FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Goldstein, JM Cohen, LS Horton, NJ Lee, H Andersen, S Tohen, M Crawford, AMK Tollefson, G AF Goldstein, JM Cohen, LS Horton, NJ Lee, H Andersen, S Tohen, M Crawford, AMK Tollefson, G TI Sex differences in clinical response to olanzapine compared with haloperidol SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; treatment response; sex; olanzapine; haloperidol ID GENDER DIFFERENCES; SCHIZOPHRENIC-PATIENTS; LONGITUDINAL DATA; MENSTRUAL-CYCLE; SAMPLING BIASES; CEREBRAL-CORTEX; FEMALE RAT; ESTROGEN; ESTRADIOL; AGE AB There is current disagreement over whether men and women respond differently to typical or atypical antipsychotic medications. This study reanalyzed a large international clinical trial of olanzapine (Olz) compared with haloperidol (Hal) to test for sex differences in treatment response, controlling for illness chronicity and menopausal status. We hypothesized that women would show a greater response to either medication than men, particularly among first admission, premenopausal women. DSM-III-R schizophrenia inpatients (700 women and 1295 men) were randomly assigned to a 6-week trial of Olz vs. Hal. Longitudinal random effect models were used to test for interactions of sex with medication, chronicity and menopausal status on treatment response. Findings showed that women on olanzapine had a greater drop in overall symptomatology by week 4 than any other group, and their level of symptomatology remained lower throughout the 6-week trial. The sex differences in treatment response in olanzapine compared with haloperidol were, in part, dependent on chronicity and, in women, menopausal status. That is, first episode women on haloperidol exhibited an increase in symptomatology over the 6-week trial compared to their male counterparts, while multiply hospitalized women had a better treatment response on haloperidol than their male counterparts. Women on olanzapine had a significantly better treatment response than men, regardless of chronicity. Finally, premenopausal women had a significantly better treatment response than postmenopausal women, regardless of treatment and chronicity. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Mental Hlth Ctr, Harvard Inst Psychiat Epidemiol & Genet, Sch Med,Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Clin Psychopharmacol Unit, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RP Goldstein, JM (reprint author), Harvard Univ, Massachusetts Mental Hlth Ctr, Harvard Inst Psychiat Epidemiol & Genet, Sch Med,Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. RI Horton, Nicholas/A-2493-2008; OI Horton, Nicholas/0000-0003-3332-4311 FU NIMH NIH HHS [R01 MH56956] NR 52 TC 38 Z9 39 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 15 PY 2002 VL 110 IS 1 BP 27 EP 37 AR PII S0165-1781(02)00028-8 DI 10.1016/S0165-1781(02)00028-8 PG 11 WC Psychiatry SC Psychiatry GA 560RU UT WOS:000176095700004 PM 12007591 ER PT J AU Gurvits, TV Carson, MA Metzger, L Croteau, HB Lasko, NB Orr, SP Pitman, RK AF Gurvits, TV Carson, MA Metzger, L Croteau, HB Lasko, NB Orr, SP Pitman, RK TI Absence of selected neurological soft signs in Vietnam nurse veterans with post-traumatic stress disorder SO PSYCHIATRY RESEARCH LA English DT Article DE nurses; Vietnam; stress disorders; post-traumatic; neurological manifestations ID SCALE AB This study examined eight neurological soft signs (NSSs), which had previously proved successful in discriminating medication-free post-traumatic stress disorder (PTSD) from non-PTSD combat veterans and sexually abused women, in 82 unmedicated female nurse Vietnam veterans, 32 with and 50 without PTSD. The increased NSSs observed in the previously studied PTSD samples were not found in the nurses with PTSD. The results fail to support the hypothesis that the stress of a traumatic event and/or resultant PTSD damages the nervous system. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Vet Affairs Med Ctr, VA Res Serv, Manchester, NH 03103 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Anselm Coll, Manchester, NH 03102 USA. RP Gurvits, TV (reprint author), Vet Affairs Med Ctr, VA Res Serv, 228 Maple St, Manchester, NH 03103 USA. NR 6 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 15 PY 2002 VL 110 IS 1 BP 81 EP 85 AR PII S0165-1781(02)00026-4 DI 10.1016/S0165-1781(02)00026-4 PG 5 WC Psychiatry SC Psychiatry GA 560RU UT WOS:000176095700009 PM 12007596 ER PT J AU Schmidtko, J Wang, RJ Wu, CL Mauiyyedi, S Harris, NL Della Pelle, P Brousaides, N Zagachin, L Ferry, JA Wang, F Kawai, T Sachs, DH Cosimi, AB Colvin, RB AF Schmidtko, J Wang, RJ Wu, CL Mauiyyedi, S Harris, NL Della Pelle, P Brousaides, N Zagachin, L Ferry, JA Wang, F Kawai, T Sachs, DH Cosimi, AB Colvin, RB TI Posttransplant lymphoproliferative disorder associated with an Epstein-Barr-related virus in cynomolgus monkeys SO TRANSPLANTATION LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RENAL-ALLOGRAFT TOLERANCE; CELL LINES; LYMPHOMA; HERPESVIRUS; EXPRESSION; ANTIGEN; CHIMERISM; IDENTIFICATION; TRANSMISSION AB Background. Human posttransplant lymphoproliferative disorder (PTLD) has been shown to be associated with Epstein-Barr virus (EBV) infection. Primate animal models of PTLD and the use of molecular markers in its diagnosis have not been reported. This study was designed to evaluate the frequency, pathology, and molecular characteristics of PTLD in cynomolgus kidney allograft recipients. Methods. Over a 5-year period (January 1995 to November 2000), 160 primate renal transplants were performed at the Massachusetts General Hospital (MGH). Of these, all cases (n=9) that developed PTLD were included. H&E stained paraffin sections of all available tissue samples from the cases were evaluated for the presence of PTLD. Immunoperoxidase staining for T cells (CD3), B cells (CD20), kappa and lambda light chains as well as EBV nuclear antigens (EBNA2) and latent membrane proteins (EBV LMP-1) was done on paraffin sections using standard immunohistochemical (IHC) methods. In situ hybridization for EBV encoded RNA (EBER) was performed in all tissue samples with atypical lymphoid proliferations, using a novel EBER nucleotide probe based on consensus gene sequences from EBV and the related herpes lymphocryptoviruses (LCV) infecting baboons and rhesus macaques. Results. Of 160 consecutive primate renal transplants performed at MGH, 5.6% developed PTLD 28103 days after transplantation. In all cases, the lymph nodes were involved and effaced by an atypical polymorphous lymphoid proliferation of EBER+ B cells, diagnostic for PTLD. Focal staining for EBNA-2 was noted in tumor cells. In 67% (six of nine) the PTLD infiltrates were present in extra nodal sites, notably liver (56%), lung (44%), heart (44%), renal allograft (44%), and native kidney (22%). The spleen was involved by PTLD in all four animals that had not undergone a pretransplant splenectomy. The PTLD morphology was similar in all cases and predominantly of the polymorphous type, however, some of these showed areas that appeared minimally polymorphous. No cases of monomorphic PTLD were seen. Conclusions. By in situ hybridization, expression of the RNA product, homologous for EBV-encoded RNA (EBER) was identified in the PTLD tumor cells of all cases, indicating latent primate EBV- related infection. This report identifies a novel animal model of EBV associated PTLD in the setting of kidney transplantation, with valuable implications for managing and understanding human PTLD and oncogenesis. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 225, Boston, MA 02114 USA. FU NHLBI NIH HHS [5R01 HL63430-02, P01-HL18646]; NIAID NIH HHS [5RO1 AI37692-05, R01 AI037692, R01 AI037692-09, R21 AI037692, R21 AI037692-06] NR 36 TC 40 Z9 42 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 MAY 15 PY 2002 VL 73 IS 9 BP 1431 EP 1439 AR UNSP 0041-1337/02/7309-1431/0 DI 10.1097/00007890-200205150-00012 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 557WZ UT WOS:000175933100009 PM 12023621 ER PT J AU Levy, O Sisson, RB Fryer, HE Goldmann, D Valore, E Ganz, T White, ML Carroll, SF Lehmann, L Guinan, EC AF Levy, O Sisson, RB Fryer, HE Goldmann, D Valore, E Ganz, T White, ML Carroll, SF Lehmann, L Guinan, EC TI Neutrophil defense in patients undergoing bone marrow transplantation: Bactericidal/permeability-increasing protein (BPI) and defensins in graft-derived neutrophils SO TRANSPLANTATION LA English DT Article ID COLONY-STIMULATING FACTOR; ESCHERICHIA-COLI; HOST-DEFENSE; IN-VITRO; GRANULOCYTE; PEPTIDES; CHILDREN; INFECTION; CANCER; AGENTS AB Background. Even after neutrophil counts return to near normal levels, patients undergoing myeloablative chemotherapy and bone marrow transplantation (BMT) are at risk for invasive bacterial infections, raising the possibility that their neutrophil function might be impaired. To assess potential qualitative defects in neutrophil function in patients undergoing BMT, we measured neutrophil content of the antimicrobial (poly)peptides BPI and defensins. Methods. Neutrophil extracts were analyzed for content of BPI by Western blotting and ELISA and for defensin peptides by acid-urea polyacrylamide gel electrophoresis (PAGE). Antibacterial activity of neutrophil extracts was measured against Escherichia coli K1/r, a clinical isolate sensitive to synergistic killing by BPI and defensins. Results. Neutrophil extract BPI content on post-BMT days +20, +30, and +100 (169+/-35, 232+/-57, and 160+/-55 ng per 10(6) neutrophils, respectively) was similar to the neutrophil BPI content of normal controls (163+/-35 ng per 10(6) neutrophils). Neutrophil defensin content also did not vary during this time-span. Activity of neutrophil extracts against E. coli K1/r did not differ between BAIT patients and controls. Conclusion. At post-BMT days +20 to +100, neutrophils derived from engrafted marrow contain normal quantities of BPI and defensins. Any deficiencies of neutrophil function during this phase are not due to inadequate expression of these antimicrobial (poly)peptides but could reflect abnormalities in other aspects of neutrophil function. C1 Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Childrens Hosp, Gen Clin Res Ctr, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. XOMA US LLC, Dept Preclin Res, Berkeley, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Levy, O (reprint author), Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [M01RR02172] NR 26 TC 7 Z9 7 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 MAY 15 PY 2002 VL 73 IS 9 BP 1522 EP 1526 DI 10.1097/00007890-200205150-00027 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 557WZ UT WOS:000175933100024 PM 12023636 ER PT J AU Olbrot, M Rud, J Moss, LG Sharma, A AF Olbrot, M Rud, J Moss, LG Sharma, A TI Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BINDING-ACTIVITY; C-MAF; DIFFERENTIATION; EXPRESSION; GLUCOSE; ENHANCER; PROTEIN; DNA; PHOSPHORYLATION; SEQUENCES AB of the three critical enhancer elements that mediate beta-cell-specific and glucose-responsive expression of the insulin gene, only the identity of the transcription factor binding to the RIPE3b element (RIPE3b1) has remained elusive. Using a biochemical purification approach, we have identified the RIPE3b1 factor as a mammalian homologue of avian MafA/L-Maf (mMafA). The avian MafA is a cell-type determination factor that expressed ectopically can trigger lens differentiation program, but no mammalian homologue of avian MafA has previously been identified. Here, we report cloning of the human mafA (hMafA) and demonstrate that it can specifically bind the insulin enhancer element RIPE3b and activate insulin-gene expression. In addition, mMafA has a very restrictive cellular distribution and is selectively expressed in pancreatic beta but not in a cells. We suggest that mMafA has an essential role in the function and differentiation of beta-cells and thus may be associated with the pathophysiological origins of diabetes. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Tufts Univ, Dept Physiol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Sharma, A (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-36836, P30 DK036836] NR 33 TC 211 Z9 217 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 MAY 14 PY 2002 VL 99 IS 10 BP 6737 EP 6742 DI 10.1073/pnas.102168499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552TZ UT WOS:000175637300041 PM 12011435 ER PT J AU Hodi, FS Schmollinger, JC Soiffer, RJ Salgia, R Lynch, T Ritz, J Alyea, EP Yang, JH Neuberg, D Mihm, M Dranoff, G AF Hodi, FS Schmollinger, JC Soiffer, RJ Salgia, R Lynch, T Ritz, J Alyea, EP Yang, JH Neuberg, D Mihm, M Dranoff, G TI ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VACUOLAR H+-ATPASE; COLONY-STIMULATING FACTOR; ACCESSORY SUBUNIT AC45; METASTATIC MELANOMA; INFILTRATING LYMPHOCYTES; ANTITUMOR IMMUNITY; CANCER ANTIGENS; CELL RESPONSE; IN-VIVO; PEPTIDE AB An important goal of cancer immunology is the identification of antigens associated with tumor destruction. Vaccination with irradiated tumor cells engineered to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) generates potent, specific, and long-lasting antitumor immunity in multiple murine tumor models. A phase I clinical trial of this vaccination strategy in patients with advanced melanoma demonstrated the consistent induction of dense CD4(+) and CD8(+) T lymphocyte and plasma cell infiltrates in distant metastases, resulting in extensive tumor destruction, fibrosis, and edema. Antimelanoma antibody and cytotoxic T cell responses were associated with tumor cell death. To characterize the targets of these responses, we screened an autologous cDNA expression library prepared from a densely infiltrated metastasis with postvaccination sera from a long-term responding patient. High-titer IgG antibodies detected ATP6S1, a putative accessory unit of the vacuolar H+-ATPase complex. A longitudinal analysis of this patient revealed an association between the vaccine-induced increase in antibodies to ATP6S1 and tumor destruction. Three additional vaccinated melanoma patients and three metastatic non-small cell lung carcinoma patients vaccinated with autologous GM-CSF-secreting tumor cells similarly showed a correlation between humoral responses to ATP6S1 and tumor destruction. Moreover, a chronic myelogenous leukemia patient who experienced a complete remission after CD4+ donor lymphocyte infusions also developed high-titer antibodies to ATP6S1. Lastly, vaccination with GM-CSF-secreting B16 melanoma cells stimulated high-titer antibodies to ATPS1 in a murine model. Taken together, these findings demonstrate that potent humoral responses to ATP6S1 are associated with immune-mediated destruction of diverse tumors. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA74886, CA39542, CA78880, P01 CA039542, R01 CA074886] NR 36 TC 38 Z9 39 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 2002 VL 99 IS 10 BP 6919 EP 6924 DI 10.1073/pnas.102025999 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552TZ UT WOS:000175637300073 PM 11983866 ER PT J AU Xue, L Chu, F Cheng, Y Sun, XJ Borthakur, A Ramarao, M Pandey, P Wu, M Schlossman, SF Prasad, KVS AF Xue, L Chu, F Cheng, Y Sun, XJ Borthakur, A Ramarao, M Pandey, P Wu, M Schlossman, SF Prasad, KVS TI Siva-1 binds to and inhibits BCL-X-L-mediated protection against UV radiation-induced apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NECROSIS-FACTOR RECEPTOR; CAPSID PROTEIN VP2; TRANSGENIC MICE; PROAPOPTOTIC PROTEIN; CELL SURVIVAL; T-CELLS; IN-VIVO; C-MYC; CD27; GENE AB We previously cloned Siva-1 by using the cytoplasmic tail of CD27, a member of the tumor necrosis factor receptor family, as the bait in the yeast two-hybrid system. The Siva gene is organized into four exons that code for the predominant full-length Siva-1 transcript, whereas its alternate splice form, Siva-2, lacks exon 2 coding sequence. Various groups have demonstrated a role for Siva-1 in several apoptotic pathways. Interestingly, the proapoptotic properties of Siva-1 are lacking in Siva-2. The fact that Siva-1 is partly localized to mitochondria despite the absence of any mitochondrial targeting signal, it harbors a 20-aa-long putative amphipathic helical structure that is absent in Siva-2, and that its expression is restricted to double-positive (CD3(+), CD4(+), CD8(+)) thymocytes like BCL-X-L, prompted us to test for a potential interaction between Siva-1 and BCL-XL. Here, we show that Siva-1 binds to and inhibits BCL-X-L-mediated protection against UV radiation-induced apoptosis. Indeed, the unique amphipathic helical region (SAH) present in Siva-1 is required for its binding to BCL-XL and sensitizing cells to UV radiation. Natural complexes of Siva-1/BCL-X-L are detected in HUT78 and murine thymocyte, suggesting a potential role or Siva-1 in regulating T cell homeostasis. C1 Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Prasad, KVS (reprint author), Univ Illinois, Dept Microbiol & Immunol, 835 S Wolcott Ave,Room 820, Chicago, IL 60612 USA. FU NIGMS NIH HHS [GM56706] NR 39 TC 54 Z9 59 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 MAY 14 PY 2002 VL 99 IS 10 BP 6925 EP 6930 DI 10.1073/pnas.102182299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552TZ UT WOS:000175637300074 PM 12011449 ER PT J AU Niederman, TMJ Ghogawala, Z Carter, BS Tompkins, HS Russell, MM Mulligan, RC AF Niederman, TMJ Ghogawala, Z Carter, BS Tompkins, HS Russell, MM Mulligan, RC TI Antitumor activity of cytotoxic T lymphocytes engineered to target vascular endothelial growth factor receptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR-TOXIN CONJUGATE; TUMOR VASCULATURE; CELL PROLIFERATION; IN-VIVO; ADOPTIVE TRANSFER; SOLID TUMORS; ANGIOGENESIS; VEGF; GENE; INHIBITION AB The demonstration that angiogenesis is required for the growth of solid tumors has fueled an intense interest in the development of new therapeutic strategies that target the tumor vasculature. Here we report the development of an immune-based antiangiogenic strategy that is based on the generation of T lymphocytes that possess a killing specificity for cells expressing vascular endothelial growth factor receptors (VEGFRs). To target VEGFR-expressing cells, recombinant retroviral vectors were generated that encoded a chimeric T cell receptor comprised of VEGF sequences linked to intracellular signaling sequences derived from the zeta chain of the T cell receptor, After transduction of primary murine CD8 lymphocytes by such vectors, the transduced cells were shown to possess an efficient killing specificity for cells expressing the VEGF receptor, Flk-1, as measured by in vitro cytotoxicity assays. After adoptive transfer into tumor-bearing mice, the genetically modified cytotoxic T lymphocytes strongly inhibited the growth of a variety of syngeneic murine tumors and human tumor xenografts. An increased effect on in vivo tumor growth inhibition was seen when this therapy was combined with the systemic administration of TNP-470, a conventional angiogenesis inhibitor. The utilization of the immune system to target angiogenic markers expressed on tumor vasculature may prove to be a powerful means for controlling tumor growth. C1 Childrens Hosp, Div Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Mulligan, RC (reprint author), Childrens Hosp, Div Mol Med, Enders 861, Boston, MA 02115 USA. FU NCI NIH HHS [CA73133-01, CA83772-02, F32 CA073133] NR 47 TC 70 Z9 76 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 MAY 14 PY 2002 VL 99 IS 10 BP 7009 EP 7014 DI 10.1073/pnas.092562399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 552TZ UT WOS:000175637300088 PM 11997459 ER PT J AU Walsh, CR Larson, MG Leip, ER Vasan, RS Levy, D AF Walsh, CR Larson, MG Leip, ER Vasan, RS Levy, D TI Serum potassium and risk of cardiovascular disease - The Framingham Heart Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CREATININE ASSAYS; DIETARY POTASSIUM; STROKE MORTALITY; SODIUM; MAGNESIUM; MEN AB Background: Published studies of the association between serum potassium concentration and risk for cardiovascular disease in community-based populations have reported conflicting results. We sought to determine the association between serum potassium concentration and cardiovascular disease risk in the Framingham Heart Study. Methods: A total of 3151 participants (mean age, 43 years; 48% men) in the Framingham Heart Study who were free of cardiovascular disease and not taking medications affecting potassium homeostasis had serum potassium levels measured (1979-1983). Proportional hazards models were used to determine the association of serum potassium concentration at baseline with the incidence of cardiovascular disease at follow-up. Results: During mean follow-up of 16 years, 313 cardiovascular disease events occurred, including 46 cardiovascular disease-related deaths. After adjustment for age, serum potassium level was marginally associated with risk of cardiovascular disease (hazard ratio [HR] per I mg/dL increment, 1.03; 95% confidence interval [CI], 1.00-1.05; P=.02). However, after further adjustment for multiple confounders, serum potassium level was not significantly associated with cardiovascular disease risk (HR, 1.00; 95% Cl, 0.98-1.03). There were no significant associations between serum potassium level and cardiovascular disease-related death in either age- and sex-adjusted models (HR, 1.06; 95% Cl, 0.99-1.12) or multivariable-adjusted models (HR, 1.04; 95% CI, 0.97-1.11). Conclusion. In our community-based sample of individuals free of cardiovascular disease and not taking medications that affect potassium homeostasis, serum potassium level was not associated with risk of cardiovascular disease. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Evans Dept Med, Sect Epidemiol & Prevent Med, Boston, MA 02118 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [1K24 HL04334, N01-HC-38038] NR 21 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 13 PY 2002 VL 162 IS 9 BP 1007 EP 1012 DI 10.1001/archinte.162.9.1007 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 550PW UT WOS:000175512300007 PM 11996610 ER PT J AU Mortensen, EM Coley, CM Singer, DE Marrie, TJ Obrosky, DS Kapoor, WN Fine, MJ AF Mortensen, EM Coley, CM Singer, DE Marrie, TJ Obrosky, DS Kapoor, WN Fine, MJ TI Causes of death for patients with community-acquired pneumonia - Results from the pneumonia patient outcomes research team cohort study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MORTALITY; DISEASE; CARE AB Background: To our knowledge, no previous study has systematically examined pneumonia-related and pneumonia-unrelated mortality. This study was performed to identify the cause(s) of death and to compare the timing and risk factors associated with pneumonia-related and pneumonia-unrelated mortality. Methods: For all deaths within 90 days of presentation, a synopsis of all events preceding death was independently reviewed by 2 members of a 5-member review panel (C.M.C., D.E.S., T.J.M., W.N.K., and M.J.F.). The underlying and immediate causes of death and whether pneumonia had a major, a minor, or no apparent role in the death were determined using consensus. Death was defined as pneumonia related if pneumonia was the underlying or immediate cause of death or played a major role in the cause of death. Competing-risk Cox proportional hazards regression models were used to identify baseline characteristics associated with mortality. \ Results: Patients (944 outpatients and 1343 inpatients) with clinical and radiographic evidence of pneumonia were enrolled, and 208 (9%) died by 90 days. The most frequent immediate causes of death were respiratory failure (38%), cardiac conditions (13%), and infectious conditions (11%); the most frequent underlying causes of death were neurological conditions (29%), malignancies (24%), and cardiac conditions (14%). Mortality was pneumonia related in 110 (53%) of the 208 deaths. Pneumonia-related deaths were 7.7 times more likely to occur within 30 days of presentation compared with pneumonia-unrelated deaths. Factors independently associated with pneumonia-related mortality were hypothermia, altered mental status, elevated serum urea nitrogen level, chronic liver disease, leukopenia, and hypoxemia. Factors independently associated with pneumonia-unrelated mortality were dementia, immunosuppression, active cancer, systolic hypotension, male sex, and multilobar pulmonary infiltrates. Increasing age and evidence of aspiration were independent predictors of both types of mortality. Conclusions: For patients with community-acquired pneumonia, only half of all deaths are attributable to their acute illness. Differences in the timing of death and risk factors for mortality suggest that future studies of community-acquired pneumonia should differentiate all-cause and pneumonia-related mortality. C1 VA Pittsburgh Healthcare Syst, Ctr Study Hlth Dispar, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Alberta, Dept Med, Div Infect Dis, Edmonton, AB, Canada. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Study Hlth Dispar, Univ Dr C,Locat 11E127,Mail Stop 130-U, Pittsburgh, PA 15240 USA. OI Mortensen, Eric/0000-0002-3880-5563 FU AHRQ HHS [R01 HS06468, F32 HS00135] NR 19 TC 213 Z9 221 U1 1 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 MAY 13 PY 2002 VL 162 IS 9 BP 1059 EP 1064 DI 10.1001/archinte.162.9.1059 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 550PW UT WOS:000175512300015 PM 11996618 ER PT J AU Scheijen, B Griffin, JD AF Scheijen, B Griffin, JD TI Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease SO ONCOGENE LA English DT Review DE leukemia; lymphoma; protein tyrosine kinase; signal transduction; translocation ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; LARGE-CELL LYMPHOMA; GROWTH-FACTOR RECEPTOR; CHRONIC MYELOGENOUS LEUKEMIA; FACTOR-BETA-RECEPTOR; SRC HOMOLOGY-2 DOMAIN; NON-HODGKINS-LYMPHOMA; INFLAMMATORY MYOFIBROBLASTIC TUMOR; CHRONIC MYELOMONOCYTIC LEUKEMIA AB Tyrosine kinase oncogenes are formed as a result of mutations that induce constitutive kinase activity. Many of these tyrosine kinase oncogenes that are derived from genes, such as c-Abl, c-Fes, FIt3, c-Fms, c-Kit and PDGFRbeta, that are normally involved in the regulation of hematopoiesis or hematopoietic cell function. Despite differences in structure, normal function, and subcellular location, many of the tyrosine kinase oncogenes signal through the same pathways, and typically enhance proliferation and prolong viability. They represent excellent potential drug targets, and it is likely that additional mutations will be identified in other kinases, their immediate downstream targets, or in proteins regulating their function. 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. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Scheijen, Blanca/E-3523-2016 OI Scheijen, Blanca/0000-0001-8029-9230 NR 371 TC 109 Z9 111 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 13 PY 2002 VL 21 IS 21 BP 3314 EP 3333 DI 10.1038/sj/onc/1205317 PG 20 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 552RL UT WOS:000175633300007 PM 12032772 ER PT J AU Cantor, AB Orkin, SH AF Cantor, AB Orkin, SH TI Transcriptional regulation of erythropoiesis: an affair involving multiple partners SO ONCOGENE LA English DT Article DE GATA-1; FOG-1; PU.1; EKLF; transcription factor; cross-antagonism ID T-CELL LEUKEMIA; ZINC-FINGER PROTEIN; FACTOR GATA-1; DNA-BINDING; ERYTHROID-DIFFERENTIATION; MICE LACKING; MEGAKARYOCYTIC DIFFERENTIATION; HEMATOPOIETIC LINEAGES; VASCULAR DEVELOPMENT; HEART MORPHOGENESIS AB Previous work has demonstrated that lineage-specific transcription factors play essential roles in red blood cell development. More recent studies have shown that these factors participate in critical protein-protein interactions in addition to binding DNA. The zinc finger transcription factor GATA-1, a central mediator of erythroid gene expression, interacts with multiple proteins including FOG-1, EKLF, SP1, CBP/p300 and PU.1. The mechanisms by which these interactions influence GATA-1 function, as well as any possible relationships between these seemingly disparate complexes, remain incompletely understood. However, several new findings have provided further insight into the functional significance of some of these interactions. Studies involving point mutants of GATA-1 have shown that a direct physical interaction between GATA-I and FOG-1 is essential for normal human erythroid and megakaryocyte maturation in vivo. In addition, evidence has emerged that physical interaction between GATA-I and the myeloid/lymphoid specific factor PU.1, an oncogene implicated in murine erythroleukemia, acts to functionally cross-antagonize one another. This provides a possible mechanism by which dysregulated expression of hematopoietic transcription factors leads to lineage maturation arrest in leukemias. C1 Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [K08 CA 82175-02] NR 76 TC 394 Z9 404 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 13 PY 2002 VL 21 IS 21 BP 3368 EP 3376 DI 10.1038/sj/onc/1205326 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 552RL UT WOS:000175633300010 PM 12032775 ER PT J AU Keire, DA Solomon, TE Reeve, JR AF Keire, DA Solomon, TE Reeve, JR TI NMR evidence for different conformations of the bioactive region of rat CCK-8 and CCK-58 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE N-15-NMR; HSQC; cholecystokinin; CCK-58; CCK-8; tertiary structure ID FOLDING INITIATION SITES; FLUORESCENCE-TRANSFER MEASUREMENTS; CORRELATION SPECTROSCOPY; PEPTIDE MODELS; H-1-NMR SPECTROSCOPY; IMPROVED SENSITIVITY; CHOLECYSTOKININ; FRAGMENTS; MYOGLOBIN; H-1 AB Sulfated CCK-58 and CCK-8 have identical bioactive C-terminal primary sequences but distinct C-terminal solution structures and different bioactivities. To examine structural differences in greater detail, rat CCK-58 and -8 were synthesized with isotopic enrichment of C-terminal residues with N-15 at alpha-amino nitrogens. Proton and nitrogen chemical shift assignments of peptide solutions were obtained by homo- and heteronuclear NMR methods. These data show that the tertiary structure ensembles of C-terminal CCK-8 and CCK-58 differ significantly. Thus, distinct solution conformations may explain differences in CCKA and CCKB receptor interactions of large and small molecular forms of CCK. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Greater Los Angeles Vet Hlth Care Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Digest Dis Branch, Los Angeles, CA 90023 USA. RP Keire, DA (reprint author), Greater Los Angeles Vet Hlth Care Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-33850, DK41301, DK-56805] NR 45 TC 23 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 10 PY 2002 VL 293 IS 3 BP 1014 EP 1020 AR PII S0006-291X(02)00309-1 DI 10.1016/S0006-291X(02)00309-1 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 552VM UT WOS:000175640800021 PM 12051761 ER PT J AU Rose, ME Huerbin, MB Melick, J Marion, DW Palmer, AM Schiding, JK Kochanek, PM Graham, SH AF Rose, ME Huerbin, MB Melick, J Marion, DW Palmer, AM Schiding, JK Kochanek, PM Graham, SH TI Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury SO BRAIN RESEARCH LA English DT Article DE brain microdialysis; glucose; glutamate; traumatic brain injury ID TRAUMATIC BRAIN INJURY; HUMAN HEAD-INJURY; GLUTAMATE RELEASE; RAT; BW619C89; DAMAGE; ANTAGONISTS; LAMOTRIGINE; ASPARTATE; MECHANISM AB Increases in brain interstitial excitatory amino acid (EAA(1)) concentrations after ischemia are ameliorated by use-dependent Na+ channel antagonists and by supplementing interstitial glucose, but the regulation of EAA, after traumatic brain injury (TBI) is unknown. We studied the regulation of EAA, after TBI using the controlled cortical impact model in rats. To monitor changes in EAA,. microdialysis probes were placed in the cortex adjacent to the contusion and in the ipsilateral hippocampus. Significant increases in dialysate EAA, after TBI were found compared to levels measured in sham controls. Treatment with the use-dependent Na+ channel antagonist 619C89 (30 mg/kg i.v.) did not significantly decrease dialysate glutamate compared to vehicle controls in hippocampus (10.4 +/- 2.4 vs. 11.9 +/- 1.6 muM), but there was significant decrease in dialysate glutamate in cortex after 619C89 treatment (19.3 +/- 3 vs. 12.6 +/- 1.1 muM P < 0.05). Addition of 30 mM glucose to the dialysate, a treatment that decreases EAA, after ischemia, had no significant effect upon dialysate glutamate after TBI in cortex (20.0 +/- 4.9 vs. 11.7 +/- 3.4 muM) or in hippocampus ( 10.9 +/- 2.0 vs. 8.9 +/- 2.4 muM). These results suggest that neither increased release of EAAs due to Na+ channel-mediated depolarization nor failure of glutamate reuptake due to glucose deprivation can explain the majority of the increase in EAA, following TBI. (C) 2002 Published by Elsevier Science B.V. C1 VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15240 USA. Cerebus Ltd, Wokingham, England. Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA USA. Univ Pittsburgh, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Graham, SH (reprint author), VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15240 USA. FU NINDS NIH HHS [P50 NS 30318] NR 27 TC 19 Z9 22 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 10 PY 2002 VL 935 IS 1-2 BP 40 EP 46 AR PII S0006-8993(02)02445-9 DI 10.1016/S0006-8993(02)02445-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 555PN UT WOS:000175802600006 PM 12062471 ER PT J AU Hinkle, PM Pekary, AE Senanayaki, S Sattin, A AF Hinkle, PM Pekary, AE Senanayaki, S Sattin, A TI Role of TRH receptors as possible mediators of analeptic actions of TRH-like peptides SO BRAIN RESEARCH LA English DT Article DE TRH; EEP; TRH receptor; calcium signaling ID THYROTROPIN-RELEASING-HORMONE; RAT-BRAIN; CALCIUM; ANALOGS; SYSTEM; CELLS AB A large family of TRH-like peptides in the limbic region of rat brain including pGlu-Glu-Pro-NH2 (EEP), pGlu-Val-Pro-NH, (Val(2) -TRH), Leu(2) -TRH, Phe(2) -TRH and Tyr(2)-TRH has recently been discovered. TRH (pGlu-His-Pro-NH2) has antidepressant, neuroprotcetive, analeptic, anticonvulsant, antiamnesic and euphoric properties, and other TRH-like peptides such as EEP exert several of these effects. A new TRH receptor (TRHR2) has been reported which is highly expressed in regions of rat brain that regulate attention and learning, arousal, sleep and processing of sensory information. The TRHR1 predominates in limbic structures involved in regulation of mood and in pituitary. This study examined the possibility that some of the newly discovered TRH-like peptides bind with high affinity to TRHR2, and that this receptor acts as the transducer for some of the CNS effects of this new class of neuropeptides. EEP, Val(2)-TRH and Leu(2)-TRH were analeptics, like TRH, but Phe(2) -TRH and Tyr2-TRH were not. The affinity and efficacy of TRH-like peptides for TRHR1 and TRHR2 were measured in HEK293 cells stably expressing these receptors. The IC50 values of TRH-like peptides for displacement of [H-3]TRH from TRHR2 were TRH <<< (Leu(2)-, Phe(2) -TRH)<(Gln(2)-, Ser(2) -TRH) << (Val(2) -, Tyr(2)-, Arg(2)-, Thr(2)-, and Glu(2) -TRH). The IC50 for Leu(2)-TRH was about 100 times that for TRH. When tested at the calculated IC50 values, TRH-like peptides stimulated calcium responses in cells expressing TRHR1 and TRHR2, indicating that the peptides act as weak agonists at both receptors. These results indicate that TRHR1 and TRHR2 do not mediate the behavioral effects of TRH-like peptides. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Rochester, Sch Med & Dent, Dept Physiol & Pharmacol, Rochester, NY 14642 USA. VA Greater Los Angeles Healthcare Syst, Psychiat & Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. RP Hinkle, PM (reprint author), Univ Rochester, Sch Med & Dent, Dept Physiol & Pharmacol, Box 711,601 Elmwood Ave, Rochester, NY 14642 USA. FU NIDDK NIH HHS [DK 19974] NR 18 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 10 PY 2002 VL 935 IS 1-2 BP 59 EP 64 AR PII S0006-8993(02)02454-X DI 10.1016/S0006-8993(02)02454-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA 555PN UT WOS:000175802600008 PM 12062473 ER PT J AU Short, MK Krykbaev, RA Jeffrey, PD Margolies, MN AF Short, MK Krykbaev, RA Jeffrey, PD Margolies, MN TI Complementary combining site contact residue mutations of the anti-digoxin Fab 26-10 permit high affinity wild-type binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PARA-AZOPHENYLARSONATE FAB-36-71; DIRECTED MUTAGENESIS; ANTIDIGOXIN ANTIBODY-26-10; 3-DIMENSIONAL STRUCTURE; MONOCLONAL-ANTIBODY; VARIABLE REGION; HAPTEN BINDING; SPECIFICITY; LYSOZYME; INCREASE AB Antibody 26-10, obtained in a secondary immune response, binds digoxin with high affinity (K-a = 1.3 x 10(10) M-1) because of extensive shape complementarity. We demonstrated previously that mutations of the hapten contact residue HTrp-100 to Arg (where H refers to the heavy chain) resulted in increased specificity for digoxin analogs substituted at the cardenolide 16 position. However, mutagenesis of H:CDRI did not result in such a specificity change despite the proximity of the H:CDR1 hapten contact residue Asn-35 to the cardenolide 16 position. Here we constructed a bacteriophage-displayed library containing randomized mutations at H chain residues 30-35 in a 26-10 mutant containing Arg-100 (26-10-RRALD). Phage were selected by panning against digoxin, gitoxin (16-OH), and 16-acetylgitoxin coupled to bovine serum albumin. Clones that retained wild-type Asn at position 35 showed preferred binding to gitoxin, like the 26-10-RRALD parent. In contrast, clones containing Val-35 selected mainly on digoxin-bovine serum albumin demonstrated a shift back to wild-type specificity. Several clones containing Val-35 bound digoxin with increased affinity, approaching that of the wild type in a few instances, in contrast to the mutation Val-35 in the wild-type 26-10 background, which reduces affinity for digoxin 90-fold. It has therefore proven possible to reorder the 26-10 binding site by mutations including two major contact residues on opposite sides of the site and yet to retain high affinity for binding for digoxin. Thus, even among antibodies that have undergone affinity maturation in vivo, different structural solutions to high affinity binding may be revealed. C1 Massachusetts Gen Hosp, Dept Surg, Antibody Engn Lab, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Cellular Biochem & Biophys, New York, NY 10021 USA. RP Margolies, MN (reprint author), Massachusetts Gen Hosp, Dept Surg, Antibody Engn Lab, 15 Parkman St,WACC 465, Boston, MA 02114 USA. FU NHLBI NIH HHS [HLCA24432, HL47415] NR 25 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 2002 VL 277 IS 19 BP 16365 EP 16370 DI 10.1074/jbc.M110444200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 551MB UT WOS:000175564500004 PM 11854275 ER PT J AU Friedrich, EB Sinha, S Li, L Dedhar, S Force, T Rosenzweig, A Gerszten, RE AF Friedrich, EB Sinha, S Li, L Dedhar, S Force, T Rosenzweig, A Gerszten, RE TI Role of integrin-linked kinase in leukocyte recruitment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLOW CONDITIONS; CELL-ADHESION; PHOSPHOINOSITIDE 3-KINASE-GAMMA; VASCULAR ENDOTHELIUM; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; BETA-GAMMA; IN-VITRO; ACTIVATION AB Chemokines modulate leukocyte integrin avidity to coordinate adhesion and subsequent transendothelial migration, although the sequential signaling pathways involved remain poorly characterized. Here we show that integrin-linked kinase (ILK), a 59-kDa serine-threonine protein kinase that interacts principally with beta(1), integrins, is highly expressed in human mononuclear cells and is activated by exposure of leukocytes to the chemokine monocyte chemoattractant protein-1. Biochemical inhibitor studies show that chemokine-triggered activation of ILK is downstream of phosphoinositide 3-kinase. In functional assays under physiologically relevant flow conditions, overexpression of wild-type ILK in human monocytic cells diminishes beta(1), integrin/vascular cell adhesion molecule-1-dependent firm adhesion to human endothelial cells. These data implicate ILK in the dynamic signaling events involved in the regulation of leukocyte integrin avidity for endothelial substrates. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Med Sch, Boston, MA USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6H 3Z6, Canada. Vancouver Gen Hosp & Hlth Serv Ctr, Jack Bell Canc Ctr, Vancouver, BC V6H 3Z6, Canada. Tufts Univ, Sch Med, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, E 8307,149 13tg St, Charlestown, MA 02129 USA. OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL59521, HL65584, HL54202, HL67768, HL61688]; NIAID NIH HHS [AI40970] NR 32 TC 42 Z9 44 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 2002 VL 277 IS 19 BP 16371 EP 16375 DI 10.1074/jbc.M201240200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 551MB UT WOS:000175564500005 PM 11856758 ER PT J AU Hideshima, T Chauhan, D Richardson, P Mitsiades, C Mitsiades, N Hayashi, T Munshi, N Dang, L Castro, A Palombella, V Adams, J Anderson, KC AF Hideshima, T Chauhan, D Richardson, P Mitsiades, C Mitsiades, N Hayashi, T Munshi, N Dang, L Castro, A Palombella, V Adams, J Anderson, KC TI NF-kappa B as a therapeutic target in multiple myeloma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; MARROW STROMAL CELLS; RESISTANCE CAM-DR; INDUCED APOPTOSIS; ACTIVATION; INTERLEUKIN-6; THALIDOMIDE; INHIBITION; GROWTH; KINASE AB We have shown that thalidomide (Thal) and its immunomodulatory derivatives (IMiDs), proteasome inhibitor PS-341, and As2O3 act directly on multiple myeloma (MM) cells and in the bone marrow (BM) milieu to overcome drug resistance. Although Thal/IMiDs, PS-341, and As2O3 inhibit nuclear factor (NF)-kappaB activation, they also have multiple and varied other actions. In this study, we therefore specifically address the role of NF-kappaB blockade in mediating anti-AM activity. To characterize the effect of specific NF-kappaB blockade on AM cell growth and survival in vitro, we used an IkappaB kinase (IKK) inhibitor (PS-1145). Our studies demonstrate that PS-1145 and PS-341 block TNFalpha-induced NF-kappaB activation in a dose- and time-dependent fashion in AM cells through inhibition of IkappaBalpha phosphorylation and degradation of IkappaBalpha, respectively. Dexamethasone (Dex) which up-regulates IkappaBalpha protein, enhances blockade of NF-kappaB activation by PS-1145. Moreover, PS-1145 blocks the protective effect of IL-6 against Dex-induced apotosis. TNFa-induced intracellular adhesion molecule (ICAM)-1 expression on both RPM18226 and MMAS cells is also inhibited by PS-1145. Moreover, PS-1145 inhibits both IL-6 secretion from BMSCs triggered by AM cell adhesion and proliferation of AM cells adherent to BMSCs. However, in contrast to PS-341, PS-1145 only partially (20-50%) inhibits AM cell proliferation, suggesting that NF-kappaB blockade cannot account for all of the anti-AM activity of PS-341. Importantly, however, TNFalpha induces AM cell toxicity in the presence of PS-1145. These studies demonstrate that specific targeting of NF-kappaB can overcome the growth and survival advantage conferred both by tumor cell binding to BMSCs and cytokine secretion in the BM milieu. Furthermore, they provide the framework for clinical evaluation of novel AM therapies based upon targeting NF-kappaB. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU PHS HHS [P0-1 78378] NR 45 TC 656 Z9 691 U1 8 U2 40 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 2002 VL 277 IS 19 BP 16639 EP 16647 DI 10.1074/jbc.M200360200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 551MB UT WOS:000175564500041 PM 11872748 ER PT J AU Ogawa, H Ishiguro, K Gaubatz, S Livingston, DM Nakatani, Y AF Ogawa, H Ishiguro, K Gaubatz, S Livingston, DM Nakatani, Y TI A complex with chromatin modifiers that occupies E2F-and Myc-responsive genes in G(0) cells SO SCIENCE LA English DT Article ID TRANSCRIPTION FACTOR; HISTONE H3; E2F FAMILY; LYSINE 9; PROTEINS; BINDING; DOMAIN; MEMBER; PRB; INTERACTS AB E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism of repression by E2F-6, we have purified the factor from cultured cells. E2F-6 is found in a multimeric protein complex that contains Mga and Max, and thus the complex can bind not only to the E2F-binding site but also to Myc- and Brachyury-binding sites. Moreover, the complex contains chromatin modifiers such as a novel histone methyltransferase that modifies lysine 9 of histone H3, Hp1gamma, and Polycomb group (PcG) proteins. The E2F-6 complex preferentially occupies target promoters in G(0) cells rather than in G(1) cells. These data suggest that these chromatin modifiers contribute to silencing of E2F- and Myc-responsive genes in quiescent cells. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nakatani, Y (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 21 TC 487 Z9 509 U1 2 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 10 PY 2002 VL 296 IS 5570 BP 1132 EP 1136 DI 10.1126/science.1069861 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 551MG UT WOS:000175565000058 PM 12004135 ER PT J AU Brkanac, Z Fernandez, M Matsushita, M Lipe, H Wolff, J Bird, TD Raskind, WH AF Brkanac, Z Fernandez, M Matsushita, M Lipe, H Wolff, J Bird, TD Raskind, WH TI Autosomal dominant sensory/motor neuropathy with ataxia (SMNA): Linkage to chromosome 7q22-q32 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE sensory ataxia; cerebellar ataxia; sensory/motor neuropathy; linkage ID SPINOCEREBELLAR ATAXIA; PERIPHERAL NEUROPATHY; INHERITANCE; GENOTYPE; POLYNEUROPATHY; DISEASE; FAMILY; LOCUS; MAPS AB The autosomal dominant (AD) spinocerebellar ataxias (SCAs) and hereditary sensory neuropathies (HSN) are heterogeneous disorders characterized by variable clinical, electrophysiological, and neuropathological profiles. The SCAs are clinically characterized by slowly progressive incoordination of gait often associated with poor coordination of hands, speech, and eyes. Peripheral neuropathy is not a frequent part of the SCA syndrome. In contrast, the HSNs are primarily characterized by progressive sensory loss. There is substantial clinical overlap between the various SCAs and the various HSNs, and they often cannot be differentiated on the basis of clinical or neuro-imaging studies. We have identified a five-generation American family of Irish ancestry with a unique neurological disorder displaying an AD pattern of inheritance. There was variable expressivity and severity of symptoms including sensory loss, ataxia, pyramidal tract signs, and muscle weakness. Nerve conduction studies were consistent with a sensory axonal neuropathy. Muscle biopsy revealed neurogenic atrophy and brain MRI showed mild cerebellar atrophy. To identify the responsible locus we pursued a whole genome linkage analysis. After analyzing 114 markers, linkage to D7S486 was detected with a two point LOD score of 4.79 at theta = 0.00. Evaluation of additional markers in the region provided a maximum LOD score of 6.36 at theta = 0.00 for marker D7S2554. Haplotype analysis delimited an approximately 14-cM region at 7q22-q32 between markers D7S2418 and D7S1804 cosegregating with the disease. Because this disorder does not easily fall into either the SCA or HSN categories, it is designated sensory/motor neuropathy with ataxia (SMNA). (C) 2002 Wiley-Liss, Inc. C1 Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res & Educ & Clin, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, VISN Mental Illness Res Ctr 20, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Educ Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Clin, Seattle, WA USA. RP Bird, TD (reprint author), Univ Washington, Vet Affairs Med Ctr, Geriatr Res Serv, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [1 T32 AG00258-01A1] NR 25 TC 37 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 8 PY 2002 VL 114 IS 4 BP 450 EP 457 DI 10.1002/ajmg.10361 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 547WM UT WOS:000175355800013 PM 11992570 ER PT J AU Lu, S Hoestje, SM Choo, EM Epner, DE AF Lu, S Hoestje, SM Choo, EM Epner, DE TI Methionine restriction induces apoptosis of prostate cancer cells via the c-Jun N-terminal kinase-mediated signaling pathway SO CANCER LETTERS LA English DT Article DE methionine; neoplasms; prostate; signal transduction; apoptosis ID ACTIVATED PROTEIN-KINASES; CYTOCHROME-C; METABOLIC DEFECT; TISSUE-CULTURE; JNK ACTIVATION; BCL-2 FAMILY; IN-VIVO; GROWTH; TUMOR; MITOCHONDRIA AB Tumors are relatively more sensitive to methionine restriction than corresponding normal tissues, a phenomenon known as methionine auxotrophy. The current studies were undertaken to elucidate the molecular mechanisms for methionine auxotrophy of prostate cancer cells. We found that the activity of c-Jun N-terminal kinase 1 (JNK1) increased dramatically in response to methionine restriction. Over expression of wild type JNK1 by transient transfection enhanced apoptosis in response to methionine restriction, whereas over expression of a kinase inactive mutant of JNK1 protected PC-3 human prostate cancer cells from apoptosis. We conclude that JNK1 plays a critical role in signaling cancer cells to undergo apoptosis in response to methionine restriction. Published by Elsevier Science Ireland Ltd. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston VA Med Ctr, Med Serv 111H, Houston, TX 77030 USA. RP Epner, DE (reprint author), Baylor Coll Med, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [R29CA78355, 1F32 CA80333] NR 49 TC 9 Z9 11 U1 1 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 8 PY 2002 VL 179 IS 1 BP 51 EP 58 AR PII S0304-3835(01)00852-7 DI 10.1016/S0304-3835(01)00852-7 PG 8 WC Oncology SC Oncology GA 542CW UT WOS:000175026800007 PM 11880182 ER PT J AU Cummings, JL Cole, G AF Cummings, JL Cole, G TI Alzheimer disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; QUALITY STANDARDS SUBCOMMITTEE; ACADEMY-OF-NEUROLOGY; DOUBLE-BLIND; PRACTICE PARAMETER; COGNITIVE IMPAIRMENT; RISK-FACTORS; DEMENTIA; POPULATION; INHIBITORS C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG16570] NR 49 TC 239 Z9 250 U1 3 U2 19 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 MAY 8 PY 2002 VL 287 IS 18 BP 2335 EP 2338 DI 10.1001/jama.287.18.2335 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 548PF UT WOS:000175397000002 PM 11988038 ER PT J AU Nathan, DG AF Nathan, DG TI Careers in translational clinical research - Historical perspectives, future challenges SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INSTITUTES-OF-HEALTH; INVESTIGATOR; SCIENTIST C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St,Room D1642, Boston, MA 02115 USA. FU NCI NIH HHS [P30 CA06516]; NCRR NIH HHS [M01 RR02172]; NHLBI NIH HHS [P50 HL54785] NR 30 TC 64 Z9 65 U1 0 U2 3 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 MAY 8 PY 2002 VL 287 IS 18 BP 2424 EP 2427 DI 10.1001/jama.287.18.2424 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 548PF UT WOS:000175397000031 PM 11988063 ER PT J AU Stone, EG Morton, SC Hulscher, ME Maglione, MA Roth, EA Grimshaw, JM Mittman, BS Rubenstein, LV Rubenstein, LZ Shekelle, PG AF Stone, EG Morton, SC Hulscher, ME Maglione, MA Roth, EA Grimshaw, JM Mittman, BS Rubenstein, LV Rubenstein, LZ Shekelle, PG TI Interventions that increase use of adult immunization and cancer screening services: A meta-analysis SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; INFLUENZA VACCINATION RATES; FECAL OCCULT BLOOD; INNER-CITY WOMEN; COLORECTAL-CANCER; CERVICAL-CANCER; GENERAL-PRACTICE; PREVENTIVE CARE; BREAST-CANCER; MAMMOGRAPHY UTILIZATION AB Purpose: The relative effectiveness of the diverse approaches used to promote preventive care activities, such as cancer screening and adult immunization, is unknown. Despite many high-quality published studies, practices and policymakers attempting to improve preventive care have little definitive information on which to base decisions. Thus, we quantitatively assessed the relative effectiveness of previously studied approaches for improving adherence to adult immunization and cancer screening guidelines. Data Sources: MEDLINE, the Cochrane Effective Practice and Organization of Care Review Group register, previous systematic reviews, and the Medicare Health Care Quality Improvement Project database. Study Selection: Controlled clinical trials that assessed interventions to increase use of immunizations for influenza and pneumococcal pneumonia and screening for colon, breast, and cervical cancer in adults. Data Extraction: Two reviewers independently extracted data on characteristics and outcomes from unmasked articles. Intervention components to increase use of services were classified as reminder, feedback, education, financial incentive, legislative action, organizational change, or mass media campaign. \ Data Synthesis: Of 552 abstracts and articles, 108 met the inclusion criteria. To assess the effect of intervention components, meta-regression models were developed for immunizations and each cancer screening service by using 81 studies with a usual care or control group. The most potent intervention types involved organizational change (the adjusted odds ratios for increased use of services from organizational change ranged from 2.47 to 17.6). Organizational change interventions included the use of separate clinics devoted to prevention, use of a planned care visit for prevention, or designation of nonphysician staff to do specific prevention activities. The next most effective intervention components were patient financial incentives (adjusted odds ratios, 1.82 to 3.42) and patient reminders (adjusted odds ratios, 1.74 to 2.75); the adjusted odds ratios ranged from 1.29 to 1.53 for patient education and from 1.10 to 1.76 for feedback. Conclusions: Rates of adult immunization and cancer screening are most likely to improve when a health care organization supports performance of these activities through organizational changes in staffing and clinical procedures. Involving patients in self-management through patient financial incentives and reminders is also likely to positively affect performance. C1 RAND Corp, So Calif Evidence Based Practice Ctr, Hlth Div, Santa Monica, CA 90407 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Greater Los Angeles Vet Adm Hlth Care Syst, Los Angeles, CA 90048 USA. Ctr Study Hlth Care Provider Behav, Sepulveda, CA USA. Univ Nijmegen, Ctr Qual Care Res, Nijmegen, Netherlands. Univ Aberdeen, Hlth Serv Res Unit, Aberdeen, Scotland. RP Shekelle, PG (reprint author), RAND Corp, So Calif Evidence Based Practice Ctr, Hlth Div, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. RI Grimshaw, Jeremy/D-8726-2013; Hulscher, Marlies/B-1229-2014; OI Grimshaw, Jeremy/0000-0001-8015-8243 NR 91 TC 386 Z9 390 U1 5 U2 25 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 7 PY 2002 VL 136 IS 9 BP 641 EP 651 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 547XK UT WOS:000175357900001 PM 11992299 ER PT J AU Oboler, SK Prochazka, AV Gonzales, R Xu, S Anderson, RJ AF Oboler, SK Prochazka, AV Gonzales, R Xu, S Anderson, RJ TI Public expectations and attitudes for annual physical examinations and testing SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ADULTS; CARE AB Background: Recent guidelines for adult prevention do not recommend a comprehensive annual physical examination, but current public expectations in light of this change are unknown. Objective: To determine public belief in the need for and content of an annual physical examination and to examine the effect of financial charges on these beliefs. Design: Telephone survey. Setting: Three U.S. cities. Participants: Adult English-speaking respondents. Measurements: Percentage of respondents answering that an annual physical examination is necessary and percentage desiring individual components of the history, physical examination, and laboratory testing, with and without knowledge of charges. Results: Of 1203 respondents, 66% (67% in Denver, Colorado; 71% in Boston, Massachusetts; and 58% in San Diego, California) believed that in addition to regular care, an annual physical examination is necessary, Among the 600 respondents presented with charge information, interest decreased from 63% to 33% if payment were required. For history, greater than 90% believed that diet, exercise, and tobacco and alcohol use should be discussed, while 60% believed that seatbelt use and sexual history should be discussed. For the physical examination, greater than 90% felt that blood pressure should be measured and that the heart and lungs, abdomen, reflexes, and prostate should be examined. However, fewer than 80% thought that hearing and vision should be tested. Many tests, including the Papanicolaou smear (75%), mammography (71%), cholesterol measurement (65%), prostate-specific antigen test (65%), urinalysis (40%), blood glucose measurement (41%), fecal occult blood testing (39%), and chest radiography (36%), were desired. Interest in these tests decreased substantially when the charges were known. Conclusion: Public desire for a comprehensive annual physical examination is high across the United States and is sensitive to charges. C1 Denver Kaiser Permanente, Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Oboler, SK (reprint author), Denver Kaiser Permanente, Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. NR 29 TC 58 Z9 60 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 7 PY 2002 VL 136 IS 9 BP 652 EP 659 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 547XK UT WOS:000175357900002 PM 11992300 ER PT J AU Baumgarten, G Knuefermann, P Kalra, D Gao, F Taffet, GE Michael, L Blackshear, PJ Carballo, E Sivasubramanian, N Mann, DL AF Baumgarten, G Knuefermann, P Kalra, D Gao, F Taffet, GE Michael, L Blackshear, PJ Carballo, E Sivasubramanian, N Mann, DL TI Load-dependent and -independent regulation of proinflammatory cytokine and cytokine receptor gene expression in the adult mammalian heart SO CIRCULATION LA English DT Article DE hypertrophy; gene expression; growth factors; cytokines; remodeling ID NECROSIS-FACTOR-ALPHA; FELINE MYOCARDIUM; PROTEIN EXPRESSION; TRANSGENIC MICE; PATHWAY; FAILURE AB Background-Although previous studies have examined the effects of acute hemodynamic pressure overload on proinflammatory cytokine gene expression, the effects of sustained hemodynamic overloading have not been examined. Methods and Results-Sustained hemodynamic pressure overloading was produced in mice by transverse constriction of the aorta. Proinflammatory cytokine and cytokine receptor gene expression were determined by ribonuclease protection assays (RPA) at 6 hours and at 3, 7, 14 and 35 days after banding. M-mode echocardiography was used to assess left ventricular structure and function at identical time points. RPA showed that tumor necrosis factor (TNF), interleukin (IL)-1beta, and IL-6 mRNA levels were maximal at 6 hours and returned to baseline levels within 72 hours. There was a significant increase in IL-1RII and IL-6Ralpha receptor mRNA levels after overloading but no significant increase in TNFR1, TNFR2, IL-1RI, or gp130 mRNA levels. The transient increase in expression of proinflammatory cytokine gene expression was not explained by changes in left ventricular loading conditions, left ventricular wall stress, desensitization of proinflammatory genes, or decreased nuclear factor-kappabeta activation. It is interesting that transverse constriction of the aorta provoked an increase in the expression of tristetraprolin, a homeostatic zinc finger protein that is known to destabilize TNF mRNA. Conclusion-Sustained hemodynamic overloading provokes a transient increase in proinflammatory cytokine and cytokine receptor gene expression; however, the decrease in proinflammatory cytokine gene expression occurred in the absence of changes in loading conditions, suggesting that the expression of proinflammatory cytokines in the heart is regulated, at least in part, by load-dependent and load-independent mechanisms. C1 Houston VAMC, Dept Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Baylor Coll Med, DeBakey Heart Ctr, Houston, TX 77030 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Mann, DL (reprint author), Houston VAMC, Dept Med, Winters Ctr Heart Failure Res, MS 524,6565 Fannin, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL-42250-10/10, P50 HL-O6H, R01 HL58081-01, R01 HL61543-01] NR 14 TC 83 Z9 83 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 7 PY 2002 VL 105 IS 18 BP 2192 EP 2197 DI 10.1161/01.CIR.0000015608.37608.18 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 550KK UT WOS:000175502000014 PM 11994254 ER PT J AU Wright, CI Martis, B Shin, LM Fischer, H Rauch, SL AF Wright, CI Martis, B Shin, LM Fischer, H Rauch, SL TI Enhanced amygdala responses to emotional versus neutral schematic facial expressions SO NEUROREPORT LA English DT Article DE cerebral cortex; faces; functional magnetic resonance imaging; human; limbic system ID HUMAN BRAIN; FACE; RECOGNITION; STIMULI; FEARFUL; HABITUATION; DAMAGE; MRI AB Human facial emotional expressions are complex. This may confound studies examining brain responses to these stimuli in control and clinical populations. However, several lines of evidence suggest that a few elementary facial features convey the gist of emotional expressions. Using fMRI, we assessed brain responses to line drawings of emotionally valenced (i.e. angry and happy) and neutral faces in healthy human subjects. Significantly increased fMRI signal was found in the amygdala, hippocampus and prefrontal cortex in response to emotional vs neutral schematic faces. Although direct comparisons of schematic and human faces will be needed, these initial results suggest that schematic faces may be useful for studying brain responses to emotional stimuli because of their simplicity relative to human faces. NeuroReport 13:785-790 (C) 2002 Lippincott Williams Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Karolinska Inst, Aging Res Ctr, Stockholm, Sweden. Stockholm Univ, S-10691 Stockholm, Sweden. RP Wright, CI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Grp, 13th St,BLdg 149,CNY-9, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH-60219] NR 29 TC 50 Z9 50 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 7 PY 2002 VL 13 IS 6 BP 785 EP 790 DI 10.1097/00001756-200205070-00010 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 549KE UT WOS:000175442400012 PM 11997687 ER PT J AU Neurath, MF Weigmann, B Finotto, S Glickman, J Nieuwenhuis, E Iijima, H Mizoguchi, A Mizoguchi, E Mudter, J Galle, PR Bhan, A Autschbach, F Sullivan, BM Szabo, SJ Glimcher, LH Blumberg, RS AF Neurath, MF Weigmann, B Finotto, S Glickman, J Nieuwenhuis, E Iijima, H Mizoguchi, A Mizoguchi, E Mudter, J Galle, PR Bhan, A Autschbach, F Sullivan, BM Szabo, SJ Glimcher, LH Blumberg, RS TI The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T-bet; GATA-3; cytokines; colitis; IFN-gamma ID INFLAMMATORY-BOWEL-DISEASE; GROWTH-FACTOR-BETA; TGF-BETA; INTERFERON-GAMMA; TARGETED DISRUPTION; GENE-EXPRESSION; IFN-GAMMA; LINEAGE COMMITMENT; SIGNAL TRANSDUCER; CYTOKINE AB The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-gamma/interleukin (IL)-4 and transforming growth factor (TGF)-beta activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1-and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L(+) CD4(+) T cells exacerbated colitis in reconstituted SCID mice, T-bet-deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet-deficient CD62L(-) CD4(+) T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-beta signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-gamma/IL-4 and TGF-beta responses and the development of chronic intestinal inflammation in T cell-mediated colitis. Furthermore, TGF-beta was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-beta and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell-mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes. C1 Univ Mainz, Med Clin, Lab Immunol 1, D-55131 Mainz, Germany. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Univ Heidelberg, Inst Pathol, D-49569 Heidelberg, Germany. RP Neurath, MF (reprint author), Univ Mainz, Med Clin, Lab Immunol 1, Langenbeckstr, D-55131 Mainz, Germany. FU NIAID NIH HHS [AI37833, P01 AI037833]; NIDDK NIH HHS [DK44319, DK51362, DK53056, R01 DK044319, R01 DK051362, R01 DK053056, R37 DK044319] NR 68 TC 381 Z9 401 U1 1 U2 13 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 MAY 6 PY 2002 VL 195 IS 9 BP 1129 EP 1143 DI 10.1084/jem.20011956 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 560ZF UT WOS:000176110700005 PM 11994418 ER PT J AU Chua, KF Alt, FW Manis, JP AF Chua, KF Alt, FW Manis, JP TI Commentary - The function of AID in somatic mutation and class switch recombination: Upstream or downstream of DNA breaks SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID CYTIDINE DEAMINASE AID; DOUBLE-STRAND BREAKS; HEAVY-CHAIN SWITCH; IMMUNOGLOBULIN GENES; B-CELLS; HYPERMUTATION; DELETION; SITES; LINE C1 Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Manis, JP (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31541, P01 AI031541, U19 AI031541] NR 36 TC 20 Z9 20 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 6 PY 2002 VL 195 IS 9 BP F37 EP F41 DI 10.1084/jem.20020380 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 560ZF UT WOS:000176110700001 PM 11994429 ER PT J AU Etemad-Moghadam, B Rhone, D Steenbeke, T Sun, Y Manola, J Gelman, R Fanton, JW Racz, P Tenner-Racz, K Axthelm, MK Letvin, NNL Sodroski, J AF Etemad-Moghadam, B Rhone, D Steenbeke, T Sun, Y Manola, J Gelman, R Fanton, JW Racz, P Tenner-Racz, K Axthelm, MK Letvin, NNL Sodroski, J TI Understanding the basis of CD4(+) T-cell depletion in macaques infected by a simian-human immunodeficiency virus SO VACCINE LA English DT Article; Proceedings Paper CT Sympopsium on Global HIV Therapeutics - HIV Vaccines CY JUN 07-09, 2001 CL KAROLINSKA INST, STOCKHOLM, SWEDEN HO KAROLINSKA INST DE CD4(+) T-cell depletion; simian-human immunodeficiency virus; membrane fusion ID ENVELOPE GLYCOPROTEIN; RHESUS-MONKEYS; IN-VIVO; LYMPHOCYTE DEPLETION; TYPE-1; DETERMINANTS; LYSIS AB The efficacy of candidate AIDS vaccines to mediate protection against viral infection and pathogenesis is evaluated, at a preclinical stage, in animal models. One model that is favored because the infecting virus is closely related to HIV-1 and because of the rapidity of pathogenic outcomes is the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae. We investigated the basis for the depletion of CD4(+) T lymphocytes in a SHIV-macaque model. Molecularly cloned SHIVs, SHIV-89.6 and SHIV-KB9, differ in the ability to cause CD4(+) T-cell loss at a given level of virus replication in monkeys. The envelope glycoproteins of the pathogenic SHIV-KB9 mediate membrane-fusion in cultured T lymphocytes more efficiently than the envelope glycoproteins of the non-pathogenic SHIV-89.6. The minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity was sufficient to convert SHIV-89.6 into a virus that causes profound CD4(+) T-cell depletion in monkeys. Conversely, two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins also attenuated the CD4(+) T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus. the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4(+) T lymphocytes in vivo. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Pathol,Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Bernhard Nocht Inst Trop Med, Dept Pathol, D-20359 Hamburg, Germany. Bernhard Nocht Inst Trop Med, Korber Lab, D-20359 Hamburg, Germany. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Pathol,Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 9 TC 10 Z9 10 U1 0 U2 1 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 MAY 6 PY 2002 VL 20 IS 15 SI SI BP 1934 EP 1937 AR PII S0264-410X(02)00072-5 DI 10.1016/S0264-410X(02)00072-5 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 552MR UT WOS:000175624600011 PM 11983249 ER PT J AU Xu, WD Hofmann-Lehmann, R McClure, HM Ruprecht, RM AF Xu, WD Hofmann-Lehmann, R McClure, HM Ruprecht, RM TI Passive immunization with human neutralizing monoclonal antibodies: correlates of protective immunity against HIV SO VACCINE LA English DT Article; Proceedings Paper CT Sympopsium on Global HIV Therapeutics - HIV Vaccines CY JUN 07-09, 2001 CL KAROLINSKA INST, STOCKHOLM, SWEDEN HO KAROLINSKA INST DE human immunodeficiency virus (HIV); simian-human immunodeficiency virus (SHIV) neutralizing monoclonal antibodies (mAbs); passive immunization ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNERGISTIC NEUTRALIZATION; IN-VIVO; TYPE-1; TRANSMISSION; INFECTION; GLYCOPROTEIN; MACAQUES; COMBINATIONS; PREVENTION AB Passive immunization with synergistic combinations of human monoclonal antibodies (mAbs) directed against conserved epitopes of the human immunodeficiency virus (HIV) envelope completely protected 13 out of 16 rhesus monkeys challenged intravenously or orally with chimeric simian-human immunodeficiency virus (SHIV) strains; partial protection was seen in another two. A high degree of protection was seen among orally challenged neonates. Thus, we propose that passive immunization with synergistic combinations of neutralizing human mAbs may be effective in preventing maternal HIV transmission when given as post-exposure prophylaxis at birth and as prophylaxis against milk-borne transmission. Because we only used mAbs with well-defined epitope specificities, our studies also yield key information for designing AIDS vaccines: the correlates of immune protection. Vaccine strategies that can evoke antibody responses to epitopes recognized by the mAbs used in our primate studies could be important components of successful AIDS vaccines. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30329 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 FU NCRR NIH HHS [RR 00165]; NIAID NIH HHS [P01 AI 48240, R01 AI 34266] NR 31 TC 38 Z9 39 U1 0 U2 0 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 MAY 6 PY 2002 VL 20 IS 15 SI SI BP 1956 EP 1960 AR PII S0264-410X(02)00077-4 DI 10.1016/S0264-410X(02)00077-4 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 552MR UT WOS:000175624600016 PM 11983253 ER PT J AU Johnson, RP AF Johnson, RP TI Mechanisms of protection against simian immunodeficiency virus infection SO VACCINE LA English DT Article; Proceedings Paper CT Sympopsium on Global HIV Therapeutics - HIV Vaccines CY JUN 07-09, 2001 CL KAROLINSKA INST, STOCKHOLM, SWEDEN HO KAROLINSKA INST DE cytotoxic T lymphocyte; simian immunodeficiency viruses; HIV; attenuated vaccines ID CD8(+) T-LYMPHOCYTES; ATTENUATED VACCINE; RESPONSES; IMMUNITY; MUCOSAL; VIREMIA; NONPROGRESSORS; PREVENTION; CHALLENGE; INDUCTION AB One of the obstacles to the development of an effective AIDS vaccine has been the limited information on the mechanisms of protective immunity to HIV. In macaques, immunization with attenuated simian immunodeficiency viruses (SIV) has proved to be one of the most effective strategies to induce protection against infection or disease with pathogenic lentiviruses. Infection with attenuated SIV strains induces a broad range of SIV-specific immune responses, including relatively potent cytotoxic T lymphocyte (CTL) and antibody responses. Several studies of macaques vaccinated with attenuated SIV have demonstrated correlations between CTL responses or antibody responses and protection but more detailed studies are needed to document the relative importance of these responses in protective immunity. