAMILY; PERFORMANCE; ANTECEDENTS; PREDICTORS AB Relations between nonmaternal child care and ratings of maternal sensitivity and child positive engagement during mother-child interaction at 6, 15, 24, and 36 months were examined for 1,274 mothers and their children participating in the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care. In longitudinal analyses that controlled for selection, child, and family predictors, child care was a small but significant predictor of maternal sensitivity and child engagement. For the whole sample, including families who did and did not use child care, more hours of child care predicted less maternal sensitivity and less positive child engagement. For children who were observed in child care, higher quality child care predicted greater maternal sensitivity, and more child-care hours predicted less child engagement. The effects of child care on mother-child interaction were much smaller in the analytical models than the effects of maternal education but were similar in size to the effects of maternal depression and child difficult temperament. Patterns of association with child care did not differ significantly across ages of assessment. C1 Vanderbilt Univ, Nashville, TN 37240 USA. Penn State Univ, University Pk, PA 16802 USA. Univ Washington, Seattle, WA 98195 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Calif Irvine, Irvine, CA USA. NICHD, Bethesda, MD USA. Temple Univ, Philadelphia, PA 19122 USA. Res Triangle Inst, Res Triangle, NC USA. Univ New Hampshire, Durham, NH 03824 USA. Univ Kansas, Lawrence, KS 66045 USA. Natl Res Council, Washington, DC 20418 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Wisconsin, Madison, WI 53706 USA. RP Appelbaum, M (reprint author), NICHD, Early Child Care Res Network, CRMC, 6100 Execut Blvd,4B05, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012 NR 79 TC 259 Z9 259 U1 6 U2 26 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 1999 VL 35 IS 6 BP 1399 EP 1413 PG 15 WC Psychology, Developmental SC Psychology GA 253JH UT WOS:000083553000005 ER PT J AU Powell, MB Roberts, KP Ceci, SJ Hembrooke, H AF Powell, MB Roberts, KP Ceci, SJ Hembrooke, H TI The effects of repeated experience on children's suggestibility SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT European Psychology and Law Conference CY SEP, 1998 CL KRAKOW, POLAND ID EVENT MEMORY; QUESTIONS; AGE AB The effect of suggestive questions on 3- to 5-year-old and 6- to g-year-old children's recall of the final occurrence of a repeated event was examined. The event included fu;ed (identical) items as well as variable items where a new instantiation represented the item in each occurrence of the series. Relative to reports of children who participated in a single occurrence, children's reports about fixed items of the repeated event were more accurate and less contaminated by false suggestions. For variable items, repeated Experience led to a decline in memory of the specific occurrence; however, there was no increase in susceptibility to suggestions about details that had not occurred. Most errors after repeated experience were intrusions of details from nontarget occurrences. Although younger children and children who were interviewed a while after the event were more suggestible, respectively, than older children and those interviewed soon after the event, repeated experience attenuated these effects. C1 Deakin Univ, Sch Psychol, Burwood, NSW 3125, Australia. NICHHD, Bethesda, MD 20892 USA. Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA. RP Powell, MB (reprint author), Deakin Univ, Sch Psychol, 221 Burwood Highway, Burwood, NSW 3125, Australia. NR 35 TC 69 Z9 69 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 1999 VL 35 IS 6 BP 1462 EP 1477 DI 10.1037//0012-1649.35.6.1462 PG 16 WC Psychology, Developmental SC Psychology GA 253JH UT WOS:000083553000010 PM 10563735 ER PT J AU Weyer, C Bogardus, C Pratley, RE AF Weyer, C Bogardus, C Pratley, RE TI Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INSULIN-SECRETION; PIMA-INDIANS; OBESE INDIVIDUALS; BETA-CELL; NIDDM; RESISTANCE; RISK; INTOLERANCE; DYSFUNCTION AB With the release of the new 1997 American Diabetes Association diagnostic criteria, a new category was introduced, termed "impaired fasting glucose" (IFG). The metabolic abnormalities of individuals with IFG, compared with those with impaired glucose tolerance (IGT) (World Health Organization criteria), remain to be elucidated. We assessed insulin action (hyperinsulinemic clamp), insulin secretion (25-g intravenous glucose tolerance test), and endogenous glucose output (EGO) (3-H-3-glucose) in 434 nondiabetic Pima Indians with either normal (NFG; <6.1 mmol/l) or impaired (IFG; 6.1-7.0 mmol/l) fasting glucose and with either normal (NGT; 2-h glucose <7.8 mmol/l) or impaired (IGT; 2-h glucose 7.8-11.1 mmol/l) glucose tolerance: NFG/NGT (n = 307), IFG/NGT (n = 11), NFG/IGT (n = 98), and IFG/IGT (n = 18). Compared with the NFG/NGT group, individuals with IFG/NGT had lower maximal insulin-stimulated glucose disposal (M; -20%, P < 0.01), a lower acute insulin response (AIR) to intravenous glucose (-33%, P < 0.05), and higher EGO (8%, P = 0.055). Individuals with NFG/IGT also had lower M (-21%, P < 0.001) and lower AIR (-8%, P < 0.05), but normal EGO (-1%, NS). Individuals with IFG/IGT showed the most severe abnormalities in M (-27%), AIR (-51%), and EGO (+13%) (all P < 0.001 compared with NFG/NGT). These group differences could be explained by the observation that AIR and EGO, but not M, were more strongly related to the fasting than to the 2-h glucose concentration. Thus, Pima Indians with isolated IFG and isolated IGT show similar impairments in insulin action, but those with isolated IFG have a more pronounced defect in early insulin secretion and, in addition, increased EGO. More severe metabolic abnormalities are present in Pima Indians with combined IFG and IGT. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Weyer, C (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 5-41, Phoenix, AZ 85016 USA. NR 50 TC 182 Z9 195 U1 3 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1999 VL 48 IS 11 BP 2197 EP 2203 DI 10.2337/diabetes.48.11.2197 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 248GR UT WOS:000083267200012 PM 10535454 ER PT J AU Savage, PJ Narayan, KMV AF Savage, PJ Narayan, KMV TI Reducing cardiovascular complications of type 2 diabetes - A complex but achievable and affordable task SO DIABETES CARE LA English DT Editorial Material ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; COST-EFFECTIVENESS C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20817 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Savage, PJ (reprint author), NHLBI, Div Epidemiol & Clin Applicat, Rockledge 2,6700 Rockledge Dr, Bethesda, MD 20817 USA. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 13 TC 4 Z9 4 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1999 VL 22 IS 11 BP 1769 EP 1770 DI 10.2337/diacare.22.11.1769 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247FB UT WOS:000083209500002 PM 10546005 ER PT J AU Meyer, TW Bennett, PH Nelson, RG AF Meyer, TW Bennett, PH Nelson, RG TI Podocyte number predicts long-term urinary albumin excretion in Pima Indians with Type II diabetes and microalbuminuria SO DIABETOLOGIA LA English DT Article DE Type II diabetes mellitus; diabetic nephropathies; epithelial cell; glomerulus; Indians; North American ID PROGRESSION; NEPHROPATHY; INJURY AB Aims/hypothesis. The predictive value of glomerular structure on progression of renal disease was examined in patients with Type II (non-insulin-dependent) diabetes and microalbuminuria (urinary albumin-to-creatinine ratio = 30-299 mg/g). Methods. Kidney biopsy specimens were obtained from 16 diabetic Pima Indians (6 men, 10 women). Progression of renal disease was assessed by measuring urinary albumin excretion 4 years after the biopsy (UAE(4 years)) and by computing the change in urinary albumin excretion during the study (Delta UAE). Results. At baseline, the duration of diabetes averaged 13.3 years (range = 4.0-23.8 years) and the mean glomerular filtration rate was 159 ml . min(-1) . 1.73m(-2) (range = 98 - 239 ml . min(-1) . 1.73m(-2)). Median urinary albumin excretion was 67mg/g (range = 25-136 mg/g) and it increased to 625mg/g (range = 9-13471mg/g) after 4 years; 10 subjects (63%; 4 men, 6 women) developed macroalbuminuria (urinary albumin-to-creatinine ratio greater than or equal to 300 mg/g). Neither mean arterial pressure nor HbA(1c) changed substantially during follow-up. Among the glomerular morphologic characteristics, the number of visceral epithelial cells, or podocytes, per glomerulus was the strongest predictor of renal disease progression (UAE(4 years) r = -0.49, p = 0.05; Delta UAE, r = -0.57, p = 0.02), with fewer cells predicting more rapid progression. Glomerular basement membrane thickness did not predict progression (UAE(4 years) r = 0.11, p = 0.67; Delta UAE, r = 0.09,p = 0.73) and mesangial volume fraction had only a modest effect (UAE(4 years) r = 0.42, p = 0.11; Delta UAE, r = 0.48,p = 0.06). Conclusion/interpretation. Whether lower epithelial cell number per glomerulus among those that progressed was due to cellular destruction, a reduced complement of epithelial cells, or both is uncertain. Nevertheless, these findings suggest that podocytes play an important part in the development and progression of diabetic renal disease. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. VA Palo Alto Healthcare Syst, Dept Med, Stanford, CA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Nelson, RG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [N01-DK-6-2285, N01-DK-7-2291] NR 10 TC 252 Z9 272 U1 0 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 1999 VL 42 IS 11 BP 1341 EP 1344 DI 10.1007/s001250051447 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 250KR UT WOS:000083388000009 PM 10550418 ER PT J AU Harada, N Tamai, Y Ishikawa, T Sauer, B Takaku, K Oshima, M Taketo, MM AF Harada, N Tamai, Y Ishikawa, T Sauer, B Takaku, K Oshima, M Taketo, MM TI Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene SO EMBO JOURNAL LA English DT Article DE cell adhesion; cell migration; colon cancer; Tcf-Lef; Wnt signaling ID TUMOR-SUPPRESSOR PROTEIN; APC(DELTA-716) KNOCKOUT MICE; SITE-SPECIFIC RECOMBINATION; TRANSCRIPTION FACTOR LEF-1; ACID-BINDING-PROTEIN; HEPATOCELLULAR CARCINOMAS; FUNCTIONAL INTERACTION; TARGETED DISRUPTION; MOUSE DEVELOPMENT; TRANSGENIC MICE AB Ectopic expression of certain Wnt genes in mouse mammary tissue is tumorigenic, and mutations that stabilize beta-catenin are found in various human cancers including colorectal cancer. To determine the role of stabilized beta-catenin in intestinal tumorigenesis in mice, we constructed by embryonic stem (ES) cell-mediated homologous recombination, a mutant beta-catenin allele whose exon 3 was sandwiched by loxP sequences. When the germline heterozygotes were crossed with mice expressing Cre rccombinase in the intestines, the serines and threonine encoded by exon 3 and to be phosphorylated by glycogen synthase kinase 3 beta (GSK3 beta) were deleted in the offspring intestines, which caused adenomatous intestinal polyps resembling those in ApC(Delta 716) knockout mice. Some nascent microadenomas were also found in the colon. These results present experimental genetic evidence that activation of the Wnt signaling pathway can cause intestinal and colonic tumors. C1 Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Biomed Genet, Bunkyo Ku, Tokyo 1130033, Japan. Banyu Tsukuba Res Inst Merck, Tsukuba, Ibaraki 3002611, Japan. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Taketo, MM (reprint author), Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Biomed Genet, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. NR 50 TC 693 Z9 703 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 1999 VL 18 IS 21 BP 5931 EP 5942 DI 10.1093/emboj/18.21.5931 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 254EX UT WOS:000083599900014 PM 10545105 ER PT J AU Kiernan, RE Vanhulle, C Schiltz, L Adam, E Xiao, H Maudoux, F Calomme, C Burny, A Nakatani, Y Jeang, KT Benkirane, M Van Lint, C AF Kiernan, RE Vanhulle, C Schiltz, L Adam, E Xiao, H Maudoux, F Calomme, C Burny, A Nakatani, Y Jeang, KT Benkirane, M Van Lint, C TI HIV-1 Tat transcriptional activity is regulated by acetylation SO EMBO JOURNAL LA English DT Article DE acetylation; HIV-1 Tat; p300; PCAF; transcriptional activity ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-II; CARBOXY-TERMINAL DOMAIN; PROTEINS SPECIFICALLY ASSOCIATE; CREB-BINDING-PROTEIN; HISTONE ACETYLTRANSFERASE; TYPE-1 TAT; IN-VITRO; P-TEFB; ACTIVATED TRANSCRIPTION AB The human immunodeficiency virus (HIV) transactivator protein, Tat, stimulates transcription from the viral long-terminal repeats (LTR) through an RNA hairpin element, trans-activation responsive region (TAR). We and others have shown that trans-activator protein (Tat)-associated histone acetyltransferases (TAHs), p300 and p300/CBP-associating factor (PCAF), assist functionally in the activation of chromosomally integrated HIV-1 LTR. Here, we show that p300 and PCAF also directly acetylate Tat. We defined two sites of acetylation located in different functional domains of Tat. p300 acetylated Lys50 in the TAR RNA binding domain, while PCAF acetylated Lys28 in the activation domain of Tat. In support of a functional role for acetylation irt vivo, histone deacetylase inhibitor (trichostatin A) synergized with Tat in transcriptional activation of the HIV-1 LTR. Synergism was TAR-dependent and required the intact presence of both Lys28 and Lys50. Mechanistically, acetylation at Lys28 by PCAF enhanced Tat binding to the Tat-associated kinase, CDK9/P-TEFb, while acetylation by p300 at Lys50 of Tat promoted the dissociation of Tat from TAR RNA that occurs during early transcription elongation. These data suggest that acetylation of Tat regulates two discrete and functionally critical steps in transcription, binding to an RNAP II CTD-kinase and release of Tat from TAR RNA. C1 Inst Genet Humaine, Lab Virol Mol & Transfert Gene, UPR1142, F-34396 Montpellier, France. Free Univ Brussels, Inst Biol & Med Mol, Chim Biol Lab, B-6041 Gosselies, Belgium. NIAID, Mol Microbiol Lab, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD 20892 USA. RP Van Lint, C (reprint author), Inst Genet Humaine, Lab Virol Mol & Transfert Gene, UPR1142, F-34396 Montpellier, France. RI Jeang, Kuan-Teh/A-2424-2008 NR 67 TC 298 Z9 304 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 1999 VL 18 IS 21 BP 6106 EP 6118 DI 10.1093/emboj/18.21.6106 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 254EX UT WOS:000083599900030 PM 10545121 ER PT J AU Schwartz, B Rabinovich, NR AF Schwartz, B Rabinovich, NR TI Stimulating the development of orphan (and other) vaccines SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Schwartz, B (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV-DEC PY 1999 VL 5 IS 6 BP 832 EP 832 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 268HK UT WOS:000084408100017 PM 10603222 ER PT J AU Caprio, M Isidori, AM Carta, AR Moretti, C Dufau, ML Fabbri, A AF Caprio, M Isidori, AM Carta, AR Moretti, C Dufau, ML Fabbri, A TI Expression of functional leptin receptors in rodent Leydig cells SO ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the Endocrine-Society CY JUN 12-16, 1999 CL SAN DIEGO, CA SP Endocrine Soc ID CORTICOTROPIN-RELEASING-FACTOR; OBESE GENE-PRODUCT; LUTEINIZING-HORMONE; SERUM LEPTIN; RAT TESTIS; SIGNAL-TRANSDUCTION; INTERSTITIAL-CELLS; GENDER-DIFFERENCES; INSULIN-SECRETION; REPRODUCTIVE AXIS AB Several studies indicate that the size of body fat stores and the circulating levels of the adipocyte-derived hormone leptin are able to influence the activity of the hypothalamic-pituitary-gonadal axis. The leptin-hypothalamic-pituitary-gonadal interactions have been mainly studied at the level of the central nervous system. In this study, we investigated the possibility that leptin may have direct effects on the rodent Leydig cell function. To probe this hypothesis, we first analyzed the expression of leptin receptors (OB-R) in rodent Leydig cells in culture. RT-PCR studies showed that rat Leydig cells express both the long (OB-Rb) and short isoform (OB-Ra) of leptin receptor, whereas MLTC-1 cells (a murine Leydig tumor cell line) express only the long isoform. Short-term (30-90 min) incubation of rat Leydig cells with increasing concentrations of leptin (2-500 ng/ml) led to a significant and dose-dependent inhibition of human (h)CG-stimulated testosterone (T) production (similar to 60% reduction, IC50 = 20 ng/ml) but no change in basal androgen release. Also, leptin (150 ng/ml) amplified hCG-induced intracellular cAMP formation (1- to 2-fold) without modifying basal cAMP levels. Subsequent experiments showed that leptin inhibited 8Br-cAMP-stimulated T production, indicating that leptin's effect is exerted beyond cAMP. The inhibitory effect of leptin on hCG-induced T secretion was accompanied by a significant reduction of androstenedione and a concomitant rise of the precursor metabolites pregnenolone, progesterone, and 17-OH-progesterone, conceivable with a leptin-induced lesion of 17,20 lyase activity. Separate experiments performed with the MLTC-1 cells (not expressing cytochrome P450-17 alpha) showed that leptin, though amplifying hCG-stimulated cAMP production, did not modify hCG-stimulated pregnenolone and progesterone release. These results further indicate that leptin action on steroidogenesis occurs downstream of progesterone synthesis. Northern Blot experiments showed no acute effect of leptin on cytochrome P450-17 alpha messenger RNA accumulation in rat Leydig cells in basal and hCG-stimulated conditions, excluding that the rapid changes observed were caused by messenger RNA degradation. In conclusion, these findings, for the first time, show that leptin has direct, receptor-mediated actions on rodent Leydig cells in culture, at concentrations within the range of obese men. C1 Univ London St Bartholomews Hosp Med Coll, Dept Endocrinol, London EC1A 7BE, England. Univ Roma La Sapienza, Cattedra Androl, Policlin Umberto I, I-00161 Rome, Italy. NIMH, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Roma Tor Vergata, Cattedra Endocrinol, I-00100 Rome, Italy. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Fabbri, A (reprint author), Univ London St Bartholomews Hosp Med Coll, Dept Endocrinol, London EC1A 7BE, England. EM a.fabbri@caspur.it RI Isidori, Andrea/F-3062-2010; Caprio, Massimiliano/J-3020-2012; OI Isidori, Andrea/0000-0002-9037-5417; Caprio, Massimiliano/0000-0003-0722-7163; MORETTI, COSTANZO/0000-0003-4006-2575 NR 70 TC 148 Z9 154 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1999 VL 140 IS 11 BP 4939 EP 4947 DI 10.1210/en.140.11.4939 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600004 PM 10537117 ER PT J AU Liu, JL LeRoith, D AF Liu, JL LeRoith, D TI Insulin-like growth factor I is essential for postnatal growth in response to growth hormone SO ENDOCRINOLOGY LA English DT Article ID LONGITUDINAL BONE-GROWTH; TRANSGENIC MICE; IGF-I; ALKALINE-PHOSPHATASE; NEGATIVE FEEDBACK; GENE-EXPRESSION; BODY GROWTH; DEFICIENCY; RECEPTOR; MOUSE AB Insulin-like growth factor I(IGF-I) is essential for cell growth and intrauterine development while both IGF-I and GH are required for postnatal growth. To explore the possibility of direct GH action on body growth, independent of IGF-I production, we have studied the effects of GH in an IGF-I-deficient mouse line created by the Cre/loxP system. The IGF-I null mice are born with 35% growth retardation and show delayed onset of peripubertal growth, grow significantly slower, and do not attain puberty. Their adult body weight was approximately one third and body length about two thirds that of their wild-type Litter mates. Injection of recombinant human GH (rhGH, 3 mg/kg, twice daily, sc) between postnatal day 14 (P14) to P56 failed to stimulate their growth as measured as both body weight and length. In contrast, wild-type mice receiving the same doses of rhGH exhibited accelerated growth starting at P21 that continued until P56, when their body weight was increased by 30% and length by 12% compared with control mice treated with diluent. Despite the lack of response in growth, IGF-I null mice have normal levels of GH receptor expression in the liver and increased liver Jun B expression and liver size in response to rhGH treatment. Our results support an essential role for IGF-I in GH-induced postnatal body growth in mice. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bldg 10,Room 8D12,10 Ctr Dr, Bethesda, MD 20892 USA. EM Derek@helix.nih.gov NR 49 TC 147 Z9 157 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1999 VL 140 IS 11 BP 5178 EP 5184 DI 10.1210/en.140.11.5178 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600034 PM 10537147 ER PT J AU Barrera-Hernandez, G Park, KS Dace, A Zhan, QM Cheng, SY AF Barrera-Hernandez, G Park, KS Dace, A Zhan, QM Cheng, SY TI Thyroid hormone-induced cell proliferation in GC cells is mediated by changes in G1 cyclin/cyclin-dependent kinase levels and activity SO ENDOCRINOLOGY LA English DT Article ID TUMOR-SUPPRESSOR P53; HUMAN BREAST-CANCER; D-TYPE CYCLINS; STIMULATES GROWTH; NUCLEAR RECEPTOR; PHOSPHORYLATION; EXPRESSION; INDUCTION; ESTROGEN; D1 AB The thyroid hormone, 3,3', 5-triiodo-L-thyronine (T-3), is essential for growth and regulation of metabolic functions. The biological activities of T-3 are mediated by its interaction with the thyroid hormone nuclear receptors (TRs). The mechanism by which TRs mediate cell growth is unknown. We found that T-3 stimulated cell growth in GC cells by shortening the doubling time approximately S-fold. Flow cytometric analysis indicated that the growth stimulatory effect was mainly due to shortening of G1 phase accompanied by increases in S and G2/M: phases of the cell cycle. These changes correlated with T-3-induced increases in messenger RNA and protein levels of two key regulators of G1 progression, cyclins D1 and E, as well as cdk2. Furthermore, the kinase activities associated with cyclin D1 and E were activated up to 4-fold by T-3, which led to increased phosphorylation of the retinoblastoma protein (Rb), the driving force in G1 to S cell cycle progression. These results show for the first time that the growth promoting effect of T-3 in GC cells is mediated, at least in part, by increases in cyclin/cdk activities and the phosphorylation state of Rb. The functional link of T-3 to Rb has important implications for the understanding of the biology of normal and cancer cells. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 2D24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM sycheng@helix.nih.gov NR 31 TC 46 Z9 50 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1999 VL 140 IS 11 BP 5267 EP 5274 DI 10.1210/en.140.11.5267 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600044 PM 10537157 ER PT J AU Glasgow, E Kusano, K Chin, HM Mezey, E Young, WS Gainer, H AF Glasgow, E Kusano, K Chin, HM Mezey, E Young, WS Gainer, H TI Single cell reverse transcription-polymerase chain reaction analysis of rat supraoptic magnocellular neurons: Neuropeptide phenotypes and high voltage-gated calcium channel subtypes SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; BETA-SUBUNIT HETEROGENEITY; CA2+ CHANNELS; LACTATING RATS; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; FUNCTIONAL IMPLICATIONS; NEUROSECRETORY-CELLS; GENE-EXPRESSION; VASOPRESSIN; OXYTOCIN AB Magnocellular neurosecretory cells (MNCs) in the hypothalamoneurohypophysial system that express and secrete the nonapeptides oxytocin (OT) and vasopressin (VP) were evaluated for the expression of multiple genes in single magnocellular neurons from the rat supraoptic nucleus using a single cell RT-PCR protocol. We found that all cells representing the two major phenotypes, the OT and VP MNCs, express a small, but significant, amount of the other nonapeptide's messenger RNA (mRNA). In situ hybridization histochemical analyses confirmed this observation. A third phenotype, containing equivalent amounts of OT and VP mRNA, was detected in about 19% of the MNCs from lactating female supraoptic nuclei. Analyses of these phenotypes for other coexisting peptide mRNAs (e.g. CRH, cholecystokinin, galanin, dynorphin, and the calcium-binding protein, calbindin) generally confirmed expectations from the literature, but revealed cell to cell variation in their coexpression. Our results also show that the high voltage-activated calcium channel subunit genes, alpha 1A-D, alpha 2, and beta 1-4 are expressed in virtually all MNCs. However, the alpha 1E subunit gene is not expressed at detectable levels in these cells. The expression of all of the beta-subunit genes in each MNC may account for the variations in physiological and pharmacological properties of the high voltage-activated channels found in these neurons. C1 NINDS, Neurochem Lab, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. NINDS, BNP, Situ Facil, Bethesda, MD 20892 USA. NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, Basic Neurosci Program, NIH, Bldg 36,Room 4D20, Bethesda, MD 20892 USA. EM hgatnih@codon.nih.gov RI Young, W Scott/A-9333-2009; OI Young, W Scott/0000-0001-6614-5112; Glasgow, Eric/0000-0001-7729-3954 NR 46 TC 70 Z9 72 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1999 VL 140 IS 11 BP 5391 EP 5401 DI 10.1210/en.140.11.5391 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600058 PM 10537171 ER PT J AU Elsasser, TH Sartin, JL Martinez, A Kahl, S Montuenga, L Pio, R Fayer, R Miller, MJ Cuttitta, F AF Elsasser, TH Sartin, JL Martinez, A Kahl, S Montuenga, L Pio, R Fayer, R Miller, MJ Cuttitta, F TI Underlying disease stress augments plasma and tissue adrenomedullin (AM) responses to endotoxin: Colocalized increases in AM and inducible nitric oxide synthase within pancreatic islets SO ENDOCRINOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ENDOCRINE PANCREAS; FACTOR-ALPHA; EXPRESSION; INSULIN; METABOLISM; AUTOCRINE; SEPSIS; CALVES; CELLS AB Rapid onset metabolic impairments accompany the initiation of the acute phase response to many disease stresses, whereas more chronic metabolic perturbations may prolong the recovery period. In the present experiment the application of a mild endotoxin challenge [lipopolysaccharide (LPS)] alone or additive to a chronic subclinical parasitic infection (Sarcocystis cruzi; LPS + PI) in calves was used as a model to investigate and define a dynamic axis coordinated between adrenomedullin (AM) and nitric oxide in response to immune challenge. Plasma AM and NO2/NO3 concentration responses after LPS (0.45 mu g/kg, iv) were rapid in onset and of higher magnitude and longer duration in PI + LPS calves than in those challenged with LPS alone. The post-LPS increase in plasma insulin was significantly greater in PI + LPS than in LPS; following refeeding of calves, insulin secretion was most blunted in PI + LPS calves, consistent with the inhibitory effects of NO and AM on insulin secretion. A more chronic response to the immune challenge (organ specific) was in evidence in tissues harvested 24 h after LPS challenge. Where lung and Liver showed no immunostaining for inducible nitric oxide (iNOS), iNOS immunostaining was present in the pancreas, localized to islets only. The percentages of iNOS-immunopositive cells in islets were 1.7%, 21%, 6.7%, and 24% for control(C; saline infused), PI, LPS, and PI + LPS calves, respectively. AM immunostaining was not evident in the liver and was present, but not differentially affected by treatment, in airway epithelium in the lung. The number of islet cells with positive immunostaining for AM was increased in LPS, PI, and PI + LPS calves. The percentages of AM-immunopositive cells in islets were 8%, 27%, 20%, and 33% for C, PI, LPS, and PI + LPS, respectively. Immunostaining for AM and iNOS was colocalized with cells positive for pancreatic polypeptide. By triple label confocal fluorescence immunocytochemistry, colocalization of intense AM and iNOS immunostaining was confirmed in peripheral islet cells. A weaker, more diffuse iNOS signal was also apparent in insulin-containing cells in PI + LPS. We conclude that chronic low level infection potentiates the severity of metabolic perturbations that arise with additive sudden onset immune challenge, as can occur with bacterial toxins. These metabolic disturbances are reflected in and possibly mediated by early onset increases in plasma tumor necrosis factor-alpha, insulin, and AM and up-regulated iNOS activity. These acute complications rapidly progress into a more chronic state characterized by diminished insulin response to feeding stimulus and colocalized increases in pancreatic islet AM and iNOS. The pancreatic responses in AM and iNOS may play a major role in mediating prolonged disturbances in nutrient use by tissues through their influences on temporal patterns of pancreatic hormone secretion during chronic illness. C1 USDA ARS, Beltsville, MD 20705 USA. Auburn Univ, Dept Physiol & Pharmacol, Auburn, AL 36849 USA. NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. RP Elsasser, TH (reprint author), USDA ARS, Beltsville, MD 20705 USA. EM elsasser@lpsi.barc.usda.gov RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 NR 39 TC 22 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1999 VL 140 IS 11 BP 5402 EP 5411 DI 10.1210/en.140.11.5402 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600059 PM 10537172 ER PT J AU Suzuki, K Mori, A Saito, J Moriyama, E Ullianich, L Kohn, LD AF Suzuki, K Mori, A Saito, J Moriyama, E Ullianich, L Kohn, LD TI Follicular thyroglobulin suppresses iodide uptake by suppressing expression of the sodium/iodide symporter gene SO ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTION FACTOR-I; VASCULAR-PERMEABILITY FACTOR; THYROID-STIMULATING HORMONE; HUMAN TSH-RECEPTOR; GROWTH-FACTOR-I; FRTL-5 CELLS; IMMUNOHISTOCHEMICAL-DEMONSTRATION; IMMUNOGOLD TECHNIQUE; NODULAR GOITER; MESSENGER-RNA AB A major function of the thyrocyte is to take up and concentrate iodide. This is needed for thyroid hormone synthesis and is accomplished by the sodium iodide symporter (NIS), whose expression and activity are up-regulated by TSH. Recently, we reported that follicular thyroglobulin (TG) is a potent suppressor of thyroid-specific gene expression and can overcome TSH-increased gene expression. We suggested this might be a negative feedback, autoregulatory mechanism that counterbalanced TSH stimulation of follicular function. In this report, we support this hypothesis by coordinately evaluating TG regulation of NIS gene expression and iodide transport. We show that physiological concentrations of TG similarly and significantly suppress TSH-increased NIS promoter activity, NIS protein, and NIS-dependent iodide uptake as well as RNA levels. We show, in vivo, that TG accumulation at the apical membrane of a thyrocyte facing the follicular lumen is associated with decreased uptake of radioiodide. It is likely, therefore, that TG suppresses NIS-dependent iodide uptake and NIS gene expression in vivo, as is the case in vitro. RNA levels of NIS and vascular endothelial growth factor/vascular permeability factor, which has been reported to be TSH regulated and possibly associated with TSH-increased iodide uptake, are coordinately decreased by follicular TG as a function of concentration and time. Also, removal of follicular TG from the medium, but not TSH, coordinately returns NIS and vascular endothelial growth factor/vascular permeability factor RNA levels to their TSH-stimulated state. TG accumulated in the follicular lumen appears, therefore, to be a negative feedback regulator of critical TSH-increased follicular functions, iodide uptake, and vascular permeability. C1 NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Kohn, LD (reprint author), NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bldg 10,Room 9C101B, Bethesda, MD 20892 USA. EM lenk@bdg10.niddk.nih.gov NR 56 TC 56 Z9 59 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1999 VL 140 IS 11 BP 5422 EP 5430 DI 10.1210/en.140.11.5422 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600061 PM 10537174 ER PT J AU Field, RW Steck, DJ Parkhurst, MA Mahaffey, JA Alavanja, MCR AF Field, RW Steck, DJ Parkhurst, MA Mahaffey, JA Alavanja, MCR TI Intercomparison of retrospective radon detectors SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE case-control studies; dose-response relationship (radiation); epidemiologic methods; epidemiologic studies; lung neoplasms; radon; radon progeny; smoking ID LUNG-CANCER; RESIDENTIAL RADON; INDOOR RADON; EXPOSURE; RISK; WOMEN; PRODUCTS; PO-210; GLASS AB We performed both a laboratory and a field intercomparison of two novel glass-based retrospective radon detectors previously used in major radon case-control studies performed in Missouri and Iowa. The new detectors estimate retrospective residential radon exposure from the accumulation of a long-lived radon decay product, Pb-210, in glass. The detectors use track registration material in direct contact with glass surfaces to measure the alpha-emission of a Pb-210-decay product, Po-210. The detector's track density generation rate (tracks per square centimeter per hour) is proportional to the surface a-activity. In the absence of other strong sources of alpha-emission in the glass, the implanted surface alpha-activity should be proportional to the accumulated Po-210, and hence to the cumulative radon gas exposure. The goals of the intercomparison were to a) perform collocated measurements using two different glass-based retrospective radon detectors in a controlled laboratory environment to compare their relative response to implanted polonium in the absence of environmental variation, b) perform collocated measurements using two different retrospective radon progeny detectors in a variety of residential settings to compare their detection of glass-implanted polonium activities, and c) examine the correlation between track density rates and contemporary radon gas concentrations. The laboratory results suggested that the materials and methods used by the studies produced similar track densities in detectors exposed to the same implanted Po-210 activity. The field phase of the intercomparison found excellent agreement between the track density rates for the two types of retrospective detectors. The correlation between the track density rates and direct contemporary radon concentration measurements was relatively high, considering that no adjustments were performed to account for either the residential depositional environment or glass surface type. Preliminary comparisons of the models used to translate track rate densities to average long-term radon concentrations differ between the two studies. Further calibration of the retrospective detectors' models for interpretation of track rate density may allow the pooling of studies that use glass-based retrospective radon detectors to determine historic residential radon exposures. C1 Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA 52242 USA. St Johns Univ, Dept Phys, Collegeville, MN 56321 USA. Pacific NW Natl Lab, Richland, WA USA. Natl Canc Inst, Bethesda, MD USA. RP Field, RW (reprint author), Univ Iowa, Dept Epidemiol, Coll Publ Hlth, N222 Oakdale Hall, Iowa City, IA 52242 USA. FU NIEHS NIH HHS [P30 ES05605]; PHS HHS [263-MQ-820009] NR 30 TC 13 Z9 14 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1999 VL 107 IS 11 BP 905 EP 910 DI 10.2307/3454479 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 258NW UT WOS:000083846100030 PM 10545336 ER PT J AU Piver, WT Ando, M Ye, F Portier, CJ AF Piver, WT Ando, M Ye, F Portier, CJ TI Temperature and air pollution as risk factors for heat stroke in Tokyo, July and August 1980-1995 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollutants; generalized linear regression models; heat stroke; maximum daily temperatures ID HEALTH-EFFECTS RESEARCH; NITROGEN-DIOXIDE; PULMONARY-FUNCTION; RESPIRATORY HEALTH; CHILDREN; MORTALITY; EXPOSURE; QUALITY; HOMES; WAVE AB Heat stroke is associated with prolonged exposures to high air temperatures that usually occur in the summer months of July and August in Tokyo, Japan. Also during July and August, residents of Tokyo are often exposed simultaneously to high concentrations of air pollutants. To assess the impacts of these combined exposures, daily numbers of heat stroke emergency transport cases/million residents for Tokyo were stratified by gender and three groups: 0-14, 15-64, and > 65 years of age, for the months of July and August in 1980-1995. A regression model was constructed using daily maximum temperature (T-max) and daily average concentrations of NO2 and O-3 as model covariates. Classification indices were added to make it possible to compare the expected number of heat stroke cases by age and gender. Lag times of 1-4 days in T-max and air quality covariates and terms to account for interactions between pairs of model covariates were also included as additional risk factors. Generalized linear models (GLMs), assuming a Poisson error structure for heat stroke emergency transport cases, were used to determine which covariates were significant risk factors for heat stroke for the three age groups of males and females. Same-day Tm, and concentrations of NO2 were the most significant risk factors for heat stroke in all age groups of males and females. The number of heat stroke emergency transport cases/million residents was greater in males than in females in the same age groups. The smallest number of heat stroke emergency transport cases/million residents occurred for females 0-14 years of age and the greatest number of heat stroke emergency transport cases/million residents occurred for males > 65 years of age. