FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Grey, ST Arvelo, MB Hasenkamp, W Bach, FH Ferran, C AF Grey, ST Arvelo, MB Hasenkamp, W Bach, FH Ferran, C TI A20 inhibits cytokine-induced apoptosis and nuclear factor kappa B-dependent gene activation in islets SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE A20; beta cells; nuclear factor kappa B; nitric oxide; apoptosis ID NITRIC-OXIDE SYNTHASE; PANCREATIC BETA-CELLS; ZINC-FINGER PROTEIN; NONOBESE DIABETIC MICE; TRANSCRIPTION FACTOR; INTERFERON-GAMMA; ENDOTHELIAL-CELLS; INSULIN-SECRETION; EXPRESSION; AUTOIMMUNE AB Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease resulting from apoptotic destruction of beta cells in the islets of Langerhans. Low expression of antioxidants and a predilection to produce nitric oxide (NO) have been shown to underscore beta cell apoptosis. With this perspective in mind, we questioned whether beta cells could mount an induced protective response to inflammation. Here we show that human and rat islets can be induced to rapidly express the antiapoptotic gene A20 after interleukin (IL)-1 beta activation. Overexpression of A20 by means of adenovirus-mediated gene transfer protects islets from IL-1 beta and interferon gamma-induced apoptosis. The cytoprotective effect of A20 against apoptosis correlates with and is dependent on the abrogation of cytokine-induced NO production. The inhibitory effect of A20 on cytokine-stimulated NO production is due to transcriptional blockade of inducible NO synthase (iNOS) induction; A20 inhibits the activation of the transcription factor nuclear factor kappa B at a level upstream of I kappa B alpha degradation. These data demonstrate a dual antiapoptotic and antiinflammatory function for A20 in beta cells. This qualifies A20 as part of the physiological cytoprotective response of islets. We propose that A20 may have therapeutic potential as a gene therapy candidate to achieve successful islet transplantation and the cure of IDDM. C1 Harvard Univ, Sch Med, Immunobiol Res Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Ferran, C (reprint author), Harvard Univ, Sch Med, Immunobiol Res Ctr, Beth Israel Deaconess Med Ctr, 99 Brookline Ave, Boston, MA 02215 USA. RI Grey, Shane/B-3020-2008 OI Grey, Shane/0000-0003-2160-1625 FU NIDDK NIH HHS [1PO1DK53087/01] NR 89 TC 147 Z9 158 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 18 PY 1999 VL 190 IS 8 BP 1135 EP 1145 DI 10.1084/jem.190.8.1135 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 248LV UT WOS:000083277000010 PM 10523611 ER PT J AU Kathiresan, S Jordan, MK Gimelli, G Lopez-Cuellar, J Madhi, N Jang, IK AF Kathiresan, S Jordan, MK Gimelli, G Lopez-Cuellar, J Madhi, N Jang, IK TI Frequency of silent myocardial ischemia following coronary stenting SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID UNSTABLE ANGINA; BALLOON ANGIOPLASTY; ARTERY DISEASE; PROGNOSIS AB To detect silent myocardial ischemia, 12-lead continuous electrocardiographic monitoring was performed in patients undergoing 1-vessel coronary stenting. Despite successful angiographic results, one third of the patients experienced silent myocardial ischemia during the postprocedural period. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 5 Z9 5 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 OCT 15 PY 1999 VL 84 IS 8 BP 930 EP + DI 10.1016/S0002-9149(99)00469-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 246AV UT WOS:000083141700014 PM 10532514 ER PT J AU Narula, J Malhotra, A Yasuda, T Talwar, KK Reddy, KS Chopra, P Southern, JF Vasan, RS Tandon, R Bhatia, ML Khaw, BA Strauss, HW AF Narula, J Malhotra, A Yasuda, T Talwar, KK Reddy, KS Chopra, P Southern, JF Vasan, RS Tandon, R Bhatia, ML Khaw, BA Strauss, HW TI Usefulness of antimyosin antibody imaging for the detection of active myocarditis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RHEUMATIC-FEVER; CARDITIS; DIAGNOSIS AB Myocarditis constitutes an important component of rheumatic carditis. Antimyosin scintigraphy, which allows noninvasive assessment of myocyte damage, can be used for documentation of cardiac involvement in patients with rheumatic fever where clinical diagnosis is not unequivocal. C1 Hahneman Univ, Sch Med, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. All India Inst Med Sci, New Delhi, India. RP Narula, J (reprint author), Hahnemann Univ Hosp, Broad & Vine,Mail Stop 115, Philadelphia, PA 19102 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 NR 20 TC 5 Z9 6 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 OCT 15 PY 1999 VL 84 IS 8 BP 946 EP + DI 10.1016/S0002-9149(99)00476-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 246AV UT WOS:000083141700021 PM 10532521 ER PT J AU Myles-Worsley, M Coon, H McDowell, J Brenner, C Hoff, M Lind, P Bennett, P Freedman, R Clementz, B Byerley, W AF Myles-Worsley, M Coon, H McDowell, J Brenner, C Hoff, M Lind, P Bennett, P Freedman, R Clementz, B Byerley, W TI Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article ID SACCADIC EYE-MOVEMENTS; SMOOTH-PURSUIT; SCHIZOPHRENIC-PATIENTS; NEUROPHYSIOLOGICAL EVIDENCE; ANTISACCADE PERFORMANCE; BIOLOGICAL RELATIVES; SUSCEPTIBILITY GENE; AFFECTIVE-DISORDERS; PSYCHOTIC-PATIENTS; POTENTIAL LINKAGE AB Eight Utah multigenerational families, each with three to six cases of schizophrenia, were phenotyped with two specific measures of inhibitory neurophysiological functioning, P50 auditory sensory gating (P50), and antisaccade ocular motor performance (AS), A genomewide linkage analysis was performed to screen for loci underlying a qualitative phenotype combining the P50 and AS measures. For this composite inhibitory phenotype, the strongest evidence for linkage was to the D22s315 marker on chromosome 22q (lod score=3.55, theta=0) under an autosomal dominant model. Simulation analyses indicate that this 3.55 lod score is unlikely to represent a false positive result. Lod scores were 2.0 or greater for markers flanking D22s315, A nonparametric linkage (NPL) analysis of the chromosome 22 data showed evidence for allele sharing over the broad region surrounding D22s315 with a maximum NPL score of 3.83 (p =.002) for all pedigrees combined. (C) 1999 Wiley-Liss, Inc. C1 Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84132 USA. Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. RP Myles-Worsley, M (reprint author), Univ Utah, Sch Med, Dept Psychiat, 50 N Med Dr, Salt Lake City, UT 84132 USA. OI Coon, Hilary/0000-0002-8877-5446 FU NIMH NIH HHS [MH42643, MH44212, MH52055] NR 59 TC 72 Z9 73 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 15 PY 1999 VL 88 IS 5 BP 544 EP 550 DI 10.1002/(SICI)1096-8628(19991015)88:5<544::AID-AJMG20>3.0.CO;2-V PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 239QQ UT WOS:000082781500020 PM 10490714 ER PT J AU Sato, T Laver, JH Ogawa, M AF Sato, T Laver, JH Ogawa, M TI Reversible expression of CD34 by murine hematopoietic stem cells SO BLOOD LA English DT Article ID MARROW-CELLS; FLT3/FLK-2 LIGAND; PERIPHERAL-BLOOD; IN-VIVO; TRANSPLANTATION AB We used a mouse transplantation model to address the recent controversy about CD34 expression by hematopoietic stem cells. Cells from Ly-5.1 C57BL/6 mice were used as donor cells and Ly-5.2 mice were the recipients, The test cells were transplanted together with compromised marrow cells of Ly-5.2 mice. First, we confirmed that the majority of the stem cells with long-term engraftment capabilities of normal adult mice are CD34(-). We then observed that, after the injection of 150 mg/kg 5-fluorouracil (5-FU), stem cells may be found in both CD34(-) and CD34(+) cell populations. These results indicated that activated stem cells express CD34. We tested this hypothesis also by using in vitro expansion with interleukin-11 and steel factor of lineage(-) c-kit(+) Sca-1(+) CD34(-) bone marrow cells of normal mice. When the cells expanded for 1 week were separated into CD34(-) and CD34(+) cell populations and tested for their engraftment capabilities, only CD34(+) cells were capable of 2 to 5 months of engraftment. Finally, we tested reversion of CD34(+) stem cells to CD34(-) state. We transplanted Ly-5.1 CD34(+) post-5-FU marrow cells into Ly-5.2 primary recipients and, after the marrow achieved steady state, tested the Ly-5.1 cells of the primary recipients for their engraftment capabilities in Ly-5.2 secondary recipients. The majority of the Ly-5.1 stem cells with long-term engraftment capability were in the CD34(-) cell fraction, indicating the reversion of CD34(+) to CD34(-) stem cells. These observations clearly demonstrated that CD34 expression reflects the activation state of hematopoietic stem cells and that this is reversible. (C) 1999 by The American Society of Hematology. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK/HL 48714, R01-DK32294] NR 19 TC 280 Z9 300 U1 1 U2 5 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 OCT 15 PY 1999 VL 94 IS 8 BP 2548 EP 2554 PG 7 WC Hematology SC Hematology GA 244PM UT WOS:000083060000002 PM 10515856 ER PT J AU Anderson, B AF Anderson, B TI Kohonen neural networks and language SO BRAIN AND LANGUAGE LA English DT Article DE neural networks; language; simulation; Kohonen ID INFANTS; SIGNAL AB Kohonen neural networks are a type of self-organizing network that recognizes the statistical characteristics of input datasets. The application of this type of neural network to language theory is demonstrated in the present note by showing three brief applications: recognizing word borders, learning the limited phonemes of one's native tongue, and category-specific naming impairments. (C) 1999 Academic Press. C1 Birmingham VA Med Ctr, Neurol Serv 127, Birmingham, AL 35233 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. RP Anderson, B (reprint author), Birmingham VA Med Ctr, Neurol Serv 127, 700 S 19th St, Birmingham, AL 35233 USA. NR 11 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 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 15 PY 1999 VL 70 IS 1 BP 86 EP 94 DI 10.1006/brln.1999.2145 PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 250XP UT WOS:000083415800005 PM 10534373 ER PT J AU Wasserman, TH Petroni, GR Millard, FE Chung, CT Barcos, M Johnson, JL Canellos, GP Peterson, BA AF Wasserman, TH Petroni, GR Millard, FE Chung, CT Barcos, M Johnson, JL Canellos, GP Peterson, BA TI Sequential chemotherapy (etoposide, vinblastine, and doxorubicin) and subtotal lymph node radiation for patients with localized Hodgkin disease and unfavorable prognostic features - A phase II Cancer and Leukemia Group B study (9051) SO CANCER LA English DT Article DE Hodgkin disease; chemotherapy; combined modality therapy; Cancer and Leukemia Group B ID COMBINED-MODALITY; CLINICAL STAGES; IRRADIATION; MOPP; ABVD; RISK AB BACKGROUND. The aim of this study was to evaluate a regimen of sequential chemotherapy and radiotherapy for patients with Hodgkin disease. METHODS. The Cancer and Leukemia Group B conducted a Phase II study of three cycles of etoposide, vinblastine, and doxorubicin (EVA) chemotherapy followed by subtotal lymph node radiation for patients with localized Hodgkin disease and unfavorable prognostic features. Fifty-nine patients were enrolled in the study. Fifty-three patients met all study eligibility criteria; 48 of them (91%) had medias tinal disease and 29 (55%) had bulky mediastinal disease. RESULTS. A complete response (CR) occurred in 35 of the patients (66%). Of all patients who had CR, 26% had the CR after the chemotherapy and before the radiation, and 74% after the chemotherapy and radiation. Twenty percent of the patients who had CR experienced disease progression; in these patients, the progression was outside the radiotherapy field in the lung and involved widespread disease. CONCLUSIONS. EVA offers a nonbleomycin-containing alternative for patients in whom preexisting pulmonary disease may be exacerbated by bleomycin and radiation therapy. EVA, as given in this study tin three cycles), was insufficient chemotherapy for patients who had disease in areas outside the radiation fields (occult disease). (C) 1999 American Cancer Society. C1 Washington Univ, Barnes Jewish Hosp, Dept Radiat Oncol, St Louis, MO 63110 USA. Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. USN, Med Ctr, Div Hematol Oncol, San Diego, CA 92152 USA. SUNY Hlth Sci Ctr, Dept Radiat Oncol, Syracuse, NY 13210 USA. Roswell Pk Canc Inst, Div Pathol, Buffalo, NY USA. CALGB, Ctr Stat, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Div Oncol, Mason Canc Ctr, Minneapolis, MN 55455 USA. RP Wasserman, TH (reprint author), Washington Univ, Barnes Jewish Hosp, Dept Radiat Oncol, St Louis, MO 63110 USA. FU NCI NIH HHS [CA21060, CA59518, CA32291] NR 17 TC 11 Z9 11 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 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1999 VL 86 IS 8 BP 1590 EP 1595 DI 10.1002/(SICI)1097-0142(19991015)86:8<1590::AID-CNCR29>3.0.CO;2-4 PG 6 WC Oncology SC Oncology GA 245WJ UT WOS:000083130900029 PM 10526290 ER PT J AU Friedberg, JW Van den Abbeele, AD Kehoe, K Singer, S Fletcher, CD Demetri, GD AF Friedberg, JW Van den Abbeele, AD Kehoe, K Singer, S Fletcher, CD Demetri, GD TI Uptake of radiolabeled somatostatin analog is detectable in patients with metastatic foci of sarcoma SO CANCER LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 16-19, 1998 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol DE sarcoma; octreotide; somatostatin; metastases; scintigraphy; indium-111 pentetreotide ID RECEPTOR SCINTIGRAPHY; NEUROENDOCRINE TUMORS; RADIONUCLIDE THERAPY; OCTREOTIDE; MANAGEMENT; CHEMOTHERAPY; CANCER; ANGIOGENESIS; INHIBITION; IFOSFAMIDE AB BACKGROUND. Somatostatin receptors are present on many types of epithelial tumors, and ligands targeting these receptors are used to treat patients with neuroendocrine malignancies. Preclinical studies have demonstrated the presence of somatostatin receptors on a variety of mesenchymal tumors by in vitro receptor autoradiography. The use of radiolabeled somatostatin analogs to assess the presence of somatostatin receptors in vivo has been established, but use of this technique to evaluate human sarcomas has not been reported previously. METHODS. Seventeen patients (13 females and 4 males) with metastatic sarcoma underwent imaging via somatostatin-receptor scintigraphy. Scans were performed using indium -111 pentetreotide. Planar studies and single photon emission computed tomography imaging were performed at 4 and 24 hours, and results of scintigraphy were correlated with computed tomography findings. RESULTS. Twelve of 17 scans showed increased uptake in regions of known metastatic disease. There was no apparent correlation with scan positivity and patient age, histology, site of disease, or duration of diagnosis. CONCLUSIONS. Seventy-one percent of patients with advanced soft-tissue sarcomas had positive scintigraphy scans demonstrating tumor expression of somatostatin receptors subtype 2 in vivo. Imaging with indium-lll pentetreotide could be studied as an adjunct to conventional imaging modalities for assessment of sarcoma patients. Further research is needed to determine the prognostic implications of somatostatin receptor subtype 2 positivity, including larger studies to evaluate any potential correlation with metastatic behavior and other clinical outcomes. (C) 1999 American Cancer Society. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Nucl Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Friedberg, JW (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 11 Z9 11 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1999 VL 86 IS 8 BP 1621 EP 1627 DI 10.1002/(SICI)1097-0142(19991015)86:8<1621::AID-CNCR33>3.0.CO;2-M PG 7 WC Oncology SC Oncology GA 245WJ UT WOS:000083130900033 PM 10526294 ER PT J AU Kolodner, RD Tytell, JD Schmeits, JL Kane, MF Das Gupta, R Weger, J Wahlberg, S Fox, EA Peel, D Ziogas, A Garber, JE Syngal, S Anton-Culver, H Li, FP AF Kolodner, RD Tytell, JD Schmeits, JL Kane, MF Das Gupta, R Weger, J Wahlberg, S Fox, EA Peel, D Ziogas, A Garber, JE Syngal, S Anton-Culver, H Li, FP TI Germ-line msh6 mutations in colorectal cancer families SO CANCER RESEARCH LA English DT Article ID MISMATCH REPAIR GENES; MICROSATELLITE INSTABILITY; CELL-LINES; TUMOR; HMLH1; SUSCEPTIBILITY; EXPRESSION; CARCINOMA; DEFICIENT; HMSH2 AB Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due primarily to inherited mutations in two mismatch repair genes, MSH2 and MLH1, whereas germ-line mutations in other mismatch repair genes are rare. We examined the frequency of germ-line msh6 mutations in a population-based series of 140 colorectal cancer patients, including 45 sporadic cases, 91 familial non-HNPCC cases, and 4 HNPCC cases. Among the 91 population-based familial non-HNPCC cases, germ-hue msh6 mutations were found in 6 patients (7.1% of probands analyzed; median age at diagnosis, 61 years). These mutations included a splice site mutation, a frameshift mutation, two missense mutations that were demonstrated to be loss of function mutations, and two missense mutations for which functional studies were not possible. In contrast, germ-line msh6 mutations were not found in any of the 45 sporadic cases and the 4 HNPCC eases in the population-based series or In the second series of 58 clinic-based, primarily HNPCC families. Our data suggest that germ-line msh6 mutations predispose individuals to primarily late-onset, familial colorectal carcinomas that do not fulfill classic criteria for HNPCC. C1 Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92697 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kolodner, RD (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM rkolodner@ucsd.edu FU NCI NIH HHS [CA67151] NR 27 TC 256 Z9 264 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1999 VL 59 IS 20 BP 5068 EP 5074 PG 7 WC Oncology SC Oncology GA 248GU UT WOS:000083267400004 PM 10537275 ER PT J AU Chuang, YYE Chen, Q Brown, JP Sedivy, JM Liber, HL AF Chuang, YYE Chen, Q Brown, JP Sedivy, JM Liber, HL TI Radiation-induced mutations at the autosomal thymidine kinase locus are not elevated in p53-null cells (vol 59, pg 3073, 1999) SO CANCER RESEARCH LA English DT Correction C1 Massachusetts Gen Hosp, Boston, MA 02115 USA. Brown Univ, Providence, RI 02912 USA. Roslin Inst, Roslin, Midlothian, Scotland. RP Chuang, YYE (reprint author), Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1999 VL 59 IS 20 BP 5400 EP 5400 PG 1 WC Oncology SC Oncology GA 248GU UT WOS:000083267400055 ER PT J AU Celli, J Duijf, P Hamel, BCJ Bamshad, M Kramer, B Smits, APT Newbury-Ecob, R Hennekam, RCM Van Buggenhout, G van Haeringen, B Woods, CG van Essen, AJ de Waal, R Vriend, G Haber, DA Yang, A McKeon, F Brunner, HG van Bokhoven, H AF Celli, J Duijf, P Hamel, BCJ Bamshad, M Kramer, B Smits, APT Newbury-Ecob, R Hennekam, RCM Van Buggenhout, G van Haeringen, B Woods, CG van Essen, AJ de Waal, R Vriend, G Haber, DA Yang, A McKeon, F Brunner, HG van Bokhoven, H TI Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome SO CELL LA English DT Article ID SPLIT FOOT LOCUS; LIMB DEVELOPMENT; GENE; PROTEIN; EXPRESSION; SEQUENCE; DATABASE; COMPLEX; DEFECTS; MODEL AB EEC syndrome is an autosomal dominant disorder characterized by ectrodactyly, ectodermal dysplasia, and facial clefts. We have mapped the genetic defect in several EEC syndrome families to a region of chromosome 3q27 previously implicated in the EEC-like disorder, limb mammary syndrome (LMS). Analysis of the p63 gene, a homolog of p53 located in the critical LMS/EEC interval, revealed heterozygous mutations in nine unrelated EEC families. Eight mutations result in amino acid substitutions that are predicted to abolish the DNA binding capacity of p63. The ninth is a frameshift mutation that affects the p63 alpha, but not p63 beta and p63 gamma isotypes. Transactivation studies with these mutant p63 isotypes provide a molecular explanation for the dominant character of p63 mutations in EEC syndrome. C1 Univ Nijmegen Hosp, Dept Human Genet 417, NL-6500 HB Nijmegen, Netherlands. Univ Utah, Hlth Sci Ctr, Dept Pediat, Salt Lake City, UT 84112 USA. Shriners Hosp Children, Intermt Unit, Salt Lake City, UT 84112 USA. Royal Hosp Sick Children, United Bristol Healthcare NHS Trust Clin Genet Se, Bristol BS2 8BJ, Avon, England. Univ Amsterdam, Acad Med Ctr, Inst Human Genet, NL-1105 AZ Amsterdam, Netherlands. Univ Hosp Gasthuisberg, Ctr Human Genet, B-3000 Louvain, Belgium. Leiden Univ, Med Ctr, Dept Clin Genet, NL-2333 SA Leiden, Netherlands. St James Univ Hosp, Dept Clin Genet, Leeds LS9 7TF, W Yorkshire, England. Univ Groningen, Dept Med Genet, NL-9713 AW Groningen, Netherlands. Univ Nijmegen Hosp, Dept Pathol, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen, CMBI, NL-6500 GL Nijmegen, Netherlands. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP van Bokhoven, H (reprint author), Univ Nijmegen Hosp, Dept Human Genet 417, Box 9101, NL-6500 HB Nijmegen, Netherlands. RI woods, christopher/A-1361-2010; Vriend, Gert/D-6730-2011; van Bokhoven, Hans/D-8764-2012; Duijf, Pascal/E-7110-2012; Brunner, Han/C-9928-2013; Vriend, G./H-8112-2014; Bokhoven, J.H.L.M./H-8015-2014; Waal, R.M.W./L-4739-2015 OI Duijf, Pascal/0000-0001-8646-9843; NR 43 TC 443 Z9 461 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 15 PY 1999 VL 99 IS 2 BP 143 EP 153 DI 10.1016/S0092-8674(00)81646-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 246JB UT WOS:000083159700005 PM 10535733 ER PT J AU Bjorbaek, C El-Haschimi, K Frantz, JD Flier, JS AF Bjorbaek, C El-Haschimi, K Frantz, JD Flier, JS TI The role of SOCS-3 in leptin signaling and leptin resistance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OBESE GENE; ERYTHROPOIETIN RECEPTOR; DIABETIC MICE; DB/DB MICE; OB/OB MICE; PROTEIN; ACTIVATION; CELLS; IDENTIFICATION; EXPRESSION AB We earlier demonstrated that leptin induces expression of SOCS-3 mRNA in the hypothalamus. Furthermore, transfection data suggest that SOCS-3 is an inhibitor of leptin signaling. However, little is known about the regulation of SOCS-3 expression by leptin and the mechanism by which SOCS-3 inhibits leptin action. We here show that in CHO cells stably expressing the long form of the leptin receptor (CHO-OBRl), leptin induces transient expression of endogenous SOCS-3 mRNA but not of CIS, SOCS-1, or SOCS-2 mRNA. SOCS-3 protein levels were maximal after 2-3 h of leptin treatment and remained elevated at 20 h. Furthermore, in leptin-pretreated CHO-OBRl cells, proximal leptin signaling was blocked for more than 20 h after pretreatment, thus correlating with increased SOCS-3 expression. Leptin pretreatment did not affect cell surface expression of leptin receptors as measured by I-125-Peptin binding assays. In transfected COS cells, forced expression of SOCS-3 results in inhibition of leptin-induced tyrosine phosphorylation of JAK2. Finally, JAK2 co-immunoprecipitates with SOCS-3 in lysates from leptin-treated COS cells. These results suggest that SOCS-3 is a leptin-regulated inhibitor of proximal leptin signaling in vivo. Excessive SOCS-3 activity in leptin-responsive cells is therefore a potential mechanism for leptin resistance, a characteristic feature in human obesity. C1 Harvard Univ, Sch Med, Dept Med, Div Endocrinol,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Flier, JS (reprint author), Harvard Univ, Sch Med, Dept Med, Div Endocrinol,Beth Israel Deaconess Med Ctr, 99 Brookline Ave,Res N, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK R37 28082] NR 44 TC 404 Z9 431 U1 0 U2 12 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 OCT 15 PY 1999 VL 274 IS 42 BP 30059 EP 30065 DI 10.1074/jbc.274.42.30059 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246QQ UT WOS:000083176400071 PM 10514492 ER PT J AU Parhami-Seren, B Bell, C Margolies, MN Haupert, GT AF Parhami-Seren, B Bell, C Margolies, MN Haupert, GT TI Monoclonal antibodies that distinguish between two related digitalis glycosides, ouabain and digoxin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AZOPHENYLARSONATE-SPECIFIC ANTIBODIES; BOVINE ADRENOCORTICAL-CELLS; SODIUM-TRANSPORT INHIBITOR; HIGH-AFFINITY; ENDOGENOUS OUABAIN; PHAGE DISPLAY; HUMAN PLASMA; COMPOUND; BINDING; HYPOTHALAMUS AB The exogenous digitalis glycosides, ouabain and digoxin, have been widely used in humans to treat congestive heart failure and cardiac arrhythmias, Several reports have also pointed to the existence of endogenous ouabain- and digoxin-like compounds, hut their precise roles in mammalian physiology and various disorders of the circulation are not clear. In an attempt to produce specific Abs for the purification and identification of endogenous ouabain-like compounds, somatic cell fusion was used to produce mAbs specific for ouabain, Our attempts to produce ouabain-specific mAbs were unsuccessful when ouabain was coupled to exogenous proteins such as bovine gamma-globulins, BSA, and human serum albumin. However, when ouabain was coupled to an Ab of A/J mice origin and the same strain of mouse was used for immunization with ouabain-ab conjugate, three Abs (1-10, 5A12, and 7-1) specific for ouabain were obtained. In assays of fluorescence quenching and saturation equilibrium with tritiated ouabain, Ab 1-10 exhibited 200 nM affinity for ouabain, These three mAbs are distinguished from existing Abs to ouabain and digoxin by their specificity for ouabain and lack of cross-reactivity with digoxin. Specificity studies showed that the loss of cross-reactivity was correlated with the presence of a hydroxyl group at either position 12 beta (digoxin) or 16 beta (gitoxin) of the steroid ring. These Abs can be used to develop assays for detection and characterization of ouabain-like molecules in vivo. C1 Massachusetts Gen Hosp, CNY8, Renal Unit, Dept Surg, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Med Serv, Charlestown, MA 02129 USA. RP Haupert, GT (reprint author), Massachusetts Gen Hosp, CNY8, Renal Unit, Dept Surg, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA24432]; NHLBI NIH HHS [R01HL52282]; NIAID NIH HHS [R29AI33175] NR 39 TC 5 Z9 5 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 OCT 15 PY 1999 VL 163 IS 8 BP 4360 EP 4366 PG 7 WC Immunology SC Immunology GA 243AK UT WOS:000082974800037 PM 10510376 ER PT J AU Lian, JP Huang, RY Robinson, D Badwey, JA AF Lian, JP Huang, RY Robinson, D Badwey, JA TI Activation of p90(RSK) and cAMP response element binding protein in stimulated neutrophils: Novel effects of the pyridinyl imidazole SB 203580 on activation of the extracellular signal-regulated kinase cascade SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAP KINASE; TYROSINE PHOSPHORYLATION; P21-ACTIVATED KINASES; RAPID ACTIVATION; S6 KINASE; IN-VITRO; P38; INHIBITORS; SUBSTRATE; FMLP AB Neutrophils stimulated with the chemoattractant FMLP or the phorbol ester PMA are known to exhibit activation of a 90-kDa renaturable protein kinase. Activation of this kinase was maximal at similar to 1-3 min after cell stimulation and the time course for activation was similar to that of the extracellular-regulated kinases (ERKs) and p38-mitogen activated protein kinase (p38(MAPK)). Compounds that block activation of ERK-1/2 (PD 98059) or that inhibit the activity of p38(MARK) (SB 203580) blocked activation of this 90-kDa kinase. SE 203580 is a highly selective inhibitor of p38(MARK) in vitro and is under intense study as a lead compound for developing novel anti-inflammatory agents. However, we demonstrate that SB 203580 at concentrations greater than or equal to 10 mu M can also inhibit activation of ERK-1/2 in neutrophils. An Ab to the protein kinase p90(RSK2) (also referred to as MAPKAP-K1b, or p90(rsk)) immunoprecipitated the active 90-kDa kinase from lysates of stimulated neutrophils. No activity was observed for this enzyme in immunoprecipitates obtained from unstimulated cells, and the amounts of activity were markedly reduced if the cells mere treated with PD 98059 or SE 203580 before stimulation. Neutrophils stimulated with FMLP exhibited phosphorylation of the cAMP response element binding protein (CREB), and this reaction was inhibited by SB 203580 and PD 98059. These data establish that the renaturable 90-kDa protein kinase is p90(RSK2) and that CREB may be a substrate for this enzyme in these cells. Novel effects of compound SB 203580 on stimulated neutrophils are also described. C1 Boston Biomed Res Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02114 USA. RP Badwey, JA (reprint author), Boston Biomed Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI 23323]; NIAMS NIH HHS [AR 43518]; NIDDK NIH HHS [DK 50015] NR 60 TC 43 Z9 43 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1999 VL 163 IS 8 BP 4527 EP 4536 PG 10 WC Immunology SC Immunology GA 243AK UT WOS:000082974800057 PM 10510396 ER PT J AU Thies, MJW Mayer, J Augustine, JG Frederick, CA Lilie, H Buchner, J AF Thies, MJW Mayer, J Augustine, JG Frederick, CA Lilie, H Buchner, J TI Folding and association of the antibody domain C(H)3: Prolyl isomerization preceeds dimerization SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE crystal structure; antibody; protein folding; C(H)3 domain; PPIase ID IMMUNOGLOBULIN LIGHT CHAIN; BETA-SHEET; GUANIDINE-HYDROCHLORIDE; CONSTANT FRAGMENT; ATOMIC MODELS; FC FRAGMENT; PROTEIN; DENATURATION; STABILITY; EQUILIBRIUM AB The simplest naturally occuring model system for studying immunoglobulin folding and assembly is the non-covalent homodimer formed by the C-terminal domains (C(H)3) of the heavy chains of IgG. Here, we describe the structure of recombinant C(H)3 dimer as determined by X-ray crystallography and an analysis of the folding pathway of this protein. Under conditions where prolyl isomerization does not contribute to the folding kinetics, formation of the beta-sandwich structure is the rate-limiting step. beta-Sheet formation of C(H)3 is a slow process, even compared to other antibody domains, while the subsequent association of the folded monomers is fast. After long-time denaturation, the majority of the unfolded C(H)3 molecules reaches the native state in two serial reactions, involving the re-isomerization of the Pro35-peptide bond to the cis configuration. The species with the wrong isomer accumulate as a monomeric intermediate. Importantly, the isomerization to the correct cis configuration is the prerequisite for dimerization of the C(H)3 domain. In contrast, in the Fab fragment of the same antibody, prolyl isomerization occurs after dimerization demonstrating that within one protein, comprised of highly homologous domains, both the kinetics of beta-sandwich formation and the stage at which prolyl isomerization occurs during the folding process can be completely different. (C) 1999 Academic Press. C1 Tech Univ Munich, Inst Organ Chem & Biochem, D-85747 Garching, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Halle Wittenberg, Inst Biotechnol, D-06120 Halle, Germany. RP Buchner, J (reprint author), Tech Univ Munich, Inst Organ Chem & Biochem, Lichtenbergerstr 4, D-85747 Garching, Germany. RI Buchner, Johannes/A-2651-2010 NR 51 TC 68 Z9 68 U1 0 U2 3 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 OCT 15 PY 1999 VL 293 IS 1 BP 67 EP 79 DI 10.1006/jmbi.1999.3128 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 247TL UT WOS:000083236000007 PM 10512716 ER PT J AU Lewis, SE Mannion, RJ White, FA Coggeshall, RE Beggs, S Costigan, M Martin, JL Dillmann, WH Woolf, CJ AF Lewis, SE Mannion, RJ White, FA Coggeshall, RE Beggs, S Costigan, M Martin, JL Dillmann, WH Woolf, CJ TI A role for HSP27 in sensory neuron survival SO JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; axotomy; nerve growth factor; heat shock protein; dorsal root ganglion; neonatal ID ROOT GANGLION NEURONS; HEAT-SHOCK-PROTEIN; NERVE GROWTH-FACTOR; DORSAL-ROOT; CELL-DEATH; SCIATIC-NERVE; DEVELOPMENTAL REGULATION; CONSTITUTIVE EXPRESSION; SYMPATHETIC NEURONS; CONFERS RESISTANCE AB Peripheral nerve injury in neonatal rats results in the death of the majority of the axotomized sensory neurons by 7 d after injury. In adult animals, however, all sensory neurons survive for at least 4 months after axotomy. How sensory neurons acquire the capacity to survive axonal injury is not known. Here we describe how the expression of the small heat shock protein 27 (HSP27) is correlated with neuronal survival after axotomy in vivo and after NGF withdrawal in vitro. The number of HSP27-immunoreactive neurons in the L4 DRG is low at birth and does not change significantly for 21 d after postnatal day 0 (P0) sciatic nerve axotomy. In contrast, in the adult all axotomized neurons begin to express HSP27. One week after P0 sciatic nerve section the total number of neurons in the L4 DRG is dramatically reduced, but all surviving axotomized neurons, as identified by c-jun immunoreactivity, are immunoreactive for HSP27. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling reveals that very few HSP27-expressing neurons are dying 48 hr after neonatal axotomy. In vitro, a similar correlation exists between HSP27 expression and survival; in P0 DRG cultures, neurons that express HSP27 preferentially survive NGF withdrawal. Finally, overexpression of human HSP27 in neonatal rat sensory and sympathetic neurons significantly increases survival after NGF withdrawal, with nearly twice as many neurons surviving at 48 hr. Together these results suggest that HSP27 in sensory neurons plays a role in promoting survival after axotomy or neurotrophin withdrawal. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. UCL, Dept Anat, London, England. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp E, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St, Charlestown, MA 02129 USA. RI White, Fletcher/F-2895-2012 FU NINDS NIH HHS [NS38253-01] NR 41 TC 129 Z9 134 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1999 VL 19 IS 20 BP 8945 EP 8953 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 244VY UT WOS:000083072500027 PM 10516313 ER PT J AU Rowitch, DH St-Jacques, B Lee, SMK Flax, JD Snyder, EY McMahon, AP AF Rowitch, DH St-Jacques, B Lee, SMK Flax, JD Snyder, EY McMahon, AP TI Sonic hedgehog regulates proliferation and inhibits differentiation of CNS precursor cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Sonic hedgehog; tumorigenesis; GAL4; central nervous system; proliferation; differentiation; Wnt-1; medulloblastoma; transgenic mice ID DORSAL SPINAL-CORD; MOTOR-NEURON INDUCTION; CENTRAL-NERVOUS-SYSTEM; VENTRAL MIDLINE CELLS; LOOP-HELIX FACTORS; SIGNALING PATHWAY; GENE-EXPRESSION; FLOOR PLATE; HUMAN HOMOLOG; OLIGODENDROCYTE LINEAGE AB Activation of the Sonic hedgehog (Shh) signal transduction pathway is essential for normal pattern formation and cellular differentiation in the developing CNS. However, it is also thought to be etiological in primitive neuroectodermal tumors. We adapted GAL4/UAS methodology to ectopically express full-length Shh in the dorsal neural tube of transgenic mouse embryos commencing at 10 d postcoitum (dpc), beyond the period of primary dorsal-ventral pattern formation and floor-plate induction. Expression of Shh was maintained until birth, permitting us to investigate effects of ongoing exposure to Shh on CNS precursors in vivo. Proliferative rates of spinal cord precursors were twice that of wild-type littermates at 12.5 dpc. In contrast, at late fetal stages (18.5 dpc), cells that were Shh-responsive but postmitotic were present in persistent structures reminiscent of the ventricular zone germinal matrix. This tissue remained blocked in an undifferentiated state. These results indicate that cellular competence restricts the proliferative response to Shh in vivo and provide evidence that proliferation and differentiation can be regulated separately in precursor cells of the spinal cord. Thus, Hedgehog signaling may contribute to CNS tumorigenesis by directly enhancing proliferation and preventing neural differentiation in selected precursor cells. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. FU NICHD NIH HHS [HD01182, HD30249]; NINDS NIH HHS [NS32691] NR 74 TC 255 Z9 264 U1 4 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1999 VL 19 IS 20 BP 8954 EP 8965 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 244VY UT WOS:000083072500028 PM 10516314 ER PT J AU McManus, MF Chen, LC Vallejo, I Vallejo, M AF McManus, MF Chen, LC Vallejo, I Vallejo, M TI Astroglial differentiation of cortical precursor cells triggered by activation of the cAMP-dependent signaling pathway SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neural precursor cells; astrocyte differentiation; cortical development; cAMP; conditional immortalization; GFAP; nestin ID FIBROBLAST GROWTH-FACTOR; ELEMENT-BINDING PROTEIN; CENTRAL-NERVOUS-SYSTEM; BONE MORPHOGENETIC PROTEINS; CYCLIC-AMP; PROGENITOR CELLS; STEM-CELLS; IN-VITRO; HIPPOCAMPAL-NEURONS; CEREBRAL-CORTEX AB In the developing brain, differentiation of neural precursors into neurons or glial cells occurs in response to neurotrophic factors acting on the cell surface. Intracellular signaling mechanisms that relay information to initiate differentiative responses of neural precursor cells are poorly understood. To investigate whether stimulation of the cAMP-dependent signaling pathway participates in differentiative responses of cells in the developing CNS, we performed experiments using both conditionally immortalized neural precursor cells (RC2.E10 cells) and primary cultures of cells from developing rat cortex. Initially, we determined that RC2.E10 cells retain phenotypic features of neural precursors after inactivation of the immortalizing oncogene, a temperature-sensitive mutant of the simian virus 40 large-T antigen (SV40T). We found that, once SV40T is inactivated, RC2.E10 cells cease to divide and die. However, RC2.E10 cells can proliferate in the presence of basic fibroblast growth factor. In addition, they express nestin, a marker of neural precursor cells. Both RC2.E10 cells and primary cortical precursor cells undergo astroglial differentiation in response to cAMP stimulation by treatment with 8-bromo-cAMP. In both cases, cAMP-induced astrocyte differentiation is characterized by morphological changes, stimulation of glial fibrillary acidic protein expression, downregulation of nestin expression, and decreased proliferation. No increases in the expression of neuronal or oligodendrocytic markers were observed. Our results support the notion that the developing CNS contains neural precursor cells with the capacity of undergoing astrocyte differentiation in response to increased intracellular cAMP concentrations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Vallejo, M (reprint author), CSIC, Inst Invest Biomed, Arturo Duperier 4, E-28029 Madrid, Spain. OI Vallejo Fernandez de la Reguera, Inmaculada/0000-0002-7047-9219 FU NIDDK NIH HHS [DK-49670] NR 73 TC 48 Z9 50 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1999 VL 19 IS 20 BP 9004 EP 9015 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 244VY UT WOS:000083072500032 PM 10516318 ER PT J AU Morrill, JA Cannon, SC AF Morrill, JA Cannon, SC TI Effects of mutations causing hypokalaemic periodic paralysis on the skeletal muscle L-type Ca2+ channel expressed in Xenopus laevis oocytes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GENOTYPE-PHENOTYPE CORRELATIONS; CALCIUM CURRENT ACTIVATION; DIHYDROPYRIDINE RECEPTOR; SODIUM-CHANNELS; CHARGE MOVEMENT; BETA-SUBUNIT; S4 SEGMENT; REPEAT-I; INACTIVATION; VOLTAGE AB 1.A truncated form of the rabbit alpha(1S) Ca2+ channel subunit (alpha(1S Delta C)) was expressed with the beta(1b), alpha(2)delta and gamma auxiliary subunits in Xenopus laevis oocytes. After 5-7 days, skeletal muscle L-type currents were measured (469 +/- 48 nA in 10 mM Ba2+). All three of the auxiliary subunits were necessary to record significant L-type current. A rapidly inactivating, dihydropyridine-insensitive endogenous Ba2+ current was observed in oocytes expressing the auxiliary subunits without an exogenous alpha subunit. Expression of full-length alpha(1S) gave 10-fold smaller currents than the truncated form. 2. Three missense mutations causing hypokalaemic periodic paralysis (R528H in domain II S4 of the alpha(1S) subunit; R1239H and R1239G in domain IV S4) were introduced into alpha(1S Delta C) and expressed in oocytes. L-type current was separated from the endogenous current by nimodipine subtraction. All three of the mutations reduced L-type current amplitude (similar to 40 % for R528H, similar to 60-70 % for R1239H and R1239G). 3. The disease mutations altered the activation properties of L-type current. R528H shifted the G(V) curve similar to 5 mV to the left and modestly reduced the voltage dependence of the activation time constant, tau(act). R1239H and R1239G shifted the Q(V) curve similar to 5-10 mV to the right and dramatically slowed tau(act) at depolarized test potentials. 4. The voltage dependence of steady-state inactivation was not significantly altered by any of the disease mutations. 5. Wild-type and mutant L-type currents were also measured in the presence of (-)-Bay K8644, which boosted the amplitude similar to 5- to 7-fold, The effects of the mutations on the position of the G(V) curve and the voltage dependence of tau(act) were essentially the same as in the absence of agonist. Bay K-enhanced tail currents were slowed by R528H and accelerated by R1239H and R1239G. 6.We conclude that the domain IV mutations R1239H and R1239G; have similar effects on the gating properties of the skeletal muscle L-type Ca2+ channel expressed in Xenopus oocytes, while the domain II mutation R528H has distinct effects. This result implies that the location of the substitutions is more important than their degree of conservation in determining their biophysical consequences. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02214 USA. Harvard Univ, Sch Med, Div Med Sci, Program Neurosci, Boston, MA 02214 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02214 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, Dept Neurol, EDR 413A, Boston, MA 02214 USA. FU NIAMS NIH HHS [R01 AR042703, R37 AR042703, AR42703] NR 48 TC 47 Z9 51 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 15 PY 1999 VL 520 IS 2 BP 321 EP 336 DI 10.1111/j.1469-7793.1999.00321.x PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 252RX UT WOS:000083517000002 PM 10523403 ER PT J AU Morgalla, MH Stumm, F Hesse, G AF Morgalla, MH Stumm, F Hesse, G TI A computer-based method for continuous single pulse analysis of intracranial pressure waves SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE ICP monitoring; ICP single pulse analysis; ICP wave analysis ID SYSTEMS-ANALYSIS; MONITOR AB Introduction: The single pulse analysis of intracranial pressure waves provides valuable information about the autoregulative processes after head injury. This method has not been used for routine clinical assessment as yet. Current methods for evaluation of intracranial pressure waves are based on spectral analysis or related techniques. This imposes restrictions on the wave sequences available for the investigation of ICP attributes. Therefore, we have developed a computer-based method, which enables continuous analysis of each pulse of the ICP wave, in any clinical setting. Method: Firstly, the raw data of the ICP wave is continuously recorded by the Multifunctional Anaesthetic Record System (MARS, Hewlett Packard). The recorded data is then subjected to single pulse wave analysis by our software. Each single pulse is identified by the algorithm. The maximum, minimum and mean value, as well as amplitude and gradient are calculated in each pulse pressure. All conceivable correlations of the listed parameters can be examined. Results: We applied our software in 9 cases with head injury and evaluated the measurements over 59 days (1400 h). More than 7 million single pulse pressures have been analyzed off-line. The software proved to be accurate and easy to apply. It was possible to calculate correlations between the different wave attributes on a broad basis of data. Parameters of special clinical interest were the amplitude of the single pulse pressure and the gradient. Conclusion: This method is an improvement on ICP single pulse pressure analysis and facilitates its clinical application. It creates the possibility for continuous long-term analysis of the ICP wave attributes under any clinical condition without loss of data. There are indications that the amplitude and the gradient of the ICP pulse pressure could provide valuable additional information for clinical assessment. However, further evaluation is required. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Univ Tuebingen, Div Neurosurg, Tuebingen, Germany. Data Ctr Schleswig Holstein, Kiel, Germany. RP Morgalla, MH (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, 32 Fruit St, Boston, MA 02114 USA. NR 26 TC 18 Z9 18 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 1999 VL 168 IS 2 BP 90 EP 95 DI 10.1016/S0022-510X(99)00137-9 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 252UA UT WOS:000083519600004 PM 10526189 ER PT J AU Golub, TR Slonim, DK Tamayo, P Huard, C Gaasenbeek, M Mesirov, JP Coller, H Loh, ML Downing, JR Caligiuri, MA Bloomfield, CD Lander, ES AF Golub, TR Slonim, DK Tamayo, P Huard, C Gaasenbeek, M Mesirov, JP Coller, H Loh, ML Downing, JR Caligiuri, MA Bloomfield, CD Lander, ES TI Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring SO SCIENCE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ALVEOLAR RHABDOMYOSARCOMA; SACCHAROMYCES-CEREVISIAE; BURKITT-LYMPHOMA; SURFACE-ANTIGENS; TRANSLOCATION; CELLS; MICROARRAY; FUSION AB Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute Leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid Leukemia (AML) and acute Lymphoblastic Leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Canc & Leukemia Grp B, Columbus, OH 43210 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Golub, TR (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 52 TC 6473 Z9 6857 U1 56 U2 505 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 15 PY 1999 VL 286 IS 5439 BP 531 EP 537 DI 10.1126/science.286.5439.531 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245RD UT WOS:000083121200061 PM 10521349 ER PT J AU Goldmann, WH Teodoridis, JM Sharma, CP Alonso, JL Isenberg, G AF Goldmann, WH Teodoridis, JM Sharma, CP Alonso, JL Isenberg, G TI Fragments from alpha-actinin insert into reconstituted lipid bilayers SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN SECONDARY STRUCTURE; ACIDIC-PHOSPHOLIPID-BILAYERS; VINCULIN; BINDING; TEMPERATURE; NETWORKS; IDENTIFICATION; CYTOSKELETON; ASSOCIATION; PREDICTION AB Recent experiments have indicated that alpha-actinin interacts with phospholipid membranes. Using computer analysis methods we determined two possible lipid binding sites capable of membrane attachment/insertion, residues 281-300 and 720-739 of the primary amino acid sequence on smooth muscle cu-actinin. Having expressed these regions as fusion proteins with schistosomal GST (glutathione S-transferase), we used differential scanning calorimetry (DSC) to investigate their interaction with mixtures of zwitterionic (dimyristoyl-L-alpha-phosphatidylcholine, DMPC) and anionic (dimyristoyl-L-alpha-phosphatidylglycerol, DMPG) phospholipids in reconstituted lipid bilayers. Calorimetric measurements showed that as fusion protein concentration increased, the main chain transition enthalpy decreased and chain melting temperatures shifted, which is indicative of partial protein insertion into the hydrophobic region of the lipid membranes. Centrifugation assay and subsequent SDS/Page chromatography confirmed this finding. (C) 1999 Academic Press. C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Charlestown, MA USA. Boston Bioprod, Ashland, MA USA. Tech Univ Munich, Dept Biophys E22, D-8046 Garching, Germany. RP Goldmann, WH (reprint author), Childrens Hosp, Dept Pathol, 300 Longwood Ave,Enders 10, Boston, MA 02115 USA. RI Alonso, Jose Luis/G-7961-2012; Goldmann, Wolfgang/H-5572-2013 NR 38 TC 11 Z9 11 U1 0 U2 2 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 OCT 14 PY 1999 VL 264 IS 1 BP 225 EP 229 DI 10.1006/bbrc.1999.1495 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 246FJ UT WOS:000083153500040 PM 10527869 ER PT J AU DiPetrillo, MD Tibbetts, T Kleanthous, H Killeen, KP Hohmann, EL AF DiPetrillo, MD Tibbetts, T Kleanthous, H Killeen, KP Hohmann, EL TI Safety and immunogenicity of phoP/phoQ-deleted Salmonella typhi expressing Helicobacter pylori urease in adult volunteers SO VACCINE LA English DT Article DE Salmonella typhi; Helicobacter pylori; bacterial vector; innoculation, oral; urease; human study ID VACCINE STRAIN; ESCHERICHIA-COLI; IMMUNE-RESPONSE; PURB GENE; IMMUNIZATION; CONSTRUCTION; PROTECTION; ANTIGEN; VECTOR; MICE AB Salmonella typhi Ty800, deleted for the Salmonella phoP/phoQ virulence regulon has been shown to be a safe and immunogenic single dose oral typhoid fever vaccine in volunteers. This promising Vaccine strain was modified to constitutively express a heterologous protein of Gram negative bacterial origin, Helicobacter pylori urease subunits A and B, yielding S. typhi strain Ty1033. Seven volunteers received single oral doses of greater than or equal to 10(10) colony forming units of Ty1033; an eighth volunteer received two doses 3 months apart. Side effects were similar to those observed previously in volunteers who received the unmodified vector Ty800. All volunteers had strong mucosal immune responses to vaccination as measured by increases in IgA-secreting cells in peripheral blood directed against S, typhi antigens. Seven of eight volunteers had convincing seroconversion as measured by increases in serum IgG directed against S, typhi flagella and lipopolysaccharide antigens by ELISA. No volunteer had detectable mucosal or humoral immune responses to the urease antigen after immunization with single doses of Ty1033. A. subset of three volunteers received an oral booster vaccination consisting of recombinant purified H. pylori urease A/B and E. coli heat labile toxin adjuvant 15 days after immunization with Ty1033. None of three had detectable humoral or mucosal immune responses to urease. Expression of a stable immunogenic protein in an appropriately attenuated S. typhi vector did not engender detectable mucosal or systemic antibody responses; additional work will be needed to define variables important for immunogenicity of heterologous antigens carried by live S. typhi vectors in humans. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. OraVax Inc, Cambridge, MA 02139 USA. Avant Immunotherapeut, Needham, MA USA. RP Hohmann, EL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR01066-21]; NIAID NIH HHS [R29AI40672] NR 33 TC 116 Z9 121 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 14 PY 1999 VL 18 IS 5-6 BP 449 EP 459 DI 10.1016/S0264-410X(99)00246-7 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 250PR UT WOS:000083397200010 PM 10519934 ER PT J AU Takasu, H Gardella, TJ Luck, MD Potts, JT Bringhurst, FR AF Takasu, H Gardella, TJ Luck, MD Potts, JT Bringhurst, FR TI Amino-terminal modifications of human parathyroid hormone (PTH) selectively alter phospholipase C signaling via the type 1 PTH receptor: Implications for design of signal-specific PTH ligands SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; HUMAN PTH/PTHRP RECEPTOR; OSTEOBLAST-LIKE CELLS; OSTEOSARCOMA CELLS; ADENYLYL-CYCLASE; FUNCTIONAL EXPRESSION; INTRACELLULAR STORES; PHOSPHATE-TRANSPORT; ACTIVATION DOMAIN AB Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) activate the PTH/PTHrP receptor to trigger parallel increases in adenylyl cyclase (AC) and phospholipase C (PLC). The amino (N)-terminal region of PTH-(1-34) is essential for AC activation. Ligand domains required for activation of PLC, PKC, and other effecters have been less well-defined, although some studies in rodent systems have identified a core region [hPTH-(29-32)] involved in PKC activation. To determine the critical ligand domain(s) for PLC activation, a series of truncated hPTH-(1-34) analogues were assessed using LLC-PK1 cells that stably express abundant transfected human or rat PTH/PTHrP receptors. Phospholipase C signaling and ligand-binding affinity were reduced by carboxyl (C)-terminal truncation of hPTH-(1-34) but were coordinately restored when a binding-enhancing substitution (Glu(19) --> Arg(19)) was placed within hPTH-(1-28), the shortest hPTH peptide that could fully activate both AC and PLC. Phospholipase C, but not AC, activity was reduced by substituting Gly(1) for Ser(1) in hPTH-(1-34) and was eliminated entirely by removing either residue 1 or the alpha-amino group alone. These changes did not alter binding affinity. These findings led to design of an analogue, [Gly(1),Arg(19)]hPTH-(1-28), that was markedly signal-selective, with full AC but no PLC activity. Thus, the extreme N-terminus of hPTH constitutes a critical activation domain for coupling to PLC. The C-terminal region, especially hPTH-(28-31), contributes to PLC activation through effects upon receptor binding but is not required for full PLC activation. The N-terminal determinants of AC and PLC activation in hPTH-(1-34) overlap but are not identical, as subtle modifications in this region may dissociate activation of these two effecters. The [Gly(1),Arg(19)]hPTH-(1-28) analogue, in particular, should prove useful in dissociating AC- from PLC-dependent actions of PTH. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Bringhurst, FR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK11794] NR 57 TC 75 Z9 82 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 12 PY 1999 VL 38 IS 41 BP 13453 EP 13460 DI 10.1021/bi990437n PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250MC UT WOS:000083391300002 PM 10521252 ER PT J AU Shefner, JM Reaume, AG Flood, DG Scott, RW Kowall, NW Ferrante, RJ Siwek, DF Upton-Rice, M Brown, RH AF Shefner, JM Reaume, AG Flood, DG Scott, RW Kowall, NW Ferrante, RJ Siwek, DF Upton-Rice, M Brown, RH TI Mice lacking cytosolic copper/zinc superoxide dismutase display a distinctive motor axonopathy SO NEUROLOGY LA English DT Article DE ALS; SOD1; motor unit estimation ID AMYOTROPHIC-LATERAL-SCLEROSIS; SKELETAL-MUSCLE; UNIT ESTIMATION; NUMBER; AGE; MODEL; RAT AB Objective: To characterize the motor neuron dysfunction in two models by performing physiologic and morphometric studies. Background: Mutations in the gene encoding cytosolic superoxide dismutase 1 (SOD1) account for 25% of familial ALS (FALS), Transgenes with these mutations produce a pattern of lower motor neuron degeneration similar to that seen in patients with FALS. In contrast, mice lacking SOD1 develop subtle motor symptoms by approximately 6 months of age. Methods: Physiologic measurements, including motor conduction and motor unit estimation, were analyzed in normal mice, mice bearing the human transgene for FALS (mFALS mice), and knockout mice deficient in SOD1 (SOD1-KO). In addition, morphometric analysis was performed on the spinal cords of SOD1-KO and normal mice. Results: In mFALS mice, the motor unit number in the distal hind limb declined before behavioral abnormalities appeared, and motor unit size increased. Compound motor action potential amplitude and distal motor latency remained normal until later in the disease. In SOD1-KO mice, motor unit numbers were reduced early but declined slowly with age. In contrast with the mFALS mice, SOD1-KO mice demonstrated only a modest increase in motor unit size. Morphometric analysis of the spinal cords from normal and SOD1-KO mice showed no significant differences in the number and size of motor neurons. Conclusions: The physiologic abnormalities in mFALS mice resemble those in human ALS. SOD1-deficient mice exhibit a qualitatively different pattern of motor unit remodeling that suggests that axonal sprouting and reinnervation of denervated muscle fibers are functionally impaired in the absence of SOD1. C1 SUNY Hlth Sci Ctr, Dept Neurol, Syracuse, NY 13210 USA. Cephalon Inc, W Chester, PA USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Boston, MA 02114 USA. RP Shefner, JM (reprint author), SUNY Hlth Sci Ctr, Dept Neurol, 750 E Adams St, Syracuse, NY 13210 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [AG13846]; NINDS NIH HHS [1P01 NS31248-02, NS37102] NR 23 TC 122 Z9 128 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1239 EP 1246 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200016 PM 10522879 ER PT J AU Kennedy, DN O'Craven, KM Ticho, BS Goldstein, AM Makris, N Henson, JW AF Kennedy, DN O'Craven, KM Ticho, BS Goldstein, AM Makris, N Henson, JW TI Structural and functional brain asymmetries in human situs inversus totalis SO NEUROLOGY LA English DT Article DE situs inversus totalis; cerebral lateralization; asymmetry; functional MRI; language lateralization ID CEREBRAL ASYMMETRIES; LATERALITY; HANDEDNESS; MUTATION; AREAS; ADULT AB Objective: To determine whether individuals with situs inversus totalis CSI), a condition in which there is a mirror-image reversal of asymmetric visceral organs, have alterations in brain asymmetries. Background: The human brain is asymmetric in structure and function. Although correlations between anatomic asymmetries and functional lateralization in human brain have been demonstrated, it has been difficult tu further analyze them. Characterization of asymmetries of brain structure and function in SI might advance the understanding of these relationships. Methods: Using anatomic and functional MRI techniques, we analyzed asymmetries in the brains of three individuals with SI. Results: Two major anatomic asymmetries of the cerebral hemispheres, the frontal and occipital petalia, were reversed in individuals with SI. In contrast, SI subjects had left cerebral hemisphere language dominance on functional MRI analysis as well as strong right=handedness. Conclusion: These observations suggest that the developmental factors determining anatomic asymmetry of the cerebral petalia and viscera are distinct from those producing the functional lateralization of language. C1 Massachusetts Gen Hosp E, Ctr Morphometr Anal, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp E, Ctr Morphometr Anal, 149 13th St, Charlestown, MA 02129 USA. RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA09467]; NINDS NIH HHS [NS34189] NR 32 TC 89 Z9 91 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1260 EP 1265 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200019 PM 10522882 ER PT J AU Gomez-Tortosa, E Newell, K Irizarry, MC Albert, M Growdon, JH Hyman, BT AF Gomez-Tortosa, E Newell, K Irizarry, MC Albert, M Growdon, JH Hyman, BT TI Clinical and quantitative pathologic correlates of dementia with Lewy bodies SO NEUROLOGY LA English DT Article DE dementia; Lewy bodies; AD ID BODY DISEASE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; FEATURES; VARIANT; IMMUNOCYTOCHEMISTRY; NEUROFILAMENT; CONSORTIUM; DIAGNOSIS AB Objectives: To examine the distribution of cortical Lewy bodies (LB) and their contribution to the clinical syndrome in dementia with LB (DLB) and to address their relationship to the pathologic markers of AD and PD. Methods: We studied 25 cases meeting neuropathologic criteria for DLB: 13 cases without AD (Braak stage I or II) and 12 cases with concomitant AD changes (Braak stages III to V). Age at onset, disease duration, and clinical symptoms were reviewed for each case. We quantified the regional distribution of LB in substantia nigra, paralimbic areas (cingulate gyrus, insula, entorhinal cortex, and hippocampus), and neocortex (frontal and occipital association areas) using anti-alpha-synuclein immunostaining. We compared the LB pathology between groups of patients with different symptoms at onset or with specific clinical phenotypes. Results: There were no significant differences in clinical symptoms or LB density between cases with or without concomitant AD. LB density showed a consistent gradient as follows: substantia nigra > entorhinal cortex > cingulate gyrus > insula > frontal cortex > hippocampus > occipital cortex. LB density in substantia nigra and neocortex was not significantly different in cases that started with parkinsonism compared with those that started with dementia. There were no significant differences in LB density in any region among patients with or without cognitive fluctuations, visual hallucinations, delusions, recurrent falls, or parkinsonism. Duration of the disease correlated with a global LB burden for each case (p = 0.02) but did not-correlate with LB density in any individual area. Paralimbic and neocortical LB density were highly correlated with each other (p < 0.0001), but neither of these correlated well with the number of LB in substantia nigra. LB density did not correlate with Braak stage or frequency of neuritic plaques. Conclusions: There is a consistent pattern of vulnerability to LB formation across subcortical, paralimbic, and neocortical structures that is similar for DLB cases with or without-concomitant AD. Paralimbic and neocortical LB do not correlate with LB in substantia nigra, suggesting that DLB should not be considered just a severe form of PD, LB density correlates weakly with clinical symptoms and disease duration. C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, Dept Neurol, 149 13th St,Room 6405, Charlestown, MA 02129 USA. FU NIA NIH HHS [R01-AG07370, AG08487, P50-AG05134] NR 49 TC 133 Z9 133 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1284 EP 1291 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200023 PM 10522886 ER PT J AU MacDonald, ME Vonsattel, MP Shrinidhi, J Couropmitree, NN Cupples, LA Bird, ED Gusella, JF Myers, RH AF MacDonald, ME Vonsattel, MP Shrinidhi, J Couropmitree, NN Cupples, LA Bird, ED Gusella, JF Myers, RH TI Evidence for the GluR6 gene associated with younger onset age of Huntington's disease SO NEUROLOGY LA English DT Article DE Huntington's disease; glutamate receptor; modifier gene AB Huntington's disease (HD) is attributed to a triplet. CAG repeat mutation, and about half of the variation in onset age can be explained by the size of the repeat expansion. Recently, a TAA repeat polymorphism in close linkage to the kainate receptor, GluR6, was reported related to onset age in HD. We examined this polymorphism in 258 unrelated HD-affected persons (172 from a clinic sample and 86 from a postmortem series). This study confirms that the 155 allele is associated with younger onset age of HD and suggests that it is in linkage disequilibrium with a variant of the GluR6 gene or another gene in this region. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, Boston, MA USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brain Tissue Resource Ctr, McLean Hosp, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St, Boston, MA 02118 USA. FU NINDS NIH HHS [NS31862, R0-1NS16367] NR 10 TC 87 Z9 90 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1330 EP 1332 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200030 PM 10522893 ER PT J AU Gonzalez, E Bamshad, M Sato, N Mummidi, S Dhanda, R Catano, G Cabrera, S McBride, M Cao, XH Merrill, G O'Connell, P Bowden, DW Freedman, BI Anderson, SA Walter, EA Evans, JS Stephan, KT Clark, RA Tyagi, S Ahuja, SS Dolan, MJ Ahuja, SK AF Gonzalez, E Bamshad, M Sato, N Mummidi, S Dhanda, R Catano, G Cabrera, S McBride, M Cao, XH Merrill, G O'Connell, P Bowden, DW Freedman, BI Anderson, SA Walter, EA Evans, JS Stephan, KT Clark, RA Tyagi, S Ahuja, SS Dolan, MJ Ahuja, SK TI Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHEMOKINE RECEPTOR-5; PROGRESSION; GENE; TRANSMISSION; INFECTION; VARIANTS; ALLELE; VIRUS; POLYMORPHISMS; MUTATION AB Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals, We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed. C1 Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. Worldwide Clin Trials, Kennesaw, GA 30144 USA. Brooke Army Med Ctr, Dept Clin Invest, Ft Sam Houston, TX 78234 USA. Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Med, Winston Salem, NC 27157 USA. Publ Hlth Res Inst City New York Inc, Dept Mol Genet, New York, NY 10016 USA. RP Ahuja, SK (reprint author), Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU NHLBI NIH HHS [R01 HL043521, HL43521]; NIAID NIH HHS [AI43279, AI46326, R01 AI043279, R01 AI046326, R21 AI046326, R37 AI046326] NR 24 TC 184 Z9 189 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 12 PY 1999 VL 96 IS 21 BP 12004 EP 12009 DI 10.1073/pnas.96.21.12004 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246MD UT WOS:000083166800059 PM 10518566 ER PT J AU Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Wilson, PWF Levy, D AF Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Wilson, PWF Levy, D TI Cross-classification of JNC VI blood pressure stages and risk groups in the framingham heart study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HYPERTENSION; PREVALENCE; HEALTH; POPULATION; DISEASE; METAANALYSIS; THERAPIES; OUTCOMES AB Background: The recently published Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) includes a classification of blood pressure stages and a new risk stratification component. Patients with high-normal blood pressure or hypertension are strati fled into risk group A (no associated cardiovascular disease risk factors, no target organ damage or cardiovascular disease); group B (1 greater than or equal to associated cardiovascular disease risk factor excluding diabetes, no target organ damage or cardiovascular disease); or group C (diabetes or target organ damage or cardiovascular disease). Objective: To examine the prevalence of risk groups and blood pressure stages in a community-based sample. Methods: We evaluated 4962 subjects from the Framingham Heart Study and Framingham Offspring Study examined between 1990 and 1995. We cross-classified men and women separately according to their JNC VI blood pressure stages and risk groups. Results: In the whole sample, 43.7% had optimal or normal blood pressure and 13.4% had high-normal blood pressure; 12.9% had stage 1 hypertension and 30.0% had stage 2 or greater hypertension or were receiving medication. As blood pressure stage increased, the proportion of subjects in group A decreased, whereas the proportion in group C increased. Among those with high-normal blood pressure or hypertension, only 2.4% (all women) were in risk group a, 59.3% were in group B, and 38.2% were in group C. In the high-normal or by pertensive group, 39.4% qualified for lifestyle modification as the initial intervention according to JNC VI recommendations, whereas 60.6% were eligible for initial drug therapy or were already receiving drug therapy. Nearly one third of high-normal subjects were in risk group C, in which early drug therapy may be needed. Among those in stage 1, only 4.0% were in group A, in which prolonged lifestyle modification is recommended. Conclusions: These results protide a foundation for estimating the number of individuals with hypertension who fall into different risk groups that require different treatment approaches. With nearly 50 million individuals with hypertension in the United States, there are important implications for clinicians and policymakers if JNC VI recommendations are widely adopted in clinical practice. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-38038] NR 27 TC 32 Z9 36 U1 1 U2 2 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 OCT 11 PY 1999 VL 159 IS 18 BP 2206 EP 2212 DI 10.1001/archinte.159.18.2206 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 247EY UT WOS:000083208700012 PM 10527298 ER PT J AU van Kammen, DP McAllister-Sistilli, CG Kelley, ME Gurklis, JA Yao, JK AF van Kammen, DP McAllister-Sistilli, CG Kelley, ME Gurklis, JA Yao, JK TI Elevated interleukin-6 in schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; serum; CSF; interleukin-6 ID NERVOUS-SYSTEM INVOLVEMENT; STIMULATORY FACTOR-II; CEREBROSPINAL-FLUID; PLASMA-LEVELS; HALOPERIDOL WITHDRAWAL; RHEUMATOID-ARTHRITIS; SERUM INTERLEUKIN-6; CYTOKINE LEVELS; HUMAN BLOOD; IL-6 AB Interleukin 6 (IL-6) levels have been shown to be increased in a number of autoimmune disorders and have recently been shown to be elevated in the serum of schizophrenic patients. Given the involvement of the CNS in schizophrenia, levels of interleukin-6 in the CSF are also of interest. Thus, we examined levels of both CSF and serum IL-6 concomitantly to determine if these levels were different from control values. In addition, we examined these measures in patients both on and off antipsychotic drugs to determine if any medication or exacerbation effects may account for the difference from controls. CSF IL-6 was measured by ELISA in 61 drug-free male schizophrenic (DSM-IIIR) patients and 25 well-screened healthy male control subjects. Serum IL-6 was measured in 43 of the 61 patients, and in 16 control subjects. Serum IL-6 was significantly higher in the schizophrenic patients compared to control subjects. CSF IL-6 was also higher in the patients, but the difference was not statistically significant. Paired data showed no medication or exacerbation effects on CSF IL-6, but plasma IL-6 significantly decreased in patients that experienced an exacerbation after medication withdrawal. The results indicate that IL-6 levels may be altered in schizophrenia. The relative decrease in exacerbated patients following haloperidol withdrawal may be indicative of a compensatory response of plasma IL-6 levels to relapse. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15260 USA. RP van Kammen, DP (reprint author), RW Johnson Pharmaceut Res Inst, 920 Route 202,POB 300, Raritan, NJ 08869 USA. EM dvankamm@prius.jnj.com NR 51 TC 53 Z9 53 U1 3 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT 11 PY 1999 VL 87 IS 2-3 BP 129 EP 136 DI 10.1016/S0165-1781(99)00053-0 PG 8 WC Psychiatry SC Psychiatry GA 247ZB UT WOS:000083249900004 ER PT J AU Brody, AL Saxena, S Silverman, DHS Alborzian, S Fairbanks, LA Phelps, ME Huang, SC Wu, HM Maidment, K Baxter, LR AF Brody, AL Saxena, S Silverman, DHS Alborzian, S Fairbanks, LA Phelps, ME Huang, SC Wu, HM Maidment, K Baxter, LR TI Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE [(18)F]fluorodeoxyglucose positron emission tomography; FDG-PET; treatment response prediction; depression; ventrolateral prefrontal cortex; anterior cingulate gyrus ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; OBSESSIVE-COMPULSIVE DISORDER; MOOD DISORDERS; BASAL GANGLIA; UNIPOLAR DEPRESSION; FUNCTIONAL-ANATOMY; GLUCOSE-UTILIZATION; CORTEX; ABNORMALITIES AB Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal,gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scare of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Neuropsychiat Inst & Hosp, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med & Mol Pharmacol, Los Angeles, CA 90024 USA. Univ Alabama, Dept Behav Neurobiol, Birmingham, AL 35294 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Neuropsychiat Inst & Hosp, Room 67-468,760 Westwood Blvd, Los Angeles, CA 90024 USA. EM abrody@ucla.edu FU NIMH NIH HHS [R01 MH-53565] NR 47 TC 186 Z9 189 U1 2 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD OCT 11 PY 1999 VL 91 IS 3 BP 127 EP 139 DI 10.1016/S0925-4927(99)00034-7 PG 13 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 255DD UT WOS:000083653500001 PM 10641577 ER PT J AU Lori, F Rosenberg, E Lieberman, J Foli, A Maserati, R Seminari, E Alberici, F Walker, B Lisziewicz, J AF Lori, F Rosenberg, E Lieberman, J Foli, A Maserati, R Seminari, E Alberici, F Walker, B Lisziewicz, J TI Hydroxyurea and didanosine long-term treatment prevents HIV breakthrough and normalizes immune parameters SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; T-CELLS; INFECTION; COMBINATION; SUPPRESSION; REPLICATION; DISEASE; LYMPHOCYTES; RESERVOIR AB Hydroxyurea and didanosine treatment suppressed HIV replication for more than 2 years, in the absence of viral breakthrough, in chronically infected patients. The profile of viral load reduction was unusual for a two- drug combination, since a continuous gradual decrease in viremia persisted despite residual viral replication. The increase in CD4(+) T cell counts was not robust. However, unlike those of patients treated by other therapies, CD4(+) T lymphocytes were functionally competent against HIV, mediating a vigorous HIV-specific helper T cell response in half of these patients. In addition, the percentages of naive CD4(+) and CD8(+) T lymphocytes were not different from those in uninfected individuals. These results demonstrate that prolonged antiretroviral therapy with a simple, well-tolerated combination of two affordable drugs can lead to sustained control of HIV, normalization of immune parameters, and specific anti-HIV immune response. C1 RIGHT, Washington, DC 20007 USA. Policlin San Matteo, Res Inst Genet & Human Therapy, I-27100 Pavia, Italy. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Ctr Blood Res, Boston, MA 02115 USA. Policlin San Matteo, Clin Malattie Infett, I-27100 Pavia, Italy. Div Malattie Infett, I-29100 Piacenza, Italy. RP Lori, F (reprint author), RIGHT, Med-Dent Bldg SW307,3900 Reservoir Rd NW, Washington, DC 20007 USA. RI Lieberman, Judy/A-2717-2015 NR 31 TC 27 Z9 27 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT 10 PY 1999 VL 15 IS 15 BP 1333 EP 1338 DI 10.1089/088922299310034 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 242LE UT WOS:000082941900002 PM 10515148 ER PT J AU Costantini, LC Jacoby, DR Wang, S Fraefel, C Breakefield, XO Isacson, O AF Costantini, LC Jacoby, DR Wang, S Fraefel, C Breakefield, XO Isacson, O TI Gene transfer to the nigrostriatal system by hybrid herpes simplex virus/adeno-associated virus amplicon vectors SO HUMAN GENE THERAPY LA English DT Review ID RECOMBINANT ADENOASSOCIATED VIRUS; CENTRAL-NERVOUS-SYSTEM; EXPRESSING TYROSINE-HYDROXYLASE; GLUCOSE-TRANSPORTER GENE; COLI BETA-GALACTOSIDASE; IN-VIVO; PARKINSONS-DISEASE; LONG-TERM; TRANSGENE EXPRESSION; ESCHERICHIA-COLI AB To improve gene transfer to CNS neurons, critical elements of herpes simplex virus 1 (HSV-1) amplicons and recombinant adeno-associated virus (AAV) vectors were combined to construct a hybrid amplicon vector, and then packaged via a helper virus-free system. We tested the HSV/AAV hybrid amplicon vectors for transduction efficiency and stability of transgene expression (green fluorescent protein) in primary neuronal cultures from rat fetal ventral mesencephalon, in comparison with traditional HSV amplicon, AAV, or adenovirus (Ad) vectors at the same multiplicity of infection. The HSA/AAV hybrid vectors transduced the highest number of primary neurons in culture 2 days after infection. As compared with all other vectors tested, only hybrid vectors containing the AAV rep gene maintained the 2-day level of transgene expression over 12 days in culture. This rep-containing hybrid vector was then tested for efficiency and safety in the brain. One month after injection into adult rat striatum(1 x 10(6) transducing units injected), transgene expression was observed within the striatum (ranging from 564 to 8610 cells) and the substantia nigra (via retrograde transport, ranging from 130 to 809 neurons). The HSV/AAV hybrid amplicon vectors transduced predominantly neurons within the striatum, and showed transduction efficacy similar to and in many cases higher than that of HSV amplicon vectors, No immune response was observed in the HSA/AAV hybrid vector-injected brains, as determined by immune markers specific for helper T lymphocytes, cytotoxic T lymphocytes, and microglia, This HSV/AAV hybrid system shows high transduction efficiency and stability in culture. The effective and safe transgene delivery into the nigrostriatal system illustrates its potential for therapeutic application for neurologic disorders, such as Parkinson and Huntington disease. C1 Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Costantini, LC (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02178 USA. FU NIMH NIH HHS [T32 MH 19905-05]; NINDS NIH HHS [NS2429] NR 105 TC 67 Z9 70 U1 0 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 OCT 10 PY 1999 VL 10 IS 15 BP 2481 EP 2494 DI 10.1089/10430349950016825 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 248AE UT WOS:000083252500005 PM 10543613 ER PT J AU Poznansky, MC La Vecchio, J Silva-Arietta, S Porter-Brooks, J Brody, K Olszak, IT Adams, GB Ramstedt, U Marasco, WA Scadden, DT AF Poznansky, MC La Vecchio, J Silva-Arietta, S Porter-Brooks, J Brody, K Olszak, IT Adams, GB Ramstedt, U Marasco, WA Scadden, DT TI Inhibition of human immunodeficiency virus replication and growth advantage of CD4(+) T cells and monocytes derived from CD34(+) cells transduced with an intracellular antibody directed against human immunodeficiency virus type 1 Tat SO HUMAN GENE THERAPY LA English DT Article ID TRANSDOMINANT REV PROTEIN; HIV-INFECTED INDIVIDUALS; GENE-THERAPY; PROGENITOR CELLS; RETROVIRAL VECTORS; EXPRESSION; RIBOZYME; DISEASE; BLOOD; AIDS AB Current clinical gene therapy protocols for the treatment of human immunodeficiency virus type 1 (HIV-1) infection involve the ex vivo transduction and expansion of CD4(+) T cells derived from HIV-positive patients at a late stage in their disease (CD4(+) cell count <400 cells/mm(3)). We examined the efficiency of transduction and transgene expression in adult bone marrow (BM)- and umbilical cord blood (UCB)-derived CD34(+) cells induced to differentiate into T cells and monocytes in vitro with an MuLV-based vector encoding the neomycin resistance gene and an intracellular antibody directed against the Tat protein of HIV-1 (sFvtat1-C-kappa). The expression of the marker gene and the effects of antiviral construct on subsequent challenge with monocytotropic and T cell-tropic HIV-1 isolates were monitored in vitro in purified T cells and monocytes generated in culture from the transduced CD34(+) cells. Transduction efficiencies of CD34(+) cells ranged between 22 and 27%, Differentiation of CD34(+) cells into T cells or monocytes was not significantly altered by the transduction process. HIV-1 replication in monocytes and CD4(+) T cells derived from CD34(+) cells transduced with the intracellular antibody gene was significantly reduced in comparison with the degree of HIV replication seen in monocytes and CD4(+) T cells derived from CD34(+) cells transduced with the neomycin resistance gene alone. Further, T cells and monocytes derived from CD34(+) cells transduced with the intracellular antibody gene were demonstrated to express the sFvtat1-C-kappa transgene by RT-PCR and had a selective growth advantage in cultures that had been challenged with HIV-1, These data demonstrate that sFvtat1-C-kappa inhibits HIV-1 replication in T cells and monocytes developing from CD34(+) cells and supports the continuing development of a stem cell gene therapy for the treatment of HIV-1 infection. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Immunol & AIDS Res, Boston, MA 02115 USA. Virus Res Inst Inc, Cambridge, MA 02129 USA. RP Poznansky, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 13th St,Bldg 149,Room 52120, Charlestown, MA 02129 USA. NR 30 TC 14 Z9 17 U1 0 U2 0 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 OCT 10 PY 1999 VL 10 IS 15 BP 2505 EP 2514 DI 10.1089/10430349950016843 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 248AE UT WOS:000083252500007 PM 10543615 ER PT J AU Schultze, J Johnson, P AF Schultze, J Johnson, P TI A stimulating new target for cancer immunotherapy SO LANCET LA English DT Editorial Material ID FOLLICULAR LYMPHOMA-CELLS; IN-VITRO; B-CELLS; T-CELLS; CD40; HELP C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Southampton, Southampton Gen Hosp, Sch Med, Canc Sci Div,CRC,Dept Med Oncol, Southampton SO16 6YD, Hants, England. RP Schultze, J (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 16 TC 10 Z9 10 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 9 PY 1999 VL 354 IS 9186 BP 1225 EP 1227 DI 10.1016/S0140-6736(99)90130-7 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 243RE UT WOS:000083010400005 PM 10520628 ER PT J AU Hussain, MA Habener, JF AF Hussain, MA Habener, JF TI Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-SPECIFIC EXPRESSION; PROGLUCAGON GENE; BINDING-PROTEINS; ISLET CELLS; DOMAIN; CBP; DIFFERENTIATION; COACTIVATORS; PANCREAS; REVEALS AB In the endocrine pancreas, alpha-cell-specific expression of the glucagon gene is mediated by DNA-binding proteins that interact with the proximal GL promoter element, which contains several AT-rich domains. The homeodomain transcription factors brain-4, pax-6, and cdx-2 have been shown to bind to these sites and to transactivate glucagon gene expression. In the present study, we investigated the interaction of cdx-2 and pax-6 with p300, a co-activator coupled to the basal transcription machinery. In transient transfection-expression experiments, we found that the transactivating effects of cdx-2 and pax-6 on the glucagon gene were greatly enhanced by the additional expression of p300. This enhancement was due to direct protein-protein interactions of both pax-6 and cdx-2 with the N-terminal C/H1 domain of p300. pax-6 and cdx-2 also directly interacted with one another at the protein level. pax-6, bound to its DNA recognition site in the glucagon G1 promoter element, tethered cdx-2 to the molecular complex of pax-g and p300. Further, we found that the presence of cdx-2 enhanced the interaction of pax-g with p300, thus establishing a molecular complex of transcription factors implicated in tissue-specific glucagon gene expression with the basal transcriptional machinery. C1 Howard Hughes Med Inst, Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Howard Hughes Med Inst, Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK30834] NR 24 TC 84 Z9 85 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 OCT 8 PY 1999 VL 274 IS 41 BP 28950 EP 28957 DI 10.1074/jbc.274.41.28950 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800020 PM 10506141 ER PT J AU Lim, S Naisbitt, S Yoon, J Hwang, JI Suh, PG Sheng, M Kim, E AF Lim, S Naisbitt, S Yoon, J Hwang, JI Suh, PG Sheng, M Kim, E TI Characterization of the Shank family of synaptic proteins - Multiple genes, alternative splicing, and differential expression in brain and development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; TUMOR-SUPPRESSOR PROTEIN; NITRIC-OXIDE SYNTHASE; POSTSYNAPTIC DENSITY; NMDA RECEPTOR; INTERACTING PROTEIN; ALPHA-DYSTROGLYCAN; BINDING PROTEIN; PSD-95 FAMILY; PDZ DOMAIN AB Shank1, Shank2, and Shank3 constitute a family of proteins that may function as molecular scaffolds in the postsynaptic density (PSD). Shank directly interacts with GKAP and Homer, thus potentially bridging the N-methyl-D-aspartate receptor-PSD-95-GKAP complex and the mGluR-Homer complex in synapses (Naisbitt, S., Kim, E., Tu, J. C., Xiao, B., Sala, S., Valtschanoff, J., Weinberg, R J., morley, P. F., and Sheng, M. (1999) Neuron 23, 569-582; Tu, J. C., Xiao, B., Naisbitt, S., Yuan, J. P., Petralia, R. S., Brakeman, P., Dean, A., Aakalu, V. K., Lanahan, A. A., Sheng, M., and Worley, P. F. (1999) Neuron 23, 583-592). Shank contains multiple domains for protein-protein interaction including ankyrin repeats, an SH3 domain, a PSD-95/DIg/ZO-1 domain, a sterile a motif domain, and a proline-rich region. By characterizing Shank cDNA clones and RT-PCR products, we found that there are four sites far alternative splicing in Shank1 and another four sites in Shank2, some of which result in deletion of specific domains of the Shank protein. In addition, the expression of the splice variants is differentially regulated in different regions of rat brain during development. Immunoblot analysis of Shank proteins in rat brain using five different Shank antibodies reveals marked heterogeneity in size (120-240 kDa) and differential. spatiotemporal expression. Shank1 immunoreactivity is concentrated at excitatory synaptic sites in adult brain, and the punctate staining of Shank1 is seen in developing rat brains as early as postnatal day 7. These results suggest that alternative splicing in the Shank family may be a mechanism that regulates the molecular structure of Shank and the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain. C1 Pusan Natl Univ, Dept Pharmacol, Pusan 609735, South Korea. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea. RP Kim, E (reprint author), Pusan Natl Univ, Dept Pharmacol, Pusan 609735, South Korea. RI Suh, Pann-Ghill/F-3610-2010; Kim, Eunjoon/C-1566-2011 FU NINDS NIH HHS [NS35050] NR 51 TC 150 Z9 155 U1 0 U2 15 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 OCT 8 PY 1999 VL 274 IS 41 BP 29510 EP 29518 DI 10.1074/jbc.274.41.29510 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800095 PM 10506216 ER PT J AU Blasina, A Price, BD Turenne, GA McGowan, CH AF Blasina, A Price, BD Turenne, GA McGowan, CH TI Caffeine inhibits the checkpoint kinase ATM SO CURRENT BIOLOGY LA English DT Article ID DNA-DAMAGE; MAMMALIAN-CELLS; PROTEIN-KINASE; PHOSPHORYLATION; RADIOSENSITIZATION; REPLICATION; P53; ACTIVATION; COMPLETION; RADIATION AB The basis of many anti-cancer therapies is the use of genotoxic agents that damage DNA and thus kill dividing cells. Agents that cause cells to override the DNA damage checkpoint are predicted to sensitize cells to killing by genotoxic agents. They have therefore been sought as adjuncts in radiation therapy and chemotherapy. One such compound, caffeine, uncouples cell-cycle progression from the replication and repair of DNA [1,2]. Caffeine therefore serves as a model compound in establishing the principle that agents that override DNA-damage checkpoints can be used to sensitize cells to the killing effects of genotoxic drugs [3]. But despite more than 20 years of use, the molecular mechanisms by which caffeine affects the cell cycle and checkpoint responses have not been identified. We investigated the effects of caffeine on the G2/M DNA-damage checkpoint in human cells. We report that the radiation induced activation of the kinase Cds1 [4] (also known as Chk2 [5]) is inhibited by caffeine in vivo and that ATM kinase activity is directly inhibited by caffeine in vitro. Inhibition of ATM provides a molecular explanation of the attenuation of DNA-damage checkpoint responses and for the increased radiosensitivity of caffeine-treated cells [6-8]. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP McGowan, CH (reprint author), Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. NR 23 TC 227 Z9 236 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 7 PY 1999 VL 9 IS 19 BP 1135 EP 1138 DI 10.1016/S0960-9822(99)80486-2 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 244VQ UT WOS:000083071800027 PM 10531013 ER PT J AU O'Craven, KM Downing, PE Kanwisher, N AF O'Craven, KM Downing, PE Kanwisher, N TI fMRI evidence for objects as the units of attentional selection SO NATURE LA English DT Article ID VISUAL-ATTENTION; BRAIN POTENTIALS; NEURAL MECHANISMS; HUMAN MT; MODULATION; PERCEPTION; SPOTLIGHT; CORTEX; AREAS; COLOR AB Contrasting theories of visual attention emphasize selection by spatial location(1), visual features (such as motion or colour)(2-4) or whole objects(5,6). Here we used functional magnetic resonance imaging (fMRI) to test key predictions of the object-based theory, which proposes that pre-attentive mechanisms segment the visual array into discrete objects, groups, or surfaces, which serve as targets for visual attention(5-9). Subjects viewed stimuli consisting of a face transparently superimposed on a house, with one moving and the other stationary. In different conditions, subjects attended to the face, the house or the motion. The magnetic resonance signal from each subject's fusiform face area(10), parahippocampal place area(11) and area MT/MST12 provided a measure of the processing of faces, houses and visual motion, respectively. Although all three attributes occupied the same location, attending to one attribute of an object (such as the motion of a moving face) enhanced the neural representation not only of that attribute but also of the other attribute of the same object (for example, the face), compared with attributes of the other object (for example, the house). These results cannot be explained by models in which attention selects locations or features, and provide physiological evidence that whole objects are selected even when only one visual attribute is relevant. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Radcliffe Coll, Bunting Inst, Cambridge, MA 02138 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Kanwisher, N (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. NR 30 TC 498 Z9 505 U1 8 U2 57 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 7 PY 1999 VL 401 IS 6753 BP 584 EP 587 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 244MG UT WOS:000083054900049 PM 10524624 ER PT J AU Yuan, ZM Huang, YY Ishiko, T Nakada, S Utsugisawa, T Shioya, H Utsugisawa, Y Shi, Y Weichselbaum, R Kufe, D AF Yuan, ZM Huang, YY Ishiko, T Nakada, S Utsugisawa, T Shioya, H Utsugisawa, Y Shi, Y Weichselbaum, R Kufe, D TI Function for p300 and not CBP in the apoptotic response to DNA damage SO ONCOGENE LA English DT Article DE ionizing radiation; apoptosis; p53 tumor suppressor ID ABL TYROSINE KINASE; ACTIVATED PROTEIN-KINASE; FACTOR-KAPPA-B; IONIZING-RADIATION; C-ABL; GROWTH ARREST; P53; BINDING; TRANSCRIPTION; EXPRESSION AB The cellular response to ionizing radiation (IR) includes the induction of apoptosis, The p300/CBP proteins possess histone acetyltransferase activity and function as transcriptional coactivators of p53. We have prepared cells deficient in p300 or CBP to define the roles of these proteins in the cellular response to DNA damage, The present results demonstrate that p300, but not CBP, contributes to IR sensitivity of cells. The results also demonstrate that IR-induced apoptosis is impaired in the p300-, but not CBP-, deficient cells. These findings indicate that p300 functions in the apoptotic response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Yuan, ZM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA55241] NR 31 TC 47 Z9 47 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 7 PY 1999 VL 18 IS 41 BP 5714 EP 5717 DI 10.1038/sj.onc.1202930 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 243UW UT WOS:000083016500012 PM 10523850 ER PT J AU Mitsiades, N Poulaki, V Leone, A Tsokos, M AF Mitsiades, N Poulaki, V Leone, A Tsokos, M TI Fas-mediated apoptosis in Ewing's sarcoma cell lines by metalloproteinase inhibitors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OVARIAN-CARCINOMA XENOGRAFTS; SOLUBLE FORM; MATRIX METALLOPROTEINASES; DOWN-REGULATION; IN-VIVO; PANCREATIC-CANCER; LIGAND EXPRESSION; MOLECULAR-CLONING; INTERFERON-GAMMA; IMMUNE PRIVILEGE AB Background: Fas ligand (FasL) is a transmembrane protein that induces apoptosis (programmed cell death) in susceptible cells by interacting with its receptor, Fas. Transmembrane Fast is cleaved by a metalloproteinase enzyme into a soluble form that is released into the extracellular medium. Tumors of the Ewing's sarcoma family express functional transmembrane Fast and release soluble Fast. This cleavage is inhibited by a matrix metalloproteinase inhibitor (MMPI). We therefore hypothesized that MMPIs can lead to apoptosis of tumor cells by inducing accumulation of transmembrane FasL. Methods: Ewing's sarcoma and neuroblastoma cell lines were treated with two synthetic MMPIs (BB-3103 and A-151011) and examined for apoptosis and expression of FasL and Fas, Results: Although MMPIs increase levels of FasL and Fas proteins on the surface of all tumor cells studied, they induced apoptosis in Fas-sensitive but not in Fas-resistant cell lines; the induction of apoptosis was inhibited by a Fas-neutralizing antibody. The increase in protein expression was not associated with enhanced transcription. Treatment with an MMPI sensitized the Ewing's sarcoma cells to Fas-activating antibody and to doxorubicin-induced apoptosis. Conclusions: MMPIs cause accumulation of transmembrane FasL by inhibiting its cleavage, accumulation of Fas (probably secondarily to FasL cleavage inhibition), and decreased levels of soluble FasL. These effects lead to apoptosis in Fas-sensitive cell lines. The observed cooperative action of MMPIs and doxorubicin suggests a possible role of MMPIs in combination treatments with standard apoptosis-inducing chemotherapeutic agents. C1 NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Mitsiades, N (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149 13th St,7th Floor, Charlestown, MA 02129 USA. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 57 TC 42 Z9 42 U1 2 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 6 PY 1999 VL 91 IS 19 BP 1678 EP 1684 DI 10.1093/jnci/91.19.1678 PG 7 WC Oncology SC Oncology GA 242GP UT WOS:000082932400016 PM 10511596 ER PT J AU Walton, SP Stephanopoulos, GN Yarmush, ML Roth, CM AF Walton, SP Stephanopoulos, GN Yarmush, ML Roth, CM TI Prediction of antisense oligonucleotide binding affinity to a structured RNA target SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE antisense; hybridization; affinity; RNA folding ID OF-THE-ART; IN-VITRO; MESSENGER-RNA; SECONDARY STRUCTURE; VIRUS TYPE-1; INHIBITION; DNA; OLIGODEOXYNUCLEOTIDES; HYBRIDIZATION; EXPRESSION AB Antisense oligonucleotides, which act through the pairing of complementary bases to an RNA target sequence, are showing great promise in research and clinical applications. However, the selection of effective antisense oligonucleotides has proven more difficult than initially presumed. We developed a prediction algorithm to identify those sequences with the highest predicted binding affinity for their target mRNA based on a thermodynamic cycle that accounts for the energetics of structural alterations in both the target mRNA and the oligonucleotide. The model was used to predict the binding affinity of antisense oligonucleotides complementary to the rabbit beta-globin (RBG) and mouse tumor necrosis factor-alpha (TNF alpha) mRNAs, for which large experimental datasets were available. Of the top ten candidates identified by the algorithm for the RBG mRNA, six were the most strongly binding sequences determined from an experimental assay. The prediction for the TNF alpha mRNA also identified high affinity sequences with similar to 60% accuracy. Computational prediction of antisense efficacy is more cast-efficient and faster than in vitro or in vivo selection and can potentially speed the development of sequences for both research and clinical applications. (C) 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 65: 1-9, 1999. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Roth, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, 55 Fruit St,GRB1401, Boston, MA 02114 USA. RI Walton, S. Patrick/A-7007-2008; OI Walton, S. Patrick/0000-0003-1708-8603; Roth, Charles/0000-0002-4924-0721 NR 27 TC 38 Z9 39 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD OCT 5 PY 1999 VL 65 IS 1 BP 1 EP 9 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 229CU UT WOS:000082176600001 PM 10440665 ER PT J AU Malgrange, B Rigo, JM Van de Water, TR Staecker, H Moonen, G Lefebvre, PP AF Malgrange, B Rigo, JM Van de Water, TR Staecker, H Moonen, G Lefebvre, PP TI Growth factor therapy to the damaged inner ear: clinical prospects SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article; Proceedings Paper CT 7th International Congress of Pediatric Otorhinolaryngology CY JUN 07-10, 1998 CL HELSINKI, FINLAND SP Amer Acad Pediat, Sect Otolaryngol & Bronchesphagol, Amer Soc Pediat Otolaryngol, Australian Soc Pediat Oto Rhino Laryngol, British Assoc Pediat Oto Rhino Laryngol, Dutch Flemish Working Grp Pediat Otorhinolaryngol, Finnish Soc Otorhinolaryngol, Head & Neck Surg, Hearing int, Int Pediat Otorhinolaryngol Charitable Fund, Japan Soc Pediat Otorhinolaryngol, Congress Comm Homepage DE cell culture; cochlea; hearing impairment; inner ear; ototoxicity ID AUDITORY HAIR-CELLS; SENSORY EPITHELIA; DEVELOPING ORGAN; ACOUSTIC TRAUMA; RETINOIC ACID; REGENERATION; NEURONS; PROLIFERATION; SURVIVAL; CULTURE AB Most hearing loss results from lesions of the sensory cells and/or of the neurons of the auditory part of the inner ear. There is currently no treatment able to stop the progression of a hearing loss or to restore a lost auditory function. In this paper, we review the progress which has been made with respect to the regeneration and the protection of the hair cells and of the auditory neurons in the cochlea. In particular, we emphasize the control by growth factors of the protection/repair mechanisms of the neurosensory structures within the inner ear, in the prospect of the possible clinical use of these molecules. Finally, we discuss the different approaches which can be used to deliver these therapeutic agents to the inner ear. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Liege, Dept Human Physiol & Pathophysiol, B-4020 Liege, Belgium. Univ Liege, Dept Otorhinolaryngol, B-4020 Liege, Belgium. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Otolaryngol, Bronx, NY 10467 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lefebvre, PP (reprint author), Univ Liege, Dept Human Physiol & Pathophysiol, Pl Delcour 17, B-4020 Liege, Belgium. RI Rigo, Jean-Michel/E-3456-2010; OI Rigo, Jean-Michel/0000-0002-0031-526X; Malgrange, Brigitte/0000-0002-8957-2528 NR 34 TC 14 Z9 14 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD OCT 5 PY 1999 VL 49 SU 1 BP S19 EP S25 DI 10.1016/S0165-5876(99)00126-3 PG 7 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 254UU UT WOS:000083631200005 PM 10577769 ER PT J AU Arrunategui-Correa, V Baltatzis, S Foster, CS AF Arrunategui-Correa, V Baltatzis, S Foster, CS TI The role of cytokines in experimental herpes simplex keratitis SO ACTA VIROLOGICA LA English DT Article DE herpes simplex virus 1; herpes simplex keratitis; cytokines; gene expression; reverse transcription; polymerase chain reaction ID CELL DEFICIENT MICE; STROMAL KERATITIS; IFN-GAMMA; T-CELLS; GENE-EXPRESSION; VIRUS TYPE-1; IN-VIVO; MURINE; LYMPHOCYTES; TRANSCRIPTION AB Experimental corneal infection with herpes simplex virus 1 (HSV-1) resulted in 11-21 days in herpes simplex keratitis (HSK) in C.A1-20 but not C.B-17 strain of BALB/c Igh-1-disparate mice. Formation of mRNAs of various pro-inflammatory cytokines was analyzed in corneas and draining lymph nodes (LNs) of HSK-susceptible C.A1-20 and HSK-resistant C.B-17 mice following HSV-1 conceal inoculation by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. Transcripts for interleukin (IL)-2 and interferon (IFN)-gamma were expressed in LNs of susceptible but not resistant mice. The level of IL-6 expression in the cornea correlated with the severity of keratitis in susceptible mice, being evident at days 4 and 14 after virus inoculation and thus showing a biphasic response. Resistant mice did not develop HSK and did not express IL-6. The IL-1 beta and IL-4 gene transcription began early (day 7) in the corneas of resistant mice and then ceased, while in the corneas of susceptible mice, it began later (day 11). Taken together, these results indicate that IL-1 beta, IL-4, IL-6, and IL-7 participate in the local inflammatory response in HSK. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Hilles Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Rhoads Mol Immunol Lab, Boston, MA 02114 USA. Univ Athens, Athens, Greece. Vanderbilt Univ, Dept Microbiol & Immunol, Nashville, TN USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Hilles Immunol Lab, 243 Charles St, Boston, MA 02114 USA. NR 34 TC 6 Z9 9 U1 0 U2 0 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57 NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0001-723X J9 ACTA VIROL JI Acta Virol. PD OCT PY 1999 VL 43 IS 5 BP 325 EP 330 PG 6 WC Virology SC Virology GA 260EA UT WOS:000083935500009 PM 10757234 ER PT J AU Campbell, AJ Robertson, MC Gardner, MM Norton, RN Buchner, DM AF Campbell, AJ Robertson, MC Gardner, MM Norton, RN Buchner, DM TI Falls prevention over 2 years: a randomized controlled trial in women 80 years and older SO AGE AND AGEING LA English DT Article DE community; falls; old age; physical activity; randomized controlled trial ID EXTERNAL HIP PROTECTORS; COMMUNITY; FRACTURES; EXERCISE; RISK AB Background: after 1 year, a home-based programme of strength and balance retraining exercises was effective in reducing falls and injuries in women aged 80 years and older. The exercise programme had been individually prescribed by a physiotherapist during the first 2 months of a randomized controled trial. Objective: we aimed to assess the effectiveness of the programme over 2 years. Setting: 17 general practices in Dunedin, New Zealand. Subjects: women from both the control group and the exercise group completing a 1-year trial (213 out of the original 233) were invited to continue for a further year. Methods: falls and compliance to the exercise programme were monitored for 2 years. Results: 81 (74%) in the control group and 71 (69%) in the exercise group agreed to continue in the study. After 2 years, the rate of falls remained significantly lower in the exercise group than in the control group. The relative hazard for all falls for the exercise group was 0.69 (95% confidence interval 0.49-0.97). The relative hazard for a fall resulting in a moderate or severe injury was 0.63 (95% confidence interval 0.42-0.95). Those complying with the exercise programme at 2 years had a higher level of physical activity at baseline, were more likely to have reported falling in the year before the study and had remained more confident in the first year about not falling compared with the rest of the exercise group. Conclusions: falls and injuries can be reduced by an individually tailored exercise programme in the home. For those who keep exercising, the benefit continues over a 2-year period. C1 Otago Med Sch, Dunedin Sch Med, Dept Med, Dunedin, New Zealand. Univ Auckland, Sch Med, Injury Prevent Res Ctr, Auckland, New Zealand. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Campbell, AJ (reprint author), Otago Med Sch, Dunedin Sch Med, Dept Med, POB 913, Dunedin, New Zealand. RI Robertson, Mary Clare/A-3964-2009 NR 11 TC 235 Z9 242 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD OCT PY 1999 VL 28 IS 6 BP 513 EP 518 DI 10.1093/ageing/28.6.513 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 257UT UT WOS:000083800900003 PM 10604501 ER PT J AU Saghir, M Blodget, E Laposata, M AF Saghir, M Blodget, E Laposata, M TI The hydrolysis of fatty acid ethyl esters in low-density lipoproteins by red blood cells, white blood cells and platelets SO ALCOHOL LA English DT Article DE ethanol; lipids; fatty acids; fatty acids; ethanol abuse; addiction ID ETHANOL-METABOLISM; RAT; PURIFICATION; ORGANS AB Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been implicated as toxic mediators of ethanol ingestion. In this study, we investigated the in vitro hydrolysis of FALL reconstituted in low-density lipoproteins (LDL) when incubated with human blood, cell free plasma, red blood cells, white blood cells, and platelets. We also determined the metabolic fate of the fatty acid originally incorporated in the FAEE following FAEE hydrolysis. When FAEE were incubated with human red blood cells, white blood cells, or platelets, at physiologic cell counts, 80% of the FAEE were hydrolyzed at 2 h. The FAEE-derived fatty acid was predominantly found in phospholipid and free fatty acid fractions. Cell free plasma contained minimal FAEE hydrolytic activity. These studies demonstrate that FAEE are degraded to free fatty acids and ethanol by the cellular elements in the blood. The generation of free fatty acids from extensive hydrolysis of FAEE adds support to the growing concept that at least some of the toxic effects of FAEE are mediated by the free fatty acids generated upon hydrolysis of the ethyl esters. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Clin Labs, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Clin Labs, Room 235,Gray Bldg, Boston, MA 02114 USA. NR 27 TC 10 Z9 12 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD OCT PY 1999 VL 19 IS 2 BP 163 EP 168 DI 10.1016/S0741-8329(99)00035-X PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 248QM UT WOS:000083286900009 PM 10548161 ER PT J AU Morris, N Kim, CS Doye, AA Hajjar, RJ Laste, N Gwathmey, JK AF Morris, N Kim, CS Doye, AA Hajjar, RJ Laste, N Gwathmey, JK TI A pilot study of a new chicken model of alcohol-induced cardiomyopathy SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE chicken; ethanol; cardiac dysfunction ID INDUCED CONGESTIVE CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; ANIMAL-MODEL; CONTRACTILE PERFORMANCE; NUTRITIONAL-STATUS; CARDIAC-FUNCTION; HEART-MUSCLE; ETHANOL; RATS; TURKEYS AB Background: Excessive alcohol consumption is recognized as a common cause of left ventricular (LV) dysfunction. It is currently thought that 36% of all cases of dilated cardiomyopathy are due to excessive alcohol intake. Suitable animal models are needed to study the pathogenic mechanisms of ethanol-induced LV dysfunction. We have therefore created a new model of ethanol-induced LV dysfunction in the chicken. Methods: For 12 weeks, adult chickens were given, twice a day, by gavage, 73% of their total calculated daily water intake containing a 20% ethanol concentration. Twenty percent ethanol also was placed in the water and provided ad libitum. Control chickens received the same volume of water by gavage twice a day without ethanol. Water without ethanol was given ad libitum to control birds. Results: Our study shows that after a relatively short duration of ethanol ingestion, chickens developed LV dilatation and LV dysfunction. The serum concentrations of ethanol attained in this new model were similar to those reported in humans. Furthermore, unlike other currently available animal models of ethanol-induced cardiac disease, this model demonstrates myocyte hypertrophy, interstitial fibrosis, and myocytolysis, similar to observations in human ethanol-induced cardiac dysfunction. Conclusions: We conclude that this new avian model should provide a useful tool for investigating the mechanism(s) and pathophysiology of ethanol-induced dilated cardiomyopathy and heart failure. C1 Angell Mem Anim Hosp, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Whitaker Cardiovasc Res Inst, Boston, MA 02118 USA. Gwathmey Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Gwathmey, JK (reprint author), 763 Concord Ave,Bldg E, Cambridge, MA 02138 USA. FU NHLBI NIH HHS [KO8-HL03561, R44-HL 52249, 2RO1-HL49574]; NIAAA NIH HHS [R44 AA066758-02] NR 39 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1999 VL 23 IS 10 BP 1668 EP 1672 DI 10.1097/00000374-199910000-00015 PG 5 WC Substance Abuse SC Substance Abuse GA 248MP UT WOS:000083279500016 PM 10550000 ER PT J AU Bretsky, PM Buckwalter, JG Seeman, TE Miller, CA Poirier, J Schellenberg, GD Finch, CE Henderson, VW AF Bretsky, PM Buckwalter, JG Seeman, TE Miller, CA Poirier, J Schellenberg, GD Finch, CE Henderson, VW TI Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; apolipoprotein E; gender; risk factors ID E EPSILON-4 ALLELE; E POLYMORPHISM; RISK; DEMENTIA; ONSET; AGE; SEX; ASSOCIATION; ESTROGEN; CONSORTIUM AB Carriers of the apolipoprotein E (APOE) epsilon 4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon 4 by gender, although indicated in the literature, require further verification. A total of 195 past or current control or AD participants in an ongoing longitudinal study of aging and dementia were genotyped. All subjects were at least 60 years old; demented subjects met clinical or pathologic criteria for late-onset AD. Logistic regression analysis and proportional hazard models were used to evaluate joint effects of APOE and gender. A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis. Women carrying one or more APOE-epsilon 4 allele were more likely to develop AD [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 3.2-19.1]. For men, the presence of the APOE-epsilon 4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3). The interaction term in the proportional hazards model neared (p = 0.07) statistical significance, and a similar but reduced gender effect was shown. The analysis suggests that the presence of one or more APOE-epsilon 4 allele confers a substantially greater risk of AD to women than to men. These findings in part may account for reports of increased risk of AD faced by women. C1 Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90033 USA. Univ So Calif, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Dept Neurol & Psychiat, Los Angeles, CA 90033 USA. Univ So Calif, Sch Gerontol, Los Angeles, CA 90033 USA. Mcgill Ctr Studies Aging, Verdun, PQ, Canada. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bretsky, PM (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,MS 44,POB 33800, Los Angeles, CA 90033 USA. FU NIA NIH HHS [AG05136, AG05142, AG13499] NR 34 TC 83 Z9 84 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 1999 VL 13 IS 4 BP 216 EP 221 DI 10.1097/00002093-199910000-00007 PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 268NV UT WOS:000084423200006 PM 10609670 ER PT J AU Chasan-Taber, L Willett, WC Seddon, JM Stampfer, MJ Rosner, B Colditz, GA Speizer, FE Hankinson, SE AF Chasan-Taber, L Willett, WC Seddon, JM Stampfer, MJ Rosner, B Colditz, GA Speizer, FE Hankinson, SE TI A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE cataract; cataract extraction; diet; women; prospective studies; vitamin A; carotene; lutein; zeaxanthin; carotenoids; Nurses' Health Study; food-frequency questionnaire ID SERUM CAROTENOIDS; LENS OPACITIES; BREAST-CANCER; DIETARY-FAT; PIGMENT; NUCLEAR; REPRODUCIBILITY; QUESTIONNAIRE; TOCOPHEROLS; VEGETABLES AB Background: Oxidation of lens proteins plays a central role in the formation of age-related cataracts, suggesting that dietary antioxidants may play a role in prevention. However, the relation between specific antioxidants and risk of cataract remains uncertain. Objective: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in women. Methods: A prospective cohere of registered female nurses aged 45-71 y and free of diagnosed cancer was followed; in 1980, 50461 were included and others were added as they became 45 y of age for a total of 77466. Information on nutrient intake was assessed by repeated administration of a food-frequency questionnaire during 12 y of follow-up. Results: During 761 762 person-years of follow-up, 1471 cataracts were extracted. After age, smoking, and other potential cataract risk factors were controlled for, those with the highest intake of lutein and zeaxanthin had a 22% decreased risk of cataract extraction compared with those in the lowest quintile (relative risk: 0.78; 950/0 CI: 0.63, 0.95; P for trend = 0.04). Other carotenoids (alpha-carotene, X-carotene, lycopene, and beta-cryptoxanthin), vitamin A, and retinol were not associated with cataract in multivariate analysis. Increasing frequency of intakes of spinach and kale, foods rich in lutein, was associated with a moderate decrease in risk of cataract. Conclusions: Lutein and zeaxanthin and foods rich in these carotenoids may decrease the risk of cataracts severe enough to require extraction. C1 Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chasan-Taber, L (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, 405 Arnold House, Amherst, MA 01003 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356]; NEI NIH HHS [EY09611] NR 37 TC 173 Z9 181 U1 2 U2 14 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 OCT PY 1999 VL 70 IS 4 BP 509 EP 516 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 239PR UT WOS:000082779100014 PM 10500020 ER PT J AU Brown, L Rimm, EB Seddon, JM Giovannucci, EL Chasan-Taber, L Spiegelman, D Willett, WC Hankinson, SE AF Brown, L Rimm, EB Seddon, JM Giovannucci, EL Chasan-Taber, L Spiegelman, D Willett, WC Hankinson, SE TI A prospective study of carotenoid intake and risk of cataract extraction in US men SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE cataract; cataract extraction; diet; men; prospective studies; vitamin A; carotene; lutein; zeaxanthin; carotenoids; food-frequency questionnaire; Health Professionals Follow-up Study ID MALE HEALTH-PROFESSIONALS; CIGARETTE-SMOKING; LENS OPACITIES; SERUM CAROTENOIDS; NUTRIENT INTAKE; UNITED-STATES; ALCOHOL-USE; VITAMIN-E; PLASMA; REPRODUCIBILITY AB Background: Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. Objective: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. Design: US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. Results: We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative td men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. Conclusions: Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA USA. RP Harvard Univ, Sch Publ Hlth, Dept Nutr, 677 Huntington Ave, Boston, MA 02115 USA. EM lisa.brown@channing.harvard.edu FU NCI NIH HHS [CA55075]; NEI NIH HHS [EY09611]; NHLBI NIH HHS [HL35464] NR 48 TC 183 Z9 196 U1 0 U2 10 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1999 VL 70 IS 4 BP 517 EP 524 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 239PR UT WOS:000082779100015 PM 10500021 ER PT J AU Laposata, M AF Laposata, M TI Assessment of ethanol intake - Current tests and new assays on the horizon SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Review DE alcohol; toxicology; carbohydrate-deficient transferrin; fatty acid ethyl ester; drug abuse ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; ACID ETHYL-ESTERS; RECENT ALCOHOL-CONSUMPTION; LIVER-DISEASE; MARKER; ABUSE; BLOOD; PHOSPHATIDYLETHANOL; 5-HYDROXYTRYPTOPHOL; METABOLISM C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, 55 Fruit St,Gray 235, Boston, MA 02114 USA. NR 34 TC 31 Z9 32 U1 1 U2 2 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 1999 VL 112 IS 4 BP 443 EP 450 PG 8 WC Pathology SC Pathology GA 239DV UT WOS:000082754300001 PM 10510667 ER PT J AU Thomas, SH Borczuk, P Shackelford, J Ostrander, J Silver, D Evans, M Stein, J AF Thomas, SH Borczuk, P Shackelford, J Ostrander, J Silver, D Evans, M Stein, J TI Patient and physician agreement on abdominal pain severity and need for opioid analgesia SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE abdominal pain; opioids; analgesia ID RELIEF AB Whereas controversy surrounds emergency department (ED) analgesia administration to patients with undifferentiated abdominal pain, few studies have addressed the level of patient-physician agreement on abdominal pain severity and need for opioid analgesia. This prospective study was undertaken to assess concordance between emergency physicians and patients on abdominal pain severity. Study subjects were a convenience sample of 30 adults seen in an urban university-affiliated tertiary care ED (annual census 65,000) who had undifferentiated abdominal pain meeting an initial severity threshold of 5 on a 10cm visual analog scale (VAS) marked by the patient, Patients' and physicians' VAS scores, obtained in blinded fashion at presentation (t0) and at one (t1) and two (t2) hours into the ED stay, were compared with t test (VAS scores) and sign-rank (percent change in VAS scores) analyses, In addition, patients and physicians were asked at each assessment time, in blinded fashion, "Is the pain severe enough to warrant morphine?" The kappa statistic was used to characterize the degree of agreement between physician and patient assessments as to whether opioids were indicated. At t0, t1, and t2, patients' mean VAS scores (7.5, 6.7, and 5.1) were significantly (P < .05) higher than the corresponding physicians' VAS scores (5.3, 4.7, and 3.9). Though VAS scores for physicians started lower than those of patients, the percentage changes in scores from one assessment to the next were similar by Wilcoxon sign-rank testing (P > .50 for time intervals t0 - t1 and t1 - t2). Overall, patients and physicians agreed on the question of whether pain was sufficient to warrant opioids in 71 of 90 (78.9%) assessments; the corresponding kappa statistic of .57 indicated moderate agreement (P < .0001), These results, indicating that patients and physicians usually agree on whether opioids are warranted for abdominal pain, have important implications for further research an ED analgesia in this population. Copyright (C) 1999 by W.B Saunders Company. C1 Harvard Univ, Sch Med, Div Emergency Med, Cambridge, MA 02138 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 115,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 28 Z9 30 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 1999 VL 17 IS 6 BP 586 EP 590 DI 10.1016/S0735-6757(99)90203-6 PG 5 WC Emergency Medicine SC Emergency Medicine GA 244MY UT WOS:000083056400020 PM 10530541 ER PT J AU Sepulveda, AR Santos, AC Yamaoka, Y Wu, L Gutierrez, O Kim, JG Graham, DY AF Sepulveda, AR Santos, AC Yamaoka, Y Wu, L Gutierrez, O Kim, JG Graham, DY TI Marked differences in the frequency of microsatellite instability in gastric cancer from different countries SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; NONPOLYPOSIS COLORECTAL-CANCER; HIGH-RISK POPULATION; INTESTINAL-TYPE; FAMILY HISTORY; MUTATIONS; CARCINOMA; GENES; ADENOCARCINOMA; HOMOLOG AB OBJECTIVE: Previous studies have reported variable rates of microsatellite instability (MST) in gastric cancer. We investigated the frequency of MSI in invasive gastric carcinoma of patients from three geographic regions. METHODS: Genomic DNA from gastric cancer and nontumor tissue from 22 Korean, 20 Colombian, and 26 U.S. patients was amplified with five microsatellite markers. RESULTS: MSI was more frequently seen in gastric cancer from Korea, affecting 50% of patients, in contrast with gastric cancers From the U.S. (7%) and Colombia (15%) (p = 0.003 and p = 0.03, respectively). MSI at one locus was significantly more frequent in gastric cancer from individuals >65 yr (p= 0.01). MSI was similarly associated with both diffuse and intestinal types of gastric cancer. CONCLUSIONS: MSI affects the two major histological types of gastric cancer, and was more frequent in gastric cancer from Korea than in the other countries, suggesting that the relative importance of different pathways of gastric carcinogenesis may vary in diverse regions of the world. (C) 1999 by Am. Cell. of Gastroenterology. C1 Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Korea Univ, Guro Hosp, Coll Med, Seoul 136701, South Korea. Univ Nacl Colombia, Bogota, Colombia. RP Sepulveda, AR (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 39 TC 33 Z9 37 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 1999 VL 94 IS 10 BP 3034 EP 3038 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 243DD UT WOS:000082981000044 PM 10520865 ER PT J AU Annunen, S Korkko, J Czarny, M Warman, ML Brunner, HG Kaariainen, H Mulliken, JB Tranebjaerg, L Brooks, DG Cox, GF Cruysberg, JR Curtis, MA Davenport, SLH Friedrich, CA Kaitila, I Krawczynski, MR Latos-Bielenska, A Mukai, S Olsen, BR Shinno, N Somer, M Vikkula, M Zlotogora, J Prockop, DJ Ala-Kokko, L AF Annunen, S Korkko, J Czarny, M Warman, ML Brunner, HG Kaariainen, H Mulliken, JB Tranebjaerg, L Brooks, DG Cox, GF Cruysberg, JR Curtis, MA Davenport, SLH Friedrich, CA Kaitila, I Krawczynski, MR Latos-Bielenska, A Mukai, S Olsen, BR Shinno, N Somer, M Vikkula, M Zlotogora, J Prockop, DJ Ala-Kokko, L TI Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SENSITIVE GEL-ELECTROPHORESIS; STICKLER-SYNDROME; XI COLLAGEN; WEISSENBACHER-ZWEYMULLER; PCR PRODUCTS; DISEASES; COL2A1; SUBSTITUTION; CARTILAGE; SPECTRUM AB Stickler and Marshall syndromes are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities of different manifestations of a single syndrome. Several mutations causing Stickler syndrome have been found in the COL2A1 gene, and one mutation causing Stickler syndrome and one causing Marshall syndrome have been detected in the COL11A1 gene. We characterize here the genomic structure of the COL11A1 gene. Screening of patients with Stickler, Stickler-like, or Marshall syndrome pointed to 23 novel mutations. Genotypic-phenotypic comparison revealed an association between the Marshall syndrome phenotype and splicing mutations of 54-bp exons in the C-terminal region of the COL11A1 gene. Null-allele mutations in the COL2A1. gene led to a typical phenotype of Stickler syndrome. Some patients, however, presented with phenotypes of both Marshall and Stickler syndromes. C1 Univ Oulu, Dept Med Biochem, SF-90220 Oulu, Finland. Univ Oulu, Bioctr, Collagen Res Unit, Oulu, Finland. Univ Helsinki, Cent Hosp, Dept Med Genet, Helsinki, Finland. Med Coll Penn & Hahnemann Univ, Ctr Gene Therapy, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Med, Div Med Genet, Philadelphia, PA 19104 USA. Karol Marcinkowski Univ Med Sci, Dept Med Genet, Poznan, Poland. Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. Univ Nijmegen Hosp, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen Hosp, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands. Massachusetts Eye & Ear Infirm, Boston, MA USA. Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Univ Tromso Hosp, Dept Med Genet, N-9012 Tromso, Norway. Univ Arkansas Med Sci, Dept Pediat, Div Clin Genet, Little Rock, AR 72205 USA. Sensory Genet Neuro Dev, Bloomington, MN USA. Kaiser Permanente W, Dept Clin Genet, Los Angeles, CA USA. Christian de Duve Inst, Lab Human Mol Genet, Brussels, Belgium. Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Human Genet, Jerusalem, Israel. RP Ala-Kokko, L (reprint author), Univ Oulu, Dept Med Biochem, Kajaanintie 52A, SF-90220 Oulu, Finland. RI Brunner, Han/C-9928-2013; Cruysberg, Johannes/D-4313-2009; OI Cruysberg, Johannes/0000-0002-5330-0774; Vikkula, Miikka/0000-0002-6236-338X NR 40 TC 127 Z9 134 U1 0 U2 5 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 OCT PY 1999 VL 65 IS 4 BP 974 EP 983 DI 10.1086/302585 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 241XW UT WOS:000082910000006 PM 10486316 ER PT J AU Acierno, JS Gusella, JF Slaugenhaupt, SA AF Acierno, JS Gusella, JF Slaugenhaupt, SA TI A cost-effective, time-efficient scanning strategy for genome scans of recessive diseases. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Genom Core Facil, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 504 BP A97 EP A97 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800505 ER PT J AU Antonellis, A Curtis, SC Pezzolesi, MG Moczulski, DK Krolewski, AS AF Antonellis, A Curtis, SC Pezzolesi, MG Moczulski, DK Krolewski, AS TI Rapid identification of polymorphisms in genomic DNA using long range PCR and transposon based sequencing. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1214 BP A220 EP A220 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801214 ER PT J AU Blacker, D O'Brien, LM Tanzi, RE Laird, NM AF Blacker, D O'Brien, LM Tanzi, RE Laird, NM TI Comparing odds ratios from family based and case-control association studies: application to Alzheimer's disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Sch Pub Hlth, Dept Epidemiol, Boston, MA USA. Harvard Sch Pub Hlth, Dept Biostat, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1083 BP A197 EP A197 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801082 ER PT J AU Blakley, PM Holmes, LB Casey, RE AF Blakley, PM Holmes, LB Casey, RE TI Microcephaly-micromelia syndrome in the Cree Indians of Northern Saskatchewan. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Royal Univ Hosp, Dept Pediat, Saskatoon, SK S7N 0W8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 769 BP A143 EP A143 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800772 ER PT J AU Chen, H DePaulo, D Rochino, GN Huo, Y Swift-Scanlan, T Ross, CA McInnis, IG Sklar, P AF Chen, H DePaulo, D Rochino, GN Huo, Y Swift-Scanlan, T Ross, CA McInnis, IG Sklar, P TI Genes on human chromosome 18q21 identified using exon trapping: towards the determination of bipolar susceptibility loci. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1485 BP A266 EP A266 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801486 ER PT J AU Choy, YS Dabora, SL Hall, F Ramesh, V Niida, Y Franz, D Kaprzyk-Obara, J Reeve, MP Kwiatkowski, DJ AF Choy, YS Dabora, SL Hall, F Ramesh, V Niida, Y Franz, D Kaprzyk-Obara, J Reeve, MP Kwiatkowski, DJ TI Superiority of Denaturing High Performance Liquid Chromatography (DHPLC) over single-strand conformation polymorphism (SSCP) and conformation-sensitive gel electrophoresis (CSGE) for mutation detection in TSC2. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Heme Div, Genet Lab, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Childrens Hosp, Med Ctr, Div Pediat Neurol, Cincinnati, OH 45229 USA. Childrens Mem Hosp, Dept Child Neurol, Warsaw, Poland. NR 0 TC 0 Z9 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1233 BP A223 EP A223 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801234 ER PT J AU Collins, JS Perry, RT Watson, B Harrell, LE Acton, RT Blacker, D Albert, MS Tanzi, R McInnis, MG Bassett, MS Go, RCP AF Collins, JS Perry, RT Watson, B Harrell, LE Acton, RT Blacker, D Albert, MS Tanzi, R McInnis, MG Bassett, MS Go, RCP TI TNF polymorphisms in siblings with late-onset Alzheimer disease - The NIMH Genetics Initiative AD Study Group. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD USA. RI McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 435 BP A83 EP A83 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800438 ER PT J AU Dabora, SL Franz, D Jozwiak, S Kwiatkowski, DJ AF Dabora, SL Franz, D Jozwiak, S Kwiatkowski, DJ TI Identification and characterization of 4 large (1.4 kb-34 kb) deletions in TSC2 using long range PCR suggests diverse deletion mechanisms. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Med Ctr, Div Pediat Neurol, Cincinnati, OH 45229 USA. Childrens Mem Hosp, Dept Child Neurol, Warsaw, Poland. NR 0 TC 1 Z9 1 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 OCT PY 1999 VL 65 IS 4 SU S MA 570 BP A108 EP A108 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800572 ER PT J AU Duerr, EM Gimm, O Kum, JB Clifford, SC Toledo, SP Maher, ER Dahia, PL Eng, C AF Duerr, EM Gimm, O Kum, JB Clifford, SC Toledo, SP Maher, ER Dahia, PL Eng, C TI Two polymorphisms in the VHL-associated gene CUL2 are over-represented in pheochromocytoma patients without somatic CUL2 mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Birmingham, Dept Pediat & Child Hlth, Birmingham, W Midlands, England. Univ Sao Paulo, Endocrine Genet Unit, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 660 BP A124 EP A124 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800662 ER PT J AU Eng, C Sarraf, P Smith, WM Mueller, E Kum, JB Wright, HM Aaltonen, LA de la Chapelle, A Spiegelman, BM AF Eng, C Sarraf, P Smith, WM Mueller, E Kum, JB Wright, HM Aaltonen, LA de la Chapelle, A Spiegelman, BM TI Loss of function mutations in the gene encoding peroxisome proliferator-activated receptor gamma (PPARgamma) in colorectal carcinomas SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Helsinki, Helsinki, Finland. RI Aaltonen, Lauri/A-5375-2010 OI Aaltonen, Lauri/0000-0001-6839-4286 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 319 BP A61 EP A61 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800320 ER PT J AU Faber, PW Hart, AC AF Faber, PW Hart, AC TI Analysis of polyglutamine-mediated cellular dysfunction in Caenorhabditis elegans. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 149 BP A29 EP A29 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800148 ER PT J AU Fernandez, M Raskind, W Wolff, J Matsushita, M Lipe, H Bird, T AF Fernandez, M Raskind, W Wolff, J Matsushita, M Lipe, H Bird, T TI A novel form of autosomal dominant movement disorder: familial dyskinesia and facial myokymia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 356 BP A68 EP A68 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800356 ER PT J AU Freund, CL Huang, A Liu, Y Muskat, B Jacobson, SG Seddon, J Zack, DJ McInnes, RR AF Freund, CL Huang, A Liu, Y Muskat, B Jacobson, SG Seddon, J Zack, DJ McInnes, RR TI CRX mutation analysis in age-related macular degeneration (AMD). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Johns Hopkins Med Sch, Baltimore, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1655 BP A295 EP A295 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801655 ER PT J AU Gaedigk, R Fitzgerald, KM Giambrone, SA Cibis, GW Pinson, DM Brunken, WJ White, RA AF Gaedigk, R Fitzgerald, KM Giambrone, SA Cibis, GW Pinson, DM Brunken, WJ White, RA TI Gene targeting of dystrophin Dp260 isoform. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Childrens Mercy Hosp, Kansas City, MO 64108 USA. Univ Kansas, Sch Med, Dept Pathol, Kansas City, KS USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 572 BP A108 EP A108 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800573 ER PT J AU Gill, SP Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Chadwick, BP Slaugenhaupt, SA AF Gill, SP Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Chadwick, BP Slaugenhaupt, SA TI Genomic structure and localization of the IKBKAP gene to the Familial Dysautonomia candidate region on 9q31. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Inst Human Genet, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NYU Med Ctr, New York, NY 10016 USA. RI Brownstein, Michael/B-8609-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1023 BP A186 EP A186 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801024 ER PT J AU Hirschorn, JN Altshuler, D Sklar, P Bolk, S Lindblad, K Lindgren, C Lim, YM Lane, CR Nemesh, J Groop, L Lander, ES AF Hirschorn, JN Altshuler, D Sklar, P Bolk, S Lindblad, K Lindgren, C Lim, YM Lane, CR Nemesh, J Groop, L Lander, ES TI Application of high-throughout SNP genotyping to complex endocrine diseases. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Lund, Malmo, Sweden. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 1 Z9 1 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 OCT PY 1999 VL 65 IS 4 SU S MA 1418 BP A254 EP A254 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801419 ER PT J AU Ji, L Klupa, T Antonellis, A Malecki, M Warram, JH Krolewski, AS AF Ji, L Klupa, T Antonellis, A Malecki, M Warram, JH Krolewski, AS TI Nuclear receptor co-activator (ACTR), a candidate gene for type 2 diabetes identified by fine mapping of 20q13.1: results of mutation analysis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1546 BP A277 EP A277 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801547 ER PT J AU Krahe, R Palatini, J Ashizawa, T Virtaneva, K AF Krahe, R Palatini, J Ashizawa, T Virtaneva, K TI DNA microarray-based profiling of global gene expression changes in myotonic dystrophy (DM). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Ohio State Univ, Comp Canc Ctr, Div Human Canc Genet, Columbus, OH 43210 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1720 BP A306 EP A306 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801723 ER PT J AU Leyne, M Mull, J Gill, SP Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Chadwick, BP Gusella, JF Slaugenhaupt, SA AF Leyne, M Mull, J Gill, SP Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Chadwick, BP Gusella, JF Slaugenhaupt, SA TI Complete genomic sequence of the 471 kb Familial Dysautonomia candidate region on chromosome 9q31. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Inst Human Genet, Boston, MA USA. NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NYU, Med Ctr, New York, NY 10016 USA. RI Brownstein, Michael/B-8609-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 481 BP A92 EP A92 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800481 ER PT J AU Ligon, AH Bruns, GAP Gusella, JF Korf, BR Maas, RL MacDonald, ME Michelson, AM Quade, BJ Morton, CC AF Ligon, AH Bruns, GAP Gusella, JF Korf, BR Maas, RL MacDonald, ME Michelson, AM Quade, BJ Morton, CC TI DGAP: Developmental Genome Anatomy Project. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept OB GYN, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurogenet, Charlestown, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2068 BP A366 EP A366 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802067 ER PT J AU Lunetta, KL Laird, NM AF Lunetta, KL Laird, NM TI Power and Significance levels of tests incorporating the unaffected sibs in families ascertained on the basis of one or more affected offspring. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1460 BP A261 EP A261 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801461 ER PT J AU Maas, RL Peters, H Heaney, S Adams, J Brown, MC Xu, PX AF Maas, RL Peters, H Heaney, S Adams, J Brown, MC Xu, PX TI Eya1 is required for cell survival and tissue interactions during ear and kidney formation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 120 BP A24 EP A24 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800120 ER PT J AU MacCollin, M Blakley, P Louis, D Mankin, H Short, MP AF MacCollin, M Blakley, P Louis, D Mankin, H Short, MP TI A clinical study of patients with isolated multiple neurofibromas. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1877 BP A333 EP A333 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801879 ER PT J AU Matsuura, T Khajavi, M de Silva, R Ashizawa, T AF Matsuura, T Khajavi, M de Silva, R Ashizawa, T TI Very large SCA7 CAG expansion is compatible with cell viability in somatic mosaicism. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. So Gen Hosp, Inst Neurosci, Glasgow, Lanark, Scotland. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2611 BP A460 EP A460 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802613 ER PT J AU McKinnon, WC Guttmacher, AE Jacoby, LB MacCollin, M AF McKinnon, WC Guttmacher, AE Jacoby, LB MacCollin, M TI Multiple schwannomas in identical twins. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Vermont, Coll Med, Dept Pediat, Burlington, VT USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1884 BP A334 EP A334 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801883 ER PT J AU Myers, RH Novelletto, A Cupples, LA DeStefano, A Srinidhi, J Kornbluth, I Gusella, JF MacDonald, ME AF Myers, RH Novelletto, A Cupples, LA DeStefano, A Srinidhi, J Kornbluth, I Gusella, JF MacDonald, ME TI Linked modifier at the Huntington's disease locus. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Roma Tor Vergata, Rome, Italy. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 527 BP A100 EP A100 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800528 ER PT J AU Nelson, HH Wiencke, JK Christiani, DC Mark, EJ Wain, JC Kelsey, KT AF Nelson, HH Wiencke, JK Christiani, DC Mark, EJ Wain, JC Kelsey, KT TI P53 mutation spectrum in non-small cell lung cancer: results from a prospective study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RI Kelsey, Karl/I-1252-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1755 BP A312 EP A312 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801754 ER PT J AU Nijda, Y Lawrence-Smith, N Lewis, J Beauchamp, RL Sims, K Ramesh, V Ozelius, L AF Nijda, Y Lawrence-Smith, N Lewis, J Beauchamp, RL Sims, K Ramesh, V Ozelius, L TI Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2297 BP A406 EP A406 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802299 ER PT J AU Noll, M Bateman, RL D'Andrea, A Grompe, M AF Noll, M Bateman, RL D'Andrea, A Grompe, M TI Cyclophosphamide mediated selection of hematopoietic stem cells corrected by gene therapy in a model of Fanconi Anemia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2860 BP A502 EP A502 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802859 ER PT J AU Parry, DM Bromley, CM Courcoutsakis, N Katzman, GL MacCollin, M Patronas, N AF Parry, DM Bromley, CM Courcoutsakis, N Katzman, GL MacCollin, M Patronas, N TI Spinal magnetic resonance (MR) imaging findings In neurofibromatosis 2 (NF2) and correlations with NF2 germline mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 1768 BP A314 EP A314 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801769 ER PT J AU Patenaude, AF Dorval, M DiGianni, L Kalkbrenner, K Schneider, KA Kieffer, SA Garber, JE AF Patenaude, AF Dorval, M DiGianni, L Kalkbrenner, K Schneider, KA Kieffer, SA Garber, JE TI Measuring distress in individuals presenting for cancer genetic testing: A single interview question versus standard measures. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2299 BP A406 EP A406 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802300 ER PT J AU Persichetti, F Trettel, F Wheeler, V Huang, C Namura, S Hirt, L Timmers, M Moskowitz, M Gusella, J MacDonald, M AF Persichetti, F Trettel, F Wheeler, V Huang, C Namura, S Hirt, L Timmers, M Moskowitz, M Gusella, J MacDonald, M TI Exploring mutant Huntingtin's conformational properties in vivo. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Univ Utrecht, Phys Chem Lab, Utrecht, Netherlands. RI Hirt, Lorenz/G-3553-2010 OI Hirt, Lorenz/0000-0002-2921-5000 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2642 BP A465 EP A465 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802641 ER PT J AU Rich, SS Warram, JH Krolewski, AS AF Rich, SS Warram, JH Krolewski, AS TI Familial aggregation of nephropathy-associated phenotypes in pedigrees ascertained for type 2 diabetes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC USA. Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2235 BP A395 EP A395 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802234 ER PT J AU Schneider, KA Digianni, L Kieffer, S Chittenden, A Shannon, K Patenaude, A Garber, J AF Schneider, KA Digianni, L Kieffer, S Chittenden, A Shannon, K Patenaude, A Garber, J TI Assessing patient satisfaction in a BRCA1/2 testing program. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Alberta Hosp, Edmonton, AB T6G 2B7, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 59 BP A13 EP A13 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800060 ER PT J AU Scott, LJ Krolewski, A Rogus, JJ AF Scott, LJ Krolewski, A Rogus, JJ TI Comparison of the power of the transmission distortion test (TDT) for affected and unaffected trios when disease is highly prevalent. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2248 BP A397 EP A397 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802249 ER PT J AU Seltzer, WK McIntosh, N Myers, RH AF Seltzer, WK McIntosh, N Myers, RH CA US Huntingtons Dis Genetic Testing TI How do US Laboratories do Huntington disease testing for at-risk individuals? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Athena Diagnost, Worcester, MA USA. DIANON Syst Inc, Stratford, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 469 BP A89 EP A89 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800468 ER PT J AU Shannon, KM Lubratovich, ML Finkelstein, D Goggins, W Haber, DA Seiden, MV AF Shannon, KM Lubratovich, ML Finkelstein, D Goggins, W Haber, DA Seiden, MV TI Uptake of free BRCA1/2 testing in women at risk for BRCA1/2 germline mutations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 1999 VL 65 IS 4 SU S MA 1811 BP A322 EP A322 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801812 ER PT J AU Slaugenhaupt, SA Acierno, JS Helbling, LA Bove, C Bach, G Ashworth, L Goldin, E Schiffmann, R AF Slaugenhaupt, SA Acierno, JS Helbling, LA Bove, C Bach, G Ashworth, L Goldin, E Schiffmann, R TI Minimization of the Mucolipidosis Type IV candidate region on human chromosome 19 by haplotype analysis and detailed physical mapping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel. Univ Calif Lawrence Livermore Natl Lab, Ctr Human Genome, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 533 BP A101 EP A101 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800534 ER PT J AU Smoller, JW Acierno, JS Rosenbaum, JF Pollack, MH Biederman, C White, C Helbling, L Gusella, JF Slaugenhaupt, SA AF Smoller, JW Acierno, JS Rosenbaum, JF Pollack, MH Biederman, C White, C Helbling, L Gusella, JF Slaugenhaupt, SA TI Targeted genome screen of panic disorder and anxiety proneness using homology to murine QTL regions. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 1999 VL 65 IS 4 SU S MA 2661 BP A468 EP A468 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802662 ER PT J AU Tan, EK Matsuura, T Nagamitsu, S Khajavi, M Jankovic, J Ashizawa, T AF Tan, EK Matsuura, T Nagamitsu, S Khajavi, M Jankovic, J Ashizawa, T TI Polymorphism of NACP-Rep 1 in patients with Parkinson's disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Neurol Serv, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2667 BP A469 EP A469 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802668 ER PT J AU Teixeira, CAF Sena-Esteves, M Breakefield, XO Mirando, MCS Ribeiro, MG AF Teixeira, CAF Sena-Esteves, M Breakefield, XO Mirando, MCS Ribeiro, MG TI Retroviral mediated transfer and expression of beta-hexosaminidase alpha-chain gene in human fibroblasts from B and B1 variant G(M2)-Gangliosidosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 IBMC, Genet Neurobiol, Porto, Portugal. Inst Med Genet, Unidad Enzimol, Porto, Portugal. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2866 BP A503 EP A503 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802867 ER PT J AU Tranebjaerg, L Lindal, S Merchant, S Ingebretsen, OC Hamel, B Fung, V Hayes, M Koehler, C Nilssen, O van Ghelue, M AF Tranebjaerg, L Lindal, S Merchant, S Ingebretsen, OC Hamel, B Fung, V Hayes, M Koehler, C Nilssen, O van Ghelue, M TI Mohr-Tranebjaerg syndrome is an X-linked recessive disorder characterized by mitochondrial dysfunction associated with neuronal cell death. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Hosp, Dept Med Genet, Tromso, Norway. Univ Hosp, Dept Pathol, Tromso, Norway. Univ Hosp, Dept Clin Chem, Tromso, Norway. Massachusetts Gen Hosp, Temporal Bone Registry, Boston, MA 02114 USA. Univ Nijmegen Hosp, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands. Westmead Hosp, Dept Neurol, Westmead, NSW 2145, Australia. Univ Basel, Biozentrum, Basel, Switzerland. NR 0 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2811 BP A494 EP A494 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802812 ER PT J AU Whetsell, A Wright, M Shrag, D Garber, J Syngal, S Miller, GA Pomponio, RJ AF Whetsell, A Wright, M Shrag, D Garber, J Syngal, S Miller, GA Pomponio, RJ TI The use of cheek brush DNA and allele specific oligonucleotides in screening for the APC I1307K allelic variant in Ashkenazim. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Genzyme, Mol Profiling Lab, Framingham, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 2332 BP A412 EP A412 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879802332 ER PT J AU Yeh, JJ Lunetta, KL Dahia, PLM Eng, C AF Yeh, JJ Lunetta, KL Dahia, PLM Eng, C TI Mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinoma and differential mtDNA sequence variants in cases with malignant versus benign thyroid tumors. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1999 VL 65 IS 4 SU S MA 51 BP A11 EP A11 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800053 ER PT J AU Goetz, AM Kedzuf, S Wagener, M Muder, RR AF Goetz, AM Kedzuf, S Wagener, M Muder, RR TI Feedback to nursing staff as an intervention to reduce catheter-associated urinary tract infections SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; PREVENTION AB Because of high incidence of catheter-related urinary tract infections (UTIs) in our Veterans Affairs medical center we began providing nursing staff with unit-specific UTI rates. In our preintervention period, the first quarter of 1995, 38 infections occurred in 1186 catheter-patient-days or 32/1000 catheter-patient-days (95% CI, 22.9-43.7). Thereafter, nursing staff members were provided with a quarterly report with catheter-related UTI rates depicted graphically by unit. In the 18 months after this intervention, the mean UTI rate decreased to 17.4/1000 catheter-patient-days (95% CT, 14.6-20.6, P = .002). We estimated a cost savings of $403,000. We conclude that unit-specific feedback of nosocomial UTI rates to nursing staff is a highly effective method of reducing infection rates and reducing costs associated with nosocomial UTI. C1 VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Muder, RR (reprint author), Vet Adm Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. NR 14 TC 45 Z9 45 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD OCT PY 1999 VL 27 IS 5 BP 402 EP 404 DI 10.1016/S0196-6553(99)70005-2 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 244NL UT WOS:000083057600005 PM 10511486 ER PT J AU Frankenfield, DL Rocco, MV Frederick, PR Pugh, J McClellan, WM Owen, WF AF Frankenfield, DL Rocco, MV Frederick, PR Pugh, J McClellan, WM Owen, WF CA Natl ESRD Core Indicators Work Grp TI Racia/ethnic analysis of selected intermediate outcomes for hemodialysis patients: Results from the 1997 ESRD Core Indicators Project SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemodialysis; demographics; race; Hispanic; ethnicity; Health Care Financing Administration ID STAGE RENAL-DISEASE; MEXICAN-AMERICANS; UNITED-STATES; HEALTH; DIALYSIS; SURVIVAL; RISK; RACE AB Principal goals of the End-Stage Renal Disease (ESRD) Core Indicators Project are to improve the care provided to ESRD patients and to identify categorical variability in intermediate outcomes of dialysis care. The purpose of the current analysis is to extend our observations about the variability of intermediate outcomes of ESRD care among different racial and gender groups to a previously unreported group, Hispanic Americans. This group is a significant and growing minority segment of the ESRD population, A random sample of Medicare-eligible adult, in-center, hemodialysis patients was selected and stratified from an end-of-year ESRD patient census for 1996, Of the 6,858 patients in the final sample, 45% were non-Hispanic whites, 36% were non-Hispanic blacks, and 11% were Hispanic, Whites were older than blacks or Hispanics (P < 0,001), Hispanics were more likely to have diabetes mellitus as a primary diagnosis than either blacks or whites (P < 0,001). Even though they received longer hemodialysis times and were treated with high-flux hemodialyzers, blacks had significantly lower hemodialysis doses than white or Hispanic patients (P < 0.001). The intradialytic weight losses were greater for blacks (P < 0,05), The delivered hemodialysis dose was lower for blacks than for whites or Hispanics whether measured as a urea reduction ratio (URR) or as the Kt/V calculated by the second generation formula of Daugirdas (median 1,32, 1,36, and 1.37, respectively, P < 0,001), Hispanics and whites had modestly higher hematocrits than blacks (33,2, 33,2, and 33.0%, respectively, P < 0.01), There was no significant difference among groups in the weekly prescribed epoetin alfa dose (similar to 172 units/kg/week), A significantly greater proportion of Hispanic patients had transferrin saturations greater than or equal to 20% compared with the other two groups (P < 0.001), Logistic regression modeling revealed that whites were significantly more likely to have serum albumin < 3.5(BCG)/3.2(BCP) gm/dL (OR 1.4, p < 0.01); blacks were significantly more likely to have a delivered Kt/V < 1.2 (OR 1,4, P < 0.001) and hematocrit < 30%, (OR 1,2; P < 0.05) and both blacks and Hispanics were significantly more likely to have a delivered URR < 65% (OR 1.5, P < 0.001 and 1,2, P < 0.05, respectively). C1 Hlth Care Financing Adm, Off Clin Standards & Qual, Baltimore, MD 21244 USA. Wake Forest Univ, Sch Med, Nephrol Sect, Winston Salem, NC 27109 USA. S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. Emory Univ, Sch Med, Program Hypertens & Renal Dis Hlth Serv Res, Atlanta, GA USA. Emory Univ, Sch Med, Div Renal, Atlanta, GA USA. Duke Univ, Med Ctr, Inst Renal Outcomes Res & Hlth Policy, Durham, NC USA. RP Frankenfield, DL (reprint author), Hlth Care Financing Adm, Off Clin Standards & Qual, Mailstop S3-02-01,7500 Secur Blvd, Baltimore, MD 21244 USA. NR 34 TC 53 Z9 55 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 1999 VL 34 IS 4 BP 721 EP 730 DI 10.1016/S0272-6386(99)70399-9 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 243MM UT WOS:000083001900019 PM 10516355 ER PT J AU Tesch, GH Kelley, VR AF Tesch, GH Kelley, VR TI Chemokines as therapeutic targets in renal inflammation - Reply SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CRESCENTIC GLOMERULONEPHRITIS; MICE; NEPHRITIS; SUPPRESSION; EXPRESSION; DISEASE; INJURY C1 Brigham & Womens Hosp, Howard Hughes Med Inst, Dept Med, Div Renal, Boston, MA 02115 USA. RP Kelley, VR (reprint author), Brigham & Womens Hosp, Howard Hughes Med Inst, Dept Med, Div Renal, 77 Ave Louis Pasteur, Boston, MA 02115 USA. NR 23 TC 0 Z9 0 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 1999 VL 34 IS 4 BP 765 EP 767 DI 10.1016/S0272-6386(99)70411-7 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 243MM UT WOS:000083001900027 ER PT J AU Bartzokis, G Goldstein, IB Hance, DB Beckson, M Shapiro, D Lu, PH Edwards, N Mintz, J Bridge, P AF Bartzokis, G Goldstein, IB Hance, DB Beckson, M Shapiro, D Lu, PH Edwards, N Mintz, J Bridge, P TI The incidence of T2-weighted MR imaging signal abnormalities in the brain of cocaine-dependent patients is age-related and region-specific SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID MIDDLE CEREBRAL-ARTERY; POSITRON EMISSION TOMOGRAPHY; NEUROVASCULAR COMPLICATIONS; SUBCORTICAL LESIONS; ALKALOIDAL COCAINE; LACUNAR INFARCTS; CRACK COCAINE; YOUNG-ADULTS; BLOOD-FLOW; STROKE AB BACKGROUND AND PURPOSE: Cocaine and its metabolites can produce vasospasm, and cocaine-dependent patients are at increased risk for stroke. Based on previous case reports. we hypothesized that the incidence of hyperintense brain lesions observed on T2-weighted MR images would also be increased in asymptomatic cocaine-dependent individuals. METHODS: Sixty-two male "crack" (smoked) cocaine-dependent participants ranging in age from 25 to 66 years were compared with 116 normal male control participants ranging in age from 25 to 80 years. Those with histories of neurologic symptoms or illnesses were excluded. The severity of hyperintense lesions was rated on a 0- to 3-point scale. and ratings of 3 were used in the data analysis as an indicator of a probable pathologic process. Three regions were separately rated: the cerebral white matter. insular subcortex white matter, and subcortical gray matter (basal ganglia and thalamus region). RESULTS: Significantly increased risk of severe lesions was observed in the two white matter regions of the cocaine-dependent group (odds ratio of 16.7 and 20.3) but not in the subcortial gray matter region (odds ratio of 1.4). In the insula subcortex white matter. the risk of lesions increased with age in the cocaine-dependant sample. but remained essentially absent among normal controls through the age of 80 years. In the cerebral white matter, the relationship of age and risk of lesion among normal participants was similar in shape to that in cocaine-dependent participants. but equivalent risk was seen 20 years earlier among cocaine-dependent participants. CONCLUSIONS: Cocaine-dependent participants had a significantly increased age-related risk of white matter damage. The possible clinical implications of this damage are discussed. C1 Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. VA Greater Los Angeles Healthcare Syst, W Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. NIDA, Div Medicat Dev, Rockville, MD USA. RP Bartzokis, G (reprint author), N Little Rock VA Med Ctr, 2200 Ft Roots Dr,Bldg 170,116A NLR, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG-11595]; NIDA NIH HHS [1YO1 DA 50038] NR 74 TC 42 Z9 42 U1 1 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 OCT PY 1999 VL 20 IS 9 BP 1628 EP 1635 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 250ER UT WOS:000083376500012 PM 10543632 ER PT J AU Caughey, AB Shipp, TD Repke, JT Zelop, CM Cohen, A Lieberman, E AF Caughey, AB Shipp, TD Repke, JT Zelop, CM Cohen, A Lieberman, E TI Rate of uterine rupture during a trial of labor in women with one or two prior cesarean deliveries SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Symposium on Sheet Metal Forming Technology, at the TMS Annual Meeting CY FEB 28-MAR 04, 1999 CL SAN DIEGO, CALIFORNIA SP Minerals Met & Mat Soc, Mat Proc & Mfg Div DE vaginal birth after cesarean delivery; trial of labor; uterine rupture; cesarean delivery ID VAGINAL BIRTH; SECTION AB OBJECTIVE: We sought to determine whether there is a difference in the rate of symptomatic uterine rupture after a trial of labor in women who have had 1 versus 2 prior cesarean deliveries. STUDY DESIGN: The medical records of all women with a history of either 1 or 2 prior cesarean deliveries who elected to undergo a trial of labor during a 12-year period (July 1984-June 1996) at the Brigham and Women's Hospital were reviewed. Rates of uterine rupture were compared for these 2 groups. Potential confounding variables were controlled by using logistic regression analyses. RESULTS: Women with 1 prior cesarean delivery (n = 3757) had a rate of uterine rupture of 0.8%, whereas women with 2 prior cesarean deliveries (n = 134) had a rate of uterine rupture of 3.7% (P = .001). in a logistic regression analysis that was controlled for maternal age, use of epidural analgesia, oxytocin induction, oxytocin augmentation, the use of prostaglandin E-2 gel, birth weight, gestational age, type of prior hysterotomy, year of trial of labor. and prior Vaginal delivery, the odds ratio for uterine rupture in those patients with 2 prior cesarean deliveries was 4.8 (95% confidence interval, 1.8-13.2) CONCLUSIONS: Women with a history of 2 prior cesarean deliveries have an almost 5-fold greater risk of uterine rupture than those with only 1 prior cesarean delivery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Omaha, NE USA. Univ Chicago, Chicago Lying In Hosp, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Shipp, TD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Founders 430, Boston, MA 02114 USA. NR 14 TC 78 Z9 81 U1 1 U2 3 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 OCT PY 1999 VL 181 IS 4 BP 872 EP 876 DI 10.1016/S0002-9378(99)70317-0 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 247EX UT WOS:000083208600019 PM 10521745 ER PT J AU Zelop, CM Shipp, TD Repke, JT Cohen, A Caughey, AB Lieberman, E AF Zelop, CM Shipp, TD Repke, JT Cohen, A Caughey, AB Lieberman, E TI Uterine rupture during induced or augmented labor in gravid women with one prior cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT Symposium on Sheet Metal Forming Technology, at the TMS Annual Meeting CY FEB 28-MAR 04, 1999 CL SAN DIEGO, CALIFORNIA SP Minerals Met & Mat Soc, Mat Proc & Mfg Div DE vaginal birth after cesarean delivery induction; augmentation of labor; uterine rupture ID SECTION; INDUCTION; PROSTAGLANDIN-E2; MULTICENTER; OXYTOCIN; TRIAL AB OBJECTIVE: Our purpose was to examine the risk of uterine rupture during induction or augmentation of labor in gravid women with 1 prior cesarean delivery. STUDY DESIGN: The medical records of all gravid women with history of cesarean delivery who attempted a trial of labor during a 12-year period at a single center were reviewed. The current analysis was limited to women at term with 1 prior cesarean delivery and no other deliveries. The rate of uterine rupture in gravid women within that group undergoing induction was compared with that in spontaneously laboring women. The association of oxytocin induction, oxytocin augmentation, and use of prostaglandin Ee gel with uterine rupture was determined. Logistic regression analysis was used to examine these associations, with control for confounding factors. RESULTS: Of 2774 women in the analysis, 2214 had spontaneous onset of labor and 560 women had labor induced with oxytocin or prostaglandin Ep gel. The overall rate of rupture among all patients With induction of labor was 2.3%, in comparison with 0.7% among women with spontaneous labor (P = .001). Among 1072 patients receiving oxytocin augmentation, the rate of uterine rupture was 1.0%, in comparison with 0.4% in nonaugmented, spontaneously laboring patients (P=.1). In a logistic regression model with control for birth weight, use of epidural, duration of labor, maternal age, year of delivery, and years since last birth, induction with oxytocin was associated with a 4.6-fold increased risk of uterine rupture compared with no oxytocin use (95% confidence interval, 1.5-14.1). In that model, augmentation with oxytocin was associated with an odds ratio of 2.3 (95% confidence interval, 0.8-7.0), and use of prostaglandin E-2 gel was associated with an odds ratio of 3.2 (95% confidence interval, 0.9-10.9). These differences were not statistically significant. CONCLUSION: Induction of labor with oxytocin is associated with an increased rate of uterine rupture in gravid women with 1 prior uterine scar in comparison with the rate in spontaneously laboring women. Although the rate of uterine rupture was not statistically increased during oxytocin augmentation, use of oxytocin in such cases should proceed with caution. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Omaha, NE USA. RP Shipp, TD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Founders 430, Boston, MA 02114 USA. NR 13 TC 109 Z9 110 U1 0 U2 4 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 OCT PY 1999 VL 181 IS 4 BP 882 EP 886 DI 10.1016/S0002-9378(99)70319-4 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 247EX UT WOS:000083208600021 PM 10521747 ER PT J AU Pfeifer, W Levi, E Petrogiannis-Haliotis, T Lehmann, L Wang, ZX Kadin, ME AF Pfeifer, W Levi, E Petrogiannis-Haliotis, T Lehmann, L Wang, ZX Kadin, ME TI A murine xenograft model for human CD30+anaplastic large cell lymphoma - Successful growth inhibition with an anti-CD30 antibody (HeFi-1) SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; REED-STERNBERG CELLS; POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMAS; SCID MOUSE MODEL; CD30 LIGAND; BG MICE; DISEASE; ENGRAFTMENT; IMMUNOTOXIN AB To develop a model for the biology and treatment of CD30+ anaplastic large cell lymphoma (ALCL), we transplanted leukemic tumor cells from a 22-month-old girl with multiple relapsed ALCL, Tumor cells were inoculated intraperitoneally into a 4-week-old SCID/bg mouse and produced a disseminated tumor within 8 weeks; this tumor was serially transplanted by subcutaneous injections to other mice. Morphology, immunohistochemistry, and molecular genetics which demonstrated the NPM-ALK fusion protein, resulting from the t(2;5)(p23;q35), confirmed the identity of the xenograft with the original tumor. The tumor produced transcripts for interleukin-1 alpha, tumor necrosis factor-alpha, and interferon-gamma which could explain the patient's B-symptoms. Treatment of mice with monoclonal antibody (HeFi-1) which activates CD30 antigen administered on day 1 after tumor transplantation prevented tumor growth. Treatment with HeFi-1 after tumors had reached a 0.2 cm(3) volume caused tumor growth arrest and prevention of tumor dissemination. We conclude that transplantation of CD30+ ALCL to SCID/bg mice may provide a valuable model for the study of the biology and design of treatment modalities for CD30+ ALCL. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kadin, ME (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, YA 309,330 Brookline Ave, Boston, MA 02215 USA. NR 27 TC 40 Z9 40 U1 0 U2 1 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 OCT PY 1999 VL 155 IS 4 BP 1353 EP 1359 DI 10.1016/S0002-9440(10)65237-6 PG 7 WC Pathology SC Pathology GA 246UU UT WOS:000083183600038 PM 10514417 ER PT J AU Hayashi, T Hirshman, MF Dufresne, SD Goodyear, LJ AF Hayashi, T Hirshman, MF Dufresne, SD Goodyear, LJ TI Skeletal muscle contractile activity in vitro stimulates mitogen-activated protein kinase signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE exercise; soleus muscle; glucose transport; glycogen; mitogen-activated protein kinase kinase inhibitor ID MAP-KINASE; S6 KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; INSULIN STIMULATION; MOLECULAR MECHANISM; GLUCOSE-TRANSPORT; RAF-1 KINASE; TRANSLOCATION; EXERCISE; PHOSPHORYLATION AB Physical exercise is a potent stimulator of mitogen-activated protein (MAP) kinase signaling. To determine if this activation is secondary to systemic responses to exercise or due to muscle contractile activity per se, an isolated muscle preparation was developed. Contractile activity in vitro significantly increased p44(MAPK) and p42(MAPK) phosphorylation by 2.9- and 2.4-fold, respectively. Contraction-stimulated MAP kinase phosphorylation was not decreased in the presence of D-tubocurarine or calphostin C, suggesting that neither pleurotransmitter release nor diacylglycerol-sensitive protein kinase C mediates the contraction-induced activation of this signaling cascade. However, PD-98059, an inhibitor of MAP kinase kinase (MEK), inhibited the contraction-induced increases in MAP kinase phosphorylation. PD-98059 did not alter contraction-induced increases in glucose uptake or glycogen synthase activity, demonstrating that MAP kinase signaling is not necessary for these important metabolic effects of contractile activity in skeletal muscle. These data suggest that contractile activity of the skeletal muscle fibers per se, and not responses to neurotransmitter release, hormones, or other systemic factors, is responsible for the stimulation of MAP kinase signaling with physical exercise. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR-42238] NR 38 TC 59 Z9 60 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 1999 VL 277 IS 4 BP C701 EP C707 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 259XK UT WOS:000083919100013 PM 10516100 ER PT J AU Kaiyala, KJ Prigeon, RL Kahn, SE Woods, SC Porte, D Schwartz, MW AF Kaiyala, KJ Prigeon, RL Kahn, SE Woods, SC Porte, D Schwartz, MW TI Reduced beta-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feeding SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose tolerance; glucose effectiveness; insulin secretion; diabetes; obesity ID INDUCED INSULIN-RESISTANCE; JAPANESE-AMERICAN MEN; DIETARY-FAT; INTRAVENOUS GLUCOSE; ENERGY-EXPENDITURE; DIABETES-MELLITUS; WEIGHT-LOSS; CARBOHYDRATE; SENSITIVITY; SECRETION AB Reduced beta-cell function contributes to impaired glucose tolerance in dogs made obese by high-fat feeding. The ability to increase beta-cell function in the face of reduced insulin sensitivity is essential for normal glucose tolerance. Because high-fat feeding reduces both insulin sensitivity and glucose tolerance, we hypothesized that it also reduces beta-cell compensation. To test this hypothesis, we used intravenous glucose tolerance testing with minimal model analysis to measure glucose tolerance (K-g), insulin sensitivity (S-I), and the acute insulin response to glucose (AIR,) in nine dogs fed a chow diet and again after 7 wk of high-fat feeding. Additionally, we measured the effect of consuming each diet on 24-h profiles of insulin and glucose. After high-fat feeding, S-I decreased by 57% (P = 0.003) but AIR(g) was unchanged. This absence of beta-cell compensation to insulin resistance contributed to a 41% reduction of K-g (P = 0.003) and abolished the normal hyperbolic relationship between AIR(g) and S-I observed at baseline. High-fat feeding also elicited a 44% lower 24-h insulin level (P = 0.004) in association with an 8% reduction of glucose (P = 0.0003). We conclude that high-fat feeding causes insulin resistance that is not compensated for by increased insulin secretion and that this contributes to the development of glucose intolerance. These effects of high-fat. feeding may be especially deleterious to individuals predisposed to type 2 diabetes mellitus. C1 Vet Affairs Puget Sound Hlth Care Syst, Metab 151, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA. RP Schwartz, MW (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Metab 151, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-12829, DK-17047, DK-35816] NR 59 TC 43 Z9 43 U1 0 U2 2 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 OCT PY 1999 VL 277 IS 4 BP E659 EP E667 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 259XJ UT WOS:000083919000011 PM 10516125 ER PT J AU Thorell, A Hirshman, MF Nygren, J Jorfeldt, L Wojtaszewski, JFP Dufresne, SD Horton, ES Ljungqvist, O Goodyear, LJ AF Thorell, A Hirshman, MF Nygren, J Jorfeldt, L Wojtaszewski, JFP Dufresne, SD Horton, ES Ljungqvist, O Goodyear, LJ TI Exercise and insulin cause GLUT-4 translocation in human skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose transporters; glucose uptake; Akt; glucose disposal; muscle contraction ID PROTEIN-KINASE-B; DEPENDENT DIABETES-MELLITUS; INDUCED GLUCOSE-TRANSPORT; PLASMA-MEMBRANE; 3T3-L1 ADIPOCYTES; SENSITIVITY; AKT; CONTRACTION; BINDING; CELLS AB Exercise and insulin cause GLUT-I translocation in human skeletal muscle. Studies in rodents have established that GLUT-4 translocation is the major mechanism by which insulin and exercise increase glucose uptake in skeletal muscle. In contrast, much less is known about the translocation phenomenon in human skeletal muscle. In the current study, nine healthy volunteers were studied on two different days. On one day, biopsies of vastus lateralis muscle were taken before and after a 2-h euglycemic-hyperinsulinemic clamp (0.8 mU . kg(-1) . min(-1)). On another day, subjects exercised for 60 min at 70% of maximal oxygen consumption (VO2max), a biopsy was obtained, and the same clamp and biopsy procedure was performed as that during the previous experiment. Compared with insulin treatment alone, glucose infusion rates were significantly:increased during the postexercise clamp for the periods 0-30 min, 30-60 min, and 60-90 min, but not during the last 30 min of the clamp. Plasma membrane GLUT-4 content was significantly increased in response to physiological hyperinsulinemia (32% above rest), exercise (35%), and the combination of exercise plus insulin (44%). Phosphorylation of Akt, a putative signaling intermediary for GLUT-4 translocation, was increased in response to insulin (640% above rest), exercise (280%), and exercise plus insulin (1,000%). These data demonstrate that two normal physiological Conditions, moderate intensity exercise and physiological hyperinsulinemia similar to 56 uU/ml, cause GLUT-4 translocation and Akt phosphorylation in human skeletal muscle. C1 Joslin Diabet Ctr, Metab Sect, Boston, MA 02215 USA. Huddinge Univ Hosp, Dept Surg, S-14186 Huddinge, Sweden. Karolinska Hosp, Dept Surg, S-17177 Stockholm, Sweden. Karolinska Hosp, Dept Thorac Clin Physiol, S-17177 Stockholm, Sweden. Karolinska Inst, S-17177 Stockholm, Sweden. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. RI Wojtaszewski, Jorgen /P-6583-2014 OI Wojtaszewski, Jorgen /0000-0001-9785-6830 FU NIAMS NIH HHS [AR-42238, AR-45670] NR 52 TC 110 Z9 112 U1 1 U2 7 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 OCT PY 1999 VL 277 IS 4 BP E733 EP E741 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 259XJ UT WOS:000083919000020 PM 10516134 ER PT J AU Wojtaszewski, JFP Lynge, J Jakobsen, AB Goodyear, LJ Richter, EA AF Wojtaszewski, JFP Lynge, J Jakobsen, AB Goodyear, LJ Richter, EA TI Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE glucose and amino acid transport; glycogen synthase; phosphatidylinositol 3-kinase; extracellular signal-regulated kinase; MEK; PD-98059; LY-294002; wortmannin ID ACTIVATED PROTEIN-KINASE; GLYCOGEN-SYNTHASE KINASE-3; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING PATHWAYS; GLUCOSE-TRANSPORTER-4 TRANSLOCATION; GLUCOSE-TRANSPORT; 3T3-L1 ADIPOCYTES; GROWTH-FACTOR; S6 KINASE; WORTMANNIN AB Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications. We have investigated the activation of the extracellular signal-regulated Era kinases (ERK1 and ERK2) by muscle contraction and insulin in perfused rat skeletal muscle. Both stimuli activated ERK1 and ERK2 by an upstream kinase MAP/ERK kinase (MEK)dependent mechanism, as the MEK inhibitor PD-98059 inhibited ERK phosphorylation. The presence of the phosphatidylinositol (PI) 3-kinase inhibitors LY-294002 and wortmannin totally eradicated ERK1 and ERK2 phosphorylation in response to insulin but not contraction. Insulin and muscle contraction activated muscle glucose transport, glycogen synthase, and amino acid transport independently of ERK signaling, whereas the PI 3-kinase inhibitors abolished the stimulatory effects of insulin but not those of contraction on these three cellular processes. We conclude that 1) insulin and contraction activate ERK signaling in skeletal muscle; 2) ERK signaling is not necessary for activation of glucose and amino acid transport or glycogen synthase activity by contraction and insulin in skeletal muscle; and 3) insulin-induced activation of MEK, the upstream activator of ERK, is dependent on PI 3-kinase, whereas contraction utilizes a different mechanism. C1 Univ Copenhagen, August Krogh Inst, Copenhagen Muscle Res Ctr, DK-2100 Copenhagen, Denmark. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Wojtaszewski, JFP (reprint author), Univ Copenhagen, August Krogh Inst, Copenhagen Muscle Res Ctr, 13 Univ Parken, DK-2100 Copenhagen, Denmark. RI Wojtaszewski, Jorgen /P-6583-2014 OI Wojtaszewski, Jorgen /0000-0001-9785-6830 FU NIAMS NIH HHS [R0-1-AR-42238] NR 59 TC 64 Z9 64 U1 0 U2 0 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 OCT PY 1999 VL 277 IS 4 BP E724 EP E732 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 259XJ UT WOS:000083919000019 PM 10516133 ER PT J AU Mashimo, H Goyal, RK AF Mashimo, H Goyal, RK TI Lessons from genetically engineered animal models IV. Nitric oxide synthase gene knockout mice SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE l-arginine; vasodilation; gut motility ID SMOOTH-MUSCLE; LACKING; RELAXATION; DISRUPTION; RESPONSES; SHOCK AB Nitric oxide is a ubiquitous molecule implicated in a variety of biological processes. The specific action of nitric oxide depends on its enzymatic sources, namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), each having distinct tissue localization. Conventional pharmacological antagonists could not distinguish these enzymes or provide models of chronic nitric oxide depletion in whole animals. Several lines of knockout mice have been generated to distinguish the roles of nitric oxide from each enzyme: nitric oxide from nNOS is a major inhibitory neurotransmitter, nitric oxide from eNOS regulates blood flow under physiological conditions, and nitric oxide from iNOS causes hypotension during severe inflammatory conditions. Moreover, the nitric oxides from each isoform have different roles in tissue injury and inflammation. Studies of NOS-deficient animals,have also identified redundant and compensatory pathways and revealed the consequences of life-long deficiency of these enzymes. The nNOS-deficient mice develop gastric dilation and stasis, the eNOS-deficient mice develop hypotension and lack vasodilatory responses to injury, and iNOS-deficient mice are more susceptible to inflammatory damage but more resistant to septic shock. C1 Dept Vet Affairs Med Ctr, Res & Dev Serv 151, W Roxbury, MA 02132 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Goyal, RK (reprint author), Dept Vet Affairs Med Ctr, Res & Dev Serv 151, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NIDDK NIH HHS [DK-31092, K08-DK-02462] NR 27 TC 124 Z9 126 U1 0 U2 0 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 OCT PY 1999 VL 277 IS 4 BP G745 EP G750 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 259XH UT WOS:000083918900001 PM 10516139 ER PT J AU Raybould, HE AF Raybould, HE TI Nutrient Tasting and Signaling Mechanisms in the Gut I. Sensing of lipid by the intestinal mucosa SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE long-chain fatty acids; chylomicrons; cholecystokinin A receptors; vagal afferents ID APOLIPOPROTEIN-A-IV; FATTY-ACIDS; ENDOCRINE-CELLS; RAT; CHOLECYSTOKININ; SECRETION; INHIBITION; TRANSPORT; RELEASE; LYMPH AB It is well recognized that lipid in the intestine is a potent inhibitor of gastric secretomotor function. Progress has been made in the identification of the "sensor" for lipid in the intestinal wall. Long-chain free fatty acids are the stimulus both for release of CCK and for the production of functional effects. Long-chain triglyceride requires chylomicron formation for absorption, and there is strong evidence that the postabsorptive products of long-chain triglyceride absorption, including chylomicrons and apolipoproteins, are involved in sensory transduction in the intestinal wall. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. RP Raybould, HE (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41004] NR 30 TC 68 Z9 73 U1 0 U2 3 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 OCT PY 1999 VL 277 IS 4 BP G751 EP G755 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 259XH UT WOS:000083918900002 PM 10516140 ER PT J AU Tuxworth, WJ Wada, H Ishibashi, Y McDermott, PJ AF Tuxworth, WJ Wada, H Ishibashi, Y McDermott, PJ TI Role of load in regulating eIF-4F complex formation in adult feline cardiocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertrophy; protein synthesis; translation; initiation factors ID INITIATION-FACTOR 4E; ACTIVATED PROTEIN-KINASE; PHAS-I PHOSPHORYLATION; TRANSLATION INITIATION; CARDIAC-HYPERTROPHY; 3T3-L1 ADIPOCYTES; RAT-HEART; 4E-BINDING PROTEIN-1; TISSUE DISTRIBUTION; MUSCLE-CELLS AB This study examined whether cardiocyte load increases eIF-4F complex formation. To increase load in vitro, adult feline cardiocytes were electrically stimulated to contract (1 Hz, 5-ms pulses). eIF-4F complex formation, measured by eIF-4G association with eIF-4E, increased 57 +/- 16% after 4 h of contraction compared with controls. eIF-4F complex formation did not increase on electrical stimulation with 2,3-butanedione monoxime (BDM), an inhibitor of active tension. Both insulin and phorbol ester increased eIF-4F complex formation, but these increases were unaffected by BDM. Insulin caused a shift of eIF-4E binding proteins (4E-BPs) into their hyperphosphorylated gamma-isoforms and dissociation of 4E-BPs from eIF-4E. Rapamycin inhibited 4E-BP phosphorylation in response to insulin but had no effect on eIF-4F complex formation. Electrically stimulated contraction caused a partial shift of 4E-BP1 and 4E-BP2 into the gamma-isoforms, but it had no effect on 4E-BP association with eIF-4E. Rapamycin blocked the increase in eIF-4F complex formation in electrically stimulated cardiocytes and depressed contractility. These data indicate that cardiocyte load causes a tension-dependent increase in eIF-4F complex formation that does not require dissociation of 4E-BPs from eIF-4E. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP McDermott, PJ (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Strom Thurmond Biomed Res Bldg,Rm 303,114 Doughty, Charleston, SC 29425 USA. FU NHLBI NIH HHS [P01 HL-48788] NR 42 TC 13 Z9 14 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 1999 VL 277 IS 4 BP H1273 EP H1282 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 259XN UT WOS:000083919400003 PM 10516161 ER PT J AU Sonawalla, SB Renshaw, PF Moore, CM Alpert, JE Nierenberg, AA Rosenbaum, JF Fava, M AF Sonawalla, SB Renshaw, PF Moore, CM Alpert, JE Nierenberg, AA Rosenbaum, JF Fava, M TI Compounds containing cytosolic choline in the basal ganglia: A potential biological marker of true drug response to fluoxetine SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 151st Annual Meeting of the American-Psychiatric-Association CY MAY 30-JUN 05, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID HUMAN-BRAIN; SPECTROSCOPY; DEPRESSION; PATTERN AB Objective: Studies have identified two types of antidepressant response: true drug response and placebo pattern response. This study examined the relationship between true drug response and choline-creatine ratios in the basal ganglia of depressed patients treated with fluoxetine. Method: The authors evaluated drug-free outpatients with major depression before (N=41) and after (N=15) 8 weeks of fluoxetine treatment, 20 mg/day, by using proton magnetic resonance spectroscopy. Results: There was a significant difference in the degree of change from baseline to week 8 in choline-creatine ratios between the true drug response group (N=8) and the placebo pattern response/nonresponse group (N=7); the true drug response patients had a 20% increase in choline-creatine ratios, and the placebo pattern response/nonresponse patients had a 12% decrease in choline-creatine ratios. Conclusions: These data suggest that true drug response to fluoxetine treatment in depression may be associated with an increase in choline-creatine ratios in the basal ganglia. C1 Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med,Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, McLean Brain Imaging Ctr, Belmont, MA 02178 USA. RP Sonawalla, SB (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Sch Med,Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [MH-48483] NR 13 TC 43 Z9 43 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 1999 VL 156 IS 10 BP 1638 EP 1640 PG 3 WC Psychiatry SC Psychiatry GA 241RN UT WOS:000082896500026 PM 10518178 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI Informed consent when using medical devices for indications not approved by the Food and Drug Administration SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Rush Med Coll, Chicago, IL 60612 USA. RP Smith, JJ (reprint author), Rush N Shore Med Ctr, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 3 TC 7 Z9 7 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1999 VL 173 IS 4 BP 879 EP 882 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 238MW UT WOS:000082714900002 PM 10511140 ER PT J AU Frank, MS Dreyer, KJ Mehta, A AF Frank, MS Dreyer, KJ Mehta, A TI The megapixel digital camera: Value for creating publication-quality illustrations SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Frank, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 0 TC 13 Z9 13 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1999 VL 173 IS 4 BP 883 EP 887 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 238MW UT WOS:000082714900003 PM 10511141 ER PT J AU Yeh, ED Keel, SB Slanetz, PJ AF Yeh, ED Keel, SB Slanetz, PJ TI Intraductal papilloma of the breast SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID BENIGN C1 Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yeh, ED (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Breast Imaging, ACC 219,15 Parkman St, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1999 VL 173 IS 4 BP 936 EP 936 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 238MW UT WOS:000082714900014 PM 10511152 ER PT J AU Scott, JA AF Scott, JA TI Using artificial neural network analysis of global ventilation-perfusion scan morphometry as a diagnostic tool SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SUSPECTED PULMONARY-EMBOLISM; SCINTIGRAPHY; CRITERIA AB OBJECTIVE. The purpose of this study was to determine whether global statistical data from radionuclide ventilation-perfusion scans could predict the likelihood of pulmonary embolism. MATERIALS AND METHODS. Digital data were obtained from 161 patients undergoing both radionuclide ventilation-perfusion scanning and subsequent pulmonary angiography. Morphometric data characterizing whole-lung perfusion and ventilation parameters were input into artificial neural networks in an attempt to predict the likelihood of pulmonary embolism. RESULTS. The performance of artificial neural networks using only automated global region of interest-based data was superior to that of clinicians in predicting the likelihood of acute pulmonary embolism in patients with normal findings on chest radiographs with segmental or larger emboli (p < .005) and in patients with normal findings on chest radiographs and emboli of any size (p < .01). Network performance did not significantly differ from clinician performance in patients with abnormal findings on chest radiographs. CONCLUSION. The adjunctive use of artificial neural networks using only user-independent, standard image statistics can significantly improve accuracy in the diagnosis of pulmonary embolism in patients with normal findings on chest radiographs. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Scott, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 55 Fruit St, Boston, MA 02114 USA. NR 18 TC 15 Z9 16 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1999 VL 173 IS 4 BP 943 EP 948 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 238MW UT WOS:000082714900016 PM 10511154 ER PT J AU Aquino, SL Schechter, MS Chiles, C Ablin, DS Chipps, B Webb, WR AF Aquino, SL Schechter, MS Chiles, C Ablin, DS Chipps, B Webb, WR TI High-resolution inspiratory and expiratory CT in older children and adults with bronchopulmonary dysplasia SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PULMONARY-FUNCTION; BRONCHIOLITIS OBLITERANS; LUNG TRANSPLANTATION; FOLLOW-UP; CHILDHOOD; SEQUELAE; ABNORMALITIES; DIAGNOSIS; SURVIVORS; FIBROSIS AB OBJECTIVE. The objective of this study is to correlate high-resolution inspiratory and expiratory CT findings with pulmonary function results in older children and adults who have bronchopulmonary dysplasia. SUBJECTS AND METHODS. High-resolution inspiratory and expiratory CT of the thorax was performed prospectively on 26 patients (16 male, 10 female) with a clinical history of bronchopulmonary dysplasia. The median age was 10 years old (range, 5-18 years). High-resolution CT during inspiration was scored for areas of decreased density and evidence of interstitial lung disease; expiratory CT was scored for air trapping. Findings were correlated with pulmonary function measurements and clinical history. RESULTS. Twenty-four (92%) of the 26 patients had abnormal CT findings. Of these 24, 22 had reticular opacities and IS had areas of architectural distortion. Twenty patients had areas of relatively decreased density. in 24 patients, air trapping was seen on expiratory CT. Abnormal pulmonary function correlated significantly (p < .05) with abnormal decreases in density, air trapping on expiratory CT, and architectural distortion. CONCLUSION. Abnormal findings on inspiratory and expiratory high-resolution CT of older children with bronchopulmonary dysplasia include scarring and air trapping with architectural distortion. The correlation between these findings and physiologic evidence of air trapping and obstructive lung disease was statistically significant. C1 Massachusetts Gen Hosp, Dept Radiol FND 202, Boston, MA 02114 USA. Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. Univ Calif Davis, Sch Med, Dept Radiol, Sacramento, CA 95817 USA. Sutter Community Hosp, Dept Allergy & Resp Dis, Sacramento, CA 95819 USA. Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94143 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol FND 202, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 48 Z9 54 U1 3 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1999 VL 173 IS 4 BP 963 EP 967 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 238MW UT WOS:000082714900020 PM 10511158 ER PT J AU Nielsen, GP Selig, MK O'Connell, JX Keel, SB Dickersin, GR Rosenberg, AE AF Nielsen, GP Selig, MK O'Connell, JX Keel, SB Dickersin, GR Rosenberg, AE TI Hyalinizing spindle cell tumor with giant rosettes - A report of three cases with ultrastructural analysis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE soft tissue; hyalinizing spindle cell tumor with giant rosettes; ultrastructure ID GRADE FIBROMYXOID SARCOMA AB We report the light microscopic, ultrastructural appearance and immunohistochemical staining profile of three distinctive soft-tissue tumors recently designated hyalinizing spindle cell tumor with giant rosettes. The tumors occurred in two men, 41 and 54 years old, and one woman, 62 years old. Two tumors arose in the lower extremities and one in the upper arm. Two tumors were resected and measured 3 and 13.2 cm in greatest diameter; a biopsy only was done of the third tumor. Grossly, the tumors had a tan, pink, or white cut surface. The largest tumor exhibited central cystic change. Microscopically, they all displayed similar features and were composed of fibromyxoid regions, with areas of hyalinization in two tumors and focal ossification in one tumor. Scattered throughout each of the tumors were rosette-like structures in which neoplastic cells were arranged around a central collagenous core. Ultrastructurally, the neoplastic cells demonstrated the features of fibroblasts. In all tumors, there was abundant extracellular collagen fibers and in one there were large aggregates of amorphous extracellular external lamina-like material. The center of the rosette-like structures was composed of banded collagen fibers and the cells at the periphery of the rosettes had ultrastructural features similar to the neoplastic spindle cells located elsewhere in the tumor. Immunohistochemically, the tumor cells stained for vimentin. There was focal staining of the widely distributed spindle cells and cells that formed the rosettes for Leu-7, S-100 protein, and CD34. In one tumor, there was faint diffuse staining of the spindle cells for neuron-specific enolase. One tumor (with the amorphous extracellular material) stained for type TV collagen. There was no staining for desmin, muscle actin, smooth muscle actin, keratin, or epithelial membrane antigen. These results demonstrate that hyalinizing spindle cell tumor with giant rosettes is composed of fibroblasts. We did not demonstrate any ultrastructural or immunohistochemical differences between the spindle cells that comprised the majority of the mass and those that surrounded the rosette-like structures. There was no ultrastructural evidence of neural differentiation to explain the focal S-100 protein and Leu-7 staining of the tumor cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Nielsen, GP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 5 TC 26 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1999 VL 23 IS 10 BP 1227 EP 1232 DI 10.1097/00000478-199910000-00007 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 244NH UT WOS:000083057300007 PM 10524523 ER PT J AU Rosow, CE AF Rosow, CE TI An overview of remifentanil SO ANESTHESIA AND ANALGESIA LA English DT Article ID ANESTHESIA; MODELS C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Rosow, CE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 15 TC 33 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 1999 VL 89 IS 4 SU S BP S1 EP S3 PG 3 WC Anesthesiology SC Anesthesiology GA 241AZ UT WOS:000082860700001 PM 10511070 ER PT J AU Lowenstein, E AF Lowenstein, E TI Warren Zapol: True-life adventures in science, medicine, and innovation - Recipient of the 1999 Excellence in Research Award SO ANESTHESIOLOGY LA English DT Biographical-Item DE ASCCA; circulatory physiology and hemodynamics; critical care; lung function and disease; nitric oxide; nitric oxide synthase; oxygen; oxygen transport C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lowenstein, E (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 1999 VL 91 IS 4 BP 917 EP 919 DI 10.1097/00000542-199910000-00009 PG 3 WC Anesthesiology SC Anesthesiology GA 241PR UT WOS:000082892200005 PM 10519492 ER PT J AU Xu, LJ Koumenis, IL Tilly, JL Giffard, RG AF Xu, LJ Koumenis, IL Tilly, JL Giffard, RG TI Overexpression of bcl-x(L) protects astrocyte from glucose deprivation and is associated with higher glutathione, ferritin, and iron levels SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 15-22, 1998 CL ORLANDO, FLORIDA SP Amer Soc Anesthesiologists DE antioxidant; bcl-2; free radical; hydrogen peroxide; hypoglycemia; ischemia; mouse; primary culture; retrovirus ID FOCAL CEREBRAL-ISCHEMIA; BCL-X; CELL-DEATH; GLOBAL-ISCHEMIA; REGIONAL DISTRIBUTION; FREE-RADICALS; NEURAL CELLS; CNS NEURONS; RAT-BRAIN; IN-VITRO AB Background: The possibility of altering outcome from ischemia-like injury by overexpressing the anti-cell death gene bcl-x(L) was studied. Cells are known to die by different pathways including apoptosis, or programmed cell death, and necrosis, The bcl-x(L) gene Is a member of a family of apoptosis regulating genes and often displays the death-inhibiting properties of the prototype of this family, bcl-2. It is of special interest to study bcl-x(L) for possible brain protection, because, unlike bcl-2, it is important for normal brain development, Methods: Overexpression of bcl-x(L), was achieved in primary astrocyte cultures using a retroviral vector. Cultures of astrocytes overexpressing bcl-x(L), or a control gene were injured by hydrogen peroxide, glucose deprivation, or combined oxygen and glucose deprivation. Outcome was assessed morphologically and by release of lactate dehydrogenase. We assessed antioxidant effects by measuring glutathione using monochlorobimane, ferritin by immunoblotting, the level of iron spectrophotometrically, and superoxide using iodonitrotetra-zolium violet and dihydroethidium. Results: Protection by bcl-x(L), was found against glucose deprivation and hydrogen peroxide exposure but not combined oxygen and glucose deprivation. Higher levels of superoxide were found, without increased levels of lipid peroxidation. Overexpression of bcl-x(L), was associated with elevated glutathione levels, elevated ferritin levels, and increased amounts of Icon. The increased glutathione contributed to the protection from glucose deprivation. Conclusions: Overexpression of bcl-x(L), protects astrocytes from oxidative injury with the same spectrum of protection seen previously for bcl-2. The Increased antioxidant defense observed should be beneficial against both apoptotic and necrotic cell death. The effects on levels of ferritin and iron are novel and identify a new area of interest for this gene family. Whether this relates to the effects of these genes on mitochondrial function remains to be elucidated. C1 Stanford Univ, Med Ctr, Dept Anesthesia, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. RP Giffard, RG (reprint author), Stanford Univ, Med Ctr, Dept Anesthesia, Sch Med, Room S-272, Stanford, CA 94305 USA. FU NIGMS NIH HHS [GM49831] NR 62 TC 40 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 1999 VL 91 IS 4 BP 1036 EP 1046 DI 10.1097/00000542-199910000-00024 PG 11 WC Anesthesiology SC Anesthesiology GA 241PR UT WOS:000082892200020 PM 10519507 ER PT J AU Steudel, W Hurford, WE Zapol, WM AF Steudel, W Hurford, WE Zapol, WM TI Inhaled nitric oxide - Basic biology and clinical applications SO ANESTHESIOLOGY LA English DT Review DE adult respiratory distress syndrome; lung; primary pulmonary hypertension of the newborn; pulmonary hypertension; review ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; PERSISTENT PULMONARY-HYPERTENSION; CONGENITAL HEART-DISEASE; TUMOR-NECROSIS-FACTOR; RIGHT-VENTRICULAR HYPERTROPHY; PARTIAL LIQUID VENTILATION; LOW-DENSITY-LIPOPROTEIN; METHACHOLINE-INDUCED BRONCHOCONSTRICTION; REDUCES ENDOTHELIAL EXPRESSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 FU NHLBI NIH HHS [HL-42397] NR 333 TC 89 Z9 98 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 1999 VL 91 IS 4 BP 1090 EP 1121 DI 10.1097/00000542-199910000-00030 PG 32 WC Anesthesiology SC Anesthesiology GA 241PR UT WOS:000082892200026 PM 10519513 ER PT J AU Nguyen, L Blust, M Bailin, M Melendez, L Raines, DE AF Nguyen, L Blust, M Bailin, M Melendez, L Raines, DE TI Photosensitivity and perioperative polyneuropathy complicating orthotopic liver transplantation in a patient with erythropoietic protoporphyria SO ANESTHESIOLOGY LA English DT Article DE hepatic failure; phototoxicity; porphyria; protoporphyrin C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Clin Engn, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia, 32 Fruit St, Boston, MA 02114 USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 1999 VL 91 IS 4 BP 1173 EP 1175 DI 10.1097/00000542-199910000-00038 PG 3 WC Anesthesiology SC Anesthesiology GA 241PR UT WOS:000082892200034 PM 10519521 ER PT J AU Koroshetz, WJ Gonzales, RG AF Koroshetz, WJ Gonzales, RG TI Imaging stroke in progress: Magnetic resonance advances but computed tomography is poised for counterattack SO ANNALS OF NEUROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Stroke & Clin Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Neuroradiol, Boston, MA 02114 USA. RP Koroshetz, WJ (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. NR 9 TC 21 Z9 21 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 OCT PY 1999 VL 46 IS 4 BP 556 EP 558 DI 10.1002/1531-8249(199910)46:4<556::AID-ANA2>3.0.CO;2-3 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 241ZV UT WOS:000082914500002 PM 10514091 ER PT J AU Jimenez, RE Warshaw, AL Z'graggen, K Hartwig, W Taylor, DZ Compton, CC Castillo, CFD AF Jimenez, RE Warshaw, AL Z'graggen, K Hartwig, W Taylor, DZ Compton, CC Castillo, CFD TI Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 119th Annual Scientific Session of the American-Surgical-Association CY APR, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Srg Assoc ID TUMOR-SUPPRESSOR GENE; SEROUS CYSTADENOMAS; ONCOGENE MUTATIONS; PROTEIN; ADENOCARCINOMA; EXPRESSION; CANCER; TRANSFORMATION; PRODUCT; LESIONS AB Objective Pancreatic mucinous cystic neoplasms (MCNs) provide a spectrum of neoplastic changes ranging from benign to malignant. The authors have correlated K-ras mutations and p53 overexpression with the evolution of these tumors. Methods Areas of mild, moderate, or severe dysplasia were microdissected from paraffin-embedded tissue sections of 28 different MCNs (10 benign, 9 borderline, 9 malignant). Nonneoplastic pancreatic ducts were also microdissected from tissues adjacent to the tumors. Ten serous cystadenomas served as negative controls. K-ras codon 12 mutations were identified by a mutant-enriched nested polymerase chain reaction-restriction fragment length polymorphism assay acid confirmed by sequencing, p53 overexpression was demonstrated by immunohistochemistry. Results K-ras mutations were detected in 20% of benign, 33% of borderline, and 89% of malignant MCNs. Histologically, mutations were found in 26% (7/27) of MCN epithelia with mild dysplasia, 38% (5/13) of MCN epithelia with moderate dysplasia, and 89% (8/9) of MCN epithelia with severe dysplasia or carcinoma. Ten percent (4/39) of nonneoplastic pancreatic ducts at the margins of MCN harbored mutations, all associated with borderline or malignant tumors. Overexpression of p53 occurred in none of the benign or borderline MCNs but in 44% (4/9) of the malignant tumors (p = 0.006 benign/borderline vs. malignant). p53 immunoreactivity was concentrated in areas of severe dysplasia/carcinoma or invasion, where K-ras mutation had been detected. Conclusion These findings demonstrate a sequential accumulation of genetic changes in the carcinogenesis of MCN, K-ras mutations appear early and increase in proportion with increasing dysplasia. Overexpression of p53 is a late finding observed only in carcinomas, and in combination with mutated K-ras genes. The presence of K-ras mutations in nonneoplastic ducts supports formal pancreatic resection over enucleation for treatment. Mucinous cystic neoplasms may be a useful model to study the evolution of pancreatic ductal adenocarcinomas, in which precursor lesions remain unknown. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Castillo, CFD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, WACC 336, Boston, MA 02114 USA. NR 50 TC 88 Z9 89 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 1999 VL 230 IS 4 BP 501 EP 509 DI 10.1097/00000658-199910000-00006 PG 9 WC Surgery SC Surgery GA 243RV UT WOS:000083011800011 PM 10522720 ER PT J AU Tanabe, KK AF Tanabe, KK TI Ephemeral seeds: Microembolization of tumor cells during surgery SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Cox 626, Boston, MA 02114 USA. NR 4 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT-NOV PY 1999 VL 6 IS 7 BP 631 EP 632 DI 10.1007/s10434-999-0631-1 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 258XK UT WOS:000083864800005 PM 10560846 ER PT J AU Rehring, TF Deutchman, A Cross, JS AF Rehring, TF Deutchman, A Cross, JS TI Polymorphous hemangioendothelioma SO ANNALS OF THORACIC SURGERY LA English DT Article AB Polymorphous hemangioendothelioma is a rare vascular tumor only 5 patients have been previously described. Half of all cases described have occurred in the thoracic cavity, all being discovered on chest radiologic studies obtained for other reasons. This report presents the case of a female patient with polymorphous hemangioendothelioma and a brief review of the current literature. (C) 1999 by The Society of Thoracic Surgeons. C1 Univ Colorado, Hlth Sci Ctr, St Anthonys Hosp, Dept Surg, Denver, CO USA. RP Rehring, TF (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, WAC 458,15 Parkman St, Boston, MA 02114 USA. NR 2 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 1999 VL 68 IS 4 BP 1396 EP 1397 DI 10.1016/S0003-4975(99)00708-0 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 248GB UT WOS:000083265800070 PM 10543515 ER PT J AU Taylor, CR Duke, D AF Taylor, CR Duke, D TI Blistering, scarring, and photosensitivity in a male teenager - Diagnosis - Hydroa vacciniforme (HV) SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ULTRAVIOLET-A C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Gange Photomed Ctr, Boston, MA 02115 USA. RP Taylor, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Gange Photomed Ctr, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 1999 VL 135 IS 10 BP 1267 EP + DI 10.1001/archderm.135.10.1267 PG 2 WC Dermatology SC Dermatology GA 244DK UT WOS:000083036400016 PM 10522677 ER PT J AU Di Patre, PL Read, SL Cummings, JL Tomiyasu, U Vartavarian, LM Secor, DL Vinters, HV AF Di Patre, PL Read, SL Cummings, JL Tomiyasu, U Vartavarian, LM Secor, DL Vinters, HV TI Progression of clinical deterioration and pathological changes in patients with Alzheimer disease evaluated at biopsy and autopsy SO ARCHIVES OF NEUROLOGY LA English DT Article ID SENILE PLAQUES; NEUROFIBRILLARY TANGLES; DYSTROPHIC NEURITES; APOLIPOPROTEIN-E; FRONTAL-CORTEX; SYNAPSE LOSS; BRAIN; SEVERITY; DEMENTIA; PROTEIN AB Objectives: To quantify the progression of senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, and microglial activation in the cortex and white matter of patients with Alzheimer disease evaluated at both biopsy and subsequent autopsy and correlate these changes with the progression of neurologic impairment. Setting: Academic referral center for patient with Alzheimer disease. Patients: Four patients meeting the clinical criteria for Alzheimer disease, enrolled in a pilot study for the evaluation of response to intracerebroventricular administration of bethanechol chloride. The patients were followed up until death occurred and autopsy was performed. Results: all 4 patients had progressive deterioration from the time of biopsy to autopsy (9-11 years). Pathological investigations showed a striking increase in the density of senile plaques and neurofibrillary tangles in 2 of 4 patients from biopsy to autopsy, and a significant increase in microglial activation in 1 of 4 cases. Severity of cerebral amyloid angiopathy varied significantly among patients, 1 of whom displayed striking amyloid deposition with associated subcortical white matter atrophy. Conclusions: These unique data demonstrate that the progressive neurologic impairment in Alzheimer disease is accompanied by a significant increase in senile plaque and neurofibrillary tangle counts in the frontal cortex and, possibly in some patients, by increased microglial cell activation. Cerebral amyloid angiopathy was associated with significant white matter disease. C1 Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Neuropathol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Pathol, Los Angeles, CA 90073 USA. RP Di Patre, PL (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, CHS 18-170, Los Angeles, CA 90095 USA. FU NIA NIH HHS [P30 AG 10123]; NINDS NIH HHS [P01 NS 12435] NR 34 TC 29 Z9 29 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 1999 VL 56 IS 10 BP 1254 EP 1261 DI 10.1001/archneur.56.10.1254 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 243TC UT WOS:000083012500010 PM 10520942 ER PT J AU Wilson, RS Beckett, LA Bennett, DA Albert, MS Evans, DA AF Wilson, RS Beckett, LA Bennett, DA Albert, MS Evans, DA TI Change in cognitive function in older persons from a community population - Relation to age and Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID JAPANESE-AMERICAN MEN; LONGITUDINAL DATA; PROGRESSION; DEMENTIA; PREVALENCE; DECLINE; ONSET; PREDICTORS; DETERIORATION; EDUCATION AB Objective: To examine change in cognitive function in older persons sampled from a community population, and its relation to age and Alzheimer disease. Design: Prospective cohort study with an average of 3.5 years of follow-up. Setting: East Boston, Mass-a geographically defined, urban, working-class community. Participants: A stratified, random sample of persons 65 years and older underwent uniform, structured clinical evaluation for Alzheimer disease. The 388 persons (89.2% of those eligible) who completed at least 1 annual follow-up evaluation were studied: 97 had Alzheimer dis ease at baseline; 95 developed Alzheimer disease during the study; and 196 were unaffected. Outcome Measures: Eight cognitive performance tests were administered, then converted to population-weighted z scores and averaged to create a composite summary measure of cognitive function. Initial level of and change in this score were the outcome measures. Results: In the population as a whole, many persons experienced a decline in cognitive performance, and age was related to both initial level and rate of decline. Analyses were conducted in 3 subgroups: persons with Alzheimer disease at baseline, those who developed Alzheimer disease during the study, and those who remained unaffected. In both Alzheimer disease subgroups, substantial cognitive decline was observed, but neither initial level nor rate of decline was related to age. In unaffected persons, little cognitive decline was evident, and there was a small, inverse association of age with initial level of cognitive function. Conclusion: In a general population sample, there was little evidence of cognitive decline during a 3.5-year period among persons who remained free of Alzheimer disease. C1 Rush Inst Healthy Aging, Chicago, IL 60612 USA. Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA. Rush Univ, Dept Med, Chicago, IL 60612 USA. Rush Univ, Dept Psychol, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Psychiat & Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat & Neurol, Boston, MA 02115 USA. RP Wilson, RS (reprint author), Rush Inst Healthy Aging, 1645 W Jackson Blvd,Suite 675, Chicago, IL 60612 USA. FU NIA NIH HHS [N01-AG-0-2107, N01-AG-1-2106, AG05362] NR 37 TC 76 Z9 78 U1 2 U2 4 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 OCT PY 1999 VL 56 IS 10 BP 1274 EP 1279 DI 10.1001/archneur.56.10.1274 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 243TC UT WOS:000083012500013 PM 10520945 ER PT J AU Oaklander, AL AF Oaklander, AL TI The pathology of shingles - Head and Campbell's 1900 monograph SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSTHERPETIC NEURALGIA AB Shingles (herpes zoster) and postherpetic neuralgia, a chronic neuropathic pain syndrome that can persist after the shingles lesions heal,(1) were studied by eminent neurologists of the 19th century. Autopsy studies were used to establish sensory neural pathways in the peripheral and central nervous systems. More recently, tester and postherpetic neuralgia have served as models for the study of the pathogenesis and treatment of neuropathic pain. Postherpetic neuralgia has the cardinal clinical features of all neuropathic pain syndromes, including sensory abnormalities, ongoing pain, and allodynia (touch-induced pain). Unlike most other neuropathic pain syndromes, such as trigeminal neuralgia or nerve root compressions, shingles has a well-defined pathogenesis and onset, as well as visible lesions, and is therefore uniquely suitable for study. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, 55 Fruit St, Boston, MA 02114 USA. NR 24 TC 11 Z9 19 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 OCT PY 1999 VL 56 IS 10 BP 1292 EP 1294 DI 10.1001/archneur.56.10.1292 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 243TC UT WOS:000083012500016 PM 10520948 ER PT J AU Bressler, NM AF Bressler, NM CA Treatment Age Related Macular Degeneration TI Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin - One-year results of 2 randomized clinical trials - TAP report 1 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LIPOPROTEIN-DELIVERED BENZOPORPHYRIN; MACULOPATHY; PREVALENCE; TUMOR AB Objective: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) call safely reduce the risk of vision loss in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). Design: Two multicenter, double-masked, placebo-controlled, randomized clinical trials. Setting: Twenty-two ophthalmology practices in Europe and North America. Participants: Patients with subfoveal CNV lesions caused by AMD measuring 5400 mu m or less in greatest linear dimension with evidence of classic CNV and best-corrected visual acuity of approximately 20/40 to 20/200. Methods: Six hundred nine patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) administered via intravenous infusion of 30 mt over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm(2) at an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 mu m larger than the greatest linear dimension of the CNV lesion. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The primary outcome was the proportion of eyes with fewer than 15 letters lost (approximately <3 lines of loss), adhering to an intent-to-treat analysis. Results: In each group, 94% of patients completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month-12 examination, 246 (61%) of 402 eyes assigned to verteporfin compared with 96 (46%) of 207 eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline (P<.001). In subgroup analyses the visual acuity benefit (<15 letters lost) of verteporfin therapy was clearly demonstrated (67% VS 39%; P<.001) when the area of classic CNV occupied 50% or more of the area of the entire lesion (termed predominantly classic CNV lesions), especially when there was no occult CNV. No statistically significant differences in visual acuity were noted when the area of classic CNV was more than 0% but less than 50% of the area of the entire lesion. Few ocular or other systemic adverse events were associated with verteporfin treatment, compared with placebo, including transient visual disturbances (18% vs 12%), injection-site adverse events (13% vs 3%), transient photosensitivity reactions (3% vs 0%), and infusion-related low back pain (2% vs 0%). Conclusions: Since verteporfin therapy of subfoveal CNV from AMD can safely reduce the risk of vision loss, we recommend verteporfin therapy for treatment of patients with predominantly classic CNV from AMD. C1 Aberdeen Royal Infirm, Eye Outpatients, Aberdeen, Scotland. Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA. Inst Microcirugia Ocular Barcelona, Barcelona, Spain. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. Retina Associates Cleveland, Cleveland, OH USA. Texas Retina Associates, Dallas, TX USA. Univ Geneva, Hop Cantonal, CH-1211 Geneva, Switzerland. Univ Lausanne, Hop Ophthalmol, Lausanne, Switzerland. Royal Liverpool Univ Hosp, St Pauls Eye Unit, Liverpool, Merseyside, England. Univ Lubeck, Klin Augenheilkunde, D-2400 Lubeck, Germany. Zweng Mem Retinal Res Fdn, Menlo Park, CA USA. Univ Miami, Bascom Palmer Eye Inst, Miami, FL 33152 USA. Vitreous Retina Macula Consultants New York, New York, NY USA. Hop Intercommunal Creteil, Dept Ophthalmol, Paris, France. Retina Vitreous Consultants, Pittsburgh, PA USA. Devers Eye Inst, Portland, OR USA. Associated Retinal Consultants, Royal Oak, MI USA. Hop Bellevue, Serv Ophthalmol, St Etienne, France. Univ Toronto, Eye Res Inst Canada, Toronto, ON, Canada. Univ British Columbia, Vancouver Hosp, Eye Care Ctr, Vancouver, BC V5Z 1M9, Canada. Allgemeines Krankenhaus, Klin Augenheilkunde & Optometrie, Vienna, Austria. Endpoint Res Ltd, Mississauga, ON, Canada. CIBA Vis Corp, Duluth, MN USA. CIBA Vis AG, Bulach, Switzerland. QLT PhotoTherapeut Inc, Vancouver, BC, Canada. RP Bressler, NM (reprint author), 9th Floor,550 N Broadway, Baltimore, MD 21205 USA. NR 30 TC 1102 Z9 1138 U1 15 U2 52 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 1999 VL 117 IS 10 BP 1329 EP 1345 PG 17 WC Ophthalmology SC Ophthalmology GA 244MQ UT WOS:000083055700006 ER PT J AU Metson, R Cosenza, M Gliklich, RE Montgomery, WW AF Metson, R Cosenza, M Gliklich, RE Montgomery, WW TI The role of image-guidance systems for head and neck surgery SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ENDOSCOPIC SINUS SURGERY; ACCURACY; TRACKING AB Background: Although image-guidance systems have gained widespread acceptance for neurosurgical procedures, their role for extracranial surgery of the head and neck is yet to be defined. Objective: To describe the authors' experience with image-guidance systems and to measure the effects of image-guided technology on the performance of minimally invasive otolaryngological procedures. Design: Prospective cohort study. Methods: Optical- and electromagnetic-based image-guidance systems were used during the performance of endoscopic surgery on patients with disease of the paranasal sinuses, orbit, skull base, and temporal bone (n = 79). Results were compared with those in control patients who underwent similar surgery without image guidance during the same period (n = 42). Results: Intraoperative anatomical localization was accurate to within 2 mm at the start of surgery in all cases. Accuracy degraded by 0.89 +/- 0.20 mm (mean +/- SE) during the operative procedure. The use of an image-guidance system increased operating room time by a mean of 17.4 minutes per case (image-guidance group, 137.3 +/- 6.0 minutes [mean +/- SE]; control group, 119.9 +/- 5.7 minutes; P = .006) and increased hospital charges by approximately $496 per case. Intraoperative blood loss (image-guidance group, 178.4 +/- 18.0 mt [mean +/- SE]; control group, 149.4 +/- 20.1 mL) and complication rates (image-guidance group, 2.7%; control group, 4.7%) did not differ significantly between groups. Conclusions: Image-guidance systems can provide the head and neck surgeon with accurate information regarding anatomical localization in cases with poor surgical landmarks caused by extensive disease or prior surgery; however, the use of such systems is associated with increased operative time and expense. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 12 TC 66 Z9 69 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 1999 VL 125 IS 10 BP 1100 EP 1104 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 244ML UT WOS:000083055300004 PM 10522501 ER PT J AU Cheyne, HA Nuss, RC Hillman, RE AF Cheyne, HA Nuss, RC Hillman, RE TI Electroglottography in the pediatric population SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 14-16, 1997 CL SCOTTSDALE, ARIZONA SP Amer Soc Pediat Otolaryngol AB Objective: To establish normative electroglottography (EGG) data in the pediatric population. Design: Clinical study with EGG data gathered on children with normal voices. Setting: Major children's hospital and specialty eye and ear hospital. Patients: A total of 164 children, 79 girls and 85 boys, aged 3 to 16 years. Methods: Children with normal voices, determined through subjective evaluation and a voice use history questionnaire, underwent EGG recording. The EGG data were analyzed with commercially available software for fundamental frequency, jitter, open quotient, closing quotient, and opening quotient. Results: Normative EGG data were established for children aged 3 to 16 years. Jitter, open quotient, closing quotient, and opening quotient were all found to have no significant dependence on age. Conclusions: Children as young as 3 years can easily tolerate EGG, making it possible to establish this initial set of normative pediatric EGG data. These preliminary results suggest that EGG may have potential to assist clinicians with noninvasive documentation of vocal function in the pediatric population. This maybe particularly important for tracking treatment-related changes in the vocal function of children who are difficult to examine endoscopically. C1 Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Speech & Hearing Sci Grad Program, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Childrens Hosp, Dept Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Commun Sci & Disorders, Boston, MA 02114 USA. RP Cheyne, HA (reprint author), Massachusetts Eye & Ear Infirm, Voice & Speech Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01DC00266] NR 15 TC 13 Z9 13 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 1999 VL 125 IS 10 BP 1105 EP 1108 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 244ML UT WOS:000083055300005 PM 10522502 ER PT J AU Kahn, JA Chiou, V Allen, JD Goodman, E Perlman, SE Emans, SJ AF Kahn, JA Chiou, V Allen, JD Goodman, E Perlman, SE Emans, SJ TI Beliefs about Papanicolaou smears and compliance with Papanicolaou smear follow-up in adolescents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID ABNORMAL PAP SMEARS; INCOME MINORITY WOMEN; CERVICAL-CANCER; HEALTH-CARE; BEHAVIOR; ADHERENCE; NONCOMPLIANCE; SATISFACTION; COLPOSCOPY; DYSPLASIA AB Objective: To explore qualitatively adolescent girls' understanding of Papanicolaou smears and barriers to compliance with Papanicolaou smear follow-up appointments. Design: Qualitative analysis, using 3 focus groups and 15 in-depth, semistructured individual interviews. Setting: Adolescent Clinic and Young Parents' Program at Children's Hospital, Boston, Mass. Main Outcome Measures: Beliefs and attitudes about Papanicolaou smears and barriers to compliance with Papanicolaou smear follow-up. Results: The mean (+/-SD) age of the 15 interview participants was 18.7 (+/-1.9) years. Knowledge about Papanicolaou smears and pelvic examinations was poor. Most participants believed that their peers receive Papanicolaou smear screening and perceived teenagers to be susceptible to cervical cancer. Perceived benefits to getting Papanicolaou smears were prevention and early detection or diagnosis, and reported barriers included pain or discomfort, embarrassment, fear of finding a problem, fear of the unknown, denial, poor communication or rapport with the provider, not wanting to look for trouble, lack of knowledge, and peers' advice. Participant-generated strategies for how providers could overcome barriers to Papanicolaou smear screening included education and the development of trusting, consistent relationships with providers. Participant-generated strategies for how providers could enhance appointment-keeping among adolescents included telephone and written reminders. Conclusions: These data support a behavioral theory-based model of adolescent compliance with Papanicolaou smear follow-up, which may help to develop strategies to enhance compliance with Papanicolaou smear follow-up appointments. These strategies include providing in-depth education about Papanicolaou smears, addressing barriers to Papanicolaou smear follow-up, focusing on appropriate provider behaviors, and instituting an appointment reminder system. C1 Childrens Hosp, Med Ctr, Div Adolescent Med, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Div Gynecol, Cincinnati, OH 45229 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kahn, JA (reprint author), Childrens Hosp, Med Ctr, Div Adolescent Med, 3333 Burnet Ave, Cincinnati, OH 45229 USA. RI Allen, Jennifer/M-2113-2015; OI Emans, S. Jean/0000-0002-4535-7850 FU PHS HHS [MCJ-MA259195] NR 42 TC 49 Z9 51 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD OCT PY 1999 VL 153 IS 10 BP 1046 EP 1054 PG 9 WC Pediatrics SC Pediatrics GA 243TH UT WOS:000083013000006 PM 10520612 ER PT J AU Niam, S Cheung, W Sullivan, PE Kent, S Gu, X AF Niam, S Cheung, W Sullivan, PE Kent, S Gu, X TI Balance and physical impairments after stroke SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID POSTURAL CONTROL; BRAIN INJURY; RELIABILITY; STABILITY; SWAY; VALIDITY; PERFORMANCE; WALKING; STANCE; SCALE AB Objective: To investigate the relationship among laboratory and clinical balance measures and physical impairments. Design: A descriptive correlational study. Setting: Research laboratory. Participants: Thirty subjects with stroke, recruited through convenience sampling. Main Outcome Measures: Postural sway was calculated in terms of center of pressure (COP) parameters including spectral characteristics. Clinical balance was measured using the Balance Scale. The assessed physical impairments included stages of lower limb motor recovery, ankle proprioception, and passive dorsiflexion range of the involved limb. Results: The Balance Scale was correlated with COP speed (r = -.57), COP root mean square speed (r = -.50), and COP mean frequency (r = -.50) in the anterior-posterior direction only. Moderate to high correlations were found among most of the COP parameters except spectral characteristics. Significant differences in postural sway were found among different stance in eyes-open (p = .00 to .02) and eyes-closed conditions (p = .00 to .04). Subjects with impaired ankle proprioception had significantly increased postural sway and decreased Balance Scale scores when compared with the subjects with intact ankle proprioception. Conclusions: Some of the clinical and laboratory balance assessments were related, indicating that some components of the tests are similar, but some measured different aspects of balance. Postural sway was related to visual condition, stance position, and proprioception. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Tan Tock Seng Hosp, Physiotherapy Dept, Singapore 308433, Singapore. Kowloon Hosp, Hong Kong, Hong Kong. Harvard Univ, Sch Med, Dept Orthoped, Boston, MA USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA USA. Royal Perth Hosp, Perth, WA, Australia. Beijing Hosp, Rehabil Dept, Beijing, Peoples R China. RP Niam, S (reprint author), Tan Tock Seng Hosp, Physiotherapy Dept, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. NR 37 TC 75 Z9 81 U1 7 U2 17 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 1999 VL 80 IS 10 BP 1227 EP 1233 DI 10.1016/S0003-9993(99)90020-5 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 244AW UT WOS:000083030500003 PM 10527078 ER PT J AU Maurer, BT Stern, AG Kinossian, B Cook, KD Schumacher, HR AF Maurer, BT Stern, AG Kinossian, B Cook, KD Schumacher, HR TI Osteoarthritis of the knee: Isokinetic quadriceps exercise versus an educational intervention SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID HEALTH-STATUS INSTRUMENTS; OSTEO-ARTHRITIS; RHEUMATOID-ARTHRITIS; RESISTANCE EXERCISE; MEDICAL-MANAGEMENT; PATIENT EDUCATION; FUNCTIONAL STATUS; STRENGTH; WEAKNESS; PROGRAM AB Objective: To evaluate the effects of isokinetic exercise versus a program of patient education on pain and function in older persons with knee osteoarthritis. Design: A randomized, comparative clinical trial, with interventions lasting 8 weeks and evaluations of 12 weeks. Setting: An outpatient Veterans Affairs Medical Center clinic and an affiliated university hospital. Patients: One hundred thirteen men and women between 50 and 80 years old with diagnosed osteoarthritis of the knee; 98 completed the entire assigned treatment. Intervention: Patients received either a regimen of isokinetic exercise of the quadriceps muscle three times weekly over 8 weeks or a series of 4 discussions and lectures led by health care professionals. Main Outcome Measures: Variables studied for change were isokinetic and isometric quadriceps strength, pain and function determined by categorical and visual analog scales, and overall status using physician and patient global evaluations by the Arthritis Impact Scale, version 2, Western Ontario McMaster's Arthritis Index, and Medical Outcome Study Short Form 36. Results: Both treatment groups showed significant strength gains (p < .05), which occurred over a wider velocity spectrum for the exercise group. Exercised patients also had improved pain scores for more of the variables measured than those receiving education. Both groups had positive functional outcomes and slightly improved measures of overall status. Conclusions: Isokinetic exercise is an effective and well-tolerated treatment for knee osteoarthritis, but a much less costly education program also showed some benefits. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Thomas Jefferson Univ, Dept Vet Affairs Med Ctr, Jefferson Med Coll, Med Res Serv, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Dept Vet Affairs Med Ctr, Jefferson Med Coll, Dept Med, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Dept Vet Affairs Med Ctr, Jefferson Med Coll, Rheumatol Immunol Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Thomas Jefferson Univ, Dept Vet Affairs Med Ctr, Jefferson Med Coll, Med Res Serv, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 63 TC 123 Z9 133 U1 2 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 1999 VL 80 IS 10 BP 1293 EP 1299 DI 10.1016/S0003-9993(99)90032-1 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 244AW UT WOS:000083030500015 PM 10527090 ER PT J AU Felson, DT LaValley, MP Baldassare, AR Block, JA Caldwell, JR Cannon, GW Deal, C Evans, S Fleischmann, R Gendreau, RM Harris, ER Matteson, EL Roth, SH Schumacher, HR Weisman, MH Furst, DE AF Felson, DT LaValley, MP Baldassare, AR Block, JA Caldwell, JR Cannon, GW Deal, C Evans, S Fleischmann, R Gendreau, RM Harris, ER Matteson, EL Roth, SH Schumacher, HR Weisman, MH Furst, DE TI The Prosorba column for treatment of refractory rheumatoid arthritis - A randomized, double-blind, sham-controlled trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COMPLEMENT ACTIVATION; DISEASE AB Objective, To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. Methods. A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point, A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. Results. Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. Conclusion. Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments. C1 Boston Univ, Arthrit Ctr, Sch Med, Boston, MA 02118 USA. St Louis Univ, Sch Med, St Louis, MO USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Halifax Clin Res, Gainesville, FL USA. Dept Vet Affairs Med Ctr, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rheumatol Res Int, Dallas, TX USA. Cypress Biosci Inc, San Diego, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Mayo Clin & Mayo Grad Sch Med, Rochester, MN 55901 USA. Phoenix Reg Med Ctr, Phoenix, AZ USA. Univ Penn, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Virginia Mason Res Ctr, Seattle, WA 98101 USA. Univ Washington, Seattle, WA 98195 USA. RP Felson, DT (reprint author), Boston Univ, Arthrit Ctr, Sch Med, 715 Albany St,A-203, Boston, MA 02118 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCRR NIH HHS [M01-RR00064] NR 17 TC 78 Z9 84 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1999 VL 42 IS 10 BP 2153 EP 2159 DI 10.1002/1529-0131(199910)42:10<2153::AID-ANR16>3.0.CO;2-W PG 7 WC Rheumatology SC Rheumatology GA 246FH UT WOS:000083153400016 PM 10524687 ER PT J AU Seidman, LJ Faraone, SV Goldstein, JM Goodman, JM Kremen, WS Toomey, R Tourville, J Kennedy, D Makris, N Caviness, VS Tsuang, MT AF Seidman, LJ Faraone, SV Goldstein, JM Goodman, JM Kremen, WS Toomey, R Tourville, J Kennedy, D Makris, N Caviness, VS Tsuang, MT TI Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: An MRI-based morphometric analysis SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on the State of the Art of Schizophrenia Research CY OCT 08, 1998 CL SANTA FE, NEW MEXICO DE schizophrenia; relatives; genetics; MRI; amygdala-hippocampus; thalamus ID 4-SUBTEST SHORT FORMS; WAIS-R; BRAIN ABNORMALITIES; NEUROPSYCHOLOGICAL FUNCTION; NONPSYCHOTIC RELATIVES; UNAFFECTED SIBLINGS; PSYCHIATRIC SAMPLE; VENTRICULAR SIZE; HUMAN NEOCORTEX; BASAL GANGLIA AB Background: Schizophrenia is characterized by subcortical and cortical brain abnormalities. Evidence indicates that some nonpsychotic relatives of schizophrenic patients manifest biobehavioral abnormalities, Including brain abnormalities. The goal of this study was to determine whether amygdala-hippocampal and thalamic abnormalities are present in relatives of schizophrenic patients. Methods: Subjects were 28 nonpsychotic, and nonschizotypal, first-degree adult relatives of schizophrenics and 26 normal control subjects. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter and cerebrospinal fluid (CSF) were segmented using a semi-automated intensity contour mapping algorithm. Analyses of covariance of the volumes of brain regions, controlling for expected intellectual (i.e., reading) ability and diagnosis, were used to compare groups. Results: The main findings were that relatives had significant volume reductions bilaterally in the amygdala-hippocampal region and thalamus compared to control subjects. Marginal differences were noted in the pallidum, putamen, cerebellum and third and fourth ventricles. Conclusions: Results support the hypothesis that core components of the vulnerability to schizophrenia include structural abnormalities in the thalamus and amygdala-hippocampus. These findings require further work to determine if the abnormalities are an expression of the genetic liability to schizophrenia. Biol Psychiatry 1999; 46:941-954 (C) 1999 Society of Biological psychiatry. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat,Neuropsychol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, Dept Psychiat, Brockton, MA 02401 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. Univ Calif Davis, Napa Psychiat Res Ctr, Sacramento, CA 95817 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Ctr Morphometr Anal, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Serv,Ctr Morphometr Anal, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Seidman, LJ (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat,Neuropsychol Lab, 74 Fenwood Rd, Boston, MA 02115 USA. RI Kennedy, David/H-3627-2012; OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K21 MH 00976, MH 43518, MH 46318] NR 91 TC 180 Z9 183 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 1999 VL 46 IS 7 BP 941 EP 954 DI 10.1016/S0006-3223(99)00075-X PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 239RE UT WOS:000082782800009 PM 10509177 ER PT J AU Jensen, LJ Stuart-Tilley, AK Peters, LL Lux, SE Alper, SL Breton, S AF Jensen, LJ Stuart-Tilley, AK Peters, LL Lux, SE Alper, SL Breton, S TI Immunolocalization of AE2 anion exchanger in rat and mouse epididymis SO BIOLOGY OF REPRODUCTION LA English DT Article ID CARBONIC-ANHYDRASE; COLLECTING DUCT; CELLS; ACIDIFICATION; SPERMATOZOA; ATPASE; PH; CONDUCTANCES; TRANSPORT; MAMMALS AB A low-bicarbonate concentration and an acidic pH in the luminal fluid of the epididymis and vas deferens are important for sperm maturation. These factors help maintain mature sperm in an immotile but viable state during storage in the cauda epididymidis and vas deferens. Two proton extrusion mechanisms, an Na(+)/H(+) exchanger and an H(+)ATPase, have been proposed to be involved in this luminal acidification process. The Na(+)/H(+) exchanger has not yet been localized in situ, but we have reported that H(+)ATPase is expressed on the apical membrane of apical (or narrow) and clear cells of the epididymis. These cells are enriched in carbonic anhydrase II, indicating the involvement of bicarbonate in the acidification process and suggesting that the epididymis is a site of bicarbonate reabsorption. Previous unsuccessful attempts to localize the Cl/HCO(3) anion exchanger AE1 in rat epididymis did not investigate other anion exchanger (AE) isoforms. In this report, we used a recently described SDS antigen unmasking treatment to localize the Cl/HCO(3) exchanger AE2 in rat and mouse epididymis. AE2 is highly expressed in the initial segment, intermediate zone, and caput epididymidis, where it is located on the basolateral membrane of epithelial cells. The cauda epididymidis and vas deferens also contain basolateral AE2, but in lower amounts. The identity of the AE2 protein was further confirmed by the observation that basolateral AE2 expression was unaltered in the epididymis of AE1-knockout mice. Basolateral AE2 may participate in bicarbonate reabsorption and luminal acidification, and/or may be involved in intracellular pH homeostasis of epithelial cells of the male reproductive tract. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Mol Med Unit, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA 02215 USA. Childrens Hosp, Div Hematol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM sbreton@receptor.mgh.harvard.edu RI Jensen, Lars/A-9340-2008 FU NHLBI NIH HHS [R01 HL064885]; NIDDK NIH HHS [DK34854, DK 38452, DK43495] NR 45 TC 40 Z9 42 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 1999 VL 61 IS 4 BP 973 EP 980 DI 10.1095/biolreprod61.4.973 PG 8 WC Reproductive Biology SC Reproductive Biology GA 240JE UT WOS:000082821500017 PM 10491632 ER PT J AU Lu, L Heinrich, MC Wang, LS Dai, MS Zigler, AJ Chai, L Broxmeyer, HE AF Lu, L Heinrich, MC Wang, LS Dai, MS Zigler, AJ Chai, L Broxmeyer, HE TI Retroviral-mediated gene transduction of c-kit into single hematopoietic progenitor cells from cord blood enhances erythroid colony formation and decreases sensitivity to inhibition by tumor necrosis factor-alpha and transforming growth factor-beta 1 SO BLOOD LA English DT Article ID HUMAN-ERYTHROPOIETIN RECEPTOR; HUMAN BONE-MARROW; MYELOGENOUS LEUKEMIA BLASTS; TGF-BETA; STROMAL CELLS; STIMULATING FACTOR; TYROSINE KINASE; STEM-CELLS; PROTOONCOGENE PRODUCT; INTERFERON-GAMMA AB The c-kit receptor and its ligand, steel factor (SLF), are critical for optimal hematopoiesis. We evaluated effects of transducing cord blood (CB) progenitor cells with a retrovirus encoding human c-kit cDNA, CD34(+) cells were sorted as a population or as 1 cell/well for cells expressing high levels of CD34(+++) and different levels of c-kit ((++), (+), (Lo/-)), transduced and then cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, erythropoietin (Epo) +/- SLF in the absence of serum. At a single-cell level, transduction with c-kit, but not with control (neo only), virus significantly increased colony formation, especially by erythroid and multipotential progenitors. The enhancing effect of c-kit transduction was inversely correlated with expression of c-kit protein before transduction. The greatest enhancing effects were noted in CD34(+++) kit(Lo/-) cells transduced with c-kit. The stimulating effect was apparent even in the absence of exogenously added SLF, but in the presence of GM-CSF, IL-3, IL-6, and Epo. Enzyme-linked immunosorbent assay (ELISA) of SLF protein, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of SLF mRNA expression in CD34(+) cells, and use of neutralizing antibodies to SLF and/or c-kit suggested the presence of endogenous, although probably very low level, expression of SLF by these progenitor cells. Transduction of c-kit significantly decreased sensitivity of progenitor cells to the inhibitory effects of transforming growth factor-pr and tumor necrosis factor-a. c-kit-transduced cells had increased expression of c-kit protein and decreased spontaneous or cytokine-induced apoptosis. Our results suggest that transduced c-kit into selected progenitor cells can enhance proliferation and decrease apoptosis and that endogenous SLF may mediate this effect. (C) 1999 by The American Society of Hematology. C1 Indiana Univ, Sch Med, Walther Oncol Ctr, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Walther Oncol Ctr, Dept Med Hematol Oncol, Indianapolis, IN 46202 USA. Walther Canc Inst, Indianapolis, IN USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Div Hematol & Med Oncol, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Lu, L (reprint author), Indiana Univ, Sch Med, Walther Oncol Ctr, Dept Microbiol & Immunol, 1044 W Walnut St,Room 302, Indianapolis, IN 46202 USA. FU NHLBI NIH HHS [R01 HL56416, R01 HL 54037]; NIDDK NIH HHS [R01 DK 53674] NR 63 TC 22 Z9 28 U1 0 U2 1 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 OCT 1 PY 1999 VL 94 IS 7 BP 2319 EP 2332 PG 14 WC Hematology SC Hematology GA 242HT UT WOS:000082935000020 PM 10498604 ER PT J AU Aguiar, RCT Yakushijin, Y Kharbanda, S Tiwari, S Freeman, GJ Shipp, MA AF Aguiar, RCT Yakushijin, Y Kharbanda, S Tiwari, S Freeman, GJ Shipp, MA TI PTPROt: An alternatively spliced and developmentally regulated B-lymphoid phosphatase that promotes G0/G1 arrest SO BLOOD LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; MOLECULAR-CLONING; CELL-LINES; EXPRESSION; IDENTIFICATION; GROWTH; GENE; PHOSPHORYLATION; DIFFERENTIATION; INVOLVEMENT AB Protein tyrosine phosphatases (PTP) regulate the proliferation, differentiation, and viability of lymphocytes by modulating their signaling pathways. By using the differential display assay, we have cloned a putative receptor-type PTP, which is predominantly expressed in B-lymphoid tissues (lymph nodes and spleen). This PTP, termed PTPROt (truncated), is a tissue-specific alternatively-spliced form of a human epithelial PTP, PTPRO (PTPU2/GLEPP1). Whereas the epithelial PTPRO includes an approximate to 800-amino acid extracellular domain, the major (3 kb) PTPROt cDNA predicts a unique 5' untranslated region and truncated (8 amino acids) extracellular domain with a conserved transmembrane region and single catalytic domain. PTPROt cDNAs encode functional similar to 47-kD and similar to 43-kD PTPs, which are most abundant in normal naive quiescent B cells and decreased or absent in germinal center B cells and germinal center-derived diffuse large B-cell lymphomas. Because PTPROt was predominantly expressed in naive quiescent B cells, the enzyme's effects on cell-cycle progression were examined. When multiple stable PTPROt sense, antisense, and vector only B-cell transfectants were grown in reduced serum and synchronized with nocodazole, PTPROt sense clones exhibited markedly increased G0/G1 arrest. Taken together, these data implicate PTPROt in the growth control of specific B-cell subpopulations. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Tiwari, Sanjay/Q-1853-2016 OI Tiwari, Sanjay/0000-0002-3804-3300 FU NCI NIH HHS [CA66996] NR 35 TC 56 Z9 59 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 OCT 1 PY 1999 VL 94 IS 7 BP 2403 EP 2413 PG 11 WC Hematology SC Hematology GA 242HT UT WOS:000082935000029 PM 10498613 ER PT J AU Haaijman, A Karperien, M Lanske, B Hendriks, J Lowik, CWGM Bronckers, ALJJ Burger, EH AF Haaijman, A Karperien, M Lanske, B Hendriks, J Lowik, CWGM Bronckers, ALJJ Burger, EH TI Inhibition of terminal chondrocyte differentiation by bone morphogenetic protein 7 (OP-1) in vitro depends on the periarticular region but is independent of parathyroid hormone-related peptide SO BONE LA English DT Article DE bone morphogenetic protein 7 (BMP-7); parathyroid hormone (PTH)-related peptide; Indian hedgehog (Ihh); endochondral ossification; chondrocyte hypertrophy ID MESSENGER-RNA EXPRESSION; GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; INDIAN HEDGEHOG; SONIC HEDGEHOG; LONG BONES; MICE; CARTILAGE; RECEPTOR; BMP-7 AB Bone morphogenetic protein-7, or BMP-7 (OP-l), is highly expressed in the perichondrium of embryonic long bones and is thought to play a role in endochondral ossification. Previously we have shown that BMP-7 inhibits terminal chondrocyte differentiation; that is, chondrocyte hypertrophy and mineralization in cultured explants of embryonic mouse metatarsals. However, the mechanism of this inhibition and the target cells of BMP-7 are still unknown, In this study we show that BMP-7 inhibits terminal chondrocyte differentiation indirectly, via an interaction with the periarticular region of the explants, This region also expresses parathyroid hormone-related peptide (PTHrP), PTHrP regulates terminal chondrocyte differentiation by inhibiting hypertrophic differentiation of prehypertrophic chondrocytes, The differentiating center in turn regulates PTHrP expression via a feedback loop involving Indian hedgehog (Ihh), which is expressed in the prehypertrophic chondrocytes, Ihh is thought to act on perichondrial cells, which in turn start to express an as yet unknown mediator that stimulates PTHrP expression in the periarticular region, It has been suggested that this factor belongs to the BMP-family, We investigated whether the inhibition of terminal chondrocyte differentiation by BMP-7 was due to upregulation of the PTHrP-Ihh feedback loop and whether BMP-7 was the unknown factor in the loop. Here we show that exogeneous BMF-7 did not upregulate the mRNA expression of PTHrP, Ihh, or the PTH/PTHrP receptor in cultured wild-type embryonic metatarsals, Furthermore, BMP-7 could still inhibit terminal chondrocyte differentiation in the metatarsals of PTHrP-deficient (PTHrP-/-) mouse embryos, These data indicate that the BMP-7-mediated inhibition of terminal chondrocyte differentiation in vitro is independent of the PTHrP-Ihh feedback loop. We concluded that BMP-7 modulates terminal chondrocyte differentiation and cartilage mineralization of fetal bone explants in vitro via as yet unknown inhibitory factor(s) produced in the periarticular region, (C) 1999 by Elsevier Science Inc. All rights reserved. C1 Free Univ Amsterdam, Dept Oral Cell Biol ACTA, NL-1081 BT Amsterdam, Netherlands. Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pediat, Leiden, Netherlands. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Netherlands Inst Dev Biol, Utrecht, Netherlands. RP Bronckers, ALJJ (reprint author), Free Univ Amsterdam, Dept Oral Cell Biol ACTA, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. NR 49 TC 37 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 1999 VL 25 IS 4 BP 397 EP 404 DI 10.1016/S8756-3282(99)00189-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237MW UT WOS:000082661000002 PM 10511105 ER PT J AU Toh, HC McAfee, SL Sackstein, R Cox, BF Colby, C Spitzer, TR AF Toh, HC McAfee, SL Sackstein, R Cox, BF Colby, C Spitzer, TR TI Late onset veno-occlusive disease following high-dose chemotherapy and stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE late onset VOD; high-dose chemotherapy; peripheral blood stem cell transplantation; ursodeoxycholic acid; VOD risk factors ID BONE-MARROW TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; LIVER; DIAGNOSIS; TOXICITY; COHORT; BLOOD AB The original definition of hepatic veno-occlusive disease (VOD), which is still widely accepted, includes onset of the clinical syndrome before day +20 following high-dose chemotherapy (HDC) and stem cell transplantation (SCT), We retrospectively identified four patients following HDC and SCT presenting with late onset VOD occurring at day +24, day +27, day +34 and day +42 post SCT, All patients had moderate VOD, with successful resolution of the VOD before day +100 with optimal supportive therapy. Common risk factors for VOD shared by all four patients included an older age (median age: 60 years), and use of a busulphan-containing regimen. Mean and maximum bilirubin levels for all patients during the VOD syndrome,were 2.02, 1.76, 5.09, 2.87 mg/dl and 2.5, 2.2, 8.9 and 4.1 mg/dl, respectively, which correlated well with duration of VOD, All patients encountered platelet transfusion-dependent thrombocytopenia during VOD, Ursodeoxycholic acid was used as VOD prophylaxis beginning at a mean of 33 days prior to onset of VOD, As the cellular target of hepatic VOD is as yet unidentified, it is uncertain whether ursodiol or other common characteristics of patients with late onset VOD influence the pathogenesis and natural history of this disease, We believe that the uncommon clinical entity of late onset VOD, a potentially fatal regimen-related toxicity, should not be ignored as a diagnosis of liver disease after 3 or more weeks following HDC and SCT. C1 Massachusetts Gen Hosp, Bone Marrow Transplant Program, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 21 TC 27 Z9 28 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1999 VL 24 IS 8 BP 891 EP 895 DI 10.1038/sj.bmt.1701994 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 249ME UT WOS:000083336200013 PM 10516702 ER PT J AU Colby, C McAfee, SL Sackstein, R Finkelstein, DM Fishman, JA Spitzer, TR AF Colby, C McAfee, SL Sackstein, R Finkelstein, DM Fishman, JA Spitzer, TR TI A prospective randomized trial comparing the toxicity and safety of atovaquone with trimethoprim/sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis following autologous peripheral blood stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE atovaquone; Pneumocystis carinii pneumonitis; autologous PBSC transplantation; prophylaxis; toxicity ID BONE-MARROW TRANSPLANTATION; TRIMETHOPRIM-SULFAMETHOXAZOLE; PENTAMIDINE; PREVENTION; AIDS; DAPSONE; THERAPY AB Pneumonia due to Pneumocystis carinii is an infrequent complication following autologous stem cell transplantation (ASCT) which is associated with a high mortality, Although administration of trimethoprim/sulfamethoxazole (TMP/SMX) is an effective prophylactic strategy for Pneumocystis carinii pneumonia (PCP), treatment-associated toxicity frequently results in discontinuation of therapy, We have conducted a prospective randomized trial comparing atovaquone, a new anti-Pneumocystis agent, with TMP/SMX for PCP prophylaxis following autologous peripheral blood stem cell (PBSC) transplantation, Thirty-nine patients were studied, Twenty patients received atovaquone suspension and 19 patients received TMP/SMX. The median ages were 44 (range 20-68) and 47 (range 32-63) years, respectively, A similar number of patients with solid tumors (14 vs 15) and hematologic malignancies (five vs five) were treated in each group, Either TMP/SMX (160/800 mg) or atovaquone (1500mg) was administered daily from transplant day -5 until day -1, discontinued from day 0 to engraftment, then resumed 3 days per week until day +100 post-transplant. The median time to engraftment (ANC >0.5 x 10(9)/I) was similar in both groups, Eighty percent of the patients randomized to atovaquone prophylaxis completed the study, Four atovaquone-treated patients were removed from study; two patients (10%) did not receive a transplant and two patients (10%) were removed due to a protocol violation, None of the 16 patients treated with atovaquone experienced treatment-associated adverse effects, Of the 19 patients randomized to receive TMP/SMX, 55% completed the study, Nine TMP/SMX-treated patients were removed from the study; one patient (5%) did not receive a transplant and eight patients (40%) were removed due to drug intolerance (P < 0.003), The rate of intolerance to TMP/SMX led to the early discontinuation of this randomized trial, Intolerance of TMP/SMX included elevated transaminase levels (n = 1), nausea or vomiting (n = 3), thrombocytopenia (n = 2) and neutropenia (n = 2), All episodes of TMP/SMP intolerance occurred following transplantation after a median duration of 17.5 (range 2-48) days and a median of 7 (range 1-20) doses, Resolution of adverse side-effects occurred in all eight patients within a median of 7 (range 2-20) days following discontinuation of therapy, Neither PCP nor bacterial infections were identified in any of the patients treated, This prospective randomized study demonstrated that atovaquone is well-tolerated for anti-Pneumocystis prophylaxis in autologous PBSC transplant patients intolerant of TMP/SMX. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program, Cox 640,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 52 Z9 52 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 1999 VL 24 IS 8 BP 897 EP 902 DI 10.1038/sj.bmt.1702004 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 249ME UT WOS:000083336200014 PM 10516703 ER PT J AU Caplan, D Waters, G AF Caplan, D Waters, G TI Online syntactic processing in aphasia: Studies with auditory moving window presentation SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID LANGUAGE COMPREHENSION; COMPLEXITY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Boston, MA 02215 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 1 PY 1999 VL 69 IS 3 BP 330 EP 333 PG 4 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 242JB UT WOS:000082935800029 ER PT J AU Wambaugh, JL Doyle, PJ Linebaugh, CW Spencer, KA Kalinyak-Fliszar, M AF Wambaugh, JL Doyle, PJ Linebaugh, CW Spencer, KA Kalinyak-Fliszar, M TI Effects of deficit-oriented treatments on lexical retrieval in a patient with semantic and phonological deficits SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID NAMING DISORDERS; THERAPY C1 Vet Adm Med Ctr, Salt Lake City, UT USA. Univ Utah, Dept Commun Disorders, Salt Lake City, UT USA. GRECC, VA Pittsburgh Healthcare Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. George Washington Univ, Washington, DC USA. NR 7 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 1 PY 1999 VL 69 IS 3 BP 446 EP 450 PG 5 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 242JB UT WOS:000082935800066 ER PT J AU Pohl, U Cairncross, JG Louis, DN AF Pohl, U Cairncross, JG Louis, DN TI Homozygous deletions of the CDKN2C/p18(INK4C) gene on the short arm of chromosome 1 in anaplastic oligodendrogliomas SO BRAIN PATHOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; HUMAN ASTROCYTOMAS; INHIBITOR; P18; 19Q; GLIOMAS; CANCER; CDKN2C; CDK6 AB Allelic deletions of the short arm of chromosome 1 are common in oligodendrogliomas and have been correlated with chemosensitivity and better prognosis in patients with high-grade oligodendrogliomas. In these tumors, Ip loss is also inversely related to deletions of the CDKN2A gene on 9p, which encodes the key cell cycle regulatory molecule p16(INK4A). Because the CDKN2C gene, which encodes the homologous p18(INK4C) cell cycle regulatory protein, maps to chromosomal band 1p32, CDKN2C is an attractive candidate for the oligodendroglioma suppressor gene on chromosome 1. To evaluate this possibility, we studied 39 high-grade oligodendrogliomas for homozygous deletions and point mutations of the CDKN2C gene, as well as for allelic loss of Ip. Although no mutations were detected in the CDKN2C coding region, two tumors had homozygous deletions that involved CDKN2C. Interestingly, these cases did not have CDKN2A gene deletions. Coupled with the recent report of rare point mutations of CDKN2C in oligodendrogliomas, these findings suggest that CDKN2C inactivation may be oncogenic in a small percentage of human oligodendrogliomas. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Expt Oncol, London, ON N6A 4L6, Canada. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, CNY6,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA57683] NR 30 TC 34 Z9 35 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 1999 VL 9 IS 4 BP 639 EP 643 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 244CG UT WOS:000083033800003 PM 10517502 ER PT J AU Boppart, SA Goodman, A Libus, J Pitris, C Jesser, CA Brezinski, ME Fujimoto, JG AF Boppart, SA Goodman, A Libus, J Pitris, C Jesser, CA Brezinski, ME Fujimoto, JG TI High resolution imaging of endometriosis and ovarian carcinoma with optical coherence tomography: feasibility for laparoscopic-based imaging SO BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID GYNECOLOGIC DISEASE; OPERATIVE LAPAROSCOPY; BIOPSY; MANAGEMENT; ULTRASOUND; CANCER AB High resolution imaging of gynaecological tissue offers the potential for identifying pathological changes at early stages when interventions are more effective. Optical coherence tomography (OCT) is a high resolution high speed optical imaging technology which is analogous to ultrasound B-mode imaging except reflections of light are detected rather than sound. The OCT technology is capable of being integrated with laparoscopy for real-time subsurface imaging. In this report, the feasibility of OCT for differentiating normal and pathologic laparoscopically-accessible gynaecologic tissue is demonstrated. Differentiation is based on architectural changes of in vitro tissue morphology. OCT has the potential to improve conventional laparoscopy by enabling subsurface imaging near the level of histopathology. C1 MIT, Dept Comp Sci & Elect Engn, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Kings Coll, Dept Biol, Philadelphia, PA USA. RP Boppart, SA (reprint author), MIT, Dept Comp Sci & Elect Engn, Elect Res Lab, 77 Massachusetts Ave,Room 36-345, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [NIH-1-RO1-CA75289-01]; NEI NIH HHS [NIH-9-RO1-EY11289-11]; NHLBI NIH HHS [NIH-1-R29-HL55686-01A1] NR 26 TC 32 Z9 34 U1 1 U2 8 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 OCT PY 1999 VL 106 IS 10 BP 1071 EP 1077 DI 10.1111/j.1471-0528.1999.tb08116.x PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 247HF UT WOS:000083214800013 PM 10519434 ER PT J AU Breathnach, OS Ishibe, N Williams, J Linnoila, RI Caporaso, N Johnson, BE AF Breathnach, OS Ishibe, N Williams, J Linnoila, RI Caporaso, N Johnson, BE TI Clinical features of patients with stage IIIB and IV bronchioloalveolar carcinoma of the lung SO CANCER LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 16-19, 1998 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol DE bronchioloalveolar carcinoma; lung carcinoma; carcinoma; nonsmall cell; clinical trials; chemotherapy ID BRONCHIOLAR CARCINOMA; CELL-CARCINOMA; ALVEOLAR CELL; PHASE-I; CANCER; ADENOCARCINOMA; PROGNOSIS; SURVIVAL; CT AB BACKGROUND. The incidence of bronchioloalveolar carcinoma of the lung (BAC), a pathologically distinct type of nonsmall cell lung carcinoma (NSCLC), appears to be rising. In this study, the authors compared data on the clinical presentation and clinical courses of patients with Stage IIIB and IV BAC with data on other types of NSCLC. METHODS. The authors collected clinical, radiographic, and pathology information about 28 patients with Stage IIIB and IV BAC and 124 patients with other histologic types of NSCLC. RESULTS. Twelve of 28 BAC patients (43%) were women, compared with 40 of 124 control patients (32%). Nine (32%) of the patients with BAC had never smoked cigarettes, versus 20 controls (16%) (P = 0.02). Eighteen patients (64%) with BAC had bilateral multilobar or multicentric pulmonary involvement, compared with 13 controls (15%) (P < 0.001). Patients with advanced stage (IIIB and TV) BAC had a median survival of 15 months from the time of diagnosis; for patients with other types of Stage IIIB and IV NSCLC, had a median survival of 10 months (P = 0.01). CONCLUSIONS. Patients with BAC of the lung have clinical, radiographic, and pathologic characteristics that distinguish them from patients with other types of NSCLC. A greater proportion of women and nonsmokers present with BAC than with other types of NSCLC. Patients with advanced stage BAC are more likely to have bilateral diffuse pulmonary involvement, are less likely to develop brain metastases, and have longer survival than patients with other types of Stage IIIB and IV NSCLC. Further research is warranted to define etiology, molecular abnormalities, and more effective therapeutic interventions. Cancer 1999;86:1165-73. (C) 1999 American Cancer Society. C1 Natl Naval Med Ctr, Med Branch, Div Clin Sci, Bethesda, MD USA. Natl Naval Med Ctr, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. Natl Naval Med Ctr, Dept Pathol, Bethesda, MD USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dana 1234,44 Binney St, Boston, MA 02115 USA. NR 42 TC 55 Z9 60 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 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1999 VL 86 IS 7 BP 1165 EP 1173 DI 10.1002/(SICI)1097-0142(19991001)86:7<1165::AID-CNCR10>3.0.CO;2-9 PG 9 WC Oncology SC Oncology GA 239BP UT WOS:000082749200010 PM 10506700 ER PT J AU Oh, WK Manola, J Richie, JP Loughlin, KR Kantoff, PW AF Oh, WK Manola, J Richie, JP Loughlin, KR Kantoff, PW TI A phase II trial of methotrexate, cisplatin, 5-fluorouracil, and leucovorin in the treatment of invasive and metastatic urothelial carcinoma SO CANCER LA English DT Article DE bladder carcinoma; combination chemotherapy; metastatic; muscle invasive ID TRANSITIONAL-CELL-CARCINOMA; BLADDER-CANCER; ONCOLOGY-GROUP; CHEMOTHERAPY; VINBLASTINE; PACLITAXEL; DOXORUBICIN; CARBOPLATIN; TRACT; COMBINATION AB BACKGROUND, The current treatment of advanced urothelial carcinoma generates high response rates but is associated with poor overall survival. The current study evaluated the efficacy and toxicity of a new combination of active drugs in the treatment of urothelial carcinoma. METHODS. Twenty-four patients with muscle invasive or metastatic urothelial carcinoma were enrolled. Fifteen patients (63%) had metastatic disease whereas 9 patients had T2-T4 disease. Three patients were unevaluable for response because of significant toxicity. Patients were treated every 28 days with methotrexate, 60 mg/m(2), intravenously (i.v.) on Day 1; cisplatin, 25 mg/m(2)/day, by continuous i.v. infusion on Days 2-6; 5-flurouracil (5-FU) 800 mg/m(2)/day by continuous i.v. infusion on Days 3-6; and leucovorin, 500 mg/m(2)/day, by continuous i.v. infusion on Days 2-6. Dosage in subsequent cycles was adjusted according to toxicity. RESULTS. The median follow-up was 81 months (range, 53-97+ months). The overall response rate (complete response + partial response) for all 24 patients was 63% (95% confidence interval, 41-81%). The median survival was 65 months in the patients with muscle invasive disease and 17 months in the patients with metastatic disease. The duration of response in patients with metastatic disease was 6 months (range, 4-19 months). Toxicity was significant, with 82% of patients experiencing Common Toxicity Criteria Grade 3 or 4 neutropenia and 63% experiencing Grade 3 or 4 thrombocytopenia. However, only three patients developed febrile neutropenia and gastrointestinal and neurologic toxicity was moderate. CONCLUSIONS. The combination of methotrexate, cisplatin, 5-fluorouracil, and leucovorin represents an active regimen in the treatment of urothelial carcinoma with a moderate toxicity profile. As new drugs are found to treat urothelial carcinoma, further studies will be needed to evaluate the role of traditional agents such as 5-fluorouracil and methotrexate in new combination chemotherapeutic regimens. Cancer 1999;86:1329-34, (C) 1999 American Cancer Society. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 27 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 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1999 VL 86 IS 7 BP 1329 EP 1334 DI 10.1002/(SICI)1097-0142(19991001)86:7<1329::AID-CNCR31>3.0.CO;2-R PG 6 WC Oncology SC Oncology GA 239BP UT WOS:000082749200031 PM 10506721 ER PT J AU Alberts, DS Colvin, GM Conney, AH Ernster, VL Garber, JE Greenwald, P Gudas, LJ Hong, WK Kelloff, GJ Kramer, RA Lerman, CE Mangelsdorf, DJ Matter, A Minna, JD Nelson, WG Pezzuto, JM Prendergast, F Rusch, VW Sporn, MB Wattenberg, LW Weinstein, IB AF Alberts, DS Colvin, GM Conney, AH Ernster, VL Garber, JE Greenwald, P Gudas, LJ Hong, WK Kelloff, GJ Kramer, RA Lerman, CE Mangelsdorf, DJ Matter, A Minna, JD Nelson, WG Pezzuto, JM Prendergast, F Rusch, VW Sporn, MB Wattenberg, LW Weinstein, IB TI Prevention of cancer in the next millennium: Report of the Chemoprevention Working Group to the American Association for Cancer Research SO CANCER RESEARCH LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; HEPATITIS-B VIRUS; REPUBLIC-OF-CHINA; NONSTEROIDAL ANTIINFLAMMATORY DRUG; RANDOMIZED CONTROLLED TRIAL; ORAL PREMALIGNANT LESIONS; ACID RECEPTOR-BETA; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; VITAMIN-A C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Rutgers State Univ, Coll Pharm, Dept Biol Chem, Piscataway, NJ 08854 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, Dept Pharmacol, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Chemotherapy Branch, Div Canc Prevent & Control, Rockville, MD 20852 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75235 USA. Novartis Pharma AG, Oncol & Virol Dept, CH-4002 Basel, Switzerland. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75235 USA. Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Mayo Clin & Mayo Fdn, Mayo Canc Ctr, Rochester, MN 55905 USA. Mem Sloan Kettering Canc Ctr, Thorac Serv, New York, NY 10021 USA. Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03755 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Columbia Univ Coll Phys & Surg, Columbia Presbyterian Canc Ctr, New York, NY 10032 USA. RP Sporn, MB (reprint author), Dartmouth Med Sch, Dept Pharmacol, Remsen 524, Hanover, NH 03755 USA. NR 134 TC 133 Z9 138 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1999 VL 59 IS 19 BP 4743 EP 4758 PG 16 WC Oncology SC Oncology GA 244AC UT WOS:000083028800002 ER PT J AU Hahnfeldt, P Panigrahy, D Folkman, J Hlatky, L AF Hahnfeldt, P Panigrahy, D Folkman, J Hlatky, L TI Tumor development under angiogenic signaling: A dynamical theory of tumor growth, treatment response, and postvascular dormancy SO CANCER RESEARCH LA English DT Article ID LEWIS LUNG-CARCINOMA; ANGIOSTATIN; RESISTANCE; INHIBITOR; CANCER; NEOPLASMS; STRATEGY; THERAPY; MODEL AB The effects of the angiogenic inhibitors endostatin, angiostatin, and TNP-470 on tumor growth dynamics are experimentally and theoretically investigated. On the basis of the data, we pose a quantitative theory for tumor growth under angiogenic stimulator/inhibitor control that is both explanatory and clinically implementable. Our analysis offers a ranking of the relative effectiveness of these inhibitors. Additionally, it reveals the existence of an ultimate limitation to tumor size under angiogenic control, where opposing angiogenic stimuli come into dynamic balance, which can be modulated by antiangiogenic therapy. The competitive influences of angiogenically driven growth and inhibition underlying this framework may have ramifications for tissue size regulation in general. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Pediat Surg, Boston, MA 02115 USA. RP Hlatky, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, JFB,Room 523, Boston, MA 02115 USA. FU NCI NIH HHS [1RO1-CA-78496, R01-CA-64481] NR 22 TC 348 Z9 357 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1999 VL 59 IS 19 BP 4770 EP 4775 PG 6 WC Oncology SC Oncology GA 244AC UT WOS:000083028800006 PM 10519381 ER PT J AU Fox, JG Dangler, CA Taylor, NS King, A Koh, TJ Wang, TC AF Fox, JG Dangler, CA Taylor, NS King, A Koh, TJ Wang, TC TI High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice SO CANCER RESEARCH LA English DT Article ID STOMACH-CANCER MORTALITY; SODIUM-CHLORIDE; TRANSGENIC MICE; JAPANESE POPULATIONS; ATROPHIC GASTRITIS; FELIS INFECTION; RISK; RATS; N-METHYL-N'-NITRO-N-NITROSOGUANIDINE; PROLIFERATION AB A high-salt diet in humans and experimental animals is known to cause gastritis, has been associated with a high risk of atrophic gastritis, and is considered a gastric tumor promoter. In laboratory rodents, salt is known to cause gastritis, and when coadministered, it promotes the carcinogenic effects of known gastric carcinogens. Because Helicobacter pylori has been associated with a progression from gastritis to gastric cancer, we designed a study to determine whether excessive dietary NaCl would have an effect on colonization and gastritis in the mouse model of H. pylori infection. Seventy-two, 8-week-old female C57BL/6 mice were infected with H. pylori strain Sydney, and 36 control mice were dosed with vehicle only, One-half of the infected and control mice were fed a high-salt diet (7.5% verses 0.25%) for 2 weeks prior to dosing and throughout the entire experiment. Twelve infected and 6 control animals from the high-salt and normal diet groups were euthanized at 4, 8, and 16 weeks. At 8 and 16 weeks postinfection (WPI), the colony-forming units per gram of tissue were significantly higher (P < 0.05) in the corpus and antrum of animals in the high-salt diet group compared with those on the normal diet. Quantitative urease was significantly higher (P < 0.05) at 4 and 8 WPI in the corpus and antrum of animals on the high-salt diet when compared with controls, At 16 WPI, mice in both the normal and the high-salt diet groups developed moderate to marked atrophic gastritis of the corpus in response to H. pylori infection. However, the gastric pits of the corpus mucosa in mice on the high-salt diet were elongated and colonized by H. pylori more frequently than those in mice on the normal diet. The high-salt diet was also associated with a significant increase in proliferation in the proximal corpus and antrum and a multifocal reduction in parietal cell numbers in the proximal corpus, resulting in the elongation of gastric pits, We conclude that excessive NaCl intake enhances H, pylori colonization in mice and in humans and that chronic salt intake may exacerbate gastritis by increasing H, pylori colonization, Furthermore, elevated salt intake may potentiate H, pylori-associated carcinogenesis by inducing proliferation, pit cell hyperplasia, and glandular atrophy. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02144 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Room 825C, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01 CA67463]; NIAID NIH HHS [R01 AI/RR 37750] NR 45 TC 143 Z9 155 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 OCT 1 PY 1999 VL 59 IS 19 BP 4823 EP 4828 PG 6 WC Oncology SC Oncology GA 244AC UT WOS:000083028800016 PM 10519391 ER PT J AU Cambria, RP AF Cambria, RP TI Thoracoabdominal aortic aneurysm repair: how I do it SO CARDIOVASCULAR SURGERY LA English DT Article DE infrarenal aneurysm; thoracoabdominal aortic aneurysm ID ISCHEMIC SPINAL-CORD; DEEP HYPOTHERMIA; EXPERIENCE; SURGERY; COMPLICATIONS; PARAPLEGIA; OPERATIONS; PROTECTS AB There remains no consensus on the operative management of Thoracoabdominal aortic aneurysm (TAA). Our approach emphasizes operative expediency and simplicity (without circulatory assist techniques), avoiding anticoagulation and systemic hypothermia. The technique involves a fundamental clamp/sew method with specific adjuncts directed against the principle complications: epidural cooling (introduced in 1993) for spinal cord protection, regional renal hypothermia, and in-line mesenteric shunting to minimize visceral ischemia. In a cohort of over 200 TAA patients (50% Types I & II) treated during the past decade perioperative mortality has been 8% and paraparesis/paraplegia occured in 7%. These figures are halved for patients treated in elective circumstances. (C) 1999 on behalf of The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc Surg, 15 Parkman St, Boston, MA 02114 USA. NR 21 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-2109 J9 CARDIOVASC SURG JI Cardiovasc. Surg. PD OCT PY 1999 VL 7 IS 6 BP 597 EP 606 DI 10.1016/S0967-2109(99)00038-1 PG 10 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 235BD UT WOS:000082518100007 PM 10519667 ER PT J AU Lee, JT Lu, NF AF Lee, JT Lu, NF TI Targeted mutagenesis of Tsix leads to nonrandom X inactivation SO CELL LA English DT Article ID CHROMOSOME INACTIVATION; XIST GENE; MOUSE EMBRYOS; INSITU HYBRIDIZATION; LINKED GENES; RNA; DIFFERENTIATION; STABILIZATION; EXPRESSION; INTERPHASE AB During X inactivation, mammalian female cells make the selection of one active and one inactive X chromosome. X chromosome choice occurs randomly and results in Xist upregulation on the inactive X. We have hypothesized that the antisense gene, Tsix, controls Xist expression. Here, we create a targeted deletion of Tsix in female and male mouse cells. Despite a deficiency of Tsix RNA, X chromosome counting remains intact: female cells still inactivate one X, while male cells block X inactivation. However, heterozygous female cells show skewed Xist expression and primary nonrandom inactivation of the mutant X. The ability of the mutant X to block Xist accumulation is compromised. We conclude that Tsix regulates Xist in cis and determines X chromosome choice without affecting silencing. Therefore, counting, choice, and silencing are genetically separable. Contrasting effects in XX and XY cells argue that negative and positive factors are involved in choosing active and inactive Xs. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01 GM58839A01] NR 47 TC 316 Z9 323 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 1 PY 1999 VL 99 IS 1 BP 47 EP 57 DI 10.1016/S0092-8674(00)80061-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 243DK UT WOS:000082981600007 PM 10520993 ER PT J AU del Rio, MS Bakker, D Wu, O Agosti, R Mitsikostas, DD Ostergaard, L Wells, WA Rosen, BR Sorensen, G Moskowitz, MA Cutrer, FM AF del Rio, MS Bakker, D Wu, O Agosti, R Mitsikostas, DD Ostergaard, L Wells, WA Rosen, BR Sorensen, G Moskowitz, MA Cutrer, FM TI Perfusion weighted imaging during migraine: spontaneous visual aura and headache SO CEPHALALGIA LA English DT Article DE fMRI; hemodynamic changes; migraine; migraine aura; perfusion weighted imaging ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; CLASSIC MIGRAINE; BRAIN; HYPEREMIA; ATTACKS; ACTIVATION; TRACKING AB Using perfusion weighted imaging, we studied 28 spontaneous migraine episodes; 7 during visual aura (n=6), 7 during the headache phase following visual aura (n=3), and 14 cases of migraine without aura (n = 13). The data were analyzed using a region-of-interest-based approach. During aura, relative cerebral blood flow (rCBF) was significantly decreased (27%+/-0.07) in occipital cortex contralateral to the affected hemifield. rCBV was decreased (15%+/-0.12) and mean transit time increased (32%+/-0.3), persisting up to 2.5 h into the headache phase. Other brain regions did not show significant perfusion changes. During migraine without aura, no significant hemodynamic changes were observed. In one patient who experienced both migraine with and without aura, perfusion deficits were observed only during migraine with aura. These findings suggest that decremental blood flow changes in occipital lobe are most characteristic of migraine with aura. C1 Massachusetts Gen Hosp, Dept Neurol, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP del Rio, MS (reprint author), Massachusetts Gen Hosp, 149 13th St,CNY 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 NR 35 TC 108 Z9 108 U1 0 U2 6 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD OCT PY 1999 VL 19 IS 8 BP 701 EP 707 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 251JF UT WOS:000083441500006 ER PT J AU Bloch, KD AF Bloch, KD TI Regulation of endothelial NO synthase mRNA stability - RNA-binding proteins crowd on the 3 '-untranslated region SO CIRCULATION RESEARCH LA English DT Editorial Material DE cis-acting sequences; poly(A) tail; endothelial cell ID NITRIC-OXIDE SYNTHASE; MESSENGER-RNA C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Bloch, KD (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 1 PY 1999 VL 85 IS 7 BP 653 EP 655 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 239YT UT WOS:000082798700011 PM 10506491 ER PT J AU Uko, GP Lu, LY Asuquo, MA Fici, D Mahan, S Awdeh, Z Udim, ER Ding, W Umana, U Adewole, T Fraser, PA AF Uko, GP Lu, LY Asuquo, MA Fici, D Mahan, S Awdeh, Z Udim, ER Ding, W Umana, U Adewole, T Fraser, PA TI HLA-DRB1 leprogenic motifs in Nigerian population groups SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE leprosy; leprogenic motif; HLA-DRB1; net charge; shared epitope ID MYCOBACTERIUM-LEPRAE; TUBERCULOID LEPROSY; T-CELLS; LEPROMATOUS LEPROSY; HLA; SUSCEPTIBILITY; POLYMORPHISM; ALLELES; SEGREGATION; LYMPHOCYTES AB Amino acid residues involved in the peptide binding groove of HLA-DRB1 alleles were examined in three Nigerian ethnic groups with leprosy (n = 287) and 170 controls to determine the role of DRB1 alleles in disease outcome with Mycobacterium leprae. Nine positively charged motifs and two others with neutral charge to the binding groove were detected. These motifs occurred more frequently in leprosy (leprogenic) than was expected by chance (P < 0.0001). In contrast, five motifs with net negative or 'modified' neutral charges to the pocket were negatively associated with leprosy. We conclude that clinical outcome of infection with M. leprae is largely determined by a shared epitope in DRB1 alleles marked by several motifs. These motifs occur in otherwise normal DRB1 alleles, characterized by net positive or neutral charges in the binding groove. We hypothesize that these polarities cause poor binding of DRB1 to M. leprae. On presentation, the signal via the T cell receptor results in muted cell-mediated immunity. The resulting response translates to various forms of leprosy depending on degree of charge consonance between M. leprae and host DRB1 allele. Other factors within or without the HLA complex, such as the T cell receptor repertoire, may also influence the resulting disease. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Nigerian Inst Med Res, Lagos, Nigeria. Vet Gen Hosp, Kaohsiung, Taiwan. RP Fraser, PA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI42374] NR 35 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD OCT PY 1999 VL 118 IS 1 BP 56 EP 62 PG 7 WC Immunology SC Immunology GA 246TE UT WOS:000083180000009 PM 10540160 ER PT J AU Avigan, D Wu, ZK Gong, JL Joyce, R Levine, J Elias, A Richardson, P Milano, J Kennedy, L Anderson, K Kufe, D AF Avigan, D Wu, ZK Gong, JL Joyce, R Levine, J Elias, A Richardson, P Milano, J Kennedy, L Anderson, K Kufe, D TI Selective in vivo mobilization with granulocyte macrophage colony-stimulating factor (GM-CSF)/granulocyte-CSF as compared to G-CSF alone of dendritic cell progenitors from peripheral blood progenitor cells in patients with advanced breast cancer undergoing autologous transplantation SO CLINICAL CANCER RESEARCH LA English DT Article ID EPIDERMAL LANGERHANS CELLS; TUMOR-NECROSIS-FACTOR; HUMAN BONE-MARROW; C-KIT-LIGAND; TNF-ALPHA; T-CELLS; GENERATION; INVITRO; DIFFERENTIATION; IMMUNOGENICITY AB Dendritic cells (DCs) are potent antigen-presenting cells that are essential for the initiation of T cell-mediated immunity. DCs develop from myeloid progenitor populations under the influence of granulocyte macrophage colony-stimulating factor (GM-CSF) and pass through an intermediate stage of maturation that is characterized by CD14 expression. Interest has focused on generating human-derived DCs for antigen-specific tumor vaccines to be used as adjuvant immunotherapy in minimal disease settings, such as after autologous transplantation. In the present study, mobilized peripheral blood progenitor cells (PBPCs) were obtained from 18 patients with locally advanced or metastatic breast cancer preparing to undergo autologous stem cell transplantation. PBPCs mobilized in 10 patients with GM-CSF for 1 week, followed by the combination of GM-CSF and G-CSF, were compared with those obtained from patients receiving G-CSF alone with respect to the presence of DC progenitors and the capacity to generate functionally active mature DCs, PBPCs mobilized with GM-CSF/G-CSF were markedly enriched for CD14+ DC progenitor cells as compared with those mobilized with G-CSF alone. Consistent with an immature progenitor population, the CD14+ cells express Ki-67 antigen but not nonspecific esterase, CD14+ cells purified by fluorescence-activated cell sorting from PBPCs mobilized with either regimen and cultured for 1 week in GM-CSF and interleukin-4 generated nearly pure populations of cells with characteristic DC phenotype and function. The addition of GM-CSF to the mobilization regimen resulted in greater yields of functionally active DCs for potential use in posttransplant immunotherapy. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Avigan, D (reprint author), 330 Brookline Ave, Boston, MA 02215 USA. NR 28 TC 26 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1999 VL 5 IS 10 BP 2735 EP 2741 PG 7 WC Oncology SC Oncology GA 248DD UT WOS:000083259300011 PM 10537336 ER PT J AU Shapiro, GI Koestner, DA Matranga, CB Rollins, BJ AF Shapiro, GI Koestner, DA Matranga, CB Rollins, BJ TI Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; ACTIVITY IN-VIVO; CARCINOMA-CELLS; BREAST-CANCER; RETINOBLASTOMA-PROTEIN; ENDOTHELIAL-CELLS; RAS MUTATIONS; DNA-DAMAGE; INDUCTION; EXPRESSION AB Flavopiridol, a synthetic flavone that inhibits tumor growth in vitro and in vivo, is a potent cyclin-dependent kinase (cdk) inhibitor presently in clinical trials. In the present study, the effect of 100-500 nM flavopiridol on a panel of non-small cell lung cancer cell lines was examined. All express a wild-type retinoblastoma susceptibility protein and lack p16(INK4A), and only A549 cells are known to express wild-type p53, During 72 h of treatment, flavopiridol was shown to be cytotoxic to all seven cell lines, as measured by trypan blue exclusion, regardless of whether cells were actively cycling. In most cycling cells, cytotoxicity was preceded or accompanied by cell cycle arrest. Cell death resulted in the appearance of cells with a sub-G, DNA content, suggestive of apoptosis, which was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and by demonstration of cleavage of caspase targets including poly(ADP-ribose) polymerase, p21(Waf1) and p27(Kip1). At doses at or below 500 nM, maximal cytotoxicity required 72 h of exposure, Although flavopiridol resulted in the accumulation of p53 in A549 cells, flavopiridol-mediated apoptosis was p53 independent because it occurred to the same degree in A549 cells in which p53 was targeted for degradation by HPV16E6 expression. The data indicate that flavopiridol has activity against non-small cell lung cancers in vitro and is worthy of continued clinical development in the treatment of this disease. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer 422,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA72573] NR 62 TC 103 Z9 106 U1 1 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 OCT PY 1999 VL 5 IS 10 BP 2925 EP 2938 PG 14 WC Oncology SC Oncology GA 248DD UT WOS:000083259300037 PM 10537362 ER PT J AU Seminara, S Crowley, WF AF Seminara, S Crowley, WF TI Hypogonadotrophic hypogonadism: a unique biological opportunity - Commentary SO CLINICAL ENDOCRINOLOGY LA English DT Editorial Material ID GONADOTROPIN-RELEASING-HORMONE; ADRENAL HYPOPLASIA CONGENITA; GENE; MUTATIONS; RECEPTOR; EXPRESSION; INDUCTION; SYSTEM C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St,Bartlett Hall Extens 5, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu FU NICHD NIH HHS [T32 HD007396, P30 HD028138, R01 HD015788] NR 17 TC 0 Z9 0 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 OCT PY 1999 VL 51 IS 4 BP 385 EP 386 DI 10.1046/j.1365-2265.1999.00860.x PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253EK UT WOS:000083543500001 PM 10583302 ER PT J AU Carling, T Imanishi, Y Gaz, RD Arnold, A AF Carling, T Imanishi, Y Gaz, RD Arnold, A TI RAD51 as a candidate parathyroid tumour suppressor gene on chromosome 15q: absence of somatic mutations SO CLINICAL ENDOCRINOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; MEN1 GENE; ADENOMAS; DNA; HYPERPARATHYROIDISM; RECOMBINATION; REPAIR; MOUSE AB OBJECTIVE Loss of heterozygosity (LOH) at chromosome 15q is frequent in parathyroid adenomas, but no tumour suppressor gene of importance to parathyroid tumour development has been isolated from this region. The RAD51 gene has been localized to chromosome 15q and possesses regulatory functions involving DNA stability and cell proliferation, suggesting its possible role in tumorigenesis, Additionally, mutations in the RAD51 gene cause reduced resistance to ionizing radiation, which is a major risk factor for primary hyperparathyroidism, RAD51 was therefore analysed as a candidate tumour suppressor gene in a group of parathyroid adenomas for which mutations in a 15q tumour suppressor should be most readily detectable. PATIENTS AND DESIGN From a total of 55 parathyroid adenomas, nine were selected based on their LOH pattern showing DNA loss at chromosome 15q in the vicinity of the RAD51 gene. RAD51 mRNA expression was investigated by reverse transcription-polymerase chain reaction (RT-PCR), and sequence analysis of the entire coding region of the RAD51 cDNA was performed in all nine adenomas. RESULTS RAD51 mRNA expression was substantiated in all parathyroid adenomas, Compared with the normal RAD51 cDNA sequence, no point mutations or microdeletions could be found in the parathyroid tumor cDNA, CONCLUSION These observations suggest that somatic inactivating mutations of the RAD51 gene are uncommonly, if ever, associated with parathyroid tumourigenesis. C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. NR 36 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 1999 VL 51 IS 4 BP 403 EP 407 DI 10.1046/j.1365-2265.1999.00779.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253EK UT WOS:000083543500004 PM 10583305 ER PT J AU Lavoie, HB Taylor, AE Sharpless, JL Anderson, EJ Strauss, CC Hall, JE AF Lavoie, HB Taylor, AE Sharpless, JL Anderson, EJ Strauss, CC Hall, JE TI Effects of short-term hormone replacement on serum leptin levels in postmenopausal women SO CLINICAL ENDOCRINOLOGY LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; GENDER DIFFERENCES; FAT DISTRIBUTION; SEX-HORMONES; BODY-FAT; OBESE; MEN; EXPRESSION; SECRETION; HUMANS AB OBJECTIVE Leptin is a hormone which is secreted by adipocytes and appears to influence the reproductive axis. Previous studies have demonstrated higher leptin levels in relation to body fat mass in women compared to men, higher levels in normally cycling compared to postmenopausal women, and a decrease in leptin levels with increased age. The purpose of this study was to determine whether oestrogen replacement with or without progesterone increases serum leptin levels in postmenopausal women, independently of changes in body fat, and to determine if ageing affects leptin levels at baseline or in response to hormone replacement. PATIENTS Twenty-one healthy postmenopausal women on no hormone replacement were studied at baseline, after I month of oestrogen (E-2: estraderm 50 mu g/day) and after a further month of oestrogen and 7 days of progesterone (P: progesterone 100 mg per vagina bid) designed to achieve physiological hormone levels. Subjects included 11 younger (45-55 years) and 10 older (70-80 years) postmenopausal women. RESULTS The relationship between leptin and the absolute fat mass (% body fat x weight [kg]) at baseline was not different between the younger and older postmenopausal women. The adequacy of physiological hormone replacement was confirmed in all subjects. Despite the absence of an effect of hormone replacement on weight, body mass index (BMI), % and absolute fat mass (bioimpedance) or waist-hip ratio, there was an increase in serum leptin levels with hormone replacement (15.4 +/- 1.7, 17.6 +/- 1.7, and 18.1 +/- 1.6 mu g/l; mean +/- SEM at baseline, with E-2, and with E-2 + P, respectively; P < 0.001 vs, baseline) for the group as a whole. An increase in leptin with hormonal treatment was seen in both the younger (15.1 +/- 2.1, 18.1 +/- 2.4, and 18.5 +/- 1.9 mu g/l; P < 0.01) and the older (15.7 +/- 2.8, 17.0 +/- 2.5, 17.7 +/- 2.8 mu g/l; P= 0.06) postmenopausal women. CONCLUSIONS (1) Short-term physiological oestrogen replacement increases serum leptin levels in postmenopausal women independently of changes in fat mass; and (2) physiological progesterone replacement does not influence leptin levels in postmenopausal women. C1 Massachusetts Gen Hosp, Natl Ctr Infertil Res, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Dept Med, Boston, MA 02114 USA. PROCREA BioSci Inc, Quebec City, PQ, Canada. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Natl Ctr Infertil Res, Dept Med, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIA NIH HHS [R01 AG013241, R01-AG-13241]; NICHD NIH HHS [P30-HD-28138] NR 38 TC 36 Z9 37 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 1999 VL 51 IS 4 BP 415 EP 422 DI 10.1046/j.1365-2265.1999.00796.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253EK UT WOS:000083543500006 PM 10583307 ER PT J AU Liu, ZC Wong, JT AF Liu, ZC Wong, JT TI Proliferative and regenerative capacities of CD4(+) T cells upon TCR stimulation SO CLINICAL IMMUNOLOGY LA English DT Article DE CD4(+) T cells; proliferation; TCR; CD45RO; bispecific ID BISPECIFIC MONOCLONAL-ANTIBODIES; TUMOR INFILTRATING LYMPHOCYTES; CELLULAR SENESCENCE; PERIPHERAL-BLOOD; HIV-1 INFECTION; VIRUS; CD4+; CULTURE; PLASMA; LENGTH AB Proliferation of activated CD4(+) T cells effectively amplifies the immune response. Based on a model of selective CD4(+) T cell proliferation using an anti-CD3: anti-CD8 bispecific monoclonal antibody that leads to selective proliferation of CD4(+) T cells, we demonstrated that the peripheral CD4(+) T cells of normal subjects can divide for 17 to 38 generations, expanding 1.7 x 10(5) to 3 x 10(11) fold, following a single short period of anti-TCR stimulation. The proliferating CD4(+) T cells maintained IL2R expression. A large subgroup from each subject maintained the CD45RA(hi)CD45RO(lo) phenotype, demonstrating that activation and proliferation do not automatically convert CD4(+) T cells into CD45RA(lo)CD45RO(hi) phenotype. The enormous number of cells generated demonstrated that the peripheral CD4(+) T cells have remarkable regenerative expansion capacity. The high, but substantially variable, proliferative capacities among subjects have important implications for diseases in which CD4(+) T cells play an important role, such as HIV-infection, graft rejection, and autoimmunity. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wong, JT (reprint author), Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [AI36611, AI41409] NR 23 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD OCT PY 1999 VL 93 IS 1 BP 16 EP 23 DI 10.1006/clim.1999.4766 PG 8 WC Immunology SC Immunology GA 243QY UT WOS:000083009800003 PM 10497007 ER PT J AU Haenel, LC Gordon, BM Sagel, J AF Haenel, LC Gordon, BM Sagel, J TI Radioiodine-induced thyrotoxicosis and thyroiditis after ablative therapy for papillary carcinoma - A case discussion and literature review SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE hyperthyroidism; 1-131 ablation; thyroid cancer; thyroiditis ID CANCER AB The preferred treatment for patients with multifocal thyroid carcinoma or a single focus of malignancy larger than 1.5 cm is near-total thyroidectomy followed by radioiodine ablation therapy of the remaining thyroid tissue. The authors describe a patient who had a 2.6-cm papillary thyroid carcinoma but no evidence of metastatic disease. This malignancy was not diagnosed during intraoperative frozen section examination, but rather at the final pathologic analysis. The unilateral thyroid lobectomy resulted in a recurrent laryngeal nerve palsy. During subsequent I-131 therapy of the remaining lobe, features of acute radiation thyroiditis, including thyrotoxicosis, developed. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Div Nucl Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Haenel, LC (reprint author), 25 E Laurel Rd, Stratford, NJ 08084 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 1999 VL 24 IS 10 BP 741 EP 743 DI 10.1097/00003072-199910000-00001 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 238HC UT WOS:000082704000001 ER PT J AU Schollmeier, G Uhthoff, HK Lewandrowski, KU Fukuhara, K AF Schollmeier, G Uhthoff, HK Lewandrowski, KU Fukuhara, K TI Role of bone bark during growth in width of tubular bones - A study in human fetuses SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PERICHONDRIAL OSSIFICATION GROOVE; PLATE AB The morphologic features of bone bark, a structure surrounding the distal and proximal ends of long bones, were studied in the distal femur, proximal tibia, and proximal fibula of 77 spontaneously aborted human fetuses varying in gestational age from 10 to 20 weeks. Standard histologic techniques used in addition to in situ immunohistochemical staining allowed the examination of the structure of the bone bark and localization of Types 1, 2, and 3 collagens at different gestational ages. The bone bark was shaped like a cylindrical sheath of bony lamellae of varying thickness. The epiphyseal end of the bone bark, known as the groove of Ranvier, was covered outwardly by a fibrous layer and inwardly by the epiphyseal cartilage and contained mesenchymal cells, chondroblastic precursor cells, and densely packed cells differentiating into osteoblasts, Neither the cell density in the groove nor the thickness of the bone bark were identical circumferentially, indicating an unequal growth in width. In addition, the presence of periosteal apposition and endosteal resorption of the bone bark on one side and of endosteal bone deposition accompanied by periosteal resorption of the bone bark on the opposite side support the concept of a spatial drift of bones. These observations furnish histologic proof that groove and bone bark, although assuring an equal growth in length, contribute to an unequal and eccentric growth in width. C1 Univ Ottawa, Fac Med, Dept Surg, Ottawa, ON, Canada. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. RP Uhthoff, HK (reprint author), Univ Ottawa, Dept Orthopaed Surg, Div Orthopaed Surg, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. FU NIAMS NIH HHS [AR 45062] NR 29 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1999 IS 367 BP 291 EP 299 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 247AJ UT WOS:000083198200036 PM 10546627 ER PT J AU Aquino, SL Chen, MYM Kuo, WT Chiles, C AF Aquino, SL Chen, MYM Kuo, WT Chiles, C TI The CT appearance of pleural and extrapleural disease in lymphoma SO CLINICAL RADIOLOGY LA English DT Article DE lymphoma; CT; pleura; neoplasm ID HODGKINS-DISEASE; INVOLVEMENT; EFFUSIONS; THERAPY AB OBJECTIVE: Pleural effusions in patients with lymphoma that are assumed to be related to malignancy are attributed to either lymphatic obstruction by tumour with resultant decreased clearance of pleural fluid, or direct tumour involvement of the pleura, The purpose of our study was to determine how often pleural or extrapleural disease was detected by computed tomography (CT) of patients with pleural effusions and primary or recurrent lymphoma. METHODS AND MATERIALS: We reviewed CT examinations showing evidence of pleural effusion in 61 patients with a diagnosis of primary or recurrent lymphoma and no history of other systemic disorders, including infection. The study population consisted of patients with non-Hodgkin's lymphoma (n = 44) or Hodgkin's disease (n = 17); both primary disease (n = 11) and recurrent disease (IL = 50) were represented. Each CT examination was evaluated for the presence of disease involving the visceral and parietal pleura and extrapleural space, mediastinal adenopathy, and pulmonary parenchymal disease. RESULTS: Fourteen patients (23%) (nine with non-Hodgkin's lymphoma and five with Hodgkin's disease) had parietal pleural disease (thickening or nodules), Eighteen patients (30%) (14 with non-Hodgkin's lymphoma, four with Hodgkin's disease) had tumour or enlarged lymph nodes in the extrapleural space, Forty-three patients (70%) had mediastinal lymphadenopathy, Patients who received intravenous contrast did not have evidence of visceral pleural abnormalities or underlying pulmonary parenchymal disease, CONCLUSION: Forty-one percent of the patients with lymphoma and pleural effusions had CT evidence of pleural and/or extrapleural disease. The majority of the patients with extrapleural disease had adjacent posterior mediastinal disease. (C) 1999 The Royal College of Radiologists. C1 Massachusetts Gen Hosp, Dept Radiol FND 202, Boston, MA 02114 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol FND 202, 55 Fruit St, Boston, MA 02114 USA. NR 15 TC 19 Z9 24 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 OCT PY 1999 VL 54 IS 10 BP 647 EP 650 DI 10.1016/S0009-9260(99)91084-X PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 245WL UT WOS:000083137900005 PM 10541388 ER PT J AU Dobscha, SK Delucchi, K Young, ML AF Dobscha, SK Delucchi, K Young, ML TI Adherence with referrals for outpatient follow-up from a VA psychiatric emergency room SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article AB This study identifies patient characteristics associated with adherence to outpatient mental health treatment referrals from a VA psychiatric emergency department. Attendance of outpatient appointments was monitored for 12 weeks following emergency department visits (N = 241). Overall attendance of the first appointments was 53%, ranging from 34% of the homeless, to 82% of patients with alcoholism in remission. Characteristics associated with initial adherence included having a place to live and the diagnosis of depression. At twelve weeks, the diagnosis of substance abuse was associated with worse ongoing adherence. The results underscore the need to develop interventions targeting patients at highest risk of poor adherence. C1 Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97207 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Sch Nursing, Boulder, CO 80309 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Div Mental Hlth, POB 1034,P71DMH, Portland, OR 97207 USA. NR 10 TC 24 Z9 25 U1 0 U2 0 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD OCT PY 1999 VL 35 IS 5 BP 451 EP 458 DI 10.1023/A:1018786512676 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 246JK UT WOS:000083160500006 PM 10547120 ER PT J AU Kushak, RI Winter, HS AF Kushak, RI Winter, HS TI Regulation of intestinal peptidases by nutrients in human fetuses and children SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY LA English DT Article DE butyric acid; colon; development; human; nutrient interactions; peptidases; small intestine; tributyrin ID BRUSH-BORDER MEMBRANE; SODIUM-BUTYRATE; IMMUNE-SYSTEM; CANCER; AMINOPEPTIDASE; NUTRITION; COLITIS AB Nutrient interactions during intestinal digestion has been established in animals. The present study investigated the effect of different nutrients on intestinal dipeptidase, tripeptidase, carboxypeptidase (EC 3.4.12.-) and aminopeptidase N (ApN) (EC 3.4.11.2) activities in human fetuses and children. The effect of nutrients on isolated porcine kidney ApN was also studied. Sucrose, lactose and tributyrin had no effect on di-, tri-, and carboxypeptidase activities of mucosal homogenates, but tributyrin significantly (20-50%) inhibited both fetal and postnatal ApN activity in the small intestine and colon. The pH-independent inhibition of ApN is specific for tributyrin and to the product of its hydrolysis, butyric acid. Glycerol, triolein, and natural oils did not affect ApN activity. The inhibition of ApN by tributyrin was dose and time dependent and occurred in enterocyte brush border membranes as well as in the purified enzyme from porcine kidney. The kinetics of the purified ApN showed that the tributyrin effect is primarily competitive and associated mainly with an increase in K-m. These observations demonstrate the possibility of intestinal and kidney ApN regulation by lipids and products of their hydrolysis. We speculate that nutrient interactions arose quite early in the evolution and represent a mechanism for the regulation of food digestion. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston Univ,Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kushak, RI (reprint author), Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston Univ,Sch Med,Massachusetts Gen Hosp, 55 Fruit St,VBK 107, Boston, MA 02114 USA. NR 26 TC 4 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD OCT PY 1999 VL 124 IS 2 BP 191 EP 198 DI 10.1016/S1095-6433(99)00109-9 PG 8 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 258AD UT WOS:000083815100011 PM 10629959 ER PT J AU Sykes, M AF Sykes, M TI Bone marrow and solid organ transplantation start to converge - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02128 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02128 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1999 VL 11 IS 5 BP 493 EP 496 DI 10.1016/S0952-7915(99)00018-7 PG 4 WC Immunology SC Immunology GA 241BP UT WOS:000082862400003 ER PT J AU Kawai, T Sachs, DH Cosimi, AB AF Kawai, T Sachs, DH Cosimi, AB TI Tolerance to vascularized organ allografts in large-animal models SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOTAL LYMPHOID IRRADIATION; PRIMATE RENAL-ALLOGRAFTS; DONOR-SPECIFIC TOLERANCE; T-CELL DEPLETION; TRANSPLANTATION TOLERANCE; MINIATURE SWINE; BONE-MARROW; CLASS-I; CYNOMOLGUS MONKEYS AB Although studies of tolerance induction in large animals remain limited compared with murine studies, a number of encouraging observations have been recently reported - especially in nonhuman primate models. The development of antibodies or proteins binding to costimulatory molecules and of an immunotoxin that is active on T cells have been particularly important advances leading to expanded opportunities for extending strategies for tolerance induction to large animals. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Kawai, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Room White 510,55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R21 AI037692, R21 AI037692-06] NR 36 TC 37 Z9 37 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1999 VL 11 IS 5 BP 516 EP 520 DI 10.1016/S0952-7915(99)00009-6 PG 5 WC Immunology SC Immunology GA 241BP UT WOS:000082862400007 PM 10508708 ER PT J AU Sheen, J Zhou, L Jang, JC AF Sheen, J Zhou, L Jang, JC TI Sugars as signaling molecules SO CURRENT OPINION IN PLANT BIOLOGY LA English DT Review ID GENE-EXPRESSION; ALPHA-AMYLASE; SACCHAROMYCES-CEREVISIAE; ARABIDOPSIS-THALIANA; PROTEIN-KINASES; PLANT HORMONES; GLUCOSE; REPRESSION; TRANSDUCTION; TOBACCO AB Recent studies indicate that, in a manner similar to classical plant hormones, sugars can act as signaling molecules that control gene expression and developmental processes in plants. Crucial evidence includes uncoupling glucose signaling from its metabolism, identification of glucose sensors, and isolation and characterization of mutants and other regulatory components in plant sugar signal transduction pathways. The emerging scenario points to the existence of a complex signaling network that interconnects transduction pathways from sugars and other hormone and nutrient signals. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biol Mol,Dept Genet, Boston, MA 02114 USA. Ohio State Univ, Dept Hort & Crop Sci, Columbus, OH 43210 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biol Mol,Dept Genet, Boston, MA 02114 USA. NR 65 TC 326 Z9 368 U1 5 U2 39 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5266 J9 CURR OPIN PLANT BIOL JI Curr. Opin. Plant Biol. PD OCT PY 1999 VL 2 IS 5 BP 410 EP 418 DI 10.1016/S1369-5266(99)00014-X PG 9 WC Plant Sciences SC Plant Sciences GA 243DC UT WOS:000082980900012 PM 10508760 ER PT J AU Carpo, BG Grevelink, SV Brady, S Gellis, S Grevelink, JM AF Carpo, BG Grevelink, SV Brady, S Gellis, S Grevelink, JM TI Treatment of cutaneous lesions of xanthoma disseminatum with a CO2 laser SO DERMATOLOGIC SURGERY LA English DT Article ID INVOLVEMENT AB We describe a case of a 15-year-old African American girl with widespread papulonodular lesions of xanthoma disseminatum especially in the periorbital area and on the flexural surfaces of the neck, axillae, arms, and legs. There were no mucosal lesions. An initial trial in the distant past of liquid nitrogen cryotherapy resulted in partial shrinking of cutaneous lesions but was too painful for the patient. She then underwent surgical excision of bilateral eyelid lesions with improvement, but additional procedures were deemed impractical when considering the great number and size of the lesions. Consequently we treated the patient with a carbon dioxide (CO2) laser with excellent results. The relatively great speed at which the CO2 laser procedure can be performed has made the removal of multiple lesions in each session possible. Additional advantages included precise vaporization of lesions, hemostasis during the operative procedure, and minimal postoperative pain and edema. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Grevelink, JM (reprint author), Massachusetts Gen Hosp, Profess Off Bldg,5th Floor,Suite 501,275 Cambridg, Boston, MA 02114 USA. NR 17 TC 14 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 1999 VL 25 IS 10 BP 751 EP 754 DI 10.1046/j.1524-4725.1999.99082.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 244PA UT WOS:000083058900005 PM 10594575 ER PT J AU Porcher, C Liao, EC Fujiwara, Y Zon, LI Orkin, SH AF Porcher, C Liao, EC Fujiwara, Y Zon, LI Orkin, SH TI Specification of hematopoietic and vascular development by the bHLH transcription factor SCL without direct DNA binding SO DEVELOPMENT LA English DT Article DE SCL/tal-1; bHLH transcription factor; hematopoiesis; vasculogenesis; phenotypic rescue; zebrafish mutant; cloche ID T-CELL LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-PRODUCT; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; TRANSGENIC MICE; ZEBRAFISH GENE; PROTEINS; TAL1; ACTIVATION AB Transcription factors, such as those of the basie-helix-loop-helix (bHLH) and homeodomain classes, are primary regulators of cell fate decisions and differentiation. It is considered axiomatic that they control their respective developmental programs via direct binding to cognate DNA sequences in critical targets genes. Here we test this widely held paradigm by in vivo functional assay of the leukemia oncoprotein SCL, a bHLH factor that resembles myogenic and neurogenic proteins and is essential for both hematopoietic and vascular development in vertebrates. Contrary to all expectation, we find that SCL variants unable to bind DNA rescue hematopoiesis from gene-targeted SCL-/- embryonic stem cells and complement hematopoietic and vascular deficits in the zebrafish mutant cloche. Our findings establish DNA-binding-independent functions of SCL critical for transcriptional specification, and should encourage reassessment of presumed requirements for direct DNA binding by other transcription factors during initiation of developmental programs. C1 Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol & Oncol, 300 Longwood Ave, Boston, MA 02115 USA. RI Porcher, Catherine/D-7026-2016 NR 57 TC 120 Z9 122 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 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 1999 VL 126 IS 20 BP 4603 EP 4615 PG 13 WC Developmental Biology SC Developmental Biology GA 255RE UT WOS:000083683300019 PM 10498694 ER PT J AU Duh, E Aiello, LP AF Duh, E Aiello, LP TI Vascular endothelial growth factor and diabetes - The agonist versus antagonist paradox SO DIABETES LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; OXYGEN-INDUCED RETINOPATHY; PROTEIN-KINASE-C; MESSENGER-RNA EXPRESSION; COLLATERAL BLOOD-FLOW; PERMEABILITY FACTOR; CARDIOVASCULAR-DISEASE; RETINAL ISCHEMIA; IN-VIVO; AUTONOMIC NEUROPATHY AB Much of the morbidity and mortality associated with diabetes is primarily attributable to sequelae of microvascular and macrovascular disease. Over the past decade, dramatic progress has been achieved in elucidating the fundamental processes underlying the pathogenesis of these complications. Angiogenic factors in particular now appear to play a pivotal role in the development of microvascular complications as well as the response to macrovascular disease. Hyperglycemia, other growth factors, advanced glycation end products, oxidative stress, and ischemia can increase growth factor expression. In some microvascular tissues, the result is pathologic neovascularization and increased vascular permeability. These responses account for much of the visual loss associated with diabetic retinopathy and may, in addition, serve a significant role in nephropathy and neuropathy. In contrast, recent data suggest that vascular collateralization resulting from ischemia-induced growth factor release in tissues compromised by macrovascular disease may be important in reducing clinical symptoms and tissue damage. This angiogenic response, which may be beneficial in coronary artery and peripheral limb disease, appears to be reduced in patients with diabetes. Thus, two apparently diametrically opposed therapeutic paradigms are arising for the treatment of vascular complications in diabetes. Indeed, growth factor antagonists have been used successfully in diabetes-related animal models to block angiogenic and permeability complications in the retina and kidney. Conversely, growth factor agonists have been successfully used to stimulate collateral vessel formation and reduce ischemic symptoms from macrovascular disease in the coronary arteries and peripheral limbs. Both of these approaches are currently being evaluated in clinical trials for their respective indications. Thus, as these divergent therapeutic modalities begin to enter the clinical arena, this apparent paradox necessitates careful consideration of the potential risks, benefits, and interactions of the opposing regimens. Using vascular endothelial growth factor as a classic example of growth factor involvement, we discuss the current preclinical and clinical data supporting these approaches and the implications arising from the probable coexistence of these two therapeutic modalities. C1 Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, Baltimore, MD 21287 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Beetham Eye Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu NR 102 TC 205 Z9 219 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD OCT PY 1999 VL 48 IS 10 BP 1899 EP 1906 DI 10.2337/diabetes.48.10.1899 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240FJ UT WOS:000082815000001 PM 10512352 ER PT J AU Gazdag, AC Dumke, CL Kahn, CR Cartee, GD AF Gazdag, AC Dumke, CL Kahn, CR Cartee, GD TI Calorie restriction increases insulin-stimulated glucose transport in skeletal muscle from IRS-1 knockout mice SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; RECEPTOR SUBSTRATE (IRS)-2; DIETARY RESTRICTION; WEIGHT-LOSS; RATS; RESISTANCE; METABOLISM; SENSITIVITY; DISRUPTION AB Calorie restriction (CR), even for brief periods (4-20 days), results in increased whole-body insulin sensitivity, in large part due to enhanced insulin-stimulated glucose transport by skeletal muscle. Evidence suggests that the cellular alterations leading to this effect are postreceptor steps in insulin signaling. To determine whether insulin receptor substrate (IRS)-1 is essential for the insulin-sensitizing effect of CR, we measured in vitro 2-deoxyglucose (2DG) uptake in the presence and absence of insulin by skeletal muscle isolated from wild-type (WT) mice and transgenic mice lacking IRS-I (knockout [KO]) after either ad libitum (AL) feeding or 20 days of CR (60% of ad libitum intake). Three muscles (soleus, extensor digitorum longus [EDL], and epitrochlearis) from male and female mice (4.5-6 months old) were studied. In each muscle, insulin-stimulated 2DG uptake was not different between genotypes. For EDL and epitrochlearis, insulin-stimulated 2DG uptake a-as greater in CR compared to AL groups, regardless of sex. Soleus insulin-stimulated 2DG uptake was greater in CR compared with AL in males but not females. The diet effect on 2DG uptake was not different for WT and KO animals. Genotype also did not alter the CR-induced decrease in plasma constituents (glucose, insulin, and leptin) or body composition (body weight, fat pad/body weight ratio). Consistent sith previous studies in rats, IRS-1 protein expression in muscle was reduced in WT-CR compared with WT-AL mice, and muscle IRS-2 abundance was unchanged by diet. Skeletal muscle IRS-2 protein expression was significantly lower in WT compared with KO mice. These data demonstrate that IRS-1 is not essential for the CR-induced increase in insulin-stimulated glucose transport in skeletal muscle, and the absence of IRS-1 does not modify any of the characteristic adaptations of CR that were evaluated. C1 Univ Wisconsin, Biodynam Lab, Madison, WI 53706 USA. Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Harvard Univ, Sch Med, Div Res, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Cartee, GD (reprint author), Univ Wisconsin, Biodynam Lab, 2000 Observ Dr, Madison, WI 53706 USA. RI Biguzzi, Felipe/E-4724-2015; OI Cartee, Gregory/0000-0001-5311-1722 FU NIA NIH HHS [AG000213, AG10026] NR 33 TC 52 Z9 52 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1999 VL 48 IS 10 BP 1930 EP 1936 DI 10.2337/diabetes.48.10.1930 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240FJ UT WOS:000082815000005 PM 10512356 ER PT J AU Kishi, Y Schmelzer, JD Yao, JK Zollman, PJ Nickander, KK Tritschler, HJ Low, PA AF Kishi, Y Schmelzer, JD Yao, JK Zollman, PJ Nickander, KK Tritschler, HJ Low, PA TI alpha-lipoic acid: Effect on glucose uptake, sorbitol pathway, and energy metabolism in experimental diabetic neuropathy SO DIABETES LA English DT Article ID NERVE BLOOD-FLOW; TRANSPORTER MESSENGER-RNA; PIGMENT EPITHELIAL-CELLS; DORSAL-ROOT-GANGLIA; PERIPHERAL-NERVE; PYRUVATE-DEHYDROGENASE; CONDUCTION-VELOCITY; PERINEURIAL CELLS; SKELETAL-MUSCLE; OXYGEN-TENSION AB The peripheral nerve of experimental diabetic neuropathy (EDN) is reported to be ischemic and hypoxic, with an increased dependence on anaerobic metabolism, requiring increased energy substrate stores. When glucose stores become reduced, fiber degeneration has been reported. We evaluated glucose uptake, nerve energy metabolism, the polyol pathway, and protein kinase C (PKC) activity in EDN induced by streptozotocin. Control and diabetic rats received lipoic acid (0, 10, 25, 50, 100 mg/kg). Duration of diabetes was 1 month, and alpha-lipoic acid was administered intraperitoneally 5 times per week for the final week of the experiment. Nerve glucose uptake was reduced to 60, 37, and 30% of control values in the sciatic nerve, L5 dorsal root ganglion, and superior cervical ganglion (SCG), respectively, in rats with EDN. alpha-Lipoic acid supplementation had no effect on glucose uptake in normal nerves at any dose, but reversed the deficit in EDN, with a threshold between 10 and 25 mg/kg. Endoneurial glucose, fructose, sorbitol, and myo-inositol were measured in sciatic nerve. or-lipoic acid had no significant effect on either energy metabolism or polyol pathway of normal nerves. In EDN, endoneurial glucose, fructose, and sorbitol were significantly increased, while myo-inositol was significantly reduced. or-lipoic acid had a biphasic effect: it dose-dependently increased fructose, glucose, and sorbitol, peaking at 25 mg/kg, and then fell beyond that dose, and it dose-dependently increased myo-inositol. Sciatic nerve cytosolic PKC was increased in EDN. ATP, creatine phosphate, and lactate were measured in sciatic nerve and SCG. alpha-Lipoic acid prevented the reduction in SCG creatine phosphate. We conclude that glucose uptake is reduced in EDN and that this deficit is dose-dependently reversed by alpha-lipoic acid, a change associated with an improvement in peripheral nerve function. C1 Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. VA Pittsburgh Hlth Care Syst, Pathol & Lab Med Serv 113A, Pittsburgh, PA USA. Asta Med, Frankfurt, Germany. RP Mayo Clin & Mayo Fdn, Dept Neurol, 200 1st St SW, Rochester, MN 55905 USA. EM low@mayo.edu FU NINDS NIH HHS [R01 NS22352] NR 71 TC 76 Z9 82 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD OCT PY 1999 VL 48 IS 10 BP 2045 EP 2051 DI 10.2337/diabetes.48.10.2045 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240FJ UT WOS:000082815000021 PM 10512372 ER PT J AU Singh, R Alavi, N Singh, AK Leehey, DJ AF Singh, R Alavi, N Singh, AK Leehey, DJ TI Role of angiotensin II in glucose-induced inhibition of mesangial matrix degradation SO DIABETES LA English DT Article ID GROWTH-FACTOR-BETA; DEGRADING NEUTRAL PROTEINASE; CONVERTING ENZYME-INHIBITION; DIABETIC NEPHROPATHY; GENE-EXPRESSION; CELLS; RAT; MELLITUS; SYSTEM; PROLIFERATION AB Accumulation of mesangial matrix in diabetic nephropathy is caused by increased synthesis and decreased degradation We have previously demonstrated that incubation in high-glucose medium decreases mesangial cell collagenase activity (Diabetes 44:929-935, 1995). Because angiotensin II (AII) is involved in the pathogenesis of diabetic nephropathy, the present studies were performed to determine if AII mediates glucose-induced 1) inhibition of mesangial collagenase activity, 2) mesangial matrix accumulation, and 3) in-crease in transforming growth factor (TGF)-beta 1 secretion in mesangial cells. The direct effect of high glucose on AII generation in mesangial cells a-as also determined. Primary mesangial cells from normal Sprague-Dawley rats were used in all studies. Collagenase activity in cell medium was determined using three methods: I) zymography; 2) quantitative assay using fluoresceinated gelatin as substrate; and 3) a new enzyme-linked immunosorbent assay (ELISA) that specifically measures 72-kDa collagenase (MMP-2), the principal collagenase synthesized by mesangial cells. Matrix accumulation was estimated by immunoperoxidase assay on cell layers using anti-glomerular basement membrane (GBM) antibodies. TGF-beta 1 and AII levels were determined by ELISA. Exposure of mesangial cells to 30 mmol/l glucose thigh glucose) vs. 5 mmol/l glucose (normal glucose) for 5 days resulted in a significant decrease in collagenase activity (25%) that was normalized by 10(-4) mol/l. losartan, a type 1 angiotensin II (AT(1)) receptor antagonist. High glucose increased anti-GBM binding compared with normal glucose; this effect of glucose was reversed by losartan. Incubation of cells with 30 mmol/l glucose increased total TGF-beta I secretion, which was also normalized by losartan. Addition of AII (10(-6) mol/l) for 24 h to the culture medium inhibited collagenase activity by 33%; losartan (10(-4) mol/l) blocked this inhibition of enzyme activity Also, AII decreased collagenase (MMP-2) levels but stimulated TGF-beta I secretion in mesangial cells. Finally, glucose increased mesangial AII generation in a concentration-dependent manner with incubation in 30 mmol/l glucose increasing AII by 25%, compared with 5 mmol/l glucose, We conclude that glucose increases AII production by mesangial cells, which results in stimulation of TGF-beta 1 secretion, decreased matrix degradation, and increased matrix accumulation. These effects of AII are mediated by the AT(1) receptor. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Westside Vet Affairs Hosp, Chicago, IL USA. Hektoen Inst Med Res, Chicago, IL 60612 USA. Loyola Univ, Sch Med, Maywood, IL 60153 USA. RP Leehey, DJ (reprint author), VA Hines 111L, Hines, IL 60141 USA. NR 39 TC 125 Z9 146 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1999 VL 48 IS 10 BP 2066 EP 2073 DI 10.2337/diabetes.48.10.2066 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240FJ UT WOS:000082815000024 PM 10512375 ER PT J AU Plengvidhya, N Antonellis, A Wogan, LT Poleev, A Borgschulze, M Warram, JH Ryffel, GU Krolewski, AS Doria, A AF Plengvidhya, N Antonellis, A Wogan, LT Poleev, A Borgschulze, M Warram, JH Ryffel, GU Krolewski, AS Doria, A TI Hepatocyte nuclear factor-4 gamma - cDNA sequence, gene organization, and mutation screening in early-onset autosomal-dominant type 2 diabetes SO DIABETES LA English DT Article; Proceedings Paper CT 59th Scientific Session of the American-Diabetes-Association Annual Meeting CY JUN 18-22, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Diabet Assoc ID YOUNG MODY1; EXPRESSION AB The aim of this study was to investigate whether mutations in hepatocyte nuclear factor (HNF)-4(gamma), a transcription factor homologous to HNF-4 alpha, contribute to the etiology of early-onset type 2 diabetes. Linkage between diabetes and two polymorphic markers at the HNF-4 gamma locus (D8S286 and D8S548) was evaluated in 32 multigenerational families with early-onset autosomal-dominant type 2 diabetes unlinked to known maturity-onset diabetes of the young genes. Total logarithm of odds (LOD) scores were strongly negative (-50.3 at D8S286 and -46.2 at D8S548), but linkage could not be excluded in 15 families having LOD scores >-2.0. To screen these pedigrees for HNF-4 gamma mutations, the gene structure was defined. Because reverse transcriptase-polymerase chain reaction experiments indicated that the first 1,674 bp of the published cDNA sequence (3,248 bp) were a cloning artifact, the correct cDNA sequence was determined by 5' rapid amplification of cDNA ends (RACE) and primer extension assay. Based on the new cDNA sequence (1,731 bp), 11 exons were found. After screening the 5' flanking region and all coding exons for mutations, we identified several polymorphisms, one of which affected the amino acid sequence (M190I). However, no mutations segregating with diabetes could be found in these families. Fire conclude that genetic variability in the HNF-4 gamma gene is unlikely to play a major role in the etiology of early-onset autosomal-dominant type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Essen Gesamthsch, Inst Cell Biol, Essen, Germany. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-55523, DK-47475, DK-36836] NR 16 TC 13 Z9 16 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1999 VL 48 IS 10 BP 2099 EP 2102 DI 10.2337/diabetes.48.10.2099 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240FJ UT WOS:000082815000029 PM 10512380 ER PT J AU Almind, K Frederiksen, SK Bernal, D Hansen, T Ambye, L Urhammer, S Ekstrom, CT Berglund, L Reneland, R Lithell, H White, MF Van Obberghen, E Pedersen, O AF Almind, K Frederiksen, SK Bernal, D Hansen, T Ambye, L Urhammer, S Ekstrom, CT Berglund, L Reneland, R Lithell, H White, MF Van Obberghen, E Pedersen, O TI Search for variants of the gene-promoter and the potential phosphotyrosine encoding sequence of the insulin receptor substrate-2 gene: evaluation of their relation with alterations in insulin secretion and insulin sensitivity SO DIABETOLOGIA LA English DT Article DE insulin receptor substrate-2; mutations; Type II diabetes; insulin secretion; insulin sensitivity ID AMINO-ACID POLYMORPHISMS; CAUCASIANS AB Aims/hypothesis. The aim of this study was to screen part of the putative promoter sequence in addition to 14 potential phosphotyrosine residues of human IRS-2 for genetic variability which might cause changes in protein expression or function. Furthermore, the potential impact on insulin secretion and sensitivity of a previously identified IRS-2 variant (Gly1057Asp) was analysed Methods. The screenings were carried out by the SSCP-heteroduplex technique on DNA from Type II (non-insulin-dependent) diabetic patients. The impact of the Gly1057Asp variant was analysed in four glucose-tolerant Scandinavian study groups. Results. The results showed no nucleotide substitutions in the promoter sequence, however, a novel heterozygous amino acid variant was identified (Leu647-Val). In an association study, the new variant was found in 3 of 413 diabetic patents and in none of 280 glucose tolerant subjects. The variant did not affect the binding of IRS-2 to the insulin receptor or p85 alpha of phosphatidylinositol 3-kinase when measured in the yeast two-hybrid system. Examination of the common Gly1057Asp variant in 363 young healthy subjects and in 228 glucose tolerant offspring of one diabetic parent showed no differences in insulin secretion or insulin sensitivity after an intravenous glucose tolerance test. Glucose tolerant middle-aged subjects homozygous for the polymorphism (n = 31), however, had on average a 25% decrease in fasting serum insulin concentrations (p = 0.009) and 28% (p = 0.01) and 34% (p = 0.003) reductions in serum insulin concentrations at 30 and 60 min, respectively, during an OGTT compared with wildtype carriers (n = 107). In a cohort of 639 elderly Swedish men the amino acid variant did not have any detectable impact on insulin secretion after an OGIT. Conclusion/interpretation. No genetic variability was found in the IRS-2 promoter. A rare IRS-2 variant at codon 647 has been identified in Type II diabetic patients. The prevalent codon 1057 polymorphism had no consistent effect on insulin secretion or insulin sensitivity. C1 Steno Diabet Ctr, DK-2820 Gentofte, Copenhagen, Denmark. Hagedorn Res Inst, Copenhagen, Denmark. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Valencia, Dept Biochem & Mol Biol, E-46003 Valencia, Spain. Univ Uppsala, Dept Geriatr, S-75105 Uppsala, Sweden. Univ Nice, Fac Med, INSERM, U145, F-06108 Nice 2, France. RP Almind, K (reprint author), Steno Diabet Ctr, Niels Steensens Vej 2, DK-2820 Gentofte, Copenhagen, Denmark. RI Bernal, Dolores/K-7769-2014; OI Bernal, Dolores/0000-0003-4627-8393; Berglund, Lars/0000-0002-7437-9047; Ekstrom, Claus Thorn/0000-0003-1191-373X FU NIDDK NIH HHS [DK-43808] NR 10 TC 46 Z9 51 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1999 VL 42 IS 10 BP 1244 EP 1249 DI 10.1007/s001250051299 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 242HY UT WOS:000082935500014 PM 10525667 ER PT J AU Wu, CJ Qian, XL O'Rourke, DM AF Wu, CJ Qian, XL O'Rourke, DM TI Sustained mitogen-activated protein kinase activation is induced by transforming erbB receptor complexes SO DNA AND CELL BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HUMAN GLIOBLASTOMA CELLS; MAP-KINASE; EGF RECEPTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASE; CYCLE PROGRESSION; GENE-EXPRESSION; TERMINAL KINASE; ADAPTER PROTEIN AB We used a genetic approach to characterize features of mitogen-activated protein kinase (MAPK) activation occurring as a consequence of expression of distinct erbB receptor combinations in transformed human cells. Kinase-deficient erbB proteins reduced epidermal growth factor (EGF)-induced tyrosine phosphorylation of endogenous Shc proteins and also reduced immediate and sustained EGF-induced ERK MAPK activities in human glioblastoma cells, although basal ERK MAPK activities were unaffected. Basal and EGF-induced JNK and p38 MAPK kinase activities were equivalent in parental cancer cells and EGFR-inhibited subclones, When ectopically overexpressed in murine fibroblasts and human glioblastoma cells, a constitutively activated human EGF receptor oncoprotein (Delta EGFR) induced EGF-independent elevation of basal ERK MAPK activity. Basal JNK MAPK kinase activity was also specifically induced by Delta EGFR, which correlated with increased phosphorylation of a 54-kDa JNK2 protein observed in Delta EGFR-containing cells. The JNK activities in response to DNA damage were comparably increased in cells containing wildtype EGFR or Delta EGFR. Consistent with the notion that transforming erbB complexes induce sustained and unregulated MAPK activities, coexpression of p185(neu) and EGFR proteins to levels sufficient to transform murine fibroblasts also resulted in prolonged EGF-induced ERK in vitro kinase activation. Transforming erbB complexes, including EGFR homodimers, Delta EGFR homodimers, and p185(neu)/EGFR heterodimers, appear to induce sustained, unattenuated activation of MARK activities that may contribute to increased transformation and resistance to apoptosis in primary human glioblastoma cells. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Canc, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Surg Neurosurg, Philadelphia, PA 19104 USA. Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP O'Rourke, DM (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Room 288,John Morgan Bldg,36th & Hamilton Walk, Philadelphia, PA 19104 USA. NR 72 TC 29 Z9 30 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1999 VL 18 IS 10 BP 731 EP 741 DI 10.1089/104454999314872 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 249EV UT WOS:000083320700001 PM 10541432 ER PT J AU Bouchard, C Thieke, K Maier, A Saffrich, R Hanley-Hyde, J Ansorge, W Reed, S Sicinski, P Bartek, J Eilers, M AF Bouchard, C Thieke, K Maier, A Saffrich, R Hanley-Hyde, J Ansorge, W Reed, S Sicinski, P Bartek, J Eilers, M TI Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27 SO EMBO JOURNAL LA English DT Article DE Cdk2; cyclin D2; Mad-1; Myc; p27 ID DEPENDENT KINASE INHIBITOR; C-MYC; TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE; FUNCTIONAL-ANALYSIS; PROTEIN-KINASE; GROWTH ARREST; GENE-TRANSFER; N-COR; E-BOX AB Ectopic expression of Myc induces Cdk2 kinase activity in quiescent cells and antagonizes association of p27(kip1) with Cdk2, The target gene(s) by which Myc mediates this effect is largely unknown. We now show that p27 is rapidly and transiently sequestered by cyclin D2-Cdk4 complexes upon activation of Myc and that cyclin D2 is a direct target gene of Myc. The cyclin D2 promoter is repressed by Mad-Max complexes and derepressed by Myc via a single highly conserved E-box element. Addition of trichostatin A to quiescent cells mimics activation of Myc and induces cyclin D2 expression, suggesting that cyclin D2 is repressed in a histone deacetylase-dependent manner in quiescent cells. Inhibition of cyclin D2 function in established cell lines, either by; ectopic expression of p16 or by antibody injection, inhibits Myc-dependent dissociation of p27 from Cdk2 and Myc-induced cell cycle entry. Primary mouse fibroblasts that are cyclin D2-deficient undergo accelerated senescence in culture and are not immortalized by Myc; induction of apoptosis by Myc is unimpaired in such cells. Our data identify a downstream effector pathway that links Myc directly to cell cycle progression. C1 Univ Marburg, Inst Mol Biol & Tumour Res, D-35033 Marburg, Germany. EMBL, Biol Instrumentat Programme, D-69112 Heidelberg, Germany. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Canc Biol, DK-2100 Copenhagen, Denmark. RP Eilers, M (reprint author), Univ Marburg, Inst Mol Biol & Tumour Res, Emil Mannkopff Str 2, D-35033 Marburg, Germany. RI Bartek, Jiri/G-5870-2014 NR 63 TC 348 Z9 356 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 1 PY 1999 VL 18 IS 19 BP 5321 EP 5333 DI 10.1093/emboj/18.19.5321 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 246AK UT WOS:000083140800017 PM 10508165 ER PT J AU Teixeira, J Fynn-Thompson, E Payne, AH Donahoe, PK AF Teixeira, J Fynn-Thompson, E Payne, AH Donahoe, PK TI Mullerian-inhibiting substance regulates androgen synthesis at the transcriptional level SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; MCCUNE-ALBRIGHT SYNDROME; LEYDIG-CELLS; SEXUAL DEVELOPMENT; TRANSGENIC MICE; II RECEPTOR; EXPRESSION; DIFFERENTIATION; GENE; PUBERTY AB Mullerian-inhibiting substance (MIS) is a hormone produced by Sertoli cells of the fetal testes that causes regression of the Mullerian ducts, the precursors to female reproductive tract structures that are present in the bipotential urogenital ridge. MIS is also produced in the adult gonads of both males and females, albeit at much lower levels than those measured during the fetal and perinatal periods. Adult transgenic mice chronically overexpressing MIS exhibit severe gonadal abnormalities and, in males, dramatically reduced levels of testosterone, which might lead to the incomplete virilization observed in some of the males. To understand the roles played by MIS in the adult gonad, we performed Northern analyses to show that the MIS type II receptor is expressed in purified Leydig cells and in two rodent Leydig cell lines, R2C and MA-10. Addition of purified recombinant human MIS to cultures of both R2C and MA-10 cells reduced steroid production. With MA-10 cells, the reduction of testosterone secretion into the medium was reduced to 1/10th of that in the control culture, which provided us with a means to study the molecular mechanisms underlying MIS-mediated suppression of testosterone synthesis. Northern analysis revealed that after stimulation with cAMP, the expression of messenger RNA for P450c17 hydroxylase/lyase, the enzyme that catalyzes the conversion of progesterone to androstenedione, was reduced to background levels in the presence of MIS. Addition of cycloheximide, a protein synthesis inhibitor, did not prevent the effect of MIS, indicating a direct effect of MIS signal transduction on the expression of P450c17. Analysis of the transcriptional activity of Cyp17, the gene for murine P450c17, with Cyp17 promoter/luciferase reporter constructs shows that MIS regulates the transcription of Cyp17 in a concentration- and time-dependent manner. From our results, we conclude that MIS might play a physiological role in maintaining testosterone homeostasis. These findings will allow us in the future to use the transcriptional regulation of Cyp17 as a model to uncover the signal transduction pathways of MIS and the molecular mechanisms of its suppression of androgen synthesis. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs WRN1024, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Stanford Univ, Dept Obstet Gynecol, Div Reprod Biol, Palo Alto, CA 94305 USA. RP Massachusetts Gen Hosp, Pediat Surg Res Labs WRN1024, 32 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu NR 47 TC 67 Z9 73 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1999 VL 140 IS 10 BP 4732 EP 4738 DI 10.1210/en.140.10.4732 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237RC UT WOS:000082669000045 PM 10499532 ER PT J AU McCauley, LA Joos, SK Spencer, PS Lasarev, M Shuell, T AF McCauley, LA Joos, SK Spencer, PS Lasarev, M Shuell, T TI Strategies to assess validity of self-reported exposures during the Persian Gulf War SO ENVIRONMENTAL RESEARCH LA English DT Article DE Persian Gulf War; exposure assessment; epidemiology; reporting bias; reliability ID PYRIDOSTIGMINE AB Research in the area of Persian Gulf War Unexplained Illnesses (PGWUI) is heavily dependent on self-reports of exposures, The Portland Environmental Hazards Research Center (PEHRC) conducted a population-based case-control study utilizing techniques to measure the magnitude of potential error in self-reports of exposure. While it is impossible to verify most exposures in the Persian Gulf War (PGW), results of our study reveal significant overreporting of exposures that can be verified based on the time period served in the Persian Gulf. Test-retest reliability estimates indicate inconsistency in frequency and rate of self-reported exposures during the PGW. Unexplained illness in PGW veterans has received much political and scientific attention. Self-reported exposures in surveys returned preceeding and following media reports on particular exposure such as nerve gas or pesticides are presented. These results are useful in the interpretation of findings related to the PGWUI and in the design of future investigations. (C) 1999 Academic Press. C1 Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP McCauley, LA (reprint author), Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, 3181 SW Sam Jackson Pk Rd,L606, Portland, OR 97201 USA. OI Lasarev, Michael R/0000-0002-1896-2705 NR 18 TC 50 Z9 50 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1999 VL 81 IS 3 BP 195 EP 205 DI 10.1006/enrs.1999.3977 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 246BF UT WOS:000083142700003 PM 10585015 ER PT J AU McCauley, LA Joos, SK Lasarev, MR Storzbach, D Bourdette, DN AF McCauley, LA Joos, SK Lasarev, MR Storzbach, D Bourdette, DN TI Gulf War unexplained illnesses: Persistence and unexplained nature of self-reported symptoms SO ENVIRONMENTAL RESEARCH LA English DT Article DE Gulf War; health symptoms; case-control studies; survey questionnaires; clinical evaluation ID INSTRUCTIONS AB Most published reports of health symptoms among Gulf War (GW) veterans have been based on self-reported questionnaire data. The presence of these symptoms at the time of a clinical evaluation and the unexplained nature of the symptoms have not been described. We report the findings of a sample of symptomatic veterans that were examined as part of a population-based case-control study of GW unexplained illnesses. Participants in the case-control study were selected from responders to a cross-sectional survey of a random sample of GW veterans residing in the northwestern United States. The initial survey questionnaire solicited information on the presence of fatigue and psychological/cognitive, gastrointestinal, musculoskeletal, and dermatological problems, The persistence of the symptoms and possible explanatory diagnoses were explored at the time of the clinical evaluation. Findings from the first 225 participants who completed clinical examinations indicate significant differences between self-reported symptoms on the survey questionnaire and those confirmed at the time of clinical exam. The agreement between symptoms reported both on the survey and at the time of examination varies across the symptom groups. While self-reported unexplained fatigue was confirmed at the time of clinical encounter in 79% of participants, self-reported gastrointestinal symptoms were confirmed at the clinical encounter in only 20% of participants, Differences between symptoms reported on the survey questionnaire and those confirmed at the time of clinical encounter were attributable to finding a clinical diagnosis for the symptom, resolution of symptom(s) between time of questionnaire and clinical exam, and inadvertent endorsement of the symptom on the questionnaire. These findings suggest that due to the possibility of outcome misclassification, inappropriate conclusions may be drawn about the association between exposures and unexplained illnesses in GW veterans from data derived solely from self-administered questionnaires. (C) 1999 Academic Press. C1 Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Med Informat & Outcome Res, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP McCauley, LA (reprint author), Oregon Hlth Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. OI Lasarev, Michael R/0000-0002-1896-2705 NR 19 TC 22 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1999 VL 81 IS 3 BP 215 EP 223 DI 10.1006/enrs.1999.3973 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 246BF UT WOS:000083142700005 PM 10585017 ER PT J AU Gong, JL Avigan, D Chen, DS Wu, ZK Koido, S Kashiwaba, M Kufe, D AF Gong, JL Avigan, D Chen, DS Wu, ZK Koido, S Kashiwaba, M Kufe, D TI Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1999 VL 35 SU 5 MA 60 BP S30 EP S30 PG 1 WC Oncology SC Oncology GA 251GE UT WOS:000083435600062 ER PT J AU Hing, HK Bangalore, L Sun, X Artavanis-Tsakonas, S AF Hing, HK Bangalore, L Sun, X Artavanis-Tsakonas, S TI Mutations in the heatshock cognate 70 protein (hsc4) modulate Notch signaling SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE Notch signaling; heatshock cognate protein; hsc4 ID SPLIT COMPLEX GENES; DROSOPHILA-MELANOGASTER; RECEPTOR ACTIVITY; ANKYRIN REPEATS; SUPPRESSOR; DELTEX; NEUROGENESIS; ENHANCER; PATHWAY; LOCUS AB In our effort to dissect the Notch signaling mechanism we have conducted a screen for mutations that reduce Notch signaling activity. We recovered nine complementation groups as modifiers of the hypomorphic Notch allele notchoid. Apart from the known Notch signaling modulators Notch, Delta and mastermind we isolated alleles in vestigial, wingless, scalloped and clipped, genes known to affect wing morphogenesis, In addition, we identified mutations in Bag, the gene encoding clathrin heavy chain and a dominant mutation of the cytosolic 70 kDa heatshock cognate protein encoded by the hsc4 gene, as Notch signaling modifier. We focused our attention on the latter mutation because it displays dramatic genetic interactions with mutations of the Notch receptor as well as several additional Notch signaling pathway elements. We discuss how hsc4, a gene thought to be involved in subcellular trafficking, may affect the number of functional Notch receptors on the cell surface. C1 Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90024 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Dev Biol, San Francisco, CA 94143 USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, New Haven, CO USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Biol, New Haven, CO USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Cell Biol, New Haven, CO USA. RP Artavanis-Tsakonas, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS26084] NR 31 TC 19 Z9 19 U1 0 U2 3 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX NO.100 537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD OCT PY 1999 VL 78 IS 10 BP 690 EP 697 PG 8 WC Cell Biology SC Cell Biology GA 253VF UT WOS:000083576000002 PM 10569241 ER PT J AU Andree, C Page, CP Slama, J Stark, GB Eriksson, E AF Andree, C Page, CP Slama, J Stark, GB Eriksson, E TI Naturally occurring growth factors in porcine wounds treated with autologous keratinocytes in a liquid environment SO EUROPEAN JOURNAL OF PLASTIC SURGERY LA English DT Article DE chamber wound healing model; naturally occurring growth factors; keratinocyte transplantation ID SKIN; EXPRESSION; REPAIR; INVIVO; GENE AB A step toward an improved understanding of the complex mechanisms of growth factor interactions may lie in the detection of endogenous growth factors during normal wound healing. The findings of this study on standardized full thickness wounds in swine, provide direct evidence that growth factors were present in the wound fluid in the picogram range (highest concentrations ranging from 1273 pg/ml for transforming growth factor-beta (TGF beta) to 85.6 pg/ml for platelet-derived growth factor-AB (PDGF-AB)during healing. The presence of transplanted autologous keratinocyte suspensions and cultured epithelial sheet graft had no significant effect upon the observed growth factor levels, although transplanted keratinocyte cell suspensions (KCS) and cultured epidermal autografts (CEA) did accelerate healing in comparison to control wounds in our model (KCS treated wounds healed in 13.2+/-0.9 days, CEA in 13.7 days+/-0.8 and control wounds in 14.7 days+/-0.3). The variable occurrence of growth factors during normal wound healing may suggest possible mechanisms of growth factor interaction which could have an impact on the future design of their therapeutic use. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. Univ Freiburg, Dept Plast Surg, D-79106 Freiburg, Germany. RP Eriksson, E (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0930-343X J9 EUR J PLAST SURG JI Eur. J. Plast. Surg. PD OCT PY 1999 VL 22 IS 7 BP 322 EP 325 PG 4 WC Surgery SC Surgery GA 248RX UT WOS:000083290100009 ER PT J AU Kacmarek, RM AF Kacmarek, RM TI High frequency oscillation versus conventional ventilation: is one superior? SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; HYALINE-MEMBRANE DISEASE; LUNG INJURY; MECHANICAL VENTILATION; PRETERM INFANTS; SURFACTANT; TRIAL; OXYGENATION; PULMONARY; FAILURE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 1999 VL 14 IS 4 BP 733 EP 734 DI 10.1034/j.1399-3003.1999.14d01.x PG 2 WC Respiratory System SC Respiratory System GA 254MB UT WOS:000083614800001 PM 10573212 ER PT J AU Reddy, SV Menaa, C Singer, FR Cundy, T Cornish, J Whyte, MP Roodman, GD AF Reddy, SV Menaa, C Singer, FR Cundy, T Cornish, J Whyte, MP Roodman, GD TI Measles virus nucleocapsid transcript expression is not restricted to the osteoclast lineage in patients with Paget's disease of bone SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE osteoclast; measles virus; Paget's disease of bone ID POLYMERASE CHAIN-REACTION; CANINE-DISTEMPER VIRUS; HUMAN MARROW CULTURES; IN-VITRO; CELLS; AMPLIFICATION; PRECURSORS; SEQUENCE; ANTIGENS; ACID AB Abundant evidence supports a viral etiology for Paget's disease of bone (PD), however, an infectious virus has not been isolated from PD patients. Thus, it is unclear how the virus is maintained for the many years that the disease persists in patients, We considered if a primitive multipotential hematopoietic stem cell (HSC), which is self-renewing, passes the virus to its differentiated progeny and serves as a reservoir for the pathogen, If a primitive stem cell harbored measles virus (MV), then other hematopoietic lineages derived from this stem cell in PD patients should also express MV transcripts. Therefore, because the human hematopoietic stem cell has not been clearly identified or isolated in large numbers, we isolated RNA from highly purified erythroid and multipotential hematopoietic progenitors that are the precursors for erythroid, granulocyte, megakaryocyte and macrophages (CFU-GEMM), and used RT-PCR to deter-mine if MV nucleocapsid transcripts were present. MV transcripts were detected in PD patients in early erythroid (BFU-E) and more primitive multipotential myeloid progenitors (CFU-GEMM), Nonhematopoietic stromal cells from PD patients did not ex-press MV transcripts. The expression of MV transcripts in erythroid progenitors was further confirmed by in situ hybridization using antisense riboprobes to MV nucleocapsid transcripts. Thus, our findings suggest that the pluripotent HSCs may be a potential reservoir for the virus. We propose that when HSCs, which contain MV, divide they produce a second HSC that serves as a reservoir for the virus and also transmit the virus to their more differentiated progeny in the erythroid and myeloid lineages. This mechanism would permit a defective virus to persist in HSCs of PD patients for many Sears, since HSCs are usually in GU phase, and then be transmitted to more differentiated cells. This model further suggests that a mature complete virus that affects cell function could only act pathogenetically in the osteoclast lineage, which offers a permissive milieu. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. John Wayne Canc Inst, Santa Monica, CA USA. Univ Auckland, Auckland 1, New Zealand. Washington Univ, Sch Med, Barnes Jewish Hosp, St Louis, MO USA. RP Roodman, GD (reprint author), Audie Murphy Vet Adm Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. OI Cundy, Timothy/0000-0003-4890-9400 FU NIA NIH HHS [AG13625]; NIAMS NIH HHS [AR41336, AR44603] NR 20 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 1999 VL 27 IS 10 BP 1528 EP 1532 DI 10.1016/S0301-472X(99)00097-1 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 240TR UT WOS:000082841700007 PM 10517494 ER PT J AU Castells, A Ino, Y Louis, DN Ramesh, V Gusella, JF Rustgi, AK AF Castells, A Ino, Y Louis, DN Ramesh, V Gusella, JF Rustgi, AK TI Mapping of a target region of allelic loss to a 0.5-cM interval on chromosome 22q13 in human colorectal cancer SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Gastroenterological-Association CY MAY, 1999 CL ORLANDO, FLORIDA SP Amer Gastroenterol Assoc ID TUMOR-SUPPRESSOR GENE; MICROSATELLITE MUTATOR PHENOTYPE; SOMATIC FRAMESHIFT MUTATIONS; DNA MISMATCH REPAIR; NEUROFIBROMATOSIS-2 GENE; HETEROZYGOSITY; CARCINOMAS; TUMORIGENESIS; LOCALIZATION; LOCI AB Background & Aims: Chromosomal allelic losses have a varying frequency in colorectal cancer. The aim of this study was to define the target region of allelic loss on chromosome 22q in human colorectal carcinogenesis. Methods: Fifty-seven pairs of matched normal colonic mucosa and tumor specimens from patients with colorectal cancer, as well as 15 colon cancer-derived cell lines, were genotyped using 15 microsatellite markers spanning chromosome 22q. A potential candidate gene was analyzed by a single-strand conformation polymorphism (SSCP)/direct DNA sequencing approach. Results: After excluding I tumors with evidence of microsatellite instability, allelic loss was observed in 11 of the informative tumors (22%), 5 of which exhibited losses in all informative loci. The remaining 6 tumors showed variable patterns of partial allelic loss on chromosome 22q, thereby localizing a minimal region of allelic deletion between markers D22S1171 and D22S928. Physical mapping showed that this interval was 0.57 cM consisting of approximately 425 kilobases. Database searches identified the NBK/BIK gene, a proapoptotic BCL-2 family member, as a candidate gene in that region. However, SSCP/sequencing analysis excluded mutations of this gene. Conclusions: This study provides evidence for the involvement of putative tumor-suppressor gene(s) on chromosome 22q in human colorectal carcinogenesis. The identification of a 0.5-cM interval serves as the basis for the isolation of such a gene by positional cloning. C1 Univ Penn, Div Gastroenterol, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA USA. RP Rustgi, AK (reprint author), Univ Penn, Div Gastroenterol, Dept Genet, 415 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA 67583]; NIDDK NIH HHS [DK 56645]; NINDS NIH HHS [NS24279] NR 37 TC 37 Z9 39 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 1999 VL 117 IS 4 BP 831 EP 837 DI 10.1016/S0016-5085(99)70341-0 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 241FR UT WOS:000082872500016 PM 10500065 ER PT J AU Rosen, HR Hinrichs, DJ Gretch, DR Koziel, MJ Chou, S Houghton, M Rabkin, J Corless, CL Bouwer, HGA AF Rosen, HR Hinrichs, DJ Gretch, DR Koziel, MJ Chou, S Houghton, M Rabkin, J Corless, CL Bouwer, HGA TI Association of multispecific CD4(+) response to hepatitis C and severity of recurrence after liver transplantation SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Annual Digestive Disease Week - 25 Years of Endoscopic Papillotomy CY MAY 16-22, 1998 CL NEW ORLEANS, LOUISIANA ID CYTOTOXIC T-LYMPHOCYTES; VIRUS-INFECTION; NONSTRUCTURAL PROTEIN-3; MAJOR GENOTYPES; CELL; RECIPIENTS; ANTIGENS; VIREMIA; HCV; PERSISTENT AB Background & Aims: After liver transplantation for hepatitis C virus (HCV), reinfection of the allograft invariably occurs. Indirect evidence suggests that the cellular immune response may play a central role. The purpose of this analysis was to determine the correlation between HCV-specific peripheral CD4(+) T-cell responses and the severity of recurrence after liver transplantation. Methods: Fifty-eight HCV-seropositive patients, including 43 liver transplant recipients with at least 1 year of histological follow-up, were studied. Peripheral blood mononuclear cells (PBMCs) were isolated from fresh heparinized blood and stimulated with either recombinant HCV antigens (core, E2, NS3, NS4, and NS5) or control antigens. Results: Fourteen (40%) of 35 patients with mild or no evidence of histological recurrence within their allografts responded to at least 1 of the HCV antigens. Eleven responded to NS3, 5 to all the nonstructural antigens, and 3 to the HCV core polypeptide alone. In contrast, in the 8 patients with severe HCV recurrence, no proliferation in response to; any of the HCV antigens was seen (P = 0.03) despite responses to the control antigens. Conclusions: Despite immunosuppression, HCV-specific, major histocompatibility complex class II-restricted CD4(+) T-cell responses are detectable in patients with minimal histological recurrence after liver transplantation. In contrast, PBMCs from patients with severe HCV recurrence, despite being able to proliferate in response to non-HCV antigens, fail to respond to the HCV antigens. These findings suggest that the inability to generate virus-specific T-cell responses plays a contributory role in the pathogenesis of HCV-related graft injury after liver transplantation. It is hoped that further characterization of the immunoregulatory mechanisms related to recurrent HCV will provide the rationale for novel therapeutic strategies and diminish the incidence of inevitable graft loss. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Mol Microbiol & Immunol, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Surg, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Pathol, Portland, OR 97207 USA. Earle A Chilles Res Inst, Portland, OR USA. Univ Washington, Div Virol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Chiron Corp, Emeryville, CA 94608 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, 3710 SW US Vet Hosp Rd,POB 1034,P3-GI, Portland, OR 97207 USA. FU NIAID NIH HHS [AI40032-02, AI41563-01, AI39049-02] NR 34 TC 120 Z9 121 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 OCT PY 1999 VL 117 IS 4 BP 926 EP 932 DI 10.1016/S0016-5085(99)70352-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 241FR UT WOS:000082872500027 PM 10500076 ER PT J AU Krupnik, VE Sharp, JD Jiang, C Robison, K Chickering, TW Amaravadi, L Brown, DE Guyot, D Mays, G Leiby, K Chang, B Duong, T Goodearl, ADJ Gearing, DP Sokol, SY McCarthy, SA AF Krupnik, VE Sharp, JD Jiang, C Robison, K Chickering, TW Amaravadi, L Brown, DE Guyot, D Mays, G Leiby, K Chang, B Duong, T Goodearl, ADJ Gearing, DP Sokol, SY McCarthy, SA TI Functional and structural diversity of the human Dickkopf gene family SO GENE LA English DT Article DE antagonist; frizzled related protein; in situ hybridization; secreted protein; soggy; wingless; Xenopus ID SECRETED PROTEINS; SPEMANN ORGANIZER; XENOPUS-EMBRYOS; WNT; EXPRESSION; MEMBER; IDENTIFICATION; DROSOPHILA; RECEPTORS; PATHWAY AB Wnt proteins influence many aspects of embryonic development, and their activity is regulated by several secreted antagonists, including the Xenopus Dickkopf-1 (xDkk-1) protein. xDkk-1 inhibits Wnt activities in Xenopus embryos and may play a role in induction of head structures. Here, we characterize a family of human Dkk-related genes composed of Dkk-1, Dkk-2, Dkk-3, and Dkk-4, together with a unique Dkk-3 related protein termed Soggy (Sgy). hDkks 1-4 contain two distinct cysteine-rich domains in which the positions of 10 cysteine residues are highly conserved between family members. Sgy is a novel secreted protein related to Dkk-3 but which lacks the cysteine-rich domains. Members of the Dkk-related family display unique patterns of mRNA expression in human and mouse tissues, and are secreted when expressed in 293T cells. Furthermore, secreted hDkk-2 and hDkk-4 undergo proteolytic processing which results in cleavage of the second cysteine-rich domain from the full-length protein. Members of the human Dkk-related family differ not only in their structures and expression patterns, but also in their abilities to inhibit Wnt signaling. hDkk-1 and hDkk4, but not hDkk-2, hDkk-3 or Sgy, suppress Wnt-induced secondary axis induction in Xenopus embryos. hDkk-1 and hDkk4 do not block axis induction triggered either by Xenopus Dishevelled (Xdsh) or Xenopus Frizzled-8 (Xfz8), both of which function to transduce signals from Wnt ligands. Thus, hDkks 1 and 4 may inhibit Wnt activity by a mechanism upstream of Frizzled. Our findings highlight the structural and functional heterogeneity of human Dkk-related proteins. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Millennium BioTherapeut Inc, Cambridge, MA 02139 USA. Eli Lilly & Co, Lilly Res Lab, Div Res Technol & Prot, Indianapolis, IN 46285 USA. Beth Deaconess Med Ctr, Div Mol Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02215 USA. RP McCarthy, SA (reprint author), Millennium BioTherapeut Inc, 640 Mem Dr, Cambridge, MA 02139 USA. NR 39 TC 312 Z9 340 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 1 PY 1999 VL 238 IS 2 BP 301 EP 313 DI 10.1016/S0378-1119(99)00365-0 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 244XL UT WOS:000083076000003 PM 10570958 ER PT J AU Marasco, WA LaVecchio, J Winkler, A AF Marasco, WA LaVecchio, J Winkler, A TI Human anti-HIV-1 tat sFv intrabody gene therapy for advanced HIV-1 infection and AIDS. SO GENE THERAPY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 1999 VL 6 SU 1 MA 30 BP S8 EP S8 PG 1 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 254VJ UT WOS:000083632600032 ER PT J AU Mercer, GT Molinari, V Kunik, ME Orengo, CA Snow, L Rezabek, P AF Mercer, GT Molinari, V Kunik, ME Orengo, CA Snow, L Rezabek, P TI Rehospitalization of older psychiatric inpatients: An investigation of predictors SO GERONTOLOGIST LA English DT Article DE rehospitalization; older adults; inpatients; predictors ID EPIDEMIOLOGIC-CATCHMENT-AREA; RATING-SCALE BPRS; GEROPSYCHIATRIC RESEARCH; SCHIZOPHRENIC-PATIENTS; SOCIAL SUPPORT; DISORDERS; SERVICES; CARE; INDICATORS; POPULATION AB The purpose of this study was to identify a combination of variables that could predict rehospitalization among a sample of 150 geropsychiatric inpatients. Logistic regression analyses testing a modified model identified risk factors for geropsychiatric rehospitalization and correctly classified approximately 80% of inpatients who were rehospitalized for subsequent treatment. Patients' psychiatric diagnosis (mood or schizophrenic disorder), poor general psychiatric functioning, depressive and agitated behavior at discharge, little or no supervision in living arrangements following discharge, limited social support, change in the social support system preceding hospitalization, and maladaptive family functioning could significantly predict geropsychiatric rehospitalization. The strongest independent predictor was maladaptive family functioning. C1 Houston Vet Affairs Med Ctr, Psychol Serv, Houston, TX 77030 USA. St Louis Behav Med Inst, St Louis, MO USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Vet Affairs Vet Integrated Serv Network, MIRECC 16, Houston, TX USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Molinari, V (reprint author), Houston Vet Affairs Med Ctr, Psychol Serv, 116B,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 41 TC 12 Z9 12 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 1999 VL 39 IS 5 BP 591 EP 598 PG 8 WC Gerontology SC Geriatrics & Gerontology GA 331UU UT WOS:000088037700008 PM 10568083 ER PT J AU Newburg, DS Shen, ZJ Warren, CD AF Newburg, DS Shen, ZJ Warren, CD TI Analysis of the acidic oligosaccharides of human milk by capillary eletrophoresis SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 Shriver Ctr, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 1999 VL 9 IS 10 MA 156 BP 1142 EP 1142 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240DF UT WOS:000082810000171 ER PT J AU Vescio, R Berenson, J AF Vescio, R Berenson, J TI Autologous transplantation - Purging and the impact of minimal residual disease SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID BONE-MARROW TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMA; MONOCLONAL PLASMA-CELLS; HIGH-DOSE CHEMOTHERAPY; MULTIPLE-MYELOMA; MYELOGENOUS LEUKEMIA; TUMOR CONTAMINATION; RANDOMIZED TRIAL AB Autograft purging is feasible but of uncertain necessity. Despite encouraging phase II studies in patients with leukemia and lymphoma, few of these studies have been completed and those that have been completed have yet to mature. Patients undergoing tandem transplants or with highly responsive malignancies are most likely to benefit from autograft purging. New methods for monitoring minimal residual disease should help determine which disease conditions may benefit from autograft manipulation. The rationale for these statements are discussed in this article. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Vescio, R (reprint author), DVA W Los Angeles 111H, Bldg 500,Room 4237,11301 Wilshore Blvd, Los Angeles, CA 90073 USA. NR 45 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 1999 VL 13 IS 5 BP 969 EP + DI 10.1016/S0889-8588(05)70105-2 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA 250ZA UT WOS:000083419100005 PM 10553257 ER PT J AU Reid, AE Chang, Y Hight, AM Weissman, JS AF Reid, AE Chang, Y Hight, AM Weissman, JS TI Regional variation in liver transplantation among blacks SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 99 BP 185A EP 185A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700099 ER PT J AU Talwalkar, J Lalan, S Hauser, S Grace, N Reid, AE Corasanti, J Fiarman, G Shaw-Stiffel, T Thiim, M Uchman, S Gollan, J AF Talwalkar, J Lalan, S Hauser, S Grace, N Reid, AE Corasanti, J Fiarman, G Shaw-Stiffel, T Thiim, M Uchman, S Gollan, J TI Combination therapy with interferon-alfa-2b (INTRON-A) and ribavirin (REBETOL) in chronic hepatitis c patients previously relapsing or not responding to interferon alone SO HEPATOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Faulkner Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lahey Clin, Burlington, MA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Rhode Isl Hosp, Providence, RI USA. NR 0 TC 1 Z9 1 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 147 BP 197A EP 197A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700147 ER PT J AU Perrillo, RP Schiff, ER Dienstag, JL Gish, RG Dickson, RC Adams, PC Brown, NA Gardner, SD Anschuetz, GC AF Perrillo, RP Schiff, ER Dienstag, JL Gish, RG Dickson, RC Adams, PC Brown, NA Gardner, SD Anschuetz, GC TI Lamivudine for prevention of recurrent hepatitis B after liver transplantation: Final results of a US/Canadian multicenter trial. SO HEPATOLOGY LA English DT Meeting Abstract C1 Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Univ Miami, Miami, FL 33152 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. CA Pacific Med Ctr, San Francisco, CA USA. Univ Florida, Gainesville, FL USA. Univ London London Hosp, London, ON, Canada. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. NR 0 TC 9 Z9 9 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 245 BP 222A EP 222A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700246 ER PT J AU Rudolph, KL Chang, S Schreiber-Agus, N Artandi, S Gottlieb, GJ Depinho, RA AF Rudolph, KL Chang, S Schreiber-Agus, N Artandi, S Gottlieb, GJ Depinho, RA TI Impaired liver regeneration and decreased hepatocarcinogenesis in telomerase deficient mice. SO HEPATOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. CIP Lab, Beachwood, OH USA. NR 0 TC 1 Z9 1 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 624 BP 316A EP 316A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700622 ER PT J AU Heintges, T Putlitz, JZ Wands, JR AF Heintges, T Putlitz, JZ Wands, JR TI Characterization and binding of intracellular antibody fragments to the hepatitis C virus core protein SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 770 BP 353A EP 353A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700770 ER PT J AU Chung, RT Saquib, A He, WP Chawla, A Schmidt, EV AF Chung, RT Saquib, A He, WP Chawla, A Schmidt, EV TI Successful synthesis of negative strand HCV RNA in mammalian cells using a binary expression system SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 774 BP 354A EP 354A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700774 ER PT J AU Wong, DKH Lechner, F Dohrenwend, PB Chung, R Robbins, G Klenerman, P Walker, BD AF Wong, DKH Lechner, F Dohrenwend, PB Chung, R Robbins, G Klenerman, P Walker, BD TI Dynamics of the CD8+and CD4+T cell immune response during acute HCV infection with spontaneous resolution. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. John Radcliffe Hosp, Oxford OX3 9DU, England. RI Robbins, Gregory/F-7988-2011 NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 775 BP 354A EP 354A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794700773 ER PT J AU Sevigny, J Lemmens, R Csizmadia, E Smith, NR Robson, SC AF Sevigny, J Lemmens, R Csizmadia, E Smith, NR Robson, SC TI Canalicular ecto-ATPase is a novel member of the GDA 1/CD39 NTPase family. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Limburgs Univ Ctr, Diepenbeek, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Sevigny, Jean/E-8039-2012 OI Sevigny, Jean/0000-0003-2922-1600 NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 1344 BP 496A EP 496A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794701342 ER PT J AU Reid, AE Chang, YC Hight, AM Weissman, JS AF Reid, AE Chang, YC Hight, AM Weissman, JS TI Outcome of blacks with ESLD referred for liver transplantation. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 SU S MA 2016 BP 664A EP 664A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239XE UT WOS:000082794702011 ER PT J AU Dienstag, JL Schiff, ER Mitchell, M Casey, DE Gitlin, N Lissoos, T Gelb, LD Condreay, L Crowther, L Rubin, M Brown, N AF Dienstag, JL Schiff, ER Mitchell, M Casey, DE Gitlin, N Lissoos, T Gelb, LD Condreay, L Crowther, L Rubin, M Brown, N TI Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy SO HEPATOLOGY LA English DT Article ID HIGH-LEVEL RESISTANCE; E-ANTIGEN; REVERSE-TRANSCRIPTASE; ALPHA-INTERFERON; CONTROLLED TRIAL; VIRUS-INFECTION; LIVER-DISEASE; PREDNISONE WITHDRAWAL; MUTATION; INVITRO AB In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg); posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%), Therapy was discontinued after HBeAg loss/seroconversion in 7 patients, and HBeAg status was maintained in all. Four of the patients with HBeAg responses lost HBsAg at least once. In 10 (43%) of 23 patients tested, we identified HBV polymerase YMDD mutations, 3 with detectable HBV DNA (2 with ALT elevations) and 7 without virological/biochemical breakthrough, In conclusion, up to 18 months of lamivudine therapy was well tolerated, suppressed HBV replication consistently and tripled the frequency of HBeAg losses observed during brief-duration therapy; HBeAg loss/seroconversion remained durable posttreatment, The emergence of YMDD-variant HBV was relatively common but occurred typically without reappearance of detectable HBV DNA or ALT elevation. Our observations suggest that lamivudine can be stopped after confirmed HBeAg loss or seroconversion. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Liver Biliary Pancreas Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Miami, Med Ctr, Dept Med, Miami, FL 33152 USA. Univ Miami, Med Ctr, Ctr Liver, Miami, FL 33152 USA. Emory Univ, Sch Med, Div Gastroenterol, Atlanta, GA USA. Washington Univ, Sch Med, St Louis, MO USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1RR01066] NR 31 TC 158 Z9 165 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1999 VL 30 IS 4 BP 1082 EP 1087 DI 10.1002/hep.510300427 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239RZ UT WOS:000082784600035 PM 10498663 ER PT J AU Garcia-Olmo, D Garcia-Olmo, DC Ontanon, J Martinez, E Vallejo, M AF Garcia-Olmo, D Garcia-Olmo, DC Ontanon, J Martinez, E Vallejo, M TI Tumor DNA circulating in the plasma might play a role in metastasis. The hypothesis of the genometastasis SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE tumor DNA; plasma; metastasis pathways; colon adenocarcinoma; rat ID POLYMERASE CHAIN-REACTION; COLORECTAL-CANCER; CARCINOMA-CELLS; SERUM; BLOOD; MUTATIONS; ONCOGENES; THERAPY; LIVER; GENE AB Background: Clinical and experimental observations suggest that more than one pathway might be involved in the development of metastases. In the present study, we examined the presence of tumor DNA in plasma using an experimental model in which tumor cells were modified with a genome-associated tag. We also investigated whether plasma of tumor-bearing rats had any effect on cultured cells and healthy animals. Methods: Transfected cancer cells (DHD/K12-PROb stably transfected with pCDNA3.1CAT.) were injected subcutaneously into the chest of BD-IX rats. Animals were divided into ten groups according to the time between injection of tumor cells and euthanasia. Prior to euthanasia (2-14 week), blood samples were collected by cardiac puncture. To detect circulating tumor cells and CAT-encoding DNA in plasma, we performed PCR with nested primers. Fifty samples of plasma were chosen at random to supplement the medium of fifty cultures of DHD cells for 10-12 days. PCR for the detection of CAT DNA in cells was performed approximately one to two months later. Four healthy rats received an intraperitoneal injection of plasma from a tumor-bearing rat five times at week for 4 to 6 weeks. Animals were sacrificed and samples of liver, kidney, spleen, omentum, blood and lung were processed by PCR for the detection of CAT DNA. Results: Detection of CAT DNA in plasma was slightly more frequent than in the buffy-coat fraction. All surviving cultures that had been supplemented with plasma were positive at some point for CAT DNA. In all four healthy animals injected with plasma of tumor-bearing rats, the marker gene for CAT was found in extracts of lungs. Conclusion: Our present observation lead us to propose the following hypothesis. Metastases might develop as a result of transfection of susceptible cells in distant target organs with dominant oncogenes that are present in the circulating plasma and are derived from the primary tumor. C1 Hosp Gen Albacete, Unidad Invest, Dept Gen Surg, Albacete 02006, Spain. Hosp Gen Albacete, Expt Res Unit, Albacete 02006, Spain. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA USA. RP Garcia-Olmo, D (reprint author), Hosp Gen Albacete, Unidad Invest, Dept Gen Surg, Hnos Falco S-N, Albacete 02006, Spain. RI Garcia-Olmo, Dolores C./L-5733-2014 NR 22 TC 57 Z9 62 U1 0 U2 4 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD OCT PY 1999 VL 14 IS 4 BP 1159 EP 1164 PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 234DY UT WOS:000082470300016 PM 10506932 ER PT J AU Kim, HG Kassis, J Souto, JC Turner, T Wells, A AF Kim, HG Kassis, J Souto, JC Turner, T Wells, A TI EGF receptor signaling in prostate morphogenesis and tumorigenesis SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE organogenesis; prostate carcinoma; development; signaling; tumor invasion ID EPIDERMAL-GROWTH-FACTOR; DOMINANT-NEGATIVE MUTANT; CANCER CELL-LINE; FACTOR-ALPHA; CARCINOMA-CELLS; TYROSINE KINASE; TARGETED EXPRESSION; ANDROGEN-BINDING; MOUSE PROSTATE; MESSENGER-RNA AB The growth and differentiation of the prostate gland are largely dependent on extracellular signaling factors. In addition to androgens, many polypeptide growth factors function through autocrine or paracrine networks. The paracrine interaction between stromal and epithelial cells is critical for androgen regulation, morphogenesis, epithelial cell proliferation, and secretory differentiation. Efforts to identify the essential growth factors and studies on their effects have been prompted by the fact that prostate cells in culture need substances other than androgens for proliferation. In this context, transforming growth factor-a and epidermal growth factor, among others, have been studied extensively. Recent advances have suggested that these EGF receptor (EGFR) ligands play roles not only during glandular development but also during neoplastic transformation and tumor progression. The cell responses most relevant to the role of this receptor signaling are both mitogenesis and cell motility. The aim of the review is to provide an overview of current knowledge about EGFR and its ligands in the organogenesis and tumorigenesis of the prostate gland. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. Tuskegee Univ, Dept Biol, Tuskegee, AL 36088 USA. RP Wells, A (reprint author), Univ Alabama, Dept Pathol, LHRB 531,701 19th St S, Birmingham, AL 35294 USA. OI Wells, Alan/0000-0002-1637-8150 NR 78 TC 78 Z9 92 U1 1 U2 5 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD OCT PY 1999 VL 14 IS 4 BP 1175 EP 1182 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 234DY UT WOS:000082470300018 PM 10506934 ER PT J AU Murley, YM Carroll, PA Skorupski, K Taylor, RK Calderwood, SB AF Murley, YM Carroll, PA Skorupski, K Taylor, RK Calderwood, SB TI Differential transcription of the tcpPH operon confers biotype-specific control of the Vibrio cholerae ToxR virulence regulon SO INFECTION AND IMMUNITY LA English DT Article ID EL-TOR BIOTYPES; COORDINATE EXPRESSION; GENETIC ORGANIZATION; ADENYLATE-CYCLASE; MEMBRANE PROTEINS; COREGULATED PILUS; ESCHERICHIA-COLI; BINDING PROTEIN; REGULATORY GENE; ARAC FAMILY AB Epidemic strains of Vibrio cholerae O1 are divided into two biotypes, classical and El Tor. In both biotypes, regulation of virulence gene expression depends on a cascade in which ToxR activates expression of ToxT, and ToxT activates expression of cholera toxin and other virulence genes. In the classical biotype, maximal expression of this ToxR regulon in vitro occurs at 30 degrees C at pH 6.5 (ToxR-inducing conditions), whereas in the El Tor biotype, production of these virulence genes only occurs under very limited conditions and not in response to temperature and pH; this difference between biotypes is mediated at the level of toxT transcription. In the classical biotype, two other proteins, TcpP and TcpH, are needed for maximal toxT transcription. Transcription of tcpPH in the classical biotype is regulated by pll and temperature independently of ToxR or ToxT, suggesting that TcpP and TcpH couple environmental signals to transcription of toxT. In this study, we show a near absence of tcpPH message in the El Tor biotype under ToxR-inducing conditions of temperature and pH. However, once expressed, El Tor TcpP and TcpH appear to be as effective as classical TcpP and TcpH in activating toxT transcription. These results suggest that differences in regulation of virulence gene expression between the biotypes of V. cholerae primarily result from differences in expression of tcpPH message in response to environmental signals. We present an updated model for control of the ToxR virulence regulon in V. cholerae. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Dartmouth Coll, Sch Med, Dept Microbiol, Hanover, NH 03755 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI039654, R01AI34968, R01AI39654, R29 AI041558, R29AI41558] NR 52 TC 33 Z9 36 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 OCT PY 1999 VL 67 IS 10 BP 5117 EP 5123 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 240ET UT WOS:000082813500019 PM 10496885 ER PT J AU Goetz, A Posey, K Fleming, J Jacobs, S Boody, L Wagener, MM Muder, RR AF Goetz, A Posey, K Fleming, J Jacobs, S Boody, L Wagener, MM Muder, RR TI Methicillin-resistant Staphylococcus aureus in the community: A hospital-based study SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CARRIAGE; INFECTION; OUTBREAK; STAFF AB To determine the proportion of methicillin-resistant Staphylococcus aureus (MRSA) among patients presenting for hospitalization and to assess risk factors for MRSA carriage, we conducted a study for 13 months at five Pittsburgh-area hospitals. Of 504 S aureus identified, 125 (25%) were MRSA. Independent risk factors for MRSA included organ transplantation, employment in a healthcare facility, pressure sores, tube feeding, and hospitalization within the preceding year (Infect Control Hosp Epidemiol 1999;20:689-691). C1 Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Mercy Hosp, Pittsburgh, PA 15219 USA. St Clair Hosp, Pittsburgh, PA USA. Forbes Reg Hosp, Pittsburgh, PA USA. RP Muder, RR (reprint author), Vet Adm Med Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. NR 12 TC 54 Z9 56 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 1999 VL 20 IS 10 BP 689 EP 691 DI 10.1086/501567 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 245UX UT WOS:000083127500009 PM 10530648 ER PT J AU Sakai, E Bottaro, A Alt, FW AF Sakai, E Bottaro, A Alt, FW TI The Ig heavy chain intronic enhancer core region is necessary and sufficient to promote efficient class switch recombination SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE E mu; enhancer; gene targeting; Ig class switching; matrix attachment region ID MATRIX-ATTACHMENT REGIONS; IMMUNOGLOBULIN GENE-TRANSCRIPTION; CHROMOSOMAL LOOP ANCHORAGE; DNA-REPLICATION; DELETION; LOCUS; EXON; EXPRESSION; ELEMENTS; MURINE AB The intronic IgH enhancer E-mu, which consists of the core enhancer (cE(mu)) flanked by 5' and 3' matrix attachment regions (MAR), has been implicated in the control of IgH locus recombination and transcription. Both cE(mu) and the MAR are required to enhance transcription of an IgH transgene, To elucidate the regulatory functions of cE(mu) versus its associated MAR in IgH class switch recombination (CSR), we have assayed ES cell lines which have targeted deletions of these elements, both individually and in combination, by the Rag-2-deficient blastocyst complementation method. Mutant B cells from chimeric mice were activated in culture and the influence of the mutations on CSR was assessed by analysis of B cell hybridomas. We find that the cE(mu) is necessary and sufficient for providing the functions of E-mu required for efficient CSR at the IgH locus. However, the 5' and 3' MAR sequences, as well as the known I-mu transcription start sites and the bulk of I-mu coding sequences, were dispensable for the process. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI20047, AI35714] NR 45 TC 27 Z9 27 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1999 VL 11 IS 10 BP 1709 EP 1713 DI 10.1093/intimm/11.10.1709 PG 5 WC Immunology SC Immunology GA 246KE UT WOS:000083162300014 PM 10508189 ER PT J AU Oliva, E Young, RH Clement, PB Scully, RE AF Oliva, E Young, RH Clement, PB Scully, RE TI Myxoid and fibrous endometrial stromal tumors of the uterus: A report of 10 cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE endometrial stromal tumors; myxoid change; fibrous change ID MESENCHYMAL TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; CLINICOPATHOLOGICAL ANALYSIS; MALIGNANT SCHWANNOMA; UTERINE CERVIX; NEOPLASMS; SARCOMAS; LEIOMYOMATOSIS; LEIOMYOSARCOMA; EXPRESSION AB Ten endometrial stromal tumors of the uterus with a prominent myxoid or fibrous appearance, or both, that led to problems in interpretation are reported. The patients were 32 to 52 (mean 39) years of age. Three presented with dysfunctional uterine bleeding and one with abdominal pain. An enlarged uterus or a pelvic mass was palpated in five patients; the tumor was an incidental postpartum finding in one patient. All patients underwent hysterectomy. The tumors ranged from 4 to 20 cm in greatest dimension. Six were soft. polypoid intracavitary masses and four were predominantly intramyometrial: two were gelatinous. On microscopic examination, nine tumors infiltrated the myometrium (stromal sarcomas) and one was well circumscribed (stromal nodule), Six tumors had a predominantly fibrous component with the neoplastic cells separated by variable amounts of collagen: extensive areas of hyalinization were present in three tumors. Two tumors were predominantly composed of hypocellular areas with an abundant myxoid matrix, and two had both components in roughly equal proportions. Alcian blue staining was positive, with the staining eliminated by hyaluronidase predigestion. in the myxoid areas. The typical morphologic features of endometrial stromal neoplasia were present focally in four tumors. All of them contained numerous small thin-walled vessels. Vimentin and smooth muscle actin were positive in nine of nine and seven of nine tumors, respectively, whereas desmin was negative in six of nine tumors and only focally positive in the other three. One patient had omental nodules at the time of the initial diagnosis and another had a pelvic recurrence 2 years after hysterectomy. Follow-up information is unavailable or short in the other cases. These tumors should be considered of endometrial stromal origin in view of the typical location of most of them, their growth pattern, content of characteristic arterioles. presence of typical endometrial stromal neoplasia in the primary or recurrent tumor in some cases, and absence of evidence of origin from a cell type other than endometrial stroma. These rumors may be identical, in some instances at least, to tumors referred to in the older literature as "myxofibrosarcomas." C1 Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC, Canada. RP Oliva, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 42 TC 80 Z9 86 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1999 VL 18 IS 4 BP 310 EP 319 DI 10.1097/00004347-199910000-00004 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 245RW UT WOS:000083122800004 PM 10542938 ER PT J AU Seetharam, S Staba, MJ Schumm, LP Schreiber, K Schreiber, H Kufe, DW Weichselbaum, RR AF Seetharam, S Staba, MJ Schumm, LP Schreiber, K Schreiber, H Kufe, DW Weichselbaum, RR TI Enhanced eradication of local and distant tumors by genetically produced interleukin-12 and radiation SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE fibrosarcoma; gene therapy; cytokines; anti-angiogenic ID CANCER; THERAPY; CELLS; CHEMOTHERAPY; INHIBITION; ANTITUMOR; CYTOKINE AB Ionizing radiation (IR) is frequently unsuccessful in the treatment of cancer because of local failure or distant metastases. The efficacy of systemically administered cytokines for cancer therapy is often limited by toxicity. We report that intratumoral injection of an adenoviral vector with interleukin-12 (IL-12) enhances local anti-tumor effects of irradiation (IR). We demonstrate that microscopic tumor growth at a distant site is suppressed following treatment of the primary tumor with adeno-murine IL-12 (Adm.IL-12). The results support a model in which the anti-angiogenic effects of IL-12 contribute to the local anti-tumor effects of radiation, while IL-12 induced immunity suppresses growth of microscopic tumors distant from the primary irradiated site. These data suggest that combining radiotherapy with IL-12 improves both local and distant tumor control compared to either treatment alone. Immunoradiotherapy may be employed in addition to or in place of current conventional therapies to increase local control and decrease distant tumor growth. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. FU NCI NIH HHS [CA 41068-10] NR 22 TC 30 Z9 30 U1 1 U2 1 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 OCT PY 1999 VL 15 IS 4 BP 769 EP 773 PG 5 WC Oncology SC Oncology GA 239UC UT WOS:000082787200021 PM 10493960 ER PT J AU Prosnitz, RG Schneider, L Manola, J Rocha, S Loffredo, M Lopes, L D'Amico, AV AF Prosnitz, RG Schneider, L Manola, J Rocha, S Loffredo, M Lopes, L D'Amico, AV TI Tamsulosin palliates radiation-induced urethritis in patients with prostate cancer: Results of a pilot study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; complications; Flomax; urethritis; conformal external beam radiation therapy ID OBSTRUCTION SYMPTOMATIC BPH; SELECTIVE ALPHA(1A)-ADRENOCEPTOR ANTAGONIST; HYPERPLASIA; MULTICENTER; RECEPTOR; MORBIDITY; TRIAL; CDNA AB Purpose: A pilot study was performed to determine the effectiveness of Flomax (tamsulosin HCl) in the management of acute radiation urethritis in prostate cancer patients undergoing conformal external beam radiation therapy (RT). Potential predictors of response to Flomax were evaluated. Methods and Materials: From January 1998 to April 1998, 26 consecutive patients who developed symptoms of radiation urethritis while undergoing RT for prostate cancer were treated with Flomax, a superselective alpha(1A)-adrenergic antagonist. A genitourinary review of systems served as the instrument used to assess baseline urinary function and treatment response. Results: The initial response rate to Flomax was 62% (16/26) at the 0.4 mg level and 60% (6/10) at the 0.8 mg level. Half of the 16 patients who initially responded to 0.4 mg subsequently progressed. Three-fourths of those patients who progressed, however, achieved a durable response with the 0.8 mg dose. Therefore urinary symptoms were ultimately controlled in 77% (20/26) of the patients. After correcting for the testing of multiple hypotheses (n = 5), the presence of benign prostatic hyperplasia (BPH) approached statistical significance for predicting the initial response to the 0.4 mg dose of Flomax (78% vs, 25%,p = 0.03). Conclusion: Flomax appears to be effective in relieving the symptoms of radiation urethritis. A Phase II trial is justified and in progress. (C) 1999 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. RP Prosnitz, RG (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave,5th Floor, Boston, MA 02215 USA. NR 16 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 1999 VL 45 IS 3 BP 563 EP 566 DI 10.1016/S0360-3016(99)00246-1 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 243EA UT WOS:000082983000007 PM 10524406 ER PT J AU Borgelt, BB Stone, C AF Borgelt, BB Stone, C TI Ambulatory patient classifications and the regressive nature of medicare reform: Is the reduction in outpatient health care reimbursement worth the price? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE ambulatory patient classifications; medicare reform; reimbursement; radiation oncology; cost analysis ID RELATIVE VALUE SCALE; VALUE UNITS; PRODUCTIVITY AB Purpose: To evaluate the impact of the proposed Ambulatory Patient Classification (APC) system on reimbursement for hospital outpatient Medicare procedures at the Massachusetts General Hospital (MGH) Department of Radiation Oncology. Methods and Materials: Treatment and cost data for the MGH Department of Radiation Oncology for the fiscal year 1997 were analyzed. This represented 66,981 technical procedures and 41 CPT-4 codes. The cost of each procedure was calculated by allocating departmental costs to the relative value units (RVUs) for each procedure according to accepted accounting principles, Net reimbursement for each CPT-4 procedure was then calculated by subtracting its cost from the allowed 1998 Boston area Medicare reimbursement or from the proposed Boston area APC reimbursement. The impact of the proposed APC reimbursement system on changes in reimbursement per procedure and on volume-adjusted changes in overall net reimbursements per procedure was determined. Results: Although the overall effect of APCs on volume-adjusted net reimbursements for Medicare patients was projected to be budget-neutral, treatment planning revenues would have decreased by 514% and treatment delivery revenues would have increased by 151%, Net reimbursements for less complicated courses of treatment would have increased while those for treatment courses requiring more complicated or more frequent treatment planning would have decreased. Net reimbursements for a typical prostate interstitial implant and a three-treatment high-dose-rate intracavitary application would have decreased by 481% and 632%, respectively. Conclusion: The financial incentives designed into the proposed APC reimbursement structure could lead to compromises in currently accepted standards of care, and may make it increasingly difficult for academic institutions to continue to fulfill their missions of research and service to their communities, The ability of many smaller, low patient volume, high Medicare mix hospital-based radiation oncology departments to continue to deliver their current level of care could be compromised. APC reform may carry monetary and opportunity costs which far outweigh its apparent savings. As payment systems continue to place pressure on operating margins, it becomes even more critical that both academic and community radiation oncology practices know the cost of providing services, (C) 1999 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Borgelt, BB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 1999 VL 45 IS 3 BP 729 EP 734 DI 10.1016/S0360-3016(99)00233-3 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 243EA UT WOS:000082983000030 PM 10524429 ER PT J AU Leonardo, MR Moser, DP Barbieri, E Brantner, CA MacGregor, BJ Paster, BJ Stackebrandt, E Nealson, KH AF Leonardo, MR Moser, DP Barbieri, E Brantner, CA MacGregor, BJ Paster, BJ Stackebrandt, E Nealson, KH TI Shewanella pealeana sp nov., a member of the microbial community associated with the accessory nidamental gland of the squid Loligo pealei SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article DE Shewanella pealeana; Loligo pealei; sulfur reducer; choline ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DNA HYBRIDIZATION; GLYCINE BETAINE; ALTEROMONAS-PUTREFACIENS; FACULTATIVE ANAEROBE; FORBESI CEPHALOPODA; RENATURATION RATES; TEICHOIC-ACID; REDUCTION; CHOLINE AB A new, mesophillic, facultatively anaerobic, psychrotolerant bacterium, strain ANG-SQ1(T) (T = type strain), was isolated from a microbial community colonizing the accessory nidamental gland of the squid Loligo pealei. It was selected from the community on the basis of its ability to reduce elemental sulfur. The cells are motile, Gram-negative rods (2.0-3.0 mu m long, 0.4-0.6 mu m wide). ANG-SQ1T grows optimally over the temperature range of 25-30 degrees C and a ph range of 6.5-7.5 degrees C in media containing 0.5 M NaCl. 16S rRNA sequence analysis revealed that this organism belongs to the gamma-3 subclass of the Proteobacteria. The closest relative of ANG-SQ1(T) is Shewanella gelidimarina, with a 16S rRNA sequence similarity of 97.0%. Growth occurs with glucose, lactate, acetate, pyruvate, glutamate, citrate, succinate, Casamino acids, yeast extract or peptone as sole energy source under aerobic conditions. The isolate grows anaerobically by the reduction of iron, manganese, nitrate, fumarate, trimethylamine-N-oxide, thiosulfate or elemental sulfur as terminal electron acceptor with lactate. Growth of ANG-SQ1(T) was enhanced by the addition of choline chloride to growth media lacking Casamino acids. The addition of leucine or valine also enhanced growth in minimal growth media supplemented with choline. The results of both phenotypic and genetic characterization indicate that ANG-SQ1T is a Shewanella species. Thus it is proposed that this new isolate be assigned to the genus Shewanella and that it should be named Shewanella pealeana sp. nov., in recognition of its association with L. pealei. C1 Univ Wisconsin, Ctr Great Lakes Studies, Milwaukee, WI 53204 USA. Univ Urbino, Ist Sci Tossicog Ingienst & Ambientali, I-61029 Urbino, Italy. Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. Northwestern Univ, Dept Civil Engn, Evanston, IL 60208 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Deutsch Sammlung Mikroorganismen & Zellkulturen G, D-38124 Braunschweig, Germany. CALTECH, Jet Prop Labs, Pasadena, CA 91109 USA. RP Leonardo, MR (reprint author), Univ Alabama, Dept Biol Sci, Box 870206, Tuscaloosa, AL 35487 USA. RI MacGregor, Barbara/D-9911-2013; OI MacGregor, Barbara/0000-0003-1238-5799; Brantner, Christine/0000-0001-8172-901X; Barbieri, Elena/0000-0002-3480-7983 NR 60 TC 49 Z9 51 U1 3 U2 13 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1999 VL 49 BP 1341 EP 1351 PN 4 PG 11 WC Microbiology SC Microbiology GA 251NB UT WOS:000083450800002 PM 10555311 ER PT J AU Lilly, CM Woodruff, PG Camargo, CA Nakamura, H Drazen, JM Nadel, ES Hanrahan, JP AF Lilly, CM Woodruff, PG Camargo, CA Nakamura, H Drazen, JM Nadel, ES Hanrahan, JP TI Elevated plasma eotaxin levels in patients with acute asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE chemokines; emergency medicine; lung; pulmonary diseases ID BRONCHOALVEOLAR LAVAGE; ATOPIC ASTHMA; RECEPTOR CCR3; EXPRESSION; INFLAMMATION; CELLS; EOSINOPHILS; ACTIVATION; CHEMOKINES; POPULATION AB Background: The eosinophil chemotactic and activating effects of eotaxin and the known association of eosinophils with asthma suggest that eotaxin expression is increased during asthma exacerbations. Objective: We sought to determine whether plasma eotaxin levels are elevated in patients presenting for emergency treatment of acute asthma and to correlate eotaxin levels with disease activity and responses to treatment. Methods: A case-control study of plasma eotaxin levels was performed in the 36 patients who presented for emergency asthma treatment and 133 age-, sex-, and ethnicity-matched subjects with stable asthma, Results: Plasma eotaxin levels were significantly higher in 36 patients with acute asthma symptoms and airflow obstruction (520 pg/mL [250, 1100 pg/mL]; geometric mean [-1 SD, +1 SD]) than in 133 subjects with stable asthma (350 pg/mL [190, 620 pg/ml]; P = .0008), Among the patients with emergency asthma flares, those who responded to asthma treatment with an increase in peak expiratory flow rate by an amount equal to at least 20% of their predicted normal value had lower eotaxin levels than those who did not (410 pg/mL [210, 800 pg/mL] and 660 pg/mL [300, 1480 pg/mL], respectively; P = .01). Conclusion: These findings imply that eotaxin either is mechanistically involved in acute asthma or series as a biomarker for activity of the CCR3 receptor ligand system, which is functionally linked to asthma. C1 Brigham & Womens Hosp, Div Resp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lilly, CM (reprint author), Brigham & Womens Hosp, Div Resp, Combined Program Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-03283, HL-03533, HL-07427] NR 19 TC 68 Z9 72 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 1999 VL 104 IS 4 BP 786 EP 790 PN 1 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 248NG UT WOS:000083281200009 PM 10518822 ER PT J AU Holden, WE Wilkins, JP Harris, M Milczuk, HA Giraud, GD AF Holden, WE Wilkins, JP Harris, M Milczuk, HA Giraud, GD TI Temperature conditioning of nasal air: effects of vasoactive agents and involvement of nitric oxide SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE temperature regulation; nose; vasoconstrictor; vasodilator ID EXHALED AIR; HUMANS; SYNTHASE; MUCOSA; PHYSIOLOGY; EXERCISE AB Nitric oxide(NO) is released into nasal air,but its function is unknown. We hypothesized that nasal vascular tone and/or flow influences temperature conditioning of nasal air and that NO participates in this process. We measured nasal air temperature (via a thermocouple) and exhaled nasal NO release (by chemiluminescence) in five humans and examined the effects of an aerosolized vasoconstrictor (oxymetazoline), a vasodilator(papaverine), N-G-nitro-L-arginine methyl ester, an inhibitor of NO synthase, or saline (control). Compared with saline (which caused no changes in nasal air temperature or exhaled NO release), oxymetazoline (0.05%) reduced nasal air temperature and NO release (130.8 +/- 15.1 to 81.3 +/- 12.8 nl.min(-1).m(-2); P < 0.01). Papaverine (0.01 M) increased nasal air temperature and NO release (131.8 +/- 13.1 to 157.2 +/- 17.4 nl.min(-1).m(-2); P < 0.03). N-G-nitro-L-arginine methyl ester reduced nasal air temperature and NO release (123.7 +/- 14.2 to 44.2 +/- 23.7 nl.min(-1).m(-2); P < 0.01). The results suggest that vascular tone and/or flow modulates temperature conditioning and that NO may participate in that function. C1 Portland Vet Affairs Med Ctr, Pulm & Crit Care Sect, Med Serv, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Holden, WE (reprint author), Portland Vet Affairs Med Ctr, Pulm & Crit Care Sect, Med Serv, 3710 SW US Vet Rd, Portland, OR 97201 USA. NR 25 TC 20 Z9 20 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 OCT PY 1999 VL 87 IS 4 BP 1260 EP 1265 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 244NP UT WOS:000083057900003 PM 10517750 ER PT J AU Rubin, DA Juppner, H AF Rubin, DA Juppner, H TI Zebrafish express the common parathyroid hormone/parathyroid hormone-related peptide receptor (PTH1R) and a novel receptor (PTH3R) that is preferentially activated by mammalian and fugufish parathyroid hormone-related peptide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; PTH/PTHRP RECEPTOR; SUPRAOPTIC NUCLEUS; PROTEIN; RAT; GENE; BINDING; CELLS; PTHRP; IDENTIFICATION AB To further explore the evolution of receptors for parathyroid hormone (PTH) and PTH-related peptide (PTHrP), we searched for zebrafish (z) homologs of the PTH/PTHrP receptor (PTH1R). In mammalian genes encoding this receptor, exons M6/7 and M7 are highly conserved and separated by 81-84 intronic nucleotides. Genomic polymerase chain reaction using degenerate primers based on these exons led to two distinct DNA fragments comprising portions of genes encoding the zPTH1R and the novel zPTH3R. Sequence comparison of both full-length teleost receptors revealed 69% similarity (61% identity), but less homology with zPTH2R, When compared with hPTH1R, zPTH1R showed 76% and zPTH3R 67% amino acid sequence similarity; similarity with hPTH2R was only 59% for both teleost receptors. When expressed in COS-7 cells, zPTH1R bound [TyrS4]hPTH-(1-34)-amide (hPTH), [Tyr(36)]hPTHrP(1-36)-amide (hPTHrP), and [Ala(29),Glu(30),Ala(34),Glu(35), Tyr(36)]fugufish PTHrP-(1-36)-amide (fuguPTHrP) with a high apparent affinity (IC50: 1.2-3.5 nM), and was efficiently activated by all three peptides (EC50: 1.1-1.7 nM). In contrast, zPTH3R showed higher affinity for fuguPTHrP and hPTHrP (IC50: 2.1-11.1 nM) than for hPTH (IC50: 118.2-127.0 nM); cAMP accumulation was more efficiently stimulated by fugufish and human PTHrP (EC50: 0.47 +/- 0.27 and 0.45 +/- 0.16, respectively) than by hPTH (EC50: 9.95 +/- 1.5 nM). Agonist-stimulated total inositol phosphate accumulation was observed with zPTH1R, but not zPTH3R. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK09500, F32 DK09500, DK-11794] NR 29 TC 76 Z9 77 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 1999 VL 274 IS 40 BP 28185 EP 28190 DI 10.1074/jbc.274.40.28185 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700020 PM 10497171 ER PT J AU Jin, YJ Yun, CL Burakoff, SJ AF Jin, YJ Yun, CL Burakoff, SJ TI Human 70-kDa SHP-1L differs from 68-kDa SHP-1 in its C-terminal structure and catalytic activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; HEMATOPOIETIC-CELL PHOSPHATASE; MOTH-EATEN MICE; ANTIGEN RECEPTOR; SH2 DOMAINS; INHIBITORY RECEPTOR; SIGNAL-TRANSDUCTION; LYMPHOCYTE-ACTIVATION; CRYSTAL-STRUCTURE; T-CELLS AB The tyrosine phosphatase SHP-1 functions as a negative regulator in hematopoietic cell development, proliferation, and receptor-mediated cellular activation. In Jurkat T cells, a major 68-kDa band and a minor 70-kDa band were immunoprecipitated by a monoclonal antibody against the SHP-1 protein-tyrosine phosphatase domain, while an antibody against the SHP-1 C-terminal 19 amino acids recognized only the 68-kDa SHP-1. The SDS-gel-purified 70-kDa protein was subjected to tryptic mapping and microsequencing, which was followed by molecular cloning. It revealed that the 70-kDa protein, termed SHP-1L, is a C-terminal alternatively spliced form of SHP-1. SHP-1L is 29 amino acids longer than SHP-1, and its 66 C-terminal amino acids are different from SHP-1. The C terminus of SHP-1L contains a proline-rich motif PVPGPPVLSP, a potential Src homology 3 domain-binding site. In contrast to SHP-1, tyrosine phosphorylation of SHP-1L is not detected upon stimulation in Jurkat T cells. This is apparently due to the lack of a single in vivo tyrosine phosphorylation site, which only exists in the C terminus of SHP-1 (Y564). COS cell expressed glutathione S-transferase-SHP-1L can dephosphorylate tyrosine-phosphorylated ZAP70. At pH 7.4, SHP-1L was shown to be more active than SHP-1 in the dephosphorylation of ZAP70, At pH 5.4, SHP-1L and SHP-1 exhibited similar catalytic activity. It is likely that these two isoforms play different roles in the regulation of hematopoietic cell signal transduction. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Jin, YJ (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Rm M654,44 Binney St, Boston, MA 02115 USA. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 FU NCI NIH HHS [R01 CA 70758] NR 54 TC 24 Z9 26 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 OCT 1 PY 1999 VL 274 IS 40 BP 28301 EP 28307 DI 10.1074/jbc.274.40.28301 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700036 PM 10497187 ER PT J AU Veale, M Raab, M Li, ZW da Silva, AJ Kraeft, SK Weremowicz, S Morton, CC Rudd, CE AF Veale, M Raab, M Li, ZW da Silva, AJ Kraeft, SK Weremowicz, S Morton, CC Rudd, CE TI Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE SUBSTRATE; CELL RECEPTOR; MOLECULAR-CLONING; CD4 ENDOCYTOSIS; ZAP-70 KINASE; ACTIVATION; TCR; PHOSPHORYLATION; DOMAIN; VAV AB T-cell activation involves the participation of protein-tyrosine kinases p56(lck) and ZAP-70/SYK. as well as lymphoid proteins such as SLP-76 and FYB/SLAP. FYB/SLAP has the hallmarks of an adaptor protein that binds to the SH2 domains of the Src kinase FYN-T and SLP-76, Whereas two forms of FYB at 120 and 130 kDa have been identified biochemically, a cDNA encoding only the lower molecular weight isoform has been cloned (termed FYB-120 or SLAP-130), In this study, we report the isolation of an alternative isoform of FYB with a molecular mass of 130 kDa (FYB-130) that has the same structure as FYB-130 except for an insertion of 46 amino acids toward the carboxyl-terminal region of the protein. FYB-120 and FYB-130 share an ability to bind to the SH2 domains of FYN-T and SLP-76, to act as substrates for p59(FYN-T), and to be expressed in the cytoplasm and nucleus of T-cells, Differences were noted between the isoforms in the efficiency of binding to SLP-76 and in the preferential expression of FYB-130 in mature T-cells. When co-expressed together with FYN-T and SLP-76, FYB-130 caused a significant increase in anti-CD3-driven NF-AT transcription. Finally, fluorescence in situ hybridization analysis localized the FYB gene to human chromosome 5 at position p13.1. FYB-130 therefore represents a novel variant of FYB protein that can up-regulate T-cell receptor-driven interleukin 2 production in mature T-cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 46 TC 46 Z9 48 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 OCT 1 PY 1999 VL 274 IS 40 BP 28427 EP 28435 DI 10.1074/jbc.274.40.28427 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700053 PM 10497204 ER PT J AU Abcouwer, SF Schwarz, C Meguid, RA AF Abcouwer, SF Schwarz, C Meguid, RA TI Glutamine deprivation induces the expression of GADD45 and GADD153 primarily by mRNA stabilization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUCOSE-REGULATED PROTEINS; MESSENGER-RNA DEGRADATION; AMINO-ACID LIMITATION; ENDOPLASMIC-RETICULUM; DNA-DAMAGE; P53-REGULATED PROTEIN; MALFOLDED PROTEINS; EPITHELIAL-CELLS; RICH ELEMENTS; CHOP GADD153 AB The expression of the growth arrest- and DNA damage-inducible genes, GADD45 and GADD153/CHOP (C/EBP-homologous protein), as well as GRP78 (glucose-regulated protein of 78 kDa) was examined in several human breast cell lines subjected to acute glutamine (GLN) deprivation. GLN deprivation caused rapid elevation of GADD45 and GADD153/CHOP mRNA levels in cells that were highly dependent upon GLN for growth and viability. Both GADD mRNAs were rapidly elevated up to several hundred-fold. In contrast, GRP78 expression was elevated by no more than 4-fold by GLN deprivation. The magnitude of GADD up-regulation roughly correlated with the extent of GLN dependence of each cell line. The levels of all three mRNAs were responsive to alterations of ambient GLN content in a physiologically relevant concentration range that corresponded to the affinities of cellular GLN transporters. Provision of GLN-derived metabolites partially inhibited the induction of GADD expression in GLN-deprived cells. Nuclear run-on assays and mRNA decay studies suggested that the primary mechanism leading to increased GADD mRNA levels was not transcriptional, but rather that GADD45 and GADD153/CHOP expression mere up-regulated in response to GLN deprivation via marked stabilization of these mRNAs. These results suggest that the expression of GADD genes contributes to growth arrest and/or protection from metabolic damage during GLN-poor conditions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Surg Oncol Res Labs, Boston, MA 02114 USA. RP Abcouwer, SF (reprint author), Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Biochem & Mol Biol, Basic Sci Bldg 249, Albuquerque, NM 87131 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NIDDK NIH HHS [P30-DK40561] NR 38 TC 63 Z9 63 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 OCT 1 PY 1999 VL 274 IS 40 BP 28645 EP 28651 DI 10.1074/jbc.274.40.28645 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700082 PM 10497233 ER PT J AU Huggins, GS Chin, MT Sibinga, NES Lee, SL Haber, E Lee, ME AF Huggins, GS Chin, MT Sibinga, NES Lee, SL Haber, E Lee, ME TI Characterization of the mUBC9-binding sites required for E2A protein degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-CONJUGATING ENZYME; LOOP-HELIX PROTEINS; KAPPA-B-ALPHA; CELL DEVELOPMENT; C-JUN; SACCHAROMYCES-CEREVISIAE; PROTEASOME PATHWAY; MAMMALIAN-CELLS; DNA-BINDING; GENE AB Mammalian Ubc9 (mUbc9) is required for rapid degradation of the E2A proteins E12 and E47 by the ubiquitin-proteasome system. We have shown elsewhere that mUbc9 interacts with amino acids 477-530 of E12/E47. Here we test the hypothesis that this region, rich in proline, glutamic acid, serine, and threonine (PEST) residues, serves as the E2A protein degradation domain (DD), An E2A protein lacking this region, E47 Delta(478-531), was significantly more stable than wild-type E47(half-life of more than 6 h versus 55 min). Deletion of the E2A DD had no effect on the E-box-binding and transcriptional activity of E47, We mapped two discreet mUbc9-interacting regions within the E2A DD: amino acids 476-494 and 505-513. E2A(505-513) interacted with mUbc9 but not with human Ubc5, MyoD, ids, or the polymyositis-scleroderma autoantigen, Substitution of the E2A(505-513) central hydrophobic residues with basic residues abolished interaction with mUbc9, Also, full-length E47 lacking the second mUbc9-interacting region was significantly more stable than wild-type E47, Reintroduction of the E2A DD into the long-lived, naturally occurring chimeric oncoprotein E2A-HLF (hepatic leukemic factor) destabilized it, suggesting that this domain can transfer a degradation signal to a heterologous protein. E2A-HLF-DD chimeric protein was stabilized by the proteasome inhibitor LLNL, indicating the role of the ubiquitin-proteasome system mediating degradation through the E2A degradation domain. Our experiments indicate that the E2A DD mediates E2A protein interactions with the ubiquitin-proteasome system and that the E2A DD is required for metabolism of these widely expressed proteins. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Lee, ME (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 677 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [K08 HL03667-01A1] NR 51 TC 27 Z9 27 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 1999 VL 274 IS 40 BP 28690 EP 28696 DI 10.1074/jbc.274.40.28690 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700088 PM 10497239 ER PT J AU Mirzabekov, T Bannert, N Farzan, M Hofmann, W Kolchinsky, P Wu, LJ Wyatt, R Sodroski, J AF Mirzabekov, T Bannert, N Farzan, M Hofmann, W Kolchinsky, P Wu, LJ Wyatt, R Sodroski, J TI Enhanced expression, native purification, and characterization of CCR5, a principal HIV-1 coreceptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; GP120 ENVELOPE GLYCOPROTEIN; ATOMIC-STRUCTURE; HUMAN CD4; HETEROLOGOUS EXPRESSION; CHEMOKINE RECEPTORS; FUSION; ENTRY; GP41; GENE AB Seven-transmembrane segment, G protein-coupled receptors (GPCRs) play important roles in many biological processes in which pharmaceutical intervention may be useful. High level expression and native purification of GPCRs are important steps in the biochemical and structural characterization of these molecules. Here, we describe enhanced mammalian cell expression and purification of a codon-optimized variant of the chemokine receptor CCR5, a GPCR that plays a central role in the entry of the human immunodeficiency virus-1 (HIV-1) into immune cells. CCR5 could be solubilized in its native state as determined by its ability to be precipitated by 2D7, a conformation-dependent anti-CCR5 antibody, and by the HIV-1 gp120 envelope glycoprotein. The 2D7 antibody recognized immature and mature forms of CCR5 equally, whereas gp120 preferentially recognized the mature form, a result that underscores a role for posttranslational modification of CCR5 in its HIV-1 coreceptor function. The methods described herein contribute to the analysis of CCR5 and are likely to be applicable to many other GPCRs. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Leukosite Inc, Cambridge, MA 02142 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI41851] NR 39 TC 110 Z9 113 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 OCT 1 PY 1999 VL 274 IS 40 BP 28745 EP 28750 DI 10.1074/jbc.274.40.28745 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 241ZA UT WOS:000082912700095 PM 10497246 ER PT J AU Reddy, SV Menaa, C Singer, FR Demulder, A Roodman, GD AF Reddy, SV Menaa, C Singer, FR Demulder, A Roodman, GD TI Cell biology of Paget's disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 3rd International Symposium on Pagets Disease CY NOV 29-30, 1998 CL NAPA, CALIFORNIA ID HUMAN MARROW CULTURES; FORMED IN-VITRO; BONE TISSUE; MONOCLONAL-ANTIBODIES; VIRAL-ANTIGENS; OSTEOCLASTS; INTERLEUKIN-6; PRECURSORS; RECEPTOR; VIRUS AB Paget's disease is characterized by markedly increased osteoclast formation and bone resorption followed by excessive new bone formation. Osteoclasts in Paget's disease are increased both in number and size, contain paramyxoviral-like nuclear inclusions, and can have up to 100 nuclei per cell. Marrow culture studies have identified several abnormalities in osteoclast formation in Paget's disease. Osteoclast-like multinucleated cells formed more rapidly in marrow cultures from patients with Paget's disease, produced increased levels of interleukin-6 (IL-6), and expressed high levels of IL-6 receptors compared to normals. IL-6 levels were also increased in bone marrow and peripheral blood of patients with Paget's disease. In addition, osteoclast precursors from patients with Paget's disease are hyperresponsive to 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and calcitonin, The increased sensitivity of osteoclast precursors to 1,25(OH)(2)D-3 is mediated through the vitamin D receptor (VDR), since 24-hydroxylase activity is also up-regulated at concentrations of 1,25(OH)(2)D-3 that are one log less than that needed to induce 24-hydroxylase activity in osteoclast precursors from normals. However, VDR numbers and affinity for 1,25(OH)(2)D-3 do not differ in osteoclast precursors from Paget's patients compared to those from normals. Synergistic interactions between cytokines such as IL-6 and 1,25(OH)(2)D-3 also cannot explain the enhanced sensitivity of osteoclast precursors from patients with Paget's disease to 1,25(OH)(2)D-3. Interestingly, coculture studies of osteoclast precursors and cells from the marrow:microenvironment of patients with Paget's disease and normals have demonstrated that the marrow microenvironment is more osteoclastogenic than normal. Thus, studies of the cell biology of osteoclasts in Paget's disease have demonstrated an increased rate of osteoclast formation and abnormalities in both osteoclast precursors and the marrow microenvironment, Enhanced IL-6 production by osteoclasts in Paget's disease may further amplify the increased osteoclast formation already ongoing in the pagetic lesion, and may explain the increased bone turnover at uninvolved sites distant from the pagetic lesion. C1 Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX USA. John Wayne Canc Ctr, Santa Monica, CA USA. Brugmann Hosp, Brussels, Belgium. Audie Murphy Vet Adm Hosp, San Antonio, TX USA. RP Roodman, GD (reprint author), Res Hematol 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR 36125, AR 41336, AR 44603] NR 28 TC 37 Z9 38 U1 1 U2 2 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 OCT PY 1999 VL 14 SU 2 BP 3 EP 8 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240AZ UT WOS:000082804600002 PM 10510206 ER PT J AU Leach, RJ Singer, FR Cody, JD Roodman, GD AF Leach, RJ Singer, FR Cody, JD Roodman, GD TI Variable disease severity associated with a Paget's disease predisposition gene SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 3rd International Symposium on Pagets Disease CY NOV 29-30, 1998 CL NAPA, CALIFORNIA ID FAMILIAL EXPANSILE OSTEOLYSIS; CHROMOSOME 18Q; BONE; LINKAGE AB We have recently identified a region on the long arm of chromosome 18 that carries a predisposition gene for Paget's disease using linkage analysis. This region was explored because of earlier studies demonstrating the presence of a gene for another bone disorder, familial expansile osteolysis (FEO) within this region. FEO has many similarities to Paget's disease including osteoclast abnormalities and viral-like nuclear inclusions, Therefore, it was proposed that FEO and Paget's disease are disorders resulting from mutations at the same locus. For our linkage study, we utilized a large kindred with a high incidence of Paget's disease. The propositus in this family had polyostotic disease symptoms beginning at age 31, During the process of characterizing this family, four other family members were diagnosed with Paget's disease. One of the proband's siblings was asymptomatic but had high normal serum alkaline phosphatase levels; Paget's disease was identified only after bone scanning (at age 50), This implies that the predisposition gene does not consistently cause severe disease and raises a question concerning the mechanism of predisposition: Does the predisposition gene affect the age of onset and/or the severity of disease? To further explore this question, two individuals from this kindred, under age 30 and carrying the affected haplotype, were evaluated for early onset Paget's disease. No evidence of disease was observed after thorough evaluation. This implies that the age of onset is highly variable for this locus, indicating variable expression of disease in individuals carrying the same mutation. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78284 USA. St Johns Hlth Ctr, John Wayne Canc Inst, Santa Monica, CA USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Vet Adm Hosp, Dept Med, San Antonio, TX USA. RP Leach, RJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR08482, AR44919] NR 14 TC 12 Z9 12 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 OCT PY 1999 VL 14 SU 2 BP 17 EP 20 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240AZ UT WOS:000082804600004 PM 10510208 ER PT J AU Ruskin, JN AF Ruskin, JN TI Idiopathic ventricular fibrillation: Is there a role for electrophysiologic-guided antiarrhythmic drug therapy? SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Ruskin, JN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 32 Fruit St, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 1999 VL 10 IS 10 BP 1313 EP 1315 DI 10.1111/j.1540-8167.1999.tb00184.x PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241MC UT WOS:000082886200002 PM 10515553 ER PT J AU Keane, D Ruskin, JN AF Keane, D Ruskin, JN TI Mechanism of induction of atrial flutter SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Cardiac Unit, Boston, MA 02114 USA. RP Keane, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Cardiac Unit, 32 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 1999 VL 10 IS 10 BP 1432 EP 1432 DI 10.1111/j.1540-8167.1999.tb00201.x PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 241MC UT WOS:000082886200019 PM 10515570 ER PT J AU Espaillat, A To, K Perlman, EM AF Espaillat, A To, K Perlman, EM TI Effect of collagen implants in the reduction of high astigmatism induced by penetrating keratoplasty SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID SURGICAL-CORRECTION; RELAXING INCISIONS; KERATOTOMY AB Purpose: To evaluate the insertion of EagleVision(R) collagen plugs as spacers between corneal relaxing incisions to correct significant residual astigmatism after penetrating keratoplasty (PKP). Setting: Ambulatory Clinic of the Department of Ophthalmology, Rhode Island Hospital, and Rhode Island Eye institute, Providence, Rhode Island, USA. Methods: This study comprised 8 patients meeting the following criteria: had previous PKP, had at least 5.0 diopters of residual keratometric astigmatism with all the sutures removed, were free from eye infection, and were at least 21 years old. Ali 8 patients had unilateral high astigmatism after PKP. Four eyes were randomly assigned to the control group of astigmatic keratectomy (AK) incisions without the collagen implants and 4 eyes to the experimental group of AK incisions with collagen implants. Results: Best corrected visual acuity 1 day, 3 weeks, and 1, 2, and 6 months after AK showed decreased astigmatism in all the patients who had the relaxing incisions. The amount of astigmatism was lower in patients who received AK incisions with collagen implants (P < .28). Minimal adverse effects were noted. Conclusion: Implanting a biocompatible material into AK incisions to correct post-PKP astigmatism appears to be safe and may enhance astigmatic correction. (C) 1999 ASCRS and ESCRS. C1 Brown Univ, Rhode Isl Hosp, Dept Ophthalmol, Sch Med, Providence, RI 02903 USA. RP Espaillat, A (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CATARACT REFRACTIVE SURGERY PI FAIRFAX PA 4000 LEGATO RD, SUITE 850, FAIRFAX, VA 22030 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD OCT PY 1999 VL 25 IS 10 BP 1336 EP 1340 DI 10.1016/S0886-3350(99)00210-2 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 240QT UT WOS:000082837200012 PM 10511931 ER PT J AU Mikhailenko, I Considine, W Argraves, KM Loukinov, D Hyman, BT Strickland, DK AF Mikhailenko, I Considine, W Argraves, KM Loukinov, D Hyman, BT Strickland, DK TI Functional domains of the very low density lipoprotein receptor: molecular analysis of ligand binding and acid-dependent ligand dissociation mechanisms SO JOURNAL OF CELL SCIENCE LA English DT Article DE VLDL receptor; urokinase; RAP; endocytosis; immunofluorescence ID APOLIPOPROTEIN-E RECEPTOR; PROTEIN ALPHA-2-MACROGLOBULIN RECEPTOR; CELLULAR INTERNALIZATION; FAMILIAL HYPERCHOLESTEROLEMIA; MEDIATES ENDOCYTOSIS; VLDL RECEPTOR; EXPRESSION; GENE; DEGRADATION; REPEATS AB The very low density lipoprotein (VLDL) receptor is closely related in structure to the low density lipoprotein receptor. The ectodomain of these endocytic receptors is composed of modules which include clusters of cysteine-rich class A repeats, epidermal growth factor (EGF)-like repeats, tyrosine-tryptophan-threonine-aspartic acid (YWTD) repeats and an O-linked sugar domain. To identify important functional regions within the ectodomain of the VLDL receptor, we produced a mutant receptor in which the EGF, YWTD and O-linked sugar domains were deleted. Cells transfected with the mutant receptor were able to bind and internalize I-125-labeled receptor associated protein (RAP), In contrast to the wild-type receptor, however, RAP did not dissociate from the mutant receptor and consequently was not degraded. Immunofluoresence data indicated that once bound to the mutant receptor, fluorescent-labeled RAP co-localized with markers of the endosomal pathway, whereas, in cells expressing the wildtype receptor, RAP fluorescence co-localized with lysosomal markers. Thus this deleted region is responsible for ligand uncoupling within the endosomes, To identify regions responsible for ligand recognition, soluble receptor fragments containing the eight cysteine-rich class A repeats were produced. I-125-RAP and I-125-labeled urokinase-type plasminogen activator:plasminogen activator inhibitor type I(uPA:PAI-1) complexes bound to the soluble fragment with K-D,K-app values of 0.3 and 14 nM, respectively, Deletion analysis demonstrate that high affinity RAP binding requires the first four cysteine-rich class A repeats (L1-4) in the VLDL receptor while the second repeat (L2) appears responsible for binding uPA:PAI-1 complexes. Together, these results confirm that ligand uncoupling occurs via an allosteric-type mechanism in which pH induced changes in the EGF and/or YWTD repeats alter the ligand binding properties at the amino-terminal portion of the molecule. C1 Amer Red Cross, Holland Lab, Dept Vasc Biol, Rockville, MD 20855 USA. Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Boston, MA 02129 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, Rockville, MD 20855 USA. EM strickla@usa.redcross.org FU NHLBI NIH HHS [P01HL5710, HL50784] NR 45 TC 43 Z9 46 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD OCT PY 1999 VL 112 IS 19 BP 3269 EP 3281 PG 13 WC Cell Biology SC Cell Biology GA 250JK UT WOS:000083385100010 PM 10504332 ER PT J AU Echtermeyer, F Baciu, PC Saoncella, S Ge, YM Goetinck, PF AF Echtermeyer, F Baciu, PC Saoncella, S Ge, YM Goetinck, PF TI Syndecan-4 core protein is sufficient for the assembly of focal adhesions and actin stress fibers SO JOURNAL OF CELL SCIENCE LA English DT Article DE syndecan; heparan sulfate proteoglycan; cell attachment; actin cytoskeleton; Chinese hamster ovary cell ID HEPARAN-SULFATE PROTEOGLYCAN; OVARY CELL MUTANTS; KINASE-C; EXTRACELLULAR-MATRIX; INTEGRIN; BINDING; LAMININ; ORGANIZATION; BIOSYNTHESIS; CYTOSKELETAL AB The formation of focal adhesions and actin stress fibers on fibronectin is dependent on signaling through beta 1 integrins and the heparan sulfate proteoglycan syndecan-4, and we have analyzed the requirement of the glycosamimoglycan chains of syndecan-4 during these events. Chinese hamster ovary cells with mutations in key enzymes of the glycanation process do not synthesize glycosaminoglycan chains and are unable to assemble actin stress fibers and focal contacts when cultured on fibronectin. Transfection of the mutant cells with a cDNA that encodes the core protein of chicken syndecan-4 leads to the production of unglycanated core protein. The overexpression of syndecan-4 core protein in these mutant cells increases cell spreading and is sufficient for these cells to assemble actin stress fibers and focal adhesions similar to wild-type cells seeded on fibronectin and vitronectin matrices. Syndecan-4 core protein colocalizes to focal contacts in mutant cells that have been transfected with the syndecan-4 core protein cDNA. These data indicate an essential role for the core protein of syndecan-4 in the generation of signals leading to actin stress fiber and focal contact assembly. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Goetinck, PF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [HD 37490, HD-22016] NR 39 TC 74 Z9 75 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 OCT PY 1999 VL 112 IS 20 BP 3433 EP 3441 PG 9 WC Cell Biology SC Cell Biology GA 257NC UT WOS:000083787200004 PM 10504292 ER PT J AU Jones, AT Spiro, DJ Kirchhausen, T Melancon, P Wessling-Resnick, M AF Jones, AT Spiro, DJ Kirchhausen, T Melancon, P Wessling-Resnick, M TI Studies on the inhibition of endosome fusion by GTP gamma S-bound ARF SO JOURNAL OF CELL SCIENCE LA English DT Article DE ADP-ribosylation factor; endosome fusion; coat protein ID ADP-RIBOSYLATION FACTOR; INTRA-GOLGI TRANSPORT; COATED VESICLES; PHOSPHOLIPASE-D; IN-VITRO; PROTEIN COMPLEX; TRANSFERRIN RECEPTOR; DEPENDENT FORMATION; ADAPTER COMPLEX; BINDING PROTEIN AB Using a cell free assay, we have previously shown that ARF is not required for endosome fusion but that inhibition of fusion by GTP gamma S is dependent on a cytosolic pool of ARFs, Since ARF is proposed to function in intracellular membrane traffic by promoting vesicle biogenesis, and components of clathrin- and COP-coated vesicles have been localized on endosomal structures, we investigated whether ARF-mediated inhibition of early endosome fusion involves the recruitment or irreversible association of these proteins onto endosomal membranes. We now report that depletion of components of clathrin coated vesicles (clathrin, AP-1 and AP-2) or COPI vesicles (beta COP) does not affect the capacity of GTP gamma S-activated ARF to inhibit endosome fusion, Inhibition of fusion by activated ARF is also independent of endosomal acidification since assays performed in the presence of the vacuolar ATPase inhibitor bafilomycin A1 are equally sensitive to GTP gamma S-bound ARF. Finally, in contrast to reported effects on lysosomes, we demonstrate that ARF-GTP gamma S does not induce endosomal lysis. These combined data argue that sequestration of known coat proteins to membranes by activated ARF is not involved in the inhibition of early endosome fusion and that its capacity to inhibit fusion involves other specific interactions with the endosome surface. These results contrast with the mechanistic action of ARF on intra-Golgi transport and nuclear envelope assembly. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Cell Biol, Boston, MA 02115 USA. Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada. RP Wessling-Resnick, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RI Jones, Arwyn/E-4787-2010; OI Jones, Arwyn/0000-0003-2781-8905; Melancon, Paul/0000-0002-8085-3032 NR 63 TC 8 Z9 8 U1 0 U2 3 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 OCT PY 1999 VL 112 IS 20 BP 3477 EP 3485 PG 9 WC Cell Biology SC Cell Biology GA 257NC UT WOS:000083787200008 PM 10504296 ER PT J AU Foley, JE Marks, SL Munson, L Melli, A Dewhirst, FE Yu, SL Shen, ZL Fox, JG AF Foley, JE Marks, SL Munson, L Melli, A Dewhirst, FE Yu, SL Shen, ZL Fox, JG TI Isolation of Helicobacter canis from a colony of Bengal cats with endemic diarrhea SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; CHRONIC ACTIVE HEPATITIS; SP-NOV; BACTERIAL-INFECTION; PYLORI INFECTION; HOMOSEXUAL MEN; MICE; ANIMALS; CAMPYLOBACTERS; TRANSMISSION AB On the basis of biochemical, phenotypic, and 16S rRNA analyses, Helicobacter canis was isolated from Bengal cats with and,without chronic diarrhea, Because the cats were coinfected with other potential pathogens, including Campylobacter helveticus, and because H, canis was isolated from nondiarrheic cats, the causal role of H. canis in producing the diarrhea could not be proven. Histologically, the colons of the four affected cats were characterized by mild to moderate neutrophilic, plasmacytic, and histocytic infiltrates in the lamina propria. Rare crypt abscesses were also noted for three cats but were a more prominent feature of the colonic lesions noted for the fourth cat. This is the first observation of H, canis in cats and raises the possibility that H. canis, like H. hepaticus and H. bills in mice, can cause inflammation of the colon, particularly in hosts with immune dysregulation. Further studies are needed to determine the importance of H. canis as a primary enteric pathogen in cats and the role of cats in the possible zoonotic spread of H. canis to humans. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Univ Calif Davis, Sch Vet Med, Dept Med & Epidemiol, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Ctr Compan Anim Hlth, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. Forsyth Inst, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Room 825C, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01 CA067529, R01CA67529]; NCRR NIH HHS [RR07036, T32 RR007036]; NIDCR NIH HHS [R01 DE010374]; NIDDK NIH HHS [R01 DK052413, R01DK52413] NR 46 TC 42 Z9 43 U1 0 U2 3 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 OCT PY 1999 VL 37 IS 10 BP 3271 EP 3275 PG 5 WC Microbiology SC Microbiology GA 237FN UT WOS:000082644800034 PM 10488191 ER PT J AU Glantz, MJ LaFollette, S Jaeckle, KA Shapiro, W Swinnen, L Rozental, JR Phuphanich, S Rogers, LR Gutheil, JC Batchelor, T Lyter, D Chamberlain, M Maria, BL Schiffer, C Bashir, R Thomas, D Cowens, W Howell, SB AF Glantz, MJ LaFollette, S Jaeckle, KA Shapiro, W Swinnen, L Rozental, JR Phuphanich, S Rogers, LR Gutheil, JC Batchelor, T Lyter, D Chamberlain, M Maria, BL Schiffer, C Bashir, R Thomas, D Cowens, W Howell, SB TI Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; INVOLVEMENT; COMPLICATIONS; PROPHYLAXIS; METASTASES; THERAPY AB Purpose: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chi ran Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days. Patients and Methods: Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks ar free ara-C 50 mg twice a week for 1 month. patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 5-week cycle. Results: The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P = .006). All of the patients on the DepoCyt arm but only 53% of those on the aro-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trended in fervor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P > .05). DepoCyt treatment war associated with an improved mean change in Karnofsky performance score at the end of induction (P = .041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease. Conclusion: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative ta that produced by free ara-C injected twice a week. (C) 1999 by American Society of Clinical Oncology. C1 Brown Univ, Sch Med, Dept Med, Providence, RI 02912 USA. Univ Chicago, Dept Hematol Oncol, Chicago, IL 60637 USA. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. Illinois Masonic Canc Ctr, Chicago, IL USA. Rush Canc Inst, Chicago, IL USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. H Lee Moffit Canc Ctr & Res Inst, Dept Neurooncol, Tampa, FL USA. Wayne State Univ, Dept Neurol, Detroit, MI USA. Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA. Sidney Kimmel Canc Ctr, La Jolla, CA 92093 USA. Univ Florida, Ctr Canc, Gainesville, FL USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. Univ Nebraska, Ctr Canc, Omaha, NE 68182 USA. Chiron Corp, Emeryville, CA 94608 USA. Skye Pharma Inc, San Diego, CA USA. Univ Calif San Diego, Ctr Canc, Dept Med 0058, La Jolla, CA 92093 USA. RP Howell, SB (reprint author), Univ Calif San Diego, Ctr Canc, Dept Med 0058, La Jolla, CA 92093 USA. NR 18 TC 224 Z9 232 U1 2 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 OCT PY 1999 VL 17 IS 10 BP 3110 EP 3116 PG 7 WC Oncology SC Oncology GA 241YQ UT WOS:000082911800014 PM 10506606 ER PT J AU Friedberg, JW Neuberg, D Stone, RM Alyea, E Jallow, H LaCasce, A Mauch, PM Gribben, JG Ritz, J Nadler, LM Soiffer, RJ Freedman, AS AF Friedberg, JW Neuberg, D Stone, RM Alyea, E Jallow, H LaCasce, A Mauch, PM Gribben, JG Ritz, J Nadler, LM Soiffer, RJ Freedman, AS TI Outcome in patients with myelodysplastic syndrome after autologous bone marrow transplantation for non-Hodgkin's lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; FOLLICULAR LYMPHOMA; LATE COMPLICATION; TELOMERE LENGTH; POOR-PROGNOSIS; BREAST-CANCER; SELF-RENEWAL; THERAPY; SECONDARY AB Purpose: The absolute risk of myelodysplastic syndrome (MDS) after autologous bone marrow transplant (ABMT) for non-Hodgkin's lymphoma (NHL) exceeds 5% in several reported series. We report the outcome of a large cohort of patients who developed MDS after ABMT for NHL. Patients and Methods: Between December 1982 and December 1997, 552 patients underwent ABMT for NHL, with a uniform ablative regimen of cyclophosphamide and total body irradiation followed by reinfusion of obtained marrow purged with monoclonal antibodies, MDS was strictly defined, using the French-American-British classification system, as requiring bone marrow dysplasia in at least two cell lines, with associated unexplained persistent cytopenias. Results: Forty-one patients developed MDS at a median of 47 months after ABMT, The incidence of MDS was 7.4%, and actuarial incidence at 10 years is 19.8%, without evidence of a plateau, Patients who developed MDS received significantly fewer numbers of cells reinfused per kilogram at ABMT (P = .0003). Karyotypes were performed on bane marrow samples of 33 patients, and 29 patients had either del(7) or complex abnormalities. The median survival from diagnosis of MDS was 9.4 months. The international prognostic Scoring System for MDS failed to predict outcome in these patients. Thirteen patients underwent allogeneic BMT as treatment far MDS, and all have died of BMT-related complications (11 patients) or relapse (two patients), with a median survival of only 1.8 months. Conclusion: tong-term follow-vp demonstrates a high incidence of MDS after ABMT for NHL. The prognosis for these patients is uniformly poor, and novel treatment strategies are needed for this fatal disorder. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996] NR 54 TC 120 Z9 122 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 OCT PY 1999 VL 17 IS 10 BP 3128 EP 3135 PG 8 WC Oncology SC Oncology GA 241YQ UT WOS:000082911800017 PM 10506609 ER PT J AU Baldini, EH Goldberg, J Jenner, C Manola, JB Demetri, GD Fletcher, CDM Singer, S AF Baldini, EH Goldberg, J Jenner, C Manola, JB Demetri, GD Fletcher, CDM Singer, S TI Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAR 20-25, 1995 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol ID ADJUVANT RADIATION-THERAPY; LOCAL RECURRENCE; POSTOPERATIVE RADIOTHERAPY; CONSERVATIVE SURGERY; PROGNOSTIC FACTORS; LIMB SALVAGE; SURVIVAL; IRRADIATION; BRACHYTHERAPY; RESECTION AB Purpose: To define the rate of local recurrence (LR) and identify prognostic factors for LR for patients with soft tissue sarcoma (STS) treated with function-sparing surgery (FSS) without radiotherapy (RT). Patients and Methods: Between 1970 and 1994, 242 patients with STS of the trunk and extremity presented with primary localized disease, 74 of whom were treated with FSS without RT (31%). The median tumor size was 4 cm (range, 0.5 to 31 cm), There were 40 patients with grade 1 tumors and 34 with grade 2 and 3 tumors. Median follow-up was 126 months. Results: The 10-year actuarial local control rate was 93% +/- 4%, Resection margin status was ct significant predictor for LR. patients with closest histologic resection margins of less than 1 cm herd a 10-year local control rate of 87% +/- 6% compared with 100% for patients with closest histologic resection margins of greater than or equal to 1 cm (P = .04). There was no significant association between LR and tumor grade, size, site (truncal v extremity), or depth (superficial v deep). For all patients, the 10-year actuarial survival rate was 73% +/- 6%. Conclusion: The 7% LR rate after treatment of STS with FSS without RT reported herein is comparable to published rates following treatment where adjuvant RT is used. These results suggest there may be a select subset of patients with STS in whom carefully per formed FSS may serve as definitive therapy and in whom adjuvant RT may not he necessary. However, further study is needed to carefully define this subset of patients and to identify the optimal surgical approach and technique for patients treated without RT. (C) 1999 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Surg Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Pathol, Boston, MA 02115 USA. RP Singer, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. NR 39 TC 93 Z9 100 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1999 VL 17 IS 10 BP 3252 EP 3259 PG 8 WC Oncology SC Oncology GA 241YQ UT WOS:000082911800035 PM 10506627 ER PT J AU Cutler, C Gragoudas, ES AF Cutler, C Gragoudas, ES TI Choroidal metastases - Case 2: Lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Cutler, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. NR 4 TC 2 Z9 2 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 OCT PY 1999 VL 17 IS 10 BP 3358 EP 3359 PG 2 WC Oncology SC Oncology GA 241YQ UT WOS:000082911800047 PM 10506639 ER PT J AU Stilley, CS Miller, DJ Gayowski, T Marino, IR AF Stilley, CS Miller, DJ Gayowski, T Marino, IR TI Psychological characteristics of candidates for liver transplantation: Differences according to history of substance abuse and UNOS listing SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID HEART-TRANSPLANTATION; PSYCHOSOCIAL PREDICTORS; SURVIVAL; OPTIMISM; RECIPIENTS; DISTRESS; DISEASE; HEALTH AB Liver transplantation for patients with a history of substance abuse remains controversial. Resumption of heavy alcohol use postoperatively is a threat to long-term survival, but recidivism among transplanted alcoholics is reportedly low. An argument against psychological evaluation prior to transplantation revolves around the speculation that candidates will attempt to portray themselves as more desirable prior to listing with UNOS (United Network for Organ Sharing). This study measured psychological distress. coping styles, optimism, selected personality features, and perception of family environment among 73 U.S. military veterans who were candidates for liver transplantation. Candidates with positive histories of substance abuse revealed significantly more distress, less adaptive coping styles, and more character pathology than their counterparts. The only significant difference according to UNOS listing was on one measure of family environment. Results support preoperative psychological assessment and intervention on a more extensive level for substance abusers and raise questions for future research. (C) 1999 John Wiley & Sons. Inc. C1 Univ Pittsburgh, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Stilley, CS (reprint author), Univ Pittsburgh, 460 Victoria bldg,3500 Victoria St, Pittsburgh, PA 15261 USA. NR 34 TC 7 Z9 7 U1 2 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD OCT PY 1999 VL 55 IS 10 BP 1287 EP 1297 DI 10.1002/(SICI)1097-4679(199910)55:10<1287::AID-JCLP9>3.0.CO;2-Z PG 11 WC Psychology, Clinical SC Psychology GA 240ZW UT WOS:000082857500009 PM 11045777 ER PT J AU Tollefson, GD Dellva, MA Mattler, CA Kane, JM Wirshing, DA Kinon, BJ AF Tollefson, GD Dellva, MA Mattler, CA Kane, JM Wirshing, DA Kinon, BJ CA Collaborative Crossover Study Grp TI Controlled, double-blind investigation of the clozapine discontinuation symptoms with conversion to either olanzapine or placebo SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ATYPICAL ANTIPSYCHOTIC-DRUGS; DOPAMINE-RECEPTORS; WITHDRAWAL; RISPERIDONE; PSYCHOSIS; RELAPSE; SEROTONIN; SUPERSENSITIVITY; SCHIZOPHRENIA; NEUROLEPTICS AB The abrupt appearance of clozapine discontinuation symptoms represents a particularly unique situation that has not been characterized in a double-blind, placebo-controlled trial. A randomized, double-blind comparison of placebo (N = 53) and olanzapine 10 mg (N = 53) for 3 to 5 days following the abrupt discontinuation of clozapine (less than or equal to 300 mg/day) was carried out. Subjects were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale of Severity, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Mini-Mental State Evaluation. Subsequently both groups received open-label olanzapine (10-25 mg/day) for an additional 9 weeks. Statistically significantly more placebo-treated (24.5%) than olanzapine-treated (7.5%) patients experienced clozapine discontinuation symptoms (p = 0.017). Core symptoms included delusions, hallucinations, hostility, and paranoid reaction and translated into a significantly higher worsening from baseline on the PANSS total, PANSS General Psychopathology subscale, and MADRS among subjects randomly assigned to receive placebo. After open-label treatment with olanzapine for 9 weeks, both groups were clinically stable, suggesting that the discontinuation symptoms were transient. However, subjects who had been randomly assigned to the 3- to 5-day placebo discontinuation segment achieved somewhat less global clinical improvement. Although a pharmacologic interpretation is speculative, evidence of a clozapine discontinuation syndrome was apparent. In most cases, the direct substitution of a pharmacologically similar agent (olanzapine) prevented the syndrome. Clozapine discontinuation or noncompliance should be considered in the differential assessment of an acutely emergent psychosis. The possibility that subjects who experience a clozapine discontinuation syndrome may take longer or are less likely to clinically restabilize warrants further investigation. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Psychopharmacol Div, Indianapolis, IN 46285 USA. Long Isl Jewish Med Ctr, Albert Einstein Coll Med, Glen Oaks, NY USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Tollefson, GD (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Psychopharmacol Div, Drop Code 0538, Indianapolis, IN 46285 USA. NR 51 TC 37 Z9 38 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 1999 VL 19 IS 5 BP 435 EP 443 DI 10.1097/00004714-199910000-00007 PG 9 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 238EP UT WOS:000082698200007 PM 10505585 ER PT J AU Connolly, MB Crits-Christoph, P Shelton, RC Hollon, S Kurtz, J Barber, JP Butler, SF Baker, S Thase, ME AF Connolly, MB Crits-Christoph, P Shelton, RC Hollon, S Kurtz, J Barber, JP Butler, SF Baker, S Thase, ME TI The reliability and validity of a measure of self-understanding of interpersonal patterns SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article ID TERM DYNAMIC PSYCHOTHERAPY; THERAPEUTIC FACTORS; PSYCHOLOGICAL MINDEDNESS; PSYCHOMETRIC PROPERTIES; INVENTORY; PERCEPTIONS; INPATIENT; ANXIETY AB Change in self-understanding of maladaptive interpersonal patterns has been an important mechanism of symptom change in theories of dynamic psychotherapy and has been specified as an important treatment outcome by psychotherapy clients. The current investigation evaluated the reliability and validity of a new self-report measure of Self-Understanding of Interpersonal patterns (SUIP). The measure was administered to 3 clinical samples and a student sample. The measure demonstrated good internal consistency, test-retest reliability, and discriminant validity. The SUIP further demonstrated convergent validity with measures of analytical and self-improving personality traits in a clinical sample. Finally there was significantly greater change in self-understanding in a dynamic psychotherapy as compared with a medication treatment condition, despite comparable symptom change across both treatment conditions. C1 Univ Penn, Med Ctr, Ctr Psychotherapy Res, Dept Psychiat, Philadelphia, PA 19104 USA. Villanova Univ, Dept Psychol, Villanova, PA 19085 USA. Vanderbilt Univ, Dept Psychiat, Nashville, TN 37240 USA. Innovat Training Syst Inc, Newton, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. RP Connolly, MB (reprint author), Univ Penn, Med Ctr, Ctr Psychotherapy Res, Dept Psychiat, 3600 Market St,7th Floor, Philadelphia, PA 19104 USA. OI Butler, Stephen/0000-0002-6132-5883; barber, jacques/0000-0002-8762-2595 NR 47 TC 9 Z9 9 U1 3 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD OCT PY 1999 VL 46 IS 4 BP 472 EP 482 PG 11 WC Psychology, Educational; Psychology, Applied SC Psychology GA 250FW UT WOS:000083379200005 ER PT J AU LeBlanc, ES Laws, A AF LeBlanc, ES Laws, A TI Benefits and risks of third-generation oral contraceptives SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE contraceptives, oral; desogestrel; thromboembolism; myocardial infarction; cerebrovascular disorders ID ACUTE MYOCARDIAL-INFARCTION; ACTIVATED PROTEIN-C; VENOUS THROMBOEMBOLISM; YOUNG-WOMEN; ETHINYL ESTRADIOL; NORGESTIMATE; EFFICACY; STROKE; MULTICENTER; THROMBOSIS AB OBJECTIVE: To evaluate the risks and benefits of third-generation oral contraceptives. DATA SOURCES: A MEDLINE search was done for English language articles published from 1985 through 1998 relating to the side-effect profile of third-generation oral contraceptives or their association with cardiovascular or thromboembolic disease, All articles containing original data were included. DATA SYNTHESIS: The risk of venous thromboembolism appears to be 1.5- to 2.7-fold greater in users of third-generation, compared with second-generation, oral contraceptives. Compared with nonusers, women who use third-generation oral contraceptives may have a 4.8- to 9.4-fold greater risk of venous thromboembolism. Users of third-generation oral contraceptives do not appear to have an increased risk of myocardial infarction compared with nonusers and may have risk of myocardial infarction of 0.26 to 0.7 compared with second-generation users. Whether third-generation oral contraceptives are associated with a decreased stroke risk is still not clear. CONCLUSIONS: Although third-generation oral contraceptives most likely increase a user's risk of venous thromboembolism, their improved side-effect profile and their possible decreased association with myocardial infarction and stroke may make them a useful new class of oral contraceptives for most women except those at increased risk of venous thrombosis. C1 Portland Vet Affairs Med Ctr, Dept Internal Med, Portland, OR USA. RP LeBlanc, ES (reprint author), Stanford Med Grp, 900 Blake Wilbur Dr,W2080, Palo Alto, CA 94304 USA. NR 63 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 1999 VL 14 IS 10 BP 625 EP 632 DI 10.1046/j.1525-1497.1999.08108.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 248YD UT WOS:000083303600007 PM 10571709 ER PT J AU Ohashi, Y Iwata, S Kamiguchi, K Morimoto, C AF Ohashi, Y Iwata, S Kamiguchi, K Morimoto, C TI Tyrosine phosphorylation of Crk-associated substrate lymphocyte-type is a critical element in TCR- and beta(1) integrin-induced T lymphocyte migration SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOCAL ADHESION KINASE; IN-VIVO; DOCKING PROTEIN; CELL ACTIVATION; CROSS-LINKING; CD4 CELLS; C-CRK; CAS-L; BINDING; FIBRONECTIN AB Crk-associated substrate (Cas) lymphocyte-type (Cas-L) is a 105-kDa cytoplasmic protein consisting of Src homology-3 domain and multiple YXXP motifs (substrate domain). Our previous studies showed that Cas-L is tyrosine-phosphorylated following the ligation of TCR and beta(1) integrins in T lymphocytes. Here we show that Cas-L is involved in T cell motility following the ligation of TCR and beta(1) integrin. Peripheral T lymphocytes showed a marked increase of migration on fibronectin (FN) after the ligation of TCR, In contrast, the migrating Jurkat cells, in which Cas-L was marginally expressed, were less than one-tenth in number on the same condition. Transfection of wild-type Cas-L into Jurkat cells resulted in restoring CD3 plus FN-induced cell migration. Furthermore, following the ligation of beta(1) integrin alone, the Cas-L transfectants significantly migrated better than the vector control. Mutational analysis of Cas-L revealed that the substrate domain is required for both FN- and CD3-induced tyrosine phosphorylation of Cas-L and cell migration caused by FN alone and CD3 plus FN, In contrast, the Src homology-3 domain is required only for the FN-induced tyrosine phosphorylation of Cas-L and cell migration, but not for CD3-induced tyrosine phosphorylation or CD3 plus FN-induced cell migration. These data strongly suggest that Cas-L is a key molecule in T cell migration induced by the ligation of CD3 and beta(1) integrins and that tyrosine phosphorylation of Cas-L is essential for T cell migration. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Tokyo, Japan. Univ Tokyo, Inst Med Sci, AIDS Res Ctr, Tokyo, Japan. RP Iwata, S (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI29530]; NIAMS NIH HHS [AR33713] NR 46 TC 43 Z9 44 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1999 VL 163 IS 7 BP 3727 EP 3734 PG 8 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900022 PM 10490968 ER PT J AU Haller, GW Esnaola, N Yamada, K Wu, A Shimizu, A Hansen, A Ferrara, VR Allison, KS Colvin, RB Sykes, M Sachs, DH AF Haller, GW Esnaola, N Yamada, K Wu, A Shimizu, A Hansen, A Ferrara, VR Allison, KS Colvin, RB Sykes, M Sachs, DH TI Thymic transplantation across an MHC class I barrier in swine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; RENAL-ALLOGRAFTS; T-CELLS; MONOCLONAL-ANTIBODIES; NEGATIVE SELECTION; POSITIVE SELECTION; TOLERANCE; GRAFTS; MICE AB Thymic tissue transplantation has been performed previously in adult mice to induce donor-specific tolerance across allogeneic and xenogeneic barriers. We have now attempted to extend this technique to a large animal preclinical model and describe here our initial studies of allogeneic thymic transplantation in miniature swine. Two miniature swine were thymectomized before thymic tissue transplantation, and two remained euthymic. Donor thymic tissue was harvested from SLA class I-mismatched juvenile pigs and placed into recipient sternocephalicus muscle, kidney capsule, and omentum, A 12-day course of cyclosporin A was started on the day of transplantation. Allogeneic thymic engraftment could only be achieved in euthymic and not in thymectomized miniature swine using this treatment regimen. Both nonthymectomized animals showed good graft development, with evidence of thymopoiesis, as indicated by positive CD1 and host-type SLA class I immunoperoxidase staining of immature graft-infiltrating cells, Both animals also demonstrated donor-specific T cell hyporesponsiveness, as measured by MLR and cell-mediated lympholysis. The thymic grafts continued to develop despite the appearance of high levels of anti-donor specific cytotoxic IgG Abs, Thus, thymic tissue transplanted across an SLA class I barrier can engraft and support host thymopoiesis in euthymic miniature swine. The presence of the host thymus was required for engraftment, These data support the potential of thymic transplantation as part of a regimen to induce donor-specific tolerance to xenogeneic organ grafts. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 41 TC 27 Z9 27 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 OCT 1 PY 1999 VL 163 IS 7 BP 3785 EP 3792 PG 8 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900030 PM 10490976 ER PT J AU Ahuja, SS Reddick, RL Sato, N Montalbo, E Kostecki, V Zhao, WG Dolan, MJ Melby, PC Ahuja, SK AF Ahuja, SS Reddick, RL Sato, N Montalbo, E Kostecki, V Zhao, WG Dolan, MJ Melby, PC Ahuja, SK TI Dendritic cell (DC)-based anti-infective strategies: DCs engineered to secrete IL-12 are a potent vaccine in a murine model of an intracellular infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; IN-VIVO; IMMUNE-RESPONSE; IFN-GAMMA; MYCOBACTERIAL INFECTION; VISCERAL LEISHMANIASIS; NAKED DNA; T-CELLS; INTERLEUKIN-12; DISEASES AB Infections with intracellular pathogens such as Leishmania donovani and Mycobacterium tuberculosis pose serious health problems worldwide. Effective vaccines for these pathogens are not available. Furthermore, despite optimal therapy, disease progression is often seen with several intracellular infections. For these reasons, we initiated studies to develop novel anti-infective vaccine and treatment strategies that couple the potent Ag-presenting capacity of dendritic cells (DC) with paracrine delivery of potent anti-infective cytokines such as IL-12 to local immune response sites. We tested this strategy in a murine model of visceral leishmaniasis, Adoptive transfer of DCs pulsed ex vivo with soluble L. donovani Ags (SLDA) to naive mice induced the Ag-specific production of IFN-gamma, and increased the percentage of activation markers on spleen lymphocytes. SLDA-pulsed DCs engineered by retroviral gene transfer techniques to secrete high levels of biologically active murine IL-12 augmented this immune response further. In several different vaccination and immunotherapy protocols, compared with sham-treated mice, animals receiving SLDA-pulsed DCs either before or following infection had 1-3 log lower parasite burdens, and this protection was associated with a pronounced enhancement in the parasite-specific IFN-gamma response, The augmentation of this protection by IL-12-engineered DCs was striking. First, live parasites were not detected in the liver of mice vaccinated with IL-12-transduced, SLDA-pulsed DCs, Second, this parasitological response was associated with a nearly normal liver histology, In contrast, parasites and granulomas were found in mice vaccinated with SLDA-pulsed, nontransduced DCs. Collectively, these studies provide the rationale for the development of potent DC-based immunotherapies. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, Dept Med, Infect Dis Serv, Lackland AFB, TX 78236 USA. RP Ahuja, SS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAID NIH HHS [AI43279] NR 55 TC 100 Z9 107 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 OCT 1 PY 1999 VL 163 IS 7 BP 3890 EP 3897 PG 8 WC Immunology SC Immunology GA 238ZP UT WOS:000082744900043 PM 10490989 ER PT J AU Brown, AJL Gunthard, HF Wong, JK D'Aquila, RT Johnson, VA Kuritzkes, DR Richman, DD AF Brown, AJL Gunthard, HF Wong, JK D'Aquila, RT Johnson, VA Kuritzkes, DR Richman, DD TI Sequence clusters in human immunodeficiency virus type 1 reverse transcriptase are associated with subsequent virological response to antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 2nd International Workshop on HIV Drug Resistance and Treatment Strategies CY JUN 24-27, 1998 CL LAKE MAGGIORE, ITALY ID HIV-1 INFECTION; PHENOTYPIC ASSOCIATIONS; RESISTANCE MUTATIONS; ZIDOVUDINE TREATMENT; PROTEASE INHIBITORS; CLADISTIC-ANALYSIS; VIRAL RESISTANCE; DRUG-RESISTANCE; RESTRICTION; VARIANTS AB Many amino acid (aa) sites in reverse transcriptase (RT) have been implicated in resistance to nucleoside (NRTI) and nonnucleoside antiretrovirals, Interactions between these in response to combination therapy remain poorly understood. In a trial (ACTG 241) of zidovudine/didanosine (ddI) versus zidovudine/ddI/nevirapine in nucleoside-experienced patients, baseline sequence data from the RT coding region was analyzed from 55 individuals. Sequences were clustered by use of a parsimony method and the virological responses (ratio of baseline viral load to viral load after of therapy) for each cluster were analyzed at week 8 and week 48. Both clusters and genotype at aa 215 were significantly associated with virological response at both time points, whereas viral load showed a stronger association with sequence clusters. Sequence clusters identified one group of patients who never developed high-level resistance to NRTIs despite prior nucleoside exposure and poor suppression of viral replication. C1 Univ Edinburgh, Ctr HIV Res, Inst Cell Anim & Populat Biol, Edinburgh EH9 3JN, Midlothian, Scotland. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. San Diego Vet Affairs Med Ctr, La Jolla, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alabama, Dept Infect Dis, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO USA. Vet Affairs Med Ctr, Denver, CO USA. RP Brown, AJL (reprint author), Univ Edinburgh, Ctr HIV Res, Inst Cell Anim & Populat Biol, Waddington Bldg,W Mains Rd, Edinburgh EH9 3JN, Midlothian, Scotland. RI Leigh Brown, Andrew/F-3802-2010; gunthard, huldrych/F-1724-2011 OI gunthard, huldrych/0000-0002-1142-6723 FU FIC NIH HHS [TW00767]; NIAID NIH HHS [K11 AI01361, AI 27670] NR 32 TC 11 Z9 11 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 OCT PY 1999 VL 180 IS 4 BP 1043 EP 1049 DI 10.1086/315017 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 243WB UT WOS:000083019500015 PM 10479129 ER PT J AU Fedyk, ER Ryan, DH Ritterman, I Springer, TA AF Fedyk, ER Ryan, DH Ritterman, I Springer, TA TI Maturation decreases responsiveness of human bone marrow B lineage cells to stromal-derived factor 1 (SDF-1) SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemotaxis; CXCR4; B lymphopoiesis; affinity; B lymphocyte; pro B cell ID CHEMOKINE RECEPTOR CXCR4; HEMATOPOIETIC PROGENITOR CELLS; LYMPHOCYTE CHEMOATTRACTANT; FACTOR-I; LYMPHOPOIESIS; HIV-1; MIGRATION; LIGAND; LOCALIZATION; MYELOPOIESIS AB We compared the chemotactic responsiveness of different subsets of human B lineage cells to stromal derived factor-1 (SDF-1), High percentages (30-40% of input) of purified bone marrow progenitors including non-B lineage progenitors, pro-B cells, and pre-B cells migrated to SDF-1 alpha, demonstrating that SDF-1 is an efficacious chemoattractant of these cells, Pro-B cells responded optimally to a lower concentration of SDF-1 than other subsets, demonstrating that SDF-I is a more potent chemoattractant of this subset. A lower percentage (10-15% of input) of mature B lymphocytes migrated to SDF-1 alpha than pro-B cells, demonstrating that responsiveness of B lineage cells to SDF-1 decreases during differentiation. Inhibition by anti-CXCR4 mAb demonstrated that migration of B lineage cells to SDF-1 was completely dependent on CXC chemokine receptor-P (CXCR4). Mature B cells expressed higher levels of CXCR4 receptors than uncommitted progenitors and pro-B cells, despite differences in responsiveness to SDF-1, CXCR4 receptors expressed by unresponsive and SDF-1-responsive B cells bound SDF-1 alpha with similar affinities (K-D = 1.7-3.3 X 10(-9) M), Therefore, elements downstream from CXCR4 appear to regulate responsiveness of B cells to SDF-1, We speculate that SDF-1 and CXCR4 direct migration of progenitor cells in microenvironments that promote B lymphopoiesis. C1 Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA. RP Springer, TA (reprint author), Ctr Blood Res, Dept Pathol, 200 Longwood Ave,Room 251, Boston, MA 02115 USA. FU NCI NIH HHS [CA69502]; NHLBI NIH HHS [HL 48675] NR 25 TC 49 Z9 50 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 1999 VL 66 IS 4 BP 667 EP 673 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 245ZM UT WOS:000083138700020 PM 10534124 ER PT J AU van Orsouw, NJ Dhanda, RK Elhaji, Y Narod, SA Li, FP Eng, C Vijg, J AF van Orsouw, NJ Dhanda, RK Elhaji, Y Narod, SA Li, FP Eng, C Vijg, J TI A highly accurate, low cost test for BRCA1 mutations SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE genetic testing; two dimensional gene scanning (TDGS) ID OVARIAN-CANCER FAMILIES; BREAST-CANCER; GERMLINE MUTATIONS; GENETIC-HETEROGENEITY; COWDEN-DISEASE; RB1; PCR AB The hereditary breast and ovarian cancer syndrome is associated with a high frequency of BRCA1 mutations. However, the widespread use of BRCA1 testing has been limited to date by three principal concerns: the fear of loss of health and life insurance, the uncertain clinical value of a positive test result, and the current lack of an inexpensive and sensitive screening test for BRCA1 mutations. We have developed an inexpensive system for gene mutational scanning, based on a combination of extensive multiplex PCR amplification and two dimensional electrophoresis. The efficiency of this system, as a screening test for BRCA1 mutations, was evaluated in a panel of 60 samples from high risk women, 14 of which contained a previously identified mutation in BRCA1. All 14 mutations were identified, as well as an additional five that had previously escaped detection. In addition to the 19 mutations, a total of 15 different polymorphic variants were scored, most of which were recurring. All were confirmed by nucleotide sequencing. The cost of screening per sample was calculated to be approximately US$70 for the manual technique used in this study, and may be reduced to approximately US$10 with the introduction of commercially available PCR robotics and fluorescent imaging. Implementation of this method of mutation screening in the research and clinical setting should permit rapid accrual of quantitative data on genotype-phenotype associations for the evaluation of diagnostic testing. C1 Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA. Mosaic Technol Inc, Boston, MA 02215 USA. Princess Margaret Hosp, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Populat Sci, Boston, MA 02115 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. RP van Orsouw, NJ (reprint author), Canc Therapy & Res Ctr, Inst Drug Dev, 8122 Datapoint Dr,Suite 700, San Antonio, TX 78229 USA. OI Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [IP30AG13314-01] NR 23 TC 29 Z9 29 U1 0 U2 1 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 OCT PY 1999 VL 36 IS 10 BP 747 EP 753 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 244EG UT WOS:000083038400005 PM 10528853 ER PT J AU Su, XF Brower, G Janicki, JS Chen, YF Oparil, S Dell'Italia, LJ AF Su, XF Brower, G Janicki, JS Chen, YF Oparil, S Dell'Italia, LJ TI Differential expression of natriuretic peptides and their receptors in volume overload cardiac hypertrophy in the rat SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE natriuretic peptides; hypertrophy; receptors; heart failure ID CONGESTIVE-HEART-FAILURE; GENE-EXPRESSION; CLEARANCE RECEPTOR; FUNCTIONAL EXPRESSION; COMPLEMENTARY-DNA; SEQUENCE-ANALYSIS; TRANSGENIC MICE; MESSENGER-RNAS; BINDING-SITES; FISTULA RAT AB Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) upregulation are genetic markers for the chronic hypertrophic phenotype but also have important acute physiologic effects on salt and water balance and blood pressure control. The presence of a dual NP-system led us to hypothesize a differential expression of ANP and BNP in response to an acute hemodynamic stress of volume overload in the left ventricle (LV) and right ventricle (RV). Accordingly, we examined the temporal relationship between the RV and LV expression of ANP and BNP mRNA and NP receptor mRNA levels on days 1, 2, 3, and 7 after induction of aortocaval fistula in the rat. LV end-diastolic pressure was increased 1.5-fold by day 3 and 2.0-fold by day 7 compared to control (P<0.05). LV weight increased by day 7 compared to control (2.34 +/- 0.04 vs 3.07 +/- 0.10 mg/g, P<0.05) while RV weight did not change over the 7 days. There was a 7-fold increase of ANP mRNA in LV at day 1, which was sustained through day 7, while LV BNP mRNA levels did not differ from controls over the 7 days. In contrast, RV mRNA transcript levels for ANP and BNP were increased >2-fold by day 2 and this increase was sustained throughout 7 days, NP clearance receptor was decreased by 75% by day 7 in the LV but did not change in the RV. Thus, LV ANP mRNA levels increased before the onset of LV hypertrophy and RV BNP mRNA levels increased in the absence of RV hypertrophy. The disparate response of BNP and the NP clearance receptor transcript levels in the LV and RV may be related to differences in load and/or differential expression of the NP system in the LV and RV in response to acute haemodynamic stress. (C) 1999 Academic Press. C1 Univ Alabama, Dept Med, Div Cardiovasc Dis,Vasc Biol & Hypertens Program, Birmingham Vet Affairs Med Ctr,Univ Stn, Birmingham, AL 35294 USA. Auburn Univ, Coll Vet Med, Auburn, AL 36849 USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Dept Med, Div Cardiol, 834 MCLM,1918 Univ Blvd,1530 3rd Ave S, Birmingham, AL 35294 USA. EM dell'italia@physiology.uab.edu FU NHLBI NIH HHS [R01 HL54816, HL44195, HL50147] NR 43 TC 33 Z9 35 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD OCT PY 1999 VL 31 IS 10 BP 1927 EP 1936 DI 10.1006/jmcc.1999.1025 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 241LP UT WOS:000082885000013 PM 10525429 ER PT J AU Qiu, ZH Strickland, DK Hyman, BT Rebeck, GW AF Qiu, ZH Strickland, DK Hyman, BT Rebeck, GW TI alpha(2)-macroglobulin enhances the clearance of endogenous soluble beta-amyloid peptide via low-density lipoprotein receptor-related protein in cortical neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; apolipoprotein E; lactoferrin; immunoblot; amyloid precursor protein ID HUMAN CEREBROSPINAL-FLUID; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; ALPHA-2-MACROGLOBULIN RECEPTOR; PRECURSOR PROTEIN; FIBRIL FORMATION; MESSENGER-RNA; HUMAN BRAIN; DEGRADATION AB Apolipoprotein E and alpha(2)-macroglobulin (alpha 2M) are genetic risk factors for late-onset Alzheimer's disease, and both bind a cell surface receptor, the low-density lipoprotein receptor-related protein (LRP). To investigate the role of LRP on preventing the accumulation of beta-amyloid peptide (A beta), we examined the effects of alpha 2M on the clearance of endogenous A beta. Studies were performed in primary Tg2576 transgenic mouse cortical neuronal cultures expressing human mutant amyloid precursor protein (APP) 695, This system allowed us to follow endogenous A beta using immunoblots to detect monomeric forms of the peptide. A beta and APP levels were measured in conditioned media. We found that activated alpha 2M (alpha 2M*) substantially decreased soluble A beta levels and had no effect on secreted or full-length APP levels. Native alpha 2M, which is not a ligand for LRP, did not affect A beta levels. The receptor-associated protein, which inhibits interaction of all ligands with LRP in vitro, prevented alpha 2M*-induced decreases of soluble A beta levels. These data suggest that alpha 2M* affects soluble A beta clearance rather than A beta production. Further studies showed that similar A beta clearance via an LRP-mediated pathway was observed after treatment with another LRP ligand, lactoferrin. Taken together, these data demonstrate that alpha 2M* enhances the clearance of soluble A beta via LRP in cortical neurons. C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Amer Red Cross, Holland Lab, Rockville, MD USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG14473, AG12406] NR 38 TC 105 Z9 106 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1999 VL 73 IS 4 BP 1393 EP 1398 DI 10.1046/j.1471-4159.1999.0731393.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 236TZ UT WOS:000082616200007 PM 10501182 ER PT J AU Aarsland, D Larsen, JP Lim, NG Janvin, C Karlsen, K Tandberg, E Cummings, JL AF Aarsland, D Larsen, JP Lim, NG Janvin, C Karlsen, K Tandberg, E Cummings, JL TI Range of neuropsychiatric disturbances in patients with Parkinson's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE Parkinson's disease; psychiatric symptoms; neuropsychiatric inventory ID DEPRESSION; ANXIETY; APATHY AB Objectives-Disturbances of cognition and emotion are common in patients with Parkinson's disease. Most previous studies of psychopathology in Parkinson's disease have focused on a single psychiatric diagnosis or condition. The objective of this study was to describe the range of neuropsychiatric symptoms in a representative sample of patients with Parkinson's disease. Methods-The sample of 139 patients was drawn from an epidemiological study of Parkinson's disease in Rogaland county, Norway, and represented 93% of those who had survived during the 4 years since the initial assessment. The diagnosis of Parkinson's disease was based on published criteria. Neuropsychiatric symptoms were assessed using the neuropsychiatric inventory, a caregiver based structured interview, which assesses severity and frequency of 10 psychiatric symptoms present during the past month. Results-At least one psychiatric symptom was reported in 61% of the sample. The most common behaviours were depression (38%) and hallucinations (27%), and the least common symptoms were euphoria and disinhibition. The highest mean scores were found for depression, apathy, and hallucinations. Factor analysis showed that hallucinations, delusions, and irritability clustered into one factor, and apathy and anxiety constituted another factor. Psychiatric symptoms were more common among patients living in nursing homes compared with home dwelling patients, and correlated with stage of disease and cognitive impairment, but not with age or duration of disease. No relation to left or right sided parkinsonism was found. Conclusion-This study emphasises the importance of psychiatric symptoms in Parkinson's disease, which were present in most patients. Clinicians should focus on the emotional and cognitive disturbances in addition to the motor manifestations of the disease. C1 Rogaland Psychiat Hosp, Sect Geriatr Psychiat, N-4004 Stavanger, Norway. Cent Hosp Rogaland, Dept Neurol, Stavanger, Norway. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Behav Neurosci Sect, Los Angeles, CA 90073 USA. RP Aarsland, D (reprint author), Rogaland Psychiat Hosp, Sect Geriatr Psychiat, POB 1163, N-4004 Stavanger, Norway. OI Aarsland, Dag/0000-0001-6314-216X FU NIA NIH HHS [AG10123] NR 26 TC 327 Z9 338 U1 1 U2 14 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 OCT PY 1999 VL 67 IS 4 BP 492 EP 496 DI 10.1136/jnnp.67.4.492 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 238WY UT WOS:000082738800017 PM 10486397 ER PT J AU Mendola, JD Dale, AM Fischl, B Liu, AK Tootell, RBH AF Mendola, JD Dale, AM Fischl, B Liu, AK Tootell, RBH TI The representation of illusory and real contours in human cortical visual areas revealed by functional magnetic resonance imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuroimaging; shape perception; stereopsis; surface segmentation; visual cortex; lateral occipital ID HUMAN CEREBRAL-CORTEX; SUBJECTIVE CONTOURS; HUMAN BRAIN; SENSORY STIMULATION; PERCEPTION; MECHANISMS; FMRI; ORGANIZATION; BRIGHTNESS; SURFACES AB Illusory contours (perceived edges that exist in the absence of local stimulus borders) demonstrate that perception is an active process, creating features not present in the light patterns striking the retina. Illusory contours are thought to be processed using mechanisms that partially overlap with those of "real" contours, but questions about the neural substrate of these percepts remain. Here, we employed functional magnetic resonance imaging to obtain physiological signals from human visual cortex while subjects viewed different types of contours, both real and illusory. We sampled these signals independently from nine visual areas, each defined by retinotopic or other independent criteria. Using both within- and across-subject analysis, we found evidence for overlapping sites of processing; most areas responded to most types of contours. However, there were distinctive differences in the strength of activity across areas and contour types. Two types of illusory contours differed in the strength of activation of the retinotopic areas, but both types activated crudely retinotopic visual areas, including V3A, V4v, V7, and V8, bilaterally. The extent of activation was largely invariant across a range of stimulus sizes that produce illusory contours perceptually, but it was related to the spatial frequency of displaced-grating stimuli. Finally, there was a striking similarity in the pattern of results for the illusory contour-defined shape and a similar shape defined by stereoscopic depth. These and other results suggest a role in surface perception for this lateral occipital region that includes V3A, V4v, V7, and V8. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Mendola, JD (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St 2301, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NEI NIH HHS [EY07980] NR 62 TC 293 Z9 298 U1 2 U2 19 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 1999 VL 19 IS 19 BP 8560 EP 8572 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 240BG UT WOS:000082805400043 PM 10493756 ER PT J AU Demas, GE Kriegsfeld, LJ Blackshaw, S Huang, P Gammie, SC Nelson, RJ Snyder, SH AF Demas, GE Kriegsfeld, LJ Blackshaw, S Huang, P Gammie, SC Nelson, RJ Snyder, SH TI Elimination of aggressive behavior in male mice lacking endothelial nitric oxide synthase SO JOURNAL OF NEUROSCIENCE LA English DT Article DE aggression; hypertension; 7-nitroindazole; nitroarginine; nitric oxide synthase; endothelium ID RAT-BRAIN; LOCALIZATION; INHIBITION; KNOCKOUT; VESSELS; CLONING; LTP AB Male mice with targeted deletion of the gene encoding the neuronal isoform of nitric oxide synthase (nNOS(-/-)) display increased aggressive behavior compared with wild-type (WT) mice. Specific pharmacological inhibition of nNOS with 7-nitroindazole also augments aggressive behavior. We report here that male mice with targeted deletion of the gene encoding endothelial NOS (eNOS(-/-)) display dramatic reductions in aggression. The effects are selective, because an extensive battery of behavioral tests reveals no other deficits. In the resident-intruder model of aggression, resident eNOS(-/-) males show virtually no aggression. Latency for aggression onset is 25-30 times longer in eNOS(-/-) males compared with WT males in the rare instances of aggressive behaviors. Similarly, a striking lack of aggression is noted in tests of aggression among groups of four mice monitored in neutral cages. Although eNOS(-/-) mice are hypertensive (similar to 14 mmHg blood pressure elevation), hypertension does not appear responsible for the diminished aggression. Reduction of hypertension with hydralazine does not change the prevalence of aggression in eNOS(-/-) mice. Extensive examination of brains from eNOS(-/-) male mice reveals no obvious neural damage from chronic hypertension. In situ hybridization in WT animals reveals eNOS mRNA in the brain associated exclusively with blood vessels and no neuronal localizations. Accordingly, vascular eNOS in the brain appears capable of influencing behavior with considerable selectivity. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Psychol, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. RP Snyder, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 725 N Wolfe St, Baltimore, MD 21218 USA. FU NIMH NIH HHS [MH-18501, MH-57535, MH-57760] NR 26 TC 53 Z9 55 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 1999 VL 19 IS 19 AR RC30 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 240BG UT WOS:000082805400003 PM 10493775 ER PT J AU Rao, VLR Dogan, A Bowen, KK Dempsey, RJ AF Rao, VLR Dogan, A Bowen, KK Dempsey, RJ TI Traumatic injury to rat brain upregulates neuronal nitric oxide synthase expression and L-[H-3]nitroarginine binding SO JOURNAL OF NEUROTRAUMA LA English DT Article DE mRNA; nitric oxide; neuronal nitric oxide synthase, L-nitroarginine; RT-PCR; traumatic brain injury; Western blotting ID CORTICAL IMPACT INJURY; TRANSIENT FOCAL ISCHEMIA; NITROARGININE BINDING; NMDA RECEPTORS; MUTANT MICE; MITOCHONDRIAL; SYNAPTOSOMES; PHARMACOLOGY; MECHANISMS; INHIBITION AB Overstimulation of N-methyl-D-aspartate (NMDA) receptors is felt to precipitate the neuronal damage following traumatic brain injury (TBI). NMDA receptor-mediated, glutamate-induced excitotoxicity is thought to be mediated via nitric oxide (NO) formed by neuronal nitric oxide synthase (nNOS), The present study examined the mRNA and protein levels of nNOS in the ipsilateral and contralateral cortex of rats as a function of time (5 minutes to 1 week) after controlled cortical impact (CCI) brain injury, Sham-operated rats served as controls. TBI resulted in a significant increase in the levels of nNOS mRNA (1.5- to 2.8-fold, p <.05) between 2 and 4 hours after the injury, There was also a significant increase in the levels of nNOS protein (by 55% to 90%,p <.05) and binding densities of the nNOS-specific ligand L-[H-3]nitroarginine (L-[H-3]NOARG) (by 35% to 59%,p <.05) between 2 and 12 hours after the injury, Increased nNOS expression and function may contribute to the concomitant excitotoxic neuronal death after TBI. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Hosp, Madison, WI USA. RP Dempsey, RJ (reprint author), Univ Wisconsin, Dept Neurol Surg, H4-336 CSC,600 Highland Ave, Madison, WI 53792 USA. NR 72 TC 36 Z9 39 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 1999 VL 16 IS 10 BP 865 EP 877 DI 10.1089/neu.1999.16.865 PG 13 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 246JD UT WOS:000083159900002 PM 10547096 ER PT J AU Noviski, N Ben Yehuda, Y Serour, F Gorenstein, A Mandelberg, A AF Noviski, N Ben Yehuda, Y Serour, F Gorenstein, A Mandelberg, A TI Does the size of nasogastric tubes affect gastroesophageal reflux in children? SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE children; gastroesophageal reflux; nasogastric tubes ID ENTERAL NUTRITION SUPPORT; PULMONARY ASPIRATION; PNEUMONIA; INFANTS; APNEA; ESOPHAGEAL AB Background: To evaluate the effects of nasogastric tube insertion and different nasogastric tube sizes on gastroesophageal reflux in children. Methods: During a prospective randomized study, 29 patients aged 1 month to 4 years (median, 9 months) underwent 24 hours of continuous esophageal pH monitoring to rule out gastroesophageal reflux as the cause of severe pulmonary problems. Each patient was monitored without nasogastric tube for 16 hours (baseline), and thereafter the first nasogastric tube, small (8-Fr) or large (10-Fr or 12-Fr), was placed. Four hours later, the original nasogastric tube was replaced by a new one of large (instead of small) size or of small (instead of large) size. We selected the times of wakefulness in these study periods and compared the number of reflux episodes (NREs), the number of reflux episodes that lasted more than 5 minutes (NRE > 5), and the percentage of time with esophageal pH less than 4 (PTP < 4). Results: The 12-Fr group in comparison with the 8-Fr group and baseline showed significant difference (P < 0.05) in the NRE>S and PTP<4 parameters. No significant differences were found when comparing 8-Fr versus 10-Fr groups and baseline. In children with (n = 20) and without (n = 9) gastroesophageal reflux, comparison of the various reflux parameters between baseline and the different sizes of nasogastric tubes showed the same results. Conclusions: Size of the nasogastric tubes is a significant factor in predisposing the child to gastroesophageal reflux. Large nasogastric tubes interfere with the clearance of the refluxed acid from the esophagus. C1 Edith Wolfson Med Ctr, Div Pediat Surg, IL-58100 Holon, Israel. Edith Wolfson Med Ctr, Pediat Pulm Unit, IL-58100 Holon, Israel. Edith Wolfson Med Ctr, Pediat Intens Care Unit, IL-58100 Holon, Israel. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Serour, F (reprint author), Edith Wolfson Med Ctr, Div Pediat Surg, POB 5, IL-58100 Holon, Israel. NR 26 TC 10 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD OCT PY 1999 VL 29 IS 4 BP 448 EP 451 DI 10.1097/00005176-199910000-00014 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 239VH UT WOS:000082790000014 PM 10512406 ER PT J AU Stoler, JM Holmes, LB AF Stoler, JM Holmes, LB TI Under-recognition of prenatal alcohol effects in infants of known alcohol abusing women SO JOURNAL OF PEDIATRICS LA English DT Article ID HEAD CIRCUMFERENCE; BIRTH-WEIGHT; FETAL; EXPOSURE; CONSUMPTION; PREGNANCY; CHILDREN; GROWTH AB Medical records of 124 women and their infants were analyzed for: (1) documentation of maternal alcohol and other substance abuse and (2) evaluation of exposed infants. These results were compared with the study interview and infant examination. More obstetric nurses documented the presence or absence of alcohol and substance abuse than did pediatricians. More women reported using alcohol in the study interview than documented in the medical records. There was slightly better documentation for cocaine use than for alcohol use in the medical records. One of the 19 infants with documentation of maternal alcohol use was noted to have possible alcohol-related features by the pediatrician, in contrast to 7 infants identified by the study examiner. In addition, 2 of these 19 infants were determined by the study examiner to have fetal alcohol syndrome; neither case was diagnosed by the pediatricians. Continued efforts at education regarding the importance of asking about prenatal alcohol exposure and the spectrum of fetal alcohol effects are needed for early diagnosis. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Med Sch, Serv Pediat, Genet & Teratol Unit, Cambridge, MA USA. RP Stoler, JM (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 48 Z9 51 U1 1 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 OCT PY 1999 VL 135 IS 4 BP 430 EP 436 DI 10.1016/S0022-3476(99)70164-2 PG 7 WC Pediatrics SC Pediatrics GA 246DU UT WOS:000083149800009 PM 10518076 ER PT J AU Garner, EIO Chang-Lee, WY Lu, KH Goldstein, DP Berkowitz, RS AF Garner, EIO Chang-Lee, WY Lu, KH Goldstein, DP Berkowitz, RS TI Trophoblastic pulmonary embolization after hysterectomy for invasive complete mole - A case report SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE trophoblastic neoplasms; pulmonary embolism; hysterectomy; invasive mole ID PREGNANCY; COMPLICATIONS AB BACKGROUND: Trophoblastic pulmonary embolization usually occurs after evacuation of a molar pregnancy when the uterus is larger than dates and the human chorionic gonadotropin level is >100,000 mIU/mL. If has a dramatic onset, with dyspnea, tachypnea, bilateral pulmonary infiltrates and low Po-2 levels. Treatment requires supportive measures only. Intubation is rarely required. The clinical course is shout-lived, with gradual improvement after 48 hours and complete resolution in 72 hours. There are no long-term sequelae. Differential diagnosis includes pulmonary embolization,fluid overload and aspiration. CASE: A 27-year-old, Caucasian woman, gravida 4, para 2, spontaneous abortion 1, developed presumed trophoblastic pulmonary embolization following abdominal hysterectomy for an invasive mole. The clinical course was typical of this condition, with spontaneous cleaving in 72 hours with supportive measures only. CONCLUSION: Trophoblastic pulmonary embolization can occur following abdominal hysterectomy for invasive mole as well as after molar evacuation and should be considered part of the differential diagnosis if patients present postoperatively with acute respiratory distress. C1 Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 15 Z9 15 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD OCT PY 1999 VL 44 IS 10 BP 908 EP 912 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249KK UT WOS:000083332100019 PM 10554759 ER PT J AU Weinblatt, ME Reda, D Henderson, W Giobbie-Hurder, A Williams, D Diani, A Docsa, S AF Weinblatt, ME Reda, D Henderson, W Giobbie-Hurder, A Williams, D Diani, A Docsa, S TI Sulfasalazine treatment for rheumatoid arthritis: A metaanalysis of 15 randomized trials SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE sulfasalazine; rheumatoid arthritis; metaanalysis ID DOUBLE-BLIND; COMPARING SULFASALAZINE; PLACEBO; SULPHASALAZINE; HYDROXYCHLOROQUINE; PENICILLAMINE; COMBINATION AB Objective. To assess the efficacy and safety of sulfasalazine (SSZ) compared to placebo and other disease modifying drugs. Methods. A metaanalysis was performed on 15 randomized clinical trials of rheumatoid arthritis (RA) that included SSZ (3 g/day average dose, 36 weeks average followup) as a treatment. Eight trials included a placebo group (PL), 2 hydroxychloroquine (HCQ) (350 mg/day average dose), 3 D-penicillamine (D-Pen) (667 mg/day average dose), and 3 gold sodium thiomalate or aurothioglucose (GST) (25 mg, 1 g/wk). Results. Compared to PL, SSZ was superior for improvement in erythrocyte sedimentation rate (ESR) (SSZ 37%, PL 14%; p < 0.0001), morning stiffness duration (SSZ 61%, PL 33%; p = 0.008), pain visual analog scale (SZ 42%, PL 15%; p < 0.0001), articular index (SSZ 46%, PL 20%; p < 0.0001), number of swollen joints (SSZ 51%, PL 26%; p < 0.0001). number of painful joints (SSZ 59%, PL 33%; p = 0.004), and patient global assessment (SSZ 26%, PL 14%; ; p = 0.02). Withdrawals from study because of adverse drug reactions were increased (SSZ 24%, PL 7%; p < 0.0001). but lack of efficacy dropouts were decreased (SSZ 8%, PL 21%; p < 0.0001). Compared to HCQ, SSZ tended to have fewer lack of efficacy dropouts (SSZ 5%, HCQ 15%; p = 0.055) and improved ESR (SSZ 43%, HCQ 26%; p = 0.10) and morning stiffness duration (SSZ 59%, HCQ 40%; p = 0.09). Compared to GST, adverse drug reaction dropouts were significantly fewer (SSZ 12%, GST 29%; p < 0.0001), while withdrawals due to lack of efficacy were greater (SSZ 13%, GST 4%; p = 0.006). More patients tended to complete treatment taking SSZ (SSZ 69%, GST 61%; p = 0.09). Conclusion. Over all, the metaanalysis provides data that support the effectiveness of SSZ as a treatment for RA. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. US Dept Vet Affairs, Edward Hines Jr Hosp, Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. Pharmacia & Upjohn US Market Co, Med Affairs, Kalamazoo, MI USA. RP Weinblatt, ME (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 21 TC 20 Z9 21 U1 0 U2 3 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 OCT PY 1999 VL 26 IS 10 BP 2123 EP 2130 PG 8 WC Rheumatology SC Rheumatology GA 243TY UT WOS:000083014300012 PM 10529127 ER PT J AU Dawson, TM Starkebaum, G AF Dawson, TM Starkebaum, G TI Isolated central nervous system vasculitis associated with hepatitis C infection SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE CNS vasculitis; hepatitis C; cerebral vasculitis ID MIXED CRYOGLOBULINEMIA; VIRUS-INFECTION; NEUROPATHY; ANGIITIS; ANTIBODY AB Since its identification in 1989, hepatitis C has been implicated in the pathogenesis of an increasing number of diseases previously believed to be primary or idiopathic. We report 2 rarely seen cases of isolated central nervous system (CNS) vasculitis in patients with hepatitis C infection. Patient 1. A 43-year-old man with 4 day right temporal headache developed a left hemiparesis. Weakness was his only physical finding, Computed tomography (CT) scan demonstrated a large right frontotemporal hemorrhage, and angiography revealed focal dilatations and irregularities of multiple branches of the right middle and anterior cerebral arteries. Cerebral decompression was performed and leptomeningeal biopsies showed granulomatous angiitis. Laboratory results were normal except for elevated liver biochemical tests. Later testing for hepatitis C was positive. His neurological symptoms improved with corticosteroids and cyclophosphamide. Patient 2. A 39 yr old male developed 3 days of left sided weak ness, slurred speech and difficulty swallowing fluids. Physical findings were limited to his weakness. Magnetic resonance imaging demonstrated a right superior pontine subacute infarct with a small left internal capsule lacunar infarct. Angiography revealed multiple areas of focal narrowing with no areas of abrupt vessel cut off. Cerebral spinal fluid showed 71 PMN. 29 RBC, normal glucose, elevated protein (64 mg/dl), no oligoclonal bands, and low myelin basic protein, Other laboratory analyses were normal including liver biochemical tests, However, hepatitis C serology was positive and mixed cryoglobulins were detected, CNS vasculitis was diagnosed and nearly full recovery was achieved with corticosteroids, cyclophosphamide and warfarin. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle Div, Med Serv,Dev & Arthrit Sect, Seattle, WA 98108 USA. Univ Washington, Hlth Serv Res, Seattle, WA 98108 USA. Univ Washington, Div Rheumatol, Seattle, WA 98108 USA. RP Dawson, TM (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle Div, Med Serv,Dev & Arthrit Sect, 1600 S Columbian Way, Seattle, WA 98108 USA. NR 16 TC 38 Z9 39 U1 1 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 OCT PY 1999 VL 26 IS 10 BP 2273 EP 2276 PG 4 WC Rheumatology SC Rheumatology GA 243TY UT WOS:000083014300040 PM 10529155 ER PT J AU Roberts, JL Fiedler, V Imperato-McGinley, J Whiting, D Olsen, E Shupack, J Stough, D DeVillez, R Rietschel, R Savin, R Bergfeld, W Swinehart, J Funicella, T Hordinsky, M Lowe, N Katz, I Lucky, A Drake, L Price, VH Weiss, D Whitmore, E Millikan, L Muller, S Gencheff, C Carrington, P Binkowitz, B Kotey, P He, W Bruno, K Jacobsen, C Terranella, L Gormley, GJ Kaufman, KD AF Roberts, JL Fiedler, V Imperato-McGinley, J Whiting, D Olsen, E Shupack, J Stough, D DeVillez, R Rietschel, R Savin, R Bergfeld, W Swinehart, J Funicella, T Hordinsky, M Lowe, N Katz, I Lucky, A Drake, L Price, VH Weiss, D Whitmore, E Millikan, L Muller, S Gencheff, C Carrington, P Binkowitz, B Kotey, P He, W Bruno, K Jacobsen, C Terranella, L Gormley, GJ Kaufman, KD TI Clinical dose ranging studies with finasteride, a type 2 5 alpha-reductase inhibitor, in men with male pattern hair loss SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; STEROID 5-ALPHA-REDUCTASE; ANDROGENETIC ALOPECIA; MULTIPLE ENDPOINTS; SCALP SKIN; DIHYDROTESTOSTERONE; BALDNESS; EXPRESSION; ISOZYME; GROWTH AB Background: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5 alpha-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone. Objective: Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition. Methods: Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences. Results: Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to! lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials. Conclusion: Finasteride 1 mg/day is the optimal dose for,the treatment of men with male pattern hair loss and was subsequently identified for further clinical development. C1 NW Cutaneous Res Specialists, Portland, OR USA. Univ Illinois, Chicago, IL USA. Cornell Univ, Coll Med, New York, NY USA. Dallas Associated Dermatologists, Dallas, TX USA. Duke Univ, Med Ctr, Durham, NC USA. NYU, Med Ctr, New York, NY 10016 USA. Stough Clin, Hot Springs, AK USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Savin Dermatol Ctr, New Haven, CT USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Colorado Med Res Ctr, Denver, CO USA. DermRes Inc, Austin, TX USA. Univ Minnesota Twin Cities, Minneapolis, MN USA. Clin Res Specialists, Santa Monica, CA USA. Minnesota Clin Study Ctr, Fridley, MN USA. Dermatol Res Associates, Cincinnati, OH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Plast Surg & Dermatol Associates, Fairlawn, NJ USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Lakeview Med Ctr, Madison, WI USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Merck Res Labs, Dept Biostat, Rahway, NJ USA. Merck Res Labs, Dept Clin Res, Rahway, NJ USA. Merck & Co Inc, Clin Dev, US Med & Sci Affairs, Horsham, PA USA. RP Kaufman, KD (reprint author), Merck Res Labs, Clin Res Endocrinol & Metab, POB 2000, Rahway, NJ 07065 USA. NR 25 TC 56 Z9 56 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 1999 VL 41 IS 4 BP 555 EP 563 DI 10.1016/S0190-9622(99)70296-3 PG 9 WC Dermatology SC Dermatology GA 241VA UT WOS:000082903300006 PM 10495375 ER PT J AU Moreno, PR Fallon, JT Murcia, AM Leon, MN Simosa, H Fuster, V Palacios, IF AF Moreno, PR Fallon, JT Murcia, AM Leon, MN Simosa, H Fuster, V Palacios, IF TI Tissue characteristics of restenosis after percutaneous transluminal coronary angioplasty in diabetic patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 69th Annual Scientific Session of the American-Heart-Association CY NOV 09-16, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc, Hoechst Marion Roussel Inc, Kansas City ID SERIAL INTRAVASCULAR ULTRASOUND; BALLOON ANGIOPLASTY; UNSTABLE ANGINA; MELLITUS; PLACEMENT; STENT AB The purposes of this study were to analyze coronary specimens from patients with diabetes mellitus (DM) and to compare them with specimens from patients without DM. BACKGROUND Diabetes mellitus is associated with an increased incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Increased hypercellular smooth muscle cell proliferation with exaggerated intimal hyperplasia formation may be responsible for this predisposition. METHODS Eighteen coronary atherectomy specimens with restenosis after PTCA from patients with DM were compared with 18 coronary atherectomy specimens with restenosis after PTCA from patients without DMI. Total and segmental areas were quantified on trichrome-stained tissue of hypercellular tissue, collagen-rich sclerotic tissue, atheroma and thrombus. Demographic and angiographic data were similar in both groups. RESULTS The percentage of total plaque area composed of hypercellular tissue was lower in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (19 +/- 6% vs. 44 +/- 5%; p = 0.003). The percentage of collagen-rich sclerotic tissue area was larger in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (77 +/- 9% vs. 53 +/- 4%; p = 0.004). The percentages of atheroma and thrombus were similar in both groups. CONLUSIONS Intimal hypercellular tissue content is reduced in restenotic tissue from patients with DM. Collagen-rich sclerotic content is increased in restenotic lesions from patients with DM. These results suggest an accelerated fibrotic rather than a proliferative response in diabetic lesions from patients with restenosis after PTCA.. (J Am Cell Cardiol 1999;34:1045-9) (C) 1999 by the American College of Cardiology. C1 Univ Kentucky, Gill Heart Inst, Lexington, KY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Cardiovasc Inst, New York, NY USA. RP Moreno, PR (reprint author), Vet Affairs Med Ctr, 111B-CDD,2250 Leestown Rd, Lexington, KY 40511 USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 23 TC 41 Z9 41 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 OCT PY 1999 VL 34 IS 4 BP 1045 EP 1049 DI 10.1016/S0735-1097(99)00338-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242JN UT WOS:000082936900014 PM 10520788 ER PT J AU Leon, MN Harrell, LC Simosa, HF Mahdi, NA Pathan, A Lopez-Cuellar, J Inglessis, I Moreno, PR Palacios, IF AF Leon, MN Harrell, LC Simosa, HF Mahdi, NA Pathan, A Lopez-Cuellar, J Inglessis, I Moreno, PR Palacios, IF TI Mitral balloon valvotomy for patients with mitral stenosis in atrial fibrillation - Immediate and long-term results SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID FOLLOW-UP; SURGICAL COMMISSUROTOMY; VALVULOPLASTY; CATHETER; PREDICTORS; COMPLICATIONS; REGURGITATION AB OBJECTIVES The purpose of this study was to examine the effect of atrial fibrillation (AF) on the immediate and long-term outcome of patients undergoing percutaneous mitral balloon valvuloplasty (PMV). BACKGROUND There is controversy as to whether the presence of AF has a direct negative effect on the outcome after PMV. METHODS The immediate procedural and the long-term clinical outcome after PMV of 355 patients with AF were prospectively collected and compared with those of 379 patients in normal sinus rhythm (NSR). RESULTS Patients with AF were older (62 +/- 12 vs. 48 +/- 14 years; p < 0.0001) and presented more frequently with New York Heart Association (NYHA) class IV (18.3% vs. 7.9%; p < 0.0001), echocardiographic score >8 (40.1% vs. 25.1%; p < 0.0001), calcified valves under fluoroscopy (32.4% vs. 18.8%, p < 0.0001) and with history of previous surgical commissurotomy (21.7% vs. 16.4%; p = 0.0002). In patients with AF, PMV resulted in inferior immediate and long-term outcomes, as reflected in a smaller post-PMV mitral valve area (1.7 +/- 0.7 vs. 2 +/- 0.7 cm(2); p <: 0.0001) and a lower event free survival (freedom of death, redo-PMV and mitral valve surgery) at a mean follow-up time of 60 months (32% vs. 61%; p < 0.0001). In the group of patients in AF, severe post-PMV mitral regurgitation (greater than or equal to 3+) (p = 0.0001), echocardiographic score >8 (p = 0.004) and pre-PMV NYHA class IV (p = 0.046) were identified as independent predictors of combined events at follow-up. CONCLUSIONS Patients with AF have a worse immediate and long-term outcomes after PMV. However, the presence of AF by itself does not unfavorably influence the outcome, but is a marker for clinical and morphologic features associated with inferior results after PMV. (J Am Coll Cardiol 1999;34:1145-52) (C) 1999 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Cardiac Catheterizat Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Cardiac Catheterizat Labs, Boston, MA 02114 USA. NR 44 TC 14 Z9 16 U1 0 U2 0 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 OCT PY 1999 VL 34 IS 4 BP 1145 EP 1152 DI 10.1016/S0735-1097(99)00310-1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 242JN UT WOS:000082936900030 PM 10520804 ER PT J AU Scherrer-Crosbie, M Steudel, W Hunziker, PR Liel-Cohen, N Ullrich, R Zapol, WM Picard, MH AF Scherrer-Crosbie, M Steudel, W Hunziker, PR Liel-Cohen, N Ullrich, R Zapol, WM Picard, MH TI Three-dimensional echocardiographic assessment of left ventricular wall motion abnormalities in mouse myocardial infarction SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID MICE; DEFICIENCY; MASS AB We applied S-dimensional echocardiographic reconstruction to assess left ventricular (LV) volumes, function, and the extent of wall motion abnormalities in a murine model of myocardial infarction (MI). Consecutive parasternal short-axis planes were obtained at l-mm intervals with a 13-MHz linear array probe. End-diastolic and end-systolic LV volumes were calculated by Simpson's rule, and the ejection fraction and cardiac output were derived. Echocardiography-derived cardiac output was validated by an aortic flow probe in 6 mice. Echocardiography was then performed in 9 mice before and after the left anterior descending coronary artery was ligated. Wall motion was assessed, and the ratio of the abnormally to normally contracting myocardium was calculated. After MI occurred, LV end-diastolic volume and LV end-systolic volume increased (33 +/- 10 vs 24 +/- 6 mu L, P < .05 and 24 +/-. 9 vs 10 +/- 4 mu L, P < .001), whereas cardiac output decreased (4.2 +/- 1.5 mL/min vs 6.6 +/- 2.3 mL/min, P < .01). Forty percent of the myocardium was normokinetic, 24% was hypokinetic, and 36% was akinetic. Echocardiography can measure LY volumes and regional and global function in a murine model of myocardial infarction, thereby providing the potential to quantitate and compare the responses of various transgenic mice to MI and its therapies. C1 Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med,Div Cardiol, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Sch Med,Dept Med, VBK 508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 20 TC 53 Z9 54 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 1999 VL 12 IS 10 BP 834 EP 840 DI 10.1016/S0894-7317(99)70188-4 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 248BJ UT WOS:000083255200009 PM 10511652 ER PT J AU Collins, AB Schneeberger, EE Pascual, MA Saidman, SL Williams, WW Tolkoff-Rubin, N Cosimi, AB Colvin, RB AF Collins, AB Schneeberger, EE Pascual, MA Saidman, SL Williams, WW Tolkoff-Rubin, N Cosimi, AB Colvin, RB TI Complement activation in acute humoral renal allograft rejection: Diagnostic significance of C4d deposits in peritubular capillaries SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 31st Congress of the American-Society-of-Nephrology CY OCT 25-28, 1998 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Nephrol ID DECAY-ACCELERATING FACTOR; DISEASED HUMAN GLOMERULI; NORMAL HUMAN-KIDNEY; VASCULAR REJECTION; PATHOLOGICAL FEATURES; ENDOTHELIAL-CELLS; ANTIBODY; TRANSPLANTATION; LOCALIZATION; IDENTIFICATION AB The distinction between acute humoral rejection (AHR) and acute cellular rejection (ACR) in renal allografts is therapeutically important, but pathologically difficult. Since AHR is probably mediated by antibodies to the donor endothelium that activate the classical complement pathway, it was hypothesized that peritubular capillary C4d deposition might distinguish this group. Renal biopsies (n = 16) from 10 patients with AHR who had acute graft dysfunction, neutrophils in peritubular capillaries, and a concurrent positive crossmatch were stained for C4d by immunofluorescence. Control biopsies for comparison showed ACR (n = 14), cyclosporin A toxicity (n = 6), or no abnormality (n = 4). Peribiopsy sera were tested for anti-donor HLA antibody. C4d deposited prominently and diffusely in the peritubular capillaries in all AHR biopsies (16 of 16). IgM and/or C3 were also present in 19 and 44% respectively. With two-color immunofluorescence, C4d was localized in basement membranes (type IV colagen(+)) and in the endothelium (Ulex europaeus agglutinin-I+). In ACR, no more than trace C4d was found in peritubular capillaries (P < 0.0001 verses AHR), and no patient had anti-donor HLA antibodies (0 of 8); 27% had neutrophils in peritubular capillaries. One of six biopsies with cyclosporin A toxicity had similar C4d deposits, and circulating anti-donor class I antibody was detected. Grafts with AHR were lost (40%) more often than those with ACR (0%; P < 0.02). C4d in peritubular capillary wails distinguishes AHR from ACR, is more specific and sensitive than traditional criteria, and is a potentially valuable adjunct in the diagnosis of graft dysfunction. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01-HL18686] NR 29 TC 349 Z9 385 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1999 VL 10 IS 10 BP 2208 EP 2214 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 239BA UT WOS:000082747900017 PM 10505698 ER PT J AU Okubo, K Mark, EJ Flieder, D Wain, JC Wright, CD Moncure, AC Grillo, HC Mathisen, DJ AF Okubo, K Mark, EJ Flieder, D Wain, JC Wright, CD Moncure, AC Grillo, HC Mathisen, DJ TI Bronchoalveolar carcinoma: Clinical, radiologic, and pathologic factors and survival SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 03-06, 1998 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID BRONCHIOLOALVEOLAR CARCINOMA; CELL-CARCINOMA; LUNG-CANCER AB Background: The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. Methods: We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed, We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed, Results: Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P < .0001), Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P = .006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P = .003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection, Mitosis or nuclear grade of tumor cells did not correlate with survival. Conclusions: Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures; Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival. C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. NR 18 TC 61 Z9 64 U1 0 U2 1 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 OCT PY 1999 VL 118 IS 4 BP 702 EP 709 DI 10.1016/S0022-5223(99)70016-4 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 245VT UT WOS:000083129400023 PM 10504637 ER PT J AU Bankier, AA Stauffer, F Lomoschitz, F Brunner, C AF Bankier, AA Stauffer, F Lomoschitz, F Brunner, C TI Mycobacterium xenopi infection of a 50-year-old oil plombage complicated by bronchopleural and pleurocutaneous fistulas SO JOURNAL OF THORACIC IMAGING LA English DT Article DE oil plombage; complication; fistula; bronchopleural fistula; pleurocutaneous fistula; Mycobacterium xenopi ID PULMONARY INFECTION; OLEOTHORAX; TUBERCULOSIS; CT; DISEASE AB We report the rare combination of simultaneous bronchopleural and pleurocutaneous fistulas 50 years after oil plombage, together with infection of both the plombage and the contralateral lung with Mycobacterium xenopi. Our case documents imaging patterns of complex fistula formation and subsequent infection resulting from oil plombage. Our case also emphasizes the infectious potential of Mycobacterium xenopi. C1 Univ Vienna, Dept Radiol, A-1010 Vienna, Austria. RP Bankier, AA (reprint author), Harvard Univ, Sch Med, Beth Deaconess Med Ctr, Sect MRI Res,Dept Radiol, East Campus,Ansin 234,330 Brookline Ave, Boston, MA 02215 USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD OCT PY 1999 VL 14 IS 4 BP 307 EP 311 DI 10.1097/00005382-199910000-00013 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 242GK UT WOS:000082932000013 PM 10524814 ER PT J AU Bonn, J Cho, KJ Cipolle, M Ferris, E Geller, S Grassi, C Greenfield, LJ Lilly, M McGowan, TC McFarland, D Okhi, S Pais, SO Proctor, MC Ricco, JB Rutherford, RB Simon, M Venbrux, A Vogelzang, R AF Bonn, J Cho, KJ Cipolle, M Ferris, E Geller, S Grassi, C Greenfield, LJ Lilly, M McGowan, TC McFarland, D Okhi, S Pais, SO Proctor, MC Ricco, JB Rutherford, RB Simon, M Venbrux, A Vogelzang, R TI Recommended reporting standards for vena caval filter placement and patient follow-up (vol 10, pg 1013, 1999) SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Correction C1 Thomas Jefferson Univ, Dept Radiol, Philadelphia, PA 19107 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Lehigh Valley Hosp, Dept Surg, Allentown, PA USA. Univ Arkansas, Dept Radiol, Fayetteville, AR 72701 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Maryland, Dept Surg, College Pk, MD 20742 USA. Univ Nebraska, Dept Radiol, Lincoln, NE 68583 USA. Univ Maryland, Dept Radiol, College Pk, MD 20742 USA. Univ Poitiers, Dept Surg, Poitiers, France. Univ Colorado, Dept Surg, Boulder, CO 80309 USA. Harvard Univ, Neth Israel Deaconess, Dept Radiol, Cambridge, MA 02138 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21218 USA. Northwestern Univ, Dept Radiol, Evanston, IL 60208 USA. RP Bonn, J (reprint author), Thomas Jefferson Univ, Dept Radiol, Philadelphia, PA 19107 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 1999 VL 10 IS 9 BP 1270 EP 1270 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 245DJ UT WOS:000083090700019 ER PT J AU Kolchinsky, P Mirzabekov, T Farzan, M Kiprilov, E Cayabyab, M Mooney, LJ Choe, H Sodroski, J AF Kolchinsky, P Mirzabekov, T Farzan, M Kiprilov, E Cayabyab, M Mooney, LJ Choe, H Sodroski, J TI Adaptation of a CCR5-using, primary human immunodeficiency virus type 1 isolate for CD4-independent replication SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; SOLUBLE CD4 BINDING; T-LYMPHOTROPIC RETROVIRUS; CONFORMATIONAL-CHANGES; CHEMOKINE RECEPTORS; AIDS VIRUS; SYNCYTIUM FORMATION; HIV-1 VIRIONS; CELL-LINE; HTLV-III AB The gp120 envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-I) promotes virus entry by sequentially binding CD4 and chemokine receptors on the target cell. Primary, clinical HIV-1 isolates require interaction with CD4 to allow gp120 to bind the CCR5 chemokine receptor efficiently. We adapted a primary HIV-1 isolate, ADA, to replicate in CD4-negative canine cells expressing human CCR5. The gp120 changes responsible for the adaptation were limited to alteration of glycosylation addition sites in the V2 loop-V1-V2 stem. The gp120 glycoproteins of the adapted viruses bound CCR5 directly, without prior interaction with CD4. Thus, a major function of CD4 binding in the entry of primary HN-I isolates can be bypassed by changes in I-he gp120 V1-V2 elements, which allow the envelope glycoproteins to assume a conformation competent for CCR5 binding. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Perlmutter Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Div Human Retrovirol, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [P30 AI028691, AI24755, AI28691, AI41851, R01 AI041851, R01 AI043891, R37 AI024755] NR 78 TC 143 Z9 145 U1 1 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 OCT PY 1999 VL 73 IS 10 BP 8120 EP 8126 PG 7 WC Virology SC Virology GA 235QP UT WOS:000082554300023 PM 10482561 ER PT J AU Tong, SP Li, JS Wands, JR AF Tong, SP Li, JS Wands, JR TI Carboxypeptidase D is an avian hepatitis B virus receptor SO JOURNAL OF VIROLOGY LA English DT Article ID PRE-S DOMAIN; AMINOPEPTIDASE-N; ENVELOPE PROTEIN; HEPADNAVIRUS; INFECTION; REPLICATION; BINDING; HEPATOCYTES; PARTICLES; EPITOPES AB The receptor molecules for human and animal hepatitis B viruses have not been defined. Previous studies have described a 170 to 180 kDa molecule (p170 or gp180) that binds in vitro to the pre-S domain of the large envelope protein of duck hepatitis B virus (DHBV); cDNA cloning revealed the binding protein to be duck carboxypeptidase D (DCPD), In the present study, the DCPD cDNA was transfected into several nonpermissive human-, monkey-, and avian species-derived cell lines. Cells transfected with a plasmid encoding the full-length DCPD protein bound DHBV particles, whereas cells expressing truncated versions of DCPD protein that fail to bind the pre-S protein did not. The DHBV binding to DCPD-reconstituted cells was blocked by a monoclonal antibody that neutralizes DHBV infection of primary duck hepatocytes (PDH) and also by a pre-S peptide previously shown to inhibit DHBV infection of PDH. In addition to promoting virus binding, DCPD expression was associated with internalization of viral particles. The entry process was prevented by incubation of reconstituted cells with DHBV at 4 degrees C and by the addition of energy-depleting agents known to block DHBV entry into PDH, These results demonstrated that DCPD is a DWBV receptor. However, the lack of complete viral replication in DCPD-reconstituted cells suggested that additional factors are required for postentry events in immortalized cell lines. C1 Massachusetts Gen Hosp, Mol Hepatol Lab, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Wands, JR (reprint author), Liver Res Ctr, 55 Claverick St,4th Floor, Providence, RI 02903 USA. FU NCI NIH HHS [CA-35711, R01 CA035711, R37 CA035711]; NIAAA NIH HHS [AA-02169, AA-02666, R01 AA002666, R37 AA002666] NR 29 TC 37 Z9 41 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 OCT PY 1999 VL 73 IS 10 BP 8696 EP 8702 PG 7 WC Virology SC Virology GA 235QP UT WOS:000082554300085 PM 10482623 ER PT J AU Etemad-Moghadam, B Sun, Y Nicholson, EK Karlsson, GB Schenten, D Sodroski, J AF Etemad-Moghadam, B Sun, Y Nicholson, EK Karlsson, GB Schenten, D Sodroski, J TI Determinants of neutralization resistance in the envelope glycoproteins of a simian-human immunodeficiency virus passaged in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; AIDS-LIKE DISEASE; RECEPTOR-BINDING; RHESUS-MONKEYS; SOLUBLE CD4; TYPE-1 NEUTRALIZATION; LYMPHOCYTE DEPLETION; GP120 GLYCOPROTEIN; HIV-1 INFECTION; V1/V2 REGION AB In vivo passage of a simian-human immunodeficiency virus (SHIV-89.6) generated a virus, SHIV-89.6P, that exhibited increased resistance to some neutralizing antibodies (G. B. Karlsson et al., J. Exp. Med. 188:1159-1171, 1998). Here we examine the range of human immnnodeficiency virus type 1 (HIV-1) neutralizing antibodies to which the passaged virus became resistant and identify envelope glycoprotein determinants of antibody resistance. Compared with the envelope glycoproteins derived from the parental SHIV-89.6, the envelope glycoproteins of the passaged virus were resistant to antibodies directed against the gp120 V3 variable loop and the CD4 binding site. By contrast, both viral envelope glycoproteins were equally sensitive to neutralization by two antibodies, 2G12 and 2F5, that recognize poorly immunogenic structures on gp120 and gp41, respectively. Changes in the V2 and V3 variable loops of gp120 were necessary and sufficient for full resistance to the IgG1b12 antibody, which is directed against the CD4 binding site. Changes in the V3 loop specified complete resistance to a V3 loop-directed antibody, while changes in the V1/V2 loops conferred partial resistance to this antibody. The epitopes of the neutralizing antibodies were not disrupted by the resistance-associated changes. These results indicate that in vivo selection occurs for HIV-1 envelope glycoproteins with variable loop conformations that restrict the access of antibodies to immunogenic neutralization epitopes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Human Retrovirol, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Human Retrovirol, Dept Canc Immunol & AIDS,Dept Pathol, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI031783, AI33832, AI31783, R01 AI033832] NR 64 TC 43 Z9 43 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 OCT PY 1999 VL 73 IS 10 BP 8873 EP 8879 PG 7 WC Virology SC Virology GA 235QP UT WOS:000082554300108 PM 10482646 ER PT J AU Fortinsky, RH Covinsky, KE Palmer, RM Landefeld, CS AF Fortinsky, RH Covinsky, KE Palmer, RM Landefeld, CS TI Effects of functional status changes before and during hospitalization on nursing home admission of older adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID ACUTE MEDICAL ILLNESS; LONG-TERM-CARE; OUTCOMES; RISK; INSTITUTIONALIZATION; PLACEMENT; PREDICTORS; MORBIDITY; DECLINE; IMPROVE AB Background. Functional status changes before and during hospitalization may have important effects on outcomes in older adults, but these effects are not well understood. We determined the influence of functional status changes on the risk of nursing home (NH) admission after hospitalization. Methods. Subjects were 551 general medical patients greater than or equal to 70 years old (66% female; mean age = 80 years) admitted from home to a large Midwestern teaching hospital. Functional status change measures were based on patients' need for assistance in five personal activities of daily living (ADL) 2 weeks prior to hospital admission, the day of admission, and the day of discharge. Sociodemographic and clinical characteristics were included in multivariate models predicting NH admission. Results. Functional status change categories were: stable in function before and during hospitalization (45% of study patients): decline in function before and improvement during hospitalization (26%); stable before and decline during hospitalization (15%): decline before and no improvement during hospitalization (13%). In multivariate analyses, patients in the: decline-no improvement group (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.46-6.96) and patients in the stable-decline group (OR = 2.77; 95% CI = 1.29-5.96) were at greater risk for NH admission than patients in the stable-stable group. In a multivariate model that controlled for ADL function at hospital discharge, functional status change was no longer statistically significantly associated with NH admission. Conclusions. Discharge function is a key risk factor for NH admission among hospitalized older adults. Because functional status changes before and during hospitalization are key determinants of discharge function, they provide important clues about the potential to modify that risk. Functional recovery during a hospital stay after prior functional decline, and prevention of in-hospital functional decline after prior functional stability, are important targets for clinical intervention to minimize the risk of NH admission. C1 Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Div Geriatr, Farmington, CT 06030 USA. Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. Cleveland Clin Fdn, Geriatr Med Sect, Cleveland, OH 44195 USA. RP Fortinsky, RH (reprint author), Univ Connecticut, Ctr Hlth, Ctr Aging, 263 Farmington Ave, Farmington, CT 06030 USA. FU NIA NIH HHS [1K08AG00714-03, AG-10418-05] NR 26 TC 105 Z9 106 U1 7 U2 9 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 OCT PY 1999 VL 54 IS 10 BP M521 EP M526 DI 10.1093/gerona/54.10.M521 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XK UT WOS:000088043800013 PM 10568535 ER PT J AU Kaelin, W AF Kaelin, W TI The cdk/pRB/E2F pathway in human cancer SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract ID RETINOBLASTOMA PROTEIN; CELL-CYCLE; E2F C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 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 OCT PY 1999 VL 56 IS 4 BP 1183 EP 1183 DI 10.1046/j.1523-1755.1999.0560041183.x PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 237GV UT WOS:000082648200003 ER PT J AU Eggers, PW Gohdes, D Pugh, J AF Eggers, PW Gohdes, D Pugh, J TI Nontraumatic lower extremity amputations in the Medicare end-stage renal disease population SO KIDNEY INTERNATIONAL LA English DT Article DE diabetic nephropathy; peripheral vascular disease; leg amputation; ulceration; gangrene ID DIABETES-RELATED AMPUTATIONS; RISK-FACTORS; LIMB AMPUTATION; PIMA-INDIANS; FOOT; PREVENTION; EPIDEMIOLOGY; NETHERLANDS; MANAGEMENT; REVASCULARIZATION AB Background Nontraumatic lower limb amputation is a serious complication of both diabetic neuropathy and peripheral vascular disease. Many people with end-stage renal disease (ESRD) suffer from advanced progression of these diseases. This study presents descriptive information on the rate of lower limb amputation among people with ESRD who are covered by the Medicare program. Methods. Using hospital bill data for the years 1991 through 1994 from the Health Care Financing Administration's ESRD program management and medical information system (PMMIS), amputations were based on ICDB coding. These hospitalizations were then linked back to the PMMIS enrollment database for calculation of rates. Results. The rate of lower limb amputation increased during the four-year period from 4.8 per 100 person years in 1991 to 6.2 in 1994. Among persons whose renal failure was attributed to diabetic nephropathy, the rates in 1991 and 1994 were 11.8 and 13.8, respectively. The rate among diabetic persons with ESRD was 10 times as great as among the diabetic population at large. Two thirds died within two years following the first amputation. Conclusions. The ESRD population is at an extremely high risk of lower limb amputation. Coordinated programs to screen for high-risk feet and to provide regular foot care for those at high risk combined with guidelines for treatment and referral of ulceration are needed. C1 HealthCare Financing Adm, Div Hlth Informat & Outcomes, Baltimore, MD USA. Mid S Fdn Med Care, Memphis, TN USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Eggers, PW (reprint author), HealthCare Financing Adm, Div Beneficiary Res, 7500 Secur Blvd,C-3-19-07, Baltimore, MD USA. OI Pugh, Jacqueline/0000-0003-4933-141X NR 47 TC 128 Z9 133 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1999 VL 56 IS 4 BP 1524 EP 1533 DI 10.1046/j.1523-1755.1999.00668.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 237GV UT WOS:000082648200060 PM 10504504 ER PT J AU Merchant, SN AF Merchant, SN TI A method for quantitative assessment of vestibular otopathology SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Laryngological-Rhinological-and-Otological-Society CY APR 26-28, 1999 CL PALM DESERT, CALIFORNIA SP Amer Laryngol Rhinol & Otol Soc DE vestibular system; temporal bone; pathology; hair cells ID HAIR-CELLS; EPITHELIA; PATTERNS; NEURONS; NERVE AB Background Quantitative studies of the vestibular system using serial sections from human temporal bones have been Limited because it has been generally difficult to reliably differentiate hair cells from supporting cells and type I from type II hair cells. Objectives: 1, To develop a new method to overcome the above limitations and permit quantitative assessments of types I and II vestibular hair cells in archival temporal bone sections. 2, To demonstrate that this method is reliable, valid, and repeatable. 3, To describe the advantages of this method compared with other traditional techniques. 4, To discuss the potential of this method to provide new insight into the etiology, pathology, and pathophysiology of vestibular disorders. Study Design Examination of archival human temporal sections prepared for conventional Light microscopy. Methods: The method used Nomarski (differential interference contrast) microscopy to permit visualization of the cuticular plate and stereociliary bundle, to allow unambiguous identification of hair cells. Types I and II hair cells were distinguished by their morphological characteristics. The method was used to measure the density of types I and II hair cells in each vestibular sense organ. Raw-density counts were corrected for potential double counting using Abercrombie's formula. Results: Intrarater and interrater reliability was strong as judged by high Pearson and Spearman correlation values (P <.01), Abercrombie's formula was shown Do be valid by comparison with counts made by an unbiased calibration technique using the optical disector principle (correlation coefficients > 0.9, P <.01), Conclusions: The method described in this report has several advantages when compared with alternative techniques such as surface preparations. The method is applicable to archival bones, permits simultaneous evaluation of the rest of the labyrinth, is relatively inexpensive, and does not preclude other techniques of study (e.g., polymerase chain reaction and immunostaining). Case studies of temporal bones with aminoglycoside ototoxicity and Meniere's disease are used to show how this method has the potential to provide new insight into the pathology and pathophysiology of vestibular disorders. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 36 TC 36 Z9 36 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 1999 VL 109 IS 10 BP 1560 EP 1569 DI 10.1097/00005537-199910000-00004 PG 10 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 244KL UT WOS:000083050300004 PM 10522922 ER PT J AU White, WM Rajadhyaksha, M Gonzalez, S Fabian, RL Anderson, RR AF White, WM Rajadhyaksha, M Gonzalez, S Fabian, RL Anderson, RR TI Noninvasive imaging of human oral mucosa in vivo by confocal reflectance microscopy SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 13-16, 1998 CL SAN ANTONIO, TEXAS SP Amer Acad Otolaryngol Head & Neck Surg DE human; imaging/noninvasive; blood flow/microvasculature; microscopy; confocal; mouth mucosa; anatomy; histology; chemistry; cytology ID SCANNING LASER OPHTHALMOSCOPE; HUMAN SKIN; BIOPSY AB Objectives/Hypothesis: To study the microscopic anatomy of normal oral tissues in vivo using confocal reflectance microscopy (CRM), This novel and noninvasive imaging modality can define and characterize healthy oral mucosa and thus this work serves as the foundation for studying oral diseases in vivo. Study Design: This was a pilot observational cohort study comparing noninvasive CRM images with histology, Materials and Methods: Lip and tongue mucosa were imaged by CRM in six healthy human subjects. In CRM living tissue is illuminated by a laser source and backscattered (or reflected) light is collected by a detector, Image contrast is determined by natural differences in refractive indices of organelles and other subcellular structures within the tissues. Gray-scale images were displayed in real-time on a video monitor and represented horizontal (en face) optical sections through the tissue. Motion of the oral tissue relative to the objective lens was minimized with a tissue stabilizer, After imaging, biopsies were taken from the same site of lip mucosa to correlate noninvasive confocal images with conventional histology, Results: Confocal images correlated well with conventional histology, both qualitatively (visual analysis) and quantitatively (stereology), Imaging was possible up to depths of 490 and 250 mu m in the lip and tongue, respectively. Cells and organelles including nuclei, circulating blood cells, and extracellular matrix were clearly observed. Conclusion: CRM provides details of normal human oral mucosa at the cellular level without the artifacts of histological processing, and thus has the potential for further development and use in clinical practice as a diagnostic tool for the early detection of oral cancer and precancer. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Head & Neck Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Lucid Inc, Henrietta, NY USA. RP Fabian, RL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Head & Neck Serv, 243 Charles St, Boston, MA 02114 USA. NR 41 TC 80 Z9 80 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 1999 VL 109 IS 10 BP 1709 EP 1717 DI 10.1097/00005537-199910000-00029 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 244KL UT WOS:000083050300029 PM 10522947 ER PT J AU Perumpanani, AJ Norbury, J AF Perumpanani, AJ Norbury, J TI Numerical interactions of random and directed motility during cancer invasion SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE mixed hyperbolic parabolic; cancer invasion; operator splitting ID MATHEMATICAL-MODELS; TUMOR-GROWTH; ANGIOGENESIS; CELLS; CHEMOTAXIS; SPHEROIDS; SCHEMES; MATRIX AB The continuum modelling of cell migration during cancer invasion results in the coupling of parabolic and hyperbolic partial differential equations (PDEs) arising from the random motility of normal tissue and the directed movement up substrate gradients of malignant cells. The numerical solution of such systems of equations require different stability criteria being simultaneously satisfied. We show that in such a coupled system, the origins of numerical instability can be identified by analyzing the fastest growing mode in a numerically unstable solution. In general, stability can be achieved by choosing an appropriate grid size representing the more stringent of the conditions for hyperbolic and parabolic stability. However, this induces variable degrees of numerical diffusion because of a changing CFL (Courant, Friedrichs, and Lewy) number. Solving the hyperbolic and parabolic PDEs on separate grids results in a better convergence of the solution. Finally, we discuss the use of higher-order schemes for the solution of such problems. Cancer modelling brings together directed and random motility in a unique way thereby presenting interesting new numerical problems. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Cambridge, MA 02139 USA. Univ Oxford, Inst Math, Oxford OX3 9DU, England. RP Perumpanani, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Bldg 1400 W,1 Kendall Sq, Cambridge, MA 02139 USA. NR 28 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD OCT PY 1999 VL 30 IS 7-8 BP 123 EP 133 DI 10.1016/S0895-7177(99)00169-7 PG 11 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 244KA UT WOS:000083049300011 ER PT J AU Nickerson, CAE AF Nickerson, CAE TI Assessing convergent validity of health-state utilities obtained using different scaling methods SO MEDICAL DECISION MAKING LA English DT Article DE convergent validity; equivalence technique; health-state preferences; health-state utilities; magnitude estimation; person tradeoff; rating scale; scaling; standard gamble; time tradeoff; willingness-to-pay ID QUALITY-OF-LIFE; TIME TRADE-OFF; COST-EFFECTIVENESS ANALYSIS; MEDICAL DECISION-MAKING; VISUAL ANALOG SCALE; WILLINGNESS-TO-PAY; PATIENT UTILITIES; STANDARD-GAMBLE; MAGNITUDE ESTIMATION; OUTCOME MEASURES AB A number of empirical studies have attempted to assess the convergent validity of health-state utilities obtained using two or more scaling methods (standard gamble, time tradeoff, rating scale, magnitude estimation, equivalence technique, and willingness-to-pay). The data from these studies can be mapped onto an N x K matrix, where Nand K are the numbers of respondents and health states, respectively, and each matrix cell consists of a pair of health-state utilities, one obtained using scaling method X and the other obtained using scaling method Y. The Pearson's r assessing convergent validity can then be computed as 1) the unraveled correlation over all N x K data pairs, 2) the mean within-respondent correlation, 3) the mean within-health-state correlation, or 4) the correlation of the across-respondents means. These four different ways of computing the correlation do not necessarily yield the same results. The appropriateness of each method of computing the correlation is considered. C1 Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia Vet Affairs Med Ctr,Sect Gen Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Operat & Informat Management, Philadelphia, PA 19104 USA. RP Nickerson, CAE (reprint author), Univ Illinois, Dept Psychol, M-C 716,603 E Daniel St, Champaign, IL 61820 USA. NR 62 TC 6 Z9 6 U1 2 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD OCT-DEC PY 1999 VL 19 IS 4 BP 487 EP 498 DI 10.1177/0272989X9901900417 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 244MV UT WOS:000083056100017 PM 10520687 ER PT J AU Biggs, PJ Nogueira, IP AF Biggs, PJ Nogueira, IP TI Measurement of the collection efficiency of a large volume spherical ionization chamber in megavoltage therapy beams SO MEDICAL PHYSICS LA English DT Article DE ionization chamber; megavoltage x-ray beams; ion chamber collection efficiency; two-voltage technique; Boag theory ID ION RECOMBINATION; PULSED RADIATION; ELECTRON AB The collection efficiency of a 5.7 cm diameter spherical ionization chamber has been measured in 4 MV and 10 MV x-ray beams at various distances from the source. This chamber was found to have a substantial inefficiency due to its large volume and the high dose rate and pulsed nature of the therapy beams. It was also found that the efficiency depended on the dose rate of the machine because the inter-pulse separation time of the linac is significantly less than the ion transit-time for this chamber. Thus, ionization from more than one beam pulse is collected by the chamber at the same time. The efficiency was determined using three techniques (i) the two-voltage technique, (ii) the voltage extrapolation technique and (iii) a method originally devised for determining the collection efficiency of large volume ionization chambers in diagnostic radiology. The results show that methods (ii) and (iii) agree well, but that the two-voltage technique predicts a much lower efficiency. At about 4 m from the source, the collection efficiency for this chamber varied between 98% and 97% for dose rates between 50 and 250 cGy/min for 4 MV and between 97% and 90% for dose rates between 100 and 600 cGy/min for 10 MV. At isocenter, the comparable figures were 78% and 56% respectively for 4 MV and 65% and 38% respectively for 10 MV. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)01110-4]. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Div Radiat Biophys, Boston, MA 02114 USA. RP Biggs, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Div Radiat Biophys, Boston, MA 02114 USA. NR 15 TC 4 Z9 4 U1 1 U2 3 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 1999 VL 26 IS 10 BP 2107 EP 2112 DI 10.1118/1.598726 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 247CD UT WOS:000083202300007 PM 10535627 ER PT J AU Sykes, M AF Sykes, M TI Inducing tolerance for pig-to-primate xenografts SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Ramon-Areces-Foundation International Meeting on Xenotransplantation - a Solution for the Future CY FEB 09-10, 1999 CL MADRID, SPAIN SP Ramon Areces Fdn C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD OCT PY 1999 VL 21 IS 8 BP 566 EP 567 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 257MB UT WOS:000083784700013 ER PT J AU Hamid, N Gustavsson, A Andersson, K McGee, K Persson, C Rudd, CE Fallman, M AF Hamid, N Gustavsson, A Andersson, K McGee, K Persson, C Rudd, CE Fallman, M TI YopH dephosphorylates Cas and Fyn-binding protein in macrophages SO MICROBIAL PATHOGENESIS LA English DT Article DE Yersinia pseudotuberculosis; phagocytosis; Cas; FYB; focal complexes; PTPase ID FOCAL ADHESION KINASE; YERSINIA TYROSINE PHOSPHATASE; VIRULENCE DETERMINANT; CELL-ADHESION; SIGNAL-TRANSDUCTION; MAMMALIAN-CELLS; TARGET-CELL; P130(CAS); PSEUDOTUBERCULOSIS; PHOSPHORYLATION AB The tyrosine phosphatase YopH is an essential virulence effector of pathogenic Yersinia spp. YopH, which is translocated from extracellularly located bacteria into interacting target cells, blocks phagocytosis by professional phagocytes. We show here that immunoprecipitation of YopH from lysates of J774 cells infected with Y: pseudotuberculosis expressing an inactive form of YopH resulted in co-precipitation of certain phosphotyrosine proteins. The association between the inactive YopH and phosphotyrosine proteins in the 120 kDa range was rapid and could be detected after 2 min of infection. The proteins were identified as the docking proteins Cas and Fyn-binding protein (FYB). Upon infection of J774 cells with Y: pseudotuberculosis lacking YopH expression both of these proteins became tyrosine phosphorylated. Moreover, this infection caused recruitment of Cas to peripheral focal complexes, and FYB was relocalized to areas surrounding these structures. Both Cas and FYB became dephosphorylated upon infection with Y. pseudotuberculosis expressing active YopH, and this was associated with disruption of focal complexes. With regard to the previous identification of Cas and focal complexes as targets of YopH in HeLa cells, the present study supports an important role for these targets in a general mechanism of bacterial uptake. C1 Umea Univ, Dept Cell & Mol Biol, S-90187 Umea, Sweden. Linkoping Univ, Dept Med Microbiol, S-58185 Linkoping, Sweden. Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Fallman, M (reprint author), Umea Univ, Dept Cell & Mol Biol, S-90187 Umea, Sweden. RI McGee, Karen/B-4937-2009 NR 49 TC 90 Z9 92 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD OCT PY 1999 VL 27 IS 4 BP 231 EP 242 DI 10.1006/mpat.1999.0301 PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA 245EK UT WOS:000083093100006 PM 10502464 ER PT J AU Laj, A Lee, JM Yang, WM DeCaprio, JA Kaelin, WG Seto, E Branton, PE AF Laj, A Lee, JM Yang, WM DeCaprio, JA Kaelin, WG Seto, E Branton, PE TI RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE ARREST; TRANSCRIPTIONAL REPRESSION; ADENOVIRUS E1A; GENE-PRODUCT; DOMAIN; BINDING; E2F1; ACETYLATION; PROMOTER; CLONING AB Retinoblastoma (RB) tumor suppressor family proteins block cell proliferation in part by repressing certain E2F-specific promoters, Both histone deacetylase (HDAC)-dependent and -independent repression activities are associated with the RE "pocket." The mechanism by which these two repression functions occupy the pocket is unknown. A known RE-binding protein, RBP1, was previously found by our group to be an active corepressor which, if overexpressed, represses E2F-mediated transcription via its association with the pocket. We show here that RBP1 contains two repression domains, one of which binds all three known HDACs and represses them in an HDAC-dependent manner while the other domain functions independently of the HDACs. Thus, RE family members repress transcription by recruiting RBP1 to the pocket. RBP1, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. C1 McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada. Univ S Florida, Mol Oncol Program, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Branton, PE (reprint author), McGill Univ, Dept Biochem, McIntyre Med Bldg,3655 Drummond St, Montreal, PQ H3G 1Y6, Canada. EM branton@med.mcgill.ca NR 49 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 6632 EP 6641 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200016 ER PT J AU Adler, HT Chinery, R Wu, DY Kussick, SJ Payne, JM Fornace, AJ Tkachuk, DC AF Adler, HT Chinery, R Wu, DY Kussick, SJ Payne, JM Fornace, AJ Tkachuk, DC TI Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and associate with the GADD34 and hSNF5/INI1 proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HERPES-SIMPLEX VIRUS; YEAST SWI/SNF COMPLEX; DAMAGE-INDUCIBLE GENE; SWI-SNF COMPLEX; 11Q23 REARRANGEMENTS; MLL GENE; CHROMOSOMAL TRANSLOCATIONS; DROSOPHILA-TRITHORAX; TUMOR PROGRESSION AB One of the most common chromosomal abnormalities in acute leukemia is a reciprocal translocation involving the HRX gene (also called MLL, ALL-1, or HTRX) at chromosomal locus 11q23, resulting in the formation of HRX fusion proteins. Using the yeast two-hybrid system and human cell culture coimmunoprecipitation experiments, we show here that HRX proteins interact directly with the GADD34 protein. We have found that transfected cells overexpressing GADD34 display a significant increase in apoptosis after treatment with ionizing radiation, indicating that GADD34 expression not only correlates with apoptosis but also can enhance apoptosis. The amino-terminal third of the GADD34 protein was necessary for this observed increase in apoptosis. Furthermore, coexpression of three different HRX fusion proteins (HRX-ENL, HRX-AF9, and HRX-ELL) had an anti-apoptotic effect, abrogating GADD34-induced apoptosis. In contrast, expression of wild-type HRX gave rise to an increase in apoptosis. The difference observed here between wild-type HRX and the leukemic HRX fusion proteins suggests that inhibition of GADD34-mediated apoptosis may be important to leukemogenesis, We also show here that GADD34 binds the human SNF5/INI1 protein, a member of the SNF/SWI complex: that can remodel chromatin and activate transcription. These studies demonstrate, for the first time, a gain of function for leukemic HRX fusion proteins compared to wild-type protein. We propose that the role of HRX fusion proteins as negative regulators of post-DNA-damage-induced apoptosis is important to leukemia progression. C1 VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA. NCI, Div Basic Sci, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Tkachuk, DC (reprint author), VA Puget Sound Hlth Care Syst, Dept Pathol, 1660 S Columbian Way,Mail Stop 113, Seattle, WA 98108 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [CA73969, CA 68485, P30 CA068485] NR 60 TC 112 Z9 119 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1999 VL 19 IS 10 BP 7050 EP 7060 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 237MM UT WOS:000082660200056 PM 10490642 ER PT J AU Poy, F Yaffe, MB Sayos, J Saxena, K Morra, M Sumegi, J Cantley, LC Terhorst, C Eck, MJ AF Poy, F Yaffe, MB Sayos, J Saxena, K Morra, M Sumegi, J Cantley, LC Terhorst, C Eck, MJ TI Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition SO MOLECULAR CELL LA English DT Article ID LINKED LYMPHOPROLIFERATIVE-DISEASE; T-CELL ACTIVATION; ENCODING GENE; REFINEMENT; MUTATIONS; RECEPTOR; MOLECULE; PEPTIDE; BINDING; SLAM AB SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TlpYXX(V/I). C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. RI Sayos, Joan/B-6119-2009; Cantley, Lewis/D-1800-2014 OI Sayos, Joan/0000-0002-4664-3461; Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM056203] NR 29 TC 178 Z9 183 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD OCT PY 1999 VL 4 IS 4 BP 555 EP 561 DI 10.1016/S1097-2765(00)80206-3 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249WR UT WOS:000083356700010 PM 10549287 ER PT J AU Rosen, ED Sarraf, P Troy, AE Bradwin, G Moore, K Milstone, DS Spiegelman, BM Mortensen, RM AF Rosen, ED Sarraf, P Troy, AE Bradwin, G Moore, K Milstone, DS Spiegelman, BM Mortensen, RM TI PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro SO MOLECULAR CELL LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; EMBRYONIC STEM-CELLS; ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; CANCER CELLS; OXIDIZED LDL; IN-VITRO; LIGAND; INDUCTION; GROWTH AB The process of adipogenesis is known to involve the interplay of several transcription factors. Activation of one of these factors, the nuclear hormone receptor PPAR gamma, is known to promote fat cell differentiation in vitro. Whether PPAR gamma is required for this process in vivo has remained an open question because a viable loss-of-function model for PPAR gamma has been lacking. We demonstrate here that mice chimeric for wild-type and PPAR gamma null cells show little or no contribution of null cells to adipose tissue, whereas most other organs examined do not require PPAR gamma for proper development. In vitro, the differentiation of ES cells into fat is shown to be dependent on PPAR gamma gene dosage. These data provide direct evidence that PPAR gamma is essential for the formation of fat. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Vasc Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. FU NHLBI NIH HHS [R01-HL58606]; NIDDK NIH HHS [KO8-DK02535, R37 DK-31405] NR 27 TC 1181 Z9 1243 U1 8 U2 52 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD OCT PY 1999 VL 4 IS 4 BP 611 EP 617 DI 10.1016/S1097-2765(00)80211-7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249WR UT WOS:000083356700015 PM 10549292 ER PT J AU Solow, BT Harada, S Goldstein, BJ Smith, JA White, MF Jarett, L AF Solow, BT Harada, S Goldstein, BJ Smith, JA White, MF Jarett, L TI Differential modulation of the tyrosine phosphorylation state of the insulin receptor by IRS (insulin receptor subunit) proteins SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SRC HOMOLOGY-2 DOMAINS; DEPENDENT DIABETES-MELLITUS; PHOSPHATIDYLINOSITOL 3-KINASE; INTACT-CELLS; PHOSPHATASE LAR; IN-VITRO; SIGNAL-TRANSDUCTION; KINASE-ACTIVITY; SUBSTRATE-1; ACTIVATION AB In response to insulin, tyrosine kinase activity of the insulin receptor is stimulated, leading to autophosphorylation and tyrosine phosphorylation of proteins including insulin receptor subunit (IRS)-1, IRS-2, and Shc. Phosphorylation of these proteins leads to activation of downstream events that mediate insulin action. Insulin receptor kinase activity is requisite for the biological effects of insulin, and understanding regulation of insulin receptor phosphorylation and kinase activity is essential to understanding insulin action. Receptor tyrosine kinase activity may be altered by direct changes in tyrosine kinase activity, itself, or by dephosphorylation of the insulin receptor by protein-tyrosine phosphatases. After 1 min of insulin stimulation, the insulin receptor was tyrosine phosphorylated 8-fold more and Shc was phosphorylated 50% less in 32D cells containing both IRS-1 and insulin receptors (32D/IR+IRS-1) than in 32D cells containing only insulin receptors (32D/IR), insulin receptors and IRS-2 (32D/IR+IRS-2), or insulin receptors and a form of IRS-1 that cannot be phosphorylated on tyrosine residues (32D/IR+IRS-1(F18)). Therefore, IRS-1 and IRS-2 appeared to have different effects an insulin receptor phosphorylation and downstream signaling. Preincubation of cells with pervanadate greatly decreased protein-tyrosine phosphatase activity in all four cell lines. After pervanadate treatment, tyrosine phosphorylation of insulin receptors in insulin-treated 32D/IR, 32D/IR+IRS-2, and 32D/IR+IRS-1(F18) cells was markedly increased, but pervanadate had no effect on insulin receptor phosphorylation in 32D/IR+IRS-1 cells. The presence of tyrosine-phosphorylated IRS-1 appears to increase insulin receptor tyrosine phosphorylation and potentially tyrosine kinase activity via inhibition of protein-tyrosine phosphatase(s). This effect of IRS-1 on insulin receptor phosphorylation is unique to IRS-1, as IRS-2 had no effect on insulin receptor tyrosine phosphorylation. Therefore, IRS-1 and IRS-2 appear to function differently in their effects on signaling downstream of the insulin receptor. IRS-1 may play a major role in regulating insulin receptor phosphorylation and enhancing downstream signaling after insulin stimulation. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dorrance H Hamilton Res Labs, Div Endocrinol Diabet & Metab Dis,Dept Med, Philadelphia, PA 19107 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Jarett, L (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, B103 Richards Bldg,37th & Hamilton Walk, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [5T32DK-07314]; PHS HHS [R01 43396] NR 63 TC 19 Z9 20 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1999 VL 13 IS 10 BP 1784 EP 1798 DI 10.1210/me.13.10.1784 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 242AF UT WOS:000082915500014 PM 10517679 ER PT J AU Song, WJ Sullivan, MG Legare, RD Hutchings, S Tan, XL Kufrin, D Ratajczak, J Resende, IC Haworth, C Hock, R Loh, M Felix, C Roy, DC Busque, L Kurnit, D Willman, C Gewirtz, AM Speck, NA Bushweller, JH Li, FP Gardiner, K Poncz, M Maris, JM Gilliland, DG AF Song, WJ Sullivan, MG Legare, RD Hutchings, S Tan, XL Kufrin, D Ratajczak, J Resende, IC Haworth, C Hock, R Loh, M Felix, C Roy, DC Busque, L Kurnit, D Willman, C Gewirtz, AM Speck, NA Bushweller, JH Li, FP Gardiner, K Poncz, M Maris, JM Gilliland, DG TI Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia SO NATURE GENETICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PLATELET DISORDER; TRANSCRIPTIONAL ACTIVATION; CHROMOSOMAL TRANSLOCATIONS; DEFINITIVE HEMATOPOIESIS; FUSION TRANSCRIPT; GENE; AML1; T(12-21) AB Familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML, MIM 601399) is an autosomal dominant disorder characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukaemia (AML). Informative recombination events in 6 FPD/AML pedigrees with evidence of linkage to markers on chromosome 21q identified an 880-kb interval containing the disease gene. Mutational analysis of regional candidate genes showed nonsense mutations or intragenic deletion of one allele of the haematopoietic transcription factor CBFA2 (formerly AML1) that co-segregated with the disease in four FPD/AML pedigrees. We identified heterozygous CBFA2 missense mutations that co-segregated with the disease in the remaining two FPD/AML pedigrees at phylogenetically conserved amino acids R166 and R201, respectively. Analysis of bone marrow or peripheral blood cells from affected FPD/AML individuals showed a decrement in megakaryocyte colony formation, demonstrating that CBFA2 dosage affects megakaryopoiesis. Our findings support a model for FPD/AML in which haploinsufficiency of CBFA2 causes an autosomal dominant congenital platelet defect and predisposes to the acquisition of additional mutations that cause leukaemia. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brown Univ, Women & Infants Hosp, Program Womens Oncol, Providence, RI USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Leicester Royal Infirm, Leicester, Leics, England. St Vincent Hosp, Childrens Ctr Canc & Blood Dis, Indianapolis, IN USA. Univ Montreal, Maisonneuve Rosemont Hosp, Dept Hematol, Montreal, PQ H3C 3J7, Canada. Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ H3C 3J7, Canada. Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Ctr Canc, Albuquerque, NM 87131 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Biochem, Hanover, NH 03756 USA. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA USA. Eleanor Roosevelt Inst, Denver, CO USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA78545, R01 CA81932]; NIAID NIH HHS [R29 AI39536] NR 49 TC 638 Z9 652 U1 3 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1999 VL 23 IS 2 BP 166 EP 175 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 240LM UT WOS:000082827500015 PM 10508512 ER PT J AU Cho, RJ Mindrinos, M Richards, DR Sapolsky, RJ Anderson, M Drenkard, E Dewdney, L Reuber, TL Stammers, M Federspiel, N Theologis, A Yang, WH Hubbell, E Au, M Chung, EY Lashkari, D Lemieux, B Dean, C Lipshutz, RJ Ausubel, FM Davis, RW Oefner, PJ AF Cho, RJ Mindrinos, M Richards, DR Sapolsky, RJ Anderson, M Drenkard, E Dewdney, L Reuber, TL Stammers, M Federspiel, N Theologis, A Yang, WH Hubbell, E Au, M Chung, EY Lashkari, D Lemieux, B Dean, C Lipshutz, RJ Ausubel, FM Davis, RW Oefner, PJ TI Genome-wide mapping with biallelic markers in Arabidopsis thaliana SO NATURE GENETICS LA English DT Article ID DENSITY OLIGONUCLEOTIDE ARRAYS; MUTATION DETECTION; YEAST GENOME; PLANT; DNA; HYBRIDIZATION; POLYMORPHISMS; INFORMATION; LINKAGE; RPS2 AB Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms(1,2). Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations(3-6). The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment(3,7). It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination(8-11) to disease resistance(12,13) have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic: map consisting of easily genotyped DNA markers(14). We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F-2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism. C1 Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Genencor, Palo Alto, CA 94304 USA. Univ Nottingham, Div Plant Sci Univ Pk, Nottingham Arabidopsis Stock Ctr, Nottingham NG7 2RD, England. John Innes Ctr Plant Sci Res, Dept Mol Genet, Norwich NR4 7UH, Norfolk, England. Stanford DNA Sequencing & Technol Ctr, Palo Alto, CA 94304 USA. Plant Gene Express Ctr Genome Sequencing Lab, Albany, CA 94710 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Incyte Pharmaceut, Fremont, CA 94555 USA. York Univ, Dept Biol, N York, ON M3J 1P3, Canada. RP Oefner, PJ (reprint author), Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. RI Oefner, Peter/K-1116-2016 OI Oefner, Peter/0000-0002-1499-3977 FU NHGRI NIH HHS [3R37 HG00198-23] NR 26 TC 195 Z9 220 U1 3 U2 22 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1999 VL 23 IS 2 BP 203 EP 207 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 240LM UT WOS:000082827500021 PM 10508518 ER PT J AU Hahn, WC Stewart, SA Brooks, MW York, SG Eaton, E Kurachi, A Beijersbergen, RL Knoll, JHM Meyerson, M Weinberg, RA AF Hahn, WC Stewart, SA Brooks, MW York, SG Eaton, E Kurachi, A Beijersbergen, RL Knoll, JHM Meyerson, M Weinberg, RA TI Inhibition of telomerase limits the growth of human cancer cells SO NATURE MEDICINE LA English DT Article ID CATALYTIC SUBUNIT GENE; HUMAN FIBROBLASTS; IMMORTAL CELLS; RNA COMPONENT; FISSION YEAST; LIFE-SPAN; IN-VITRO; P53; SENESCENCE; APOPTOSIS AB Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. In most human somatic cells, telomerase expression is repressed, and telomeres shorten progressively with each cell division. In contrast, most human tumors express telomerase, resulting in stabilized telomere length. These observations indicate that telomere maintenance is essential to the proliferation of tumor cells. We show here that expression of a mutant catalytic subunit of human telomerase results in complete inhibition of telomerase activity, reduction in telomere length and death of tumor cells. Moreover, expression of this mutant telomerase eliminated tumorigenicity in vivo. These observations demonstrate that disruption of telomere maintenance limits cellular lifespan in human cancer cells, thus validating human telomerase reverse transcriptase as an important target for the development of anti-neoplastic therapies. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol,Cytogenet Serv, Boston, MA 02115 USA. RP Weinberg, RA (reprint author), MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Meyerson, Matthew/E-7123-2012; Stewart, Sheila/C-5213-2012 NR 57 TC 777 Z9 815 U1 7 U2 57 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 1999 VL 5 IS 10 BP 1164 EP 1170 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 242GY UT WOS:000082933200043 PM 10502820 ER PT J AU Gohongi, T Fukumura, D Boucher, Y Yun, CO Soff, GA Compton, C Todoroki, T Jain, RK AF Gohongi, T Fukumura, D Boucher, Y Yun, CO Soff, GA Compton, C Todoroki, T Jain, RK TI Tumor-host interactions in the gallbladder suppress distal angiogenesis and tumor growth: Involvement of transforming growth factor beta 1 SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL-CELLS; GROWTH-FACTOR-BETA-1; CANCER; CARCINOMA; MICROENVIRONMENT; PROLIFERATION; METASTASIS; EXPRESSION; MICE AB Angiogenesis inhibitors produced by a primary tumor can create a systemic anti-angiogenic environment and maintain metastatic tumor cells in a state of dormancy(1,2). We show here that the gallbladder microenvironment modulates the production of transforming growth factor (TGF)-beta 1, a multifunctional cytokine that functions as an endogenous anti-angiogenic and antitumor factor in a cranial window preparation. We found that a wide variety of human gallbladder tumors express TGF-beta 1 irrespective of histologic type. We implanted a gel impregnated with basic fibroblast growth factor(3) or Mz-ChA-2 tumor in the cranial windows of mice without tumors or mice with subcutaneous or gallbladder tumors to study angiogenesis and tumor growth at a secondary site. Angiogenesis, leukocyte-endothelial interaction in vessels and tumor growth in the cranial window were substantially inhibited in mice with gallbladder tumors. The concentration of TGF-beta 1 in the plasma of mice with gallbladder tumors was 300% higher than that in the plasma of mice without tumors or with subcutaneous tumors. In contrast, there was no difference in the plasma levels of other anti- and pro-angiogenic factors. Treatment with neutralizing antibody against TGF-beta 1 reversed both angiogenesis suppression and inhibition of leukocyte rolling induced by gallbladder tumors. TGF-beta 1 also inhibited Mz-ChA-2 tumor cell proliferation. Our results indicate that the production of anti-angiogenesis/proliferation factors is regulated by tumor-host interactions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Univ Tsukuba, Inst Clin Med, Dept Surg, Tsukuba, Ibaraki 305, Japan. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RI Yun, Chae-Ok/P-3698-2015 FU NCI NIH HHS [R35-CA56591] NR 25 TC 107 Z9 109 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 1999 VL 5 IS 10 BP 1203 EP 1208 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 242GY UT WOS:000082933200050 PM 10502827 ER PT J AU Elangovan, L Felsenfeld, AJ Kleeman, CR AF Elangovan, L Felsenfeld, AJ Kleeman, CR TI Spontaneous resolution and recurrence of hypercalcemia in primary hyperparathyroidism - anecdotal observations with potential implications for parathyroid pathophysiology in renal disease SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcium; hypercalcemia; parathyroid hormone; parathyroid infarction; primary hyperparathyroidism ID RADIATION-ASSOCIATED HYPERPARATHYROIDISM; HORMONE GENE-EXPRESSION; SPONTANEOUS REMISSION; SPONTANEOUS INFARCTION; ADENOMA; ANGIOGENESIS; THERAPY; CALCIUM; CELLS C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 41 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 1999 VL 14 IS 10 BP 2323 EP 2327 DI 10.1093/ndt/14.10.2323 PG 5 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 243UU UT WOS:000083016300013 PM 10528653 ER PT J AU Kosinski, CM Cha, JH Young, AB Schwarz, M AF Kosinski, CM Cha, JH Young, AB Schwarz, M TI Chorea Huntington: Animal models direct the way to a better pathophysiological understanding and new therapeutical approaches SO NERVENARZT LA German DT Review DE Huntington's disease; transgenic mice; exitotoxicity; CAG-triplet diseases; neurodegeneration ID NEURONAL INTRANUCLEAR INCLUSIONS; DISEASE GENE; NEURODEGENERATIVE DISEASES; CAG REPEAT; 3-NITROPROPIONIC ACID; POLYGLUTAMINE TRACT; STRIATAL NEURONS; TRANSGENIC MICE; BRAIN; EXPRESSION AB Huntington's disease (HD) is member of a growing family of neurodegenerative diseases which are caused by a CAG-Triplet expansion in the coding region of their respective genes. The results of the research of the last years is very suggestive of a common pathomechanisms of all these diseases even though their clinical appearance may be quite different. The development of new animal models by transferring the human gene defect into the mouse genome has led to the finding of so-called intranuclear inclusion bodies. This new observation allowed to come closer to solving the problem how this genetic defect causes neurodegeneration. Recent studies on transgenic HD mice could also demonstrate a possible connection between the genetic defect and glutamate exitotoxicity in the neurodegenerative process of HD which had been emphasized by earlier animal models of the disease. Transgenic animal models of HD will have an important impact on the understanding of the disease mechanisms and may contribute to a faster development and testing of new therapeutic approaches. C1 Rhein Westfal TH Aachen, Fak Med, Neurol Klin, D-52074 Aachen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Dept Neurol, Boston, MA USA. RP Kosinski, CM (reprint author), Rhein Westfal TH Aachen, Fak Med, Neurol Klin, Pauwelsstr 30, D-52074 Aachen, Germany. NR 54 TC 7 Z9 7 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD OCT PY 1999 VL 70 IS 10 BP 878 EP 888 PG 15 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 249PA UT WOS:000083340400004 PM 10554779 ER PT J AU Persichetti, F Trettel, F Huang, CC Fraefel, C Timmers, HTM Gusella, JF MacDonald, ME AF Persichetti, F Trettel, F Huang, CC Fraefel, C Timmers, HTM Gusella, JF MacDonald, ME TI Mutant huntingtin forms in vivo complexes with distinct context-dependent conformations of the polyglutamine segment SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease; huntingtin; aggregation; polyglutamine; 1F8 mAb ID INTRANUCLEAR NEURONAL INCLUSIONS; SIMPLEX VIRUS TYPE-1; AGGREGATES IN-VITRO; GLUTAMINE REPEATS; NEURODEGENERATIVE DISEASES; TISSUE TRANSGLUTAMINASE; LOCALIZATION; EXPRESSION; MECHANISM; PROTEIN AB Huntington's disease (HD) is caused by an expanded glutamine tract, which confers a novel aggregation-promoting property on the 350-kDa huntingtin protein. Using specific antibodies, we have probed the structure of the polyglutamine segment in mutant huntingtin complexes formed in cell culture from either truncated or full-length protein, Complexes formed by a mutant amino terminal fragment most frequently entail a change in conformation that eliminates reactivity with the polyglutamine-specific mAb 1F8, coincident with production of insoluble aggregate. By contrast, complexes formed by the full-length mutant protein remain soluble and are invariably 1F8-reactive, indicating a soluble polyglutamine conformation. Therefore, aggregates in HD may form by different biochemical mechanisms that invoke different possibilities for the pathogenic process. If pathogenesis is triggered by a truncated fragment, it probably involves the formation of an insoluble aggregate. However, the observation of soluble complexes in which an HD-specific pathogenic conformation of the glutamine tract remains accessible suggests that pathogenesis could also be triggered at the level of full-length huntingtin by abnormal aggregation with normal or abnormal protein partners. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Univ Utrecht, Physiol Chem Lab, NL-3438 GD Utrecht, Netherlands. Univ Utrecht, Ctr Biomed Genet, NL-3438 GD Utrecht, Netherlands. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. OI trettel, flavia/0000-0002-7983-2955 FU NINDS NIH HHS [NS32765, NS16367] NR 34 TC 46 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 1999 VL 6 IS 5 BP 364 EP 375 DI 10.1006/nbdi.1999.0260 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 245YH UT WOS:000083135900006 PM 10527804 ER PT J AU Panzara, MA Gussoni, E Begovich, AB Murray, RS Zang, YQ Appel, SH Steinman, L Zhang, JW AF Panzara, MA Gussoni, E Begovich, AB Murray, RS Zang, YQ Appel, SH Steinman, L Zhang, JW TI T cell receptor BV gene rearrangements in the spinal cords and cerebrospinal fluid of patients with amyotrophic lateral sclerosis SO NEUROBIOLOGY OF DISEASE LA English DT Article DE neuromuscular diseases; amyotrophic lateral sclerosis; T-cell antigen receptors; polymerase chain reaction; cellular immunity ID MYELIN BASIC-PROTEIN; DUCHENNE MUSCULAR-DYSTROPHY; NONRADIOACTIVE OLIGONUCLEOTIDE PROBES; CALCIUM CHANNELS; SUPEROXIDE-DISMUTASE; SELECTIVE EXPANSION; ANTIGEN EXPRESSION; AUTOIMMUNE-DISEASE; AMPLIFIED DNA; SUPERANTIGENS AB Amyotrophic lateral sclerosis (ALS) is a fatal disorder whose etiology and pathogenesis remain unknown. Recent studies, however, have demonstrated the presence of inflammatory infiltrates within ALS spinal cord and suggested the possibility of an immune-mediated process in motor neuron degeneration. We have analyzed the diversity of T-cells in the spinal cord in ALS. Reverse transcriptase polymerase chain reaction (RT-PCR) with variable (V) region sequence specific oligonucleotide primers was used to amplify T-cell receptor (TCR)BV transcripts from spinal cords obtained at autopsy from patients with ALS, patients who died without inflammatory disease of the central nervous system, brains from patients with ALS, and brains from patients who died with inflammatory CNS disease. Sequencing was then performed on the amplified transcripts. An overall increase in the level of TCRBV 2 transcripts was detected in ALS specimens when compared to controls. This result was independent of the HLA genotype of the individual. Furthermore, enrichment of TCRBV2-positive T cells could be demonstrated in cerebrospinal fluid derived from patients with ALS, using PCR analysis and a T cell stimulation assay with toxic shock syndrome toxin-l (TSST-1), a V beta 2-specific superantigen. Our results suggest that an immunological process involving the specific expansion of V beta 2 TCR-positive T-cells may be important in the pathogenesis of ALS. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Childrens Hosp, Howard Hughes Med Inst, Div Genet, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Roche Mol Syst, Dept Human Genet, Alameda, CA 94501 USA. Rocky Mt MS Ctr, Englewood, CO 80150 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Vet Affairs Med Ctr, Neurol Serv, Houston, TX 77030 USA. RP Panzara, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM mpanzara@partners.org NR 63 TC 17 Z9 17 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 1999 VL 6 IS 5 BP 392 EP 405 DI 10.1006/nbdi.1999.0252 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 245YH UT WOS:000083135900008 PM 10527806 ER PT J AU Caplan, D AF Caplan, D TI Activating brain systems for syntax and semantics SO NEURON LA English DT Editorial Material ID COMPREHENSION; ANATOMY C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02116 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02116 USA. NR 8 TC 8 Z9 8 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1999 VL 24 IS 2 BP 292 EP 293 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 251BA UT WOS:000083423700004 PM 10571223 ER PT J AU Tritos, NA Maratos-Flier, E AF Tritos, NA Maratos-Flier, E TI Two important systems in energy homeostasis: melanocortins and melanin-concentrating hormone SO NEUROPEPTIDES LA English DT Article ID PROOPIOMELANOCORTIN MESSENGER-RNA; AGOUTI-RELATED PROTEIN; AUDITORY GATING PARADIGM; YELLOW A(Y) MUTATION; NEUROPEPTIDE-Y; ALPHA-MSH; FEEDING-BEHAVIOR; RAT HYPOTHALAMUS; BODY-WEIGHT; OBESE GENE AB Our understanding of the regulation of appetite and energy balance has advanced significantly over the past decade as several peptides, centrally or peripherally expressed, have been characterized and shown to profoundly influence food intake and energy expenditure.(1) The growing number of putative appetite-regulating neuropeptides includes peptides that are orexigenic (appetite-stimulating) signals and anorectic peptides. Neuropeptide Y (NPY), melanin concentrating hormone (MCH), orexins A and B, galanin, and agouti-related peptide (AgRP) all act to stimulate feeding while alpha-melanocyte stimulating hormone (alpha MSH), corticotropin releasing hormone (CRH), cholecystokinin (CCK), cocaine and amphetamine regulated transcript (CART), neurotensin, glucagon-like peptide 1 (GLP 1), and bombesin have anorectic actions.(1) Leptin, expressed in the periphery in white adipose tissue, acts in the CNS to modulate the expression of several of these hypothalamic peptides.(1) This creates a functional link between the adipose tissue and the brain that translates the information on body fat provided by leptin to input into energy balance regulating processes. In the current review we examine the significant role of the melanocortin system (alpha MSH, agouti and AgRP peptides, and their receptors and mahogany protein) and melanin concentrating hormone in the regulation of energy balance. (C) 1999 Harcourt Publishers Ltd. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Tritos, NA (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 98 TC 105 Z9 106 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD OCT PY 1999 VL 33 IS 5 BP 339 EP 349 DI 10.1054/npep.1999.0055 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 256UK UT WOS:000083744600003 PM 10657511 ER PT J AU Cha, JHJ Frey, AS Irizarry, MC Hyman, BT Young, AB Penney, JB AF Cha, JHJ Frey, AS Irizarry, MC Hyman, BT Young, AB Penney, JB TI Metabotropic receptors in transgenic mouse models of human neurodegenerative diseases SO NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT PY 1999 VL 38 IS 10 MA 34 BP A11 EP A11 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 238ZA UT WOS:000082743600053 ER PT J AU Orlando, LR Dunah, AW Standaert, DG Penney, JB Young, AB AF Orlando, LR Dunah, AW Standaert, DG Penney, JB Young, AB TI NMDA and metabotropic receptors regulate tyrosine phosphorylation of striatal glutamate receptors SO NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Program Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT PY 1999 VL 38 IS 10 MA 106 BP A33 EP A33 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 238ZA UT WOS:000082743600125 ER PT J AU Standaert, DG Testa, CM Kosinski, CM Bradley, SR Conn, PJ AF Standaert, DG Testa, CM Kosinski, CM Bradley, SR Conn, PJ TI Localization of metabotropic glutamate receptor proteins in the rat basal ganglia SO NEUROPHARMACOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. RI Conn, Peter/D-7848-2012 NR 0 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 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT PY 1999 VL 38 IS 10 MA 141 BP A44 EP A44 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 238ZA UT WOS:000082743600160 ER PT J AU Drazen, DL Klein, SL Burnett, AL Wallach, EE Crone, JK Huang, PL Nelson, RJ AF Drazen, DL Klein, SL Burnett, AL Wallach, EE Crone, JK Huang, PL Nelson, RJ TI Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE ovulation; fertility; estrous cycle; knockout; ovary ID LUTEINIZING-HORMONE; PENILE ERECTION; ESTROUS-CYCLE; RAT; OVULATION; BEHAVIOR; HAMSTER; ABNORMALITIES; EXPRESSION; RELEASE AB Nitric oxide (NO) acts as a neuronal messenger in both the central and peripheral nervous systems and has been implicated in reproductive physiology and behavior, Pharmacological inhibition of nitric oxide synthase (NOS) with the nonspecific NOS inhibitor, L-N-G-nitro-Arg-methyl ester (L-NAME), induced deficits in both the number of ovarian rupture sites and the number of oocytes recovered in the oviducts of mice, Female neuronal NOS knockout (nNOS-/-) mice have normal numbers of rupture sites, but reduced numbers of oocytes recovered following systemic injections of gonadotropins, suggesting that NO produced by nNOS accounts, in part, for deficits in ovulatory efficiency observed after L-NAME administration. Additionally, endothelial NOS knockout (eNOS-/-) mice have reduced numbers of ovulated oocytes after superovulation, Because endothelial NOS has been identified in ovarian follicles, and because of the noted reduced breeding efficiency of eNOS-/- mice, the present study sought to determine the role of NO from eNOS in mediating the number of rupture sites present after ovulation, Estrous cycle length and variability were consistently reduced in eNOS-/- females. The number of rupture sites was normal in eNOS-/- mice under natural conditions and after administration of exogenous GnRH. After exogenous gonadotropin administration, eNOS-/-females displayed a significant reduction in the number of ovarian rupture sites. Female eNOS-/- mice also produced fewer pups/litter compared to WT mice. These data suggest that NO from endothelial sources might play a role in mediating rodent ovulation and may be involved in regulation of the timing of the estrous cycle. (C) 1999 Academic Press. C1 Johns Hopkins Univ, Dept Psychol, Behav Neuroendocrinol Grp, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Neurosci, Behav Neuroendocrinol Grp, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Obstet & Gynecol, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Drazen, DL (reprint author), Johns Hopkins Univ, Dept Psychol, Behav Neuroendocrinol Grp, 225 Ames Hall, Baltimore, MD 21218 USA. OI Nelson, Randy/0000-0002-8194-4016 FU NHLBI NIH HHS [HL57818]; NIDDK NIH HHS [1 K08 DK02568-01]; NIMH NIH HHS [MH 57760] NR 47 TC 36 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD OCT PY 1999 VL 3 IS 5 BP 366 EP 374 DI 10.1006/niox.1999.0251 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 253ZK UT WOS:000083586900002 PM 10534440 ER PT J AU Thadhani, R Stampfer, MJ Hunter, DJ Manson, JE Solomon, CG Curhan, GC AF Thadhani, R Stampfer, MJ Hunter, DJ Manson, JE Solomon, CG Curhan, GC TI High body mass index and hypercholesterolemia: Risk of hypertensive disorders of pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HEALTHY NULLIPAROUS WOMEN; LOW-DOSE ASPIRIN; PREVENT PREECLAMPSIA; UNITED-STATES; EPIDEMIOLOGY; WEIGHT; LIPOPROTEIN; METABOLISM; ECLAMPSIA; OUTCOMES AB Objective: To examine the relationship between pregravid body mass index (BMI), elevated cholesterol level, and the development of hypertensive disorders of pregnancy. Methods: We studied 15,262 women who gave birth between 1991 and 1995. Pregravid exposures including BMI and self-reported history of elevated cholesterol were ascertained by biennial mailed questionnaires. Gestational hypertension or preeclampsia was confirmed by medical record review according to standard criteria. Proportional hazards analysis was used to adjust for potential confounding variables. Results: We confirmed 216 cases of gestational hypertension and 86 cases of preeclampsia. The risk of gestational hypertension increased as pregravid BMI increased (P <.01). Compared with women with a pregravid BMI of 21-22.9 kg/m(2), the relative risk (RR) of gestational hypertension was 1.6 (95% confidence interval [CI] 1.0, 2.3) for women with BMI of 23-24.9 kg/m(2), 2.0 (95% CI 1.3, 3.0) for BMI 25-29.9 kg/m(2), and 2.6 (95% CI 1.6, 4.4) for BMI over 30 kg/m(2). Leaner women (BMI less than 21 kg/m(2)) had a reduced risk (RR 0.7, 95% CI 0.4, 1.0). For preeclampsia, the RR of women with pregravid BMI over 30 kg/m(2) was 2.1 (95% CI 1.0, 4.6) (P for trend 0.09). A history of elevated cholesterol was not associated with the risk of gestational hypertension (RR 0.9, 95% CI, 0.6, 1.4). In contrast, the RR of preeclampsia in women with a history of elevated cholesterol was 2.0 (95% CI 1.2, 3.3). Conclusion: Pregravid BMI and hypercholesterolemia could identify women at higher risk for hypertensive disorders during pregnancy. (Obstet Gynecol 1999;94:543-50. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Thadhani, R (reprint author), 55 Fruit St,Founders 036, Boston, MA 02114 USA. FU NCI NIH HHS [CA50385]; NHLBI NIH HHS [K08HL03804-01] NR 54 TC 119 Z9 122 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1999 VL 94 IS 4 BP 543 EP 550 DI 10.1016/S0029-7844(99)00400-7 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 239QN UT WOS:000082781300011 PM 10511356 ER PT J AU Tuncer, ZS Bernstein, MR Goldstein, DP Lu, KH Berkowitz, RS AF Tuncer, ZS Bernstein, MR Goldstein, DP Lu, KH Berkowitz, RS TI Outcome of pregnancies occurring within 1 year of hydatidiform mole SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID GESTATIONAL TROPHOBLASTIC DISEASE AB Objective: To determine the outcome of subsequent pregnancies in patients with partial or complete molar pregnancy who conceive before completing the recommended hCG follow-up of at least 6 months. Methods: Retrospective record review of patients with partial or complete mole who conceived before the standard gonadotropin follow-up of 6 months was completed during 1980-1998. Results: Sixty-seven patients with molar pregnancy who conceived before completion of hCG follow-up were identified. Thirty-five (52.2%) patients had a prior partial mole, and 32 (47.8%) had a prior complete mole. The mean interval from first achieving undetectable hCG level to new pregnancy was 3.1 and 3.4 months in patients with partial and complete mole, respectively. Eleven patients underwent elective termination, and 12 were lost to follow-up. Of the remaining 44 patients, 33 (75.0%) had live births, 10 had spontaneous abortions, and one had an ectopic pregnancy. A viable pregnancy outcome was achieved in 20 (83.3%) of 24 patients with partial mole and 13 (65.0%) of 20 patients with complete mole. None of the patients developed any evidence of postmolar persistent gestational trophoblastic tumor. None of the live births had any detectable fetal anomalies. Conclusion: The risk of persistent tumor is low and reproductive outcome is favorable once undetectable hCG levels are achieved. Pregnancies occurring before the completion of recommended hCG follow-up may be allowed to continue under careful surveillance. (Obstet Gynecol 1999; 94:588-90. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 Brigham & Womens Hosp, New England Trophoblast Dis Ctr, Gillette Ctr Womens Canc,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1999 VL 94 IS 4 BP 588 EP 590 DI 10.1016/S0029-7844(99)00395-6 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 239QN UT WOS:000082781300019 PM 10511364 ER PT J AU Loeffler, JS AF Loeffler, JS TI Stereotactic radiosurgery for brain metastases - The Boyd/Mehta article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 1999 VL 13 IS 10 BP 1409 EP 1410 PG 2 WC Oncology SC Oncology GA 392WF UT WOS:000166435000019 ER PT J AU Reinke, MH Canakis, C Husain, D Michaud, N Flotte, TJ Gragoudas, ES Miller, JW AF Reinke, MH Canakis, C Husain, D Michaud, N Flotte, TJ Gragoudas, ES Miller, JW TI Verteporfin photodynamic therapy retreatment of normal retina and choroid in the cynomolgus monkey SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID NEOVASCULARIZATION; BENZOPORPHYRIN; MACULOPATHY AB Objective: This study evaluated the effect of repeated photodynamic therapy (PDT) applications on normal primate retina and choroid using an intravenous infusion of liposomal benzoporphyrin derivative (verteporfin). Design: This was an experimental study in a primate model. Animals/Controls: Six cynomolgus monkeys were used as experimental subjects and one monkey was used as a control subject. Intervention: Three consecutive PDT treatments at 2-week intervals were applied over the center of the fovea or the optic nerve of each eye. Verteporfin was delivered by intravenous infusion at a dose of 6 mg/m(2), 12 mg/m(2), or 18 mg/m(2). Laser irradiation was then applied using a diode laser (689 nm) with light doses and spot sizes kept constant. Main Outcome Measures: Findings were documented by fundus photography, fluorescein angiography, and light and electron microscopy. Results: A cumulative dose response was seen angiographically and histologically with more severe damage to the retina and choroid noted at higher dye doses. Photodynamic therapy applied to the macula using the 6-mg/m(2) verteporfin dose showed recovery of choriocapillaris, with mild retinal pigment epithelium and outer photoreceptor damage at 6 weeks. At this dose, the optic nerve showed few focal sites of axon atrophy and capillary loss. Treatments over the macula using the 12-mg/m(2) and 18-mg/m(2) doses led to chronic absence of choriocapillaris and photoreceptors at 6 weeks. One of two optic nerves became atrophic after PDT applications using dye doses of 12 mg/m(2), and both optic nerves became atrophic in the 18-mg/m(2) dye dose group. Conclusion: Limited damage to the retina, choroid, and optic nerve was present in primates treated with multiple PDT sessions using 6 mg/m(2) verteporfin with light doses and the timing of irradiation kept constant. However, PDT using higher dye doses of 12 mg/m(2) and 18 mg/m(2) led to significant chronic damage to the normal retina, choroid, and optic nerve. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Laser Res Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Laser Res Lab, 243 Charles St, Boston, MA 02114 USA. NR 24 TC 83 Z9 91 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1999 VL 106 IS 10 BP 1915 EP 1923 DI 10.1016/S0161-6420(99)90401-3 PG 9 WC Ophthalmology SC Ophthalmology GA 241YU UT WOS:000082912100024 PM 10519585 ER PT J AU Wiedman, M Tabin, GC AF Wiedman, M Tabin, GC TI High-altitude retinopathy and altitude illness SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY NOV 08-09, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Acad Ophthalmol AB Objective: To determine the relationship between high-altitude retinopathy (HAR) and other altitude-related illnesses and establish a classification system for HAR. Design: Observational case series. Participants: All 40 climbers among 3 Himalayan expeditions who ascended to altitudes between 16,000 and 29,028 feet above sea level (summit of Mt. Everest) were examined for signs of HAR and altitude illness (AI). Methods: All subjects had dilated fundus examinations before the ascent, intermittent fundus, and medical examinations during the climb and a dilated fundus and medical examination within 2 days after attaining their highest altitude. Main Outcome Measures: Careful fundus drawings or fundus photography or both were obtained for all participants. All subjects gave a subjective assessment of their symptoms of acute mountain sickness (AMS) and were assessed clinically for signs of high-altitude cerebral edema (HACE). Results: Nineteen of 21 climbers who ascended above 25,000 feet developed HAR. Fourteen of 19 climbers who attained altitudes between 16,000 and 25,000 feet were found to have retinopathy. A grading system for HAR describing the severity of the retinopathy was developed. Correlation of the retinopathy with other AI showed that AMS was endemic and that a statistically significant correlation exists between HAR and HACE (P = 0.0240). Conclusion: Recognizing advancing grades of HAR may allow physicians to recommend initiating empiric treatment with oxygen, steroids, diuretics and immediate descent to prevent HAR progression, macular involvement, or potentially fatal HACE. High-altitude retinopathy is both a significant component of and a predictor of progressive AI. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Univ Vermont, Coll Med, Burlington, VT USA. RP Wiedman, M (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Zero Emerson Pl, Boston, MA 02114 USA. NR 9 TC 37 Z9 40 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1999 VL 106 IS 10 BP 1924 EP 1926 DI 10.1016/S0161-6420(99)90402-5 PG 3 WC Ophthalmology SC Ophthalmology GA 241YU UT WOS:000082912100025 PM 10519586 ER PT J AU Tomford, WW Mankin, HJ AF Tomford, WW Mankin, HJ TI Bone banking - Update on methods and materials SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHAIN-REACTION AB Bone allografts are being used in increasing numbers by orthopedic surgeons, yet many surgeons are unfamiliar with their preparation and processing, as well as their use as safe and effective transplants. This article reviews current sources of bone allografts, new methods of processing to achieve optimal results, the biology of incorporation of allografts, and new bone substitutes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,MGH Bone Bank, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Oncol Unit, Boston, MA 02114 USA. RP Tomford, WW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,MGH Bone Bank, 55 Fruit St,Gray 607, Boston, MA 02114 USA. NR 17 TC 74 Z9 79 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 1999 VL 30 IS 4 BP 565 EP + DI 10.1016/S0030-5898(05)70109-7 PG 7 WC Orthopedics SC Orthopedics GA 242UM UT WOS:000082960100004 PM 10471761 ER PT J AU Friedlander, GE Strong, DM Tomford, WW Mankin, HJ AF Friedlander, GE Strong, DM Tomford, WW Mankin, HJ TI Long-term follow-up of patients with osteochondral allografts - A correlation between immunologic responses and clinical outcome SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID BONE; TRANSPLANTATION AB This article confirms immunologic responses in humans to histocompatibility antigens (Class I and II) presented by frozen osteochondral allografts. These observations include a correlation of immune responses with longterm clinical outcome. As found in animal models, matching of histocompatibility antigens, particularly to Class II, improves clinical and, presumably, biologic success following implantation of massive frozen bone allografts in humans. The presence of sensitization clearly does not preclude a satisfactory outcome, nor have other reconstructive alternatives (e.g., metallic implants) been shown to be superior in their long-term results. C1 Yale Univ, Sch Med, Dept Orthopaed & Rehabil, New Haven, CT 06520 USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. NW Tissue Ctr, Seattle, WA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Friedlander, GE (reprint author), Yale Univ, Sch Med, Dept Orthopaed & Rehabil, POB 208071, New Haven, CT 06520 USA. FU NCI NIH HHS [CA 32968] NR 30 TC 70 Z9 72 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 1999 VL 30 IS 4 BP 583 EP + DI 10.1016/S0030-5898(05)70111-5 PG 7 WC Orthopedics SC Orthopedics GA 242UM UT WOS:000082960100006 PM 10471763 ER PT J AU Behairy, Y Jasty, M AF Behairy, Y Jasty, M TI Bone grafts and bone substitutes in hip and knee surgery SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID 10-YEAR FOLLOW-UP; REPLACEMENT; RECONSTRUCTION; DISLOCATION; INTERFACE; BIOLOGY AB Bone grafts and bone substitutes are an essential part of the armamentarium of orthopedic surgeons. This article presents the current knowledge about bone replacements and reviews the available sources, techniques, and indications of the various types of autograft; allograft, and synthetic agents that are used in contemporary hip and knee replacement surgery. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Biomech Lab,Adult Reconstruct Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Biomech Lab,Hip & Implant Unit, Boston, MA 02114 USA. RP Behairy, Y (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Biomech Lab,Adult Reconstruct Surg Unit, GRJ 1124, Boston, MA 02114 USA. NR 56 TC 17 Z9 17 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 1999 VL 30 IS 4 BP 661 EP + DI 10.1016/S0030-5898(05)70118-8 PG 13 WC Orthopedics SC Orthopedics GA 242UM UT WOS:000082960100013 PM 10471770 ER PT J AU Hornicek, FJ Gebhardt, MC Sorger, JI Mankin, HJ AF Hornicek, FJ Gebhardt, MC Sorger, JI Mankin, HJ TI Tumor reconstruction SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID BONE-TUMORS; UPPER EXTREMITY; FIBULAR GRAFT; RESECTION; MANAGEMENT; FEMUR AB This article discusses opinions for reconstruction of bony defects created by tumor resections. The literature is reviewed, and the results of different reconstruction methods from the Massachusetts General and Children's Hospitals' database are discussed. The authors' treatment goals and algorithms are reviewed as well as the rationale behind them. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston Childrens Hosp, Orthopaed Oncol Unit, Boston, MA 02114 USA. RP Hornicek, FJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Oncol Unit, 55 Fruit St,Gray Bldg 604, Boston, MA 02114 USA. NR 50 TC 11 Z9 16 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 1999 VL 30 IS 4 BP 673 EP + DI 10.1016/S0030-5898(05)70119-X PG 13 WC Orthopedics SC Orthopedics GA 242UM UT WOS:000082960100014 PM 10471771 ER PT J AU Spencer, T Biederman, J Wilens, T AF Spencer, T Biederman, J Wilens, T TI Attention-deficit/hyperactivity disorder and comorbidity SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; CONDUCT DISORDER; TOURETTES DISORDER; PANIC DISORDER; DOUBLE-BLIND; FOLLOW-UP; CHILDREN; ADOLESCENTS; METHYLPHENIDATE; BEHAVIOR AB Studies of children with ADHD consistently document high rates of comorbid psychiatric conditions, including conduct disorders, depression and other mood disorders, anxiety disorders, and tic disorders. Ln diagnosing children with ADHD, one must be careful not to dismiss other symptomatology as secondary. Poor social skills, problems with parents, low academic functioning, and other correlates of ADHD can be construed as causal factors. Although these should not be ignored, neither should the possibility that a child suffers from another psychiatric disorder that might respond to appropriate pharmacotherapy. A variety of behavior rating scales are available to the practitioner as the first steps in this process. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, ACC 725,Fruit St, Boston, MA 02114 USA. FU NIMH NIH HHS [K20 MH01169-01] NR 49 TC 124 Z9 136 U1 1 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 1999 VL 46 IS 5 BP 915 EP + DI 10.1016/S0031-3955(05)70163-2 PG 14 WC Pediatrics SC Pediatrics GA 244BV UT WOS:000083032700008 PM 10570696 ER PT J AU Tomeo, CA Field, AE Berkey, CS Colditz, GA Frazier, AL AF Tomeo, CA Field, AE Berkey, CS Colditz, GA Frazier, AL TI Weight concerns, weight control behaviors, and smoking initiation SO PEDIATRICS LA English DT Article DE children; adolescents; cigarettes; tobacco; weight concerns; weight control ID CIGARETTE-SMOKING; ADOLESCENT SMOKING; HEALTH BEHAVIORS; SAMPLE; GIRLS; RISK; OBESITY; ONSET; MALES; DIET AB Objective. To examine the cross-sectional relationships between weight concerns, weight control behaviors, and initiation of tobacco use among youths. Study Design. Smoking status, weight concerns, and weight control behaviors were assessed in a cross-sectional sample of 16 862 children, 9 to 14 years of age, in 1996. Logistic regression was used to examine the relationship between weight concerns, weight control behaviors, and early stages of smoking initiation (precontemplation, contemplation, and experimentation). All analyses were adjusted for age, body mass index, and known predictors of initiation. Results. Approximately 9% of participants had experimented with cigarettes, and 6% were contemplating cigarette smoking. Contemplation of tobacco use was associated with misperception of being overweight (boys: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.10-2.48), unhappiness with appearance (girls: OR, 2.05; 95% CI, 1.48-2.84; boys: OR, 1.60; 95% CI, 1.05-2.42), and a tendency to change eating patterns around peers (girls: OR, 2.87; 95% CI, 2.28-3.62; boys: OR, 1.83; 95% CI, 1.25-2.66). Experimentation with cigarettes was associated with daily exercise to control weight among boys (OR, 1.92; 95% CI, 1.07-3.43) and with monthly purging (OR, 2.54; 95% CI, 1.27-5.07) and daily dieting among girls (OR, 1.79; 95% CI, 1.09-2.96). Conclusions. Our findings suggest that, among both girls and boys, contemplation of smoking is positively related to weight concerns. Experimentation seems to be positively related to weight control behaviors. It is important for both pediatricians and comprehensive school health programs to address healthy methods of weight maintenance and to dispel the notion of tobacco use as a method of weight control. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Frazier, AL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NIDDK NIH HHS [DK46834] NR 40 TC 94 Z9 95 U1 2 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1999 VL 104 IS 4 BP 918 EP 924 DI 10.1542/peds.104.4.918 PG 7 WC Pediatrics SC Pediatrics GA 241WR UT WOS:000082907300010 PM 10506235 ER PT J AU Brown, GC Brown, MM Sharma, S Tasman, W Brown, HC AF Brown, GC Brown, MM Sharma, S Tasman, W Brown, HC TI Cost-effectiveness of treatment for threshold retinopathy of prematurity SO PEDIATRICS LA English DT Article DE threshold retinopathy of prematurity; laser therapy; cryotherapy; cost-effectiveness ID LASER PHOTOCOAGULATION; PATIENTS PREFERENCES; CLINICAL-TRIALS; CRYOTHERAPY; HEALTH; GUIDE AB Objective. Retinopathy of prematurity (ROP) is a leading cause of adverse visual outcomes in premature infants. Both laser photocoagulation and cryotherapy have been demonstrated in clinical trials to be efficacious in reducing the incidence of visual loss occurring secondary to threshold ROP. Visual data recently have become available concerning the long-term clinical efficacy of both treatments, as have data concerning the utility value of visual states in general. Accordingly, we undertook an analysis to ascertain the cost-effectiveness of laser photocoagulation and cryotherapy in the treatment of threshold ROP. Design. A computer simulation economic model is presented to evaluate the cost-effectiveness of cryotherapy and laser photocoagulation therapy, compared with the natural course of the disease, for treating premature infants with threshold ROP. The model applies longterm visual data from previous clinical trials, utility analysis, decision analysis, and economic principles, such as present value analysis, to account for the time value of money to arrive at a cost per quality-adjusted life-year (QALY) gained. Outcome Measures. Cost per QALY gained from laser therapy and cryotherapy. Results. Laser photocoagulation therapy for threshold ROP costs $678 1998 US dollars (at a 3% discount rate to account for the time value of money) for each QALY gained from treatment. Cryotherapy for the same disease costs $1801 per QALY at a similar discount rate. Conclusions. From the point of view of cost-effectiveness, laser therapy seems to have an advantage over cryotherapy for the treatment of threshold ROP. C1 Ctr Evidence Based Healthcare, Flourtown, PA 19031 USA. Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Retina Serv, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Cataract & Primary Eye Care Serv, Philadelphia, PA 19107 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Epidemiol Unit, Boston, MA USA. RP Brown, GC (reprint author), Ctr Evidence Based Healthcare, Suite 210,1107 Bethlehem Pike, Flourtown, PA 19031 USA. NR 39 TC 29 Z9 29 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1999 VL 104 IS 4 AR e47 DI 10.1542/peds.104.4.e47 PG 6 WC Pediatrics SC Pediatrics GA 241WR UT WOS:000082907300023 PM 10506272 ER PT J AU Redmond, RW Gamlin, JN AF Redmond, RW Gamlin, JN TI A compilation of singlet oxygen yields from biologically relevant molecules SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Review ID LASER-FLASH-PHOTOLYSIS; WATER-SOLUBLE PORPHYRINS; HUMAN-SERUM-ALBUMIN; PHOTODYNAMIC THERAPEUTIC AGENTS; VISIBLE-LIGHT PHOTOCHEMISTRY; TIME-RESOLVED LUMINESCENCE; UNILAMELLAR LIPID VESICLES; STEADY-STATE PHOTOLYSIS; PHOTOPHYSICAL PROPERTIES; QUANTUM YIELDS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, W-224, Boston, MA 02114 USA. FU NCI NIH HHS [CA68524] NR 284 TC 539 Z9 554 U1 10 U2 103 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 1999 VL 70 IS 4 BP 391 EP 475 DI 10.1111/j.1751-1097.1999.tb08240.x PG 85 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 249VQ UT WOS:000083354300003 PM 10546544 ER PT J AU Adili, F van Eps, RGS LaMuraglia, GM AF Adili, F van Eps, RGS LaMuraglia, GM TI Significance of dosimetry in photodynamic therapy of injured arteries: Classification of biological responses SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID EXPERIMENTAL CORNEAL NEOVASCULARIZATION; EXPERIMENTAL INTIMAL HYPERPLASIA; FIBROBLAST GROWTH-FACTOR; ALUMINUM PHTHALOCYANINE; RESTENOSIS; RAT; INHIBITION; ACID AB With conflicting results in the literature on the ability of photodynamic therapy (PDT) to inhibit intimal hyperplasia (IH), the present study systematically investigated the effects of drug and light dosimetry on the biologic responses in the artery wall. The rat common carotid artery was balloon-injured and pressurized with benzoporphyrin-derivative monoacid ring (BPD), Then, PDT was performed with an external laser at different fluences and the biologic responses of the artery wall were histologically examined at 24 h and at 2 weeks, Photodynamic therapy effects on injured arteries can be classified into four stages: low-dose PDT using 0.5 mu g/mL BPD at 50 J/cm(2) (stage I) resulted in incomplete cell eradication and significant LH at 2 weeks. Irradiation with 100 J/cm(2) at the same BPD concentration (stage II) completely eradicated the cells in the artery wall at 24 h but still led to IH at 2 weeks, However, 25 mu g/mL BPD at 100 J/cm(2) (stage IH) resulted in total cell eradication at 24 h and inhibition of IH at 2 weeks, In contrast, high-dose PDT with 25 mu g/mL BPD and 200 J/cm(2) (stage IV) led to thrombus development and vascular occlusion at 24 h, These data, demonstrating the different stages of PDT effects on injured arteries, emphasize the critical importance of appropriate PDT dosimetry for the effective inhibition of IH. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, ACC 464, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 02583] NR 28 TC 11 Z9 13 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 1999 VL 70 IS 4 BP 663 EP 668 DI 10.1111/j.1751-1097.1999.tb08267.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 249VQ UT WOS:000083354300030 PM 10546562 ER PT J AU Kollias, N Bykowski, JL AF Kollias, N Bykowski, JL TI Immediate pigment darkening thresholds of human skin to monochromatic (362 nm) ultraviolet A radiation are fluence rate dependent SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE immediate pigment darkening; fluence rate; skin type; sunscreen; UVA radiation ID ERYTHEMA; UVA AB When human skin is irradiated with ultraviolet radiation (340-400 nm) there is an immediate pigment response, termed Immediate Pigment Darkening (IPD). This reaction is thought to be due to photooxidation of preexisting melanin, precursors and/or melanin metabolites because it appears during exposure. It has been demonstrated that UVA-induced skin reactions, including erythema and pigmentation, are oxygen dependent. Therefore, these reactions should also be irradiance (fluence rate) dependent. The purpose of this investigation was to determine the dependence of the IPD threshold on fluence rate. We exposed the forearm of 12 volunteers (skin type II-V) to monochromatic UVA radiation (362 nm) at a range of fluence rates of 6-115 mW/cm(2) and determined the fluence at which pigment was perceptible. The threshold fluence for the IPD reaction increased by a factor of 2.7 as the fluence rate increased by a factor of 18. Therefore, we conclude that the IPD react:ion following exposure to 362 nm radiation is dependent on fluence rate, and independent of skin type. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Bykowski, JL (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St,BHX 630, Boston, MA 02114 USA. NR 16 TC 12 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD OCT PY 1999 VL 15 IS 5 BP 175 EP 178 PG 4 WC Dermatology SC Dermatology GA 248BU UT WOS:000083256100004 PM 10540939 ER PT J AU Asawanonda, P Ortel, B Taylor, CR AF Asawanonda, P Ortel, B Taylor, CR TI Temperatures reached inside stand-up ultraviolet treatment boxes SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE temperature; PUVA; UVB; eczema; ventilation ID ATOPIC-DERMATITIS; PHOTOTHERAPY AB Heat generated within ultraviolet treatment units can exacerbate eczema. To document the actual temperature changes within the treatment units, we measured the air temperatures in standard stand-up psoralen plus ultraviolet A (PUVA), narrowband ultraviolet B (UVB), broadband UVB, and combination UVA/UVB cabinets using a thermocouple thermometer. For the latter unit, we also measured the air temperatures with and without ventilation systems, and actual skin temperatures on individuals undergoing light treatment. The air temperatures rose significantly in all the treatment units, more so with PUVA and narrowband UVB boxes, and were highest with the ventilation systems shut off. Skin temperatures also rose significantly, but less dramatically. Ventilation is essential in maintaining comfortable temperatures within ultraviolet treatment units. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Taylor, CR (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,BAR 410, Boston, MA 02114 USA. NR 3 TC 2 Z9 2 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD OCT PY 1999 VL 15 IS 5 BP 179 EP 182 PG 4 WC Dermatology SC Dermatology GA 248BU UT WOS:000083256100005 PM 10540940 ER PT J AU Taylor, CR Baron, ED AF Taylor, CR Baron, ED TI Hand and foot PUVA soaks: An audit of the Massachusetts General Hospital's experience from 1994 to 1998 SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE 8-MOP; PUVA soak; psoriasis; eczema ID THERAPY; PALMOPLANTAR; 8-METHOXYPSORALEN; PSORIASIS; ECZEMA; BATH AB Palmoplantar psoriasis and eczema can be chronic recalcitrant dermatoses. Oral psoralen plus ultraviolet A (PUVA) has proven effective for these, but has a number of unwanted side effects. Previous studies have shown that regional PUVA therapy using the 8-methoxypsoralen (8-MOP) soak method followed by immediate WA irradiation is also beneficial and well tolerated. The purpose of this audit was to determine the efficacy of hand and foot PUVA soaks by reviewing the experience of the Massachusetts General Hospital's Phototherapy Unit with this treatment modality. Phototherapy records of all patients who underwent hand and foot PUVA soaks from 1994 to 1998 were reviewed. Details regarding the treatment procedure, patient compliance, patient response and incidence of side effects were noted and, summarized. Of the 56 patients who underwent at least 20 treatments, 29% had excellent response, 42% had minimal to moderate response, and 29% had poor response. The average number of treatments to induce clearing was 41. The average maximum treatment dose at clearing was 5.85 J/cm(2), while the average cumulative dose to achieve clearing was 267.17 J/cm(2). 8-MOP PUVA soak therapy is quite useful for chronic hand and foot dermatoses. Patient compliance must be emphasized to obtain favorable results. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Phototherapy Unit, Boston, MA 02114 USA. RP Taylor, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Phototherapy Unit, Boston, MA 02114 USA. NR 9 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD OCT PY 1999 VL 15 IS 5 BP 188 EP 192 PG 5 WC Dermatology SC Dermatology GA 248BU UT WOS:000083256100007 PM 10540942 ER PT J AU Kriegsfeld, LJ Demas, GE Huang, PL Burnett, AL Nelson, RJ AF Kriegsfeld, LJ Demas, GE Huang, PL Burnett, AL Nelson, RJ TI Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS-/-) SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE mating; erection; rodent; reproduction; copulatory behavior; gene knockout ID HUMAN CORPUS CAVERNOSUM; MEDIAL PREOPTIC AREA; PENILE ERECTION; SUPRACHIASMATIC NUCLEUS; MALE-RATS; COPULATION; BEHAVIOR; DOPAMINE; EXPRESSION; INHIBITORS AB Nitric oxide (NO) has been established as a neurotransmitter in both the central and peripheral nervous systems. Three isoforms of its synthetic enzyme, NO synthase (NOS), have been identified: 1) in the endothelial lining of blood vessels (eNOS), 2) an inducible form found in macrophages (iNOS), and 3) in neurons (nNOS). Previous studies using pharmacological agents that block all three isoforms of NOS have revealed that NO mediates several aspects of reproductive physiology and behavior, including anomalies in male sexual behavior and erectile function. To determine the specific contribution of the endothelial isoform of NOS in male reproductive behavior, we studied mice missing the gene for only eNOS (eNOS-/-). Wild-type (WT) and eNOS-/- animals were placed with an estrous WT female and observed for 45 min. Both WT and eNOS-/- mice displayed equivalent motivation to mount the stimulus female. However, eNOS-/- mice exhibited striking anomalies in ejaculatory function. A higher percentage of eNOS-/- than WT mice ejaculated during the testing period (p < 0.001). This increased propensity to ejaculate was apparently due to reduced stimulation required to elicit ejaculation; eNOS-/- mice required significantly fewer mounts (p < 0.003) and intromissions (p < 0.001) to ejaculate compared to WT mice. Taken together, these results suggest that NO synthesized by eNOS may be involved in ejaculatory physiology, but not sexual motivation. (C) 1999 Elsevier Science Inc. C1 Johns Hopkins Univ, Dept Psychol, Behav Neuroendocrinol Grp, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Nelson, RJ (reprint author), Johns Hopkins Univ, Dept Psychol, Behav Neuroendocrinol Grp, Baltimore, MD 21218 USA. OI Nelson, Randy/0000-0002-8194-4016 FU NIDDK NIH HHS [DK02565-01]; NIMH NIH HHS [MH57535, MH57760] NR 38 TC 56 Z9 58 U1 3 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD OCT PY 1999 VL 67 IS 4 BP 561 EP 566 DI 10.1016/S0031-9384(99)00100-6 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 248TL UT WOS:000083291400011 PM 10549894 ER PT J AU Butler, PEM Sims, CD Randolph, MA Menkes, D Onorato, J Lee, WPA AF Butler, PEM Sims, CD Randolph, MA Menkes, D Onorato, J Lee, WPA TI A comparative study of nerve healing in adult, neonatal, and fetal rabbits SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Plastic-Surgery-Research-Council CY MAY 17-21, 1995 CL NEW YORK, NEW YORK SP Plast Surg Res Council ID SURGERY; REGENERATION; DIAGNOSIS; WOUNDS; MODEL; RAT AB This experiment quantitatively compared the human equivalent of a nerve repair following surgical division in the fetal, adult, and early childhood period of development using a rabbit as an experimental animal model. Twelve time-dated pregnant New Zealand White rabbits at 24 days' gestation (term = 31 days) underwent hysterotomy; one hind limb was delivered through the uterine opening. The sciatic nerve was divided and repaired by primary neurorrhaphy using mio 11-0 epineural sutures. Sciatic nerve repair was also performed in 10 neonatal and 10 adult New Zealand White rabbits. Following repair, each group was assessed using electromyography examination, measuring distal motor latency and amplitude at 1, 2, 3, and 4 months postrepair. There was no difference in any of the groups in distal motor latency. The amplitude rose incrementally in all groups, and the fetal group had significantly higher amplitudes (p < 0.02) at 1, 2, 3, and 4 months in comparison with the adult group. There was no statistically significant difference between fetal and neonatal nerve repairs at ally of the time periods. At the completion of the study, the nerve repair sites were harvested for histologic estimation of mean myelinated fiber density and fiber diameter distribution distal and proximal to the repair site. A greater percentage of myelinated axons crossed the repair site in the fetal group (83 percent) in comparison with the adult group (63 percent) (p < 0.03). Our study also demonstrated significant increases in the number of larger myelinated fibers crossing the repair site in comparison with the neonatal and adult groups (p < 0.04). This study found that fetal nerve healing following surgical repair is superior to that found in adult animals and results in a higher number of larger myelinated fibers crossing the repair site in comparison with adult and neonatal repairs. C1 Massachusetts Gen Hosp, Ambulatory Care Ctr 453, Div Plast Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Massachusetts Gen Hosp, Ambulatory Care Ctr 453, Div Plast Surg, Boston, MA 02114 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1999 VL 104 IS 5 BP 1386 EP 1392 DI 10.1097/00006534-199910000-00022 PG 7 WC Surgery SC Surgery GA 241FF UT WOS:000082871500022 PM 10513922 ER PT J AU Rivas-Vazquez, RA Johnson, SL Blais, MA Rey, GJ AF Rivas-Vazquez, RA Johnson, SL Blais, MA Rey, GJ TI Selective serotonin reuptake inhibitor discontinuation syndrome: Understanding, recognition, and management for psychologists SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID WITHDRAWAL SYNDROME; ANTIDEPRESSANT DISCONTINUATION; ABRUPT DISCONTINUATION; PANIC DISORDER; ADVERSE EVENTS; VENLAFAXINE; DEPRESSION; PAROXETINE; MECHANISMS; SYMPTOMS AB Psychologists increasingly provide psychotherapeutic services to patients receiving concomitant pharmacotherapy. Ongoing experience with the relatively new selective serotonin reuptake inhibitors and other atypical antidepressants has revealed a discontinuation syndrome that emerges following abrupt or tapered withdrawal from these agents. The syndrome has both somatic and psychological characteristics, which tend to be mild and transient but can also be more distressing and become temporarily debilitating. Psychologists need to be aware of the potential for these events, as they are in an optimal position to collaborate with physicians and other prescribing clinicians to prevent or manage this syndrome. C1 Univ Miami, Sch Med, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rivas-Vazquez, RA (reprint author), 8940 N Kendall Dr,Suite 802-E, Miami, FL 33176 USA. NR 40 TC 3 Z9 3 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD OCT PY 1999 VL 30 IS 5 BP 464 EP 469 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 240VX UT WOS:000082848700005 ER PT J AU Fabbro, D Batt, D Rose, P Schacher, B Roberts, TM Ferrari, S AF Fabbro, D Batt, D Rose, P Schacher, B Roberts, TM Ferrari, S TI Homogeneous purification of human recombinant GST-Akt/PKB from Sf9 cells SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID PROTEIN-KINASE-B; PLECKSTRIN HOMOLOGY DOMAIN; PHOSPHOINOSITIDE 3-KINASE; ACTIVATION; SURVIVAL; PHOSPHORYLATION; BINDING; ALPHA; DEATH; RAS AB The plethora of extracellular stimuli modulating the status of a cell results in the engagement of relatively few pathways responsible for transducing signals to the interior of the cell. One such pathway is the activation of phosphatidylinositol 3-kinase (PI-3K), which results in the generation of a membrane-restricted second messenger, polyphosphatidylinositide 3'-phosphate. Among the enzymes activated by 3'-phosphorylated inositol lipids is Akt/protein kinase B (PKB), Here we describe a protocol for the expression and one-step purification of human recombinant GST-PKB in Sf9 cells. This scheme allows generating large amounts of homogeneously purified GST-PKB with high specific activity to be employed in high-throughput screening or structural studies. (C) 1999 Academic Press. C1 Novartis Pharma AG, Dept Oncol, Unit Biol Basel, CH-4057 Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Novartis Pharma AG, Dept Growth Control, Klybeckstr 141, CH-4002 Basel, Switzerland. EM ferrari@pharma.novartis.com RI Ferrari, Stefano/I-7357-2016 OI Ferrari, Stefano/0000-0002-6607-215X NR 30 TC 9 Z9 9 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 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 1999 VL 17 IS 1 BP 83 EP 88 DI 10.1006/prep.1999.1102 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 243NN UT WOS:000083004300011 PM 10497072 ER PT J AU Lev, MH Farkas, J Gemmete, JJ Hossain, ST Hunter, GJ Koroshetz, WJ Gonzalez, G AF Lev, MH Farkas, J Gemmete, JJ Hossain, ST Hunter, GJ Koroshetz, WJ Gonzalez, G TI Acute stroke: Improved nonenhanced CT detection - Benefits of soft-copy interpretation by using variable window width and center level settings SO RADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-of-North-American CY NOV, 1998 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE brain, CT; brain, infarction; brain, ischemia ID CEREBRAL-ARTERY INFARCTION; ACUTE ISCHEMIC STROKE; THROMBOLYTIC THERAPY; INTRAVENOUS THROMBOLYSIS; MAGNETIC-RESONANCE; PROGNOSTIC VALUE; ANGIOGRAPHY; SENSITIVITY; DIAGNOSIS; OCCLUSION AB PURPOSE: To assess the use of nonstandard, variable window width and level review settings in computed tomography (CT) without contrast material administration in the detection of acute stroke. MATERIALS AND METHODS: Nonenhanced CT was performed in 21 patients with acute (<6 hours) middle cerebral arterial stroke and nine control patients. Two blinded neuroradiologists rated all scans for presence of parenchymal hypoattenuation. Images were reviewed at a picture archiving and communication system (PACS) workstation, with standard, locally determined center level and window width settings of 20 and 80 HU and with variable soft-copy settings initially centered at a level of 32 HU with a width of 8 HU. Reviewers altered settings to accentuate gray and white matter contrast. RESULTS: With standard viewing parameters, sensitivity and specificity for stroke detection were 57% and 100%. Sensitivity increased to 71% with variable window width and center level settings, without loss of specificity. Receiver operating characteristic analysis revealed a significant improvement in accuracy with nonstandard, soft-copy review settings (P =.03, one-tailed z test). CONCLUSION: In nonenhanced CT of the head, detection of ischemic brain parenchyma is facilitated by soft-copy review with variable window width and center level settings to accentuate the contrast between normal and edematous tissue. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB285,14 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR 1321]; NINDS NIH HHS [NS 34626] NR 38 TC 138 Z9 143 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1999 VL 213 IS 1 BP 150 EP 155 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 239ML UT WOS:000082771900027 PM 10540655 ER PT J AU Rossbacher, J Wagner, L Pasternack, MS AF Rossbacher, J Wagner, L Pasternack, MS TI Inhibitory effect of haptoglobin on granulocyte chemotaxis, phagocytosis and bactericidal activity SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; EXPRESSION; NEUTROPHILS; LYMPHOCYTE; CHEMOKINE; MONOCYTES; PROTEINS; KINETICS; GENE AB Human haptoglobin (Hp) is synthesized at hepatic and extrahepatic sites as an acute-phase reactant protein (APP). We investigated the effects of Hp on granulocyte function. The chemotaxis of freshly isolated human granulocytes and differentiated HL-60 cells in response to the bacterial tripeptide, f-met-leu-phe, was inhibited in the presence of a physiological concentration of Hp, but chemotaxis in the presence of the proinflammatory cytokine interleukin-8 (IL-8) was not inhibited. Phagocytosis of viable Escherichia coli, as well as fluoresceinated nonviable E, coli, was inhibited. Hp also reduced granulocyte intracellular bactericidal activity against E. coli. The observed inhibitory effects of Hp on granulocyte function are similar to those reported for C-reactive protein and suggest that APPs dampen the acute inflammatory response. C1 Univ Vienna, Dept Med 3, A-1090 Vienna, Austria. Massachusetts Gen Hosp, Serv Pediat, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rossbacher, J (reprint author), Univ Vienna, Dept Med 3, Wahringer Gurtel 18-10, A-1090 Vienna, Austria. NR 24 TC 28 Z9 30 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD OCT PY 1999 VL 50 IS 4 BP 399 EP 404 DI 10.1046/j.1365-3083.1999.00609.x PG 6 WC Immunology SC Immunology GA 241PK UT WOS:000082891600009 PM 10520180 ER PT J AU Hoffbrand, AV Herbert, V AF Hoffbrand, AV Herbert, V TI Nutritional anemias SO SEMINARS IN HEMATOLOGY LA English DT Article ID CORONARY HEART-DISEASE; PLASMA HOMOCYSTEINE; TRANSFERRIN RECEPTOR; IRON-METABOLISM; RISK FACTOR; HEREDITARY HEMOCHROMATOSIS; VASCULAR-DISEASE; MESSENGER-RNA; FOLIC-ACID; FOLATE C1 Royal Free Hosp, Dept Haematol, London NW3 2QG, England. UCL, Sch Med, London W1N 8AA, England. Mt Sinai Hosp, Dept Hematol, Bronx, NY USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Hoffbrand, AV (reprint author), Royal Free Hosp, Dept Haematol, Ponds St, London NW3 2QG, England. NR 67 TC 16 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1999 VL 36 IS 4 SU 7 BP 13 EP 23 PG 11 WC Hematology SC Hematology GA 260QL UT WOS:000083961300003 PM 10595751 ER PT J AU DeVita, VT Canellos, GP AF DeVita, VT Canellos, GP TI The lymphomas SO SEMINARS IN HEMATOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; REED-STERNBERG CELLS; COMBINATION CHEMOTHERAPY; CLINICAL-SIGNIFICANCE; MONOCLONAL-ANTIBODY; GASTRIC LYMPHOMA; DISEASE; THERAPY; VIRUS C1 Yale Univ, Sch Med, Ctr Canc, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP DeVita, VT (reprint author), Yale Univ, Sch Med, Ctr Canc, 333 Cedar St, New Haven, CT 06520 USA. NR 70 TC 11 Z9 12 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 1999 VL 36 IS 4 SU 7 BP 84 EP 94 PG 11 WC Hematology SC Hematology GA 260QL UT WOS:000083961300009 PM 10595757 ER PT J AU Berenson, JR AF Berenson, JR TI Etiology of multiple myeloma: What's new SO SEMINARS IN ONCOLOGY LA English DT Review ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; DENDRITIC CELLS; ACTIVATING MUTATIONS; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8; GENES; TRANSLOCATIONS; ABNORMALITIES; BREAKPOINTS C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Berenson, JR (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Dept Med, 11301 Wilshire Blvd,111H, Los Angeles, CA 90073 USA. NR 44 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1999 VL 26 IS 5 SU 13 BP 2 EP 9 PG 8 WC Oncology SC Oncology GA 248VF UT WOS:000083295900002 PM 10528889 ER PT J AU Oh, WK Kantoff, PW AF Oh, WK Kantoff, PW TI Docetaxel (Taxotere)-based chemotherapy for hormone-refractory and locally advanced prostate cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID ESTRAMUSTINE PHOSPHATE; TRIAL; CARCINOMA; COMBINATION; PLATINUM C1 Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Oh, WK (reprint author), 44 Binney St,Dana 1230, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 31 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1999 VL 26 IS 5 SU 17 BP 49 EP 54 PG 6 WC Oncology SC Oncology GA 265JK UT WOS:000084239400011 PM 10604270 ER PT J AU Treon, SP Shima, Y Preffer, FI Doss, DS Ellman, L Schlossman, RL Grossbard, ML Belch, AR Pilarski, LM Anderson, KC AF Treon, SP Shima, Y Preffer, FI Doss, DS Ellman, L Schlossman, RL Grossbard, ML Belch, AR Pilarski, LM Anderson, KC TI Treatment of plasma cell dyscrasias by antibody-mediated immunotherapy SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Symposium on Recent Advances and Future Directions using Monoclonal Antibodies for B-Cell Malignancies CY JAN, 1999 CL KAUPULEHU, HAWAII SP Northwestern Univ, Robert H Lurie Comprehens Canc Ctr ID PHASE-II TRIAL; ANTI-CD20 MONOCLONAL-ANTIBODY; HUMAN INTERFERON-GAMMA; HUMAN MYELOMA CELLS; MULTIPLE-MYELOMA; PERIPHERAL-BLOOD; BONE-MARROW; B-CELLS; WALDENSTROMS MACROGLOBULINEMIA; PROGENITOR CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 59 TC 40 Z9 42 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1999 VL 26 IS 5 SU 14 BP 97 EP 106 PG 10 WC Oncology SC Oncology GA 253TP UT WOS:000083572100014 PM 10561024 ER PT J AU Schrag, D Weeks, J AF Schrag, D Weeks, J TI Costs and cost-effectiveness of colorectal cancer prevention and therapy SO SEMINARS IN ONCOLOGY LA English DT Review ID DETECT HEREDITARY PREDISPOSITION; COLON-CANCER; GENE TESTS; SURVEILLANCE; STAGE; CHEMOTHERAPY; INFUSION; HEALTH; MODEL; RECOMMENDATIONS C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Schrag, D (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. NR 33 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1999 VL 26 IS 5 BP 561 EP 568 PG 8 WC Oncology SC Oncology GA 247LC UT WOS:000083221400013 PM 10528905 ER PT J AU Ubel, PA AF Ubel, PA TI How stable are people's preferences for giving priority to severely ill patients? SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE cost-effectiveness analysis; allocation; rationing; ethics; survey; attitudes; QALYs ID PERSON TRADE-OFF; HEALTH-CARE; COST-EFFECTIVENESS; OREGON; EQUITY AB Background: Previous studies have suggested that people favor allocating resources to severely ill patients even when they benefit less from treatment than do less severely ill patients. This study explores the stability of people's preferences for treating severely ill patients. Methods: This study surveyed prospective jurors in Philadelphia and asked them to decide how they would allocate scarce health care resources between a severely ill group of patients who would improve a little with treatment and moderately ill patients who would improve considerably with treatment. Subjects were randomized to receive one of six questionnaire versions, which altered the wording of the scenarios and altered whether subjects were given an explicit option of dividing resources evenly between the two groups of patients. Results: Four hundred and seventy nine subjects completed surveys. The preference subjects placed on allocating resources to severely ill patients depended on relatively minor wording changes in the scenarios. In addition, when given the explicit option of dividing resources evenly between the two groups of patients, the majority of subjects chose to do so. Conclusion: People's preferences for allocating resources to severely ill patients can be significantly decreased by subtle wording changes in scenarios. However, this study adds to evidence suggesting that many people place priority on allocating resources to severely ill patients, even when they would benefit less from treatment than others. Published by Elsevier Science Ltd. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Vet Affairs Med Ctr, Philadelphia, PA USA. NR 30 TC 52 Z9 52 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 1999 VL 49 IS 7 BP 895 EP 903 DI 10.1016/S0277-9536(99)00174-4 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 224JV UT WOS:000081895500004 PM 10468394 ER PT J AU Shafqat, S Kvedar, JC Guanci, MM Chang, YC Schwamm, LH AF Shafqat, S Kvedar, JC Guanci, MM Chang, YC Schwamm, LH TI Role for telemedicine in acute stroke - Feasibility and reliability of remote administration of the NIH stroke scale SO STROKE LA English DT Article DE reliability; strobe assessment; stroke, ischemic; telemedicine AB Background and Purpose-Immediate access to physicians experienced in acute stroke treatment may improve clinical outcomes in patients with acute stroke. Interactive telemedicine can make stroke specialists available to assist in the evaluation of patients at multiple urban or remote rural facilities. We tested whether interrater agreement for the NIH Stroke Scale (NIHSS), a critical component of acute stroke assessment, would persist if performed over a telemedicine link. Methods-One bedside and 1 remote NIHSS score were independently obtained on each of 20 patients with ischemic stroke. The bedside examination was performed by a stroke neurologist at the patient's bedside, The remote examination was performed by a second stroke neurologist through an interactive high-speed audio-video link, assisted by a nurse at the patient's bedside. Kappa coefficients were calculated for concordance between bedside and remote scores. Results-Remote assessments took slightly longer than bedside assessments (mean 9.70 versus 6.55 minutes, P<0.001). NIHSS scores ranged from 1 through 24. Based on weighted kappa coefficients, 4 items (orientation, motor arm, motor leg, and neglect) displayed excellent agreement, 6 items (language, dysarthria, sensation, visual fields, facial palsy, and gaze) displayed good agreement, and 2 items (commands and ataxia) displayed poor agreement. Total NIHSS scores obtained by bedside and remote methods were strongly correlated (r = 0.97, P<0.001). Conclusions-The NIH Stroke Scale remains a swift and reliable clinical instrument when used over interactive video. Application of this technology can bring stroke expertise to the bedside, regardless of patient location. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Partners Healthcare Inc, Ctr Telemed, Boston, MA USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,55 Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 16 TC 122 Z9 128 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 1999 VL 30 IS 10 BP 2141 EP 2145 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 243EC UT WOS:000082983200023 PM 10512919 ER PT J AU Zaharchuk, G Mandeville, JB Bogdanov, AA Weissleder, R Rosen, BR Marota, JJA AF Zaharchuk, G Mandeville, JB Bogdanov, AA Weissleder, R Rosen, BR Marota, JJA TI Cerebrovascular dynamics of autoregulation and hypoperfusion - An MRI study of CBF and changes in total and microvascular cerebral blood volume during hemorrhagic hypotension SO STROKE LA English DT Article DE magnetic resonance imaging; autoregulation; global ischemia; cerebral blood volume; cerebral blood flow ID POSITRON-EMISSION-TOMOGRAPHY; MEAN TRANSIT-TIME; MAGNETIC-SUSCEPTIBILITY; ARTERY OCCLUSION; TRANSVERSE RELAXATION; CONTRAST AGENTS; FOCAL ISCHEMIA; HUMAN BRAIN; FLOW; PERFUSION AB Background and Purpose-To determine how cerebral blood flow (CBF), total and microvascular cerebral blood volume (CBV), and blood oxygenation level-dependent (BOLD) contrast change during autoregulation and hypotension using hemodynamic MRI. Methods-Using arterial spin labeling and steady-state susceptibility contrast, we measured CBF and changes in both total and microvascular CBV during hemorrhagic hypotension in the rat (n = 9). Results-We observed CBF autoregulation for mean arterial blood pressure (MABP) between 50 and 140 mm Hg, at which average CBF was 1.27 +/- 0.44 mL.g(-1).min(-1) (mean +/- SD). During autoregulation, total and microvascular CBV changes were small and not significantly different from CBF changes. Consistent with this, no significant BOLD changes were observed. For MABP between 10 and 40 mm Hg, total CBV in the striatum increased slightly (+7 +/- 12%, P<0.05) whereas microvascular CBV decreased (-15 +/- 17%, P<0.01); on the cortical surface, total CBV increases were larger (+21 +/- 18%, P<0.01) and microvascular CBV was unchanged (3 +/- 22%, P>0.05). With severe hypotension, both total and microvascular CBV decreased significantly. Over the entire range of graded global hypoperfusion, there were increases in the CBV/CBF ratio. Conclusions-Parenchymal CBV changes are smaller than those of previous reports but are consistent with the small arteriolar fraction of total blood volume. Such measurements allow a framework for understanding effective compensatory vasodilation during autoregulation and volume-flow relationships during hypoperfusion. C1 Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr 2301, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Zaharchuk, G (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr 2301, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01-HL39810]; NIDA NIH HHS [5 PO1-DA09467]; NINDS NIH HHS [R01-NS35258-01] NR 73 TC 94 Z9 94 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 1999 VL 30 IS 10 BP 2197 EP 2204 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 243EC UT WOS:000082983200035 PM 10512929 ER PT J AU Taghian, AG Powell, SN AF Taghian, AG Powell, SN TI The role of radiation therapy for primary breast cancer SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; SURGICAL ADJUVANT BREAST; CARCINOMA IN-SITU; EXTENSIVE INTRADUCTAL COMPONENT; COLLAGEN VASCULAR DISEASES; COMPARING TOTAL MASTECTOMY; LOCALLY ADVANCED-CARCINOMA; POSITIVE AXILLARY NODES; MAMMARY CHAIN TREATMENT; CONSERVATIVE SURGERY AB The last 2 decades have seen the role of radiation therapy defined clearly. It is now realized that radiation therapy not only improves local control of breast cancer but also works with surgery and chemotherapy to improve the probability of survival. The major lines of evidence supporting the use of radiation therapy in DCIS, early-stage invasive disease, postmastectomy radiation, and locally advanced breast cancer are outlined in this article, with an analysis of the remaining controversies concerning treatment and potential complications of treatment. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Canc Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Breast Canc Unit, Box 3, Boston, MA 02114 USA. NR 138 TC 11 Z9 11 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD OCT PY 1999 VL 79 IS 5 BP 1091 EP + DI 10.1016/S0039-6109(05)70063-3 PG 26 WC Surgery SC Surgery GA 245RP UT WOS:000083122200010 PM 10572553 ER PT J AU Haase, J Magnussen, IB Ogilvy, CS Ojemann, RG Meyer, FB Quest, DO Lawton, MT McDougall, CG Spetzler, RF Samson, D Takahashi, A Yoshimoto, T Ausman, JI Charbel, FT Debrun, G Aletich, V Dujovny, M AF Haase, J Magnussen, IB Ogilvy, CS Ojemann, RG Meyer, FB Quest, DO Lawton, MT McDougall, CG Spetzler, RF Samson, D Takahashi, A Yoshimoto, T Ausman, JI Charbel, FT Debrun, G Aletich, V Dujovny, M TI Evaluating patients with vertebrobasilar transient ischemic attacks SO SURGICAL NEUROLOGY LA English DT Article ID ANGIOPLASTY; STENOSIS C1 Aalborg Hosp, Dept Neurosurg, Aalborg, Denmark. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Haase, J (reprint author), Aalborg Hosp, Dept Neurosurg, Aalborg, Denmark. NR 11 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD OCT PY 1999 VL 52 IS 4 BP 386 EP 392 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 254FU UT WOS:000083601900022 PM 10555845 ER PT J AU Li, J Xia, Y Kuter, DJ AF Li, J Xia, Y Kuter, DJ TI Platelets undergo apoptosis during storage SO TRANSFUSION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1999 VL 39 IS 10 SU S BP 1S EP 1S PG 1 WC Hematology SC Hematology GA 247EK UT WOS:000083207500004 ER PT J AU Wu, X Goldsmith, K Okoh, V Garver, RI AF Wu, X Goldsmith, K Okoh, V Garver, RI TI Antineoplastic 'multimodality adenovirus' containing E1A and a therapeutic transgene SO TUMOR TARGETING LA English DT Article DE adenoviridae; gene therapy; E1A ID TUMOR-NECROSIS-FACTOR; IN-VIVO; P53 STATUS; CELLS; GENE; INFECTION; APOPTOSIS; PROTEINS; TRANSFORMATION; SUSCEPTIBILITY AB A recombinant adenovirus, AdE1A-tk, was constructed with a complete El A transcription unit and a therapeutic transgene (herpes simplex virus thymidine kinase). Both genomic and protein analysis of cells infected with AdE1A-tk demonstrated the presence of the expected coding sequences, and products of those sequences in the absence of any functional E1B. Evidence presented here demonstrated that the E1A-encoding sequences enhanced the expression of the CMV-directed HSVTK and inhibited growth of carcinoma cell lines even in the absence of ganciclovir. Importantly, the E1A also supported limited and preferential replication of AdE1A-tk in a lung cancer cell line compared to primary, non-transformed human respiratory epithelial cells. It is concluded that both the El A and therapeutic transgene within this adenoviral prototype confer antineoplastic effects, and hence are designated 'multimodality adenoviruses'. C1 Birmingham VAMC, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Garver, RI (reprint author), Birmingham VAMC, Dept Med, Div Pulm Allergy & Crit Care Med, 701 S 19th St LHRB 339, Birmingham, AL 35294 USA. NR 38 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1351-8488 J9 TUMOR TARGET JI Tumor Target. PD OCT PY 1999 VL 4 IS 3 BP 170 EP 178 PG 9 WC Materials Science, Multidisciplinary; Medicine, Research & Experimental SC Materials Science; Research & Experimental Medicine GA 278DB UT WOS:000084971700005 ER PT J AU Tigrani, VS Bhargava, V Shinohara, K Presti, JC AF Tigrani, VS Bhargava, V Shinohara, K Presti, JC TI Number of positive systematic sextant biopsies predicts surgical margin status at radical prostatectomy SO UROLOGY LA English DT Article ID DIGITAL RECTAL EXAMINATION; RETROPUBIC PROSTATECTOMY; PREOPERATIVE PREDICTION; CANCER; SPECIMENS; EXTENSION; PROGRESSION; CARCINOMA; ANTIGEN; IMPACT AB Objectives. To determine whether the number of positive sextant biopsies contributes to the prediction of positive surgical margins, as the value of systematic prostate biopsies in predicting margin status at radical prostatectomy is unclear. Methods. Consecutive patients (n = 108) who underwent radical retropubic prostatectomy and systematic sextant biopsies were retrospectively evaluated. Serum prostate-specific antigen, digital rectal examination, primary Gleason grade, Gleason score, and the number and location of positive sextant biopsies were recorded for each patient. Radical prostatectomy specimens were evaluated by step-section techniques at 3 to 5-mm intervals. Univariate com parisons for each of these variables was performed between the positive and negative margin groups using the Mann-Whitney U test or chi-square analysis. Logistic regression analysis was performed for these variables. Results. Twenty-two (20.4%) of 108 patients had a positive surgical margin because of extension of the tumor through the capsule. Patients with three or more positive biopsies were at higher risk of having a positive surgical margin (P = 0.009). Patients with bilaterally positive biopsies at either the base or midprostate were more likely to have a positive surgical margin. The risk of a positive surgical margin was not significantly determined by the primary Gleason grade, Gleason score, or prostate-specific antigen. Multivariate logistic regression models were created that consistently demonstrate that the number of positive biopsies was the best predictor of margin status. Conclusions. This study demonstrated that the number of positive sextant biopsies contributes to the prediction of margin status at radical prostatectomy. UROLOGY 54: 689-693, 1999. (C) 1999, Elsevier Science Inc. C1 Univ Calif San Francisco, Mt Zion Canc Ctr, Sch Med, Dept Urol, San Francisco, CA 94115 USA. Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Presti, JC (reprint author), Univ Calif San Francisco, Mt Zion Canc Ctr, Sch Med, Dept Urol, 5th Floor,2356 Sutter St, San Francisco, CA 94115 USA. NR 20 TC 38 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD OCT PY 1999 VL 54 IS 4 BP 689 EP 693 DI 10.1016/S0090-4295(99)00211-3 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 239WK UT WOS:000082792700021 PM 10510929 ER PT J AU Oyama, T Maluf, H Koerner, F AF Oyama, T Maluf, H Koerner, F TI Atypical cystic lobules: an early stage in the formation of low-grade ductal carcinoma in situ SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF 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 atypical ductal hyperplasia; ductal carcinoma in situ; estrogen receptor; keratin 19; cyclin D1 ID TERM FOLLOW-UP; BENIGN BREAST DISEASE; MANTLE CELL LYMPHOMA; IN-SITU; CYCLIN D1; HYPERPLASIA; PROTEIN; LESIONS; INSITU; CANCER AB Evidence from many studies has established the neoplastic potential of ductal carcinoma in situ, but the origin and the morphological characteristics of the early stages of this proliferation remain unidentified. Workers writing in the early twentieth century observed a cystic transformation of lobules and proposed that it represented one such early stage, and contemporary European and Japanese pathologists have reached the same conclusion. We describe the characteristics of this cystic transformation, which we call us "atypical cystic lobules," and present evidence to support the proposal that the alteration is a step in the formation of low-grade ductal carcinoma in situ. Atypical cystic lobules are a proliferation of luminal cells showing low-grade cytological atypia without architectural atypia. The study group comprised 21 cases of atypical cystic lobules from specimens also showing conventional low-grade ductal carcinoma in situ or lobular neoplasia. Immunohistochemical staining for hormone receptors, keratin 19, and cyclin D1 revealed that atypical cystic lobules demonstrated a consistent immunophenotype, which differs from the pattern shown by normal lobules and benign lesions and matches that of low-grade ductal carcinoma in situ. In about 40% of the cases, atypical cystic lobules merged with fully established micropapillary/cribriform ductal carcinoma in situ. The similarities in the cytological and immunohistochemical features and the proximity of the two types of proliferation suggest that atypical cystic lobules represent an early stage in the formation of certain types of low-grade ductal carcinoma in situ. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Gunma Univ, Sch Med, Dept Pathol 2, Maebashi, Gumma 371, Japan. Washington Univ, Sch Med, Div Surg Pathol, St Louis, MO USA. RP Koerner, F (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. NR 39 TC 68 Z9 75 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD OCT PY 1999 VL 435 IS 4 BP 413 EP 421 DI 10.1007/s004280050419 PG 9 WC Pathology SC Pathology GA 245JJ UT WOS:000083103600004 PM 10526005 ER PT J AU Glassman, PA Hunter-Hayes, J Nakamura, T AF Glassman, PA Hunter-Hayes, J Nakamura, T TI Pharmaceutical advertising revenue and physician organizations: how much is too much? SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID POINTS-OF-VIEW; DRUG COMPANIES; MEDICAL JOURNALS; REPRESENTATIVES; ATTITUDES; INDUSTRY; ISSUES; GIFTS; ADVERTISEMENTS; EDUCATION AB Objective To determine if revenue generated from pharmaceutical advertisements in medical journals creates potential financial conflicts of interest for nonprofit physician organizations that own those journals. Design Convenience sample of six professional medical societies and their respective journals. Calculation of pharmaceutical advertising revenue generated by these journals for their respective professional medical societies, Methods Random selection of each journal for one month per quarter in calendar year 1996 and tabulation per edition of the average number of pharmaceutical advertising pages for each journal. Outcome measures Published advertising rates were used to estimate pharmaceutical advertising revenue for calendar year 1996 and compared with each organization's gross revenue and membership dues and assessments, based on Internal Revenue Service documents for the last available fiscal year (1995). Results Estimated pharmaceutical advertising revenue ranged from $715,000 to $18,630,000. Five organizations raised more than 10% of their gross income (range 2% to 30%) from a single journal's pharmaceutical advertising. Four organizations raised as much or more From pharmaceutical advertising as from members (range 17% to 790%). Conclusions Potential financial conflicts of interest arising from pharmaceutical advertisements in medical journals may be substantial. The impact on professional societies' financial independence and behavior is unknown. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Western Univ Hlth Sci, VA Greater Los Angeles Healthcare Syst, Pomona, CA USA. RP Glassman, PA (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, W Los Angeles Campus,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 39 TC 24 Z9 26 U1 0 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD OCT PY 1999 VL 171 IS 4 BP 234 EP 238 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 253AX UT WOS:000083535400011 PM 10578674 ER PT J AU Lipsitz, SR Ibrahim, JG Chen, MH Peterson, H AF Lipsitz, SR Ibrahim, JG Chen, MH Peterson, H TI Non-ignorable missing covariates in generalized linear models SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Conference on Medical Statistics CY JUL 22-25, 1997 CL DE MONTFORT UNIV, DE MONTFORT, ENGLAND SP Montfort Univ HO DE MONTFORT UNIV ID EM ALGORITHM; VARIABLES AB We propose a likelihood method for estimating parameters in generalized linear models with missing covariates and a non-ignorable missing data mechanism. In this paper, we focus on one missing covariate. We use a logistic model for the probability that the covariate is missing, and allow this probability to depend on the incomplete covariate. We allow the covariates, including the incomplete covariate, to be either categorical or continuous. We propose an EM algorithm in this case. For a missing categorical covariate, we derive a closed form expression for the E- and M-steps of the EM algorithm for obtaining the maximum likelihood estimates (MLEs). For a missing continuous covariate, we use a Monte Carlo version of the EM algorithm to obtain the MLEs via the Gibbs sampler. The methodology is illustrated using an example from a breast cancer clinical trial in which time to disease progression is the outcome, and the incomplete covariate is a quality of life physical well-being score taken after the start of therapy. This score may be missing because the patients are sicker, so this covariate could be non-ignorably missing. Copyright (C) 1999 John Whey & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. RP Lipsitz, SR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA55576, CA70101, CA74015] NR 14 TC 19 Z9 19 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1999 VL 18 IS 17-18 BP 2435 EP 2448 DI 10.1002/(SICI)1097-0258(19990915/30)18:17/18<2435::AID-SIM267>3.3.CO;2-2 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 234WR UT WOS:000082507800020 PM 10474151 ER PT J AU Molenberghs, G Goetghebeur, EJT Lipsitz, SR Kenward, MG Lesaffre, E Michiels, B AF Molenberghs, G Goetghebeur, EJT Lipsitz, SR Kenward, MG Lesaffre, E Michiels, B TI Missing data perspectives of the fluvoxamine data set: A review SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Conference on Medical Statistics CY JUL 22-25, 1997 CL DE MONTFORT UNIV, DE MONTFORT, ENGLAND SP Montfort Univ HO DE MONTFORT UNIV ID ORDINAL DATA; MAXIMUM-LIKELIHOOD; CATEGORICAL-DATA; OUTCOME SUBJECT; INCOMPLETE DATA; DROP-OUT; NONRESPONSE; MODELS; REGRESSION AB Fitting models to incomplete categorical data requires more care than fitting models to the complete data counterparts, not only in the setting of missing data that are non-randomly missing, but even in the familiar missing at random setting. Various aspects of this point of view have been considered in the literature. We review it using data from a multi-centre trial on the relief of psychiatric symptoms. First, it is shown how the usual expected information matrix (referred to as naive information) is biased even under a missing at random mechanism. Second, issues that arise under non-random missingness assumptions are illustrated. It is argued that at least some of these problems can be avoided using contextual information. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. State Univ Ghent, Dept Appl Math, B-9000 Ghent, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. London Sch Hyg & Trop Med, London WC1, England. Katholieke Univ Leuven, Ctr Biostat, Louvain, Belgium. RP Molenberghs, G (reprint author), Limburgs Univ Ctr, Ctr Stat, Univ Campus, B-3590 Diepenbeek, Belgium. NR 19 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1999 VL 18 IS 17-18 BP 2449 EP 2464 DI 10.1002/(SICI)1097-0258(19990915/30)18:17/18<2449::AID-SIM268>3.0.CO;2-W PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 234WR UT WOS:000082507800021 PM 10474152 ER PT J AU Sammel, M Lin, XH Ryan, L AF Sammel, M Lin, XH Ryan, L TI Multivariate linear mixed models for multiple outcomes SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 2nd International Conference on Medical Statistics CY JUL 22-25, 1997 CL DE MONTFORT UNIV, DE MONTFORT, ENGLAND SP Montfort Univ HO DE MONTFORT UNIV ID LONGITUDINAL DATA-ANALYSIS AB We propose a multivariate linear mixed (MLMM) for the analysis of multiple outcomes, which generalizes the latent variable model of Sammel and Ryan, The proposed model assumes a flexible correlation structure among the multiple outcomes, and allows a global test of the impact of exposure across outcomes. In contrast to the Sammel-Ryan model, the MLMM separates the mean and correlation parameters so that the mean estimation will remain reasonably robust even if the correlation is misspecified. The model is applied to birth defects data, where continuous data on the size of infants who were exposed to anticonvulsant medications in utero are compared to controls. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Harvard Univ, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Sammel, M (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Blockley Hall Rm 605,423 Guardian Dr, Philadelphia, PA 19104 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 15 TC 36 Z9 36 U1 0 U2 11 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 30 PY 1999 VL 18 IS 17-18 BP 2479 EP 2492 DI 10.1002/(SICI)1097-0258(19990915/30)18:17/18<2479::AID-SIM270>3.3.CO;2-6 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 234WR UT WOS:000082507800023 PM 10474154 ER PT J AU Chen, YI Brownell, AL Galpern, W Isacson, O Bogdanov, M Beal, MF Livni, E Rosen, BR Jenkins, BG AF Chen, YI Brownell, AL Galpern, W Isacson, O Bogdanov, M Beal, MF Livni, E Rosen, BR Jenkins, BG TI Detection of dopaminergic cell loss and neural transplantation using pharmacological MRI, PET and behavioral assessment SO NEUROREPORT LA English DT Article DE amphetamine; BOLD; CBV; beta-CFT; dopamine; microdialysis; MRI; neural transplantation; PET ID HUMAN BRAIN; SENSORY STIMULATION; RAT; MICRODIALYSIS; METABOLISM; TERMINALS; DISEASE; MODEL AB WE: demonstrate the use of magnetic resonance imaging (MRI) for detection of neurotransmitter stimulation using the dopamine transporter ligands amphetamine and CFT (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane)'ias pharmacological challenges, We demonstrate that the unilateral loss of a hemodynamic response to either amphetamine or CFT challenge by unilateral 6-hydroxydopamine lesioning is restored by transplantation of fetal dopamine neurons in the striatum,The time course for the hemodynamic changes parallels the time-courses for dopamine release, measured by prior microdialysis studies, and also for the rotational behavior in the unilaterally lesioned animals. Transplantation of the fetal cells results in hemodynamic time courses after CFT or amphetamine challenges at the graft Site that are identical to those induced both before transplantation and on the intact contralateral side. The:transplantation also results in complete behavioral recovery. The spatial extent of the dopaminergic recovery: in the lesioned striatum is the same when measured using either PET of tracer levels of [C-11]CFT binding or MRI. These results show great promise for the application of pharmacological MRI for application to studies Of dopamine cell loss and potential recovery in Parkinson's disease. (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, PET Lab, Boston, MA 02114 USA. McLean Hosp, Neuroregenet Lab, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Neurol, Neurochem Lab, Boston, MA 02114 USA. RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. NR 24 TC 60 Z9 63 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 29 PY 1999 VL 10 IS 14 BP 2881 EP 2886 DI 10.1097/00001756-199909290-00001 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 241CV UT WOS:000082865500004 PM 10549790 ER PT J AU Anderson, AC O'Neil, RH Filman, DJ Frederick, CA AF Anderson, AC O'Neil, RH Filman, DJ Frederick, CA TI Crystal structure of a brominated RNA helix with four mismatched base pairs: An investigation into RNA conformational variability SO BIOCHEMISTRY LA English DT Article ID SECONDARY STRUCTURE; RECOGNITION; RESOLUTION; DODECAMER; RIBOZYME AB The X-ray crystal structure of a brominated RNA helix with four mismatched base pairs and sequence r(UG(Br)C(Br)CAGUUCGCUGGC)(2) was determined to 2.1 Angstrom using the methods of multiwavelength anomalous diffraction (MAD) applied to the bromine K-absorption edge. There are three molecules in the asymmetric unit with unique crystal-packing environments, revealing true conformational variability at high resolution for this sequence. The structure shows that the sequence itself does not define a consistent pattern of solvent molecules, with the exception of the mismatched base pairs, implying that specific RNA-protein interactions would occur only with the nucleotides. There are a number of significant tertiary interactions, some of which are a result of the brominated base pairs and others that are directly mediated by the RNA 2' hydroxyl groups. The mismatched base pairs exhibit a solvent network as well as a stacking pattern with their nearest neighbors that validate previous thermodynamic analysis. C1 Harvard Univ, Comm Biophys, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Frederick, CA (reprint author), Harvard Univ, Comm Biophys, 44 Binney St,S1036, Boston, MA 02115 USA. NR 38 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 28 PY 1999 VL 38 IS 39 BP 12577 EP 12585 DI 10.1021/bi9904508 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VQ UT WOS:000083018500006 PM 10504226 ER PT J AU Freeman, MW AF Freeman, MW TI Effluxed lipids: Tangier Island's latest export SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HIGH-DENSITY-LIPOPROTEIN; REVERSE CHOLESTEROL TRANSPORT; APOLIPOPROTEIN-A-I; INTRACELLULAR CHOLESTEROL; ABC TRANSPORTERS; CELL-SURFACE; DISEASE; FIBROBLASTS; RECEPTOR; BINDING C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. NR 32 TC 6 Z9 6 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 28 PY 1999 VL 96 IS 20 BP 10950 EP 10952 DI 10.1073/pnas.96.20.10950 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 241DY UT WOS:000082868500003 PM 10500104 ER PT J AU Robinson, SD Frenette, PS Rayburn, H Cummiskey, M Ullman-Cullere, M Wagner, DD Hynes, RO AF Robinson, SD Frenette, PS Rayburn, H Cummiskey, M Ullman-Cullere, M Wagner, DD Hynes, RO TI Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROLLING IN-VIVO; ENDOTHELIAL SELECTINS; MICE; EOSINOPHIL; ADHESION; EXPRESSION; CELLS; FLOW; SUSCEPTIBILITY; NEUTROPHILS AB We extend our previous analyses of mice deficient in selectins by describing the generation and comparative phenotype of mice lacking one, two, or three selectins after sequential ablation of the murine genes encoding P-, E-, add L-selectins. All mice deficient in selectins are viable and fertile as homozygotes. However, mice missing both P- and E-selectins (PE-/-), and mice missing all three selectins (ELP-/-) develop mucocutaneous infections that eventually lead to death. Mice deficient in multiple selectins display varying degrees of leukocytosis, resulting in part from alterations in leukocyte rolling and recruitment. PE-/- mice, ELP-/- mice,and mice missing both P- and L-selectins (PL-/-) show drastic reductions in leukocyte rolling and in extravasation of neutrophils in thioglycollate-induced peritonitis, In a separate inflammatory model (ragweed-induced peritoneal eosinophilia), we demonstrate P-selectin to be both necessary and sufficient for the recruitment of eosinophils, The phenotype of mice missing both E- and L-selectins (EL-/-) is less severe than those seen in the other double knockouts. Comparisons among the double knockouts suggest that P-selectin normally cooperates with both E- and L-selectins, Our results indicate a preeminent role for P-selectin in regulating leukocyte behavior in mice. Data from the ELP-/- mice indicate, however, that all three selectins are important to leukocyte homeostasis and efficient neutrophil recruitment. C1 MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Dept Biol, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hynes, RO (reprint author), MIT, Dept Biol, Howard Hughes Med Inst, 77 Massachusetts Ave,Bldg E17,Room 227, Cambridge, MA 02139 USA. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [P01 HL41484, R01 HL053756, HL53756] NR 33 TC 149 Z9 150 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 28 PY 1999 VL 96 IS 20 BP 11452 EP 11457 DI 10.1073/pnas.96.20.11452 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 241DY UT WOS:000082868500096 PM 10500197 ER PT J AU Esclapez, M Houser, CR AF Esclapez, M Houser, CR TI Up-regulation of GAD65 and GAD67 in remaining hippocampal GABA neurons in a model of temporal lobe epilepsy SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE glutamate decarboxylase; hippocampus; rats; pilocarpine; seizures ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; MESSENGER-RNA LEVELS; NONRADIOACTIVE INSITU HYBRIDIZATION; SPONTANEOUS RECURRENT SEIZURES; IN-SITU HYBRIDIZATION; PILOCARPINE-INDUCED SEIZURES; LESION-INDUCED INCREASES; RAT CEREBRAL-CORTEX; DENTATE GYRUS AB In the pilocarpine model of chronic limbic seizures, subpopulations of glutamic acid decarboxylase (GAD)-containing neurons within the hilus of the dentate gyrus and stratum oriens of the CA1 hippocampal region are vulnerable to seizure-induced damage. However, many gamma-aminobutyric acid (GABA) neurons remain in these and other regions of the hippocampal formation. To determine whether long-term changes occur in the main metabolic pathway responsible for GABA synthesis in remaining GABA neurons, the levels of mRNA and protein labeling for the two forms of GAD (GAD65 and GAD67) were studied in pilocarpine-treated animals that had developed spontaneous seizures. Qualitative and semiquantitative analyses of nonradioactive in situ hybridization experiments demonstrated marked increases in the relative amounts of GAD65 and GAD67 mRNAs in remaining hippocampal GABA neurons. In addition, immunohistochemical studies demonstrated parallel increases in the intensity of terminal labeling for both GAD65 and CAD67 isoforms throughout the hippocampal formation. These increases mere most striking for CAD65, the isoform of GAD that is particularly abundant in axon terminals. These findings demonstrate that, in a neuronal network that is capable of generating seizures, both GAD65 and GAD67 are up-regulated at the gene and protein levels in the remaining GABA neurons of the hippocampal formation. This study provides further evidence for the complexity of changes in the GABA system in this model of temporal lobe epilepsy. (C) 1999 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90095 USA. Hop Port Royal, INSERM U29, F-75014 Paris, France. W Los Angeles Vet Affairs Med Ctr, Serv Neurol, Wadsworth Div, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Wadsworth Div, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurobiol, 73-235 CHS, Los Angeles, CA 90095 USA. RI Esclapez, Monique/O-6509-2016 OI Esclapez, Monique/0000-0002-8558-1363 NR 71 TC 130 Z9 138 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 27 PY 1999 VL 412 IS 3 BP 488 EP 505 PG 18 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 227TN UT WOS:000082096200008 PM 10441235 ER PT J AU Orloff, SL Yin, Q Corless, CL Loomis, CB Rabkin, JM Wagner, CR AF Orloff, SL Yin, Q Corless, CL Loomis, CB Rabkin, JM Wagner, CR TI A rat small bowel transplant model of chronic rejection: Histopathologic characteristics SO TRANSPLANTATION LA English DT Article ID EXPERIMENTAL GRAFT ARTERIOSCLEROSIS; CARDIAC ALLOGRAFT VASCULOPATHY; CORONARY-ARTERY DISEASE; INTESTINAL TRANSPLANTATION; HEART; CELLS; IDENTIFICATION; CYCLOSPORINE; MORPHOLOGY; THERAPY AB Background, The major impediment to long-term success in solid organ transplantation is the development of chronic rejection (CR), The vascular lesion of CR, transplant vascular sclerosis (TVS) is characterized by neointimal smooth muscle cell proliferation, and is driven by both immune- and nonimmune-mediated mechanisms. Although the features of chronic heart and kidney allograft rejection have been well characterized, the more immunogenic small bowel allograft has not received similar study. Methods. F344 small bowel (SB) was transplanted heterotopically into Lewis recipients that were treated with low-dose Cyclosporine A for 15 days. Lewis recipients of F344 or Lewis SE grafts without immunosuppression, served as controls. Grafts were assessed histologically when recipients showed clinical signs of rejection or at predetermined time points. The immunological components involved in the chronic rejection process were evaluated by immunohistochemical staining. Results. All SE allografts (100%) developed histologic evidence of CR Cyclosporine A TVS was seen in 36 of the 46 (78%) of these allografts, The median time to develop TVS was 45 days. Immunohistochemical staining of chronically rejected grafts showed infiltration predominantly by CD4(+) cells and macrophages, uniform up-regulation of class II NHC molecule expression, moderate to intense ICAM-1 staining in grafts harvested at postoperative day 45, and uniform neointimal cell staining for smooth muscle cell alpha-actin in the TVS lesions. Conclusions, This F344 to Lewis SB transplant model is a useful model that reproduces significant features of CR The highly immunogenic: nature of the SE allografts allows this model to serve as a stringent test for protocols designed to prevent CR. C1 Portland VA Med Ctr, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Res Serv, Portland, OR USA. RP Orloff, SL (reprint author), Portland VA Med Ctr, Dept Surg, M-C P8 Liver,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 42 TC 21 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 27 PY 1999 VL 68 IS 6 BP 766 EP 779 DI 10.1097/00007890-199909270-00008 PG 14 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 241NH UT WOS:000082889100008 PM 10515376 ER PT J AU Huang, CA Yamada, K Murphy, MC Shimizu, A Colvin, RB Neville, DM Sachs, DH AF Huang, CA Yamada, K Murphy, MC Shimizu, A Colvin, RB Neville, DM Sachs, DH TI In vivo T cell depletion in miniature swine using the swine CD3 immunotoxin, pCD3-CRM9 SO TRANSPLANTATION LA English DT Article ID MIXED ALLOGENEIC CHIMERAS; DIPHTHERIA-TOXIN; MONOCLONAL-ANTIBODIES; TRANSPLANTATION TOLERANCE; RENAL-ALLOGRAFTS; GROWTH-FACTOR; INDUCTION; BLOOD; EXPRESSION; RECEPTOR AB Background. Partially inbred miniature swine developed in this laboratory provide a unique preclinical large animal model for studying transplant tolerance. The importance of in vivo T cell depletion for establishing stable mixed hematopoietic cell chimerism using a clinically relevant sublethal regimen has been well documented in murine studies (1). Until now, the lack of an effective in vivo T cell-depleting reagent in swine has limited the progress of studies involving hematopoietic cell transplants. Methods. The swine CD3 immunotoxin, pCD3-CRM9, was prepared by conjugating our porcine-specific CD3 monoclonal antibody 898H2-6-15 to the diphtheria toxin derivative, CRM9, The resultant immunotoxin was administered i.v, to several miniature swine at doses ranging from 0.15-0.2 mg/kg either in a single dose or two doses 2 days apart. T-cell depletion was monitored in the peripheral blood, mesenteric lymph node, and thymus by flow cytometric analysis and histological examination. Results, T cells were depleted to less than 1% of their pretreatment levels based on absolute numbers in the peripheral blood. Fluorescence activated cell sorter analysis and histological examination of serial lymph node biopsies confirmed depletion of the CD3+ T cells rather than down modulation or masking of the surface CD3 expression. Depletion of the CD3 bright medullary thymocytes could also be detected by flow cytometry and histological examination after immunotoxin treatment. Conclusions. Administration of the immunotoxin i.v. drastically depletes mature T cells from the peripheral blood, lymph node, and thymus compartments of the pig. This first description of an effective in vivo T-cell depleting reagent for the pig provides a valuable tool for studies of transplant tolerance in this large animal model. It also makes possible preclinical studies of T cell depletion with anti-CD3 immunotoxin in this large animal model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, Boston, MA 02129 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [1RO1 CA61537]; NIAID NIH HHS [5RO1 AI39755] NR 33 TC 42 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 27 PY 1999 VL 68 IS 6 BP 855 EP 860 DI 10.1097/00007890-199909270-00019 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 241NH UT WOS:000082889100019 PM 10515387 ER PT J AU White, AR Reyes, R Mercer, JFB Camakaris, J Zheng, H Bush, AI Multhaup, G Beyreuther, K Masters, CL Cappai, R AF White, AR Reyes, R Mercer, JFB Camakaris, J Zheng, H Bush, AI Multhaup, G Beyreuther, K Masters, CL Cappai, R TI Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice SO BRAIN RESEARCH LA English DT Article DE metals; amyloid precursor protein; copper; oxidative stress; knockout ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; BETA-PROTEIN; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; NEURONAL DEATH; BINDING-SITE; CELLS; EXPRESSION; ZINC AB The pathological process in Alzheimer's disease (AD) involves amyloid beta (A beta) deposition and neuronal cell degeneration. The neurotoxic AP peptide is derived from the amyloid precursor protein (APP), a member of a larger gene family including the amyloid precursor-like proteins, APLP1 and APLP2. The APP and APLP2 molecules contain metal binding sites for copper and zinc. The zinc binding domain (ZnBD) is believed to have a structural rather than a catalytic role. The activity of the copper binding domain (CuBD) is unknown, however, APP reduces copper (IT) to copper (I) and this activity could promote copper-mediated neurotoxicity. The expression of APP and APLP2 in the brain suggests they could have an important direct or indirect role in neuronal metal homeostasis. To examine this, we measured copper, zinc and iron levels in the cerebral cortex, cerebellum and selected non-neuronal tissues from APP (APP(-/-)) and APLP2 (APLP2(-/-)) knockout mice using atomic absorption spectrophotometry. Compared with matched wild-type (WT) mice, copper levels were significantly elevated in both APP(-/-) and APLP2(-/-) cerebral cortex (40% and 16%, respectively) and liver (80% and 36%, respectively). Copper levels were not significantly different between knockout and WT cerebellum, spleen or serum samples. There were no significant differences observed between APP(-/-), APLP2(-/-) and WT mice zinc or iron levels in any tissue examined. These findings indicate APP and APLP2 expression specifically modulates copper homeostasis in the liver and cerebral cortex, the latter being a region of the brain particularly involved in AD. Perturbations to APP metabolism and in particular, its secretion or release from neurons may alter copper homeostasis resulting in increased A beta accumulation and free radical generation. These data support a novel mechanism in the APP/A beta pathway which leads to AD. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst, Parkville, Vic 3052, Australia. Royal Childrens Hosp, Murdoch Inst, Scobie & Claire Mackinnon Trace Elements Lab, Parkville, Vic 3052, Australia. Deakin Univ, Sch Biol & Chem Sci, Ctr Cellular & Mol Biol, Burwood, Vic 3125, Australia. Univ Melbourne, Dept Genet, Parkville, Vic 3052, Australia. Merck & Co Inc, Merck Sharp & Dohme Res Labs, Dept Genet & Mol Biol, Rahway, NJ 07065 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Univ Heidelberg, Ctr Mol Biol, D-69120 Heidelberg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Cappai, R (reprint author), Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RI White, Anthony/P-5596-2016; Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007 OI White, Anthony/0000-0003-1802-9891; Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069 NR 42 TC 207 Z9 218 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 25 PY 1999 VL 842 IS 2 BP 439 EP 444 DI 10.1016/S0006-8993(99)01861-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 245TZ UT WOS:000083125400017 PM 10526140 ER PT J AU Bax, WA Cluysenaer, OJJ Bartelink, AKM Aerts, PC Ezekowitz, RAB van Dijk, H AF Bax, WA Cluysenaer, OJJ Bartelink, AKM Aerts, PC Ezekowitz, RAB van Dijk, H TI Association of familial deficiency of mannose-binding lectin and meningococcal disease SO LANCET LA English DT Article AB We report the case of an 18-year-old man with meningococcal meningitis and low serum concentrations of mannose-binding lectin (MBL). His mother and grandfather, who had also had meningitis in early adulthood, also had low concentrations of MBL in their serum. C1 Eemland Hosp, Dept Internal Med, NL-3800 BM Amersfoort, Netherlands. Eemland Hosp, Dept Immunol, NL-3800 BM Amersfoort, Netherlands. Univ Utrecht, Med Ctr, Eljkman Winkler Inst Microbiol Infect Dis & Infla, Utrecht, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. RP Bax, WA (reprint author), Eemland Hosp, Dept Internal Med, POB 1502, NL-3800 BM Amersfoort, Netherlands. NR 2 TC 49 Z9 51 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 25 PY 1999 VL 354 IS 9184 BP 1094 EP 1095 DI 10.1016/S0140-6736(99)02563-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 239PA UT WOS:000082777500019 PM 10509505 ER PT J AU Keats, BJB Corey, DP AF Keats, BJB Corey, DP TI The Usher syndromes SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Review DE hearing impairment; pigmentary retinopathy; myosin VIIa; genetic heterogeneity; clinical heterogeneity ID MYOSIN-VIIA GENE; SYNDROME TYPE-I; SYNDROME TYPE-IIA; TEMPORAL BONE REPORT; COCHLEAR HAIR-CELLS; SYNDROME TYPE 1C; RETINITIS PIGMENTOSA; INNER-EAR; UNCONVENTIONAL MYOSINS; RECESSIVE DEAFNESS AB Mutations in the gene (MYO7A) encoding myosin-Vlla, a member of the large superfamily of myosin motor proteins that move on cytoplasmic actin filaments, and in the USH2A gene, which encodes a novel protein resembling an extracellular matrix protein or a cell adhesion molecule, both cause Usher syndrome (USH), a clinically heterogeneous autosomal recessive disorder comprising hearing and visual impairment. Patients with USH1 have severe to profound congenital hearing impairment, vestibular dysfunction, and retinal degeneration beginning in childhood, while those with USH2 have moderate to severe hearing impairment normal vestibular function, and later onset of retinal degeneration. USH3 is characterized by progressive hearing loss and variable age of onset of retinal degeneration. The phenotype resulting from MYO7A and USH2A mutations is variable. While most MYO7A mutations cause USH1, some cause nonsyndromic hearing impairment, and one USH3 phenotype has been described. USH2A mutations cause atypical USH as well as USH2. MYO7A is on chromosome region 11q13 and USH2A is on 1q41. Seven other USH genes have been mapped but have nor yet been identified. USH1A, USH1C, USH1D, USH1E, and USH1F have been assigned to chromosome bands 14q32, 11p15.1, 10q, 21q21, and 10, respectively, while USH2B is on 5q, and USH3 is at 3q21-q25. Myosin Vlla mutations also result in the shaker-1 (sh1) mouse, providing a model for functional studies. One possibility is that myosin-Vlla is required for linking stereocilia in the sensory hair bundle; another is that it may be needed for membrane trafficking. The ongoing studies of myosin-Vlla, the USH2A protein, and the yet to be identified proteins encoded by the other USH genes will advance understanding of the Usher syndromes and contribute to the development of effective therapies. (C) 2000 Wiley-Liss, Inc. C1 Louisiana State Univ, Med Ctr, Dept Biometry & Genet, Hlth Sci Ctr,Mol & Human Genet Ctr, New Orleans, LA 70112 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. RP Keats, BJB (reprint author), Louisiana State Univ, Med Ctr, Dept Biometry & Genet, Hlth Sci Ctr,Mol & Human Genet Ctr, 1901 Perdido St, New Orleans, LA 70112 USA. OI Corey, David/0000-0003-4497-6016 NR 110 TC 88 Z9 91 U1 2 U2 10 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 SEP 24 PY 1999 VL 89 IS 3 BP 158 EP 166 DI 10.1002/(SICI)1096-8628(19990924)89:3<158::AID-AJMG6>3.0.CO;2-# PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 287ZZ UT WOS:000085538500006 PM 10704190 ER PT J AU Heintges, T Putlitz, JZ Wands, JR AF Heintges, T Putlitz, JZ Wands, JR TI Characterization and binding of intracellular antibody fragments to the hepatitis C virus core protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GENE-EXPRESSION; ESCHERICHIA-COLI; CELL-LINES; INHIBITION; OLIGODEOXYNUCLEOTIDES; EPIDEMIOLOGY; IMMUNIZATION; HEPATOCYTES; INTRABODIES; RIBOZYMES AB The monoclonal antibody C7-50 binds to the HCV core protein with high sensitivity and specificity. The coding sequences of the variable domains of the antibody were determined following cDNA cloning of the Fab and sFv fragments. Subsequently, intracellular expression and binding of these antibody fragments to the HCV core protein as a potential antiviral approach were studied. There was high specificity and sensitivity of binding of bacterially expressed, recombinant C7-50 Fab to HCV core as measured by EIA and immunoblot, For expression in mammalian cells, the C7-50 antibody was subcloned in the sFv format by the introduction of a (Gly(4)Ser)(3) linker spaced between light and heavy chains. Northern and Western blot analysis as well as confocal microscopy established the targeted expression of the C7-50 sFv antibody fragment in the endoplasmic reticulum of transfected cells. The colocalization and intracellular binding of the antibody fragment to HCV core protein was confirmed by immunoprecipitation and subsequent immunoblot analysis. This study demonstrates that gene delivery of cDNA coding sequences inducing intracellular expression of C7-50 antibody fragments leads to binding of the antibody fragment to the HCV core protein within the secretory compartment of transfected cells. Intracellular immunization represents a promising antiviral approach to interfere with the life cycle of HCV. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Wands, JR (reprint author), Brown Univ, Rhode Isl Hosp, Sch Med, Liver Res Ctr, 55 Claverick St,4th Floor, Providence, RI 02903 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 37 TC 11 Z9 13 U1 1 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 SEP 24 PY 1999 VL 263 IS 2 BP 410 EP 418 DI 10.1006/bbrc.1999.1350 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 243UV UT WOS:000083016400026 PM 10491307 ER PT J AU Plath, T Hocker, M Riecken, EO Wang, TC Wiedenmann, B Rosewicz, S AF Plath, T Hocker, M Riecken, EO Wang, TC Wiedenmann, B Rosewicz, S TI Interferon-alpha inhibits chromogranin A promoter activity in neuroendocrine pancreatic cancer cells SO FEBS LETTERS LA English DT Article DE neuroendocrine tumor; chromogranin A gene regulation; hypersecretion syndrome; interferon-alpha; cAMP-responsive element binding protein; cAMP-responsive element binding protein binding protein ID GASTROENTEROPANCREATIC SYSTEM; CARCINOID-TUMORS; ADENOVIRUS E1A; GENE; P300; CBP AB Interferon-cr (IFN-a) treatment ran suppress the hypersecretion syndrome associated with functional neuroendocrine tumors. Chromogramin A (CpA) is a matrix protein of neuroendocrine secretory vesicles and appears to be essential for an appropriate neuroendocrine secretory function. To test the hypothesis that IFN-a can directly interfere with CgA gene transcription, we performed transient transfection studies in pancreatic neuroendocrine tumor cells employing CgA-luciferase reporter gene constructs shelving that IFN-a inhibited basal and protein kinase C-dependent CgA promoter activity. Using 5'-deletion constructs in combination with mutational analysis of the proximal CgA core promoter, a cyclic AMP response element (CRE) at -71 to -64 bp was identified as the IFN-cr response element of the CgA gene. Furthermore, functional studies indicated that IFN-cl exerts its effect on the CgA promoter via interferace,with CRE binding protein (CREB)/CREB binding protein (CBP)-dependent transactivation of the CgA-CRE. (C) 1999 Federation of European Biochemical Societies. C1 Humboldt Univ, Klinikum Charite, Med Klin Schwerpunkt Hepatol & Gastroenterol, D-13353 Berlin, Germany. Free Univ Berlin, Klinikum Benjamin Franklin, Med Klin 1, Berlin, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. RP Rosewicz, S (reprint author), Humboldt Univ, Klinikum Charite, Med Klin Schwerpunkt Hepatol & Gastroenterol, Campus Virchow Klinikum,Augustenburger Pl 1, D-13353 Berlin, Germany. NR 21 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 24 PY 1999 VL 458 IS 3 BP 378 EP 382 DI 10.1016/S0014-5793(99)01187-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 240ZL UT WOS:000082856600022 PM 10570944 ER PT J AU Carling, T Imanishi, Y Gaz, RD Arnold, A AF Carling, T Imanishi, Y Gaz, RD Arnold, A TI Analysis of the RAD54 gene on chromosome 1p as a potential tumor-suppressor gene in parathyroid adenomas SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MEN1 GENE; PRIMARY HYPERPARATHYROIDISM; GENOMIC INSTABILITY; DNA; SACCHAROMYCES; LOCALIZATION; MUTATIONS; CANDIDATE; MUTANT; REPAIR AB Parathyroid adenomas causing primary hyperparathyroidism (pHPT) frequently exhibit allelic loss of DNA markers on the short arm of chromosome I, indicating the presence of one or more tumor-suppressor genes on 1p, Since the development of pHPT is enhanced in individuals exposed to ionizing radiation to the neck, it could be anticipated that genes involved in DNA repair and recombination may be special targets for mutation in parathyroid tumorigenesis, whether irradiation-associated or not. RAD54 is a member of a family of genes involved in such functions, and RAD54 knockout mice show increased sensitivity to ionizing radiation. The localization of the RAD54 gene to 1p32 has therefore elevated it to a most compelling candidate parathyroid tumor-suppressor gene. Twelve parathyroid adenomas demonstrating allelic loss at chromosome Ip were selected from 55 parathyroid adenomas previously analyzed for loss of heterozygosity using polymorphic microsatellite markers, All 18 exons of the RAD54 gene were fully analyzed by automated sequencing for detection of point mutations or microdeletions in each parathyroid adenoma, No mutational aberrations were detected in the RAD54 gene, strongly suggesting that complete somatic inactivation of RAD54 is infrequently, if ever, associated with the development of parathyroid adenomas, Whether genes controlling DNA repair and recombination are involved in parathyroid neoplasia remains to be determined. (C) 1999 Wiley-Liss. Inc. C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. NR 25 TC 15 Z9 16 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 SEP 24 PY 1999 VL 83 IS 1 BP 80 EP 82 DI 10.1002/(SICI)1097-0215(19990924)83:1<80::AID-IJC15>3.0.CO;2-E PG 3 WC Oncology SC Oncology GA 231AK UT WOS:000082283700015 PM 10449612 ER PT J AU Li, JS Tong, SP Wands, JR AF Li, JS Tong, SP Wands, JR TI Identification and expression of glycine decarboxylase (p120) as a duck hepatitis B virus pre-S envelope-binding protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OVERLAP EXTENSION; CLEAVAGE SYSTEM; MAMMALIAN-CELLS; INITIATION; TRANSLATION; GENE; PARTICLES; VICTORIN; CHICKEN; EPITOPE AB A 120-kilodalton protein (p120) was identified in the duck liver that binds to several truncated versions of duck hepatitis B virus (DHBV) pre-S envelope protein, suggesting p120 may serve as a DHBV co-receptor. The amino acid sequences of tryptic peptides from purified p120 were found to be the duck p protein of the glycine decarboxylase complex (DGD). DGD cDNA cloning revealed extensive protein conservation with the chicken homologue except for several insertions in the N-terminal leader sequence. The DGD cDNA contained no in-frame AUG codon at the predicted initiation site of the open reading frame, and site directed mutagenesis experiments established an AUU codon as the translational initiator. The DGD protein expressed in rabbit reticulocyte lysates bound truncated DHBV pre-S protein identical to that of p120 derived from duck liver confirming DGD as p120. Moreover, transfection studies in liver- and kidney derived cells revealed both cell surface and cytoplasmic expression of the protein. Cloning of the glycine decarboxylase cDNA will permit a direct test of whether it functions as a cell surface co-receptor or as a co-factor in the DHBV replication cycles. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Wands, JR (reprint author), Liver Res Ctr, 55 Claverick St,4th Floor, Providence, RI 02903 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666] NR 22 TC 20 Z9 22 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 SEP 24 PY 1999 VL 274 IS 39 BP 27658 EP 27665 DI 10.1074/jbc.274.39.27658 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238XB UT WOS:000082739100045 PM 10488106 ER PT J AU Choi, SJ Reddy, SV Devlin, RD Menaa, C Chung, HY Boyce, BF Roodman, GD AF Choi, SJ Reddy, SV Devlin, RD Menaa, C Chung, HY Boyce, BF Roodman, GD TI Identification of human asparaginyl endopeptidase (legumain) as an inhibitor of osteoclast formation and bone resorption SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MARROW CULTURES; NORMAL MICE; CLONING; CELLS; OSTEOPROTEGERIN; INTERLEUKIN-1; DEGRADATION; EXPRESSION; HEMOGLOBIN; PROTEIN AB We screened a human osteoclast (OCL) cDNA expression library for OCL inhibitory factors and identified a clone that blocked both human and murine OCL formation and bone resorption by more than 60%. This clone was identical to human legumain, a cysteine endopeptidase. Legumain significantly inhibited OCL-like multinucleated cell formation induced by 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) and parathyroid hormone-related protein (PTHrP) in mouse and human bone marrow cultures, and bone resorption in the fetal rat long bone assay in a dose-dependent manner. Legumain was detected in freshly isolated marrow plasma from normal donors and conditioned media from human marrow cultures. Furthermore, treatment of human marrow cultures with an antibody to legumain induced OCL formation to levels that were as high as those induced by 1,25-(OH)(2)D-3. Implantation in nude mice of 293 cells transfected with the legumain cDNA and constitutively expressing high levels of the protein significantly reduced hypercalcemia induced by PTHrP by about 50%, and significantly inhibited the increase in OCL surface and in OCL number expressed per mm(2) bone area and per mm bone surface induced by PTHrP. These results suggest that legumain may be a physiologic local regulator of OCL activity that can negatively modulate OCL formation and activity. C1 Audie L Murphy Mem Vet Adm Med Ctr, Res Serv 151, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. RP Audie L Murphy Mem Vet Adm Med Ctr, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM roodman@uthscsa.edu FU NIA NIH HHS [AG13625]; NIAMS NIH HHS [AR41336, AR44603] NR 23 TC 70 Z9 72 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 24 PY 1999 VL 274 IS 39 BP 27747 EP 27753 DI 10.1074/jbc.274.39.27747 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238XB UT WOS:000082739100057 PM 10488118 ER PT J AU Yang, XY Chen, YZ Gabuzda, D AF Yang, XY Chen, YZ Gabuzda, D TI ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF-kappa B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; TUMOR NECROSIS FACTOR; ACTIVE ANTIRETROVIRAL THERAPY; PROTEIN-KINASE; GENE-EXPRESSION; T-CELLS; TRANSCRIPTION FACTORS; MONOCYTIC CELLS; BINDING-SITES AB Human immunodeficiency virus type 1 (HIV-1) can establish latent infection following provirus integration into the host genome. NF-kappa B plays a critical role in activation of HIV-1 gene expression by cytokines and other stimuli, but the signal transduction pathways that regulate the switch from latent to productive infection have not been defined. Here, we show that ERK1/ERK2 mitogen-activated protein kinase (MAPK) plays a central role in linking signals at the cell surface to activation of HIV-1 gene expression in latently infected cells. MAPK was activated by cytokines and phorbol 12-myristate 13-acetate in latently infected U1 cells. The induction of HIV-1 expression by these stimuli was inhibited by PD98059 and U0126, which are specific inhibitors of MAPK activation. Studies using constitutively active MEK or Raf kinase mutants demonstrated that MAPK activates the HIV-1 long terminal repeat (LTR) through the NF-kappa B sites. Most HIV-1 inducers activated NF-kappa B via a MAPK-independent pathway, indicating that activation of NF-kappa B is not sufficient to explain the activation of HIV-1 gene expression by MAPK. In contrast, all of the stimuli activated AP-1 via a MAPK-dependent pathway. NF-kappa B and AP-1 components c-Fos and c-Jun were shown to physically associate by yeast two-hybrid assays and electrophoretic mobility shift assays. Coexpression of NF-kappa B and c-Fos or c-Jun synergistically transactivated the HIV-1 LTR through the NF-kappa B sites. These studies suggest that MAPK acts by stimulating AP-1 and a subsequent physical and functional interaction of AP-1 with NF-kappa B, resulting in a complex that synergistically transactivates the HIV-1 LTR. These results define a mechanism for signal-dependent activation of HIV-1 replication in latently infected cells and suggest potential therapeutic strategies for unmasking latent reservoirs of HIV-1. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF 816,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI36186, AI28691] NR 77 TC 137 Z9 141 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 24 PY 1999 VL 274 IS 39 BP 27981 EP 27988 DI 10.1074/jbc.274.39.27981 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 238XB UT WOS:000082739100087 PM 10488148 ER PT J AU Jin, JK Choi, JK Lee, HG Kim, YS Carp, RI Choi, EK AF Jin, JK Choi, JK Lee, HG Kim, YS Carp, RI Choi, EK TI Increased expression of CaM kinase II alpha in the brains of scrapie-infected mice SO NEUROSCIENCE LETTERS LA English DT Article DE CaM kinase II alpha; synaptic plasticity; scrapie; Western blot; immunohistochemistry ID LONG-TERM POTENTIATION; DEPENDENT PROTEIN-KINASE; GLUTAMATE RECEPTORS; PRION PROTEIN; PHOSPHORYLATION; MECHANISMS; KII AB We investigated the distribution of calcium/calmodulin-dependent protein kinase II (CaM kinase II) in the brains of mice infected with ME7 scrapie strain. CaM kinase II is an enzyme that plays a major role in the regulation of long-term potentiation, a form of synaptic plasticity associated with learning and memory. Immunoreactivity of CaM kinase II alpha, measured by Western blot, increased markedly in scrapie-infected brains compared with control brains. Immunohistochemically, CaM kinase II alpha immunoreactivity was upregulated in the cerebral cortex and hippocampal CA1 area of scrapie-positive mice infected with ME7 scrapie strain. This result implies that this enzyme is associated with aberrant function of synaptic transmission and LTP of the pyramidal neurons in the hippocampal CA1 area of mice infected with ME7 scrapie strain. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Hallym Univ, Hallym Acad Sci, Inst Environm & Life Sci, Chunchon 200702, South Korea. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. RP Hallym Univ, Hallym Acad Sci, Inst Environm & Life Sci, Chunchon 200702, South Korea. EM ejchoi@sun.hallym.ac.kr RI Lee, Hyoung-gon/A-9637-2009 NR 20 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 24 PY 1999 VL 273 IS 1 BP 37 EP 40 DI 10.1016/S0304-3940(99)00622-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 238NR UT WOS:000082716800010 PM 10505646 ER PT J AU Aramburu, J Yaffe, MB Lopez-Rodriguez, C Cantley, LC Hogan, PG Rao, A AF Aramburu, J Yaffe, MB Lopez-Rodriguez, C Cantley, LC Hogan, PG Rao, A TI Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A SO SCIENCE LA English DT Article ID TRANSCRIPTION FACTOR NFAT1; T-CELLS; CALCINEURIN; ACTIVATION; FAMILY; DOMAIN; COMPONENTS; MECHANISM; PATHWAY; KINASES AB The flow of information from calcium-mobilizing receptors to nuclear factor of activated T cells (NFAT)-dependent genes is critically dependent on interaction between the phosphatase calcineurin and the transcription factor NFAT. A high-affinity calcineurin-binding peptide was selected from combinatorial peptide Libraries based on the calcineurin docking motif of NFAT, This peptide potently inhibited NFAT activation and NFAT-dependent expression of endogenous cytokine genes in T cells, without affecting the expression of other cytokines that require calcineurin but not NFAT. Substitution of the optimized peptide sequence into the natural calcineurin docking site increased the calcineurin responsiveness of NFAT. Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are Less toxic than current drugs. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Harvard Inst Med, Dept Cell Biol, Boston, MA 02215 USA. CBR Labs, Boston, MA 02115 USA. RP Hogan, PG (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Cantley, Lewis/D-1800-2014; Lopez-Rodriguez, C/G-4482-2014; Aramburu, J/G-8991-2014 OI Cantley, Lewis/0000-0002-1298-7653; Lopez-Rodriguez, C/0000-0002-2311-2406; Aramburu, J/0000-0001-9279-9523 FU NHLBI NIH HHS [R01 HL 03601]; NIAID NIH HHS [R01 AI 40127, R43 AI 43726]; NIGMS NIH HHS [R01 GM056203] NR 39 TC 397 Z9 407 U1 1 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 24 PY 1999 VL 285 IS 5436 BP 2129 EP 2133 DI 10.1126/science.285.5436.2129 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 238VF UT WOS:000082734300043 PM 10497131 ER PT J AU Jung, ME Yang, EC Vu, BT Kiankarimi, M Spyrou, E Kaunitz, J AF Jung, ME Yang, EC Vu, BT Kiankarimi, M Spyrou, E Kaunitz, J TI Glycosylation of fluoroquinolones through direct and oxygenated polymethylene linkages as a sugar-mediated active transport system for antimicrobials SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID INVITRO ACTIVITY; NALIDIXIC-ACID; ANTIBACTERIAL AGENTS; ESCHERICHIA-COLI; PHOSPHOTRANSFERASE SYSTEM; CIPROFLOXACIN; QUINOLONES; TOPOISOMERASES; LOMEFLOXACIN; NORFLOXACIN AB We report herein the synthesis and biological testing of several glycosylated derivatives of some fluoroquinolone antibiotics. In particular, we have prepared several glycosylated derivatives of ciprofloxacin (2) in which the carbohydrate units are linked to the free secondary amine of the piperazine unit by: (a) no linker (e.g., a glycosylamine), (b) a beta-oxyethyl linker, and (c) a gamma-oxypropyl linker. Both glucose and galactose were used as carbohydrates so that six compounds of this type were prepared, e.g., no linker 4a,b, oxyethyl linker 5a,b, and oxypropyl linker 6a,b. In addition the aryl glycosides of glucose and galactose (7a,b) were prepared from the active 1-(4-hydroxyphenyl)fluoroquinolone (3.) The syntheses of the glycosylamines 4a,b involved the direct condensation of glucose and galactose with the hydrochloride salt of ciprofloxacin (2). For the oxyalkyl-linked compounds, we first prepared the peracetylated omega-bromoalkyl glycopyranosides 14a,b and 15a,b and then coupled them to the allyl ester of ciprofloxacin (11) to give, after saponification to remove all of the esters, the desired fluoroquinolone carbohydrates 5a,b and 6a,b. The final series was prepared from 2,4,5-trifluorobenzoyl chloride (22) which gave 3 in four precedented steps. Coupling of 3 with the peracetylated glucosyl and galactosyl halides 12a,b and 26 afforded, after saponification, the desired aryl glycosides 7a,b. Six of these derivatives of ciprofloxacin-4a,b, 5a,b, and 6a,b-were subjected to microbiological screening. Of the six, compound 6a showed the highest activity. Since 6a would give the hydroxypropyl-substituted ciprofloxacin on hydrolysis and its activity is similar to 4-8 times less than that of ciprofloxacin (2), this implies that compound 6a is probably being actively transported. Thus preliminary results suggest that some of the compounds are stable in culture conditions and may be differentially transported by multiple resistant organisms. In some cases, the addition of a linker and a carbohydrate to ciprofloxacin lessens, but does not eliminate, antimicrobial activity. C1 Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90024 USA. RP Jung, ME (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. NR 49 TC 25 Z9 25 U1 0 U2 7 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 SEP 23 PY 1999 VL 42 IS 19 BP 3899 EP 3909 DI 10.1021/jm990015b PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 239RJ UT WOS:000082783200014 PM 10508438 ER PT J AU Leonard, KA Nelen, MI Simard, TP Davies, SR Gollnick, SO Oseroff, AR Gibson, SL Hilf, R Chen, LB Detty, MR AF Leonard, KA Nelen, MI Simard, TP Davies, SR Gollnick, SO Oseroff, AR Gibson, SL Hilf, R Chen, LB Detty, MR TI Synthesis and evaluation of chalcogenopyrylium dyes as potential sensitizers for the photodynamic therapy of cancer SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SELECTIVE MITOCHONDRIAL ACCUMULATION; NILE BLUE PHOTOSENSITIZERS; CARCINOMA-CELLS; CHALCOGENAPYRYLIUM DYES; ANTICARCINOMA ACTIVITY; RHODACYANINE MKT-077; ANTITUMOR-ACTIVITY; MOLECULAR-OXYGEN; CYTO-TOXICITY; RHODAMINE-123 AB A series of thiopyrylium (2), selenopyrylium (3), and telluropyrylium dyes (4) was prepared via the addition of Grignard reagents to either 2,6-di(4-dimethylamino)phenylchalcogenopyran-4-ones (5a) or 2-[4-(dimethylamino)phenyl] -6-phenylchalcogenopyran-4-ones (5b) followed by elimination and ion exchange to give the chloride salts. The absorption spectra and quantum yields for singlet oxygen generation of these dyes suggested that the dyes would have utility as sensitizers for PDT. Selenopyrylium dyes 3a and 3d with quantum yields for singlet oxygen generation of 0.040 and 0.045, respectively, were phototoxic to Colo-26 cells in culture. The toxicity of the dyes 2-4 was evaluated in clonogenic assays of human carcinoma cell lines. Importantly, the presence of a sulfur, selenium, or tellurium heteroatom in the molecules had no predictable impact on the toxicity of any particular dye set. Substituents at the 2-, 4-, and 6-positions of the dye had a much greater impact on cytotoxicity. The IC50 values determined in the clonogenic assays did not correlate with chemical properties in the dye molecules such as reduction potential or lipophilicity. Initial in vivo toxicity studies showed no toxicity for these dyes at dosages between 7.2 and 38 mu mol/kg in BALB/c mice. C1 SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. SUNY Buffalo, Dept Med Chem, Buffalo, NY 14260 USA. Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. Roswell Pk Canc Inst, Dept Dermatol, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, PDT Ctr, Buffalo, NY 14263 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Detty, MR (reprint author), SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA. FU NCI NIH HHS [CA69155, CA36856] NR 55 TC 44 Z9 45 U1 0 U2 11 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 SEP 23 PY 1999 VL 42 IS 19 BP 3953 EP 3964 DI 10.1021/jm990245q PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 239RJ UT WOS:000082783200019 PM 10508443 ER PT J AU Kaluza, GL Ali, NM Abukhalil, JM Waksman, R Oesterle, SN Raizner, AE AF Kaluza, GL Ali, NM Abukhalil, JM Waksman, R Oesterle, SN Raizner, AE TI Intracoronary beta-radiation is equally effective after stenting and balloon angioplasty: A subanalysis of the PREVENT trial. SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 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 SEP 22 PY 1999 VL 84 IS 6A SU S BP 10P EP 11P PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238PX UT WOS:000082719600025 ER PT J AU Kiesz, RS Bouknight, D Miller, OL Rozek, MM Moody, JM Sepeda, JM Sako, EY Garza, L O'Rouke, R AF Kiesz, RS Bouknight, D Miller, OL Rozek, MM Moody, JM Sepeda, JM Sako, EY Garza, L O'Rouke, R TI Multivessel percutaneous coronary interventions versus bypass surgery: Long term results. SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 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 SEP 22 PY 1999 VL 84 IS 6A SU S BP 31P EP 31P PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238PX UT WOS:000082719600075 ER PT J AU Little, SJ Daar, ES D'Aquila, RT Keiser, PH Connick, E Whitcomb, JM Hellmann, NS Petropoulos, CJ Sutton, L Pitt, JA Rosenberg, ES Koup, RA Walker, BD Richman, DD AF Little, SJ Daar, ES D'Aquila, RT Keiser, PH Connick, E Whitcomb, JM Hellmann, NS Petropoulos, CJ Sutton, L Pitt, JA Rosenberg, ES Koup, RA Walker, BD Richman, DD TI Reduced antiretroviral drug susceptibility among patients with primary HIV infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ZIDOVUDINE RESISTANCE; REVERSE-TRANSCRIPTASE; NUCLEOSIDE ANALOGS; THERAPY; LAMIVUDINE; TRANSMISSION; NEVIRAPINE; INDINAVIR; VIREMIA AB Context The transmission of drug-resistant hu man immunodeficiency virus (HIV) has been documented, but the prevalence of such transmission is unknown. Objective To assess the spectrum and frequency of antiretroviral susceptibility among subjects with primary HIV infection. Design, Setting, and Patients Retrospective analysis of 141 subjects identified from clinical research centers in 5 major metropolitan areas, enrolled from 1989 to 1998, with HIV seroconversion within the preceding 12 months and no more than 7 days' prior antiretroviral (ARV) therapy. Main Outcome Measures Phenotypic and genotypic ARV susceptibility of HIV from plasma samples. Results The transmission of drug-resistant HIV as assessed by a greater than 10-fold reduction in ARV susceptibility to 1 or more drugs was observed in 3 (2%) of 141 subjects, including to a nonnucleoside reverse transcriptase inhibitor in 1 patient and to a nucleoside reverse transcriptase inhibitor and a protease inhibitor in 2 patients. Population-based sequence analysis of these 3 samples identified multidrug-resistance mutations in reverse transcriptase (M184V, T215Y, K219K/R) and protease (L10I/V, K20R, M36I, M46I, G48V, L63P, A71T, V77I, V82T, I84V, L90M) in the 2 latter patient samples, along with numerous polymorphisms. A reduction in susceptibility of greater than 2.5- to 10-fold to 1 or more drugs was observed in viral isolates from 36 patients (26%). Sequence analysis of these 36 samples identified well-characterized drug resistance mutation in reverse transcriptase and protease in only 1 of these patients. Conclusions Reductions in drug susceptibility of more than 10-fold were rare among this cohort of recently HIV-infected subjects and were distributed among each of the 3 major classes of ARV drugs tested. Reductions in susceptibility of more than 2.5- to 10-fold to certain ARV drugs of unknown clinical significance were highly prevalent among newly infected patients. Resistance testing may be warranted to monitor the frequency of drug resistance over time and to assess the potential for geographic variability. C1 Univ Calif San Diego, Treatment Ctr, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. Dept Vet Affairs Med Ctr, San Diego, CA USA. Cedars Sinai Burns & Allen Res Inst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Dept Vet Affairs Med Ctr, Denver, CO USA. ViroLog Inc, S San Francisco, CA USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Merck & Co Inc, Blue Bell, PA USA. Bristol Myers Squibb Co, Glaxo Wellcome, Princeton, NJ USA. Agouron Inst, La Jolla, CA 92037 USA. Roxane, Columbus, OH USA. RP Little, SJ (reprint author), Univ Calif San Diego, Treatment Ctr, Dept Med, 2760 5th Ave,Suite 300, San Diego, CA 92103 USA. FU NIAID NIH HHS [AI36214, AI27670, AI01541] NR 39 TC 264 Z9 271 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 22 PY 1999 VL 282 IS 12 BP 1142 EP 1149 DI 10.1001/jama.282.12.1142 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 236JJ UT WOS:000082596200029 PM 10501117 ER PT J AU Koh, S Storey, TW Santos, TC Mian, AY Cole, AJ AF Koh, S Storey, TW Santos, TC Mian, AY Cole, AJ TI Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood SO NEUROLOGY LA English DT Article DE development; seizures; status epilepticus; kainate; injury; memory ID TEMPORAL-LOBE EPILEPSY; NEURONAL MIGRATION DISORDERS; KAINIC ACID; STATUS EPILEPTICUS; FEBRILE SEIZURES; CHILDHOOD; PATTERNS; CONSEQUENCES; CONVULSIONS; MECHANISMS AB Background: Early childhood convulsions have been correlated with the finding of subsequent hippocampal neuronal loss and memory impairment in patients with intractable temporal lobe epilepsy. There is little direct evidence, however, that links early seizures with the later development of epilepsy and selective hippocampal neuronal loss. Objective: To study the long-term effect of early seizures on later seizure-induced neuronal damage and behavior. Methods: We used a "two hit" rat seizure made in which systemic kainate was used to induce seizures during the second week of life (P15) and again in adulthood (P45). Memory was subsequently tested using a Morris water maze, and brains were examined for histologic evidence of injury. Results: Although the first kainate-induced seizure is not associated with detectable injury or cell death, it predisposes animals to more extensive neuronal injury after kainate-induced seizures in adulthood. Moreover, although early-life kainate-induced seizures cause no impairment of spatial learning, animals that have early-life and adult kainate-induced seizures perform significantly worse than those that have seizures only as adults. Conclusions: We concluded that early-life seizures, without causing overt cellular injury, predispose the brain to the damaging effect of seizures later in life. C1 Harvard Univ, Epilepsy Serv, Massachusetts Gen Hosp, Sch Med,Epilepsy Res Lab, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Harvard Univ, Epilepsy Serv, Massachusetts Gen Hosp, Sch Med,Epilepsy Res Lab, VBK 830,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS036224] NR 45 TC 98 Z9 99 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 22 PY 1999 VL 53 IS 5 BP 915 EP 921 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 236DG UT WOS:000082582500007 PM 10496246 ER PT J AU Green, RL Hutsler, JJ Loftus, WC Tramo, MJ Thomas, CE Silberfarb, AW Nordgren, RE Nordgren, RA Gazzaniga, MS AF Green, RL Hutsler, JJ Loftus, WC Tramo, MJ Thomas, CE Silberfarb, AW Nordgren, RE Nordgren, RA Gazzaniga, MS TI The caudal infrasylvian surface in dyslexia - Novel magnetic resonance imaging-based findings SO NEUROLOGY LA English DT Article DE cerebral hemisphere; brain morphology; dyslexia; MRI ID PLANUM TEMPORALE ASYMMETRY; DEVELOPMENTAL DYSLEXIA; BRAIN MORPHOLOGY; LANGUAGE IMPAIRMENT; CEREBRAL STRUCTURE; SCHIZOPHRENIA; CHILDREN; CORTEX; AREA; MRI AB Objective: To detect anatomic abnormalities of auditory association cortex in dyslexia by measuring the area of the perisylvian region known as the caudal infrasylvian surface(s) (cIS) in dyslexic and control subjects. Background: Several quantitative morphometric investigations of cortical areas in dyslexia have focused on the cIS, which encompasses the supratemporal plane and the inferior bank of the posterior ascending ramus of the sylvian fissure. Inconsistencies in the results of these studies may be attributable in part to the use of measurement methods that do not account fully for surface undulations of the cIS. Methods: The authors used an MRI-based surface reconstruction technique that models the curvature of the cerebral cortex in three dimensions to obtain whole-hemisphere and regional surface area estimates. Measurements were obtained in both hemispheres of eight right-handed male dyslexic subjects and eight right-handed male control subjects. Results: The cIS area of dyslexic subjects was significantly larger than that of control subjects, and this result was not attributable to a difference in whole-hemisphere surface area. Neither the dyslexic nor control subjects showed a left or right asymmetry in this region, although there was a trend toward less variance of the asymmetry scores in dyslexic subjects. Conclusions: The gross anatomic organization of this region is different in dyslexic subjects, and elucidation of the precise nature of these differences may be aided by surface modeling techniques. C1 Dartmouth Med Sch, Dept Psychiat, Lebanon, NH 03756 USA. Dartmouth Med Sch, Dept Pediat & Neurol, Lebanon, NH 03756 USA. Dartmouth Coll, Ctr Cognit Neurosci, Hanover, NH 03755 USA. Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. Harvard Univ, Sch Med, Dept Neurobiol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cognit Behav Neurol Unit, Boston, MA 02114 USA. RP Green, RL (reprint author), Dartmouth Med Sch, Dept Psychiat, 1 Med Ctr Dr, Lebanon, NH 03756 USA. FU NIDCD NIH HHS [DC00071]; NINDS NIH HHS [NS17778] NR 40 TC 17 Z9 18 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 22 PY 1999 VL 53 IS 5 BP 974 EP 981 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 236DG UT WOS:000082582500016 PM 10496255 ER PT J AU Matsuda, C Aoki, M Hayashi, YK Ho, MF Arahata, K Brown, RH AF Matsuda, C Aoki, M Hayashi, YK Ho, MF Arahata, K Brown, RH TI Expedited publication - Dysferlin is a surface membrane-associated protein that is absent in Miyoshi myopathy SO NEUROLOGY LA English DT Article DE dysferlin; protein; Miyoshi myopathy ID GIRDLE MUSCULAR-DYSTROPHY; CAENORHABDITIS-ELEGANS; GENE AB Recently we reported that mutations in a muscle protein "dysferlin" are present in limb girdle muscular dystrophy-2B and a related, adult-onset, distal dystrophy known as Miyoshi myopathy (MM). We report that antibodies to dysferlin identify a protein of approximately 230 kDa and show that dysferlin is located in the muscle membrane. This protein is absent in MM and LGMD-2B muscle. By contrast, dystrophin and other dystrophin-associated proteins are normal in these patients. Thus, dysferlin is a membrane-associated protein that is not likely to be an integral component of the dystrophin complex. Although it is not essential for initial myogenesis, it appears to be critical for sustained normal function in mature muscle. C1 Massachusetts Gen Hosp East, Day Neuromusc Res Lab, Charlestown, MA 02129 USA. Agcy Ind Sci & Technol, Natl Inst Biosci & Human Technol, Tsukuba, Ibaraki, Japan. Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromusc Res, Tokyo, Japan. RP Brown, RH (reprint author), Massachusetts Gen Hosp East, Day Neuromusc Res Lab, Room 6627,Bldg 149,13th St,Navy Yard, Charlestown, MA 02129 USA. NR 8 TC 93 Z9 98 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 22 PY 1999 VL 53 IS 5 BP 1119 EP 1122 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 236DG UT WOS:000082582500038 PM 10496277 ER PT J AU Greenberg, SM O'Donnell, HC Schaefer, PW Kraft, E AF Greenberg, SM O'Donnell, HC Schaefer, PW Kraft, E TI MRI detection of new hemorrhages: Potential marker of progression in cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article DE hemorrhage; amyloid angiopathy; MRI; noninvasive ID LOBAR HEMORRHAGE AB The authors used serial gradient-echo MRIs to detect new small hemorrhages in patients with previous lobar hemorrhage. Of 24 lobar hemorrhage patients (17 diagnosed with probable and 7 with possible amyloid angiopathy) who prospectively underwent repeat MRI 1.5 years after initial study, 9 (38%) demonstrated additional hemorrhages at follow-up. Interrater agreement was high. New hemorrhages were more frequent in patients with probable amyloid angiopathy (8 of 17, 47%) with more hemorrhages at baseline (p < 0.01). These results suggest a role for gradient-echo MRI in assessing disease progression in amyloid angiopathy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02115 USA. RP Greenberg, SM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Wang ACC 836, Boston, MA 02115 USA. FU NIA NIH HHS [AG00725] NR 10 TC 133 Z9 144 U1 0 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 SEP 22 PY 1999 VL 53 IS 5 BP 1135 EP 1138 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 236DG UT WOS:000082582500044 PM 10496283 ER PT J AU Cai, TH Moody, JM Sako, EY AF Cai, TH Moody, JM Sako, EY TI Mitral valve aneurysm due to severe aortic valve regurgitation SO CIRCULATION LA English DT Article C1 Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, Div Thorac Surg, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, Div Cardiol, San Antonio, TX 78284 USA. RP Sako, EY (reprint author), Univ Texas, Hlth Sci Ctr, Div Thorac Surg, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 0 TC 7 Z9 8 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 SEP 21 PY 1999 VL 100 IS 12 BP E53 EP E56 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 237CU UT WOS:000082638400001 PM 10491384 ER PT J AU Shand, N Weber, F Mariani, L Bernstein, M Gianella-Borradori, A Long, Z Sorensen, AG Barbier, N AF Shand, N Weber, F Mariani, L Bernstein, M Gianella-Borradori, A Long, Z Sorensen, AG Barbier, N CA GLI328 European-Canadian Study Grp TI A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir SO HUMAN GENE THERAPY LA English DT Article ID VECTOR PRODUCER CELLS; BRAIN-TUMORS; GLIOMA-CELLS; IN-VIVO; BRACHYTHERAPY; ASTROCYTOMA; REGRESSION; INVIVO; RATS AB This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies. C1 Novartis Pharma, Oncol Clin Res, CH-4002 Basel, Switzerland. Univ Dusseldorf, Neurochirurg Klin, D-40225 Dusseldorf, Germany. Univ Spital, Neurochirurg Klin, CH-3010 Bern, Switzerland. Toronto Hosp, Div Neurosurg, Toronto, ON M5T 2S8, Canada. Genet Therapy Inc, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Novartis Pharma, Dept Biostat, CH-4002 Basel, Switzerland. RP Shand, N (reprint author), Novartis Pharma, Oncol Clin Res, S-27-2-043, CH-4002 Basel, Switzerland. NR 22 TC 179 Z9 189 U1 0 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 SEP 20 PY 1999 VL 10 IS 14 BP 2325 EP 2335 DI 10.1089/10430349950016979 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 239JT UT WOS:000082765500006 PM 10515452 ER PT J AU Shimada, H Germana, S Sonntag, KC Banerjee, P Moore, D Sachs, DH LeGuern, C AF Shimada, H Germana, S Sonntag, KC Banerjee, P Moore, D Sachs, DH LeGuern, C TI MHC class II alpha/beta heterodimeric cell surface molecules expressed from a single proviral genome SO HUMAN GENE THERAPY LA English DT Article ID RETROVIRUS-MEDIATED TRANSFER; DISPARATE RENAL-ALLOGRAFTS; MINIATURE SWINE; BONE-MARROW; GENE-THERAPY; MONOCLONAL-ANTIBODIES; GRAFT-SURVIVAL; VECTOR; TOLERANCE; TRANSPLANTATION AB Transplantation tolerance to renal allografts can be induced in large animal preclinical models if the donor and recipient have identical major histocompatibility complex (MHC) class II loci. Such class II matching is, however, not clinically achievable owing to the extreme diversity of class II sequences. With the ultimate goal of creating a somatic class II match in the bone marrow of an allograft recipient, the aim of the study is to develop a double-copy retrovirus construct to express both chains of the MHC class II DQ glycoprotein on a single transduced cell. Analysis of the expression patterns of the retroviral DQ transgenes in both virus producer and transduced fibroblasts revealed correct transcription and stable surface expression of the DQ heterodimers, In addition, we demonstrate that both the DQA and DQB sequences are functional within the same proviral copy, a prerequisite for efficient induction of transplantation tolerance following transduction of bone marrow precursor cells. The DQ double-copy retrovirus vector showed efficient expression of the transferred class II cDNA in murine colony-forming units for the granulocyte-monocyte lineage (CFU-GM), indicating that it is suitable for gene therapy of multimeric proteins in hematopoietic cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. BioTransplant Inc, Boston, MA 02129 USA. RP LeGuern, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. RI Moore, Daniel/A-4924-2008 OI Moore, Daniel/0000-0002-6889-9345 FU NIAID NIH HHS [2RO1 AI33053] NR 46 TC 6 Z9 6 U1 0 U2 0 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 SEP 20 PY 1999 VL 10 IS 14 BP 2397 EP 2405 DI 10.1089/10430349950017040 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 239JT UT WOS:000082765500013 PM 10515459 ER PT J AU DePinho, RA Jacks, T AF DePinho, RA Jacks, T TI Mouse models of cancer - Introductory comments SO ONCOGENE LA English DT Editorial Material C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, 77 Massachusetts Ave,Bldg E17-517, Cambridge, MA 02139 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 20 PY 1999 VL 18 IS 38 BP 5248 EP 5248 DI 10.1038/sj.onc.1203108 PG 1 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 240CP UT WOS:000082808400001 ER PT J AU Chin, L AF Chin, L TI Modeling malignant melanoma in mice: pathogenesis and maintenance SO ONCOGENE LA English DT Article DE melanoma; RAS; tumor maintenance; mouse model ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; CELL-CYCLE ARREST; INK4A LOCUS; P53-DEPENDENT APOPTOSIS; CUTANEOUS MELANOMAS; MELANOCYTIC LESIONS; FAMILIAL MELANOMA; FACTOR EXPRESSION; P53 C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 44 Binney St,M413, Boston, MA 02115 USA. NR 65 TC 12 Z9 12 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 20 PY 1999 VL 18 IS 38 BP 5304 EP 5310 DI 10.1038/sj.onc.1203106 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 240CP UT WOS:000082808400008 PM 10498882 ER PT J AU Tuveson, DA Jacks, T AF Tuveson, DA Jacks, T TI Modeling human lung cancer in mice: similarities and shortcomings SO ONCOGENE LA English DT Review DE lung cancer; mouse models; genetic modifiers; K-ras; p53; Rb ID INDUCED PULMONARY ADENOMAS; STRAIN-A MICE; RETINOBLASTOMA SUSCEPTIBILITY GENE; TUMOR-SUPPRESSOR GENE; SMALL-CELL CARCINOMA; K-RAS GENE; MOUSE LUNG; TRANSGENIC MICE; NONSMALL CELL; P53 GENE AB Lung cancer kills more Americans yearly than any other neoplastic process. Mortality rates have changed little over the past several decades, despite improvements in surgical techniques, radiation therapy and chemotherapy. The identification of mutations in oncogenes and tumor suppressor genes in human lung tumor specimens, including K-ras, p53, p16(INK4a) and Rb, offers molecular explanations for tumor development and resistance to therapy. Mouse models of human lung cancer may advance our understanding of this disease. The examination of mice which develop lung cancer either spontaneously or due to carcinogen exposure, and the creation of mouse strains harboring the specific genetic mutations found in human lung cancer are among strategies being pursued. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Jacks, T (reprint author), MIT, Ctr Canc Res, E17-518,40 Ames St, Cambridge, MA 02139 USA. FU NCI NIH HHS [T32CA71345] NR 108 TC 83 Z9 86 U1 2 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 20 PY 1999 VL 18 IS 38 BP 5318 EP 5324 DI 10.1038/sj.onc.1203107 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 240CP UT WOS:000082808400010 PM 10498884 ER PT J AU McClatchey, AI AF McClatchey, AI TI Modeling metastasis in the mouse SO ONCOGENE LA English DT Article DE metastasis; mouse model; invasion; RhoGTPase ID IN-VIVO; INTEGRIN ALPHA-4-BETA-1; MALIGNANT PROGRESSION; INTESTINAL NEOPLASIA; CELL INTRAVASATION; CANCER INVASION; SUPPRESSOR GENE; MAJOR MODIFIER; MELANOMA-CELLS; PHAGE DISPLAY C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP McClatchey, AI (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 62 TC 20 Z9 20 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 20 PY 1999 VL 18 IS 38 BP 5334 EP 5339 DI 10.1038/sj.onc.1203086 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 240CP UT WOS:000082808400012 PM 10498886 ER PT J AU O'Connor, AM Rostom, A Fiset, V Tetroe, J Entwhistle, V Llewellyn-Thomas, H Holmes-Rovner, M Barry, M Jones, J AF O'Connor, AM Rostom, A Fiset, V Tetroe, J Entwhistle, V Llewellyn-Thomas, H Holmes-Rovner, M Barry, M Jones, J TI Decision aids for patients facing health treatment or screening decisions: systematic review SO BRITISH MEDICAL JOURNAL LA English DT Article ID RANDOMIZED TRIAL; PROSTATE-CANCER; HORMONE-THERAPY; INFORMATION; WOMEN; CIRCUMCISION; EDUCATION; FRAMEWORK; SUPPORT AB Objective To conduct a systematic review of randornised trials of patient decision aids in improving decision making and outcomes. Design We included randomised trials of interventions providing structured, detailed, and specific information on treatment or screening options and outcomes to aid decision making. Two reviewers independently screened and extracted data on several evaluation criteria. Results were pooled by using weighted mean differences and relative risks. Results 17 studies met the inclusion criteria. Compared with the controls, decision aids produced higher knowledge scores (weighted mean difference = 19/100, 95% confidence interval 14 to 25); lower decisional conflict scores (weighted mean difference = -0.3/5, -0.4 to -0.1); more active patient participation in decision making (relative risk = 2.27, 95% confidence interval 1.3 to 4); and no differences in anxiety, satisfaction with decisions (weighted mean difference = 0.6/100, -3 to 4), or satisfaction with the decision malting process (2/100, -3 to 7). Decision aids had a variable effect on decisions. When complex decision aids were compared with simpler versions, they were better at reducing decisional conflict, improved knowledge marginally, but did not affect satisfaction. Conclusions Decision aids improve knowledge, reduce decisional conflict, and stimulate patients to be more active in decision making without increasing their anxiety. Decision aids have little effect on satisfaction and a variable effect on decisions. The effects on outcomes of decisions (persistence with choice, quality of life) remain uncertain. C1 Univ Ottawa, Sch Nursing, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Fac Med, Loeb Hlth Res Inst, Clin Epidemiol Unit,Ottawa Hosp, Ottawa, ON K1Y 4E9, Canada. Sisters Charity Ottawa Hlth Serv, Ottawa, ON, Canada. Univ Aberdeen, Hlth Serv Res Unit, Aberdeen, Scotland. Univ Toronto, INst Clin Evaluat Sci, N York, ON, Canada. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP O'Connor, AM (reprint author), Univ Ottawa, Sch Nursing, Ottawa, ON K1Y 4E9, Canada. OI Entwistle, Vikki/0000-0002-0856-4025 NR 32 TC 492 Z9 498 U1 1 U2 12 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 SEP 18 PY 1999 VL 319 IS 7212 BP 731 EP 734 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 238GA UT WOS:000082701500014 PM 10487995 ER PT J AU Marsischky, GT Kolodner, RD AF Marsischky, GT Kolodner, RD TI Biochemical characterization of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 complex and mispaired bases in DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MISMATCH-REPAIR PROTEINS; NONPOLYPOSIS COLORECTAL-CANCER; MUTS-ENCODED PROTEIN; ESCHERICHIA-COLI; MICROSATELLITE INSTABILITY; HETERODUPLEX DNA; CELL-LINES; DUPLEX OLIGONUCLEOTIDES; TRANSLOCATION MECHANISM; SPECIFICALLY BINDS AB The interaction of the Saccharomyces cerevisiae MSH2-MSH6 complex with mispaired bases was analyzed using gel mobility shift assays and surface plasmon resonance methods. Under equilibrium binding conditions, MSH2-MSH6 bound to homoduplex DNA with a K-d of 3.9 nM and bound oligonucleotide duplexes containing T:G, +1, +2, +4, and +10 insertion/deletion loop (IDL) mispairs with K-d values of 0.20, 0,25, 11, 3.2, and 0.55 nM, respectively. Competition binding experiments using 65 different substrates repealed a 10-fold range in mispair discrimination. In general, base-base mispairs and a +1 insertion/deletion mispair were recognized better than intermediate sized insertion/deletion mispairs of 2-8 bases. Larger IDL mispairs (>8 bases) were recognized almost as well as the +1 IDL mispair. Recognition of mispairs by MSH2-MSH6 was influenced by sequence context, with the 6-nucleotide region surrounding the mispair being primarily responsible for influencing mispair recognition. Effects of sequences as far away as 15 nucleotides were also observed, Differential effects of ATP on the stability of MSH2-MSH6-mispair complexes suggested that base-base mispairs and the smaller IDL mispairs were recognized by a different binding mode than larger IDL mispairs, consistent with genetic experiments indicating that MSH2-MSH6 functions primarily in the repair of base-base and small IDL mispairs. C1 Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Charles A Dana Div Human Canc Genet, Boston, MA 02115 USA. RP Kolodner, RD (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, CMME3080,9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIGMS NIH HHS [GM50006] NR 91 TC 102 Z9 105 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 17 PY 1999 VL 274 IS 38 BP 26668 EP 26682 DI 10.1074/jbc.274.38.26668 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 235YD UT WOS:000082570700008 PM 10480869 ER PT J AU Kern, P Hussey, RE Spoerl, R Reinherz, EL Chang, HC AF Kern, P Hussey, RE Spoerl, R Reinherz, EL Chang, HC TI Expression, purification, and functional analysis of murine ectodomain fragments of CD8 alpha alpha and CD8 alpha beta dimers SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CD8 CORECEPTOR FUNCTION; T-CELL DEVELOPMENT; CLASS-I MOLECULE; CRYSTAL-STRUCTURE; BETA-CHAIN; MONOCLONAL-ANTIBODIES; SURFACE EXPRESSION; H-2K(B) MOLECULE; LYMPHOCYTES-T; ACTIVATION AB Soluble mouse CD8 alpha alpha and CD8 alpha beta dimers corresponding to the paired ectodomains (CD8(f)) or their respective component Ig-like domains (CD8) were expressed in Chinese hamster ovary cells or the glycosylation variant Lec3.2.8.1 cells as secreted proteins using a leucine zipper strategy. The affinity of CD8 alpha alpha(f) for H-2K(b) as measured by BIAcore revealed a similar to 65 mu M K-d, similar to that of CD8 alpha beta(f). Consistent with this result, CD8 alpha alpha(f) as well as CD8 alpha beta(f) blocked the effector function of N15 T cell receptor transgenic cytolytic T cells in a comparable, dose-dependent fashion. Furthermore, both Lec3.2.8.1-produced and Chinese hamster ovary-produced CD8 homodimers and heterodimers were active in the inhibition assay. These results suggest that the Ig-like domains of CD8 molecules are themselves sufficient to block the requisite transmembrane CD8-pMHC interaction between cytolytic T lymphocytes and target cells. Moreover, given the similarities in co-receptor affinities for pMHC, the findings suggest that the greater efficiency of CD8 alpha beta versus CD8 alpha alpha co-receptor function on T cells is linked to differences within their membrane-bound stalk regions and/or intracellular segments. As recently shown for sCD8 alpha alpha, the yield, purity and homogeneity of the deglycosylated protein resulting from this expression system is sufficient for crystallization and x-ray diffraction at atomic resolution. C1 Dana Farber Canc Inst, Immunol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Chang, HC (reprint author), Dana Farber Canc Inst, Immunol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI19807, AI39098] NR 50 TC 61 Z9 61 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 17 PY 1999 VL 274 IS 38 BP 27237 EP 27243 DI 10.1074/jbc.274.38.27237 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 235YD UT WOS:000082570700081 PM 10480942 ER PT J AU Holschneider, DP Scremin, OU Chen, K Shih, JC AF Holschneider, DP Scremin, OU Chen, K Shih, JC TI Lack of protection of monoamine oxidase B-deficient mice from age-related spatial learning deficits in the Morris water maze SO LIFE SCIENCES LA English DT Article DE MAO; learning; memory; Morris water maze; aging; mice ID ALZHEIMER-TYPE DEMENTIA; L-DEPRENYL; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; SELEGILINE; RATS; BRAIN; AMPHETAMINE; INHIBITION; LONGEVITY AB Monoamine oxidase B (MAO-B) increases in brain in response to aging and neurodegeneration. Whether such increases represent a risk factor to further neuronal damage or simply represent epiphenomena remains unclear. L-deprenyl, an inhibitor of MAO-B, has been shown to improve learning in aged rodents. However, recent data suggests this may occur through mechanisms independent of its enzymatic inhibition. This study investigates visualspatial learning of MAO-B deficient mice and examines what effects absence of MAO-B has on age-related cognitive decline. Learning was tested in the Morris Water Maze in male transgenic MAO-B knockout mice (KO) ages 2 months (n = 9), 7 months (n = 7), and 17 months (n = 8). Performance was compared to that of wild type (WT) littermates. Animals were given four 60 second trials per day with the submerged platform in the "North" position. Animals received 7 days of learning in which they were introduced into the pool facing the wall, alternating between the "East" and "West" positions. A single probe trial followed on day 8, followed by continuation of the original learning paradigm on days 9 and 10. Subsequently, the platform position was changed to the diagonally opposite quadrant and learning continued on days 11-13, followed by a cue phase in which the platform was made visible. Total distance traveled and latency to the platform was increased in 7- and 17- month old mice, most significantly at the beginning of the acquisition phase. This effect reappeared again in 17- month old mice during the reversal phase. No predominant genotypic differences in latency or distance were observed during any phase of the experiment. Our results show that presence or absence of MAO-B does not appear to alter performance in the Morris water maze. Furthermore, presence or absence of MAO-B does not provide protection from the age-dependent deficits in spatial learning. C1 Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Holschneider, DP (reprint author), Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, 1985 Zonal Ave,Rm 512, Los Angeles, CA 90033 USA. FU NIA NIH HHS [K12-AG-00521]; NIMH NIH HHS [R37 MH39085, K05 MH 00796] NR 34 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD SEP 17 PY 1999 VL 65 IS 17 BP 1757 EP 1763 DI 10.1016/S0024-3205(99)00428-2 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 239KC UT WOS:000082766400005 PM 10576555 ER PT J AU Rebeck, GW Cheung, BS Growdon, WB Deng, A Akuthota, P Locascio, J Greenberg, SM Hyman, BT AF Rebeck, GW Cheung, BS Growdon, WB Deng, A Akuthota, P Locascio, J Greenberg, SM Hyman, BT TI Lack of independent associations of apolipoprotein E promoter and intron 1 polymorphisms with Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE apolipoprotein E; allelic imbalance; Th1/E47; genetic linkage ID REGULATORY REGION; E EPSILON-4; APOE; RISK; GENE; POPULATION; EXPRESSION; DEMENTIA; ALLELE AB Several studies have demonstrated genetic associations between Alzheimer's disease (AD) and polymorphisms in the promoter/enhancer regions of the apolipoprotein E (APOE) gene. These studies raise the possibility that APOE transcription control may be involved in altered risks for AD. We evaluated polymorphic sites in the intron-1 enhancer element (IE-1G/C) and in the APOE promoter (-219G/T). For the IE-1 polymorphism, we analyzed 433 individuals (183 AD and 250 controls), and found a strong linkage between the IE-1G allele and APOE-epsilon 4. When we controlled for this linkage using log-linear model analysis, we found no independent association between the IE-1 polymorphism and AD. For the -219 polymorphism, we analyzed 475 individuals (168 AD cases, 234 controls, and 73 cases of cerebral amyloid angiopathy (CAA)). We found strong linkages between the -219G allele and APOE-epsilon 2 and between the -219 T allele and APOE-epsilon 4. Controlling for these linkages, we found no independent association between the -219 polymorphism and AD or CAA. Thus, our studies do not support independent associations between AD and either the IE-1 or the -219 polymorphisms. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG05134, AG12406] NR 17 TC 33 Z9 36 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 17 PY 1999 VL 272 IS 3 BP 155 EP 158 DI 10.1016/S0304-3940(99)00602-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 238NW UT WOS:000082717200004 PM 10505604 ER PT J AU Eisenstat, SA Bancroft, L AF Eisenstat, SA Bancroft, L TI Domestic violence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID PHYSICAL ABUSE; PREGNANT-WOMEN; BATTERED WOMEN; MEDICAL-CARE; SEXUAL ABUSE; VICTIMS; VICTIMIZATION; EXPERIENCES; PREVALENCE; EMERGENCY C1 Massachusetts Gen Hosp, Womens Hlth Associates, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, HAVEN Program, Hosp Helping Abuse & Violence End Now, Boston, MA 02114 USA. RP Eisenstat, SA (reprint author), Massachusetts Gen Hosp, Womens Hlth Associates, Dept Med, Blake 10, Boston, MA 02114 USA. NR 69 TC 113 Z9 118 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 16 PY 1999 VL 341 IS 12 BP 886 EP 892 DI 10.1056/NEJM199909163411206 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 235XL UT WOS:000082569100006 PM 10486421 ER PT J AU Shinobu, LA Frosch, MP Budzik, RF AF Shinobu, LA Frosch, MP Budzik, RF TI A 68-year-old woman with rapidly progressive dementia and a gait disorder - Creutzfeldt-Jakob disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BOVINE SPONGIFORM ENCEPHALOPATHY; HIGH SIGNAL INTENSITY; PRION PROTEIN; TRANSGENIC MICE; BASAL GANGLIA; VARIANT CJD; INVOLVEMENT; EXPRESSION; DIAGNOSIS; ETIOLOGY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Shinobu, LA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 48 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 16 PY 1999 VL 341 IS 12 BP 901 EP 908 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 235XL UT WOS:000082569100008 ER PT J AU Smith, NL Reiber, GE Psaty, BM Heckbert, SR Siscovick, DS Ritchie, JL Every, NR Koepsell, TD AF Smith, NL Reiber, GE Psaty, BM Heckbert, SR Siscovick, DS Ritchie, JL Every, NR Koepsell, TD TI Trends in the post-hospitalization medical treatment of unstable angina pectoris: 1990 to 1995 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CLINICAL-TRIALS; HEART-DISEASE; BETA-BLOCKER; DOUBLE-BLIND; ASPIRIN; OUTCOMES; PROPRANOLOL; DILTIAZEM; PREVENTION AB This study provides data on post-hospitalization medication treatment trends for unstable angina between 1990 and 1995, We conducted an observational cohort study at the Veterans Affairs Puget Sound Health Care System (VAPSHCS), Computerized records of hospital discharges and cardiac catheterizations were used to identify unstable angina diagnoses among veterans between 1990 and 1995. Discharge medications issued within 90 days after discharge were ascertained from computerized outpatient pharmacy records, Of the 1,100 veterans discharged with unstable angina, 885 (80%) filled a prescription through the VAPSHCS within 90 days after discharge. Neither use of aspirin nor use of beta blockers increased between 1990 and 1995: overall use averaged 76% for aspirin (78% of those without potential contraindications) and 32% for beta blockers (36% of those without potential contraindications). Use of non-dihydropyridine calcium antagonists-primarily diltiazem-decreased from 57% to 40% (p <0.01), whereas use of dihydropyridine calcium antagonists increased from 12% to 26% (p <0.01), Thus, pharmacy records indicated that aspirin use was high although it was,lower than expected, possibly due to ready availability outside the VAPSHCS pharmacy, The low frequency of beta-blocker use and the increasing reliance on dihydropyridine calcium antagonists through 1995 to treat unstable angina may be an opportunity to improve veteran care according to Agency for Health Care Policy Research recommendations. (C) 1999 by Excerpta Medica, Inc. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Serv Cardiol, Seattle, WA USA. RP Smith, NL (reprint author), Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. NR 30 TC 4 Z9 4 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 SEP 15 PY 1999 VL 84 IS 6 BP 632 EP 638 DI 10.1016/S0002-9149(99)00407-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 235HK UT WOS:000082536100003 PM 10498130 ER PT J AU Dangas, G Smith, DA Badimon, JJ Unger, AH Shao, JH Meraj, P Cohen, AM Levine, D Fallon, JT Ambrose, JA AF Dangas, G Smith, DA Badimon, JJ Unger, AH Shao, JH Meraj, P Cohen, AM Levine, D Fallon, JT Ambrose, JA TI Gender differences in blood thrombogenicity in hyperlipidemic patients and response to pravastatin SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DEPENDENT CORONARY VASOMOTION; PLASMINOGEN-ACTIVATOR; PLASMA-FIBRINOGEN; CHOLESTEROL; WOMEN; DEPOSITION; REDUCTION; DISEASE; EVENTS; MEN AB Thrombotic risk in hyperlipidemic women and its response to lipid therapy is unknown. We prospectively studied 28 men and 29 women with high low-density lipoprotein (LDL) cholesterol during 6 months of therapy with pravastatin. Women had significantly higher high- density lipoprotein (HDL) cholesterol (54.2 +/- 1.7 vs 39.5 +/- 2.2 mg/dl, p <0.01), lower prevalence of coronary artery disease (41% vs 67%, p = 0.04), and otherwise similar baseline characteristics compared with men. Both genders achieved a 33% reduction in LDL at 6 weeks (188 +/- 6 to 133 +/- 5 mg/dl) and maintained similar LDL levels throughout the study. Systemic hemostatic markers and thrombus formation under dynamic flow conditions were evaluated at baseline, and at 3 and 6 months of follow-up. Prothrombin fragment F-1.2, a marker of thrombin generation, was higher in women versus men at baseline (2.4 +/- 0.2 vs 1.4 +/- 0.3 nmol/L, p = 0.02). The levels decreased in women to 2.0 +/- 0.3 nmol/L at 3 months and to 1.6 +/- 0.2 nmol/L at 6 months (p <0.045, analysis of variance), whereas it remained unchanged in men. Plasminogen activator inhibitor-1 significantly decreased at 3 and 6 months of follow-up: by 12.6% and 18.7%, respectively, in women, and by 18.8% and 23.5%, respectively, in men. Similarly, tissue plasminogen activator decreased;significantly by 7.4% in women and 11.8% in men at 6 months compared with baseline. Fibrinogen showed an increase in both genders at follow-up. Thrombus formation was similar at baseline between the 2 genders, and decreased at 3 and 6 months compared with baseline by 12.5% and 29.5% in women, and by 18.6% and 19.4% in men (p <0.04 at 6 months vs baseline in both men and women). Other markers, including C-reactive protein, fibrinopeptide A, D-dimer, and factor VIIa, did not differ between genders and did not change with therapy. Thus, despite higher HDL, and lower incidence of coronary disease, women with high LDL had a comparable thrombotic and/or fibrinolytic profile to men and even evidence of increased thrombin generation at baseline. Blood thrombogenicity was reduced with pravastatin in both genders; in addition, thrombin generation was gradually reduced in women to a level similar to that of men by 6 months of follow-up. (C) 1999 by Excerpta Medica, Inc. C1 Washington Hosp Ctr, Cardiovasc Res Fdn, Washington, DC 20010 USA. Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cornell Univ, Coll Med, Rogosin Inst, New York, NY USA. RP Dangas, G (reprint author), Washington Hosp Ctr, Cardiovasc Res Fdn, 110 Irving Ctr NW,Suite 4B-1, Washington, DC 20010 USA. FU NCRR NIH HHS [5 M01 RR00071] NR 21 TC 27 Z9 27 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 SEP 15 PY 1999 VL 84 IS 6 BP 639 EP 643 DI 10.1016/S0002-9149(99)00408-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 235HK UT WOS:000082536100004 PM 10498131 ER PT J AU Burger, AJ Weinrauch, LA D'Elia, JA Aronson, D AF Burger, AJ Weinrauch, LA D'Elia, JA Aronson, D TI Effect of glycemic control on heart rate variability in type I diabetic patients with cardiac autonomic neuropathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SUBCUTANEOUS INSULIN INFUSION; SPECTRAL-ANALYSIS; FOLLOW-UP; DYSFUNCTION; DISEASE AB Diabetic cardiac autonomic neuropathy (CAN) is associated with a high risk of cardiovascular events. Previous studies have shown that strict glycemic control slows the deterioration of CAN as assessed by standard autonomic function tests but fails to show reversibility, The aim of this study was to evaluate the effect of glycemic control on early and advanced CAN in type I diabetic patients using power spectral analysis of heart rate variability (HRV). Ten patients with early and 13 patients with advanced CAN were enrolled in a program of intensified insulin treatment. Standard autonomic function tests and 24-hour time and frequency domain HRV parameters were obtained at baseline, 3, 6, and 12 months. Hemoglobin A,, decreased from 9.5 +/- 0.4% to 8.4 +/-: 0.5% (p = 0.02) in the early CAN group, and from 9.3 +/- 0.4% to 8.2 +/- 0.5% (p = 0.006) in the advanced CAN group. In general, both time and frequency domain HRV indexes tended to improve in patients with early CAN but continued to deteriorate in patients with advanced CAN. The low- and high-frequency power increased in patients with early CAN (229 +/- 95 to 626 +/- 563 ms(2) and 62 +/- 30 to 183 +/- 168 ms(2), respectively). The high-frequency power significantly improved at 12 months over baseline (p = 0.04), indicating increased parasympathetic tone. By contrast, these parameters continued to deteriorate in patients with advanced CAM (65 +/- 32 to 46 +/- 8 ms(2) and 193 +/- 75 to 144 +/- 33 ms(2), respectively). Autonomic function tests showed no significant change in both groups. These data show that a reversible metabolic component of CAN exists in patients with early CAN. Power spectral analysis of HRV allows early identification of potential reversibility as early as 1 year after the institution of strict glycemic control. (C) 1999 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, Div Cardiol, Noninvas Cardiol Lab, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Burger, AJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiol, Noninvas Cardiol Lab, West Campus,Baker 3,1 Deaconess Rd, Boston, MA 02215 USA. RI Aronson, Doron/F-3390-2010; OI Weinrauch, Larry/0000-0003-1357-9528 NR 28 TC 38 Z9 39 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 SEP 15 PY 1999 VL 84 IS 6 BP 687 EP 691 DI 10.1016/S0002-9149(99)00417-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 235HK UT WOS:000082536100013 PM 10498140 ER PT J AU Mao, CG Saba, JD Obeid, LM AF Mao, CG Saba, JD Obeid, LM TI The dihydrosphingosine-1-phosphate phosphatases of Saccharomyces cerevisiae are important regulators of cell proliferation and heat stress responses SO BIOCHEMICAL JOURNAL LA English DT Article DE sphingolipid metabolism; cell proliferation; sphingosine phosphate phosphatases ID LONG-CHAIN BASES; CERAMIDE; SPHINGOSINE-1-PHOSPHATE; SPHINGOLIPIDS; IDENTIFICATION; KINASE; GENE; SPHINGANINE; INHIBITION; GROWTH AB We have identified YSR2 and YSR3 of Saccharomyces cerevisiae as genes encoding dihydrosphingosine-1-phosphate phophatases which are involved in regulation of sphingolipid metabolism [Mao, Wadleigh, Jenkins, Hannun and Obeid (1997) J. Biol, Chem. 272, 28690-28694]. In this study, we explored the physiological roles that these enzymes may have in S. cerevisiae, Deletion of either YSR2, YSR3 or both did not affect viability or growth rate of yeast cells. However, overexpression of YSR2 significantly prolonged the doubling time of cell growth, whereas overexpression of YSR3 affected cell growth only slightly. Cell cycle analysis suggested that overexpression of either YSR2 or, to a lesser extent, YSR3 caused cell cycle arrest at the G1 phase, Disruption of YSR2, but not YSR3, conferred increased thermotolerance, On the other hand, overexpression of either YSR2 or YSR3 diminished thermotolerance. Using labelled dihydro-sphingosine and dihydrosphingosine-1-P (DHS-1-P), we found that overexpression of YSR2 significantly increased ceramide formation, whereas deletion of YSR2, YSR3, or both, accumulated DHS-1-P, and deletion of YSR2 decreased ceramide formation. Together, these results show that the phenotypes of YSR2 are associated with changes in endogenous levels of the different sphingolipids. Green fluorescent protein tagging showed that in the exponentially growing cells, YSR2 and YSR3 had the same cellular localization to endoplasmic reticulum. However, YSR2 and YSR3 differ in mRNA levels: YSR2 had significantly higher mRNA levels than YSR3, This discrepancy might result in the functional differences that these proteins exhibited. In addition, this study implicates sphingolipids and their metabolism in the regulation of growth and heat stress responses of the yeast S, cerevisiae. C1 Ralph H Johnson Vet Adm Hosp, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. RP Div Gen Internal Med, 114 Doughty St,Room 602 STB,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG-12467-05] NR 29 TC 90 Z9 93 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD SEP 15 PY 1999 VL 342 BP 667 EP 675 DI 10.1042/0264-6021:3420667 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 240VT UT WOS:000082848300022 PM 10477278 ER PT J AU Raskind, MA Peskind, ER Holmes, C Goldstein, DS AF Raskind, MA Peskind, ER Holmes, C Goldstein, DS TI Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer's disease SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Alzheimer's disease; aging; cerebrospinal fluid; norepinephrine; dihydroxyphenylglycol; dihydroxyphenylacetic acid ID TYROSINE-HYDROXYLASE ACTIVITY; LOCUS-CERULEUS; RAT-BRAIN; SENILE DEMENTIA; NOREPINEPHRINE KINETICS; SUBTOTAL DESTRUCTION; ADRENERGIC-RECEPTORS; L-DOPA; PLASMA; NEURONS AB Background: High cerebrospinal fluid (CSF) norepinephrine (NE) concentrations in aging and Alzheimer's disease (AD) could reflect decreased NE clearance from central nervous system (CNS) extracellular fluid or increased release of NE into CNS extracellular fluid, Measuring CSF concentrations of the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), an estimate of NE clearance, and the NE precursor dihydroxyphenylacetic acid (DOPA), an estimate of NE biosynthesis, can help differentiate these mechanisms. Methods: NE, DHPG, and DOPA were determined by HPLC in CSF and plasma obtained following yohimbine, clonidine, and placebo. Ten AD, 10 older and II young subjects were studied. Results: CSF DOPA following yohimbine was higher in alder and AD than in young subjects. CSF DHPG did not differ among groups. Plasma DOPA following yohimbine was higher in AD than in young subjects. Conclusions: During alpha-2 adrenoreceptor blockade in bath aging and AD, there are increased responses of CNS NE biosynthesis and release with unchanged CNS NE clearance, This pattern is consistent with partial lass of CNS noradrenergic neurons with compensatory activation of remaining CNS noradrenergic neurons. Given the marked loss of locus coeruleus (LC) noradrenergic neurons in AD, achievement of high CSF NE suggests particularly prominent compensatory activation of remaining LC neurons in this disorder. (C) 1999 Society of Biological Psychiatry. C1 NW Network Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 116,1660 S Columbian Way, Seattle, WA 98108 USA. NR 50 TC 54 Z9 55 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1999 VL 46 IS 6 BP 756 EP 765 DI 10.1016/S0006-3223(99)00008-6 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 235ZZ UT WOS:000082574900005 PM 10494443 ER PT J AU Oken, MM Leong, T Lenhard, RE Greipp, PR Kay, NE Van Ness, B Keimowitz, RM Kyle, RA AF Oken, MM Leong, T Lenhard, RE Greipp, PR Kay, NE Van Ness, B Keimowitz, RM Kyle, RA TI The addition of interferon or high dose cyclophosphamide to standard chemotherapy in the treatment of patients with multiple myeloma - Phase III Eastern Cooperative Oncology Group clinical trial EST 9486 SO CANCER LA English DT Article DE multiple myeloma; interferon; randomized clinical trial; survival; complete remission ID COMBINATION CHEMOTHERAPY; MELPHALAN-PREDNISONE; RANDOMIZED TRIAL; MAINTENANCE THERAPY; CENTRAL SWEDEN; SURVIVAL; ALPHA; VINCRISTINE; INDUCTION; QUANTITATION AB BACKGROUND, Interferon (IFN) has demonstrated activity in the treatment of patients with multiple myeloma. A previous Eastern Cooperative Oncology Group (ECOG) study suggested that the rates of complete response (CR) and survival were increased with a regimen that alternated IFN with chemotherapy. The current study was designed to evaluate the effect of adding alternating cycles of IFN or early intensification with high dose cyclophosphamide (HiCy) to the VBMCP regimen for the treatment of multiple myeloma patients. METHODS, From February 1988 to May 1992, the ECOG entered previously untreated patients with active multiple myeloma on a study in which they were randomized to VBMCP (vincristine 1.2 mg/m(2) administered intravenously [i.v.] on Day 1, BCNU 20 mg/m(2) i.v. on Day 1, melphalan 8 mg/m(2) administered orally [p.o.] on Days 1-4, cyclophosphamide 400 mg/m(2) i.v. on Dap 1, and prednisone 40 mg/m(2) p.o. on Days 1-7; 5-week cycles) or VBMCP + rIFN(alpha 2), the latter given at 5 Mu/m(2) 3 times a week starting on Day 22 of each 6-week cycle after 2 initial cycles of VBMCP. Patients younger than 70 years were also randomized to a third treatment that substituted cyclophosphamide 600 mg/m(2) i.v. on Days 1-4 and prednisone 100 mg/m(2) p.o. on Days 1-4 for cycles 3 and 5 of VBMCP (VBMCP + HiCy). Treatment was continued for 2 years. RESULTS, Of the 653 patients entered, 628 were eligible for the study. All were evaluated for response. With median follow-up for surviving patients of 54 months, the median survival duration was 42 months-1 year longer than usually reported for melphalan combined with prednisone. A comparison of the three regimens revealed no significant difference in the rates of survival or objective response (OR). However, CRs were increased among patients treated with VBMCP + rIFN(alpha 2) compared with VBMCP alone (18% vs. 10%, P = 0.03). Patients treated with VBMCP + rIFN(alpha 2) had a longer response duration than patients treated with VBMCP alone (30 vs. 25 months, P = 0.035). There was a greater response rate with the IFN regimen among elderly patients (OR and CR = 67% and 31%, respectively) and patients with immunoglobulin A (IgA) myeloma (OR and CR = 83% and 29%, respectively). Severe infections were seen as often with VBMCP as with VBMCP + rIFN(alpha 2) (13% vs. 15%), but they were more frequent with VBMCP + HiCy (25%). CONCLUSIONS, VBMCP + rIFN(alpha 2) yields a higher rate of CR and a longer response duration than VBMCP alone but appears to make no difference in the rates of overall response or survival compared with VBMCP or VBMCP + HiCy. The superior ability of VBMCP + rIFN(alpha 2) induction therapy to produce CR and more durable responses, as well as its activity in older patients and in those with IgA myeloma, suggest that this therapy has important biologic activity in myeloma and merits further clinical investigation. (C) 1999 American Cancer Society. C1 Virginia Piper Canc Inst, Minneapolis, MN 55407 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. Mayo Clin, Rochester, MN USA. Univ Minnesota, Minneapolis, MN USA. Gundersen Clin Ltd, Lacrosse, WI USA. RP Oken, MM (reprint author), Virginia Piper Canc Inst, 800 E 28th St, Minneapolis, MN 55407 USA. FU NCI NIH HHS [CA 13650, CA 20365, CA23318] NR 63 TC 42 Z9 44 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 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 1999 VL 86 IS 6 BP 957 EP 968 PG 12 WC Oncology SC Oncology GA 236DL UT WOS:000082582900010 PM 10491521 ER PT J AU Nelson, HH Christiani, DC Wiencke, JK Mark, EJ Wain, JC Kelsey, KT AF Nelson, HH Christiani, DC Wiencke, JK Mark, EJ Wain, JC Kelsey, KT TI k-ras mutation and occupational asbestos exposure in lung adenocarcinoma: Asbestos-related cancer without asbestosis SO CANCER RESEARCH LA English DT Article ID CIGARETTE-SMOKING; GENE; P53; ASSOCIATION AB Environmental carcinogen exposure is requisite for the development of nearly all lung cancer, and it is well known that asbestos exposure interacts synergistically with tobacco smoke to induce lung cancer. However, the precise molecular lesions induced by asbestos are unknown, Furthermore, it is also unknown whether asbestos carcinogenesis proceeds in a fashion independent of or dependent upon the induction of fibrosis in workers with high asbestos exposures. Previous studies have suggested that asbestos is associated with the presence of a k-ras mutation in adenocarcinoma of the lung. We aimed to test whether occupational asbestos exposure was associated with k-ras codon 12 mutations in lung adenocarcinoma tumors and to determine whether this was conditional on the presence of asbestosis. All newly diagnosed, resectable lung cancer patients receiving treatment at the Massachusetts General Hospital between November 1992 and December 1996 were eligible to participate, Because k-ras mutation is very strongly associated with adenocarcinoma, and men were more likely to be occupationally exposed to asbestos, the study was restricted to males with this histological diagnosis, There were 84 male patients with available questionnaire-derived work history data and paraffin-embedded tumor tissue for determination of k-ras mutation status. Chest radiographic evaluation was done for all of the patients who reported occupational exposure to asbestos. The prevalence of k-ras mutation was higher among those with a history of occupational asbestos exposure (crude odds ratio, 4.8; 95% confidence interval, 1.5-15.4) compared to those without asbestos exposure, and this association remained after adjustment for age and pack-years smoked (adjusted odds ratio, 6.9; 95% confidence interval, 1.7-28.6), An index score that weights both the dates of exposure and the estimated intensity of exposure indicated that those with k-ras mutations had significantly greater asbestos exposures than those without mutations (P < 0.01). Analysis of the descriptive components of exposure indicated that the duration of exposure was not associated with k-ras mutation, but that the time since initial exposure was significantly associated with mutation status. The association of k-ras mutation and reported asbestos exposure was not dependent on the presence of radiographic evidence of asbestos-related disease. These data suggest that asbestos exposure increases the likelihood of mutation at k-ras codon 12 and that this process occurs independently of the induction of interstitial fibrosis. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Lab Mol Epidemiol, San Francisco, CA 94143 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002, ES04705, ES08357] NR 24 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1999 VL 59 IS 18 BP 4570 EP 4573 PG 4 WC Oncology SC Oncology GA 235KV UT WOS:000082541600017 PM 10493509 ER PT J AU Luo, H Asha, H Kockel, L Parke, T Mlodzik, M Dearolf, CR AF Luo, H Asha, H Kockel, L Parke, T Mlodzik, M Dearolf, CR TI The Drosophila Jak kinase hopscotch is required for multiple developmental processes in the eye SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; eye development; hopscotch; Jak kinase; ommatidial polarity ID MICE LACKING JAK3; CELL-FATE; PHOSPHATIDYLINOSITOL 3-KINASE; HEMATOPOIETIC-CELLS; CYTOKINE RECEPTORS; SIGNALING PATHWAY; TISSUE POLARITY; PLANAR POLARITY; PROTEIN; GENE AB Jak kinases are critical signaling components in hematopoiesis. While a large number of studies have been conducted on the roles of Jak kinases in the hematopoietic cells, much less is known about the requirements for these tyrosine kinases in other tissues. We have used loss of function mutations in the Drosophila Jak kinase Hopscotch (Hop) to determine the role of Hop in eye development. We find that Hop is required for cell proliferation/survival in the eye imaginal disc, for the differentiation of photoreceptor cells, and for the establishment of the equator and of ommatidial polarity. These results indicate that hop activity is required for multiple developmental processes in the eye, both cell-autonomously and nonautonomously. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. European Mol Biol Lab, Dev Biol Programme, D-69117 Heidelberg, Germany. RP Dearolf, CR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Jackson 1402, Boston, MA 02114 USA. NR 57 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 1999 VL 213 IS 2 BP 432 EP 441 DI 10.1006/dbio.1999.9390 PG 10 WC Developmental Biology SC Developmental Biology GA 238WA UT WOS:000082736400016 PM 10479459 ER PT J AU Kingston, RE Narlikar, GJ AF Kingston, RE Narlikar, GJ TI ATP-dependent remodeling and acetylation as regulators of chromatin fluidity SO GENES & DEVELOPMENT LA English DT Review ID RNA-POLYMERASE-II; YEAST SWI/SNF COMPLEX; HISTONE ACETYLTRANSFERASE COMPLEXES; TUMOR VIRUS PROMOTER; TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; NUCLEOSOMAL DNA; IN-VIVO; GLUCOCORTICOID RECEPTOR; ACTIVATE TRANSCRIPTION C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. NR 122 TC 549 Z9 557 U1 0 U2 25 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 15 PY 1999 VL 13 IS 18 BP 2339 EP 2352 DI 10.1101/gad.13.18.2339 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 240DM UT WOS:000082810600001 PM 10500090 ER PT J AU Liu, SM Ajani, U Chae, C Hennekens, C Buring, JE Manson, JE AF Liu, SM Ajani, U Chae, C Hennekens, C Buring, JE Manson, JE TI Long-term beta-carotene supplementation and risk of type 2 diabetes mellitus - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INSULIN ACTION; DIET; ANTIOXIDANT; WOMEN AB Context Recent data suggest a protective role of carotenoids in the development of type 2 diabetes mellitus (DM), possibly via an antioxidant effect, but no randomized trial has directly assessed the efficacy of beta-carotene to prevent DM. Objective To determine whether long-term beta-carotene supplementation reduces the risk of developing type 2 DM, Design, Setting, and Participants A total of 22 071 healthy US male physicians aged 40 to 84 years in a randomized, double-blind, placebo-controlled trial, from 1982 to 1995. More than 99% of the participants had complete follow-up (median duration, 12 years). Intervention Subjects were randomly assigned to receive beta-carotene (50 mg on alternate days) or placebo. Main Outcome Measure Incidence of type 2 DM. Results A total of 10 756 subjects were assigned to beta-carotene and 10 712 to placebo. Incidence of type 2 DM did not differ between groups: 396 men in the beta-carotene group and 402 men in the placebo group developed type 2 DM (relative risk, 0.98; 95% confidence interval, 0.85-1.12). The lack of association between beta-carotene supplementation and incidence of type 2 DM persisted despite multivariate adjustment, There was no evidence of benefit when the period of risk was subdivided into years of follow-up or increasing duration of treatment. Conclusion In this trial of apparently healthy men, supplementation with beta-carotene for an average of 12 years had no effect on the risk of subsequent type 2 DM. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Liu, SM (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA34944, CA40360]; NHLBI NIH HHS [HL-26490] NR 18 TC 71 Z9 74 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 SEP 15 PY 1999 VL 282 IS 11 BP 1073 EP 1075 DI 10.1001/jama.282.11.1073 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 234YQ UT WOS:000082512300032 PM 10493207 ER PT J AU Ghosh, PM Moyer, ML Mott, GE Kreisberg, JI AF Ghosh, PM Moyer, ML Mott, GE Kreisberg, JI TI Effect of cyclin E overexpression on lovastatin-induced G1 arrest and RhoA inactivation in NIH3T3 cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE p27(kip1); C3 transferase; morphology; cell cycle; actin stress fibers ID RETINOBLASTOMA GENE-PRODUCT; BINDING PROTEIN-RHO; ACTIN STRESS FIBERS; DEPENDENT KINASES; MAMMALIAN FIBROBLASTS; TRANSCRIPTION FACTOR; INHIBITOR P27(KIP1); SMALL GTPASE(S); CDC42 GTPASES; GROWTH-FACTOR AB The HMG-CoA reductase inhibitor, lovastatin, blocks targeting of the Rho and Ras families of small GTPases to their active sites by inhibiting protein prenylation. Control NIH3T3 cells, and those overexpressing human cyclin E protein were treated with lovastatin for 24 h to determine the effects of cyclin E overexpression on lovastatin-induced growth arrest and cell rounding. Lovastatin treatment (10 mu M) of control 3T3 cells resulted in growth arrest at G1 accompanied by actin stress fiber disassembly, cell rounding, and decreased active RhoA from the membranous protein fraction. By contrast, in NIH3T3 cells overexpressing cyclin E, lovastatin did not cause loss of RhoA from the membrane (active) protein fraction, actin stress fiber disassembly, cell rounding or growth arrest within 24 h. Analysis of cell cycle proteins showed that 24 h of lovastatin treatment in the control cells caused an elevation in the levels of the cyclin-dependent kinase inhibitor p27(kip1), inhibition of both cyclin E- and cyclin A-dependent kinase activity, and decreased levels of hyperphosphorylated retinoblastoma protein (pRb). By contrast, lovastatin treatment of the cyclin E overexpressors did not suppress either cyclin E- or cyclin A-dependent kinase activity, nor did it alter the level of maximally phosphorylated pRb, despite increased levels of p27(kip1). However, by 72 h, the cyclin E overexpressors rounded up but remained attached to the substratum, indicating a delayed response to lovastatin. In contrast with lovastatin, inactivation of membrane-bound Rho proteins (i.e., GTP-bound RhoA, RhoB, RhoC) with botulinum C3 transferase caused cell rounding and G1 growth arrest in both cell types but did not inhibit cyclin E-dependent histone kinase activity in the cyclin E overexpressors. In addition, 24 h of cycloheximide treatment caused depletion of RhoA from the membrane (active) fraction in neo cells, but in the cells overexpressing cyclin E, RhoA remained in the active (membrane-associated) fraction. Our observations suggest that (1) RhoA activation occurs downstream of cyclin E-dependent kinase activation, and (2) overexpression of cyclin E decreased the turnover rate of active RhoA. (C) 1999 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Branch, San Antonio, TX 78284 USA. RP Kreisberg, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 57 TC 24 Z9 25 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 15 PY 1999 VL 74 IS 4 BP 532 EP 543 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 223JD UT WOS:000081837200003 PM 10440923 ER PT J AU Yan, J Vetvicka, V Xia, Y Coxon, A Carroll, MC Mayadas, TN Ross, GD AF Yan, J Vetvicka, V Xia, Y Coxon, A Carroll, MC Mayadas, TN Ross, GD TI beta-glucan, a "Specific" biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STRUCTURAL CHARACTERIZATION; TUMORICIDAL ACTIVITY; INTEGRIN CD11B/CD18; ANTITUMOR-ACTIVITY; CANDIDA-ALBICANS; GRIFOLA-FRONDOSA; MICE DEFICIENT; LECTIN SITE; T-CELL; IMMUNITY AB beta-Glucans were identified 36 years ago as a biologic response modifier that stimulated tumor rejection, In vitro studies have shown that beta-glucans bind to a lectin domain within complement receptor type 3 (CR3; known also as Mac-1, CD11b/CD18, or alpha(M)beta(2)-integrin, that functions as an adhesion molecule and a receptor for factor I-cleaved C3b, i.e., iC3b) resulting in the priming of this iC3b receptor for cytotoxicity of iC3b-opsonized target cells. This investigation explored mechanisms of tumor therapy with soluble beta-glucan in mice. Normal mouse sera were shown to contain low levels of Abs reactive with syngeneic or allogeneic tumor lines that activated complement, depositing C3 onto tumors. Implanted tumors became coated with IgM, IgG, and C3, and the absent C3 deposition on tumors in SCID mice was reconstituted with IgM or IgG isolated from normal sera. Therapy of mice with glucan- or mannan-rich soluble polysaccharides exhibiting high affinity for CR3 caused a 57-90% reduction in tumor weight. In young mice with lower levels of tumor-reactive Abs, the effectiveness of beta-glucan was enhanced by administration of a tumor-specific mAb, and in SCID mice, an absent response to beta-glucan was reconstituted with normal IgM or IgG, The requirement for C3 on tumors and CR3 on leukocytes was highlighted by therapy failures in C3- or CR3-deficient mice. Thus, the tumoricidal function of CR3-binding polysaccharides such as beta-glucan in vivo is defined by natural and elicited Abs that direct iC3b deposition onto neoplastic cells, making them targets for circulating leukocytes bearing polysaccharide-primed CR3, Therapy fails when tumors lack iC3b, but can be restored by tumor-specific Abs that deposit iC3b onto the tumors. C1 Univ Louisville, Dept Pathol, Div Expt Immunol & Immunopathol, Louisville, KY 40292 USA. Univ Louisville, Dept Pathol, Dept Microbiol & Immunol, Louisville, KY 40292 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ross, GD (reprint author), Univ Louisville, Dept Pathol, Div Expt Immunol & Immunopathol, Louisville, KY 40292 USA. RI Yan , Jun/A-8988-2008 FU NIAID NIH HHS [AI36389, R01 AI27771]; NIDDK NIH HHS [DK51643] NR 50 TC 100 Z9 109 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1999 VL 163 IS 6 BP 3045 EP 3052 PG 8 WC Immunology SC Immunology GA 235QH UT WOS:000082553700010 PM 10477568 ER PT J AU Kawai, T Seki, M Hiromatsu, K Eastcott, JW Watts, GFM Sugai, M Smith, DJ Porcelli, SA Taubman, MA AF Kawai, T Seki, M Hiromatsu, K Eastcott, JW Watts, GFM Sugai, M Smith, DJ Porcelli, SA Taubman, MA TI Selective diapedesis of Th1 cells induced by endothelial cell RANTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTES; TRANSENDOTHELIAL MIGRATION; T-HELPER-2 CELLS; CUTTING EDGE; CHEMOKINE; ADHESION; EXPRESSION; RECEPTOR; CHEMOATTRACTANT; CYTOKINES AB Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-la or monocyte chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18 and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Hiroshima Univ, Dept Microbiol, Fac Dent, Hiroshima, Japan. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-03420] NR 48 TC 92 Z9 99 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1999 VL 163 IS 6 BP 3269 EP 3278 PG 10 WC Immunology SC Immunology GA 235QH UT WOS:000082553700038 PM 10477596 ER PT J AU Shi, CS Leonardi, A Kyriakis, J Siebenlist, U Kehrl, JH AF Shi, CS Leonardi, A Kyriakis, J Siebenlist, U Kehrl, JH TI TNF-Mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; TERMINAL KINASE; CELL-DEATH; TRAF2; RIP; APOPTOSIS; COMPLEX; HOMOLOG; DOMAIN AB TNF-induced activation of stress activated protein kinases (SAPKs, Jun NH2-terminal kinases) requires TNF receptor associated factor 2 (TRAF2). TRAF2 is a potent activator of a 95-kDa serine/threonine kinase termed germinal center kinase related (GCKR, also referred to as KHS1), which signals activation of the SAPK pathway. Consistent with a role for GCKR in TNF- induced SARK activation, a kinase-inactive mutant of GCKR is a dominant negative inhibitor of TRAF2-induced SAPK activation. Here we show that TRAF2 interacts with GCKR, This interaction depended upon the TRAF domain of TRAF2 and the C-terminal 150 aa of GCKR, The full activation of GCKR by TRAF2 required the TRAF2 RING finger domain. TNF treatment of a T cell line, Jurkat, increased both GCRK and SAPK activity and enhanced the coimmunoprecipitation of GCKR with TRAF2, Similar results were found with the B cell line HS-Sultan. These findings are consistent with a model whereby TNF signaling results in the recruitment and activation of GCKR by TRAF2 which leads to SAPK activation. C1 NIAID, Immunoregulat Lab, B Cell Mol Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, Immune Activat Sect, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, B Cell Mol Immunol Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X; LEONARDI, Antonio/0000-0001-8636-9623 NR 28 TC 42 Z9 42 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 SEP 15 PY 1999 VL 163 IS 6 BP 3279 EP 3285 PG 7 WC Immunology SC Immunology GA 235QH UT WOS:000082553700039 PM 10477597 ER PT J AU Watson, FL Heerssen, HM Moheban, DB Lin, MZ Sauvageot, CM Bhattacharyya, A Pomeroy, SL Segal, RA AF Watson, FL Heerssen, HM Moheban, DB Lin, MZ Sauvageot, CM Bhattacharyya, A Pomeroy, SL Segal, RA TI Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retrograde signaling; retrograde transport; c-fos; neurotrophin; Trk; DRG ID NERVE GROWTH-FACTOR; RAT SYMPATHETIC NEURONS; TYROSINE PROTEIN-KINASE; SIGNAL-TRANSDUCTION; AXONAL-TRANSPORT; COMPARTMENTED CULTURES; SENSORY NEURONS; HORSERADISH-PEROXIDASE; TRKA; CREB AB Target-derived neurotrophins initiate signals that begin at nerve terminals and cross long distances to reach the cell bodies and regulate gene expression. Neurotrophin receptors, Trks, themselves serve as retrograde signal carriers. However, it is not yet known whether the retrograde propagation of Trk activation reflects movement of Trk receptors from neurites to cell bodies or reflects serial activation of stationary Trk molecules. Here, we show that neurotrophins selectively applied to distal neurites of sensory neurons rapidly induce phosphorylation of the transcription factor cAMP response element-binding protein (CREB) and also cause a slower increase in Fos protein expression. Both nuclear responses require activation of neurotrophin receptors (Trks) at distal nerve endings and retrograde propagation of Trk activation to the nerve cell bodies. Using photobleach and recovery techniques to follow biologically active, green fluorescent protein (GFP)-tagged BDNF receptors (TrkB-GFP) in live cells during retrograde signaling, we show that TrkB-GFP moves rapidly from neurites to the cell bodies. This rapid movement requires ligand binding, Trk kinase activity, and intact axonal microtubules. When they reach the cell bodies, the activated TrkB receptors are in a complex with ligand. Thus, the retrograde propagation of activated TrkB from neurites to cell bodies, although rapid, reflects microtubule-dependent transport of phosphorylated Trk-ligand complexes. Moreover, the relocation of activated Trk receptors from nerve endings to cell bodies is required for nuclear signaling responses. Together, these data support a model of retrograde signaling whereby rapid vesicular transport of ligand-receptor complex from the neurites to the cell bodies mediates the nuclear responses. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [HD 18655]; NINDS NIH HHS [NS35148, NS35701] NR 55 TC 202 Z9 203 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1999 VL 19 IS 18 BP 7889 EP 7900 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 235KB UT WOS:000082539900023 PM 10479691 ER PT J AU He, SG Jin, ZF Masland, RH AF He, SG Jin, ZF Masland, RH TI The nondiscriminating zone of directionally selective retinal ganglion cells: Comparison with dendritic structure and implications for mechanism SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retina; direction selectivity; mechanism; anatomy; physiology; structure ID STARBURST AMACRINE CELLS; VISUAL-MOTION DETECTION; RABBIT RETINA; RECEPTIVE-FIELDS; RESPONSES; NEURONS; SPINES; ACETYLCHOLINE; PLASTICITY; LIGHT AB We have studied, at high resolution, the sizes and pattern of dendrites of directionally selective retinal ganglion cells in the rabbit. The dendrites had a distinctive pattern of branching. The major dendritic trunks were relatively thick, beginning at similar to 1 mu m and tapering to similar to 0.5 mu m in diameter. Higher order dendrites exiting from them generally stepped abruptly to a diameter of 0.4-0.6 mu m, which they maintained throughout their length. Recording confirmed the existence of a zone within the receptive field, usually occupying 20-25% of its area, where direction of movement was only weakly discriminated. The dendritic arbors of cells, injected with Lucifer yellow after recording, revealed no difference in dendritic structure between the discriminating and nondiscriminating zones. The nondiscriminating zone was located on the preferred side of the receptive field (the side from which movement in the preferred direction originates). This is consistent with a mechanism of direction selectivity based on inhibition generated by movement in the null direction but not with feedforward excitation, as occurs in flies and is postulated in some models of mammalian direction selectivity. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 429, Boston, MA 02114 USA. NR 38 TC 23 Z9 26 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1999 VL 19 IS 18 BP 8049 EP 8056 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 235KB UT WOS:000082539900037 PM 10479705 ER PT J AU Duska, LR Hamblin, MR Miller, JL Hasan, T AF Duska, LR Hamblin, MR Miller, JL Hasan, T TI Combination photoimmunotherapy and cisplatin: Effects on human ovarian cancer ex vivo SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PHOTODYNAMIC THERAPY; MONOCLONAL-ANTIBODY; DNA-DAMAGE; SELECTIVE PHOTODESTRUCTION; SUBCELLULAR-LOCALIZATION; PLATINUM RESISTANCE; XENOGRAFT MODEL; TUMOR-CELLS; APOPTOSIS; CARCINOMA AB Background: Patients with ovarian cancer that is clinically resistant to cisplatin-based chemotherapy have little hope of a cure of their disease. Photoimmunotherapy, which involves the antibody-targeted delivery of a nontoxic photosensitizer that is activated to a cytotoxic state with visible light, may offer a new treatment option. Photoimmunotherapy may be applied intraperitoneally to target disseminated tumor, We tested the hypothesis that this treatment in combination with cisplatin potentiates cytotoxicity in ovarian cancer cell lines and primary cultures of human tumors. Methods: Five human cancer cell lines (ovarian and breast) and 19 primary cultures were studied. The primary cultures were from solid and ascites tumor samples obtained from 14 patients with ovarian cancer who were undergoing primary surgery. The photosensitizer chlorin e(6) was conjugated to the F(ab')(2) fragment of the murine monoclonal antibody OC-125, which is directed against the antigen CA 125, Cytotoxicity was measured by the microculture tetrazolium assay. Treatments consisted of cisplatin alone, photoimmunotherapy alone, and photoimmunotherapy followed by cisplatin. The fractional product method was used to assess synergy in treatment effects. Ex vivo cultured human cells exhibiting 80% or greater survival at cisplatin concentrations of 10 mu M for 24 hours were defined as cisplatin resistant for this study, Results: When all cell types (cisplatin sensitive and cisplatin resistant) were considered together, combination treatment yielded cytotoxicity that was, on average, 6.9 times (95% confidence interval = 1.86-11.94) greater than that of cisplatin alone (two-sided P =.023). Cisplatin-resistant cells showed a synergistic effect of the two treatments (two-sided P = .044), while cisplatin-sensitive cells showed an additive effect. Conclusion: These ex vivo data suggest that platinum resistance in human ovarian cancer cells may be reversible by pretreatment with OC-125-targeted photoimmunotherapy, Further studies are required to confirm the efficacy of this approach in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 FU NIAMS NIH HHS [R01AR40352] NR 47 TC 65 Z9 70 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 SEP 15 PY 1999 VL 91 IS 18 BP 1557 EP 1563 DI 10.1093/jnci/91.18.1557 PG 7 WC Oncology SC Oncology GA 237EB UT WOS:000082641400010 PM 10491432 ER PT J AU Stone, M AF Stone, M TI Children's health. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stone, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD SEP 15 PY 1999 VL 124 IS 15 BP 68 EP 68 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 236UQ UT WOS:000082617900011 ER PT J AU Sippel, JM Giraud, GD Holden, WE AF Sippel, JM Giraud, GD Holden, WE TI Nasal administration of the nitric oxide synthase inhibitor L-NAME induces daytime somnolence SO SLEEP LA English DT Article DE nitric oxide; L-name; NG-nitro-L-arginine methyl ester; nasal; nose; sleep; multiple sleep latency test ID MUCOSA AB In preliminary studies, human subjects complained of drowsiness after aerosolization of NG-nitro-L-arginine methyl ester (L-NAME) into the nasal passages. We compared the effects of a nasal aerosol of L-NAME (0.5 M, 4 ml) to those of saline on sleep onset latency and exhaled nasal nitric oxide(NO). L-NAME decreased sleep onset latency and exhaled nasal NO. Vasoconstriction and local effects of L-NAME on NO synthesis are unlikely to explain this effect since oxymetazoline, a vasoconstrictor, decreased exhaled NO but had no effect on sleep onset latency. We conclude that aerosolization of L-NAME to the nasal passages induces daytime sleepiness. C1 Portland VA Med Ctr, Pulm & Crit Care Sect, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Holden, WE (reprint author), Portland VA Med Ctr, Pulm & Crit Care Sect, 3710 SW US Vet Rd, Portland, OR 97201 USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD SEP 15 PY 1999 VL 22 IS 6 BP 786 EP 788 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 237QN UT WOS:000082667700009 PM 10505824 ER PT J AU Flye, MW Pennington, L Kirkman, R Weber, B Sindelar, W Sachs, DH AF Flye, MW Pennington, L Kirkman, R Weber, B Sindelar, W Sachs, DH TI Spontaneous acceptance or rejection of orthotopic liver transplants in outbred and partially inbred miniature swine SO TRANSPLANTATION LA English DT Article ID DISPARATE RENAL-ALLOGRAFTS; DONOR IRRADIATION; CLASS-I; TOLERANCE; CHIMERISM; SURVIVAL AB Background. Results of clinical liver transplantation have shown that rejection and loss of human liver allografts occurs despite immunosuppression, because genetic disparity and liver immunogenicity remain a matter of controversy, we reexamined the fate of outbred liver allografts without immunosuppression and used partially inbred miniature swine, in which the genetics of major histocompatibility complex (MHC) antigens have been characterized and can be controlled. Methods. Orthotopic liver transplantation was performed between pairs of outbred domestic farm pigs and between pairs of inbred miniature swine with genetically defined major histocompatibility (SLA) loci. A passive splenic and vena caval to jugular vein shunt with systemic heparinization prevented hypotension during the anhepatic phase. Immunological responses were monitored by mixed lymphocyte culture (MLC), CML, skin graft rejection, liver biopsies, and serial serum chemistries. Results, Median survival of technically successful liver allografts between pairs of outbred pigs (n=20) was 38 days and between partially inbred swine matched at the SLA locus (n=17) was 79 days. MLC responsiveness did not correlate with the development of rejection. Five of 20 (25%) outbred pigs and 6 of 17 (35%) MHC matched inbred miniature swine survived more than 100 days. In the long-term survivors, donor, but not third party, MHC matched skin graft survival times were prolonged. In contrast, all SLA-mismatched inbred recipients (n=26) died rapidly from massive liver rejection, with a median survival time of 9 days. In these rejecting animals, the marked MLC responsiveness to donor lymphocytes evident pretransplant diminished rapidly after transplantation, but an undiminished PHA responsiveness and a blunted third party MLC response persisted. Conclusion The length of survival and the degree and incidence of rejection were similar in outbred pigs and in SLA-matched inbred miniature pigs, indicating that the outbred animals were, therefore, probably closely related and shared relevant genes, However, survival was significantly shortened and liver allograft rejection was accelerated in SLA-mismatched inbred swine. These results indicate that major histocompatibility differences play an important role in the rejection of liver allografts, as is true for other vascularized grafts in the unimmunosuppressed recipient. The development of liver allograft rejection across non-MHC differences is variable and, when present, appears to be a chronic process. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Dept Surg, Charlestown, MA 02129 USA. RP Flye, MW (reprint author), Washington Univ, Sch Med, Dept Surg, 1 Barnes Hosp Plaza,Suite 5103 Queeny Tower, St Louis, MO 63110 USA. NR 43 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 1999 VL 68 IS 5 BP 599 EP 607 DI 10.1097/00007890-199909150-00002 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 242KE UT WOS:000082939200002 PM 10507476 ER PT J AU Arita, S Smith, CV Nagai, T Sakamoto, Y Ochiai, M Maruyama, M Tanabe, Y Shevlin, L Mullen, Y AF Arita, S Smith, CV Nagai, T Sakamoto, Y Ochiai, M Maruyama, M Tanabe, Y Shevlin, L Mullen, Y TI Improved human islet isolation by a tube method for collagenase infusion SO TRANSPLANTATION LA English DT Article ID HUMAN PANCREATIC-ISLETS; TRANSPLANTATION AB Background. Collagenase infusion into the pancreatic duct is an essential step in human islet isolation. We developed a new method for ductal canulation and collagenese infusion. Methods. A total of 53 pancreata were divided into two groups: group 1 (n=23), the new tube method, and group 2 (n=30), the standard angiocatheter method. In group I, a polyethylene tube was inserted into the duct and pushed to the tail. The tail was first expanded, followed by expansion of the body and then the head, by pulling out the tube, Results. Total islet number and number/g pancreas (mean+/-SE) were significantly higher in group 1 (481,123+/-43,218 and 8,010+/-722) (mean+/-SE) than in group 2 (300,974+/-35,122 and 5,090+/-515, P<0.01). Total islet equivalent number and islet equivalent number per gram pancreas were also significantly higher in group 1 (319,176+/-39,354 and 5,455+/-652) than in group 2 (202,022+/-23,331 and 3,722+/-468, P<0.04). Islet purity and fragmentation showed no differences between the groups. Conclusions. The tube method improved islet yields. We recommended this method for human islet isolation. C1 W Los Angeles Vet Affairs Med Ctr, Islet Transplant Program, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Islet Transplant Program, Sch Med, Dept Surg, Los Angeles, CA 90073 USA. RP W Los Angeles Vet Affairs Med Ctr, Islet Transplant Program, Dept Surg, Bldg 304,Room E1-206,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 10 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 1999 VL 68 IS 5 BP 705 EP 707 DI 10.1097/00007890-199909150-00019 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 242KE UT WOS:000082939200019 PM 10507493 ER PT J AU Fishman, MC AF Fishman, MC TI Zebrafish genetics: The enigma of arrival SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID CARDIOVASCULAR-SYSTEM; DANIO-RERIO; MUTATIONS; GENES; ORGANS; MODEL C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 36 TC 36 Z9 37 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 14 PY 1999 VL 96 IS 19 BP 10554 EP 10556 DI 10.1073/pnas.96.19.10554 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 235ZQ UT WOS:000082574100004 PM 10485858 ER PT J AU Miyamoto, K Khosrof, S Bursell, SE Rohan, R Murata, T Clermont, AC Aiello, LP Ogura, Y Adamis, AP AF Miyamoto, K Khosrof, S Bursell, SE Rohan, R Murata, T Clermont, AC Aiello, LP Ogura, Y Adamis, AP TI Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LEUKOCYTE ADHESION; IN-VIVO; RETINAL MICROCIRCULATION; BARRIER BREAKDOWN; RATS; NEOVASCULARIZATION; REPERFUSION; DYSFUNCTION; ANTIBODIES; INJURY AB Diabetic retinopathy is a leading cause of adult vision loss and blindness, Much of the retinal damage that characterizes the disease results horn retinal vascular leakage and nonperfusion, This study shows that diabetic retinal vascular leakage and nonperfusion are temporally and spatially associated with retinal leukocyte stasis (leukostasis) in the rat model of streptozotocin-induced diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1), ICAM-1 blockade with a mAb prevents diabetic retinal leukostasis and vascular leakage by 48.5% and 85.6%, respectively. These data identify the causal role of leukocytes in the pathogenesis of diabetic retinopathy and establish the potential utility of ICAM-1 inhibition as a therapeutic strategy for the prevention of diabetic retinopathy. C1 Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab,Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Ophthalmol,Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Nagoya City Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 467, Japan. RP Adamis, AP (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab,Joslin Diabet Ctr, Boston, MA 02115 USA. NR 21 TC 411 Z9 448 U1 4 U2 8 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 SEP 14 PY 1999 VL 96 IS 19 BP 10836 EP 10841 DI 10.1073/pnas.96.19.10836 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 235ZQ UT WOS:000082574100058 PM 10485912 ER PT J AU Cohen, SS Li, C Ding, LN Cao, YZ Pardee, AB Shevach, EM Cohen, DI AF Cohen, SS Li, C Ding, LN Cao, YZ Pardee, AB Shevach, EM Cohen, DI TI Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVATION-INDUCED APOPTOSIS; GP120 ENVELOPE GLYCOPROTEIN; PROGRAMMED CELL-DEATH; TRANSGENIC MICE; T-CELLS; FAS-LIGAND; PROTEIN; INFECTION; TYPE-1 AB HIV infection is accompanied by an early immune dysfunction limiting host control of virus and likely contributing to difficulties in achieving a successful vaccine against HIV. We report here that the HIV Tat protein is strongly immunosuppressive, both immediately after immunization of mice with soluble protein (sTat), and in seroconverting humans, and propose that Tat-induced suppression cripples immune surveillance to HIV infection. We show that macrophages are sensitive to sTat stimulation at concentrations 1,000-fold lower (500 pM) than T cells, and this stimulation is accompanied by the immunosuppressive induction of Fas ligand on the macrophage. T cell proliferative defects induced by sTat in vitro can be completely (at lower concentrations of sTat) or partially (at higher concentrations) reversed by antagonists to Fas/Fas ligand interaction. We further report a method to preserve immunogenicity while inactivating Tat immunosuppression through oxidation, which advances the use of oxidized Tat as a component of an anti-HIV vaccine. These observations define additional methods to study the immunosuppressive functions of sTat that now may be rapidly applied to primary isolates from individuals with differing clinical courses. Our Endings have immediate relevance for vaccine development, by describing and supporting a strategy that includes inactivated sTat in a multicomponent, anti-HIV vaccine. C1 Queens Coll, Bernard & Gloria Salick Ctr Mol & Cellular Biol, Flushing, NY 11367 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Rockefeller Univ, Aaron Diamond Res Ctr, New York, NY 10016 USA. RP Cohen, DI (reprint author), Queens Coll, Bernard & Gloria Salick Ctr Mol & Cellular Biol, Remsen Hall 117, Flushing, NY 11367 USA. NR 33 TC 85 Z9 85 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 14 PY 1999 VL 96 IS 19 BP 10842 EP 10847 DI 10.1073/pnas.96.19.10842 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 235ZQ UT WOS:000082574100059 PM 10485913 ER PT J AU Siegel, AJ Sholar, MB Mendelson, JH Lukas, SE Kaufman, MJ Renshaw, PF McDonald, JC Lewandrowski, KB Apple, FS Stec, JJ Lipinska, I Tofler, GH Ridker, PM AF Siegel, AJ Sholar, MB Mendelson, JH Lukas, SE Kaufman, MJ Renshaw, PF McDonald, JC Lewandrowski, KB Apple, FS Stec, JJ Lipinska, I Tofler, GH Ridker, PM TI Cocaine-induced erythrocytosis and increase in von Willebrand factor - Evidence for drug-related blood doping and prothrombotic effects SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CARDIAC TROPONIN-I; ACUTE MYOCARDIAL-INFARCTION; SICKLE-CELL TRAIT; ACUTE CHEST PAIN; HEMOSTATIC FACTORS; SUDDEN-DEATH; VONWILLEBRAND-FACTOR; SUBMAXIMAL EXERCISE; INTRANASAL COCAINE; PHYSICAL-ACTIVITY AB Background: Mechanisms that mediate cocaine-induced cardiovascular events following vasoconstriction are incompletely understood. Objective: To examine the effects of cocaine in moderate doses on hematologic and hemostatic parameters that influence blood viscosity and thrombotic potential. Methods: Changes in hemoglobin concentration, hematocrit, and red blood cell counts were measured in human subjects who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for long-term cocaine abuse, before and sequentially after moderate intranasal and intravenous doses of cocaine. Hemostatic parameters, including von Willebrand factor, fibrinolytic activity, fibrinogen, plasminogen activator inhibitor antigen, and tissue-type plasminogen activator antigen, were sequentially measured after intravenous cocaine or saline placebo with cardiac troponin subunits T and I. Results: Hemoglobin level (P=.002), hematocrit (P=.01), and red blood cell counts (P =.04) significantly increased from 4% to 6% over baseline from 10 to 30 minutes after intranasal (n = 14) and intravenous (n = 7) cocaine administration in doses of 0.9 mg/kg and 0.4 mg/kg, respectively, with no change in white blood cell or platelet counts. There was a significant increase (P=.03) in von Willebrand factor from 30 to 240 minutes, peaking at 40% over baseline following intravenous cocaine administration in a dose of 0.4 mg/kg (n = 12), with no change after 0.2 mg/kg (n=3) or placebo (n=6). Other hemostatic factors, creatinine, blood urea nitrogen, and cardiac troponin subunits T and I showed no changes. Conclusions: Cocaine induced a transient erythrocytosis that may increase blood viscosity while maintaining tissue oxygenation during vasoconstriction. An increase in von Willebrand factor without a compensatory change in endogenous fibrinolysis may trigger platelet adhesion, aggregation, and intravascular thrombosis. C1 McLean Hosp, Dept Med, Belmont, MA 02178 USA. McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02178 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. McLean Hosp, Dept Pharm, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Clin Lab, Boston, MA 02114 USA. Hennepin Cty Med Ctr, Dept Labs, Minneapolis, MN 55415 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, Boston, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Siegel, AJ (reprint author), McLean Hosp, Dept Internal Med, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [DA00064, DA04059, DA09448] NR 59 TC 27 Z9 28 U1 0 U2 3 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 SEP 13 PY 1999 VL 159 IS 16 BP 1925 EP 1929 DI 10.1001/archinte.159.16.1925 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 234ZC UT WOS:000082513400011 PM 10493323 ER PT J AU Cote, RJ Peterson, HF Chaiwun, B Gelber, RD Goldhirsch, A Castiglione-Gertsch, M Gusterson, B Neville, AM AF Cote, RJ Peterson, HF Chaiwun, B Gelber, RD Goldhirsch, A Castiglione-Gertsch, M Gusterson, B Neville, AM CA Int Breast Canc Study Grp TI Role of immunohistochemical detection of lymph-node metastases in management of breast cancer SO LANCET LA English DT Article ID TUMOR-CELLS; PROGNOSTIC-SIGNIFICANCE; BONE-MARROW; STAGE-I; MICROMETASTASES; CARCINOMA; FUTURE AB Background This study was designed to ascertain whether immunohistochemical methods could improve the detection of metastases in primary breast-cancer patients whose axillary lymph nodes were classified, by conventional methods, as disease free. Methods Ipsilateral lymph nodes (negative for metastases by routine histology) from 736 patients (participants in Trial V of the International [Ludwig] Breast Cancer Study) were examined by serial sectioning and staining with haematoxylin and eosin (two sections from each of six levels) and by immunohistochemistry of a single section (with two anticytokeratins AE-1 and CAM 5.2). After median follow-up of 12 years, disease-free and overall survival were estimated by Kaplan-Meier methods. Findings Occult nodal metastases were detected by serial sectioning and haematoxylin and eosin in 52 (7%) of 736 patients and by immunohistochemistry in 148 (20%). Only two (3%) of 64 invasive lobular or mixed invasive lobular and ductal cancers had node micrometastases, detected by haematoxylin and eosin, compared with 25 (39%) by immunohistochemistry. Occult metastases, detected by either method, were associated with significantly poor disease-free and overall survival in postmenopausal but not in premenopausal patients. Immunohistochemically detected occult lymph-node metastases remained an independent and highly significant predictor of recurrence even after control for tumour grade, tumour size, oestrogen-receptor status, vascular invasion, and treatment assignment (hazard ratio 1.79 [95% CI 1.17-2.74], p=0.007). Interpretation The immunohistochemical examination of ipsilateral axillary lymph nodes is a reliable, prognostically valuable, and simple method for the detection of occult nodal metastases. Immunohistochemistry is recommended as a standard method of node examination in postmenopausal patients. C1 Ludwig Inst Canc Res, London SW1E 5AG, England. USC Sch Med, Norris Canc Ctr, Dept Pathol, Los Angeles, CA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Int Breast Canc Study Grp Stat Ctr, Boston, MA USA. European Inst Oncol, Milan, Italy. Inst Canc Res, Breakthrough Toby Robins Breast Canc Res Ctr, London SW3 6JB, England. Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. RP Neville, AM (reprint author), Ludwig Inst Canc Res, 6th Floor,Glen House,Stag Pl, London SW1E 5AG, England. RI gusterson, barry/D-3752-2009 FU NCI NIH HHS [CA-75362] NR 21 TC 366 Z9 378 U1 0 U2 10 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 11 PY 1999 VL 354 IS 9182 BP 896 EP 900 DI 10.1016/S0140-6736(98)11104-2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 234YK UT WOS:000082511800011 PM 10489948 ER PT J AU Pennington, BF Filipek, PA Lefly, D Churchwell, J Kennedy, DN Simon, JH Filley, CM Galaburda, A Alarcon, M DeFries, JC AF Pennington, BF Filipek, PA Lefly, D Churchwell, J Kennedy, DN Simon, JH Filley, CM Galaburda, A Alarcon, M DeFries, JC TI Brain morphometry in reading-disabled twins SO NEUROLOGY LA English DT Article DE dyslexia; reading disability; brain morphometry; structural MRI ID CORPUS-CALLOSUM MORPHOLOGY; DEVELOPMENTAL DYSLEXIA; PLANUM-TEMPORALE; MRI; CHILDREN; HYPERACTIVITY; INTELLIGENCE; CHROMOSOME-6; ABILITIES; DISORDER AB Objective: To test for brain structure differences in reading disability (RD) by means of MRI-based morphometry. Background: Consensus is lacking on the brain structural correlates of RD. The current study reports on a wider set of structures in the largest sample yet studied, controlling for age, gender, IQ, and attention deficit hyperactivity disorder (ADHD), Methods: A case-control study was performed that was comprised of 75 individuals with RD (mean age, 17.43 +/- 4.29 years) and 22 control subjects without RD (mean age, 18.69 +/- 3.75 years), each a single member of a twin pair. The two groups were similar in age, gender, and handedness, but differed in full-scale IQ (FSIQ), with the RD group having a lower mean FSIQ (101.8 +/- 9.9 versus 118.3 +/- 10.3). Using three group-by-structure analyses of covariance, groups were compared in terms of volume tin cubic centimeters) of major neocortical subdivisions, subcortical structures, and midsagittal areas tin square millimeters) of three subdivisions of the corpus callosum. Results: Controlling for age, gender, and IQ, the authors found a significant group-by-structure interaction for the major neocortical subdivisions (p = 0.002), reflecting a different developmental pattern in the RD group, with the insula and anterior superior neocortex being smaller and the retrocallosal cortex being larger in the RD group. In contrast, they found no group main or interaction effects for the subcortical or callosal structures. The pattern of results was essentially the same in subjects without ADHD. Conclusions: Most brain structures do not differ in size in RD, but cortical development is altered subtly. This study replicates in a larger sample previous findings of insular differences in RD and demonstrates further that those differences are not attributable to comorbid ADHD. C1 Univ Denver, Denver, CO 80208 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Colorado, Sch Med, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Colorado, Boulder, CO 80309 USA. RP Univ Denver, 2155 S Race St, Denver, CO 80208 USA. RI Kennedy, David/H-3627-2012 FU NICHD NIH HHS [P30 HD04024, P50 HD27802]; NIMH NIH HHS [K02 MH00419] NR 46 TC 30 Z9 30 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD SEP 11 PY 1999 VL 53 IS 4 BP 723 EP 729 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 235BF UT WOS:000082518300012 PM 10489032 ER PT J AU Yasuda, M Kawamata, T Komure, O Kuno, S D'Souza, I Poorkaj, P Kawai, J Tanimukai, S Yamamoto, Y Hasegawa, H Sasahara, M Hazama, F Schellenberg, GD Tanaka, C AF Yasuda, M Kawamata, T Komure, O Kuno, S D'Souza, I Poorkaj, P Kawai, J Tanimukai, S Yamamoto, Y Hasegawa, H Sasahara, M Hazama, F Schellenberg, GD Tanaka, C TI A mutation in the microtubule-associated protein tau in pallido-nigroluysian degeneration SO NEUROLOGY LA English DT Article DE mutation; microtubule-associated protein tau; pallido-nigro-luysian degeneration ID PONTO-NIGRAL DEGENERATION; FRONTOTEMPORAL DEMENTIA; GENE; CHROMOSOME-17; PARKINSONISM; MISSENSE AB We detected a missense mutation in exon 10 of tau that causes a substitution at codon 279 (N279K)in a Japanese patient with a familial background of parkinsonism and dementia originally described as pallido-nigro-luysian degeneration. This mutation is the same as one seen in a Caucasian family with pallido-ponto-nigral degeneration. The similarities between these two families suggest a common genetic mechanism that may account for the peculiar distribution of neuroglial degeneration with tauopathy. C1 Hyogo Inst Aging Brain & Cognit Disorders, Himeji, Hyogo 6700981, Japan. Natl Utano Hosp, Dept Neurol, Kyoto, Japan. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Res Educ Clin Ctr, Seattle, WA USA. Univ Washington, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA USA. Univ Washington, Dept Pharmacol, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA USA. Shiga Univ Med Sci, Dept Pathol, Otsu, Shiga 52021, Japan. RP Yasuda, M (reprint author), Hyogo Inst Aging Brain & Cognit Disorders, 520 Siasho-ko, Himeji, Hyogo 6700981, Japan. FU NIA NIH HHS [AG1176-03] NR 10 TC 65 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 11 PY 1999 VL 53 IS 4 BP 864 EP 868 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 235BF UT WOS:000082518300037 PM 10489057 ER PT J AU Hagopian, K AF Hagopian, K TI Preparative electrophoretic method for the purification of a hydrophobic membrane protein: Subunit c of the mitochondrial ATP synthase from rat liver SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE mitochondria; ATPase; subunit c purification; preparative electrophoresis; FPLC ID CEROID-LIPOFUSCINOSIS; BATTEN-DISEASE; COMPLEX; IDENTIFICATION; DETERGENT; STORAGE; DICYCLOHEXYLCARBODIIMIDE; LIPOPIGMENT; MECHANISM AB A method is described for the purification of subunit c of ATP synthase from rat liver mitochondria. After sample preparation and solvent extraction, the protein was purified to homogeneity by a single-step preparative electrophoretic procedure, using aqueous buffer and containing lithium dodecyl sulfate. The subunit is an extremely hydrophobic and insoluble protein and all solubilization attempts, using a variety of detergents, were unsuccessful except for lithium dodecyl sulfate. Buffer exchange and FPLC gel filtration removed the detergent from the purified sample, leaving the protein in a soluble form. The mammalian protein is composed of 75 amino acid residues, with a molecular mass of 7602 Da and is classified as a proteolipid. Subunit c accounts for 25 and 85% of the intralysosomal accumulation, within neurons, of storage material in juvenile and late-infantile forms of Batten's disease, respectively. This purification procedure allows access to a continuous supply of pure subunit c from a conventional source such as rat liver and preserves precious autopsy materials. The protein could be used as substrate in future proteolytic studies involving pepstatin-insensitive lysosomal proteases and for raising of more specific antibodies. The procedure could also be adapted/modified and used as a model for purifying other extremely insoluble proteins. (C) 1999 Academic Press. C1 Inst Neurol, Dept Neurochem, London WC1N 3BG, England. RP Hagopian, K (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC-D5,2500 Overlook Terrace, Madison, WI 53705 USA. EM khagopian@facstaff.wisc.edu NR 36 TC 10 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 10 PY 1999 VL 273 IS 2 BP 240 EP 251 DI 10.1006/abio.1999.4219 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 238MA UT WOS:000082713000013 PM 10469495 ER PT J AU Growdon, WB Cheung, BS Hyman, BT Rebeck, GW AF Growdon, WB Cheung, BS Hyman, BT Rebeck, GW TI Lack of allelic imbalance in APOE epsilon 3/4 brain mRNA expression in Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE apolipoprotein epsilon 3/4 genotype; apolipoprotein E promoter polymorphism; allelic imbalance; quantitative RT-PCR; Alzheimer's disease ID APOLIPOPROTEIN-E; REGULATORY REGION; POLYMORPHISM; ASSOCIATION; DEMENTIA; RISK; POPULATION; GENE AB Although the APOE epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD), it is not deterministic, as many APOE epsilon 3/4 individuals do not develop AD. It has been hypothesized that this incomplete penetrance is due, in part, to an imbalance of allele expression in heterozygous individuals. In this regard, Lambert et at. (1998) reported that AD individuals have a higher APOE epsilon 4/total APOE ratio than non-demented control subjects. We tested this hypothesis using radioactive RT-PCR to quantitate APOE epsilon 3 and epsilon 4 allele expression levels in AD and non-AD brain samples from APOE epsilon 3/4 individuals. Quantitative analyses of amplified products within the linear range of amplification (18-20 cycles) revealed no difference from the expected 1:1 ratio in genomic DNA and in cDNA from AD and control brains. Using high PCR cycle numbers (similar to 30), we observed an artificial elevation of the APOE epsilon 3/total APOE ratio in both DNA and cDNA samples, possibly due to DNA heteroduplex formation. Our results do not support the hypothesis that allelic imbalance contributes to the risk of developing AD among APPE epsilon 3/4 heterozygote individuals. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Alzheimer Dis Res Ctr, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Dis Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 20 TC 17 Z9 17 U1 0 U2 3 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 SEP 10 PY 1999 VL 272 IS 2 BP 83 EP 86 DI 10.1016/S0304-3940(99)00557-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 238CQ UT WOS:000082693700003 PM 10507547 ER PT J AU Weiss, T Miltner, WHR Adler, T Bruckner, L Taub, E AF Weiss, T Miltner, WHR Adler, T Bruckner, L Taub, E TI Decrease in phantom limb pain associated with prosthesis-induced increased use of an amputation stump in humans SO NEUROSCIENCE LETTERS LA English DT Article DE phantom limb pain; amputation; Sauerbruch prosthesis; cosmetic prosthesis; increased use; cortical reorganization; treatment ID INDUCED MOVEMENT THERAPY; CORTICAL REORGANIZATION; DEAFFERENTATION; MONKEYS; PLASTICITY; CORTEX; STROKE AB The experience of phantom limb pain, non-painful phantom limb sensation and telescoping was ascertained by questionnaire in a group of upper extremity amputees wearing a functionally effective Sauerbruch prosthesis which permits extensive use of the affected limb and in a group of patients wearing a cosmetic prosthesis that did little to increase the utilization of the amputation stump. The Sauerbruch prosthesis group exhibited a significant and large decrease in amount of phantom limb pain while the cosmetic prosthesis group showed no change. Neither group experienced a decrease in non-painful phantom limb sensation or telescoping. The amount of phantom limb pain has been found to be highly correlated with the amount of injury-related, afferent-decrease cortical reorganization. It is possible that the increased use of the amputation stump induced by wearing a Sauerbruch prosthesis produced a countervailing use-dependent, afferent-increase type of cortical reorganization that reversed the phantom limb pain. These preliminary results require replication. Their therapeutic implications are discussed. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Jena, Dept Biol & Clin Physiol, Inst Psychol, D-07743 Jena, Germany. Moritz Klin Bad Klosterlausnitz, Dept Orthoped, D-07639 Bad Klosterlausnitz, Germany. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. BIrmingham Vet Affairs Med Ctr, Phys Med & Rehabil Serv, Birmingham, AL 35233 USA. RP Miltner, WHR (reprint author), Univ Jena, Dept Biol & Clin Physiol, Inst Psychol, Steiger 3,Haus 1, D-07743 Jena, Germany. NR 19 TC 66 Z9 73 U1 5 U2 13 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 SEP 10 PY 1999 VL 272 IS 2 BP 131 EP 134 DI 10.1016/S0304-3940(99)00595-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 238CQ UT WOS:000082693700015 PM 10507559 ER PT J AU Muller, JE AF Muller, JE TI Sexual activity as a trigger for cardiovascular events: What is the risk? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Heart Disease and Sexual Health - What Do Cardiologists Need to Know CY NOV 08, 1998 CL DALLAS, TEXAS SP Pfizer Inc, US Pharmaceut Grp, New York ID ACUTE MYOCARDIAL-INFARCTION; PHYSICAL EXERTION; CIRCADIAN VARIATION; ONSET AB An important component in the rehabilitation program of patients with cardiac disease is assisting them in resuming sexual activity. In many cases, cardiac disease creates fear, particularly in the spouse, that sexual activity will trigger a cardiac event. Assessment of the possibility that sexual activity may lead to cardiac disease has been aided by advances in the study of triggers of cardiovascular disease. The acute onset of cardiovascular disease has, in many cases, proved to result from the exposures and activities of patients. Nonfatal myocardial infarction, sudden cardiac death, stroke, transient myocardial ischemia, and most arrhythmias have a marked peak during the period between 6:00 A.M, and noon. Wake-time-adjusted data indicate that peak occurrence follows waking and rising. In addition to this marked dependence of disease onset on time of day and awakening, it has been established that there are numerous other triggers of cardiovascular events. For nonfatal infarction, the triggers of heavy exertion, anger, sexual activity, and awakening account for approximately 17% of all cases. Other triggers are still being identified. A new epidemiologic method, the case-crossover method, has greatly enhanced identification of triggering. Regular exertion can reduce the incidence of triggering. It is possible, though unproved, that an acute event can be triggered by rupture of a vulnerable atherosclerotic plaque. With regard to sexual activity, the low absolute risk generated by a potential trigger is useful information with which to reassure patients. (C) 1999 by Excerpta Medica, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Muller, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 840 Bigelow,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 30 Z9 29 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 SEP 9 PY 1999 VL 84 IS 5B SI SI BP 2N EP 5N PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238UU UT WOS:000082731900002 PM 10503569 ER PT J AU Kloner, RA Zusman, RM AF Kloner, RA Zusman, RM TI Cardiovascular effects of sildenafil citrate and recommendations for its use SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Heart Disease and Sexual Health - What Do Cardiologists Need to Know CY NOV 08, 1998 CL DALLAS, TEXAS SP Pfizer Inc, US Pharmaceut Grp, New York ID ERECTILE DYSFUNCTION; ORAL SILDENAFIL; SEXUAL-ACTIVITY; NITRIC-OXIDE; IMPOTENCE; DISEASE; RISK AB Siidenafil citrate is the first orally active therapy proved to be effective and safe treatment for erectile dysfunction (ED), Because men with cardiovascular disease are at increased risk of developing ED, and because ED and cardiovascular disease share important risk factors, attention has focused recently on the use of sildenafil in these men. When used in combination with nitroglycerin and other nitric oxide (NO) donors, sildenafil may potentiate major drops in blood pressure, Use of nitrate antianginal agents are an absolute contraindication to sildenafil use. In normotensive men and in men receiving antihypertensive medications evaluated in Phase II/III clinical trials, sildenafil use at the recommended doses (25-100 mg 1 hour before sexual intercourse and no more than once daily) was associated with modest, transient reductions in blood pressure and negligible effects on heart rate. In a more recent study, sildenafil was well tolerated in patients receiving antihypertensive medications and was not associated with major decreases in blood pressure. From the time of its approval in the United States in March 1998 through mid-November 1998, with approximately 6 million prescriptions written, 130 deaths were reported by the US Food and Drug Administration (FDA). Seventy-seven of the men who died had documented cardiovascular events. Sixteen men took or were administered nitroglycerin or an organic nitrate; 3 others had nitroglycerin in their possession. Physician prescribing guidelines issued by the American College of Cardiology/American Heart Association (ACC/AHA) recommend caution when prescribing sildenafil to men with certain cardiovascular conditions, liver or kidney disease, and to those taking medications that may prolong sildenafil's half-life (e.g., erythromycin or cimetidine), Those with known or suspected coronary artery disease may benefit from an exercise test to determine whether resumption of sexual activity with use of sildenafil is likely to be associated with an increased risk of myocardial ischemia. (C) 1999 by Excerpta Medica, Inc. C1 Hosp Good Samaritan, Inst Heart, Los Angeles, CA 90017 USA. Univ So Calif, Los Angeles, CA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Hypertens & Vasc Med, Boston, MA 02114 USA. RP Kloner, RA (reprint author), Hosp Good Samaritan, Inst Heart, 9th Floor Res,637 S Lucas St, Los Angeles, CA 90017 USA. RI Kloner, Robert/B-2971-2012 NR 20 TC 43 Z9 45 U1 1 U2 2 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 SEP 9 PY 1999 VL 84 IS 5B SI SI BP 11N EP 17N PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238UU UT WOS:000082731900004 PM 10503571 ER PT J AU Rosowsky, A Forsch, RA Null, A Moran, RG AF Rosowsky, A Forsch, RA Null, A Moran, RG TI 5-deazafolate analogues with a rotationally restricted glutamate or ornithine side chain: Synthesis and binding interaction with folylpolyglutamate synthetase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CCRF-CEM CELLS; GLYCINAMIDE RIBONUCLEOTIDE FORMYLTRANSFERASE; METHOTREXATE DERIVATIVES BEARING; FOLYL POLYGLUTAMATE SYNTHETASE; DENOVO PURINE SYNTHESIS; TERMINAL L-ORNITHINE; BIOLOGICAL EVALUATION; DIHYDROFOLATE-REDUCTASE; THYMIDYLATE SYNTHASE; ANTITUMOR-ACTIVITY AB Rotationally restricted analogues of 5-deazapteroyl-L-glutamate and (6R,6S)-5-deaza-5,6,7,8-tetrahydropteroyl-L-glutamate with a one-carbon bridge between the amide nitrogen and the 6'-position of the p-aminobenzoyl moiety were synthesized and tested as substrates for folylpolyglutamate synthetase (FPGS), a key enzyme in folate metabolism and an important determinant of the therapeutic potency and selectivity of classical antifolates. The corresponding bridged analogues of 5-deazapteroyl-L-ornithine and (6R,6S)-5-deaza-5,6,7,8-tetrahydropteroyl L-ornithine were also synthesized as potential inhibitors. Condensation of diethyl L-glutamate wi th methyl 2-bromomethyl-4-nitrobenzoate followed by catalytic reduction of the nitro group, reductive coupling with 2-acetamido-6-formylpyrido[2,3-d]pyrimid in the presence of dimethylaminoborane, and acidolysis with HBr/AcOH yielded 2-L-[5-[N-2-acetamido-4(3H)oxopyrido[2,3-d]pyrimidin-6-yl)methylamino]-2,3-dihydro-1-oxo-2(1H)-isoindolyl]glutaric acid (1). When acidolysis was preceded by catalytic hydrogenation, the final product was the corresponding (6R,GS)-tetrahydro derivative 2. A similar sequence starting from methyl N-delta-benzyloxycarbonyl-L-ornithine led to 2-L-[5-[N-(2-amino-4(3H)-oxopyrido[2,3-d]methylamino]-2,3-dihydro-1-oxo-2(1H)-isoindolyl]-5-aminopentanoic acid (3) and the (6R,6S)tetrahydro derivative 4. Compounds 3 and 4 were powerful inhibitors of recombinant human FPGS, whereas 1 and 2 were exceptionally efficient FPGS substrates, with the reduced compound 2 giving a K-m, (0.018 CIM) lower than that of any other substrate identified to date. (6R,6S)-5-Deazatetrahydrofolate, in which the side chain is free to rotate, was rapidly converted to long-chain polyglutamates. In contrast, the reaction of 1 and 2 was limited to the addition of a single molecule of glutamic acid. Hence rotational restriction of the side chain did not interfere with the initial FPGS-catalyzed reaction and indeed seemed to facilitate it, but the ensuing gamma-glutamyl adduct was no longer an efficient substrate for the enzyme. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol Toxicol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. RP Rosowsky, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA39687, R01-CA63064] NR 96 TC 9 Z9 9 U1 1 U2 2 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 SEP 9 PY 1999 VL 42 IS 18 BP 3510 EP 3519 DI 10.1021/jm9807205 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 235HH UT WOS:000082535900010 PM 10479284 ER PT J AU Choi, SW Elmaleh, DR Hanson, RN Fischman, AJ AF Choi, SW Elmaleh, DR Hanson, RN Fischman, AJ TI Design, synthesis, and biological evaluation of novel non-piperazine analogues of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines as dopamine transporter inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; REUPTAKE INHIBITORS; HIGH-AFFINITY; BINDING DOMAINS; UPTAKE COMPLEX; COCAINE; GBR-12909; POTENT; GBR12935; RAT AB A series of novel diamine, amine-amide, and piperazinone analogues of N-[2-(bisarylmethoxy)ethyl]-N'-(phenylpropyl)piperazines, GBR 12909 and 12935, were synthesized and evaluated as inhibitors of presynaptic monoamine neurotransmitter transporters. The primary objective of the study was to determine the structural requirements for selectivity of ligand binding and potency for neurotransmitter reuptake inhibition. In general, the target compounds retained transporter affinity; however, structural variations produced significant effects on reuptake inhibition and transporter selectivity. For example, analogues prepared by replacing the piperazine ring in the GBR structure with an N,N'-dimethylpropyldiamine moiety displayed enhanced selectivity for binding and reuptake inhibition at the norepinephrine (NE) transporter site (e.g. 4 and 5). Congeners in which the amide nitrogen atom was attached to the aralkyl moiety of the GBR molecule showed moderate affinity (K-i = 51-61 nM) and selectivity for the dopamine transporter (DAT) site. In contrast, introduction of a carbonyl group adjacent to either nitrogen atom of the piperazine ring (e.g. 25 and 27) was not well tolerated. From the compounds prepared, analogue 16 was selected for further evaluation. With this congener, locomotor activity induced by cocaine at a dose of 20 mg/kg was attenuated with an AD(50) (dose attenuating cocaine-induced stimulation by 50%) of 60.0 +/- 3.6 mg/kg. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. FU NIDA NIH HHS [N01DA-7-8071] NR 36 TC 20 Z9 20 U1 2 U2 3 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 SEP 9 PY 1999 VL 42 IS 18 BP 3647 EP 3656 DI 10.1021/jm990161h PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 235HH UT WOS:000082535900022 PM 10479296 ER PT J AU Lee-Fruman, KK Kuo, CJ Lippincott, J Terada, N Blenis, J AF Lee-Fruman, KK Kuo, CJ Lippincott, J Terada, N Blenis, J TI Characterization of S6K2, a novel kinase homologous to S6K1 SO ONCOGENE LA English DT Article DE p70(S6k); S6K1; S6K2; rapamycin; wortmannin; PDK1 ID PROTEIN-SYNTHESIS; RAPAMYCIN; ACTIVATION; PHOSPHORYLATION; TRANSLATION; P70(S6K); CELLS; LOCALIZATION; REQUIREMENT; EXPRESSION AB Rapamycin is an immunosuppressant which antagonizes cellular proliferation by inhibiting the function of mTOR. The mTOR:FKBP12:rapamycin complex blocks G1/S transition by inhibiting downstream targets essential for cell cycle progression. One such target is p70(S6k1) (S6K1), a serine/threonine kinase which is inactivated by the mTOR:FKBP12: rapamycin complex, and which has been linked to translational control by virtue of its ability to phosphorylate the ribosomal protein S6. In the current work, me describe cloning and characterization of a novel S6K1 homolog, p54 S6 kinase 2 (p54(S6k2)/S6K2). Similar to S6K1, S6K2 is activated by mitogens and by constitutively active PI3K, and is inhibited by rapamycin as well as wortmannin. Differences between activation of S6K1 and S6K2 by PDK1 were observed, suggesting potential differences in the regulation of these homologs. Strikingly, S6K2 activity and S6 phosphorylation were both intact in S6K1(-/-)ES cell, indicating a possible role for S6K2 in in vivo S6 phosphorylation. Interestingly, we found two isoforms of S6K2 which are localized to distinct cellular compartments; the smaller form resides in the detergent-soluble fraction, whereas the larger form is found in the particulate fraction. Our findings demonstrate the existence of a family of rapamycin-sensitive protein kinases potentially involved in S6 phosphorylation, translational control, and transduction of mTOR signals. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Jewish Med & Res Ctr, Dept Pediat, Div Basic Sci, Denver, CO 80206 USA. RP Blenis, J (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM51405] NR 33 TC 94 Z9 99 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 9 PY 1999 VL 18 IS 36 BP 5108 EP 5114 DI 10.1038/sj.onc.1202894 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 234RA UT WOS:000082497100010 PM 10490847 ER PT J AU McKeon-O'Malley, C Wells, J Fine, R Ullman, MD Volicer, L AF McKeon-O'Malley, C Wells, J Fine, R Ullman, MD Volicer, L TI PC12 cells transfected with a C-terminal fragment of the amyloid precursor protein (APP C-100), exhibit enhanced sensitivity to the calcium ionophore A23187, and diminished sensitivity to hydrogen peroxide SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; A beta; calcium; hydrogen peroxide; PC12; A23187 ID GROWTH; INJURY; LINE AB Extracellular neuritic plaques are a hallmark of Alzheimer's disease. The core protein of plaques is AP, a 39-43 amino acid peptide derived from the amyloid precursor protein (APP). APP C-100 is a C-terminal fragment of APP, 100 amino acids long, whose sequence includes AP. To determine whether APP C-100 expression alters cellular vulnerability to calcium and H2O2, rat PC12 cells were modified to overexpress APP C-100. Cellular survival (as measured in the MTT assay) was determined as a function of concentration for the calcium ionophore, A23187, and for H2O2 in APP C-100 transfectants and vector-transfected controls. APP C-100 expression significantly increased cellular vulnerabiIity to A23187, and decreased vulnerability to H2O2. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Genet & Aging Unit, Cambridge, MA 02139 USA. Harvard Univ, Genet & Aging Unit, Cambridge, MA 02139 USA. VAMC, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA USA. Boston Univ, Sch Med, Dept Pharmacol, Boston, MA USA. EK Shriver Ctr, Waltham, MA 02254 USA. RP McKeon-O'Malley, C (reprint author), Massachusetts Gen Hosp, Genet & Aging Unit, 149 13th St, Cambridge, MA 02139 USA. NR 12 TC 7 Z9 7 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 SEP 8 PY 1999 VL 72 IS 1 BP 103 EP 107 DI 10.1016/S0169-328X(99)00228-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 239KH UT WOS:000082766900011 ER PT J AU Huang, PL Sun, YT Chen, HC Kung, HF Huang, PL Lee-Huang, S AF Huang, PL Sun, YT Chen, HC Kung, HF Huang, PL Lee-Huang, S TI Proteolytic fragments of anti-HIV and anti-tumor proteins MAP30 and GAP31 are biologically active SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID POKEWEED ANTIVIRAL PROTEIN; RICIN-A-CHAIN; INHIBITION; ANGSTROM; GAP-31; DNA; REPLICATION; INFECTION; TYPE-1; MAP-30 AB We analyzed the structural and functional organization of anti-HIV and anti-tumor proteins MAP30 and GAP31 by limited proteolysis with endopeptidases Lys-C and Glu-C (V8), MAP30 and GAP31 are resistant to proteolytic digestion under conditions of as much as 5% (w/w) proteases. In the presence of 10% (w/w) protease, the central regions of the proteins are still. resistant to proteolysis, whereas the N- and C-termini are accessible. Peptide fragments were purified by FPLC on Superdex 75 columns, characterized by gel electrophoresis, identified by amino acid sequencing, and analyzed for anti-HIV, anti-tumor, and other biochemical activities. We report here that limited proteolysis yields biologically active fragments of both MAP30 and GAP31. These fragments are active against HIV-1 and tumor cells with EC(50)s in the sub-nanomolar ranges, 0.2-0.4 nM. At the dose levels used in the assays, little cytotoxicity to normal cells was observed. In addition, these fragments remain fully active in HIV-integrase inhibition and HIV-LTR topological inactivation, but not ribosome inactivation. These results demonstrate that the antiviral and anti-tumor activities of MAP30 and GAP31 are independent of ribosome inactivation activity. In addition, we demonstrate that portions of the N- and C-termini are not essential for antiviral and anti-tumor activities, but do appear to be required for ribosome inactivation. These results may provide novel strategies for rational design and targeted development of mimetic antiviral and anti-tumor therapeutics, (C) 1999 Academic Press. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Amer Biosci, New York, NY 10021 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. FU NIAID NIH HHS [R01 AI-31343] NR 28 TC 29 Z9 38 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 SEP 7 PY 1999 VL 262 IS 3 BP 615 EP 623 DI 10.1006/bbrc.1999.1213 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 235AH UT WOS:000082516200010 PM 10471373 ER PT J AU Simonova, M Weissleder, R Sergeyev, N Vilissova, N Bogdanov, A AF Simonova, M Weissleder, R Sergeyev, N Vilissova, N Bogdanov, A TI Targeting of green fluorescent protein expression to the cell surface SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID IN-VIVO; GENE-EXPRESSION; MUTANTS; GFP; TIME AB We have previously reported on GPI-anchored fusion proteins that bind radioactive isotopes. We targeted their expression to the cell surface to obtain a marker protein detectable by nuclear and optical imaging (1, 2). Here we suggest a novel approach for targeting a model protein (GFP) to the exoplasmic surface of the plasma membrane. An expression vector (pcPEP-GFP) was constructed containing GFP cDNA fused with the fragment encoding the N-terminal cytoplasmic domain and signal peptide/membrane anchoring domain of the rabbit neutral endopeptidase (PEP-GFP), Flow cytometry showed green fluorescence in 45% of cells transfected with GFP and in 34% of cells transfected with PEP-GFP (24 h after transfection). Fluorescence microscopy of fixed cells stained with rhodaminated anti-GFP antibodies showed positive reaction only in the case of PEP-GFP-transfected cells indicating cell-surface expression. The PEP-GFP fusion protein was identified as a component of the light microsomal and Golgi fractions by immunoblotting. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Rm 5420,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [5RO1 CA74424-01]; NINDS NIH HHS [5RO1 NS35258-03] NR 24 TC 16 Z9 18 U1 0 U2 7 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 SEP 7 PY 1999 VL 262 IS 3 BP 638 EP 642 DI 10.1006/bbrc.1999.1251 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 235AH UT WOS:000082516200014 PM 10471377 ER PT J AU Kickhoefer, VA Siva, AC Kedersha, NL Inman, EM Ruland, C Streuli, M Rome, LH AF Kickhoefer, VA Siva, AC Kedersha, NL Inman, EM Ruland, C Streuli, M Rome, LH TI The 193-kD vault protein, VPARP, is a novel Poly(ADP-ribose) polymerase SO JOURNAL OF CELL BIOLOGY LA English DT Article DE vaults; ribonucleoprotein particle; poly(ADP-ribose) polymerase; poly(ADP-ribose); mitotic spindle ID RIBONUCLEOPROTEIN-PARTICLES; MAMMALIAN TELOMERASE; ESCHERICHIA-COLI; CANCER CELL; DNA-DAMAGE; SMALL RNA; IN-VIVO; IDENTIFICATION; PURIFICATION; PHOSPHATASE AB Mammalian vaults are ribonucleoprotein (RNP) complexes, composed of a small ribonucleic acid and three proteins of 100, 193, and 240 kD in size. The 100-kD major vault protein (MVP) accounts for >70% of the particle mass. We have identified the 193-kD vault protein by its interaction with the MVP in a yeast two-hybrid screen and confirmed its identity by peptide sequence analysis. Analysis of the protein sequence revealed a region of similar to 350 amino acids that shares 28% identity with the catalytic domain of poly(ADP-ribose) polymerase (PARP), PARP is a nuclear protein that catalyzes the formation of ADP-ribose polymers in response to DNA damage, The catalytic domain of p193 was expressed and purified from bacterial extracts. Like PARP, this domain is capable of catalyzing a poly(ADP-ribosyl)ation reaction; thus, the 193-kD protein is a new PARP. Purified vaults also contain the poly(ADP-ribosyl)ation activity, indicating that the assembled particle retains enzymatic activity. Furthermore, we show that one substrate for this vault-associated PARP activity is the MVP. Immunofluorescence and biochemical data reveal that p193 protein is not entirely associated with the vault particle, suggesting that it map interact with other protein(s). A portion of p193 is nuclear and localizes to the mitotic spindle. C1 Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. Brigham & Womens Hosp, Div Rheumatol & Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Kickhoefer, VA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Biol Chem, 33-257 CHS, Los Angeles, CA 90095 USA. RI Rome, Leonard/E-8786-2016; OI Rome, Leonard/0000-0002-1236-2063; Kickhoefer, Valerie/0000-0002-0048-0580 FU NCI NIH HHS [CA55547]; NIGMS NIH HHS [GM38097] NR 53 TC 270 Z9 275 U1 0 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 6 PY 1999 VL 146 IS 5 BP 917 EP 928 DI 10.1083/jcb.146.5.917 PG 12 WC Cell Biology SC Cell Biology GA 234FV UT WOS:000082474600002 PM 10477748 ER PT J AU Sun, L Adebanjo, OA Moonga, BS Corisdeo, S Anandatheerthavarada, HK Biswas, G Arakawa, T Hakeda, Y Koval, A Sodam, B Bevis, PJR Moser, AJ Lai, FA Epstein, S Troen, BR Kumegawa, M Zaidi, M AF Sun, L Adebanjo, OA Moonga, BS Corisdeo, S Anandatheerthavarada, HK Biswas, G Arakawa, T Hakeda, Y Koval, A Sodam, B Bevis, PJR Moser, AJ Lai, FA Epstein, S Troen, BR Kumegawa, M Zaidi, M TI CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Ca2+ channel; ryanodine receptor; bone resorption; cADPr; osteoporosis ID CYCLIC ADP-RIBOSE; TRANSMEMBRANE GLYCOPROTEIN CD38; ISOLATED RABBIT OSTEOCLASTS; EXTRACELLULAR CALCIUM; MATURE OSTEOCLASTS; RECEPTOR; CELLS; RAT; ACTIVATION; CA2+ AB The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca2+ release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts. confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CB38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD(+) surrogate, NGD(+), to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD(+)) triggered a cytosolic Ca2+ signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca2+ change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr. C1 Med Coll Penn & Hahnemann Univ, Dept Med, Ctr Osteoporosis & Skeletal Aging, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Lankanau Med Res Ctr, Merion, PA 19066 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Univ Cardiff, Dept Med, Cardiff, S Glam, Wales. RP Zaidi, M (reprint author), CUNY Mt Sinai Sch Med, Div Endocrinol, Box 1055,1 Gustave Levy Pl, New York, NY 10029 USA. FU NIA NIH HHS [R01-AG14702-01] NR 55 TC 51 Z9 56 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 6 PY 1999 VL 146 IS 5 BP 1161 EP 1171 DI 10.1083/jcb.146.5.1161 PG 11 WC Cell Biology SC Cell Biology GA 234FV UT WOS:000082474600021 PM 10477767 ER PT J AU Burette, A Wyszynski, M Valtschanoff, JG Sheng, M Weinberg, RJ AF Burette, A Wyszynski, M Valtschanoff, JG Sheng, M Weinberg, RJ TI Characterization of glutamate receptor interacting protein-immunopositive neurons in cerebellum and cerebral cortex of the albino rat SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE glutamate; AMPA receptors; GABA; immunogold; calcium-binding proteins; GluR2 ID CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; POSTSYNAPTIC DENSITY; SILENT SYNAPSES; AMPA RECEPTORS; SYNAPTIC DISTRIBUTION; MOLECULAR MECHANISMS; CA2+ PERMEABILITY; GABAERGIC NEURONS; VISUAL-CORTEX AB Glutamate receptor interacting protein (GRIP) binds to the C-terminus of the glutamate receptor 2 (GluR2) subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in vitro and may play an important role in the synaptic organization of these receptors. To determine the distribution of GRIP in vivo, GRIP was localized immunocytochemically in cerebellum and cerebral cortex of adult Sprague-Dawley rats. In the cerebellar cortex, GRIP staining was prominent in perikarya and proximal dendrites of Purkinje cells, whereas Golgi cells were stained more weakly. Double labeling revealed that GRIP and GluR2 were colocalized in Purkinje cells but not in Golgi cells. In the cerebral cortex, GRIP-stained dendrites and somata of nonpyramidal neurons were scattered throughout cortical layers, whereas pyramidal cells were only weakly immunopositive. GRIP was especially prominent in a subset of GluR2-containing cells that also expressed a high level of GluR1. The large majority of strongly GRIP-positive cells in neocortex were immunopositive for gamma-aminobutyric acid (GABA), including the overwhelming majority of calbindin-positive cells in superficial cortical layers, most of the parvalbumin-positive cells, and half of the calretinin-positive interneurons. Staining in the neuropil became more punctate after antigen was unmasked with proteinase K. Electron microscopic localization in the cerebral cortex by postembedding immunogold showed that somatic GRIP was associated with rough endoplasmic reticulum and Golgi apparatus. GRIP was seen over the postsynaptic density of axospinous and axodendritic asymmetric synapses and at high levels in dendrites of GABA-positive neurons. The present data support a role for GRIP in anchoring AMPA receptors and suggest that GRIP trafficking may be especially active in GABAergic neurons. (C) 1999 Wiley-Liss, Inc. C1 Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Weinberg, RJ (reprint author), Univ N Carolina, Dept Cell Biol & Anat, CB 7090, Chapel Hill, NC 27599 USA. FU PHS HHS [R01-35050, R01-35527] NR 65 TC 35 Z9 37 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 SEP 6 PY 1999 VL 411 IS 4 BP 601 EP 612 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 221PF UT WOS:000081734900006 PM 10421871 ER PT J AU Dijkhuizen, RM Beekwilder, JP van der Worp, HB van der Sprenkel, JWB Tulleken, KAF Nicolay, K AF Dijkhuizen, RM Beekwilder, JP van der Worp, HB van der Sprenkel, JWB Tulleken, KAF Nicolay, K TI Correlation between tissue depolarizations and damage in focal ischemic rat brain SO BRAIN RESEARCH LA English DT Article DE focal cerebral ischemia; reperfusion; cortical spreading depression; ischemic depolarization; magnetic resonance imaging; rat brain ID MIDDLE CEREBRAL-ARTERY; CORTICAL SPREADING DEPRESSION; DIFFUSION-WEIGHTED MRI; OCCLUSION; ANTAGONIST; POTASSIUM; PENUMBRA; LESION; MK-801; VOLUME AB Ischemia-induced depolarizations may play a key role in the development of cerebral ischemic injury. Our goal was to assess the relationship between tissue depolarizations and tissue damage in focal ischemia. We performed multi-electrode cortical direct current (DC) potential recording and, subsequently, diffusion-weighted and T-2-weighted magnetic resonance imaging (MRI) in rats after i) cortical application of KCI, and ii) permanent and transient middle cerebral artery (MCA)-occlusion in rats. Cortical KCI application induced 10.0 +/- 2.2 transient negative DC potential shifts per h on the ipsilateral hemisphere (i.e. cortical spreading depressions) (n = 4). During 6 h of permanent MCA-occlusion (n = 9) 1-10 DC potential shifts were observed, dependent on the brain location. Anoxic depolarization developed in the ischemic core. Outside ischemic areas DC potential shifts resembled cortical spreading depressions. Depolarizations in cortical ischemic borderzones were also transient, but generally long-lasting. Reperfusion induced 1 (n = 5) or 3 h (n = 6) after MCA-occlusion resulted in repolarization in 2.9 +/- 1 5 min. Ischemic lesion volumes after 7 h, calculated from diffusion-weighted and T-2-weighted MR images, correlated significantly with total depolarization time in cortical perifocal zones (R = 0.741, p < 0.05), but not with the number of depolarizations. The extent of ischemic damage, as measured from alterations in the water diffusion coefficient and T-2, was also significantly related to the total time of depolarization (R = 0.762 and 0.738, respectively, p < 0.01). We conclude that early ischemic tissue injury is related to the total duration of tissue depolarization and not to the frequency of depolarizations. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Utrecht Hosp, Dept Neurosurg, Utrecht, Netherlands. Univ Utrecht, Image Sci Inst, Dept Expt Vivo NMR, Utrecht, Netherlands. Univ Utrecht Hosp, Dept Neurol, Utrecht, Netherlands. RP Dijkhuizen, RM (reprint author), Massachusetts Gen Hosp, NMR Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. RI Dijkhuizen, Richard/A-6506-2008; Nicolay, Klaas/F-4192-2010 NR 40 TC 85 Z9 85 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 4 PY 1999 VL 840 IS 1-2 BP 194 EP 205 DI 10.1016/S0006-8993(99)01769-2 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 234GY UT WOS:000082477300025 PM 10517971 ER PT J AU Jaster, R Baek, KH D'Andrea, AD AF Jaster, R Baek, KH D'Andrea, AD TI Analysis of cis-acting sequences and trans-acting factors regulating the interleukin-3 response element of the DUB-1 gene SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE DUB-1; interleukin-3; signal transduction; AP-1; Ets; GATA ID TRANSCRIPTION FACTORS; GROWTH-FACTORS; PROTEIN-DEGRADATION; SIGNAL-TRANSDUCTION; MAMMALIAN-CELLS; AP-1 COMPLEX; BETA-SUBUNIT; RECEPTOR; DNA; JUN AB The murine DUE-I gene is a hematopoietic-specific, immediate-early gene that encodes a growth-regulatory deubiquitinating enzyme. DUE-I contains an IL-3-inducible enhancer element that is activated in a JAK2-dependent, STAT5-independent manner. In this study, we have further characterized this novel IL-3 response element. Transcriptional reporter assays in Ba/F3 cells revealed that two AP-1 sites, a GATA motif, and an Ets site are required for induction of DUB-1 enhancer activity. Cel shift assays indicated that IL-3 activates the binding of an AP-I complex containing JunD to the API sites and the binding of another protein complex to the Ets motif. The latter complex was not detectable in Ba/F3 cells stably transfected with a dominant-negative mutant of JAK2. As previously shows, these cells do not express DUB-1 mRNA or protein. Furthermore, we demonstrated that GATA;I constitutively binds to the DUE-I enhancer element. The involvement of GATA-1 may be important for the hematopoietic-restricted expression pattern of DUB-1. This combination of inducible and constitutive elements of the DUE-I enhancer appears to account for the unique STAT-independent expression characteristics of DUB-1. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. OI Baek, Kwang-Hyun/0000-0001-7662-7190 FU NIDDK NIH HHS [R01 DK 43889-01] NR 39 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD SEP 3 PY 1999 VL 1446 IS 3 BP 308 EP 316 DI 10.1016/S0167-4781(99)00095-0 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 234GP UT WOS:000082476400014 PM 10524205 ER PT J AU Lee, SB Huang, K Palmer, R Truong, VB Herzlinger, D Kolquist, KA Wong, J Paulding, C Yoon, SK Gerald, W Oliner, JD Haber, DA AF Lee, SB Huang, K Palmer, R Truong, VB Herzlinger, D Kolquist, KA Wong, J Paulding, C Yoon, SK Gerald, W Oliner, JD Haber, DA TI The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin SO CELL LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MICE LACKING GDNF; GENE-PRODUCT; KIDNEY DEVELOPMENT; DNA-BINDING; EXPRESSION; PROTEIN; PROLIFERATION; RECEPTOR; SEQUENCE AB WT1 encodes a zinc finger transcription factor implicated in kidney differentiation and tumorigenesis. In reporter assays, WT1 represses transcription from GC- and To-rich promoters, but its physiological targets remain uncertain. We used hybridization to high-density oligonucleotide arrays to search for native genes whose expression is altered following inducible expression of WT1. The major target of WT1 was amphiregulin, a member of the epidermal growth factor family. The WT1(-KTS) isoform binds directly to the amphiregulin promoter, resulting in potent transcriptional activation. The in vivo expression profile of amphiregulin during fetal kidney development mirrors the highly specific pattern of WT1 itself, and recombinant Amphiregulin stimulates epithelial branching in organ cultures of embryonic mouse kidney. These observations suggest a model for WT1 as a transcriptional regulator during kidney differentiation. C1 Massachusetts Gen Hosp, Ctr Canc, Genet Mol Lab, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Affymetrix, Santa Clara, CA 95051 USA. Cornell Univ, Dept Physiol & Biophys, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Genet Mol Lab, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA71167, CA58596] NR 42 TC 222 Z9 226 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 SEP 3 PY 1999 VL 98 IS 5 BP 663 EP 673 DI 10.1016/S0092-8674(00)80053-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 233NT UT WOS:000082433500013 PM 10490105 ER PT J AU Christmas, P Fox, JW Ursino, SR Soberman, RJ AF Christmas, P Fox, JW Ursino, SR Soberman, RJ TI Differential localization of 5-and 15-lipoxygenases to the nuclear envelope in RAW macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARACHIDONIC-ACID 15-LIPOXYGENASE; BASOPHILIC LEUKEMIA-CELLS; ACTIVATED PROTEIN-KINASE; MOLECULAR-CLONING; 5-LIPOXYGENASE-ACTIVATING PROTEIN; ALVEOLAR MACROPHAGES; HUMAN-LEUKOCYTES; TRANSLOCATION; EXPRESSION; SYNTHASE AB Leukotriene formation is initiated in myeloid cells by an increase in intracellular calcium and translocation of B-lipoxygenase from the cytoplasm to the nuclear envelope where it can utilize arachidonic acid. Monocyte-macrophages and eosinophils also express 15-lipoxygenase, which converts arachidonic acid to 15(S)-hydroxyeicosatetraenoic acid. Enhanced green fluorescent B-lipoxygenase (5-LO) and 15-lipoxygenase (15-LO) fusion proteins were expressed in the cytoplasm of RAW 264.7 macrophages, Only B-lipoxygenase translocated 60 the nuclear envelope after cell stimulation, suggesting that differential subcellular compartmentalization can regulate the generation of leukotrienes versus 15(S)-hydroxyeicosatetraenoic acid in cells that possess both lipoxygenases, A series of truncation mutants of 5-LO were created to identify putative targeting domains; none of these mutants localized to the nuclear envelope. The lack of targeting of 15-LO was then exploited to search for specific targeting motifs in 5-LO, by creating 5-LO/15-LO chimeric molecules. The only chimera that could sustain nuclear envelope translocation was one which involved replacement of the N-terminal 237 amino acids with the corresponding segment of 15-LO, Significantly, no discrete targeting domain could be identified in 5-LO, suggesting that sequences throughout the molecule are required for nuclear envelope localization. C1 Massachusetts Gen Hosp, Arthrit Unit, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Soberman, RJ (reprint author), Massachusetts Gen Hosp, Arthrit Unit, Dept Med, E 149 Navy Yard,13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [P30DK43351, P01DK-38452]; NIEHS NIH HHS [R01ES-50859] NR 46 TC 16 Z9 16 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 SEP 3 PY 1999 VL 274 IS 36 BP 25594 EP 25598 DI 10.1074/jbc.274.36.25594 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 235QN UT WOS:000082554200058 PM 10464294 ER PT J AU Mora, R Bonilha, VL Marmorstein, A Scherer, PE Brown, D Lisanti, MP Rodriguez-Boulan, E AF Mora, R Bonilha, VL Marmorstein, A Scherer, PE Brown, D Lisanti, MP Rodriguez-Boulan, E TI Caveolin-2 localizes to the Golgi complex but redistributes to plasma membrane, caveolae, and rafts when co-expressed with caveolin-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL-CELLS; ANCHORED PROTEINS; MDCK CELLS; IN-VIVO; TRANSPORT; VESICLES; VIP21-CAVEOLIN; VIP21/CAVEOLIN; CHOLESTEROL; COMPONENT AB We have characterized comparatively the subcellular distributions of caveolins-1 and -2, their interactions and their roles in caveolar formation in polarized epithelial cells. In Fischer rat thyroid (FRT) cells, which express low levels of caveolin-2 and no caveolin-1, caveolin-2 localizes exclusively to the Golgi complex but is partially redistributed to the plasma membrane upon co-expression of caveolin-1 by transfection or by adenovirus-mediated transduction. In Madin-Darby canine kidney (MDCK) cells, which constitutively express both caveolin-1 and -2, caveolin-2 localized to both the Gels complex and to the plasma membrane, where it co-distributed with caveolin-1 in flat patches and in caveolae. In FRT cells, endogenous or overexpressed caveolin-2 did not associate with low density Triton insoluble membranes that floated in sucrose density gradients but was recruited to these membranes when co-expressed together with caveolin-1. In MDCK cells, both caveolin-1 and caveolin-2 associated with low density Triton-insoluble membranes. In FRT cells, transfection of caveolin-1 promoted the assembly of plasma membrane caveolae that localized preferentially (over 99%) to the basolateral surface, like constitutive caveolae of MDCK cells. In contrast, as expected from its intracellular distribution, endogenous or overexpressed caveolin-2 did not promote the assembly of caveolae; rather, it appeared to promote the assembly of intracellular vesicles in the peri-Golgi area. The data reported here demonstrate that caveolin-1 and -2 have different and complementary subcellular localizations and functional properties in polarized epithelial cells and suggest that the two proteins co-operate to carry out specific as yet unknown tasks between the Golgi complex and the cell surface. C1 Cornell Univ, Weill Med Coll, Dyson Vis Res Inst, Dept Ophthalmol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Cell Biol, New York, NY 10021 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. RP Rodriguez-Boulan, E (reprint author), Cornell Univ, Weill Med Coll, Dyson Vis Res Inst, Dept Ophthalmol, LC300,1300 York Ave, New York, NY 10021 USA. RI Lisanti, Michael/C-6866-2013 FU NIGMS NIH HHS [GM34107, R01 GM034107, R01 GM41771] NR 31 TC 155 Z9 157 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 SEP 3 PY 1999 VL 274 IS 36 BP 25708 EP 25717 DI 10.1074/jbc.274.36.25708 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 235QN UT WOS:000082554200072 PM 10464308 ER PT J AU Polidori, MC Mecocci, P Browne, SE Senin, U Beal, MF AF Polidori, MC Mecocci, P Browne, SE Senin, U Beal, MF TI Oxidative damage to mitochondrial DNA in Huntington's disease parietal cortex SO NEUROSCIENCE LETTERS LA English DT Article DE Huntington's disease; mitochondria; DNA; oxidative stress; Free radicals; 8-Hydroxy-2-deoxyguanosine ID ALZHEIMERS-DISEASE; BRAIN; 8-HYDROXY-2'-DEOXYGUANOSINE; STRIATUM; ENERGY AB Oxidative damage to DNA may play a role in both normal aging and in neurodegenerative diseases. Using a sensitive high-performance liquid chromatography (HPLC) assay, we examined concentrations of 8-hydroxy-2-deoxyguanosine (OH(8)dG) in mitochondrial DNA (mtDNA) isolated from frontal and parietal cerebral cortex and from cerebellum in 22 Huntington's disease (HD) patients and 15 age-matched normal controls. A significant increase in OH(8)dG in mtDNA of parietal cortex was found in HD patients as compared with controls, while there were no significant changes in frontal cortex or cerebellum. The present findings are consistent with regionally specific oxidative damage in HD, which may be a further evidence of a metabolic defect. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Perugia Univ Hosp, Inst Gerontol & Geriatr, Perugia, Italy. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Polidori, MC (reprint author), Univ Dusseldorf, Inst Physiol Chem, Univ Str 1, D-40225 Dusseldorf, Germany. NR 21 TC 114 Z9 116 U1 1 U2 4 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 SEP 3 PY 1999 VL 272 IS 1 BP 53 EP 56 DI 10.1016/S0304-3940(99)00578-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 238CN UT WOS:000082693500014 PM 10507541 ER PT J AU Schacter, DL Wagner, AD AF Schacter, DL Wagner, AD TI Perspectives: Neuroscience - Remembrance of things past SO SCIENCE LA English DT Editorial Material ID SEMANTIC MEMORY; BRAIN ACTIVITY C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441, AG05778]; NIMH NIH HHS [MH57915] NR 19 TC 21 Z9 21 U1 0 U2 4 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 SEP 3 PY 1999 VL 285 IS 5433 BP 1503 EP 1504 DI 10.1126/science.285.5433.1503 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 232FD UT WOS:000082359500038 PM 10498535 ER PT J AU da Costa, LT He, TC Yu, J Sparks, AB Morin, PJ Polyak, K Laken, S Vogelstein, B Kinzler, KW AF da Costa, LT He, TC Yu, J Sparks, AB Morin, PJ Polyak, K Laken, S Vogelstein, B Kinzler, KW TI CDX2 is mutated in a colorectal cancer with normal APC/beta-catenin signaling SO ONCOGENE LA English DT Article DE CDX2; APC; colorectal cancer; mutation; regulation ID TUMOR-SUPPRESSOR PROTEIN; APC GENE-PRODUCT; BETA-CATENIN; COLON-CARCINOMA; TUMORIGENESIS; ASSOCIATION; EXPRESSION; ACTIVATION; POLYPOSIS; MUTATIONS AB The majority of human colorectal cancers have elevated beta-catenin/TCF regulated transcription due to either inactivating mutations of the APC tumor suppressor gene or activating mutations of beta-catenin, Surprisingly, one commonly used colorectal cancer cell line was found to have intact APC and beta-catenin and no demonstrable beta-catenin/TCF regulated transcription. However, this line did possess a truncating mutation in one allele of CDX2, a gene whose inactivation has recently been shown to cause colon tumorigenesis in mice. Expression of CDX2 was found to be induced by restoring expression of wild type APC in a colorectal cancer cell line. These findings raise the intriguing possibility that CDX2 contributes to APC's tumor suppressive effects. C1 Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. Johns Hopkins Univ, Program Human Genet & Mol Biol, Baltimore, MD 21231 USA. NIA, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Howard Hughes Med Inst, Baltimore, MD 20815 USA. RP Kinzler, KW (reprint author), Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. FU NCI NIH HHS [CA57345]; NIGMS NIH HHS [GM07814] NR 27 TC 101 Z9 102 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 2 PY 1999 VL 18 IS 35 BP 5010 EP 5014 DI 10.1038/sj.onc.1202872 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 231QQ UT WOS:000082321700015 PM 10490837 ER PT J AU Magnusson, AR Hedges, JR Harper, RJ Greaves, P AF Magnusson, AR Hedges, JR Harper, RJ Greaves, P TI First-postgraduate-year resident clinical time use on three specialty rotations SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE graduate medical education; resident; training; clinical practice; time study; emergency medicine; internal medicine; surgery ID INTERNAL-MEDICINE; SPEND; WORK; CALL AB Objective: To compare in-hospital time uses by first-postgraduate-year (PGY1) residents during rotations in emergency medicine (EM), internal medicine (IM), and surgery (S). This article reports the clinical components of residency time use. Methods: A cross-sectional, observational study of the clinical activities of EM PGY1 residents was performed while the residents were on duty during the three specialty rotations. The activities were recorded by an observer using a log with predetermined categories for clinical activities. A time-blocked, convenience sample of resident shifts was observed for each service rotation. The sample was proportional to the total number of hours for which a PGY1 resident was expected to be in the hospital during a rotation on that service. No attempt was made to sample the same resident at all time periods or on all rotations. Proportions were compared by chi(2); alpha = 0.0001. Results: Twelve PGY1 residents were observed for a total of 166 hours on S, 156 hours on IM, and 120 hours on EM. These hourly amounts were representative of a typical two-week. span of service on each rotation for the residents. On average, the residents spent 57% of their time on clinical or service-oriented activities. During EM and IM rotations, the residents spent most of their time performing clinical information gathering and engaging in case management and data synthesis (52% of total clinical effort). Within this category, residents on EM were more involved with case discussion and review of ancillary test results than on IM (34% vs 20% of time in this category). Conversely, proportionately less time in this category was devoted to documentation on the EM vs IM rotation (56% vs 80%; p < 0.0001). The greatest opportunity to perform procedures was on the S rotation (31% of total clinical time vs 6% for other specialties; p < 0.0001). Conclusion: Awareness of the clinical activities performed on PGY1 rotations can help residency directors anticipate educational needs to balance their residents' experience. Since 29% and 42% of total clinical time on PGY1 EM and IM rotations, respectively, is focused on documentation, efforts to enhance charting skills and efficiency are warranted. Also, efforts to enhance PGY1 procedural experience outside of the S rotation appear warranted. C1 Oregon Hlth Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Emergency Care Unit, Portland, OR USA. Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA. RP Hedges, JR (reprint author), Oregon Hlth Sci Univ, Dept Emergency Med, 3181 SW Sam Jackson Pk Rd,MP-52, Portland, OR 97201 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 1999 VL 6 IS 9 BP 939 EP 946 DI 10.1111/j.1553-2712.1999.tb01245.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 233VD UT WOS:000082447200015 PM 10490258 ER PT J AU Blumenthal, D Weissman, JS Griner, PF AF Blumenthal, D Weissman, JS Griner, PF TI Academic health centers on the front lines: Survival strategies in highly competitive markets SO ACADEMIC MEDICINE LA English DT Article AB The authors describe approaches that live academic health centers (AHCs) have taken to reduce costs, enhance quality, or improve their market positions since the onset of price competition and managed care. The five AHCs, all on the West Coast, were selected for study because they (1) are located in markets that had been highly competitive for the longest time; (2) are committed to all the major missions of AHCs; and (3) own or substantially control their major clinical teaching facilities. The study findings reflect the status of the five AHCs during the fall of 1998. Although some findings may no longer be current (especially in light of ongoing implementation of the Balanced Budget Act of 1997), they still provide insights into the options and opportunities available to many AHCs in highly competitive markets. The authors report on the institutions' financial viability (positive), levels of government support (advantageous), and competition from other AHCs (modest), They outline the study AHCs' survival strategies in three broad areas: increasing revenues via exploiting market niches, reducing costs, and reorganizing to improve internal governance and decision making, They also report how marketplace competition and the strategies the AHCs used to confront it have affected the AHCs' missions. The authors summarize the outstanding lessons that all AHCs can learn from the experiences of the AHCs studied, although adding that AHCs in other parts of the country should use caution in looking to the West Coast AHCs for answers. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Partners HealthCare Syst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Assoc Amer Med Coll, Ctr Assessment Change Acad Med, Washington, DC USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Partners HealthCare Syst, 50 Staniford St, Boston, MA 02114 USA. NR 12 TC 14 Z9 14 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1999 VL 74 IS 9 BP 1038 EP 1049 DI 10.1097/00001888-199909000-00021 PG 12 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 236NR UT WOS:000082605900027 PM 10498101 ER PT J AU Mischoulon, D AF Mischoulon, D TI An approach to the patient seeking psychiatric disability benefits SO ACADEMIC PSYCHIATRY LA English DT Article ID STRESS-DISORDER; SUBSTANCE-ABUSE; MENTAL-ILLNESS; VETERANS; COMPENSATION; PAYMENTS; WORK; DEPENDENCE; DIAGNOSES; COCAINE AB Psychiatric disability determination is a complicated task for the psychiatrist. With filings for disability benefits increasing, the task is becoming unavoidable. The increasing social cost of disability requires that psychiatrists learn how to respond appropriately to petitions for psychiatric disability benefits. However, there is a significant dearth of education on psychiatric disability assessment. The various disability programs are reviewed; criteria of disability determination and difficulties involved in making an assessment are examined. Characteristics of disability petitioners are reviewed, and practical suggestions are provided for psychiatrists on how to approach a psychiatric disability evaluation. Finally, recommendations for the inclusion of psychiatric disability assessment training in residency programs are outlined. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 35 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FAL PY 1999 VL 23 IS 3 BP 128 EP 136 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 230ND UT WOS:000082256500003 ER PT J AU Bostic, JQ Knezek, BK Smith, H Triana, L Young, C AF Bostic, JQ Knezek, BK Smith, H Triana, L Young, C TI Gone with the wind - Surviving the closing of a psychiatry residency SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Green Oaks Hosp, Dallas, TX USA. Timberlawn Psychiat Hosp, Med Staff, Dallas, TX USA. RP Bostic, JQ (reprint author), Harvard Univ, Sch Med, 15 Parkman St,WAC 725, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FAL PY 1999 VL 23 IS 3 BP 157 EP 159 PG 3 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 230ND UT WOS:000082256500007 ER PT J AU Tambouret, RH Yantiss, RK Kirby, R Eichhorn, JH AF Tambouret, RH Yantiss, RK Kirby, R Eichhorn, JH TI Mucinous adenocarcinoma of the parotid gland - Report of a case with fine needle aspiration findings and histologic correlation SO ACTA CYTOLOGICA LA English DT Article DE adenocarcinoma, mucinous; parotid neoplasms; aspiration biopsy ID SALIVARY DUCT CARCINOMA; LESIONS; DIAGNOSIS; CYTOLOGY AB BACKGROUND: Mucinous adenocarcinoma rarely arises as a primary tumor within the parotid gland, and only the histologic features of this tumor have been described. CASE: A 4-cm, firm mass arose in the right parotid gland of a 72-year-old male over a six-week period. Cystic on computed tomography, the mass, on fine needle aspiration biopsy, yielded monomorphic , moderately atypical cells, both single and clustered, associated with abundant mucoid material and focal necrosis. Tumor cells had eccentric nuclei, prominent nucleoli and occasional cytoplasmic vacuolization. A few binucleated and multinucleated ed tumor cells were present. Histologic sections of the resected gland showed mucinous adenocarcinoma. A metastatic workup was negative. The differential diagnoses on cytology included other primary tumors of the parotid gland producing mucin or a mucoid matrix and metastatic mucinous adenocarcinomas. CONCLUSION: To our knowledge, this is first cytologic description of mucinous adenocarcinoma, primary in the parotid gland. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tambouret, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. NR 15 TC 6 Z9 9 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD SEP-OCT PY 1999 VL 43 IS 5 BP 842 EP 846 PG 5 WC Pathology SC Pathology GA 237DU UT WOS:000082640700017 PM 10518140 ER PT J AU Gollub, RL Hui, KKS Stefano, GB AF Gollub, RL Hui, KKS Stefano, GB TI Acupuncture: pain management coupled to immune stimulation SO ACTA PHARMACOLOGICA SINICA LA English DT Review DE acupuncture; peptide antibiotics; magnetic resonance imaging; methionine enkephalin ID NITRIC-OXIDE RELEASE; CARDIOPULMONARY BYPASS; BETA-ENDORPHIN; INVERTEBRATE IMMUNOCYTES; OPIOID RECEPTOR; OPIATE RECEPTOR; ENKEPHALIN; MORPHINE; CELLS; PLASMA AB The phenomenon of acupuncture is both complex and dynamic. Recent information demonstrates that acupuncture may exert its actions on pain and immune processes. The coupling of these two systems occurs via common signaling molecules, ie, opioid peptides. In this regard, we surmise that opioid activation leads to the processing of opioid peptides from their precursor, proenkephalin, and the simultaneous release of antibacterial peptides contained within the precursor as well. Thus, central nervous system pain circuits may be coupled to immune enhancement. Furthermore, acupuncture needle manipulation elicited signal increases bilaterally in the region of the primary and secondary somatosensory corticies in human brain as determined by magnetic resonance imaging. The maps reveal marked signal decreases bilaterally in multiple limbic and deep gray structures including the nucleus accumbens, amygdala, hypothalamus, hippocampus, and ventral tegmental area. Taken together, we surmise a major central nervous system pathway as well as local pain and immune modulation during acupuncture. C1 SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Stefano, GB (reprint author), SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. OI Gollub, Randy L./0000-0002-9434-4044 NR 74 TC 10 Z9 10 U1 0 U2 1 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN ROAD, SHANGHAI 200031, PEOPLES R CHINA SN 0253-9756 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD SEP PY 1999 VL 20 IS 9 BP 769 EP 777 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 236MG UT WOS:000082602900001 ER PT J AU Bondestam, S Halavaara, JT Jaaskelainen, JE Kinnunen, JJ Hamberg, LM AF Bondestam, S Halavaara, JT Jaaskelainen, JE Kinnunen, JJ Hamberg, LM TI Perfusion CT of the brain in the assessment of flow alterations during brachytherapy of meningioma SO ACTA RADIOLOGICA LA English DT Article DE brain, regional blood flow; CT, meningioma; brachytherapy ID SKULL BASE AB Purpose: The aim was to investigate the use of perfusion CT of the brain in the assessment of flow alterations during brachytherapy of meningiomas. Material and Methods: Six patients with an intracranial meningioma were investigated during brachytherapy treatment by stereotactic implantation of I-125 seeds. Cerebral blood flow (CBF) in the tumour centre and the tumour periphery as well as in the normal brain parenchyma was determined by perfusion CT. Follow-up examinations were performed during the first year after the implantation. The CBF of the normal brain parenchyma was used as control. Results. In the beginning of therapy, the mean +/- SEM blood flow in the tumour centre was 231.41 +/- 58.1 ml/100 g/min and in the periphery 223.5 +/- 53.8 ml/100 g/min, Within three months after the iodine seed implantation, the tumour blood flow had decreased 41%. At the one-year follow-up, the tumour blood flow in the centre had decreased to 68.7 +/- 45.9 ml/100 g/min. In the periphery of the tumour, it remained nearly unchanged (199.3 +/- 101.0 ml/100 g/min). The CBF values obtained from normal brain parenchyma did not decrease during the treatment. Throughout the study, the mean CBF for the normal grey matter was 38.5 +/- 2.9 ml/100 g/min, and 22.3 +/- 1.2 ml/100 g/min for the normal white matter. Conclusion. Perfusion CT seems to enable accurate monitoring of the blood flow of meningiomas during brachytherapy, and could be used in clinical situations where blood flow changes in brain and tumours should be investigated. C1 Univ Helsinki, Cent Hosp, Dept Diagnost Radiol, Clin Oncol, FIN-00029 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Neurosurg, FIN-00029 Helsinki, Finland. Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Dept Radiol, Boston, MA USA. RP Bondestam, S (reprint author), Univ Helsinki, Cent Hosp, Dept Diagnost Radiol, Clin Oncol, PB 382, FIN-00029 Helsinki, Finland. NR 7 TC 11 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD SEP PY 1999 VL 40 IS 5 BP 469 EP 473 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 230LU UT WOS:000082253300001 PM 10485233 ER PT J AU Harris, NL Muller-Hermelink, HK AF Harris, NL Muller-Hermelink, HK TI Thymoma classification - A siren's song of simplicity SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID DIFFERENTIATED THYMIC CARCINOMA; HISTOGENETIC CLASSIFICATION; EPITHELIAL TUMORS; SYSTEM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. RP Harris, NL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. NR 24 TC 32 Z9 40 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 1999 VL 112 IS 3 BP 299 EP 303 PG 5 WC Pathology SC Pathology GA 230KP UT WOS:000082250600001 PM 10478132 ER PT J AU Vargas, SO Jiroutek, M D'Amico, AV Renshaw, AA AF Vargas, SO Jiroutek, M D'Amico, AV Renshaw, AA TI Distribution of carcinoma in radical prostatectomy specimens in the era of serum prostate-specific antigen testing - Implications for delivery of localized therapy SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE cancer volume; extraprostatic extension; mapping; prostate cancer; prostate-specific antigen ID PATHOLOGICAL STAGE; CANCER VOLUME; ADENOCARCINOMA; LOCATION AB Prior studies documenting the distribution of cancer in radical prostatectomy specimens were based on specimens resected before the advent of prostate-specific antigen (PSA) testing and were not specifically aimed at defining the incidence of cancer in precise regions of the gland. If localized therapy, such as brachytherapy or conformal radiation, could be minimized in areas of low, cancer incidence, such as the anterior prostate, morbidity including injury to adjacent normal tissue might also be minimized, We examined 82 recent prostatectomy specimens and noted all areas of cancer in each gland. Distribution of involvement was evaluated with respect to preoperative serum PSA level, clinical stage, and pathologic features. Prostate cancer was present posteriorly in 78 of 82 cases and anteriorly in 53 of 82 cases. The presence of anterior cancer was strongly associated with elevated PSA level (P =.003), total cancer volume (P =.0002), and extraprostatic extension (P =.006), bur runs not associated with age, Gleason grade, or clinical stage. We conclude that the incidence of anterior prostate cancer is high. its presence is strongly correlated with other variables, and thus strategies for selecting patients for limited localized therapy based on preoperative PSA and tumor volume estimates may be warranted. C1 Harvard Univ, Sch Med, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Vargas, SO (reprint author), Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. NR 19 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 1999 VL 112 IS 3 BP 373 EP 376 PG 4 WC Pathology SC Pathology GA 230KP UT WOS:000082250600012 PM 10478143 ER PT J AU Slaugenhaupt, SA Acierno, JS Helbling, LA Bove, C Goldin, E Bach, G Schiffmann, R Gusella, JF AF Slaugenhaupt, SA Acierno, JS Helbling, LA Bove, C Goldin, E Bach, G Schiffmann, R Gusella, JF TI Mapping of the mucolipidosis type IV gene to chromosome 19p and definition of founder haplotypes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MULTILOCUS LINKAGE ANALYSIS; ABNORMAL TRANSPORT; COMPUTATIONS AB Mucolipidosis type TV (MLIV) is a lysosomal storage disorder characterized by severe neurologic and ophthalmologic abnormalities. It is a rare autosomal recessive disease, and the majority of patients diagnosed, to date, are of Ashkenazi Jewish descent. We have mapped the MLIV gene to chromosome 19p13.2-13.3 by linkage analysis with 15 markers in 13 families. A maximum LOD score of 5.51 with no recombinants was observed with marker D19S873. Several markers in the linked interval also displayed significant linkage disequilibrium with the disorder. We constructed haplotypes in 26 Ashkenazi Jewish families and demonstrate the existence of two founder chromosomes in this population. The localization of MLIV to chromosome 13 will permit genetic prenatal diagnosis in affected families and will aid in the isolation of the disease gene. C1 Harvard Univ, Harvard Inst Human Genet, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. NINDS, Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel. RP Slaugenhaupt, SA (reprint author), Harvard Univ, Harvard Inst Human Genet, Sch Med, HIM Bldg,Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NINDS NIH HHS [NS36326] NR 16 TC 57 Z9 59 U1 0 U2 0 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 SEP PY 1999 VL 65 IS 3 BP 773 EP 778 DI 10.1086/302549 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 233KQ UT WOS:000082426400023 PM 10441585 ER PT J AU Borrego, MJ Martin-Malo, A Almaden, Y Rodriguez, M Aljama, P Felsenfeld, AJ AF Borrego, MJ Martin-Malo, A Almaden, Y Rodriguez, M Aljama, P Felsenfeld, AJ TI Effect of calcitriol and age on recovery from hypocalcemia in hemodialysis patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE age; calcitriol; hemodialysis; hypocalcemia; hysteresis; parathyroid hormone (PTH) ID CHRONIC-RENAL-FAILURE; PARATHYROID-HORMONE SECRETION; BONE-DISEASE; SECONDARY HYPERPARATHYROIDISM; INTRAVENOUS CALCITRIOL; IONIZED CALCIUM; ADYNAMIC BONE; NORMAL HUMANS; SET-POINT; HYSTERESIS AB Calcitriol is used to treat hyperparathyroidism in hemodialysis patients. Calcitriol treatment, either through a reduction in parathyroid hormone (PTH) levels or direct effect on bone, decreases the osteoblast and osteoclast surface and bone formation rate. Our study of 13 hemodialysis patients was designed to evaluate whether calcitriol treatment changed the rate of spontaneous recovery from hypocalcemia induced by a low-calcium dialysis. Calcitriol treatment decreased basal PM levels from 614 +/- 84 to 327 +/- 102 pg/mL (P < 0.001) and maximal PTH levels from 1,282 +/- 157 to 789 +/- 161 pg/mL (P < 0.001), but the rate of serum ionized calcium recovery from hypocalcemia did not change. When the 13 patients were separated based on the median age of 64 years, the predialysis serum ionized calcium revel was less in the younger (group I, 44 +/- 6 years; n = 6) than older (group II, 68 +/- 1 years; n = 7) patients (1.05 +/- 0.03 v 1.22 +/- 0.03 mmol/L, respectively; P < 0.01) despite similar basal (group I, 595 +/- 122 pg/mL v group II, 629 +/- 96 pg/mL) and maximal (group I, 1,114 +/- 299 pg/mL v group II, 1,425 +/- 141 pg/mL) PTH levels. Before calcitriol treatment, the rate of serum ionized calcium recovery from induced hypocalcemia was greater (P < 0.05) for similar PM levels in the older than younger patients. After calcitriol treatment, despite a similar reduction in PTH levels, the rate of calcium recovery increased (P < 0.05) in the younger patients but did not change in the older patients. We also observed that toward the end of the low-calcium hemodialysis, PTH values decreased even though serum ionized calcium level continued to decline when the rate of calcium reduction slowed. In addition, hysteresis, defined as a lower PTH value during the recovery from hypocalcemia than during the induction of hypocalcemia for the same serum calcium concentration, was present during the spontaneous recovery from hypocalcemia. In conclusion, in the hemodialysis patient: (1) age appeared to affect the bone response to PTH and calcitriol treatment, (2) the PTH response to hypocalcemia was affected by a deceleration in the rate of calcium decrease, and (3) hysteresis of the PTH response to hypocalcemia occurred during the spontaneous recovery from hypocalcemia. (C) 1999 by the National Kidney Foundation, Inc. C1 Hosp Reina Sofia, Unit Invest, Cordoba 14004, Spain. Hosp Reina Sofia, Dept Nephrol, Cordoba 14004, Spain. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Rodriguez, M (reprint author), Hosp Reina Sofia, Unit Invest, Avada Menendez Pidal S-N, Cordoba 14004, Spain. RI Rodriguez, teresa/H-5452-2011 NR 31 TC 5 Z9 5 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 1999 VL 34 IS 3 BP 456 EP 463 DI 10.1016/S0272-6386(99)70072-7 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 266ZG UT WOS:000084329700007 PM 10469855 ER PT J AU Weinger, K Kinsley, BT Levy, CJ Bajaj, M Simonson, DC Cox, DJ Ryan, CM Jacobson, AM AF Weinger, K Kinsley, BT Levy, CJ Bajaj, M Simonson, DC Cox, DJ Ryan, CM Jacobson, AM TI The perception of safe driving ability during hypoglycemia in patients with type 1 diabetes mellitus SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACCIDENT RISK PERCEPTION; COGNITIVE FUNCTION; BLOOD-GLUCOSE; MODERATE HYPOGLYCEMIA; GENDER DIFFERENCES; SYMPTOMS; INSULIN; DRIVERS; AGE; IDDM AB PURPOSE: Insulin-induced hypoglycemia and its sequelae of cognitive impairment may place patients with type 1 diabetes at risk when driving and when making decisions about driving. Little is known about the factors that influence judgments of safe driving ability during hypoglycemia in these patients. PATIENTS AND METHODS: Thirty men and 30 women with uncomplicated type I diabetes (age [mean +/- SD] 33 +/- 9 years, duration 9 +/- 3 years, hemoglobin A(1c) level 8.7% +/- 1.0%) un derwent a stepped hypoglycemic insulin damp. Serum glucose levels were reduced from 120 mg/dL to 80, 70, 60, 50, and then 40 mg/dL during 190 minutes. At ach glucose plateau, patients completed a symptom questionnaire and neuropsychological test, estimated their glucose level, and reported whether they could drive safely. RESULTS: The proportion of patients judging that they could drive safely decreased as serum glucose levels decreased from 70% at 120 mg/dL to 22% at 40 mg/dL. Men and middle-aged patients were more likely to consider it safe to drive during hypoglycemia than women and chose under 25 years of age. Those who were symptomatic and those who recognized hypoglycemia were less likely to report safe driving ability during hypoglycemia. Most patients who were cognitively impaired appeared to recognize this and reported that they could not drive safely at a serum glucose level of 40 mg/dL. CONCLUSIONS: Adults with type 1 diabetes need educational reinforcement of safe driving habits, particularly to check glucose levels before driving. Glucose levels less than 70 mg/dL should be treated before driving. This information is as important for middle-aged, experienced drivers as it is for younger, inexperienced drivers. (C) 1999 by Excerpta Medica, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr, Boston, MA USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Weinger, K (reprint author), Joslin Diabet Ctr, Sect Behav & Mental Hlth Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Bajaj, Mandeep/B-6060-2009 FU NINDS NIH HHS [NSRA07157]; PHS HHS [42315] NR 35 TC 20 Z9 21 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1999 VL 107 IS 3 BP 246 EP 253 DI 10.1016/S0002-9343(99)00221-1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 235RV UT WOS:000082557100010 PM 10492318 ER PT J AU Richards, TL Dager Sr Corina, D Serafini, S Heide, AC Steury, K Strauss, W Hayes, CE Abbott, RD Craft, S Shaw, D Posse, S Berninger, VW AF Richards, TL Dager, SR Corina, D Serafini, S Heide, AC Steury, K Strauss, W Hayes, CE Abbott, RD Craft, S Shaw, D Posse, S Berninger, VW TI Dyslexic children have abnormal brain lactate response to reading-related language tasks SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 5th Meeting of the Cognitive-Neuroscience-Society CY APR 05-07, 1998 CL SAN FRANCISCO, CA SP Cognit Neurosci Soc ID MAGNETIC-RESONANCE SPECTROSCOPY; OXIDATIVE-METABOLISM; WORD RECOGNITION; ACTIVATION; CHROMOSOME-6; DISABILITY; COMPONENTS; PERFUSION; CORTEX AB BACKGROUND AND PURPOSE: Children with dyslexia have difficulty learning to recognize written words owing to subtle deficits in oral language related to processing sounds and accessing words automatically. The purpose of this study was to compare regional changes in brain lactate between dyslexic children and control subjects during oral language activation. METHODS: Brain lactate metabolism was measured during four different cognitive tasks (three language tasks and one nonlanguage task) in six dyslexic boys and in seven control subjects (age- and IQ-matched right-handed boys who are good readers) using a fast MR spectroscopic imaging technique called proton echo-planar spectroscopic imaging (1-cm(3) voxel resolution). The area under the N-acetylaspartate (NAA) and lactate peaks was measured to calculate the lactate/NAA ratio in each voxel. RESULTS: Dyslexic boys showed a greater area of brain lactate elevation (2.33 +/- SE 0.843 voxels) as compared with the control group (0.57 +/- SE 0.30 voxels) during a phonological task in the left anterior quadrant. No significant differences were observed in the nonlanguage tasks. CONCLUSION: Dyslexic and control children differ in brain lactate metabolism when performing language tasks, but do not differ in nonlanguage auditory tasks. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. Univ Washington, Coll Educ, Seattle, WA 98195 USA. Vet Affairs Puget Sound, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Forschungszentrum Julich, Inst Med, D-52425 Julich, Germany. RP Richards, TL (reprint author), Univ Washington, Dept Radiol, Box 357115, Seattle, WA 98195 USA. FU NICHD NIH HHS [P50 HD33812] NR 37 TC 36 Z9 38 U1 3 U2 4 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 SEP PY 1999 VL 20 IS 8 BP 1393 EP 1398 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 243NB UT WOS:000083003200006 PM 10512218 ER PT J AU Tievsky, AL Ptak, T Farkas, J AF Tievsky, AL Ptak, T Farkas, J TI Investigation of apparent diffusion coefficient and diffusion tensor anisotropy in acute and chronic multiple sclerosis lesions SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Neuroradiology CY MAY, 1997 CL TORONTO, CANADA SP Amer Soc Neuroradiol ID NUCLEAR-MAGNETIC-RESONANCE; FIBER ORIENTATION; MRI; DISABILITY; BRAIN AB BACKGROUND AND PURPOSE: The various stages of multiple sclerosis (MS) are characterized by de- and remyelination as well as by inflammation, Diffusion MR imaging is sensitive to tissue water motion, which might correspond to these pathologic processes. Our purpose was to demonstrate differences in apparent diffusion coefficient (ADC) and diffusion tensor anisotropy in acute and chronic MS plaques and in normal-appearing brain. METHODS: Twelve MS patients underwent conventional and full-tenser diffusion MR imaging with B = 1221 s/mm(2). Derivation of trace ADC and calculation of anisotropic scalars, including eccentricity, relative anisotropy (RA), and fractional anisotropy (FA) was performed on a per-pixel basis. Regions of interest of plaques and normal structures were determined on coregistered maps. MS lesions were classified as acute, subacute, or chronic on the basis of their appearance on conventional images and in relation to clinical findings. RESULTS: Seven patients had acute plaques with a concentric arrangement of alternating high and low signal intensity on diffusion-weighted images, In nine acute lesions, plaque centers had high ADC with reduced anisotropy compared with rim, normal-appearing white matter (NAWM), and chronic lesions. The thin rim of diffusion-weighted hyperintensity surrounding the center showed variable ADC and anisotropic values, which were not statistically different from NAWM. Subacute and chronic MS lesions had intermediate ADC elevations/anisotropic reductions, Calculated FA pixel maps were superior to eccentricity or RA maps; however, quality was limited by signal-to-noise constraints. CONCLUSION: ADC and diffusion anisotropic scalars reflect biophysical changes in the underlying pathology of the demyelinating process. C1 George Washington Univ, Med Ctr, Dept Radiol, Div Neuroradiol CCC 2, Washington, DC 20037 USA. Boston Med Ctr, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tievsky, AL (reprint author), George Washington Univ, Med Ctr, Dept Radiol, Div Neuroradiol CCC 2, 3800 Reservoir Rd NW, Washington, DC 20037 USA. NR 20 TC 175 Z9 185 U1 0 U2 1 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 SEP PY 1999 VL 20 IS 8 BP 1491 EP 1499 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 243NB UT WOS:000083003200024 PM 10512236 ER PT J AU Grant, SM AF Grant, SM TI Who's to blame for tragic error? SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 Dana Farber Canc Inst, Nursing & Patient Care Serv, Boston, MA 02115 USA. RP Grant, SM (reprint author), Dana Farber Canc Inst, Nursing & Patient Care Serv, Boston, MA 02115 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 0002-936X J9 AM J NURS JI Am. J. Nurs. PD SEP PY 1999 VL 99 IS 9 BP 9 EP 9 DI 10.2307/3472285 PG 1 WC Nursing SC Nursing GA 251UX UT WOS:000083465700002 PM 10489569 ER PT J AU Grant, CA Azar, D AF Grant, CA Azar, D TI Ultrasound biomicroscopy in the diagnosis and management of limbal dermoid SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report time use of ultrasound biomicroscopy in the diagnosis and management of limbal dermoid. METHOD: We used ultrasound biomicroscopy to examine an 18-month-old Asian girl with a congenital limbal mass with corneal extension. A biopsy of the mass was obtained. RESULTS: Clinical examination, ultrasound biomicroscopy, and biopsy confirmed the diagnosis of limbal dermoid, CONCLUSION: Ultrasound biomicroscopy may serve as a useful diagnostic adjunct for limbal dermoids. Additionally, it may be helpful in delineating the extent of these lesions. (Am J Ophthalmol 1999;128:365-367. (C) 1999 by Elsevier Science Inc. All rights reserved.). C1 Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Boston, MA 02114 USA. RP Grant, CA (reprint author), Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 4 TC 7 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 1999 VL 128 IS 3 BP 365 EP 367 DI 10.1016/S0002-9394(99)00117-8 PG 3 WC Ophthalmology SC Ophthalmology GA 232LJ UT WOS:000082372000019 PM 10511037 ER PT J AU Espaillat, A Aiello, LP Calderon, RM Cavallerano, JD Cavicchi, RW Cordahi, G AF Espaillat, A Aiello, LP Calderon, RM Cavallerano, JD Cavicchi, RW Cordahi, G TI Preservation of vision through Weiss ring after dense vitreous hemorrhage SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report an unusual case of retained vision through a Weiss ring in the setting of dense vitreous hemorrhage. METHOD: Case report of a 55-year-old woman with a 23-year history of type 1 diabetes mellitus who presented with new onset of blurred vision in the left eye as a result of a dense vitreous hemorrhage. RESULTS: The patient had received full scatter laser photocoagulation for proliferative diabetic retinopathy in the right eye several years earlier and reported previous resolving episodes of vitreous hemorrhage in the left eye. Best-corrected visual acuity in the left eye was hand motions at 3 feet. However, with careful head positioning visual acuity improved to 20/40 through a small clear central island. Examination of the left fundus showed a dense vitreous hemorrhage with a clear, mobile opening in the posterior hyaloid corresponding to the Weiss ring, The retina could be partially visualized only through the area of the Weiss ring. CONCLUSIONS: This unusual case demonstrates the anatomical relationship between the posterior hyaloid and Weiss ring. (Am J Ophthalmol 1999;128:376-378. (C) 1999 by Elsevier Science Inc. All rights reserved.). C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Espaillat Cabral Eye Inst, Santo Domingo, Dominican Rep. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. NR 5 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 1999 VL 128 IS 3 BP 376 EP 378 DI 10.1016/S0002-9394(99)00156-7 PG 3 WC Ophthalmology SC Ophthalmology GA 232LJ UT WOS:000082372000025 PM 10511043 ER PT J AU Rauch, SD AF Rauch, SD TI Management of idiopathic sudden sensorineural hearing loss - Invited comments SO AMERICAN JOURNAL OF OTOLOGY LA English DT Editorial Material ID MEDICAL LITERATURE; USERS GUIDES; INFORMATION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 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 SEP PY 1999 VL 20 IS 5 BP 592 EP 593 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA 233HF UT WOS:000082420900006 ER PT J AU Manolis, EN Eavey, RD Sangwatanaroj, S Halpin, C Rosenbaum, S Watkins, H Jarcho, J Seidman, CE Seidman, JG AF Manolis, EN Eavey, RD Sangwatanaroj, S Halpin, C Rosenbaum, S Watkins, H Jarcho, J Seidman, CE Seidman, JG TI Hereditary postlingual sensorineural hearing loss mapping to chromosome Xq21 SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE X-chromosome; hereditary hearing loss ID X-LINKED DEAFNESS; PROGRESSIVE MIXED DEAFNESS; PERILYMPHATIC GUSHER; MENTAL DEFICIENCY; STAPES SURGERY; GENE; LINKAGE; HETEROGENEITY; MUTATIONS; BLINDNESS AB Background: Mutations on the X-chromosome clinically manifesting different phenotypes of hearing loss have been mapped to the long arm at different loci, DFN1-DFN3. Another defect in a family with sex-linked, postlingual, progressive sensorineural hearing loss was mapped to Xq. Methods: Clinically, the family was evaluated by physical and audiometric examination of 17 members including computerized tomographic (CT) evaluation of the proband. Molecular evaluation consisted of polymerase chain reaction amplification of patient genomic DNA and resolution P-32-labeled fragments by polyacrylamide gels. Inheritance of DNA alleles and deafness were analyzed using the MLINK computer program. Results: Five affected males demonstrated symmetrical sensorineural hearing loss as significant as 100 decibels (dB). Two carrier females had a milder loss with frequency findings of 10 dB to 60 dB. Computerized tomography (CT) evaluation of the temporal bones of the proband was normal. The odds were 200:1 that the responsible gene was linked to locus DXS986 (maximum lod score = 2.3 at theta = 0). Analysis of recombination events defined by family members demonstrates that the responsible gene lies in a 21 cM (30 MB) interval, between loci DXS12175 and 1106. The disease locus in this family does not appear to map to DFN1 or DFN3. Conclusion: The family described here, with affected males who have progressive, postlingual sensorineural hearing loss and mildly affected females maps most compatibly to the DFN2 locus. Analysis of hereditary deafness in this family refines the DFN2 locus to a 9.2 Mb region in chromosome X band q21 between DXS990 and DXS1106. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA USA. Brigham & Womens Hosp, Dept Genet, Boston, MA USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 30 TC 9 Z9 11 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 SEP PY 1999 VL 20 IS 5 BP 621 EP 626 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 233HF UT WOS:000082420900012 PM 10503584 ER PT J AU Arbiser, JL Raab, G Rohan, RM Paul, S Hirschi, K Flynn, E Price, ER Fisher, DE Cohen, C Klagsbrun, M AF Arbiser, JL Raab, G Rohan, RM Paul, S Hirschi, K Flynn, E Price, ER Fisher, DE Cohen, C Klagsbrun, M TI Isolation of mouse stromal cells associated with a human tumor using differential diphtheria toxin sensitivity SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; EXPRESSION CLONING; BINDING; EGF; RECEPTOR; PRECURSOR; GENE; IDENTIFICATION; MECHANISMS AB Tumor vascularization is accompanied by the migration of stromal cells, including endothelial cells, smooth muscle cells, and fibroblasts, into the tumor. The biological contributions of stromal cells to tumor vascularization have not been well-defined, partly due to the difficulty of culturing stromal cells in the presence of large numbers of fast-growing tumor cells. To address this problem, a strategy was devised to kill tumor cells but not stromal cells. Advantage was taken of the observation that diphtheria toxin (DT) kills human but not rodent cells. Human melanoma (MMAN) tumor cells were injected subcutaneously into nude mice. The tumors were excised, homogenized, and treated with 50 ng/ml DT for 24 hours. Elimination of melanoma cells by DT treatment was demonstrated by lack of detectable levels of microphthalmia, a transcription factor that is a marker for melanoma cells. The murine stromal cells were viable and found to be mostly smooth muscle cells. These cells constituted about 1.5% of the MMAN tumor. RNase protection assays using a specific murine vascular endothelial growth factor probe confirmed the murine origin of the stromal cells. This method allows rapid isolation of stromal cells and should facilitate biochemical and genetic analysis of tumor-stromal interactions. C1 Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat Hematol Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Arbiser, JL (reprint author), Emory Univ, Sch Med, Dept Dermatol, WMB 5309, Atlanta, GA 30322 USA. FU NIAMS NIH HHS [KO8AR02096, R03 AR44947]; NIGMS NIH HHS [GM 47397, R01 GM047397] NR 35 TC 26 Z9 26 U1 0 U2 0 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 SEP PY 1999 VL 155 IS 3 BP 723 EP 729 DI 10.1016/S0002-9440(10)65171-1 PG 7 WC Pathology SC Pathology GA 235JD UT WOS:000082537800009 PM 10487830 ER PT J AU King, R Weilbaecher, KN McGill, G Cooley, E Mihm, M Fisher, DE AF King, R Weilbaecher, KN McGill, G Cooley, E Mihm, M Fisher, DE TI Microphthalmia transcription factor - A sensitive and specific melanocyte marker for melanoma diagnosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; UNKNOWN PRIMARY; WAARDENBURG SYNDROME; S-100 PROTEIN; METASTATIC MELANOMA; TYROSINASE GENE; S100 PROTEIN; EXPRESSION; MUTATIONS; TUMORS AB Malignant melanomas do not uniformly retain expression of melanocytic gene products-an observation associated with diagnostic dilemmas. Microphthalmia transcription factor (Mitf) is a melanocytic nuclear protein critical for the embryonic development and postnatal viability of melanocytes. It serves as a master regulator in modulating extracellular signals, such as those triggered by alpha-MSH and c-Kit Ligand, Because of its central role in melanocyte survival and to assess its potential use as a histopathological marker for melanoma, Mitf expression was examined in histologically confirmed human melanoma specimens. Western blot analysis of melanoma cell lines revealed consistent expression of two Mitf protein isoforms differing by MAP kinase-mediated phosphorylation, In a series of 76 consecutive human melanoma surgical specimens, 100% stained positively for Mitf with a nuclear pattern of reactivity. In a side-by-side comparison, Mitf staining was positive in melanomas that failed to stain for either HMB-45 or S-100, the most common currently used melanoma markers. Of 60 non-melanoma tumors, none displayed nuclear Mitf staining and two displayed cytoplasmic staining. Although Mitf does not distinguish benign from malignant melanocytic lesions, for invasive neoplasms it appears to be a highly sensitive and specific histopathological melanocyte marker for melanoma. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Albany Med Ctr, Dept Dermatopathol, Albany, NY USA. Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [K08 00852-01] NR 48 TC 173 Z9 173 U1 0 U2 5 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 SEP PY 1999 VL 155 IS 3 BP 731 EP 738 DI 10.1016/S0002-9440(10)65172-3 PG 8 WC Pathology SC Pathology GA 235JD UT WOS:000082537800010 PM 10487831 ER PT J AU Cooper, RA Boninger, ML Shimada, SD Lawrence, BM AF Cooper, RA Boninger, ML Shimada, SD Lawrence, BM TI Glenohumeral joint kinematics and kinetics for three coordinate system representations during wheelchair propulsion SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE wheelchair; spinal cord injury; three-dimensional kinematics; inverse dynamics; repetitive strain injury ID BIOMECHANICS; FORCES AB The shoulder plays a very important role during manual wheelchair propulsion. Unfortunately, substantial numbers of manual wheelchair users eventually develop shoulder injury or pain. Recently, studies have begun to investigate the etiology of wheelchair user shoulder injuries. This study compared three coordinate systems used to represent the shoulder during wheelchair propulsion. Our results show statistically significant differences between the three shoulder representations analyzed. Differences are seen for individuals and for the subjects as a group. Based upon our results, the fixed-z model appears preferable over the other representations due to its simplicity, low hardware requirements, and the similarity of the results to the free representation. This article also provides some insight into maximal shoulder joint forces and moments recorded during manual wheelchair propulsion. Future work should include more sophisticated models of the shoulder complex. C1 Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Div Phys Med & Rehabil, Pittsburgh, PA USA. Calif State Univ Sacramento, Dept Hlth & Phys Educ, Biomech Lab, Sacramento, CA 95819 USA. RP Cooper, RA (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 29 TC 38 Z9 38 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP-OCT PY 1999 VL 78 IS 5 BP 435 EP 446 DI 10.1097/00002060-199909000-00006 PG 12 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 235RK UT WOS:000082556200005 PM 10493454 ER PT J AU Rebrin, K Steil, GM Van Antwerp, WP Mastrototaro, JJ AF Rebrin, K Steil, GM Van Antwerp, WP Mastrototaro, JJ TI Subcutaneous glucose predicts plasma glucose independent of insulin: implications for continuous monitoring SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE continuous glucose sensor; subcutaneous tissue; interstitial fluid ID THORACIC-DUCT LYMPH; ADIPOSE-TISSUE; ELECTROCHEMICAL SENSORS; INTRAVENOUS GLUCOSE; HEALTHY-VOLUNTEERS; INTERSTITIAL FLUID; DIABETIC-PATIENTS; SKELETAL-MUSCLE; MICRODIALYSIS; BLOOD AB The present study investigated the relationship between blood and subcutaneous interstitial fluid (ISF) glucose by employing an amperometric glucose sensor specifically developed for 3-day continuous glucose monitoring. The apparent sensor sensitivity and ISF glucose equilibration delay were estimated on separate days during hyperglycemic clamps in four dogs in which insulin was either suppressed with somatostatin, allowed to change, or increased with an exogenous infusion. A 2-h sensor "settling-in" period was allowed before the clamps. During insulin deficiency, the sensor sensitivity and ISF glucose delay were 0.23 +/- 0.03 nA per mg/dl and 4.4 +/- 0.8 min. Sensitivity was not affected by increases in endogenous (0.30 +/- 0.04 vs. 0.28 +/- 0.04 nA per mg/dl) or exogenous insulin (0.18 +/- 0.01 vs. 0.16 +/- 0.01 nA per mg/dl) nor was the delay (3.3 +/- 1.2 vs. 5.7 +/- 1.1 and 9.2 +/- 2.6 vs. 12.3 +/- 1.7 min; P > 0.05 for all). Sensor glucose accurately predicted plasma glucose without correcting for delays <10 min (r > 0.9 for all), whereas for longer delays a digital corrective filter was used (r = 0.91 with filter). We conclude that the relationship between blood and ISF glucose is not affected by insulin and that delays in ISF glucose equilibration can be corrected with digital filters. C1 MiniMed Inc, Sylmar, CA 91342 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rebrin, K (reprint author), MiniMed Inc, 12744 San Fernando Rd, Sylmar, CA 91342 USA. EM KerstinR@Minimed.com FU NIDDK NIH HHS [R01-DK-55337-01] NR 41 TC 164 Z9 165 U1 1 U2 8 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 SEP PY 1999 VL 277 IS 3 BP E561 EP E571 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 232CR UT WOS:000082348600023 PM 10484370 ER PT J AU Napadow, VJ Chen, Q Wedeen, VJ Gilbert, RJ AF Napadow, VJ Chen, Q Wedeen, VJ Gilbert, RJ TI Biomechanical basis for lingual muscular deformation during swallowing SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE tongue physiology; deglutition; muscle mechanics ID PHARYNGEAL PHASES; VOLUME AB Our goal was to quantify intramural mechanics in the tongue through an assessment of local strain during the physiological phases of swallowing. Subjects were imaged with an ultrafast gradient echo magnetic resonance imaging (MRI) pulse sequence after the application of supersaturated magnetized bands in the x and y directions. Local strain was defined through deformation of discrete triangular elements defined by these bands and was depicted graphically either as color-coded two-dimensional strain maps or as three-dimensional octahedra whose axes correspond to the principal strains for each element. During early accommodation, the anterior tongue showed positive strain (expansive) in the anterior-posterior direction (x), whereas the middle tongue showed negative strain (contractile) in the superior-inferior direction (y). During late accommodation, the anterior tongue displayed increased positive x-direction and y-direction strain, whereas the posterior tongue displayed increased negative y-direction strain. These findings were consistent with contraction of the anterior-located intrinsic muscles and the posterior-located genioglossus and hyoglossus muscles. During propulsion, posterior displacement of the tongue was principally associated with positive strain directed in the x and y directions. These findings were consistent with posterior passive stretch in the midline due to contraction of the laterally inserted styloglossus muscle, as well as contraction of the posterior located transversus muscle. We conclude that MRI of Lingual deformation during swallowing resolves the synergistic contractions of the intrinsic and extrinsic muscle groups. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rgilbert@mit.edu NR 11 TC 36 Z9 36 U1 0 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 SEP PY 1999 VL 277 IS 3 BP G695 EP G701 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 233BF UT WOS:000082405100025 PM 10484396 ER PT J AU Podolsky, DK AF Podolsky, DK TI Mucosal Immunity and Inflammation V. Innate mechanisms of mucosal defense and repair: the best offense is a good defense SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE growth factors; restitution; cytokines; epithelial barrier; trefoil proteins ID INTESTINAL EPITHELIAL RESTITUTION; HEPATOCYTE GROWTH-FACTOR; PRIMARY CULTURE; FACTOR-BETA; IN-VITRO; MIGRATION; CELLS; INJURY; INTEGRIN; MODEL AB Well-coordinated mechanisms have evolved that provide both innate protection against gastrointestinal mucosal injury and facilitation of rapid mucosal repair following mucosal damage. Generic protection from injury is provided by intrinsic structural features of the epithelium that form a highly competent barrier and a complex formed at the apical surface by trefoil peptides that comprise the interface between mucosa and lumen. When the epithelial barrier has been broken, regardless of the nature of the injury, epithelial surface continuity is rapidly reestablished through restitution as cells migrate and elongate. This process is promoted by trefoil peptides at the apical surface and a large array of cytokines and growth factors acting at the basolateral pole. Many of these regulatory peptides are products of the immune and other lamina propria cell populations, which are activated following disruption of the mucosal barrier. Thus efforts to repair the epithelium follow inherently from inflammatory effects after initial damage; the repair process in turn may allow abrogation of further inflammation Ultimate repair of injury requires both proliferative replacement of damaged epithelial cells and remodeling of extracellular matrix and deeper cell populations to restore normal architecture and a fully functional mucosa. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. EM Podolsky.Daniel@mgh.harvard.edu FU NIDDK NIH HHS [DK-41557, DK-46906, DK-53304] NR 29 TC 152 Z9 155 U1 3 U2 7 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 SEP PY 1999 VL 277 IS 3 BP G495 EP G499 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 233BF UT WOS:000082405100001 PM 10484372 ER PT J AU Yang, H Kawakubo, K Tache, Y AF Yang, H Kawakubo, K Tache, Y TI Intracisternal PYY increases gastric mucosal resistance: role of cholinergic, CGRP, and NO pathways SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE thyrotropin-releasing hormone receptor antisense oligodeoxy-nucleotides; prostaglandins; ethanol; calcitonin gene-related peptide-(8-37); RX-77368; gastric lesions; peptide YY; nitric oxide ID DORSAL VAGAL COMPLEX; NEUROPEPTIDE-Y; PEPTIDE-YY; ACID SECRETION; NITRIC-OXIDE; HORMONE RECEPTOR; RATS; ETHANOL; DAMAGE; STIMULATION AB The influence of intracisternal injection of peptide YY (PYY) on gastric lesions induced by ethanol was studied in urethan-anesthetized rats. Gastric lesions covered 15-22% of the corpus as monitored Ih after intragastric administration of 45% ethanol (5 ml/kg) in intracisternal vehicle control groups. PYY, at doses of 23, 47, or 117 pmol 30 min before ethanol, decreased gastric lesions by 27%, 63%, and 59%, respectively. Thyrotropin-releasing hormone (TRH) receptor antisense oligodeoxynucleotide pretreatment (intracisternally, 48 and 24 h before intracisternal PW) did not influence the gastroprotective effect of intracisternal PYY (47 pmol) but abolished that of intracisternal TRH analog RX-77368 (4 pmol). RX-77368 (2.6 pmol) and PW (6 pmol) were ineffective when injected intracisternally alone but reduced ethanol lesions by 44% when injected simultaneously. Atropine (subcutaneously), the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (intravenously), or the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, intravenously) completely abolished the gastroprotective effect of intracisternal PW (47 pmol), whereas indomethacin (intraperitoneally) had no effect. The L-NAME action was reversed by L-arginine but not by D-arginine (intravenously). These results suggest that intracisternal PYY acts independently of medullary TRH to decrease ethanol-induced gastric lesions. The PYY action involves vagal cholinergic-mediated CGRP/NO protective mechanisms. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, CURE DDRC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, CURE DDRC, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hoyang@ucla.edu FU NIDDK NIH HHS [DK-30110, DK-41301, DK-50255] NR 43 TC 31 Z9 31 U1 0 U2 0 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 SEP PY 1999 VL 277 IS 3 BP G555 EP G562 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 233BF UT WOS:000082405100009 PM 10484380 ER PT J AU Naidu, PS Velarde, V Kappler, CS Young, RC Mayfield, RK Jaffa, AA AF Naidu, PS Velarde, V Kappler, CS Young, RC Mayfield, RK Jaffa, AA TI Calcium-calmodulin mediates bradykinin-induced MAPK phosphorylation and c-fos induction in vascular cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE B-2-kinin receptor; signal transduction; extracellular regulated kinases ID SMOOTH-MUSCLE CELLS; EPIDERMAL GROWTH-FACTOR; MEMBRANE DEPOLARIZATION; SIGNALING CASCADE; TYROSINE KINASE; PROTEIN-KINASES; ANGIOTENSIN-II; NITRIC-OXIDE; ACTIVATION; TRANSCRIPTION AB The vasoactive peptide bradykinin (BK) has been implicated in the pathophysiology of a number of vascular wall abnormalities, but the cellular mechanisms by which BK generates second messengers that alter vascular function are as yet undefined. Exposure of vascular smooth muscle cells (VSMC) to BK (10(-7) M) produced a rapid and transient rise in intracellular calcium, which preceded an increase in tyrosine phosphorylation of mitogen-activated protein kinase (MAPK). MAPK activation by BK was observed as early as 1 min, peaked at 5 min, and returned to baseline by 20 min. Treatment of cells with the intracellular calcium chelator EGTA-acetoxymethyl ester inhibited BK-stimulated MAPK activation, suggesting that intracellular calcium mobilization contributes to the activation of MAPK. The calmodulin inhibitor W-7 also markedly inhibited BK-induced MAPK phosphorylation in the cytoplasm as well as in the nucleus. Moreover, the BK-induced increase in c-fos mRNA levels was significantly inhibited by the calmodulin inhibitor, indicating that calmodulin is required for BK signaling leading to c-fos induction. These results implicate the calcium-calmodulin pathway in the mechanisms for regulating MAPK activity and the resultant c-fos expression induced by BK in VSMC. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Jaffa, AA (reprint author), Med Univ S Carolina, Dept Med, 171 Ashley Ave, Charleston, SC 29425 USA. EM jaffaa@musc.edu FU NHLBI NIH HHS [HL-55782, HL-07260]; NIDDK NIH HHS [DK-46543] NR 45 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1999 VL 277 IS 3 BP H1061 EP H1068 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 231YE UT WOS:000082338300028 PM 10484429 ER PT J AU O'Donnell, JM White, LT Lewandowski, ED AF O'Donnell, JM White, LT Lewandowski, ED TI Mitochondrial transporter responsiveness and metabolic flux homeostasis in postischemic hearts SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE reperfusion; redox potential; malate-aspartate shuttle; tricarboxylic acid cycle ID CITRIC-ACID CYCLE; MALATE-ASPARTATE CYCLE; RAT-HEART; CALCIUM-IONS; STUNNED MYOCARDIUM; 2-OXOGLUTARATE; REPERFUSION; OXIDATION; HORMONES; KINETICS AB The transport of metabolites between mitochondria and cytosol via the alpha-ketoglutarate-malate carrier serves to balance flux between the two spans of the tricarboxylic acid (TCA) cycle but is reduced in stunned myocardium. To examine the mechanism for reduced transporter activity, we followed the postischemic response of metabolite influx/efflux from mitochondria to stimulation of the malate-aspartate (MA) shuttle. Isolated rabbit hearts were either perfused with 2.5 mM [2-C-13]acetate (n = 7) or similarly reperfused (n = 5) after 10-min ischemia. In other hearts, the MA shuttle was stimulated with a high cytosolic redox state (NADH) induced by 2.5 mM lactate in normal (n = 6) or reperfused hearts (n = 7). In normal hearts, the MA shuttle response accelerated transport from 8.3 +/- 3.4 to 16.2 +/- 5.0 pmol.min(-1).g dry wt(-1). Although transport was reduced in stunned hearts, the MA shuttle was responsive to cytosolic NADH load, increasing transport from 3.4 +/- 1.0 to 9.8 +/- 3.7 pmol.min(-1).g dry wt(-1). Therefore, metabolite exchange remains intact in stunned myocardium but responds to changes in TCA cycle flux regulation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Lewandowski, ED (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01-HL-49244, R01-HL-56178] NR 38 TC 13 Z9 13 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1999 VL 277 IS 3 BP H866 EP H873 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 231YE UT WOS:000082338300004 PM 10484405 ER PT J AU Scherrer-Crosbie, M Steudel, W Ullrich, R Hunziker, PR Liel-Cohen, N Newell, J Zaroff, J Zapol, WM Picard, MH AF Scherrer-Crosbie, M Steudel, W Ullrich, R Hunziker, PR Liel-Cohen, N Newell, J Zaroff, J Zapol, WM Picard, MH TI Echocardiographic determination of risk area size in a murine model of myocardial ischemia SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE contrast echocardiography; mice; myocardial infarction ID CONTRAST ECHOCARDIOGRAPHY; IN-VIVO; INFARCT SIZE; BLOOD-FLOW; MICE; MICROBUBBLES; ULTRASOUND; OVEREXPRESSION; QUANTIFICATION; DEFICIENCY AB Genetically altered mice are useful to understand cardiac physiology. Myocardial contrast echocardiography (MCE) assesses myocardial perfusion in humans. We hypothesized it could evaluate murine myocardial perfusion before and after acute coronary ligation. MCE was performed before and after this experimental myocardial infarction (MI) in anesthetized mice by intravenous injection of contrast microbubbles and transthoracic echo imaging. Time-video intensity curves were obtained for the anterior, lateral, and septal myocardial walls. After MI, MCE defects were compared with the area of no perfusion measured by Evans blue staining. In healthy animals, intramyocardial contrast was visualized in all the cardiac walls. The anterior wall had a higher baseline video intensity (53 +/- 17 arbitrary units) than the lateral (34 +/- 13) and septal (27 +/- 13) walls (P < 0.001) and a lower increase in video intensity after contrast injection [50 +/- 17 vs. 60 +/- 24 (lateral) and 65 +/- 29 (septum), P < 0.01]. After MI, left ventricular (LV) dimensions were enlarged, and the shortening fraction was decreased. A perfusion defect was imaged with MCE iii every mouse, with a correlation between MCE perfusion defect size (35 +/- 13%) and the nonperfused area by Evans blue (37 +/- 16%, y = 0.77x + 6.1, r = 0.93, P < 0.001). Transthoracic MCE is feasible in the mouse and can accurately detect coronary occlusions and quantitate nonperfused myocardium. C1 Harvard Univ, Cardiac Ultrasound Lab,Sch Med, Cardiac Unit,Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners Hlth Care Informat Syst, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Harvard Univ, Cardiac Ultrasound Lab,Sch Med, Cardiac Unit,Massachusetts Gen Hosp, Dept Med, VBK 508,55 Fruit St, Boston, MA 02114 USA. EM crosbie@olorin.mgh.harvard.edu FU NHLBI NIH HHS [HL-42397] NR 31 TC 57 Z9 58 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1999 VL 277 IS 3 BP H986 EP H992 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 231YE UT WOS:000082338300019 PM 10484420 ER PT J AU Fukuda, T Kim, DK Chin, MR Hales, CA Bonventre, JV AF Fukuda, T Kim, DK Chin, MR Hales, CA Bonventre, JV TI Increased group IV cytosolic phospholipase A(2) activity in lungs of sheep after smoke inhalation injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE eicosanoids; polymorphonuclear leukocytes; acrolein; cotton smoke ID PULMONARY-EDEMA; SULFIDOPEPTIDE LEUKOTRIENES; SIGNAL-TRANSDUCTION; SYNTHETIC SMOKE; PURIFICATION; INFLAMMATION; ACROLEIN; KIDNEY; EXPRESSION; PLATELETS AB Increased phospholipase A(2) (PLA(2)) activity was measured in cytosolic fractions of lungs fi om sheep exposed to smoke from burning cotton or to synthetic smoke consisting of carbon and acrolein, a cotton smoke toxin. Three peaks of PLA(2) activity were identified by heparin-Sepharose chromatography. The heparin-nonbinding PLA(2) activity was twofold higher in the extracts from lungs exposed to smoke than in normal lungs. This activity was identified as the group IV 85-kDa cytosolic PLA(2) (cPLA(2)). The activities of the forms of PLA(2) that bound to heparin did not change after smoke exposure. Those activities showed a pH optimum of 9.0, required a millimolar Ca2+ concentration for full activity, and were inhibited by 5 mM dithiothreitol. One activity eluted at an NaCl concentration typical for group Ib and V PLA(2) and had the expected substrate specificity. The other form of lung PLA(2) that bound heparin was a group II PLA(2). Lung myeloperoxidase activity increased progressively with increased exposure to smoke, cPLA(2) was identified in sheep neutrophils. With 30 breaths of smoke exposure, there was an increase in cPLA(2) activity without a difference in immunoreactivity on Western blot, indicating that the increased activity was not due to increased amounts of protein. In conclusion, smoke induces increases in resident lung cell cPLA(2) activity that is likely responsible for eicosanoid production, leading to lung inflammation and bronchoconstriction. C1 Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp E, Suite 4002,149 13th St, Charlestown, MA 02129 USA. EM joseph_bonventre@hms.harvard.de FU NIDDK NIH HHS [DK 38452, DK-39773]; NINDS NIH HHS [NS-10828] NR 41 TC 17 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 1999 VL 277 IS 3 BP L533 EP L542 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 233KB UT WOS:000082425100012 PM 10484460 ER PT J AU Wang, LX Cardin, S Martinez, V Tache, Y Lloyd, KCK AF Wang, LX Cardin, S Martinez, V Tache, Y Lloyd, KCK TI Duodenal loading with glucose induces Fos expression in rat brain: selective blockade by devazepide SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE cholecystokinin; nucleus of the solitary tract; area postrema; satiety; feeding ID PANCREATIC ENDOCRINE FUNCTION; NUCLEUS-TRACTUS-SOLITARIUS; INTESTINAL NUTRIENTS; SENSITIVE NEURONS; CCK ANTAGONIST; AWAKE RATS; CHOLECYSTOKININ; SUPPRESSION; INSULIN; L-364,718 AB The role of CCK in mediating neuronal activity in the brain in response to dietary carbohydrate was measured by detecting Fos immunoreactivity in response to duodenal glucose load in rats after administration of the CCK-A receptor antagonist devazepide. In adult, male Sprague-Dawley rats, infusion for 30 min of 545 mg (2.18 kcal) dextrose through a duodenal cannula induced Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), lateral division of the central nucleus of the amygdala (CeAL), and the external subnucleus of the lateral parabrachial nucleus (LPBE). Devazepide treatment (1 mg/kg) attenuated Fos expression in the NTS and AP by 81 and 78%, respectively, but not in the CeAL or LPBE. These results indicate that central neuronal activation is elicited by dietary glucose in the intestinal lumen and that activation of neurons in the NTS and AP is mediated by CCK-A receptors. C1 Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ,Dept Med & Brain Res Inst, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Lloyd, KCK (reprint author), Univ Calif Davis, Sch Vet Med, 1321 Haring Hall, Davis, CA 95616 USA. EM kclloyd@ucdavis.edu RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-45752, DK-41303]; NIMH NIH HHS [MH-00663] NR 46 TC 27 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 1999 VL 277 IS 3 BP R667 EP R674 PG 8 WC Physiology SC Physiology GA 231XN UT WOS:000082336800007 PM 10484482 ER PT J AU Abbate, M Brown, D Bonventre, JV AF Abbate, M Brown, D Bonventre, JV TI Expression of NCAM recapitulates tubulogenic development in kidneys recovering from acute ischemia SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE morphogenesis; polarity; migration; mesenchyme; atrophy; acute renal failure; neural cell adhesion molecule; integrins; adhesion molecules ID CELL-ADHESION MOLECULE; HEPARAN-SULFATE PROTEOGLYCAN; HEPATOCYTE GROWTH-FACTOR; N-CAM; POLYSIALIC ACID; RENAL-FAILURE; IDENTIFICATION; RECEPTOR; ANTIGEN; TISSUE AB Recovery of the kidney from acute renal failure relies on a sequence of events including epithelial cell dedifferentiation and proliferation followed by differentiation and restoration of the functional integrity of the nephron. The factors responsible for, and the significance of, reversion to a less differentiated cell phenotype and its relationship to the proliferative response after ischemia are poorly understood. In an attempt to identify adhesion molecules that may be influential in the recovery process, the expression of neural cell adhesion molecule (NCAM) and markers of epithelial differentiation and proliferation were analyzed at various times after an ischemic insult. In maturing nephrons, NCAM is detectable by immunohistochemistry in renal vesicles, S-shaped bodies, and early tubules. There is minimal cellular NCAM expression in normal tubules of the adult kidney. In contrast, in postischemic kidneys, NCAM expression is abundant in S3 proximal tubule cells 5 days after reperfusion. As in developing tubules, NCAM is concentrated in basal and lateral aspects of cells that have no apical gp330 or dipeptidyl peptidase TV detectable on their brush border. The expression of NCAM is preceded by disassembly of the brush border and proliferation of surviving S3 cells, which is most prominent at 2 days postischemia. NCAM expression persists in some flattened and dedifferentiated cells for up to 7 wk after ischemia. Thus proximal tubule epithelial cells of the postischemic kidney express NCAM in a pattern that recapitulates the expression of NCAM in the developing kidney. Such reversion of phenotype extends at least back to the early stages of renal vesicle formation, and this reversion may represent a critical step in the reestablishment of a normal tubule. NCAM-matrix interactions may mediate the motogenic and mitogenic responses of the dedifferentiated epithelium that are critical to reestablishment of a functional proximal tubule. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA 02129 USA. Mario Negri Inst Pharmacol Res, I-24125 Bergamo, Italy. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp East, Suite 4002,149 13th St, Charlestown, MA 02129 USA. EM joseph_bonventre@hms.harvard.edu FU NIDDK NIH HHS [DK-39773, DK-38452]; NINDS NIH HHS [NS-10828] NR 47 TC 47 Z9 50 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD SEP PY 1999 VL 277 IS 3 BP F454 EP F463 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 233BK UT WOS:000082405500017 PM 10484529 ER PT J AU Wirshing, DA Marshall, BD Green, MF Mintz, J Marder, SR Wirshing, WC AF Wirshing, DA Marshall, BD Green, MF Mintz, J Marder, SR Wirshing, WC TI Risperidone in treatment-refractory schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHOTIC-PATIENTS; RATING-SCALE; HALOPERIDOL; CLOZAPINE AB Objective: The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia. Method: Sixty-seven medication-unresponsive subjects were randomly assigned to treatment with risperidone (N=34) or haloperidol (N=33), After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments. Results: Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment, Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly less observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia, Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia. Conclusions: Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone. C1 VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Los Posadas Serv Ctr, Camarillo, CA USA. RP Wirshing, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd,Bldg 210,Rm 15 B151H, Los Angeles, CA 90073 USA. NR 26 TC 101 Z9 103 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1999 VL 156 IS 9 BP 1374 EP 1379 PG 6 WC Psychiatry SC Psychiatry GA 232FF UT WOS:000082359700011 PM 10484947 ER PT J AU Mataix-Cols, D Rauch, SL Manzo, PA Jenike, MA Baer, L AF Mataix-Cols, D Rauch, SL Manzo, PA Jenike, MA Baer, L TI Use of factor-analyzed symptom of dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CHRONIC TIC DISORDER; DOUBLE-BLIND; BEHAVIORAL TREATMENT; CONTROLLED TRIAL; TREATMENT RESPONSE; CLOMIPRAMINE; PERSONALITY; FLUVOXAMINE; FLUOXETINE; SUBTYPES AB Objective: No consistent predictors of outcome have been identified for the pharmacotherapy of obsessive-compulsive disorder (OCD). Recent factor analytic studies have identified meaningful symptom dimensions that may be related to response to serotonin reuptake inhibitors and other treatments. Method: A total of 354 outpatients with primary OCD were administered the Yale-Brown Obsessive Compulsive Scale Symptom Checklist, and its 13 main symptom categories were factor analyzed by using principal components analysis. The identified symptom dimensions were then entered into multiple regression models as outcome predictors of response to serotonin reuptake inhibitors and placebo response in a group of 150 nondepressed subjects who completed six double-blind, placebo-controlled trials with a serotonin reuptake inhibitor (clomipramine, fluvoxamine, fluoxetine, sertraline, and paroxetine). Eighty-four patients received a serotonin reuptake inhibitor and 66, placebo. Results: The principal components analysis identified five factors that explained 65.5% of variance in outcome: symmetry/ordering, hoarding, contamination/cleaning, aggressive/checking, and sexual/religious obsessions. Serotonin reuptake inhibitors were significantly superior to placebo on all outcome measures. Initial severity of OCD was related to greater posttreatment severity of OCD. Higher scores on the hoarding dimension predicted poorer outcome following treatment with serotonin reuptake inhibitors, after control for baseline severity. No predictors of placebo response were identified. Exclusion of clomipramine did not modify the overall results, suggesting a cross-serotonin reuptake inhibitor effect. Conclusions: The identified symptom dimensions are largely congruent with those identified in earlier reports. Patients with OCD vary in their response to treatment with serotonin reuptake inhibitors. The presence of hoarding obsessions and compulsions is associated with poorer response to serotonin reuptake inhibitors. C1 Univ Barcelona, Dept Psiquiatra & Psicobiol Clin, E-08035 Barcelona, Spain. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mataix-Cols, D (reprint author), Univ Barcelona, Dept Psiquiatra & Psicobiol Clin, Passeig de la Vail dHebron 171, E-08035 Barcelona, Spain. RI Mataix-Cols, David/G-3843-2010 OI Mataix-Cols, David/0000-0002-4545-0924 NR 44 TC 396 Z9 401 U1 1 U2 18 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1999 VL 156 IS 9 BP 1409 EP 1416 PG 8 WC Psychiatry SC Psychiatry GA 232FF UT WOS:000082359700017 PM 10484953 ER PT J AU Ghaemi, SN AF Ghaemi, SN TI Performative statements and the will: Mechanisms of psychotherapeutic change SO AMERICAN JOURNAL OF PSYCHOTHERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-the-Advancement-of-Philosophy-and-Psychiatry CY 1996 CL NEW YORK, NEW YORK SP Assoc Advancement Philosophy & Psychiat AB Performative statements are much discussed in the philosophy of language e.g., by the linguistic philosopher; J. L. Austin, where they are distinguished from descriptive statements. Whereas the latter merely describe a current state Of affairs from an external standpoint, performative statements enact a new stare of affairs merely by being spoken, as when a minister pronounces a couple married during a wedding ceremony. Performative statements are words and deeds at the same time. They are special kinds of statements, requiring certain unique circumstances and relationships so that they can function validly. Leston Havens has made the connection between the ability to make performative statements and the setting of psychotherapy. He has asserted that performative statements are an important part of the psychotherapeutic repertoire and may be an important force in bringing about psychotherapeutic change. In this paper; I try to locate the mechanism by which performative statements may achieve this effect, suggesting that this occurs by means of influencing the patient's will directly. Performative statements work on the will, much as descriptive statements influence the intellect. Philosophical ideas about the will, like Aristotle's notion of weakness of will, may explain some of the phenomena of psychotherapy! including resistance. C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Cambridge, MA 02138 USA. RP Ghaemi, SN (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Harvard Bipolar Res Program, 15 Parkman St,WAC-812, Boston, MA 02114 USA. NR 17 TC 1 Z9 2 U1 0 U2 1 PU ASSN ADVAN PSYCHOTHERAPY PI BRONX PA BELFER EDUC CENTER, ROOM 402 ALBERT EINSTEIN COLL MED 1300 MORRIS PARK AVE, BRONX, NY 10461-1602 USA SN 0002-9564 J9 AM J PSYCHOTHER JI Am. J. Psychother. PD FAL PY 1999 VL 53 IS 4 BP 483 EP 494 PG 12 WC Psychology, Clinical; Psychiatry; Psychology; Psychology, Psychoanalysis SC Psychology; Psychiatry GA 288JQ UT WOS:000085560000004 PM 10674150 ER PT J AU Cydulka, RK Emerman, CL Schreiber, D Molander, KH Woodruff, PG Camargo, CA AF Cydulka, RK Emerman, CL Schreiber, D Molander, KH Woodruff, PG Camargo, CA CA MARC Investigators TI Acute asthma among pregnant women presenting to the emergency department SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID AIRWAY RESPONSIVENESS; PERINATAL OUTCOMES; PREDNISONE; SEVERITY; CORTICOSTEROIDS; MANAGEMENT; GROWTH; SAFETY AB Asthma complicates up to 4% of pregnancies. Our objective was to compare emergency department (ED) visits for acute asthma among pregnant versus nonpregnant women. We performed a prospective cohort study, as part of the Multicenter Asthma Research Collaboration. ED patients who presented with acute asthma underwent a structured interview in the ED, and another by telephone 2 wk later. The study was performed at 36 EDs in 18 states. A total of 51 pregnant women and 500 nonpregnant women, age 18 to 39, were available for analysis. Pregnant women did not differ from nonpregnant women by duration of asthma symptoms (median: 0.75 versus 0.75 d, p = 0.57) or initial peak expiratory flow rate (PEFR) (51% versus 53% of predicted, p = 0.52). Despite this similarity, only 44% of pregnant women were treated with corticosteroids in the ED compared with 66% of nonpregnant women (p = 0.002). Pregnant women were equally likely to be admitted (24% versus 21%, p = 0.61) but less likely to be prescribed corticosteroids if sent home (38% versus 64%, p = 0.002). At 2-wk follow-up, pregnant women were 2.9 times more likely to report an ongoing exacerbation (95% Cl, 1.2 to 6.8). Among women presenting to the ED with acute asthma, pregnant asthmatics are less likely to receive appropriate treatment with corticosteroids. C1 Case Western Reserve Univ, Dept Emergency Med, Metrohlth Med Ctr, Sch Med, Cleveland, OH 44109 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Stanford Univ, Sch Med, UCSF Stanford Hlth Care, Div Emergency Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. RP Cydulka, RK (reprint author), Case Western Reserve Univ, Dept Emergency Med, Metrohlth Med Ctr, Sch Med, S1-203,2500 MetroHlth Dr, Cleveland, OH 44109 USA. FU NHLBI NIH HHS [HL-07427, HL-03533] NR 35 TC 69 Z9 69 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP PY 1999 VL 160 IS 3 BP 887 EP 892 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 236ND UT WOS:000082604700022 PM 10471614 ER PT J AU Khoukaz, G Gross, NJ AF Khoukaz, G Gross, NJ TI Effects of salmeterol on arterial blood cases in patients with stable chronic obstructive pulmonary disease - Comparison with albuterol and ipratropium SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ASTHMA AB Administration of P-adrenergic agonist bronchodilators to patients with airways obstruction commonly results in transient decreases in Pa,, levels despite bronchodilation, an effect that has been attributed to these drugs' pulmonary vasodilator action. We compared the acute effects on gas exchange of salmeterol with those of albuterol and the anticholinergic agent ipratropium in 20 patients with stable chronic obstructive pulmonary disease (COPD). Each agent was given in recommended dosage on separate days in a double-blind, crossover format, and the patients' arterial blood gases (ABGs) were measured at baseline and at intervals to 120 min. Small but statistically significant declines in Pa-O2 the primary outcome variable, were found after administration of both salmeterol and albuterol. The decline in Pa-O2 after salmeterol was of lesser magnitude but was more prolonged than that after albuterol, the greatest mean change being -2.74 +/- 0.89 mm Hg (mean +/- SEM) at 30 min after salmeterol, and -3.45 +/- 0.92 mm Hg at 20 min after albuterol. Following ipratropium, the corresponding change was -1.32 +/- 0.85 mm Hg at 20 min. These declines, which were almost entirely attributable to increases in the alveolar-arterial difference in oxygen tension Delta(A-a)Do(2) tended to be more marked in subjects with higher baseline Pa-O2 values. No subject experienced a decline in Pa-O2 to levels below 59 mm Hg. There were no significant differences among the three drugs studied. We conclude that despite small decreases in Pa-O2 after each of the three drugs, the declines were small, transient, and of doubtful clinical significance. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Med, Maywood, IL 60153 USA. RP Gross, NJ (reprint author), POB 1485, Hines, IL 60141 USA. NR 10 TC 28 Z9 28 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP PY 1999 VL 160 IS 3 BP 1028 EP 1030 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 236ND UT WOS:000082604700044 PM 10471636 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI Off-label use of interventional medical devices SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Rush Med Coll, Chicago, IL 60612 USA. RP Berlin, L (reprint author), Rush N Shore Med Ctr, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 4 TC 11 Z9 11 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1999 VL 173 IS 3 BP 539 EP 542 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 228EX UT WOS:000082125100005 PM 10470876 ER PT J AU Palmer, WE Kuong, SJ Elmadbouh, HM AF Palmer, WE Kuong, SJ Elmadbouh, HM TI MR imaging of myotendinous strain SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INJURIES C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Boston, MA 02114 USA. Boston Med Ctr, Dept Radiol, Boston, MA 02118 USA. Peterborough Dist Gen Hosp, Dept Radiol, Peterborough PE3 6DA, England. RP Palmer, WE (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, 15 Parkman St,Ste 515, Boston, MA 02114 USA. NR 6 TC 76 Z9 77 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1999 VL 173 IS 3 BP 703 EP 709 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 228EX UT WOS:000082125100038 PM 10470908 ER PT J AU Boiselle, PM Mansilla, AV Fisher, MS McLoud, TC AF Boiselle, PM Mansilla, AV Fisher, MS McLoud, TC TI Wandering wires: Frequency of sternal wire abnormalities in patients with sternal dehiscence SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CARDIAC-SURGERY AB OBJECTIVE. The purpose of this study is to assess the frequency of various sternal wire abnormalities on chest radiographs of patients with sternal dehiscence and to determine the role of radiography in detecting or confirming this complication. MATERIALS AND METHODS. We used our computerized hospital information system to identify all patients with a diagnosis of sternal dehiscence from January 1993 through June 1998, Clinical data were obtained by retrospective chart review. A chest radiograph from the date of diagnosis was compared with the first postoperative radiograph obtained after median sternotomy. Each radiograph was retrospectively reviewed by two radiologists who assessed three sternotomy wire abnormalities: displacement (offset of one or more wires in relation to others in the vertical row), rotation (alteration in the axis of a wire compared with its orientation on a baseline radiograph), and disruption (unraveling or fracture of a wire). We also reviewed a series of postoperative radiographs in a group of matched controls who had an uneventful postoperative course with no clinical evidence of dehiscence. RESULTS. The study cohort included 19 patients, 13 men and six women, who were 49-84 years old (mean, 66 years). The chest radiographs revealed sternal wire abnormalities in 17 (89%) of 19 patients with sternal dehiscence, including displacement in 16 (84%) of 19 patients, rotation in 10 (53%) of 19 patients, and disruption in four (21%) of 19 patients. The mean number of displaced wires per patient was 2.3 (range, 1-5), The mean distance of maximal displacement was 20 mm (range, 6-45 mm). Radiographic abnormalities preceded the clinical diagnosis in 13 (68%) of 19 patients. We observed no case of sternal wire displacement, rotation, or disruption in the control group. CONCLUSION. Sternal wire abnormalities, most notably displacement, are present in most patients with sternal dehiscence; radiographic abnormalities precede the clinical diagnosis in most cases. C1 Temple Univ Hosp, Dept Diagnost Imaging, Philadelphia, PA 19140 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Boiselle, PM (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 10 TC 16 Z9 16 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1999 VL 173 IS 3 BP 777 EP 780 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 228EX UT WOS:000082125100053 PM 10470922 ER PT J AU Ahari, HK Feldman, L Kaufman, JA Gianturco, LE AF Ahari, HK Feldman, L Kaufman, JA Gianturco, LE TI Vascular and interventional case of the day - Case 1: Peristomal varices SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID STOMAL VARICES; EMBOLIZATION C1 Boston Univ, Med Ctr, Dept Radiol, Div Vasc & Intervent Radiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Vet Adm Med Ctr, Dept Radiol, Div Vasc & Intervent Radiol, Boston, MA 02130 USA. Massachusetts Gen Hosp, Dept Radiol, Div Vasc & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Vet Adm Med Ctr, Dept Radiol, Div Nucl Radiol, Boston, MA 02130 USA. RP Ahari, HK (reprint author), Boston Univ, Med Ctr, Dept Radiol, Div Vasc & Intervent Radiol, 1 Boston Med Ctr Pl, Boston, MA 02118 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1999 VL 173 IS 3 BP 829 EP + PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 228EX UT WOS:000082125100076 PM 10470944 ER PT J AU Ahmed, E Young, RH Scully, RE AF Ahmed, E Young, RH Scully, RE TI Adult granulosa cell tumor of the ovary with foci of hepatic cell differentiation - A report of four cases and comparison with two cases of granulosa cell tumor with Leydig cells SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; granulosa cell tumor; hepatocytes; Leydig cells; immunohistochemistry ID SERUM ALPHA-FETOPROTEIN; ANDROBLASTOMA; FREQUENCY; RETIFORM AB We report four ovarian granulosa cell tumors of the adult type containing small foci of hepatic cell differentiation. The patients ranged in age from 35 to 54 years and had unilateral adnexal masses. The smallest tumor was 4.0 cm in diameter and the largest, 11.0 cm in diameter. Three tumors were solid and cystic, and one was cystic. Microscopic examination showed typical patterns of adult granulosa cell tumor, with the additional finding of scattered islands of large cells with abundant eosinophilic. slightly granular cytoplasm and central round nuclei containing single prominent nucleoli. Bile pigment was detected in canaliculi between some of the large cells in three tumors. The hepatic cells were positive immunohistochemically for cytokeratin (CAM 5.2) and epithelial membrane antigen in two cases and alpha-fetoprotein in one of two cases. Carcinoembryonic antigen was stained in a canalicular pattern in two cases. Staining for vimentin and alpha-inhibin was negative. Liver cells in granulosa cell tumors must be differentiated from Leydig cells, which are found very rarely in granulosa cell tumors, and luteinized stromal and granulosa cells, which an present more commonly in these tumors; all three of the latter cell types are positive for alpha-inhibin. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mem Hlth Care, Dept Pathol, Worcester, MA USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 18 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 1999 VL 23 IS 9 BP 1089 EP 1093 DI 10.1097/00000478-199909000-00012 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 232CU UT WOS:000082348800012 PM 10478669 ER PT J AU Kaplan, RF Uejima, T Lobel, G Goudsouzian, N Ginsberg, B Hannallah, R Cote, CJ Denman, W Griffith, R Clarke, C Hummer, K AF Kaplan, RF Uejima, T Lobel, G Goudsouzian, N Ginsberg, B Hannallah, R Cote, CJ Denman, W Griffith, R Clarke, C Hummer, K TI Intramuscular rocuronium in infants and children - A multicenter study to evaluate tracheal intubating conditions, onset, and duration of action SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 1997 Annual Meeting of American-Society-of-Anesthesiologists CY OCT 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Anesthesiologists DE muscle relaxant; neuromuscular relaxants; pediatric ID SUCCINYLCHOLINE AB Background: This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia. Methods: Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites. Anesthesia was maintained with halothane and oxygen (1% end-tidal concentration if < 2.5 yr; 0.80% end-tidal concentration if > 2.5 yr) for 5 min. One half of the patients received 0.45 mg/kg intravenous rocuronium. The others received 1 mg/kg (infants) or 1.8 mg/kg (children) of intramuscular rocuronium into the deltoid muscle. Intubating conditions and mechanomyographic responses to ulnar nerve stimulation were assessed. Results: The conditions for tracheal intubation at 2.5 and 3 min in infants and children, respectively, were inadequate in a high percentage of patients in the intramuscular group. Nine of 16 infants and 10 of 17 children had adequate or better intubating conditions at 3.5 and 4 min, respectively, after intramuscular rocuronium. Better-than-adequate intubating conditions were achieved in 14 of 15 infants and 16 of 17 children given intravenous rocuronium. Intramuscular rocuronium provided greater than or equal to 98% blockade in 7.4 +/- 3.4 min (in infants) and 8 +/- 6.3 min (in children). Twenty-five percent recovery occurred in 79 +/- 26 min (in infants) and in 86 +/- 22 min (in children). Conclusions: Intramuscular rocuronium, in the doses and conditions tested, does not consistently provide satisfactory tracheal intubating conditions in infants and children and is not an adequate alternative to intramuscular succinylcholine when rapid intubation is necessary. C1 Childrens Natl Med Ctr, Dept Anesthesiol, Washington, DC 20010 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. RP Kaplan, RF (reprint author), Childrens Natl Med Ctr, Dept Anesthesiol, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3 BP 633 EP 638 DI 10.1097/00000542-199909000-00012 PG 6 WC Anesthesiology SC Anesthesiology GA 232KE UT WOS:000082369300007 PM 10485771 ER PT J AU Ang, SB Chow, CM D'Ambra, MN AF Ang, SB Chow, CM D'Ambra, MN TI Effects of antifibrinolytics on patients after deep hypothermic circulatory arrest for aortic surgery SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A436 BP U240 EP U240 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600436 ER PT J AU Barach, P Small, SD Kaplan, H Carroll, J AF Barach, P Small, SD Kaplan, H Carroll, J TI In-depth study of thirty major incident reporting systems with a focus on near miss reporting in medical, aviation, nuclear power, and petrochemical industries SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA 1209 BP U474 EP U474 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480601208 ER PT J AU D'Ambra, MN Elman, I Koski, G Abdi, S deBros, F AF D'Ambra, MN Elman, I Koski, G Abdi, S deBros, F TI Reversal of opiate dependency under general anesthesia (ROD/GA): Hemodynamic, respiratory, neuroendocrine effects and long-term outcome SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A779 BP U356 EP U356 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600780 ER PT J AU Dershwitz, M Walsh, J Krause, S Makris, N Gollub, R AF Dershwitz, M Walsh, J Krause, S Makris, N Gollub, R TI Using functional magnetic resonance imaging to measure opioid effects in discrete brain regions SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A367 BP U223 EP U223 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600369 ER PT J AU Hirose, M Kaneki, M Ibebunjo, C Sugita, H Martyn, J AF Hirose, M Kaneki, M Ibebunjo, C Sugita, H Martyn, J TI Immobilization affects insulin signaling in muscle SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A229 BP U186 EP U186 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600230 ER PT J AU Hirose, M Kaneki, M Sugita, H Yasuhara, S Martyn, J AF Hirose, M Kaneki, M Sugita, H Yasuhara, S Martyn, J TI Denervation decreases insulin signaling in muscle SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A228 BP U185 EP U185 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600229 ER PT J AU Martinez-Ruiz, R Montero-Huerta, P Zapol, WM Head, AC AF Martinez-Ruiz, R Montero-Huerta, P Zapol, WM Head, AC TI Inhaled nitric oxide (NO) improves survival rates without no preloading in a mouse model of sickle cell disease during acute, severe hypoxia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A660 BP U324 EP U324 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600659 ER PT J AU Mayfield, JB Quigley, JD AF Mayfield, JB Quigley, JD TI BIS monitoring reduces Phase IPACU admissions in an ambulatory surgical unit (ASU) SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A28 BP U121 EP U121 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600029 ER PT J AU Raines, DE Zachariah, VT AF Raines, DE Zachariah, VT TI Kinetic modeling of isoflurane's effect on nicotinic acetylcholine receptor desensitization implicates a reduction in the agonist dissociation constant SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A332 BP U214 EP U214 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600332 ER PT J AU Raines, DE Zachariah, VT AF Raines, DE Zachariah, VT TI General anesthetics increase the apparent agonist affinity of the nicotinic acetylcholine receptor: A case of (super)family resemblance SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A331 BP U214 EP U214 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600333 ER PT J AU Raveh, Y Ichinose, F Ullrich, RL Bloch, KD Zapol, WM AF Raveh, Y Ichinose, F Ullrich, RL Bloch, KD Zapol, WM TI Role of free radical scavengers on the impaired pulmonary vasodilator response to inhaled NO (INO) in endotoxin (ETX) challenged mice SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A713 BP U337 EP U337 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600713 ER PT J AU Small, SC Barach, P Raemer, D Carroll, J AF Small, SC Barach, P Raemer, D Carroll, J TI Description of a new RRC and ABA approved simulation elective, and resident attitudes towards expanded simulation training SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A1150 BP U460 EP U460 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480601149 ER PT J AU Ullrich, RL Ichinose, F Raveh, Y Bloch, KD Zapol, WM AF Ullrich, RL Ichinose, F Raveh, Y Bloch, KD Zapol, WM TI Preservation of V/Q-matching maintains systemic arterial oxygenation in endotoxin-challenged mice with congenital NOS2 deficiency SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A659 BP U324 EP U324 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600660 ER PT J AU Vu, TN Caneris, OA Stojanovic, MP AF Vu, TN Caneris, OA Stojanovic, MP TI Epidural steroid injections: A prospective analysis of epidurograms and the efficacy of the loss-of-resistance technique SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1999 VL 91 IS 3A SU S MA A928 BP U397 EP U397 PG 1 WC Anesthesiology SC Anesthesiology GA 234JH UT WOS:000082480600927 ER PT J AU Letko, E Bhol, K Pinar, V Foster, CS Ahmed, AR AF Letko, E Bhol, K Pinar, V Foster, CS Ahmed, AR TI Tacrolimus (FK 506) SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID CALCINEURIN PHOSPHATASE-ACTIVITY; ADHESION MOLECULE EXPRESSION; COLLAGEN-INDUCED ARTHRITIS; CORNEAL GRAFT-REJECTION; CELL ACTIVATION GENES; CYCLOSPORINE-A; IMMUNOSUPPRESSIVE AGENT; ATOPIC-DERMATITIS; TOPICAL FK506; FK-506 IMMUNOSUPPRESSION AB Objective: The focus of this review is to summarize the mechanism of action, animal and clinical studies, and adverse effects of tacrolimus (FK 506) in treatment after solid organ transplantation and in treatment of autoimmune diseases. Data sources: A detailed search of the literature was done. Both human and animal studies considered relevant and important were used. Study selection: Material was taken only from peer reviewed journals. Results: FK 506 is a macrolide lactone antibiotic with potent immunosuppressive activity. It acts primarily on CD4+ T helper lymphocytes by inhibiting the production of lymphokines, which are required for cell growth and differentiation, principally interleukin-2, at the transcriptional level. It was first clinically used in patients after liver transplantation. Tacrolimus-based immunosuppression has been proven to be beneficial in prolonging the survival of liver, kidney, heart, lung, pancreas, pancreatic islet, and intestinal allografts. Autoimmune diseases in which the immunosuppressive efficacy of tacrolimus has been tested experimentally include arthritis, systemic lupus erythematosus, uveitis, type-1 diabetes, thyroiditis, autoimmune renal disorders, experimental autoimmune encephalomyelitis, myocarditis, myasthenia gravis, colitis, and alopecia areata. Tacrolimus has been used for treatment of selected human diseases, such as psoriasis, uveitis, corticosteroid-resistant nephrotic syndrome, recalcitrant pyoderma gangrenosum, new onset type 1 diabetes, autoimmune chronic active hepatitis, pediatric autoimmune enteropathy, Crohn's disease and atopic dermatitis. Conclusion: Tacrolimus is a potent immunosuppressive drug in treatment of patients after solid organ transplantation and in selected autoimmune diseases. Further studies are necessary to better understand intracellular mechanism of action and specify therapeutic indications. C1 Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med, 188 Longwood Ave, Boston, MA 02115 USA. NR 135 TC 28 Z9 31 U1 0 U2 8 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD SEP PY 1999 VL 83 IS 3 BP 179 EP 189 DI 10.1016/S1081-1206(10)62636-1 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 240BM UT WOS:000082805900002 PM 10507260 ER PT J AU Choy, YS Dabora, SL Hall, F Ramesh, V Niida, Y Franz, D Kasprzyk-Obara, J Reeve, MP Kwiatkowski, DJ AF Choy, YS Dabora, SL Hall, F Ramesh, V Niida, Y Franz, D Kasprzyk-Obara, J Reeve, MP Kwiatkowski, DJ TI Superiority of Denaturing High Performance Liquid Chromatography over single-stranded conformation and conformation-sensitive gel electrophoresis for mutation detection in TSC2 SO ANNALS OF HUMAN GENETICS LA English DT Article ID TUBEROUS-SCLEROSIS PATIENTS; GENE AB We evaluated denaturing high pressure liquid chromatography (DHPLC) as a scanning method for mutation detection in TSC2, and compared it to conformation-sensitive gel electrophoresis (CSGE) and single-stranded conformation polymorphism analysis (SSCP). The first 20 exons of TSC2 were amplified from 84 TSC patients and screened initially by CSGE and then by DHPLC. Optimization of DHPLC analysis of each exon was carried out by design of primers with minimum variation in the melting temperature of the amplicon, and titration of both elution gradient and temperature. CSGE analysis identified 40 shifts (21 unique) in the 84 patients and 20 exons. All of these variants were detected by DHPLC, and an additional 27 changes (14 unique) were identified. Overall 15 of 28 (54 %) unique single base substitutions were detected by CSGE; all were detected by DHPLC. 25 definite or probable mutations were found in these 84 patients (30 %) in exons 1-20 of TSC2. In a subsequent blinded analysis of 15 samples with 18 distinct TSC2 sequence variants originally detected by SSCP in another centre, all variants were detected by DHPLC except one where the variation occurred within the primer. Ten other (7 unique) sequence variants were detected in these samples which had not been detected by SSCP. Overall, 11 of 16 (69 %) unique single base substitutions were detected by SSCP; all were detected by DHPLC. We conclude that DHPLC is superior to both CSGE and SSCP for detection of DNA sequence variation in TSC2, particularly for single base substitution mutations. C1 Brigham & Womens Hosp, Div Hematol, Genet Lab, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02114 USA. Childrens Hosp, Med Ctr, Div Pediat Neurol, Cincinnati, OH 45229 USA. Childrens Mem Hosp, Dept Child Neurol, Warsaw, Poland. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, Div Hematol, Genet Lab, 221 Longwood Ave,LMRC 301, Boston, MA 02115 USA. EM dk@zk.bwh.harvard.edu FU NCI NIH HHS [CA71445]; NINDS NIH HHS [NS31535] NR 27 TC 81 Z9 94 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0003-4800 EI 1469-1809 J9 ANN HUM GENET JI Ann. Hum. Genet. PD SEP PY 1999 VL 63 BP 383 EP 391 DI 10.1046/j.1469-1809.1999.6350383.x PN 5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 294WB UT WOS:000085932400001 PM 10735580 ER PT J AU Burstein, HJ Ramirez, MJ Petros, WP Clarke, KD Warmuth, MA Marcom, PK Matulonis, UA Parker, LM Harris, LN Winer, EP AF Burstein, HJ Ramirez, MJ Petros, WP Clarke, KD Warmuth, MA Marcom, PK Matulonis, UA Parker, LM Harris, LN Winer, EP TI Phase I study of Doxil and vinorelbine in metastatic breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE Doxil; metastatic breast cancer; phase I; vinorelbine ID LIPOSOMAL DOXORUBICIN; INTRAVENOUS VINORELBINE; FIRST-LINE; TRIAL; THERAPY AB Background: Vinorelbine and Doxil (liposomal doxorubicin) are active chemotherapeutic agents in metastatic breast cancer. A phase I study was designed to evaluate combination therapy. Patients and methods: Thirty women with metastatic breast cancer were enrolled. Dose-limiting toxicity was determined through a dose escalation scheme, and defined for the first treatment cycle, only. Pharmacokinetic studies were performed during the first cycle of treatment. Results: In the first cohort of Doxil 30 mg/m(2) day 1 and vinorelbine 25 mg/m(2) days 1 and 8, patients experienced severe neutropenia. Vinorelbine administration was changed thereafter to days 1 and 15 of each cycle. Dose limiting toxicity was observed at Doxil 50 mg/m(2) and vinorelbine 25 mg/m(2). Doxil 40 mg/m(2) and vinorelbine 30 mg/m(2) was defined as the maximally tolerated dose. Few toxicities (principally neutropenia) were seen at this dose level, with the notable absence of significant nausea, vomiting, or alopecia. Though 63% of patients had received prior anthracycline-based chemotherapy, only one patient developed grade 2 cardiac toxicity. Pharmacokinetic studies revealed prolonged exposure to high doxorubicin concentrations for several days following Doxil administration. Conclusions: Combination chemotherapy with Doxil and vinorelbine affords treatment with two active drugs in women with metastatic breast cancer, and appears to have a favorable toxicity profile. A schedule of Doxil 40 mg/m(2) day 1 and vinorelbine 30 mg/m(2) days 1 and 15 given every 28 days is recommended for phase II studies. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Div Hematol Oncol, Durham, NC USA. RP Winer, EP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Dana Farber Canc Inst,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 12 TC 34 Z9 34 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1999 VL 10 IS 9 BP 1113 EP 1116 DI 10.1023/A:1008323200102 PG 4 WC Oncology SC Oncology GA 239NN UT WOS:000082775000020 PM 10572612 ER PT J AU Zeitels, SM AF Zeitels, SM TI Universal modular glottiscope system: The evolution of a century of design and technique for direct laryngoscopy SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 26-27, 1999 CL PALM DESERT, CALIFORNIA SP Amer Broncho Esophagol Assoc DE direct laryngoscopy; laryngoscope; microlaryngoscopy; microsurgery; phonomicrosurgery; phonosurgery; vocal cords; vocal folds ID CLINICAL EXPERIENCE; LASER SURGERY; MICROFLAP; CO2-LASER; EXPOSURE AB Since Kirstein introduced formal direct examination (autoscopy) of the glottis in 1895, a great number of laryngoscopes have been produced to view the vocal folds; however, none have had universal appeal. The primary goals for the designs have been to optimize exposure and to facilitate instrumentation of the glottis. An analysis of more than 50 laryngoscopes was done to assess key design characteristics that would ideally be present in a laryngoscope for optimally viewing the musculomembranous vocal folds. The Pro/Engineer and Pro/Mechanica computer programs were used to model the universal modular glottiscope. This new laryngoscope comprises a plurality of specially designed examining tubes that are bivalved proximally to improve utilization of hand instrumentation, and form a single tube distally to achieve internal distention of the supraglottal tissues. The distal lumen has an arcuate isosceles-triangular conformation to optimally expose the glottis. The base of the tube is detachable for the difficult intubation or the placement of bronchoscopes. The examining tubes vary in size and dimension to accommodate the diversity of human anatomy. The tubes are easily attachable to and detachable from an ergodynamically designed universal handle that can be joined to fulcrum laryngoscope holders or suspension gallows. The universal modular glottiscope evolved from the selective integration of optimal 20th-century design modifications of Kirstein's original autoscope. This new laryngoscope is ideally suited for phonomicro-surgery as well as for difficult intubation. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 107 TC 5 Z9 5 U1 0 U2 4 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 SEP PY 1999 VL 108 IS 9 SU 179 BP 2 EP 24 PN 2 PG 23 WC Otorhinolaryngology SC Otorhinolaryngology GA 237HR UT WOS:000082650200001 ER PT J AU Rabkin, JM Smith, MJ Orloff, SL Corless, CL Stenzel, P Olyaei, AJ AF Rabkin, JM Smith, MJ Orloff, SL Corless, CL Stenzel, P Olyaei, AJ TI Fatal fulminant hepatitis associated with bromfenac use SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE hepatic failure; bromfenac AB OBJECTIVE: To report a case of fulminant hepatic failure associated with the use of bromfenac, a new analog of the phenyl acetate class of nonsteroidal antiinflammatory drugs. CASE SUMMARY: A 60-year-old white woman with liver failure who had no known history of chronic liver disease was transferred to the liver transplant unit for evaluation. For three months preceding her illness, the patient was treated with bromfenac 25 mg po qid for arthritic pain, Prior to the initiation of bromfenac, her liver function test results were normal. Etiologic evaluation at presentation was unremarkable. The patient's condition continued to deteriorate, with the development of hepatic encephalopathy and worsening Liver function test results while awaiting liver transplantation. Progressive hepatic and renal dysfunction along with respiratory decompensation ensued, and the patient died 48 days after initial presentation. CONCLUSION: Fulminant hepatic failure associated with the prolonged use of bromfenac appears to be an idiosyncratic response consistent with experience with other agents of its class. This case along with other cases of serious hepatotoxicity associated with the use of this agent ultimately resulted in bromfenac's removal from the market. C1 Oregon Hlth Sci Univ, Dept Surg, Sect Liver Pancreas Transplantat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. RP Rabkin, JM (reprint author), Oregon Hlth Sci Univ, Dept Surg, Sect Liver Pancreas Transplantat, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 9 TC 21 Z9 21 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD SEP PY 1999 VL 33 IS 9 BP 945 EP 947 DI 10.1345/aph.18364 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 232ZM UT WOS:000082401100011 PM 10492497 ER PT J AU Khuri, SF Daley, J Henderson, W Hur, K Hossain, M Soybel, D Kizer, KW Aust, JB Bell, RH Chong, V Demakis, J Fabri, PJ Gibbs, JO Grover, F Hammermeister, K McDonald, G Passaro, E Phillips, L Scamman, F Spencer, J Stremple, JF AF Khuri, SF Daley, J Henderson, W Hur, K Hossain, M Soybel, D Kizer, KW Aust, JB Bell, RH Chong, V Demakis, J Fabri, PJ Gibbs, JO Grover, F Hammermeister, K McDonald, G Passaro, E Phillips, L Scamman, F Spencer, J Stremple, JF CA VA Natl Surgical Quality Improvement Program TI Relation of surgical volume to outcome in eight common operations - Results from the VA National Surgical Quality Improvement Program SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 119th Annual Meeting of the American-Surgical-Association CY APR 15-17, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Surg Assoc ID NEW-YORK-STATE; ABDOMINAL AORTIC-ANEURYSMS; HOSPITAL VOLUME; CAROTID ENDARTERECTOMY; LAPAROSCOPIC CHOLECYSTECTOMY; POSTOPERATIVE MORTALITY; RISK ADJUSTMENT; SURGERY; CARE; EXPERIENCE AB Objective To examine. in the Veterans Health Administration (VHA), the relation between surgical volume and outcome in eight commonly performed operations of intermediate complexity. Summary Background Data In multihospital health care systems such as VHA, consideration is often given to closing low-volume surgical services, with the assumption that better surgical outcomes are achieved in hospitals with larger surgical volumes. Literature data to support this assumption in intermediate-complexity operations are either limited or controversial. Methods The VHA National Surgical Quality Improvement Program data on nonruptured abdominal aortic aneurysmectomy, vascular infrainguinal reconstruction, carotid endarterectomy (CEA), lung lobectomy/pneumonectomy, open and laparoscopic cholecystectomy, partial colectomy, and total hip arthroplasty were used. Pearson correlation, analysis of variance, mixed effects hierarchical logistic regression. and automatic interaction detection analysis were used to assess the association of annual procedure/specialty volume with risk-adjusted 30-day death (and stroke in CEA), Results Eight major surgical procedures (68,631 operations) were analyzed. No statistically significant associations between procedure or specialty volume and 30-day mortality rate (or 30-day stroke rate in CEA) were found. Conclusions In VHA hospitals, the procedure and surgical specialty volume in eight prevalent operations of intermediate complexity are not associated with risk-adjusted 30-day mortality rate from these operations, or with the risk-adjusted 30-day stroke rate from CEA. Volume of surgery in these operations should not be used as a surrogate for quality of surgical care. C1 Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. Hines VA Cooperat Studies Program Coordinating Ct, Hines, IL USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA. VA Puget Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Vet Integrated Serv Network 17, Grand Prairie, TX USA. Tampa VA Med Ctr, Tampa, FL USA. Univ S Florida, Coll Med, Tampa, FL USA. Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Dept Vet Affairs Headquarters, Dept Surg, Washington, DC USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Integrated Serv Network 11, Ann Arbor, MI USA. Natl Anesthesia Serv, Dept Anesthesia, Iowa City, IA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Pittsburgh VA Med Ctr, Pittsburgh, PA USA. RP Khuri, SF (reprint author), Brockton W Roxbury Vet Affairs Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 41 TC 202 Z9 202 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 1999 VL 230 IS 3 BP 414 EP 429 DI 10.1097/00000658-199909000-00014 PG 16 WC Surgery SC Surgery GA 234ZT UT WOS:000082514800027 PM 10493488 ER PT J AU Souba, WW Mahon, J AF Souba, WW Mahon, J TI Competing in the new health care environment: Strategies for surgical oncology SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID MEDICAL-SCHOOLS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. Boston Univ, Sch Management, Dept Management Policy, Boston, MA 02215 USA. RP Souba, WW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, 100 Blossom St,Cox 626, Boston, MA 02114 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 1999 VL 6 IS 6 BP 614 EP 622 DI 10.1007/s10434-999-0614-2 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 234FQ UT WOS:000082474200020 PM 10493633 ER PT J AU Hooper, BA Domankevitz, Y Lin, CP Anderson, RR AF Hooper, BA Domankevitz, Y Lin, CP Anderson, RR TI Precise, controlled laser delivery with evanescent optical waves SO APPLIED OPTICS LA English DT Article ID ABLATION; ERBIUM; WATER AB Precise laser surgery is possible with laser pulses at wavelengths that are strongly absorbed at the surface of tissue. However, pulses at these wavelengths (far UV, far infrared) are not compatible with fiber-optic transmission, making endoscopic surgical procedures inside the body difficult. We use evanescent optical waves to demonstrate an alternative for confining energy near the tissue surface. Precise, superficial tissue ablation is achieved with evanescent waves generated at a sapphire-tissue interface by a free-electron laser, where the ablation depth may be varied. A new class of precise, controlled laser surgical tools may be achieved in this novel approach for use in endoscopic procedures. Electromagnetic theory governing evanescent-wave tissue ablation is presented. (C) 1999 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Duke Univ, Dept Phys, Free Elect Laser Lab, Durham, NC 27708 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. RP Hooper, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. EM hoop@fel.duke.edu NR 17 TC 4 Z9 4 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD SEP 1 PY 1999 VL 38 IS 25 BP 5511 EP 5517 DI 10.1364/AO.38.005511 PG 7 WC Optics SC Optics GA 232JQ UT WOS:000082367900034 PM 18324060 ER EF