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Studies, Tsukuba, Ibaraki, Japan. RP Piver, WT (reprint author), NIEHS, POB 12233,EC-14, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 27 TC 26 Z9 34 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 1999 VL 107 IS 11 BP 911 EP 916 DI 10.2307/3454480 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 258NW UT WOS:000083846100031 PM 10544159 ER PT J AU Cooper, GS Sandler, DP Bohlig, M AF Cooper, GS Sandler, DP Bohlig, M TI Active and passive smoking and the occurrence of natural menopause SO EPIDEMIOLOGY LA English DT Article DE menopause; smoking; age ID CIGARETTE-SMOKING; AGE; WOMEN AB We examined smoking in relation to natural menopause in 543 women who prospectively recorded menstrual data from their 20s. Mean age at natural menopause was 0.8 years younger (95% CL = -1.5, -0.0) in 98 women who smoked at menopause compared with 362 never-smokers (RR 1.3, 95% CI = 1.0-1.7). We did not observe a decrease in age at natural menopause in former smokers, a dose-response among current smokers, or a lower age at menopause with passive smoke exposure at home. These results suggest that the effect of smoking on ovarian senescence is limited to active smoking during the menopausal transition. C1 NIEHS, Epidemiol Branch A3 05, Res Triangle Pk, NC 27709 USA. CODA Inc, Res Triangle Pk, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch A3 05, POB 12233, Res Triangle Pk, NC 27709 USA. OI Sandler, Dale/0000-0002-6776-0018 FU NCRR NIH HHS [M01-RR00064] NR 15 TC 77 Z9 78 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1999 VL 10 IS 6 BP 771 EP 773 DI 10.1097/00001648-199911000-00021 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 248TB UT WOS:000083290500020 PM 10535795 ER PT J AU Soudeyns, H Paolucci, S Chappey, C Daucher, MB Graziosi, C Vaccarezza, M Cohen, OJ Fauci, AS Pantaleo, G AF Soudeyns, H Paolucci, S Chappey, C Daucher, MB Graziosi, C Vaccarezza, M Cohen, OJ Fauci, AS Pantaleo, G TI Selective pressure exerted by immunodominant HIV-1-specific cytotoxic T lymphocyte responses during primary infection drives genetic variation restricted to the cognate epitope SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE HIV-1; cytotoxic T lymphocyte; viral escape mutation ID VIRUS EXPRESSION VECTOR; VACCINIA VIRUS; DISEASE PROGRESSION; HIV-INFECTION; VIRAL LOAD; CELL; ESCAPE; VARIANTS; VIREMIA; AIDS AB HIV-specific cytotoxic T lymphocytes (CTL) play a central role in the control of HIV-I replication during primary infection. it has been hypothesized that the appearance of CTL escape mutants represents an important mechanism by which HIV-1 escapes the host cell-mediated immune response. However, evidences for a direct relationship between CTL responses and emergence of CTL escape mutants are still limited. Here we report detailed longitudinal analysis of DNA sequence variation performed over the entire HIV-1 envelope in two subjects during primary HIV infection. Estimates of the frequencies of synonymous (dS) and non-synonymous (dN) nucleotide substitutions were used to identify regions of the HIV-1 envelope which were subjected to significant levels of selective pressure. These regions were shown to comprise defined epitopes recognized by CTL. Furthermore, dN mutation fixed within these epitopes effectively abolished recognition by the host CTL response. These results provide compelling evidence that the CTL epitope mutations directly resulted from the selective pressure exerted by the virus-specific cytotoxic response. C1 CHU Vaudois, Hop Beaumont, Lab AIDS Immunopahtogenesis, Dept Internal Med, CH-1011 Lausanne, Switzerland. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD USA. RP Pantaleo, G (reprint author), CHU Vaudois, Hop Beaumont, Lab AIDS Immunopahtogenesis, Dept Internal Med, 29 Rue Beaumont, CH-1011 Lausanne, Switzerland. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 24 TC 33 Z9 33 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 1999 VL 29 IS 11 BP 3629 EP 3635 DI 10.1002/(SICI)1521-4141(199911)29:11<3629::AID-IMMU3629>3.0.CO;2-O PG 7 WC Immunology SC Immunology GA 255UT UT WOS:000083689100023 PM 10556818 ER PT J AU Leviton, LC Finnegan, JR Zapka, JG Meischke, H Estabrook, B Gilliland, J Linares, A Weitzman, ER Raczynski, J Stone, E AF Leviton, LC Finnegan, JR Zapka, JG Meischke, H Estabrook, B Gilliland, J Linares, A Weitzman, ER Raczynski, J Stone, E TI Formative research methods to understand patient and provider responses to heart attack symptoms SO EVALUATION AND PROGRAM PLANNING LA English DT Article DE acute myocardial infarction; community trials; community interventions; focus groups; formative research; qualitative methods ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; ACUTE CHEST PAIN; THROMBOLYTIC THERAPY; MEDIA CAMPAIGN; PREHOSPITAL DELAY; PUBLIC-EDUCATION; HOSPITAL ARRIVAL; EMERGENCY; CARE AB Formative research is often required for program planning, and for reducing uncertainty about generalizability of program effects. This article describes and justifies methods of formative research conducted for the REACT study (Rapid Early Action for Coronary Treatment), a multi-center collaborative randomized community trial aimed at reducing patient delay in seeking care for acute myocardial infarction (AMI). Formative research cast light on patient and community members' decision-making process in seeking help for AMI, as well as barriers and facilitators of this process. Investigators at all five REACT Field Centers participated in the formative research. The process consisted of: (1) developing a common theoretical framework for the study intervention; (2) conducting a literature review and qualitative research to identify and address gaps in knowledge; and (3) developing a common protocol for the REACT study that accommodated the diversity of the target communities in terms of services, resources, history, and ethnicity. Analysis employed triangulation, defined as an explicit search for heterogeneous data sources to reduce uncertainty about forces at work and opportunities for intervention across settings and populations. Because the collection and interpretation of data went in stages, staff of several REACT Field Centers had independent input to the overall synthesis, then shared and revised the results. Advantages and limitations of this approach are discussed. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Alabama, Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL 35294 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. King Cty Dept Emergency Serv, Seattle, WA USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NHLBI, Bethesda, MD 20892 USA. RP Leviton, LC (reprint author), Univ Alabama, Sch Publ Hlth, Dept Hlth Behav, Suite 227,1665 Univ Blvd, Birmingham, AL 35294 USA. NR 72 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7189 J9 EVAL PROGRAM PLANN JI Eval. Program Plan. PD NOV PY 1999 VL 22 IS 4 BP 385 EP 397 DI 10.1016/S0149-7189(99)00025-7 PG 13 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 270VC UT WOS:000084557000002 ER PT J AU Reed, SF Porges, SW Newlin, DB AF Reed, SF Porges, SW Newlin, DB TI Effect of alcohol on vagal regulation of cardiovascular function: Contributions of the polyvagal theory to the psychophysiology of alcohol SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID HEART-RATE-VARIABILITY; TOLERANCE; BLOCKADE; STRESS; MODEL AB Research was conducted to evaluate the influence of acute alcohol consumption on vagal regulation of heart rate, Nine men with histories of polydrug use participated in this residential study. On 5 separate days, they drank liquids consisting of cold water (on 2 days), a moderate dose of alcohol (0.64 g/kg), a high dose of alcohol (1.12 g/kg), and a placebo. Continuous recordings of heart period were quantified to produce 3 measures of heart rate variability, reflecting the amplitude of 3 neurophysiologically mediated rhythms. Heart period, respiratory rhythm (i.e., respiratory sinus arrhythmia [RSA]), and the 0.06-0.10-Hz vasomotor rhythm were significantly lower during the high alcohol dose condition, relative to the placebo and water conditions. Because the neural regulation of the heart by the vagus contributes to these variables, these findings suggest that alcohol reduces cardiac vagal tone. In support of this explanation, alcohol also decreased the coupling between changes in heart period and changes in RSA. This study demonstrated that alcohol produces a dysregulated state in which heart rate is relatively uncoupled from vagal activity. C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. RP Newlin, DB (reprint author), Natl Inst Drug Abuse, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 30 TC 34 Z9 35 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD NOV PY 1999 VL 7 IS 4 BP 484 EP 492 DI 10.1037//1064-1297.7.4.484 PG 9 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 264HV UT WOS:000084175500019 PM 10609983 ER PT J AU Chen, R Corwell, B Hallett, M AF Chen, R Corwell, B Hallett, M TI Modulation of motor cortex excitability by median nerve and digit stimulation SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE motor cortex; magnetic stimulation; excitability; nerve stimulation; cortical rhythm ID MAGNETIC BRAIN-STIMULATION; CUTANEOUS SILENT PERIOD; SELF-PACED MOVEMENTS; PERIPHERAL-NERVE; F-WAVE; TRANSCRANIAL STIMULATION; NEURON EXCITABILITY; EVOKED-POTENTIALS; NONINVASIVE EVALUATION; THALAMIC PROJECTIONS AB We investigated the time course of changes in motor cortex excitability after median nerve and: digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APE, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200-600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Chen, R (reprint author), Univ Hlth Network, Toronto Western Hosp, Div Neurol, EC8-025,399 Bathurst St, Toronto, ON M5T 2S8, Canada. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 70 TC 160 Z9 160 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD NOV PY 1999 VL 129 IS 1 BP 77 EP 86 DI 10.1007/s002210050938 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 250TC UT WOS:000083403400006 PM 10550505 ER PT J AU List, HJ Smith, CL Rodriguez, O Danielsen, M Riegel, AT AF List, HJ Smith, CL Rodriguez, O Danielsen, M Riegel, AT TI Inhibition of histone deacetylation augments dihydrotestosterone induction of androgen receptor levels: An explanation for trichostatin A effects on androgen-induced chromatin remodeling and transcription of the mouse mammary tumor virus promoter SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE androgen receptor; transcription; chromatin; histone deacetylase inhibitor; MMTV promoter ID MMTV PROMOTER; IN-VIVO; GENE-EXPRESSION; NUCLEOSOME; ACTIVATION; ACETYLTRANSFERASE; COMPLEX; ACETYLATION; SPECIFICITY; DISRUPTION AB The integrated mouse mammary tumor virus (MMTV) promoter has provided an excellent model system with which to study the impact of steroid hormones on transcriptional activation in the context of a defined chromatin structure. The hormone response element (HRE) of this promoter is positioned on a phased nucleosome which becomes remodeled in response to steroids. One possible mechanism of chromatin remodeling by steroid receptors could involve recruitment of coactivators which alter the histone acetylation status of the HRE nucleosome. To examine how the androgen receptor (AR) influences transcription and chromatin remodeling and to assess whether changes in histone acetylation are involved in these effects, we determined whether the specific histone deacetylase inhibitor trichostatin A (TSA) influenced basal- and androgen-mediated transcriptional activation of the integrated MMTV promoter in the mouse L-cell fibroblast cell line 29+. These cells harbor the MMTV promoter integrated in the genome and express only one steroid hormone receptor subtype, i.e., the AR. Surprisingly, we found that treatment of the cells with TSA alone had virtually no effect on transcription and chromatin remodeling of the MMTV promoter nor on AR levels. However, pretreatment with TSA augmented the DHT effects on all three parameters. These results suggest that histone acetylation changes at the MMTV B nucleosome per se are not alone sufficient to induce chromatin remodeling and subsequent induction of MMTV transcription. Rather, the histone deacetylase inhibitor TSA exerts a portion of its effect on MMTV chromatin remodeling and transcriptional activation indirectly through increases in AR levels. (C) 1999 Academic Press. C1 Georgetown Univ, Dept Pharmacol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Dept Biochem & Mol Biol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Riegel, AT (reprint author), Georgetown Univ, Dept Pharmacol, Vincent T Lombardi Canc Res Ctr, Res Bldg E307,3970 Reservoir Rd, Washington, DC 20007 USA. RI Danielsen, Mark/B-1606-2008 OI Danielsen, Mark/0000-0002-0923-9945 NR 40 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 1 PY 1999 VL 252 IS 2 BP 471 EP 478 DI 10.1006/excr.1999.4638 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 255BW UT WOS:000083650500023 PM 10527637 ER PT J AU Ikonemevic, MD Mizukami, K Warde, D Sheffield, R Hamilton, R Wenthold, RJ Armstrong, DM AF Ikonemevic, MD Mizukami, K Warde, D Sheffield, R Hamilton, R Wenthold, RJ Armstrong, DM TI Distribution of glutamate receptor subunit NMDAR1 in the hippocampus of normal elderly and patients with Alzheimer's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; hippocampus; glutamate; receptors; excitotoxicity; immunohistochemistry ID METHYL-D-ASPARTATE; SUBTYPE IMMUNOREACTIVITY; ENTORHINAL CORTEX; NEURITIC PLAQUES; MONKEY HIPPOCAMPUS; TCP BINDING; DENTATE GYRUS; SUBSTANCE-P; GLUR2(4); NEURONS AB Immunocytochemical techniques were employed to study the distribution and cytological features of NMDAR1-immunoreactive elements in the? human hippocampal formation. Subjects with Alzheimer's disease (AD), presenting with a wide range of neuropathology and classified into six Braak stages (I-VI), and nondemented age-matched controls were examined, In control cases, the most intense NMDAR1 immunoreactivity was observed within the soma and dendrites of granule cells in the dentate gyrus and pyramidal neurons in Ammon's horn. Whereas small variations in the pattern of immunoreactivity were noted in control cases, AD subjects were characterized with intersubject variability which in most instances correlated with neuropathologic severity. For example, AD cases, particularly those with mild/modest pathology (Braak I-UI), were indistinguishable from controls in the overall pattern of immunolabeling. In contrast, in those more severe AD eases (Braak IV-VI) the intensity of immunolabeling within the CA fields was greater than observed in controls and those with mild AD pathology In addition, in pathologically severe cases numerous NMDAR1-positive pyramidal neurons were: characterized by unique morphologic features including long and often tortuous apical dendrites. These latter findings were most prevalent in the CA1 region and subiculum. In contrast to the marked increase in immunolabeling in the CA fields, in the dentate gyrus we observed a reduction in NMDAR1 labeling particularly within the outer molecular layer (i.e., termination zone of the perforant pathway). This latter region was also the site of a number of NMDAR1-labeled plaques. Notably, the overall pattern of NMDAR1 immunoreactivity is distinct from that observed with antibodies against AMPA receptor subunits and suggests a differential role of various inotropic glutamate receptors in hippocampal plasticity in AD. (C) 1999 Academic Press. C1 Allegheny Univ Hlth Sci, Neurosci Res Ctr, Pittsburgh, PA 15212 USA. Univ Tsukuba, Inst Clin Med, Dept Psychiat, Tsukuba, Ibaraki 305, Japan. Presbyterian Univ Hosp, Div Neuropathol, Pittsburgh, PA 15213 USA. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Ikonemevic, MD (reprint author), Allegheny Univ Hlth Sci, Neurosci Res Ctr, Allegheny Campus, Pittsburgh, PA 15212 USA. FU NIA NIH HHS [AG05133, AG08206] NR 34 TC 43 Z9 47 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1999 VL 160 IS 1 BP 194 EP 204 DI 10.1006/exnr.1999.7196 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 257QE UT WOS:000083792400019 PM 10630204 ER PT J AU Wang, J Zhou, J Bondy, CA AF Wang, J Zhou, J Bondy, CA TI Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy SO FASEB JOURNAL LA English DT Article DE glucose transporter; IGF action; insulin; proliferation; epiphysis; short stature ID FACTOR-I; SIGNAL-TRANSDUCTION; PLATE; HORMONE; MICE; EXPRESSION; CARTILAGE; RECEPTOR; ZONES; RATS AB Longitudinal bone growth, and hence stature, are functions of growth plate chondrocyte proliferation and hypertrophy, Insulin-like growth factor 1 (Igf1) is reputed to augment longitudinal bone growth by stimulating growth plate chondrocyte proliferation. In this study, however, we demonstrate that chondrocyte numbers and proliferation are normal in Igf1 null mice despite a 35% reduction in the rate of long bone growth. Igf1 null hypertrophic chondrocytes differentiate normally in terms of expressing specialized proteins such as collagen X and alkaline phosphatase, but are smaller than wildtype at all levels of the hypertrophic zone, The terminal hypertrophic chondrocytes, which form the scaffold on which long bone growth extends, are reduced in linear dimension by 30% in Igf1 null mice, accounting for most of their decreased longitudinal growth, The expression of the insulin-sensitive glucose transporter, GLUT4, is significantly decreased and the insulin-regulated enzyme glycogen synthase kinase 3 beta (GSK3) is hypo-phosphorylated in ISf1 null chondrocytes, Glycogen levels were significantly decreased and ribosomal RNA levels were reduced by almost 75% in Igf1 null chondrocytes, These data suggest that Igf1 promotes longitudinal bone growth by 'insulin-like' anabolic actions which augment chondrocyte hypertrophy.-Wang, J., Zhou, J., Bendy, C. A. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Rm 10N262,10 Ctr Dr 1862, Bethesda, MD 20892 USA. NR 27 TC 151 Z9 152 U1 3 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 1999 VL 13 IS 14 BP 1985 EP 1990 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 255GG UT WOS:000083660700010 PM 10544181 ER PT J AU Nelson, EL Strobl, S Subleski, J Prieto, D Kopp, WC Nelson, PJ AF Nelson, EL Strobl, S Subleski, J Prieto, D Kopp, WC Nelson, PJ TI Cycling of human dendritic cell effector phenotypes in response to TNF-alpha: modification of the current 'maturation' paradigm and implications for in vivo immunoregulation SO FASEB JOURNAL LA English DT Article DE antigen presenting cells; cytokines; chemokines; and dendritic cell activation ID NECROSIS-FACTOR-ALPHA; COLONY-STIMULATING FACTOR; IN-VITRO; T-CELLS; HUMAN BLOOD; IMMUNE-RESPONSE; CYTOKINE; PROGENITORS; GENERATION; ACTIVATION AB Dendritic cells (DCs) are potent antigen presenting cells reported to undergo irreversible functional 'maturation' in response to inflammatory signals such as TNF-alpha. The current paradigm holds that this DC maturation event is required for full functional capacity and represents terminal differentiation of this cell type, culminating in apoptotic cell death. This provides a possible mechanism for avoiding dysregulated immunostimulatory activity, but imposes constraints on the capacity of DCs to influence subsequent immune responses and to participate in immunological memory. We report that the cell surface and functional effects induced by TNF-alpha are reversible and reinducible. These effects are accompanied by a concordant modulation of cytokine mRNA expression that includes the induction of proinflammatory factors (IL-15, IL-12, LT-a!, LT-beta, TNF-alpha, RANTES) which is coincident with the down-regulation of counter-regulatory cytokines (IL-10, TGF-beta 1, TGF-beta 2, IL-1 RA, MCP-1). The resultant net effect is a dendritic cell activation state characterized by a transient proinflammatory posture. These results demonstrate that 1) human DCs do not undergo terminal 'maturation' in response to TNF-alpha, 2) DC phenotypes are more pleiotropic than previously thought, and 3) DCs are potential immunoregulatory effector cells with implications for control of immune responses in both in vivo and in vitro systems.-Nelson, E. L., Strobl, S., Subleski, J., Prieto, D., Kopp, W. C., Nelson, P. J. Cycling of human dendritic cell effector phenotypes in response to TNF-alpha: modification of the current 'maturation' paradigm and implications for in vivo immunoregulation. Cycling of human dendritic cell effector phenotypes in response to TNF-alpha modification of the current 'maturation' paradigm and implications for in vivo immunoregulation. C1 NCI, Immunotherapy Lab, FCRDC, Div Clin Sci, Frederick, MD 21702 USA. NCI, Clin Support Lab, FCRDC, Div Clin Sci, Frederick, MD 21702 USA. Univ Munich, Med Poliklin, D-8000 Munich, Germany. RP Nelson, EL (reprint author), NCI, Immunotherapy Lab, FCRDC, Div Clin Sci, Bldg 1050,Boyles St, Frederick, MD 21702 USA. EM enelson@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 46 TC 37 Z9 39 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 1999 VL 13 IS 14 BP 2021 EP 2030 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 255GG UT WOS:000083660700014 PM 10544185 ER PT J AU Leshner, AI AF Leshner, AI TI We can conquer drug addiction SO FUTURIST LA English DT Article C1 NIDA, Bethesda, MD 20892 USA. RP Leshner, AI (reprint author), NIDA, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WORLD FUTURE SOCIETY PI BETHESDA PA 7910 WOODMONT AVE, SUITE 450, BETHESDA, MD 20814 USA SN 0016-3317 J9 FUTURIST JI Futurist PD NOV PY 1999 VL 33 IS 9 BP 22 EP 25 PG 4 WC Social Issues SC Social Issues GA 246TY UT WOS:000083181700016 ER PT J AU Fuss, IJ Marth, T Neurath, MF Pearlstein, GR Jain, A Strober, W AF Fuss, IJ Marth, T Neurath, MF Pearlstein, GR Jain, A Strober, W TI Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; HAPTEN-INDUCED MODEL; GROWTH-FACTOR-BETA; IFN-GAMMA; ULCERATIVE-COLITIS; INTERFERON-GAMMA; CROHNS-DISEASE; IMMUNOREGULATORY FUNCTIONS; ORAL TOLERANCE; EXPRESSION AB Background & Aims: Trinitrobenzene sulfonic acid (TNBS)-induced colitis is a T-helper 1 (Th1) T cell-mediated inflammation that is rapidly reversed by administration of anti-interleukin (IL) 12. This study sought to define the mechanism of this curative effect. Methods: Cells and tissue from mice with TNBS colitis receiving treatment with anticytokines were analyzed for phenotype, cytokine production, and apoptosis. Results: In initial studies, we found that treatment of mice with TNBS-induced colitis with anti-IL-12 was more effective than with anti-interferon (IFN)-gamma, and that anti-IL-12 led to complete normalization of IFN-gamma production by lamina propria T cells ex vivo, whereas anti-IFN-gamma did not. These data suggesting that anti-IL-12 leads to reversal of colitis by elimination of the Th1 T cells were substantiated by studies showing that anti-IL-12 treatment led to increased numbers of apoptotic cells in the lamina propria and spleen by both TUNEL staining of tissues and dispersed spleen cell populations. Finally, we found that the observed apoptosis was mediated by the Fas pathway because (1) MRL/MpJ-lpr(fas) mice lacking Fas function develop colitis that responds poorly to treatment with anti-IL-12; and (2) SJL/J mice with TNBS colitis that received Fas-Fc to block the Fas pathway were resistant to anti-IL-12 treatment. Conclusions: These studies show that a main mechanism of action of anti-IL-12 in TNBS-induced colitis is the induction of Fas-mediated apoptosis of the Th1 T cells, causing inflammation. C1 NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. Univ Saarlandes Kliniken, Div Gastroenterol, Homburg, Germany. Univ Mainz, Immunol Lab, Med Clin 1, D-6500 Mainz, Germany. RP Fuss, IJ (reprint author), NIAID, Mucosal Immun Sect, NIH, Bldg 10,Room 11N238, Bethesda, MD 20892 USA. NR 40 TC 205 Z9 207 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1999 VL 117 IS 5 BP 1078 EP 1088 DI 10.1016/S0016-5085(99)70392-6 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 250NH UT WOS:000083394100010 PM 10535870 ER PT J AU Lau, DTY Kleiner, DE Park, Y Di Bisceglie, AM Hoofnagle, JH AF Lau, DTY Kleiner, DE Park, Y Di Bisceglie, AM Hoofnagle, JH TI Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy SO GASTROENTEROLOGY LA English DT Article ID B SURFACE-ANTIGEN; VIRUS-INFECTION; LIVER FIBROSIS; ALPHA; MULTICENTER; CARRIERS; SERUM AB Chronic delta hepatitis is an uncommon but severe form of chronic viral hepatitis for which there is currently no satisfactory therapy. A patient with chronic delta hepatitis was treated with;interferon alfa, 5 million units daily for 12 years. Serial serum samples were tested for routine liver tests and selected samples for quantitative levels of hepatitis B surface antigen (HBsAg) and hepatitis delta virus RNA, Liver biopsies were performed before, during, and after an initial 1-year course of therapy and again after 3 and 10 years of continuous therapy. With initiation of interferon therapy, serum aminotransferase levels decreased to normal range, became abnormal again when the dose was reduced, and increased to pretreatment levels when therapy was stopped. With reinstitution and prolonged therapy, aminotransferase levels became persistently normal; after several years, both hepatitis delta virus RNA and serum HBsAg became undetectable. Liver biopsy, which initially revealed cirrhosis, showed gradual improvement in inflammatory and fibrosis scores and, after 10 years, no abnormalities or fibrosis, Therapy was stopped, and the patient remained free of evidence of infection. In conclusion, long-term therapy with interferon alfa in high doses led to resolution of chronic delta hepatitis, disappearance of hepatitis delta and B virus markers, and improvement in fibrosis. C1 NIDDKD, Digest Dis Branch, Liver Dis Sect, NCI, Bethesda, MD USA. Warren E Magnuson Clin Ctr, Dept Nursing, NIH, Bethesda, MD USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A23, Bethesda, MD 20892 USA. OI Kleiner, David/0000-0003-3442-4453 NR 26 TC 85 Z9 90 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1999 VL 117 IS 5 BP 1229 EP 1233 DI 10.1016/S0016-5085(99)70409-9 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 250NH UT WOS:000083394100027 PM 10535887 ER PT J AU Lee, TH Yu, SL Kim, SU Lee, KK Rhee, SG Yu, DY AF Lee, TH Yu, SL Kim, SU Lee, KK Rhee, SG Yu, DY TI Characterization of mouse peroxiredoxin I genomic DNA and its expression SO GENE LA English DT Article DE anti-oxidant enzyme; mouse Prx I gene; retrotransposition ID THIOL-SPECIFIC ANTIOXIDANT; MAMMALIAN PEROXIREDOXIN; CLONING; PROTEIN; REDUCTASE; GENE; MUTATION; FAMILY AB Peroxiredoxins (Prxs) are a newly defined family of anti-oxidant proteins that have been implicated, via their anti-oxidant activity, in a number of cellular functions, including cell proliferation and differentiation, protection of other proteins from oxidative damage, and intracellular signaling. We isolated genomic DNA sequences of the Prx I genes from the mouse, and characterized their molecular genetic features. Prx I was found to form a small gene family with two and three members; one functional and two pseudogenes. The Prx I-1 gene has splice donor/acceptor site sequences and five or six exons, whereas the Prx I-2 clone has several structural features characteristic of a typical retroposon found to have ORF sequences. We analyzed the expression of pseudogenes, which were not expressed on the transcription levels in the investigated organs. The functional copy of the Prx I-1 gene was expressed abundantly in liver and kidney of the adult, as well as in early developing embryos. This report, together with amino acid/nucleotide sequence similarity between human and mice, provides a basis for speculating on an even earlier event in the evolution of the Prx I gene family, i.e. the Prx I gene was well conserved in human and mice via its antioxidant activity. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Korea Res Inst Biosci & Biotechnol, Taejon 305600, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Yu, DY (reprint author), Korea Res Inst Biosci & Biotechnol, POB 115, Taejon 305600, South Korea. NR 16 TC 11 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 1 PY 1999 VL 239 IS 2 BP 243 EP 250 DI 10.1016/S0378-1119(99)00413-8 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 255HH UT WOS:000083663100005 PM 10548725 ER PT J AU Kashuba, VI Gizatullin, RZ Protopopov, AI Li, J Vorobieva, NV Fedorova, L Zabarovska, VI Muravenko, OV Kost-Alimova, M Domninsky, DA Kiss, C Allikmets, R Zakharyev, VM Braga, EA Sumegi, J Lerman, M Wahlestedt, C Zelenin, AV Sheer, D Winberg, G Grafodatsky, A Kisselev, LL Klein, G Zabarovsky, ER AF Kashuba, VI Gizatullin, RZ Protopopov, AI Li, J Vorobieva, NV Fedorova, L Zabarovska, VI Muravenko, OV Kost-Alimova, M Domninsky, DA Kiss, C Allikmets, R Zakharyev, VM Braga, EA Sumegi, J Lerman, M Wahlestedt, C Zelenin, AV Sheer, D Winberg, G Grafodatsky, A Kisselev, LL Klein, G Zabarovsky, ER TI Analysis of NotI linking clones isolated from human chromosome 3 specific libraries SO GENE LA English DT Article DE gene discovery; gene mapping; CpG islands; NotI map ID TUMOR-SUPPRESSOR GENE; IN-SITU HYBRIDIZATION; ENTIRE LONG ARM; HUMAN GENOME; RESTRICTION MAP; FAMILY MEMBER; SOLID TUMORS; CPG ISLANDS; ALU-PCR; HUMAN-CHROMOSOME-3 AB We have partially sequenced more than 1000 NotI linking clones isolated from human chromosome S-specific libraries. Of these clones, 152 were unique chromosome 3-specific clones. The clones were precisely mapped using a combination of fluorescence in situ hybridization (FISH) and hybridization to somatic cell or radiation hybrids. Two- and three-color FISH was used to order the clones that mapped to the same chromosomal region, and in some cases, chromosome jumping was used to resolve ambiguous mapping. When this NotI restriction map was compared with the yeast artificial chromosome (YAC) based chromosome 3 map, significant differences in several chromosome 3 regions were observed. A search of the EMBL, nucleotide database with these sequences revealed homologies (90-100%) to more than 100 different genes or expressed sequence tags (ESTs). Many of these homologies were used to map new genes to chromosome 3. These results suggest that sequencing NotI linking clones, and sequencing CpG islands in general, may complement the EST project and aid in the discovery of all human genes by sequencing random cDNAs. This method may also yield information that cannot be obtained by the EST project alone; namely, the identification of the 5' ends of genes, including potential promoter/enhancer regions and other regulatory sequences (C) 1999 Elsevier Science B.V. All rights reserved. C1 Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. Karolinska Inst, Ctr Genom Res, S-17177 Stockholm, Sweden. Ukrainian Acad Sci, Inst Mol Biol & Genet, UA-252627 Kiev, Ukraine. Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Novosibirsk 630090, Russia. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. NCI, Intramural Res Support Program, SAIC Frederick, FCRDC, Ft Detrick, MD 21702 USA. Russian State Genet Ctr, Moscow 113545, Russia. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. NCI, FCRDC, Ft Detrick, MD 21702 USA. Imperial Canc Res Fund, London WC2A 3PX, England. RP Kashuba, VI (reprint author), Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden. RI Wahlestedt, Claes/A-7039-2009; Zabarovsky, Eugene/A-6645-2010; Sheer, Denise/C-6705-2011; Winberg, Gosta/I-5686-2013; Graphodatsky, Alexander/B-4922-2010; Vorobieva, Nadezhda/N-6461-2015; Braga, Eleonora/P-5574-2016; OI Sheer, Denise/0000-0001-9067-1796; Graphodatsky, Alexander/0000-0002-8282-1085; Winberg, Gosta/0000-0002-3371-4056 FU Cancer Research UK [A3585] NR 36 TC 31 Z9 33 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 NOV 1 PY 1999 VL 239 IS 2 BP 259 EP 271 DI 10.1016/S0378-1119(99)00411-4 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 255HH UT WOS:000083663100007 PM 10548727 ER PT J AU Tajima, T Okada, T Ma, XM Ramsey, WJ Bornstein, SR Aguilera, G AF Tajima, T Okada, T Ma, XM Ramsey, WJ Bornstein, SR Aguilera, G TI Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochrome P450 21-hydroxylase into the adrenal gland of 21-hydroxylase-deficient mice SO GENE THERAPY LA English DT Article DE gene therapy; adenovirus; 21-hydroxylase; mice; adrenal; CAH ID RECOMBINANT ADENOVIRUS; HYPERPLASIA; EXPRESSION; VECTORS; GENE; DELETION; TYPE-5; REGION; CELLS AB 21-Hydroxylase deficiency, a potentially fatal disease due to deletions or mutations of the cytochrome P450 21-hydroxylase gene (CYP21), causes congenital adrenal hyperplasia (CAH) with low or absent glucocorticoid and mineralocorticoid production. The feasibility of gene therapy for CAH was studied using 21OH-deficient mice (21OH-) and a replication-deficient adenovirus containing the genomic sequence of human CYP21 (hAdCYP21). Intra-adrenal injection of hAdCYP21 in 21OH- mice induced hCYP21 mRNA with the highest expression from 2 to 7 days before a gradual decline. 21OH activity measured in adrenal tissue increased from undetectable to levels found in wild-type mice 2 to 7 days after AdhCYP21 injection. Adrenal morphology of 21OH- mice showed lack of zonation, and hypertropy and hyperplasia of adrenocortical mitochondria with few tubulovesicular christae. These morphological abnormalities were markedly improved 7 days after hAdCYP21 gene therapy. Plasma corticosterone increased from undetectable levels to values similar in wild-type mice 7 and 14 days, declining over the next 40 days. This is the first demonstration that a single intra-adrenal injection of an adenoviral vector encoding CYP21 can compensate for the biochemical, endocrine and histological alterations in 21OH-deficient mice, and shows that gene therapy could be a feasible option for treatment of CAH. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Clin Gene Therapy Branch, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10,Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. RI Toshihiro, Tajima/A-5720-2012 NR 28 TC 29 Z9 30 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD NOV PY 1999 VL 6 IS 11 BP 1898 EP 1903 DI 10.1038/sj.gt.3301018 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 252LT UT WOS:000083503500014 PM 10602386 ER PT J AU Lopez, J Cuesta, N Martinez, A Montuenga, L Cuttitta, F AF Lopez, J Cuesta, N Martinez, A Montuenga, L Cuttitta, F TI Proadrenomedullin N-terminal 20 peptide (PAMP) immunoreactivity in vertebrate juxtaglomerular granular cells identified by both light and electron microscopy SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article DE adrenomedullin; PAMP; juxtaglomerular cells; kidney; mammals; vertebrates ID RAT ADRENOMEDULLIN RECEPTOR; STIMULATES RENIN RELEASE; N-TERMINAL-20 PEPTIDE; HYPOTENSIVE PEPTIDE; MESANGIAL CELLS; HYPERTENSIVE RATS; PULMONARY TUMORS; MESSENGER-RNA; HUMAN LUNG; EXPRESSION AB The gene for adrenomedullin (AM), a multifunctional peptide hormone, is expressed in mammalian renal tissue and has been shown to stimulate renin release. The exact cell source of this peptide and its gene-related partner, proadrenomedullin N-terminal 20 peptide (PAMP), in kidney is still uncertain. In the present study we have identified PAMP-immunoreactive cells in the kidney of different mammalian species, including man, by light microscopy. In addition, these cells have been further studied in mouse kidney by both light and electron microscopic techniques. At the light microscopic level, PAMP immunolabeling is preferentially located in the subendothelial cells of the enlarged glomerular afferent arterioles, that is, in the juxtaglomerular cells. However, these cells do not show immunolabeling for AM. At the electron microscopic level, the immunostaining appears inside the renin-containing secretory granules of the juxtaglomerular cells. These results confirm the direct link between renin and the AM peptide family and provide a morphological basis for studying the potential modulatory function of AM and PAMP in the control of renin activity. In contrast, neither AM nor PAMP immunoreactivities were detected in the kidney of nonmammalian vertebrates, other than in blood vessels of particular species, providing a new phylogenetic difference in the juxtaglomerular apparatus between mammalian and nonmammalian vertebrates. (C) 1999 Academic Press. C1 Univ Autonoma Madrid, Dept Biol, Cell Biol Unit, Fac Sci, Madrid, Spain. NCI, Dept Cell & Canc Biol, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. RP Lopez, J (reprint author), Univ Autonoma Madrid, Dept Biol, Cell Biol Unit, Fac Sci, Madrid, Spain. RI Cuesta, Natalia/C-1358-2012; Martinez, Alfredo/A-3077-2013; Cuesta, Natalia/J-7761-2015 OI Martinez, Alfredo/0000-0003-4882-4044; Cuesta, Natalia/0000-0003-0809-2934 NR 55 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD NOV PY 1999 VL 116 IS 2 BP 192 EP 203 DI 10.1006/gcen.1999.7365 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259ZW UT WOS:000083924700005 PM 10562449 ER PT J AU McKenzie, LM Pecon-Slattery, J Carrington, M O'Brien, SJ AF McKenzie, LM Pecon-Slattery, J Carrington, M O'Brien, SJ TI Taxonomic hierarchy of HLA class I allele sequences SO GENES AND IMMUNITY LA English DT Article DE evolution; HLA; phylogenetic; peptide binding region ID MAJOR HISTOCOMPATIBILITY COMPLEX; MHC-CLASS-I; INTERALLELIC RECOMBINATION; NUCLEOTIDE SUBSTITUTION; OVERDOMINANT SELECTION; MOLECULAR ANALYSIS; A ALLELES; ANTIGENS; GENES; LOCI AB The markedly high levels of polymorphism present in classical class I loci of the human major histocompatibility complex have been implicated in infectious and immune disease recognition. The large numbers of alleles present at these loci have, however, limited efforts to verify associations between individual alleles and specific diseases. As an approach to reduce allele diversify to hierarchical evolutionarily related groups, we performed phylogenetic analyses of available HLA-A, B and C allele complete sequences (n = 216 alleles) using different approaches (maximum parsimony, distance-based minimum evolution and maximum likelihood). Full nucleotide and amino acid sequences were considered as well as abridged sequences from the hypervariable peptide binding region, known to interact in vivo, with HLA presented foreign peptide. The consensus analyses revealed robust clusters of 36 HLA-C alleles concordant for full and PBR sequence analyses. HLA-A alleles (n = 60) assorted into 12 groups based on full nucleotide and amino acid sequence which with few exceptions recapitulated serological groupings, however the patterns were largely discordant with clusters prescribed by PER sequences. HLA-B which has the most alleles (n = 120) and which unlike HLA-A and -C is thought to be subject to frequent recombinational exchange, showed limited phylogenetic structure consistent with recent selection driven retention of maximum heterozygosity and population diversify. Those allele categories recognized offer an explicit phylogenetic criterion for grouping alleles potentially relevant for epidemiologic associations, for inferring the origin of MHC genome organization, and for comparing functional constraints in peptide presentation of HLA alleles. C1 NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Bldg 560, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 44 TC 21 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD NOV PY 1999 VL 1 IS 2 BP 120 EP 129 DI 10.1038/sj.gene.6363648 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 342TW UT WOS:000088662100005 PM 11196658 ER PT J AU Liang, Y Wang, AH Belyantseva, IA Anderson, DW Probst, FJ Barber, TD Miller, W Touchman, JW Jin, L Sullivan, SL Sellers, JR Camper, SA Lloyd, RV Kachar, B Friedman, TB Fridell, RA AF Liang, Y Wang, AH Belyantseva, IA Anderson, DW Probst, FJ Barber, TD Miller, W Touchman, JW Jin, L Sullivan, SL Sellers, JR Camper, SA Lloyd, RV Kachar, B Friedman, TB Fridell, RA TI Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2 SO GENOMICS LA English DT Article ID SYNDROME TYPE 1B; SMOOTH-MUSCLE; HAIR-CELLS; VIIA GENE; RECESSIVE DEAFNESS; SENSORY EPITHELIA; BINDING PROTEIN; SH3 DOMAINS; MEMBRANE; IDENTIFICATION AB Mutations in myosin XV are responsible for congenital profound deafness DFNB3 in humans and deafness and vestibular defects in shaker 2 mice. By combining direct cDNA analyses with a comparison of 95.2 kb of genomic DNA sequence from human chromosome 17p11.2 and 88.4 kb from the homologous region on mouse chromosome ii, we have determined the genomic and mRNA structures of the human (MY015) and mouse (Myo15) myosin XV genes. Our results indicate that full-length myosin XV transcripts contain 66 exons, are >12 kb in length, and encode 365-kDa proteins that are unique among myosins in possessing very long similar to 1200-aa N-terminal extensions preceding their conserved motor domains. The tail regions of the myosin XV proteins contain two MS THC domains, two regions with similarity to the membrane attachment FERM domain, and a putative SH3 domain. Northern and dot blot analyses revealed that myosin XV is expressed in the pituitary gland in both humans and mice. Myosin XV transcripts were also observed by in situ hybridization within areas corresponding to the sensory epithelia of the cochlea and vestibular systems in the developing mouse inner ear. Immunostaining of adult mouse organ of Corti revealed that myosin XV protein is concentrated within the cuticular plate and stereocilia of cochlear sensory hair cells. These results indicate a likely role for myosin XV in the formation or maintenance of the unique actin-rich structures of inner ear sensory hair cells. (C) 1999 Academic Press. C1 NIDCD, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Michigan State Univ, Grad Program Genet, E Lansing, MI 48824 USA. NIDCD, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. NIH, NIH Intramural Sequencing Ctr, Gaithersburg, MD 20877 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. NIDCD, Mol Biol Lab, NIH, Rockville, MD 20850 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Fridell, RA (reprint author), NIDCD, Mol Genet Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. OI Camper, Sally/0000-0001-8556-3379 FU NCI NIH HHS [CA37231, CA42951]; NICHD NIH HHS [R01HD30428] NR 59 TC 94 Z9 98 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV 1 PY 1999 VL 61 IS 3 BP 243 EP 258 DI 10.1006/geno.1999.5976 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 258ED UT WOS:000083824400003 PM 10552926 ER PT J AU Goldberg, DB Goldberg, ME AF Goldberg, DB Goldberg, ME TI Brain policy: How the new neuroscience will change our lives and our politics SO HEALTH AFFAIRS LA English DT Book Review C1 George Washington Univ, Sch Med, Washington, DC 20052 USA. NEI, Sect Neuroophthalmol Mech, Bethesda, MD 20892 USA. RP Goldberg, DB (reprint author), George Washington Univ, Sch Med, Washington, DC 20052 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 1999 VL 18 IS 6 BP 243 EP 244 DI 10.1377/hlthaff.18.6.243 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 255UD UT WOS:000083687800026 ER PT J AU Lavigne, JV Brown, KM Gidding, S Evans, M Stevens, VJ von Almen, TK Ewart, C Weil, C AF Lavigne, JV Brown, KM Gidding, S Evans, M Stevens, VJ von Almen, TK Ewart, C Weil, C TI A cholesterol-lowering diet does not produce adverse psychological effects in children: Three-year results from the dietary intervention study in children SO HEALTH PSYCHOLOGY LA English DT Article DE dietary intervention; cholesterol-lowering diets; psychosocial safety ID N-3 FATTY-ACIDS; BRAIN; ESSENTIALITY; FAILURE; GROWTH; RETINA AB The Dietary Intervention Study in Children (DISC), a 2-arm, multicenter intervention study, examined the efficacy and safety of a diet lower in total fat, saturated fatty acids, and cholesterol than the typical American child's diet. A total of 663 8- to 10-year-old children with elevated low-density lipoprotein cholesterol levels were randomly assigned to either an intervention or a usual-care group. Intervention included group and individual counseling sessions to assist participants in adopting a dietary pattern containing 28% or less of calories from total fat (<8% as saturated fat, up to 9% as polyunsaturated fat, and 11% as monounsaturated fat) and dietary cholesterol intake of less than 75 mg/1,000 kcal. The dietary intervention reduced low-density lipoprotein cholesterol levels, and 3-year results showed no adverse effects for children in the intervention group in terms of academic functioning, psychological symptoms, or family functioning. C1 Childrens Mem Hosp, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. Northwestern Univ, Med Ctr, Evanston, IL 60208 USA. Maryland Med Res Inst, Baltimore, MD USA. Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. New Orleans Childrens Hosp, Family Advocacy Care & Educ Serv Dept, New Orleans, LA USA. Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. RP Lavigne, JV (reprint author), Childrens Mem Hosp, Dept Child & Adolescent Psychiat, 10,2300 Childrens Plaza, Chicago, IL 60614 USA. FU NHLBI NIH HHS [UO1-HL-37947, UO1-HL-37948, UO1-HL-37954] NR 36 TC 11 Z9 11 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 1999 VL 18 IS 6 BP 604 EP 613 DI 10.1037/0278-6133.18.6.604 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 262QN UT WOS:000084078100007 PM 10619534 ER PT J AU Adobati, E Zacchetti, A Perico, ME Cremonesi, F Rasi, G Vallebona, PS Hagenaars, M Kuppen, PJK Pastan, I Panza, L Russo, G Colnaghi, MI Canevari, S AF Adobati, E Zacchetti, A Perico, ME Cremonesi, F Rasi, G Vallebona, PS Hagenaars, M Kuppen, PJK Pastan, I Panza, L Russo, G Colnaghi, MI Canevari, S TI Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: Implication for the development of human-derived cancer vaccines SO HISTOCHEMICAL JOURNAL LA English DT Article ID TUMOR-ASSOCIATE ANTIGENS; MONOCLONAL-ANTIBODY; HUMAN-BREAST; OLIGOSACCHARIDES; MBR1; CARCINOMA; CELLS; COLON; MODEL; GLYCOSPHINGOLIPIDS AB CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of expression provides a therapeutic window for passive or active immunotherapy and points to the promise of a vaccine against carcinomas overexpressing this antigen. In this context, an animal model that closely mimics the human situation would be extremely useful. We, therefore, utilised the murine monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect the molecule targeted for vaccine development on canine and feline spontaneous breast and uterus tumours and on their normal counterparts, and on rat normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryostat sections revealed homogeneous CaMBr1 expression only in normal feline uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and heterogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissues from dogs and cats, respectively. In contrast, the data obtained in rat tissues were reproducible in the strains tested and showed that CaMBr1 was expressed in all epithelial tissues of the digestive tract, although with variable intensities. Monoclonal antibody staining appeared to correspond to membrane-bound structures as well as mucinous secretions. Similarly, secretion products of lactating mammary glands expressed CaMBr1. The spectrum of expression on rat digestive tract was broader than that in humans but the specificity of MBr1 reactivity was confirmed by competition assay with a synthetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, only one of two clonal derivatives of the rat breast carcinoma line RAMA 25 expressed CaMBr1, and a negative cell subset was evident in repeated experiments. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed staining with MBr1, albeit at different levels of intensity, and no evidence of a negative subset. The cell line CC531 maintained or even increased CaMBr1 expression levels following transplantation in syngeneic immunocompetent animals. Our data suggest the usefulness of the rat as a test model for vaccines against human cancers overexpressing the CaMBr1 antigen. C1 Ist Nazl Tumori, Dept Expt Oncol, Mol Therapies Unit, I-20133 Milan, Italy. Univ Milan, Fac Med Vet, Ist Clin Ostetr, Milan, Italy. CNR, Ist Med Sperimentale, I-00137 Rome, Italy. Univ Roma Tor Vergata, Dipartimento Med Sperimentale & Sci Biochim, Rome, Italy. Leiden Univ, Fac Med, Dept Pathol, NL-2300 RA Leiden, Netherlands. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Dept Surg, Leiden, Netherlands. RP Canevari, S (reprint author), Ist Nazl Tumori, Dept Expt Oncol, Mol Therapies Unit, Via Venezian 1, I-20133 Milan, Italy. RI Kuppen, Peter/J-2342-2016; OI Kuppen, Peter/0000-0002-0294-3251; Cremonesi, Fausto/0000-0001-8399-4626; PANZA, Luigi/0000-0002-0785-0409 NR 34 TC 3 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD NOV PY 1999 VL 31 IS 11 BP 729 EP 737 DI 10.1023/A:1003900631953 PG 9 WC Cell Biology SC Cell Biology GA 267NZ UT WOS:000084367300006 PM 10646838 ER PT J AU Wildner, O Blaese, RM Morris, JC AF Wildner, O Blaese, RM Morris, JC TI Synergy between the herpes simplex virus tk/Ganciclovir prodrug suicide system and the topoisomerase I inhibitor topotecan SO HUMAN GENE THERAPY LA English DT Article ID THYMIDINE KINASE GENES; MURINE MELANOMA-CELLS; NUCLEOSIDE ANALOGS; DNA-POLYMERASE; BRAIN-TUMORS; E1A ONCOGENE; GANCICLOVIR; THERAPY; CAMPTOTHECIN; VECTORS AB An established principle of antineoplastic chemotherapy is that multidrug regimens are generally superior to single-agent therapy. This prompted us to elucidate whether the topoisomerase inhibitor topotecan (TPT) could enhance the efficacy of the herpes simplex virus thymidine kinase gene/ganciclovir (HSV-tk/GCV) system for the treatment of cancer. We assessed the interaction between these two treatments in murine MC38 and human HT-29 colon carcinoma cell lines that were genetically modified to constitutively express HSV-tk, sensitizing them to GCV, Synergistic cell killing was observed in a clonogenic assay over most of the cytotoxic dose range by the median-effect principle of Chou and Talalay (Adv, Enzyme Regul. 1984; 22:27-55), Subcutaneous tumor models, using the same cell lines in C57BL/6 and athymic nude mice, respectively, demonstrated that the combination of GCV and TPT resulted in statistically significant enhanced survival relative to single-agent treatment. In addition, nude mice bearing HT-29 tumor xenografts were treated with an Ad5 E1b M-r 55,000 attenuated replication-competent adenovirus expressing HSV-tk (Ad.TKRC) either alone or in combination with GCV and/or TPT, These experiments demonstrated that Ad.TKRC followed by GCV and TPT was more efficacious than any other treatment tested. Our results suggest that for antineoplastic therapy, molecular chemotherapy based on the HSV-tk/GCV system combined with traditional chemotherapy is a logical and practical future direction to pursue. C1 NIH, Clin Gene Therapy Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Wildner, O (reprint author), NIH, Clin Gene Therapy Branch, Natl Human Genome Res Inst, Bldg 10,10 Ctr Dr,Room 10C103, Bethesda, MD 20892 USA. NR 47 TC 25 Z9 25 U1 1 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 1 PY 1999 VL 10 IS 16 BP 2679 EP 2687 DI 10.1089/10430349950016726 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 252VD UT WOS:000083522200012 PM 10566896 ER PT J AU Roessler, E Mittaz, L Du, YZ Scott, HS Chang, J Rossier, C Guipponi, M Matsuda, SPT Muenke, M Antonarakis, SE AF Roessler, E Mittaz, L Du, YZ Scott, HS Chang, J Rossier, C Guipponi, M Matsuda, SPT Muenke, M Antonarakis, SE TI Structure of the human Lanosterol Synthase gene and its analysis as a candidate for holoprosencephaly (HPE1) SO HUMAN GENETICS LA English DT Article ID LEMLI-OPITZ-SYNDROME; ABNORMAL CHOLESTEROL-METABOLISM; SONIC-HEDGEHOG GENE; MOLECULAR-CLONING; DELTA-7-STEROL REDUCTASE; AUTOPROCESSING DOMAIN; CRYSTAL-STRUCTURE; MUTATIONS; PROTEINS; 21Q22.3 AB Holoprosencephaly (HPE) is the most common birth defect of the brain in humans. It involves various degrees of incomplete separation of the cerebrum into distinct left and right halves, and it is frequently accompanied by craniofacial anomalies. The HPE1 locus in human chromosome 21q22.3 is one of a dozen putative genetic loci implicated in causing HPE. Here, we report the complete gene structure of the human lanosterol synthase (LS) gene, which is located in this interval, and present its mutational analysis in HPE patients. We considered LS an excellent candidate HPE gene because of the requirement for cholesterol modification of the Sonic Hedgehog protein for the correct patterning activity of this HPE-associated protein. Despite extensive pedigree analysis of numerous polymorphisms, as well as complementation studies in yeast on one of the missense mutations, we find no evidence that the LS gene is in fact HPE1, implicating another gene located in this chromosomal region in HPE pathogenesis. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Childrens Hosp, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Geneva, Sch Med, Div Med Genet, CH-1211 Geneva, Switzerland. Rice Univ, Dept Chem, Houston, TX 77251 USA. Rice Univ, Dept Biochem, Houston, TX 77251 USA. Rice Univ, Dept Cell Biol, Houston, TX 77251 USA. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bld 10 10C101, Bethesda, MD 20892 USA. RI Scott, Hamish/B-2122-2009; Antonarakis, Stylianos/N-8866-2014 OI Scott, Hamish/0000-0002-5813-631X; Antonarakis, Stylianos/0000-0001-8907-5823 FU NIAID NIH HHS [AI41598]; NICHD NIH HHS [HD28732, HD29862] NR 37 TC 8 Z9 9 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1999 VL 105 IS 5 BP 489 EP 495 DI 10.1007/s004390051135 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 261VB UT WOS:000084029400017 PM 10598817 ER PT J AU Lin, BC Hiraiwa, H Pan, CJ Nordlie, RC Chou, JY AF Lin, BC Hiraiwa, H Pan, CJ Nordlie, RC Chou, JY TI Type-1c glycogen storage disease is not caused by mutations in the glucose-6-phosphate transporter gene SO HUMAN GENETICS LA English DT Article AB Glycogen storage disease type 1 (GSD-1) is a group of autosomal. recessive disorders caused by deficiencies in glucose-6-phosphatase (G6Pase) and the associated substrate/product transporters. Molecular genetic studies have demonstrated that GSD-1a and GSD-1b are caused by mutations in the G6Pase enzyme and a glucose-6-phosphate transporter (G6PT), respectively. While kinetic studies of G6Pase catalysis predict that the index GSD-1c patient is deficient in a pyrophosphate/phosphate transporter, the existence of a separate locus for GSD-1c remains unclear. We have previously shown that the G6Pase gene of the index GSD-1c patient is intact; we now show that the G6PT gene of this patient is normal, strongly suggesting the existence of a distinct GSD-1c locus. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ N Dakota, Sch Med, Dept Biochem & Mol Biol, Grand Forks, ND USA. RP Chou, JY (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA. RI Lin, Baochuan/A-8390-2009 OI Lin, Baochuan/0000-0002-9484-0785 NR 7 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1999 VL 105 IS 5 BP 515 EP 517 DI 10.1007/s004390051140 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 261VB UT WOS:000084029400022 PM 10598822 ER PT J AU Kimber, WL Hsieh, P Hirotsune, S Yuva-Paylor, L Sutherland, HF Chen, A Ruiz-Lozano, P Hoogstraten-Miller, SL Chien, KR Paylor, R Scambler, PJ Wynshaw-Boris, A AF Kimber, WL Hsieh, P Hirotsune, S Yuva-Paylor, L Sutherland, HF Chen, A Ruiz-Lozano, P Hoogstraten-Miller, SL Chien, KR Paylor, R Scambler, PJ Wynshaw-Boris, A TI Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse SO HUMAN MOLECULAR GENETICS LA English DT Article ID GOOSECOID-LIKE GSCL; DIGEORGE-SYNDROME; POTENTIAL LINKAGE; MICE LACKING; VELOCARDIOFACIAL SYNDROMES; CHROMOSOME 22Q12-Q13.1; BEHAVIORAL PHENOTYPES; FOLLOW-UP; 22Q11; GENE AB Deletions or rearrangements of human chromosome 22q11 lead to a variety of related clinical syndromes such as DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS), In addition, patients with 22q11 deletions have an increased incidence of schizophrenia and several studies have mapped susceptibility loci for schizophrenia to this region. Human molecular genetic studies have so far failed to identify the crucial genes or disruption mechanisms that result in these disorders. We have used gene targeting in the mouse to delete a defined region within the conserved DGS critical region (DGCR) on mouse chromosome 16 to prospectively investigate the role of the mouse DGCR in 22q11 syndromes. The deletion spans a conserved portion (similar to 150 kb) of the proximal region of the DGCR, containing at least seven genes (Znf741, Idd, Tsk1, Tsk2, Es2, Gscl and Ctp), Mice heterozygous for this deletion display no findings of DGS/VCFS in either inbred or mixed backgrounds. However, heterozygous mice display an increase in prepulse inhibition of the startle response, a manifestation of sensorimotor gating that is reduced in humans with schizophrenia, Homozygous deleted mice die soon after implantation, demonstrating that the deleted region contains genes essential for early post-implantation embryonic development, These results suggest that heterozygous deletion of this portion of the DGCR is sufficient for sensorimotor gating abnormalities, but not sufficient to produce the common features of DGS/VCFS in the mouse. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Res Scholars Program, NIH, Bethesda, MD 20814 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Univ London, Coll Med, Inst Child Hlth, London, England. Univ Calif San Diego, Sch Med, Dept Med, Salk NHLBI,Program Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ctr Genet Mol, La Jolla, CA 92093 USA. RP Wynshaw-Boris, A (reprint author), Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. RI Scambler, Peter/C-4998-2008 OI Scambler, Peter/0000-0002-1487-4628 FU NICHD NIH HHS [P30HD24064-11]; Wellcome Trust NR 43 TC 71 Z9 72 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1999 VL 8 IS 12 BP 2229 EP 2237 DI 10.1093/hmg/8.12.2229 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 255FL UT WOS:000083658800012 PM 10545603 ER PT J AU Greene, AL Snipe, JR Gordenin, DA Resnick, MA AF Greene, AL Snipe, JR Gordenin, DA Resnick, MA TI Functional analysis of human FEN1 in Saccharomyces cerevisiae and its role in genome stability SO HUMAN MOLECULAR GENETICS LA English DT Article ID CELL NUCLEAR ANTIGEN; HUMAN FLAP ENDONUCLEASE-1; DNA MISMATCH REPAIR; NUCLEOTIDE EXCISION-REPAIR; PCNA BINDING; MAMMALIAN 5'-EXONUCLEASE; METHANOCOCCUS-JANNASCHII; SUBSTRATE-BINDING; IN-VITRO; YEAST AB The flap endonuclease, FEN1, is an evolutionarily conserved component of DNA replication from archaebacteria to humans. Based on in vitro results, it processes Okazaki fragments during replication and is involved in base excision repair. FEN1 removes the last primer ribonucleotide on the lagging strand and it cleaves a 5' flap that may result from strand displacement during replication or during base excision repair. Its biological importance has been revealed largely through studies in the yeast Saccharomyces cerevisiae where deletion of the homologous gene RAD27 results in genome instability and mutagen sensitivity. While the in vivo function of Rad27 has been well characterized through genetic and biochemical approaches, little is understood about the in vivo functions of human FEN1, Guided by our recent results with yeast RAD27, we explored the function of human FEN1 in yeast. We found that the human FEN1 protein complements a yeast rad27 null mutant for a variety of defects including mutagen sensitivity, genetic instability and the synthetic lethal interactions of a rad27 rad51 and a rad27 pol3-01 mutant. Furthermore, a mutant form of FEN1 lacking nuclease function exhibits dominant-negative effects on cell growth and genome instability similar to those seen with the homologous yeast rad27 mutation. This genetic impact is stronger when the human and yeast PCNA-binding domains are exchanged. These data indicate that the human FEN1 and yeast Rad27 proteins act on the same substrate in vivo. Our study defines a sensitive yeast system for the identification and characterization of mutations in FEN1. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), NIEHS, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 75 TC 29 Z9 29 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1999 VL 8 IS 12 BP 2263 EP 2273 DI 10.1093/hmg/8.12.2263 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 255FL UT WOS:000083658800016 PM 10545607 ER PT J AU Sahoo, T Johnson, EW Thomas, JW Kuehl, PM Jones, TL Dokken, CG Touchman, JW Gallione, CJ Lee-Lin, SQ Kosofsky, B Kurth, JH Louis, DN Mettler, G Morrison, L Gil-Nagel, A Rich, SS Zabramski, JM Boguski, MS Green, ED Marchuk, DA AF Sahoo, T Johnson, EW Thomas, JW Kuehl, PM Jones, TL Dokken, CG Touchman, JW Gallione, CJ Lee-Lin, SQ Kosofsky, B Kurth, JH Louis, DN Mettler, G Morrison, L Gil-Nagel, A Rich, SS Zabramski, JM Boguski, MS Green, ED Marchuk, DA TI Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1) SO HUMAN MOLECULAR GENETICS LA English DT Article ID CHROMOSOME 7Q; TUBEROUS SCLEROSIS; NATURAL-HISTORY; YAC CONTIG; HUMAN DNA; RAS; IDENTIFICATION; PRODUCT; LINKAGE; FAMILIES AB Cerebral cavernous malformations (CCM) are congenital vascular anomalies of the brain that can cause significant neurological disabilities, including intractable seizures and hemorrhagic stroke. One locus for autosomal dominant CCM (CCM1) maps to chromosome 7q21-q22. Recombination events in linked family members define a critical region of similar to 2 Mb and a shared disease haplotype associated with a presumed founder effect in families of Mexican-American descent points to a potentially smaller region of interest. Using a genomic sequence-based positional cloning strategy, we have identified KRIT1, encoding a protein that interacts with the Krev-1/rap1a tumor suppressor, as the CCM1 gene. Seven different KRIT1 mutations have been identified in 23 distinct CCM1 families. The identical mutation is present in 16 of 21 Mexican-American families analyzed, substantiating a founder effect in this population. Other Mexican-American and non-Hispanic Caucasian CCM1 kindreds harbor other KRIT1 mutations. Identification of a common Mexican-American mutation has potential clinical significance for presymptomatic diagnosis of CCM in this population. In addition, these data point to a key role for the Krev-1/rap1a signaling pathway in angiogenesis and cerebrovascular disease. C1 Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. St Joseph Hosp, Barrow Neurol Inst, Dept Neurogenet, Phoenix, AZ 85013 USA. St Joseph Hosp, Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ 85013 USA. Natl Human Genome Res Inst, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Marshfield Clin, Ctr Med Genet, Marshfield, WI 54449 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Childrens Hosp Eastern Ontario, Div Genet, Ottawa, ON K1H 8L1, Canada. Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. Hosp Ruber Int, Madrid 28034, Spain. Bowman Gray Sch Med, Dept Publ Hlth Sci & Neurol, Winston Salem, NC 27157 USA. RP Marchuk, DA (reprint author), Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. OI Morrison, Leslie/0000-0002-0092-193X NR 55 TC 203 Z9 208 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1999 VL 8 IS 12 BP 2325 EP 2333 DI 10.1093/hmg/8.12.2325 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 255FL UT WOS:000083658800023 PM 10545614 ER PT J AU Kumar, S Perlman, E Pack, S Davis, M Zhang, H Meltzer, P Tsokos, M AF Kumar, S Perlman, E Pack, S Davis, M Zhang, H Meltzer, P Tsokos, M TI Absence of EWS/FLI1 fusion in olfactory neuroblastomas indicates these tumors do not belong to the Ewing's sarcoma family SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 1999 CL SAN FRANCISCO, CALIFORNIA SP US & Canadian Acad Pathol DE sinonasal tumors; olfactory neuroblastoma; Ewing's sarcoma; t(11;22); fluorescence in situ hybridization; formalin-fixed tissue ID PRIMITIVE NEUROECTODERMAL TUMOR; NASAL CAVITY; ESTHESIONEUROBLASTOMA; TRANSCRIPTS; KIDNEY; FOSSA AB The balanced reciprocal translocation t(11;22)(q24;q12) is a specific molecular marker for the Ewing's sarcoma family of tumors (ESFT). Based on the detection of this translocation in some olfactory neuroblastomas (ONBs), it has been proposed that ONBs also belong to the ESFT. Others hare challenged this hypothesis; however, the rarity of ONBs, as well as the lack of molecular techniques that work reliably on formalin fixed tissue, have precluded the molecular analysis of a significant number of cases. We evaluated the immunophenotypic and molecular features of 17 paranasal small round neuroectodermal tumors using routinely fixed tissue. Probes localizing to 22q12 (EWS) and 11q24 (FLI-1) were used in a standard 2-color fluorescence in situ hybridization (FISH) assay to evaluate EWS/FLI1 fusion on the der(22). Sixteen tumors were mic-2 negative, whereas 1 tumor was mic-2 positive, compatible with ONE and ESFT, respectively Thirteen of 15 ONBs could be evaluated by FISH, and all 18 were negative for the EWS/FLI1 fusion. Distinct fusion signals were identified in the single paranasal ESFT. Our findings indicate that ONBs lack the EWS/FLI1 fusion and are unrelated to the ESFT; however, true ESFTs may rarely occur as primary sinonasal tumors. Copyright (C) 1999 by W.B. Saunders Company. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. JW Riley Hosp Children, Indianapolis, IN USA. RP Kumar, S (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A09,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 26 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 1999 VL 30 IS 11 BP 1356 EP 1360 DI 10.1016/S0046-8177(99)90068-0 PG 5 WC Pathology SC Pathology GA 254DP UT WOS:000083596900014 PM 10571517 ER PT J AU Hara, T Nakano, Y Tanaka, M Tamura, K Sekiguchi, T Minehata, K Copeland, NG Jenkins, NA Okabe, M Kogo, H Mukouyama, Y Miyajima, A AF Hara, T Nakano, Y Tanaka, M Tamura, K Sekiguchi, T Minehata, K Copeland, NG Jenkins, NA Okabe, M Kogo, H Mukouyama, Y Miyajima, A TI Identification of podocalyxin-like protein 1 as a novel cell surface marker for hemangioblasts in the murine aorta-gonad-mesonephros region SO IMMUNITY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; ENDOTHELIAL-CELLS; MOUSE EMBRYO; YOLK-SAC; PROGENITORS; LEUKEMIA; MICE; VASCULOGENESIS; EXPRESSION; SCL/TAL-1 AB Recent studies with avian embryos and murine embryonic stem cells have suggested that hematopoietic cells are derived from hemangioblasts, the common precursors of hematopoietic and endothelial cells. We molecularly cloned podocalyxin-like protein 1 (PCLP1) as a novel surface marker for endothelial-like cells in the aorta-gonad-mesonephros (AGM) region of mouse embryos, where long-term repopulating hematopoietic stem cells (LTR-HSCs) are known to arise. PCLP1(+) CD45(-) cells in the AGM region incorporated acetylated low-density lipoprotein and produced both hematopoietic and endothelial cells when cocultured with OP9 stromal cells. Moreover, multiple lineages of hematopoietic cells were generated in vivo when PCLP1(+)CD45(-) cells were injected into neonatal liver of busulfan-treated mice. Thus, PCLP1 can be used to separate hemangioblasts that give rise to LTR-HSCs. C1 Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan. Univ Tokyo, Core Res Evolut Sci & Technol, Bunkyo Ku, Tokyo 1130032, Japan. Tokyo Univ Pharm & Life Sci, Hachioji, Tokyo 1920355, Japan. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Osaka Univ, Genome Informat Res Ctr, Suita, Osaka 5650871, Japan. RP Hara, T (reprint author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan. RI Okabe, Masaru/B-6917-2015 OI Okabe, Masaru/0000-0002-0803-9044 NR 49 TC 86 Z9 87 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1999 VL 11 IS 5 BP 567 EP 578 DI 10.1016/S1074-7613(00)80132-6 PG 12 WC Immunology SC Immunology GA 260LM UT WOS:000083952200009 PM 10591182 ER PT J AU Natarajan, K Boyd, LF Schuck, P Yokoyama, WM Eilat, D Margulies, DH AF Natarajan, K Boyd, LF Schuck, P Yokoyama, WM Eilat, D Margulies, DH TI Interaction of the NK cell inhibitory receptor Ly49A with H-2D(d): Identification of a site distinct from the TCR site SO IMMUNITY LA English DT Article ID NATURAL-KILLER-CELLS; CLASS-I MHC; SURFACE-PLASMON RESONANCE; T-CELLS; LY-49A RECOGNIZES; ANTIGEN RECEPTOR; VIRAL PEPTIDE; COMPLEX; SPECIFICITY; BINDING AB Natural killer cell function is controlled by interaction of NK receptors with MHC I molecules expressed on target cells. We describe the binding of bacterially expressed Ly49A, the prototype murine NK inhibitory receptor, to similarly engineered H-2D(d). Despite its homology to c-type lectins, Ly49A binds independently of carbohydrate and Ca2+ and shows specificity for MHC I but not bound peptide. The affinity of the Ly49A/H-2D(d) interaction as determined by surface plasmon resonance is from 6 to 26 mu M at 25 degrees C and is greater by ultracentrifugation at 4 degrees C. Biotinylated Ly49A stains H-2D(d)-expressing cells. Competition experiments indicate that the Ly49A and T cell receptor (TCR) binding sites on MHC I are distinct, suggesting complex regulation of cells that bear both TCR and NK cell receptors. C1 NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIH, Mol Interact Resource Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, Div Rheumatol, St Louis, MO 63110 USA. Hadassah Univ Hosp, Div Med, IL-91120 Jerusalem, Israel. RP Margulies, DH (reprint author), NIAID, Mol Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375; Schuck, Peter/0000-0002-8859-6966 NR 75 TC 47 Z9 47 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1999 VL 11 IS 5 BP 591 EP 601 DI 10.1016/S1074-7613(00)80134-X PG 11 WC Immunology SC Immunology GA 260LM UT WOS:000083952200011 PM 10591184 ER PT J AU Sousa, CRE Yap, G Schulz, O Rogers, N Schito, M Aliberti, J Hieny, S Sher, A AF Sousa, CRE Yap, G Schulz, O Rogers, N Schito, M Aliberti, J Hieny, S Sher, A TI Paralysis of dendritic cell IL-12 production by microbial products prevents infection-induced immunopathology SO IMMUNITY LA English DT Article ID TOXOPLASMA-GONDII; IN-VIVO; T-CELLS; IFN-GAMMA; INTERLEUKIN-10-DEFICIENT MICE; MONOCLONAL-ANTIBODIES; ENDOTOXIN TOLERANCE; CYTOKINE PRODUCTION; MEDIATED-IMMUNITY; INDUCED APOPTOSIS AB Interleukin-12 plays a major role in immunity to intracellular pathogens by governing the development of IFN gamma-dependent host resistance. Nevertheless, unregulated IL-12 synthesis can lead to immunopathology, an outcome prevented by the concurrent expression of interleukin-10. Dendritic cells (DC) are an important source of the initial IL-12 stimulated by microbial agents. Here, we show that, following systemic triggering, DC can no longer be restimulated to produce IL-12 in vivo while continuing to respond in vitro. When infected with Toxoplasma gondii during this refractory state, mice mount impaired acute IFN gamma responses and, in the case of IL-10-deficient animals, are protected from cytokine-induced mortality. These findings demonstrate a previously unrecognized form of immunologic paralysis involving DC that can protect from infection-induced immunopathology. C1 Imperial Canc Res Fund, Immunobiol Lab, London WC2A 3PX, England. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sousa, CRE (reprint author), Imperial Canc Res Fund, Immunobiol Lab, 44 Lincolns Inn Fields, London WC2A 3PX, England. EM caetano@icrf.icnet.uk; alan_sher@nih.gov RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 40 TC 134 Z9 135 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD NOV PY 1999 VL 11 IS 5 BP 637 EP 647 PG 11 WC Immunology SC Immunology GA 260LM UT WOS:000083952200015 ER PT J AU Bhattacharyya, SP Mekori, YA Hoh, D Paolini, R Metcalfe, DD Bianchine, PJ AF Bhattacharyya, SP Mekori, YA Hoh, D Paolini, R Metcalfe, DD Bianchine, PJ TI Both adhesion to immobilized vitronectin and Fc epsilon RI cross-linking cause enhanced focal adhesion kinase phosphorylation in murine mast cells SO IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; IMMUNOGLOBULIN-E; PP125(FAK); FIBRONECTIN; AGGREGATION; RECEPTORS AB Murine mast cells adhere spontaneously to plate-bound vitronectin (VNPB) via alpha(v)-containing integrins, and this adhesive interaction results in an augmented interleukin-3 (IL-3)-dependent mast-cell proliferation. In this report we demonstrate that the activation of murine mast cells through alpha(v)-integrin, as well as through the high affinity immunoglobulin E (IgE) receptor (Fc epsilon RI), results in enhanced tyrosine phosphorylation of focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase involved in mitogenic and oncogenic signal transduction. While mast cell adhesion to VNPB resulted in enhanced FAK phosphorylation, treatment with soluble vitronectin (VNSOL) failed to do so. Spontaneous mast cell adhesion to entactin (EN) did not induce tyrosine phosphorylation of FAK, demonstrating that not all adhesive interactions lead to the same sequence of biochemical events. Because FAK has intrinsic tyrosine kinase activity, we examined whether activating mast cells via alpha(v)-integrins, or via Fc epsilon RI-cross-linking stimulated the in vitro kinase activity of FAK. Both pathways were found independently to activate FAK in mast cells and together appeared additive. Protein kinase C depletion in mast cells and calcium depletion in the medium caused decreased tyrosine phosphorylation of FAK, indicating that optimal tyrosine phosphorylation of FAK is regulated by both pathways. These data are consistent with the conclusion that the tyrosine phosphorylation of FAK represents at least one example of a point of convergence in the intracellular tyrosine phosphorylation cascades induced by alpha(v) integrin-and Fc epsilon RI-mediated signal transduction pathways in mast cells. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ La Sapienza, Dept Expt Med & Pathol, Rome, Italy. Tel Aviv Univ, Sackler Sch Med, Dept Med, IL-69978 Tel Aviv, Israel. RP Bhattacharyya, SP (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. NR 18 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1999 VL 98 IS 3 BP 357 EP 362 DI 10.1046/j.1365-2567.1999.00883.x PG 6 WC Immunology SC Immunology GA 260RE UT WOS:000083963000007 PM 10583594 ER PT J AU Kossaczka, Z Lin, FYC Ho, VA Thuy, NTT Van Bay, P Thanh, TC Khiem, HB Trach, DD Karpas, A Hunt, S Bryla, DA Schneerson, R Robbins, JB Szu, SC AF Kossaczka, Z Lin, FYC Ho, VA Thuy, NTT Van Bay, P Thanh, TC Khiem, HB Trach, DD Karpas, A Hunt, S Bryla, DA Schneerson, R Robbins, JB Szu, SC TI Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2-to 4-year-old children in Vietnam SO INFECTION AND IMMUNITY LA English DT Article ID RESISTANT SALMONELLA-TYPHI; CAPSULAR POLYSACCHARIDE VACCINE; ADIPIC ACID DIHYDRAZIDE; ESCHERICHIA-COLI; TY21A VACCINE; PROTEIN; IMMUNIZATION; EFFICACY; PREVENTION; PROTECTION AB The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using either N-succinimidyl-3-(2-pyridyidithio)-propionate (SPDP; Vi-rEPA(1)) or adipic acid dihydrazide (ADN; Vi-rEPA(2)) as linkers. None of the recipients experienced a temperature of >38.5 degrees C or significant local reactions. One injection of Vi-rEPA(2) into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA(2), Vi-rEPA(1), and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA(2), Vi-rEPA(1), and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)); all were higher than the preinjection levels (P = 0.0001). Vi-REPA(2) also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA(2) elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA(1) (P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA(2) and from 28.9 to 83.0 EU for Vi-rEPA(1). At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA(2) and 12.8 versus 0.33 for Vi-rEPA(1); P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elf cited by two injections of Vi-rEPA(2) in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA(2) conjugate warrant further investigation. C1 NIH, Bethesda, MD 20892 USA. Huu Nghi Hosp, Cao Lanh Dist, Dong Thap Prov, Vietnam. Inst Pasteur, Ho Chi Minh City, Vietnam. Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. RP Szu, SC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-7-3269] NR 38 TC 68 Z9 73 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1999 VL 67 IS 11 BP 5806 EP 5810 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000035 PM 10531232 ER PT J AU Laithwaite, JE Benn, SJ Yamate, J FitzGerald, DJ LaMarre, J AF Laithwaite, JE Benn, SJ Yamate, J FitzGerald, DJ LaMarre, J TI Enhanced macrophage resistance to Pseudomonas exotoxin A is correlated with decreased expression of the low-density lipoprotein receptor-related protein SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; VASCULAR ENDOTHELIAL-CELLS; HEMOLYTIC-UREMIC SYNDROME; SHIGA-LIKE TOXINS; ALPHA-2-MACROGLOBULIN RECEPTOR; AERUGINOSA EXOTOXIN; PLASMINOGEN-ACTIVATOR; PLASMA-CLEARANCE; BINDING-PROTEIN; GROWTH-FACTOR AB Cellular intoxification by exotoxin A of Pseudomonas aeruginosa (PEA) begins when PEA binds to its cellular receptor, the low-density lipoprotein receptor-related protein (LRP). This receptor is particularly abundant on macrophages. We hypothesize here that inducible changes in cellular expression levels of the LRP represent an important mechanism by which macrophage susceptibility to PEA is regulated by the host. We have examined the effect of lipopolysaccharide (LPS) on LRP expression and PEA sensitivity in the macrophage-like cell line HS-P. Using a [H-3]leucine incorporation assay to measure inhibition of protein synthesis, we have demonstrated that HS-P macrophages are highly sensitive to PEA and that PEA toxicity is decreased by the LRP antagonist receptor-associated protein. LPS pretreatment decreases HS-P PEA sensitivity in a time- and dose-dependent manner. The dose of toxin required to inhibit protein synthesis by 50% increased from 11.3 +/- 1.2 ng/ml in untreated cells to 25.7 +/- 2.0 ng/ml in cells treated with LPS. In pulse experiments, involving brief exposure to saturating concentrations of PEA, [H-3]leucine incorporation was more than threefold higher in cells pretreated with LPS than in untreated macrophages. These changes in HS-P PEA sensitivity following LPS treatment were consistently associated with a fivefold decrease in HS-P LRP mRNA expression as measured by Northern blot analysis and a three-and-a-half-fold decrease in HS-P LRP-specific ligand internalization as determined by activated alpha(2)-macroglobulin internalization studies. These data demonstrate for the first time that modulation of LRP levels by extracellular signaling molecules can alter cellular PEA sensitivity. C1 Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. Univ Osaka Prefecture, Coll Agr, Dept Vet Pathol, Sakai, Osaka 593, Japan. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP LaMarre, J (reprint author), Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. NR 49 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1999 VL 67 IS 11 BP 5827 EP 5833 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000039 PM 10531236 ER PT J AU Cooper, PJ Espinel, I Wieseman, M Paredes, W Espinel, M Guderian, RH Nutman, TB AF Cooper, PJ Espinel, I Wieseman, M Paredes, W Espinel, M Guderian, RH Nutman, TB TI Human onchocerciasis and tetanus vaccination: Impact on the postvaccination antitetanus antibody response SO INFECTION AND IMMUNITY LA English DT Article ID SCHISTOSOMA-MANSONI; NONENDEMIC POPULATIONS; CLINICAL PRESENTATION; CYTOKINE RESPONSES; VOLVULUS INFECTION; IMMUNE-RESPONSES; CELL; ANTIGENS; CHILDREN; IMMUNOGENICITY AB To investigate whether helminth infections may affect the efficacy of vaccines by impairing the immune response to nonparasite vaccine antigens, we compared the antibody responses to tetanus toroid (TT) after tetanus vaccination in 193 subjects with Onchocerca volvulus infection with 85 comparable noninfected controls. After vaccination, the proportions of subjects in each group attaining protective levels of antitetanus antibodies were similar (96.9% infected versus 97.6% noninfected). Postvaccination increases in antitetanus immunoglobulin G (IgG) and the predominant IgG isotype, IgG1,were equivalent in both groups, as were increases in specific IgG1 and IgE; however, significantly greater increases in specific IgG2 (P < 0.05) and IgG3 (P < 0.001) were observed in the noninfected group. Stratification of the O. volvulus-infected group into two groups representing light and heavy infections revealed a significantly impaired antitetanus IgG response in those with heavy infections compared to those with light infections (P < 0.01) or no infection (P < 0.05). The impact of concurrent intestinal helminth infections on the antitetanus response was also examined; an increased IgG4/IgE ratio was seen in those infected with Strongyloides stercoralis (P < 0.05) and when all helminth infections were combined as a single group (P < 0.05). These findings indicate that concurrent infection with O. volvulus does not prevent the development of a protective antitetanus response, although heavier O. volvulus infections are able to alter the magnitude of this response, and concurrent helminth infections (O. volvulus and intestinal helminths) may alter TT-specific antibody isotype responses. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Hosp Vozandez, Dept Clin Invest, Quito, Ecuador. Minist Publ Hlth, Quito, Ecuador. RP Cooper, PJ (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 41 TC 45 Z9 45 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1999 VL 67 IS 11 BP 5951 EP 5957 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000056 PM 10531253 ER PT J AU Konadu, E Donohue-Rolfe, A Calderwood, SB Pozsgay, V Shiloach, J Robbins, JB Szu, SSC AF Konadu, E Donohue-Rolfe, A Calderwood, SB Pozsgay, V Shiloach, J Robbins, JB Szu, SSC TI Syntheses and immunologic properties of Escherichia coli O157O-specific polysaccharide and Shiga toxin 1 B subunit conjugates in mice SO INFECTION AND IMMUNITY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; VIBRIO-CHOLERAE; O157-H7; PURIFICATION; VACCINE; LIPOPOLYSACCHARIDE; LOCALIZATION; PERSPECTIVE; INFECTION; IMMUNITY AB Escherichia coli O157 is the major cause of diarrhea-associated hemolytic uremic syndrome (HUS). Strains causing HUS contain either Shiga toxin 1 (Stx1) or Stx2, or both. In adult volunteers, conjugate vaccines of detoxified lipopolysaccharide (LPS) elicited bactericidal antibodies to E. coli O157. Here, the detoxified LPS was conjugated with improved schemes to the nontoxic B subunit of Stx1. Mice injected with these bivalent conjugates elicited both bactericidal antibodies to E. coli O157 and neutralization antibodies to Stx1. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Vet Med, Medford, MA 01536 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Szu, SSC (reprint author), NICHHD, NIH, Room 424,Bldg 6, Bethesda, MD 20892 USA. NR 28 TC 21 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1999 VL 67 IS 11 BP 6191 EP 6193 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000091 PM 10531288 ER PT J AU Kant, AK Graubard, BI AF Kant, AK Graubard, BI TI Variability in selected indexes of overall diet quality SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Article DE overall diet quality; dietary diversity; variability; intraindividual variation; interindividual variation; CSFII; components of variance; dietary measurement; nutrition survey; diet quality indexes ID UNITED-STATES; NATIONAL-HEALTH; FOOD GROUPS; DIVERSITY; DESIGN; CANCER; POPULATION; NUTRITION; MORTALITY; FREQUENCY AB We examined the intra- and interindividual variability in selected measures of overall diet quality in relation to socio-demographic, Lifestyle, and health-related characteristics. Three days of dietary data from the Continuing Survey of Food intakes by Individuals (CSFII), 1989-91 (7841 respondents, 3337 men and 4504 women. aged greater than or equal to 19 years), were examined. Measures of overall diet quality were: 1. the Dietary Diversity Score (DDS), a measure of variety among the major food groups: 2. the Overall Variety Score (OVS), examined the number of nutrient-dense foods reported; and 3, the Nutrient Adequacy Score (NAS 100). evaluated the number of nutrients consumed at least at the level of the RDA from a total of 11. The ratio of intra- to interindividual variance for DDS, OVS, and NAS 100 was 1.66, 1.09, and 1.21, respectively, indicating higher intraindividual variability relative to interindividual variability For each of the three stores, gender, income, education, and smoking were associated with greater intraindividual variability; however, age, and special diet status were associated with lower variability, Thus. the reliability of a given dietary assessment protocol for evaluating ''usual" diet quality is likely to vary by the socio-demographic and lifestyle characteristics of the study population. C1 CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Remsen Hall,Room 306 E,65-30 Kissena Blvd, Flushing, NY 11367 USA. NR 35 TC 7 Z9 7 U1 0 U2 5 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PD NOV PY 1999 VL 69 IS 6 BP 419 EP 427 DI 10.1024/0300-9831.69.6.419 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 271HY UT WOS:000084589200007 PM 10642900 ER PT J AU Egan, CA Zone, JJ AF Egan, CA Zone, JJ TI Linear IgA bullous dermatosis SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Review ID BASEMENT-MEMBRANE; DERMATITIS-HERPETIFORMIS; TARGET ANTIGENS; ERYTHEMA MULTIFORME; VII COLLAGEN; LAMINA-LUCIDA; DISEASE; CHILDHOOD; ANTIBODIES; ADULTS C1 Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. Vet Affairs Med Ctr, Med Serv, Dermatol Sect, Salt Lake City, UT 84148 USA. RP Egan, CA (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr MSC 1908, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK50678-01A1] NR 100 TC 48 Z9 51 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD NOV PY 1999 VL 38 IS 11 BP 818 EP 827 DI 10.1046/j.1365-4362.1999.00813.x PG 10 WC Dermatology SC Dermatology GA 274YH UT WOS:000084792300003 PM 10583613 ER PT J AU Nonaka, K Shum, L Takahashi, I Takahashi, K Ikura, T Dashner, R Nuckolls, GH Slavkin, HC AF Nonaka, K Shum, L Takahashi, I Takahashi, K Ikura, T Dashner, R Nuckolls, GH Slavkin, HC TI Convergence of the BMP and EGF signaling pathways on Smad1 in the regulation of chondrogenesis SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE Sox9; type II collagen; mandible; organ culture; micromass culture ID EPIDERMAL GROWTH-FACTOR; FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; BONE MORPHOGENETIC PROTEIN-2; II COLLAGEN; GENE-EXPRESSION; LIMB-BUD; ARTICULAR CHONDROCYTES; RETINOIC ACID; FACTOR-BETA; IN-VITRO AB Bone morphogenetic protein 4 (BMP4) induces, whereas epidermal growth factor (EGF) inhibits chondrogenesis. We hypothesize that BMP4 and EGF mediated intracellular signals are both coupled in the regulation of Meckel's cartilage development. Two chondrogenic experimental model systems were employed to test the hypothesis: (1) an ex vivo, serum-free, organ culture system for mouse embryonic mandibular processes, and (2) a micromass culture system for chicken embryonic mandibular processes. Chondrogenesis was assayed by alcian blue staining and expression of Sox9 and type II collagen. Exogenous EGF inhibited and BMP4 induced ectopic cartilage in a dose-dependent manner. When BMP4- and EGF-soaked beads were implanted in juxtaposition within embryonic day 10 mouse mandibular processes, the incidence and amount of ectopic cartilage, and Sox9 and type II collagen expression induced by BMP4, were significantly reduced as the concentration of EGF was increased. Similarly, in chicken serum-free micromass cultures, expression of a constitutively active BMP receptor type IB by replication competent avian retrovirus system promoted the rate and extent of chondrogenesis; however, exogenous EGF attenuated this effect. In micromass cultures, BMP signaling resulted in nuclear translocation and accumulation of the signaling molecule Smad1, whereas the addition of EGF inhibited this event. Our results suggest that BMP4 and EGF function antagonistically, yet are coupled in the regulation of initial chondrogenesis. Smad1 serves as a point of convergence for the integration of two different growth factor signaling pathways during chondrogenesis.. C1 NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20814 USA. RP Nonaka, K (reprint author), NIAMS, Craniofacial Dev Sect, NIH, 6 Ctr Dr,MSC 2745,Bldg 6,Room 324, Bethesda, MD 20814 USA. FU NIAMS NIH HHS [Z01-AR41114] NR 81 TC 32 Z9 32 U1 2 U2 4 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD NOV PY 1999 VL 43 IS 8 BP 795 EP 807 PG 13 WC Developmental Biology SC Developmental Biology GA 274MM UT WOS:000084769700003 PM 10707903 ER PT J AU Wang, D Kanuma, T Takama, F Mizumuma, H Ibuki, Y Wake, N Mogi, A Shitara, Y Hagiwara, K Takenoshita, S AF Wang, D Kanuma, T Takama, F Mizumuma, H Ibuki, Y Wake, N Mogi, A Shitara, Y Hagiwara, K Takenoshita, S TI Mutation analysis of the Smad3 gene in human ovarian cancers SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE Smad3; TGF-beta; mutation; polymorphism; ovarian cancer ID GROWTH-FACTOR-BETA; II RECEPTOR GENE; TUMOR-SUPPRESSOR GENE; IN-VIVO ALTERATIONS; HUMAN LUNG CANCERS; TGF-BETA; MICROSATELLITE INSTABILITY; COLORECTAL CANCERS; DPC4 GENE; CELLS AB The Smad3 gene is a member of the Smad family, vertebrate homologues of Drosophila Mad, and its gene product is a cytoplasmic element in the transforming growth factor-beta (TGF-beta) signaling pathway. Mutations in TGF-beta receptors and their cytoplasmic elements of transduction signals commonly accompany various cancers. Using PCR-SSCP analysis we searched for the presence of Smad3 gene mutations in 36 human ovarian cancers, and found that 15 cases (41.7%) had a polymorphism at codon 103. Because this mutation was not accompanied by amino acid replacement, the present results show that the mutations in the Smad3 gene are unlikely to be involved in human ovarian cancers. C1 Gunma Univ, Sch Med, Dept Obstet & Gynecol, Maebashi, Gumma 3718511, Japan. Gunma Univ, Sch Med, Dept Surg 1, Maebashi, Gumma 3718511, Japan. Kyushu Univ, Med Inst Bioregulat, Dept Reprod Physiol & Endocrinol, Beppu, Oita, Japan. Fukushima Med Univ, Dept Surg 2, Fukushima, Japan. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Mizumuma, H (reprint author), Gunma Univ, Sch Med, Dept Obstet & Gynecol, 3-39-22 Showa Machi, Maebashi, Gumma 3718511, Japan. NR 31 TC 22 Z9 24 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1999 VL 15 IS 5 BP 949 EP 953 PG 5 WC Oncology SC Oncology GA 251EW UT WOS:000083432500013 PM 10536178 ER PT J AU Silver, PB Chan, CC Wiggert, B Caspi, RR AF Silver, PB Chan, CC Wiggert, B Caspi, RR TI The requirement for pertussis to induce EAU is strain-dependent: B10.RIII, but not B10.A mice, develop EAU and Th1 responses to IRBP without pertussis treatment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEITIS; BORDETELLA-PERTUSSIS; GENETIC SUSCEPTIBILITY; CELLS; ENCEPHALOMYELITIS; UVEORETINITIS; SENSITIZATION; LYMPHOCYTES; EXPRESSION; LYMPHOKINE AB PURPOSE. Experimental autoimmune uveoretinitis (EAU) in mice is an important model for elucidating basic mechanisms in autoimmune eye disease. The need for pertussis toxin (PTX) as an additional adjuvant to elicit EAU has limited the usefulness of this model in some types of studies by introducing a pleiotropic factor with confounding effects on the immune response. METHODS. In the present study the authors examined the ability of B10.RIII mice, the most susceptible strain known so far, to develop EAU in response to the retinal antigen, interphotoreceptor retinoid-binding protein (IRBP). anti to a major uveitogenic epitope of IRBP, peptide (p)161-180, in the absence of PTS treatment. RESULTS. The data indicate that high disease scores in response to IRBP and p161-180 were found in B10.RIII mice, without the need for PTX as part of the immunization protocol. Unlike the B10.A strain in which appreciable disease did not develop without PTX, B10.RIII mice mounted a high IFN-gamma response to IRBP in the absence of PTX treatment. Interestingly, and unlike the effect with IRBP, in vitro recall response to p161-180 was low in IFN-gamma. despite good EAU scores. CONCLUSIONS. The data indicate that an important mechanism through which PTX facilitates induction of cell-mediated autoimmunity is by promoting a Th1 polarization of the immune response. The propensity of B10.RIII mice to mount a more polarized Th1 response to IRBP than other strains may contribute to their ability to develop EAU without pertussis adjuvant. Nevertheless, the induction of EAU by p161-180 in the context of a relatively limited IFN-gamma production indicates that non-Th1- and Th-related mechanisms are likely to act in concert to determine the outcome of disease. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222,10 Ctr Dr,MSC 1857, Bethesda, MD 20892 USA. NR 28 TC 65 Z9 68 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1999 VL 40 IS 12 BP 2898 EP 2905 PG 8 WC Ophthalmology SC Ophthalmology GA 250UN UT WOS:000083406700020 PM 10549650 ER PT J AU Arai, AE Epstein, FH Bove, KE Wolff, SD AF Arai, AE Epstein, FH Bove, KE Wolff, SD TI Visualization of aortic valve leaflets using black blood MRI SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc DE magnetic resonance imaging; aortic valve; bicuspid aortic valve; pulmonic valve; mitral valve ID REGURGITATION; QUANTIFICATION; STENOSIS; HEART; VOLUMES; IMAGES AB Although magnetic resonance imaging (MRI) is capable of imaging various physiological parameters associated with the heart valves, it has generally been difficult to visualize the valve leaflets directly. The aortic valve was imaged in 120 patients referred for cardiac MRI to assess myocardial volumes or mass. The average patient age was 37 and ranged from 9 to 75 years, Heart rate ranged from 43 to 100 bpm, Imaging was performed on a 1.5 T scanner equipped with enhanced gradients and a cardiac phased-array coil, A double inversion recovery fast spin-echo sequence was used to acquire short-axis images of the aortic valve in a breathhold (15 +/- 3 seconds). All three leaflets of the aortic valve were seen in 102 of 120 studies (85%), Two leanets were detected in another 15 subjects. No leaflets were seen in three individuals. Seven cases of a bicuspid or thickened aortic valves were clearly distinguished from normal valves, The signal-to-noise ratio of aortic leaflets (14 +/- 5) was significantly higher than that of the residual blood signal in the aortic root (7 +/- 4, P < 0.001). MR images showed the aortic valve leaflets in a high fraction of people with suspected normal aortic valves and detected seven cases of abnormal aortic valves. The potential of MRI to study both the anatomic and functional consequences of valvular heart disease warrants further study. (C) 1999 Wiley-Liss, Inc. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Rm B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [K08 HL03135] NR 23 TC 29 Z9 30 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD NOV PY 1999 VL 10 IS 5 BP 771 EP 777 DI 10.1002/(SICI)1522-2586(199911)10:5<771::AID-JMRI22>3.0.CO;2-Q PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 323NP UT WOS:000087572100022 PM 10548787 ER PT J AU Hisada, M Stuver, SO Okayama, A Mueller, NE AF Hisada, M Stuver, SO Okayama, A Mueller, NE TI Gender difference in skin reactivity to purified protein derivative among carriers of HTLV-I in Japan SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE gender difference; HTLV-I; purified protein derivative ID VIRUS TYPE-I; CELL LEUKEMIA LYMPHOMA; IMMUNE-RESPONSE; MIYAZAKI COHORT; GENE-EXPRESSION; PROVIRAL DNA; RISK; TUBERCULOSIS; SUPPRESSION; LYMPHOCYTES AB The incidence of malignancies due to oncogenic virus infections tends to be higher in men than in women. Gender-related differences in cell-mediated immunity, which plays a role in Viral pathogenesis, may explain this observation. To explore this possibility in the context of HTLV-I infection, we examined skin reactivity to purified protein derivative (PPD) among 128 residents of an HTLV-I endemic area in Japan, who were born before 1921 and are assumed to have been exposed to M. tuberculosis bacilli. The odds ratio (OR) for reduced PPD reactivity (erythema <10 mm in diameter) was calculated by multiple logistic regression analysis. Men were significantly less likely than women to have reduced PPD reactivity among HTLV-I-negative individuals (26% Versus 59%; p < .01); whereas this gender difference was not apparent among HTLV-I carriers (63% versus 62%; p = .87). HTLV-I positivity was strongly associated with reduced PPD reactivity in men, but not in women (odds ratio [OR], 7.3 versus 1.2; p = .05). Although this observation may be due, in part, to a longer average duration of HTLV-I infection in men compared with women, the finding also raises the possibility that men may be inherently more susceptible to loss of PPD reactivity by HTLV-I infection. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Miyazaki Med Sch, Dept Internal Med 2, Miyazaki, Japan. RP Hisada, M (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8011, Rockville, MD 20852 USA. FU NCI NIH HHS [2R01-CA38450] NR 37 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD NOV 1 PY 1999 VL 22 IS 3 BP 302 EP 307 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 283JZ UT WOS:000085273600013 PM 10770352 ER PT J AU Postolache, TT Doty, RL Wehr, TA Jimma, LA Han, L Turner, EH Matthews, JR Neumeister, A No, C Kroger, H Bruder, GE Rosenthal, NE AF Postolache, TT Doty, RL Wehr, TA Jimma, LA Han, L Turner, EH Matthews, JR Neumeister, A No, C Kroger, H Bruder, GE Rosenthal, NE TI Monorhinal odor identification and depression scores in patients with seasonal affective disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE seasonal affective disorder; olfaction; hemispheric laterality ID BRAIN ELECTRICAL ASYMMETRIES; OLFACTORY FUNCTION; LIGHT TREATMENT; BRIGHT LIGHT; PERCEPTUAL ASYMMETRY; RECOGNITION MEMORY; PREFRONTAL CORTEX; WINTER DEPRESSION; CONTROLLED TRIAL; PLEASANT ODORS AB Background: Visual and olfactory pathways are interconnected. Olfactory deafferentation unmasks photoperiodic responsiveness in some nonphotoperiodic animals such as laboratory rats. By analogy, we hypothesized that olfactory deficits may unmask seasonal rhythms in certain individuals, namely those with seasonal affective disorder (SAD). Since previous studies suggest lateralized hemispheric dysfunction in SAD, and since olfactory neurons' primary projections are largely ipsilateral, we assessed olfactory identification performance on both the right and left side of the nose. Methods: Twenty-four patients with SAD and 24 matched controls were studied using a phenyl ethyl alcohol detection threshold test bilaterally and the University of Pennsylvania Smell Identification Test unilaterally. Subjects rated their mood using the Self Assessment Mood Scale for SAD. Patients' testing was done in both 'depressed' and 'improved on light' states. Results: No difference in olfactory performance was found between patients and controls or between patients before and after light treatment. However, right-side identification scores were negatively correlated with 'typical' depression scores (r = -0.56, P = 0.006), while left-side olfactory scores were not. Atypical depression scores were unrelated to olfactory performance. Similar correlations emerged between the olfactory identification laterality quotient (Right - Left)/(Right + Left) and typical depressive scores (r = - 0.64, P < 0.001) and total depression scores (r = -0.59, P < 0.004). Limitations: We studied a demographically heterogeneous sample and did not control for menstrual factors. Discussion: Our results add to previous evidence of lateralized hemispheric involvement in SAD and suggest that olfaction may be related to seasonal emotional rhythms in humans. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Sect Biol Rythms, Bethesda, MD 20892 USA. Univ Penn, Med Ctr, Ctr Smell & Taste, Philadelphia, PA 19104 USA. New York State Psychiat Inst, Dept Biopsychol, New York, NY 10032 USA. RP Postolache, TT (reprint author), NIMH, Sect Biol Rythms, 10 Ctr Dr,Room 3S231, Bethesda, MD 20892 USA. RI Doty, Richard/B-7623-2012; Turner, Erick/A-4848-2008; Doty, Richard/G-1602-2013 OI Turner, Erick/0000-0002-3522-3357; FU PHS HHS [P01 00161] NR 73 TC 34 Z9 34 U1 7 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 1999 VL 56 IS 1 BP 27 EP 35 DI 10.1016/S0165-0327(99)00027-0 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 269PY UT WOS:000084487800004 PM 10626777 ER PT J AU Denicoff, KD Ali, SO Mirsky, AF Smith-Jackson, EE Leverich, GS Duncan, CC Connell, EG Post, RM AF Denicoff, KD Ali, SO Mirsky, AF Smith-Jackson, EE Leverich, GS Duncan, CC Connell, EG Post, RM TI Relationship between prior course of illness and neuropsychological functioning in patients with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc DE bipolar disorder; life chart method; course of illness; neuropsychological functioning ID LITHIUM-CARBONATE; SCHIZOPHRENIA; PERFORMANCE; MEMORY AB Background: This study investigated the relationship between prior course of illness and neuropsychological deficits in relatively high functioning outpatients with bipolar disorder. Method: Forty-nine bipolar I or II patients, in a relatively euthymic state during treatment with mood stabilizers, were administered neuropsychological tests that assessed a variety of functions, including verbal memory, sustained attention and vigilance, and intelligence. A detailed retrospective life chart was completed for each patient using the NIMH Life Chart Method(TM) to define variables reflecting duration and severity of illness, and frequency of episodes. Results: Stepwise multiple regression analyses show that several different measures of a more severe course of prior illness related to greater duration and a larger number of affective episodes and hospitalizations were associated with poorer performance on tests of abstraction, attention and memory. Conclusion: The results indicate that bipolar patients with a more severe prior course of illness and a greater number of affective episodes have more impaired neuropsychological functioning. The direction of causality and the pathophysiological mechanisms remain to be explored. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Sect Psychobiol, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, Sect Clin & Expt Neuropsychol, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Denicoff, KD (reprint author), NIMH, Sect Psychobiol, Biol Psychiat Branch, Bldg 10,Room 3N212,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Ali, Syed/0000-0003-3131-3299 NR 27 TC 102 Z9 105 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 1999 VL 56 IS 1 BP 67 EP 73 DI 10.1016/S0165-0327(99)00028-2 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 269PY UT WOS:000084487800009 PM 10626782 ER PT J AU Packer, C Altizer, S Appel, M Brown, E Martenson, J O'Brien, SJ Roelke-Parker, M Hofmann-Lehmann, R Lutz, H AF Packer, C Altizer, S Appel, M Brown, E Martenson, J O'Brien, SJ Roelke-Parker, M Hofmann-Lehmann, R Lutz, H TI Viruses of the Serengeti: patterns of infection and mortality in African lions SO JOURNAL OF ANIMAL ECOLOGY LA English DT Article DE epidemic; population density; seroprevalence; susceptibles; virulence ID FELINE IMMUNODEFICIENCY VIRUS; WILD DOGS; PHYLOGENETIC ASPECTS; LEUKEMIA-VIRUS; DOMESTIC CATS; NATIONAL-PARK; MASAI-MARA; POPULATION; EVOLUTION; DISEASES AB 1. We present data on the temporal dynamics of six viruses that infect lions (Panthera lee) in the Serengeti National Park and Ngorongoro Crater, Tanzania, These populations have been studied continuously for the past 30 years, and previous research has documented their seroprevalence for feline herpesvirus, feline immunodeficiency virus (FIV), feline calicivirus, feline parvovirus, feline coronavirus and canine distemper virus (CDV), A seventh virus, feline leukaemia virus (FeLV), was absent from these animals, 2. Comprehensive analysis reveals that feline herpesvirus and FIV were consistently prevalent at high levels, indicating that they were endemic in the host populations. Feline calici-, parvo- and coronavirus, and CDV repeatedly showed a pattern of seroprevalence that was indicative of discrete disease epidemics: a brief period of high exposure for each virus was followed by declining seroprevalence. 3. The timing of viral invasion suggests that different epidemic viruses are associated with different minimum threshold densities of susceptible hosts, Furthermore, the proportion of susceptibles that became infected during disease outbreaks was positively correlated with the number of susceptible hosts at the beginning of each outbreak. 4. Examination of the relationship between disease outbreaks and host fitness suggest that these viruses do not affect birth and death rates in lions, with the exception of the 1994 outbreak of canine distemper virus. Although the endemic viruses (FHV and FIV) were too prevalent to measure precise health effects, there was no evidence that FIV infection reduced host longevity. C1 Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA. Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA. NCI, Viral Carcinogenesis Lab, Frederick, MD USA. Univ Zurich, Dept Vet Internal Med, Clin Lab, CH-8001 Zurich, Switzerland. RP Packer, C (reprint author), Univ Minnesota, Dept Ecol Evolut & Behav, 1987 Upper Buford Circle, St Paul, MN 55108 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 NR 57 TC 116 Z9 119 U1 3 U2 67 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0021-8790 J9 J ANIM ECOL JI J. Anim. Ecol. PD NOV PY 1999 VL 68 IS 6 BP 1161 EP 1178 DI 10.1046/j.1365-2656.1999.00360.x PG 18 WC Ecology; Zoology SC Environmental Sciences & Ecology; Zoology GA 265BJ UT WOS:000084218700008 ER PT J AU Combs, CA Aletras, AH Balaban, RS AF Combs, CA Aletras, AH Balaban, RS TI Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE phosphorus 31-nuclear magnetic resonance; tibialis anterior; oxidative capacity; phosphocreatine; adenosine 5 '-triphosphate ID KNEE EXTENSION; IN-VIVO; EXERCISE; PHOSPHORYLATION; ENERGY; ATP; SPECTROSCOPY; TEMPERATURE; RESYNTHESIS; EFFICIENCY AB A recent report suggests that differences in aerobic capacity exist between concentric and eccentric muscle action in human muscle (T. W. Ryschon, M. D. Fowler, R. E. Wysong, A. R. Anthony, and R. S. Balaban. J. Appl. Physiol. 83: 867-874, 1997). This study compared oxidative response, in the form of phosphocreatine (PCr) resynthesis rates, with matched levels of metabolic strain (i.e., changes in ADP concentration or the free energy of ATP hydrolysis) in tibialis anterior muscle exercised with either muscle action in vivo (n = 7 subjects). Exercise was controlled and metabolic strain measured by a dynamometer and P-31-magnetic resonance spectroscopy, respectively. Metabolic strain was varied to bring cytosolic ADP concentration up to 55 mu M or decrease the free energy of ATP hydrolysis to -55 kJ/mol with no change in cytoplasmic pH. PCr resynthesis rates after exercise ranged from 31.9 to 462.5 and from 21.4 to 405.4 mu mol PCr/s for concentric and eccentric action, respectively. PCr resynthesis rates as a function of metabolic strain were not significantly different between muscle actions (P > 0.40), suggesting that oxidative capacity is dependent on metabolic strain, not muscle action. Pooled data were found to more closely conform to previous biochemical measurements when a term for increasing oxidative capacity with metabolic strain was added to models of respiratory control. C1 NHLBI, LCE, NIH, Bethesda, MD 20892 USA. RP Combs, CA (reprint author), NHLBI, LCE, NIH, 10 B1D416,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; OI Balaban, Robert/0000-0003-4086-0948; Aletras, Anthony/0000-0002-3786-3817 NR 37 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1999 VL 87 IS 5 BP 1768 EP 1775 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 255NA UT WOS:000083675000029 PM 10562621 ER PT J AU McLenigan, MP Kulaeva, OI Ennis, DG Levine, AS Woodgate, R AF McLenigan, MP Kulaeva, OI Ennis, DG Levine, AS Woodgate, R TI The bacteriophage P1 HumD protein is a functional homolog of the prokaryotic UmuD '-like proteins and facilitates SOS mutagenesis in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA-REPAIR GENES; SALMONELLA-TYPHIMURIUM; RECA PROTEIN; MUTATOR ACTIVITY; RNA-POLYMERASE; UMUDC OPERON; CLEAVAGE; DAMAGE; EXPRESSION; PLASMID AB The Escherichia coli umuD and umuC genes comprise an operon and encode proteins that are involved in the mutagenic bypass of normally replication-inhibiting DNA lesions. UmuD is, however, unable to function in this process until it undergoes a RecA-mediated cleavage reaction to generate UmnD'. Many homologs of umuDC have now been identified. Mast are located on bacterial chromosomes or on broad-host-range R plasmids. One such putative homolog, humD (homolog of umuD) is, however, found on the bacteriophage P1 genome. Interestingly, humD differs from other umuD homologs in that it encodes a protein similar in size to the posttranslationally generated UmuD' protein and not UmuD, nor is it in an operon with a cognate umuC partner. To determine if HumD is, in fact, a bona fide homolog of the prokaryotic UmuD'-like mutagenesis proteins, we have analyzed the ability of HumD to complement UmuD' functions in vivo as well as examined HumD's physical properties in vitro. When expressed from a high-copy-number plasmid, HumD restored cellular mutagenesis and increased UV survival to normally nonmutable recA430 lexA(Def) and UV-sensitive Delta umuDC recA718 lexA(Def) strains, respectively. Complementing activity was reduced when HumD was expressed from a low-copy-number plasmid, but this observation is explained by immunoanalysis which indicates that HumD is normally poorly expressed in vivo, In vitro analysis revealed that like UmuD', HumD forms a stable dimer in solution and is able to interact with E. coli UmuC and RecA nucleoprotein filaments. We conclude, therefore, that bacteriophage P1 HumD is a functional homolog of the UmuD'-like proteins, and we speculate as to the reasons why P1 might require the activity of such a protein in vivo. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Louisiana Univ, Dept Biol, Lafayette, LA 70504 USA. RP Woodgate, R (reprint author), NICHD, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 NR 49 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 1999 VL 181 IS 22 BP 7005 EP 7013 PG 9 WC Microbiology SC Microbiology GA 257PG UT WOS:000083790200018 PM 10559166 ER PT J AU Hawkins, V Shen, Q Chiueh, CC AF Hawkins, V Shen, Q Chiueh, CC TI Kynostatin and 17 beta-estradiol prevent the apoptotic death of human neuroblastoma cells exposed to HIV-1 protease SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE AIDS dementia complex; antioxidants; apoptosis; cerebral atrophy; gp120; HIV-1 protease; human neuroblastoma cell; neuroprotection; protease inhibitor (KNI-272) ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; OXIDATIVE STRESS; TYPE-1 PROTEASE; BRAIN; NEUROTOXICITY; PEPTIDE; LOCALIZATION; INHIBITORS; INFECTION AB A significant number of adult male patients with acquired immunodeficiency syndrome develop cerebral atrophy and progressive brain disorders such as dementia complex and neuropsychiatric problems. Upon entering the brain via activated macrophages or microglias, the human immunodeficiency type 1 virus (HIV-1) may produce cytotoxic factors such as HIV-1 envelope protein (gp120) and protease, Owing to significant proteolysis of nonviral proteins, the protease derived from HIV-1 may be detrimental to brain cells and neurons. Our results revealed that HIV-1 protease, at nanomolar concentrations, was as potent as gp120 in causing neurotoxicity in human neuroblastoma neurotypic SH-SY5Y cells. As shown by the Oncor ApopTag staining procedure, HIV-1 protease significantly increased the number of apoptotic cells over the serum-free controls. Moreover, HIV-1 protease-induced neurotoxicity was blocked by a selective protease inhibitor, kynostatin (KNI-272), Antioxidants such as 17 beta-estradiol, melatonin, and S-nitrosoglutathione also prevented protease-induced neurotoxicity. These findings indicate that oxidative proteolysis may mediate HIV-1 protease-induced apoptosis and the degeneration of neurons and other brain cells. Centrally active protease inhibitors and antioxidants may play an important role in preventing cerebral atrophy and associated dementia complex caused by HIV-1. C1 NIMH, Unit Neurodegenerat & Neuroprotect, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD USA. RP Chiueh, CC (reprint author), NIMH, Unit Neurodegenerat & Neuroprotect, Clin Sci Lab, NIH, 10-3D-41, Bethesda, MD 20892 USA. NR 42 TC 8 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD NOV-DEC PY 1999 VL 6 IS 6 BP 433 EP 438 DI 10.1159/000025419 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 249VZ UT WOS:000083355100009 PM 10545779 ER PT J AU Riminucci, M Fisher, LW Majolagbe, A Corsi, A Lala, R De Sanctis, C Robey, PG Bianco, P AF Riminucci, M Fisher, LW Majolagbe, A Corsi, A Lala, R De Sanctis, C Robey, PG Bianco, P TI A novel GNAS1 mutation, R201G, in McCune-Albright syndrome SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID ACTIVATING G(S)ALPHA MUTATION; STIMULATORY G-PROTEIN; FIBROUS DYSPLASIA; ALPHA-SUBUNIT; ADENYLYL CYCLASE; BONE; IDENTIFICATION; CHAIN; GENE C1 Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Osped Regina Margherita, Div Endocrinol Pediat, Turin, Italy. RP Bianco, P (reprint author), Univ Aquila, Dipartimento Med Sperimentale, Via Vetoio Coppito 2, I-67100 Laquila, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 13 TC 36 Z9 39 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 1999 VL 14 IS 11 BP 1987 EP 1989 DI 10.1359/jbmr.1999.14.11.1987 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 250BF UT WOS:000083368600022 PM 10571700 ER PT J AU Koike, M Awaji, T Kataoka, M Tsujimoto, G Kartasova, T Koike, A Shiomi, T AF Koike, M Awaji, T Kataoka, M Tsujimoto, G Kartasova, T Koike, A Shiomi, T TI Differential subcellular localization of DNA-dependent protein kinase components Ku and DNA-PKcs during mitosis SO JOURNAL OF CELL SCIENCE LA English DT Article DE cell cycle; chromosome periphery; DNA-PK; Ku70; Ku80; localization ID STRAND BREAK REPAIR; SV40-TRANSFORMED HUMAN KERATINOCYTES; HELA-CELL NUCLEI; SACCHAROMYCES-CEREVISIAE; V(D)J RECOMBINATION; MESSENGER-RNA; ANTIGEN-KU; EXPRESSION; BINDING; GROWTH AB The Ku protein is a complex of two subunits, Ku70 and Ku80, Ku plays an important role in DNA-PKcs-dependent double-strand break repair and V(D)J recombination, and in growth regulation, which is DNA-PKcs-independent. We studied the expression and the subcellular localization of Ku and DNA-PKcs throughout the cell cycle in several established human cell lines, Using immunofluorescence analysis and confocal laser scanning microscopy, we detected Ku70 and Ku80 in the nuclei in interphase cells, In mitotic cells (1) most of Ku protein was found diffused in the cytoplasm, (2) a fraction was detected at the periphery of condensed chromosomes, (3) no Ku protein was present in the chromosome interior, Association of Ku with isolated chromosomes was also observed, On the other hand, DNA-PKcs was detected in the nucleus in interphase cells and not at the periphery of condensed chromosomes during mitosis, Using indirect immunoprecipitation, we found that throughout the cell cycle, Ku70 and Ku80 were present as heterodimers, some in complex with DNA-PKcs, Our findings suggest that the localization of Ku at the periphery of metaphase chromosomes might be imperative for a novel function of Ku in the G(2)/M phase, which does not require DNA-PKcs. C1 Natl Inst Radiol Sci, Genome Res Grp, Inage Ku, Chiba 2638555, Japan. Natl Childrens Med Res Ctr, Dept Mol Cell Pharmacol, Setagaya Ku, Tokyo 154, Japan. NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD USA. RP Koike, M (reprint author), Natl Inst Radiol Sci, Genome Res Grp, Inage Ku, 4-9-1 Anagawa, Chiba 2638555, Japan. NR 49 TC 69 Z9 72 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV PY 1999 VL 112 IS 22 BP 4031 EP 4039 PG 9 WC Cell Biology SC Cell Biology GA 263ZL UT WOS:000084155100019 PM 10547363 ER PT J AU Waldvogel, D van Gelderen, P Ishii, K Hallett, M AF Waldvogel, D van Gelderen, P Ishii, K Hallett, M TI The effect of movement amplitude on activation in functional magnetic resonance imaging studies SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE functional magnetic resonance imaging; brain activation; movement amplitude; cerebral blood flow ID CEREBRAL BLOOD-FLOW; PRIMARY MOTOR CORTEX; FINGER MOVEMENTS; MONKEY; AREA; PET; KINEMATICS; DISCHARGE; BRAIN; MRI AB To evaluate the effect of movement amplitude on the "blood oxygen level-dependent effect," the authors studied six normal subjects while they extended their index finger with two different amplitudes. Images were analyzed using SPM96. In five subjects, the signal intensity increase in the primary sensorimotor area was significantly greater with the larger amplitude movement. In other areas of interest (supplementary motor area, premotor cortex, insula, postcentral area, cerebellum), the large-amplitude movement often showed significant activation when the small-amplitude movement did not. The authors conclude that, in studies of the motor system, movement amplitude needs to be controlled. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, In Vivo NMR Res Ctr, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. NR 33 TC 43 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1999 VL 19 IS 11 BP 1209 EP 1212 PG 4 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 276NJ UT WOS:000084884000004 PM 10566966 ER PT J AU Haugen, BR Pacini, F Reiners, C Schlumberger, M Ladenson, PW Sherman, SI Cooper, DS Graham, KE Braverman, LE Skarulis, MC Davies, TF DeGroot, LJ Mazzaferri, EL Daniels, GH Ross, DS Luster, M Samuels, MH Becker, DV Maxon, HR Cavalieri, RR Spencer, CA McEllin, K Weintraub, BD Ridgway, EC AF Haugen, BR Pacini, F Reiners, C Schlumberger, M Ladenson, PW Sherman, SI Cooper, DS Graham, KE Braverman, LE Skarulis, MC Davies, TF DeGroot, LJ Mazzaferri, EL Daniels, GH Ross, DS Luster, M Samuels, MH Becker, DV Maxon, HR Cavalieri, RR Spencer, CA McEllin, K Weintraub, BD Ridgway, EC TI A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HAMSTER OVARY CELLS; THYROGLOBULIN MEASUREMENT; STIMULATING HORMONE; CARCINOMA; PAPILLARY; THERAPY; I-131; BIOACTIVITY; METASTASES AB Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence. C1 Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO 80262 USA. Univ Pisa, Div Endocrinol, I-56124 Pisa, Italy. Univ Wurzburg, Nukl Med Klin & Poliklin, D-97070 Wurzburg, Germany. Inst Gustave Roussy, Nucl Med Serv, F-94805 Villejuif, France. Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD 21287 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med Specialties, Houston, TX 77030 USA. Sinai Hosp, Div Endocrinol, Baltimore, MD 21215 USA. Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97201 USA. Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA. Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. Ohio State Univ, Ctr Hlth Sci, Dept Internal Med, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Cornell Univ, Med Ctr, New York Hosp, Div Nucl Med, New York, NY 10021 USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ So Calif, Dept Med, Los Angeles, CA 90033 USA. Genzyme Transgen Corp, Boston, MA 02139 USA. Univ Maryland, Sch Med, Mol Endocrinol Lab, Baltimore, MD 21201 USA. RP Haugen, BR (reprint author), Univ Colorado, Hlth Sci Ctr, Div Endocrinol, B151,4200 E 9th Ave, Denver, CO 80262 USA. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 FU NCRR NIH HHS [M01-RR-43] NR 23 TC 381 Z9 401 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1999 VL 84 IS 11 BP 3877 EP 3885 DI 10.1210/jc.84.11.3877 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800004 PM 10566623 ER PT J AU Katzur, AC Koshimizu, TA Tomic, M Schultze-Mosgau, A Ortmann, O Stojilkovic, SS AF Katzur, AC Koshimizu, TA Tomic, M Schultze-Mosgau, A Ortmann, O Stojilkovic, SS TI Expression and responsiveness of P2Y(2) receptors in human endometrial cancer cell lines SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACTIVATED PROTEIN-KINASE; FOCAL TYROSINE KINASE; HIGH-AFFINITY BINDING; EXTRACELLULAR ATP; OVARIAN-CANCER; GROWTH-FACTOR; ADENOSINE-TRIPHOSPHATE; PURINERGIC RECEPTORS; PHOSPHOLIPASE-D; NERVOUS-SYSTEM AB In single endometrial carcinoma HEC-1A and Ishikawa cells, ATP induced a rapid and extracellular Ca2+-independent rise in cytosolic Ca2+ concentration ([Ca2+](i)) in a dose-dependent manner, with an ED50 of about 10 mu M. The spike phase was followed by a sustained plateau phase that was dependent on Ca2+ influx through voltage-insensitive Ca2+ channels, whose gating was controlled by a capacitative Ca2+ entry mechanism. ADP was less potent in raising the cystolic Ca2+ concentration, and AMP and adenosine were ineffective. The order of agonist potency for this receptor was ATP = UTP > ATP-gamma-S much greater than ADP. Several other agonists, including beta,gamma-methylene-ATP, 2-MeS-ATP, and BzATP were ineffective. This ligand-selective profile indicates the expression of the P2Y(2)R subtype in endometrial cells. Accordingly, reverse transcription-PCR using P2Y(2) primers amplified the expected transcript from both cell lines. The coupling of these receptors to phospholipase C was confirmed by the ability of ATP to increase inositol 1,4,5-trisphosphate and diacylglycerol productions. These receptors are also coupled to the phospholipase D-l pathway, leading to accumulation of phosphatidic;acid, Activation of P2Y(2) receptors by a slowly degradable ATP analog, ATP-gamma-S, was associated with a significant suppression of cell proliferation without affecting the cellular apoptosis. These results indicate that P2Y(2) receptors may participate in control of the cell cycle of endometrial carcinoma cells. C1 NICHHD, Endocrinol & Reprod Res Branch, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA. Univ Lubeck, Dept Obstet & Gynecol, D-23538 Lubeck, Germany. RP Stojilkovic, SS (reprint author), NICHHD, Endocrinol & Reprod Res Branch, Sect Cellular Signaling, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Tomic, Melanija/C-3371-2016; OI Koshimizu, Taka-aki/0000-0001-5292-7535 NR 46 TC 33 Z9 37 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1999 VL 84 IS 11 BP 4085 EP 4091 DI 10.1210/jc.84.11.4085 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800035 PM 10566654 ER PT J AU Colman, RJ Kemnitz, JW Lane, MA Abbott, DH Binkley, N AF Colman, RJ Kemnitz, JW Lane, MA Abbott, DH Binkley, N TI Skeletal effects of aging and menopausal status in female rhesus macaques SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MONKEYS MACACA-FASCICULARIS; BONE-MINERAL DENSITY; DEGENERATIVE JOINT DISEASE; X-RAY ABSORPTIOMETRY; PARATHYROID-HORMONE; TRABECULAR BONE; AGE; OVARIECTOMY; MARKERS; WOMEN AB To further define the nonhuman primate as a model of the adult human skeleton, we explored the impact of growth, natural menopause, and osteoarthritis on bone mass, serum markers of bone turnover (osteocalcin and C-terminal telopeptide of type I collagen) and measures of skeletal relevance (PTH, 25-hydroxyvitamin D, total alkaline phosphatase, calcium, phosphorus, creatinine, and albumin). Fifty-eight female (aged 4-30 yr) rhesus macaques were defined as growing (G; n = 12; less than or equal to 10 yr old), adult premenopausal (APre; n = 30; >10 yr old; eumenorrheic, high serum estradiol and low FSH), or postmenopausal (Post; n = 16; amenorrheic for at least I yr, with low serum estradiol and high FSH). Total body and posterior-anterior spinal bone masses were lower in G than APre animals (P < 0.05). Post females had lower total body, distal radius, and spinal bone mass than premenopausal animals (P < 0.05). Osteocalcin was higher in Post than APre animals (P < 0.01). Other measures showed no relationship with menopausal status. In older monkeys, spinal osteoarthritis became common, causing increased dual-energy x-ray absorptiometry-measured bone mass in the lumbar spinal posterior-anterior projection. In conclusion, after natural menopause, rhesus monkeys have lower bone mass and higher skeletal turnover without alteration of the calcium-vitamin D axis. As such, they are an excellent model of human estrogen-depletion bone loss. C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI 53706 USA. Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. NIA, Gerontol Res Ctr, Intramural Res Program, Mol Phyiol & Genet Sect,NIH, Baltimore, MD 21224 USA. RP Kemnitz, JW (reprint author), Univ Wisconsin, Wisconsin Reg Primate Res Ctr, 1223 Capitol Court, Madison, WI 53715 USA. FU NCRR NIH HHS [P51-RR-00167]; NIA NIH HHS [K08-AG-00801, P01-AG-11915] NR 36 TC 43 Z9 43 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1999 VL 84 IS 11 BP 4144 EP 4148 DI 10.1210/jc.84.11.4144 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800044 PM 10566663 ER PT J AU Koch, CA Azumi, N Furlong, MA Jha, RC Kehoe, TE Trowbridge, CH O'Dorisio, TM Chrousos, GP Clement, SC AF Koch, CA Azumi, N Furlong, MA Jha, RC Kehoe, TE Trowbridge, CH O'Dorisio, TM Chrousos, GP Clement, SC TI Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NEURO-ENDOCRINE CARCINOMA; FEMALE GENITAL-TRACT; SMALL-CELL-CARCINOMA; 5-HYDROXYINDOLEACETIC ACID; NEUROENDOCRINE CARCINOMA; ARGENTAFFIN CELLS; PEPTIDE-HORMONES; TUMORS; ADENOCARCINOMA; SEROTONIN AB Neuroendocrine tumors of the cenix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient's liver lesions and original cervical lesion ("adenocarcinoma") suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Endocrinol & Metab, Washington, DC 20020 USA. Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20020 USA. Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20020 USA. Ohio State Univ, Med Ctr, Dept Endocrinol & Metab, Columbus, OH 43210 USA. RP Koch, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 44 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1999 VL 84 IS 11 BP 4209 EP 4213 DI 10.1210/jc.84.11.4209 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800057 PM 10566674 ER PT J AU Wolkersdorfer, GW Lohmann, T Marx, C Schroder, S Pfeiffer, R Stahl, HD Scherbaum, WA Chrousos, GP Bornstein, SR AF Wolkersdorfer, GW Lohmann, T Marx, C Schroder, S Pfeiffer, R Stahl, HD Scherbaum, WA Chrousos, GP Bornstein, SR TI Lymphocytes stimulate dehydroepiandrosterone production through direct cellular contact with adrenal zona reticularis cells: A novel mechanism of immune-endocrine interaction SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SULFATE DHEAS LEVELS; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; SERUM DEHYDROEPIANDROSTERONE; ADRENOCORTICAL-CELLS; ANDROGEN SECRETION; T-LYMPHOCYTES; RECOMBINANT INTERLEUKIN-6; CORTISOL PRODUCTION AB Adrenal androgen production was reduced by 80% in patients receiving T lymphocyte-suppressive medications compared to that in age-matched controls. In vitro, however, neither tacrolimus nor cyclosporin A reduced dehydroepiandrosterone (DHEA) release by adrenocortical cells. Therefore, we examined the potential role of lymphocytes in adrenal androgen production, using cocultures of human T lymphocytes and adrenocortical primary or transformed cells. Cocultures led to a 4-fold elevation of DHEA levels (490.4 +/- 94.8% over basal), which was greater than the increase observed after the addition of maximal concentrations of ACTH (117.4 +/- 14.8%). Separation of cells by semipermeable membranes abolished this effect, and transfer of leukocyte-conditioned medium had little androgen-stimulating effect. These data suggested that the observed stimulation of androgen secretion required cell contact rather than soluble paracrine factor(s). Furthermore, we examined human adrenal glands for the presence of T lymphocytes and contact between these cells and steroid-secreting cells of the zona reticularis. Indeed, T lymphocytes expressing CD4 and CD8 antigens were present within human adrenal zona reticularis by immunohistochemical subtyping. Electron microscopic analyses demonstrated direct cell-cell contact between T lymphocytes and adrenocortical cells in situ. This study provides evidence for a novel mechanism of immune-endocrine interactions of direct T lymphocyte-adrenocortical cell contact-mediated stimulation of adrenal androgen secretion. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Diabet Res Inst, D-40001 Dusseldorf, Germany. Univ Leipzig, Dept Internal Med, D-04103 Leipzig, Germany. RP Wolkersdorfer, GW (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM WolkersdoerferG@netscape.net NR 66 TC 33 Z9 34 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1999 VL 84 IS 11 BP 4220 EP 4227 DI 10.1210/jc.84.11.4220 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800059 PM 10566676 ER PT J AU Yang, YL Ashwell, JD AF Yang, YL Ashwell, JD TI Thymocyte apoptosis SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Review DE thymocyte apoptosis ID T-CELL RECEPTOR; GLUCOCORTICOID-INDUCED APOPTOSIS; IMPAIRED NEGATIVE SELECTION; POSITIVE SELECTION; MICE LACKING; CYTOCHROME-C; CD4(+)CD8(+) THYMOCYTES; CD28-DEFICIENT MICE; CLONAL DELETION; DNA-BINDING AB Apoptosis is the fate of most thymocytes. Many molecules participate in the decision of whether a thymocyte is to live or to die, including cell surface receptors, such as the T cell receptor for antigen, Notch-1, and costimulatory receptors, ligand-regulated nuclear transcription factors such as the glucocorticoid receptor, signaling, and effector proteases, and direct regulators of the apoptotic machinery such IAPs. In this review we discuss recent data concerning these molecules and pathways and their implication for understanding the mechanisms underlying thymocyte death, survival, and the generation of immunocompetent T cells. C1 NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Room 1B 40,Bldg 10, Bethesda, MD 20892 USA. NR 148 TC 19 Z9 19 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 1999 VL 19 IS 6 BP 337 EP 349 DI 10.1023/A:1020594531159 PG 13 WC Immunology SC Immunology GA 273NL UT WOS:000084713700001 PM 10634208 ER PT J AU Wiest, R Das, S Cadelina, G Garcia-Tsao, G Milstien, S Groszmann, RJ AF Wiest, R Das, S Cadelina, G Garcia-Tsao, G Milstien, S Groszmann, RJ TI Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; PORTAL-HYPERTENSIVE RATS; NECROSIS-FACTOR-ALPHA; CYTOKINE-GENERATING ORGAN; VEIN ENDOTHELIAL-CELLS; CHRONIC LIVER-DISEASES; HYPERDYNAMIC CIRCULATION; INTESTINAL BACTERIA; SHEAR-STRESS; ARTERIAL VASODILATION AB Nitric oxide (NO) has been implicated in the arterial vasodilation and associated vascular hyporesponsiveness to vasoconstrictors observed in liver cirrhosis. Bacteria, potent activators of NO and TNF-alpha synthesis, are found in the mesenteric lymph nodes (MLNs) of ascitic cirrhotic rats. Here, we investigated the impact of bacterial translocation (BT) to MLNs on TNF-alpha production, vascular NO release, and contractility in the mesenteric vasculature of ascitic cirrhotic rats. Vascular response to the alpha-adrenoagonist methoxamine, which is diminished in the superior mesenteric arterial beds of cirrhotic rats, is further blunted in the presence of BT. BT promoted vascular NO release in cirrhotic rats, an effect that depended on pressure-induced shear stress and was blocked by the NO inhibitor N-omega-nitro-L-arginine. Removing the endothelium had the same effect. Endothelial NO synthase (eNOS), but not the inducible isoform (iNOS), was present in mesenteric vasculature of cirrhotic rats with and without BT, and its expression was enhanced compared with controls. TNF-alpha was induced in MLNs by BT and accumulated in parallel in the serum. This TNF-alpha production was associated with elevated levels of tetrahydrobiopterin (BH4), a TNF-alpha-stimulated cofactor and enhancer of eNOS-derived NO biosynthesis and NOS activity in mesenteric vasculature. These findings establish a link between BT to MLNs and increased TNF-alpha production and elevated BH4 levels enhancing eNOS-derived NO overproduction, further impairing contractility in the cirrhotic mesenteric vasculature. C1 Vet Adm Med Ctr, Hepat Hemodynam Lab, W Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. NIMH, Bethesda, MD 20892 USA. RP Groszmann, RJ (reprint author), Vet Adm Med Ctr, Hepat Hemodynam Lab, 950 Campbell Ave, W Haven, CT 06516 USA. NR 75 TC 197 Z9 202 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1999 VL 104 IS 9 BP 1223 EP 1233 DI 10.1172/JCI7458 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WL UT WOS:000083469300011 PM 10545521 ER PT J AU Wank, SA AF Wank, SA TI PACAP upsets stomach theory SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID GASTRIC-ACID; CELLS; RAT; HISTAMINE; SECRETION C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Wank, SA (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1999 VL 104 IS 10 BP 1341 EP 1342 DI 10.1172/JCI8732 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 256RF UT WOS:000083738700006 PM 10562295 ER PT J AU Highbarger, HC Alvord, WG Jiang, MK Shah, AS Metcalf, JA Lane, HC Dewar, RL AF Highbarger, HC Alvord, WG Jiang, MK Shah, AS Metcalf, JA Lane, HC Dewar, RL TI Comparison of the Quantiplex version 3.0 assay and a sensitized Amplicor Monitor assay for measurement of human immunodeficiency virus type 1 RNA levels in plasma samples SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REVERSE TRANSCRIPTION-PCR; ENHANCED-SENSITIVITY; QUANTITATION; COMBINATION; INFECTION; THERAPY AB This study evaluated correlation and agreement between version 3 of the Quantiplex human immunodeficiency virus type 1 (HIV-1) RNA assay (v3 branched DNA [bDNA]) and a sensitized Amplicor HIV-1 Monitor assay (reverse transcription [RT]-PCR) for the measurement of HIV RNA. Three hundred eighteen samples from 59 randomly selected, HIV-1-seropositive persons on various drug protocols from the National Institute of Allergy and Infectious Diseases HIV outpatient clinic were studied. The results indicate that v3 bDNA and RT-PCR are highly correlated (r = 0.98) and are in good agreement (mean difference in log(10) copies/ml +/- 2 standard deviations = 0.072 +/- 0.371). The relationship between values obtained by both assays is given by the following equation: log(10)v3 bDNA = -0.0915 + 1.0052.log(10)RT-PCR This represents a 1.026-fold difference between log(10)RT-PCR values and log(10)v3 bDNA values. C1 NCI, Frederick Canc Res & Dev Ctr, Virus Isolat Lab, Clin Serv Prog,SAIC Frederick, Frederick, MD 21702 USA. Data Management Serv Inc, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Dewar, RL (reprint author), NCI, Frederick Canc Res & Dev Ctr, Virus Isolat Lab, Clin Serv Prog,SAIC Frederick, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 11 TC 33 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1999 VL 37 IS 11 BP 3612 EP 3614 PG 3 WC Microbiology SC Microbiology GA 246FT UT WOS:000083154300033 PM 10523562 ER PT J AU Mima, T Hallett, M AF Mima, T Hallett, M TI Corticomuscular coherence: A review SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE coherence; phase spectra; EEG; EMG ID FIELD POTENTIAL OSCILLATIONS; PRIMATE MOTOR CORTEX; SENSORIMOTOR CORTEX; CORTICOSPINAL PROJECTIONS; ISOMETRIC CONTRACTION; CORTICAL POTENTIALS; FINGER MOVEMENTS; NEURONS INVITRO; VISUAL-CORTEX; AWAKE MONKEYS AB Corticomuscular coherence measured between electroencephalography (EEG), magnetoencephalography, or local field potentials and electromyography (EMG) should be helpful in understanding the conical control of movement. EEG-EMG coherence and phase spectra depend on the types of EEG derivation and current source density function of EEG appears to be the most appropriate for computation of EEG-EMG coherence. A new model for the interpretation of the phase spectra ("constant phase shift plus constant time lag model") shows that conical surface negative potentials are phase-locked to EMG firing. There are functional differences of EEG-EMG coherence among the alpha, beta, and gamma bands suggesting differences in their possible generator mechanisms. Since corticomuscular coherence is a noninvasive measure of corticomotoneuronal function in a specific frequency range, clinical application of this method might be very fruitful in tremor research. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. OI Mima, Tatsuya/0000-0001-7783-1599; Mima, Tatsuya/0000-0001-7787-4855 NR 69 TC 165 Z9 166 U1 4 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD NOV PY 1999 VL 16 IS 6 BP 501 EP 511 DI 10.1097/00004691-199911000-00002 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 261HX UT WOS:000084004700002 PM 10600018 ER PT J AU McCaskill-Stevens, W Hawk, ET Flynn, PJ Lippman, SM AF McCaskill-Stevens, W Hawk, ET Flynn, PJ Lippman, SM TI National Cancer Institute-supported cancer chemoprevention research: Coming of age SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; PREMALIGNANT ORAL LESIONS; SQUAMOUS-CELL CARCINOMA; BETA-CAROTENE; BREAST-CANCER; CARDIOVASCULAR-DISEASE; RECEPTOR-BETA; MOUSE MODEL C1 NCI, Div Canc Biol, Bethesda, MD 20892 USA. Metro Minnesota Community Clin Oncol Program, St Louis Pk, MN USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. RP McCaskill-Stevens, W (reprint author), NCI, Div Canc Biol, 6130 Execut Blvd,Rm 300, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA16672] NR 58 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1999 VL 17 IS 11 SU S BP 53 EP 62 PG 10 WC Oncology SC Oncology GA 252AX UT WOS:000083479500015 PM 10630263 ER PT J AU Fisher, B Anderson, S DeCillis, A Dimitrov, N Atkins, JN Fehrenbacher, L Henry, PH Romond, EH Lanier, KS Davila, E Kardinal, CG Laufman, L Pierce, HI Abramson, N Keller, AM Hamm, JT Wickerham, DL Begovic, M Tan-Chiu, E Tian, W Wolmark, N AF Fisher, B Anderson, S DeCillis, A Dimitrov, N Atkins, JN Fehrenbacher, L Henry, PH Romond, EH Lanier, KS Davila, E Kardinal, CG Laufman, L Pierce, HI Abramson, N Keller, AM Hamm, JT Wickerham, DL Begovic, M Tan-Chiu, E Tian, W Wolmark, N TI Further evaluation of intensified and increased total dose of cyclophosphamide for the treatment of primary breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-25 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PREMENOPAUSAL WOMEN; RANDOMIZED TRIAL; CHEMOTHERAPY; RADIOTHERAPY AB Purpose: In 1989, the National Surgical Adjuvant Breast and Bowel Project initiated the B-22 trial to determine whether intensifying or intensifying and increasing the total dose of cyclophosphamide in a doxorubicin-cyclophosphamide combination would benefit women with primary breast cancer and positive axillary nodes. B-25 was initiated to determine whether further intensifying and increasing the cyclophosphamide dose would yield more favorable results. Patients and Methods: patients(n = 2,548)were randomly assigned to three groups. The dose and intensity of doxorubicin were similar in all groups. Group 1 received four courses, ie, double the dose and intensity of cyclophosphamide given in the B-22 standard therapy group; group 2 received the same dose of cyclophosphamide as in group I,administered in two courses (intensified); group 3 received double the dose of cyclophosphamide (intensified and increased) given in group 1. All patients received recombinant human granulocyte colony-stimulating factor. Life-table estimates were used to determine disease-free survival [DFS) and overall survival. Results: No significant difference war observed in DFS (P = .20), distant DFS (P = .31), or survival (P = .76) among the three groups. At 5 years, the DFS in groups 1 and 2 (61% v 64%, respectively; P = .29) was similar to bur slightly lower than that in group 3 (61% v 66%, respectively; P = 08). Survival in group I was concordant with that in groups 2 (78% v 77%, respectively; P = .71) and 3 (78% v 79%, respectively; P = .86). Grade 4 toxicity was 20%, 34%, and 49% in groups 1, 2, and 3, respectively, Severe infection and septic episodes increased in group 3. The decrease in the amount and intensity of cyclophosphamide and delays in therapy were greatest in courses 3 and 4 in group 3. The incidence of acute myeloid leukemia increased in all groups. Conclusion: Because intensifying and increasing cyclophosphamide two or four times that given in standard clinical practice did not substantively improve outcome, such therapy should be reserved for the clinical trial setting. (C) 1999 by American Society of Clinical Oncology. C1 Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Allegheny Univ Hlth Sci, Natl Surg Adjuvant Breast & Bowel Project, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. OI Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10-CA-69651, U10-CA-12027, U10-CA-37377] NR 35 TC 151 Z9 153 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1999 VL 17 IS 11 BP 3374 EP 3388 PG 15 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700003 PM 10550131 ER PT J AU Smith, RE Brown, AM Mamounas, EP Anderson, SJ Lembersky, BC Atkins, JH Shibata, HR Baez, L DeFusco, PA Davila, E Tipping, SJ Bearden, JD Thirlwell, MP AF Smith, RE Brown, AM Mamounas, EP Anderson, SJ Lembersky, BC Atkins, JH Shibata, HR Baez, L DeFusco, PA Davila, E Tipping, SJ Bearden, JD Thirlwell, MP TI Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National surgical adjuvant breast and bowel project protocol B-26 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; PHASE I/II TRIAL; II TRIAL; THERAPY; TAXOL; CHEMOTHERAPY AB Purpose: Paclitaxel is an active drug for the treatment of breast cancer; however, the appropriate duration of administration is unknown. We assessed and compared the response rate, event-free survival, survival, and toxicity of paclitaxel 250 mg/m(2) delivered every 3 weeks as a 3-hour or 24-hour infusion. Patients and Methods: A total of 563 women with stage IV or IIIB breast cancer were randomized into one of two groups: 279 received 3-hour paclitaxel and 284 received 24-hour paclitaxel, Patients were stratified by age, stage of disease, and prior therapy. Results: A significantly higher rate of tumor response occurred in the first four cycles of therapy in patients who received the 24-hour infusion of paclitaxel (51% v 41%, respectively; P = .025), Tumor response over all cycles was also significantly higher in the group that received 24-hour infusion (51% v 44%, respectively; P = .023), There were no significant differences in event-free survival or survival between the two arms of the study (P = .9 and .8, respectively), No treatment by stage or by age interactions were observed. During the first four cycles of therapy, at least one episode of greater than or equal to grade 3 toxicity (excluding nadir hematologic values, alopecia, and weight change) occurred in 45% of patients who received the 3-hour paclitaxel infusion and in 50% of those who received the 24-hour paclitaxel infusion. Febrile neutropenia, greater than or equal to grade 3 infection, and greater than or equal to grade 3 stomatitis were less frequent, and severe neurosensory toxicity was more frequent in those who received the 3-hour paclitaxel infusion. Ten treatment-related deaths occurred in the first tour cycles. Age, stage, and prior chemotherapy did not influence the effect of treatment. Conclusion: When administered as a continuous 24-hour infusion, high-dose paclitaxel results in a higher tumor response rate-than when administered as a 3-hour infusion but does not significantly improve event-free survival or survival, paclitaxel as a 24-hour infusion results in increased hematologic toxicity and decreased neurosensory toxicity. (C) 1999 by American Society of Clinical Oncology. C1 Four Allegheny Ctr, Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, Pittsburgh, PA 15212 USA. Four Allegheny Ctr, Natl Surg Adjuvant Breast & Bowel Project, Ctr Biostat, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA USA. Mt Sinai Ctr Breast Hlth, Beachwood, OH USA. S Eastern Med Oncol Ctr, Goldsboro, NC USA. Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. VA Med Ctr, San Juan, PR USA. Hartford Hosp, Canc Clin Res Off, Hartford, CT 06115 USA. Mt Sinai Med Ctr, Miami, FL USA. Marshfield Med Res Fdn, Marshfield, WI 54449 USA. Spartanburg Reg Med Ctr, Spartanburg, SC USA. RP Smith, RE (reprint author), Four Allegheny Ctr, Natl Surg Adjuvant Breast & Bowel Project, Operat Ctr, E Commons Profess Bldg,5th Floor, Pittsburgh, PA 15212 USA. OI Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10-CA-69974, U10-CA-37377, U10-CA12027] NR 31 TC 109 Z9 109 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1999 VL 17 IS 11 BP 3403 EP 3411 PG 9 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700006 PM 10550134 ER PT J AU Bubley, GJ Carducci, M Dahut, W Dawson, N Daliani, D Eisenberger, M Figg, WD Freidlin, B Halabi, S Hudes, G Hussain, M Kaplan, R Myers, C Oh, W Petrylak, DP Reed, E Roth, B Sartor, O Scher, H Simons, J Sinibaldi, V Small, EJ Smith, MR Trump, DL Vollmer, R Wilding, G AF Bubley, GJ Carducci, M Dahut, W Dawson, N Daliani, D Eisenberger, M Figg, WD Freidlin, B Halabi, S Hudes, G Hussain, M Kaplan, R Myers, C Oh, W Petrylak, DP Reed, E Roth, B Sartor, O Scher, H Simons, J Sinibaldi, V Small, EJ Smith, MR Trump, DL Vollmer, R Wilding, G TI Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: Recommendations from the prostate-specific antigen working group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THERAPY; MARKER; CARCINOMA AB Purpose: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it wets important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. Result: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. Conclusion: Through this consensus conference, we believe we have developed practical guidelines for using PSA as ct measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Med Branch, Bethesda, MD 20892 USA. Dana Farber Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Durham, NC USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Wayne State Univ, Detroit, MI USA. Univ Virginia, Charlottesville, VA USA. Columbia Univ, New York, NY USA. Vanderbilt Univ, Louisiana State Med Ctr, New Orleans, LA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Wisconsin, Madison, WI USA. RP Figg, WD (reprint author), NCI, Med Branch, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Oh, William/B-9163-2012; Figg Sr, William/M-2411-2016 OI Oh, William/0000-0001-5113-8147; NR 25 TC 733 Z9 755 U1 0 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1999 VL 17 IS 11 BP 3461 EP 3467 PG 7 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700015 PM 10550143 ER PT J AU Wolmark, N Rockette, H Mamounas, E Jones, J Wieand, S Wickerham, DL Bear, HD Atkins, JN Dimitrov, NV Glass, AG Fisher, ER Fisher, B AF Wolmark, N Rockette, H Mamounas, E Jones, J Wieand, S Wickerham, DL Bear, HD Atkins, JN Dimitrov, NV Glass, AG Fisher, ER Fisher, B TI Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: Results from national surgical adjuvant breast and bowel project C-04 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THERAPY; CANCER AB Purpose: To compare the efficacy of leucovorin-modulated fluorouracil (FU+LV) with that of fluorouracil and levamisole (FU+LEV) or with the combination of FU + LV and levamisole (FU + LV + LEV). Patients and Methods: Between July 1989 and December 1990, 2,151 patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the colon were entered onto National Surgical Adjuvant Breast and Bowl project protocol C-04, patients were randomly assigned to receive FU+LV (weekly regimen), FU + LEV, or the combination of FU+LV+LEV, The average time on study was 86 months. Results: A pairwise comparison between patients treated with FU+LV or FU+LEV disclosed a prolongation in disease-free survival (DFS) in favor of the FU+LV group (65% v 60%; P = .04); there was a small prolongation in overall survival that was of borderline significance (74% v 70%; P = .07), There was no difference in the pairwise comparison between patients who received FU + LV or FU+LV+LEV for either DFS (65% v 64%; P = .67) or overall survival (74% v 73%; P = .99), There was no interaction between Dukes' stage and the effect of treatment, Conclusion: In patients with Dukes' B and C carcinoma of the colon, treatment with FU+LV seems to confer a small DFS advantage and a borderline prolongation in overall survival when compared with treatment with FU+LEV, The addition of LEV to FU+LV does not provide any additional benefit over and above that achieved with FU+LV, These findings support the use of adjuvant FU+LV as an acceptable therapeutic standard in patients with Dukes' B and C carcinoma of the colon. (C) 1999 by American Society of Clinical Oncology. C1 Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Pittsburgh, PA 15212 USA. RP Wolmark, N (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, 5th Floor, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-37377, U10-CA-12027, U10-CA-39086] NR 16 TC 290 Z9 298 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1999 VL 17 IS 11 BP 3553 EP 3559 PG 7 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700026 PM 10550154 ER PT J AU Roca, CA Schmidt, PJ Rubinow, DR AF Roca, CA Schmidt, PJ Rubinow, DR TI A follow-up study of premenstrual syndrome SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DISORDER; DEPRESSION AB Background: Previous data suggest that premenstrual syndrome (PMS) and affective disorder are related. The purpose of this preliminary study was to ascertain (1) whether women with PMS have an increased risk for future major depressive episodes compared with controls and (2) whether PMS is a stable diagnosis over time. Method: Patients with prospectively confirmed PMS, along with retrospective DSM-IV premenstrual dysphoric disorder, and asymptomatic controls were studied at 5- to 12-year follow-up using a structured clinical interview. Additionally, those women who still had regular cycles and were medication-free were asked to complete 2 months of prospective daily ratings. Results: Women with PMS (N = 27) had a nonsignificantly higher incidence of new-onset depressive episodes (DSM-III-R and Schedule for Affective Disorders and Schizophrenia-Lifetime Version [SADS-L] criteria) during a 5- to 12-year follow-up compared with controls (N = 21). Differences in incidence disappeared when patients and controls without prior history of depression were compared. Prospective ratings completed during follow-up confirmed original diagnoses of PMS patients (N = 7) and controls (N = 11). Conclusion: While preliminary, these results suggest that the higher rate of major depression in patients with PMS during follow-up reflects the higher risk attendant to the history of major depression that existed at baseline. Additionally, at least in a small subsample, PMS appears to be a stable diagnosis over time. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Roca, CA (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10 Room 3N238,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. NR 13 TC 18 Z9 18 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 1999 VL 60 IS 11 BP 763 EP 766 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 258JV UT WOS:000083836800008 PM 10584765 ER PT J AU Krauzlis, RJ Zivotofsky, AZ Miles, FA AF Krauzlis, RJ Zivotofsky, AZ Miles, FA TI Target selection for pursuit and saccadic eye movements in humans SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID SMOOTH; ATTENTION; INITIATION; SEARCH; BACKGROUNDS; MONKEY AB Eye movements were recorded from three subjects as they initiated tracking of a small circle ("target") moving leftward or rightward, above or below the horizontal meridian, either alone or in the presence of a small square ("distractor") moving leftward or rightward on the other side of the horizontal meridian. At the start of each trial, subjects were provided with either a "form" cue (always centrally positioned and having the circular shape and color of the upcoming moving target) or a "location" cue (a small white square positioned where the upcoming target would appear). The latency of pursuit increased in the presence of an oppositely moving distracter when subjects were provided the form cues but not when they were provided the location cues. The latency of saccades showed similar, but smaller, increases when subjects were given the form cues. On many trials with the form cues, pursuit started in the direction of the distracter and then reversed to follow the target. On these trials, the initial saccade often, but not always, also followed the distracter These results indicate that the mechanisms of target selection for pursuit and saccades are tightly coordinated but not strictly yoked. The shared effects of the distracter on the latencies of pursuit and saccades probably reflect the common role of visual attention in filtering the inputs that guide these two types of eye movements. The differences in the details of the effects on pursuit and saccades suggest that the neural mechanisms that trigger these two movements can be independently regulated. C1 Salk Inst Biol Studies, La Jolla, CA 92037 USA. NEI, Bethesda, MD 20892 USA. RP Krauzlis, RJ (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. NR 22 TC 42 Z9 42 U1 0 U2 4 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD NOV PY 1999 VL 11 IS 6 BP 641 EP 649 DI 10.1162/089892999563706 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 265BL UT WOS:000084219000006 PM 10601745 ER PT J AU Silver, J Mi, ZH Takamoto, K Bungay, P Brown, J Powell, A AF Silver, J Mi, ZH Takamoto, K Bungay, P Brown, J Powell, A TI Controlled formation of low-volume liquid pillars between plates with a lattice of wetting patches by use of a second immiscible fluid SO JOURNAL OF COLLOID AND INTERFACE SCIENCE LA English DT Article DE microdroplets; arrays; wetting patches; Surface Evolver ID SURFACES AB We describe a method for forming an array of microdroplets between two plates, at least one of which is patterned with a lattice of wetting patches, using a second immiscible fluid to control droplet formation. The method may be useful for performing multiple, small-volume biochemical reactions in parallel, We analyze the forces responsible for droplet formation, describe results of a computer simulation using Surface Evolver, and derive an analytic criterion for droplet formation in terms of the contact angles of the droplet:second fluid interface on the wetting patches and surrounding surface, the diameter of the wetting patches, the distance between wetting patches, and the distance between the plates. (C) 1999 Academic Press. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NIH, Bioengn & Phys Sci Program, Bethesda, MD 20892 USA. Cytonix Corp, Beltsville, MD 20705 USA. Natl Inst Stand & Technol, Met Div 855, Gaithersburg, MD 20899 USA. RP Silver, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4-338, Bethesda, MD 20892 USA. NR 12 TC 17 Z9 17 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0021-9797 J9 J COLLOID INTERF SCI JI J. Colloid Interface Sci. PD NOV 1 PY 1999 VL 219 IS 1 BP 81 EP 89 DI 10.1006/jcis.1999.6422 PG 9 WC Chemistry, Physical SC Chemistry GA 246LM UT WOS:000083165300009 ER PT J AU Robbins, J AF Robbins, J TI Management of thyroglobulin-positive, body scan-negative thyroid cancer patients: Evidence for the utility of I-131 therapy SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Editorial Material ID METASTASES C1 NIDDKD, US Dept HHS, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Robbins, J (reprint author), NIDDKD, US Dept HHS, Genet & Biochem Branch, NIH, Bldg 10,Room 6C 201A,10 Ctr Dr MSC 1587, Bethesda, MD 20892 USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD NOV PY 1999 VL 22 IS 10 BP 808 EP 810 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259HM UT WOS:000083888500012 PM 10614533 ER PT J AU Ritchie, JWA Peter, GJ Shi, YB Taylor, PM AF Ritchie, JWA Peter, GJ Shi, YB Taylor, PM TI Thyroid hormone transport by 4F2hc-IU12 heterodimers expressed in Xenopus oocytes SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID AMINO-ACID-TRANSPORT; TRIIODOTHYRONINE TRANSPORT; MOLECULAR-CLONING; CELL ACTIVATION; SYSTEM-T; MEMBRANE; PROTEIN; IDENTIFICATION; HEPATOCYTES; ASTROCYTES AB Thyroid hormone (TH) action and metabolism require hormone transport across cell membranes. We have investigated the possibility that TH are substrates of amino acid transport (System L) mediated by heterodimers of 4F2 heavy-chain (hc) and the light-chain (Ic) permease IU12. Coexpression of 4F2hc and IU12 cDNAs injected into Xenopus oocytes induces saturable, Na+-independent transport of triiodothyronine (T-3), thyroxine (T-4) (K-m of 1.8 and 6.3 mu M respectively), tryptophan and phenylalanine. Induced TH and tryptophan uptakes are inhibited by excess BCH (synthetic System L substrate). Induced TH uptake is also inhibited by excess reverse tri-iodothyronine (rT(3)), but not by triodothyroacetic acid (TRIAC) (TH analogue lacking an amino acid moiety). T-3 and tryptophan exhibit reciprocal inhibition of their 4F2hc-IU12 induced uptake. Transport pathways produced by 4F2hc-1c permease complexes may therefore be important routes for movement and exchange of TH (as well as amino acids) across vertebrate cell membranes, with a potential role in modulating TH action. C1 Univ Dundee, Dept Anat & Physiol, Dundee DD1 4HN, Scotland. NICHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Taylor, PM (reprint author), Univ Dundee, Dept Anat & Physiol, Dundee DD1 4HN, Scotland. RI Taylor, Peter/A-4667-2010; Ritchie, James/B-9377-2013 NR 30 TC 48 Z9 48 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 1999 VL 163 IS 2 BP R5 EP R9 DI 10.1677/joe.0.163R005 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 330RJ UT WOS:000087974700027 PM 10556789 ER PT J AU Hortin, GL Dey, SK Hall, M Robinson, CA AF Hortin, GL Dey, SK Hall, M Robinson, CA TI Detection of azide in forensic samples by capillary electrophoresis SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; forensic toxicology; azide; capillary electrophoresis; poisoning ID SODIUM-AZIDE; ION CHROMATOGRAPHY; INGESTION; POISONINGS; SUICIDE AB Azide salts are highly toxic compounds that have been difficult to detect in forensic samples. Here, anion analysis by capillary electrophoresis with indirect spectrophotometric detection was applied to detect azide in forensic specimens from two suicide victims. Gastric specimens from the victims were shown to have high azide concentrations; azide represented one of the major anionic components and no corresponding component occurred in normal gastric juice. Samples of blood and bile had low concentrations of azide near the limits of detection. The method described for azide analysis used simple steps for sample preparation and analysis time was less than 10 min per sample. It offers a simple and reliable method for detecting azide in biological fluids. C1 Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Hortin, GL (reprint author), Dept Clin Pathol, NIH, Bldg 10,Room 2C-407,10 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1999 VL 44 IS 6 BP 1310 EP 1313 PG 4 WC Medicine, Legal SC Legal Medicine GA 293BA UT WOS:000085830600031 PM 10582374 ER PT J AU Silins, I Wang, ZH Avall-Lundqvist, E Frankendal, B Vikmanis, U Sapp, M Schiller, JT Dillner, J AF Silins, I Wang, ZH Avall-Lundqvist, E Frankendal, B Vikmanis, U Sapp, M Schiller, JT Dillner, J TI Serological evidence for protection by human papillomavirus (HPV) type 6 infection against HPV type 16 cervical carcinogenesis SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID SQUAMOUS INTRAEPITHELIAL LESIONS; HERPES-SIMPLEX VIRUS; SEXUAL-BEHAVIOR; CANCER; WOMEN; ANTIBODIES; RISK; IMMUNIZATION; CARCINOMA; CAPSIDS AB Human papillomavirus (HPV) exists as more than 100 genotypes. It is not well-established whether the different HPV types interfere with infection or pathogenesis by each other. Possible interactions in cervical carcinogenesis between infection with the most common HPV types (6, 11, 16, 18 and 33) were studied in a seroepidemiological case-control study of 218 women with primary untreated cervical cancer and 219 healthy age-matched control women. As previously shown, HPV-16 seropositivity was associated with cervical cancer risk [odds ratio (OR), 2.39], but HPV-16 was not associated with cervical cancer risk among HPV-6 seropositive women (OR, 1.0). The relative excess risk due to interaction between HPV-6 and -16 was -2.35 (95 % confidence interval, -0.04 to -4.65), indicating significant antagonism. The results suggest that infection with HPV-6 may interfere with HPV-16-associated cervical carcinogenesis. C1 Karolinska Inst, Microbiol & Tumor Biol Ctr, S-17177 Stockholm, Sweden. Karolinska Hosp, Dept Gynecol Oncol, Radiumhemmet, S-10401 Stockholm, Sweden. Univ Latvia, Riga, Latvia. Univ Mainz, Dept Med Microbiol, D-6500 Mainz, Germany. Natl Canc Inst, Lab Cellular Oncol, Bethesda, MD USA. Natl Publ Hlth Inst, Dept Infect Dis Epidemiol, Helsinki, Finland. RP Dillner, J (reprint author), Karolinska Inst, Microbiol & Tumor Biol Ctr, Box 280, S-17177 Stockholm, Sweden. RI Avall-Lundqvist, Elisabeth/C-9292-2009 NR 35 TC 44 Z9 47 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 1999 VL 80 BP 2931 EP 2936 PN 11 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 251VD UT WOS:000083466300016 PM 10580926 ER PT J AU Akari, H Uchiyama, T Fukumori, T Iida, S Koyama, AH Adachi, A AF Akari, H Uchiyama, T Fukumori, T Iida, S Koyama, AH Adachi, A TI Pseudotyping human immunodeficiency virus type 1 by vesicular stomatitis virus G protein does not reduce the cell-dependent requirement of Vif for optimal infectivity: functional difference between Vif and Nef SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; SOR GENE; REVERSE TRANSCRIPTION; VIRION INCORPORATION; DNA-SYNTHESIS; HIV-1; REPLICATION; LYMPHOCYTES; MUTANTS; GENERATION AB The functions of Vif and Nef in human immunodeficiency virus type 1 (HIV-1) infection have some similarities: Vif- and Nef-dependent enhancement of HIV-1 replication is cell type-specific, and defective mutations in these genes result in restricted proviral DNA synthesis in infected cells. It has recently been shown that pseudotyping HIV-1 by the envelope glycoprotein of vesicular stomatitis virus (VSV-G) targets HIV-1 entry to an endocytic pathway and suppresses the requirement of Nef for virus infectivity. In this study, we examined whether VSV-G pseudotyping suppresses the requirement of Vif for HIV-1 infectivity. It was found that pseudotyping HIV-1 by VSV-G did not compensate for the Vif function. Together with the findings that Vif does not influence virus binding/entry and virion incorporation of Env, it is concluded that Vif enhances HIV-1 infectivity at the post-entry step(s) independently of the Env function by a different mechanism to that of Nef. C1 Univ Tokushima, Sch Med, Dept Virol, Tokushima 7708503, Japan. RP Akari, H (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 33 Z9 33 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 1999 VL 80 BP 2945 EP 2949 PN 11 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 251VD UT WOS:000083466300018 PM 10580056 ER PT J AU Jobes, DV Friedlaender, JS Mgone, CS Koki, G Alpers, MP Ryschkewitsch, CF Stoner, GL AF Jobes, DV Friedlaender, JS Mgone, CS Koki, G Alpers, MP Ryschkewitsch, CF Stoner, GL TI A novel JC virus variant found in the Highlands of Papua New Guinea has a 21-base pair deletion in the agnoprotein gene SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE JCV; agnoprotein; Papua New Guinea; evolution; human migration ID SEQUENCE-ANALYSIS; COMPLETE GENOMES; DNA; URINE AB Objectives: This paper describes a unique JC virus (JCV) variant recovered from the Highlands of Papua New Guinea that contains an inframe 21-bp deletion in the agnoprotein gene. We characterize the mutation and suggest possible roles for the deletion in JCV evolution. Study Design/Methods: JCV DNA was extracted from urine and polymerase chain reaction (PCR) amplified using whole genome primers. PCR products were cloned, and multiple clones were sequenced. The JCV agnogene was PCR amplified to verify the presence of the agnogene deletion. Results: This mutation creates a 21-bp deletion near the 3' end, which alters the predicted secondary structure of the messenger RNA and changes local codon usage at the 3' end of the agnogene. Protein secondary structure predictions suggest the deleted portion of the agnoprotein may be a flexible surface feature. Conclusions: We describe the first stable coding region deletion in JCV that presumably signifies a single evolutionary event that led to the split from other Highlands viral groups and occurred well after the human expansions that led to the peopling of the Southwest Pacific. C1 NINDS, 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. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-27, Bethesda, MD 20892 USA. NR 27 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD NOV-DEC PY 1999 VL 2 IS 6 BP 350 EP 358 PG 9 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 288BR UT WOS:000085542400005 PM 10774552 ER PT J AU Makrigiannis, AP Gosselin, P Mason, LH Taylor, LS McVicar, DW Ortaldo, JR Anderson, SK AF Makrigiannis, AP Gosselin, P Mason, LH Taylor, LS McVicar, DW Ortaldo, JR Anderson, SK TI Cloning and characterization of a novel activating Ly49 closely related to Ly49A SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; NK CELLS; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; LYMPHOCYTES-T; RECEPTORS; LY-49D; PHOSPHATASE; EXPRESSION; GENES AB The majority of the known Ly49 family members have been isolated from either C57BL/6 (B6) or BALB/c mice, Interestingly, the anti-Ly49 Ab reactivities observed in 129/J mice are different from those of B6 mice. Furthermore, immunoprecipitation of 129/J NK cell lysates with YE1/32 and YE1/48, Abs specific for the inhibitory Ly49A in B6, resulted in detection of the activation-associated DAP12 molecule. These results indicated a need for a more detailed study of this strain. Therefore, cloning strategy was devised to isolate Ly49 cDNAs from 129/J mice. An immunoreceptor tyrosine-based inhibitory motif-containing, Ly49D-related clone was discovered that we have named Ly49O, and one immunoreceptor tyrosine-based inhibitory motif-lacking, Ly49A-related clone was discovered that we have named Ly49P. No anti-Ly49 mAb reacted with Ly49O, whereas the molecule encoded by the Ly49P cDNA was found to react with YE1/32 and YE1/48. Ly49P was found to associate with mouse DAP12, and Ah-mediated cross-linking of Ly49P resulted in mouse DAP12 phosphorylation and Ca2+ mobilization, indicating that Ly49P is a competent activation receptor. Ly49P, therefore, represents a novel member of the Ly49 activating receptor subfamily. C1 NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; FU NCI NIH HHS [N01-CO-56000] NR 21 TC 34 Z9 34 U1 0 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 NOV 1 PY 1999 VL 163 IS 9 BP 4931 EP 4938 PG 8 WC Immunology SC Immunology GA 248BT UT WOS:000083256000040 PM 10528196 ER PT J AU Masumoto, M Tanaka, T Kaisho, T Sanjo, H Copeland, NG Gilbert, DJ Jenkins, NA Akira, S AF Masumoto, M Tanaka, T Kaisho, T Sanjo, H Copeland, NG Gilbert, DJ Jenkins, NA Akira, S TI A novel LPS-inducible C-type lectin is a transcriptional target of NF-IL6 in macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CA2+-DEPENDENT ANIMAL LECTINS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SITE-DIRECTED MUTAGENESIS; MANNOSE-BINDING PROTEIN; NATURAL-KILLER-CELLS; MOLECULAR-CLONING; LEUCINE ZIPPER; C/EBP FAMILY; TUMORICIDAL MACROPHAGES; N-ACETYLGALACTOSAMINE AB C-type lectins serve multiple functions through recognizing carbohydrate chains. Here we report a novel C-type lectin, macrophage-inducible C-type lectin (Mincle), as a downstream target of NF-IL6 in macrophages, NF-IL6 belongs to the CCAAT/enhancer binding protein (C/EBP) of transcription factors and plays a crucial role in activated macrophages, However, what particular genes are regulated by NF-IL6 has been poorly defined in macrophages. Identification of downstream targets is required to elucidate the function of NF-IL6 in more detail. To identify downstream genes of NF-IL6, we screened a subtraction library constructed from wild-type and NF-IL6-deficient peritoneal macrophages and isolated Mincle that exhibits the highest homology to the members of group II C-type lectins, Mincle mRNA expression was strongly induced in response to several inflammatory stimuli,: such as LPS, TNF-alpha, IL-6, and IFN-gamma in wild-type macrophages, In contrast, NF-IL6-deficient macrophages displayed a much lower level of Mincle mRNA induction following treatment with these inflammatory reagents. The mouse Mincle proximal promoter region contains an indispensable NF-IL6 binding element, demonstrating that Mincle is a direct target of NF-IL6, The Mincle gene locus was mapped at 0.6 centiMorgans proximal to CD4 on mouse chromosome 6. C1 Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka 5650871, Japan. Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Osaka, Japan. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NCI, Mammalian Genet Lab, Adv Biosci Labs, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Akira, S (reprint author), Osaka Univ, Microbial Dis Res Inst, Dept Host Def, 3-1 Yamadaoka, Osaka 5650871, Japan. RI Akira, Shizuo/C-3134-2009; Kaisho, Tsuneyasu/B-4130-2012; Tanaka, Takashi/O-8254-2015 NR 50 TC 1 Z9 1 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1999 VL 163 IS 9 BP 5039 EP 5048 PG 10 WC Immunology SC Immunology GA 248BT UT WOS:000083256000053 ER PT J AU Kaufman, HL Rao, JB Irivine, KR Bronte, V Rosenberg, SA Restifo, NP AF Kaufman, HL Rao, JB Irivine, KR Bronte, V Rosenberg, SA Restifo, NP TI Interleukin-10 enhances the therapeutic effectiveness of a recombinant poxvirus-based vaccine in an experimental murine tumor model SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interleukin-10; recombinant vaccinia virus; poxvirus; murine tumor model ID INHIBITS CYTOKINE PRODUCTION; T-CELLS; ANTIGEN PRESENTATION; FOWLPOX VIRUS; IL-10; EXPRESSION; IMMUNOTHERAPY; MONOCYTES; ELICITS; CANCER AB Interleukin-10 (IL-10) has a wide range of in vivo biological activities and is a key regulatory cytokine of immune-mediated inflammation. The authors found that murine IL-10 given 12 hours after a recombinant vaccinia Virus (rVV) containing the LacZ gene significantly enhanced the treatment of mice bearing 3-day-old pulmonary metastases expressing beta-galactosidase. Because IL-10 has been shown to inhibit the functions of key elements of both innate and acquired immune responses, the authors hypothesized that IL-IO might act by inhibiting clearance of the rW, thus prolonging exposure to the experimental antigen. However, evidence that IL-IO was not acting primarily through such negative regulatory mechanisms included the following: (a) IL-IO also enhanced the therapeutic effectiveness of a recombinant fowlpox virus, which cannot replicate in mammalian cells; (b) Titers of rVV in immunized mice were lower, not higher; and (c) Although IL-10 did not alter levels of anti-vaccinia antibodies or natural killer cell activity, rVV-primed mice treated with IL-10 had enhanced vaccinia-specific cytotoxic T-lymphocyte activity. Thus, IL-10 enhanced the function of a recombinant poxvirus-based anti-cancer vaccine and may represent a potential adjuvant in the vaccination against human cancers using recombinant poxvirus-based vaccines. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Kaufman, HL (reprint author), Albert Einstein Canc Ctr, 1300 Morris Pk Ave,Chanin 302E, Bronx, NY 10461 USA. RI Restifo, Nicholas/A-5713-2008; Bronte, Vincenzo/K-7902-2016; OI Bronte, Vincenzo/0000-0002-3741-5141; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 33 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1999 VL 22 IS 6 BP 489 EP 496 DI 10.1097/00002371-199911000-00003 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 252RU UT WOS:000083516700003 PM 10570747 ER PT J AU Wideroff, L Schiffman, M Haderer, P Armstrong, A Greer, CE Manos, MM Burk, RD Scott, DR Sherman, ME Schiller, JT Hoover, RN Tarone, RE Kirnbauer, R AF Wideroff, L Schiffman, M Haderer, P Armstrong, A Greer, CE Manos, MM Burk, RD Scott, DR Sherman, ME Schiller, JT Hoover, RN Tarone, RE Kirnbauer, R TI Seroreactivity to human papillomavirus types 16, 18, 31, and 45 virus-like particles in a case-control study of cervical squamous intraepithelial lesions SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNOGLOBULIN-G RESPONSES; SERUM ANTIBODIES; RISK FACTOR; WOMEN; CANCER; INFECTION; NEOPLASIA; DYSPLASIA; COHORT; DNA AB Serum IgG antibodies to human papillomavirus (HPV) types 16, 18, 31, and 45 virus-like particles were measured in a nested case-control study of cervical squamous intraepithelial lesions. HPV-16 seroreactivity was strongly associated with HPV-16 DNA detection (odds ratio, 9.0; 95% confidence interval, 4.4-19.4), and similar type specificity was observed for HPV-31 and -45. In contrast, seroreactivity to any type was associated with elevated seroreactivity to all others. Among cases and controls, HPV-16 showed the highest seroprevalence, with 23.8% of 80 cases and 10.5% of 258 controls seroreactive to HPV-16 alone, and another 27.5% and 5.4%, respectively, seroreactive to HPV-16 plus other types. Overall, 24 (30.0%) cases and 17 (6.6%) controls were seroreactive to multiple types. These data suggest that seroreactivity to a given type reflects mainly type-specific HPV infection as measured by DNA detection and may also signal past exposure to other types that are now only serologically detected. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Univ Vienna, Sch Med, Dept Dermatol, Div Immunol Allergy & Infect Dis, A-1010 Vienna, Austria. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Cetus Corp, Emeryville, CA 94608 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Wideroff, L (reprint author), NCI, ARB, EPN 313, MSC 7344, 6130 Execut Blvd, Bethesda, MD 20892 USA. RI Hernandez, Jessica/G-6527-2011 NR 22 TC 46 Z9 47 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1999 VL 180 IS 5 BP 1424 EP 1428 DI 10.1086/315055 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 252TZ UT WOS:000083519500002 PM 10515799 ER PT J AU Gao, SJ Zhang, YJ Deng, JH Rabkin, CS Flore, O Jenson, HB AF Gao, SJ Zhang, YJ Deng, JH Rabkin, CS Flore, O Jenson, HB TI Molecular polymorphism of Kaposi's sarcoma - associated herpesvirus (Human herpesvirus 8) latent nuclear antigen: Evidence for a large repertoire of viral genotypes and dual infection with different viral genotypes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID EPSTEIN-BARR-VIRUS; STRAIN VARIABILITY; DNA-SEQUENCES; CELL-LINES; A-TYPE; HUMAN-HERPESVIRUS-8; ANTIBODIES; VARIANTS; LESIONS; ESTABLISHMENT AB Molecular polymorphism was found in Kaposi's sarcoma-associated herpesvirus (KSHV) latent nuclear antigen (LNA), mapped to the internal repeat domain of the encoding orf73 gene, and used to develop a novel genotyping technique, KSHV LNA genotyping (KVNA-typing). KVNAtype was stable during latent and lytic viral replication in cell culture and in humans. Diverse KVNAtypes were identified in 43 specimens: 6 KSHV cell lines and 6 Kaposi's sarcoma (KS) and 4 primary effusion lymphoma (PEL) tumor samples from the United States, 15 KS tumor samples from Italy, and 12 KS tumor samples from Zambia, A single KVNAtype was detected in each of 41 specimens, and 2 KVNAtypes were detected in each of 2 KS specimens. Multifocal KS from 3 patients showed the same single KVNAtype at all sites in each patient. These results demonstrate a large repertoire of KSHV genotypes and suggest that the development of most KSs and PELs is associated with a single viral genotype. C1 Univ Texas, Hlth Sci Ctr, Dept Pediat, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. NCI, Viral Epidemiol Branch, Bethesda, MD USA. Cornell Univ, Med Ctr, New York Hosp, Dept Pathol, New York, NY 10021 USA. RP Gao, SJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pediat, Div Infect Dis, San Antonio, TX 78284 USA. RI Gao, Shou-Jiang/B-8641-2012; OI Jenson, Hal/0000-0002-6549-860X NR 37 TC 54 Z9 56 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1999 VL 180 IS 5 BP 1466 EP 1476 DI 10.1086/315098 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 252TZ UT WOS:000083519500008 PM 10515805 ER PT J AU Manns, A Miley, WJ Wilks, RJ Morgan, OSC Hanchard, B Wharfe, G Cranston, B Maloney, E Welles, SL Blattner, WA Waters, D AF Manns, A Miley, WJ Wilks, RJ Morgan, OSC Hanchard, B Wharfe, G Cranston, B Maloney, E Welles, SL Blattner, WA Waters, D TI Quantitative proviral DNA and antibody levels in the natural history of HTLV-I infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th International Conference on Human Retrovirology: HTLV CY JUN, 1997 CL RIO JANEIRO, BRAZIL ID VIRUS TYPE-I; T-CELL LEUKEMIA; TROPICAL SPASTIC PARAPARESIS; RISK-FACTORS; SPINAL-CORD; MYELOPATHY; TRANSFUSION; SEROCONVERSION; TRANSMISSION; ASSOCIATION AB The pathogenesis of human T-cell lymphotropic virus type I (HTLV-I) in adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) is poorly understood. We prospectively followed up and evaluated the virologic correlates of infection in transfusion recipients after seroconversion, in asymptomatic carriers, and in ATL and HAM/TSP patients. Proviral DNA levels (copies/10(5) lymphocytes) were determined by real-time automated polymerase chain reaction and antibody titers by endpoint dilution by use of an HTLV-I enzyme-linked immunoassay, In early infection, proviral load was initially elevated (median, 212 copies/10(5) lymphocytes at time 1) and later decreased (median, 99 copies at time 2, and 27 copies at time 3), Corresponding antibody titers were low at time 1 (1 :2154), had significantly increased by time 2 (1 : 12312), and were stable by time 3 (1 :4694), These viral markers were significantly lower in asymptomatic carriers than in HAM/TSP or ATL patients. Therefore, proviral load and antibody titers may be useful as predictive markers of disease among carriers. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ W Indies, Trop Metab Res Unit, Dept Hematol, Kingston 7, Jamaica. Univ W Indies, Dept Med, Kingston 7, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. RP Manns, A (reprint author), 6120 Execut Blvd,Rm 8008, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CP-40548] NR 36 TC 89 Z9 91 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1999 VL 180 IS 5 BP 1487 EP 1493 DI 10.1086/315088 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 252TZ UT WOS:000083519500010 PM 10515807 ER PT J AU Kalish, LA McIntosh, K Read, JS Diaz, C Landesman, SH Pitt, J Rich, KC Shearer, WT Davenny, K Lew, JF AF Kalish, LA McIntosh, K Read, JS Diaz, C Landesman, SH Pitt, J Rich, KC Shearer, WT Davenny, K Lew, JF TI Evaluation of human immunodeficiency virus (HIV) type 1 load, CD4 T cell level, and clinical class as time-fixed and time-varying markers of disease progression in HIV-1 - Infected children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PLASMA VIRAL LOAD; RNA LEVELS; ANTIRETROVIRAL THERAPY; PROGNOSTIC INDICATORS; LYMPHOCYTE COUNT; INFANTS; AIDS; TRANSMISSION; DEATH; BIRTH AB Human immunodeficiency virus (HIV) type 1 RNA load, CD4 T cell level, and Centers for Disease Control and Prevention (CDC) clinical class history were measured as potential correlates of a CDC class C diagnosis or death in 165 HIV-l-infected children followed from birth. These covariates were assessed at fixed "landmark" ages from 6 to 24 months and were also assessed as time-varying values, Virus load was associated with progression in all analyses, even after adjusting for immunologic and clinical status. This confirms its importance for monitoring pediatric disease progression, CD4 T cell level was associated with disease progression in time-varying but not in adjusted landmark analysis, suggesting that CD4 cells reflects immediate risk more than long-term risk, The distinction between clinical class B and lower classes is prognostic during the first 18 months of life; class C versus classes N/A/B becomes more important as the patient ages. Virologic, immunologic, and clinical status all provide information regarding disease progression risk. C1 New England Res Inst, Watertown, MA 02472 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. NIAID, Pediat Adolescent & Maternal AIDS Branch, NICHHD, Bethesda, MD 20892 USA. NIAID, Div Acquired Immunodeficiency Syndrome, Bethesda, MD 20892 USA. NIDA, Ctr AIDS & Other Med Consequences Drug Abuse, Rockville, MD USA. Univ Puerto Rico, Dept Pediat, San Juan, PR 00936 USA. Brookdale Univ Hosp & Med Ctr, Div Infect Dis, Brooklyn, NY USA. Columbia Univ Coll Phys & Surg, Dept Pediat, Div Infect Dis, New York, NY 10032 USA. Univ Illinois, Dept Pediat, Chicago, IL USA. Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA. RP Kalish, LA (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. FU NIAID NIH HHS [AI-34858, AI-34856]; NICHD NIH HHS [HD-8-2913] NR 29 TC 20 Z9 23 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1999 VL 180 IS 5 BP 1514 EP 1520 DI 10.1086/315064 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 252TZ UT WOS:000083519500013 PM 10515810 ER PT J AU Wang, Y Livingston, E Patil, S McKinney, RE Bardeguez, AD Gandia, J O'Sullivan, MJ Clax, P Huang, S Unadkat, JD AF Wang, Y Livingston, E Patil, S McKinney, RE Bardeguez, AD Gandia, J O'Sullivan, MJ Clax, P Huang, S Unadkat, JD TI Pharmacokinetics of didanosine in antepartum and postpartum human immunodeficiency virus-infected pregnant women and their neonate: An AIDS clinical trials group study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CD4 CELL COUNTS; COMBINATION THERAPY; PIGTAILED MACAQUES; CUBIC MILLIMETER; RENAL-FUNCTION; ZIDOVUDINE; CHILDREN; DIDEOXYINOSINE; INDINAVIR AB Didanosine (ddI) pharmacokinetics in antepartum and postpartum human immunodeficiency virus (HIV)-infected women and their neonates were studied, HIV-infected pregnant women received an intravenous (iv) ddI infusion (1.6 mg/kg/h) or an oral dose (200 mg bid or 125 mg bid) at 31 weeks antepartum and 6 weeks postpartum. Blood samples were obtained regularly up to 6 or 8 h after drug administration. The same oral dose of ddI (bid) was administered until labor began. Then, ddI was infused iv until delivery. An oral pharmacokinetic study (60 mg/m(2)) was conducted in infants at day 1 and at week 6 after birth, Plasma concentrations of ddI were measured by radioimmunoassay, After iv ddI administration, only the maternal plasma clearance was found to be significantly increased antepartum (1028 +/- 231 mL/min) versus postpartum (707 +/- 213 mL/min). No pharmacokinetic parameters after oral administration were significantly affected by pregnancy. The pharmacokinetics of ddI in the neonates were highly variable. We conclude that the oral ddI dose need not be adjusted during pregnancy. C1 Univ Washington, Sch Pharm, Dept Pharmaceut, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Duke Pediat AIDS Clin Trial Unit, Durham, NC USA. Duke Univ, Med Ctr, Duke S Hosp, Durham, NC USA. SITEK Res, Drug Metab Pharmacokinet, Rockville, MD USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. San Juan City Hosp, San Juan, PR USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33101 USA. NIAID, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. RP Unadkat, JD (reprint author), Univ Washington, Sch Pharm, Dept Pharmaceut, Box 357610, Seattle, WA 98195 USA. FU NIAID NIH HHS [UO1 AI38858] NR 28 TC 35 Z9 35 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1999 VL 180 IS 5 BP 1536 EP 1541 DI 10.1086/315067 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 252TZ UT WOS:000083519500016 PM 10515813 ER PT J AU Strickler, HD Goedert, JJ Bethke, FR Trubey, CM O'Brien, TR Palefsky, J Whitman, JE Ablashi, D Zeichner, S Shearer, GM AF Strickler, HD Goedert, JJ Bethke, FR Trubey, CM O'Brien, TR Palefsky, J Whitman, JE Ablashi, D Zeichner, S Shearer, GM TI Human herpesvirus 8 cellular immune responses in homosexual men SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; T-LYMPHOCYTE RESPONSES; KAPOSIS-SARCOMA; INDIVIDUALS; COFACTORS; INFECTION; VIRUS; AIDS AB Little is known about cellular immunity to human herpesvirus 8 (HHV-8), the virus associated with Kaposi's sarcoma (KS). T cell proliferative responses to purified HHV-8 were measured in homosexual men, a group with elevated HHV-8 seroprevalence and high risk of KS. None of 20 blood donor controls had T cell responses to HHV-8. Among human immunodeficiency virus (HIV)-negative homosexual men, 8 (42%) of 19 HHV-8 seropositive men responded as did 4 (16%) of 25 HHV-8 seronegative men. Among HIV-positive homosexual men, however, none of 21 HHV-8 seropositives had T cell responses to HHV-8, even though most responded to common recall antigens, and 10 had greater than or equal to 400 CD4 cells/mm(3). The results suggest that HHV-8 T cell proliferative responses are common in HIV-negative homosexual men and that HIV infection may be associated with diminished HHV-8 cellular immunity, possibly before there is substantial depletion of CD4 cells. If correct, this could explain why KS occurs relatively early in HIV infection/AIDS. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. Applicat Int Corp, Frederick, MD USA. Adv Biotechnol Inc, Columbia, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Strickler, HD (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Social Med, 1300 Morris Pk Ave,Belfer 1308-B, Bronx, NY 10461 USA. FU NCI NIH HHS [CP-40521] NR 15 TC 24 Z9 25 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1999 VL 180 IS 5 BP 1682 EP 1685 DI 10.1086/315056 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 252TZ UT WOS:000083519500035 PM 10515832 ER PT J AU Musser, JM Amin, A Ramaswamy, S AF Musser, JM Amin, A Ramaswamy, S TI Mutations in genes associated with drug resistance in Mycobacterium tuberculosis isolates from Italy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID ETHAMBUTOL C1 Baylor Coll Med, Dept Pathol, Inst Study Human Bacterial Pathogenesis, Houston, TX 77030 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1999 VL 180 IS 5 BP 1751 EP 1752 DI 10.1086/315101 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 252TZ UT WOS:000083519500055 PM 10515850 ER PT J AU Tsigos, C Papanicolaou, DA Kyrou, I Raptis, SA Chrousos, GP AF Tsigos, C Papanicolaou, DA Kyrou, I Raptis, SA Chrousos, GP TI Dose-dependent effects of recombinant human interleukin-6 on the pituitary-testicular axis SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; HORMONE SECRETION; ADRENAL AXIS; LEYDIG-CELLS; FACTOR-ALPHA; ENDOCRINE; CYTOKINES; IMMUNE; PLASMA; IL-6 AB Inflammatory cytokines are soluble mediators of immune function that also regulate intermediate metabolism and several endocrine axes. To examine the effects of interleukin-6 (IL-6), the main circulating cytokine, on the hypothalamic-pituitary-testicular axis in men, we performed dose-response studies of recombinant human IL-6 (rHuIL-6) in normal volunteers. Increasing single doses of IL-6 (0.1, 0.3, 1.0, 3.0, and 10.0 mu g/kg body weight) were injected subcutaneously into 15 healthy male volunteers (3 at each dose) in the morning. We measured the circulating levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone binding globulin (SHBG) at baseline and then at 24 h, 48 h, and 7 days after the IL-6 injection. LH and FSH levels were also measured half-hourly for the first 4 h after the IL-6 injection. All IL-6 doses were tolerated well and produced no significant adverse effects. Mean peak plasma IL-6 levels achieved after IL-6 administration were 8 +/- 1, 22 +/- 5, 65 +/- 22, 290 +/- 38, and 4050 +/- 149 pg/ml, respectively for the five doses. We observed no significant changes in plasma testosterone levels after the two smaller IL-6 doses. The three higher IL-6 doses, however, caused significant decreases in testosterone levels by 24 h, which persisted at 48 h and returned to baseline by 7 days. The higher testosterone suppression was after the 3.0 mu g/kg dose, making the dose-response curve bell-shaped. There also appeared to be small but not significant increases in LH levels after the three higher IL-6 doses, which were not acute and seemed to follow temporally the testosterone decreases. The concurrent plasma levels of FSH and SHBG were not appreciably affected by any IL-6 dose. In conclusion, subcutaneous IL-6 administration, which caused acute elevations in circulating IL-6 levels of a similar magnitude to those observed in severe inflammatory and noninflammatory stress, induced prolonged suppression in testosterone levels in healthy men without apparent changes in gonadotropin levels. This suggests that IL-6 might induce persistent testicular resistance to LH action or suppression of Leydig cell steroidogenesis or both, with potential adverse effects on male reproductive function. C1 Hellen Natl Ctr Res Prevent & Treatment Diabet Me, Athens 10675, Greece. Univ Athens, Evangelismos Hosp, Res Inst & Diabet Ctr, Propedeut Dept Internal Med 2, Athens, Greece. NICHD, Natl Inst Hlth, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Tsigos, C (reprint author), Hellen Natl Diabet Ctr, 3 Ploutarchou St, Athens 10675, Greece. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 28 TC 45 Z9 47 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD NOV PY 1999 VL 19 IS 11 BP 1271 EP 1276 DI 10.1089/107999099312948 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 255RN UT WOS:000083684100007 PM 10574620 ER PT J AU Tycko, R Berger, AE AF Tycko, R Berger, AE TI Dual processing of two-dimensional exchange data in magic angle spinning NMR of solids SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE solid state NMR; molecular structure; molecular dynamics; two-dimensional spectroscopy; magic angle spinning ID STATE NMR; ROTATING SOLIDS; SPECTROSCOPY; PEPTIDE AB We discuss procedures for processing data in rotor-synchronized two-dimensional magic angle spinning (2D MAS) NMR exchange measurements for both structural and dynamical studies. We show, both mathematically and experimentally, that there are two distinct data processing procedures that lead to 2D MAS exchange spectra with purely absorptive crosspeaks. One procedure is that described previously by Hagemeyer, Schmidt-Rohr, and Spiess (HSS), The other procedure is related, but different, and leads to crosspeak intensities given by the formulae of Herzfeld, Roberts, acid Griffin (HRG), In 2D MAS exchange experiments on doubly C-13-labeled L-alanylglycylglycine, we demonstrate that the HSS and HRG crosspeak intensities can be extracted separately from the same data set and contain independent information. Processing and analysis of 2D MAS exchange data with both the HSS and the HRG procedures may enhance utilization of the information content of 2D MAS exchange measurements. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. USN, Ctr Surface Warfare, Dahlgren, VA 22448 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. NR 16 TC 17 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 1999 VL 141 IS 1 BP 141 EP 147 DI 10.1006/jmre.1999.1877 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 254XH UT WOS:000083639100015 PM 10527751 ER PT J AU Callen, DF Eyre, H Fang, YY Guan, XY Veleba, A Martin, NJ McGill, J Haan, EA AF Callen, DF Eyre, H Fang, YY Guan, XY Veleba, A Martin, NJ McGill, J Haan, EA TI Origins of accessory small ring marker chromosomes derived from chromosome 1 SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE ring chromosome 1; microdissection; chromosome painting ID IN-SITU HYBRIDIZATION; MOLECULAR CHARACTERIZATION; IDENTIFICATION; PROBES AB Three patients with accessory small, ring chromosomes derived from chromosome 1 are presented together with additional clinical details and cytogenetic analyses of a previously reported patient. Cytogenetic analysis was undertaken by FISH using a reverse painting probe generated from one of the patients by microdissection of the r(1) chromosome and with a BAC923C6 which maps to 1p12. Results indicated that patients with r(1) chromosomes consisting of 1q12 heterochromatin and short arm pericentric euchromatin which extends to at least the BAC923C6 were associated with a normal or mild phenotype. Patients with abnormal phenotypes possessed two types of rings. One patient had evidence for contiguous pericentric short arm euchromatin which extended from the centromere to beyond the BAC923C6. Two patients showed molecular cytogenetic results which were compatible with non-contiguous chromosome 1 euchromatin. The diversity of origin of r(1)s will hamper attempts to define phenotype/genotype relationships. C1 Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, Adelaide, SA 5006, Australia. Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD USA. Mater Adult Hosp, Cytogenet Unit, Brisbane, Qld, Australia. Univ Queensland, Royal Brisbane Hosp, Cytogenet Unit, Herston, Qld, Australia. Royal Childrens Hosp, Clin Genet Serv, Herston, Qld, Australia. Womens & Childrens Hosp, S Australian Clin Genet Serv, N Adelaide, SA, Australia. RP Callen, DF (reprint author), Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, Adelaide, SA 5006, Australia. RI Guan, Xin-Yuan/A-3639-2009; Callen, David/G-1975-2012; OI Guan, Xin-Yuan/0000-0002-4485-6017; Callen, David/0000-0002-6189-9991 NR 14 TC 20 Z9 20 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 1999 VL 36 IS 11 BP 847 EP 853 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 255FE UT WOS:000083658200008 PM 10544230 ER PT J AU Meng, XJ Dea, S Engle, RE Friendship, R Lyoo, YS Sirinarumitr, T Urairong, K Wang, D Wong, D Yoo, DW Zhang, YJ Purcell, RH Emerson, SU AF Meng, XJ Dea, S Engle, RE Friendship, R Lyoo, YS Sirinarumitr, T Urairong, K Wang, D Wong, D Yoo, DW Zhang, YJ Purcell, RH Emerson, SU TI Prevalence of antibodies to the hepatitis E virus in pigs from countries where hepatitis E is common or is rare in the human population SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE swine HEV; IgG anti-HEV; zoonotic; enzootic ID E INFECTION; UNITED-STATES; SWINE; HEV; IDENTIFICATION; SEROREACTIVITY; FAILURE AB Hepatitis E virus (HEV) is a very important public health concern in many developing countries where epidemics of hepatitis E are common. Sporadic cases of clinical hepatitis E not only occur in these countries but also occur uncommonly in patients with no known epidemiological exposure to HEV in industrialized countries. The source of infection in industrialized countries is unknown but it has been suggested that animals might serve as a reservoir for HEV in both settings. We recently identified and characterized an HEV strain (swine HEV) that infects large numbers of pigs in the United States. To assess the potential of pigs to serve as a global reservoir of HEV, we measured the prevalence of HEV antibodies in pigs in two countries where hepatitis E is endemic and two countries where it is not. Swine herds in all four countries contained many pigs that were seropositive for IgG anti-HEV, although the percentage of seropositive pigs varied greatly from herd to herd. A very limited number of pig handlers in the two endemic countries were also tested and most of them were found to be seropositive for HEV. The results from this study suggest that hepatitis E is enzootic in pigs regardless of whether HEV is endemic in the respective human population. Published 1999 Wiley-Liss, Inc.(dagger). C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Quebec, Inst Armand Frappier, INRS, Ctr Mirobiol & Biotechnol, Laval, PQ, Canada. Georgetown Univ, Ctr Med, Div Mol Virol & Immunol, Rockville, MD USA. Univ Guelph, Ontario Vet Coll, Guelph, ON N1G 2W1, Canada. KonKuk Univ, Coll Vet Med, Seoul, South Korea. Kasetsart Univ, Fac Med Vet, Kamphaengsaen, Thailand. Natl Control Inst Vet Bioprod & Pharmaceut, Beijing, Peoples R China. RP Meng, XJ (reprint author), Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Ctr Mol Med & Infect Dis, 1410 Prices Fork Rd, Blacksburg, VA 24061 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 33 TC 138 Z9 143 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD NOV PY 1999 VL 59 IS 3 BP 297 EP 302 DI 10.1002/(SICI)1096-9071(199911)59:3<297::AID-JMV6>3.0.CO;2-3 PG 6 WC Virology SC Virology GA 242HQ UT WOS:000082934800006 PM 10502259 ER PT J AU Forns, X Hegerich, P Darnell, A Emerson, SU Purcell, RH Bukh, J AF Forns, X Hegerich, P Darnell, A Emerson, SU Purcell, RH Bukh, J TI High prevalence of TT virus (TTV) infection in patients on maintenance hemodialysis: Frequent mixed infections with different genotypes and lack of evidence of associated liver disease SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE nosocomial transmission; blood transfusion; hepatitis ID HEPATITIS-G VIRUS; DNA VIRUS; POSTTRANSFUSION HEPATITIS; UNKNOWN ETIOLOGY; BLOOD-DONORS; SEQUENCES; UNIT AB Recently, a novel DNA virus, TT virus (TTV), was identified in patients with post-transfusion non-A-G hepatitis. We analyzed the prevalence and clinical implications of TTV infection in a cohort of 96 Spanish patients on long-term hemodialysis. TTV DNA was detected by nested PCR in 51 (53%) of 96 patients, a prevalence significantly higher than that found in healthy blood donors. Persistent liver test abnormalities were found in only 2 (7.7%) of 26 patients infected with TTV alone, compared with 12 (75%) of 16 patients infected with hepatitis C or hepatitis B virus, or both (P < 0.01). Mixed infections with multiple strains of TTV, including different major genotypes, were common in patients on hemodialysis. These patients had received a significantly greater number of blood units (22.7 +/- 20) compared with patients apparently infected with a single strain of TTV (8.9 +/- 11) (P = 0.01). Phylogenetic analyses of TTV from infected patients identified strains of genotypes 1, 2, 3, and 4. In summary, TTV infection was common in patients on hemodialysis but was not associated with liver disease. (C) 1999 Wiley-Liss, Inc. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Barcelona, Hosp Clin & Prov, Dept Nephrol, Barcelona, Spain. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 7,Room 201,7 Ctr Dr MSC 0740, Bethesda, MD 20892 USA. FU PHS HHS [C0-56000] NR 18 TC 49 Z9 55 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD NOV PY 1999 VL 59 IS 3 BP 313 EP 317 DI 10.1002/(SICI)1096-9071(199911)59:3<313::AID-JMV9>3.0.CO;2-B PG 5 WC Virology SC Virology GA 242HQ UT WOS:000082934800009 PM 10502262 ER PT J AU Parloff, MB AF Parloff, MB TI The psychotherapy relationship: Theory, research, and practice. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review ID COMPONENTS C1 NIMH, Treatments Res Branch, Bethesda, MD 20892 USA. RP Parloff, MB (reprint author), NIMH, Treatments Res Branch, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1999 VL 187 IS 11 BP 700 EP 701 DI 10.1097/00005053-199911000-00011 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256WM UT WOS:000083749500011 ER PT J AU Greve, P Alonso-Gomez, A Bernard, M Ma, MH Haque, R Klein, DC Iuvone, PM AF Greve, P Alonso-Gomez, A Bernard, M Ma, MH Haque, R Klein, DC Iuvone, PM TI Serotonin N-acetyltransferase mRNA levels in photoreceptor-enriched chicken retinal cell cultures: Elevation by cyclic AMP SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE photoreceptor; retina; melatonin; serotonin N-acetyltransferase; cyclic AMP; gene expression ID PROTEIN-SYNTHESIS INHIBITORS; RAT PINEAL-GLAND; MELATONIN SYNTHESIS; CIRCADIAN EXPRESSION; MESSENGER-RNA; MOUSE RETINA; LIGHT; RHYTHM; DARK; PHOSPHORYLATION AB Serotonin N-acetyltransferase (AA-NAT; arylalkylamine N-acetyltransferase; EG 2.3.1.87) is a key regulatory enzyme in the biosynthesis of melatonin. Previous studies have shown that the activity of this enzyme in the chicken retina is regulated by a cyclic AMP-dependent mechanism. In the present report, we investigated whether cyclic AMP can regulate the levels of AA-NAT mRNA in photoreceptor-enriched chick retinal cell cultures. AA-NAT mRNA levels were elevated by acute treatment with cyclic AMP protagonists, including forskolin; this response was blocked by H-89, a selective inhibitor of cyclic AMP-dependent protein kinase. Forskolin did not alter the rate of disappearance of AA-NAT mRNA in enhances transcription of the AA-NAT gene. Forskolin-induced elevation of AA-NAT mRNA levels was enhanced by cycloheximide, which decreased the degradation of the transcript in cells treated with actinomycin D. These studies indicate that the abundance of AA-NAT mRNA is regulated in part through a cyclic AMP-dependent mechanism. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Pharmacol, 1510 Clifton Rd, Atlanta, GA 30322 USA. RI Alonso-Gomez, Angel/F-4033-2016 OI Alonso-Gomez, Angel/0000-0003-3219-2265 FU NEI NIH HHS [EY 04864, R01 EY004864] NR 42 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1999 VL 73 IS 5 BP 1894 EP 1900 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 247AV UT WOS:000083199200013 PM 10537047 ER PT J AU Wenning, GK Scherfler, C Granata, R Bosch, S Verny, M Chaudhuri, KR Jellinger, K Poewe, W Litvan, I AF Wenning, GK Scherfler, C Granata, R Bosch, S Verny, M Chaudhuri, KR Jellinger, K Poewe, W Litvan, I TI Time course of symptomatic orthostatic hypotension and urinary incontinence in patients with postmortem confirmed parkinsonian syndromes: a clinicopathological study SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE orthostatic hypotension; urinary incontinence; parkinsonism ID MULTIPLE-SYSTEM ATROPHY; PROGRESSIVE SUPRANUCLEAR PALSY; RICHARDSON-OLSZEWSKI-SYNDROME; LEWY BODY DISEASE; NATURAL-HISTORY; INTERNATIONAL WORKSHOP; AUTONOMIC DYSFUNCTION; CLINICAL-FEATURES; DIAGNOSIS; DEGENERATION AB Objective-Although both orthostatic hypotension and urinary incontinence have been reported in a number of parkinsonian syndromes, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of these features have not been studied systematically in pathologically confirmed cases. Methods-77 cases with pathologically confirmed parkinsonian syndromes (PD, n=11; MSA, n=15; DLB, n=14; CBD, n=13; PSP, n=24), collected up to 1994, formed the basis for a multicentre clinicopathological study organised by the NINDS to improve the differential diagnosis of parkinsonian disorders. The present study determined the time course-that-is, latency to onset and duration from onset to death, of symptomatic orthostatic hypotension, and urinary incontinence in the NINDS series. Furthermore, the diagnostic validity of a predefined latency to onset within 1 year of disease onset of symptomatic orthostatic hypotension or urinary incontinence was analysed. Results-Significant group differences for latency, but not duration, of symptomatic orthostatic hypotension and urinary incontinence were found. Latencies to onset of either feature were short in patients with MSA, intermediate in patients with DLB, CBD, and PSP, and long in those with PD. Symptomatic orthostatic hypotension occurring within the first year after disease onset predicted MSA in 75% of cases; early urinary incontinence was less predictive for MSA (56%). Conclusion-Latency to onset, but not duration, of symptomatic orthostatic hypotension or urinary incontinence differentiates PD from other parkinsonian syndromes, particularly MSA. C1 Univ Innsbruck Hosp, Dept Neurol, A-6020 Innsbruck, Austria. Hop La Pitie Salpetriere, INSERM, U360, Raymond Escourolle Neuropathol Lab, Paris, France. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Lainz Hosp, Ludwig Boltzmann Inst Clin Neurobiol, A-1130 Vienna, Austria. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Litvan, I (reprint author), Henry M Jackson Fdn, Def & Vet Head Injury Program, Neuropharmacol Unit, Fed Bldg,Room 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 27 TC 99 Z9 100 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 1999 VL 67 IS 5 BP 620 EP 623 DI 10.1136/jnnp.67.5.620 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 247TQ UT WOS:000083236400015 PM 10519868 ER PT J AU Eifuku, S Wurtz, RH AF Eifuku, S Wurtz, RH TI Response to motion in extrastriate area MSTl: Disparity sensitivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TEMPORAL VISUAL AREA; CLASSICAL RECEPTIVE-FIELD; PURSUIT EYE-MOVEMENTS; MACAQUE MONKEY; CORTICAL-NEURONS; FUNCTIONAL-PROPERTIES; BINOCULAR DISPARITY; RHESUS-MONKEY; IMAGE MOTION; CORTEX AB Response to motion in extrastriate area MST1: disparity sensitivity. J. Neurophysiol. 82: 2462-2475, 1999. Many neurons in the lateral-ventral region of the medial superior temporal area (MST1) have a clear center surround separation in their receptive fields. Either moving or stationary stimuli in the surround modulates the response to moving stimuli in the center, and this modulation could facilitate the perceptual segmentation of a moving object from its background. Another mechanism that could facilitate such segmentation would be sensitivity to binocular disparity in the center and surround regions of the receptive fields of these neurons. We therefore investigated the sensitivity of these MST1 neurons to disparity ranging from three degrees crossed disparity (near) to three degrees uncrossed disparity (far) applied to both the center and the surround regions. Many neurons showed clear disparity sensitivity to stimulus motion in the center of the receptive field. About 1/3 of 104 neurons had a clear peak in their response, whereas another 1/3 had broader tuning. Monocular stimulation abolished the tuning. The prevalence of cells broadly tuned to near and far disparity and the reversal of preferred directions at different disparities observed in MSTd were not found in MST1. A stationary surround at zero disparity simply modulated up or down the response to moving stimuli at different disparities in the receptive field (RF) center but did not alter the disparity tuning curve. When the RF center motion was held at zero disparity and the disparity of the stationary surround was varied, some surround disparities produced greater modulation of MST1 neuron response than did others. Some neurons with different disparity preferences in center and surround responded best to the relative disparity differences between center and surround, whereas others were related to the absolute difference between center and surround. The combination of modulatory surrounds and the sensitivity to relative difference between center and surround disparity make these MST1 neurons particularly well suited for the segmentation of a moving object from the background. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. NR 41 TC 57 Z9 57 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1999 VL 82 IS 5 BP 2462 EP 2475 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 259CE UT WOS:000083875700039 PM 10561419 ER PT J AU Poremba, A Gabriel, M AF Poremba, A Gabriel, M TI Amygdala neurons mediate acquisition but not maintenance of instrumental avoidance behavior in rabbits SO JOURNAL OF NEUROSCIENCE LA English DT Article DE muscimol; GABA(A) agonist; temporary lesion; fiber-sparing lesion; rabbits; instrumental learning; avoidance learning; discriminative conditioning; retention ID FEAR-POTENTIATED STARTLE; BASOLATERAL AMYGDALA; HIPPOCAMPAL-FORMATION; SYNAPTIC PLASTICITY; TEMPORAL GRADIENT; EMOTIONAL MEMORY; BRAIN SYSTEMS; LESIONS; STIMULATION; EXPRESSION AB Whereas the amygdala is generally understood to be involved in aversively motivated learning, the specific associative function of the amygdala remains controversial. This study addressed the amygdalar role in mediation of discriminative instrumental avoidance learning of rabbits. Bilateral microinjection of the GABA receptor agonist muscimol centered in the basolateral nucleus of the amygdala was given to inactivate amygdalar neurons at each of three stages of acquisition. The absence of behavioral learning in rabbits trained immediately after amygdalar inactivation confirmed previous results with electrolytic lesions. The absence of savings during training after muscimol had become ineffective indicated an amygdalar role in the establishment of acquisition-relevant neural plasticity, not simply in the expression of the learned response. A time-limited role of the amygdala in instrumental avoidance learning was indicated by the finding that intra-amygdalar muscimol failed to disrupt performance of the well-established avoidance response. The passage of time alone (with no training trials) was sufficient to reduce amygdalar involvement in response performance. These results and demonstrations that other limbic system areas make time-limited contributions to learning indicate that the amygdala is part of a larger intermediate memory system that supports learning and performance before habit consolidation. C1 Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. RP Gabriel, M (reprint author), Univ Illinois, Beckman Inst, 405 N Mathews, Urbana, IL 61801 USA. FU NINDS NIH HHS [NS26736] NR 62 TC 51 Z9 51 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1999 VL 19 IS 21 BP 9635 EP 9641 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 246RG UT WOS:000083177900050 PM 10531465 ER PT J AU Chen, RW Saunders, PA Wei, HF Li, ZW Seth, P Chuang, DM AF Chen, RW Saunders, PA Wei, HF Li, ZW Seth, P Chuang, DM TI Involvement of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and p53 in neuronal apoptosis: Evidence that GAPDH is upregulated by p53 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE p53; GAPDH; cerebellar granule cell; PC12; cytosine arabinoside; apoptosis; adenovirus ID CEREBELLAR GRANULE CELLS; TUMOR-SUPPRESSOR GENE; WILD-TYPE P53; ARABINOSIDE-INDUCED APOPTOSIS; CENTRAL-NERVOUS-SYSTEM; CYTOSINE-ARABINOSIDE; INTRANUCLEAR INCLUSIONS; P53-DEPENDENT APOPTOSIS; PROTECTS NEURONS; TRANSGENIC MICE AB We recently reported that cytosine arabinoside (AraC)-induced apoptosis of cerebellar neurons involves the overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The present study was undertaken to investigate whether p53 and/or Bax overexpression participates in the AraC-induced apoptosis of cerebellar granule cells and, if so, the relationship between p53 induction and GAPDH overexpression in these cells. AraC-induced apoptosis of cerebellar granule cells was preceded by an increase in levels of p53 mRNA and protein detected between 1 and 8 hr after treatment. The mRNA level for a p53 target gene, Bax, was also increased. The increase in GAPDH mRNA lasted longer than that of either p53 or Bax, and the level of GAPDH protein in the particulate fraction increased after induction of GAPDH mRNA. The antisense oligonucleotide to p53 protected granule cells from AraC-induced chromatin condensation, internucleosomal cleavage, and apoptotic death. The inhibition of p53 expression by the p53 antisense oligonucleotide not only blocked the expression of Bax but also partially suppressed the increased GAPDH mRNA and protein levels. Conversely, the suppression of GAPDH expression and subsequent attenuation of apoptosis of granule cells by GAPDH antisense oligonucleotide did not influence the expression of p53 or Bax. Cerebellar granule cells prepared from p53 knock-out mice were resistant to AraC toxicity, and the p53 gene knock-out suppressed AraC-upregulated GAPDH expression. Moreover, infection of PC12 cells with an adenoviral vector containing p53 gene dramatically increased GAPDH expression and triggered cell apoptosis. These results suggest that AraC-induced apoptosis of cerebellar granule cells involves the expression of both GAPDH and p53 and that, similar to Bax, GAPDH is upregulated by p53 after exposure to the apoptotic insult. C1 NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Breast Canc Sect, Med Branch, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 51 TC 90 Z9 97 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1999 VL 19 IS 21 BP 9654 EP 9662 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 246RG UT WOS:000083177900052 PM 10531467 ER PT J AU Nakae, J Accili, D AF Nakae, J Accili, D TI The mechanism of insulin action SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT ISPAD Postgraduate Courses in Pediatric Diabetology in Veneto CY APR, 1999 CL GARDA, ITALY SP ISPAD ID DEPENDENT DIABETES-MELLITUS; PROTEIN-KINASE-B; GLUCOSE-TRANSPORT; RECEPTOR SUBSTRATE-1; TYROSINE PHOSPHORYLATION; 3T3-L1 ADIPOCYTES; SIGNALING SYSTEM; RESISTANCE; AKT; NIDDM C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Accili, D (reprint author), Bldg 10,Room 10D18, Bethesda, MD 20892 USA. NR 40 TC 23 Z9 23 U1 1 U2 2 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD NOV PY 1999 VL 12 SU 3 BP 721 EP 731 PG 11 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 265JL UT WOS:000084239500002 PM 10626262 ER PT J AU Dorman, SE Uzel, G Roesler, J Bradley, JS Bastian, J Billman, G King, S Filie, A Schermerborn, J Holland, SM AF Dorman, SE Uzel, G Roesler, J Bradley, JS Bastian, J Billman, G King, S Filie, A Schermerborn, J Holland, SM TI Viral infections in interferon-gamma receptor deficiency SO JOURNAL OF PEDIATRICS LA English DT Article ID CALMETTE-GUERIN INFECTION; HERPES-SIMPLEX VIRUS; IFN-GAMMA; MYCOBACTERIAL INFECTION; LEISHMANIA-MAJOR; MICE; TUBERCULOSIS; RESPONSES; IMMUNE; SUSCEPTIBILITY AB Interferon-gamma receptor deficiency is a recently described immunodeficiency that is associated with onset of severe mycobacterial infections in childhood. We describe the occurrence of symptomatic and often severe viral infections in 4 patients with interferon-gamma receptor deficiency and mycobacterial disease. The viral pathogens included herpes viruses, parainfluenza virus type 3, and respiratory syncytial virus. We conclude that patients with interferon-gamma receptor deficiency and mycobacterial disease have increased susceptibility to some viral pathogens. C1 NIH, Host Def Lab, NIAID, Dept Pathol, Bethesda, MD 20892 USA. NIH, Off Clin Direct, Bethesda, MD 20892 USA. Univ Calif San Diego, Childrens Hosp, Dept Pediat, San Diego, CA 92103 USA. Univ Calif San Diego, Childrens Hosp, Dept Pathol, San Diego, CA 92103 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. RP Holland, SM (reprint author), NIH, Host Def Lab, NIAID, Dept Pathol, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 30 TC 105 Z9 106 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1999 VL 135 IS 5 BP 640 EP 643 DI 10.1016/S0022-3476(99)70064-8 PG 4 WC Pediatrics SC Pediatrics GA 252TY UT WOS:000083519400020 PM 10547254 ER PT J AU Kitchen, BJ Moser, A Lowe, E Balis, FM Widemann, B Anderson, L Strong, J Blaney, SM Berg, SL O'Brien, M Adamson, PC AF Kitchen, BJ Moser, A Lowe, E Balis, FM Widemann, B Anderson, L Strong, J Blaney, SM Berg, SL O'Brien, M Adamson, PC TI Thioguanine administered as a continuous intravenous infusion to pediatric patients is metabolized to the novel metabolite 8-hydroxy-thioguanine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ALDEHYDE OXIDASE; 6-MERCAPTOPURINE; CHEMOTHERAPY; IDENTIFICATION; TRIAL AB Thiopurine antimetabolites have been in clinical use for more than 40 years, yet the metabolism of thiopurines remains only partially understood. Data from our previous pediatric phase 1 trial of continuous i.v. infusion of thioguanine (CIVI-TG) suggested that TG was eliminated by saturable mechanism, with conversion of the drug to an unknown metabolite. In this study we have identified this metabolite as 8-hydroxy-thioguanine (8-OH-TG). The metabolite coeluted with the 8-OH-TG standard on HPLC and had an identical UV spectrum, with a lambda(max) of 350 nm. On mass spectroscopy, the positive ion, single quad scan of 8-OH-TG yielded a protonated molecular ion at 184 Da and contained diagnostic ions at m/z 167, 156, 142, and 125 Da. Incubation of TG in vitro with partially purified aldehyde oxidase resulted in 8-OH-TG formation. 8-OH-TG is the predominant circulating metabolite found in patients receiving CIVI-TG and is likely generated by the action of aldehyde oxidase. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Anderson, L (reprint author), Childrens Hosp Philadelphia, Abramson Pediat Res Ctr, Suite 902,3516 Civ Ctr Blvd, Philadelphia, PA 19104 USA. RI MOSER, ASHER/F-1873-2012 NR 27 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1999 VL 291 IS 2 BP 870 EP 874 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 246DW UT WOS:000083150000056 PM 10525111 ER PT J AU Monaco, R Friedman, FK Hyde, MJ Chen, JM Manolatus, S Adler, V Ronai, Z Koslosky, W Pincus, MR AF Monaco, R Friedman, FK Hyde, MJ Chen, JM Manolatus, S Adler, V Ronai, Z Koslosky, W Pincus, MR TI Identification of a glutathione-S-transferase effector domain for inhibition of jun kinase, by molecular dynamics SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE glutathione-S-transferase; molecular dynamics; average structure; effector domains; jun kinase ID COMPUTED 3-DIMENSIONAL STRUCTURES; ONCOGENIC FORMS; P21 PROTEIN; WILD-TYPE; P21(RAS); RAS-P21; BINDING; JNK; GTP; GDP AB We have recently found that the glutathione-S-transferase pi-isozyme (GST-pi), a cellular detoxification enzyme, potently and selectively inhibits activation of jun protein by its upstream kinase, jun kinase (JNK). This newly identified regulatory activity of GST-pi is strongly inhibited by a group of agents that inhibit its enzymatic activity. Since loss of enzymatic activity in general does not correlate with loss of regulatory activity, it is likely that inhibitor binding induces changes in the structure of one or more domains of GST that block its interaction with JNK. To identify regions of GST that change conformation on the binding of inhibitors, we have performed molecular dynamics calculations on GST-pi to compute its average structure in the presence and absence of the inhibitor, glutathione sulfonate. Superposition of the two average structures reveals that several regions change local structure depending upon whether the inhibitor is bound or not bound. Two of these regions, residues 36-50 and 194-201, are highly exposed. We have synthesized peptides corresponding to these two segments and find that the 194-201 sequence strongly inhibits the ability of GST-pi to block the in vitro phosphorylation of jun by JNK. These results suggest that this region of GST-pi is critical to its functioning as a newly discovered regulator of signal transduction. C1 Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. NIH, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Adv Comp Serv, Dewitt, NY 13214 USA. Wyeth Ayerst Corp, Pearl River, NY USA. Vet Adm Med Ctr, Dept Radiat Oncol, Brooklyn, NY 11209 USA. Mt Sinai Med Ctr, Ruttenberg Canc Ctr, New York, NY 10029 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. RP Pincus, MR (reprint author), Vet Adm Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016; OI RONAI, ZEEV/0000-0002-3859-0400 FU NCI NIH HHS [CA 42500] NR 20 TC 26 Z9 27 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD NOV PY 1999 VL 18 IS 8 BP 859 EP 866 DI 10.1023/A:1020679229110 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315BM UT WOS:000087092800006 PM 10839622 ER PT J AU Chen, JM Friedman, FK Hyde, MJ Monaco, R Pincus, MR AF Chen, JM Friedman, FK Hyde, MJ Monaco, R Pincus, MR TI Molecular dynamics analysis of the structures of ras-guanine nucleotide exchange protein (SOS) bound to wild-type and oncogenic ras-p21. Identification of effector domains of SOS SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE ras-SOS; molecular dynamics; average structure; effector domains; jun kinase ID COMPUTED 3-DIMENSIONAL STRUCTURES; ENCODED P21 PROTEIN; JUN PROTEINS; ACTIVATION; KINASE; P21(RAS); BINDING; FORMS; GTP; GDP AB The X-ray crystal structure of the ras oncogene-encoded p21 protein bound to SOS, the guanine nucleotide exchange-promoting protein, has been determined. We have undertaken to determine if there are differences between the three-dimensional structures of SOS bound to normal and oncogenic (Val 12-p21) proteins. Using molecular dynamics, we have computed the average structures for both complexes and superimposed them. We find four domains of SOS that differ markedly in structure: 631-641, 676-691, 718-729, and 994-1004. Peptides corresponding to these sequences have been synthesized and found to be powerful modulators of oncogenic p21 in cells as described in an accompanying paper. We find that the SOS segment from 809-815 makes contacts with multiple domains of ras-p21 and can facilitate correlated conformational changes in these domains. C1 Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Wyeth Ayerst Corp, Comp Chem Div, Pearl River, NY 10965 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Adv Comp Serv, DeWitt, NY 13214 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. RP Pincus, MR (reprint author), Vet Adm Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 22 TC 14 Z9 15 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD NOV PY 1999 VL 18 IS 8 BP 867 EP 874 DI 10.1023/A:1020631313180 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315BM UT WOS:000087092800007 PM 10839623 ER PT J AU Chie, L Chen, JM Friedman, FK Chung, DL Amar, S Michl, J Yamaizumi, Z Brandt-Rauf, PW Pincus, MR AF Chie, L Chen, JM Friedman, FK Chung, DL Amar, S Michl, J Yamaizumi, Z Brandt-Rauf, PW Pincus, MR TI Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the guanine-nucleotide exchange protein, SOS, identified from molecular dynamics calculations, selective inhibition of oncogenic ras-p21 SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE ras-p21-SOS complex; effector domain; oocyte maturation; inhibitory peptides; signal transduction ID RAS-BINDING DOMAIN; RAF-P74 PROTEIN; INSULIN; COMPLEXES; P21(RAS); KINASE; RAP-1A AB In the preceding paper we performed molecular dynamics calculations of the average structures of the SOS protein bound to wild-type and oncogenic ras-p21. Based on these calculations, we have identified four major domains of the SOS protein, consisting of residues 631-641, 676-691, 718-729, and 994-1004, which differ in structure between the two complexes. We have now microinjected synthetic peptides corresponding to each of these domains into Xenopus laevis oocytes either together with oncogenic (Val 12)-p21 or into oocytes subsequently incubated with insulin. We find that the first three peptides inhibit both oncogenic and wild-type p21-induced oocyte maturation, while the last peptide much more strongly inhibits oncogenic p21 protein-induced oocyte maturation. These results suggest that each identified SOS region is involved in ras-stimulated signal transduction and that the 994-1004 domain is involved uniquely with oncogenic ras-p21 signaling. C1 Harbor VA Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Long Isl Univ, Dept Chem, Brooklyn, NY 11201 USA. Long Isl Univ, Dept Biol, Brooklyn, NY 11201 USA. Wyeth Ayerst Corp, Computat Chem Div, Pearl River, NY 10965 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. SUNY Hlth Sci Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. SUNY Hlth Sci Ctr, Dept Microbiol, Brooklyn, NY 11203 USA. Natl Canc Inst, Tokyo, Japan. Columbia Univ Coll Phys & Surg, Div Environm Sci, New York, NY 10032 USA. RP Pincus, MR (reprint author), Harbor VA Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [R01-CA 42500] NR 13 TC 11 Z9 11 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD NOV PY 1999 VL 18 IS 8 BP 875 EP 879 DI 10.1023/A:1020683330019 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315BM UT WOS:000087092800008 PM 10839624 ER PT J AU Chie, L Chen, JM Friedman, FK Chung, DL Amar, S Michl, J Yamaizumi, Z Brandt-Rauf, PW Pincus, MR AF Chie, L Chen, JM Friedman, FK Chung, DL Amar, S Michl, J Yamaizumi, Z Brandt-Rauf, PW Pincus, MR TI Identification of the site of inhibition of oncogenic ras-p21-induced signal transduction by a peptide from a ras effector domain SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE p21 35-47 peptide; raf inhibition; JNK and jun; selective inhibition of oncogenic ras-p21 ID MOLECULAR-DYNAMICS; OOCYTE MATURATION; RAF-P74 PROTEIN; RAS-P21 PROTEIN; BINDING DOMAIN; JUN PROTEINS; WILD-TYPE; COMPLEXES; P21(RAS); KINASE AB We have previously found that a peptide corresponding to residues 35-47 of the ras-p21 protein, from its switch 1 effector domain region, strongly inhibits oocyte maturation induced by oncogenic p21, but not by insulin-activated cellular wild-type p21. Another ras-p21 peptide corresponding to residues 96-110 that blocks ras-jun and jun kinase (JNK) interactions exhibits a similar pattern of inhibition. We have also found that c-raf strongly induces oocyte maturation and that dominant negative c-raf strongly blocks oncogenic p21-induced oocyte maturation. We now find that the p21 35-47, but not the 96-110, peptide completely blocks c-raf-induced maturation. This finding suggests that the 35-47 peptide blocks oncogenic ras at the level of raf; that activated normal and oncogenic ras-p21 have differing requirements for raf-dependent signaling; and that the two oncogenic-ras-selective inhibitory peptides, 35-47 and 96-110, act at two different critical downstream sites, the former at raf; the latter at JNK/jun, both of which are required for oncogenic ras-p21 signaling. C1 Harbor VA Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY 11209 USA. Long Isl Univ, Dept Biol, Brooklyn, NY 11201 USA. Long Isl Univ, Dept Chem, Brooklyn, NY 11201 USA. Wyeth Ayerst Corp, Computat Chem Div, Pearl River, NY 10965 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. SUNY Hlth Sci Ctr, Dept Anat & Cell Biol, Brooklyn, NY 11203 USA. SUNY Hlth Sci Ctr, Dept Microbiol, Brooklyn, NY 11203 USA. Natl Canc Inst, Tokyo, Japan. Columbia Univ Coll Phys & Surg, Div Environm Sci, New York, NY 10032 USA. RP Pincus, MR (reprint author), Harbor VA Med Ctr, Dept Pathol & Lab Med, 800 Poly Pl, Brooklyn, NY 11209 USA. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [R01-CA 42500] NR 11 TC 9 Z9 9 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD NOV PY 1999 VL 18 IS 8 BP 881 EP 884 DI 10.1023/A:1020635414089 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 315BM UT WOS:000087092800009 PM 10839625 ER PT J AU van Turennout, M Hagoort, P Brown, C AF van Turennout, M Hagoort, P Brown, C TI The time course of grammatical and phonological processing during speaking: Evidence from event-related brain potentials SO JOURNAL OF PSYCHOLINGUISTIC RESEARCH LA English DT Article; Proceedings Paper CT Processing of Grammatical Gender Workshop CY JUL, 1998 CL LEIPZIG, GERMANY ID PICTURE-WORD INTERFERENCE; SPREADING-ACTIVATION THEORY; SENTENCE PRODUCTION; LEXICAL ACCESS; SPEECH PRODUCTION; ELECTROPHYSIOLOGICAL EVIDENCE; LANGUAGE PRODUCTION; PARTIAL INFORMATION; NOUN PHRASES; SYNTAX AB Motor-related brain potentials were used to examine the time course of grammatical and phonological processes during noun phrase production in Dutch. In the experiments, participants named colored pictures using a no-determiner noun phrase. On half of the trials a syntactic-phonological classification task had to be performed before naming. Depending on the outcome of the classifications, a left or a right push-button response was given (go trials), or no push-button response was given (no-go trials). Lateralized readiness potentials (LRPs) were derived to rest whether syntactic and phonological information affected the motor system at separate moments in time. The results showed that when syntactic information determined the response-hand decision, an LRP developed on no-go trials. However, no such effect was observed when phonological information determined response hand. On the basis of the data, it can be estimated that an additional period of at least 40 ms is needed to retrieve a word's initial phoneme once its lemma has been retrieved. These results provide evidence for the view that during speaking, grammatical processing precedes phonological processing in time. C1 Max Planck Inst Psycholinguist, Nijmegen, Netherlands. RP van Turennout, M (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,10 Ctr Dr MSC 1366, Bethesda, MD 20892 USA. RI Hagoort, Peter/B-7417-2012 NR 61 TC 23 Z9 23 U1 1 U2 9 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6905 J9 J PSYCHOLINGUIST RES JI J. Psycholinguist. Res. PD NOV PY 1999 VL 28 IS 6 BP 649 EP 676 DI 10.1023/A:1023221028150 PG 28 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 238VT UT WOS:000082735600005 PM 10510863 ER PT J AU Nietert, PJ Sutherland, SE Silver, RM Pandey, JP Dosemeci, M AF Nietert, PJ Sutherland, SE Silver, RM Pandey, JP Dosemeci, M TI Solvent oriented hobbies and the risk of systemic sclerosis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic scleroderma; solvents; hobbies; environmental exposure; risk factors; autoantibodies ID OCCUPATIONAL EXPOSURE; SCLERODERMA AB Objective, To examine whether those participating in solvent oriented hobbies (SOH) are at greater risk of developing systemic sclerosis (SSc), and if the association is modified by the presence of the anti-Sc170 antibody. Methods. Patients with SSc and controls were recruited from a university hospital rheumatology clinic. Recreational hobby and occupational histories were obtained along with blood samples. Cumulative scores were created for participation in SOH. Logistic regression was used to calculate odds ratios associated with SOH exposure after adjustment for sex, age at diagnosis, and occupational solvent exposure, and to examine the association between SOH exposure and the presence of anti-Sc170. Results. Solvent exposure based on hobbies and occupations was determined for 178 cases (141 women, 37 men) and 200 controls (138 women, 62 men). Overall participation in SOH was not associated with SSc. However, odds of high cumulative SOH exposure was 3 times greater in those patients with SSc testing positive for the anti-Sc170 antibody compared to patients testing negative (OR 2.9, 95% CI 1.1, 7.9), and twice as great as controls (OR 2.5, 95% CI 1.1, 5.9). Conclusion. While patients with SSc did not participate more often in SOH than controls over all, odds of high cumulative SOH exposure was greater among patients with SSc testing positive for anti-Sc170 compared to those testing negative and compared to controls. These results provide further evidence that environmental agents may play a role in the development of Ssc. C1 Med Univ S Carolina, Ctr Hlth Care Res, Charleston, SC 29425 USA. Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. NCI, Bethesda, MD 20892 USA. RP Nietert, PJ (reprint author), Med Univ S Carolina, Ctr Hlth Care Res, POB 250550, Charleston, SC 29425 USA. OI Nietert, Paul/0000-0002-3933-4986 NR 18 TC 18 Z9 20 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1999 VL 26 IS 11 BP 2369 EP 2372 PG 4 WC Rheumatology SC Rheumatology GA 252HA UT WOS:000083495000016 PM 10555893 ER PT J AU Brennan, MT Fox, PC AF Brennan, MT Fox, PC TI Sex differences in primary Sjogren's syndrome SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE Sjogren's syndrome; sex; serology; salivary glands; fatigue ID SYSTEMIC LUPUS-ERYTHEMATOSUS; CLASSIFICATION; HORMONES; MEN AB Objective. To examine the clinical and serologic characteristics of 14 men compared to 28 women with primary Sjogren's syndrome (SS) and contrast these findings with studies evaluating sex differences in primary SS. Methods. Patient information was collected from patients seen at the National Institutes of Health Salivary Gland Dysfunction Clinic from 1987 to 1998. A total Of 14 male patients were diagnosed with primary SS during this period. The control group consisted of 28 female patients matched according to focus score of the labial minor salivary gland biopsy. Results. Women had significantly higher antinuclear antibody titers and erythrocyte sedimentation rate than men. A significant sex difference was also noted in extraglandular manifestations, with more women reporting fatigue compared to men (68 vs 21%, respectively). Conclusion. This study indicates that women may have more positive serological findings than men and a higher prevalence of fatigue. No sex differences could be established with other extraglandular manifestations of SS. C1 NIDCR, Gene Therapy & Therapeut Branch, Clin Invest Sect, NIH, Bethesda, MD USA. RP Fox, PC (reprint author), Amarillo Biosci Inc, Res & Dev, 6509 7 Locks Rd, Cabin John, MD 20818 USA. NR 14 TC 14 Z9 15 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1999 VL 26 IS 11 BP 2373 EP 2376 PG 4 WC Rheumatology SC Rheumatology GA 252HA UT WOS:000083495000017 PM 10555894 ER PT J AU Slavkin, HC AF Slavkin, HC TI Building a better mousetrap: Toward an understanding of osteoporosis SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; RISK-FACTORS; ADOLESCENT; FEMALES; CBFA1; GENE C1 NIDCR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDCR, 31 Ctr Dr,MSC 2290,Bldg 1,Room 2C39, Bethesda, MD 20892 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1999 VL 130 IS 11 BP 1632 EP 1636 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 254GY UT WOS:000083604600032 PM 10573946 ER PT J AU Ash, JS Johnson, FE AF Ash, JS Johnson, FE TI IAIMS: An interview with Dick West SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material AB Richard T. West, IAIMS (Integrated Advanced information Management Systems) Program Officer at the National Library of Medicine for 13 years, reflects on the origin, development, effectiveness, and future of IAIMS efforts. He dwells on the changes that have taken place as the concept of IAIMS has evolved from a technology-based to an organization-based level of integration. The role of IAIMS in patient care, education, and research is discussed, along with the role of the librarian in the implementation of IAIMS programs. He sees a need for training for librarians, informaticians, and others in preparation for these efforts and for the development of academic reward systems that encourage them. He expresses a desire for those working in information technology in hospitals to gain a clearer understanding of IAIMS, because the concept fits hospitals as well as academic health science centers. He exhorts informaticians to bring to reality the futuristic fantasies of a new information world. C1 Oregon Hlth Sci Univ, Ctr Biomed Informat Commun, Portland, OR 97201 USA. Natl Lib Med, Bethesda, MD USA. RP Ash, JS (reprint author), Oregon Hlth Sci Univ, Ctr Biomed Informat Commun, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV-DEC PY 1999 VL 6 IS 6 BP 447 EP 456 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 255UJ UT WOS:000083688300003 ER PT J AU Levey, AS Greene, T Beck, GJ Caggiula, AW Kusek, JW Hunsicker, LG Klahr, S AF Levey, AS Greene, T Beck, GJ Caggiula, AW Kusek, JW Hunsicker, LG Klahr, S TI Dietary protein restriction and the progression of chronic renal disease: What have all of the results of the MDRD study shown? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID BLOOD-PRESSURE CONTROL; ANTIHYPERTENSIVE THERAPY; KIDNEY-DISEASE; FAILURE; METAANALYSIS; TRIAL; INSUFFICIENCY; DIALYSIS; NEPHROPATHY; PREDICTORS AB The Modification of Diet in Renal Disease (MDRD) Study was the largest randomized clinical trial to test the hypothesis that protein restriction slows the progression of chronic renal disease. However, the primary results published in 1994 were not, conclusive with regard to the efficacy of this intervention. Many physicians interpreted the failure of the MDRD Study to demonstrate a beneficial effect of protein restriction over a 2- to 3-yr period as proving that this therapy does not slow disease progression. The authors believe that this viewpoint is incorrect, and is the result of misinterpretation of inconclusive evidence as evidence in favor of the null hypothesis. Since then, numerous secondary analyses of the MDRD Study have been undertaken to clarify the effect of protein restriction on the rare of decline in GFR, urine protein excretion, and onset of end-stage renal disease. This review describes some of the principles of secondary analyses of randomized clinical trials, presents the results of these analyses from the MDRD Study, and compares them with results from other randomized clinical trials. Although these secondary results cannot be regarded as definitive, the authors conclude that the balance of evidence is more consistent with the hypothesis of a beneficial effect of protein restriction than with the contrary hypothesis of no beneficial effect. Until additional data became available, physicians must continue to make recommendations in the absence of conclusive results. The authors suggest that physicians incorporate the results of these secondary analyses into their interpretation of the findings of the MDRD Study. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Levey, AS (reprint author), New England Med Ctr, Div Nephrol, Box 391,750 Washington St, Boston, MA 02111 USA. NR 47 TC 198 Z9 208 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 1999 VL 10 IS 11 BP 2426 EP 2439 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 249HV UT WOS:000083328100021 PM 10541304 ER PT J AU Nguyen, DM Chen, A Mixon, A Schrump, DS AF Nguyen, DM Chen, A Mixon, A Schrump, DS TI Sequence-dependent enhancement of paclitaxel toxicity in non-small cell lung cancer by 17-allylamino 17-demethoxygeldanamycin SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 18-21, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Thorac Surg ID HUMAN-BREAST-CANCER; INTRINSIC CHEMORESISTANCE; GENE-EXPRESSION; GROWTH-FACTOR; IN-VIVO; OVEREXPRESSION; GELDANAMYCIN; DEPLETION; KINASE; TAXOL AB Objective: Overexpression of the oncogene erbB-2 contributes to chemoresistance in various malignant tumors including lung cancer. The aim of this study was to investigate whether depletion of the erbB-2 gene product (p185) by 17-allylamino 17-demethoxygeldanamycin would sensitize lung cancer cells to paclitaxel (Taxol) in vitro. Methods: Paclitaxel cytotoxicity was evaluated in a panel of non-small cell lung cancer cell lines that expressed varying levels of p185 by means in vitro proliferation assays and 2 drug combination schedules. Cell cycle kinetics and apoptosis after exposure to paclitaxel or paclitaxel plus 17-allylamino 17-demethoxygeldanamycin mere analyzed by flow cytometry. Results: The 17-allylamino 17-demethoxygeldanamycin treatment efficiently depleted p185 expression in lung cancer cells. Concurrent exposure of these cells to paclitaxel and 17-allylamino 17-demethoxygeldanamycin significantly enhanced paclitaxel-mediated cytotoxicity, particularly in cells which overexpressed p185. There was a 1.3 to more than 20-fold reduction of paclitaxel 50% inhibitory concentration values in those cells that were responding positively to the drug combination. Significant induction of apoptosis was observed after treatment of cells with the combination of paclitaxel and 17-allylamino 17-demethoxygeldanamycin. The combination cytotoxic effect was only additive in cells expressing low levels of p185. In contrast, of tung cancer cells with exposure to 17-allylamino 17-demethoxygeldanamycin before combined paclitaxel and 17-allylamino 17-demethoxygeldanamycin exposure actually rendered the cells refractory to paclitaxel cytotoxicity. Conclusion: The compound 17-allylamino 17-demethoxygeldanamycin sensitizes non-small cell lung cancer cells expressing high levels of p185 to paclitaxel-mediated growth arrest and apoptosis. These preclinical data support the evaluation of the combination of paclitaxel and 17-allylamino 17-demethoxygeldanamycin in the treatment of patients with lung cancer whose tumors exhibit p185 overexpression. C1 NCI, Surg Branch, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), NCI, Surg Branch, Thorac Oncol Sect, NIH, Room 2B07,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. NR 27 TC 30 Z9 31 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 1999 VL 118 IS 5 BP 908 EP 915 DI 10.1016/S0022-5223(99)70061-9 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 300XK UT WOS:000086278900028 PM 10534697 ER PT J AU Walther, MM Herring, J Enquist, E Keiser, HR Linehan, WM AF Walther, MM Herring, J Enquist, E Keiser, HR Linehan, WM TI von Recklinghausen's disease and pheochromocytomas SO JOURNAL OF UROLOGY LA English DT Review DE neurofibromatosis; neurofibromatosis 1; neuro fibromatosis 2; pheochromocytoma ID NEUROFIBROMATOSIS TYPE-1; VONRECKLINGHAUSENS DISEASE; MALIGNANT PHEOCHROMOCYTOMA; ENDOCRINE NEOPLASIA; CARCINOID-TUMORS; PREGNANT PATIENT; RENAL-ARTERY; SCHWANNOMA; ANEURYSMS; STENOSIS AB Purpose: We review the literature and characterize the clinical findings of von Recklinghausen's associated pheochromocytoma. Materials and Methods: A Grateful Med search for the years 1966 to 1999 was performed on the subjects, "von Recklinghausen" and "neurofibromatosis.'' Articles from the Grateful Med search were then reviewed to identify older publications. Of 325 articles 118 are included in this review. Results: Pheochromocytomas have been clinically identified in 0.1 to 5.7% of patients with von Recklinghausen's disease. Mean patient age was 42 years (range 1.5 to 74) in 87 women and 61 men at presentation with pheochromocytoma. Of the 148 patients 84% had solitary adrenal tumors, 9.6% bilateral adrenal disease and 6.1% ectopic pheochromocytomas. Symptoms related to pheochromocytoma or hypertension were noted in 78% of the patients. Tumors secreted epinephrine and norepinephrine, and 87% demonstrated metaiodobenzylguanidine uptake. Of the 148 patients 6% died during pregnancy or a medical procedure, or due to hypertensive crisis without apparent provocation, 8.8% had gastrointestinal carcinoid tumors and 11.5% had metastases or local invasion from pheochromocytoma. Conclusions: Pheochromocytomas occur in a small but defined number of patients with von Recklinghausen's disease, and can be associated with significant morbidity and mortality if not detected. Screening of patients with von Recklinghausen's disease and hypertension or before provocative procedures or pregnancy seems to be indicated. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 118 TC 141 Z9 151 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1999 VL 162 IS 5 BP 1582 EP 1586 DI 10.1016/S0022-5347(05)68171-2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 243MQ UT WOS:000083002200002 PM 10524872 ER PT J AU Qiu, JT Song, RJ Dettenhofer, M Tian, CJ August, T Felber, BK Pavlakis, GN Yu, XF AF Qiu, JT Song, RJ Dettenhofer, M Tian, CJ August, T Felber, BK Pavlakis, GN Yu, XF TI Evaluation of novel human immunodeficiency virus type 1 Gag DNA vaccines for protein expression in mammalian cells and induction of immune responses SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; REV-INDEPENDENT EXPRESSION; DEPENDENT MANNER; MATRIX PROTEIN; MESSENGER-RNA; ELEMENT; HIV; INFECTION; TRANSPORT; SEQUENCE AB Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) are an important parameter of host defenses that limit viral replication after infection. Induction of effective CTL against conserved viral proteins such as Gag may be essential to the development of a safe and effective HIV type 1 (HIV-1) vaccine. DNA vaccination represents a novel strategy for inducing potent CD8(+) CTL responses in vivo. However, expression of HIV-1 structural proteins by DNA vectors has been hampered by a stringent requirement for coexpression with other viral components, such as Rev and RRE. Furthermore, even with Rev and RRE present, the level of expression of HIV-1 Gag, pol, or Env is very low in murine cells. These problems have limited our ability to address the key issue of how to generate effective CTL responses to Gag in a mouse model. To overcome this problem, we compared several novel DNA expression vectors for HIV-1 Gag protein expression in primate and mouse cells and for generating immune responses in mice after DNA vaccination. A DNA vector containing wild type HIV-1 gag coding sequences did not induce detectable Gag expression in any of the cells tested. Attempts to increase nuclear export of Gag expression RNA by adding the constitutive transport element yielded only a moderate increase in Gag expression in monkey-derived COS cells and an even lower increase in Gag expression in HeLa cells or several mouse cell lines. In contrast, silent-site mutations in the HIV-1 gag coding sequences significantly increased Gag expression levels in all cells tested. Furthermore, this construct induced both Gag-specific antibody and CTL responses in mice after DNA vaccination. Using this construct, we achieved stable expression of HIV-1 Gag in the mouse cell line p815, which can now be used as a target cell for measuring HIV-1 Gag-specific CTL responses in immunized mice. The DNA vectors described in this study should make it possible to systematically evaluate the approaches for maximizing the induction of CTL responses against HIV-1 Gag in mouse and other animal systems. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. RP Pavlakis, GN (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Bldg 535,Rm 210, Frederick, MD 21702 USA. OI Dettenhofer, Markus/0000-0003-1972-7026 FU NIAID NIH HHS [AI-46324, AI-42624]; NIEHS NIH HHS [ES07141, T32 ES007141] NR 37 TC 74 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1999 VL 73 IS 11 BP 9145 EP 9152 PG 8 WC Virology SC Virology GA 244VJ UT WOS:000083071200026 PM 10516021 ER PT J AU Certo, JL Kabdulov, TO Paulson, ML Anderson, JA Hu, WS AF Certo, JL Kabdulov, TO Paulson, ML Anderson, JA Hu, WS TI The nucleocapsid domain is responsible for the ability of spleen necrosis virus (SNV) gag polyprotein to package both SNV and murine leukemia virus RNA SO JOURNAL OF VIROLOGY LA English DT Article ID PROVIRAL DNA-SYNTHESIS; HELPER-CELL LINE; REVERSE-TRANSCRIPTASE; GENOMIC RNA; ZINC-FINGER; IN-VITRO; STRAND TRANSFER; VIRAL-RNA; ANNEALING ACTIVITIES; POSSIBLE ROLES AB Murine leukemia virus (MLV)-based vector RNA can be packaged and propagated by the proteins of spleen necrosis virus (SNV). We recently demonstrated that MLV proteins cannot support the replication of an SNV-based vector; RNA analysis revealed that MLV proteins cannot efficiently package SNV-based vector RNA. The domain in Gag responsible for the specificity of RNA packaging was identified using chimeric gag-pol expression constructs. A competitive packaging system was established by generating a cell line that expresses one viral vector RNA containing the MLV packaging signal (Psi) and another viral vector RNA containing the SNV packaging signal (E), The chimeric gag-pol expression constructs were introduced into the cells, and vector titers as well as the efficiency of RNA packaging were examined. Our data confirm that Gag is solely responsible for the selection of viral RNAs. Furthermore, the nucleocapsid (NC) domain in the SNV Gag is responsible for its ability to interact with both SNV E and MLV Psi Replacement of the SNV NC with the MLV NC generated a chimeric Gag that could not package SNV RNA but retained its ability to package MLV RNA. A construct expressing SNV gag-MLV pol supported the replication of both MLV and SNV vectors, indicating that the gag and pol gene products from two different viruses can functionally cooperate to perform one cycle of retroviral replication Viral titer data indicated that SNV cia-acting elements are not ideal substrates for MLV pol gene products since infectious viruses were generated at a lower efficiency. These results indicate that the nonreciprocal recognition between SNV and MLV extends beyond the Gag-RNA interaction and also includes interactions between Pol and other cia-acting elements. C1 W Virginia Univ, Mary Babb Randolph Canc Ctr, Dept Genet & Dev Biol, Morgantown, WV 26506 USA. W Virginia Univ, Dept Microbiol & Immunol, Morgantown, WV 26506 USA. RP Hu, WS (reprint author), NCI, Frederick Canc Res & Dev Ctr, DBS, HIV Drug Resistance Program, Bldg 535, Frederick, MD 21702 USA. NR 59 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1999 VL 73 IS 11 BP 9170 EP 9177 PG 8 WC Virology SC Virology GA 244VJ UT WOS:000083071200029 PM 10516024 ER PT J AU Bell, YC Semler, BL Ehrenfeld, E AF Bell, YC Semler, BL Ehrenfeld, E TI Requirements for RNA replication of a poliovirus replicon by coxsackievirus B3 RNA polymerase SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL-RNA; 3'-NONCODING REGION; PROTEIN 3AB; 3'-UNTRANSLATED REGION; SEQUENCE-ANALYSIS; 3CD PROTEINASE; CODING REGION; 3D POLYMERASE; STRAND RNA; VIRUS AB A chimeric poliovirus type 1 (PV1) genome was constructed in which the 3D RNA polymerase (3D(pol)) coding sequences were replaced with those from coxsackievirus B3 (CVB3). No infectious virus was produced from HeLa cells transfected with the chimeric RNA. Processing of the PV1 capsid protein precursor was incomplete, presumably due to inefficient recognition of the P1 protein substrate by the chimeric 3CD proteinase containing CVB3 3D sequences. The ability of the chimeric RNA to replicate in the absence of capsid formation was measured after replacement of the P1 region with a luciferase reporter gene. No RNA synthesis was detected, despite efficient production of enzymatically active 3D(pol) from the 3D portion of the chimeric 3CD. The chimeric 3CD protein was unable to efficiently bind to the cloverleaf-like structure (CL) at the 5' end of PV1 RNA, which has been demonstrated previously to be required for viral RNA synthesis. The CVB3 3CD protein bound the PV1 CL as well as PV1 3CD. An additional chimeric PV1 RNA that contained CVB3 3CD sequences also failed to produce virus after transfection. Since processing of PV1 capsid protein precursors by the CVB3 3CD was again incomplete, a luciferase-containing replicon was also analyzed for RNA replication. The 3CD chimera replicated at 33 degrees C, but not at 37 degrees C. Replacement of the PV1 5'-terminal CL with that of CVB3 did not rescue the temperature-sensitive phenotype. Thus, there is an essential interaction(s) between 3CD and other viral P2 or P3 protein products required for efficient RNA replication which is not fully achieved between proteins from the two different members of the same virus genus. C1 Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. RP Ehrenfeld, E (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr,Room 3100, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI 22693, R01 AI022693, AI 17386] NR 65 TC 26 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1999 VL 73 IS 11 BP 9413 EP 9421 PG 9 WC Virology SC Virology GA 244VJ UT WOS:000083071200055 PM 10516050 ER PT J AU Nardelli-Haefliger, D Roden, R Balmelli, C Potts, A Schiller, J De Grandi, P AF Nardelli-Haefliger, D Roden, R Balmelli, C Potts, A Schiller, J De Grandi, P TI Mucosal but not parenteral immunization with purified human papillomavirus type 16 virus-like particles induces neutralizing titers of antibodies throughout the estrous cycle of mice SO JOURNAL OF VIROLOGY LA English DT Article ID FEMALE GENITAL-TRACT; SECRETORY IMMUNE-RESPONSES; HEAT-LABILE ENTEROTOXIN; HERPES-SIMPLEX VIRUS; HUMAN UTERINE FLUID; TOXIN-B-SUBUNIT; INTRANASAL IMMUNIZATION; VAGINAL FLUID; ESCHERICHIA-COLI; IMMUNOGLOBULIN-G AB We have recently shown that nasal immunization of anesthetized mice with human papillomavirus type 16 (HPV16) virus-like particles (VLPs) is highly effective at inducing both neutralizing immunoglobulin A (IgA) and IgG in genital secretions, while parenteral immunization induced only neutralizing IgG. Our data also demonstrated that both isotypes are similarly neutralizing according to an in vitro pseudotyped neutralization assay. However, it is known that various amounts of IgA and IgG are produced in genital secretions along the estrous cycle. Therefore, we have investigated how this variation influences the amount of HPV16 neutralizing antibodies induced after immunization with VLPs. We have compared parenteral and nasal protocols of vaccination with daily samplings of genital secretions of mice. Enzyme-linked immunosorbent assay analysis showed that total IgA and IgG inversely varied along the estrous cycle, with the largest amounts of IgA in proestrus-estrus and the largest amount of IgG in diestrus. This resulted in HPV16 neutralizing titers of IgG only being achieved during diestrus upon parenteral immunization. In contrast, nasal vaccination induced neutralizing titers of IgA plus IgG throughout the estrous cycle, as confirmed by in vitro pseudotyped neutralization assays. Our data suggest that mucosal immunization might be more efficient than parenteral immunization at inducing continuous protection of the female genital tract. C1 CHU Vaudois, Dept Gynecol, CH-1011 Lausanne, Switzerland. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Nardelli-Haefliger, D (reprint author), Inst Microbiol, Dept Gynecol, Bugnon 44, CH-1011 Lausanne, Switzerland. NR 47 TC 55 Z9 58 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1999 VL 73 IS 11 BP 9609 EP 9613 PG 5 WC Virology SC Virology GA 244VJ UT WOS:000083071200076 PM 10516071 ER PT J AU Buge, SL Murty, L Arora, K Kalyanaraman, VS Markham, PD Richardson, ES Aldrich, K Patterson, LJ Miller, CJ Cheng, SM Robert-Guroff, M AF Buge, SL Murty, L Arora, K Kalyanaraman, VS Markham, PD Richardson, ES Aldrich, K Patterson, LJ Miller, CJ Cheng, SM Robert-Guroff, M TI Factors associated with slow disease progression in macaques immunized with an adenovirus-simian immunodeficiency virus (SIV) envelope priming-gp120 boosting regimen and challenged vaginally with SIVmac251 (vol 73, pg 7430, 1999) SO JOURNAL OF VIROLOGY LA English DT Correction C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. Univ Calif Davis, Calif Reg Primate Res Ctr, Davis, CA 95616 USA. Wyeth Ayerst Res, Radnor, PA 19087 USA. RP Buge, SL (reprint author), NCI, Basic Res Lab, Bethesda, MD 20892 USA. NR 1 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1999 VL 73 IS 11 BP 9692 EP 9692 PG 1 WC Virology SC Virology GA 244VJ UT WOS:000083071200092 ER PT J AU Munoz-Barroso, I Salzwedel, K Hunter, E Blumenthal, R AF Munoz-Barroso, I Salzwedel, K Hunter, E Blumenthal, R TI Role of the membrane-proximal domain in the initial stages of human immunodeficiency virus type 1 envelope glycoprotein-mediated membrane fusion (vol 73, pg 6089, 1999) SO JOURNAL OF VIROLOGY LA English DT Correction C1 NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, Frederick, MD 21701 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Munoz-Barroso, I (reprint author), NCI, Lab Expt & Computat Biol, Div Basic Sci, NIH, Frederick, MD 21701 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1999 VL 73 IS 11 BP 9693 EP 9693 PG 1 WC Virology SC Virology GA 244VJ UT WOS:000083071200093 ER PT J AU Bordin, P Da Col, PG Peruzzo, P Stanta, G Guralnik, JM Cattin, L AF Bordin, P Da Col, PG Peruzzo, P Stanta, G Guralnik, JM Cattin, L TI Causes of death and clinical diagnostic errors in extreme aged hospitalized people: A retrospective clinical-necropsy survey SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID AUTOPSY; OLD; CENTENARIANS; CERTIFICATES; PATHOLOGY AB Background. There are little data on causes of death in extreme aged. We compared, using autopsy findings, main cause of death, overall disease status, and accuracy rate of clinical diagnoses in extreme aged and persons dying at younger ages. Methods. We reviewed the complete clinical and autopsy records of 114 consecutive inpatients (97 women, 17 men, age range 97-106, mean 99, median 98) who died in Trieste, Italy, and represented 99% of all extreme-aged person deaths in the hospital and 70% in the area. The control group included 151 patients (66 women, 85 men, age range 65-74, mean 70, median 70) who died during the same period in that hospital. Results. Vascular and respiratory diseases together caused 84% of deaths in extreme aged. The main causes of death were pneumonia (n = 40, 35%), pulmonary embolism (n = 16, 14%), stroke (n = 12, 11%), and myocardial infarction (n = 8, 7%). Cancer was responsible for 6% (7/1 14) of deaths in extreme aged and 42% (64/151) in the control group. In 5% of extreme aged, autopsy findings did not explain death. The premortem diagnostic accuracy rate for clinical diagnoses was good in 44% of extreme aged, sufficient in 18%, poor in 28%, and not evaluable in 10%, and was significantly different from controls. Pneumonia, pulmonary embolism, and myocardial infarction were markedly underestimated by clinicians in both group. Conclusions. Extreme aged die mainly of cardiovascular and respiratory diseases and, in most cases, of acute events. Senescence is a rare cause of death. Death from cancer is substantially lower than in persons dying at younger ages. In contrast to no autopsy studies, most extreme aged in our study were found to have specific diseases that explained their deaths. C1 Univ Trieste, Ist Clin Med, I-34127 Trieste, Italy. Univ Trieste, Ist Anat Patol, I-34127 Trieste, Italy. NIA, Bethesda, MD 20892 USA. RP Bordin, P (reprint author), Osped Cattinara, Ist Clin Med, Str Fiume 447, I-34149 Trieste, Italy. NR 30 TC 19 Z9 20 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 1999 VL 54 IS 11 BP M554 EP M559 DI 10.1093/gerona/54.11.M554 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XL UT WOS:000088043900010 PM 10619317 ER PT J AU Daugirdas, JT Greene, T Depner, TA Gotch, FA Star, RA AF Daugirdas, JT Greene, T Depner, TA Gotch, FA Star, RA CA Hemodialysis HEMO Study Grp TI Relationship between apparent (single-pool) and true (double-pool) urea distribution volume SO KIDNEY INTERNATIONAL LA English DT Article DE dialysis; urea kinetic modeling; volume of urea distribution; anthropometric volume ID HEMODIALYSIS AB Background. The volume of urea distribution (V) is usually derived from single-pool variable volume urea kinetics. A theoretical analysis has shown that modeled single-pool V (Vsp) is overestimated when the urea reduction ratio (URR) is greater than 65 to 70% and is underestimated when the URR is less than 65%. The "true" volume derived from double-pool kinetics (Vdp) does not exhibit this effect. An equation has been derived to adjust Vsp to the expected Vdp. Methods. To validate these theoretical predictions, we examined data from the Hemodialysis (HEMO) Study to assess the performance of Vdp as estimated from Vsp using the previously published prediction equation. For increased precision, both Vsp and Vdp were factored by anthropometric volume (Va). Patients were first dialyzed with a target equilibrated dialysis dose (eKt/V) of 1.45 during a baseline period and were then randomly assigned to eKt/V targets of either 1.05 (a URR of approximately 67%) or 1.45 (a URR of approximately 75%). A brood sample was obtained one hour after starting dialysis during one dialysis in each patient. Results. Vsp/Va was (mean +/- SD) 1.014 +/- 0.127 in 795 patients during the baseline period when the URR was approximately 1.45. During the first modeled dialysis after randomization, the Vsp/Va fell to 0.961 +/- 0.138 in the group with an eKt/V target of 1.05, but did not change significantly under the high eKt/V goal. The correction of Vsp to Vdp using the prediction equation resulted in a Vdp/Va ratio of 0.96 to 0.98 in all three circumstances without significant differences. When a blood sample was drawn one hour after starting dialysis, the apparent Vsp/Va ratio at one hour was much lower at 0.708 +/- 0.139. However, the mean Vdp/Va ratio, computed using the correction equation, was 0.968 +/- 0.322, which was similar to the Vdp/Va ratio calculated from the postdialysis blood urea nitrogen. Conclusions. These data suggest that the previously derived formula for adjusted Vsp is valid experimentally. The Vsp/Vdp correction should be useful for prescribing hemodialysis with either a very low Kt/V (for example, daily and early incremental dialysis) or a very high Kt/V. C1 NIDDK, NIH, Bethesda, MD USA. RP Daugirdas, JT (reprint author), Univ Illinois, Coll Med, Dept Med, M-C 793,1737 W Polk St, Chicago, IL 60612 USA. NR 14 TC 39 Z9 39 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 1999 VL 56 IS 5 BP 1928 EP 1933 DI 10.1046/j.1523-1755.1999.00726.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 249HZ UT WOS:000083328500034 PM 10571804 ER PT J AU Caetano, AR Lyons, LA Laughlin, TF O'Brien, SJ Murray, JD Bowling, AT AF Caetano, AR Lyons, LA Laughlin, TF O'Brien, SJ Murray, JD Bowling, AT TI Equine synteny mapping of comparative anchor tagged sequences (CATS) from human Chromosome 5 SO MAMMALIAN GENOME LA English DT Article ID ZOO-FISH; HORSE GENOME; MARKERS; MICROSATELLITES; GENE AB Comparative anchor tagged sequences (CATS) from human Chromosome 5 (HSA5) were used as PCR primers to produce molecular markers for synteny mapping in the horse, primer sets for 21 genes yielded eight horse-specific markers, which were mapped with the UC Davis horse-mouse somatic cell hybrid panel into two synteny groups: UCDl4 and UCD21. These data, in conjunction with earlier human chromosome painting studies of the horse karyotype and synteny mapping of horse microsatellite markers physically mapped by FISH, confirm the assignment of UCD21 to ECA21 and suggest that UCD14 is located on ECA14. In addition, our results can be used to substantiate previously published data which indicate that ECA21 contains material orthologous to HSA5p and HSA5q, and to propose an approximate region for an evolutionary chromosomal rearrangement event. C1 Univ Calif Davis, Vet Genet Lab, Davis, CA 95616 USA. Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genomic Divers, Frederick, MD 21702 USA. E Tennessee State Univ, Dept Biol Sci, Johnson City, TN 37614 USA. Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. RP Bowling, AT (reprint author), Univ Calif Davis, Vet Genet Lab, Davis, CA 95616 USA. RI Rodrigues Caetano, Alexandre/B-5227-2017 OI Rodrigues Caetano, Alexandre/0000-0002-3419-7337 NR 16 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1999 VL 10 IS 11 BP 1082 EP 1084 DI 10.1007/s003359901165 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 248ZA UT WOS:000083305600007 PM 10556427 ER PT J AU Tse, E Grutz, G Garner, AA Ramsey, Y Carter, NP Copeland, N Gilbert, DJ Jenkins, NA Agulnick, A Forster, A Rabbitts, TH AF Tse, E Grutz, G Garner, AA Ramsey, Y Carter, NP Copeland, N Gilbert, DJ Jenkins, NA Agulnick, A Forster, A Rabbitts, TH TI Characterization of the Lmo4 gene encoding a LIM-only protein: genomic organization and comparative chromosomal mapping SO MAMMALIAN GENOME LA English DT Article ID CELL ACUTE-LEUKEMIA; HOMEODOMAIN PROTEINS; DOMAIN PROTEINS; MESSENGER-RNAS; RHOMBOTIN; FAMILY; EXPRESSION; ONCOGENE; COMPLEX; LDB1 AB LIM-only (LMO) proteins are transcription regulators that function by mediating protein-protein interaction and include the T cell oncogenes encoding LMO1 and LMO2. The oncogenic functions of LMO1 and LMO2 are thought to be mediated by interaction with LDB1 since they form a multimeric protein complex(es). A new member of the Lmo family, Lmo4, has also recently been identified via its interaction with Ldb1. Sequence analysis of the mouse Lmo4 gene shows that it spans about 18 kb and consists of at least six exons, including two alternatively spliced 5' exons. Unlike Lmol, the two 5' exons of Lmo4 do not encode protein. Comparison of the Lmo4 gene structure with the other LMO family members shows the exon structure of Lmo4 differs in the position of exon junctions encoding the second LIM domain and in a novel exon-intron junction at the penultimate codon of the gene. Lmo4 is thus the least conserved known member of the LIM-only family in both nucleotide sequence and exon structure. Physical mapping of the Lmo4/LMO4 genes has shown mouse Lmo4 is located on Chromosome (Chr) 3 and human LMO4 on Chr 1p22.3. This chromosome location is of interest as it occurs in a region that is deleted in a number of human cancers, indicating a possible role of LMO4 in tumorigenesis, like its relatives LMO1 and LMO2. C1 MRC, Mol Biol Lab, Div Prot & Nucl Acid Chem, Cambridge CB2 2QH, England. Sanger Ctr, Cambridge CB10 1SA, England. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. RP Rabbitts, TH (reprint author), MRC, Mol Biol Lab, Div Prot & Nucl Acid Chem, Hills Rd, Cambridge CB2 2QH, England. FU Wellcome Trust NR 33 TC 12 Z9 12 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1999 VL 10 IS 11 BP 1089 EP 1094 DI 10.1007/s003359901167 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 248ZA UT WOS:000083305600009 PM 10556429 ER PT J AU Smith, MA Strickler, HD Granovsky, M Reaman, G Linet, M Daniel, R Shah, KV AF Smith, MA Strickler, HD Granovsky, M Reaman, G Linet, M Daniel, R Shah, KV TI Investigation of leukemia cells from children with common acute lymphoblastic leukemia for genomic sequences of the primate polyomaviruses JC virus, BK virus, and simian virus 40 SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE leukemia; ALL; JC virus; BK virus; simian virus 40 ID CHILDHOOD LEUKEMIA; SIMIAN-VIRUS-40; ETIOLOGY; URINE AB Background. An infectious etiology for childhood acute lymphoblastic leukemia (ALL) has long been suspected, although the characteristics of the putative childhood ALL-inducing agent(s) remain a mystery. We describe the testing of ALL leukemia cells for the presence of DNA sequences of the polyomavirus family: JC virus, BK virus, and simian virus 40 (SV40). Procedure. Cryopreserved leukemia cells from 25 children between 2 and 5 years of age at the time of diagnosis and classified as having "common" ALL (B-precursor ALL expressing the CD19 and CD10 surface antigens) were tested for the presence of polyomavirus sequences using standard PCR methods. Results. Human beta-globin gene sequences were detected in 22 of 25 leukemia specimens. However, polyomavirus sequences were not detected in any of the 22 specimens with amplifiable DNA. Conclusions. The inability to detect IC virus, BK virus, and SV40 virus DNA sequences in any of the 22 specimens with amplifiable DNA suggests that that these members of the polyomavirus family are unlikely to be causally associated with most childhood ALL. Published 1999 Wiley-Liss, Inc.(dagger) C1 NCI, Clin Invest Branch, CTEP, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. NCI, Div Canc Etiol, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Washington, DC 20052 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Smith, MA (reprint author), NCI, Clin Invest Branch, CTEP, Div Canc Treatment & Diag, Room 741 EPN,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 16 TC 17 Z9 17 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD NOV PY 1999 VL 33 IS 5 BP 441 EP 443 DI 10.1002/(SICI)1096-911X(199911)33:5<441::AID-MPO1>3.0.CO;2-P PG 3 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 251XW UT WOS:000083472500001 PM 10531566 ER PT J AU Weitzman, S Wayne, AS Arceci, R Lipton, JM Whitlock, JA De Rossi, G AF Weitzman, S Wayne, AS Arceci, R Lipton, JM Whitlock, JA De Rossi, G CA Histiocyte Soc TI Nucleoside analogues in the therapy of Langerhans cell histiocytosis: A survey of members of the Histiocyte Society and review of the literature SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE 2-CdA; Langerhans cell histiocytosis; salvage therapy ID INDOLENT LYMPHOID MALIGNANCIES; ACUTE MYELOID-LEUKEMIA; 2-CHLORODEOXYADENOSINE 2-CDA; MYELOGENOUS LEUKEMIA; 2'-DEOXYCOFORMYCIN; EFFICACY; ADULTS; LCH AB Background. Previous reports have suggested activity of the nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) in Langerhans cell histiocytosis (LCH). Procedure. To assess the efficacy of 2-CdA and 2'-DCF as salvage therapy for LCH, a survey of members of the Histiocyte Society and a literature review were undertaken. Twenty-three patients treated with 2-CdA and 4 treated with 2'-DCF were found, age range 2 months to 49 years. Results. All 15 survey patients had multiorgan involvement, and 14 were heavily pretreated. Doses of 2-CdA ranged from 0.1 mg/kg/day continuous infusion for 5-7 days (majority of patients) to 13 mg/m(2)/day for 5 days, for 1-6 courses. One of the 15 patients had an early death, 5 had no response (NR), 3 had partial response (PR), and 6 achieved complete response (CR). Among 8 published patients, 7 achieved stable CR and I NR. Among 4 patients treated with 2'-DCF (4 mg/m(2)/week for 8 weeks then q 2 weekly), 2 achieved CR fbr 16+ and 18+ months and 2 PR for 2 and 5 months. Toxicity consisted mainly of combined myelo- and immunosuppression but no significant infections occurred and there were no toxic deaths. A cumulative thrombocytopenia was noted, which in 1 case took up to 6 months to resolve. Transient gastrointestinal toxicity and elevation of liver enzymes was seen, and 2 patients developed renal tubular acidosis. The peripheral neuropathy reported in adult patients receiving high doses was not seen. Conclusions. 2-CdA and 2'-DCF appear to have a useful role in LCH and are worthy of prospective trial in patients unresponsive to routine therapy. (C) 1999 Wiley-Liss, Inc. C1 Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA. Mt Sinai Med Ctr, Div Pediat Hematol Oncol, New York, NY 10029 USA. Vanderbilt Univ, Med Ctr, Div Pediat Hematol Oncol, Nashville, TN USA. Osped Pediat Bambino Gesu, Div Hematol, Rome, Italy. RP Weitzman, S (reprint author), Hosp Sick Children, Div Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. NR 29 TC 41 Z9 44 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD NOV PY 1999 VL 33 IS 5 BP 476 EP 481 DI 10.1002/(SICI)1096-911X(199911)33:5<476::AID-MPO7>3.0.CO;2-Q PG 6 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 251XW UT WOS:000083472500007 PM 10531572 ER EF