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Johnson, RP (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR 00168]; NIAID NIH HHS [AI 45314, AI 35365] NR 21 TC 27 Z9 27 U1 0 U2 0 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 MAY 6 PY 2002 VL 20 IS 15 SI SI BP 1985 EP 1987 AR PII S0264-410X(02)00083-X DI 10.1016/S0264-410X(02)00083-X PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 552MR UT WOS:000175624600022 PM 11983259 ER PT J AU Lieberman, J Frankel, FR AF Lieberman, J Frankel, FR TI Engineered Listeria monocytogenes as an AIDS vaccine SO VACCINE LA English DT Article; Proceedings Paper CT Sympopsium on Global HIV Therapeutics - HIV Vaccines CY JUN 07-09, 2001 CL KAROLINSKA INST, STOCKHOLM, SWEDEN HO KAROLINSKA INST DE Listeria monocytogenes; D-Ala; Lmdd-gag; HIV; oral vaccine; mucosal immunity ID T-CELL EPITOPE; LYMPHOCYTES-T; VIRUS-INFECTION; GAG PROTEIN; INDUCTION; PROTECTION; IMMUNITY; MICE; STRAIN; RESPONSES AB Listeria monocytogenes (Lm) is an attractive vector to elicit T cell immunity because it infects antigen-presenting cells and because infection originates at the mucosa. Lm expressing HIV gag elicits sustained high levels of gag-specific CTL in mice. Since Lm causes disease in immunocompromised hosts, a highly attenuated strain of Lm that requires D-Ala for viability was produced. Attenuated bacteria expressing HIV-1 gag (Lmdd-gag) are as efficient as wild-type recombinants at stimulating gag-specific murine CTL when administered with D-Ala and at boosting human CTL in vitro. Lmdd-gag immunization protects mice from vaccinia-gag challenge and induces mucosal CTL, even after systemic immunization. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 28 TC 25 Z9 30 U1 0 U2 1 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 MAY 6 PY 2002 VL 20 IS 15 SI SI BP 2007 EP 2010 AR PII S0264-410X(02)00088-9 DI 10.1016/S0264-410X(02)00088-9 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 552MR UT WOS:000175624600027 PM 11983264 ER PT J AU Addo, MM Altfeld, M Rathod, A Yu, M Yu, XG Goulder, PJR Rosenberg, ES Walker, BD AF Addo, MM Altfeld, M Rathod, A Yu, M Yu, XG Goulder, PJR Rosenberg, ES Walker, BD TI HIV-1 Vpu represents a minor target for cytotoxic T lymphocytes in HIV-1-infection SO AIDS LA English DT Article ID RESPONSES; INFECTION; CTL; IDENTIFICATION; INDIVIDUALS; PROTEINS; EPITOPES AB We have previously shown that Vpu is rarely targeted by HIV-1-specific cytotoxic T lymphocytes (CTL). The present report extends these findings and describes the characterization of the first CTL epitope within HIV-1 Vpu, identified in an individual with long-term lion-progressive HIV-1 infection. The epitope was shown to be highly conserved among HIV clade B sequences and is restricted by HLA-A*3303, an HLA allele commonly seen in Asian and west-African populations. C1 Harvard Univ, Med Sch, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Infect Dis Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Addo, MM (reprint author), Harvard Univ, Med Sch, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 16 TC 18 Z9 20 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 3 PY 2002 VL 16 IS 7 BP 1071 EP 1073 DI 10.1097/00002030-200205030-00015 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 550TC UT WOS:000175517900015 PM 11953475 ER PT J AU Lechner, A Leech, CA Abraham, EJ Nolan, AL Habener, JF AF Lechner, A Leech, CA Abraham, EJ Nolan, AL Habener, JF TI Nestin-positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE stem cells; pancreas; islets of Langerhans; ABCG2; SP cells; diabetes mellitus; nestin; MDR1 ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW CELLS; IN-VIVO; P-GLYCOPROTEIN; DYE EFFLUX; EX-VIVO; MUSCLE; TRANSPLANTATION; DIFFERENTIATE; PHENOTYPES AB The disease diabetes mellitus arises as a consequence of a failure of the P-cells in the islets of Langerhans of the pancreas to produce insulin in the amounts required to meet the needs of the body. Whole pancreas or islet transplants in patients with severe diabetes effectively restore insulin production. A lack of availability of donor pancreata requires the development of alternative sources of islets such as the ex vivo culture and differentiation of stem/progenitor cells. Earlier we discovered multipotential progenitor cells in islets isolated from adult human pancreata that express the neural stem cell marker nestin: nestin-positive islet-derived progenitor cells (NIPs). Recently it was shown that the exclusion of the Hoechst 33342 dye, which defines the pluripotential side population (SP) of hematopoietic stem cells, is mediated by the ATP-binding cassette transporter, ABCG2. Here we report that the human islet-derived NIPs contain a substantial subpopulation of SP cells that co-express ABCG2, MDR1. and nestin. Thus NIPs may be a potential source of adult pluripotential stem/progenitor cells useful for the production of islet tissue for transplantation into diabetic subjects. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK R21 55365] NR 25 TC 155 Z9 168 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 3 PY 2002 VL 293 IS 2 BP 670 EP 674 AR PII S0006-291X(02)00275-9 DI 10.1016/S0006-291X(02)00275-9 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 550DP UT WOS:000175488600002 PM 12054520 ER PT J AU Shi, YY Hsu, JH Hu, LP Gera, J Lichtenstein, A AF Shi, YY Hsu, JH Hu, LP Gera, J Lichtenstein, A TI Signal pathways involved in activation of p70(S6K) and phosphorylation of 4E-BP1 following exposure of multiple myeloma tumor cells to interleukin-6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID P70 S6 KINASE; PROTEIN-SYNTHESIS; PLASMA-CELLS; AKT KINASE; IN-VITRO; APOPTOSIS; RAPAMYCIN; GROWTH; SURVIVAL; INSULIN AB Interleukin-6 (IL-6) is a prominent tumor growth factor for malignant multiple myeloma cells. In addition to its known activation of the Janus tyrosine kinase-STAT and RAS-MEK-ERK pathways, recent work suggests that IL-6 can also activate the phosphatidylinositol 3-kinase (PI3-K)/AKT kinase pathway in myeloma cells. Because activation of the PI3-K/AKT as well as RAS-MEK-ERK pathways may result in downstream stimulation of the p70(S6K) (p70) and phosphorylation of the 4E-BP1 translational repressor, we assessed these potential molecular targets in IL-6-treated myeloma cells. IL-6 rapidly activated p70 kinase activity and p70 phosphorylation. Activation was inhibited by wortmannin, rapamycin, and the ERK inhibitors PD98059 and UO126, as well as by a dominant negative mutant of AKT. The concurrent requirements for both ERK and PI3-K/AKT appeared to be a result of their ability to phosphorylate p70 on different residues. In contrast, IL-6-induced phosphorylation of 4E-BP1 was inhibited by rapamycin, wortmannin, and dominant negative ART but ERK inhibitors had no effect, indicating ERK function was dispensable. In keeping with these data, a dominant active AKT mutant was sufficient to induce 4E-BP1 phosphorylation but could not by itself activate p70 kinase activity. Prevention of IL-6-induced p70 activation and 4E-BP1 phosphorylation by the mammalian target of rapamycin inhibitors rapamycin and CCI-779 resulted in inhibition of IL-6-induced myeloma cell growth. These results indicate that both ERK and PI3-K/AKT pathways are required for optimal IL-6-induced p70 activity, but PI3-K/AKT is sufficient for 4E-BP1 phosphorylation. Both effects are mediated via mammalian target of rapamycin function, and, furthermore, these effects are critical for IL-6-induced tumor cell growth. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. RP Lichtenstein, A (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. NR 45 TC 72 Z9 76 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 2002 VL 277 IS 18 BP 15712 EP 15720 DI 10.1074/jbc.M200043200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 550PA UT WOS:000175510400067 PM 11872747 ER PT J AU Hayward, LJ Rodriguez, JA Kim, JW Tiwari, A Goto, JJ Cabelli, DE Valentine, JS Brown, RH AF Hayward, LJ Rodriguez, JA Kim, JW Tiwari, A Goto, JJ Cabelli, DE Valentine, JS Brown, RH TI Decreased metallation and activity in subsets of mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSGENIC MICE; WILD-TYPE; CU,ZN-SUPEROXIDE DISMUTASE; HYDROGEN-PEROXIDE; PULSE-RADIOLYSIS; COPPER; MUTATIONS; SOD1; ALS; DISEASE AB Over 90 different mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause similar to2% of amyotrophic lateral sclerosis (ALS) cases by an unknown mechanism. We engineered 14 different human ALS-related SOD1 mutants and obtained high yields of biologically metallated proteins from an Sf21 insect cell expression system. Both the wild type and mutant "as isolated" SOD1 variants were deficient in copper and were heterogeneous by native gel electrophoresis. By contrast, although three mutant SOD1s with substitutions near the metal binding sites (H46R, G85R, and D124V) were severely deficient in both copper and zinc ions, zinc deficiency was not a consistent feature shared by the as isolated mutants. Eight mutants (A4V, L38V, G41S, G72S, D76Y, D90A, G93A, and E133Delta) exhibited normal SOD activity over pH 5.5-10.5, per equivalent of copper, consistent with the presumption that bound copper was in the proper metal-binding site and was fully active. The H48Q variant contained a high copper content yet was 100-fold less active than the wild type enzyme and exhibited a blue shift in the visible absorbance peak of bound Cu(II), indicating rearrangement of the Cu(II) coordination geometry. Further characterization of these as-isolated SOD1 proteins may provide new insights regarding mutant SOD1 enzyme toxicity in ALS. C1 Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. RP Hayward, LJ (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01655 USA. RI Tiwari, Ashutosh/A-7458-2008; Valentine, Joan/B-6665-2008 OI Tiwari, Ashutosh/0000-0001-7373-349X; Valentine, Joan/0000-0002-7174-925X FU NIGMS NIH HHS [GM28222]; NINDS NIH HHS [P01NS31248, P01NS37912] NR 56 TC 211 Z9 213 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 2002 VL 277 IS 18 BP 15923 EP 15931 DI 10.1074/jbc.M112087200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 550PA UT WOS:000175510400095 PM 11854284 ER PT J AU Rodriguez, JA Valentine, JS Eggers, DK Roe, JA Tiwari, A Brown, RH Hayward, LJ AF Rodriguez, JA Valentine, JS Eggers, DK Roe, JA Tiwari, A Brown, RH Hayward, LJ TI Familial amyotrophic lateral sclerosis-associated mutations decrease the thermal stability of distinctly metallated species of human copper/zinc superoxide dismutase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIFFERENTIAL SCANNING CALORIMETRY; ZINC-SUBSTITUTED DERIVATIVES; CU,ZN-SUPEROXIDE DISMUTASE; CONFORMATIONAL STABILITY; ESCHERICHIA-COLI; MUTANT; BINDING; SUPEROXIDE-DISMUTASE-1; DENATURATION; SPECTROSCOPY AB We report the thermal stability of wild type (WT) and 14 different variants of human copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis (FALS). Multiple endothermic unfolding transitions were observed by differential scanning calorimetry for partially metallated SOD1 enzymes isolated from a baculovirus system. We correlated the metal ion contents of SOD1 variants with the occurrence of distinct melting transitions. Altered thermal stability upon reduction of copper with dithionite identified transitions resulting from the unfolding of copper-containing SOD1 species. We demonstrated that copper or zinc binding to a subset of "WT-like" FALS mutants (A4V, L38V, G41S, G72S, D76Y, D90A, G93A, and E133Delta) conferred a similar degree of incremental stabilization as did metal ion binding to WT SOD1. However, these mutants were all destabilized by similar to 1- 6 degreesC compared with the corresponding WT SOD1 species. Most of the "metal binding region" FALS mutants (H46R, G85R, D124V, D125H, and S134N) exhibited transitions that probably resulted from unfolding of metal-free species at similar to4-12 degreesC below the observed melting of the least stable WT species. We conclude that decreased conformational stability shared by all of these mutant SOD1s may contribute to SOD1 toxicity in FALS. C1 Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Loyola Marymount Univ, Dept Chem & Biochem, Los Angeles, CA 90045 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Hayward, LJ (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01655 USA. EM Lawrence.Hayward@umassmed.edu RI Tiwari, Ashutosh/A-7458-2008 OI Tiwari, Ashutosh/0000-0001-7373-349X FU NIGMS NIH HHS [GM28222]; NINDS NIH HHS [P01NS31248, P01NS37912] NR 29 TC 150 Z9 151 U1 1 U2 6 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 MAY 3 PY 2002 VL 277 IS 18 BP 15932 EP 15937 DI 10.1074/jbc.M112088200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 550PA UT WOS:000175510400096 PM 11854285 ER PT J AU Hussain, MA Miller, CP Habener, JF AF Hussain, MA Miller, CP Habener, JF TI Brn-4 transcription factor expression targeted to the early developing mouse pancreas induces ectopic glucagon gene expression in insulin-producing beta cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AR42J CELLS; ALPHA-CELLS; ACTIVIN-A; DIFFERENTIATION; PAX6; MICE; ELEMENT; REVEALS; TUMORS; IPF1 AB The endocrine pancreas is comprised of beta and alpha cells producing the glucostatic hormones insulin and glucagon, respectively, and arises during development by the differentiation of stem/progenitor cells in the foregut programmed by the beta cell lineage-specific homeodomain protein ldx-1. Brain-4 (Brn-4) is expressed in the pancreatic anlaga of the mouse foregut at e10 in the alpha cells and transactivates glucagon gene expression. We expressed Brn-4 in pancreatic precursors or beta cell lineage in transgenic mice by placing it under either Idx-1 or insulin promoter (rat insulin II promoter) control, respectively. Idx-1 expression occurs at developmental day e8.5, and insulin expression occurs at e9.5, respectively. Misexpression of Brn-4 by the Idx-1 promoter results in ectopic expression of the proglucagon gene in insulin-expressing pancreatic beta cells, whereas misexpression by rat insulin II promoter did not. The early developmental expression of Brn-4 appears to be a dominant regulator of the glucagon expressing a cell lineage, even in the context of the beta cell lineage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. Wyeth Ayerst Res, Inst Genet, Cambridge, MA 02140 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK55365, DK30834] NR 29 TC 44 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 2002 VL 277 IS 18 BP 16028 EP 16032 DI 10.1074/jbc.M107124200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 550PA UT WOS:000175510400108 PM 11834725 ER PT J AU O'Neill, T Giarratani, L Chen, P Iyer, L Lee, CH Bobiak, M Kanai, F Zhou, BB Chung, JH Rathbun, GA AF O'Neill, T Giarratani, L Chen, P Iyer, L Lee, CH Bobiak, M Kanai, F Zhou, BB Chung, JH Rathbun, GA TI Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE CHECKPOINT; ATAXIA-TELANGIECTASIA GENE; CELL-CYCLE REGULATION; XENOPUS EGG EXTRACTS; CDK FAMILY MEMBER; PROTEIN-KINASE; S-PHASE; SCHIZOSACCHAROMYCES-POMBE; IONIZING-RADIATION; CRYSTAL-STRUCTURE AB Mammalian Chk1 and Chk2 are two Ser/Thr effector kinases that play critical roles in DNA damage-activated cell cycle checkpoint signaling pathways downstream of ataxia telangiectasia-mutated and ataxia telangiectasia-related. Endogenous substrates have been identified for human hCds1/Chk2 and Chk1; however, the sequences surrounding the substrate residues appear unrelated, and consensus substrate motifs for the two Ser/Thr kinases remain unknown. We have utilized peptide library analyses to develop specific, highly preferred substrate motifs for hCds1/Chk2 and Chk1. The optimal motifs are similar for both kinases and most closely resemble the previously identified Chk1 and hCds1/Chk2 substrate target sequences in Cdc25C and Cdc25A, the regulation of which plays an important role in S and G(2)M arrest. Essential residues required for the definition of the optimal motifs were also identified. Utilization of the peptides to assay the substrate specificities and catalytic activities of Chk1 and hCds1/Chk2 revealed substantial differences between the two Ser/Thr kinases. Structural modeling analyses of the peptides into the Chk1 catalytic cleft were consistent with Chk1 kinase assays defining substrate suitability. The library-derived substrate preferences were applied in a genome-wide search program, revealing novel targets that might serve as substrates for hCds1/Chk2 or Chk1 kinase activity. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Ctr Blood Res, Boston, MA 02115 USA. Agouron Pharmaceut Inc, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Ctr Res Comp, Boston, MA 02115 USA. NIH, HLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. GlaxoSmithKline, Dept Oncol Res, King Of Prussia, PA 19406 USA. Harvard Univ, Beth Israel Deaconess Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Rathbun, GA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Ctr Blood Res, 200 Longwood Ave,Warren Alpert Bldg,Rm 135, Boston, MA 02115 USA. OI Iyer, Lakshmanan/0000-0001-9167-6396 NR 91 TC 106 Z9 108 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 2002 VL 277 IS 18 BP 16102 EP 16115 DI 10.1074/jbc.M111705200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 550PA UT WOS:000175510400118 PM 11821419 ER PT J AU McLean, PJ Hyman, BT AF McLean, PJ Hyman, BT TI An alternatively spliced form of rodent alpha-synuclein forms intracellular inclusions in vitro: role of the carboxy-terminus in alpha-synuclein aggregation SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; Lewy body; proteasome; carboxy-terminus; aggregation ID PARKINSONS-DISEASE; ALZHEIMER-DISEASE; LEWY BODIES; PROTEIN; PROTEASOME; COMPONENT; MUTATION; MEMBRANE; NEURONS; FAMILY AB In the rat, the alpha-synuclein gene is alternatively spliced and exists in three forms, rat synuclein 1 (rSYN1), synuclein 2 (rSYN2) and synuclein 3. rSYN2 cDNA encodes a 149 amino acid protein that is homologous to rSYN1 and human alpha-synuclein for the first 100 amino acids, but is divergent for the 49 amino acid carboxy-terminal region. We demonstrate here that rSYN2 forms small aggregates throughout the cytoplasm when overexpressed in human H4 cells, whereas rSYN1 expression is diffuse. Inhibition of the proteasome promotes the formation of larger, cytoplasmic rSYN2 inclusions in transfected cells. Although a survey of the available databases suggests that there is no human splice form equivalent of rSYN2, thus arguing against a direct role in Lewy body formation and Parkinson's disease, these data nonetheless suggest that modifications of the carboxy-terminal region of a-synuclein predispose it to inclusion formation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp East, Ctr Aging Genet & Neurodegenerat, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp East, Ctr Aging Genet & Neurodegenerat, Alzheimers Dis Res Unit, 114 16th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [P50NS38372] NR 20 TC 22 Z9 22 U1 0 U2 9 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 MAY 3 PY 2002 VL 323 IS 3 BP 219 EP 223 AR PII S0304-3940(02)00154-4 DI 10.1016/S0304-3940(02)00154-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 552QX UT WOS:000175632000014 PM 11959424 ER PT J AU Sahani, D Saini, S Sharma, R O'Malley, M Harisinghani, M Hahn, PF Mueller, PR AF Sahani, D Saini, S Sharma, R O'Malley, M Harisinghani, M Hahn, PF Mueller, PR TI Characterizing liver hemangiomas on ferumoxides-enhanced dynamic Tl-weighted imaging: Preliminary experience SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Meeting (CMR99) CY SEP 12-17, 1999 CL WOODSTOCK, VERMONT ID SUPERPARAMAGNETIC IRON-OXIDE C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2002 VL 9 SU 1 BP S255 EP S256 DI 10.1016/S1076-6332(03)80450-6 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 546VR UT WOS:000175296700067 PM 12019883 ER PT J AU Gomez-Tortosa, E Gonzalo, I Newell, K Yebenes, JG Vonsattel, JP Hyman, BT AF Gomez-Tortosa, E Gonzalo, I Newell, K Yebenes, JG Vonsattel, JP Hyman, BT TI Patterns of protein nitration in dementia with Lewy bodies and striatonigral degeneration SO ACTA NEUROPATHOLOGICA LA English DT Article DE alpha-synuclein; nitrotyrosine; oxidative stress; Lewy body; striatonigral degeneration ID MULTIPLE SYSTEM ATROPHY; ALPHA-SYNUCLEIN IMMUNOREACTIVITY; PARKINSONS-DISEASE; CYTOPLASMIC INCLUSIONS; ALZHEIMERS-DISEASE; OXIDATIVE DAMAGE; BODY DISEASE; NEURODEGENERATION; AGGREGATION; BRAINS AB The synucleinopathies are a group of neurodegenerative disorders characterized by the presence of alpha-synuclein inclusions in neurons (Lewy body diseases, LBD) or glial cells (multiple system atrophies, MSA). Recently, nitration of alpha-synuclein has been reported as the possible modification that induces its aggregation and deposition in these disorders. In this study we investigated the distribution and relationships of alpha-synuclein inclusions and 3-nitrotyrosine (3-NT), a marker of protein nitration through oxidative mechanisms, in brains diagnosed with LBD or MSA and control brains using double immunohistochemical techniques. In LBD cases, 3-NT colocalized with a-synuclein immunoreactivity in classic and cortical Lewy bodies and in dystrophic neurites in substantia nigra. However, most pale bodies and diffuse deposits in substantia nigra and Lewy neurites in hippocampus lack 3-NT immunoreactivity. A majority of cases showed diffuse cytoplasmic 3-NT staining in pyramidal cells of the CA2-3 regions of the hippocampus that was independent of alpha-synuclein deposits. All MSA cases showed 3-NT immunoreactivity in glial inclusions. 3-NT neuronal staining was restricted to pontine nuclei with three cases showing nuclear and one case cytoplasmic staining. There was no colocalization of 3-NT nuclear immunoreactivity with alpha-synuclein-immunopositive nuclear inclusions in pontine neurons. These data show that protein nitration in LBD and MSA cases has a widespread distribution and is not only associated with the alpha-synuclein deposits. The presence of alpha-synuclein-positive deposits lacking 3-NT immunoreactivity suggests that nitration is not a prerequisite for alpha-synuclein deposition. C1 Univ Complutense, Fdn Jimenez Diaz, Serv Neurol, E-28040 Madrid, Spain. Univ Complutense, Banco Tejidos Invest Neurol, E-28040 Madrid, Spain. Harvard Univ, Massachusetts Gen Hosp, Alzheimers Res Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA USA. RP Gomez-Tortosa, E (reprint author), Univ Complutense, Fdn Jimenez Diaz, Serv Neurol, E-28040 Madrid, Spain. FU NIA NIH HHS [AG05134]; NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [P50 NS38372] NR 25 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAY PY 2002 VL 103 IS 5 BP 495 EP 500 DI 10.1007/s00401-001-0495-3 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 542NF UT WOS:000175049500011 PM 11935266 ER PT J AU Israel, Y Lieber, CS AF Israel, Y Lieber, CS TI The Research Society on Alcoholism SO ADDICTION LA English DT Article DE alcoholism; biomedical; history; psychosocial; research; society AB Until the 1960s, the small amount of federal funding available in the alcohol field in the USA was provided by a division of the Alcohol, Drug and Mental Health Administration. In the late 1960s. the National Council on Alcoholism (NCA) joined the American Medical Society on Alcoholism (AMSA. which accepted only physicians). A group of physicians at NCA-AMSA felt that progress in our field needed the concerted effort of both physicians and non-physician scientists, creating the Research Society on Alcoholism (RSA) in 1977. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) had been created a few years earlier. From 2 50 members in 19 78, the RSA has grown to 1500 in 2001, with a ratio of about three PhDs (with specialities that range from gene therapy to social policy) to each MD. The society holds yearly meetings-visitors can find more information oil the web page (http://www.RSoA.org). The society publishes the journal Alcoholism: Clinical and Experimental Research. RSA committees are active in presenting the most recent findings to the public and to elected representatives, and in making recommendations on areas of research that need funding. C1 Thomas Jefferson Univ, Alcohol Res Ctr, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Univ Chile, Millennium Inst Adv Res, Santiago, Chile. Bronx Vet Adm Med Ctr, Alcohol Res Ctr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY USA. RP Israel, Y (reprint author), Thomas Jefferson Univ, Alcohol Res Ctr, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAY PY 2002 VL 97 IS 5 BP 483 EP 486 DI 10.1046/j.1360-0443.2002.00012.x PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 548UW UT WOS:000175409100003 PM 12033649 ER PT J AU Clement, PB Young, TH AF Clement, PB Young, TH TI Endometrioid carcinoma of the uterine corpus: A review of its pathology with emphasis on recent advances and problematic aspects SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE uterus; endometrium; carcinoma; ndometrioid ID ATYPICAL POLYPOID ADENOMYOMA; GYNECOLOGIC-ONCOLOGY-GROUP; MIXED ADENOSQUAMOUS CARCINOMA; ALPHA-FETOPROTEIN PRODUCTION; FEMALE GENITAL-TRACT; WOMEN 40 YEARS; PROGNOSTIC-SIGNIFICANCE; ARGYROPHIL CELLS; BREAST-CANCER; HEPATOID ADENOCARCINOMA AB This review considers the pathologic features of endometrioid carcinoma of the uterine corpus. which accounts for approximately 80% of endometrial adenocarcinomas, with an emphasis on its histologic features, recent advances, and problematic aspects, In addition to typical endometrioid carcinoma, the variants of endometrioid carcinoma covered include secretory carcinoma, villoglandular endometrioid carcinoma, endometrioid carcinoma with small nonvillous papillae, endometrioid carcinomas with microglandular and sertoliform patterns, and endometrioid carcinomas with metaplastic changes. These changes include a variety of different appearances of squamous epithelia (ranging from mature and keratinizing to immature with only subtle evidence of a squamous nature), clear cells, surface changes resembling syncytial metaplasia or microglandular hyperplasia, ciliated cells, oxyphilic cells, and spindled epithelial cells (sarcomatoid carcinoma). The last is one of several variants that may cause a biphasic appearance. all of which should be distinguished from the malignant mullerian mixed tumor. Rare findings in endometrioid carcinomas include hyalinization. psammoma bodies. and foci of stromal metaplasia such as osteoid. Unusual growth patterns of endometrioid carcinomas include involvement of adenomyosis, the "diffusely" infiltrating pattern of myoinvasion, and a previously unemphasized pattern of myoinvasion with "pinched off" glands that may be cystic or have a pseudovascular appearance. often With a myxoid stromal reaction. Other aspects of endometrioid carcinoma discussed are its immunoprofile, grading, cervical involvement (including a hitherto undescribed "burrowing" pattern of extension within the cervix that can result in underdiagnosis of stave IIB disease), carcinoma arising in the lower uterine segment, carcinoma arising in polyps and adenomyomas, carcinoma in young women, tamoxifen-related carcinoma, associated ovarian endometrioid carcinoma, and peritoneal keratin granulomas. Finally, the differential diagnosis of endometrioid carcinoma is briefly considered with a section on benign mimics, including curettage-related changes. menstrual changes, adenomyosis-related problems, metaplastic changes, atypical polypoid adenomyoma, radiation atypia, and papillary proliferations. and a section on metastatic colonic carcinoma. 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. Univ British Columbia, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC, Canada. RP Clement, PB (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 156 TC 87 Z9 96 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD MAY PY 2002 VL 9 IS 3 BP 145 EP 184 DI 10.1097/00125480-200205000-00001 PG 40 WC Pathology SC Pathology GA 543YF UT WOS:000175130400001 PM 11981113 ER PT J AU Nanji, AA Su, GL Laposata, M French, SW AF Nanji, AA Su, GL Laposata, M French, SW TI Pathogenesis of alcoholic liver disease-recent advances SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholic liver disease; cyclooxygenase; lipopolysaccharide; fatty acid esters; oxidative stress ID ACID ETHYL-ESTERS; LIPOPOLYSACCHARIDE-BINDING-PROTEIN; NONOXIDATIVE ETHANOL-METABOLISM; LOW-DENSITY-LIPOPROTEIN; NECROSIS-FACTOR-ALPHA; FACTOR-KAPPA-B; GENE-EXPRESSION; HEPG2 CELLS; HUMAN SERUM; RAT MODEL AB The article summarizes the proceedings of a symposium on recent advances in research on the pathogenesis of alcoholic liver disease at the 2001 RSA meeting in Montreal, Canada. The chairs were Amin A. Nanji and Samuel W. French. The presentations were (1) Role of inflammatory mediators in alcoholic liver injury by Amin A. Nanji, (2) Role of endotoxin, lipopolysaccharide binding protein, CD14 and Toll receptors in alcoholic liver injury by Grace Su, (3) Fatty acid ethyl esters: toxicity, metabolism and markers of ethanol intake by Michael Laposata, and (4) Cyclic changes in gene expression when rats are fed alcohol at a constant rate by Samuel W. French. C1 Queen Mary Hosp, Clin Biochem Unit, Hong Kong, Hong Kong, Peoples R China. Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Univ Michigan, Med Ctr, Dept Med, Ann Arbor, MI 48109 USA. Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Ctr Study Liver Dis, Hong Kong, Hong Kong, Peoples R China. RP Nanji, AA (reprint author), Queen Mary Hosp, Clin Biochem Unit, LG 136,Block K,102 Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. FU NIDDK NIH HHS [DK 53296] NR 59 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2002 VL 26 IS 5 BP 731 EP 736 DI 10.1111/j.1530-0277.2002.tb02598.x PG 6 WC Substance Abuse SC Substance Abuse GA 552WW UT WOS:000175643900019 PM 12045483 ER PT J AU Kahn, JA Colditz, G Aweh, GN Frazier, AL AF Kahn, JA Colditz, G Aweh, GN Frazier, AL TI Prevalence and correlates of pelvic examinations in sexually active female adolescents SO AMBULATORY PEDIATRICS LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Adolescent-Medicine CY MAR 22-24, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Adolescent Med DE adolescent medicine; pelvic examinations; preventive health behaviors; reproductive health ID SEEK HEALTH-CARE; PREVENTIVE SERVICES; ANXIETY; SMEAR; WOMEN; RISK AB Objectives.-The pelvic examination is an important component of reproductive health services for adolescent girls and is recommended for those who become sexually active. The aims of this study were to describe self-reported rates of pelvic examinations in sexually active adolescent girls and to determine factors associated with having obtained an examination. Methods.-Cross-sectional data from a national self-administered survey of nurses' adolescent daughters were used. Subjects were those girls (N=635) who reported ever having had sexual intercourse. Bivariate and multivariate analyses were used to identify demographic and psychological variables, preventive health behaviors, and risk behaviors associated with having ever obtained a pelvic examination. Results.-Median subject age A,as 16.0 years (range 12-19 years), and 46% of subjects reported having had a pelvic examination. Variables associated with having obtained an examination were older age (odd ratio [OR] 1.29, 95% confidence interval [CI] 1.09-1.53), cigarette smoking (OR 1.51, 95% CI 1.02-2.24), higher number of sexual partners (OR 1.29, 95% CI 1.14-1.47), and no condom use during last sexual intercourse (OR 1,80, 95% CI 1.19-2.70). Conclusions.-Fewer than half of these sexually active adolescents had ever obtained a pelvic examination. Younger subjects who did not smoke regularly, hand fewer partners, and used condoms were less likely to have obtained an examination: these adolescents may not be seeking reproductive health care services or be recognized by parents or providers as being in need of services. C1 Childrens Hosp, Med Ctr, Div Adolescent Med, Cincinnati, OH 45229 USA. Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Sch Med, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Kahn, JA (reprint author), Childrens Hosp, Med Ctr, Div Adolescent Med, 3333 Burnet Ave, Cincinnati, OH 45229 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL03533]; NIDDK NIH HHS [DK46834]; PHS HHS [5 T71 MC 00001-24] NR 28 TC 2 Z9 2 U1 0 U2 0 PU AMBULATORY PEDIATRIC ASSOC PI MCLEAN PA 6728 OLD MCLEAN VILLAGE DR, MCLEAN, VA 22101-3906 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD MAY-JUN PY 2002 VL 2 IS 3 BP 212 EP 217 DI 10.1367/1539-4409(2002)002<0212:PACOPE>2.0.CO;2 PG 6 WC Pediatrics SC Pediatrics GA 556EY UT WOS:000175837400006 PM 12014982 ER PT J AU Siegel, AJ Mendelson, JH Sholar, MB McDonald, JC Lewandrowski, KB Lewandrowski, EL Lipinska, I Ridker, PM Tofler, GH AF Siegel, AJ Mendelson, JH Sholar, MB McDonald, JC Lewandrowski, KB Lewandrowski, EL Lipinska, I Ridker, PM Tofler, GH TI Effect of cocaine usage on C-reactive protein, von Willebrand factor, and fibrinogen SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; APPARENTLY HEALTHY-MEN; MYOCARDIAL-INFARCTION; DISEASE; ATHEROSCLEROSIS; INFLAMMATION; MORTALITY; INCREASE AB Compared with normal values in drug-free subjects with cocaine abuse, C-reactive protein, von Willebrand factor, and fibrinogen were elevated in cocaine-dependent users without a compensatory increase in fibrinolytic activity. Measurements of these inflammatory and hemostatic markers may be useful to counsel patients, stratify risk, and guide treatment for reduction of cocaine-associated cardiovascular risk. C1 McLean Hosp, Dept Med, Belmont, MA 02478 USA. McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. RP Siegel, AJ (reprint author), McLean Hosp, Dept Internal Med, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [DA00064, DA010757, DA07252] NR 20 TC 26 Z9 26 U1 1 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2002 VL 89 IS 9 BP 1133 EP + AR PII S0002-9149(02)02289-0 DI 10.1016/S0002-9149(02)02289-0 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 548TU UT WOS:000175406600024 PM 11988210 ER PT J AU Duggan, C Gannon, J Walker, WA AF Duggan, C Gannon, J Walker, WA TI Protective nutrients and functional foods for the gastrointestinal tract SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Review ID TOTAL PARENTERAL-NUTRITION; BONE-MARROW TRANSPLANTATION; NITRIC-OXIDE SYNTHASE; CRITICALLY ILL PATIENTS; VITAMIN-A-DEFICIENCY; SMALL-BOWEL TRANSPLANTATION; AMINO-ACID-CONCENTRATIONS; PLACEBO-CONTROLLED TRIAL; IMMUNE-ENHANCING DIET; POSTOPERATIVE ENTERAL IMMUNONUTRITION AB Epithelial and other cells of the gastrointestinal mucosa rely on both luminal and bloodstream sources for their nutrition. The term functional food is used to describe nutrients that have an effect on physiologic processes that is separate from their established nutritional function, and some of these nutrients are proposed to promote gastrointestinal mucosal integrity. We review the recent in vitro, animal, and clinical experiments that evaluated the role of several types of gastrointestinal functional foods, including the amino acids glutamine and arginine, the essential micronutrients vitamin A and zinc, and 2 classes of food additives, prebiotics and probiotics. Many of the data from preclinical studies support a strong role for enteral nutrients in gastrointestinal health; in comparison, the data from human studies are limited. In some cases, impressive data from in vitro and animal studies have not been replicated in human trials. Other clinical trials have shown positive health benefits, but some of those studies were plagued by flaws in study design or analysis. The methods available to detect important changes in human gastrointestinal function and structure are still limited, but with the development of more sensitive measures of gastrointestinal function, the effects of specific nutrients may be more easily detected. This may facilitate the development of phase 3 clinical trials designed to more rigorously evaluate the effects of a particular nutrient by focusing on valid and reliable outcome measures. Regulatory changes in the way in which health claims can be made for dietary supplements should also be encouraged. C1 Massachusetts Gen Hosp, Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Nutr, Boston, MA 02138 USA. RP Duggan, C (reprint author), Childrens Hosp, Div GI Nutr, Clin Nutr Serv, 300 Longwood Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [P30-DK40561, 5 T32-DK07477] NR 294 TC 106 Z9 132 U1 1 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 MAY PY 2002 VL 75 IS 5 BP 789 EP 808 PG 20 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 545CA UT WOS:000175197600003 PM 11976152 ER PT J AU Finkel, MA AF Finkel, MA TI Traumatic injuries caused by hazing practices SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE hazing; violence; trauma; injuries; alcohol AB Hazing is defined as committing acts against an individual or forcing an individual into committing an act that creates a risk for harm in order for the individual to be initiated into or affiliated with an organization. Hazing is an enduring activity with roots that date back to the ancient and medieval eras. It has become increasingly prevalent in fraternities and sororities, high school and college athletic organizations, the military, professional sports teams, and street gangs. Scant information is available in the medical literature regarding hazing. This article reviews the history of hazing, provides statistics regarding its prevalence, presents information on specific hazing practices and consequent traumatic injuries, and assesses alcohol's influence on hazing. It also offers recommendations on how to recognize victims of hazing in the Emergency Department and proposes guidelines for their treatment. Current legislation and information on the prevention of traumatic injuries from hazing are discussed. (Am J Emerg Med 2002;20:228-233. Copyright 2002, Elsevier Science (USA). All rights reserved.) C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Finkel, MA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Fruit St, Boston, MA 02114 USA. NR 15 TC 13 Z9 15 U1 1 U2 14 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 MAY PY 2002 VL 20 IS 3 BP 228 EP 233 DI 10.1053/ajem.2002.32649 PG 6 WC Emergency Medicine SC Emergency Medicine GA 549WK UT WOS:000175469600017 PM 11992345 ER PT J AU Aspinall, MB Whittle, J Aspinall, SL Maher, RL Good, CB AF Aspinall, MB Whittle, J Aspinall, SL Maher, RL Good, CB TI Improving adverse-drug-reaction reporting in ambulatory care clinics at a Veterans Affairs hospital SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE ambulatory care; data collection; Department of Veterans Affairs; drugs, adverse reactions; pharmacy, institutional, hospital; reports ID MEDWATCH; OUTPATIENTS; MEDICATION AB The detection of adverse drug reactions (ADRs) by a traditional passive reporting system and by a method involving patient and provider interviews was studied. The study sample consisted of randomly selected outpatients seen by their primary care provider during scheduled appointments in January and February 2001 at a Veterans Affairs medical center. After ambulatory care clinic sessions, patients and providers were asked (by telephone and in person, respectively) to identify potential ADRs. Also obtained were demographic data, information about drug regimens, and the severity and management of each ADR. A standardized ADR-assessment tool was used to determine the severity of each reported reaction and its causal relationship with the medication. A total of 198 patients were included. Of these, 51 (26%) had one or more ADRs. The patient and provider interviews identified a total of 83 ADRs, compared with I ADR identified by the passive reporting system. When providers were made aware of the ADRs they had not identified, changes were made to the patient's medication regimen in 34% of cases. The risk of an ADR was not associated with age, number of medications, or provider type. Direct patient and provider interviews yielded a significantly higher rate of ADR, detection in an ambulatory care setting than did a passive ADR-reporting system. C1 UPMC Healthcare Syst, Rx Partners LTC, Pittsburgh, PA USA. Univ Kansas, Med Ctr, Div Gen & Geriatr Med, Kansas City, KS 66103 USA. Kansas City VA Med Ctr, Kansas City, KS USA. Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15260 USA. Duquesne Univ, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15219 USA. VA Pharm Benefits Management Strateg Care Grp, Med Advisory Panel, Washington, DC USA. RP Aspinall, MB (reprint author), VA Pittsburgh Healthcare Syst, Dept Pharm 132M U, Univ Dr C, Pittsburgh, PA 15240 USA. NR 14 TC 16 Z9 17 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 1 PY 2002 VL 59 IS 9 BP 841 EP 845 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 548BH UT WOS:000175368000014 PM 12004462 ER PT J AU DeStefano, AL Lew, MF Golbe, LI Mark, MH Lazzarini, AM Guttman, M Montgomery, E Waters, CH Singer, C Watts, RL Currie, LJ Wooten, GF Maher, NE Wilk, JB Sullivan, KM Slater, KM Saint-Hilaire, MH Feldman, RG Suchowersky, O Lafontaine, AL Labelle, N Growdon, JH Vieregge, P Pramstaller, PP Klein, C Hubble, JP Reider, CR Stacy, M MacDonald, ME Gusella, JF Myers, RH AF DeStefano, AL Lew, MF Golbe, LI Mark, MH Lazzarini, AM Guttman, M Montgomery, E Waters, CH Singer, C Watts, RL Currie, LJ Wooten, GF Maher, NE Wilk, JB Sullivan, KM Slater, KM Saint-Hilaire, MH Feldman, RG Suchowersky, O Lafontaine, AL Labelle, N Growdon, JH Vieregge, P Pramstaller, PP Klein, C Hubble, JP Reider, CR Stacy, M MacDonald, ME Gusella, JF Myers, RH TI PARK3 influences age at onset in Parkinson disease: A genome scan in the GenePD study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LINKAGE ANALYSIS; ASSOCIATION; TESTS AB Parkinson disease (PD) is a late-onset neurodegenerative disorder. The mean age at onset is 61 years, but the disease can range from juvenile cases to cases in the 8th or 9th decade of life. The parkin gene on chromosome 6q and loci on chromosome 1p35-36 and 1p36 are responsible for some cases of autosomal recessive early-onset parkinsonism, but they do not appear to influence susceptibility or variability of age at onset for idiopathic PD. We have performed a genomewide linkage analysis using variance-component methodology to identify genes influencing age at onset of PD in a population of affected relatives (mainly affected sibling pairs) participating in the GenePD study. Four chromosomal loci showed suggestive evidence of linkage: chromosome 2p (maximum multipoint LOD [MaxLOD] = 2.08), chromosome 9q (MaxLOD = 2.00), chromosome 20 (MaxLOD = 1.82), and chromosome 21 (MaxLOD = 2.21). The 2p and 9q locations that we report here have previously been reported as loci influencing PD affection status. Association between PD age at onset and allele 174 of marker D2S1394, located on 2p13, was observed in the GenePD sample (P=.02). This 174 allele is common to the PD haplotype observed in two families that show linkage to PARK3 and have autosomal dominant PD, which suggests that this allele may be in linkage disequilibrium with a mutation influencing PD susceptibility or age at onset of PD. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Univ So Calif, Dept Neurol, Los Angeles, CA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Miami, Dept Neurol, Miami, FL 33152 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. Univ Calgary, Dept Med Genet, Calgary, AB, Canada. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Gen Reg Hosp Bolzano, Dept Neurol, Bolzano, Italy. Barrow Clin, Dept Neurol, Phoenix, AZ USA. RP DeStefano, AL (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St T3E, Boston, MA 02118 USA. RI Pramstaller, Peter/C-2357-2008 FU NINDS NIH HHS [R01 NS036711] NR 21 TC 56 Z9 56 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2002 VL 70 IS 5 BP 1089 EP 1095 DI 10.1086/339814 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 541XT UT WOS:000175012400002 PM 11920285 ER PT J AU Herrnstadt, C Elson, JL Fahy, E Preston, G Turnbull, DM Anderson, C Ghosh, SS Olefsky, JM Beal, MF Davis, RE Howell, N AF Herrnstadt, C Elson, JL Fahy, E Preston, G Turnbull, DM Anderson, C Ghosh, SS Olefsky, JM Beal, MF Davis, RE Howell, N TI Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HEREDITARY OPTIC NEUROPATHY; POPULATIONS REVEALS; ALZHEIMER-DISEASE; MTDNA VARIATION; HUMAN-EVOLUTION; NEAR-EASTERN; GENOME; LINEAGES; ORIGIN; EXPRESSION AB The evolution of the human mitochondrial genome is characterized by the emergence of ethnically distinct lineages or haplogroups. Nine European, seven Asian (including Native American), and three African mitochondrial DNA (mtDNA) haplogroups have been identified previously on the basis of the presence or absence of a relatively small number of restriction-enzyme recognition sites or on the basis of nucleotide sequences of the D-loop region. We have used reduced-median-network approaches to analyze 560 complete European, Asian, and African mtDNA coding-region sequences from unrelated individuals to develop a more complete understanding of sequence diversity both within and between haplogroups. A total of 497 haplogroup-associated polymorphisms were identified, 323 (65%) of which were associated with one haplogroup and 174 (35%) of which were associated with two or more haplogroups. Approximately one-half of these polymorphisms are reported for the first time here. Our results confirm and substantially extend the phylogenetic relationships among mitochondrial genomes described elsewhere from the major human ethnic groups. Another important result is that there were numerous instances both of parallel mutations at the same site and of reversion (i.e., homoplasy). It is likely that homoplasy in the coding region will confound evolutionary analysis of small sequence sets. By a linkage-disequilibrium approach, additional evidence for the absence of human mtDNA recombination is presented here. C1 MitoKor, San Diego, CA 92121 USA. Newcastle Univ, Dept Neurol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Vet Adm Med Ctr, San Diego, CA 92161 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Univ Texas, Med Branch, Dept Radiat Oncol, Galveston, TX 77550 USA. RP Herrnstadt, C (reprint author), MitoKor, 11494 Sorrento Valley Rd, San Diego, CA 92121 USA. EM herrnstadtc@mitokor.com NR 54 TC 337 Z9 348 U1 4 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2002 VL 70 IS 5 BP 1152 EP 1171 DI 10.1086/339933 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA 541XT UT WOS:000175012400007 PM 11938495 ER PT J AU Silverman, EK Palmer, LJ Mosley, JD Barth, M Senter, JM Brown, A Drazen, JM Kwiatkowski, DJ Chapman, HA Campbell, EJ Province, MA Rao, DC Reilly, JJ Ginns, LC Speizer, FE Weiss, ST AF Silverman, EK Palmer, LJ Mosley, JD Barth, M Senter, JM Brown, A Drazen, JM Kwiatkowski, DJ Chapman, HA Campbell, EJ Province, MA Rao, DC Reilly, JJ Ginns, LC Speizer, FE Weiss, ST TI Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETIC EPIDEMIOLOGY; WIDE SEARCH; ASTHMA; DEFICIENCY; FAMILIES; FLOW; IDENTIFICATION; POPULATION; PROBANDS; SMOKING AB Chronic obstructive pulmonary disease (COPD) is a common, complex disease associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction; airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 s (FEV1) and the ratio of FEV1 to forced vital capacity (FVC). To identify genetic determinants of quantitative spirometric phenotypes, an autosomal 10-cM genomewide scan of short tandem repeat (STR) polymorphic markers was performed in 72 pedigrees (585 individuals) ascertained through probands with severe early-onset COPD. Multipoint variance-component linkage analysis (using SOLAR) was performed for quantitative phenotypes, including FEV1, FVC, and FEV1/FVC. In the initial genomewide scan, significant evidence for linkage to FEV1/FVC was demonstrated on chromosome 2q (LOD score 4.12 at 222 cM). Suggestive evidence was found for linkage to FEV1/FVC on chromosomes 1 (LOD score 1.92 at 120 cM) and 17 (LOD score 2.03 at 67 cM) and to FVC on chromosome 1 (LOD score 2.05 at 13 cM). The highest LOD score for FEV1 in the initial genomewide scan was 1.53, on chromosome 12, at 36 cM. After inclusion of 12 additional STR markers on chromosome 12p, which had been previously genotyped in this population, suggestive evidence for linkage of FEV1 (LOD score 2.43 at 37 cM) to this region was demonstrated. These observations provide both significant evidence for an early-onset COPD-susceptibility locus on chromosome 2 and suggestive evidence for linkage of spirometry-related phenotypes to several other genomic regions. The significant linkage of FEV1/FVC to chromosome 2q could reflect one or more genes influencing the development of airflow obstruction or dysanapsis. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Care, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. RP Silverman, EK (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Palmer, Lyle/K-3196-2014 OI Palmer, Lyle/0000-0002-1628-3055 FU NHLBI NIH HHS [HL 61575, HL 46440, HL 67204, P50 HL56383, R37 HL067204, U01 HL 66795, U01 HL066795] NR 40 TC 116 Z9 121 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2002 VL 70 IS 5 BP 1229 EP 1239 DI 10.1086/340316 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 541XT UT WOS:000175012400012 PM 11914989 ER PT J AU Lev, MH AF Lev, MH TI CT/MR perfusion imaging and alphabet soup: An appeal for standardized nomenclature SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material ID CT C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2002 VL 23 IS 5 BP 746 EP 747 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 552BW UT WOS:000175599300002 PM 12006270 ER PT J AU Slaughter, A Pasero, C Manworren, R AF Slaughter, A Pasero, C Manworren, R TI Unacceptable pain levels SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 W Los Angeles Healthcare Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Childrens Med Ctr, Dallas, TX 75235 USA. RP Pasero, C (reprint author), W Los Angeles Healthcare Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 4 TC 5 Z9 7 U1 0 U2 1 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 MAY PY 2002 VL 102 IS 5 BP 75 EP + PG 2 WC Nursing SC Nursing GA 550QJ UT WOS:000175513500048 PM 12006857 ER PT J AU Berg, AO AF Berg, AO TI Screening for skin cancer: Recommendations and rationale SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 US Prevent Serv Task Force, Agcy Healthcare Res & Qual, Clin Prevent Serv, Ctr Practice & Technol Assessment, Rockville, MD 20852 USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX USA. Tri Cty Family Med, Cohocton, NY USA. Univ Rochester, Rochester, NY USA. Natl Initiat Childrens Healthcare Qual, Boston, MA USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. Dartmouth Hitchcock Med Ctr, Dept Med, Lebanon, NH 03766 USA. Merck & Co Inc, Outcomes Res & Management, W Point, PA USA. Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Family Practice, Fairfax, VA USA. RP Berg, AO (reprint author), US Prevent Serv Task Force, Agcy Healthcare Res & Qual, Clin Prevent Serv, Ctr Practice & Technol Assessment, 6010 Exectur Blvd,Suite 300, Rockville, MD 20852 USA. NR 9 TC 1 Z9 1 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 MAY PY 2002 VL 102 IS 5 BP 97 EP + PG 3 WC Nursing SC Nursing GA 550QJ UT WOS:000175513500052 ER PT J AU Andreoli, CM Leff, GB Rizzo, JF AF Andreoli, CM Leff, GB Rizzo, JF TI Sneeze-induced visual and ocular motor dysfunction SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: The purpose of this report is to describe two neuroophthalmic complications that are related by their temporal association with a sneeze. DESIGN: We describe observational case reports of two patients. METHODS: Both patients were examined, and their conditions were diagnosed and treated according to standard indications for each neuroophthalmic condition. RESULTS: The first case describes a patient who had previously undergone intracranial surgery, including removal of the clivus and later developed a trochlear nerve paresis after a sneeze. The second case describes a patient who repeatedly demonstrates transient decreased perfusion to his right central retinal artery and an associated afferent papillary defect after sneezing. CONCLUSION: The mechanical and hemodynamic forces involved in sneezing are formidable and may cause permanent cranial neuropathy or temporarily alter ocular blood flow in certain patients. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Wayne State Univ, Kresge Eye Inst, Detroit, MI USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2002 VL 133 IS 5 BP 725 EP 727 DI 10.1016/S0002-9394(02)01388-0 PG 3 WC Ophthalmology SC Ophthalmology GA 550QL UT WOS:000175513700029 PM 11992883 ER PT J AU Ishoo, E Busaba, NY AF Ishoo, E Busaba, NY TI Ectopic gastric mucosa in the cervical esophagus SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 09-14, 2001 CL DENVER, COLORADO SP Amer Acad Otolayngol Head Neck Surg ID INLET PATCH; ADENOCARCINOMA; DUODENUM AB This study describes the clinical presentation and management of ectopic gastric mucosa (EGM) in the cervical esophagus. This is a case report of a 53-year-old male who presented with left-sided odynophagia of 3 months' duration. Office examination, including flexible fiberoptic laryngoscopy, was unremarkable. Direct larynogoscopy and rigid esophagoscopy revealed a 2 x 1-cm fleshy, red, and raised lesion in the cervical esophagus. The remainder of the esophagus was normal. Histologic examination of a biopsy specimen from the lesion showed a normal gastric epithelium consistent with the diagnosis of ectopic gastric mucosa. He was treated with 3 months of proton pump inhibitors, which resulted in complete symptom resolution. Patient was then switched to H2-blockers and has been symptom-free for one year. The medical literature regarding EGM in the cervical esophagus is reviewed with respect to its incidence, pathogenesis, clinical course, and management. In conclusion, EGM can occur in the cervical esophagus, and odynophagia is the typical presenting symptom. Adenocarcinoma developing within random, nonsyndromic EGM of the cervical esophagus is exceedingly rare. The primary mode of treatment is medical therapy. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Carle Clin Assoc, Div Otolaryngol Head & Neck Surg, Urbana, IL USA. Boston VA Healthcare Syst, Div Otollaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 27 TC 7 Z9 7 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAY-JUN PY 2002 VL 23 IS 3 BP 181 EP 184 DI 10.1053/ajot.2002.123437 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 554TG UT WOS:000175752800011 PM 12019489 ER PT J AU Corless, CL McGreevey, L Haley, A Town, A Heinrich, MC AF Corless, CL McGreevey, L Haley, A Town, A Heinrich, MC TI KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID OF-FUNCTION MUTATION; C-KIT; GERMLINE MUTATION; MUSCLE TUMORS; KINASE DOMAIN; GENE; LEIOMYOMAS; PROGNOSIS; DIAGNOSIS; EXON-13 AB Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gut wall that express the receptor tyrosine kinase KIT. Somatic mutations that result in constitutive activation of KIT kinase have been identified in a number of studies of GISTs, although the reported frequency of these mutations has varied over a wide range (20 to 92%). Several reports have suggested that KIT gene mutations are more common in malignant GISTs than in benign lesions, and it has been proposed that mutations in exon 11 of KIT are a negative prognostic factor. To maximize sensitivity for KIT mutations we have adapted denaturing high-pressure liquid chromatography as a method for screening polymerase chain reaction amplimers of exons 9, 11, 13, and 17 from GIST genomic DNA. This approach was used to assess the frequency of KIT mutations in 13 morphologically benign, incidentally discovered, GISTs identified at autopsy, endoscopy, or laparotomy for unrelated disease. Representing the smallest pathologically recognizable GISTs, these lesions ranged in size from 4 to 10 mm in diameter and were all immunohistochemically positive for KIT. Eleven of the 13 tumors had sequence-confirmed mutations in KIT, including 10 mutations in exon 11 (77%) and one mutation in exon 9 (7.7%). The remaining two tumors were wild type for exons 9, 11, and 17; one of these was also analyzed for exon 13 and was wild type in this exon as well. The mutations found in the incidental GISTs were identical to those that have been documented in larger GISTs. In addition, the overall frequency of mutations in the incidental tumors (85%) did not differ significantly from that we previously reported in a series of 72 advanced/metastatic GISTs (86%), strongly supporting the view that activating mutations in KIT are acquired very early in the development of most GISTs. The findings suggest that KIT mutations per se are of little prognostic importance in GISTs. C1 Oregon Hlth & Sci Univ, Dept Pathol L471, Div Hematol Oncol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Med, Div Hematol Oncol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Corless, CL (reprint author), Oregon Hlth & Sci Univ, Dept Pathol L471, Div Hematol Oncol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 26 TC 316 Z9 338 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2002 VL 160 IS 5 BP 1567 EP 1572 DI 10.1016/S0002-9440(10)61103-0 PG 6 WC Pathology SC Pathology GA 549VV UT WOS:000175468200005 PM 12000708 ER PT J AU Schlossmacher, MG Frosch, MP Gai, WP Medina, M Sharma, N Forno, L Ochiishi, T Shimura, H Sharon, R Hattori, N Langston, JW Mizuno, Y Hyman, BT Selkoe, DJ Kosik, KS AF Schlossmacher, MG Frosch, MP Gai, WP Medina, M Sharma, N Forno, L Ochiishi, T Shimura, H Sharon, R Hattori, N Langston, JW Mizuno, Y Hyman, BT Selkoe, DJ Kosik, KS TI Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; UBIQUITIN-PROTEIN LIGASE; RESONANCE ENERGY-TRANSFER; MUTANT ALPHA-SYNUCLEIN; SUBCELLULAR-LOCALIZATION; IN-VITRO; GENE; BODY; ASSOCIATION; MUTATIONS AB Mutations in alpha-synuclein (alphaS) and parkin cause heritable forms of Parkinson disease (PD). We hypothesized that neuronal parkin, a known E3 ubiquitin ligase, facilitates the formation of Lewy bodies (LBs), a pathological hallmark of PD. Here, we report that affinity-purified parkin antibodies labeled classical LBs in substantia nigra sections from four related human disorders: sporadic PD, inherited alphaS-linked PD, dementia with LBs (DLB), and LB-positive, parkin-linked PD. Anti-parkin antibodies also detected LBs in entorhinal and cingulate cortices from DLB brain and alphaS inclusions in sympathetic gangliocytes from sporadic PD. Double labeling with confocal microscopy of DLB midbrain sections revealed that similar to90% of anti-alphaS-reactive LBs were also detected by a parkin antibody to amino acids 342 to 353. Accordingly, parkin proteins, including the 53-kd mature isoform, were present in affinity-isolated LBs from DLB cortex. Fluorescence resonance energy transfer and immunoelectron microscopy showed that alphaS and parkin co-localized within brainstem and cortical LBs. Biochemically, parkin appeared most enriched in cytosolic and postsynaptic fractions of adult rat brain, but also in purified, alphaS-rich presynaptic elements that additionally contained parkin's E2-binding partner, UbcH7. We conclude that parkin and UbcH7 are present with alphaS in subcellular compartments of normal brain and that parkin frequently co-localizes with alphaS aggregates in the characteristic LB inclusions of PD and DLB. These results suggest that functional parkin proteins may be required during LB formation. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Unit,Dept Neurol, Boston, MA USA. Flinders Univ S Australia, Dept Physiol, Bedford Pk, SA 5042, Australia. Flinders Univ S Australia, Ctr Neurosci, Bedford Pk, SA 5042, Australia. Palo Alto Vet Adm Hlth Care Syst, Palo Alto, CA USA. Parkinsons Inst, Sunnyvale, CA USA. Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan. RP Schlossmacher, MG (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Gai, Wei-Ping/A-3700-2008; OI Medina, Miguel/0000-0002-7016-5340 FU NINDS NIH HHS [K08 NS002127, NS02127, NS38372, NS38375, P50 NS038372, P50 NS038375] NR 60 TC 207 Z9 213 U1 1 U2 12 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2002 VL 160 IS 5 BP 1655 EP 1667 DI 10.1016/S0002-9440(10)61113-3 PG 13 WC Pathology SC Pathology GA 549VV UT WOS:000175468200015 PM 12000718 ER PT J AU Joussen, AM Poulaki, V Tsujikawa, A Qin, WY Qaum, T Xu, QW Moromizato, Y Bursell, SE Wiegand, SJ Rudge, J Ioffe, E Yancopoulos, GD Adamis, AP AF Joussen, AM Poulaki, V Tsujikawa, A Qin, WY Qaum, T Xu, QW Moromizato, Y Bursell, SE Wiegand, SJ Rudge, J Ioffe, E Yancopoulos, GD Adamis, AP TI Suppression of diabetic retinopathy with angiopoietin-1 SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ADHESION MOLECULE-1; PLASMA LEAKAGE; ICAM-1 EXPRESSION; TIE2 RECEPTOR; MESSENGER-RNA; CELL-SURVIVAL; IN-VIVO; VEGF; NEOVASCULARIZATION AB Diabetic retinopathy remains a leading cause of irreversible blindness. A critical early pathology in the disease is the adhesion of leukocytes to the retinal vasculature, a process that occurs, in part, via intercellular adhesion molecule-1. Once leukocyte adhesion occurs, endothelial cell injury ensues, as does blood-retinal barrier breakdown. Here we show that angiopoietin-1 can prevent and reverse these diabetic retinal vascular changes in both new and established diabetes. Angiopoietin-1, when given intravitreally to newly diabetic rats, normalized retinal vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 mRNA and protein levels, leading to reductions in leukocyte adhesion, endothelial cell injury, and blood-retinal barrier breakdown. When an adenovirus coding for angiopoietin-1 was given systemically to mice with established diabetes, it similarly inhibited leukocyte adhesion and endothelial cell injury and blood-retinal barrier breakdown. These changes coincided with reductions in retinal eNOS, nitric oxide, Akt (protein kinase B), and MAP kinase activity, known mediators of VEGF bioactivity and leukocyte adhesion. When endogenous VEGF bioactivity was inhibited with a soluble Flt-1/Fc chimera, retinal Akt kinase activity was significantly reduced in vivo. Taken together, these data document new vascular and anti-inflammatory bioactivities for angiopoietin-1 and identify it as the first naturally occurring protein that directly protects the retinal vasculature in diabetes. C1 Massachusetts Eye & Ear Infirm, Surg Res Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Childrens Hosp, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Cologne, Ctr Ophthal, Dept Vitreoretinal Surg, Cologne, Germany. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. RP Adamis, AP (reprint author), Massachusetts Eye & Ear Infirm, Surg Res Lab, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY11627, EY12611] NR 41 TC 130 Z9 149 U1 1 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2002 VL 160 IS 5 BP 1683 EP 1693 DI 10.1016/S0002-9440(10)61115-7 PG 11 WC Pathology SC Pathology GA 549VV UT WOS:000175468200017 PM 12000720 ER PT J AU Kim, JY Koves, TR Yu, GS Gulick, T Cortright, RN Dohm, GL Muoio, DM AF Kim, JY Koves, TR Yu, GS Gulick, T Cortright, RN Dohm, GL Muoio, DM TI Evidence of a malonyl-CoA-insensitive carnitine palmitoyltransferase I activity in red skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE fatty acid oxidation; fiber-type specificity ID FATTY-ACID OXIDATION; CPT-I; MEMBRANE ENVIRONMENT; RAT MUSCLE; SENSITIVITY; MITOCHONDRIA; EXPRESSION; ISOFORMS; LIVER; INSIGHTS AB Carnitine palmitoyltransferase I (CPT I), which is expressed as two distinct isoforms in liver (alpha) and muscle (beta), catalyzes the rate-limiting step in the transport of fatty acid into the mitochondria. Malonyl-CoA, a potent inhibitor of CPT I, is considered a key regulator of fatty acid oxidation in both tissues. Still unanswered is how muscle beta-oxidation proceeds despite malonyl-CoA concentrations that exceed the IC50 for CPT Ibeta. We evaluated malonyl-CoA-suppressible [ 14 C] palmitate oxidation and CPT I activity in homogenates of red (RG) and white (WG) gastrocnemius, soleus (SOL), and extensor digitorum longus (EDL) muscles. Adding 10 muM malonyl-CoA inhibited palmitate oxidation by 29, 39, 60, and 89% in RG, SOL, EDL, and WG, respectively. Thus malonyl-CoA resistance, which correlated strongly (0.678) with absolute oxidation rates (RG > SOL > EDL > WG), was greater in red than in white muscles. Similarly, malonyl-CoA-resistant palmitate oxidation and CPT I activity were greater in mitochondria from RG compared with WG. Ribonuclease protection assays were performed to evaluate whether our data might be explained by differential expression of CPT I splice variants. We detected the presence of two CPT Ibeta splice variants that were more abundant in red compared with white muscle, but the relative expression of the two mRNA species was unrelated to malonyl-CoA resistance. These results provide evidence of a malonyl-CoA-insensitive CPT I activity in red muscle, suggesting fiber type-specific expression of distinct CPT I isoforms and/or posttranslational modulations that have yet to be elucidated. C1 Duke Univ, Med Ctr, Sch Med, Dept Med, Durham, NC 27710 USA. E Carolina Univ, Dept Biochem & Physiol, Greenville, NC 27858 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA. RP Muoio, DM (reprint author), Duke Univ, Med Ctr, Sch Med, Dept Med, POB 3327, Durham, NC 27710 USA. RI Muoio, Debbie/E-1147-2012 FU NIDDK NIH HHS [DK-46121-06, F32 DK-10017-01] NR 32 TC 60 Z9 61 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 MAY PY 2002 VL 282 IS 5 BP E1014 EP E1022 DI 10.1152/ajpendo.00233.2001 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 538EG UT WOS:000174800900005 PM 11934665 ER PT J AU Miampamba, M Maillot, C Million, M Tache, Y AF Miampamba, M Maillot, C Million, M Tache, Y TI Peripheral CRF activates myenteric neurons in the proximal colon through CRF1 receptor in conscious rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE acetylcholine; corticotropin-releasing factor; CP-154,526; enteric nervous system; Fos; NADPH-diaphorase ID CORTICOTROPIN-RELEASING FACTOR; ENTERIC NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; PIG SMALL-INTESTINE; VESICULAR ACETYLCHOLINE TRANSPORTER; GUINEA-PIG; CHOLINERGIC NEURONS; FOS EXPRESSION; MOTOR-ACTIVITY; C-FOS AB Corticotropin-releasing factor (CRF) injected peripherally induces clustered spike-burst activity in the proximal colon through CRF1 receptors in rats. We investigated the effect of intraperitoneal CRF on proximal colon ganglionic myenteric cell activity in conscious rats using Fos immunohistochemistry on the colonic longitudinal muscle/myenteric plexus whole mount preparation. In vehicle-pretreated rats, there were only a few Fos immunoreactive (IR) cells per ganglion (1.2 +/- 0.6). CRF (10 mug/kg ip) induced Fos expression in 19.6 +/- 2.1 cells/ ganglion. The CRF1/CRF2 antagonist astressin (33 mug/kg ip) and the selective CRF1 antagonist CP-154,526 (20 mg/kg sc) prevented intraperitoneal CRF-induced Fos expression in the proximal colon (number of Fos-IR cells/ ganglion: 2.7 +/- 1.2 and 1.0 +/- 1.0, respectively), whereas atropine (1 mg/kg sc) had no effect. Double labeling of Fos with protein gene product 9.5 revealed the neuronal identity of activated cells that were encircled by varicose fibers immunoreactive to vesicular acetylcholine transporter. Fos immunoreactivity was mainly present in choline acetyltransferase-IR nerve cell bodies but not in the NADPH-diaphorase-positive cells. These results indicate that peripheral CRF activates myenteric cholinergic neurons in the proximal colon through CRF1 receptor. C1 Univ Calif Los Angeles, Dept Med, Div Digest Dis,CURE DDRC, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Miampamba, M (reprint author), Univ Calif Los Angeles, Dept Med, Div Digest Dis,CURE DDRC, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-57238, DK-57238-01A1S1] NR 56 TC 56 Z9 57 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 MAY PY 2002 VL 282 IS 5 BP G857 EP G865 DI 10.1152/ajpgi.00434.2001 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 542QL UT WOS:000175055800014 PM 11960782 ER PT J AU Holschneider, DP Scremin, OU Chialvo, DR Chen, K Shih, JC AF Holschneider, DP Scremin, OU Chialvo, DR Chen, K Shih, JC TI Heart rate dynamics in monoamine oxidase-A- and -B-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE serotonin; norepinephrine; cholinergic; arrhythmia; heart rate variability; vagus nerve; sympathetic; parasympathetic ID NUCLEUS-TRACTUS-SOLITARIUS; ADAPTIVE-CHANGES; RATE-VARIABILITY; SEROTONIN; PHEOCHROMOCYTOMA; RECEPTORS; LACKING; ARRHYTHMIAS AB Heart rate (HR) dynamics were investigated in mice deficient in monoamine oxidase A and B, whose phenotype includes elevated tissue levels of norepinephrine, serotonin, dopamine, and phenylethylamine. In their home cages, spectral analysis of R-R intervals revealed more pronounced fluctuations at all frequencies in the mutants compared with wild-type controls, with a particular enhancement at 1-4 Hz. No significant genotypic differences in HR variability (HRV) or entropies calculated from Poincare' plots of the R-R intervals were noted. During exposure to the stress of a novel environment, HR increased and HRV decreased in both genotypes. However, mutants, unlike controls, demonstrated a rapid return to baseline HR during the 10-min exposure. Such modulation may result from an enhanced vagal tone, as suggested by the observation that mutants responded to cholinergic blockade with a decrease in HRV and a prolonged tachycardia greater than controls. Monoamine oxidase-deficient mice may represent a useful experimental model for studying compensatory mechanisms responsible for changes in HR dynamics in chronic states of high sympathetic tone. C1 Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Holschneider, DP (reprint author), Univ So Calif, Keck Sch Med, Dept Psychiat, LAC USC Hosp, 1200 N State St,Rm 10-621, Los Angeles, CA 90089 USA. RI Chialvo, Dante/A-4658-2009 OI Chialvo, Dante/0000-0002-1038-3637 FU NIMH NIH HHS [R37-MH-39085, R01-MH-NS-62148, K05 MH-00796, R01 MH-37020, R37 MH039085]; NINDS NIH HHS [K23 NS062148] NR 39 TC 10 Z9 10 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 MAY PY 2002 VL 282 IS 5 BP H1751 EP H1759 DI 10.1152/ajpheart.00600.2001 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 541XK UT WOS:000175011700023 PM 11959640 ER PT J AU Janech, MG Chen, RH Klein, J Nowak, MW McFee, W Paul, RV Fitzgibbon, WR Ploth, DW AF Janech, MG Chen, RH Klein, J Nowak, MW McFee, W Paul, RV Fitzgibbon, WR Ploth, DW TI Molecular and functional characterization of a urea transporter from the kidney of a short-finned pilot whale SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 2000 Meeting CY APR 14-19, 2000 CL SAN DIEGO, CA DE urea reabsorption; cetaceans; osmoregulation; urinary concentration ID RAT-KIDNEY; DELPHINAPTERUS-LEUCAS; COLLECTING DUCTS; NITRIC-OXIDE; CLONING; VASOPRESSIN; EXPRESSION; LOCALIZATION; ARGINASE; TESTIS AB Cetaceans (whales and dolphins) always excrete urine with an osmolality markedly higher than that of plasma. Although the mechanisms by which cetaceans concentrate urine have not been elucidated, data support a role for medullary urea accumulation in this process, as is the case for terrestrial mammals. Therefore, we hypothesized that facilitated urea transporters are present in the kidney of cetaceans. Using 5'/3'-rapid amplification of cDNA ends, we cloned a 2.7-kb cDNA from the kidney of the short-finned pilot whale Globicephala macrorhynchus. The putative open-reading frame encoded a 397-amino acid protein [pilot whale urea transporter A2 (whUT-A2)] that has 94% amino acid sequence identity to the A2 isoform of the human urea transporter (hUT-A2). Heterologous expression of whUT-A2 cRNA in Xenopus oocytes induced phloretin-inhibitable urea transport. Although Northern analysis and RT-PCR indicated that whUT-A2 was exclusively expressed in kidney, Western blotting using a polyclonal antibody to rat UT-A1/UT-A2 detected various immunoreactive proteins in kidney and other tissues. Furthermore, RT-PCR analysis suggested the presence of alternatively spliced UT-A transcripts in the kidney as well as extrarenal tissues. We conclude that renal urea transporters are highly conserved among mammals inhabiting terrestrial and pelagic environments. A urea-based concentrating mechanism, presumably evolved to meet the demands of an arid terrestrial environment, may have contributed a fortuitous preadaptation that enabled the ancestors of cetaceans to reinvade the sea. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Marine Biomed & Environm Sci, Charleston, SC 29412 USA. Med Univ S Carolina, Dept Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, US Dept Commerce, NOAA, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Emory Univ, Dept Med, Div Renal, Atlanta, GA 30322 USA. RP Fitzgibbon, WR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St, Charleston, SC 29425 USA. EM fitzgiwr@musc.edu OI Nowak, Mark/0000-0001-5097-2682 NR 52 TC 14 Z9 15 U1 2 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAY PY 2002 VL 282 IS 5 BP R1490 EP R1500 DI 10.1152/ajpregu.00323.2001 PG 11 WC Physiology SC Physiology GA 541MC UT WOS:000174987500031 PM 11959693 ER PT J AU Moonga, BS Li, S Iqbal, J Davidson, R Shankar, VS Bevis, PJR Inzerillo, A Abe, E Huang, CLH Zaidi, M AF Moonga, BS Li, S Iqbal, J Davidson, R Shankar, VS Bevis, PJR Inzerillo, A Abe, E Huang, CLH Zaidi, M TI Ca(2+) influx through the osteoclastic plasma membrane ryanodine receptor SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE osteoclast; calcium receptor; calcium channels; osteoporosis; calcium ID CALCIUM-SENSING RECEPTOR; EXTRACELLULAR CALCIUM; RELEASE CHANNEL; INOSITOL TRISPHOSPHATE; RAT OSTEOCLASTS; CYTOSOLIC CA2+; CA-2+ RECEPTOR; CELLS; ACTIVATION; EXPRESSION AB We predict that the type 2 ryanodine receptor isoform (RyR-2) located in the osteoclastic membrane functions as a Ca(2+) influx channel and as a divalent cation (Ca(2+)) sensor. Cytosolic Ca(2+) measurements revealed Ca(2+) influx in osteoclasts at depolarized membrane potentials. The cytosolic Ca(2+) change was, as expected, not seen in Ca(2+)-free medium and was blocked by the RyR modulator ryanodine. In contrast, at basal membrane potentials (similar to25 mV) ryanodine triggered extracellular Ca(2+) influx that was blocked by Ni(2+). In parallel, single-channel recordings obtained from inside-out excised patches revealed a divalent cation-selective similar to60-pS conductance in symmetric solutions of Ba-aspartate [Ba-Asp; reversal potential (E(rev)) similar to0 mV]. In the presence of a Ba(2+) gradient, i.e., with Ba-Asp in the pipette and Na-Asp in the bath, channel conductance increased to similar to120 pS and Erev shifted to 21 mV. The conductance was tentatively classified as a RyR-gated Ca(2+) channel as it displayed characteristic metastable states and was sensitive to ruthenium red and a specific anti-RyR antibody, Ab(34). To demonstrate that extracellular Ca(2+) sensing occurred at the osteoclastic surface rather than intracellularly, we performed protease protection assays using pronase. Preincubation with pronase resulted in markedly attenuated cytosolic Ca(2+) signals triggered by either Ni(2+) (5 mM) or Cd(2+) (50 muM). Finally, intracellular application of antiserum Ab 34 potently inhibited divalent cation sensing. Together, these results strongly suggest the existence of 1) a membrane-resident Ca(2+) influx channel sensitive to RyR modulators; 2) an extracellular, as opposed to intracellular, divalent cation activation site; and 3) a cytosolic CaM-binding regulatory site for RyR. It is likely therefore that the surface RyR-2 not only gates Ca(2+) influx but also functions as a sensor for extracellular divalent cations. C1 Mt Sinai Sch Med, Div Endocrinol, Mt Sinai Bone Program, Dept Med, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Geriatr, Mt Sinai Bone Program, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, New York, NY 10029 USA. NYU, Sch Dent, Div Basic Sci, New York, NY 10010 USA. Univ Cambridge, Dept Physiol, Cambridge CB2 3EG, England. RP Zaidi, M (reprint author), Mt Sinai Sch Med, Div Endocrinol, Mt Sinai Bone Program, Dept Med, POB 1055,1 Gustave Levy Pl, New York, NY 10029 USA. EM mone.zaidi@mssm.edu RI Huang, Christopher/A-6248-2008 FU NIA NIH HHS [R01-AG-14917-05] NR 46 TC 32 Z9 33 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 MAY PY 2002 VL 282 IS 5 BP F921 EP F932 DI 10.1152/ajprenal.00045.2000 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 537VA UT WOS:000174779200018 PM 11934703 ER PT J AU Gonzales, D Bjornson, W Durcan, MJ White, JD Johnston, JA Buist, AS Sachs, DPL Rigotti, NA Niaura, R Hays, JT Hurt, RD AF Gonzales, D Bjornson, W Durcan, MJ White, JD Johnston, JA Buist, AS Sachs, DPL Rigotti, NA Niaura, R Hays, JT Hurt, RD TI Effects of gender on relapse prevention in smokers treated with bupropion SR SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE bupropion; recurrence; gender; smoking cessation; tobacco-use disorder ID SUSTAINED-RELEASE BUPROPION; COGNITIVE-BEHAVIORAL THERAPY; INITIAL SMOKING CESSATION; NICOTINE NASAL SPRAY; CIGARETTE-SMOKING; TRANSDERMAL NICOTINE; MAJOR DEPRESSION; CONTROLLED TRIAL; DOUBLE-BLIND; LUNG HEALTH AB Background: Recent data Suggest that women smokers respond differently than men to cessation pharmacotherapies, particularly nicotine replacement therapy (NRT). Lower abstinence and higher relapse rates are often reported for women treated with NRT. Gender effects for those treated with non-nicotinic, bupropion-hydrochloride sustained release for relapse prevention have not been studied. Methods: Data from a multicenter relapse-prevention (RP) trial of bupropion (November 1995-June 1998) were analyzed for gender differences. Men and women smokers (N=784) were treated with open-label bupropion for 7 weeks. Those abstinent at Week 7 (n=432) were enrolled in the double-blind relapse-prevention phase and randomized to placebo or continued bupropion for 45 additional weeks. Results: Differences in point-prevalence abstinence rates between men (61.8%) and women (55.6%) in open-label bupropion (Week 7) were not significant. In the RP-phase Week 52, continuous abstinence rates for men and women were 37.8% and 36.4%, (bupropion) and 36.6%, and 29.9%, (placebo), respectively; point-prevalence abstinence rates for men and 3 36.6% women were 54.1% and 55.9% (bupropion) and 42.9% and 41.3%, (placebo), respectively. Abstinence rates and time to relapse were superior for both men and women who received longer treatment. Gender differences within treatment groups were not significant. Median time to relapse was equal for men and women within each treatment group: Week 32 for bupropion and Week 20 for placebo. Conclusions: Our data suggest that bupropion is a promising pharmacotherapy for preventing relapse, particularly for women. C1 Oregon Hlth Sci Univ, Smoking Cessat Ctr, Dept Med, Portland, OR 97201 USA. Glaxo Wellcome Res & Dev Ltd, Res Triangle Pk, NC USA. Palo Alto Ctr Pulm Dis Prevent, Palo Alto, CA USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Providence, RI 02912 USA. Mayo Clin, Nicotine Res Ctr, Rochester, MN USA. RP Gonzales, D (reprint author), Oregon Hlth Sci Univ, Smoking Cessat Ctr, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code CR 115, Portland, OR 97201 USA. NR 63 TC 66 Z9 66 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2002 VL 22 IS 4 BP 234 EP 239 AR PII S0749-3797(02)00419-1 DI 10.1016/S0749-3797(02)00419-1 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 549EH UT WOS:000175431200003 PM 11988379 ER PT J AU Ablon, JS Jones, EE AF Ablon, JS Jones, EE TI Validity of controlled clinical trials of psychotherapy: Findings from the NIMH Treatment of Depression Collaborative Research Program SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MENTAL-HEALTH TREATMENT; NATIONAL-INSTITUTE; THERAPY; PHARMACOTHERAPY; SEVERITY; ALLIANCE; EFFICACY; SCALE AB objective: This research extends a series of studies that have examined the process of psychotherapy. The authors hypothesized that manualized regimens of psychotherapy compared in a controlled clinical trial would overlap considerably in process and technique and that intervention strategies common to both treatments would be responsible for promoting patient change. Method: Expert therapists developed prototypes of the ideal regimens of brief interpersonal psychotherapy and cognitive behavior therapy using the Psychotherapy Process Q-Set, an instrument designed to provide a standard language for describing treatment processes. A separate set of clinical judges then used the Psychotherapy Process Q-Set to score the actual transcripts of interpersonal psychotherapy and cognitive behavior therapy sessions conducted as part of the NIMH Treatment of Depression Collaborative Research Program. The expert prototypes were then compared with actual therapy administered in order to determine the extent to which each form of therapy conformed to its ideal prototype. Results: Both the interpersonal psychotherapy and cognitive behavior therapy sessions adhered most strongly to the ideal prototype of cognitive behavior therapy. in addition, adherence to the cognitive behavior therapy prototype yielded more positive correlations with outcome measures across both types of treatment. Conclusions: Relying on brand names of therapy can be misleading. These findings suggest that the basic premise of controlled clinical trials (i.e., that the compared interventions represent separate and distinct treatments) may not have been met in the NIMH Treatment of Depression Collaborative Research Program. The implications of these findings for using controlled clinical trials to study psychotherapy are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Ablon, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, WAC 812,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [MH-11356] NR 39 TC 123 Z9 128 U1 4 U2 14 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 MAY PY 2002 VL 159 IS 5 BP 775 EP 783 DI 10.1176/appi.ajp.159.5.775 PG 9 WC Psychiatry SC Psychiatry GA 548BD UT WOS:000175367400014 PM 11986131 ER PT J AU Koenigsberg, HW Harvey, PD Mitropoulou, V Schmeidler, J New, AS Goodman, M Silverman, JM Serby, M Schopick, F Siever, LJ AF Koenigsberg, HW Harvey, PD Mitropoulou, V Schmeidler, J New, AS Goodman, M Silverman, JM Serby, M Schopick, F Siever, LJ TI Characterizing affective instability in borderline personality disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID IMPULSIVITY; INTENSITY AB Objective: This study sought to understand affective instability among patients with borderline personality disorder by examining the degree of instability in six affective domains. The authors also examined the subjective intensity with which moods are experienced and the association between instability and intensity of affect. Method: In a group of 152 patients with personality disorders, subjective affective intensity and six dimensions of affective instability were measured. The mean scores for lability and intensity for each affective domain for patients with borderline personality disorder were compared with those of patients with other personality disorders through analyses that controlled for other axis I affective disorders, age, and sex. Results: Greater lability in terms of anger and anxiety and oscillation between depression and anxiety, but not in terms of oscillation between depression and elation, was associated with borderline personality disorder. Contrary to expectation, the experience of an increase in subjective affective intensity was not more prominent in patients with borderline personality disorder than in those with other personality disorders. Conclusions: By applying a finer-grained perspective on affective instability than those of previous personality disorder studies, this study points to patterns of affective experience characteristic of patients with borderline personality disorder. C1 Bronx Vet Adm Med Ctr, Mental Hlth Patient Care Ctr 116A, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Koenigsberg, HW (reprint author), Bronx Vet Adm Med Ctr, Mental Hlth Patient Care Ctr 116A, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NCRR NIH HHS [RR-00071]; NIMH NIH HHS [MH-42827] NR 17 TC 203 Z9 207 U1 3 U2 13 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 MAY PY 2002 VL 159 IS 5 BP 784 EP 788 DI 10.1176/appi.ajp.159.5.784 PG 5 WC Psychiatry SC Psychiatry GA 548BD UT WOS:000175367400015 PM 11986132 ER PT J AU Kubicki, M Westin, CF Maier, SE Frumin, M Nestor, PG Salisbury, DF Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Kubicki, M Westin, CF Maier, SE Frumin, M Nestor, PG Salisbury, DF Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI Uncinate fasciculus findings in schizophrenia: A magnetic resonance diffusion tensor imaging study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 153rd Annual Meeting of the American-Psychiatric-Association CY MAY 13-18, 2000 CL CHICAGO, ILLINOIS SP Amer Psychiat Assoc ID LEFT-RIGHT ASYMMETRIES; WHITE-MATTER; HUMAN-BRAIN; PREFRONTAL CORTEX; WATER DIFFUSION; VERBAL FLUENCY; ABNORMALITIES; DYSFUNCTION; ANISOTROPY; MRI AB Objective. Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. Method: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. Results: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. Conclusions: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia. C1 VA Boston Healthcare Syst, Brockton Div, Dept Psychiat, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Lab Neurosci,Clin Neurosci Div, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, MRI Div, Surg Planning Lab, Boston, MA 02115 USA. RP Shenton, ME (reprint author), VA Boston Healthcare Syst, Brockton Div, Dept Psychiat, 116A,940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCRR NIH HHS [R01 RR011747, P41 RR013218, P41 RR013218-020001, R01 RR011747-02, RR-11747, RR-13218]; NIMH NIH HHS [K02 MH001110, K02 MH001110-06, MH-01110, MH-40799, MH-50747, R01 MH040799, R01 MH040799-13, R01 MH050740, R01 MH050740-06] NR 52 TC 287 Z9 297 U1 4 U2 17 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 MAY PY 2002 VL 159 IS 5 BP 813 EP 820 DI 10.1176/appi.ajp.159.5.813 PG 8 WC Psychiatry SC Psychiatry GA 548BD UT WOS:000175367400019 PM 11986136 ER PT J AU Glynn, SM Marder, SR Liberman, RP Blair, K Wirshing, WC Wirshing, DA Ross, D Mintz, J AF Glynn, SM Marder, SR Liberman, RP Blair, K Wirshing, WC Wirshing, DA Ross, D Mintz, J TI Supplementing clinic-based skills training with manual-based community support sessions: Effects on social adjustment of patients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 9th International Congress on Schizophrenia CY APR 17-21, 1999 CL SANTA FE, NEW MEXICO ID TREATMENT-RESISTANT SCHIZOPHRENIA; RISPERIDONE; HALOPERIDOL; ILLNESS; THERAPY; MEMORY AB Objective: Although skills training is a validated psychosocial treatment for schizophrenia, generalization of the skills to everyday life has not been optimal. This study evaluated a behaviorally oriented method of augmenting clinic-based skills training in the community with the aim of improving opportunities, encouragement, and reinforcement for outpatients to use their skills in their natural environment. Method: Sixty-three individuals with schizophrenia were randomly assigned to 60 weeks of clinic-based skills training alone or of clinic-based skills training supplemented with manual-based generalization sessions in the community. Patients were also randomly assigned to receive either haloperidol or risperidone. Therapists' fidelity to the manuals was measured. Patients' acquisition of the skills from pre- to posttraining was evaluated. The primary outcome measures were the Social Adjustment Scale-II and the Quality of Life Scale. Results: Seventy-one percent of the patients completed the trial. Only six participants experienced psychotic exacerbations during the trial. There was no evidence of a differential medication effect on social functioning. Social functioning improved modestly in both psychosocial conditions over time; participants who received augmented skills training in the community showed significantly greater and/or quicker improvements. Conclusions: Given judicious and effective antipsychotic medication that limited exacerbations to less than 10% during the trial, a wide range of outpatients with schizophrenia demonstrated substantial learning of illness management and social skills in the clinic. When clinic-based skills training was augmented by in vivo training and consultation, transfer of the skills to everyday life was enhanced. These benefits were established regardless of the medications prescribed. C1 VA Greater Los Angeles Hlth Care Syst W Los Angel, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Glynn, SM (reprint author), VA Greater Los Angeles Hlth Care Syst W Los Angel, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH-49573] NR 23 TC 61 Z9 62 U1 3 U2 3 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 MAY PY 2002 VL 159 IS 5 BP 829 EP 837 DI 10.1176/appi.ajp.159.5.829 PG 9 WC Psychiatry SC Psychiatry GA 548BD UT WOS:000175367400021 PM 11986138 ER PT J AU Frumin, M Golland, P Kikinis, R Hirayasu, Y Salisbury, DF Hennen, J Dickey, CC Anderson, M Jolesz, FA Grimson, WEL McCarley, RW Shenton, ME AF Frumin, M Golland, P Kikinis, R Hirayasu, Y Salisbury, DF Hennen, J Dickey, CC Anderson, M Jolesz, FA Grimson, WEL McCarley, RW Shenton, ME TI Shape differences in the corpus callosum in first-episode schizophrenia and first-episode psychotic affective disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: The corpus callosum, the largest white matter tract in the brain, is a midline structure associated with the formation of the hippocampus, septum pellucidum, and cingulate cortex, which have been implicated in the pathogenesis of schizophrenia, Corpus callosum shape deformation, therefore, may reflect a midline neurodevelopmental abnormality. Method: Corpus callosum area and shape were analyzed in 14 first-episode psychotic patients with schizophrenia, 19 first-episode psychotic patients with affective disorder, and 18 normal comparison subjects. Results: No statistically significant corpus callosum area differences between groups were found, but there were differences in the structure's shape between the patients with schizophrenia and the comparison subjects. A correlation between width and angle of the corpus callosum was found in patients with affective disorder, Conclusions: Corpus callosum shape abnormalities in first-episode psychotic patients with schizophrenia may reflect a midline neurodevelopmental abnormality. C1 VA Boston Healthcare Syst, Brockton Div, Dept Psychiat 116A, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Neurosci Lab,Clin Neurosci Div, Cambridge, MA 02138 USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Radiol, MRI Div, Surg Planning Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. McLean Hosp, Cognit Neurosci Lab, Belmont, MA 02178 USA. McLean Hosp, Biostat Lab, Belmont, MA 02178 USA. RP Shenton, ME (reprint author), VA Boston Healthcare Syst, Brockton Div, Dept Psychiat 116A, 940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCRR NIH HHS [P41 RR013218, P41 RR013218-02, P41-RR-1321, R01 RR011747, R01 RR011747-02, R01-RR-11747]; NIMH NIH HHS [MH-01110, K02 MH001110, K02 MH001110-10, MH-40799, MH-50740, R01 MH040799, R01 MH040799-13, R01 MH050740, R01 MH050740-10] NR 7 TC 40 Z9 42 U1 0 U2 0 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 MAY PY 2002 VL 159 IS 5 BP 866 EP 868 DI 10.1176/appi.ajp.159.5.866 PG 3 WC Psychiatry SC Psychiatry GA 548BD UT WOS:000175367400029 PM 11986146 ER PT J AU Xie, AL Skatrud, JB Puleo, DS Rahko, PS Dempsey, JA AF Xie, AL Skatrud, JB Puleo, DS Rahko, PS Dempsey, JA TI Apnea-hypopnea threshold for CO2 in patients with congestive heart failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE congestive heart failure; apnea threshold ID CENTRAL SLEEP-APNEA; CHEYNE-STOKES RESPIRATION; MECHANICAL VENTILATION; ZOLPIDEM; INHIBITION; CONSEQUENCES; PATHOGENESIS; PRESSURE; PLACEBO; HUMANS AB To understand the pathogenesis of central sleep apnea (CSA) in patients with congestive heart failure (CHF), we measured the end-tidal carbon dioxide pressure (PETCO2) during spontaneous breathing, the apnea-hypopnea threshold for CO2, and then calculated the difference between these two measurements in 19 stable patients with CHF with (12 patients) or without (7 patients) CSA during non-rapid eye movement sleep. Pressure support ventilation was used to reduce the PETCO2 and thereby determine the thresholds. In patients with CSA, 1.5-3% CO2 was supplied temporarily to stabilize breathing before determining the thresholds. Unlike patients without CSA whose eupneic PETCO2 increased during sleep (37.7 +/- 1.4 mm Hg versus 40.2 +/- 1.5 mm Hg, p < 0.01), patients with CSA showed no rise in PETCO2 from wakefulness to sleep (37.5 +/- 0.9 mm Hg versus 38.2 +/- 1.0 mm Hg, p = 0.2). Patients with CHF and CSA had their eupneic PETCO2 closer to the threshold PETCO2 than patients without CSA (DeltaPET(CO2) [eupneic PETCO2-threshold PETCO2] was 2.8 +/- 0.3 mm Hg versus 5.1 +/- 0.7 mm Hg for apnea, p < 0.01; 1.7 +/- 0.7 versus 4.1 +/- 0.5 mm Hg for hypopnea, p < 0.05). In summary, patients with CHF and CSA neither increase their eupneic PETCO2 during sleep nor proportionally decrease their apnea-hypopnea threshold. The resultant narrowed DeltaPET(CO2) predisposes the patient to the development of apnea and subsequent breathing instability. C1 William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Prevent Med, Madison, WI 53706 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NHLBI NIH HHS [R01 HL62561-02] NR 35 TC 115 Z9 123 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2002 VL 165 IS 9 BP 1245 EP 1250 DI 10.1164/rccm.200110-022OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 547CF UT WOS:000175314900011 PM 11991873 ER PT J AU Nakayama, H Smith, CA Rodman, JR Skatrud, JB Dempsey, JA AF Nakayama, H Smith, CA Rodman, JR Skatrud, JB Dempsey, JA TI Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during sleep SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE sleep apnea; chemoreceptors; hyperventilation; hypoventilation; apneic/hypopneic thresholds ID CONGESTIVE-HEART-FAILURE; CHEYNE-STOKES RESPIRATION; HIGH-ALTITUDE; MECHANICAL VENTILATION; APNEIC THRESHOLD; MOTOR OUTPUT; CO2; INHIBITION; HYPOXIA; HUMANS AB We determined the effects of changing ventilatory stimuli on the hypocapnia-induced apneic and hypopneic thresholds in sleeping dogs. End-tidal carbon dioxide pressure (PETCO2) was gradually reduced during non-rapid eye movement sleep by increasing tidal volume with pressure support mechanical ventilation, causing a reduction in diaphragm electromyogram amplitude until apnea/periodic breathing occurred. We used the reduction in PETCO2 below spontaneous breathing required to produce apnea (DeltaPET(CO2)) as an index of the susceptibility to apnea. DeltaPET(CO2) was -5 mm Hg in control animals and changed in proportion to background ventilatory drive, increasing with metabolic acidosis (-6.7 mm Hg) and nonhypoxic peripheral chemoreceptor stimulation (almitrine; -5.9 mm Hg) and decreasing with metabolic alkalosis (-3.7 mm Hg). Hypoxia was the exception; DeltaPET(CO2) narrowed (-4.1 mm Hg) despite the accompanying hyperventilation. Thus, hyperventilation and hypocapnia, per se, widened the DeltaPET(CO2) thereby protecting against apnea and hypopnea, whereas reduced ventilatory drive and hypoventilation narrowed the DeltaPET(CO2) and increased the susceptibility to apnea. Hypoxia sensitized the ventilatory responsiveness to CO2 below eupnea and narrowed the DeltaPET(CO2); this effect of hypoxia was not attributable to an imbalance between peripheral and central chemoreceptor stimulation, per se. We conclude that the DeltaPET(CO2) and the ventilatory sensitivity to CO2 between eupnea and the apneic threshold are changeable in the face of variations in the magnitude, direction, and/or type of ventilatory stimulus, thereby altering the susceptibility for apnea, hypopnea, and periodic breathing in sleep. C1 Univ Wisconsin, John Rankin Lab Pulm Med, Dept Populat Hlth Sci, Sch Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Dempsey, JA (reprint author), Univ Wisconsin, John Rankin Lab Pulm Med, Dept Populat Hlth Sci, Sch Med, 504 N Walnut St, Madison, WI 53705 USA. NR 53 TC 107 Z9 113 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 1 PY 2002 VL 165 IS 9 BP 1251 EP 1259 DI 10.1164/rccm.2110041 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 547CF UT WOS:000175314900012 PM 11991874 ER PT J AU Mueller, PR Berlin, L AF Mueller, PR Berlin, L TI Complications of lung abscess aspiration and drainage SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID FLUID COLLECTIONS; BIOPSY; MANAGEMENT; CHEST C1 Rush Med Coll, Dept Radiol, Chicago, IL 60612 USA. Rush N Shore Med Ctr, Skokie, IL 60075 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Berlin, L (reprint author), Rush Med Coll, Dept Radiol, Chicago, IL 60612 USA. NR 15 TC 5 Z9 6 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 MAY PY 2002 VL 178 IS 5 BP 1083 EP 1086 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 543AA UT WOS:000175077200007 PM 11959705 ER PT J AU Georgian-Smith, D Lawton, TJ Moe, RE Couser, WG AF Georgian-Smith, D Lawton, TJ Moe, RE Couser, WG TI Lupus mastitis: Radiologic and pathologic features SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ERYTHEMATOSUS C1 Univ Washington, Med Ctr, Dept Radiol, Breast Imaging Sect, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Div Nephrol, George M O Brien Kidney Res Ctr, Seattle, WA 98195 USA. RP Georgian-Smith, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Wang ACC 2190,15 Parkman St, Boston, MA 02114 USA. NR 8 TC 15 Z9 15 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 MAY PY 2002 VL 178 IS 5 BP 1233 EP 1235 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 543AA UT WOS:000175077200035 PM 11959738 ER PT J AU Barton, JB Langdale, LA Cummins, JS Stelzner, M Lynge, DC Mock, CN Nason, KS Billingsley, KG AF Barton, JB Langdale, LA Cummins, JS Stelzner, M Lynge, DC Mock, CN Nason, KS Billingsley, KG TI The utility of routine preoperative computed tomography scanning in the management of veterans with colon cancer SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 09-10, 2001 CL VICTORIA, CANADA SP N Pacific Surg Assoc DE colon neoplasms; tomography; radiograph; computed tomography; surgery; neoplasm metastasis; preoperative care ID COLORECTAL-CARCINOMA; CT AB Background: The aim of this study is to assess the clinical utility of routine preoperative computed tomography (CT) scanning in patients with cancer of the intraperitoneal colon. Methods: From November 1997 to June 2001, all patients at VA Puget Sound Healthcare System with a diagnosis of colon cancer were referred for a preoperative CT scan. Medical records and operative notes were reviewed to determine the influence of preoperative CT on clinical management. Results: Seventy patients received a CT per protocol. Preoperative CT provided information that was used in treatment planning and management in 26 (37%) cases. However, if preoperative scans had not been performed, the clinical management would have been definitively altered in only 13 (19%) patients. Conclusions: Although these data suggest potential benefit for routine preoperative CT scanning, we believe additional study, including cost analysis, should precede the adoption of CT scanning as a routine preoperative study in patients with colon cancer. (C) 2002 Excerpta Medica, Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Dept Surg 112, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Billingsley, KG (reprint author), VA Puget Sound Hlth Care Syst, Dept Surg 112, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Mock, Charles/0000-0002-0564-568X NR 11 TC 25 Z9 25 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2002 VL 183 IS 5 BP 499 EP 503 AR PII S0002-9610(02)00841-3 DI 10.1016/S0002-9610(02)00841-3 PG 5 WC Surgery SC Surgery GA 557EG UT WOS:000175894700002 PM 12034380 ER PT J AU Jobe, BA Rosenthal, E Wiesberg, TT Cohen, JI Domreis, JS Deveney, CW Sheppard, B AF Jobe, BA Rosenthal, E Wiesberg, TT Cohen, JI Domreis, JS Deveney, CW Sheppard, B TI Surgical management of gastroesophageal reflux and outcome after laryngectomy in patients using tracheoesophageal speech SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 09-10, 2001 CL VICTORIA, CANADA SP N Pacific Surg Assoc DE anti-reflux surgery; laparoscopic fundoplication; laryngectomy; tracheoesophageal speech; tracheoesophageal prosthesis; GERD ID FUNDOPLICATION; GASTROPHARYNGEAL; TOUPET AB Background: Gastroesophageal reflux disease (GERD) is common in patients with head and neck carcinoma. The impact of laparoscopic fundoplication on laryngectomy patients with tracheoesophageal prostheses for voice restoration is unknown. Methods: Nine laryngectomy patients who use tracheoesophageal speech underwent laparoscopic fundoplication for documented reflux. Preoperative and postoperative symptoms were recorded. Quality of speech was documented before and after fundoplication. Results: Although 88% of patients had resolution of GERD symptoms, all developed bloating and hyperflatulence. There was no difference in quality of esophageal speech after laparoscopic fundoplication. Conclusions: Fundoplication in laryngectomy patients that use tracheoesophageal speech eliminates symptoms of gastroesophageal reflux and resolves regurgitation associated prosthesis erosion. Although nearly all patients are satisfied with outcome, there is a high incidence of postfundoplication bloating and hyperflatulence that may be life limiting. Poor quality tracheoesophageal speech should not be used as an indication for antireflux surgery. (C) 2002 Excerpta Medica, Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Jobe, BA (reprint author), Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2002 VL 183 IS 5 BP 539 EP 543 AR PII S0002-9610(02)00828-0 DI 10.1016/S0002-9610(02)00828-0 PG 5 WC Surgery SC Surgery GA 557EG UT WOS:000175894700010 PM 12034388 ER PT J AU Rabkin, JM Corless, CL Rosen, HR Olyaei, AJ AF Rabkin, JM Corless, CL Rosen, HR Olyaei, AJ TI Immunosuppression impact on long-term cardiovascular complications after liver transplantation SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 09-10, 2001 CL VICTORIA, CANADA SP N Pacific Surg Assoc DE liver transplantation; cardiovascular complications; nephrotoxicity ID CORONARY-ARTERY DISEASE; RENAL-TRANSPLANTATION; RISK-FACTORS; HYPERTENSION; CYCLOSPORINE; TACROLIMUS; RECIPIENTS; MANAGEMENT AB Background: With current early transplant patient and allograft survivals nearly optimized, long-term medical complications have become a significant focus for potential improvement in patient outcomes. Cardiovascular disease and associated risk factors have been shown in renal transplant patients to be related to the pharmacologic immunosuppression employed. Objective: The objective of this study. is to investigate at 3 years postliver transplant (OLTx) the incidence of hypertension (HTN), hyperlipidemia (HLIP), diabetes mellitus (DM), nephrotoxicity (NTX), and cardiovascular disease (MI, angioplasty, CHF, CVA, and seborth) as well as rejection in two cohorts of liver transplant recipients who received either tacrolimus (FK-506) or cyclosporine (CSA) and to analyze the consequences of these complications on mortality following transplantation. Methods: Eighty-seven sequential patients (CSA: n = 50, mean age 48 years, M/F 32/18; and FK-506: n = 37, mean age 45 years, M/F 22/15) who underwent OLTx between 1994 and 1998, were greater than or equal to18 years, and had a minimum of 3 years of complete follow-up were included in the analysis. All OLTx candidates over age 50, who had a history of alcoholic cirrhosis, or had a history of cardiac conditions/events underwent complete cardiac consultation including an echocardiogram with additional cardiac investigation as indicated prior to OLTx. Results: At 3 years following OLTx, the incidence of acute rejection (40% versus 19%, P < 0.05), HTN (62% versus 38%, P < 0.05), HLIP (14% versus 5%, P = 0.08), and cardiovascular disease (18% versus 0%, P < 0.001), were significantly greater for the CSA patients compared with the FK-506 patients. Eight (20%) of the CSA patients who died before 3 years had their death attributed to cardiovascular events versus none in the FK-506 group. Conclusion: Compared with CSA, FK-506 was associated with significantly less rejection and a reduced incidence of HTN and cardiovascular disease. (C) 2002 Excerpta Medica, Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Surg, Div Abdominal Organ Transplantat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Rabkin, JM (reprint author), Oregon Hlth Sci Univ, Dept Surg, Div Abdominal Organ Transplantat, 3181 SW Sam Jackson Pk Rd L590, Portland, OR 97201 USA. NR 28 TC 60 Z9 65 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2002 VL 183 IS 5 BP 595 EP 599 AR PII S0002-9610(02)00826-7 DI 10.1016/S0002-9610(02)00826-7 PG 5 WC Surgery SC Surgery GA 557EG UT WOS:000175894700023 PM 12034401 ER PT J AU Henley, JD Young, RH Ulbright, TM AF Henley, JD Young, RH Ulbright, TM TI Malignant Sertoli cell tumors of the testis - A study of 13 examples of a neoplasm frequently misinterpreted as seminoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE seminoma; sex cord-stromal tumor; testicular neoplasms; Sertoli cell tumor; immunohistochemistry ID CORD-STROMAL TUMORS; I TESTICULAR SEMINOMA; RADIOTHERAPY; FEATURES AB The distinction of Sertoli cell tumors from seminoma is critical to ensure proper treatment. Although usually straight forward, we highlight herein 13 malignant Sertoli cell tumors of the testis with light microscopic features that mimicked seminoma. All of the cases were received in consultation, 10 with submitting diagnoses of seminoma, usually of classic type, but three cases of spermatocytic type, Patients ranged from 15 to 80 years of age (median 37 years); all presented with testicular masses. The tumors were typically firm, white to yellow-tan, and often had foci of hemorrhage. The dominant microscopic pattern was nested or sheet-like, with some tumors having secondary patterns of trabeculae-solid tubules, hollow tubules, and pseudofollicles. Tumor cells were polygonal with conspicuous clear cytoplasm in 12 cases; the cytoplasm was focally eosinophilic in 10 cases, but this was never conspicuous. Nine tumors had cytoplasmic vacuoles, and three of four that were investigated stained for intracytoplasmic glycogen. Nuclei were small (5) to medium-sized (8), round-to-oval (13), and vesicular with irregular contours (11). Nucleoli were present in 11 tumors (six small; five large). Stromal fibrosis (12) and lymphoid infiltrates (10) were conspicuous, and tumor necrosis (11) and vascular invasion (8) also were seen. Mitotic figures ranged from <1 to 21/10 high power fields (HPF) (median 1/10 HPF). Staining for inhibin-alpha, epithelial membrane antigen, and cytokeratin (AE1/AE3) was positive in four of four, six of six, and three of six cases, respectively; placental alkaline phosphatase was negative in all five tumors investigated. The nested growth pattern, prominence of clear cells, lymphoid infiltrate, inconspicuous tubular differentiation, cytoplasmic glycogen, and prominent nucleoli caused these tumors to be mistaken for seminomas. The smaller, less pleomorphic nuclei of Sertoli cell tumors, their lower mitotic rate, and the absence of intratubular germ cell neoplasia are helpful differential features. Immunohistochemistry is a useful adjunct in confirming the diagnosis of Sertoli cell tumor, but only if the overlapping features are appreciated by conventional microscopy and the diagnosis of Sertoli cell tumor included in the differential. C1 Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs,Dept Pathol, Boston, MA USA. RP Henley, JD (reprint author), Indiana Univ Hosp 3465, Dept Surg Pathol, 550 N Univ Blvd, Indianapolis, IN 46202 USA. NR 27 TC 50 Z9 51 U1 0 U2 1 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 MAY PY 2002 VL 26 IS 5 BP 541 EP 550 DI 10.1097/00000478-200205000-00001 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 546FJ UT WOS:000175262200001 PM 11979085 ER PT J AU Dionigi, A Oliva, E Clement, PB Young, RH AF Dionigi, A Oliva, E Clement, PB Young, RH TI Endometrial stromal nodules and endometrial stromal tumors with limited infiltration - A clinicopathologic study of 50 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE uterus; endometrial stromal nodules; endometrial stromal tumors with limited infiltration ID MESENCHYMAL TUMORS; UTERUS; NEOPLASMS; SMOOTH; DIFFERENTIATION; PHENOTYPE AB Experience with endometrial stromal nodules (ESNs) is limited, and no series has been published since the frequent misdiagnosis of highly cellular leiomyomas as ESNs was highlighted. Additionally, although the entirely well-circumscribed margin of most ESNs readily allows a separation from endometrial stromal sarcomas with their typical permeative invasion, same tumors have greater irregularity of their margin than allowable for an ESN following the guidelines of Tavassoli and Norris, but without the typical, and usually extensive, infiltration of endometrial stromal sarcomas. These have been diagnosed by us descriptively as endometrial stromal tumors with limited infiltration. Three cases of this type and 47 ESNs that occurred in patients from 3 1 to 86 years (mean 53 years) were analyzed. The tumors were typically fleshy and at least in part yellow and ranged from 1.2 to 22 cm (mean 7.1 cm). Seven tumors had one to six focal margin irregularities; in four tumors these did not extend >3 mm beyond the main border of the tumor and were up to three in number. The other three (endometrial stromal tumors with limited infiltration) had four to six irregularities extending up to 9 mm beyond the main border of the tumor. Most neoplasms were densely cellular, but nine were hypocellular with areas that were fibrous, hyalinized, myxoid, edematous, or combinations thereof. The tumor cells almost always had scant cytoplasm, but in one tumor many cells had abundant eosinophilic cytoplasm. There was minimal cytologic atypia. Forty-four tumors had mitotic rates of up to 5 per 10 high power fields, but six had higher rates. Typical arterioles, some of which had hyalinized walls in nine cases, were numerous in all 50 tumors but were conspicuous on low-power examination in only 22. Larger, sometimes thick-walled vessels were seen in 37 tumors but were much less conspicuous than in highly cellular leiomyomas and were often present near the margin of the tumor. The cleft-like spaces of highly cellular leiomyomas were not a feature of these tumors. Twenty-three tumors showed variable degrees of smooth muscle differentiation and sex cord-like differentiation occurred in 12. Cysts were present in 17 tumors and infarct-type necrosis in 34, the latter sometimes causing initial concern for a malignant neoplasm. Follow-up information, available for 32 patients, including five patients whose tumor had some margin irregularity, ranged up to 114 months (mean 43.5 months). All patients were alive with no recurrence. Follow-up information was unfortunately not available for the two tumors with the greatest degree of infiltration. The major conclusions of our study are as follows: ESNs are characteristically soft and yellow; thorough sampling of their margin is mandatory; smooth muscle metaplasia is common and irregular interdigitation of stromal neoplasia with metaplastic smooth muscle may erroneously suggest myometrial infiltration; although typically densely cellular about 20% of ESNs are hypocellular and often fibrous; cellular neoplasms are often punctuated by hyaline plaques; sex cord-like differentiation, broad zones of necrosis and rarely epithelioid cells may complicate the microscopic appearance; typical arterioles are an important microscopic finding but are not always striking, particularly on low-power evaluation; the tumors may have a component of large blood vessels more typical of highly cellular leiomyomas, but they are not as conspicuous as in the latter and the clefts that are frequent in highly cellular leiomyomas are not a feature of ESNs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 24 TC 50 Z9 52 U1 0 U2 1 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 MAY PY 2002 VL 26 IS 5 BP 567 EP 581 DI 10.1097/00000478-200205000-00003 PG 15 WC Pathology; Surgery SC Pathology; Surgery GA 546FJ UT WOS:000175262200003 PM 11979087 ER PT J AU Sang, CN Booher, S Gilron, I Parada, S Max, MB AF Sang, CN Booher, S Gilron, I Parada, S Max, MB TI Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia - Efficacy and dose-response trials SO ANESTHESIOLOGY LA English DT Article ID ASPARTATE RECEPTOR ANTAGONIST; AMINO-ACID ANTAGONISTS; DOUBLE-BLIND; RAT MODEL; PERIPHERAL NEUROPATHY; THERMAL HYPERALGESIA; NR2B SUBUNIT; DORSAL-HORN; CROSS-OVER; KETAMINE AB Background: There are few repeated dose-controlled trials of N-methyl-D-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-D-aspartate antagonists using a novel two-stage design. Methods. The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine rs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale. Results: Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorplian, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain Intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03). Conclusions: Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PUN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-D-aspartate receptors are warranted. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, Bethesda, MD USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. RP Sang, CN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM csang@partners.org FU NIDCR NIH HHS [ZO1-DE00366] NR 45 TC 139 Z9 148 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2002 VL 96 IS 5 BP 1053 EP 1061 DI 10.1097/00000542-200205000-00005 PG 9 WC Anesthesiology SC Anesthesiology GA 547EU UT WOS:000175320700004 PM 11981142 ER PT J AU Li, G Suggs, J Gill, T AF Li, G Suggs, J Gill, T TI The effect of anterior cruciate ligament injury on knee joint function under a simulated muscle load: A three-dimensional computational simulation SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE ACL; knee; biomechanics; computational model; kinematics ID PATELLAR TENDON AUTOGRAFT; 3-DIMENSIONAL MODEL; MATHEMATICAL-MODEL; IN-VIVO; GRAFT; RECONSTRUCTION; FORCES; CONTACT; GOAT AB Understanding the biomechanical effect of various factors on knee behavior after anterior cruciate ligament (ACL) injury or reconstruction is instrumental for the development of an optimal surgical treatment of ACL injury that can better restore normal knee function. This paper presents the application of a three-dimensional (313) computational knee model for parametric studies of knee kinematics in response to simulated muscle loads. The knee model was constructed using the magnetic resonance images and biomechanical experimental data of the same cadaveric human knee specimen. The kinematics of the knee predicted by the computational model was compared with that measured from different specimens in a wide range of loading conditions and flexion angles. In general, the model predictions were within the range of experimental data. The model was then used to predict knee motion, ligament forces, and contact pressure in response to a simulated quadriceps force when the knee was ACL deficient. Partial ACL injury was simulated by reducing the stiffness of the ACL in the model. The results demonstrated that even with a reduction of 75% of the ACL stiffness, the ACL still carried a significant amount of the load (more than 58%) carried by an intact ACL. The kinematics (both tibial translation and rotation) varied less than 20% compared to that of the knee with intact ACL. The 3D computational model can be a powerful tool to simulate different variables that would influence knee function after ACL reconstruction, such as the initial tension of the ACL graft, the insertion sites of the graft, multibundle grafts, graft materials, and various physiological loading conditions. (C) 2002 Biomedical Engineering Society. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab,Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Li, G (reprint author), Orthopaed Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. NR 34 TC 54 Z9 59 U1 0 U2 3 PU BIOMEDICAL ENGINEERING SOC AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAY PY 2002 VL 30 IS 5 BP 713 EP 720 DI 10.1114/1.1484219 PG 8 WC Engineering, Biomedical SC Engineering GA 567YA UT WOS:000176513600011 PM 12108845 ER PT J AU Viollet, L Barois, A Rebeiz, JG Rifai, Z Burlet, P Zarhrate, M Vial, E Dessainte, M Estournet, B Kleinknecht, B Pearn, J Adams, RD Urtizberea, JA Cros, DP Bushby, K Munnich, A Lefebvre, S AF Viollet, L Barois, A Rebeiz, JG Rifai, Z Burlet, P Zarhrate, M Vial, E Dessainte, M Estournet, B Kleinknecht, B Pearn, J Adams, RD Urtizberea, JA Cros, DP Bushby, K Munnich, A Lefebvre, S TI Mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13 SO ANNALS OF NEUROLOGY LA English DT Article ID DIAPHRAGMATIC PARALYSIS; RESPIRATORY-DISTRESS; GENE; FORM; IDENTIFICATION; LOCALIZATION AB Distal spinal muscular atrophy is a heterogeneous group of neuromuscular disorders caused by progressive anterior born cell degeneration and characterized by progressive motor weakness and muscular atrophy, predominantly in the distal parts of the limbs. Here we report on chronic autosomal recessive distal spinal muscular atrophy in a large, inbred family with onset at various ages. Because this condition had some of the same clinical features as spinal muscular atrophy with respiratory distress, we tested the disease gene for linkage to chromosome 11q and mapped the disease locus to chromosome 11q13 in the genetic interval that included the spinal muscular atrophy with respiratory distress gene (D11S1889-D11S1321, Z(max) = 4.59 at theta = 0 at locus D11S4136). The sequencing of IGHMBP2, the human homologue of the mouse neuromuscular degeneration gene (nmd) that accounts for spinal muscular atrophy with respiratory distress, failed to detect any mutation in our chronic distal spinal muscular atrophy patients, suggesting that spinal muscular atrophy with respiratory distress and chronic distal spinal muscular atrophy are caused by distinct genes located in the so-me chromosomal region. In addition, the high intrafamilial variability in age at onset raises the question of whether nonallelic modifying genes could be involved in chronic distal spinal muscular atrophy. C1 Inst Necker Enfants Malades, INSERM U 393, Unite Rech Handicaps Genet Enfant, F-75743 Paris 15, France. Hop Ray Poincare, Federat Med Enfant, Garches, France. Amer Univ Hosp, Dept Neurol & Neuropathol, Beirut, Lebanon. Specialty Clin Ctr, Dept Neurol, Beirut, Lebanon. Genethon, Evry, France. Hop Necker Enfants Malad, Serv Explorat Fonctionnelles Neurol, Paris, France. Royal Childrens Hosp, Dept Paediat & Child Hlth, Brisbane, Qld, Australia. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Newcastle Upon Tyne, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Viollet, L (reprint author), Inst Necker Enfants Malades, INSERM U 393, Unite Rech Handicaps Genet Enfant, 149 Rue Sevres, F-75743 Paris 15, France. RI Lefebvre, Suzie/D-5092-2017 NR 30 TC 28 Z9 28 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2002 VL 51 IS 5 BP 585 EP 592 DI 10.1002/ana.10182 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 545PQ UT WOS:000175226700008 PM 12112104 ER PT J AU Kann, M Jacobs, H Mohrmann, K Schumacher, K Hedrich, K Garrels, J Wiegers, K Schwinger, E Pramstaller, PP Breakefield, XO Ozelius, LJ Vieregge, P Klein, C AF Kann, M Jacobs, H Mohrmann, K Schumacher, K Hedrich, K Garrels, J Wiegers, K Schwinger, E Pramstaller, PP Breakefield, XO Ozelius, LJ Vieregge, P Klein, C TI Role of parkin mutations in 111 community-based patients with early-onset parkinsonism SO ANNALS OF NEUROLOGY LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; UBIQUITIN-PROTEIN LIGASE; RESPONSIVE DYSTONIA; GENE; DISEASE; DELETIONS; EUROPE; STRESS; DYT1 AB Early-onset parkinsonism is frequently reported in connection with mutations in the parkin gene. In this study, we present the results of extensive genetic screening for parkin mutations in 111 community-derived early-onset parkinsonism patients (age of onset <50 years) from Germany with an overall mutation rate of 9.0%. Gene dosage alterations represented 67% of the mutations found, underlining the importance of quantitative analyses of parkin. In summary, parkin mutations accounted for a low but significant percentage of early-onset parkinsonism patients in a community-derived sample. C1 Med Univ Lubeck, Neurol Klin, Dept Neurol, D-23538 Lubeck, Germany. Med Univ Lubeck, Dept Human Genet, D-23538 Lubeck, Germany. Hosp Rothenburg Wumme, Dept Neurol, Rothenburg, Germany. Gen Reg Hosp Bolzano, Dept Neurol, Bolzano, Italy. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. Lippe Lemgo Hosp, Lemgo, Germany. RP Klein, C (reprint author), Med Univ Lubeck, Neurol Klin, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. RI Pramstaller, Peter/C-2357-2008 FU NINDS NIH HHS [NS3872] NR 20 TC 92 Z9 99 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2002 VL 51 IS 5 BP 621 EP 625 DI 10.1002/ana.10179 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 545PQ UT WOS:000175226700013 PM 12112109 ER PT J AU Wayne, JD Lauwers, GY Doherty, DA Belghiti, J Yamaoka, Y Regimbeau, JM Nagorney, DM Do, KA Ellis, LM Curley, SA Pollock, RE Vauthey, JN AF Wayne, JD Lauwers, GY Doherty, DA Belghiti, J Yamaoka, Y Regimbeau, JM Nagorney, DM Do, KA Ellis, LM Curley, SA Pollock, RE Vauthey, JN TI Preoperative predictors of survival after resection of small hepatocellular carcinomas SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 113th Annual Meeting of the Southern-Surgical-Association CY DEC 03-05, 2001 CL HOT SPRINGS, VIRGINIA SP SO Surg Assoc ID PERCUTANEOUS ETHANOL INJECTION; LONG-TERM SURVIVAL; LIVER-TRANSPLANTATION; HEPATITIS-B; CLINICOPATHOLOGICAL FEATURES; INTRAHEPATIC RECURRENCE; RETROSPECTIVE ANALYSIS; CIRRHOTIC-PATIENTS; SURGICAL-TREATMENT; HEPATECTOMY AB Objective To determine preoperative predictors of survival that can guide the choice of treatment for patients with small hepatocellular cancers (HCCs). Summary Background Data The treatment of patients with small (less than or equal to5 cm in diameter) HCCs is controversial. Methods A cohort of 249 patients (69 women, 180 men; median age 62 years) who underwent resection with curative intent for small HCC was identified from a multiinstitutional database. For each patient, the clinical data and pathology slides were reviewed, Six clinical factors (age, gender, preoperative alpha-fetoprotein level, hepatitis serology, number of tumors [single vs. multiple], and Child-Pugh score) and three pathologic factors (hepatitis activity score, fibrosis score, and Edmondson-Steiner tumor grade) that can be determined before surgery were correlated with survival, Log-rank tests and Cox proportional hazards modeling were used to determine factors influencing survival. Results The median overall survival for the entire cohort was 4.2 years. The estimated overall 5- and 8-year survival rates were 41.1% and 19.8%, respectively. Multivariate Cox analysis indicated that fibrosis score, Edmondson-Steiner grade, and Child-Pugh score were simultaneously significant predictors of survival after resection. A prognostic scoring system based on these covariates was derived and applied to the entire cohort. Patients lacking all three risk factors were assigned a score of 1, patients with one risk factor were assigned a score of 2, and patients with two or three risk factors were assigned a score of 3. Pairwise log-rank tests indicated significant differences in survival between scores 1 and 2, scores 2 and 3, and scores I and 3. This scoring system retained its prognostic significance when a subset of 98 patients with positive hepatitis C serology was analyzed separately. Conclusions Patients with small HCCs who will derive the least benefit from resection can be identified before surgery using a score based on tumor grade and the severity of underlying liver disease. In these patients, transplantation and/or ablation should be considered as possible alternative therapies. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Int Cooperat Study Grp Hepatocellular Carcinoma, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Int Cooperat Study Grp Hepatocellular Carcinoma, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kyoto Univ, Grad Sch Med, Kyoto, Japan. Hop Beaujon, Paris, France. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Int Cooperat Study Grp Hepatocellular Carcinoma, 1515 Holcombe Blvd,Box 444, Houston, TX 77030 USA. FU NCI NIH HHS [P30 CA016672] NR 55 TC 124 Z9 135 U1 0 U2 4 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 MAY PY 2002 VL 235 IS 5 BP 722 EP 730 DI 10.1097/00000658-200205000-00015 PG 9 WC Surgery SC Surgery GA 547VH UT WOS:000175352700028 PM 11981219 ER PT J AU Mangi, AA Palacios, IF Torchiana, DF AF Mangi, AA Palacios, IF Torchiana, DF TI Catheter pericardiocentesis for delayed tamponade after cardiac valve operation SO ANNALS OF THORACIC SURGERY LA English DT Article ID OPEN-HEART-SURGERY; ANTIBIOTIC-PROPHYLAXIS; CEFAMANDOLE; CEFAZOLIN; ANTICOAGULANTS; REPLACEMENT; CEFUROXIME; TRIAL AB Background. Late tamponade is a rare cause of morbidity and mortality after cardiac valve operation. We describe our recent experience with this entity. Methods. This is a single institution, procedure-matched, retrospective review of patients undergoing pericardiocentesis more than 7 days after cardiac operation, during a 7-year period. Results. Pericardiocentesis for delayed tamponade was performed in 43 of 9,612 patients. Although isolated valve operation accounted for 17% of all patients overall, 76% of patients undergoing pericardiocentesis (33 of 43) had undergone isolated valve operation. The average age in this group was 58 years, compared to an average of 68 years in all patients. Patients presented with tamponade an average of 18 days after operation. Positive predictors included elevated prothrombin time on presentation. Of the patient cohort 75% presented with dyspnea, 61% with inability to diurese, and 61% with hypotension. Echocardiography detected effusions in all patients, but specific echocardiographic signs of tamponade were present in only 30%. Of the patients, 97% were successfully treated by pericardiocentesis. All were safely restarted on warfarin. One patient required pericardial window. Conclusions. Delayed cardiac tamponade is more common after isolated valve operation, as opposed to coronary artery bypass grafting and valve/coronary artery bypass grafting. It tends to occur in the third postoperative week in younger patients who are aggressively anticoagulated. Pericardiocentesis with catheter placement is highly effective, and patients can be reanticoagulated safely. This series underestimates the incidence of late tamponade, as some patients may present to outside facilities. The diagnosis is aided by a high degree of suspicion. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, 55 Fruit St,Bullfinch 112, Boston, MA 02114 USA. NR 22 TC 11 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2002 VL 73 IS 5 BP 1479 EP 1483 AR PII S0003-1975(02)03495-1 DI 10.1016/S0003-4975(02)03495-1 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 550QE UT WOS:000175513100025 PM 12022536 ER PT J AU Wright, CD Menard, MT Wain, JC Donahue, DM Grillo, HC Lynch, TJ Choi, NC Mathisen, DJ AF Wright, CD Menard, MT Wain, JC Donahue, DM Grillo, HC Lynch, TJ Choi, NC Mathisen, DJ TI Induction chemoradiation compared with induction radiation for lung cancer involving the superior sulcus SO ANNALS OF THORACIC SURGERY LA English DT Article ID SURGICAL RESECTION; RADICAL RESECTION; PANCOAST TUMOR AB Background. The usual approach of induction radiation therapy (RT) followed by resection of superior sulcus tumors results in many incomplete resections, a high local recurrence rate, and suboptimal survival. induction chemoradiotherapy (CT/RT) has been shown to reduce local and distant recurrences and improve survival in stage III lung cancer. We investigated the role of induction CT/RT in superior sulcus patients. Methods. This was a single-institution, retrospective study. Results. From 1985 to 2000, 35 consecutive patients underwent induction treatment followed by resection of a superior sulcus tumor. All patients had mediastinoscopy first to exclude N2 disease, and all were NO at final pathologic examination. Twenty patients had induction RT (mean, 39 Gy), and 15 had induction CT/RT (mean, 51 Gy) with concurrent cisplatin-based chemotherapy. There was no treatment mortality. Complete resection was performed in 16 of 20 (80%) of the RT patients and in 14 of 15 (93%) of the CT/RT patients (p = 0.15). The pathologic response from the induction treatment was complete or near complete in 7 of 20 (35%) of the RT patients and in 13 of 15 (87%) of the CT/RT patients (p = 0.001). The median follow-up was 167 months in the RT patients and 51 months in the CT/RT patients. Two-year and 4-year survival was 49% and 49% (95% confidence interval, 26% to 71%) in the RT patients and 93% and 84% (93% confidence interval, 63% to 100%) in the CT/RT patients, respectively (p = 0.01). The local recurrence rate was 6 of 20 (30%) in the RT patients and 0 in the CT/RT patients (p = 0.02). Conclusions. Induction CT/RT for superior sulcus tumors appears to offer improved survival compared with induction RT alone. C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Med Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Radiat Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, Med Oncol Unit, Blake 1570, Boston, MA 02114 USA. NR 14 TC 53 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2002 VL 73 IS 5 BP 1541 EP 1544 AR PII S0003-4975(02)03471-9 DI 10.1016/S0003-4975(02)03471-9 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 550QE UT WOS:000175513100038 PM 12022546 ER PT J AU Demetri, GD AF Demetri, GD TI ET-743: The US experience in sarcomas of soft tissues SO ANTI-CANCER DRUGS LA English DT Article; Proceedings Paper CT 11th European Cancer Conference CY OCT 24, 2001 CL LISBON, PORTUGAL DE ecteinascidin-743; soft-tissue sarcoma; chemotherapy ID ANTITUMOR-ACTIVITY; ECTEINASCIDIN-743; AGENT; CHEMOTHERAPY; COMPOUND; TUMORS AB Ecteinascidin-743 (ET-743) has shown promise as a new and effective treatment for soft-tissue sarcomas. Two independent, multicenter, Phase II studies have been performed in the USA for patients with unresectable soft-tissue sarcomas (either chemotherapy-naive or pretreated patients). The patients received ET-743 at a dose of 1500 mug/m(2) as a 24 h continuous intravenous infusion every 3 weeks on an outpatient basis. Assessments were conducted every 6 weeks until documented progressive disease, unacceptable toxicity, or withdrawal. Responses were assessed in accordance with conventional oncological criteria and toxicities were graded using the National Cancer Institute common toxicity criteria. A total of 72 patients were enrolled: 36 patients to each study. Confirmed objective response rates were 14% (95% confidence interval (CI) 5 to 30%) and 8% (95% CI 2 to 23%) in chemotherapy-naive and pretreated patients, respectively. In chemotherapy-naive patients, 12-month progression-free and overall survival rates were 18% (95% CI 4 to 32%) and 49% (95% CI 20 to 78%), respectively. For patients with progressive disease despite prior conventional chemotherapy, 12-month progression-free and overall survival rates were 11% (95% CI 2 to 24%) and 55% (95% CI 35 to 75%), respectively. The median duration of response was 11 months. The durability of major responses in a subset of patients was impressive, as was the number of patients who achieved disease stabilization without showing objective response. Overall, ET-743 had a favorable safety profile. The most common grade 3-4 toxicities included neutropenia and transiently increased transaminase concentrations. ET-743 did not cause alopecia, mucositis, cardiotoxicity or neurotoxicity. The side effects were reversible, non-cumulative and manageable. There were no treatment-associated deaths. In conclusion, ET-743 is an active chemotherapeutic agent that can induce objective responses and clinical benefit in a subset of patients with metastatic or advanced soft-tissue sarcoma. [(C) 2002 Lippincott Williams Wilkins.]. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Shields Warren Bldg,G530,44 Binney St, Boston, MA 02115 USA. NR 9 TC 24 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD MAY PY 2002 VL 13 SU 1 BP S7 EP S9 PG 3 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 565PF UT WOS:000176378100003 PM 12173492 ER PT J AU Tremblay, CL Giguel, F Kollmann, C Guan, YB Chou, TC Baroudy, BM Hirsch, MS AF Tremblay, CL Giguel, F Kollmann, C Guan, YB Chou, TC Baroudy, BM Hirsch, MS TI Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5 antagonist, with other antiretroviral agents in vitro SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FUSION INHIBITOR T-20; INFECTION IN-VITRO; SOCIETY-USA PANEL; CD4 CELL COUNTS; COMBINATION THERAPY; CUBIC MILLIMETER; HIV-1; RECOMMENDATIONS; REPLICATION; STAVUDINE AB SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine),, nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses. C1 Massachusetts Gen Hosp, Infect Dis Unit, Harvard Med Sch, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Harvard Med Sch, Gray 5,55 Fruit St, Boston, MA 02114 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NCI NIH HHS [CA12464] NR 23 TC 87 Z9 91 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2002 VL 46 IS 5 BP 1336 EP 1339 DI 10.1128/AAC.46.5.1336-1339.2002 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 543KH UT WOS:000175100800025 PM 11959565 ER PT J AU Gonzalez, GM Tijerina, R Najvar, LK Bocanegra, R Rinaldi, M Loebenberg, D Graybill, JR AF Gonzalez, GM Tijerina, R Najvar, LK Bocanegra, R Rinaldi, M Loebenberg, D Graybill, JR TI In vitro and in vivo activities of posaconazole against Coccidioides immitis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TRIAZOLE ANTIFUNGAL AGENT; IN-VITRO; AMPHOTERICIN-B; CRYPTOCOCCUS-NEOFORMANS; SCH-56592; ITRACONAZOLE; SCH56592; FLUCONAZOLE; EFFICACY; CANDIDA AB Posaconazole (SCH 565921) was tested against 25 strains of Coccidioides immitis to determine their in vitro susceptibilities. The geometric mean 48-h MIC of posaconazole (POSA) was 0.5 mug/ml, the MIC range was 0.25 to 1 mug/ml, and the MIC at which 50% of the isolates tested are inhibited (MIC50) and the MIC90 were 0.5 and 1 mug/ml, respectively. The geometric mean 48-h MIC of itraconazole (ITRA) was 0.23 mug/ml, the MIC range was 0.125 to 0.5 mug/ml, and the MIC50 and MIC90 were both 0.25 mug/ml. Two strains of C immitis were selected for in vivo studies on the basis of the POSA 48-h MICs for the isolates. POSA orally administered at 0.01, 0.1, 0.5, 1, 5, and 10 mg/kg of body weight/day was compared with ITRA administered at 10 and 30 mg/kg three times a day. The spleens and livers of mice that died or survived to day 50 were removed to measure the fungal burdens. Mice had greater than or equal to90% survival when they were treated with greater than or equal to0.5 mg of POSA per kg or 30 mg of ITRA per kg. Cultures of whole spleens and livers from mice treated with 10 mg of POSA per kg showed greater than or equal to70% sterilization. No sterilization of whole spleens and livers from mice treated with ITRA was seen. POSA displayed potent in vivo activity against the two strains of C immitis tested. C1 Univ Autonama Nuevo Leon, Dept Microbiol, Fac Med, Monterrey 64460, NL, Mexico. Univ Texas, Hlth Sci Ctr, Div Infect Dis 7881, 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 78224 USA. Schering Plough Res Inst, Kenilworth, NJ 07033 USA. RP Gonzalez, GM (reprint author), Univ Autonama Nuevo Leon, Dept Microbiol, Fac Med, Madero & Dr Eduardo A Pequeno S-N Colonia Mitras, Monterrey 64460, NL, Mexico. NR 20 TC 52 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2002 VL 46 IS 5 BP 1352 EP 1356 DI 10.1128/AAC.46.5.1352-1356.2002 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 543KH UT WOS:000175100800028 PM 11959568 ER PT J AU Sun, QN Fothergill, AW McCarthy, DI Rinaldi, MG Graybill, JR AF Sun, QN Fothergill, AW McCarthy, DI Rinaldi, MG Graybill, JR TI In vitro activities of posaconazole, itraconazole, voriconazole, amphotericin B, and fluconazole against 37 clinical isolates of zygomycetes SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO; FUNGAL-INFECTIONS; SCH-56592 AB In vitro antifungal susceptibility testing results of a new antifungal triazole, posaconazole (POS), were compared to results with amphotericin B (AMB), itraconazole (ITC), voriconazole (VRC), and fluconazole (FLC) against clinical agents of zygomycosis. The MICs of POS at which 50% and 90% of the isolates were inhibited were 0.25 and 4 mug/ml, respectively. POS was significantly more active than VRC and FLC and slightly more active than ITC. The results suggest that POS has significant potential for clinical development against the zygomycetes. C1 Univ Texas, Hlth Sci Ctr, Fungus Testing Lab, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis 7811, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Beijing Union Med Univ Hosp, Dept Dermatol, Beijing 100730, Peoples R China. RP Fothergill, AW (reprint author), Univ Texas, Hlth Sci Ctr, Fungus Testing Lab, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 14 TC 204 Z9 221 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2002 VL 46 IS 5 BP 1581 EP 1582 DI 10.1128/AAC.46.5.1581-1582.2002 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 543KH UT WOS:000175100800065 PM 11959605 ER PT J AU Gonzalez, GM Tijerina, R Sutton, DA Graybill, JR Rinaldi, MG AF Gonzalez, GM Tijerina, R Sutton, DA Graybill, JR Rinaldi, MG TI In vitro activities of free and lipid formulations of amphotericin B and nystatin against clinical isolates of Coccidioides immitis at various saprobic stages SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FILAMENTOUS FUNGI; ANTIFUNGAL AGENTS; INOCULUM; SUSCEPTIBILITIES; CONIDIA AB We investigated the susceptibilities of hyphal, mixed hyphal, ungerminated arthroconidial, and germinated arthroconidial populations of Coccidioides immitis to lipid formulations of amphotericin B and nystatin and their conventional preparations, utilizing the National Committee for Clinical Laboratory Standards M38-P broth macrodilution method. The differences in effects of the three different growth stages of the saprobic phase of C. immitis on the MIC/minimum lethal concentration (MLC) ratio were not statistically significant for any of the antifungal agents tested. These results suggest that either inocula could be used for in vitro susceptibility studies with C. immitis. C1 Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Monterrey 64460, Nuevo Leon, Mexico. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Testing Lab, San Antonio, TX 78284 USA. RP Gonzalez, GM (reprint author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Madero & Dr Eduardo A Pequeno S-N,Colonia Mitras, Monterrey 64460, Nuevo Leon, Mexico. NR 11 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2002 VL 46 IS 5 BP 1583 EP 1585 DI 10.1128/AAC.46.5.1583-1585.2002 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 543KH UT WOS:000175100800066 PM 11959606 ER PT J AU Ha, E Cho, SI Chen, DF Chen, CZ Ryan, L Smith, TJ Xu, XP Christiani, DC AF Ha, E Cho, SI Chen, DF Chen, CZ Ryan, L Smith, TJ Xu, XP Christiani, DC TI Parental exposure to organic solvents and reduced birth weight SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article DE organic solvents; parental exposure; reduced birth weight ID MATERNAL OCCUPATIONAL EXPOSURE; DRY-CLEANING WORKERS; FOR-GESTATIONAL-AGE; SPONTANEOUS-ABORTIONS; CONGENITAL-MALFORMATIONS; PATERNAL OCCUPATION; PRINTING INDUSTRY; PREGNANCY; BENZENE; WOMEN AB The authors investigated the association of birth weight with maternal and paternal exposure to organic solvents in 1,222 couples employed in a large petrochemical corporation in Beijing, China, during the period between 1994 and 1998. A trained interviewer assessed parental exposures to organic solvents. The authors used generalized additive models to examine the association between birth weight and parental exposure to organic solvents. After the authors adjusted for potential confounders, maternal exposure to solvents was significantly associated with reduced birth weight (-81.7 gm, 95% confidence interval = -106.3, -3.1), and reduced birth weights of female babies and of younger mothers' babies were statistically significant. Maternal exposure to organic solvents was associated with reduced birth weight in this population, but paternal exposure to organic solvents was not similarly associated. C1 Ewha Womans Univ, Coll Med, Dept Prevent Med, Yangchun Gu, Seoul 120750, South Korea. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Beijing Med Univ, Ctr Ecogenet, Beijing 100083, Peoples R China. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Ha, E (reprint author), Ewha Womans Univ, Coll Med, Dept Prevent Med, Yangchun Gu, 911-1 Mok 6 Dong, Seoul 120750, South Korea. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NICHD NIH HHS [HD32505]; NIEHS NIH HHS [ES08337, ES00002]; NIOSH CDC HHS [OH03027] NR 54 TC 17 Z9 17 U1 1 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD MAY-JUN PY 2002 VL 57 IS 3 BP 207 EP 214 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 628FR UT WOS:000179982400005 PM 12510663 ER PT J AU Furmark, T Tillfors, M Marteinsdottir, I Fischer, H Pissiota, A Langstrom, B Fredrikson, M AF Furmark, T Tillfors, M Marteinsdottir, I Fischer, H Pissiota, A Langstrom, B Fredrikson, M TI Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 6th International Conference of Functional Mapping of the Human Brain CY JUN 13, 2000 CL SAN ANTONIO, TEXAS ID OBSESSIVE-COMPULSIVE DISORDER; GLUCOSE METABOLIC-RATE; ANXIETY DISORDERS; MAJOR DEPRESSION; PANIC DISORDER; PET; AMYGDALA; NEUROANATOMY; HABITUATION; VALIDATION AB Background: Neurofunctional changes underlying effective antianxiety treatments are incompletely characterized. This study explored the effects of citalopram and cognitive-behavioral therapy on regional cerebral blood flow (rCBF) in social phobia. Methods: By means of positron emission tomography with oxygen 15-labeled water, rCBF was assessed in 18 previously untreated patients with social phobia during an anxiogenic public speaking task. Patients were matched for sex, age, and phobia severity, based on social anxiety questionnaire data, and randomized to citalopram medication, cognitive-behavioral group therapy, or awaiting-list control group. Scans were repeated after 9 weeks of treatment or waiting time. Outcome was assessed by subjective and psychophysiological state anxiety measures and self-report questionnaires. Questions were re-administered after 1 year. Results: Symptoms improved significantly and roughly equally with citalopram and cognitive-behavioral therapy, whereas the waiting-list group remained unchanged. Four patients in each treated group and 1 waiting-list patient were classified as responders. Within both treated groups, and in responders regardless of treatment approach, improvement was accompanied by a decreased rCBF-response to public speaking bilaterally in the amygdala, hippocampus, and the periamygdaloid, rhinal, and parahippocampal cortices. Between-group comparisons confirmed that rCBF in these regions decreased significantly more in treated groups than control subjects, and in responders than nonresponders, particularly in the right hemisphere. The degree of amygdalar-limbic attenuation was associated with clinical improvement a year later. Conclusions: Common sites of action for citalopram and cognitive-behavioral treatment of social anxiety were observed in the amygdala, hippocampus, and neighboring cortical areas, ie, brain regions subserving bodily defense reactions to threat. C1 Uppsala Univ, Dept Psychol, SE-75142 Uppsala, Sweden. Univ Uppsala, Dept Neurosci Psychiat, S-75105 Uppsala, Sweden. Univ Hosp, PET Ctr, Uppsala, Sweden. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Furmark, T (reprint author), Uppsala Univ, Dept Psychol, Box 1225, SE-75142 Uppsala, Sweden. NR 53 TC 280 Z9 290 U1 1 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2002 VL 59 IS 5 BP 425 EP 433 DI 10.1001/archpsyc.59.5.425 PG 9 WC Psychiatry SC Psychiatry GA 548VD UT WOS:000175409800004 PM 11982446 ER PT J AU Massion, AO Dyck, IR Shea, T Phillips, KA Warshaw, MG Keller, MB AF Massion, AO Dyck, IR Shea, T Phillips, KA Warshaw, MG Keller, MB TI Personality disorders and time to remission in generalized anxiety disorder, social phobia, and panic disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PROSPECTIVE FOLLOW-UP; LONG-TERM TREATMENT; AGORAPHOBIA; COMORBIDITY; RELIABILITY; MOCLOBEMIDE; CHRONICITY; DEPRESSION; PREDICTORS; SEVERITY AB Background: This investigation assessed the effect of personality disorders (PersDs) on time to remission in patients with generalized anxiety disorder, social phobia, or panic disorder. Methods: Selected Axis I and II predictors of time to remission during 5 years of follow-up were assessed in 514 patients with 1 or more of these anxiety disorders who participated in the Harvard/Brown Anxiety Research Program, a multisite, prospective, longitudinal, naturalistic study. Results: The presence of a PersD predicted a 30% lower likelihood of generalized anxiety disorder remission, a 39% lower likelihood of social phobia remission, and no difference in likelihood of panic disorder remission. More specifically, a lower likelihood of remission from generalized anxiety disorder was predicted by the presence of avoidant PersD (34% lower) and dependent PersD (14% lower). The presence of avoidant PersD predicted a 41% lower likelihood of social phobia remission. The presence of major depressive disorder did not account for these findings. Conclusions: Our findings provide new data on the pernicious effect of PersDs on the course of generalized anxiety disorder and social phobia but not panic disorder, suggesting that PersDs have a differential effect on the outcome of anxiety disorders. C1 Univ Massachusetts, Med Ctr, Dept Psychiat, Sch Worcester, Worcester, MA 01655 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI USA. Boston Univ, Sch Publ Hlth, Massachusetts Vet Epidemiol Res Informat Ctr, Boston VA Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. RP Massion, AO (reprint author), Univ Massachusetts, Med Ctr, Dept Psychiat, Sch Worcester, 55 Lake Ave N, Worcester, MA 01655 USA. FU NIMH NIH HHS [MH 51415, R01 MH051415, K24 MH063975] NR 36 TC 90 Z9 95 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2002 VL 59 IS 5 BP 434 EP 440 DI 10.1001/archpsyc.59.5.434 PG 7 WC Psychiatry SC Psychiatry GA 548VD UT WOS:000175409800005 PM 11982447 ER PT J AU Andress, DL Ozuna, J Tirschwell, D Grande, L Johnson, M Jacobson, AF Spain, W AF Andress, DL Ozuna, J Tirschwell, D Grande, L Johnson, M Jacobson, AF Spain, W TI Antiepileptic drug-induced bone loss in young male patients who have seizures SO ARCHIVES OF NEUROLOGY LA English DT Article ID ANTICONVULSANT THERAPY; VITAMIN-D; MEN; EPILEPSY; MARKERS; TESTOSTERONE; OSTEOMALACIA; HYPOGONADISM; DYSFUNCTION; RESORPTION AB Background: Long-term antiepileptic drug (AED) therapy is known risk factor for bone loss and fractures. Vitamin D deficiency is frequently cited as a cause for bone loss in patients who have seizures. Objective: To determine whether men who have seizures, but who are otherwise healthy, suffer substantial bone loss in the hip while taking AEDs. Patients and Methods: We prospectively examined femoral neck bone mineral density (BMD) by dual-energy x-ray absorptiometry in 81 consecutive men, aged between 25 and 54 years old (mean age, 45 years), who were attending an outpatient seizure clinic. Low BMD values were analyzed for known risk factors for bone loss. Dual-energy x-ray absorptiometry scans were repeated in 54 patients, 12 to 29 months later (mean, 19 months), to assess the rate of change in BMD over time. Results: Multivariate linear regression analysis revealed that age (P<.001) and time receiving AEDs (P<.003) were the 2 important risk factors associated with low femoral neck BMD. Neither vitamin D deficiency, hypogonadism, cigarette smoking, nor excess alcohol intake were associated with low BMD after correcting for age and time on AEDs. Longitudinal analysis of femoral neck BMD revealed that only those in the youngest age group (25-44 years) showed significant declines in femoral neck BMD (1.8% annualized loss; 95% confidence interval, -3.1 to -0.9; P<.003) while receiving AED therapy. There was no evidence that a specific type of AED was more causally related to bone loss in this group although most patients were taking phenytoin sodium or carbamazepine during the longitudinal assessment. Conclusions: Long-term AED therapy in young male patients who have seizures causes significant bone loss at the hip in the absence of vitamin D deficiency. Dual-energy x-ray absorptiometry scanning of the hip is useful in identifying patients who are particularly susceptible to rapid bone loss while taking AEDs. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Div Nucl Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. RP Andress, DL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, 111A,1660 S Columbian Way, Seattle, WA 98108 USA. NR 27 TC 99 Z9 100 U1 0 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 MAY PY 2002 VL 59 IS 5 BP 781 EP 786 DI 10.1001/archneur.59.5.781 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 551ZY UT WOS:000175594900015 PM 12020260 ER PT J AU Ray, S Khan, BF Dohlman, CH D'Amico, DJ AF Ray, S Khan, BF Dohlman, CH D'Amico, DJ TI Management of vitreoretinal complications in eyes with permanent keratoprosthesis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Objectives: To evaluate the spectrum and treatment of posterior segment complications in eyes that had undergone successful keratoprosthesis (KPro) placement and to determine whether transeyelid vitrectomy techniques could be effectively used in eyes otherwise vulnerable to surface exposure. Design: In the last 10 years, 110 patients received a Dohlman-Doane KPro at the Massachusetts Eye and Ear Infirmary, Boston. We evaluated 22 eyes in 18 patients that required subsequent vitreoretinal surgery to treat posterior segment complications. One surgeon using modified vitreoretinal techniques, as described below, performed all vitreoretinal procedures. Results: The posterior segment complications included 6 cases of retro-KPro membranes, 13 cases of retinal detachments, and 5 cases of isolated vitreous opacity. All 6 retro-KPro membranes were effectively removed by vitrectomy without significant complication and 3 of these patients enjoyed improvement of visual acuity of at least 5 Snellen lines. Of 13 cases of retinal detachment, 6 patients had some improvement in visual acuity, 5 showed no appreciable change, and 2 had some decline in the final visual acuity. in all 5 cases of isolated vitreous opacity, the media was effectively cleared with pars plana vitrectomy. Three patients enjoyed improvement of visual acuity of at least 3 Snellen lines. Four cases of transeyelid vitrectomy were attempted and anatomical success was achieved in all 4 and vision improved in 3 of these patients. No special surgical complications were encountered in any of the 22 eyes as a result of these modified surgical techniques. Main Outcome Measures: Best preoperative and postoperative visual acuity and anatomical success were evaluated in relation to the preoperative posterior segment complication. Conclusions: Modified vitreoretinal surgical techniques can be effectively and safely used to treat posterior segment complications in patients with KPro de-vices. Retro-KPro membranes and other vitreous opacities were the most amenable to treatment. Retinal complications posed a special challenge. However, all of these cases highlight that modified vitrectomy techniques can be used in eyes with permanent KPro devices. These techniques can be performed without additional risk to the eye. Additionally, we demonstrated that transeyelid vitrectomy techniques could be used effectively to manage complications in eyes with severe ocular surface disease without undue exposure of vulnerable tissues. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP D'Amico, DJ (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 10 TC 50 Z9 54 U1 0 U2 2 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 MAY PY 2002 VL 120 IS 5 BP 559 EP 566 PG 8 WC Ophthalmology SC Ophthalmology GA 550KZ UT WOS:000175503400003 PM 12003604 ER PT J AU Akintoye, SO Dasso, M Hay, DI Ganeshkumar, N Spielman, AI AF Akintoye, SO Dasso, M Hay, DI Ganeshkumar, N Spielman, AI TI Partial characterization of a human submandibular/sublingual salivary adhesion-promoting protein SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE antibodies; bacterial adhesion; chromatography; dental caries; hydroxyapatite; immunoglobulins; lectins; saliva; Streptococcus mutans ID PROLINE-RICH PROTEINS; SEROTYPE-C STRAINS; IN-VITRO; MICROGRAM QUANTITIES; POLYACRYLAMIDE GELS; APATITIC SURFACES; HYDROXYAPATITE; BINDING; STREPTOCOCCI; VIVO AB Human submandibular/sublinaual saliva contains a protein that promotes adhesion of Streptococcus mutans JBP serotype-c to spheroidal hydroxyapatite in vitro. A high molecular-weight (250,000-300,000 Da) adhesion-promoting protein (APP) was purified by Trisacryl 2000 M gel-filtration chromatography and gel electroelution before it was partially characterized. Lectin blotting identified that the terminal carbohydrates include N-acetyl glucosamine-beta1-4-N-acetylglucosamine, galactose and galactose-beta1-3-N-acetyl galactosamine. Antibodies to APP demonstrated no difference in the immunoreactive pattern of APP from saliva of caries-active or caries-resistant individuals belonging to four different ethnic groups: Asian, African-American, Hispanic or Caucasian. No immunological similarities to salivary mucins or parotid agglutinins were detected by Western, blotting using immuno-cross-reactivity as a criterion. APP appears to be a unique protein found in submandibular/sublingual saliva. Understanding such a protein could help prevent S. mutans attachment to the enamel surface. (C) 2002 Published by Elsevier Science Ltd. C1 NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10010 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. NE Minor Oral Hlth Res Ctr, New York, NY USA. RP Spielman, AI (reprint author), NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, 345 E 24th St, New York, NY 10010 USA. FU NIDCR NIH HHS [DE10593] NR 25 TC 2 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD MAY PY 2002 VL 47 IS 5 BP 337 EP 345 AR PII S0003-9969(02)00020-1 DI 10.1016/S0003-9969(02)00020-1 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559VK UT WOS:000176046200001 PM 12015214 ER PT J AU Klingebiel, R Thieme, N Kivelitz, D Enzweiler, C Werbs, M Lehmann, R AF Klingebiel, R Thieme, N Kivelitz, D Enzweiler, C Werbs, M Lehmann, R TI Three-dimensional imaging of the inner ear by volume-rendered reconstructions of magnetic resonance data SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID VESTIBULAR AQUEDUCT SYNDROME; COCHLEAR IMPLANTATION; CEREBELLOPONTINE ANGLE; MONDINI MALFORMATION; MR; VISUALIZATION; SEQUENCES AB Objective: To evaluate 3-dimensional inner ear visualization by volume rendering of high-resolution magnetic resonance data in patients with clinically suspected inner ear abnormality. Design: Prospective comparative study of different postprocessing techniques, based on blinded film readings. Setting: Tertiary referral hospital. Subjects: Fifty patients (17 females and 33 males) aged 1 to 77 years (average age, 42 years) with sensorineural hearing loss, vertigo, and/or tinnitus. Intervention: Postprocessing of magnetic resonance data to inner ear reconstructions by the use of volume rendering as well as maximum-intensity projection; caloric testing by electronystagmography. Main Outcome Measures: Film was read blindly by 4 radiologists using a 5-point parameter scale for image quality and diagnostic value. The assessibility of inner ear subsegments was evaluated. The specificity of volume-rendered reconstructions for detecting semicircular canal obliterations was assessed in a subgroup of 9 patients by caloric testing. The time required for data postprocessing as well as film reading was recorded by means of a stopwatch. Results: Volume-rendered inner ear reconstructions were superior in image quality (P<.001), diagnostic value (P<.001), subsegment inner ear assessment (P<.01 to P<.001), and film reading time (P<.001) compared with maximum-intensity projections. The data postprocessing time was comparable for both techniques. Caloric weakness was noted in all patients assessed by electronystagmography. Conclusion: Volume rendering is the postprocessing technique of choice for 3-dimensional inner ear visualization, performing better than maximum-intensity projections with respect to various parameters. C1 Humboldt Univ, Dept Radiol, D-10098 Berlin, Germany. Humboldt Univ, Neuroradiol Sect, D-10098 Berlin, Germany. Humboldt Univ, Dept Ear Nose & Throat, D-10098 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Klingebiel, R (reprint author), Humboldt Univ, Dept Radiol, Charite Campus Mitte,Schumannstr 20-21, D-10098 Berlin, Germany. NR 22 TC 9 Z9 11 U1 0 U2 2 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 MAY PY 2002 VL 128 IS 5 BP 549 EP 553 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 550FG UT WOS:000175492500009 PM 12003586 ER PT J AU Hartnick, CJ Rutter, M Lang, F Willging, JP Cotton, RT AF Hartnick, CJ Rutter, M Lang, F Willging, JP Cotton, RT TI Congenital high airway obstruction syndrome and airway reconstruction - An evolving paradigm SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID SYNDROME CHAOS AB Objectives: To refine the classic definition of, and provide a working definition for, congenital high airway obstruction syndrome (CHAOS) and to discuss the various aspects of long-term airway reconstruction, including the range of laryngeal anomalies and the various techniques for reconstruction. Design: Retrospective chart review. Patients: Four children (age range, 2-8 years) with CHAOS who presented to a single tertiary care children's hospital for pediatric airway reconstruction between 1995 and 2000. Conclusions: To date, CHAOS remains poorly described in the otolaryngologic literature. We propose the following working definition for pediatric cases of CHAOS: any neonate who needs a surgical airway within 1 hour of birth owing to high upper airway (ie, glottic, subglottic, or upper tracheal) obstruction and who cannot be tracheally intubated other than through a persistent tracheoesophageal fistula. Therefore, CHAOS has 3 possible presentations: (1) complete laryngeal atresia without an esophageal fistula, (2) complete laryngeal atresia with a tracheoesophageal fistula, and (3) near-complete high upper airway obstruction. Management of the airway, particularly in regard to long-term reconstruction, in children with CHAOS is complex and challenging. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp Med Ctr, Dept Pediat Otolaryngol, Cincinnati, OH USA. CHU Lausanne, Serv Otorhinolaryngol, Lausanne, Switzerland. RP Hartnick, CJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 9 Z9 9 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 MAY PY 2002 VL 128 IS 5 BP 567 EP 570 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 550FG UT WOS:000175492500012 PM 12003589 ER PT J AU Novis, DA Renner, S Friedberg, RC Walsh, MK Saladino, AJ AF Novis, DA Renner, S Friedberg, RC Walsh, MK Saladino, AJ TI Quality indicators of fresh frozen plasma and platelet utilization - Three College of American Pathologists Q-Probes studies of 8 981 796 units of fresh frozen plasma and platelets in 1639 hospitals SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID INSTITUTIONS AB Objective.-To determine the normative rates of expiration and wastage for units of fresh frozen plasma (FFP) and platelets (PLTs) in hospital communities throughout the United States, and to examine hospital blood bank practices associated with more desirable (lower) rates. Design.-In 3 separate studies, participants in the College of American Pathologists Q-Probes laboratory quality improvement program collected data retrospectively on the numbers of units of FFP and PLTs that expired (outdated) prior to being used and that were wasted clue to mishandling. Participants also completed questionnaires describing their hospitals' and blood banks' laboratory and transfusion practices. Setting and Participants.-One thousand six hundred thirty-nine public and private institutions, more than 80% of which were known to be located in the United States. Main Outcome Measures.-Quality indicators of FFP and PLT utilization: the rates of expiration and wastage of units of FFP and PLTs. Results.-Participants submitted data on 8 981 796 units of FFP and PLTs. In all 3 studies, aggregate combined FFP and PLT expiration rates ranged from 5.8% to 6.4% and aggregate combined FFP and PLT wastage rates ranged from 2.0% to 2.5%. Among the top-performing 10% of participants (90th percentile and above), FFP and PLT expiration rates were 0.6% or lower and FFP and PLT wastage rates were 0.5% or lower. Among the bottom-performing 10% of participants (10th percentile and below), expiration rates were 13.8% or higher and wastage rates were 6.8% or higher. We were unable to associate selected hospital characteristics or blood bank practices with lower rates of FFP and PLT utilization. Conclusions.-The rates of FFP and PLT expiration and wastage vary greatly among hospitals in the United States. Hospital blood bank personnel are capable of achieving FFP and PLT expiration and wastage rates below 1%. C1 Wentworth Douglass Hosp, Dept Pathol, Dover, NH 03820 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Baystate Med Ctr, Dept Pathol, Springfield, MA USA. Coll Amer Pathologist, Northfield, IL USA. Dept Vet Affairs Med Ctr, Ft Howard, MD USA. RP Novis, DA (reprint author), Wentworth Douglass Hosp, Dept Pathol, Dover, NH 03820 USA. NR 11 TC 13 Z9 13 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2002 VL 126 IS 5 BP 527 EP 532 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 545JC UT WOS:000175212800001 PM 11958656 ER PT J AU Huang, Q Muzitansky, A Mark, EJ AF Huang, Q Muzitansky, A Mark, EJ TI Pulmonary neuroendocrine carcinomas - A review of 234 cases and a statistical analysis of 50 cases treated at one institution using a simple clinicopathologic classification SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID SMALL-CELL CARCINOMA; LUNG-TUMORS; BRONCHIAL CARCINOIDS; NEOPLASMS; FEATURES; CRITERIA; P53 AB Context.-Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC. Objective.-To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications. Patients.-To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995. Results-On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (110 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded. Conclusion.-Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient. C1 Holy Family Hosp & Med Ctr, Dept Pathol, Methuen, MA 01844 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Huang, Q (reprint author), Holy Family Hosp & Med Ctr, Dept Pathol, 70 East St, Methuen, MA 01844 USA. NR 42 TC 27 Z9 29 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2002 VL 126 IS 5 BP 545 EP 553 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 545JC UT WOS:000175212800004 PM 11958659 ER PT J AU Van Cott, EM Soderberg, BL Laposata, M AF Van Cott, EM Soderberg, BL Laposata, M TI Activated protein C resistance, the factor V Leiden mutation, and a laboratory testing algorithm SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DEEP-VEIN THROMBOSIS; POOR ANTICOAGULANT RESPONSE; COAGULATION-FACTOR-V; HONG-KONG CHINESE; VENOUS THROMBOSIS; APC-RESISTANCE; MYOCARDIAL-INFARCTION; HETEROZYGOUS CARRIERS; LUPUS ANTICOAGULANT; ORAL-CONTRACEPTIVES AB Objectives.-To present the current understanding of factor V Leiden and activated protein C resistance, and to propose a laboratory testing algorithm. Data Sources.-Publications on MEDLINE with the terms factor V Leiden or activated protein C resistance through mid 2001, as well as publications in the authors' files, were screened for inclusion in this report. Study Selection.-Original studies that report a novel finding on testing or clinical features of activated protein C resistance or factor V Leiden are included. Data Extraction.-The novel or key findings from the selected studies are analyzed. Data Synthesis.-Protein C and protein S are the integral components of an anticoagulation pathway that limits fibrinogen conversion to fibrin through the degradation of factors Va and Villa. When factor Va is resistant to degradation by activated protein C, this anticoagulation pathway does not operate properly, and patients have an increased risk for thrombosis. This report describes the protein C/protein S pathway, the significance of activated protein C resistance and the factor V Leiden mutation, and the clinical testing used to detect activated protein C resistance and the factor V Leiden mutation. A proposed laboratory testing algorithm is also provided. Conclusions.-Factor V Leiden is a risk factor for venous thrombosis and it is particularly common in white populations. A laboratory testing algorithm is proposed. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. NR 59 TC 13 Z9 14 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2002 VL 126 IS 5 BP 577 EP 582 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 545JC UT WOS:000175212800009 PM 11958664 ER PT J AU Boninger, ML Souza, AL Cooper, RA Fitzgerald, SG Koontz, AM Fay, BT AF Boninger, ML Souza, AL Cooper, RA Fitzgerald, SG Koontz, AM Fay, BT TI Propulsion patterns and pushrim biomechanics in manual wheelchair propulsion SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE biomechanics; kinematics; rehabilitation; wheelchairs ID CARPAL-TUNNEL SYNDROME; UPPER EXTREMITY; PARAPLEGIA; WEIGHT; FORCES; SPEEDS AB Objectives: To classify stroke patterns of manual wheelchair users and to determine if different patterns of propulsion lead to different biomechanics. Design: Case series. Setting: Biomechanics laboratory. Participants: Thirty-eight individuals with paraplegia who use manual wheelchairs for mobility. Intervention: Subjects propelled their own wheelchair on a dynamometer at 2 different steady state speeds. Bilateral biomechanical data were obtained by using a force and moment sensing pushrim and a motion analysis system. Main Outcome Measures: The propulsive stroke of each participant for each speed and side was classified as following 1 of 4 patterns. These 4 patterns were then compared by using a mixed-model analysis of variance. The biomechanical variables that were compared were cadence, peak and rate of rise of the resultant force, mechanical effective force, push angle. and ratio of time spent pushing to time in recovery. Results: The most common propulsive stroke involved the user lifting, the hand over the pushrim during the recovery phase. The stroke pattern was independent of axle position and varied from side to side and between speeds. After controlling for subject characteristics, significant differences were observed between stroke patterns in cadence and ratio of time spent pushing to time in recovery. A stroke pattern that involves using a semicircular motion with the hand below the pushrim during the recovery phase of the propulsion stroke was associated with a lower cadence and more time spent in the push phase relative to the recovery phase. Conclusion: The semicircular motion of propulsion displayed characteristics consistent with reduced repetition and more efficient propulsion. Use of this propulsion style may reduce trauma to the upper extremities. Clinicians should consider training individuals in this propulsion style. (C) 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. A VA Ctr Excellence, Highland Dr VA Med Ctr, Human Engn Res Labs, Pittsburgh, PA USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, 151R-1,7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [5 P01 HD33989 01] NR 23 TC 115 Z9 117 U1 3 U2 17 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2002 VL 83 IS 5 BP 718 EP 723 DI 10.1053/apmr.2002.32455 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 550FY UT WOS:000175494000020 PM 11994814 ER PT J AU Abou-Sayed, H Berger, DL AF Abou-Sayed, H Berger, DL TI Blunt lower-extremity trauma and popliteal artery injuries - Revisiting the case for selective arteriography SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the New-England-Surgical-Society CY SEP 21, 2001 CL PROVIDENCE, RHODE ISLAND SP New England Surg Soc ID KNEE; DISLOCATIONS AB Hypothesis: Abandoning mandatory angiography in patients with blunt lower-extremity trauma and normal neurovascular examination results does not affect limb salvage. Design: Retrospective, nonrandomized cohort study Mean follow-up (31 of 52 patients) of 9.5 months (range 0-96 months). Setting: Single-institution, academic level I trauma center. Patients: Medical records of patients presenting emergently with knee dislocation, distal femoral fractures, or proximal tibial fractures during a 20-year period were reviewed. Fifty-three injuries occurred in 52 patients. Patients were predominantly male (81%) and young (mean age, 32.7 years). Mechanisms and side of extremity injury, coincident injuries, and neurovascular status on admission were recorded. Hard signs of arterial insufficiency or compartment syndrome were identified. Interventions: Angiographic findings and operative and nonoperative interventions were recorded to identify whether angiographic data would alter therapy dictated by clinical findings alone. Main Outcome Measures: Limb salvage rate and necessity for vascular surgical intervention based on angiographic data in patients with normal neurovascular examination results. Results: Multiorgan trauma occurred in 11 patients. Pulses were normal in 35, absent in 16, and diminished or identified by Doppler signal in 2. Arterial insufficiency or compartment syndrome was present in 29%. Twenty-seven patients (28 limbs) under-went angiography at the discretion of the attending surgeon. Of 13 abnormal arteriograms, 2 occurred in patients with normal pulses and 11 in patients with abnormal examination results. Thirteen of 36 patients with normal pulses underwent angiography; none had clinically significant arterial injuries that necessitated intervention. No vascular interventions were necessary in 23 patients with normal pulses who did not undergo angiography (P<.001). Normal neurovascular status bore a 100% negative predictive value in determining the necessity of vascular intervention. Conclusions: Angiography is unnecessary in the routine evaluation of the patient with blunt lower-extremity trauma who presents with a normal neurovascular examination result and can be used selectively for patients with diminished pulses who lack associated indications for mandatory operative exploration. C1 Massachusetts Gen Hosp, Gen Surg Serv, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Plast Surg, San Francisco, CA USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Gen Surg Serv, Room ACC 465,15 Parkman St, Boston, MA 02114 USA. NR 19 TC 40 Z9 43 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2002 VL 137 IS 5 BP 585 EP 589 DI 10.1001/archsurg.137.5.585 PG 5 WC Surgery SC Surgery GA 549RX UT WOS:000175461500021 PM 11982473 ER PT J AU Jaffer, FA O'Donnell, CJ Larson, MG Chan, SK Kissinger, KV Kupka, MJ Salton, C Botnar, RM Levy, D Manning, WJ AF Jaffer, FA O'Donnell, CJ Larson, MG Chan, SK Kissinger, KV Kupka, MJ Salton, C Botnar, RM Levy, D Manning, WJ TI Age and sex distribution of subclinical aortic atherosclerosis - A magnetic resonance imaging examination of the Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE magnetic resonance imaging; aortas; atherosclerosis; imaging; subclinical disease ID BEAM COMPUTED-TOMOGRAPHY; CORONARY-ARTERY DISEASE; INTIMA-MEDIA THICKNESS; MYOCARDIAL-INFARCTION; OLDER ADULTS; RISK-FACTORS; CARDIOVASCULAR-DISEASE; HIGH-RESOLUTION; THORACIC AORTA; BLOOD-PRESSURE AB Autopsy data demonstrate a correlation between subclinical aortic atherosclerosis and cardiovascular disease. Therefore, noninvasive cardiovascular magnetic resonance (CMR) of subclinical atherosclerosis may provide a novel measure of cardiovascular risk, but it has not been applied to an asymptomatic population-based cohort to establish age- and sex-specific normative data. Participants in the Framingham Heart Study offspring cohort who were free of clinically apparent coronary disease were randomly sampled from strata of sex, quartiles of age, and quintiles of Framingham Coronary Risk Score. Subjects (n=318, aged 60 9 years, range 36 to 78 years, 51% women) underwent ECG-gated T2-weighted black-blood thoracoabdominal aortic CMR scanning. CMR evidence of aortic atherosclerosis was noted in 38% of the women and 41% of the men. Plaque prevalence and all measures of plaque burden increased with age group and were greater in the abdomen than in the thorax for both sexes and across all age groups. In addition, the Framingham Coronary Risk Score was significantly correlated with all plaque prevalence and burden measures for women but only for men after age adjustment. These noninvasive CMR data extend the prior autopsy-based prevalence estimates of subclinical atherosclerosis and may help to lay the foundation for future studies of risk stratification and treatment of affected individuals. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Div,Harvard Thorndike Lab, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Div Cardiol, Boston, MA USA. RP Manning, WJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Div,Harvard Thorndike Lab, 330 Brookline Ave, Boston, MA 02215 USA. RI Botnar, Rene/E-6875-2012; OI Botnar, Rene/0000-0003-2811-2509; Jaffer, Farouc/0000-0001-7980-384X; Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [N01-HC-38038] NR 27 TC 124 Z9 127 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2002 VL 22 IS 5 BP 849 EP 854 DI 10.1161/01.ATV.0000012662.29622.00 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550PP UT WOS:000175511700025 PM 12006401 ER PT J AU Cai, JM Hatsukami, TS Ferguson, MS Yuan, C AF Cai, JM Hatsukami, TS Ferguson, MS Yuan, C TI In vivo high-resolution MR imaging of carotid artery: Evaluation of lesion type SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA. Marina Ferguson Inc, Seattle, WA 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2002 VL 22 IS 5 MA P195 BP A34 EP A34 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550PP UT WOS:000175511700214 ER PT J AU Fitzgerald, ML Andersson, LP Rhee, S Mendez, AJ Freeman, MW AF Fitzgerald, ML Andersson, LP Rhee, S Mendez, AJ Freeman, MW TI Topology and functional analysis of the large extracellular aminoterminal and regulatory domains SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Miami, Sch Med, Miami, FL 33152 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2002 VL 22 IS 5 MA P212 BP A37 EP A37 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550PP UT WOS:000175511700231 ER PT J AU Game, BA Lopes-Virella, MF Huang, Y AF Game, BA Lopes-Virella, MF Huang, Y TI PPAR gamma ligands 9-HODE and troglitazone stimulate matrix metalloproteinase-1 expression in vascular endothelial cells via extracellular signal-regulated kinase SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2002 VL 22 IS 5 MA P201 BP A35 EP A35 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550PP UT WOS:000175511700220 ER PT J AU Kunjathoor, VV Febbraio, M Andersson, L Silverstein, R Freeman, MW AF Kunjathoor, VV Febbraio, M Andersson, L Silverstein, R Freeman, MW TI Decreased modified lipoprotein uptake in macrophages lacking both scavenger receptor A I/II and CD36 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cornell Univ, Weill Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2002 VL 22 IS 5 MA P93 BP A16 EP A16 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550PP UT WOS:000175511700118 ER PT J AU Moore, KJ El Khoury, J Medeiros, LA Luster, AD Freeman, MW AF Moore, KJ El Khoury, J Medeiros, LA Luster, AD Freeman, MW TI Identification of a pro-inflammatory CD36-associated signal transduction pathway in macrophages SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2002 VL 22 IS 5 MA P179 BP A31 EP A31 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550PP UT WOS:000175511700199 ER PT J AU Wilasrusmee, C Da Silva, MS Yusupov, IR Sing, B Sobel, M Kittur, DS AF Wilasrusmee, C Da Silva, MS Yusupov, IR Sing, B Sobel, M Kittur, DS TI Identification of angiogenic inhibitors that also disrupt mature endothelial capillary networks SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract C1 SUNY Upstate Med Univ, Syracuse, NY USA. VA Puget Sound HCS, Seattle, WA 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 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2002 VL 22 IS 5 MA P332 BP A58 EP A58 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 550PP UT WOS:000175511700344 ER PT J AU Hoffman, GS Cid, MC Hellman, DB Guillevin, L Stone, JH Schousboe, J Cohen, P Calabrese, LH Dickler, H Merkel, PA Fortin, P Flynn, JA Locker, GA Easley, KA Schned, E Hunder, GG Sneller, MC Tuggle, C Swanson, H Hernandez-Rodriguez, J Lopez-Soto, A Bork, D Hoffman, DB Kalunian, K Klashman, D Wilke, WS Scheetz, RJ Mandell, BF Fessler, BJ Kosmorsky, G Prayson, R Luqmani, RA Nuki, G McRorie, E Sherrer, Y Baca, S Walsh, B Ferland, D Soubrier, M Choi, HK Gross, W Segal, AM Ludivico, C Puechal, X AF Hoffman, GS Cid, MC Hellman, DB Guillevin, L Stone, JH Schousboe, J Cohen, P Calabrese, LH Dickler, H Merkel, PA Fortin, P Flynn, JA Locker, GA Easley, KA Schned, E Hunder, GG Sneller, MC Tuggle, C Swanson, H Hernandez-Rodriguez, J Lopez-Soto, A Bork, D Hoffman, DB Kalunian, K Klashman, D Wilke, WS Scheetz, RJ Mandell, BF Fessler, BJ Kosmorsky, G Prayson, R Luqmani, RA Nuki, G McRorie, E Sherrer, Y Baca, S Walsh, B Ferland, D Soubrier, M Choi, HK Gross, W Segal, AM Ludivico, C Puechal, X CA INSSYS TI A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LOW-DOSE METHOTREXATE; PERMANENT VISUAL-LOSS; TEMPORAL ARTERITIS; POLYMYALGIA-RHEUMATICA; WEGENERS-GRANULOMATOSIS; CORTICOSTEROID REGIMENS; TAKAYASU ARTERITIS; DISEASE; BIOPSY; COMPLICATIONS AB Objective. To evaluate treatment with methotrexate (MTX) in patients with newly diagnosed giant cell arteritis (GCA) to determine if MTX reduces GCA relapses and cumulative corticosteroid (CS) requirements and diminishes disease- and treatment-related morbidity. Methods. This was a multicenter, randomized, double-blind study. Over 4 years, 16 centers from the International Network for the Study of Systemic Vasculitides enrolled patients with unequivocal GCA. The initial treatment was 1 mg/kg/day (less than or equal to60 mg every day) prednisone, plus either 0.15 mg/kg/week MTX (increased to 0.25 mg/kg/week, for a maximum weekly dosage of 15 mg) or placebo. Two physicians, both blinded to treatment allocation, evaluated each patient at every trial visit. One physician was responsible for providing global medical care. The other assessed GCA status according to a standard protocol. Treatment failure was defined as 2 distinct relapses or persistence of disease activity after the first relapse, in spite of increased CS therapy. Results. Ninety-eight patients were enrolled. No significant differences between treatment groups were noted with regard to age, frequency of positive findings on temporal artery biopsy (placebo 87%, MTX 79%), or comorbidities at the time of enrollment. The median dosage of MTX was 15 mg/week. The incidence of treatment failure was comparable between groups after 12 months: 57.5% in the MTX group failed treatment (95% confidence interval [95% CI] 41.6-73.4%) compared with 77.3% in the placebo group (95% CI 61.9-92.8%) (P = 0.26). In a Cox regression analysis, MTX was not associated with a reduced risk of treatment failure (relative risk 0.72; 95% CI 0.41-1.28). There were no significant differences between groups with regard to abnormal elevations of the erythrocyte sedimentation rate following initial remissions, serious morbidity due to GCA, cumulative CS dose, or treatment toxicity. In the MTX group, there were fewer cases of GCA relapse heralded by symptoms of isolated polymyalgia rheumatica (1 case versus 5 in the placebo group; P = 0.05). Conclusion. The results of this randomized, multicenter trial do not support the adjunctive use of MTX to control disease activity or to decrease the cumulative dose and toxicity of CS in patients with GCA. C1 Cleveland Clin Fdn A50, Harold C Schott Chair Rheumat & Immunol Dis, Cleveland, OH 44915 USA. Hosp Clin Barcelona, Barcelona, Spain. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Paris 08, Paris, France. Pk Nicollet Med Fdn, St Louis Pk, MN USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. McGill Univ, Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. Mayo Clin, Rochester, MN USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Univ Calif Los Angeles, Los Angeles, CA USA. Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. Ctr Rheumatol Immunol & Arthrit, Ft Lauderdale, FL USA. Rheumatol Assoc S Florida, Delray Beach, FL USA. Univ Arizona, Tucson, AZ USA. Med Univ Lubeck, D-23538 Lubeck, Germany. RP Hoffman, GS (reprint author), Cleveland Clin Fdn A50, Harold C Schott Chair Rheumat & Immunol Dis, 9500 Euclid Ave, Cleveland, OH 44915 USA. RI Easley, Kirk/K-6910-2015; OI Easley, Kirk/0000-0003-4419-2617; Luqmani, Raashid/0000-0002-4446-5841; Cid Xutgla, Maria Cinta/0000-0002-4730-0938 NR 55 TC 222 Z9 226 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2002 VL 46 IS 5 BP 1309 EP 1318 DI 10.1002/art.10262 PG 10 WC Rheumatology SC Rheumatology GA 552XU UT WOS:000175646000026 PM 12115238 ER PT J AU Apreleva, M Ozbaydar, M Fitzgibbons, PG Warner, JJP AF Apreleva, M Ozbaydar, M Fitzgibbons, PG Warner, JJP TI Rotator cuff tears: The effect of the reconstruction method on three-dimensional repair site area SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE rotator cuff tears; transosseous repair; suture-anchor repair; cadaveric model; computer modeling and visualization ID SUTURE ANCHORS; SUPRASPINATUS; FIXATION; TENDON AB Purpose: To quantitatively determine the 3-dimensional (3-D) area of the original supraspinatus insertion and compare it with the repair-site area after 4 reconstructions of a simulated supraspinatus tear. Type of Study: Ex vivo biomechanical study. Methods: The outline of the original supraspinatus insertion was obtained in 10 human cadaveric shoulders using a 3-D digitizer. A supraspinatus tear was created and 4 repair techniques were evaluated: transosseous simple suture (TOS), transosscous mattress suture (TOM), suture-anchor simple suture (SAS), suture-anchor mattress suture (SAM). The 3-D outlines of the reconstructed supraspinatus insertion were digitized after each repair. The outlines of the original supraspinatus insertion and repair areas were superimposed onto humeral geometry obtained from a laser scanner, and surface areas were calculated. Results: The original supraspinatus insertion area was larger than any of the repair-site areas (P <.05). On average, TOS provided a 20%, larger repair-site area than the other repairs (P <.05). Repair-site areas were not different Limon g TOM, SAS, or SAM repairs (P >.05) and covered 67% of the original supraspinatus insertion. Conclusions: None of the tested repairs restored the area of the original supraspinatus insertion. The larger repair-site area of the TOS repair suggests that this technique provides better potential for healing and, ultimately, greater strength of repair. C1 Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Apreleva, M (reprint author), Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. RI Ozbaydar, Mehmet/D-7391-2016 NR 32 TC 147 Z9 149 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD MAY-JUN PY 2002 VL 18 IS 5 BP 519 EP 526 DI 10.1053/jars.2002.32930 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 550EL UT WOS:000175490600012 PM 11987064 ER PT J AU Josephson, L Kircher, MF Mahmood, U Tang, Y Weissleder, R AF Josephson, L Kircher, MF Mahmood, U Tang, Y Weissleder, R TI Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes SO BIOCONJUGATE CHEMISTRY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; CATHEPSIN-B; CONTRAST AGENT; CARCINOMA PATIENTS; BREAST-CARCINOMA; MR LYMPHOGRAPHY; LYMPH-NODES; CELLS; MACROPHAGES; TUMORS AB A number of quantitative three-dimensional tomographic near-infrared fluorescence imaging techniques have recently been developed and combined with MR imaging to yield highly detailed anatomic and molecular information in living organisms (1, 2). Here we describe magnetic nanoparticle based MR contrast agents that have a near-infrared fluorescence (NIRF) that is activated by certain enzymes. The probes are prepared by conjugation of arginyl peptides to cross-linked iron oxide amine (amino-CLIO), either by a disulfide linkage or a thioether linker, followed by the attachment of the indocyanine dye Cy5.5. The NIRF of disulfide-linked conjugate was activated by DTT, while the NIRF of thioether-linked conjugate was activated by trypsin. Fluorescent quenching of the attached fluorochrome occurs in part due to the interaction with iron oxide, as evident by the activation of fluorescence with DTT when nanoparticles that have less than one dye attached per particle. With a SC injection of the probe, axillary and brachial lymph nodes were darkened on MR images and easily delineated by NIRF imaging. The probes may provide the basis for a new class of so-called smart nanoparticles, capable of pinpointing their position through their magnetic properties, while providing information on their environment by optical imaging techniques. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149 13th St,5406, Charlestown, MA 02129 USA. NR 43 TC 285 Z9 297 U1 8 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 2002 VL 13 IS 3 BP 554 EP 560 DI 10.1021/bc015555d PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 553PN UT WOS:000175684800023 PM 12009946 ER PT J AU Lin, YH Weissleder, R Tung, CH AF Lin, YH Weissleder, R Tung, CH TI Novel near-infrared cyanine fluorochromes: Synthesis, properties, and bioconjugation SO BIOCONJUGATE CHEMISTRY LA English DT Article ID DYE LABELING REAGENTS; IN-VIVO; INDOCYANINE GREEN; FLUORESCENT PROTEIN; SUCCINIMIDYL ESTERS; ENHANCEMENT; AGENTS; TUMORS; PROBES AB Recently, near-infrared (NIR) fluorescence light has been applied to image various biological events in vivo, because it penetrates tissue more efficiently than light in the visible spectrum. Compounds exhibiting fluorescent properties in the NIR range are key elements for this upcoming optical imaging technology. In this paper, we report the synthesis of four new, water-soluble NIR cyanine fluorochromes which have superior chemical stability and optical properties. Each fluorochrome was designed with a monoreactive carboxyl group for labeling purposes. When multiple fluorochromes were attached to a single macromolecule, fluorescence quenching was observed. On the basis of this property, a novel autoquenched enzyme sensitive NIR fluorescence probe was prepared. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [CA79443, CA86355, CA88365, CO97065] NR 22 TC 123 Z9 127 U1 8 U2 48 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 2002 VL 13 IS 3 BP 605 EP 610 DI 10.1021/bc0155723 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 553PN UT WOS:000175684800029 PM 12009952 ER PT J AU Richardson, P Hideshima, T Anderson, K AF Richardson, P Hideshima, T Anderson, K TI Thalidomide in multiple myeloma SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE anti-angiogenesis; immunomodulation; myeloma; thalidomide ID NECROSIS-FACTOR-ALPHA; BONE-MARROW ANGIOGENESIS; SINGLE-DOSE PHARMACOKINETICS; HUMAN-IMMUNODEFICIENCY-VIRUS; STEM-CELL TRANSPLANTATION; ERYTHEMA-NODOSUM LEPROSUM; ENDOTHELIAL GROWTH-FACTOR; HEALTHY MALE-VOLUNTEERS; NF-KAPPA-B; PERIPHERAL-BLOOD AB Thalidomide - removed from widespread clinical use by 1962 because of severe teratogenicity - has anti-angiogenic and immunomodulatory effects, including the inhibition of TNF alpha. It has returned to practice as an effective oral agent in the management of various disease states including erythema nodosum leprosum, for which it was FDA-approved in 1998, and more recently certain malignancies, including multiple myeloma. Whilst the mechanism of action of thalidomide remains incompletely understood, considerable insight has been generated by extensive preclinical studies in multiple myeloma. Moreover, clinical trials both as a single agent and in combination have confirmed benefit in relapsed and refractory disease. Thalidomide's role in treating newly diagnosed patients is currently under study and it is now established as an important therapeutic option in the treatment of multiple myeloma. (C) 2002 Editions scientifiques et medicales Elsevier SAS. C1 Harvard Univ, Sch Med, Jerome Lipper Myeloma Ctr,Div Hematol Oncol, Dept Adult Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Jerome Lipper Myeloma Ctr,Div Hematol Oncol, Dept Adult Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 93 TC 14 Z9 16 U1 1 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD MAY PY 2002 VL 56 IS 3 BP 115 EP 128 AR UNSP S0753332202001683/FLA DI 10.1016/S0753-3322(02)00168-3 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 552VK UT WOS:000175640600001 PM 12046682 ER PT J AU von Bergwelt-Baildon, MS Vonderheide, RH Maecker, B Hirano, N Anderson, KS Butler, MO Xia, ZN Zeng, WY Wucherpfennig, KW Nadler, LM Schultze, JL AF von Bergwelt-Baildon, MS Vonderheide, RH Maecker, B Hirano, N Anderson, KS Butler, MO Xia, ZN Zeng, WY Wucherpfennig, KW Nadler, LM Schultze, JL TI Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: potential for clinical application SO BLOOD LA English DT Article ID PULSED DENDRITIC CELLS; CLASS-I MOLECULES; MHC CLASS-II; INTERFERON-GAMMA; EUROPIUM FLUOROIMMUNOASSAY; TUMOR-ANTIGEN; CD40 LIGAND; VITRO; COSTIMULATION; IMMUNOTHERAPY AB CD40 engagement is the major signal that induces B cells to efficiently present antigen to T cells. We previously demonstrated that human peripheral blood-derived CD40-activated B cells (CD4D-B cells) function as antigen-presenting cells (APCs). Here, we have established a culture system to generate these APCs under clinically applicable conditions using guanylic acid-grade soluble trimeric CD40 ligand. To monitor APC function and antigen loading for these cells, simple and efficient quality control assays have been developed. Using this approach, we demonstrate that CD40-B cells from healthy donors and cancer patients are fully functional and equally expanded in long-term cultures. These B cells boost robust memory T-cell responses, but more importantly, they also prime naive T-cell responses against neoantigens ex vivo. CD40-B cells overcome current obstacles, such as the difficulty of isolation, generation, and long-term expansion observed with other APCs. Therefore, they are an excellent source of professional APCs for immune assessment, antigen discovery, and antigen-specific immunotherapy. (C) 2002 by The American Society of Hematology. C1 Univ Cologne, Dept Hematol Oncol, Tumor Immunol Lab, D-50924 Cologne, Germany. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Univ Cologne, Dept Hematol Oncol, Tumor Immunol Lab, Joseph Stelzmann Str 9,Haus 16, D-50924 Cologne, Germany. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [P01-CA-78378, K08-CA-87720-01, K08-CA-88444-01, P01-CA-66996] NR 60 TC 115 Z9 117 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2002 VL 99 IS 9 BP 3319 EP 3325 DI 10.1182/blood.V99.9.3319 PG 7 WC Hematology SC Hematology GA 545EU UT WOS:000175204300033 PM 11964299 ER PT J AU Adams, GB Chabner, KT Foxall, RB Weibrecht, KW Rodrigues, NP Dombkowski, D Fallon, R Poznansky, MC Scadden, DT AF Adams, GB Chabner, KT Foxall, RB Weibrecht, KW Rodrigues, NP Dombkowski, D Fallon, R Poznansky, MC Scadden, DT TI Heterologous cells cooperate to augment stem cell migration, homing, and engraftment SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Canc Res Inst, Indianapolis, IN USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 0 TC 0 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 2 BP 324 EP 324 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000006 ER PT J AU Adams, GB Olson, DP Szczepiorkowski, ZM Chabner, KT Clingensmith, BL Kos, C Pollak, MR Brown, EM Scadden, DT AF Adams, GB Olson, DP Szczepiorkowski, ZM Chabner, KT Clingensmith, BL Kos, C Pollak, MR Brown, EM Scadden, DT TI Calcium contributes to bone marrow localization and function of stem cells through the calcium sensing receptor. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Membrane Biol Program,Endocrine Hypertens Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA 02129 USA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 0 TC 0 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 1 BP 324 EP 324 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000005 ER PT J AU Orkin, SH AF Orkin, SH TI Control and plasticity of hematopoietic lineages. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 47 BP 341 EP 341 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000051 ER PT J AU Zhang, H Degar, B Sinning, J Forget, B AF Zhang, H Degar, B Sinning, J Forget, B TI Exploring the functional role of bicoid gene Pitx2 in hematopoiesis. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 MA 70 BP 347 EP 347 PG 1 WC Hematology SC Hematology GA 584TC UT WOS:000177484000073 ER PT J AU Jones, LN Lutskiy, MI Cooley, J Kenney, DM Rosen, FS Remold-O'Donnell, E AF Jones, LN Lutskiy, MI Cooley, J Kenney, DM Rosen, FS Remold-O'Donnell, E TI A novel protocol to identify mutations in patients with Wiskott-Aldrich syndrome SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE Wiskott-Aldrich syndrome (WAS); Wiskott-Aldrich syndrome protein (WASP); X-linked thrombocytopenia (XLT); mutation analysis; X-linked disease ID SYNDROME PROTEIN WASP; BONE-MARROW TRANSPLANTATION; X-LINKED THROMBOCYTOPENIA; SYNDROME GENE; IDENTIFICATION; EXPRESSION; CELLS; SPLENECTOMY; SEQUENCE AB Mutations of WASP (Wiskott-Aldrich syndrome protein) underlie the severe immunodeficiency/platelet disorder Wiskott-Aldrich syndrome (WAS) and its milder variant X-linked thrombocytopenia (XLT). The affected gene, a 12-exon structure on the X-chromosome, is expressed exclusively in blood cells. The encoded product WASP is a 502-amino-acid scaffolding protein that functions in stimulus-induced nucleation of actin filaments to form dynamic cell surface projections. To date, more than 150 mutations have been identified in 300 WAS/XLT kindred worldwide, generally through methodologies that include sophisticated exon screening steps such as single-strand conformation analysis. We report here a simpler protocol, which was designed for use in clinical settings to identify the mutations of newly diagnosed patients. The approach relies on directly sequencing amplified exons according to a staggered schedule based on statistical evaluation of previous cases. In a 2 1/2-year trial, samples from 28 consecutive patients were analyzed; these included 3 "blindly labeled" previously studied cases. The mutations that were identified include a broad spectrum (8 missense, 3 nonsense, 5 splice site mutations, 11 small insertion/deletions, 1 large deletion) and were broadly distributed (in 10 of the 12 exons). All mutations were verified and no discrepancies were encountered. Per patient, a mean of six DNA sequencing reactions and 6-7 h of staff effort sufficed for mutation identification and verification, indicating that the protocol is cost-effective. This cumulative experience demonstrates the suitability, reliability, and versatility of the new protocol. (C) 2002 Elsevier Science (USA). C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL059561, HL-59561] NR 26 TC 9 Z9 12 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 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2002 VL 28 IS 3 BP 392 EP 398 DI 10.1006/bcmd.2002.0523 PG 7 WC Hematology SC Hematology GA 584TC UT WOS:000177484000078 PM 12367583 ER PT J AU Doney, KC Chauncey, T Appelbaum, FR AF Doney, KC Chauncey, T Appelbaum, FR CA Seattle Bone Marrow Transplant Tea TI Allogeneic related donor hematopoietic stem cell transplantation for treatment of chronic lymphocytic leukemia SO BONE MARROW TRANSPLANTATION LA English DT Article DE chronic lymphocytic leukemia; allogeneic transplantation; conditioning regimen ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; TERM FOLLOW-UP; HOST-DISEASE; THERAPY; RECIPIENTS; BUSULFAN; LYMPHOMA; TOXICITY; TRIAL AB Between 1980 and 1999, 25 patients with chronic lymphocytic leukemia (CLL) received related donor hematopoietic stem cell transplants. Median patient age was 46.6 years. Preparative regimens included busulfan (BU) plus cyclophosphamide (CY), CY plus TBI, and etoposide, CY plus TBI. Twenty-one donors were HLA-identical siblings, one was a DR mismatched sibling, and three were identical twins. Bone marrow was the source of hematopoietic stem cells in 22 cases and G-CSF stimulated peripheral blood in three cases. Most patients received methotrexate and cyclosporine for GVHD prophylaxis. Fourteen patients developed grades 2-4 acute GVHD and 10 developed clinical extensive chronic GVHD. Late clearance of CLL cells was associated with the development of chronic GVHD in one patient. Two patients had recurrent CLL. Nonrelapse mortality at day 100 was 57% for the seven patients conditioned with BU/CY and 17% for the 18 patients conditioned with TBI-containing regimens. Actuarial survival at 5 years for the 25 patients is 32%. All patients who received BU/CY died within 3 years of transplant. For the 14 patients transplanted since 1992 and who received TBI, actuarial 5-year survival is 56%. The maximum response of CLL to hematopoietic cell transplantation may be delayed, but long-term disease-free survival can be achieved. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Med Ctr, Div Oncol, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Doney, KC (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA. NR 34 TC 59 Z9 63 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2002 VL 29 IS 10 BP 817 EP 823 DI 10.1038/sj/bmt/1703548 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 562CQ UT WOS:000176180200002 PM 12058231 ER PT J AU Stokvis, E Rosing, H Lopez-Lazaro, L Jimeno, JM Supko, JG Schellens, JHM Beijnen, JH AF Stokvis, E Rosing, H Lopez-Lazaro, L Jimeno, JM Supko, JG Schellens, JHM Beijnen, JH TI Bioanalysis of the novel peptide anticancer drug kahalalide F in human plasma by h.p.l.c. under basic conditions coupled with positive turbo-ionspray tandem mass spectrometry SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 Slotervaart Hosp, Dept Pharm & Pharmacol, Amsterdam, Netherlands. Pharma Mar SA, Res & Dev, Madrid, Spain. Massachusetts Gen Hosp, Ctr Canc, Clin Pharmacol Lab, Boston, MA USA. Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. NR 1 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD MAY PY 2002 VL 53 IS 5 BP 543P EP 543P DI 10.1046/j.1365-2125.2002.16132.x PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 549GC UT WOS:000175435300013 ER PT J AU Hirose, M Martyn, JAJ Kuroda, Y Marunaka, Y Tanaka, Y AF Hirose, M Martyn, JAJ Kuroda, Y Marunaka, Y Tanaka, Y TI Mechanism of suppression of insulin signalling with lignocaine SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE insulin receptor; lignocaine; local anaesthetic; phosphorylation; skeletal muscle; tyrosine kinase ID MYOFASCIAL TRIGGER POINT; LOCAL-ANESTHETICS; SKELETAL-MUSCLE; PI INTERACTIONS; RECEPTOR; NA+; INJECTION; MEMBRANES; LIDOCAINE; PROTEINS AB 1 Lignocaine suppresses insulin-stimulated glucose transport into the cells and insulin-stimulated glycogenesis at doses equivalent to that used in the treatment of muscle pain disorder. We evaluated the direct effect of lignocaine on insulin receptor (IR) kinase activity. 2 After lignocaine (40 mM, approximately equivalent to 1%) or an equal volume (100 mul) saline had been injected into the tibialis anterior muscle of rat, insulin (50 mm g(-1) body weight) was administered into the portal vein in vivo. Immunoprecipitation and immunoblotting were used to detect insulin-mediated tyrosine phosphorylation of both IR-beta and insulin receptor substrate (IRS)-1. and insulin-Stimulated binding of IRS-1 to p85 regulatory subunit of phosphatidylinositol 3-kinase (P13-K) in the extracted muscle. 3 In the in vitro study, purified IR from rat liver and or recombinant IRS-1 protein with adenosine triphosphate were incubated with lignocaine (4 or 40 mM). 4 Lignocaine reduced insulin-stimulated tyrosine phosphorylation of IR-beta to 12.6 +/- 5.7% (P < 0.001), and IRS-1 to 32.1 +/- 18.8% (P < 0.01). and also reduced insulin-stimulated binding of IRS-1 to p85 to 27.4 +/- 12.7 % (P<0.001) relative to control (100%) in muscle in vivo. 5 The in vitro study revealed that lignocaine directly inhibited both basal and insulin-stimulated tyrosine phosphorylation of IR. 6 These results indicate that clinically used doses of lignocaine inhibit insulin signalling in skeletal muscle. The inhibitory effect of lignocaine on tyrosine kinase activity of the IR underlies the suppression of insulin signalling with lignocaine. C1 Kyoto Prefectural Univ Med, Dept Anaesthesiol, Kamigyo Ku, Kyoto 6028566, Japan. Kyoto Prefectural Univ Med, Dept Physiol, Kamigyo Ku, Kyoto 6028566, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan. RP Hirose, M (reprint author), Kyoto Prefectural Univ Med, Dept Anaesthesiol, Kamigyo Ku, Kyoto 6028566, Japan. FU NIGMS NIH HHS [R01 GM055082, R01 GM55082, R01 GM061411, R01 GM61411, R01 GM031569, R01 GM31569] NR 21 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 2002 VL 136 IS 1 BP 76 EP 80 DI 10.1038/sj.bjp.0704691 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 548LQ UT WOS:000175389800009 PM 11976270 ER PT J AU Chen, CY Million, M Adelson, DW Martinez, V Rivier, J Tache, Y AF Chen, CY Million, M Adelson, DW Martinez, V Rivier, J Tache, Y TI Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF2 SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE astressin B; astressin(2)-B; corticotropin-releasing factor; corticotropin-releasing factor receptor 2; gastric contractility; intracisternal; NBI-27914; RX-77368; thyrotropin-releasing hormone; urocortin; gastric emptying ID CORTICOTROPIN-RELEASING FACTOR; STRESS-RELATED ALTERATIONS; COLONIC MOTOR FUNCTION; C-FOS EXPRESSION; FACTOR RECEPTORS; HIGH-AFFINITY; TRH ANALOG; GASTROINTESTINAL MOTILITY; COMPETITIVE ANTAGONISTS; ASTRESSIN ANALOGS AB 1 Corticotropin-releasing factor (CRF) acts in the brain to inhibit thyrotropin-releasing hormone (TRH) analogue, RX-77368-induced vagal stimulation of gastric motility. We investigated CRF receptor-mediated actions of rat urocortin (rUcn) injected intracisternally (ic) on gastric motor function. 2 Urethane-anaesthetized rats with strain gauges on the gastric corpus were injected i.e. with rUcn and 20 min later, with i.e. RX-77368. CRF antagonists were injected i.e. 10 min before rUcn. 3 RX-77368 (1.5, 3, 10, 30 and 100 ng, i.e.) dose-dependently increased corpus contractions, expressed as total area under the curve (AUC, mV min(-1)) to 2.6 +/- 2.5, 6.1 +/- 5.9, 9.8 +/- 2.6, 69.7 +/- 21.7 and 74.9 +/- 28.7 respectively vs 0.2 +/- 0.1 after i.e. saline. Ucn (1, 3 or 10 mug) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.e. saline+RX-77368. 4 The CRF1/CRF2 antagonist, astressin-B (60 mug, i.e.) completely blocked i.e. rUcn (3 mug, i.e.)induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5 The selective CRF2 antagonist, astressin(2)-B (30, 60 or 100 mug, i.e.) dose-dependently prevented i.e. rUCn action while the CRF1 antagonist, NBI-27914 did not. 6 In conscious rats, rUcn (0.6 or 1 mug, i.e.) inhibited gastric emptying of an ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by astressin(2)-B. 7 These data show that i.e. rUcn acts through CRF2 receptors to inhibit central vagal gastric contractile response and postoprandial emptying. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, 11301 Wilshire Blvd,Bldg 115,Rm 117B, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [P01 DK026741, P30 DK041301, R01 DK033061, DK-41301, R01 DK-41301, R37 DK033061, DK 26741, DK 33061] NR 58 TC 33 Z9 34 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 2002 VL 136 IS 2 BP 237 EP 247 DI 10.1038/sj.bjp.0704713 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 556AA UT WOS:000175824200009 PM 12010772 ER PT J AU Fisher, CM AF Fisher, CM TI Reversal of normal pressure hydrocephalus symptoms by subdural collections SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article AB Background. The pathogenesis of symptoms in normal pressure hydrocephalus (NPH) is unclear. One theory is that in the presence of enlarged lateral ventricles, the ventricular fluid exerts increased force on the ventricular walls, the cerebrospinal fluid pressure remaining normal. This is in accordance with Pascal's principle of F = PxA. It has not been possible to obtain direct evidence for this view. Method. The opportunity to gain insight into the matter arose when it was observed that two patients with symptomatic NPH were relieved of their symptoms when they developed bilateral subdural collections, one after head trauma, the other after ventriculo-peritoneal shunting for NPH. Result. In each case, concomitant with the subdural collections and the reversal of symptoms, the ventricular system became smaller. In the first patient, symptoms returned when the subdural collections were resorbed. In the second patient, symptoms returned when the subdural collections became excessive. Conclusion: Although documentation was less thorough than desired, it was concluded that relief of symptoms was related to the decrease in the ventricular size rather than lowering of the intraventricular pressure, thus providing evidence for operation of the principle F = PxA as the mechanism of symptoms in NPH. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Fruit St,VBK 910, Boston, MA 02114 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY, AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 2002 VL 29 IS 2 BP 171 EP 174 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 551FY UT WOS:000175550300012 PM 12035840 ER PT J AU Lessnick, SL Dacwag, CS Golub, TR AF Lessnick, SL Dacwag, CS Golub, TR TI The Ewing's sarcoma oncoprotein EWS/FLI induces a p53-dependent growth arrest in primary human fibroblasts SO CANCER CELL LA English DT Article ID TUMOR-SUPPRESSOR GENES; FUSION GENE; DNA-BINDING; P53; MDM2; EXPRESSION; TRANSFORMATION; P14(ARF); P19(ARF); RAS AB Ewing's sarcoma is associated with a fusion between the EWS and FLI1 genes, forming an EWS/FLI fusion protein. We developed a system for the identification of cooperative mutations in this tumor through expression of EWS/FLI in primary human fibroblasts. Gene expression profiling demonstrated that this system recapitulates many features of Ewing's sarcoma. EWS/FLI-expressing cells underwent growth arrest, suggesting that growth arrest-abrogating collaborative mutations may be required for tumorigenesis. Expression profiling identified transcriptional upregulation of p53, and the growth arrest was rescued by inhibition of p53. These data support a role for p53 as a tumor suppressor in Ewing's sarcoma and demonstrate the use of transcriptional profiling of model systems in the identification of cooperating mutations in human cancer. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. MIT, Whitehead Ctr Genome Res, Cambridge, MA 02142 USA. RP Golub, TR (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL07574-20] NR 37 TC 149 Z9 154 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2002 VL 1 IS 4 BP 393 EP 401 DI 10.1016/S1535-6108(02)00056-9 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TW UT WOS:000178352100013 PM 12086853 ER PT J AU Wadler, S Brain, C Catalano, P Einzig, AI Cella, D Benson, AB AF Wadler, S Brain, C Catalano, P Einzig, AI Cella, D Benson, AB TI Randomized phase II trial of either fluorouracil, parenteral hydroxyurea, interferon-alpha-2a, and filgrastim or doxorubicin/docetaxel in patients with advanced gastric cancer with qualityof-life assessment: Eastern cooperative oncology group study E6296 SO CANCER JOURNAL LA English DT Article DE gastric cancer; stomach cancer; interferon; hydroxyurea; docetaxel; quality of life; fatigue ID GASTROINTESTINAL-TRACT; RIBONUCLEOTIDE REDUCTASE; CELLS; ETOPOSIDE; CISPLATIN; THERAPY AB The Eastern Cooperative Oncology Group conducted a randomized phase II trial to determine the objective response rates, toxicities, and overall survival and to assess effects on quality of life for two combination regimens in patients with advanced gastric cancer. PATIENTS AND METHODS All patients had biopsy-proven, untreated metastatic gastric cancer with measurable disease. The FHIG arm employed infusional fluorouracil (F), 2.6 g/m(2), given intravenously over 24 hours once per week for 6 weeks: infusional hydroxyurea (H), 4.3 g/m(2), given intravenously over 24 hours once per week for 6 weeks; and interferon-alpha-2a (1), 9 MU given subcutaneously three times per week, once per week for 6 weeks. The AD arm employed doxorubicin (A), 50 mg/m(2), and docetaxel (D), 75 mg/m(2), both given intravenously every 21 days. Quality of life was measured by the FACT-Fatigue scale and a novel questionnaire assessing interferon-mediated fatigue. RESULTS Twenty-nine patients were enrolled; 23 were eligible and evaluable. Twelve were enrolled on FHIG and 11 on AD. The major grade greater than or equal to 3 toxicities were neuromotor (46%) in patients receiving FHIG and granulocytopenia (91%) in those receiving AD. There were two fatalities in the AD arm. There was one partial responder on FHIG (8.3%) and none on AD. The median survival was 6.6 months for FHIG and 10.1 months for AD. Quality-of-life analysis did not show substantial cumulative fatigue in patients treated with FHIG. CONCLUSIONS Neither regimen demonstrated enough activity to serve as a platform for the development of further clinical regimens against gastric carcinoma. A subset of patients receiving interferon was able to tolerate therapy without deterioration in quality of life. C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Wadler, S (reprint author), Cornell Univ, Weill Med Coll, Div Hematol Oncol, 1300 York Ave,0606, New York, NY 10021 USA. FU NCI NIH HHS [CA21115, CA66636, CA14958, CA23318, CA17145] NR 12 TC 15 Z9 15 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAY-JUN PY 2002 VL 8 IS 3 BP 282 EP 286 DI 10.1097/00130404-200205000-00013 PG 5 WC Oncology SC Oncology GA 561LM UT WOS:000176142200012 PM 12074329 ER PT J AU Ott, MJ AF Ott, MJ TI Complementary and alternative therapies in cancer symptom management SO CANCER PRACTICE LA English DT Editorial Material ID CONTROLLED CLINICAL-TRIAL; THERAPEUTIC TOUCH; MINDFULNESS MEDITATION; CHRONIC PAIN; RELAXATION; MEDICINE; IMAGERY; AROMATHERAPY; ONCOLOGY; MASSAGE C1 Dana Farber Canc Inst, Zakim Ctr Integrated Therapies, Pain & Palliat Care Program, Boston, MA 02115 USA. RP Ott, MJ (reprint author), Dana Farber Canc Inst, Zakim Ctr Integrated Therapies, Pain & Palliat Care Program, Boston, MA 02115 USA. NR 68 TC 16 Z9 18 U1 4 U2 11 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD MAY-JUN PY 2002 VL 10 IS 3 BP 162 EP 166 DI 10.1046/j.1523-5394.2002.103004.x PG 5 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 544LK UT WOS:000175159000008 PM 11972571 ER PT J AU Lynch, M Abrahm, J AF Lynch, M Abrahm, J TI Ensuring a good death - Pain and palliative care in a cancer center SO CANCER PRACTICE LA English DT Article DE good death; pain management; palliative care; quality of life ID LIFE; END AB PURPOSE: The purpose of this article is to describe how die commitment of the Dana-Farber Cancer Institute to pain management, quality of life, and optimal end-of-life care is operationalized through a comprehensive pain and palliative-care program. OVERVIEW: Institutional standards for pain management often address only die physical aspects of pain. Effective pain management requires assessment and interventions that address the multidimensional nature of pain, suffering, and quality of life throughout the cancer continuum. This approach seeks to lay the foundation of comfort and peace associated with a good death. CLINICAL IMPLICATIONS: Institutional pain management standards need to reflect the complexity of pain, especially cancer-related pain, by emphasizing comprehensive, holistic assessment and multimodality, approaches to pain control and quality-of-life issues. C1 Dana Farber Canc Inst, Pain & Palliat Care Program, Boston, MA 02115 USA. RP Lynch, M (reprint author), Dana Farber Canc Inst, Pain & Palliat Care Program, Boston, MA 02115 USA. NR 22 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD MAY-JUN PY 2002 VL 10 SU 1 BP S33 EP S38 DI 10.1046/j.1523-5394.10.s.1.9.x PG 6 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 545DE UT WOS:000175200300009 PM 12027967 ER PT J AU Ghosh, PM Bedolla, R Mikhailova, M Kreisberg, JI AF Ghosh, PM Bedolla, R Mikhailova, M Kreisberg, JI TI RhoA-dependent murine prostate cancer cell proliferation and apoptosis: Role of protein kinase C zeta SO CANCER RESEARCH LA English DT Article ID P70 S6 KINASE; CYCLIN D1 EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; GENE-PRODUCT; GROWTH; PHOSPHORYLATION; ACTIVATION; RECEPTOR; GTPASES AB We previously showed that RhoA played an important role in the proliferation of murine Weprostate cancer (TRAMP) cells (P. M. Ghosh et al., Oncogene, 18: 4120-4130, 1999). Untransfected TRAMP cells as well as those expressing constitutively active RhoA (Q63L) mutant protein (Q63L cells) were highly proliferative. In contrast, TRAMP cells expressing dominant-negative RhoA (T19N) mutant protein (T19N cells) were slow growing. In this study, we showed, in addition, that T19N cells displayed reduced rates of apoptotic cell death in response to serum deprivation, compared with TRAMP and Q63L cells, and we studied the mechanisms of the effects of RhoA on TRAMP cell proliferation and apoptosis. Both proliferation and apoptosis of TRAMP and Q63L cells were dependent on the activation of phosphatidylinositol 3-kinase (PI3K). The ubiquitous mitogen-activated Ser/Thr kinase, p70S6 kinase, a downstream effector of PI3K, was overexpressed in TRAMP and Q63L cells. Another PI3K effector, the cell survival protein Akt, displayed increased activity in T19N cells, which did not express active RhoA, compared with TRAMP and Q63L cells. The atypical protein kinase C (PKC) isoform PKCzeta, which is downstream of PI3K, was activated in cells expressing active RhoA. In addition, expression of constitutively activated PKCzeta in TRAMP cells enhanced proliferation and p70S6 kinase phosphorylation, whereas the inhibition of PKCzeta activation resulted in activation of Akt and enhanced cell survival. Thus, the effects of RhoA on TRAMP cell proliferation and apoptosis may be mediated by PKCzeta. C1 Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Ghosh, PM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [2T32HL07446-16] NR 44 TC 32 Z9 34 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2002 VL 62 IS 9 BP 2630 EP 2636 PG 7 WC Oncology SC Oncology GA 546GG UT WOS:000175265000030 PM 11980660 ER PT J AU Jalife, J Berenfeld, O Mansour, M AF Jalife, J Berenfeld, O Mansour, M TI Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation SO CARDIOVASCULAR RESEARCH LA English DT Review DE arrhythmia (mechanisms); supravetr, arrhymia ID ISOLATED SHEEP HEART; ISOLATED CARDIAC-MUSCLE; MITRAL-VALVE DISEASE; CANINE RIGHT ATRIUM; PULMONARY VEINS; SLOW CONDUCTION; STROKE PREVENTION; CATHETER ABLATION; CIRCUS MOVEMENT; ECTOPIC BEATS AB Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the major cardiac Cause of stroke. Recent studies in patients with paroxysmal AF have shown that the arrhythmia is triggered by focal sources localized usually in one of the cardiac veins. However. in chronic AF, the prevailing theory is that multiple random wavelets of activation coexist to create an unorganized atrial rhythm. Experiments in isolated hearts have demonstrated that stable, self-sustained rotors can exist in the atria and that high frequency activation by such rotors results in the complex patterns of activation that characterize AF. Studies in animals and patients Support the view that at least some cases of paroxysmal and chronic AF are the result of the uninterrupted periodic activity of discrete reentrant sites. In this brief review article. we examine historical data and more recent experimental evidence behind the hypothesis that AF may be organized by one. or a small number of high-frequency reentrant sources localized in the left atrium. We then discuss the potential implications and evidence supporting such a hypothesis for human AF. Finally. we suggest future studies designed to unravel the detailed molecular, cellular and pathophysiological mechanisms responsible for AF initiation and maintenance. The work discussed may open potentially exciting new diagnostic and therapeutic possibilities. (C) 2002 Elsevier Science B.V. All rights reserved. C1 SUNY Syracuse, Upstate Med Univ, Dept Pharmacol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. RP Jalife, J (reprint author), SUNY Syracuse, Upstate Med Univ, Dept Pharmacol, 766 Irving Ave, Syracuse, NY 13210 USA. EM jalifej@upstate.edu RI Jalife, Jose/L-4833-2015 OI Jalife, Jose/0000-0003-0080-3500 FU NHLBI NIH HHS [P01-HL39707, R01-HL60843] NR 74 TC 275 Z9 283 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 EI 1755-3245 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY PY 2002 VL 54 IS 2 BP 204 EP 216 AR PII S0008-6363(02)00223-7 DI 10.1016/S0008-6363(02)00223-7 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 553DE UT WOS:000175659600002 PM 12062327 ER PT J AU Salat, DH Kaye, JA Janowsky, JS AF Salat, DH Kaye, JA Janowsky, JS TI Greater orbital prefrontal volume selectively predicts worse working memory performance in older adults SO CEREBRAL CORTEX LA English DT Article ID AGE-RELATED-CHANGES; ORDERED POINTING TASK; TEMPORAL-LOBE LESIONS; HUMAN FRONTAL-CORTEX; CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; NEURAL ACTIVITY; DEFICITS; OBJECT; MONKEY AB Alterations of the prefrontal cortex (PFC) could contribute to cognitive decline in older adults. We examined the specificity of age-related PFC degeneration and whether cognitive abilities were related to volumetric measurements. Older and younger subjects were tested using a battery of tasks supported by different subregions within the PFC, The cognitive data from older subjects were related to PFC volumetric measurements in order to determine whether cortical morphology was predictive of individual differences in task performance within this age range (72-94 years). Working memory performance best distinguished older from younger subjects. Working memory measures but not other measures were correlated with age in both groups. A larger orbital PFC volume was related to a worse working memory performance and a larger superior PFC volume was related to worse conditional association learning. The volumes of these regions were not related to performance on other tasks. These results suggest that working memory is a sensitive measure of cognitive aging and that regional morphology is associated with specific cognitive abilities in older adults. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Salat, DH (reprint author), MGH, NMR Ctr, Dept Radiol, Bldg 149,13th St,Mail Code 149 2301, Charlestown, MA 02129 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG12611]; NIMH NIH HHS [MH11855] NR 66 TC 61 Z9 61 U1 5 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAY PY 2002 VL 12 IS 5 BP 494 EP 505 DI 10.1093/cercor/12.5.494 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 544LR UT WOS:000175159800005 PM 11950767 ER PT J AU Romero, JR Rivera, A Conlin, PR AF Romero, JR Rivera, A Conlin, PR TI Red blood cell Na+/H+ exchange activity is insulin resistant in hypertensive patients SO CLINICAL AND EXPERIMENTAL HYPERTENSION LA English DT Article ID SODIUM-HYDROGEN EXCHANGER; HUMAN-ERYTHROCYTES; ANGIOTENSIN-II; ACTIVATION; PHOSPHORYLATION; ANTIPORTER; SITES; NHE-1; RATS AB A number of ion transport defects have been described in human red blood cells (RBC) from patients with essential hypertension. Insulin resistance is also frequently present in hypertensive patients and insulin levels in vitro correlate with red blood cell Na+/H+ exchange (NHE) activity. We studied the kinetics of insulin-stimulated NHE activity in freshly isolated RBC from 14 patients with essential hypertension and 8 normotensive subjects. We measured an estimate of maximal activity (V-max) for NEE activity as net Na+ influx driven by an outward H+ gradient in acid-loaded and Na+-depleted erythrocytes. NHE activity was significantly greater in hypertensives than in normotensives (22.0 vs 14.5 mmol/L cell x h, respectively; P<0.01). When RBC were pre-incubated with a physiologic dose of insulin (100 mu U/mL), NHE activity increased significantly in both groups but the increase was greater in normotensives than in hypertensives (9.6 vs 8.5 mmol/L cell x h, respectively; P<0.05). Phosphatidylinositol-3 kinase (PI-3 kinase) inhibitors, wortmannin and LY294,002, had no effect on basal NHE activity but similarly and significantly inhibited insulin-stimulated NHE activity in both normal and hypertensive subjects. Insulin increased the K-m for extracellular Na+ in normotensive subjects but not in hypertensive patients. In addition, the dose response curve for insulin and NHE activity showed that the curve for hypertensive patients was shifted rightward in relation to the normotensive subjects. These data suggest that insulin stimulates RBC NHE activity in vitro and this activation is mediated via a pathway that includes activation of PI-3 kinase. Hypertensive patients have elevated basal NHE activity but a blunted response to insulin suggesting that RBC may be a model to study insulin resistance in essential hypertensive patients. C1 Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Med Serv, Boston, MA USA. RP Romero, JR (reprint author), Brigham & Womens Hosp, Div Endocrine Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM jromero@rics.bwh.harvard.edu FU NCRR NIH HHS [RR02635]; NHLBI NIH HHS [HL04069, HL57173]; NIDDK NIH HHS [DK54866, DK53538, DK02817] NR 23 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1064-1963 EI 1525-6006 J9 CLIN EXP HYPERTENS JI Clin. Exp. Hypertens. PD MAY PY 2002 VL 24 IS 4 BP 277 EP 287 DI 10.1081/CEH-120004231 PG 11 WC Pharmacology & Pharmacy; Peripheral Vascular Disease SC Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA 561GV UT WOS:000176132600004 PM 12069358 ER PT J AU Schilsky, RL Dressler, LM Bucci, D Monovich, L Jewell, S Suster, S Caligiuri, MA Kantoff, PW Compton, C AF Schilsky, RL Dressler, LM Bucci, D Monovich, L Jewell, S Suster, S Caligiuri, MA Kantoff, PW Compton, C TI Cooperative group tissue banks as research resources: The cancer and leukemia group B tissue repositories SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER; ADJUVANT CHEMOTHERAPY; THERAPY; ERBB-2 C1 Univ Chicago, Div Biol Sci, Chicago, IL 60637 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. McGill Univ, Dept Pathol, Montreal, PQ H2W 1S6, Canada. RP Schilsky, RL (reprint author), Cent Off Chairman, Canc & Leukemia Grp B, 208 S LaSalle St,Suite 2000, Chicago, IL 60604 USA. FU NCI NIH HHS [CA31946] NR 7 TC 13 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 943 EP 948 PG 6 WC Oncology SC Oncology GA 551EY UT WOS:000175547700002 PM 12006505 ER PT J AU Hahn, SM Bernhard, EJ Regine, W Mohiuddin, M Haller, DG Stevenson, JP Smith, D Pramanik, B Tepper, J DeLaney, TF Kiel, KD Morrison, B Deutsch, P Muschel, RJ McKenna, WG AF Hahn, SM Bernhard, EJ Regine, W Mohiuddin, M Haller, DG Stevenson, JP Smith, D Pramanik, B Tepper, J DeLaney, TF Kiel, KD Morrison, B Deutsch, P Muschel, RJ McKenna, WG TI A phase I trial of the farnesyltransferase inhibitor L-778,123 and radiotherapy for locally advanced lung and head and neck cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; HUMAN BREAST-CANCER; TUMOR-CELL LINES; H-RAS; RADIATION-RESISTANCE; NIH-3T3 CELLS; G2 DELAY; V-MYC; ONCOGENES; PROTEIN AB Purpose: Preclinical data have demonstrated that farnesyltransferase inhibitors (FTIs) are radiation sensitizers in selected cell lines. The objective of this Phase I trial was to determine the maximally tolerated dose of the FTI L-778,123 in combination with radiotherapy in non-small cell lung cancer (NSCLC) and head and neck cancer (HNC). Experimental Design: L-778,123 was given by continuous i.v. infusion and dose escalated in conjunction with standard radiotherapy. The presence of a ras mutation was not required for study entry. Results: Nine patients (six NSCLC patients and three HNC patients) were enrolled on two dose levels of FTI. No dose-limiting toxicities were observed at the first dose level of 280 mg/m(2)/day during weeks 1, 2, 4, and 5 of radiotherapy. One episode of dose-limiting toxicity, grade IV neutropenia, was observed in one of three patients treated at 560 mg/m(2)/day during weeks 1, 2, 4, 5, and 7. No episodes of dose-limiting mucositis, esophagitis, or pneumonitis were observed. Of the four patients with NSCLC with evaluable disease, three patients had a complete response to treatment and one patient had a partial response. A complete clinical response to treatment was observed in two patients with HNC. In vitro studies in tumor cells obtained from a NSCLC patient on this trial showed radiosensitization with FTI and that tumor cells accumulated in G(2)-M after L-778,123 treatment. Conclusions: The combination of L-778,123 and radiotherapy at dose level I is associated with acceptable toxicity. Local responses have been observed in four NSCLC patients without a clear increase in radiotherapy-associated toxicities. C1 Univ Penn, Sch Oncol, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Univ Penn, Sch Oncol, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Oncol, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Oncol, Div Hematol Oncol, Philadelphia, PA 19104 USA. Univ Kentucky, Dept Radiat Med, Lexington, KY 40536 USA. Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NW Mem Hosp, Dept Radiat Oncol, Chicago, IL 60611 USA. Merck Res Labs, Rahway, NJ 07065 USA. RP Hahn, SM (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 3400 Spruce St,2 Donner, Philadelphia, PA 19104 USA. NR 45 TC 70 Z9 74 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 1065 EP 1072 PG 8 WC Oncology SC Oncology GA 551EY UT WOS:000175547700017 PM 12006520 ER PT J AU Izikson, L Klein, RS Luster, AD Weiner, HL AF Izikson, L Klein, RS Luster, AD Weiner, HL TI Targeting monocyte recruitment in CNS autoimmune disease SO CLINICAL IMMUNOLOGY LA English DT Article DE EAE; MS; CCR2; MCP-1; monocyte; chemotaxis; treatment ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; CCR2B RECEPTOR ANTAGONISTS; CHEMOATTRACTANT PROTEIN-1; CHEMOKINE RECEPTOR; BETA-CHEMOKINES; DENDRITIC CELLS; CHEMOTACTIC PROTEIN-1; INTERFERON-BETA AB Monocytes and macrophages play a pathogenic role in a number of autoimmune inflammatory diseases. Recent studies in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, have identified a critical chemokine-mediated mechanism of monocyte homing to the central nervous system (CNS). Here, we summarize the current findings in EAE, develop a rationale for targeting the chemokine axis in order to treat CNS inflammatory disease, and review currently available molecule-specific therapeutics that inhibit monocyte trafficking to the CNS. (C) 2002 Elsevier Science (USA). C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Izikson, L (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. NR 59 TC 57 Z9 58 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAY PY 2002 VL 103 IS 2 BP 125 EP 131 DI 10.1006/clim.2001.5167 PG 7 WC Immunology SC Immunology GA 560KZ UT WOS:000176082400002 PM 12027417 ER PT J AU Haake, DA Dundoo, M Cader, R Kubak, BM Hartskeerl, RA Sejvar, JJ Ashford, DA AF Haake, DA Dundoo, M Cader, R Kubak, BM Hartskeerl, RA Sejvar, JJ Ashford, DA TI Leptospirosis, water sports, and chemoprophylaxis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CONTROLLED TRIAL; OUTBREAK; EPIDEMIC; SEROVARS AB Recreational activities, such as water sports and adventure travel, are emerging as an important risk factor for leptospirosis, a potentially fatal zoonosis. We report the clinical course of 2 patients who acquired leptospirosis through participation in water sports. Physicians caring for patients who participate in adventure travel involving water sports should be familiar with the risk factors for and diagnosis, prevention, and treatment of leptospirosis. C1 VA Greater LA Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. CDCP, Meningitis & Special Pathogens Branch, Div Bacterial & Mycot Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Royal Trop Inst, Koninklijk Inst Tropen Biomed Res, NL-1105 AZ Amsterdam, Netherlands. RP Haake, DA (reprint author), VA Greater LA Healthcare Syst, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. FU NIAID NIH HHS [AI-34431, R01 AI034431, R01 AI034431-06A2, R21 AI034431, R29 AI034431] NR 34 TC 48 Z9 50 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2002 VL 34 IS 9 BP E40 EP E43 DI 10.1086/339942 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539YR UT WOS:000174901600034 PM 11941571 ER PT J AU DaVanzo, WJ Ullian, ME AF DaVanzo, WJ Ullian, ME TI L-carnitine administration reverses acute mental status changes in a chronic hemodialysis patient with hepatitis C infection SO CLINICAL NEPHROLOGY LA English DT Article ID HYPERAMMONEMIC ENCEPHALOPATHY; MAINTENANCE HEMODIALYSIS; MUSCLE; SERUM; SUPPLEMENTATION; PERITONEAL; AMMONIA; ANEMIA AB Achronic hemodialysis patient presented with elevated serum ammonia concentration (189 mumol/l) and acutely altered mental status. He had been adequately dialyzed over the prior months and had no evidence of liver dysfunction, despite serological evidence for hepatitis C virus infection. His mental status deteriorated to coma despite vitamin replenishment, intensive hemodialysis, lactulose treatment, and blood pressure control over a 3-day period. Blood free L-carnitine concentration was depressed, and total carnitine concentrations was normal. Three hours after a single 2 g dose of L-carnitine was administered intravenously, the mental status reverted to normal. Hyperammonemia resolved over a 5-week period. We suspect that subclinical liver dysfunction and dialysis status in tandem contributed to the carnitine deficiency, hyperammonemia, and confusion and that the L-carnitine administration reversed these biochemical and clinical abnormalities. C1 Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. RP DaVanzo, WJ (reprint author), Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD MAY PY 2002 VL 57 IS 5 BP 402 EP 405 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 546HK UT WOS:000175268500014 PM 12036203 ER PT J AU Ring, D Psychoyios, VN Chin, KR Jupiter, JB AF Ring, D Psychoyios, VN Chin, KR Jupiter, JB TI Nonunion of nonoperatively treated fractures of the radial head SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID NECK AB Although fractures of the radial head traditionally are not associated with healing problems, delayed union and nonunion are being seen more frequently after operative and nonoperative treatment. Given the tenuous blood supply to the head of the radius, problems with healing are not surprising. As the current review of live patients with nonunion of nonoperatively treated radial head fractures treated during a 6-year period shows, healing problems rarely are symptomatic and often may go unrecognized. Even when the fracture still is apparent on radiographs obtained more than 1 year after the injury, healing still may occur. Operative treatment, although rarely necessary, achieved union in one of the current patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Orthopaed Residency Program, Boston, MA USA. RP Ring, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, ACC 52515 Parkman St, Boston, MA 02114 USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2002 IS 398 BP 235 EP 238 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 549FJ UT WOS:000175433600033 PM 11964655 ER PT J AU Mankin, HJ AF Mankin, HJ TI A computerized system for orthopaedic oncology SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB For the past 15 years, the orthopaedic oncology service at the author's institution has used a computer system to aid in the treatment of patients. The system currently uses a DOS or at times a Windows-based program known as FOXPRO which originally was created by an independent company and now is part of the Microsoft systems. This presentation describes the components of this system and defines its use in patient treatment including demographics, office and surgical records, fiscal issues, and research. C1 Massachusetts Gen Hosp, Orthopaed Serv Gray 604, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv Gray 604, Boston, MA 02114 USA. NR 0 TC 21 Z9 21 U1 0 U2 1 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 MAY PY 2002 IS 398 BP 252 EP 261 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 549FJ UT WOS:000175433600036 PM 11964658 ER PT J AU Safren, SA AF Safren, SA TI Treatment of chronic depression: Cognitive behavioral analysis system of psychotherapy SO CLINICAL PSYCHOLOGY REVIEW LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD MAY PY 2002 VL 22 IS 4 BP 629 EP 630 AR PII S0272-7358(01)00094-0 DI 10.1016/S0272-7358(01)00094-0 PG 2 WC Psychology, Clinical SC Psychology GA 563TJ UT WOS:000176271400006 ER PT J AU Rubenstein, LZ Josephson, KR AF Rubenstein, LZ Josephson, KR TI The epidemiology of falls and syncope SO CLINICS IN GERIATRIC MEDICINE LA English DT Review ID NURSING-HOME RESIDENTS; TERM-CARE FACILITY; DWELLING OLDER ADULTS; RISK-FACTORS; RECURRENT FALLS; INJURIOUS FALLS; ELDERLY PATIENTS; POSTURAL HYPOTENSION; PSYCHOTROPIC-DRUGS; HOSPITAL DISCHARGE AB Falls and syncope are two common and interrelated geriatric syndromes that cause considerable mortality and morbidity among older persons. Multiple causes and predisposing risk factors have been identified for both falls and syncope, which makes diagnosis, treatment, and particularly prevention of these two syndromes difficult clinical challenges. The most promising prevention strategies for both falls and syncope involve identifying individuals at increased risk and implementing appropriate interventions. This article provides an overview of the epidemiology of falls and syncope in both community living and institutionalized older adults and reviews the most common causes and risk factors. C1 GRECC, Sepulveda Ambulatory Care Ctr & Nursing Home, Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Rubenstein, LZ (reprint author), GRECC, Sepulveda Ambulatory Care Ctr & Nursing Home, Vet Affairs Greater Los Angeles Healthcare Syst, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 102 TC 379 Z9 398 U1 6 U2 47 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2002 VL 18 IS 2 BP 141 EP + AR PII S0749-0690(02)00002-2 DI 10.1016/S0749-0690(02)00002-2 PG 19 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 566WJ UT WOS:000176451000002 PM 12180240 ER PT J AU West, WC Holcomb, PJ AF West, WC Holcomb, PJ TI Event-related potentials during discourse-level semantic integration of complex pictures SO COGNITIVE BRAIN RESEARCH LA English DT Article DE N300; N400; event-related potentials; discourse; picture; semantic representation ID MEDIAL TEMPORAL-LOBE; DEPTH-RECORDED POTENTIALS; BRAIN-DAMAGED PATIENTS; DUAL-CODING THEORY; LANGUAGE COMPREHENSION; SPATIOTEMPORAL STAGES; MULTIPLE SEMANTICS; FIELD POTENTIALS; RIGHT-HEMISPHERE; NEURAL SYSTEMS AB This study examined event-related potentials (ERPs) elicited in response to semantic processing of non-verbal stories. ERPS were recorded from 29 scalp electrodes on 16 participants while they viewed series of complex gray-scale pictures, each of which relayed a simple story. The final picture of each story was either congruous or incongruous with the preceding context. Participants made delayed meaningfulness judgments for each story. Averaged ERPs time-locked to the onset of the final picture were more negative for incongruous than congruous pictures, Two distinct components were sensitive to congruency. The first component peaked at similar to325 ms (N300) and was distributed over central and frontal sites. The second component peaked at similar to500 ms and also had a centro-frontal maximum but was more widespread than the earlier component (anterior N400). The distinct scalp topographies of these two negativities provide strong evidence that the N300 and N400 are separate and distinguishable components, Furthermore, the presence of the N300 in this exclusively pictorial task, suggests that the N300 is specific to the semantic processing of non-verbal stimuli and is not due to linguistic mediation. This study also revealed that the N400 can be modulated by discourse-level coherence manipulations with pictures. Finally, the different patterns of ERP effects observed during the semantic processing of verbal and non-verbal information suggest that non-identical neuronal sources, and thus non-identical representational systems, are accessed by these different types of materials. These findings strongly support at least partial modularity of semantic representations and processing mechanisms in the human brain. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuropsychol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,NMR Ctr, Charlestown, MA 02129 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP West, WC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuropsychol Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 46 TC 130 Z9 134 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD MAY PY 2002 VL 13 IS 3 BP 363 EP 375 AR PII S0926-6410(01)00129-X DI 10.1016/S0926-6410(01)00129-X PG 13 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 547AX UT WOS:000175310900007 ER PT J AU Koszdin, KL Digiacomo, RF AF Koszdin, KL Digiacomo, RF TI Outbreak: Detection and investigation SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID MOUSE HEPATITIS-VIRUS; BEDDING SENTINEL SYSTEM; CHAIN-REACTION ANALYSIS; SENDAI VIRUS; NUDE-MICE; HELICOBACTER-HEPATICUS; RESPIRATORY BACILLUS; INFECTION; RATS; TRANSMISSION AB With the increased movement of rodents between institutions of various pathogen status, the risk of introducing unwanted agents into a facility is high. This situation is in direct conflict with the increasing demand for "clean" rodents for use in biomedical research. If an institution is to have any hope of attaining specific-pathogen-free status, a rational surveillance program should be in place, along with a plan of action to be undertaken when an unwanted agent is detected in the facility. This review summarizes the factors that should be considered when designing a rodent health-surveillance program and outlines a general approach to be taken when rodents in a facility become infected with an undesirable agent. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA. RP Koszdin, KL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way 1511, Seattle, WA 98108 USA. NR 60 TC 7 Z9 7 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAY PY 2002 VL 41 IS 3 BP 18 EP 27 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 555KM UT WOS:000175793300004 PM 12051656 ER PT J AU Whalen, MJ AF Whalen, MJ TI Predicting significant vasospasm in patients with subarachnoid hemorrhage: A role for bedside microdialysis? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE microdialysis; subarachnoid hemorrhage; human; glutamate; lactate; brain; prospective ID DOSE TIRILAZAD MESYLATE; INTRACEREBRAL MICRODIALYSIS; CEREBRAL MICRODIALYSIS; ANEURYSM SURGERY; DOUBLE-BLIND; BRAIN; ISCHEMIA; METABOLISM; GLUTAMATE; HUMANS C1 Massachusetts Gen Hosp, Div Pediat Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Whalen, MJ (reprint author), Massachusetts Gen Hosp, Div Pediat Crit Care Med, Boston, MA 02114 USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2002 VL 30 IS 5 BP 1171 EP 1173 DI 10.1097/00003246-200205000-00043 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 552CD UT WOS:000175600000042 PM 12006828 ER PT J AU Benjamin, RJ Anderson, KC AF Benjamin, RJ Anderson, KC TI What is the proper threshold for platelet transfusion in patients with chemotherapy-induced thrombocytopenia? SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE platelets; thrombocytopenia; prophylactic transfusion; hemorrhage; chemotherapy; leukemia; stem cell transplantation ID ACUTE MYELOID-LEUKEMIA; CONSENSUS CONFERENCE; DOSE-RESPONSE; THERAPY; POLICY; TRANSPLANTATION; CONTROVERSIES; 20,000/MU-L; MANAGEMENT; MEDICINE AB Platelet transfusion therapy is an integral part of modern oncological practice and is used to treat hemorrhage associated with thrombocytopenia. More commonly, platelets are transfused to prevent hemorrhage in thrombocytopenic patients. Conventional wisdom has suggested a threshold for prophylactic transfusion of < 20 x 10(9)/l. Many studies now support the safety of more conservative transfusion regimes that reduce patient exposure to donors and conserve precious resources, without an increase in risk of hemorrhage. This review presents the data to support the use of a prophylactic transfusion threshold of < 10 x 10(9)/l in patients without risk factors for hemorrhage and who have ready access to emergent medical care. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Boston, MA USA. RP Benjamin, RJ (reprint author), Brigham & Womens Hosp, Adult Transfus Serv, Blood Bank, 75 Francis St, Boston, MA 02115 USA. NR 49 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 2002 VL 42 IS 2 BP 163 EP 171 AR PII S1040-8428(01)00182-2 DI 10.1016/S1040-8428(01)00182-2 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 560LM UT WOS:000176083600005 PM 12007974 ER PT J AU Allan, JS Madsen, JC AF Allan, JS Madsen, JC TI Recent advances in the immunology of chronic rejection SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID COLD ISCHEMIA/REPERFUSION INJURY; CARDIAC ALLOGRAFT VASCULOPATHY; DONOR-SPECIFIC TOLERANCE; T-CELL APOPTOSIS; LUNG-TRANSPLANTATION; INDIRECT RECOGNITION; IN-VIVO; GRAFT ARTERIOSCLEROSIS; MIXED CHIMERISM; OBLITERATIVE BRONCHIOLITIS AB Chronic allograft rejection is a slowly progressive, insidious process in which the host immune system continues to mount an immunological attack on a transplanted organ, ultimately resulting in the failure of the graft. To varying degrees, all solid organ grafts are at risk for chronic rejection and undergo a stereotypic process of injury and inflammation, eventually leading to parenchymal fibrosis. The clinical consequences of chronic rejection are particularly apparent in thoracic transplantation, where both patient and graft survival decline steadily over time and the opportunities for re-transplantation or long-term extracorporeal support are limited. A variety of antigen -dependent and antigen -independent factors are known to modulate the propensity for an organ to undergo chronic rejection. Recent clinical and laboratory research has suggested that distinct immunologic mechanisms may underlie the process of chronic rejection. Ultimately, strategies to induce long-term tolerance to alloantigens will be necessary to prevent chronic rejection and to abrogate the deleterious sequelae of chronic immunosuppression. C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, EDR 105, 55 Fruit St, Boston, MA 02114 USA. NR 66 TC 13 Z9 15 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAY PY 2002 VL 11 IS 3 BP 315 EP 321 DI 10.1097/00041552-200205000-00008 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 544ZR UT WOS:000175192200008 PM 11981262 ER PT J AU Leclerc, X Huisman, TAGM Sorensen, AG AF Leclerc, X Huisman, TAGM Sorensen, AG TI The potential of proton magnetic resonance spectroscopy (H-1-MRS) in the diagnosis and management of patients with brain tumors SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID RECURRENT MALIGNANT GLIOMAS; GAMMA-KNIFE RADIOSURGERY; INTRACRANIAL MASS LESIONS; MR-SPECTROSCOPY; IN-VIVO; STEREOTACTIC BIOPSY; CHOLINE SIGNAL; DIFFERENTIATION; ACCURACY; CONTRAST AB Proton (H-1) magnetic resonance spectroscopy (MRS) is a noninvasive method that can monitor the metabolic changes in most brain diseases. This technique is now available on current 1.5 Tesla magnetic resonance units and does not require sophisticated software or time-consuming post-processing techniques. Previous studies using single-voxel techniques showed the usefulness of MRS for the diagnosis of brain tumor despite some technical issues, including spatial resolution and volume coverage. Recent advances have been made through the use of multivoxel techniques and metabolite maps, which allow assessment of both the entire volume of the lesion and the surrounding normal-appearing brain tissue. Recent studies suggest the potential of this technique to guide biopsies, to define radiotherapy targets, and to monitor patients after treatment. Some persistent drawbacks, including measurement time and spectral resolution, will probably be overcome in the near future. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. NR 55 TC 41 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2002 VL 14 IS 3 BP 292 EP 298 DI 10.1097/00001622-200205000-00007 PG 7 WC Oncology SC Oncology GA 550EK UT WOS:000175490500007 PM 11981274 ER PT J AU Wen, PY Marks, PW AF Wen, PY Marks, PW TI Medical management of patients with brain tumors SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; PNEUMOCYSTIS-CARINII PNEUMONIA; CORTICOTROPIN-RELEASING FACTOR; POSTOPERATIVE VENOUS THROMBOEMBOLISM; PEPTIC-ULCER DISEASE; HIGH-GRADE GLIOMAS; PULMONARY-EMBOLISM; UNFRACTIONATED HEPARIN; CANCER-PATIENTS AB The most common medical problems in brain tumor patients involve the management of seizures, peritumoral edema, medication side effects, and venous thromboembolism. Despite the importance of these issues, there are very few studies specifically addressing them. Nonetheless, there has been some progress in recent years. There is increasing evidence that brain tumor patients who have not had a seizure do not benefit from prophylactic antiepileptic medications. Patients taking corticosteroids are at greater risk of Pneumocystis carinii pneumonia and may benefit from prophylactic therapy. There is also growing evidence suggesting that anticoagulation may be more effective than inferior vena cava filtration devices for treating venous thromboembolism in brain tumor patients and that the risk of hemorrhage with anticoagulation is relatively small. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neuro Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Div Neuro Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neuro Oncol, SW430D,44 Binney St, Boston, MA 02115 USA. NR 126 TC 56 Z9 57 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAY PY 2002 VL 14 IS 3 BP 299 EP 307 DI 10.1097/00001622-200205000-00008 PG 9 WC Oncology SC Oncology GA 550EK UT WOS:000175490500008 PM 11981275 ER PT J AU Saunders, JB Brady, KT AF Saunders, JB Brady, KT TI The scientific basis for the prevention and treatment of substance misuse SO CURRENT OPINION IN PSYCHIATRY LA English DT Editorial Material ID COCAINE-DEPENDENCE; CANNABIS USE; DOUBLE-BLIND; DRUG-USE; NALTREXONE; ALCOHOLISM; DISORDER; TRIAL C1 Royal Brisbane Hosp, Mental Hlth Ctr, Alcohol & Drug Serv, Herston, Qld 4029, Australia. Royal Brisbane Hosp, Mental Hlth Ctr, Prince Charles Hosp Dist, Queensland Hlth, Herston, Qld 4029, Australia. Univ Queensland, Alcohol & Drug Studies, Herston, Qld, Australia. CTN, MUSC, Ralph H Johnson VAMC, Dept Psychiat, Charleston, SC USA. RP Saunders, JB (reprint author), Royal Brisbane Hosp, Mental Hlth Ctr, Alcohol & Drug Serv, Herston, Qld 4029, Australia. NR 16 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2002 VL 15 IS 3 BP 231 EP 234 DI 10.1097/00001504-200205000-00001 PG 4 WC Psychiatry SC Psychiatry GA 595RQ UT WOS:000178122900001 ER PT J AU Curley, SA Cusack, JC Tanabe, KK Ellis, LM AF Curley, SA Cusack, JC Tanabe, KK Ellis, LM TI Advances in the treatment of liver tumors SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID PORTAL-VEIN EMBOLIZATION; HERPES-SIMPLEX VIRUS; ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; HUMAN COLON-CANCER; RADIOFREQUENCY THERMAL ABLATION; POSITRON-EMISSION-TOMOGRAPHY; LASER-INDUCED THERMOTHERAPY; TOTAL VASCULAR EXCLUSION; HILAR BILE-DUCT C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Curley, SA (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 269 TC 2 Z9 2 U1 2 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD MAY PY 2002 VL 39 IS 5 BP 461 EP 571 PG 111 WC Surgery SC Surgery GA 557VK UT WOS:000175928900002 ER PT J AU Stalkup, JR Bell, K Rosen, T AF Stalkup, JR Bell, K Rosen, T TI Disseminated cutaneous sporotrichostis treated with itraconazole SO CUTIS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SPOROTHRIX-SCHENCKII FUNGEMIA; ACQUIRED IMMUNODEFICIENCY; AIDS PATIENT; LYMPHOCUTANEOUS SPOROTRICHOSIS; MAINTENANCE THERAPY; INFECTION AB A 72-year-old Hispanic man with diabetes presented with a 4-week history of a tender non-healing ulcer on the fifth digit of the left hand and a 3-day history of fever, chills, malaise. anorexia, and tender fluctuant nodules on the abdomen and left elbow. The patient, an avid gardener, was using prednisone and methotrexate for a debilitating seronegative polyarthropathy. A diagnosis of disseminated cutaneous sporotrichosis was made based on epidemiologic risk factors, clinical appearance, histopathologic examination, and a positive fungal culture. Use of prednisone was discontinued, the dosage of methotrexate was decreased, and use of oral itraconazole 400 mg/day was instituted. The patient's lesions cleared within 5 months, and no recurrence was noted during a 3-month follow-up. This case illustrates the typical association of the rare entity of disseminated cutaneous sporotrichosis with immunosuppression, an unusual lack of internal involvement, and a gratifying response to itraconazole. C1 Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Dermatol Serv, Houston, TX USA. RP Rosen, T (reprint author), 2815 Plumb, Houston, TX 77005 USA. NR 42 TC 4 Z9 4 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI CHATHAM PA 26 MAIN ST, STE A, CHATHAM, NJ 07928-2402 USA SN 0011-4162 J9 CUTIS JI Cutis PD MAY PY 2002 VL 69 IS 5 BP 371 EP 374 PG 4 WC Dermatology SC Dermatology GA 553TC UT WOS:000175690700009 PM 12041817 ER PT J AU Rubin, JB Choi, YJ Segal, RA AF Rubin, JB Choi, YJ Segal, RA TI Cerebellar proteoglycans regulate sonic hedgehog responses during development SO DEVELOPMENT LA English DT Article DE sonic hedgehog; proteoglycans; Ext; cerebellum; granule cells; mouse ID HEPARAN-SULFATE PROTEOGLYCANS; DEVELOPING MOUSE CEREBELLUM; TUMOR-SUPPRESSOR GENE; PROTEIN-KINASE-A; TOUT-VELU; POSTNATAL-DEVELOPMENT; PATCHED HOMOLOG; DEVELOPING LIMB; GRANULAR LAYER; GROWTH-FACTOR AB Sonic hedgehog promotes proliferation of developing cerebellar granule cells. As sonic hedgehog is expressed in the cerebellum throughout life it is not clear why proliferation occurs only in the early postnatal period and only in the external granule cell layer. We asked whether heparan sulfate proteoglycans might regulate sonic hedgehog-induced proliferation and thereby contribute to the specialized proliferative environment of the external granule cell layer. We identified a conserved sequence within sonic hedgehog that is essential for binding to heparan sulfate proteoglycans, but not for binding to the receptor patched. Sonic hedgehog interactions with heparan sulfate proteoglycans promote maximal proliferation of postnatal day 6 granule cells. By contrast, proliferation of less mature granule cells is not affected by sonic hedgehog-proteoglycan interactions. The importance of proteoglycans for proliferation increases during development in parallel with increasing expression of the glycosyltransferase genes, exostosin 1 and exostosin 2. These data suggest that heparan sulfate proteoglycans, synthesized by exostosins, may be critical determinants of granule cell proliferation. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. FU NICHD NIH HHS [HD 01393]; NINDS NIH HHS [NS37757] NR 53 TC 107 Z9 109 U1 0 U2 1 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 MAY PY 2002 VL 129 IS 9 BP 2223 EP 2232 AR UNSP DEV4583 PG 10 WC Developmental Biology SC Developmental Biology GA 553UT UT WOS:000175694400015 PM 11959830 ER PT J AU Ruan, H Hacohen, N Golub, TR Van Parijs, L Lodish, HF AF Ruan, H Hacohen, N Golub, TR Van Parijs, L Lodish, HF TI Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes - Nuclear factor-kappa B activation by TNF-alpha is obligatory SO DIABETES LA English DT Article ID INDUCED INSULIN-RESISTANCE; DEPENDENT DIABETES-MELLITUS; TYROSINE KINASE-ACTIVITY; RECEPTOR SUBSTRATE-1; SIGNAL-TRANSDUCTION; INDUCED INHIBITION; ADIPOSE-TISSUE; WEIGHT-LOSS; OBESITY; PHOSPHORYLATION AB Tumor necrosis factor-alpha (TNF-alpha) is a contributing cause of the insulin resistance seen in obesity and obesity-linked type 2 diabetes, but the mechanism(s) by which TNF-alpha induces Insulin resistance is not understood. By using 3T3-L1 adipocytes and oligonucleotide microarrays, we identified 142 known genes reproducibly upregulated by at least threefold after 4 h and/or 24 It of TNF-alpha treatment, and 78 known genes down-regulated by at least twofold after 24 h of TNF-alpha incubation. TNF-alpha-induced genes include transcription factors implicated in preadipocyte gene expression or NF-kappaB activation, cytokines and cytokine-induced proteins, growth factors, enzymes, and signaling molecules. Importantly, a number of adipocyte-abundant genes, including GLUT4, hormone sensitive lipase, long-chain fatty acyl-CoA synthase, adipocyte complement-related protein of 30 kDa, and transcription factors CCAAT/ enhancer binding protein-alpha, receptor retinoid X receptor-alpha, and peroxisome profilerator-activated receptor gamma were significantly downregulated by TNF-alpha treatment. Correspondingly, 24-h exposure of 3T3-L1 adipocytes to TNF-alpha resulted in reduced protein levels of GLUT4 and several insulin signaling proteins, including the insulin receptor, insulin receptor substrate 1 (IRS-1), and protein kinase B (AKT). Nuclear factor-kappaB (NF-kappaB) was activated within 15 min of TNF-alpha addition. 3T3-L1 adipocytes expressing IkappaBalpha-DN, a nondegradable NF-kappaB inhibitor, exhibited normal morphology, global gene expression, and insulin responses. However, absence of NF-kappaB activation abolished suppression of >98% of the genes normally suppressed by TNF-alpha and induction of 60-70% of the genes normally induced by TNF-alpha. Moreover, extensive cell death occurred in IkappaBalpha-DN-expressing adipocytes after 2 h of TNF-alpha treatment. Thus the changes in adipocyte gene expression induced by TNF-alpha could lead to insulin resistance. Farther, NF-kappaB is an obligatory mediator of most of these TNF-alpha responses. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Lodish, HF (reprint author), MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr,Room 601, Cambridge, MA 02142 USA. FU NIDDK NIH HHS [R37-DK-47618] NR 53 TC 301 Z9 334 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2002 VL 51 IS 5 BP 1319 EP 1336 DI 10.2337/diabetes.51.5.1319 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 550FF UT WOS:000175492400003 PM 11978627 ER PT J AU Engert, JC Vohl, MC Williams, SM Lepage, P Loredo-Osti, JC Faith, J Dore, C Renaud, Y Burtt, NP Villeneuve, A Hirschhorn, JN Altshuler, D Groop, LC Despres, JP Gaudet, D Hudson, TJ AF Engert, JC Vohl, MC Williams, SM Lepage, P Loredo-Osti, JC Faith, J Dore, C Renaud, Y Burtt, NP Villeneuve, A Hirschhorn, JN Altshuler, D Groop, LC Despres, JP Gaudet, D Hudson, TJ TI 5 ' flanking variants of resistin are associated with obesity SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; UNITED-STATES; PPAR-GAMMA; GENE; EXPRESSION; CYSTEINE; RECEPTOR; DIFFERENTIATION; POLYMORPHISM; MOLECULES AB Diabetes and obesity have long been known to be related. The recently characterized adipocyte hormone resistin (also called FIZZ3/ADSF) has been implicated as a molecular link between impaired glucose tolerance (IGT) and obesity in mice. A search for sequence variants at the human resistin locus identified nine single-nucleotide polymorphisms (SNPs) but no coding variants. An investigation into the association of these SNPs with diabetes and obesity revealed two 5' flanking variants (g.-537 and g.-420), in strong linkage disequilibrium, that are associated with BMI. In nondiabetic individuals from the Quebec City area and the Saguenay-Lac-St-Jean region of Quebec, the g.-537 mutation (allelic frequency = 0.04) was significantly associated with an increase in BMI (P = 0.03 and P = 0.01, respectively). When the data from these two populations were combined and adjusted for age and sex, both the g.-537 (odds ratio [OR] 2.72, 95% Cl 1.28-5.81) and the g.-420 variants (1.58, 1.06-2.35) were associated with an increased risk for a BMI greater than or equal to30 kg/m(2). In contrast, in case/control and family-based study populations from Scandinavia, we saw no effect on BMI with either of these promoter variants. No association was seen with diabetes in any of the population samples. C1 MUHC, MGHRI, Montreal Genome Ctr, Montreal, PQ H3G 1A4, Canada. CHU Laval, Lipid Res Ctr, Quebec City, PQ G1V 4G2, Canada. Univ Laval, Dept Food Sci & Nutr, Quebec City, PQ, Canada. Meharry Med Coll, Dept Microbiol, Nashville, TN 37208 USA. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Lund Univ, Malmo Univ Hosp, Wallenberg Lab, Dept Endocrinol, Malmo, Sweden. Laval Hosp Res Ctr, Quebec Heart Inst, St Foy, PQ, Canada. Univ Montreal, CHUM, Dyslipidemia Diabet & Atherosclerosis Grp, Chicoutimi, PQ, Canada. Univ Montreal, CHUM, Community Genom Res Ctr, Chicoutimi, PQ, Canada. Complexe Hosp Sagamie, Chicoutimi, PQ, Canada. RP Engert, JC (reprint author), MUHC, MGHRI, Montreal Genome Ctr, Montreal, PQ H3G 1A4, Canada. RI Altshuler, David/A-4476-2009; Williams, Scott/B-9491-2012; OI Altshuler, David/0000-0002-7250-4107; Hudson, Thomas/0000-0002-1376-4849 NR 25 TC 113 Z9 125 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2002 VL 51 IS 5 BP 1629 EP 1634 DI 10.2337/diabetes.51.5.1629 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 550FF UT WOS:000175492400042 PM 11978666 ER PT J AU Zheng, F He, CJ Cai, WJ Hattori, M Steffes, M Vlassara, H AF Zheng, F He, CJ Cai, WJ Hattori, M Steffes, M Vlassara, H TI Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE diabetic complication; advanced glycation; food; kidney; animal models ID GLYCATION END-PRODUCTS; MAILLARD REACTION; ADVANCED GLYCOSYLATION; EXTRACELLULAR-MATRIX; CALORIC RESTRICTION; OXIDANT STRESS; DAMAGE; RATS; AMINOGUANIDINE; GLYCOTOXINS AB Background Reactive advanced glycation end products (AGEs), known to promote diabetic tissue damage, occur endogenously as well as in heated foods and are orally absorbed. The relative contribution of diet-derived AGEs to diabetic nephropathy (DN) remains unclear. Methods We tested a standard mouse food (AIN-93G) found to be rich in AGEs (H-AGE diet) in parallel with a similar diet that contained six-fold lower AGE content (L-AGE), but equal calories, macronutrients, and micronutrients. Non-obese diabetic mice (NOD) with type 1 diabetes (T1D) and db/db mice with type 2 diabetes (T2D) were randomly assigned to each formula for either 4 or 11 months, during which time renal parameters and AGE levels were assessed. Results Compared to the progressive DN and short survival seen in NOD mice exposed to long-term H-AGE feeding, L-AGE-fed NOD mice developed minimal glomerular pathology and a modest increase in urinary albumin creatinine ratio (p<0.005), and a significantly extended survival (p<0.0001), consistent with lower serum (p<0.025) and kidney AGES (p<0.01). Also, in the 4-month study, and in contrast to the H-AGE-fed mice, L-AGE-fed NOD and db/db mice exhibited low levels of renal cortex TGFbeta-1 (p<0.05), laminin B1 mRNA (p<0.01) and alpha1 IV collagen mRNA (p<0.05) and protein, in concert with reduced serum and kidney AGEs (p<0.05, respectively). Conclusion Intake of high-level, food-derived AGES is a major contributor to DN in T1D and T2D mice. Avoidance of dietary AGES provides sustained protection against DN in mice; providing the rationale for similar studies in human diabetic patients. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Mt Sinai Sch Med, Div Expt Diabet & Aging, New York, NY 10029 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Vlassara, H (reprint author), Mt Sinai Sch Med, Div Expt Diabet & Aging, Box 1640,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIDDK NIH HHS [DK54788] NR 56 TC 126 Z9 136 U1 4 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2002 VL 18 IS 3 BP 224 EP 237 DI 10.1002/dmrr.283 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 573NY UT WOS:000176838800008 PM 12112941 ER PT J AU Hamer, I Foti, M Emkey, R Cordier-Bussat, M Philippe, J De Meyts, P Maeder, C Kahn, CR Carpentier, JL AF Hamer, I Foti, M Emkey, R Cordier-Bussat, M Philippe, J De Meyts, P Maeder, C Kahn, CR Carpentier, JL TI An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events SO DIABETOLOGIA LA English DT Article DE insulin receptor; endocytosis; insulin signalling ID CLATHRIN-MEDIATED ENDOCYTOSIS; GROWTH-FACTOR RECEPTOR; CELL-SURFACE; DOWN-REGULATION; PHOSPHOTYROSINE PROTEIN; IMPAIRS TRANSPORT; SUBSTRATE FAMILY; ALPHA-SUBUNIT; BETA-SUBUNIT; PHOSPHORYLATION AB Aims/hypothesis. We examined the properties of a mutant insulin receptor (IR) with an Arg(252) to CyS (IRR252C) substitution in the alpha-subunit originally identified in a patient with extreme insulin resistance and acanthosis nigricans. Methods. We studied IR cell biology and signalling pathways in Chinese Hamster Ovary cells overexpressing this IRR252C. Results. Our investigation showed an impairment in insulin binding to IRR252C related mostly to a reduced affinity of the receptor for insulin and to a reduced rate of IRR252C maturation; an inhibition of IRR252C-mediated endocytosis resulting, in a decreased insulin degradation and insulin-induced receptor down-regulation; a maintenance of IRR252C on microvilli even in the presence of insulin; a similar autophosphorylation of mutant IRR252C followed by IRS 1/IRS 2 phosphorylation, p85 association with IRS 1 and IRS 2 and Akt phosphorylation similar to those observed in cells expressing wild type IR (IRwt); and finally, a reduced insulin-induced She phosphorylation accompanied by decreased ERK1/2 phosphorylation and activity and of thymidine incorporation into DNA in cells expressing IRR252C as compared to cells expressing IRwt. Conclusion/interpretation. These observations suggest that: parameters other than tyrosine kinase activation participate in or control the first steps of IR internalisation or both; IR-mediated IRS 1/2 phosphorylation can be achieved from the cell surface and microvilli in particular; She phosphorylation and its subsequent signalling pathway might require IR internalisation; defective IR endocytosis correlates with an enhancement of some biological responses to insulin and attenuation of others. C1 Univ Geneva, Dept Morphol, Geneva, Switzerland. CMU, Dept Morphol, Geneva, Switzerland. Harvard Univ, Sch Med, Joslin Diabet Res Ctr, Boston, MA USA. Hop Cantonal Univ Geneva, Unit Clin Diabetol, Geneva, Switzerland. Hagedorn Res Inst, Gentofte, Denmark. RP Carpentier, JL (reprint author), Univ Geneva, Dept Morphol, Geneva, Switzerland. NR 45 TC 27 Z9 32 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2002 VL 45 IS 5 BP 657 EP 667 DI 10.1007/s00125-002-0798-5 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 564ED UT WOS:000176301300006 PM 12107746 ER PT J AU Pascual, M Tolkoff-Rubin, N Cosimi, AB AF Pascual, M Tolkoff-Rubin, N Cosimi, AB TI How to improve long-term survival after renal transplantation: State of the art in 2002 SO DIALYSIS & TRANSPLANTATION LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Dept Surg, Boston, MA 02114 USA. RP Pascual, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CREATIVE AGE PUBL PI VAN NUYS PA 7628 DENSMORE AVE, VAN NUYS, CA 91406-2088 USA SN 0090-2934 J9 DIALYSIS TRANSPLANT JI Dial. Transplant. PD MAY PY 2002 VL 31 IS 5 BP 318 EP + PG 3 WC Engineering, Biomedical; Transplantation; Urology & Nephrology SC Engineering; Transplantation; Urology & Nephrology GA 546DM UT WOS:000175256700010 ER PT J AU Tanaka, S Meiselman, HHJ Engel, E Guth, PH Furukawa, O Wenby, RB Lee, J Kaunitz, JD AF Tanaka, S Meiselman, HHJ Engel, E Guth, PH Furukawa, O Wenby, RB Lee, J Kaunitz, JD TI Regional differences of H+, HCO3-, and CO2 diffusion through native porcine gastroduodenal mucus SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE ion permeability; mucosal barrier; gastroprotection; bicarbonate ID HYDROGEN-ION DIFFUSION; GASTRIC MUCUS; MUCOSAL PROTECTION; ACID DIFFUSION; RAT; PH; BICARBONATE; SECRETION; RETARDATION; INVIVO AB Gastroduodenal mucus may play a critical role in defending the epithelium from luminal acid and in the creation of a microenvironment suitable for H. pylori. We measured transmucus permeation of H+, HCO3-, and CO2 with an in vitro perfusion chamber through freshly harvested or partially purified porcine gastric mucin. pH and CO2 concentrations were measured with selective ion electrodes; HCO3- and CO2 concentrations were derived. Viscosity was measured by rotational microviscometry. Mucin viscosity was directly related to concentration. There was a large variation in viscosity among native mucus from antrum, corpus, and duodenum. The highest viscosity was found in the antral mucus; duodenal mucus had the lowest. Diffusion coefficients of duodenal mucus for H+ and HCO3- were significantly lower than those from corpus and antrum. CO2 diffusion coefficients were invariant. In conclusion, despite large variations in viscosity, antral and corpus gastric mucus were similar in terms of ion diffusion. Surprisingly, the low viscosity duodenal mucus was a more potent barrier to ion diffusion than was gastric mucus. Consequently, duodenal mucus may play a more important role in inhibiting ion diffusion than its gastric counterpart. C1 Greater Los Angeles Vet Affairs Healthcare Syst L, Med Serv, Los Angeles, CA 90073 USA. Univ So Calif, Dept Phys & Biophys, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. Univ Calif Los Angeles, Coll Letters & Sci, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [R01-DK54221] NR 28 TC 11 Z9 12 U1 2 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2002 VL 47 IS 5 BP 967 EP 973 AR UNSP 0163-2116/02/0500-0967/0 DI 10.1023/A:1015013401863 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 550KE UT WOS:000175501500004 PM 12018922 ER PT J AU Livingston, EH AF Livingston, EH TI Acid diffusion through rat duodenal mucosal cap SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE protons; acid diffusion; mucus cap; mucus; peptic ulcer; duodenum ID PH GRADIENT; GASTRIC MUCUS; PROSTAGLANDIN SYNTHESIS; BICARBONATE SECRETION; SURFACE; INVIVO; INHIBITION; ADHERENT; AGENTS; DAMAGE AB Acid induced duodenal injury occurs immediately following exposure to strong acid but does not worsen despite continuous perfusion with the acid. A thick gelatinous cap is found overlying the duodenum when examined histologically. The purpose of this study was to quantitate the resistance to acid diffusion by native duodenal mucus and the cap material. Rat duodenum was perfused with acid. The mucus from control and acid-perfused animals was harvested and the diffusion coefficient measured. Mucus from the duodenums of anesthetized rats was mixed with bromphenol blue and placed into capillary tubes. The tubes were submersed in 0.15 N HCI at 37degreesC. The color change from blue to yellow was measured with time as the HCI migrated through the tube. From the distance and time data, the diffusion coefficient could be calculated. Controls of bromphenol blue in water were studied. The diffusion coefficient for HCl in water was 30.1 +/- 0.9 x 10(-6) cm(2)/sec. nearly identical to the standard value reported in the literature. For the duodenal mucus adhereni to the epithelial surface, it was 1.1 +/- 0.1 x 10(-6) cm(2)/sec. Following perfusion with 0.15 N HCI, a 279.6 +/- 44-mum-thick mucus cap formed over the duodenum that had a diffusion coefficient of 1.8 +/- .3 x 10(-8) cm(2)/sec. In response to injury, the duodenum protects against continued damage by producing a mucoid cap that it highly resistant to acid diffusion. C1 Univ Calif Los Angeles, Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. Greater Los Angeles VA Hlth Care Syst, Surg Serv, Los Angeles, CA USA. Greater Los Angeles VA Hlth Care Syst, Res Serv, Los Angeles, CA USA. RP Livingston, EH (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Surg, 10833 Le Conte Ave 72-215 CHS, Los Angeles, CA 90095 USA. NR 26 TC 3 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2002 VL 47 IS 5 BP 974 EP 977 AR UNSP 0163-2116/02/0500-0974/0 DI 10.1023/A:1015065418702 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 550KE UT WOS:000175501500005 PM 12018923 ER PT J AU Moore, JE McMullen, CBT Mahon, G Adamis, AP AF Moore, JE McMullen, CBT Mahon, G Adamis, AP TI The corneal epithelial stem cell SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN OCULAR SURFACE; LONG-TERM; CYTOKINE EXPRESSION; LIMBAL; TRANSPLANTATION; ORIGIN AB The aim of this paper was to develop a GFP-expressing transgenic mouse model for the keratoepithelioplasty and to use this to follow the outcome of this form of graft, when placed on an inflamed corneal surface. Further alms were to characterize both the graft and the epithelial surface of the mouse and rat cornea using putative stem cell markers (P63 and Telomerase) and marker of cell differentiation (14-3-3 sigma). Keratepithelioplasty was carried out using a GFP transgenic mouse cornea as donor tissue. Fluorescent epithelial outgrowth from each keratepithelioplasty was scored and quantified. Donor corneal graft tissue was obtained from the paracentral region or the anatomical limbal region of murine corneas. Paracentral donor grafts (n = 20) consistently demonstrated a significant increase in proliferative potential compared to grafts obtained from the anatomical limbal region of the mouse cornea (n = 25) (P = 0.000, Mann-Whitney U). Correspondingly, P63 expression was maximal in the paracentral region of the mouse cornea, in keeping with the demonstrated increased proliferative potential of donor grafts harvested from this region of the cornea. The murine corneal epithelium demonstrated decreased rather than increased cellular layers at the limbal region, in contrast to that of the rat or human epithelium. In addition, as a general finding in all species tested, there was an apparent increase noted in P63 expression in basal corneal epithelial cells in regions that had increased cellular layers (limbus in humans and rats and the paracentral corneal region in the mouse). Epithelium, which had migrated from donor grafts onto recipient corneas, retained P63 expression for the period of time examined (up to 3 days postengraftment). In addition, the conjunctival surface of an injured conjunctivalized displayed an abnormal pattern of P63 expression. Telomerase expression was widespread throughout many layers of both the murine and rat corneal epithelium. In the mouse and rat corneal epithelium P63 expression was maximal in areas of increased proliferative potential. Its expression, however, was not confined to stem cells alone. Migrating cells from transplanted keratoepithelial grafts retained P63 expression at least in the early stages post-transplantation. Finally, damaged conjunctivalized corneas displayed an abnormal P63 expression pattern when compared to either normal conjunctiva or normal cornea. C1 Queens Univ Belfast, Dept Ophthalmol, Belfast BT7 1NN, Antrim, North Ireland. Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Moore, JE (reprint author), Care of Page AB, Royal Victoria Hosp, Dept Ophthalmol, Eyes & ENT Bldg,Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland. FU NEI NIH HHS [EY 11627, EY 12611] NR 27 TC 31 Z9 33 U1 0 U2 1 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 MAY-JUN PY 2002 VL 21 IS 5-6 BP 443 EP 451 DI 10.1089/10445490260099737 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 568QD UT WOS:000176553000011 PM 12167247 ER PT J AU Schlozman, SC AF Schlozman, SC TI Ecstasy: Intimacy abridgcd SO EDUCATIONAL LEADERSHIP LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD MAY PY 2002 VL 59 IS 8 BP 85 EP 87 PG 3 WC Education & Educational Research SC Education & Educational Research GA 553AK UT WOS:000175653100019 ER PT J AU Tan, KM Zelus, BD Meijers, R Liu, JH Bergelson, JM Duke, N Zhang, R Joachimiak, A Holmes, KV Wang, JH AF Tan, KM Zelus, BD Meijers, R Liu, JH Bergelson, JM Duke, N Zhang, R Joachimiak, A Holmes, KV Wang, JH TI Crystal structure of murine sCEACAM1a[1,4]: a coronavirus receptor in the CEA family SO EMBO JOURNAL LA English DT Article DE bacterial binding; CEA family; cell adhesion; coronavirus receptor; crystal structure ID MOUSE HEPATITIS-VIRUS; CARCINOEMBRYONIC ANTIGEN CEA; BILIARY GLYCOPROTEIN CD66A; N-TERMINAL DOMAIN; CELLULAR RECEPTOR; HUMAN CD4; MHV RECEPTOR; HOT-SPOT; ADHESION; BINDING AB CEACAM1 is a member of the carcinoembryonic antigen (CEA) family. Isoforms of murine CEACAM1 serve as receptors for mouse hepatitis virus (MHV), a murine coronavirus. Here we report the crystal structure of soluble murine sCEACAM1a[1,4], which is composed of two Ig-like domains and has MHV neutralizing activity. Its N-terminal domain has a uniquely folded CC' loop that encompasses key virus-binding residues. This is the first atomic structure of any member of the CEA family, and provides a prototypic architecture for functional exploration of CEA family members. We discuss the structural basis of virus receptor activities of murine CEACAM1 proteins, binding of Neisseria to human CEACAM1, and other homophilic and heterophilic interactions of CEA family members. C1 Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Cambridge, MA 02138 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Wang, JH (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Microbiol, 4200 E 9th Ave, Denver, CO 80262 USA. RI Meijers, Rob/D-5521-2011; OI Meijers, Rob/0000-0003-2872-6279 FU NHLBI NIH HHS [HL 54734, P01 HL048675, HL48675]; NIAID NIH HHS [AI 25231, AI 26075, R01 AI026075, R01 AI025231]; NIGMS NIH HHS [GM56008] NR 56 TC 71 Z9 74 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 2002 VL 21 IS 9 BP 2076 EP 2086 DI 10.1093/emboj/21.9.2076 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 548NG UT WOS:000175393700003 PM 11980704 ER PT J AU Mothershead, JL Tonat, K Koenig, KL AF Mothershead, JL Tonat, K Koenig, KL TI Bioterrorism preparedness III: state and federal programs and response SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article AB A bioterrorism attack may rapidly overwhelm local resources, Over the past several years, legislative and executive actions designed to enhance local, state, and federal preparedness to respond to terrorist events have proliferated. Federal response operations continue to be enhanced, building on existing structures, to provide emergency mitigation and relief in the event of such an attack. This article discusses the various federal initiatives and programs targeting bioterrorism preparedness and response, and outlines the current framework for overall federal response to bioterrorism. C1 USN, Ctr Environm Hlth, Portsmouth, VA 23708 USA. US Dept HHS, Off Emergency Preparedness, Rockville, MD 20857 USA. US Dept Vet Affairs, Emergency Management Strateg Healthcare Grp, Vet Hlth Adm, Washington, DC 20001 USA. RP Mothershead, JL (reprint author), USN, Ctr Environm Hlth, 620 John Paul Jones Circle,Suite 1100, Portsmouth, VA 23708 USA. NR 41 TC 12 Z9 13 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD MAY PY 2002 VL 20 IS 2 BP 477 EP + AR PII S0733-8627(02)00004-4 DI 10.1016/S0733-8627(02)00004-4 PG 26 WC Emergency Medicine SC Emergency Medicine GA 573JX UT WOS:000176827300013 PM 12120488 ER PT J AU Sidis, Y Tortoriello, DV Holmes, WE Pan, Y Keutmann, HT Schneyer, AL AF Sidis, Y Tortoriello, DV Holmes, WE Pan, Y Keutmann, HT Schneyer, AL TI Follistatin-related protein and follistatin differentially neutralize endogenous vs. exogenous activin SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; BINDING-PROTEIN; PITUITARY-CELLS; GRANULOSA-CELLS; HEPARAN-SULFATE; II RECEPTORS; IN-VITRO; INHIBIN; STEROIDOGENESIS; IDENTIFICATION AB Follistatin-related protein (FSRP) is a new addition to the expanding follistatin (FS)-related gene family whose members contain at least one conserved 10-cysteine follistatin domain. In contrast to other members of this family, FSRP and follistatin also share a common exon/intron domain structure, substantial primary sequence homology, and an ability to irreversibly bind activin. In this study, we further explored the hypothesis that FSRP is a functional as well as structural homologue of FS. N-terminal sequencing of recombinant FSRP revealed that signal peptide cleavage occurs within exon 1, a significant structural difference from FS, in which cleavage occurs at the exon/intron boundary. Solid-phase radioligand competition assays revealed both FS and FSRP to preferentially bind activin with the next closest TGF-beta superfamily member, bone-morphogenic protein-7, being at least 500-fold less potent. Consistent with their similar activin-binding affinities, FSRP and FS both prevented exogenous (endocrine or paracrine) activin from accessing its receptor and inducing gene transcription in bioassays. However, FS was at least 100-fold more potent than FSRP in inhibiting gene transcription and FSH release mediated by endogenously produced (autocrine) activin-A or activin-B in multiple cell systems. Finally, FSRP lacks the heparin-binding sequence found in FS, and we found that it was also unable to bind cell surface heparin sulfated proteoglycans. These findings suggest that structural differences between FSRP and FS may underlie their different neutralizating capabilities with respect to exogenous vs. endogenous activin. Taken together with our previous studies showing that activin binding is essential for FS's biological activity, the differential activities of FSRP and FS further indicate that activin binding is necessary but not sufficient to account for all of FS's actions. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02144 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02144 USA. Millennium Pharmaceut, Cambridge, MA 02144 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Schneyer, AL (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit BHX5, 55 Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [HD-29164, HD-39777]; NIDDK NIH HHS [DK-53828, DK-55838] NR 45 TC 49 Z9 51 U1 1 U2 5 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2002 VL 143 IS 5 BP 1613 EP 1624 DI 10.1210/en.143.5.1613 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544QB UT WOS:000175170500007 PM 11956142 ER PT J AU Abboud, SL Woodruff, K Liu, C Shen, V Ghosh-Choudhury, N AF Abboud, SL Woodruff, K Liu, C Shen, V Ghosh-Choudhury, N TI Rescue of the osteopetrotic defect in op/op mice by osteoblast-specific targeting of soluble colony-stimulating factor-1 SO ENDOCRINOLOGY LA English DT Article ID OP OP MOUSE; FACTOR-I; GENE-THERAPY; TRANSGENIC MICE; STROMAL CELLS; GROWTH-FACTOR; MARROW-CELLS; HUMAN CSF-1; MACROPHAGE; BONE AB Soluble colony-stimulating factor-1 (sCSF-1) and membrane bound CSF-1 are synthesized by ostcoblasts and stromal cells. However, the precise role of each form in osteoclastogenesis is unclear. In the op/op mouse, absence of osteoblast-derived CSF-1 leads to decreased osteoclasts and osteopetrosis. To determine whether sCSF-1 gene replacement can cure the osteopetrotic defect, we took advantage of the osteoblast specificity of the osteocalcin promoter to selectively express sCSF-l in the bone of op/op mice. Transgenic mice harboring the human sCSF-1 cDNA under the control of the osteocalcin promoter were generated and cross-bred with heterozygous op/wt mice to establish op/op mutants expressing the transgene (op/opT. The op/op genotype and transgene expression were confirmed by PCR and Southern blot analysis, respectively. High levels of human sCSF-l protein were selectively expressed in bone. At 21/2 wk, op/opT mice showed normal growth and tooth eruption. Femurs removed at 5 and 14 wk were analyzed by peripheral quantitative computed tomography and histomorphometry. The abnormal bone mineral density, cancellous bone volume, and growth plate width observed in op/op mice was completely reversed in op/opT mice by 5 wk, and this effect persisted at 14 wk, with measurements comparable with wt/wt mice at each time point. Correction of the skeletal abnormalities in the 5-wk-old op/opT mice correlated with a marked increase in the total osteoclast number, and their number per millimeter of bone surface compared with that of op/op mutants. Ostcoclast number was maintained at 14 wk in op/opT mice and morphologically resembled a,wt/wt ostcoclasts. These results indicate that sCSF-1 is sufficient to drive normal osteoclast development and that the osteocalcin promoter provides an efficient tool for delivery of exogenous genes to the bone. Moreover, targeting sCSF-l to osteoblasts in the bone microenvironment may be a potentially useful therapeutic modality for treating bone disorders. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Skeletech Inc, Bothell, WA 98021 USA. RP Abboud, SL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR-42306, R01 AR042306] NR 39 TC 40 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2002 VL 143 IS 5 BP 1942 EP 1949 DI 10.1210/en.143.5.1942 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 544QB UT WOS:000175170500042 PM 11956177 ER PT J AU Magari, SR Schwartz, J Williams, PL Hauser, R Smith, TJ Christiani, DC AF Magari, SR Schwartz, J Williams, PL Hauser, R Smith, TJ Christiani, DC TI The association between personal measurements of environmental exposure to particulates and heart rate variability SO EPIDEMIOLOGY LA English DT Article DE particulate matter; PM2.5; heart rate variability; cardiac autonomic function ID INDOOR PARTICLE SOURCES; AIR-POLLUTION; MYOCARDIAL-INFARCTION; CARDIAC-ARRHYTHMIA; COARSE PARTICLES; MORTALITY; RISK; INDUCTION; CITIES AB Background. Epidemiologic evidence indicates that airborne particulates are associated with mortality risk, predominately from heart disease. This may occur through changes in the cardiac autonomic nervous system, witnessed by changes in heart rate variability. Methods. This short,term longitudinal study used continuous personal particulate matter measurements to examine the effects of exposure to particulate matter less than 2.5 mum in diameter (PM2.5) on heart rate and rate variability in 20 relatively young, healthy male workers. Continuous exposure and cardiac monitoring were per-formed on each subject on a nonwork day. The 5-minute standard deviation of the normal-to-normal interval was used as the main measure of heart rate variability. Results. Mixed-effects regression models estimate an average 1.4% (95% confidence limits = -2.1, -0.6) decrease in the 5-minute standard deviation of the normal-to-normal interval for each 100 mug/m(3) increase in the 3-hour PM2.5 moving average, and small increases in heart rate, after adjustment for potential confounding factors. Predicted effects of exposure were greatest using the 3-hour averaging interval for PM2.5 and decreased in magnitude using shorter and longer intervals. Conclusions. These results reveal an association between cardiac autonomic function and environmental PM2.5 exposure. These observed associations may result from decreased vagal or increased sympathetic tone. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Environm Epidemiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Environm Sci & Engn Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA. FU NIEHS NIH HHS [T32 ES07069, ES00002, ES09860]; NIOSH CDC HHS [OH00152] NR 27 TC 51 Z9 56 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 BP 305 EP 310 DI 10.1097/00001648-200205000-00011 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 544QF UT WOS:000175170900010 PM 11964932 ER PT J AU Salinsky, MC Binder, LM Oken, BS Storzbach, D Aron, CR Dodrill, CB AF Salinsky, MC Binder, LM Oken, BS Storzbach, D Aron, CR Dodrill, CB TI Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers SO EPILEPSIA LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Epilepsy-Society CY DEC 01-06, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Epilepsy Soc DE antiepileptic drugs; electroencephalography; cognition; epilepsy; gabapentin; carbamazepine ID ANTIEPILEPTIC DRUGS; EPILEPTIC PATIENTS; DOUBLE-BLIND; SERUM LEVELS; PHENYTOIN; ADULTS; PERFORMANCE; PSYCHOMOTOR; ABILITIES; ELECTROENCEPHALOGRAM AB Purpose: Antiepileptic drug (AED) therapy can be associated with neurotoxic side effects including cognitive dysfunction. Objective methods for detection of neurotoxicity in individual patients would be useful. We studied the effects of gabapentin (GBP) and carbamazepine (CBZ) on neurophysiologic and cognitive/behavioral measures in healthy volunteers. Methods: In a 12-week, randomized, double-blind, parallel-group study of CBZ and GBP in healthy volunteers, 23 subjects completed the protocol. All achieved the target dose of 1,200 mg CBZ or 3,600 mg GBP. A structured EEG for quantitative analysis and a cognitive test battery were administered before AED therapy and again after 12 weeks of therapy. Test-retest differences were compared with those of 72 untreated control subjects. Results: Both CBZ and GBP significantly decreased the peak frequency of the posterior (alpha) rhythm, with CBZ exerting a greater effect. Ten CBZ and six GBP subjects exceeded the 95% confidence interval (CI) for an individual. Cognitive tests revealed AED vs. control group effects for two of seven measures (Digit Symbol, Stroop) and all subjective measures. However, few subjects exceeded the 95% Cl for any objective test. Differences between CBZ and GBP were not significant. Greater EEG slowing was associated with greater subjective neurotoxicity and poorer test-retest performance on a cognitive test summary measure. Conclusions: Prolonged CBZ and GBP therapy induced EEG slowing that correlated with cognitive complaints and often exceeded the confidence interval for individual Subjects. Quantitative EEG measures may be useful in the objective determination of AED-related neurotoxicity. C1 Oregon Hlth Sci Univ, Epilepsy Ctr, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Warner Lambert Pharmaceut, Morris Plains, NJ USA. Univ Washington, Epilepsy Ctr, Seattle, WA 98195 USA. RP Salinsky, MC (reprint author), Oregon Hlth Sci Univ, Epilepsy Ctr, 745 SW Gaines Rd,CDW-3, Portland, OR 97201 USA. NR 62 TC 69 Z9 70 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2002 VL 43 IS 5 BP 482 EP 490 DI 10.1046/j.1528-1157.2002.22501.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 571GM UT WOS:000176709700004 PM 12027908 ER PT J AU Valencia, I Pfeifer, H Thiele, EA AF Valencia, I Pfeifer, H Thiele, EA TI General anesthesia and the ketogenic diet: Clinical experience in nine patients SO EPILEPSIA LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Epilepsy-Society CY DEC 01-06, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Epilepsy Soc DE general anesthesia; ketogenic diet; epilepsy; perioperative; metabolic acidosis AB Purpose: To determine if children actively on the ketogenic diet (KD) can safely undergo general anesthesia (GA) for surgical procedures. Methods: The records of children treated with the KD at Children's Hospital (Boston, Massachusetts) from 1995 to the present were reviewed. The charts of children who had received GA while on the diet were evaluated with regard to demographics, procedure information, anesthesia records, blood chemistries, and perioperative course. Of 71 children on the KD during the period of the study, nine (12.7%) had procedures requiring GA while on the diet. Results: Nine children received GA for surgical procedures ranging from central line placement to hemispherectomy while on the KD. At the time of GA, the children ranged from age I to 6 years, and had been on the KD for 2-60 months. The patients received carbohydrate-free intravenous solutions perioperatively. Anesthesia duration ranged from 20 min to 11.5 h; for longer procedures, serum pH, glucose, and electrolyte levels were monitored. Serum glucose levels remained stable in all patients, but serum pH typically decreased; the largest reduction was to 7.16. In three procedures, patients received intravenous bicarbonate because of level of acidosis. There were no perioperative complications. Conclusions: Children on the KD can safely undergo GA for surgical procedures. Although serum glucose levels appear to remain stable, serum pH or bicarbonate levels should be monitored because of the risk of metabolic acidosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. Childrens Hosp, Div Epilepsy & Clin Neurophysiol, Dept Neurol, Boston, MA 02115 USA. RP Thiele, EA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Epilepsy Program, VBR 830,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 19 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2002 VL 43 IS 5 BP 525 EP 529 DI 10.1046/j.1528-1157.2002.12501.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 571GM UT WOS:000176709700010 PM 12027914 ER PT J AU Braunwald, E AF Braunwald, E TI Reperfusion therapy for acute myocardial infarction: historical context and future promise SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article; Proceedings Paper CT Symposium on the Past as Prologue - Defining New Standards of Care in Acute Coronary Syndromes CY SEP 01, 2001 CL STOCKHOLM, SWEDEN DE acute myocardial infarction; cardiovascular disease; reperfusion; ST-elevation myocardial infarction; thrombolytic therapy ID INTRA-CORONARY THROMBOLYSIS; SIZE; OCCLUSION; TRIAL AB Reperfusion therapy for acute myocardial infarction is a milestone achievement in 20th century cardiology, This article tracks this therapy from the discovery that coronary thrombosis is the cause of myocardial infarction. through the pre-clinical era when studies in dogs demonstrated the benefit of early reperfusion. Then came early clinical observations in the feasibility of coronary thrombolysis in patients. followed by the early placebo-controlled megatrials (GISSI-I and ISIS-2). which showed a Substantial mortality benefit. During the past decade there ha c been important refinements using ambulance-based therapy. new bolus thrombolytics, adjunctive glycoprotein inhibitors and percutaneous coronary intervention. (C) 2002 The European Society of Cardiology. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 34 TC 8 Z9 8 U1 1 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD MAY PY 2002 VL 4 IS E BP E10 EP E14 DI 10.1016/S1520-765X(02)90081-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 555AC UT WOS:000175768700003 ER PT J AU Knowles, AF Nagy, AK Strobel, RS Wu-Weis, M AF Knowles, AF Nagy, AK Strobel, RS Wu-Weis, M TI Purification, characterization, cloning, and expression of the chicken liver ecto-ATP-diphosphohydrolase SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE ecto-ATP-diphosphohydrolase; chicken liver; E-NTPDase; expression; immunoaffinity purification ID GIZZARD SMOOTH-MUSCLE; PLASMA-MEMBRANES; SKELETAL-MUSCLE; QUATERNARY STRUCTURE; MOLECULAR-CLONING; CD39; APYRASE; ATPASES; IDENTIFICATION; BRAIN AB We previously demonstrated that the major ecto-nucleoside triphosphate phosphohydrolase in the chicken liver membranes is an ecto-ATP-diphosphohydrolase (ecto-ATPDase) [Caldwell, C., Davis, M.D. & Knowles, A.F. (1999) Arch. Biochem. Biophys . 362 , 46-58]. Enzymatic properties of the liver membrane ecto-ATPDase are similar to those of the chicken oviduct ecto-ATPDase that we have previously purified and cloned. Using antibody developed against the latter, we have purified the chicken liver ecto-ATPDase to homogeneity. The purified enzyme is a glycoprotein with a molecular mass of 85 kDa and a specific activity of approximate to 1000 U.mg protein(-1) . Although slightly larger than the 80-kDa oviduct enzyme, the two ecto-ATPDases are nearly identical with respect to their enzymatic properties and mass of the deglycosylated proteins. The primary sequence of the liver ecto-ATPDase deduced from its cDNA obtained by RT-PCR cloning also shows only minor differences from that of the oviduct ecto-ATPDase. Immunochemical staining demonstrates the distribution of the ecto-ATPDase in the bile canaliculi of the chicken liver. HeLa cells transfected with the chicken liver ecto-ATPDase cDNA express an ecto-nucleotidase activity with characteristics similar to the enzyme in its native membranes, most significant of these is stimulation of the ATPDase activity by detergents, which inhibits other members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. The stimulation of the expressed liver ecto-ATPDase by detergents indicates that this property is intrinsic to the enzyme protein, and cannot be attributed to the lipid environment of the native membranes. The molecular identification and expression of a liver ecto-ATPDase, reported here for the first time, will facilitate future investigations into the differences between structure and function of the different E-NTPDases, existence of liver ecto-ATPDase isoforms in different species, its alteration in pathogenic conditions, and its physiological function. C1 San Diego State Univ, Dept Chem, San Diego, CA 92182 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Metropolitan State Univ, Dept Nat Sci, St Paul, MN USA. RP Knowles, AF (reprint author), San Diego State Univ, Dept Chem, San Diego, CA 92182 USA. NR 51 TC 20 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAY PY 2002 VL 269 IS 9 BP 2373 EP 2382 DI 10.1046/j.1432-1033.2002.02898.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 549HH UT WOS:000175438100016 PM 11985621 ER PT J AU Fiala, M Liu, QN Sayre, J Pop, V Brahmandam, V Graves, MC Vinters, HV AF Fiala, M Liu, QN Sayre, J Pop, V Brahmandam, V Graves, MC Vinters, HV TI Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer's disease brain and damage the blood-brain barrier SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Alzheimer's disease; amyloid x beta clearance; blood-brain barrier; HIV-1 encephalitis; monocyte/macrophage; T lymphocyte ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; AMYLOID PRECURSOR PROTEIN; AIDS DEMENTIA COMPLEX; MICROGLIAL CELLS; TRANSGENIC MICE; BETA-PROTEIN; A-BETA; EXPRESSION; ACTIVATION AB Background Monocyte/macrophages are known to infiltrate the brain of patients with HIV-1 encephalitis (HIVE), In Alzheimer's disease brain, the origin of activated microglia has not been determined. Materials and methods We employed the antigen retrieval technique, immunocytochemistry, immunofluorescense, and confocal microscopy to identify macrophages and microglia in relation to amyloid-beta plaques and the blood-brain barrier in autopsy brain tissues from patients with Alzheimer's disease (AD) and HIVE. Results In both conditions, cyclooxygenase-2 positive macrophages and, to a lesser degree, T and B cells infiltrate brain perivascular spaces and neuropil. The macrophages are distinguishable from ramified microglia, and decorate the vessels at the sites of apparent of endothelial tight junction protein ZO-1 disruption. The macrophages. also infiltrate amyloid-beta plaques, display intracellular amyloid-beta and are surrounded by amyloid-D-free lacunae. Furthermore, the macrophages partially encircle the walls of amyloid-p-containing vessels in amyloid angiopathy, and exhibit intracellular amyloid-beta but not paracellular lacunae. Significantly larger zones of fibrinogen leakage surround the microvessels in HIVE brain tissues compared with AD tissues (P = 0.034), and AD tissues have significantly greater leakage than control tissues (P = 0.0339). The AD group differs from a normal control age-matched group with respect to both the area occupied by CD68 (P= 0.03) and cyclooxygenase-2 immunoreactive cells (P = 0.004). Conclusion In both HIVE and AD, blood-borne activated monocyte/macrophages and lymphocytes appear to migrate through a disrupted blood-brain barrier. The lacunae around macrophages in amyloid-beta plaques but not in vessel walls are consistent with the ability of macrophages to phagocytize and clear amyloid-beta deposits in vitro. C1 Univ Calif Los Angeles, Sch Med, Dept Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Fiala, M (reprint author), Univ Calif Los Angeles, Cardiovasc Res Lab, 3645 MRL,675 Young Dr S, Los Angeles, CA 90095 USA. FU NIA NIH HHS [P01AG12435, P50AG16570]; NIDA NIH HHS [DA10442]; NIMH NIH HHS [R24MH59656, R24MH59724] NR 71 TC 131 Z9 135 U1 3 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD MAY PY 2002 VL 32 IS 5 BP 360 EP 371 DI 10.1046/j.1365-2362.2002.00994.x PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 553JN UT WOS:000175672200012 PM 12027877 ER PT J AU Iwata, S Kobayashi, H Miyake-Nishijima, R Sasaki, T Souta-Kuribara, A Nori, M Hosono, O Kawasaki, H Tanaka, H Morimoto, C AF Iwata, S Kobayashi, H Miyake-Nishijima, R Sasaki, T Souta-Kuribara, A Nori, M Hosono, O Kawasaki, H Tanaka, H Morimoto, C TI Distinctive signaling pathways through CD82 and beta 1 integrins in human T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE human T lymphocyte; tetraspanin; beta 1 integrin; Crk-associated substrate lymphocyte type (Cas-L) ID TRANSMEMBRANE PROTEIN FAMILY; DIPHTHERIA-TOXIN RECEPTOR; SUBSTRATE-RELATED PROTEIN; LEUKEMIA-VIRUS TYPE-1; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; CAS-L; SYNCYTIUM FORMATION; GROWTH-FACTOR; CD9 ANTIGEN AB CD82, a member of tetraspan family (tetraspanin), is a multifunctional molecule that is involved in cell activation, costimulation, and cell spreading of T cells. Here we show that immobilized anti-CD82 monoclonal antibody (mAb) as well as anti-alpha4beta1 integrin mAb induced tyrosine phosphorylation of pp105/Crk-associated substrate lymphocyte type (Cas-L) in human peripheral T cells and H9 cells. Furthermore, one of anti-CD82 mAb (8E4), which induces homotypic aggregation of T cells and H9 cells but has no costimulatory activity, partially inhibited very late antigen (VLA)-4 integrin ligand-mediated costimulation of T cells, whereas it failed to inhibit VLA-5 integrin ligand-mediated costimulation. To further elucidate the relationship between CD82- and VLA-4-mediated signaling pathways we defined the IL-2 production by the costimulation of Jurkat T cells with marginal amount of Cas-L, and subsequently found that mAb against CD82 had strong costimulatory activity to CD3/TCR, whereas mAb against beta1 failed to do so in those cells. We have further demonstrated that this discrepancy between beta1 integrin- and CD82-mediated costimulation partly lies in differential activation of NF-AT, AP-1, and NF-kappaB in Jurkat T cells. In this study, although some functional overlap exists, we provide evidence for distinctive signaling of CD82- and beta1 integrin-mediated costimulation at the transcriptional level of IL-2 gene. C1 Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Clin Immunol,Minato Ku, Tokyo 1088639, Japan. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Morimoto, C (reprint author), Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Div Clin Immunol,Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. RI Iwata, Satoshi/A-8819-2011 FU NIAMS NIH HHS [AR33713] NR 42 TC 23 Z9 26 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2002 VL 32 IS 5 BP 1328 EP 1337 AR UNSP I 22176 DI 10.1002/1521-4141(200205)32:5<1328::AID-IMMU1328>3.0.CO;2-6 PG 10 WC Immunology SC Immunology GA 553VD UT WOS:000175695700014 PM 11981820 ER PT J AU Huster, KM Panoutsakopoulou, V Prince, K Sanchirico, ME Cantor, H AF Huster, KM Panoutsakopoulou, V Prince, K Sanchirico, ME Cantor, H TI T cell-dependent and -independent pathways to tissue destruction following herpes simplex virus-1 infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE autoimmunity; viral infection; inflammation; dendritic cell; rodent ID STROMAL KERATITIS; BYSTANDER ACTIVATION; AUTOIMMUNE-DISEASE; LANGERHANS CELLS; VIRAL-INFECTION; LYMPHOCYTES; IMMUNOPATHOLOGY; LESIONS AB Viral infections can trigger tissue destruction through innate and/or adaptive immune mechanisms. Here we show that these pathways can be differentially activated after infection by different strains of the herpes simplex virus-1 (HSV-1) virus. Infection of murine corneal tissue by HSV-1 (KOS) triggers an autoreactive clone of CD4 cells that is cross-reactive with an HSV-1 epitope to initiate corneal destruction. In contrast, ocular infection by the HSV-1 (RE) strain induces murine corneal destruction through direct, T cell-independent, activation of the innate immune system. Although the relative role of these two pathways to blindness following clinical HSV-1 ocular infection is unknown, this analysis suggests a general experimental approach to evaluate the relative contribution of adaptive and innate immune mechanisms to virally induced host tissue destruction. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. OI Panoutsakopoulou, Vily/0000-0002-1569-1508 FU NEI NIH HHS [EY 07032]; NIAID NIH HHS [AI 37562] NR 21 TC 15 Z9 15 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2002 VL 32 IS 5 BP 1414 EP 1419 AR UNSP I 22614 DI 10.1002/1521-4141(200205)32:5<1414::AID-IMMU1414>3.0.CO;2-Q PG 6 WC Immunology SC Immunology GA 553VD UT WOS:000175695700023 PM 11981829 ER PT J AU Anzueto, A AF Anzueto, A TI Exogenous surfactant in acute respiratory distress syndrome: more is better SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID PULMONARY SURFACTANT; LUNG SURFACTANT; LAVAGE C1 S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, Pulm Dis Sect 111E, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Med Crit Care Med, San Antonio, TX 78284 USA. RP Anzueto, A (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, Pulm Dis Sect 111E, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. NR 24 TC 13 Z9 15 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD MAY PY 2002 VL 19 IS 5 BP 787 EP 789 DI 10.1183/09031936.02.00284902 PG 3 WC Respiratory System SC Respiratory System GA 553AP UT WOS:000175653600001 PM 12030713 ER PT J AU Ishikawa, F Livingston, AG Wingard, JR Nishikawa, SI Ogawa, M AF Ishikawa, F Livingston, AG Wingard, JR Nishikawa, SI Ogawa, M TI An assay for long-term engrafting human hematopoietic cells based on newborn NOD/SCID/beta 2-microglobulin(null) mice SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; SCID MICE; BONE-MARROW; REPOPULATING ACTIVITY; NOD/SCID MICE; IN-VITRO; BLOOD; MOUSE; MODEL; EXPANSION AB Objective. Of various types of xenograft assays, the use of NOD/SCID mice has been the most popular method for quantitating candidate human stem cells. Limitations of the assay include low levels of engraftment, except when large numbers of cells are injected, and the development of thymic lymphoma, which precluded observation of long-term engraftment. In order to establish an assay that allows long-term in vivo engraftment and higher engraftment levels by a reasonable number of human cells, we tested a model based on "conditioned newborn" NOD/SCID or NOD/SCID/beta2-microglobulin(null) (BMG(null)) mice. Materials and Methods. Using human cord blood mononuclear cells, we tested various nonradiation conditioning regimens and cell injection routes. Conditioning with a combination of 5-fluorouracil (5FU) and anti-mouse c-kit blocking antibody (Ack-2) or a combination of busulfan (BU) and cyclophosphamide (CY) and the use of facial vein for the cell injection route yielded the highest levels of multilineage engraftment. Results. At 4-5 months posttransplantation, the median of engraftment level in bone marrow with 5FU/Ack-2 and BU/CY regimens were 0.9% (range: 0.2-40.5%) and 2.1% (range: 0.3-2.4%) in NOD/SCID mice, and 11.3% (range: 0.7-38%) and 14.1% (range: 0.8-52%) in NOD/SCID/BMG(null) mice, respectively. Multilineage engraftment was demonstrated by flow, cytometry and by the growth of multilineage colonies in methylcellulose culture. Secondary transplantation of the isolated human CD45(+) cells, also performed at 4-5 months posttransplantation, revealed engraftment at the levels of 1.5 +/- 0.42% at 2 months after secondary transplantation. Conclusion. Our assay may provide a quantitative method for analysis of human hematopoietic stem cells. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Med Univ S Carolina, Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Univ Florida, Div Hematol Oncol, Gainesville, FL USA. Kyoto Univ, Grad Sch Med, Dept Mol Genet, Kyoto, Japan. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. RI 石川, 文彦/L-4488-2014 FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 24 TC 40 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 2002 VL 30 IS 5 BP 488 EP 494 AR PII S0301-472X(02)00784-1 DI 10.1016/S0301-472X(02)00784-1 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 548HR UT WOS:000175383000014 PM 12031656 ER PT J AU Petersen, A Chase, K Puschban, Z DiFiglia, M Brundin, P Aronin, N AF Petersen, A Chase, K Puschban, Z DiFiglia, M Brundin, P Aronin, N TI Maintenance of susceptibility to neurodegeneration following intrastriatal injections of quinolinic acid in a new transgenic mouse model of Huntington's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE excitotoxicity; striatum; Huntington's disease ID CAG REPEAT; MICE; LENGTH; ABNORMALITIES; INCLUSIONS; RESISTANCE; MUTATION; TOXICITY; EXON-1; GENE AB A transgenic mouse model of Huntington's disease (R6/1 and R6/2 lines) expressing exon 1 of the HD gene with 115-150 CAG repeats resisted striatal damage following injection of quinolinic acid and other neurotoxins. We examined whether excitotoxin resistance characterizes mice with mutant huntingtin transgenes. In a new transgenic mouse with 3 kb of mutant human huntingtin cDNA with 18, 46, or 100 CAG repeats, we found no change in susceptibility to intrastriatal injections of the excitotoxin quinolinic acid, compared to wild-type littermates. The new transgenic mice were injected with the same dose of quinolinic acid (30 nmol) as had been the R6 mice. Our findings highlight the importance of studying pathogenetic mechanisms in different transgenic models of a disease. (C) 2002 Elsevier Science (USA). C1 Lund Univ, Wallenberg Neurosci Ctr, BMCAIO, Sect Neuronal Survival, S-22184 Lund, Sweden. Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Petersen, A (reprint author), Lund Univ, Wallenberg Neurosci Ctr, BMCAIO, Sect Neuronal Survival, S-22184 Lund, Sweden. RI Petersen, Asa/E-6064-2011 FU NIDDK NIH HHS [DK32520]; NINDS NIH HHS [NS 16367, NS 35711, NS 38194] NR 15 TC 33 Z9 34 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2002 VL 175 IS 1 BP 297 EP 300 DI 10.1006/exnr.2002.7885 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 550YN UT WOS:000175532800026 PM 12009780 ER PT J AU Sosnovik, DE Muller, JE Kathiresan, S Brady, TJ AF Sosnovik, DE Muller, JE Kathiresan, S Brady, TJ TI Non-invasive imaging of plague vulnerability: an important tool for the assessment of agents to stabilise atherosclerotic plaques SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE computed tomography; magnetic resonance imaging; molecular imaging; non-invasive imaging; ultrasound; vulnerable plaque ID ULTRASONIC TISSUE CHARACTERIZATION; MULTISLICE COMPUTED-TOMOGRAPHY; CORONARY-ARTERY DISEASE; INTIMA-MEDIA THICKNESS; IN-VIVO; HIGH-RESOLUTION; EX-VIVO; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INTRAVASCULAR ULTRASOUND; CAROTID ATHEROSCLEROSIS AB Disruption of a vulnerable atherosclerotic plaque is well-recognised as the primary cause of stroke, non-fatal myocardial infarction and sudden cardiac death. Novel therapeutic agents are being developed to stabilise such plaques. The initial evaluation of these drugs would be facilitated by the use of non-invasive imaging techniques to identify vulnerable plaque and document serial changes in plaque stability. The aim of this review is to explain the characteristics of the leading non-invasive imaging modalities and discuss their role in examining the vulnerable plaque. This knowledge will be extremely important for physicians and scientists involved in the clinical evaluation of novel agents to stabilise the vulnerable plaque. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Sosnovik, DE (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. NR 61 TC 3 Z9 4 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD MAY PY 2002 VL 11 IS 5 BP 693 EP 704 DI 10.1517/13543784.11.5.693 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 552HL UT WOS:000175613900009 PM 11996650 ER PT J AU Giri, S Jatana, M Rattan, R Won, JS Singh, I Singh, AK AF Giri, S Jatana, M Rattan, R Won, JS Singh, I Singh, AK TI Galactosylsphingosine (psychosine)-induced expression of cytokine-mediated inducible nitric oxide synthases via AP-1 and C/EBP: implications for Krabbe disease SO FASEB JOURNAL LA English DT Article DE cerebroside; GLD; iNOS; oligodendrocytes; beta-galactosidase ID GLOBOID-CELL LEUKODYSTROPHY; NF-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; TWITCHER MOUSE; PSYCHOSINE GALACTOSYLSPHINGOSINE; TRANSCRIPTION FACTORS; GENE-EXPRESSION; SPINAL-CORD; ACCUMULATION; BETA AB Globoid cell leukodystrophy (Krabbe disease) is characterized by the accumulation of a toxic metabolite, psychosine (galactosylsphingosine), which is a substrate for the deficient enzyme (galactocerebroside beta-galactosidase). This study underscores the possible role of psychosine in the effect of inducible nitric oxide synthase (iNOS) -derived NO in the pathophysiology of this demyelinating disease. For the first time, we provide evidence of the expression of iNOS in CNS of Krabbe patient and show that the iNOS-expressing cells in the CNS were astrocytes. Psychosine potentiated the LPS-induced production of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in primary rat astrocytes and regulated the cytokine-mediated production of NO in C6 glioma and primary rat astrocyte. Psychosine induced cytokine-mediated nuclear translocation of AP-1 and C/EBP by potentiating the expression of Fra-1 and C/EBP-delta proteins. This suggests that psychosine maintained or sustained the cytokine-primed expression of iNOS by further potentiating the nuclear translocation of AP-1 and C/EBP without modulating the cytokine-mediated transcription activity of NF-kappaB. This study hypothesizes that accumulated psychosine leads to production of cytokines and iNOS expression. The ensuing excessive production of NO and ONOO- may play a role in pathogenesis of Krabbe disease. C1 Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph Johnson Vet Affairs Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, 316 Clin Sci Bldg, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS-40810, NS-34741, NS 37766] NR 62 TC 78 Z9 79 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2002 VL 16 IS 7 AR UNSP 0892-6638/02/0016-0661 DI 10.1096/fj.01-0798com PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 558NR UT WOS:000175973900020 PM 11978730 ER PT J AU Stoler, LR AF Stoler, LR TI Researching sensitive topics: Stories, struggles and strategies. III. Researching childhood sexual abuse: Anticipating effects on the researcher SO FEMINISM & PSYCHOLOGY LA English DT Article C1 Vet Adm Med Ctr, Natl Ctr PTSD, Boston, MA 02130 USA. RP Stoler, LR (reprint author), Vet Adm Med Ctr, Natl Ctr PTSD, 150 Huntington Ave, Boston, MA 02130 USA. NR 8 TC 11 Z9 12 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0959-3535 J9 FEM PSYCHOL JI Feminism Psychol. PD MAY PY 2002 VL 12 IS 2 BP 269 EP 274 DI 10.1177/0959353502012002015 PG 6 WC Psychology, Multidisciplinary; Women's Studies SC Psychology; Women's Studies GA 556WT UT WOS:000175872500015 ER PT J AU Wendt, S Dedeoglu, A Speer, O Wallimann, T Beal, MF Andreassen, OA AF Wendt, S Dedeoglu, A Speer, O Wallimann, T Beal, MF Andreassen, OA TI Reduced creatine kinase activity in transgenic amyotrophic lateral sclerosis mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE creatine kinase; creatine; neuroprotection; neurodegeneration; amyotrophic lateral sclerosis; oxidative damage; free radicals ID SUPEROXIDE-DISMUTASE GENE; HIPPOCAMPAL-NEURONS; HUNTINGTONS-DISEASE; MOTOR-NEURONS; ANIMAL-MODEL; NITRIC-OXIDE; MOUSE MODEL; PEROXYNITRITE; INHIBITION; MUTANT AB Creatine (Cr), the substrate of the creatine kinase (CK) isoenzymes, was shown to be neuroprotective in several models of neurodegeneration, including amyotrophic lateral sclerosis (ALS). In order to investigate the mechanism of this beneficial effect, we determined CK activities and mitochondrial respiration rates in tissues from G93A transgenic mice, which overexpress a mutant form of human superoxide dismutase associated with familial ALS (FALS). While respiration rates of mitochondria from G93A transgenic or wild-type control mice isolated from spinal cord showed no difference, a significant and dramatic loss of CK activity could be detected in these tissues. In homogenates from spinal cord of G93A transgenic mice, CK activity decreased to 49% and in mitochondrial fractions to 67% compared to CK activities in wild-type control mice. Feeding the G93A transgenic mice with 2% Cr, the same tissues showed no statistically significant increase of CK activity compared to regular fed G93A transgenic mice. Experiments with isolated mitochondria, however, showed that Cr and adenosine triphosphate (ATP) protected mitochondrial CK activity against peroxynitrite-induced inactivation, which may play a role in tissue damage in neurodegeneration. Our data provide evidence for oxidative damage to the CK system in ALS, which may contribute to impaired energy metabolism and neurodegeneration. (C) 2002 Elsevier Science Inc. C1 ETH Honggerberg, Inst Cell Biol, CH-8093 Zurich, Switzerland. Massachusetts Gen Hosp, Neurochem Lab, Neurol Serv, Boston, MA USA. Cornell Univ, Weill Med Col, New York Presbyterian Hosp, Dept Neurol & Neurosci, New York, NY USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wallimann, T (reprint author), ETH Honggerberg, Inst Cell Biol, HPM F42, CH-8093 Zurich, Switzerland. RI Wallimann, Theo/C-6047-2008 NR 38 TC 36 Z9 36 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2002 VL 32 IS 9 BP 920 EP 926 AR PII S0891-5849(02)00784-0 DI 10.1016/S0891-5849(02)00784-0 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 546TV UT WOS:000175291200016 PM 11978494 ER PT J AU Bagley, J Bracy, JL Tian, C Kang, ES Iacomini, J AF Bagley, J Bracy, JL Tian, C Kang, ES Iacomini, J TI Establishing immunological tolerance through the induction of molecular chimerism SO FRONTIERS IN BIOSCIENCE LA English DT Article DE gene therapy; tolerance; transplantation; T cells; B cells; review ID MIXED ALLOGENEIC CHIMERISM; HUMAN NATURAL ANTIBODIES; RETROVIRAL GENE-THERAPY; CLASS-II GENES; BONE-MARROW; GRAFT-REJECTION; CELL TOLERANCE; MHC PEPTIDES; B-CELLS; T-CELLS AB One of the major goals of transplantation biology is to overcome transplant rejection without the need for life-long immunosuppression. Over the last several years, fundamental advances in our understanding of the immune response to allogeneic and xenogeneic antigens have stimulated a great deal of interest in the possibility of using gene therapy approaches to overcome the host response leading to transplant rejection while alleviating the need for non-specific immunosuppression. Here, we review recent progress in the field on the use of gene therapy to induce transplantation tolerance to donor organs and tissues. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149-5210,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [T32 AI07529, R01 AI43619, R01 AI44268] NR 60 TC 9 Z9 9 U1 1 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2002 VL 7 BP D1331 EP D1337 DI 10.2741/bagley PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 548ZE UT WOS:000175419400020 PM 11991829 ER PT J AU Knosalla, C Cooper, DKC AF Knosalla, C Cooper, DKC TI Xenotransplantation and tolerance SO FRONTIERS IN BIOSCIENCE LA English DT Article DE anti-Gal antibodies; chimerism; humoral rejection; immunological tolerance; Xenotransplantation; pig; review ID NONLETHAL PREPARATIVE REGIMEN; RAT BONE-MARROW; CD4(+) T-CELLS; MIXED CHIMERISM; THYMIC TRANSPLANTATION; XENOGENEIC BARRIER; DONOR SPLENOCYTES; SKIN ALLOGRAFTS; CD40 LIGAND; B-CELLS AB Donor organ availability has become a major limiting factor in the progress of allotransplantation. This, and advances in genetic engineering in pigs, have led to increasing interest in the use of xenogeneic organs. In view of the greater difficult encountered in overcoming immune responses to xenografts than to allografts, the success of clinical xenotransplantation may depend on finding ways of inducing specific hyporesponsiveness, or tolerance, across xenogeneic barriers rather than by relying on nonspecific immunosuppressive agents. This review discusses the barriers to xenogeneic organ transplantation and the approaches that are being developed to overcome them, with the emphasis on methods that attempt to induce tolerance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU PHS HHS [1PO1 A145897] NR 51 TC 7 Z9 8 U1 0 U2 0 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2002 VL 7 BP D1280 EP D1287 DI 10.2741/knosalla PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 548ZE UT WOS:000175419400016 PM 11991841 ER PT J AU Johnston, DR Sayegh, MH Madsen, JC AF Johnston, DR Sayegh, MH Madsen, JC TI Overcoming cardiac allograft vasculopathy (CAV) by inducing tolerance SO FRONTIERS IN BIOSCIENCE LA English DT Review DE animal; cardiac allograft vasculopathy; graft rejection; heart transplantation; human; immunology; transplantation tolerance review ID DONOR-SPECIFIC TOLERANCE; REGULATORY T-CELLS; CHRONIC REJECTION; TRANSPLANTATION TOLERANCE; INDIRECT RECOGNITION; MIXED CHIMERISM; MINIATURE SWINE; HEART-TRANSPLANTATION; MONOCLONAL-ANTIBODY; RENAL-ALLOGRAFTS AB There is compelling evidence that MHC-drive immune processes play a dominant role in the development of cardiac allograft vasculopathy. Thus, it makes intuitive sense that tolerance, which eliminates donor alloreactivity, should protect against CAV. However, in the experimental literature, there are examples of CAV occurring in recipients rendered tolerant by either peripheral or central induction protocols. Why does transplant arteriopathy occur in recipients that have achieved a robust state of tolerance or in the animals devoid of T or B cell immunity? There may be immunological blindspots that persist eve after a state of tolerance is achieved. These blindspots could contribute to the pathogenesis of chronic rejection (CR). C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Renal Div,Lan Immunogenet & Transplantat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [F32 HL69645, R01-HL54211, P01-HL18646]; NIAID NIH HHS [P01-AI150157] NR 122 TC 5 Z9 5 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2002 VL 7 BP E116 EP E128 DI 10.2741/johnston PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 548ZE UT WOS:000175419400026 PM 11991839 ER PT J AU Jensen, DM AF Jensen, DM TI Endoscopic screening for varices in cirrhosis: Findings, implications, and outcomes SO GASTROENTEROLOGY LA English DT Article ID CONTROLLED RANDOMIZED TRIAL; LARGE ESOPHAGEAL-VARICES; PROPHYLACTIC SCLEROTHERAPY; NATURAL-HISTORY; PORTAL-HYPERTENSION; LIVER-CIRRHOSIS; PRIMARY PREVENTION; BAND LIGATION; HEMORRHAGE; RISK AB At least two thirds of cirrhotic patients develop esophageal varices during their lifetime. Severe upper gastrointestinal (UGI) bleeding as a complication of portal hypertension develops in about 30%-40% of cirrhotics. Despite significant improvements in the early diagnosis and treatment of esophagogastric variceal hemorrhage, the mortality rate of first variceal hemorrhage remains high (20%-35%). Primary prophylaxis, the focus of this article, is treatment of patients who never had previous variceal bleeding to prevent the first variceal hemorrhage. The potential of preventing first variceal hemorrhage offers the promise of reducing mortality, morbidity, and associated health care costs. This article (1) reviews endoscopic grading of size and stigmata for esophageal and gastric varices, (2) describes data on prevalence and incidence of esophageal and gastric varices from prospective studies, (3) discusses independent risk factors from multivariate analyses of prospective studies for development of first esophageal or gastric variceal hemorrhage and possible stratification of patients based on these risk factors, (4) comments on the potential cost effectiveness of screening all newly diagnosed cirrhotic patients and treating high-risk patients with medical or endoscopic therapies, and (5) recommends further studies of endoscopic screening, stratification, and outcomes in prospective studies of endoscopic therapy. The author's recommendations are to perform endoscopic screening for the following subgroups of cirrhotics: all newly diagnosed cirrhotic patients and all other cirrhotics who are medically stable, willing to be treated prophylactically, and would benefit from medical or endoscopic therapies. Exclude patients who are unlikely to benefit from prophylactic therapies designed to prevent the first variceal hemorrhage, those with short life expectancy, and those with previous UGI hemorrhage (they should have already undergone endoscopy). For low or very low risk cirrhotic patients-those found to have no varices or small varices without stigmata-repeat endoscopy is recommended because screening for progression may be warranted in 2 or more years. C1 Vet Affairs Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Sch Med, Los Angeles, CA 90024 USA. RP Jensen, DM (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [M01 RR 00865]; NIDDK NIH HHS [DK 41301, R01 DK 49527, R01 K24 DK 02650] NR 53 TC 104 Z9 115 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 MAY PY 2002 VL 122 IS 6 BP 1620 EP 1630 DI 10.1053/gast.2002.33419 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 553FE UT WOS:000175664500006 PM 12016427 ER PT J AU Dodge, JE Ramsahoye, BH Wo, ZG Okano, M Li, E AF Dodge, JE Ramsahoye, BH Wo, ZG Okano, M Li, E TI De novo methylation of MMLV provirus in embryonic stem cells: CpG versus non-CpG methylation SO GENE LA English DT Article DE 5-methylcytosine; Dnmt1; Dnmt3a; Dnmt3b; embryonic stem cell ID DNA CYTOSINE-5 METHYLTRANSFERASES; DE-NOVO; ENZYMATIC-PROPERTIES; MOUSE; MAINTENANCE; SITES; REPLICATION; LETHALITY; CLONING; DNMT3A AB DNA methyltransferases, Dnmt3a and Dnmt3b, are required for do novo methylation in embryonic stem (ES) cells and postimplantation embryos. However, the mechanism of do novo methylation is largely unknown. In this study, we have analyzed the sequence specificity of Dnmt3a and Dnmt3b during do novo methylation of murine Maloney leukemia virus provirus DNA in virus-infected ES cells. Provirus DNA from infected wild-type (J1), Dmnt1-/- (c/c), and Dnmt3a3b-/- (3a3b-/-) ES cells were analyzed using the bisulfite sequencing method. We demonstrate that Dnmt3 enzymes methylate predominantly CpG sites in vivo and confirm that Dnmt3 enzymes, but not Dnmt1, are responsible for do novo methylation. However, the sequence context and CpG density do not appear to influence de novo methylation, though strand bias is detectable. Interestingly, non-CpG methylation is detected as a component of do novo methylation. CpA methylation was detected at similar to 1.4% of all sites in J1 and similar to 1.0% in c/c, but only -0.2% in 3a3b-/-. Few methylated CpT or CpC sites were detected. Similar results from nearest neighbor analysis of global endogenous methylation levels indicated a correlation between Dnmt3a and Dnmt3b presence and CpA methylation. These results demonstrate that the Dnmt3 enzymes methylate predominantly CpG sites and at a low frequency CpA sites with no apparent sequence preferences. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Massachusettes Gen Hosp, Charlestown, MA 02129 USA. Univ Edinburgh, John Hughes Bennett Lab, Dept Oncol, Edinburgh EH4 2XU, Midlothian, Scotland. RP Li, E (reprint author), Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Massachusettes Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 23 TC 70 Z9 74 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 1 PY 2002 VL 289 IS 1-2 BP 41 EP 48 AR PII S0378-1119(02)00469-9 DI 10.1016/S0378-1119(02)00469-9 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 591EP UT WOS:000177867000006 PM 12036582 ER PT J AU Friedman, JM Arbiser, J Epstein, JA Gutmann, DH Huot, SJ Lin, AE McManus, B Korf, BR AF Friedman, JM Arbiser, J Epstein, JA Gutmann, DH Huot, SJ Lin, AE McManus, B Korf, BR TI Cardiovascular disease in neurofibromatosis 1: Report of the NF1 cardiovascular task force SO GENETICS IN MEDICINE LA English DT Review DE neurofibromatosis 1; vasculopathy; hypertension; congenital heart defects ID NF1-ASSOCIATED PILOCYTIC ASTROCYTOMAS; RENAL-ARTERY STENOSIS; RENOVASCULAR HYPERTENSION; GENE-PRODUCT; FOLLOW-UP; PHEOCHROMOCYTOMA; TYPE-1; TUMOR; EXPRESSION; HAPLOINSUFFICIENCY AB Purpose: Patients with neurofibromatosis 1 (NF1) are at increased risk for a variety of cardiovascular disorders, but the natural history and pathogenesis of these abnormalities are poorly understood. Methods: The National Neurofibromatosis Foundation convened an expert task force to review current knowledge about cardiovascular manifestations of NF1 and to make recommendations regarding clinical management and research priorities related to these features of the disease. Results: This report summarizes the NF1 Cardiovascular Task Force's current understanding of vasculopathy, hypertension, and congenital heart defects that occur in association with NF1. Recommendations are made regarding routine surveillance for cardiovascular disease and diagnostic evaluation and management of cardiovascular disorders in individuals with NF1. Conclusion: Our understanding of the natural history and pathogenesis of cardiovascular disease in NF1 has improved substantially in the past few years, but many clinically important questions remain unanswered. C1 Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 1Z3, Canada. Emory Univ, Dept Dermatol, Sch Med, Atlanta, GA 30322 USA. Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners Ctr Human Genet, Boston, MA USA. RP Friedman, JM (reprint author), Univ British Columbia, Dept Med Genet, 6174 Univ Blvd, Vancouver, BC V6T 1Z3, Canada. NR 55 TC 137 Z9 146 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY-JUN PY 2002 VL 4 IS 3 BP 105 EP 111 DI 10.1097/00125817-200205000-00002 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 553LN UT WOS:000175676800002 PM 12180143 ER PT J AU Lu, R Sun, T Alberta, J Park, SK Vartanian, T Cai, L Cepko, C Stiles, C Rowitch, D AF Lu, R Sun, T Alberta, J Park, SK Vartanian, T Cai, L Cepko, C Stiles, C Rowitch, D TI Common requirement for oligodendrocyte lineage gene (Olig) function during development of oligodendrocytes and motor neurons in the mammalian spinal cord indicates a lineage connection SO GLIA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD MAY PY 2002 SU 1 MA W53 BP S7 EP S7 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 551WL UT WOS:000175586100029 ER PT J AU Wilcox-Adelman, SA Denhez, F Iwabuchi, T Saoncella, S Calautti, E Goetinck, PF AF Wilcox-Adelman, SA Denhez, F Iwabuchi, T Saoncella, S Calautti, E Goetinck, PF TI Syndecan-4: Dispensable or indispensable? SO GLYCOCONJUGATE JOURNAL LA English DT Article DE syndecan-4; cell migration; focal adhesions and cell signaling ID HEPARAN-SULFATE PROTEOGLYCANS; FIBROBLAST-GROWTH-FACTOR; PROTEIN-KINASE-C; FOCAL ADHESION KINASE; CELL-SURFACE PROTEOGLYCAN; ACTIN STRESS FIBERS; BINDING PDZ PROTEIN; SMOOTH-MUSCLE-CELLS; CYTOPLASMIC DOMAIN; DEPENDENT REGULATION AB Studies examining the role of the cell-surface heparan sulfate proteoglycan syndecan-4 have yielded a plethora of information regarding its role in both cell-matrix and growth-factor mediated signaling events. Many of the initial conclusions drawn from such research placed syndecan-4 in a keystone position within various signaling pathways though the generation of syndecan-4 null mice have surprised many in the field by indicating otherwise. These contradictory results place researchers in the frustrating and yet exhilarating position of still asking the question, "What role does syndecan-4 play in life?". C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH E,Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Wilcox-Adelman, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH E,Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. OI CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NICHD NIH HHS [HD-37490] NR 95 TC 17 Z9 17 U1 4 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD MAY-JUN PY 2002 VL 19 IS 4-5 BP 305 EP 313 DI 10.1023/A:1025304602057 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 713EU UT WOS:000184844600011 PM 12975609 ER PT J AU Beresin, E Mellman, L AF Beresin, E Mellman, L TI Competencies in psychiatry: The new outcomes-based approach to medical training and education SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Beresin, E (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bullfinch 449,Fruit St, Boston, MA 02114 USA. NR 7 TC 22 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2002 VL 10 IS 3 BP 185 EP 191 PG 7 WC Psychiatry SC Psychiatry GA 555VV UT WOS:000175814700006 PM 12023933 ER PT J AU Arluke, A Frost, R Luke, C Messner, E Nathanson, J Patronek, GJ Papazian, M Steketee, G AF Arluke, A Frost, R Luke, C Messner, E Nathanson, J Patronek, GJ Papazian, M Steketee, G CA HARC TI Health implications of animal hoarding SO HEALTH & SOCIAL WORK LA English DT Article DE animal; hoarding; pets; self-neglect; squalor AB Animal hoarding is a poorly understood phenomenon, the public health implications of which are not well documented. In this study, professionals dealing with hoarding cases submitted 71 case report forms. The hoarders' residences were characterized by extreme clutter and poor sanitation that impaired ability to maintain functional households. Appliances and utilities were frequently nonfunctional, and animal excrement sometimes accumulated to the extent that the homes were unfit for human habitation. The majority of cases satisfied criteria for adult self-neglect, and dependent elderly people, children, or disabled individuals were present in many of the residences. Animal hoarding may be a sentinel for a range of medical, social, and economic problems. More research addressing the causes and features of animal hoarding is needed to shed light on appropriate interventions. C1 Tufts Univ, Sch Vet Med, Dept Environm & Populat Hlth, North Grafton, MA 01536 USA. Smith Coll, Dept Psychol, Northampton, MA 01063 USA. Massachusetts Soc Prevent Cruelty Anim, Anim Protect Div, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Childrens Hosp, AIDS Program, Boston, MA 02115 USA. Boston Univ, Sch Social Work, Boston, MA 02215 USA. Northeastern Univ, Dept Sociol & Anthropol, Boston, MA 02115 USA. RP Arluke, A (reprint author), Tufts Univ, Sch Vet Med, Dept Environm & Populat Hlth, 200 Westboro Rd, North Grafton, MA 01536 USA. NR 12 TC 10 Z9 10 U1 0 U2 10 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 USA SN 0360-7283 J9 HEALTH SOC WORK JI Health Soc. Work PD MAY PY 2002 VL 27 IS 2 BP 125 EP 136 PG 12 WC Social Work SC Social Work GA 557RK UT WOS:000175921600006 ER PT J AU Ostrow, JD Pascolo, L Tiribelli, C AF Ostrow, JD Pascolo, L Tiribelli, C TI Mechanisms of bilirubin neurotoxicity SO HEPATOLOGY LA English DT Editorial Material ID UNCONJUGATED BILIRUBIN; OXIDATIVE STRESS; RAT ASTROCYTES; SERUM-ALBUMIN; ACTIVATION; APOPTOSIS; RECEPTORS; BINDING; NEURONS; CELLS C1 Univ Washington, Sch Med, GI Hepatol Div, Dept Med, Seattle, WA USA. Univ Trieste, Liver Res Ctr CSF, Trieste, Italy. Univ Trieste, Dept BBCM, Trieste, Italy. VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, Seattle, WA 98108 USA. RP Ostrow, JD (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 29 TC 25 Z9 25 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2002 VL 35 IS 5 BP 1277 EP 1280 DI 10.1053/jhep.2002.33432 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 546YZ UT WOS:000175305800030 PM 11981780 ER PT J AU Liu, AK Dale, AM Belliveau, JW AF Liu, AK Dale, AM Belliveau, JW TI Monte Carlo simulation studies of EEG and MEG localization accuracy SO HUMAN BRAIN MAPPING LA English DT Article DE linear estimation; Bayesian linear inverse; weighted minimum norm; forward problem; inverse problem; fMRI; brain; human ID RESOLUTION ELECTROMAGNETIC TOMOGRAPHY; DIPOLE SOURCE LOCALIZATION; TEMPORAL-LOBE EPILEPSY; SURFACE-BASED ANALYSIS; HUMAN-BRAIN; INTRACRANIAL LOCALIZATIONS; MAGNETIC LOCALIZATION; IMPLANTED SOURCES; SPATIAL-RESOLUTION; CORTICAL ACTIVITY AB Both electroencephalography (EEG) and magnetoencephalography (MEG) are currently used to localize brain activity. The accuracy of source localization depends on numerous factors, including the specific inverse approach and source model, fundamental differences in EEG and MEG data, and the accuracy of the volume conductor model of the head (i.e., the forward model). Using Monte Carlo simulations, this study removes the effect of forward model errors and theoretically compares the use of EEG alone, MEG alone, and combined EEG/MEG data sets for source localization. Here, we use a linear estimation inverse approach with a distributed source model and a realistic forward head model. We evaluated its accuracy using the crosstalk and point spread metrics. The crosstalk metric for a specified location on the cortex describes the amount of activity incorrectly localized onto that location from other locations. The point spread metric provides the complementary measure: for that same location, the point spread describes the mis-localization of activity from that specified location to other locations in the brain. We also propose and examine the utility of a "noise sensitivity normalized" inverse operator. Given our particular forward and inverse models, our results show that 1) surprisingly, EEG localization is more accurate than MEG localization for the same number of sensors averaged over many source locations and orientations; 2) as expected, combining EEG with MEG produces the best accuracy for the same total number of sensors; 3) the noise sensitivity normalized inverse operator improves the spatial resolution relative to the standard linear estimation operator; and 4) use of an a priori fMRI constraint universally reduces both crosstalk and point spread. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02139 USA. RP Belliveau, JW (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02139 USA. RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41-RR 14075, R01-RR 13609]; NINDS NIH HHS [R01-NS 37462, R01-NS 39581] NR 64 TC 205 Z9 206 U1 1 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2002 VL 16 IS 1 BP 47 EP 62 DI 10.1002/hbm.10024 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 547NZ UT WOS:000175339800005 PM 11870926 ER PT J AU Lutskiy, MI Jones, LN Rosen, FS Remold-O'Donnell, E AF Lutskiy, MI Jones, LN Rosen, FS Remold-O'Donnell, E TI An Alu-mediated deletion at Xp11.23 leading to Wiskott-Aldrich syndrome SO HUMAN GENETICS LA English DT Article ID SYNDROME PROTEIN; WASP GENE; EXPRESSION; REARRANGEMENTS; MUTATIONS; CELLS AB Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by thrombocytopenia, eczema and immunodeficiency of varying severity. The WASP gene, mutations of which are responsible for the phenotype, maps to Xp11.23. We describe here a patient with a large deletion in the Xp11.23 region. The deletion, which totals 15.8 kb, begins downstream of DXS1696 and encompasses 13 kb upstream of WASP and includes the distal and proximal promoters and exons 1-6. Analysis of the 5'-boundary region identified sequences missing in the Human Genome database and, as a result, the normal DNA sequence was revised to include 743 bp of novel sequence (AF466616). The patient's upstream breakpoint was localized to an AluSg element within a highly repetitive DNA region containing other Alu elements. A 26-bp recombinogenic element is located downstream of the 5' breakpoint. A 16-bp sequence just upstream of the 5' breakpoint shares close homology with the sequence that spans the 3' breakpoint in intron 6. A heptanucleotide of unknown origin, CAGGGGG, links the 5' and 3' breakpoints. To our knowledge this is the largest deletion in a WAS patient. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 59561] NR 19 TC 10 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2002 VL 110 IS 5 BP 515 EP 519 DI 10.1007/s00439-002-0716-4 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 562HQ UT WOS:000176191700019 PM 12073025 ER PT J AU DeMatteo, RP Heinrich, MC El-Rifai, WM Demetri, G AF DeMatteo, RP Heinrich, MC El-Rifai, WM Demetri, G TI Clinical management of gastrointestinal stromal tumors: Before and after STI-571 SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT National Institute of Health Workshop on Gastrointestinal Stromal Tumors CY APR 02-03, 2001 CL BETHESDA, MARYLAND SP Natl Inst Hlth DE gastrointestinal stromal tumor; sarcoma; STI-571; c-kit proto-oncogene; therapy; chemotherapy; surgery; radiation ID SOFT-TISSUE SARCOMAS; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; SOUTHWEST-ONCOLOGY-GROUP; C-KIT; BCR-ABL; PROGNOSTIC FACTORS; PHASE-II; EUROPEAN-ORGANIZATION; CELL-LINES AB Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Until recently, surgery has been the only effective therapy for GIST. However, even after complete resection of tumor, many patients still eventually die of disease recurrence. Conventional chemotherapy and radiation therapy have been of limited value. Within the last few years, it was discovered that most GISTs have a gain-of-function mutation in the c-kit proto-oncogene. This results in ligand-independent activation of the KIT receptor tyrosine kinase, and an unopposed stimulus for cell growth. STI-571 is a small molecule that selectively inhibits the enzymatic activity of the ABL, platelet-derived growth factor receptor, and KIT tyrosine kinases and the BCR-ABL fusion protein and is a landmark development in cancer therapy. Its clinical development marks a new era of rational and targeted molecular inhibition of cancer that emanates from direct collaborations between scientists and clinicians. It provides proof of the principle that a specific molecular inhibitor can drastically and selectively alter the survival of a neoplastic cell with a particular genetic aberration. The advent of ST71-571 has markedly altered the clinical approach to GIST. It has proven to be effective in metastatic GIST and is also under investigation as a neoadjuvant and adjuvant therapy. C1 Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA. Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. RP DeMatteo, RP (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [CA94503] NR 64 TC 370 Z9 393 U1 3 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2002 VL 33 IS 5 BP 466 EP 477 DI 10.1053/hupa.2002.124123 PG 12 WC Pathology SC Pathology GA 567QB UT WOS:000176494700004 PM 12094371 ER PT J AU Heinrich, MC Rubin, BP Longley, BJ Fletcher, JA AF Heinrich, MC Rubin, BP Longley, BJ Fletcher, JA TI Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations SO HUMAN PATHOLOGY LA English DT Article DE sarcoma; gastrointestinal neoplasm; receptor tyrosine kinase; mutation; KIT; oncogenic; cytogenetics ID RECEPTOR TYROSINE KINASE; STEM-CELL FACTOR; LIGAND-INDEPENDENT ACTIVATION; ACUTE MYELOID-LEUKEMIA; OF-FUNCTION MUTATION; WS/WS MUTANT RATS; C-KIT; INTERSTITIAL-CELLS; GERMLINE MUTATION; JUXTAMEMBRANE DOMAIN AB Recent studies have done much to reveal the biological and genetic underpinnings of gastrointestinal stromal tumors (GISTs). Constitutive activation of the KIT receptor tyrosine kinase is a central pathogenetic event in most GISTs and generally results from oncogenic point mutations which can involve either extracellular or cytoplasmic domains of the receptor. Oncogenic mutations enable the KIT receptor to phosphorylate various substrate proteins, leading to activation of signal transduction cascades which regulate cell proliferation, apoptosis, chemotaxis, and adhesion. KIT mutations can be broadly assigned to 2 groups, those that involve the "regulatory" regions responsible for modulating KIT enzymatic activity and those that involve the enzymatic region itself. In vitro studies suggest that GISTs with regulatory-region KIT mutations are more likely to respond to STI-571 than are GISTs with enzymatic-region mutations. A minority of GISTs lack demonstrable KIT mutations, but KIT is nonetheless strongly activated. Such GISTs might contain KIT mutations which are not readily detected by conventional screening methods, or alternately, KIT might be activated by nonmutational mechanisms. Most GISTs have noncomplex cytogenetic profiles, often featuring deletions of chromosomes 14 and 22. Additional chromosomal aberrations are acquired as the GISTs progress to higher histologic grade. These cytogenetic aberrations are undoubtedly important in GIST pathogenesis, but currently they do not play a key role as diagnostic adjuncts. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Med, Div Hematol Oncol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Univ Washington, Med Ctr, Dept Anat Pathol, Seattle, WA 98195 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 68 TC 308 Z9 331 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2002 VL 33 IS 5 BP 484 EP 495 DI 10.1053/hupa.2002.124124 PG 12 WC Pathology SC Pathology GA 567QB UT WOS:000176494700006 PM 12094373 ER PT J AU Duty, SM Singh, NP Ryan, L Chen, Z Lewis, C Huang, T Hauser, R AF Duty, SM Singh, NP Ryan, L Chen, Z Lewis, C Huang, T Hauser, R TI Reliability of the comet assay in cryopreserved human sperm SO HUMAN REPRODUCTION LA English DT Article DE comet assay; cryopreservation; human sperm; intra-class correlation; reliability ID DOUBLE-STRAND BREAKS; HUMAN SPERMATOZOA; GEL-ELECTROPHORESIS; INDIVIDUAL CELLS; GENETIC-DAMAGE; DNA INTEGRITY; SEMEN; TEMPERATURE; QUALITY AB BACKGROUND: Although the comet assay has potential value for measuring DNA damage in large epidemiological human sperm studies, it is impractical to perform the assay daily on fresh semen samples. Therefore, before its use in epidemiological studies, the reliability of the comet assay in measuring DNA damage in cryopreserved sperm should be compared with that in fresh human sperm. METHODS: Semen samples from 16 men were cryopreserved in liquid nitrogen (LN) using four methods: flash freezing with and without cryopreservative, and programmable freezing with and without cryopreservative. Neutral microgel electrophoresis was performed and comets were stained with YOYO-1. Comet length was measured using an eyepiece micrometer at x400 magnification. RESULTS: The highest correlation was between comet assay results obtained from fresh human semen compared with semen flash frozen without cryopreservative (R = 0.88). However, the method of cryopreservation, as compared with other sources of variability, accounted for only 6% of the variability. Inter-individual variability accounted for 20%, and individual sperm-to-sperm variability within an ejaculate accounted for 65%. CONCLUSIONS: Flash-freezing in LN without cryopreservative most closely reproduced the results obtained using fresh human semen samples, and thereby represents the most appropriate cryopreservation method for human semen in epidemiological studies utilizing the neutral comet assay. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, IVF Unit, Boston, MA 02114 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1 Room 1405,665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIEHS NIH HHS [ES00002, ES09718, T32 ES07069] NR 26 TC 50 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD MAY PY 2002 VL 17 IS 5 BP 1274 EP 1280 DI 10.1093/humrep/17.5.1274 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 548KT UT WOS:000175387700025 PM 11980751 ER PT J AU Lantelme, P Rohrwasser, A Gociman, B Hillas, E Cheng, T Petty, G Thomas, J Xiao, S Ishigami, T Herrmann, T Terreros, DA Ward, K Lalouel, JM AF Lantelme, P Rohrwasser, A Gociman, B Hillas, E Cheng, T Petty, G Thomas, J Xiao, S Ishigami, T Herrmann, T Terreros, DA Ward, K Lalouel, JM TI Effects of dietary sodium and genetic background on angiotensinogen and renin in mouse SO HYPERTENSION LA English DT Article DE angiotensinogen; renin; sodium; mouse; genetics; urine ID PROXIMAL TUBULE; BLOOD-PRESSURE; MESSENGER-RNA; RAT-KIDNEY; EXPRESSION; HYPERTENSION; MECHANISM; MICE; SALT AB Elements of a renin-angiotensin system expressed along the entire nephron, including angiotensinogen secreted by proximal tubule and renin expressed in connecting tubule, may participate in the regulation of sodium reabsorption at multiple sites of the nephron. The response of this tubular renin-angiotensin system to stepwise changes in dietary sodium was investigated in 2 mouse strains, the sodium-sensitive inbred C57BL/6 and the sodium-resistant CD1 outbred. Plasma angiotensinogen was not affected by sodium regimen, whereas plasma renin increased 2-fold under low sodium. In both strains. the variation in urinary parameters did not parallel the changes observed in plasma. Angiotensinogen and renin excretion were significantly higher under high sodium than under low sodium. Water deprivation, by contrast, induced significant activation in the tubular expression of angiotensinogen and renin. C57BL/6 exhibited significantly hi-her Urinary excretion of angiotensinogen than did CD1 animals under both conditions of sodium intake. The extent to which these urinary parameters reflect systemic or tubular responses to challenges of sodium homeostasis may depend on the relative contribution of sodium restriction and volume depletion. C1 Univ Utah, Hlth Sci Ctr, Eccles Inst Human Genet, Dept Human Genet, Salt Lake City, UT 84112 USA. Univ Lyon 1, Lyon, France. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Utah, Dept Pathol, Salt Lake City, UT USA. US Dept Vet Affairs, Salt Lake City, UT USA. RP Lalouel, JM (reprint author), Univ Utah, Hlth Sci Ctr, Eccles Inst Human Genet, Dept Human Genet, Eccles Bldg,6th Floor, Salt Lake City, UT 84112 USA. RI Lantelme, Pierre/B-4567-2013 FU NHLBI NIH HHS [HL-55000, HL-45325, HL-55812] NR 30 TC 74 Z9 75 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2002 VL 39 IS 5 BP 1007 EP 1014 DI 10.1161/01.HYP.0000016177.20565.A0 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 556MJ UT WOS:000175853300012 PM 12019284 ER PT J AU Lee, DU Agarwal, S Rao, A AF Lee, DU Agarwal, S Rao, A TI Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene SO IMMUNITY LA English DT Article ID T-CELL DIFFERENTIATION; DNA CYTOSINE-5 METHYLTRANSFERASES; REPRESS TRANSCRIPTION; HISTONE DEACETYLASE; HELPER CELL; METHYLATION; EXPRESSION; BINDING; COMPLEX; LOCUS AB The relation of CpG methylation to gene silencing is well established, but the contribution of DNA demethylation to gene expression during cell differentiation remains unclear. We show that the IL-4 locus undergoes a complex series of methylation and demethylation steps during T helper cell differentiation. The 5' region of the iL-4 locus is hypermethylated in naive T cells and becomes specifically demethylated in Th2 cells, whereas a highly conserved DNase 1-hypersensitive region at the 3' end shows the converse behavior, being hypomethylated in naive T cells and becoming methylated during Th1 differentiation. 5' demethylation is not required for chromatin remodeling or primary transcription of the IL-4 gene but is strongly associated with efficient, high-level induction of IL-4 transcripts by differentiated Th2 cells. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471, CA09141]; NIAID NIH HHS [AI44432] NR 52 TC 197 Z9 204 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2002 VL 16 IS 5 BP 649 EP 660 DI 10.1016/S1074-7613(02)00314-X PG 12 WC Immunology SC Immunology GA 555YJ UT WOS:000175820400004 PM 12049717 ER PT J AU Buch, T Rieux-Laucat, F Forster, I Rajewsky, K AF Buch, T Rieux-Laucat, F Forster, I Rajewsky, K TI Failure of HY-specific thymocytes to escape negative selection by receptor editing SO IMMUNITY LA English DT Article ID CELL ANTIGEN RECEPTOR; GERM-LINE TRANSCRIPTION; DEVELOPING T-CELLS; J-ALPHA-LOCUS; TRANSGENIC MICE; TCR-ALPHA; POSITIVE SELECTION; V-ALPHA; B-LYMPHOCYTES; GENE SEGMENTS AB Editing of autoreactive antigen receptors by secondary V(D)J recombination efficiently rescues B lymphocyte precursors from apoptosis induced by negative selection, but its role has not been rigorously assessed in T cell development. We therefore generated a transgenic mouse model in which self-reactive thymocytes could edit their TCR by secondary recombination at the TCRalpha locus. For this purpose, the ValphaJalpha exon of a male-specific TCR was inserted into the TCRalpha. locus followed by Cre-IoxP-mediated deletion of the TCRdelta locus. In this model, only few thymocytes escaped negative selection by change of specificity, probably through recombination before encounter of autoantigen. In the absence of the restricting MHC element, however, developing thymocytes replaced the inserted TCRa exon efficiently. C1 Univ Cologne, Genet Inst, D-50931 Cologne, Germany. Hop Necker Enfants Malad, INSERM U429, F-75015 Paris, France. Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Forster, Irmgard/P-8545-2016; Rieux-Laucat, Frederic/A-7916-2017 OI Rieux-Laucat, Frederic/0000-0001-7858-7866 NR 55 TC 55 Z9 56 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2002 VL 16 IS 5 BP 707 EP 718 DI 10.1016/S1074-7613(02)00312-6 PG 12 WC Immunology SC Immunology GA 555YJ UT WOS:000175820400009 PM 12049722 ER PT J AU Travi, BL Osorio, Y Melby, PC Chandrasekar, B Arteaga, L Saravia, NG AF Travi, BL Osorio, Y Melby, PC Chandrasekar, B Arteaga, L Saravia, NG TI Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp. SO INFECTION AND IMMUNITY LA English DT Article ID TRANSFORMING GROWTH-FACTOR; AMERICAN CUTANEOUS LEISHMANIASIS; MESSENGER-RNA EXPRESSION; IFN-GAMMA; INTERFERON-GAMMA; VISCERAL LEISHMANIASIS; DBA/2 MICE; METASTATIC CAPABILITY; MURINE LEISHMANIASIS; CYTOKINE PROFILE AB In regions where leishmaniasis is endemic, clinical disease is usually reported more frequently among males than females. This difference could be due to disparate risks of exposure of males and females, but gender-related differences in the host response to infection may also play a role. Experimental studies of the influence of gender on Leishmania infection have not included parasites of the subgenus Viannia, which is the most common cause of cutaneous leishmaniasis in the Americas. Mice are not readily susceptible to infection by Leishmania (Viannia) spp., but cutaneous infection of hamsters with L. (V.) panamensis or L. (V.) guyanensis resulted in chronic lesions typical of the human disease caused by these parasites. Strikingly, infection of male hamsters resulted in significantly, greater lesion size and severity, an increased rate of dissemination to distant cutaneous sites, and a greater parasite burden in the draining lymph node than infection in female animals. Two lines of evidence indicated this gender-related difference in disease evolution was determined at least in part by the sex hormone status of the animal. First, prepubertal male animals had smaller and/or less severe cutaneous lesions than adult male animals. Second, infection of testosterone-treated female animals resulted in significantly larger lesions than in untreated female animals. The increased severity of disease in male compared to female animals was associated with significantly greater intralesional expression of interleukin-4 (IL-4) (P = 0.04), IL-10 (P = 0.04), and transforming growth factor beta (TGF-beta) (P < 0.001), cytokines known to promote disease in experimental leishmaniasis. There was a direct correlation between the expression of TGF-beta mRNA and lesion size (Spearman's correlation coefficient = 0.873; P < 0.001). These findings demonstrate an inherent risk of increased disease severity, in male animals, which is associated with a more permissive immune response. C1 CIDEIM, Ctr Internacl Entrenamiento & Invest Med, Cali, Colombia. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX USA. RP Travi, BL (reprint author), CIDEIM, Ctr Internacl Entrenamiento & Invest Med, AA5390, Cali, Colombia. NR 39 TC 65 Z9 68 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2002 VL 70 IS 5 BP 2288 EP 2296 DI 10.1128/IAI.70.5.2288-2296.2002 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 543NH UT WOS:000175107700007 PM 11953362 ER PT J AU Cullen, PA Cordwell, SJ Bulach, DM Haake, DA Adler, B AF Cullen, PA Cordwell, SJ Bulach, DM Haake, DA Adler, B TI Global analysis of outer membrane proteins from Leptospira interrogans serovar Lai SO INFECTION AND IMMUNITY LA English DT Article ID IMMOBILIZED PH GRADIENTS; PATHOGENIC LEPTOSPIRA; 2-DIMENSIONAL ELECTROPHORESIS; BORRELIA-BURGDORFERI; MYCOPLASMA-HYOPNEUMONIAE; SUBTYPE HARDJOBOVIS; MAMMALIAN INFECTION; FUNCTIONAL-ANALYSIS; TREPONEMA-PALLIDUM; MOLECULAR-CLONING AB Recombinant leptospiral outer membrane proteins (OMPs) can elicit immunity to leptospirosis in a hamster infection model. Previously characterized OMPs appear highly conserved, and thus their potential to stimulate heterologous immunity is of critical importance. In this study we undertook a global analysis of leptospiral OMPs, which were obtained by Triton X-114 extraction and phase partitioning. Outer membrane fractions were isolated from Leptospira interrogans serovar Lai grown at 20, 30, and 37degreesC with or without 10% fetal calf serum and, finally, in iron-depleted medium. The OMPs were separated by two-dimensional gel electrophoresis. Gel patterns from each of the five conditions were compared via image analysis, and 37 gel-purified proteins were tryptically digested and characterized by mass spectrometry (MS). Matrix-assisted laser desorption ionization-time-of-flight MS was used to rapidly identify leptospiral OMPs present in sequence databases. Proteins identified by this approach included the outer membrane lipoproteins LipL32, LipL36, LipL41, and LipL48. No known proteins from any cellular location other than the outer membrane were identified. Tandem electrospray MS was used to obtain peptide sequence information from eight novel proteins designated pL18, pL21, pL22, pL24, pL45, pL47/49, pL50, and pL55. The expression of LipL36 and pL50 was not apparent at temperatures above 30degreesC or under iron-depleted conditions. The expression of pL24 was also downregulated after iron depletion. The leptospiral major OMP LipL32 was observed to undergo substantial cleavage under all conditions except iron depletion. Additionally, significant downregulation of these mass forms was observed under iron limitation at 30degreesC, but not at 30degreesC alone, suggesting that LipL32 processing is dependent on iron-regulated extracellular proteases. However, separate cleavage products responded differently to changes in growth temperature and medium constituents, indicating that more than one process may be involved in LipL-12 processing. Furthermore, under iron-depleted conditions there was no concomitant increase in the levels of the intact form of LipL32. The temperature- and iron-regulated expression of LipL36 and the iron-dependent cleavage of LipL-32 were confirmed by immunoblotting with specific antisera. Global analysis of the cellular location and expression of leptospiral proteins will be useful in the annotation of genomic sequence data and in providing insight into the biology of Leptospira. C1 Monash Univ, Dept Microbiol, Bacterial Pathogenesis Res Grp, Clayton, Vic 3800, Australia. Macquarie Univ, Australian Proteome Anal Facil, N Ryde, NSW 2109, Australia. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Bacterial Pathogenesis Res Grp, Clayton, Vic 3800, Australia. RI Bulach, Dieter/D-5793-2011 OI Bulach, Dieter/0000-0001-9823-6078 FU NIAID NIH HHS [R01 AI034431, R01 AI034431-06A2] NR 55 TC 132 Z9 154 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2002 VL 70 IS 5 BP 2311 EP 2318 DI 10.1128/IAI.70.5.2311-2318.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 543NH UT WOS:000175107700010 PM 11953365 ER PT J AU Shapiro, S Beenhouwer, DO Feldmesser, M Taborda, C Carroll, MC Casadevall, A Scharff, MD AF Shapiro, S Beenhouwer, DO Feldmesser, M Taborda, C Carroll, MC Casadevall, A Scharff, MD TI Immunoglobulin G monoclonal antibodies to Cryptococcus neoformans protect mice deficient in complement component C3 SO INFECTION AND IMMUNITY LA English DT Article ID MURINE PULMONARY INFECTION; CAPSULAR POLYSACCHARIDE; IMMUNOLOGICAL-UNRESPONSIVENESS; HUMAN MONOCYTES; FC RECEPTOR; BINDING; ACTIVATION; GLUCURONOXYLOMANNAN; PATHWAY; IGG AB Passive administration of monoclonal antibodies (MAbs) to the capsular polysaccharide of Cryptococcus neoformans can alter the course of infection in mice. In a murine model of cryptococcal infection, immunoglobulin G1 (IgG1), IgG2a, and IgG2b switch variants of the anti-capsular 3E5 MAb prolong the survival of lethally infected mice, whereas the 3E5 IgG3 MAb does not protect and in some cases enhances infection, shortening the life spans of infected mice. We examined the role of complement component C3 in Ab-mediated protection by determining the efficacy of the four mouse IgG subclasses against C. neoformans in mice genetically deficient in factor C3 as well as mice acutely depleted of C3. Similar to other complement-deficient animal models, C3(-/-) mice and mice depleted of C3 by cobra venom factor were more susceptible to C. neoformans infection than control mice, providing further evidence that complement is important in the host defense against the fungus. In the absence of C3, all IgG isotypes prolonged the lives of mice infected with C. neoformans, indicating that protection by IgG does not require the complement pathways. Furthermore, we observed protection with IgG3 in the complement-deficient mice, suggesting that complement is involved in the lack of protection observed with IgG3 in other mouse models. C1 Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Immunol & Microbiol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Scharff, MD (reprint author), Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Taborda, Carlos/K-1660-2016 OI Taborda, Carlos/0000-0001-9928-9809 FU NHLBI NIH HHS [HL 59842, R01 HL059842]; NIAID NIH HHS [AI 01434, AI 07506, AI 33774, AI 43937, R01 AI036389, T32 AI007506, R01 AI043937, R01 AI033774, AI36389, AI 13342, AI 01341]; NIGMS NIH HHS [T32 GM007288, T32 GM 07288] NR 58 TC 57 Z9 61 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2002 VL 70 IS 5 BP 2598 EP 2604 DI 10.1128/IAI.70.5.2598-2604.2002 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 543NH UT WOS:000175107700046 PM 11953401 ER PT J AU Mueller, NJ Wilkinson, RA Fishman, JA AF Mueller, NJ Wilkinson, RA Fishman, JA TI Listeria monocytogenes infection in caspase-11-deficient mice SO INFECTION AND IMMUNITY LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; GAMMA-INDUCING FACTOR; MESSENGER-RNA EXPRESSION; NATURAL-KILLER-CELLS; IL-1-BETA-CONVERTING ENZYME; BACTERIAL-INFECTION; YERSINIA-ENTEROCOLITICA; CRYPTOCOCCUS-NEOFORMANS; RESISTANT C57BL/6; APOPTOSIS AB Caspase-11 (Cas11) is a cysteine protease involved in programmed cell death and cytokine maturation. Through activation of Cas1 (interleukin-1beta [IL-1beta]-converting enzyme), Cas11 is directly involved in the maturation of IL-1beta and IL-18. Apoptosis is mediated through Cas3. Given the role of apoptosis and cytokine signaling during the innate immune response in intracellular infection, we examined Cas11-deficient (Cas11(-/-)) mice during infection with Listeria monocytogenes. Cas11(-/-) and wild-type C57BL/6 mice were equally susceptible to intravenous infection with L. monocytogenes, resulting in similar bacterial burdens in tissue and similar survival rates. By contrast, enhanced susceptibility was observed in control mice on a mixed genetic 129/C57BL/DBA2 background, Cas11(-/-) and wild-type mice infected with Listeria had similar hepatic microabscess formation in terms of histologic appearance, size, and number. Apoptosis of L. monocytogenes-infected hepatocytes in vivo and in vitro in primary culture was not altered by the absence of Cas11. Serum IL-18 and IL-1beta levels were similar in Cas11(-/-) mice and controls. Endotoxin (lipopolysaccharide [LPS])challenged Cas11(-/-) mice were deficient in the production of gamma interferon. IL-1beta responses in Cas11(-/-) were normal with intravenous administration of LPS but decreased with intraperitoneal administration. Our findings suggest that Cas11 deficiency does not impair the immune response to infection with L. monocytogenes. Apoptosis and maturation of IL-18 and IL-1beta were normal despite Cas11 deficiency. LPS-induced proinflammatory pathways are altered by the absence of Cas11. While Cas11-mediated Cas1 and Cas3 activation is crucial for cytokine maturation and apoptosis during inflammation, alternative pathways allow normal inflammatory and apoptotic responses during infection with L. monocytogenes. C1 Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 149 13th St,5th Floor, Charlestown, MA 02129 USA. RI Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 NR 45 TC 22 Z9 25 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2002 VL 70 IS 5 BP 2657 EP 2664 DI 10.1128/IAI.70.5.2657-2664.2002 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 543NH UT WOS:000175107700053 PM 11953408 ER PT J AU Deng, J Dekruyff, RH Freeman, GJ Umetsu, DT Levy, S AF Deng, J Dekruyff, RH Freeman, GJ Umetsu, DT Levy, S TI Critical role of CD81 in cognate T-B cell interactions leading to T(h)2 responses SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytokines; knockout; T(h)1/T(h)2; tetraspanins ID TRANSMEMBRANE-4 SUPERFAMILY; COSTIMULATORY RECEPTOR; SUBSET DIFFERENTIATION; MONOCLONAL-ANTIBODIES; CD28-DEFICIENT MICE; SIGNAL-TRANSDUCTION; IMMUNE-RESPONSES; LYMPHOCYTES-B; MOLECULE ICOS; CD28 RECEPTOR AB We previously demonstrated that CD81(-/-) mice fail to develop T(h)2-biased immune responses and allergen-induced airway hyper-reactivity. Because CD81 is expressed on both activated T and on B cells, we examined the role of CD81 expression by each cell type. We established an in vitro system by backcrossing the CD81 deletion to TCR transgenic (Tg) mice and to BCR Tg mice. Here we demonstrate that CD81 expression by T cells is critical for their induction of IL-4 synthesis by B cells. CD81(-/-) TCR Tg T cells were impaired in IL-4 production compared to CD81(+/+) TCR Tg T cells, whereas CD81(-/-) and CD81(+/+) BCR Tg B cells induced equivalent amounts of IL-4 in CD81(+/+) TCR Tg T cells. CD81(-/-) TCR Tg T cells expressed reduced levels of ICOS, GATA-3, STAT6 and phosphorylated STAT6 when activated by antigen-presenting B cells. Taken together, these results indicate that CD81 expression by T cells greatly enhances cognate T-B cell interactions and greatly augments intracellular activation pathways leading to T(h)2 polarization. C1 Stanford Univ, Med Ctr, Dept Med, Div Oncol, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Dept Pediat, Div Immunol & Transplantat Biol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Levy, S (reprint author), Stanford Univ, Med Ctr, Dept Med, Div Oncol, Stanford, CA 94305 USA. FU NIAID NIH HHS [AI45900, 5 T32 AI07290-15] NR 64 TC 51 Z9 52 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 MAY PY 2002 VL 14 IS 5 BP 513 EP 523 DI 10.1093/intimm/14.5.513 PG 11 WC Immunology SC Immunology GA 548KB UT WOS:000175386200009 PM 11978781 ER PT J AU Taneja, A Taylor, CR AF Taneja, A Taylor, CR TI Narrow-band UVB for lichen planus treatment SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID CELLS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gange Photomed Res Ctr, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Taneja, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Gange Photomed Res Ctr, Wellman Labs Photomed,Dept Dermatol, Bar 413,32 Fruit St, Boston, MA 02114 USA. NR 11 TC 25 Z9 29 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAY PY 2002 VL 41 IS 5 BP 282 EP 283 DI 10.1046/j.1365-4362.2002.01499.x PG 2 WC Dermatology SC Dermatology GA 568CU UT WOS:000176525500006 PM 12100704 ER PT J AU Evers, MM Samuels, SC Lantz, M Khan, K Brickman, AM Marin, DB AF Evers, MM Samuels, SC Lantz, M Khan, K Brickman, AM Marin, DB TI The prevalence, diagnosis and treatment of depression in dementia patients in chronic care facilities in the last six months of life SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; dementia; nursing homes ID NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; COGNITIVE IMPAIRMENT; ELDERLY PATIENTS; NATURAL-HISTORY; PSYCHIATRIC-SYMPTOMS; OLDER; RECOGNITION; TRIAL AB Objective To assess the prevalence, diagnosis and treatment of depression among dementia patients and normal controls in chronic care facilities in the last six months of life. Method We reviewed perimortal data concerning dementia severity, depressive symptoms and diagnoses, and medication use for 279 dementia patients and 24 normal controls brought to autopsy through an Alzheimer's Disease Resource Center. Results Major depression was highly prevalent among both dementia patients and normal controls in chronic care facilities in the last six months of life. This depression was under-diagnosed by physicians. Documentation of depressive symptoms by medical support staff has improved over time. However, physician diagnosis of depression has not improved. Recognition of depression was significantly lower for patients with severe dementia. Depression was under-treated in both dementia patients and normal controls, although treatment rates may be increasing. Anxiolytics and hypnotics were often used in lieu of, or in addition to, antidepressant therapy. Conclusions Major depression was highly prevalent in both dementia patients and normal controls, indicating that depression is an important issue for the elderly in the last six months of life irrespective of cognitive status. Under-diagnosis of depression may be an important clinical issue. As physician diagnosis of depression has not improved with time, further physician training and/or awareness initiatives may be warranted. Depression, a treatable cause of excess morbidity and mortality, was undertreated in all groups studied. However, treatment rates may be improving. The prevalent use of anxiolytics and hypnotics for depressed patients is problematic. Copyright (C) 2002 John Wiley Sons, Ltd. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Geriat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Marin, DB (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Box 1230 1 Gustave L Levy pl, New York, NY 10029 USA. FU NIA NIH HHS [AG 05138, AG 02219] NR 72 TC 26 Z9 26 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD MAY PY 2002 VL 17 IS 5 BP 464 EP 472 DI 10.1002/gps.634 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 554NB UT WOS:000175741100010 PM 11994936 ER PT J AU Lechpammer, S Asea, A Mallick, R Zhong, R Sherman, MY Calderwood, SK AF Lechpammer, S Asea, A Mallick, R Zhong, R Sherman, MY Calderwood, SK TI Development of an XTT tetrazolium salt-based assay for detection of specific hyperthermia sensitizers in a high-flux screening programme SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE hyperthermia; hyperthermic sensitizer; quercetin; XTT; microculture tetrazolium assay; drug discovery ID STRESS-INDUCED APOPTOSIS; N-TERMINAL KINASE; HEAT-SHOCK; PROTEIN AGGREGATION; DRUG-SENSITIVITY; CELL-GROWTH; QUERCETIN; HSP70; THERMOTOLERANCE; DENATURATION AB It is now possible to search for new drugs using high-throughput screening of chemical libraries accumulated over the past few years. To detect potential new hyperthermia sensitizers, we are screening for chemical inhibitors of thermotolerance. For the screening of a large chemical library, a rapid and simple assay based on the XTT-tetrazolium salt with the addition of intermediate electron acceptor, phenazine methosulphate (PMS) as a promoter, was developed. It was found that the sensitivity of the XTT/PMS assay is sufficient for assessing thermal cell killing and thermotolerance, although it was highly dependent on cell number and type. When the formazan assay system was challenged with the bioflavonoid drug quercetin (up to 25 mm) and validated against the clonogenic cell survival assay, significant decreases in thermotolerant cell viability were observed, directly reflecting inhibition of thermotolerance. Although short-term assays can, in some instances, underestimate overall cell killing, the dose dependency of inhibition of thermotolerance by quercetin recorded in this study by clonogenic and XTT/PMS assays was similar. Application of the XTT/PMS assay in chemical library screening was highly effective in differentiating potential thermotolerance inhibitors from both chemicals with lack of efficacy and from toxic compounds. Taken together, these results show that the XTT/PMS assay, when carried out under careful conditions, is well suited for primary high-flux screen of many thousands of compounds, thus opening up new areas for discovery of hyperthermia sensitizers. C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Calderwood, SK (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Asea, Alexzander/I-4112-2013 OI Asea, Alexzander/0000-0003-3592-3481 FU NCI NIH HHS [2R01 CA47407-11, 5R01 CA77463-03, 5P01 CA31303-12, 1R01 CA83890-02] NR 35 TC 4 Z9 4 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD MAY PY 2002 VL 18 IS 3 BP 203 EP 215 DI 10.1080/02656730110110034 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 552KY UT WOS:000175620600004 PM 12061330 ER PT J AU McAfee, SL Powell, SN Colby, C Spitzer, TR AF McAfee, SL Powell, SN Colby, C Spitzer, TR TI Dose-escalated total body irradiation and autologous stem cell transplantation for refractory hematologic malignancy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE total body irradiation; escalated dose; autologous stem cell transplant; lymphoma ID ALLOGENEIC MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; PROGNOSTIC FACTORS; MYELOID-LEUKEMIA; RANDOMIZED TRIAL; 1ST REMISSION; REGIMENS; DISEASE; PHASE AB Purpose: To evaluate the feasibility of dose escalation of total body irradiation (TBI) above the previously reported maximally tolerated dose, we have undertaken a Phase I-II trial of dose-escalated TBI with autologous peripheral blood stem cell transplantation (PBSCT) for chemotherapy-refractory lymphoma. Methods and Materials: Nine lymphoma patients with primary refractory disease (PRD) or in resistant relapse (RR) received dose-escalated TBI and PBSCT. The three dose levels of fractionated TBI (200 cGy twice daily) were 1,600 cGy, 1,800 cGy, and 2,000 cGy. Lung blocks were used to reduce the TBI transmission dose by 50%, and the chest wall dose was supplemented to the prescribed dose using electrons. Shielding of the kidneys was performed to keep the maximal renal dose at 1,600 cGy. Three patients, two with non-Hodgkin's lymphoma (NHL) in RR and one with PRD Hodgkin's disease, received 1,600 cGy + PBSCT, three patients (two NHL in RR, one PRD) received 1,800 cGy + PBSCT, and three patients with NHL (two in RR, one PRD) received 2,000 cGy + PBSCT. Results: Toxicities associated with this high-dose TBI regimen included reversible hepatic veno-occlusive disease in 1 patient, Grade 2 mucositis requiring narcotic analgesics in 8 patients, and neurologic toxicities consisting of a symmetrical sensory neuropathy (n = 4) and Lhermitte's syndrome (n = 1). Interstitial pneumonitis developed in 1 patient who received 1,800 cGy after receiving recombinant a-interferon (with exacerbation after rechallenge with interferon). Six (66%) patients achieved a response. Four (44%) patients achieved complete responses, three of which were of a duration greater than I year, and 2 (22%) patients achieved a partial response. One patient remains disease-free more than 5 years posttransplant. Corticosteroid-induced gastritis and postoperative infection resulted in the death of I patient in complete response, 429 days posttransplant. Conclusion: TBI in a dose range 1,600-2,000 cGy as preparative therapy for autologous PBSCT is feasible and has substantial activity in chemorefractory non-Hodgkin's and Hodgkin's lymphoma. (C) 2002 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Bone Marrow Transplant Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Program, Cox 640,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2002 VL 53 IS 1 BP 151 EP 156 AR PII S0360-3016(02)02743-8 DI 10.1016/S0360-3016(02)02743-8 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 548QP UT WOS:000175400500021 PM 12007954 ER PT J AU Smith, MR Kantoff, PW AF Smith, MR Kantoff, PW TI Peroxisome proliferator-activated receptor gamma (PPAR gamma) as a novel target for prostate cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE peroxisome proliferator-activated receptor gamma (PPAR gamma); prostatic neoplasm ID HUMAN BREAST-CANCER; BODY-MASS INDEX; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); ADIPOCYTE DIFFERENTIATION; TERMINAL DIFFERENTIATION; IN-VITRO; LIGAND; GENE; OBESE; PPAR-GAMMA-2 AB Peroxisome proliferator activated receptor-gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. PPARgamma is expressed at high levels in adipose tissue and plays a central role in adipocyte differentiation. Recent studies have implicated PPARgamma in the pathogenesis of several human malignancies. Here we review the evidence that PPARgamma contributes to prostate carcinogenesis and the potential for PPARgamma as a novel therapeutic target for prostate cancer. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 28 TC 24 Z9 25 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD MAY PY 2002 VL 20 IS 2 BP 195 EP 200 DI 10.1023/A:1015670126203 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 555NZ UT WOS:000175801300006 PM 12099579 ER PT J AU Gatinel, D Hoang-Xuan, J Azar, DT AF Gatinel, D Hoang-Xuan, J Azar, DT TI Volume estimation of excimer laser tissue ablation for correction of spherical myopia and hyperopia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID IN-SITU KERATOMILEUSIS; PHOTOREFRACTIVE KERATECTOMY; REFRACTIVE SURGERY; CORNEAL CURVATURE; ECTASIA AB PURPOSE. To determine the theoretical volumes of ablation for the laser treatment of spherical refractive errors in myopia and hyperopia. METHODS. The cornea was modeled as I spherical shell. The ablation profiles for myopia and hyperopia were based on an established paraxial formula. The theoretical Volumes of the ablated corneal lenticules for the correction of myopia and hyperopia were calculated by two methods: (1) mathematical approximation based on a simplified geometric model and (2) finite integration. These results were then compared for optical zone diameters of 0.5 to 11.00 turn and for initial radii of curvature of 7.5, 7.8, and 8.1 mm. RESULTS. Referring to a simplified geometrical model, the volume of ablated corneal tissue was estimated to be proportional to the magnitude of treatment (D) and to the fourth power of the treatment diameter (S-4). For refractive correction of myopia and hyperopia, volume estimations using our formula, V congruent to D (.) (S/9)(4), were similar to those obtained by finite integration for optical zone diameters of 0.5 to 8.5 mm and for corneal radii of curvature within the clinical range (7.5, 7.8, and 8.1 mm). CONCLUSIONS. The theoretical volume of corneal tissue ablated within the optical zone for spherical corrections can be accurately approximated by this simplified formula. This may be helpful in evaluating factors that Contribute to corneal ectasia after LASIK for myopia and hyperopia. Treatment diameter (S) is the most important determinant of the Volume of tissue ablation during excimer laser surgery. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Rothschild Fdn, Paris, France. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu NR 11 TC 18 Z9 18 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 IS 5 BP 1445 EP 1449 PG 5 WC Ophthalmology SC Ophthalmology GA 548FN UT WOS:000175378100025 PM 11980859 ER PT J AU Tuaillon, N Shen, DF Berger, RB Lu, B Rollins, BJ Chan, CC AF Tuaillon, N Shen, DF Berger, RB Lu, B Rollins, BJ Chan, CC TI MCP-1 expression in endotoxin-induced uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ACUTE SEPTIC PERITONITIS; RECEPTOR-DEFICIENT MICE; NECROSIS-FACTOR-ALPHA; LPS-INDUCED UVEITIS; INTERFERON-GAMMA; MESSENGER-RNA; PROTECTS MICE; LIPOPOLYSACCHARIDE AB PURPOSE. Monocyte chemoattractant protein (MCP)-1 (CCL-2) is a chemokine with chemoattractant properties for monocytes, memory T cells, natural killer cells, mast cells, and basophils. To delineate the role played by MCP-1 in acute anterior uveitis, a common ocular inflammation, MCP-/- mice and wild-type matched control mice were analyzed for the development of endotoxin-induced uveitis (EIU) in response to subcutaneous injection of a sublethal dose of lipopolysaccharide (LPS). METHODS. EIU was induced in MCP-1(-/-) and wild-type control mice by a single subcutaneous injection of Salmonella typhimurium LPS endotoxin at day 0. Alternatively, MCP-1(-/-) mice were injected subcutaneously with LPS plus recombinant MCP-1 at day 0 and with recombinant MCP-1 6 hours later. Mice were killed at day I or 3 after injection. Serum levels of IL-1alpha, Il-1beta, IL-6, IFN-gamma, TNF-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1alpha, MIP-2, regulated on activation normal T-cell expressed and secreted (RANTES), and MCP-1 were determined by ELISA. Eyes were collected and analyzed histologically and by RT-PCR for MCP-1, IFN-gamma, IL-6, TNF-alpha, beta-actin, MCP-5, RANTES, KC, inflammatory protein (IP)-10, and toll-like receptor (TLR)-4. RESULTS. EIU was strongly reduced in MCP-1(-/-) mice compared with wild-type control mice. The number of ocular inflammatory cells was significantly reduced. Moreover, intraocular IFN-gamma transcription was increased. EIU was induced in MCP-1(-/-) mice by co-administration of recombinant rat MCP-1 and LPS. CONCLUSIONS. Data indicate that MCP-1 plays a crucial role in the induction of EIU. MCP-1 may be a new therapeutic strategy for acute anterior uveitis. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 48 TC 61 Z9 65 U1 1 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 IS 5 BP 1493 EP 1498 PG 6 WC Ophthalmology SC Ophthalmology GA 548FN UT WOS:000175378100031 PM 11980865 ER PT J AU Renno, RZ Youssri, AI Michaud, N Gragoudas, ES Miller, JW AF Renno, RZ Youssri, AI Michaud, N Gragoudas, ES Miller, JW TI Expression of pigment epithelium-derived factor in experimental choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; ANGIOGENESIS; GENE; SECRETION; DYSTROPHY; MEMBRANES; EYES AB PURPOSE. To investigate the expression of pigment epithelium-derived factor (PEDF) in the rat laser-injury model of choroidal neovascularization (CNV). METHODS. Retinas were immunostained for PEDF at different times (1, 2, and 3 weeks) after laser injury. Levels of PEDF protein in the vitreous at 1, 3, 7, 14, and 28 days after laser injury were also assayed by Western blot. RESULTS. Protein levels of PEDF in the vitreous were increased during the first 7 days after CNV induction. Immunostaining for PEDF was observed throughout normal nonlasered control retinas, sham-lasered retinas, and areas remote to laser lesions, which were generally more intense in the outer nuclear layer (ONL) and less intense in the internal nuclear layer (INL). Decreased expression of PEDF was observed in flanking areas adjacent to the injury site and was confined mainly to the ONL. In the injury sites, immunostaining within the ONL was either absent or decreased for up to 3 weeks after laser injury (the duration of the study). Preadsorption of the anti-PEDF antibody with the immunizing peptide blocked specific labeling in the retina. CONCLUSIONS. These results demonstrate an inverse correlation of expression of PEDF and formation of CNV in the experimental model and suggest that decreased expression of PEDF plays a permissive role in the formation of CNV. PEDF analogues may be a reasonable treatment strategy for CNV. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Retina Res Inst, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Retina Res Inst, 243 Charles St, Boston, MA 02114 USA. EM jwmiller.@meei.harvard.edu NR 31 TC 58 Z9 62 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 IS 5 BP 1574 EP 1580 PG 7 WC Ophthalmology SC Ophthalmology GA 548FN UT WOS:000175378100042 PM 11980876 ER PT J AU Abiko, T Abiko, A Horio, N Clermont, AC Shoelson, BD King, GL Bursell, SE AF Abiko, T Abiko, A Horio, N Clermont, AC Shoelson, BD King, GL Bursell, SE TI Microsphere impaction and retinal hemodynamics SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Eye Res Sect, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1322 BP U299 EP U299 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601276 ER PT J AU Adamian, M Dryja, TP Berson, EL AF Adamian, M Dryja, TP Berson, EL TI Histologic study of dominant retinitis pigmentosa RP13: Comparison with rhodopsin Pro23His,Cys110Arg, and Glu181Lys SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1163 BP U253 EP U253 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601120 ER PT J AU Adamis, AP Poulaki, V Qaum, T Xu, Q Moromizato, Y Bursell, SE Wiegand, SJ Rudge, J Yancopoulos, G Joussen, A AF Adamis, AP Poulaki, V Qaum, T Xu, Q Moromizato, Y Bursell, SE Wiegand, SJ Rudge, J Yancopoulos, G Joussen, A TI Suppression of diabetic retinopathy with angiopoietin-1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, MEEI, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 2965 BP U837 EP U837 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700127 ER PT J AU Afshari, M Afshari, NA D'Amico, DJ AF Afshari, M Afshari, NA D'Amico, DJ TI A study of infected scleral buckles SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Yale Univ, Ctr Eye, Dept Ophthalmol, New Haven, CT USA. Duke Univ, Ctr Eye, Durham, NC USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 652 BP U141 EP U141 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600630 ER PT J AU Allingham, RR Wiggs, JL Hauser, MA LaRocque, KR Broomer, B Graham, FL del Bono, EA Shi, JR Haines, JL Pericak-Vance, MA AF Allingham, RR Wiggs, JL Hauser, MA LaRocque, KR Broomer, B Graham, FL del Bono, EA Shi, JR Haines, JL Pericak-Vance, MA TI Analysis of TJP1 (tight junction protein 1) as a candidate gene for POAG SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3380 BP U959 EP U959 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700531 ER PT J AU Ambati, BK Ambati, J Joussen, AM Anand, A Kuziel, WA Adamis, AP AF Ambati, BK Ambati, J Joussen, AM Anand, A Kuziel, WA Adamis, AP TI Corneal neovascularization: Transient inhibition by genetic ablation of CCR2 and sustained inhibition by CCR5 ablation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Duke Univ, Ctr Eye, Durham, NC USA. Univ Kentucky, Lexington, KY USA. Univ Cologne, Cologne, Germany. Univ Texas, Austin, TX 78712 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1740 BP U399 EP U399 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601696 ER PT J AU Bernardino, CR Chang, EL Fay, AM Rubin, PAD AF Bernardino, CR Chang, EL Fay, AM Rubin, PAD TI Orbital fractures associated with ocular trauma - Clincal features SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3043 BP U853 EP U853 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700194 ER PT J AU Borboli, S Pineda, R AF Borboli, S Pineda, R TI Astigmatic keratotomy for correction of mixed astigmatism after LASIK SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2074 BP U476 EP U476 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602006 ER PT J AU Bressler, NM Friedman, DS Congdon, NG Seddon, JM Klein, R AF Bressler, NM Friedman, DS Congdon, NG Seddon, JM Klein, R TI Public health impact of the age-related eye disease study (AREDS) results SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, AREDS Res Grp, Baltimore, MD 21205 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Wisconsin, Fundus Photog Reading Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 2903 BP U819 EP U819 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700065 ER PT J AU Carrasquillo, KG Ricker, J Rigas, IK Adamis, AP AF Carrasquillo, KG Ricker, J Rigas, IK Adamis, AP TI Controlled delivery of anti-VEGF aptamer EYE001 with poly(lactic-co-glycolic)acid microspheres SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Draper Labs, Scanning Electron Microscopy Lab, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2324 BP U553 EP U553 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602256 ER PT J AU Chang, JH Chang, GY Gabison, EE Fukai, N Azar, DT AF Chang, JH Chang, GY Gabison, EE Fukai, N Azar, DT TI Endostatin-like molecule generated by matrilysin cleavage of collagen type XVIII inhibits vascular endothelial cell proliferation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1867 BP U429 EP U429 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601823 ER PT J AU Chen, CC Chang, JH Savage, J Shatos, MA Gabison, E Kure, D Azar, DT AF Chen, CC Chang, JH Savage, J Shatos, MA Gabison, E Kure, D Azar, DT TI Immunohistological and biochemical characterization of cultured MMP-deficient mouse corneal epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1759 BP U402 EP U402 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601717 ER PT J AU Chew, EY Davis, MD Seddon, JM Clemons, TE Hubbard, LD AF Chew, EY Davis, MD Seddon, JM Clemons, TE Hubbard, LD TI The effect of antioxidant and zinc supplements on change in drusen size/area in the Age-Related Eve Disease Study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI 53706 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EMMES Corp, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1903 BP U437 EP U437 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601846 ER PT J AU Chiao, C Masland, RH AF Chiao, C Masland, RH TI Starburst amacrine cells symmetrically facilitate the responses of direction selective ganglion cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4762 BP U1343 EP U1343 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701916 ER PT J AU Clermont, AC Salti, HI Goddard, LE King, GL Aiello, LP AF Clermont, AC Salti, HI Goddard, LE King, GL Aiello, LP TI Diabetes-induced retinal vascular permeability is both prevented and reversed in vivo by oral administration of PKC-B selective inhibitor LY333531 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3863 BP U1109 EP U1109 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701013 ER PT J AU Collignon, NJ Feke, GT Rizzo, JF AF Collignon, NJ Feke, GT Rizzo, JF TI Optic nerve circulation in unilateral nonarteritic anterior ischemic optic neuropathy and optic neuritis: A new tool for differential diagnosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Retina Associates Fdn, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 910 BP U199 EP U199 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600880 ER PT J AU Cote, J Rosner, B Seddon, JM AF Cote, J Rosner, B Seddon, JM TI Smoking and AMD: Results from a prospective study of men and women SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4391 BP U1265 EP U1265 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701542 ER PT J AU De Erkenez, AC Berson, EL Dryja, TP AF De Erkenez, AC Berson, EL Dryja, TP TI Novel mutations in the PRPC8 gene. Encoding a pre-mRNA splicing factor in patients with autosomal dominant retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 791 BP U169 EP U169 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600765 ER PT J AU DeAngelis, MM Egan, KM Lane, AM Gragoudas, ES Dryja, TP Miller, JW AF DeAngelis, MM Egan, KM Lane, AM Gragoudas, ES Dryja, TP Miller, JW TI Extremely discordant sibpair study of the neovascular form of age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1842 BP U423 EP U423 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601800 ER PT J AU Dryja, TP Jian-Seyed-Ahmadi, B Rivolta, C Keene, J Berson, EL AF Dryja, TP Jian-Seyed-Ahmadi, B Rivolta, C Keene, J Berson, EL TI Mutations in the USH2A gene are a frequent cause of recessive nonsyndromic retinitis pigmentosa as well as Usher syndrome type II SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 795 BP U170 EP U170 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600770 ER PT J AU Durrani, K Foster, CS AF Durrani, K Foster, CS TI Intravenous pulse cyclophosphamide for treatment of ocular inflammatory disease: Efficacy and outcomes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3973 BP U1141 EP U1141 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701126 ER PT J AU Esser, PJ Joussen, AM Poulaki, V Stechschulte, SU Kirchhof, B Dart, D Fang, GH Wiegand, SJ Yancopoulos, GD Adamis, AP AF Esser, PJ Joussen, AM Poulaki, V Stechschulte, SU Kirchhof, B Dart, D Fang, GH Wiegand, SJ Yancopoulos, GD Adamis, AP TI VEGF-dependent conjunctivation of the corneal surface SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Cologne, Dept Vitreoretinal Surg, D-5000 Cologne 41, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3165 BP U877 EP U877 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700317 ER PT J AU Feke, GT Pasquale, LR McMeel, JW AF Feke, GT Pasquale, LR McMeel, JW TI Retinal hemodynamic autoregulation during postural change SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Schepens Retina Associates Fdn, Boston, MA USA. Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 841 BP U181 EP U181 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600816 ER PT J AU Figueiredo, DR Finzi, SF Rogers, K DelBono, EL Haines, JL Wiggs, JL AF Figueiredo, DR Finzi, SF Rogers, K DelBono, EL Haines, JL Wiggs, JL TI CYP1B1 mutations in Brazilian and American patients with congenital glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3395 BP U961 EP U961 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700547 ER PT J AU Fishman, GA Grimsby, JL De Erkenez, A Dryja, TP AF Fishman, GA Grimsby, JL De Erkenez, A Dryja, TP TI Fundus changes in heterozygote carriers in a family with novel mutations in the RLBP1 (CRALBP) gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Illinois, Chicago, IL USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1192 BP U274 EP U274 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601147 ER PT J AU Flynn, MF Fishman, GA Yamamoto, H Grimsby, JL Dryja, TP AF Flynn, MF Fishman, GA Yamamoto, H Grimsby, JL Dryja, TP TI Novel CRALBP mutations associated with retinitis punctata albescens: Further evidence of genetic heterogeneity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Illinois Coll Optometry, Illinois Eye Inst, Chicago, IL USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1196 BP U275 EP U275 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601152 ER PT J AU Foster, C Durrani, K AF Foster, C Durrani, K TI Psoriatic uveitis: An established clinical entity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4254 BP U1204 EP U1204 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701408 ER PT J AU Fuhr, PS Chung, KH Holmes, LD Mitchell, S Wesley, JD McIntosh, E Elliott, JL Kuyk, TK AF Fuhr, PS Chung, KH Holmes, LD Mitchell, S Wesley, JD McIntosh, E Elliott, JL Kuyk, TK TI Estimations of functional vision correlate with NEI VFQ SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama, Sch Optometry, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3813 BP U1051 EP U1051 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700965 ER PT J AU Gatinel, D Azar, DT Maler, J Hoang-Xuan, T AF Gatinel, D Azar, DT Maler, J Hoang-Xuan, T TI Theoretical analysis of the maximal SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Fdn Adolphe De Rothschild, Paris, France. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Univ Paris 06, Inst Stat, Paris, France. Univ Paris 07, Hop Bichat, Fdn Rothschild, Serv Ophtalmol, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3944 BP U1133 EP U1133 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701095 ER PT J AU Gauthier, D Husain, D Kim, IK Ezra, E Tsilimbaris, MK Connolly, E Lane, AM Gragoudas, ES O'Neill, CA Miller, JW AF Gauthier, D Husain, D Kim, IK Ezra, E Tsilimbaris, MK Connolly, E Lane, AM Gragoudas, ES O'Neill, CA Miller, JW TI Safety and efficacy of intravitreal injection of rhuFab VEGF in combination with verteporfin PDT on experimental choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Angiogenesis Lab, Boston, MA USA. Genentech Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 566 BP U113 EP U113 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600544 ER PT J AU Goddard, LE Clermont, AC Bursell, D Jones-Bolin, S Ruggeri, B Bursell, SE AF Goddard, LE Clermont, AC Bursell, D Jones-Bolin, S Ruggeri, B Bursell, SE TI Retinal vascular leakage in early diabetes is normalized in vivo by the oral VEGF receptor kinase inhibitor, CEP-7055 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Cephalon Inc, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3862 BP U1109 EP U1109 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701015 ER PT J AU Goldstein, LE Muffat, JA Cherny, RA Coccia, JA Delalle, I Ericsson, MH Moir, RD Tanzi, RE Bush, AI Chylack, LT AF Goldstein, LE Muffat, JA Cherny, RA Coccia, JA Delalle, I Ericsson, MH Moir, RD Tanzi, RE Bush, AI Chylack, LT TI Beta-amyloid promotes lens protein aggregation and is associated with supranuclear lens opacification SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Ophthalm Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neuropathol, Charlestown, MA USA. Massachusetts Gen Hosp, Genet & Aging Unit, Lab Oxidat Biol, Charlestown, MA USA. Univ Melbourne, Melbourne, Vic, Australia. RI Muffat, Julien/P-2298-2014; Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4802 BP U1352 EP U1352 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701954 ER PT J AU Gosiengfiao, DH Latina, MA Tumbocon, JA Frenkel, RE AF Gosiengfiao, DH Latina, MA Tumbocon, JA Frenkel, RE TI A crossover study to evaluate the effect of topical dorzolamide and brimonidine on ocular blood flow in patients with primary open angle glaucoma using the heidelberg retinal flowmeter SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Tufts Univ, Boston, MA 02111 USA. Univ Toronto, Toronto, ON, Canada. E Florida Eye Inst, Stuart, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3316 BP U907 EP U907 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700468 ER PT J AU Grimsby, JL Berson, EL Dryja, TP AF Grimsby, JL Berson, EL Dryja, TP TI Mutation screening of the USH3A gene in patients with retinitis pigmentosa with partial hearing loss SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 796 BP U170 EP U170 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600773 ER PT J AU Grosskreutz, CL Luukkaa, VA Pantcheva, MB Poulin, NR AF Grosskreutz, CL Luukkaa, VA Pantcheva, MB Poulin, NR TI Activation of caspase 9 in a rat model of experimental glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4058 BP U1163 EP U1163 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701209 ER PT J AU Gupta, NK Hoo, BKD Simon, JW Walton, DS AF Gupta, NK Hoo, BKD Simon, JW Walton, DS TI Heterochromia in patients with glaucoma in Sturge-Weber Syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Albany Med Coll, Albany, NY 12208 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 286 BP U55 EP U55 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600261 ER PT J AU Hatton, MP Gregory, MS Perez, VL Ksander, BR AF Hatton, MP Gregory, MS Perez, VL Ksander, BR TI Rejection of conjunctival tumors using pro-inflammatory signals SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1114 BP U243 EP U243 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601072 ER PT J AU Horikawa, Y Shatos, MA Hodges, RR Zoukhri, D Rios-Garcia, JD Rubin, PAD Chang, EL Dartt, DA AF Horikawa, Y Shatos, MA Hodges, RR Zoukhri, D Rios-Garcia, JD Rubin, PAD Chang, EL Dartt, DA TI Comparison of activation of mitogen-activated protein kinase by cholinergic agonists and epidermal growth factor in human and rat cultured conjunctival goblet cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3163 BP U876 EP U876 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700313 ER PT J AU Horio, N Clermont, AC Shoelson, BD Abiko, T Feener, EP Bursell, SE AF Horio, N Clermont, AC Shoelson, BD Abiko, T Feener, EP Bursell, SE TI Impaired endothelium-dependent vasodilatory response in diabetic rats is ameliorated with angiotensin type 1 receptor blockage using candesartan SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1333 BP U301 EP U301 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601290 ER PT J AU Ishida, S Yamashiro, K Usui, T Kaji, Y Ahmed, E Adamis, AP AF Ishida, S Yamashiro, K Usui, T Kaji, Y Ahmed, E Adamis, AP TI ICAM-1 blockade leads to suppression of retinal leukostasis in established diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Retina Res Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1325 BP U300 EP U300 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601283 ER PT J AU Jain, S Chang, MA Azar, DT AF Jain, S Chang, MA Azar, DT TI Infections following LASIK surgery: an integration of published literature SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2118 BP U485 EP U485 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602051 ER PT J AU Javier, JD Lee, JB Chang, JH Kato, T Fukai, N Olsen, B Azar, NF AF Javier, JD Lee, JB Chang, JH Kato, T Fukai, N Olsen, B Azar, NF TI Immunohistochemical characterization of developing eyes of type XVIII collagen knockout mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3221 BP U889 EP U889 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700373 ER PT J AU Jensen, RJ Ziv, OR Rizzo, JF AF Jensen, RJ Ziv, OR Rizzo, JF TI Effect of Epiretinal vs transretinal in vitro electrical stimulation of rabbit retinal ganglion cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Ctr Innovat Visual Rehabil, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4473 BP U1282 EP U1282 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701624 ER PT J AU Joussen, AM Poulaki, V Dohmen, S Koizumi, K Kirchhof, B Adamis, AP AF Joussen, AM Poulaki, V Dohmen, S Koizumi, K Kirchhof, B Adamis, AP TI Non-steroid alanti-inflammatory drugs prevent early diabetic retinopathy: Aspirinand COX-2 inhibition prevent blood-retinal barrier breakdown and leukocyte adhesion via TNF-asuppression SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Ctr Ophthalmol, Dept Virreoretinal Surg, Cologne, Germany. Massachusetts Eye & Ear Infirm, Retina Res Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 2969 BP U837 EP U837 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700129 ER PT J AU Kalayoglu, MV Galvan, CA Mahdi, OS Byrne, GI Mansour, S AF Kalayoglu, MV Galvan, CA Mahdi, OS Byrne, GI Mansour, S TI Serological association between Chlamydia pneumoniae infection and age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Ophthalmol, Palo Alto, CA 94304 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2818 BP U656 EP U656 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602750 ER PT J AU Kato, T Chang, JH Azar, DT AF Kato, T Chang, JH Azar, DT TI Expression of type XVIII collagen during wound healing of corneal incisions and keratectomy wounds SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4231 BP U1198 EP U1198 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701381 ER PT J AU King, GL AF King, GL TI Identification of IRS2's critical role in retinal development and degeneration in transgenic mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2715 BP U634 EP U634 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602647 ER PT J AU Ko, TH Drexler, W Hartl, I Ghanta, RK Paunescu, LA Schuman, JS Stur, M Bursell, SE Fujimoto, JG AF Ko, TH Drexler, W Hartl, I Ghanta, RK Paunescu, LA Schuman, JS Stur, M Bursell, SE Fujimoto, JG TI Ultrahigh resolution optical coherence tomography for imaging and quantification of retinal pathology SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 MIT, Cambridge, MA 02139 USA. Univ Vienna, Inst Med Phys, A-1010 Vienna, Austria. Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. Gen Hosp Vienna, Dept Ophthalmol, Vienna, Austria. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2561 BP U601 EP U601 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602493 ER PT J AU Koizumi, K Doehmen, S Welsandt, G Kirchhof, B Poulaki, V Joussen, AM AF Koizumi, K Doehmen, S Welsandt, G Kirchhof, B Poulaki, V Joussen, AM TI The TNF-alpha inhibitor Enbrel reduces leukocyte adhesion, vascular leakage and apoptotic cell death in endotoxin induced uveitis in vivo SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Cologne, Dept Vitreoretinal Surg, Eye Clin, Cologne, Germany. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1557 BP U346 EP U346 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601513 ER PT J AU Krause, M Xiong, J Gragoudas, ES Young, LHY AF Krause, M Xiong, J Gragoudas, ES Young, LHY TI Treatment of experimental choroidal melanoma with a Nd : YLF laser at 1047 nm SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Saarland, Dept Ophthalmol, D-6650 Homburg, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1152 BP U251 EP U251 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601109 ER PT J AU Latina, MA Gosiengfiao, DH Frenkel, RE Tumbocon, JA AF Latina, MA Gosiengfiao, DH Frenkel, RE Tumbocon, JA TI The effect of topical dorzolamide on ocular blood flow in patients with normal tension glaucoma using the Heidelberg retinal flowmeter SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Reading Hlth Ctr, Reading, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. E Florida Eye Inst, Stuart, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 322 BP U62 EP U62 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600296 ER PT J AU Le, LM Poulaki, V Lappas, A Kirchhof, B Joussen, AM AF Le, LM Poulaki, V Lappas, A Kirchhof, B Joussen, AM TI Activin A and VEGF are coregulated in choriodal neovascular membranes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Cologne, Ctr Ophthalmol, Cologne, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1302 BP U295 EP U295 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601259 ER PT J AU Lee, JB Javier, JA Chang, JH Gabison, E Kato, T Kure, T Azar, DT AF Lee, JB Javier, JA Chang, JH Gabison, E Kato, T Kure, T Azar, DT TI Corneal neovascularization following excimer laser-assisted hemi-limbal deficiency in wild-type and MMP-knockout mouse corneas SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1756 BP U401 EP U401 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601710 ER PT J AU Lee, RH Ng, PS Yu, H AF Lee, RH Ng, PS Yu, H TI Multisite and hierarchical phosphorylation in light regulation of phosducin phosphorylation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Calif Los Angeles, Mol Neurobiol Lab, Los Angeles, CA 90024 USA. VA Greater LA Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1390 BP U312 EP U312 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601346 ER PT J AU Lin, CP Alt, C Schnell, S Framme, C Schuele, G Brinkmann, R AF Lin, CP Alt, C Schnell, S Framme, C Schuele, G Brinkmann, R TI Selective targeting of the retinal pigment epithelium in vivo using a laser scanner SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Med Laser Ctr, Lubeck, Germany. RI Brinkmann, Ralf/E-6701-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2533 BP U595 EP U595 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602466 ER PT J AU Loewenstein, JI Rizzo, JF Montezuma, SR AF Loewenstein, JI Rizzo, JF Montezuma, SR TI Implantation of subretinal polyimide in Yucatan pigs SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol Retina, Boston, MA 02114 USA. VA Ctr Innovat Rehabil, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4459 BP U1280 EP U1280 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701611 ER PT J AU Maselli, M Lynch, S Yanagi, G Shi, JR DelBono, EL Haines, JL Wiggs, JL AF Maselli, M Lynch, S Yanagi, G Shi, JR DelBono, EL Haines, JL Wiggs, JL TI Genomic screen for genes responsible for early onset open angle glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Program Human Genet, Sch Med, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3396 BP U962 EP U962 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700548 ER PT J AU McGee, TL Berson, EL Dryja, TP AF McGee, TL Berson, EL Dryja, TP TI Identification of novel mutations in the PRPF31 gene (RP11) in patients with autosomal dominant retinitis pigmentosa with reduced penetrance SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 792 BP U169 EP U169 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600768 ER PT J AU McMullen, TB Frizzell, N Moore, JE Poulaki, V Campbell, JL Afshari, NA Kaji, Y Stitt, AW Archer, DB Adamis, AP AF McMullen, TB Frizzell, N Moore, JE Poulaki, V Campbell, JL Afshari, NA Kaji, Y Stitt, AW Archer, DB Adamis, AP TI A modulatory role for advanced glycation end-products (AGEs) in retinal microvascular leukostasis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1348 BP U304 EP U304 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601304 ER PT J AU Meniconi, ME Yu, EN Tufail, F Christen, WG Foster, CS AF Meniconi, ME Yu, EN Tufail, F Christen, WG Foster, CS TI Outcomes of treatment with immunomodulatory therapy in juvenile idiopathic arthritis-associated chronic iridocyclitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4274 BP U1207 EP U1207 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701427 ER PT J AU Mian, SI Borboli, S Al-Murjan, J Stechschulte, SU Paton, B Azar, DT AF Mian, SI Borboli, S Al-Murjan, J Stechschulte, SU Paton, B Azar, DT TI Moraxella catarrhalis keratitis: Risk factors. Outcomes, and complications SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1605 BP U354 EP U354 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601561 ER PT J AU Montezuma, SR Rizzo, JF Ziv, OR AF Montezuma, SR Rizzo, JF Ziv, OR TI Differential recovery of ERG and VEP following vitreoretinal surgery: Implications for acute testing of an implanted retinal prosthesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4477 BP U1283 EP U1283 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701629 ER PT J AU Moore, JE McMullen, CBT Cambell, IL Rohan, R Afshari, NA Kaji, Y Usui, T Archer, DB Adamis, AP AF Moore, JE McMullen, CBT Cambell, IL Rohan, R Afshari, NA Kaji, Y Usui, T Archer, DB Adamis, AP TI The inflammatory milieu with conjunctivalised cornea and its alteration using IL-1 Ra gene therapy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Queens Univ Belfast, Belfast, Antrim, North Ireland. Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. Scripps Res Inst, La Jolla, CA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 28 BP U1 EP U1 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600003 ER PT J AU Mucciolo, JT Frenkel, REP Latina, MA Gosengfiao, D Tumbocon, JA AF Mucciolo, JT Frenkel, REP Latina, MA Gosengfiao, D Tumbocon, JA TI Comparison of two image acquisition protocols for scanning laser Doppler Flowmetry in a glaucoma population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 E Florida Eye Inst, Eye Res Fdn, Stuart, FL USA. Tufts Univ, Med Ctr, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 335 BP U64 EP U64 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600311 ER PT J AU Nguyen, Q Do, DV Letko, E Hirose, T Foster, CS AF Nguyen, Q Do, DV Letko, E Hirose, T Foster, CS TI Unilateral chorioretinitis and subretinal neovascularization associated with eosinophilic enteritis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Wilmer Eye Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4289 BP U1211 EP U1211 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701443 ER PT J AU Obritsch, WF Coloso, SJ Van Remmen, H Yang, J Gregerson, DS Ferrington, DA AF Obritsch, WF Coloso, SJ Van Remmen, H Yang, J Gregerson, DS Ferrington, DA TI Increased apoptosis in retinal pigment epithelial cells with reduced antioxidant enzymes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Minnesota, Minneapolis, MN USA. Grecc S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 674 BP U147 EP U147 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600649 ER PT J AU Olson, PF Bajart, AM Choi, JJ Fini, ME AF Olson, PF Bajart, AM Choi, JJ Fini, ME TI Congenital Hereditary Stromal Dystrophy is not caused by a defect in the lumican gene SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Tufts Univ, New England Med Ctr, Ctr Vis Res, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 2872 BP U809 EP U809 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700032 ER PT J AU Pantcheva, MB Poulin, NR Luukkaa, VA Grosskreutz, CL AF Pantcheva, MB Poulin, NR Luukkaa, VA Grosskreutz, CL TI Death receptor complex formation after optic nerve crush in rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4054 BP U1162 EP U1162 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701204 ER PT J AU Papaliodis, GN Perez, VL Foster, C AF Papaliodis, GN Perez, VL Foster, C TI Elevated IL-6 levels in the nitreous of patients with active posterior uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4248 BP U1203 EP U1203 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701402 ER PT J AU Pasquale, LR Kang, J Willett, W Rosner, B Faberowski, N Hankinson, S AF Pasquale, LR Kang, J Willett, W Rosner, B Faberowski, N Hankinson, S TI Dietary fat consumption and primary open-angle glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 2944 BP U831 EP U831 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700106 ER PT J AU Pawlyk, BS Lee, H Wooten, BR Berson, EL Sandberg, MA AF Pawlyk, BS Lee, H Wooten, BR Berson, EL Sandberg, MA TI Ocular function and macular pigment density in non-syndromic retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Brown Univ, Walter S Hunter Lab Psychol, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1202 BP U276 EP U276 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601158 ER PT J AU Perez, VL AF Perez, VL TI Membrane Fas ligand induces while soluble Fas ligand blocks neutrophil medicated inflammation. Apoptosis and scar formation in the cornea stroma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1951 BP U449 EP U449 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601889 ER PT J AU Poulaki, V Joussen, AM Mitsiades, N Adamis, AP AF Poulaki, V Joussen, AM Mitsiades, N Adamis, AP TI The role of IGF-I in the pathogenesis of diabetic retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 2966 BP U837 EP U837 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700130 ER PT J AU Radetzky, S Joussen, AM Kirchhof, B Poulaki, V AF Radetzky, S Joussen, AM Kirchhof, B Poulaki, V TI Activin A stimulates inflammatory corneal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Cologne, Ctr Ophthalmol, D-5000 Cologne 41, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1862 BP U429 EP U429 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601818 ER PT J AU Razzaque, MS Foster, CS Ahmed, AR AF Razzaque, MS Foster, CS Ahmed, AR TI Possible role of conjunctival fibroblast-secreted m-CSF in the recruitment of macrophages in ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3153 BP U875 EP U875 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700305 ER PT J AU Renno, R Terada, Y Haddadin, MJ DeLori, FC Gragoudas, ES Miller, JW AF Renno, R Terada, Y Haddadin, MJ DeLori, FC Gragoudas, ES Miller, JW TI Selective targeting of verteporfin to choroidal neovascularization mediated by a homing peptide to VEGF-R2 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Angiongeneris & Laser Lab, Boston, MA 02114 USA. Amer Univ Beirut, Dept Chem, Beirut, Lebanon. Harvard Univ, Schepens Eye Res Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3977 BP U1143 EP U1143 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701129 ER PT J AU Rigas, IK Ahmed, E Ambati, J Carrasquillo, KG Gragoudas, ES Miller, JW Adamis, AP AF Rigas, IK Ahmed, E Ambati, J Carrasquillo, KG Gragoudas, ES Miller, JW Adamis, AP TI Pulsatile transscleral drug delivery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2301 BP U519 EP U519 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602233 ER PT J AU Rivolta, C Berson, EL Dryja, TP AF Rivolta, C Berson, EL Dryja, TP TI Uniparental primary heterodisomy with bitelomeric isodisomyh of chromosome 1 in a patient with onsyndromic retinitis pigmentosa and a mutation in the Usher syndrome gene USH2A SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2401 BP U570 EP U570 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602331 ER PT J AU Rizzo, JF Montezuma, SR Ziv, OR AF Rizzo, JF Montezuma, SR Ziv, OR TI Effect of Epiretinal vs transretinal in vivo electrical stimulation of rabbit retina on the amplitude of evoked cortical potentials SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4484 BP U1284 EP U1284 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701638 ER PT J AU Roessler, GF Goette, M Adamis, AP Bernfield, M Kirchhof, B Joussen, AM AF Roessler, GF Goette, M Adamis, AP Bernfield, M Kirchhof, B Joussen, AM TI Lack of syndecan-1 promotes leukocyte endothelial interactions in the ocular vasculature SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Cologne, Dept Ophthalmol, Cologne, Germany. Univ Munster, Dept Physiol Chem, D-4400 Munster, Germany. Massachusetts Eye & Ear Infirm, Retina Res Lab, Boston, MA 02114 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 2749 BP U641 EP U641 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606602681 ER PT J AU Rosenblatt, MI Chang, JH Chen, CC Azar, DT AF Rosenblatt, MI Chang, JH Chen, CC Azar, DT TI Gene transfer into mouse corneal epithelial cell lines using an ecdysone regulated ecotropic retroviral vector system SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1980 BP U457 EP U457 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601920 ER PT J AU Salti, HI Clermont, AC Duh, E Goddard, L Aiello, LP AF Salti, HI Clermont, AC Duh, E Goddard, L Aiello, LP TI Diabetes-induced retinal vascular permeability is reversed by intravitreal injection of pigment epithelial derived factor SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3864 BP U1109 EP U1109 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701016 ER PT J AU Sandberg, MA Rosner, B Weigel-DiFranco, C Dryja, TP Berson, EL AF Sandberg, MA Rosner, B Weigel-DiFranco, C Dryja, TP Berson, EL TI Retinitis pigmentosa due to dominant rhodopsin mutations: Rates of progression correlate with location of affected amino acid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3949 BP U1135 EP U1135 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701101 ER PT J AU Schwartz, B Takamoto, T Zarbin, M Bhagat, N Young, L Rosen, R AF Schwartz, B Takamoto, T Zarbin, M Bhagat, N Young, L Rosen, R TI Contour map of diabetic macular edema SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Glaucoma Res Inc, Boston, MA USA. Univ Med & Dent New Jersey, Newark, NJ USA. Massachusetts Eye & Ear Infirm, Boston, MA USA. New York Eye & Ear Infirm, New York, NY 10003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 541 BP U107 EP U107 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600517 ER PT J AU Seddon, JM Chew, EY Klein, R Clemons, TE AF Seddon, JM Chew, EY Klein, R Clemons, TE TI Is cholesterol a risk factor for progression to advanced AMD? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1904 BP U437 EP U437 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601849 ER PT J AU Sharon, D Sandberg, MA Berson, EL Dryja, TP AF Sharon, D Sandberg, MA Berson, EL Dryja, TP TI Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and clumped pigmentary retinal degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 809 BP U172 EP U172 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600783 ER PT J AU Shatos, MA Rubin, P Chang, E Dartt, DA AF Shatos, MA Rubin, P Chang, E Dartt, DA TI Characterization of potential stem cells front human conjunctiva SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3159 BP U876 EP U876 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700311 ER PT J AU Shire, DB Rizzo, JF Loewenstein, J AF Shire, DB Rizzo, JF Loewenstein, J TI Micromachined tacks to attach a prosthesis to the retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4482 BP U1283 EP U1283 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701634 ER PT J AU Sippel, KC Rizzo, JF AF Sippel, KC Rizzo, JF TI Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) with unexplained visual loss SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 178 BP U31 EP U31 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600155 ER PT J AU Sohelian, M Markomichelakis, NN Chatzistefanou, KI Dafni, U Christen, WG Lopez, BR Durrani, K Foster, CS AF Sohelian, M Markomichelakis, NN Chatzistefanou, KI Dafni, U Christen, WG Lopez, BR Durrani, K Foster, CS TI Intermediate uveitis: Prognostic factors and course of the disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Sch Hlth Sci, Dept Publ Hlth, Athens, Greece. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4259 BP U1205 EP U1205 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701411 ER PT J AU Sotiropoulos, K AF Sotiropoulos, K TI Protein kinase C (PKC) activation in circulating mononuclear cells - Potential surrogate marker for diabetic retinopathy and other microangiopathic diseases SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 557 BP U110 EP U110 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600534 ER PT J AU Sun, JK Rizzo, JF AF Sun, JK Rizzo, JF TI Delayed visual recovery associated with hyperbaric oxygen treatment after retinal artery occlusion SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 533 BP U106 EP U106 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600509 ER PT J AU Terada, Y Zacks, DN Connolly, EJ Michaud, N Gragoudas, ES Miller, JW AF Terada, Y Zacks, DN Connolly, EJ Michaud, N Gragoudas, ES Miller, JW TI Modified verteporfin photodynamic therapy (PDT), PDT combined with angiostatin in vitro and in vivo SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv,Angiogenesis & Laser Res Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 574 BP U114 EP U114 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606600551 ER PT J AU Thakker, MM AF Thakker, MM TI Results of retinal detachment surgery in zones I, II, and III open globe injuries SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4499 BP U1288 EP U1288 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701652 ER PT J AU Tsilimbaris, MK Lit, ES Christoforides, J D'Amico, DJ AF Tsilimbaris, MK Lit, ES Christoforides, J D'Amico, DJ TI Feasibility of retinal microvascular surgery SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Crete, Sch Med, Iraklion, Greece. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3509 BP U985 EP U985 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700660 ER PT J AU Tufail, F Yu, E Foster, CS AF Tufail, F Yu, E Foster, CS TI Mycophenolate mofetil as an immunomodulatory agent in the treatment or chronic ocular inflammatory disorders SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3971 BP U1141 EP U1141 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701125 ER PT J AU Usui, T Kaji, Y Yamashiro, K Ishida, S Isner, JM Asahara, T Adamis, AP AF Usui, T Kaji, Y Yamashiro, K Ishida, S Isner, JM Asahara, T Adamis, AP TI ICAM-1/CD18 dependent recruitment of endothelial progenitor cells to sites of inflammatory corneal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1763 BP U402 EP U402 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601719 ER PT J AU Waheed, NK Tufail, F Chu, D Miserocchi, E Foster, C AF Waheed, NK Tufail, F Chu, D Miserocchi, E Foster, C TI A double-blind randomized controlled trial to assess the efficacy of Enbrel versus placebo in preventing relapses of chronic or recurrent uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4285 BP U1209 EP U1209 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701436 ER PT J AU Wiggs, JL Allingham, RR Shi, JR Graham, FL Auguste, J Hauser, M Broomer, B DelBono, EA Pericak-Vance, M Haines, JL AF Wiggs, JL Allingham, RR Shi, JR Graham, FL Auguste, J Hauser, M Broomer, B DelBono, EA Pericak-Vance, M Haines, JL TI Identification and analysis of POAG candidate genes located on chromosome 14 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Duke Univ, Ctr Med, Ctr Human Genet, Durham, NC USA. Vanderbilt Univ, Program Human Genet, Sch Med, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 3394 BP U961 EP U961 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606700544 ER PT J AU Xiong, J Krause, M Kwong, KK Gragoudas, ES Young, LHY AF Xiong, J Krause, M Kwong, KK Gragoudas, ES Young, LHY TI MRI of blood volume with MS 325 in experimental choroidal melanoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA USA. Univ Saarland, Dept Ophthalmol, D-6650 Homburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1138 BP U248 EP U248 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601093 ER PT J AU Yamashiro, K Ishida, S Usui, T Kaji, Y Honda, Y Ogura, Y Adamis, AP AF Yamashiro, K Ishida, S Usui, T Kaji, Y Honda, Y Ogura, Y Adamis, AP TI Platelet accumulation in the diabetic retinal circulation following Fas/FasL-induced endothelial apoptosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Kyoto Univ, Grad Sch Med, Kyoto, Japan. Massachusetts Eye & Ear Infirm, Angiogensis Retina Res Lab, Boston, MA USA. Nagoya City Univ, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 1 MA 1323 BP U299 EP U299 PG 1 WC Ophthalmology SC Ophthalmology GA 709CF UT WOS:000184606601279 ER PT J AU Zhao, T Kiss, S Letko, E Qamruddin, S Foster, CS AF Zhao, T Kiss, S Letko, E Qamruddin, S Foster, CS TI Long-term follow up of patients with ocular Involvement associated with Reiter's syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4253 BP U1204 EP U1204 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701405 ER PT J AU Ziv, OR Jensen, RJ Rizzo, JF AF Ziv, OR Jensen, RJ Rizzo, JF TI In vitro activation of ganglion cells in rabbit retina: Effects of glutamate receptor agents SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2002 VL 43 SU 2 MA 4474 BP U1282 EP U1282 PG 1 WC Ophthalmology SC Ophthalmology GA 709CG UT WOS:000184606701627 ER PT J AU Swenson, ER Maggiorini, M Mongovin, S Gibbs, JSR Greve, I Mairbaurl, HH Bartsch, P AF Swenson, ER Maggiorini, M Mongovin, S Gibbs, JSR Greve, I Mairbaurl, HH Bartsch, P TI Pathogenesis of high-altitude pulmonary edema - Inflammation is not an etiologic factor SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MOUNTAIN-SICKNESS; INHALED NITRIC-OXIDE; BRONCHOALVEOLAR LAVAGE; STRESS FAILURE; HYPOXIA; LUNG; PERMEABILITY; FLUID; RABBIT; REDISTRIBUTION AB Context The pathogenesis of high-altitude pulmonary edema (HAPE) is considered an altered permeability of the alveolar-capillary barrier secondary to intense pulmonary vasoconstriction and high capillary pressure, but previous bronchoalveolar lavage (BAL) findings in well-established HAPE are also consistent with inflammatory etiologic characteristics. Objectives To determine whether inflammation is a primary event in HAPE and to define the temporal sequence of events in HAPE. Design, Setting, and Participants Case study from July through August 1999 of 10 subjects with susceptibility to HAPE and 6 subjects resistant to HAPE, all of whom are nonprofessional alpinists with previous mountaineering experience above 3000 m. Main Outcome Measures Pulmonary artery pressure measurements and BAL findings at low altitude (490 m) and shortly before or at the onset of HAPE at an altitude of 4559 m. Results Subjects who were HAPE susceptible had higher mean (SD) pulmonary artery systolic blood pressures at 4559 m compared with HAPE-resistant subjects (66 vs 37 mm Hg; P=.004). Despite development of HAPE in the majority of HAPE-susceptible subjects, there were no differences in BAL fluid total leukocyte counts between resistant and susceptible subjects or between counts taken at low and high altitudes. Subjects who developed HAPE had BAL fluid with high concentrations of plasma-derived proteins and erythrocytes, but there was no increase in plasma concentrations of surfactant protein A and Clara cell protein. The chest radiograph score was 12.7 for the 3 HAPE-susceptible subjects who developed HAPE before BAL was performed; they were lavaged within 3 to 5 hours. The remainder of the HAPE-susceptible group was lavaged before edema was apparent on radiographs. However, 6 subjects from the HAPE-susceptible group who developed HAPE on the following day had a score on bronchoscopy of 1.5, which increased to 4.6, reflective of mild pulmonary edema. In HAPE cases, there were no elevations in a number of proinflammatory cytokines and eicosanoid and nitric oxide metabolites. Conclusions Early HAPE is characterized by high pulmonary artery pressures that lead to a protein-rich and mildly hemorrhagic edema, with normal levels of leukocytes, cytokines, and eicosanoids. HAPE is a form of hydrostatic pulmonary edema with altered alveolar-capillary permeability. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Res Serv, Seattle, WA 98195 USA. Univ Zurich Hosp, Dept Internal Med, Med Intens Care Unit, Zurich, Switzerland. Univ London Imperial Coll Sci Technol & Med, Sch Sci Technol & Med, Natl Heart & Lung Inst, London, England. Univ Clin Heidelberg, Dept Med, Div Sports Med, Heidelberg, Germany. RP Swenson, ER (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Pulm & Crit Care Sect, S-111-Pulm,1660 S Columbian Way, Seattle, WA 98108 USA. NR 55 TC 166 Z9 178 U1 4 U2 10 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 MAY 1 PY 2002 VL 287 IS 17 BP 2228 EP 2235 DI 10.1001/jama.287.17.2228 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 546EZ UT WOS:000175260600023 PM 11980523 ER PT J AU Ruscio, AM Ruscio, J Keane, TM AF Ruscio, AM Ruscio, J Keane, TM TI The latent structure of posttraumatic stress disorder: A taxometric investigation of reactions to extreme stress SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Psychological-Society CY JUN, 2001 CL TORONTO, CANADA SP Amer Psychol Soc ID 2 QUANTITATIVE INDICATORS; ADMINISTERED PTSD SCALE; DETECTING TAXONICITY; PSYCHOPATHOLOGY; CLASSIFICATION; CONTINUITY; DEPRESSION; DIAGNOSIS; VALIDITY; RECOVERY AB Mental health professionals have debated whether posttraumatic stress disorder (PTSD) can be qualitatively distinguished from normal reactions to traumatic events. This debate has been fueled by indications that many trauma-exposed individuals evidence partial presentations of PTSD that are associated with significant impairment and help-seeking behavior. The authors examined the latent structure of PTSD in a large sample of male combat veterans, Three taxometric procedures-MAMBAC, MAXEIG, and L-Mode-were performed with 3 indicator sets drawn from a clinical interview and a self-report measure of PTSD. Results across procedures, consistency tests, and analysis of simulated comparison data all converged on a dimensional solution, suggesting that PTSD reflects the upper end of a stress-response continuum rather than a discrete clinical syndrome. C1 Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. Elizabethtown Coll, Dept Psychol, Elizabethtown, PA 17022 USA. Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Ruscio, AM (reprint author), Penn State Univ, Dept Psychol, 429 Bruce V Moore Bldg, University Pk, PA 16802 USA. FU NIMH NIH HHS [MH-12675-01] NR 55 TC 181 Z9 184 U1 2 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2002 VL 111 IS 2 BP 290 EP 301 DI 10.1037//0021-843X.111.2.290 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 543AN UT WOS:000175078600008 PM 12003450 ER PT J AU Nierenberg, AA Phillips, KA Petersen, TJ Kelly, KE Alpert, JE Worthington, JJ Tedlow, JR Rosenbaum, JF Fava, M AF Nierenberg, AA Phillips, KA Petersen, TJ Kelly, KE Alpert, JE Worthington, JJ Tedlow, JR Rosenbaum, JF Fava, M TI Body dysmorphic disorder in outpatients with major depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 148th Annual Meeting of the American-Psychiatric-Association CY MAY 20-26, 1995 CL MIAMI BEACH, FLORIDA SP Amer Psychiat Assoc DE body dysmorphic disorder; major depression; atypical depression; axis I comorbidity ID ATYPICAL DEPRESSION; IMAGINED UGLINESS; PREVALENCE; FEATURES AB Background: Body dysmorphic disorder (BDD) is a distressing and impairing preoccupation with an imagined or slight defect in appearance, with depression as its most frequent comorbid condition. The purpose of this study was to evaluate the rate of BDD in a cohort of consecutive outpatients with typical and atypical major depressive disorder. Methods: Three hundred and fifty consecutive outpatient subjects with major depression who entered an antidepressant treatment study were evaluated drug-free with the SCID-P, SCID-II, a diagnostic module for BDD, and other measures. Depressed subjects with comorbid BDD were compared to those without BDD with regard to demographics, course of depression, comorbid conditions, and other relevant variables. Results: Twenty-eight (8.0%) subjects had a lifetime history of BDD and 23 (6.6%) had current BDD. Those with comorbid lifetime BDD had an earlier age of onset of depression and longer duration of the current episode, but not a greater number of depressive episodes or greater severity of depression. Subjects with and without BDD were similar with respect to age, gender, and marital status. There was a higher rate of lifetime and current BDD in subjects with atypical depression than in those with non-atypical depression (14.4% compared to 5.1%; X = 6.63; P = 0.01: 11.6% vs. 4.1%; X = 7.02; P = 0.02). Subjects with BDD also had higher rates of social phobia, any eating disorder, and any somatoform disorder but not obsessive compulsive disorder. They also had higher rates of avoidant, histrionic, and dependent personality disorders. Limitations: As we did not specifically examine bipolar spectrum conditions, the present study cannot address to what extent BDD is comorbid with Bipolar-II disorder. Conclusions: BDD is frequently comorbid with major depression, is associated with an earlier age of onset of depression and longer duration of depressive episodes, and is found more frequently with atypical than non-atypical depression. (C) 2002 Elsevier Science BY. All rights reserved. C1 Massachusetts Gen Hosp, Depress Res Program, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Butler Hosp, Providence, RI 02912 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Res Program, Clin Psychopharmacol Unit, WAC 815,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01MH 48483-01, K24 MH063975] NR 25 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 2002 VL 69 IS 1-3 BP 141 EP 148 AR PII S0165-0327(01)00304-4 DI 10.1016/S0165-0327(01)00304-4 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 575EK UT WOS:000176933500014 PM 12103460 ER PT J AU Simon, NM Safren, SA Otto, MW Sharma, SG Lanka, GD Pollack, MH AF Simon, NM Safren, SA Otto, MW Sharma, SG Lanka, GD Pollack, MH TI Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE panic; panic disorder; pharmacotherapy; outcome; remission; relapse ID FOLLOW-UP; AGORAPHOBIA; ANTIDEPRESSANTS; MAINTENANCE; CLONAZEPAM; TRIAL AB Background: Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least I year [Am. J. Psychiatry 155 (1998) 1], despite a paucity of data systematically examining outcome for periods greater than 3-6 months. It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder. Methods: Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder, a prospective, naturalistic study. Participants were categorized by their maintenance treatment condition at remission: benzodiazepine alone (N = 45, 58%), antidepressant alone (N = 12, 16%), and combined treatment with a benzodiazepine and an antidepressant (N = 21, 27%). Results: Approximately half (N = 36, 46%) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period, despite continued and adequate pharmacotherapy. There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy. Limitations: Interpretation of the data is limited by the naturalistic nature of the study, and by the relatively low sample size. Conclusions: This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy, despite continued treatment. In addition, the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, 15 Parkman St,WAC 815, Boston, MA 02114 USA. NR 23 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 2002 VL 69 IS 1-3 BP 201 EP 208 AR PII S0165-0327(01)00359-7 DI 10.1016/S0165-0327(01)00359-7 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 575EK UT WOS:000176933500021 PM 12103467 ER PT J AU Simon, NM Blacker, D Korbly, NB Sharma, SG Worthington, JJ Otto, MW Pollack, MH AF Simon, NM Blacker, D Korbly, NB Sharma, SG Worthington, JJ Otto, MW Pollack, MH TI Hypothyroidism and hyperthyroidism in anxiety disorders revisited: new data and literature review SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE anxiety disorder; hyperthyroid; hypothyroid; thyroid; panic disorder; generalized anxiety disorder; social phobia ID SENSITIVE THYROTROPIN ASSAYS; PANIC DISORDER; CRITERIA; ATTACKS; HORMONE; TSH; PERFORMANCE; COMORBIDITY; DEPRESSION; DISEASE AB Background: The need for thyroid screening of patients presenting with panic disorder (PD), social phobia (SP) or generalized anxiety disorder (GAD) remains uncertain. Methods: We examined thyroid histories and serum testing in 169 patients, 92 with PD, 48 with SP, and 29 with GAD. Combined prevalence rates of hyperthyroidism and hypothyroidism were compared with expected rates (2.7%) derived from the population based Whickham Survey. Data from previously published studies were also compared with these expected rates. Results: In our sample, only 2/169 patients had thyroid dysfunction detected by serum testing, but 5/169 [1/92 (1%) with PD, 1/48 (2%) with SP, and 3/29 (10%) with GAD], all currently euthyroid, reported a history of thyroid disease. The rates were statistically significant only for GAD (10.4%; z = 2.56, p = 0.01). However, combining prior PD studies that examined both thyroid history and test results with our data also suggests significantly elevated rates of thyroid dysfunction (6.5%; z = 4.69, p < 0.0001). Limitations: As with previous data, the 95% confidence interval for our findings is broad, reflecting the instability of low rates of illness in relatively small samples. Further, methods for obtaining thyroid histories and tests were not uniform. Conclusions: Despite relatively low yields on serum testing, lifetime prevalence of thyroid dysfunction does appear elevated for GAD and PD, with minimal data addressing this issue for SP. The data support the need to query GAD and PD patients regarding thyroid history and per-form serum testing in those without prior testing. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, 15 Parkman St,WAC 815, Boston, MA 02114 USA. NR 32 TC 42 Z9 45 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 2002 VL 69 IS 1-3 BP 209 EP 217 AR PII S0165-0327(01)00378-0 DI 10.1016/S0165-0327(01)00378-0 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 575EK UT WOS:000176933500022 PM 12103468 ER PT J AU Peabody, JW Robalino, DA Kim, JH AF Peabody, JW Robalino, DA Kim, JH TI An evaluation of universal health insurance in the elderly: Burden of disease, utilization, and costs in the Republic of Korea SO JOURNAL OF AGING AND HEALTH LA English DT Article AB Objective: This article evaluates Korea's national health insurance system for the elderly by simultaneously examining disease patters, demand for care, utilization, costs of care, and facility type. Methods: Claim records (N = 8,306,976) for 1995 to 1997 were obtained from the Youndeoung-Po district for four insurance categories. Utilization is examined using a probit model, a linear regression model is used to compare costs. Findings: Insurees averaged 10.6 medical visits per year, most commonly for acute respiratory diseases. The elderly were more likely to seek care for circulatory problems, use more inpatient services, and rely on hospitals for outpatient care. Insurance costs for the elderly poor were markedly higher, and overall care for the elderly was higher per visit. Discussion: By simultaneously analyzing utilization rates, disease patterns, and relative costs of care, policy makers may be able to avert a financing crisis. Stronger pricing strategies and better disease targeting would adjust utilization and increase efficiency of health expenditures. C1 Inst Global Hlth, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94105 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RAND Corp, Santa Monica, CA 90406 USA. World Bank, Washington, DC 20433 USA. RP Peabody, JW (reprint author), Inst Global Hlth, San Francisco Vet Affairs Med Ctr, 74 New Montgomery St,Suite 508, San Francisco, CA 94105 USA. NR 9 TC 2 Z9 2 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD MAY PY 2002 VL 14 IS 2 BP 286 EP 309 DI 10.1177/089826430201400206 PG 24 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 542ZM UT WOS:000175075900006 PM 11995744 ER PT J AU Battaglino, R Kim, D Fu, J Vaage, B Fu, XY Stashenko, P AF Battaglino, R Kim, D Fu, J Vaage, B Fu, XY Stashenko, P TI C-myc is required for osteoclast differentiation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoclast differentiation; bone formation; myc ID NF-KAPPA-B; NECROSIS-FACTOR RECEPTOR; COLONY-STIMULATING FACTOR; CELL-CYCLE; PROTEASE INHIBITORS; GROWTH-FACTOR; STEM-CELLS; EXPRESSION; ACTIVATION; OSTEOPETROSIS AB The role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-a tumor necrosis factor (TNF)-related cytokine-in osteoclast formation has been established clearly. However, the downstream signaling pathways activated by this cytokine remain largely unknown. To identify genes that play a role in osteoclastogenesis, we used RAW 264.7 mouse monocytes as a model system for the differentiation of multinucleated osteoclasts from mononucleated precursors. RAW 264.7 cells were induced with RANKL to form multinucleated giant osteoclast-like cells (OCLs) that expressed a number of osteoclast-specific markers and were able to form resorption pits on both calcium phosphate films and bone slices. This system was used to identify genes that are regulated by RANKL and may play a role in osteoclast differentiation. The proto-oncogene c-myc was strongly up-regulated in RANKL-induced OCLs but was absent in undifferentiated cells. Expression of Myc partners Max and Mad, on the other hand, was constant during OCL differentiation. We expressed a dominant negative Myc in RAW 264.7 cells and were able to block RANKL-induced OCL formation. Northern Blot analysis revealed a delay and a significant reduction in the level of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K. We conclude that c-myc is a downstream target of RANKL and its expression is required for RANKL-induced osteoclastogenesis. C1 Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Stashenko, P (reprint author), Forsyth Inst, Cytokine Biol Dept, 140 Fenway, Boston, MA 02115 USA. RI battaglino, ricardo/D-2892-2015 FU NIDCR NIH HHS [DE-07378] NR 56 TC 60 Z9 69 U1 1 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2002 VL 17 IS 5 BP 763 EP 773 DI 10.1359/jbmr.2002.17.5.763 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 545QP UT WOS:000175229100003 PM 12009006 ER PT J AU Kazis, LE Liang, MH Lee, A Ren, XHS Phillips, CB Hinson, M Calvert, C Cullen, M Daugherty, MB Goodwin, CW Jenkins, M McCauley, RL Meyer, WJ Palmieri, T Pidcock, F Reilly, D Warden, G Wood, D Tompkins, R AF Kazis, LE Liang, MH Lee, A Ren, XHS Phillips, CB Hinson, M Calvert, C Cullen, M Daugherty, MB Goodwin, CW Jenkins, M McCauley, RL Meyer, WJ Palmieri, T Pidcock, F Reilly, D Warden, G Wood, D Tompkins, R TI The development, validation, and testing of a health outcomes burn questionnaire for infants and children 5 years of age and younger: American Burn Association/Shriners Hospitals for children SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID PROMPT ESCHAR EXCISION; MORTALITY AB The 12-member American Burn Association/Shriners Hospitals for Children Outcomes Task Force was charged with developing a health outcomes questionnaire for use in children 5 years of age and younger that was clinically based and valid. A 55-item form was tested using a cross-sectional design on the basis of a range of 184 infants and children between 0 and 5 years of age at 8 burn centers, nationally. A total of 131 subjects completed a follow-up health outcomes questionnaire 6 months after the baseline assessment. A comparison group of 285 normal nonburn children was also obtained. Internal consistency reliability of the scales ranged from 0.74 to 0.94. Tests of clinical validity were significant in the hypothesized direction for the majority of scales for length of hospital stay, duration since the burn, percent of body surface area burned, overall clinician assessment of severity of burn injury, and number of comorbidities. The criterion validity of the instrument was supported using the Child Developmental Inventories for Burn Children in early childhood and preschool stages of development comparing normal vs abnormal children. The instrument was sensitive to changes over time following a clinical course observed by physicians in practice. The Health Outcomes Burn Questionnaire for Infants and Children 5 years of age and younger is a clinically based reliable and valid assessment tool that is sensitive to change over time for assessing burn outcomes in this age group. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Ctr Hlth Qual, VA Hlth Serv Res & Dev Field Program, Bedford, MA USA. Brigham & Womens Hosp, Robert B Brigham Multipurpose Arthrit & Musculosk, Boston, MA 02115 USA. Shriners Hosp Children, Boston, MA USA. N Carolina Jaycee Burn Ctr, Chapel Hill, NC USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. Shriners Hosp Children, Cincinnati, OH USA. USA, Inst Surg Res, San Antonio, TX USA. Shriners Hosp Children, Galveston, TX 77550 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Shriners Hosp Children, Sacramento, CA USA. Kennedy Krieger Inst, Baltimore, MD USA. Univ So Calif, Los Angeles, CA USA. Shriners Hosp Children, Tampa, FL USA. RP Tompkins, R (reprint author), Massachusetts Gen Hosp, GRB 1302,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 39 Z9 39 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD MAY-JUN PY 2002 VL 23 IS 3 BP 196 EP 207 DI 10.1097/00004630-200205000-00009 PG 12 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 606ZF UT WOS:000178765400006 PM 12032370 ER PT J AU Sun, W Sarma, JSM Singh, BN AF Sun, W Sarma, JSM Singh, BN TI Chronic and acute effects of dronedarone on the action potential of rabbit atrial muscle preparations: Comparison with amiodarone SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE action potential; amiodarone; dronedarone; effective refractory period; frequency dependency ID PIG VENTRICULAR MYOCYTES; ANTIARRHYTHMIC AGENT; ADRENERGIC ANTAGONISM; SODIUM-CHANNELS; CARDIAC-MUSCLE; K+ CURRENT; CELLS; FIBRILLATION; SR-33589; CALCIUM AB Dronedarone, a noniodinated derivative of amiodarone, is under evaluation as a potentially less toxic anti-arrhythmic alternative to amiodarone. The acute and chronic electrophysiologic effects of dronedarone and amiodarone were compared in isolated rabbit atrial muscle by microelectrode techniques. Four-week PO treatment with dronedarone or amiodarone increased action potential duration (APD(90)) (58 +/- 4 ms control versus 69 +/- 2 ms dronedarone, p < 0.01; 68 +/- 3 ms amiodarone, p < 0.01 for a 100-mg/kg/d dose) and effective refractory period (49 6 Ins control versus 68 4 ms dronedarone, p < 0.01; 63 +/- 3 ms amiodarone, p < 0.01). The APD(90) prolonged reverse rate-dependency. In contrast, acute superfusion with 10 muM dronedarone or amiodarone decreased APD(90) (61 +/- 6 ms control versus 53 +/- 4 ms dronedarone, p < 0.05; 52 +/- 6 ms amiodarone, p < 0.05), effective refractory period (50 +/- 5 ms control versus 44 +/- 4 Ins dronedarone, p < 0.05; 43 6 ms amiodarone, p < 0.05), and the maximum upstroke slope of the action potential (V-max) (188 +/- 9 V/s control versus 182 +/- 11 V/s dronedarone p < 0.05; 182 +/- 11 V/s amiodarone, p < 0.05). Thus, chronic and acute electrophysiologic effects of dronedarone on rabbit atrial muscle are similar to those of amiodarone, suggesting a similar potential against atrial arrhythmias. C1 VA Greater Los Angeles Healthcare Syst, Dept Cardiol, Cardiovasc Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Singh, BN (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Cardiol, Cardiovasc Res Lab, 11301 Wilshire Bldg,111E, Los Angeles, CA 90073 USA. NR 37 TC 72 Z9 76 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAY PY 2002 VL 39 IS 5 BP 677 EP 684 DI 10.1097/00005344-200205000-00008 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 546FH UT WOS:000175262000008 PM 11973411 ER PT J AU Cao, GD Luo, YM Nagayama, T Pei, W Stetler, RA Graham, SH Chen, J AF Cao, GD Luo, YM Nagayama, T Pei, W Stetler, RA Graham, SH Chen, J TI Cloning and characterization of rat caspase-9: Implications for a role in mediating caspase-3 activation and hippocampal cell death after transient cerebral ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; cerebral ischemia; caspases; mitochrondria; Apaf-1 ID CYTOCHROME-C RELEASE; DELAYED NEURONAL DEATH; DNA FRAGMENTATION; IN-VIVO; ENDOGENOUS INHIBITOR; BRAIN-DEVELOPMENT; WD-40 REPEAT; FOCAL STROKE; APOPTOSIS; EXPRESSION AB Delayed hippocampal neurodegeneration after transient global ischemia is mediated. at least in part. through the activation of terminal caspases, particularly caspase-3. and the subsequent proteolytic degradation of critical Cellular proteins. Caspase-3 may be activated by the membrane receptor-initiated caspase-8-dependent extrinsic path ay and the mitochondria-initiated caspase-9-dependent intrinsic pathway: however the precise role of these deduced apoptosis-signaling pathways in activating caspase-3 in ischemic neurons remains elusive. The authors cloned the caspase-9-ene from the rat brain and investigated its potential role in mediating ischemic neuronal death in a rat model of transient global ischemia. Caspase-9 gene expression and protease activity ere extremely low in the adult brain. whereas them were developmentally upregulated in newborn rats, especially at postnatal 12 weeks. a finding consistent with the theory of an essential role for caspase-9 in neuronal apoptosis during brain development. After 15-minute transient global ischemia. caspase-9 was over-expressed and protcolytically activated in the hippocampal CAI neurons at 8 to 72 hours of reperfusion. The temporal profile of capase-9 activation coincided with that of cytochrome c release and caspase-3 activation, but preceded CAI neuronal death. Immunoprecipitation experiments, revealed that there was enhanced formation of Apaf-1/caspase-9 complex in the hippocampus 8 and 24 hours after ischemia. Furthermore. intracerebral ventricular infusion of the related specific caspase-9 inhibitor N-benzyloxycarbonyl-Leu-Glu-His-Asp- fluoro-methylketone before ischemic attenuated caspase-3-like activity and significantly enhanced neuronal survival in the CAI sector. In contrast, inhibition of caspase-8 activity had no significant effect on caspase-3 activation or neuronal survival. These results that the caspase-9-dependent intrinsic pathway may be the primary mechanism responsible for the activation of caspase-3 in ischemic hippocampal neurons. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurol Disorders, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS 35965, NS 36736, NS 38560] NR 52 TC 76 Z9 81 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2002 VL 22 IS 5 BP 534 EP 546 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 548CN UT WOS:000175371200005 PM 11973426 ER PT J AU Nathan, DM AF Nathan, DM TI Clinical review 146 - The impact of clinical trials on the treatment of diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID CORONARY-HEART-DISEASE; CONVERTING ENZYME-INHIBITION; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; INTENSIVE THERAPY; INSULIN-TREATMENT; DIETARY-PROTEIN; BLOOD-GLUCOSE C1 Massachusetts Gen Hosp, Diabet Unit, Ctr Diabet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Diabet Unit, Ctr Diabet, Bulfinch 408, Boston, MA 02114 USA. NR 74 TC 6 Z9 7 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 1929 EP 1937 DI 10.1210/jc.87.5.1929 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100002 PM 11994319 ER PT J AU Ross, DS AF Ross, DS TI Editorial: Non-palpable thyroid nodules-managing an epidemic SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID NEEDLE-ASPIRATION BIOPSY; NORTH-AMERICAN SURVEY; MANAGEMENT; ULTRASOUND; ULTRASONOGRAPHY; INCIDENTALOMAS; MALIGNANCY; PALPATION; DISEASE C1 Massachusetts Gen Hosp, Thyroid Associates ACC730, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Thyroid Associates ACC730, Boston, MA 02114 USA. EM dross@partners.org NR 21 TC 94 Z9 100 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 1938 EP 1940 DI 10.1210/jc.87.5.1938 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100003 PM 11994320 ER PT J AU Biller, BMK Samuels, MH Zagar, A Cook, DM Arafah, BM Bonert, V Stavrou, S Kleinberg, DL Chipman, JJ Hartman, ML AF Biller, BMK Samuels, MH Zagar, A Cook, DM Arafah, BM Bonert, V Stavrou, S Kleinberg, DL Chipman, JJ Hartman, ML TI Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT Conference of the Growth-Hormone-Research-Society CY SEP 07-09, 2000 CL GOTHENBURG, SWEDEN SP Growth Hormone Res Soc ID GROWTH-HORMONE DEFICIENCY; INSULIN-INDUCED HYPOGLYCEMIA; TOLERANCE-TEST; FACTOR-I; PROVOCATIVE TESTS; L-DOPA; (GH)-RELEASING HORMONE; OBESE SUBJECTS; PLUS ARGININE; IGF-I AB Although the use of the insulin tolerance test (ITT) for the diagnosis of adult GH deficiency is well established, diagnostic peak GH cut-points for other commonly used GH stimulation tests are less clearly established. Despite that fact, the majority of patients in the United States who are evaluated for GH deficiency do not undergo insulin tolerance testing. The aim of this study was to evaluate the relative utility of six different methods of testing for adult GH deficiency currently used in practice in the United States and to develop diagnostic cut-points for each of these tests. Thirty-nine patients (26 male, 13 female) with adult-onset hypothalamic-pituitary disease and multiple pituitary hormone deficiencies were studied in comparison with age-, sex-, estrogen status-, and body mass index-matched control subjects (n = 34; 20 male, 14 female). A third group of patients (n = 21) with adult-onset hypothalamic-pituitary disease and no more than one additional pituitary hormone deficiency was also studied. The primary end-point was peak serum GH response to five GH stimulation tests administered in random order at five separate visits: ITT, arginine (ARG), levodopa (L-DOPA), ARG plus L-DOPA, and ARG plus GHRH. Serum IGF-I concentrations were also measured on two occasions. For purposes of analysis, patients with multiple pituitary hormone deficiencies were assumed to be GH deficient. Three diagnostic cut-points were calculated for each test to provide optimal separation of multiple pituitary hormone deficient and control subjects according to three criteria: 1) to minimize misclassification of control subjects and deficient patients (balance between high sensitivity and high specificity); 2) to provide 95% sensitivity for GH deficiency; and 3) to provide 95% specificity for GH deficiency. The greatest diagnostic accuracy occurred with the ITT and the ARG plus GHRH test, although patients preferred the latter (P = 0.001). Using peak serum GH cut-points of 5.1 mug/liter for the ITT and 4.1 mug/liter for the ARG plus GHRH test, high sensitivity (96 and 95%, respectively) and specificity (92 and 91%, respectively) for GH deficiency were achieved. To obtain 95% specificity, the peak serum GH cut-points were lower at 3.3 mug/liter and 1.5 mug/liter for the ITT and ARG plus GHRH test, respectively. There was substantial overlap between patients and control subjects for the ARG plus L-DOPA, ARG, and L-DOPA tests, but test-specific cut-points could be defined for all three tests to provide 95% sensitivity for GH deficiency (peak GH cut-points: 1.5,1.4 and 0.64 mug/liter, respectively). However, 95% specificity could be achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut-points (0.25 and 0.21 mug/liter, respectively) and not at all with the L-DOPA test. Although serum IGF-I levels provided less diagnostic discrimination than all five GH stimulation tests, a value below 77.2 mug/liter was 95% specific for GH deficiency. In conclusion, the diagnosis of adult GH deficiency can be made without performing an ITT, provided that test-specific cut-points are used. The ARG plus GHRH test represents an excellent alternative to the ITT for the diagnosis of GH deficiency in adults. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. NYU, Med Ctr, New York, NY 10010 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,Fruit St, Boston, MA 02114 USA. EM bbiller@partners.org NR 57 TC 239 Z9 245 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 2067 EP 2079 DI 10.1210/jc.87.5.2067 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100026 PM 11994342 ER PT J AU Gill, S Sharpless, JL Rado, K Hall, JE AF Gill, S Sharpless, JL Rado, K Hall, JE TI Evidence that GnRH decreases with gonadal steroid feedback but increases with age in postmenopausal women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; LUTEINIZING-HORMONE; GENE-EXPRESSION; PROGESTERONE-RECEPTOR; HYPOTHALAMIC FUNCTION; SERUM GONADOTROPINS; PULSE FREQUENCY; MESSENGER-RNA; PREOPTIC AREA; SECRETION AB Studies of the effects of gonadal steroid negative feedback and age on the hypothalamic-pituitary axis in postmenopausal women (PMW) have identified significant but inconsistent changes in gonadotropin dynamics. In the current study, we investigated the effect of gonadal steroid replacement and age on overall GnRH secretion estimated by using submaximal. GnRH receptor blockade. Twenty-four healthy PMW, 45-55 yr (n = 13) and 70-80 yr (n 11), were studied. Subjects were studied at baseline (BL) on no hormone replacement therapy, after 1 month of transdermal estrogen (50 mug/d; E) and again after a further month of E and 7 d of transvaginal progesterone (100 mg bid; E + P). At each admission, blood was sampled every 30 min for 4 (131, and E) or 8 h (E + P) before and 10 h after se administration of a submaximal dose (5 mug/kg) of the NAL-GLU GnRH antagonist ([Ac-D2NaI(1), D4ClPhe(2), DPal(3), Arg(5), DGlu(AA)(6), DAla(10)] GnRH). Percent inhibition of LH was calculated by expressing the difference between the nadir following GnRH antagonist administration and the preantagonist baseline as a percent of the baseline. Physiologic E and P levels were achieved with the appropriate hormone replacement regimens. Mean LH levels decreased from baseline with E alone and decreased further with E + P (81.4 +/- 6.6, 68.2 +/- 8.1 and 48.0 +/- 4.3 IU/liter, respectively; P < 0.005). Percent inhibition of LH following submaximal GnRH receptor blockade decreased with age (57.6 +/- 1.8% in young PMW vs. 51.4 +/- 2.2% in old PMW, P < 0.05) implying an increase in GnRH secretion with age. There was an increase in percent inhibition of LH in response to submaximal GnRH receptor blockade with E and a further increase with E + P (54.8 +/- 1.5%, 58.8 +/- 1.9% and 69.9 +/- 2.8%, respectively; P < 0.05), indicating a progressive decrease in endogenous GnRH secretion with gonadal steroid feedback. Mean LH and FSH levels were lower at baseline in old compared with young PMW. However, the effect of gonadal steroid feedback on endogenous GnRH secretion was similar in young and old PMW. In conclusion: 1) The overall quantity of GnRH secretion increases with age as demonstrated by the progressive decrease in LH inhibition following submaximal GnRH antagonist administration with increasing age; 2) E negative feedback is associated with a decrease in GnRH secretion (as indicated by an increased percent inhibition of LH following submaximal GnRH receptor blockade); 3) E2 and P are associated with a further decease in overall amount of GnRH secreted; and 4) Age does not dampen the inhibition of hypothalamic GnRH secretion by E and P in PMW. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. EM jehall@partners.org FU NCRR NIH HHS [M01-RR-1066]; NIA NIH HHS [R01 AG013241, R01-AG-13241] NR 47 TC 57 Z9 59 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 2290 EP 2296 DI 10.1210/jc.87.5.2290 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100059 PM 11994378 ER PT J AU Gill, S Lavoie, HB Bo-Abbas, Y Hall, JE AF Gill, S Lavoie, HB Bo-Abbas, Y Hall, JE TI Negative feedback effects of gonadal steroids are preserved with aging in postmenopausal women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FREE ALPHA-SUBUNIT; LUTEINIZING-HORMONE; PULSE FREQUENCY; HYPOTHALAMIC FUNCTION; SERUM GONADOTROPINS; SECRETION; PITUITARY; PROGESTERONE; ESTROGEN AB There is now evidence for alterations in the neuroendocrine control of the reproductive axis with aging, but its sensitivity to gonadal steroid negative feedback remains controversial. To examine the independent effect of age and gonadal steroid negative feedback, younger (45-55 yr; n = 7) and older (70-80 yr; n = 6) postmenopausal women (PAW) were studied at baseline on no HRT, after I month of transdermal estrogen (50 mug/d; E) and again after a further month of E and 7 d of transvaginal progesterone (P) (100 mg bid; E + P). At each admission, blood was sampled every 5 min for 8 h for measurement of gonadotropin free a-subunit (FAS), which was used as a marker of GnRH pulse frequency. LH and FSH were measured in pooled samples. Midfollicular and midluteal phase levels of E2 and P were achieved during the E and E + P treatments and were not different between younger and older PMW. There was a negative feedback effect of E and E + P on mean LH (P < 0.0001) and an additional effect of age (P < 0.003), with older women having lower values throughout. Mean FSH was also decreased with E and E + P (P < 0.0001) and was consistently lower in the older women (P < 0.05). Mean FAS levels decreased with hormonal treatment (P < 0.0001) and age (P < 0.001), but the effect of hormonal treatment was attenuated in the older group (P < 0.005). FAS pulse frequency was unchanged with addition of E, but dramatically decreased with E + P (P < 0.002). Both hormonal replacement (P < 0.05) and age (P < 0.005) decreased FAS pulse amplitude, an effect that was attributable entirely to E as there was no additional change with E + P. These studies indicate that: 1) both age and gonadal steroids independently decrease mean LH, FSH, and FAS in PAW; 2) responsiveness to steroid negative feedback on FAS is attenuated with aging in absolute but not relative terms, whereas the effect on mean levels of LH and FSH is clearly preserved; and 3) FAS pulse frequency is unchanged with E2 administration but decreases dramatically with addition of P in both old and young PMW. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. EM jehall@partners.org FU NCRR NIH HHS [M01-RR-1066]; NIA NIH HHS [R01 AG013241, R01-AG-13241] NR 36 TC 43 Z9 45 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2002 VL 87 IS 5 BP 2297 EP 2302 DI 10.1210/jc.87.5.2297 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 552YP UT WOS:000175648100060 PM 11994380 ER PT J AU Ibrahim, SA Burant, CJ Siminoff, LA Stoller, EP Kwoh, CK AF Ibrahim, SA Burant, CJ Siminoff, LA Stoller, EP Kwoh, CK TI Self-assessed global quality of life: A comparison between African-American and white older patients with arthritis SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE quality of life; ethnicity; joint replacement; osteoathritis; ethnic disparity; older patients ID TOTAL HIP-ARTHROPLASTY; OF-VETERANS-AFFAIRS; OSTEO-ARTHRITIS; HEALTH-STATUS; OSTEOARTHRITIS; POPULATION; VALIDATION; DEPRESSION; KNEE; SYSTEM AB Quality of life (QOL) perceptions influence patient decisions and preferences for care and, more importantly, physicians may render recommendations based on their impressions of the patient's QOL. QOL is perceived differently by different ethnic groups. This may have implications for understanding ethnic disparities in medical procedure utilization such as joint replacement for osteoarthritis. In a study of 596 elderly male patients with moderate to severe symptomatic knee/hip osteoarthritis, we examined how African-American and white patients rate their overall QOL. We adjusted their responses for important demographic, clinical, and psychosocial potential confounders. African-American (44%) and white (56%) patients in this study were comparable, except that African-Americans reported lower socioeconomic status compared with whites. After adjusting for all other study covariates, African-American ethnicity (B=-0.121, P=0.004) was negatively correlated with overall QOL ratings. How ethnic variations in perceptions of QOL impact observed ethnic disparity in the utilization of joint replacement therapy needs further investigation. (C) 2002 Elsevier Science Inc. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Case Western Reserve Univ, Div Gen Internal Med,Dept Med, Univ Hosp Cleveland, Louis Stokes Dept,VA Med Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Div Hlth Care Res,Dept Med, Univ Hosp Cleveland, Louis Stokes Dept,VA Med Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, EPS, Ctr Aging & Hlth, Cleveland, OH 44106 USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11 East 130A-U, Pittsburgh, PA 15240 USA. RI Siminoff, Laura /H-6277-2012 NR 33 TC 39 Z9 40 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2002 VL 55 IS 5 BP 512 EP 517 AR PII S0895-4356(01)00501-7 DI 10.1016/S0895-4356(01)00501-7 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 550VD UT WOS:000175523500013 PM 12007555 ER PT J AU Klapow, JC Wilcox, CM Mallinger, AP Marks, R Heudebert, GR Centor, RM Lawrence, W Richter, J AF Klapow, JC Wilcox, CM Mallinger, AP Marks, R Heudebert, GR Centor, RM Lawrence, W Richter, J TI Characterization of long-term outcomes after Toupet fundoplication - Symptoms, medication use, and health status SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE fundoplication; Toupet; GERD ID GASTROESOPHAGEAL REFLUX DISEASE; CONVENTIONAL NISSEN FUNDOPLICATION; RANDOMIZED CLINICAL-TRIAL; WELL-BEING SCORES; QUALITY-OF-LIFE; LAPAROSCOPIC NISSEN; ANTIREFLUX SURGERY; PREDICTING QUALITY; FOLLOW-UP; ESOPHAGITIS AB Goals and Background: Fundoplication is increasingly used for the treatment of gastroesophageal reflux disease (GERD). Few studies have tracked patient outcomes of the Toupet method for more than I year. Further clinical, physiologic, and patient-based outcome measures have not been well characterized for this method. The cur-rent study conducts a long-term, comprehensive outcome evaluation in patients receiving Toupet fundoplication. Study: Fifty-five patients who had previously undergone fundoplication were examined. In a subset of 24 patients. esophagogastroduodenoscopy was used to assess the severity of reflux esophagitis. Manometry and ambulatory pH monitoring also Were performed. Results: Patients were studied 2.9 (+/- 0.7) years after surgery. Sixty-seven percent of the sample reported heartburn, 51% reported postoperative bloating, 33% reported regurgitation, and 20% reported dysphagia. Thirty-three percent reported the use of prescription medications for GERD-related symptoms. Health status was diminished relative to population norms. Degree of GERD severity was associated with symptom reports and medication use. Conclusions: Although fundoplication is thought to be a curative procedure, the current findings suggest that many patients take symptomatic therapies and report symptoms and diminished health status up to 2 years after the procedure. These outcomes are associated With physiologic findings. Thus, these findings suggest that symptom-free status and absence of medication use cannot be assumed for all patients after Toupet fundoplication. C1 Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Publ Hlth, Dept Hlth Care Org & Policy, Birmingham, AL 35294 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL USA. Cleveland Clin Fdn, Dept Med, Div Gastroenterol, Cleveland, OH USA. Georgetown Univ, Sch Med, Washington, DC 20057 USA. RP Klapow, JC (reprint author), Univ Alabama, Dept Psychol, 330 Ryals Publ Hlth Bldg, Birmingham, AL 35294 USA. NR 39 TC 12 Z9 13 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2002 VL 34 IS 5 BP 509 EP 515 DI 10.1097/01.MCG.0000012442.77921/39 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 544PJ UT WOS:000175168900005 PM 11960060 ER PT J AU Kushner, JA Ye, J Schubert, M Burks, DJ Dow, MA Flint, CL Dutta, S Wright, CVE Montminy, MR White, MF AF Kushner, JA Ye, J Schubert, M Burks, DJ Dow, MA Flint, CL Dutta, S Wright, CVE Montminy, MR White, MF TI Pdx1 restores beta cell function in Irs2 knockout mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INSULIN-RECEPTOR; DIABETES-MELLITUS; TRANSCRIPTION FACTOR; PANCREATIC-ISLETS; LIPID-METABOLISM; HOMEOBOX FACTOR; GENE; PROTEIN; DIFFERENTIATION; DISRUPTION AB The homeodomain transcription factor Pdx1 is required for pancreas development, including the differentiation and function of beta cells. Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic cell growth and function. To investigate whether beta cell failure in Irs2(-/-) mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2(-/-) mice. Before the onset of diabetes, Pdx1 was reduced in islets from Irs2(-/-) mice, whereas it was expressed normally in islets from wild-type or Irs1(-/-) mice, which do not develop diabetes. Whereas male Irs2(-/-) Pdx1(+/+) mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2(-/-) mice. By contrast, transgenic expression of Pdx1 restored beta cell mass and function in Irs2(-/-) mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Vanderbilt Univ, Dev Biol Program, Nashville, TN USA. Salk Inst Biol Studies, Clayton Labs Peptide Biol, La Jolla, CA USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. RI Schubert, Markus/F-5150-2010 NR 38 TC 133 Z9 140 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2002 VL 109 IS 9 BP 1193 EP 1201 DI 10.1172/JCI200214439 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 550DH UT WOS:000175488000010 PM 11994408 ER PT J AU Ordemann, R Hutchinson, R Friedman, J Burakoff, SJ Reddy, P Duffner, U Braun, TM Liu, C Teshima, T Ferrara, JLM AF Ordemann, R Hutchinson, R Friedman, J Burakoff, SJ Reddy, P Duffner, U Braun, TM Liu, C Teshima, T Ferrara, JLM TI Enhanced allostimulatory activity of host antigen-presenting cells in old mice intensifies acute graft-versus-host disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; COLONY-STIMULATING FACTOR; CYTOKINE PRODUCTION; DENDRITIC CELLS; T-CELLS; INFLAMMATORY CYTOKINES; ELDERLY PEOPLE; SMALL-BOWEL; TNF-ALPHA AB Older bone marrow transplantation (BMT) recipients are at heightened risk for acute graft-versus-host disease (GVHD) after allogeneic BMT, but the causes of this association are poorly understood. Using well-characterized murine BMT models we have explored the mechanisms of increased GVHD in older mice. GVHD mortality, morbidity, and pathologic and biochemical indices were all worse in old recipients. Donor T cell responses were significantly increased in old recipients both in vivo and in vitro when stimulated by antigen-presenting cells (APCs) from old mice, which also secreted more TNF-alpha and IL-12 after LPS stimulation. In a B6 --> B6D2F1 model, CD4(+) donor T cells but not CD8(+) T cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs in GVHD using B6D2F1 BM chimeras created with either old or young BM. Four months after chimera creation, allogeneic BMT from B6 donors caused significantly worse GVHD in old BM chimeras. APCs from these mice also stimulated greater responses from allogeneic cells in vitro. These data demonstrate a hitherto unsuspected mechanism of amplified donor T cell responses by aged allogeneic host APCs that increases acute GVHD in aged recipients in this BMT model. C1 Univ Michigan, Ctr Canc, Dept Internal Med, Div Hematol & Oncol,Blood & Marrow Transplant Pro, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Dept Pediat, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL USA. RP Ferrara, JLM (reprint author), Univ Michigan, Ctr Canc, Dept Internal Med, Div Hematol & Oncol,Blood & Marrow Transplant Pro, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012; OI teshima, takanori/0000-0002-0941-271X FU NCI NIH HHS [CA-39542, P01 CA039542]; NIA NIH HHS [R03 AG-19943-01] NR 57 TC 79 Z9 79 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2002 VL 109 IS 9 BP 1249 EP 1256 DI 10.1172/JCI200214793 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 550DH UT WOS:000175488000016 PM 11994414 ER PT J AU Hundal, RS Petersen, KF Mayerson, AB Randhawa, PS Inzucchi, S Shoelson, SE Shulman, GI AF Hundal, RS Petersen, KF Mayerson, AB Randhawa, PS Inzucchi, S Shoelson, SE Shulman, GI TI Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID INDUCED INSULIN-RESISTANCE; FREE FATTY-ACIDS; HUMANS; PHOSPHORYLATION; TROGLITAZONE; EXPRESSION; SALICYLATE; METFORMIN; MELLITUS; PATHWAYS AB Recent studies have implicated fatty acid-dependent activation of the serine kinase IKKbeta, which plays a key role in tissue inflammation, in the pathogenesis of insulin resistance. High doses of salicylates have recently been shown to inhibit IKKbeta activity and might therefore ameliorate insulin resistance and improve glucose tolerance in patients with type 2 diabetes. To rest this hypothesis, we studied nine type 2 diabetic subjects before and after 2 weeks of treatment with aspirin (similar to7 g/d). Subjects underwent mixed-meal tolerance tests and hyperinsulinemic-euglycemic clamps with [6,6-H-2(2)]glucose to assess glucose turnover before and after treatment. High-dose aspirin treatment resulted in a similar to25% reduction in fasting plasma glucose, associated with a similar to15% reduction in total cholesterol and C-reactive protein, a similar to50% reduction in triglycerides, and a similar to30% reduction in insulin clearance, despite no change in body weight. During a mixed-meal tolerance test, the areas under the curve for plasma glucose and fatty acid levels decreased by similar to20% and similar to50%, respectively. Aspirin treatment also resulted in a similar to20% reduction in basal rates of hepatic glucose production and a similar to20% improvement in insulin-stimulated peripheral glucose uptake under matched plasma insulin concentrations during the clamp. In conclusion, these data support the hypothesis that IKKbeta represents a new target for treating type 2 diabetes mellitus. C1 Yale Univ, Sch Med, Boyer Ctr Mol Med 254C, Howard Hughes Med Inst, New Haven, CT 06536 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06536 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06536 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shulman, GI (reprint author), Yale Univ, Sch Med, Boyer Ctr Mol Med 254C, Howard Hughes Med Inst, 295 Congress Ave, New Haven, CT 06536 USA. FU NCRR NIH HHS [M01 RR-00125, M01 RR000125]; NIDDK NIH HHS [K23 DK-02734, K23 DK002734, P30 DK-34576, R01 DK-49230, R01 DK-51729, R01 DK049230, R01 DK051729] NR 29 TC 419 Z9 452 U1 1 U2 20 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2002 VL 109 IS 10 BP 1321 EP 1326 DI 10.1172/JCI200214955 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 554WL UT WOS:000175760100009 PM 12021247 ER PT J AU Caliendo, AM St George, K Allega, J Bullotta, AC Gilbane, L Rinaldo, CR AF Caliendo, AM St George, K Allega, J Bullotta, AC Gilbane, L Rinaldo, CR TI Distinguishing cytomegalovirus (CMV) infection and disease with CMV nucleic acid assays SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEQUENCE-BASED AMPLIFICATION; LIVER-TRANSPLANT RECIPIENTS; PREEMPTIVE GANCICLOVIR THERAPY; SOLID-ORGAN TRANSPLANTATION; CLINICAL UTILITY; RISK FACTOR; HEART-TRANSPLANTATION; ANTIGENEMIA ASSAY; CONTROLLED TRIAL; MONITOR TEST AB Human cytomegalovirus (CMV) continues to be a significant cause of morbidity and mortality among transplant recipients. Molecular assays have been developed for the detection and quantification of CMV nucleic acid. In evaluating the clinical utility of these assays, correlations with clinical outcome are essential. The Amplicor CMV Monitor and NucliSens CMV pp67 tests were compared to the CMV antigenemia assay for 45 transplant recipients and 1 patient with Wegener's granulomatosis. Twenty-three patients remained antigenemia negative throughout the monitoring period, none of whom developed CMV disease. In this patient group, both the Amplicor and NucliSens assays showed very high specificity; only I of the 324 specimens assayed by NuchSens and none of the 303 specimens assayed by Amplicor were positive. Twenty-three patients were antigenemia positive during the monitoring period, 12 of whom developed 13 episodes of symptomatic CMV disease. In this patient group, the NucliSens assay was positive at or before the development of symptoms in 12 of the 13 episodes of CMV disease. All eight patients with symptomatic CMV disease who were tested by, the Amplicor assay were positive at or before the development of disease. For the 11 asymptomatic patients, the NucliSens assay was positive less frequently than the antigenemia or Amplicor assays. The NucliSens assay was more likely to be positive at higher antigenemia or viral load levels. Both the NucliSens and Amplicor assays appear to have clinical utility in monitoring patients for CMV disease. C1 Massachusetts Gen Hosp, Clin Microbiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Pittsburgh, Med Ctr, Clin Virol Lab, Pittsburgh, PA USA. Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. RP Caliendo, AM (reprint author), Emory Univ, Sch Med, Dept Pathol & Lab Med, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. NR 33 TC 40 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2002 VL 40 IS 5 BP 1581 EP 1586 DI 10.1128/JCM.40.5.1581-1586.2002 PG 6 WC Microbiology SC Microbiology GA 549DA UT WOS:000175428200002 PM 11980925 ER PT J AU Perea, S Gonzalez, G Fothergill, AW Sutton, DA Rinaldi, MG AF Perea, S Gonzalez, G Fothergill, AW Sutton, DA Rinaldi, MG TI In vitro activities of terbinafine in combination with fluconazole, itraconazole, voriconazole, and posaconazole against clinical isolates of Candida glabrata with decreased susceptibility to azoles SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HIV-INFECTED PATIENTS; OROPHARYNGEAL CANDIDIASIS; ANTIFUNGAL AGENTS; ALBICANS AB A checkerboard microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was used to study the in vitro interaction of terbinafine (TRB) with fluconazole (FLU), itraconazole (ITRA), voriconazole (VRC), and posaconazole (PSZ) in 24 isolates of Candida glabrata with decreased susceptibility to azoles isolated from the oral cavities of human immunodeficiency virus patients. Synergy, defined as a fractional inhibitory concentration index of less than or equal to0.5, was observed in 17% of TRB-FLU interactions, 21% of TRB-ITRA, interactions, 33% of TRB-VRC interactions, and 12% of TRB-PSZ interactions. Where synergy was not achieved, there was still a decrease in the MIC of one or both drugs when used in combination. Antagonism was not observed in any drug combination. Clinical studies are warranted to elucidate the potential utility of these combination therapies. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Perea, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. NR 14 TC 43 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2002 VL 40 IS 5 BP 1831 EP 1833 DI 10.1128/JCM.40.5.1831-1833.2002 PG 3 WC Microbiology SC Microbiology GA 549DA UT WOS:000175428200047 PM 11980970 ER PT J AU Redding, SW Kirkpatrick, WR Coco, BJ Sadkowski, L Fothergill, AW Rinaldi, MG Eng, TY Patterson, TF AF Redding, SW Kirkpatrick, WR Coco, BJ Sadkowski, L Fothergill, AW Rinaldi, MG Eng, TY Patterson, TF TI Candida glabrata oropharyngeal candidiasis in patients receiving radiation treatment for head and neck cancer SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ALBICANS; SUSCEPTIBILITY; EPIDEMIOLOGY; INFECTION AB Candida glabrata colonization is common in patients receiving radiation treatment for head and neck cancer, but to our knowledge has never been described as the infecting organism with or Oropharyngeal candidiasis (OPC). This study presents the first three patients describd with C. glabrata OPC in this patient population. Patient 1 developed C. glabrata OPC and required fluconazole, 800 mg/day, for clinical resolution. Antifungal susceptibility testing revealed a MIC of fluconazole of >64 mug/ml. Elapsed time from initial culturing to treatment decision was 7 days. Patients 2 and 3 developed C. glabrata OPC. They were patients in a study evaluating OPC infections, and cultures were taken immediately. CHROMagar Candida plates with 0, 8, and 16 mug of fluconazole/ml were employed for these cultures. Lavender colonies, consistent with C. glabrata, grew on the 0- and 8-mug plates but not on the 16-mug plate from patient 2 and grew on all three plates from patient 3. Based on these data, a fluconazole dose of 200 mg/day was chosen for patient 2 and it dose of 400 mg/day was chosen for patient 3, with clinical resolution in both. Elapsed time from initial culturing to treatment decision was 2 days. C. glabrata does cause OPC in head and neck radiation treatment patients, and the use of fluconazole-impregnated chromogenic agar may significantly reduce treatment decision time compared to that with conventional culturing and antifungal susceptibility testing. C1 Univ Texas, Hlth Sci Ctr, Dept Gen Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, San Antonio, TX 78229 USA. RP Redding, SW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Gen Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 8 TC 35 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2002 VL 40 IS 5 BP 1879 EP 1881 DI 10.1128/JCM.40.5.1879-1881.2002 PG 3 WC Microbiology SC Microbiology GA 549DA UT WOS:000175428200061 PM 11980984 ER PT J AU Umbricht, DS Wirshing, WC Wirshing, DA McMeniman, M Schooler, NR Marder, SR Kane, JM AF Umbricht, DS Wirshing, WC Wirshing, DA McMeniman, M Schooler, NR Marder, SR Kane, JM TI Clinical predictors of response to clozapine treatment in ambulatory patients with schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT VIth International Congress on Schizophrenia Research CY APR 12-17, 1997 CL COLORADO SPRINGS, COLORADO ID NEGATIVE SYMPTOMS; FLUPHENAZINE; OUTPATIENTS; HALOPERIDOL; SCALE AB Background: Despite the advent of new atypical antipsychotics, clozapine remains an important option in the treatment of patients with poor response to conventional antipsychotics. Clinicians would be well served if clinical characteristics Could be identified that predict a favorable response to clozapine. A few Studies addressing this issue have reported inconsistent results. Method: The association of clinical characteristics with a sustained response was investigated in 37 partially treatment-refractory outpatients with a DSM-III-R diagnosis of chronic schizophrenia who had been assigned to clozapine treatment in a double-blind, haloperidol-controlled. long-term (29-week) study of clozapine. Response was defined as a 20% decrease of the Brief Psychiatric Rating Scale (BPRS) psychosis factor score sustained over 2 consecutive ratings. Differences between responders and nonresponders with regard to selected baseline variables were analyzed with t tests and chi(2) tests. In addition. Cox regression analyses were performed to identify variables that best predicted a response to clozapine treatment. Results: Clozapine responders were rated as less severely ill. showed a lesser degree of negative symptoms, and demonstrated fewer extrapyramidal side effects at baseline as compared with nonresponders. In addition, higher BPRS total scores-after controlling for the effects of the other variables-were associated with a response. Conclusion: In a cohort of partially treatment-refractory outpatients, a favorable response to clozapine was associated with characteristics describing less severely ill patients. The history of patients did not affect their response to clozapine. C1 Univ Zurich, Dept Psychiat Res, Psychiat Univ Hosp Zurich, CH-8029 Zurich, Switzerland. Hillside Hosp, Res Dept, Glen Oaks, NY 11004 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. RP Umbricht, DS (reprint author), Univ Zurich, Dept Psychiat Res, Psychiat Univ Hosp Zurich, POB 68,Lenggstr 31, CH-8029 Zurich, Switzerland. FU NIMH NIH HHS [MH41960, MH46484, MH46613, MH46672] NR 25 TC 37 Z9 37 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2002 VL 63 IS 5 BP 420 EP 424 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 552AN UT WOS:000175596300008 PM 12019667 ER PT J AU Sanelli, PC Tong, S Gonzalez, RG Eskey, CJ AF Sanelli, PC Tong, S Gonzalez, RG Eskey, CJ TI Normal variation of vertebral artery on CT angiography and its implications for diagnosis of acquired pathology SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE arteries, vertebral; computed tomograph angiography ID CONVENTIONAL ANGIOGRAPHY; DISSECTION; TORTUOSITY; FORAMEN; ORIGIN AB Purpose: CT angiograpliy (CTA) is rapidly becoming a popular tool for the evaluation of cerebrovascular diseases. Noninvasive diagnosis of vertebral artery pathology using CTA relies in part on diminished vertebral artery size or eccentric position relative to the transverse foramen. However, normal variation of the vertebral artery on CT has not been systematically described. Method: Patients younger than 40 years who underwent CTA for reasons other than evaluation of vertebral artery disease were studied. Area measurements of the vertebral artery and the transverse foramen Were performed by three radiologists. Variance component analysis was performed. Results: There is marked variation in the size of the vertebral artery relative to the transverse foramen, with the vertebral artery occupying 8-85% of the foramen. In many patients, marked asymmetry in relative vertebral artery size and position was observed. This asymmetry would often vary markedly from le cl to level within the same patient. Conclusion: Vertebral artery size and position in the transverse foramina vary markedly in normal young subjects. These normal variations must be considered when evaluating vertebral artery pathology on CT angiograms. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Sanelli, PC (reprint author), New York Presbyterian Hosp, New York Weill Cornell Med Ctr, 520 E 70 St,Starr Pavil, New York, NY 10021 USA. NR 27 TC 30 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2002 VL 26 IS 3 BP 462 EP 470 DI 10.1097/01.RCT.0000014443.78502.7E PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 555NH UT WOS:000175799800027 PM 12016382 ER PT J AU Hussein, MR Wood, GS AF Hussein, MR Wood, GS TI Microsatellite instability and its relevance to cutaneous tumorigenesis SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Review ID NONPOLYPOSIS COLORECTAL-CANCER; MISMATCH REPAIR GENES; MUIR-TORRE-SYNDROME; SPORADIC ENDOMETRIAL CARCINOMAS; SPONTANEOUS MUTATION-RATES; POLYMERASE CHAIN-REACTION; DNA-REPLICATION ERRORS; BASAL-CELL CARCINOMA; SHORT TANDEM REPEATS; GASTRIC CARCINOMAS AB Increasing evidence suggests that human tumors sequentially accumulate multiple mutations that cannot be explained by the low rates of spontaneous mutations in normal cells (2-3 mutations/cell). The mathematical models estimate that for the solid tumors to develop, as many as 6-12 mutations are required in each tumor cell. Therefore, to account for such high mutation rates, it is proposed that tumor cells are genetically unstable, i.e. they have genome-wide mutations at short repetitive DNA sequences called microsatellites. Microsatellite repeats are scattered throughout the human genome, primarily in the non-coding regions, and can give rise to variants with increased or reduced lengths, i.e. microsatellite instability (MSI). This instability has been reported in an increasing number of cutaneous tumors including: melanocytic tumors, basal cell carcinomas and primary cutaneous T-cell lymphomas. Moreover, MSI has been observed in skin tumors arising in the context of some hereditary disorders such as Muir-Torre syndrome, Von Recklinghausen's disease and disseminated superficial porokeratosis. While MSI in some of these disorders reflects underlying DNA replication errors, the mechanism of instability in others is still unknown. Thus far, MSI is considered to be a distinct tumorigenic pathway that reveals surprising versatility. The ramifications for cutaneous neoplasms warrant further investigation. C1 Univ Wisconsin, Dept Med Dermatol, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Med Dermatol, Madison, WI 53705 USA. FU NIAMS NIH HHS [AR02136] NR 131 TC 17 Z9 19 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2002 VL 29 IS 5 BP 257 EP 267 DI 10.1034/j.1600-0560.2002.290501.x PG 11 WC Dermatology; Pathology SC Dermatology; Pathology GA 570CR UT WOS:000176641100001 PM 12100625 ER PT J AU Palosaari, H Ding, Y Larmas, M Sorsa, T Bartlett, D Salo, T Tjaderhane, L AF Palosaari, H Ding, Y Larmas, M Sorsa, T Bartlett, D Salo, T Tjaderhane, L TI Regulation and interactions of MT1-MMP and MMP-20 in human odontoblasts and pulp tissue in vitro SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE MMP; TGF-beta; BMP-2; odontoblasts; pulp tissue; activation ID TYPE-1 MATRIX-METALLOPROTEINASE; GELATINASE-A ACTIVATION; IN-VITRO; MESSENGER-RNA; EXPRESSION; DOMAIN; CELLS; TGF-BETA-1; IDENTIFICATION; PROGELATINASE AB MT1-MMP is a cell-membrane-bound meta-lloenzyme that activates other proMMPs such as proMMP-2 and -13. We studied MT1-MMP expression in mature human odontoblasts and pulp tissue, the regulation of MT1-MMP expression by growth factors TGF-beta1 and BMP-2, and the activation of odontoblast-derived MMP-20 by MT1-MMP. MT1-MMP mRNA is expressed by native and cultured mature human odontoblasts and pulp tissue. Western blot analysis of human odontoblasts and pulp tissue detects 65- and 51-kDa pro- and active forms of MT1-MMP, and smaller truncated MT1-MMP forms, BMP-2 down-regulates MT1-MMP expression in odontoblasts and pulp tissue, while TGF-beta1, alone or with BMP-2, decreases MT1-MMP mRNA levels only slightly. We also demonstrate that MT1-MMP is capable of converting proMMP-20 into a form corresponding to the active MMP-20. In conclusion, this study demonstrates the expression and differential regulation of MT1-MMP in human dentin-pulp complex cells, and the activation oF MMP-20 by MT1-MMP. C1 Univ Oulu, Inst Dent, Oulu 90014, Finland. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Univ Helsinki, Cent Hosp, Oral Pathol Unit & Biomedicum, Diagnost Lab, Helsinki, Finland. Oulu Univ, Cent Hosp, SF-90220 Oulu, Finland. Harvard Univ, Forsyth Inst, Dept Oral Biol, Boston, MA 02115 USA. Harvard Univ, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Univ Toronto, Fac Dent, Dept Endodont, Toronto, ON, Canada. RP Palosaari, H (reprint author), Univ Oulu, Inst Dent, POB 5281, Oulu 90014, Finland. RI Tjaderhane, Leo/J-5017-2015 OI Tjaderhane, Leo/0000-0002-5018-478X FU NIDCR NIH HHS [DE 13237, R01 DE014084] NR 28 TC 25 Z9 30 U1 0 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 2002 VL 81 IS 5 BP 354 EP 359 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 546NQ UT WOS:000175280500013 PM 12097451 ER PT J AU Liu, SW Kumar, AM Nadel, ES Brown, DFM AF Liu, SW Kumar, AM Nadel, ES Brown, DFM TI A young woman with altered mental status SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID CALCIUM C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Liu, SW (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2002 VL 22 IS 4 BP 405 EP 408 AR PII S0736-4679(02)00450-X DI 10.1016/S0736-4679(02)00450-X PG 4 WC Emergency Medicine SC Emergency Medicine GA 574WG UT WOS:000176912100014 PM 12113853 ER PT J AU Huerta, S DeShields, S Shpiner, R Li, ZP Liu, C Sawicki, M Arteaga, J Livingston, EH AF Huerta, S DeShields, S Shpiner, R Li, ZP Liu, C Sawicki, M Arteaga, J Livingston, EH TI Safety and efficacy of postoperative continuous positive airway pressure to prevent pulmonary complications after Roux-en-Y gastric bypass SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2001 CL ATLANTA, GEORGIA SP Soc Surg Alimentary Tract DE obstructive sleep apnea; anastomosis; pneumonia; anastomotic dehiscence ID VERTICAL BANDED GASTROPLASTY; OBSTRUCTIVE SLEEP-APNEA; MORBID-OBESITY; SURGERY; MASK AB Continuous positive airway pressure (CPAP) is used to prevent apneic arrest and/or hypoxia in patients suffering from obstructive sleep apnea. This modality has not been universally accepted for patients following upper gastrointestinal surgery because of concerns that pressurized air will inflate the stomach and proximal intestine, resulting in anastomotic disruption. This study was performed to assess the safety and efficacy of postoperative CPAP for patients undergoing a gastrojejunostomy as part of a Roux-en-Y gastric bypass (RYGB) procedure. A total of 1067 patients (837 women [78%] and 230 men [22%]) were prospectively evaluated for the risk of developing anastomotic leaks and pulmonary complications after the RYGB procedure. Of the 1067 patients undergoing gastric bypass, 420 had obstructive sleep apnea and 159 were dependent on CPAP. There were 15 major anastomotic leaks, two of which occurred in CPAP-treated patients. Contingency table analysis demonstrated that there was no correlation between CPAP utilization and the incidence of major anastomotic leakage (P = 0.6). Notably, no episodes of pneumonia were diagnosed in either group. Despite the theoretical risk of anastomotic injury from pressurized air delivered by CPAP, no anastomotic leaks occurred that were attributable to CPAP. There were no pulmonary complications in a patient population that is at risk for developing them postoperatively. CPAP is a useful modality for treating hypoventilation after RYGB without increasing the risk of developing postoperative anastomotic leaks. C1 Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pulm Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles, Los Angeles, CA USA. RP Huerta, S (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, 900 Vet Ave,12-217 Warren Hall,Box 951742, Los Angeles, CA 90095 USA. NR 22 TC 53 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2002 VL 6 IS 3 BP 354 EP 358 AR PII S1091-255X(01)00048-8 DI 10.1016/S1091-255X(01)00048-8 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627EN UT WOS:000179920400023 PM 12022987 ER PT J AU Stylopoulos, N Bunker, CJ Rattner, DW AF Stylopoulos, N Bunker, CJ Rattner, DW TI Development of achalasia secondary to laparoscopic Nissen fundoplication SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2001 CL ATLANTA, GEORGIA SP Soc Surg Alimentary Tract DE achalasia; dysphagia; fundoplication; gastroesophageal reflux disease ID ESOPHAGEAL SPHINCTER RELAXATION; ANTIREFLUX SURGERY; DYSPHAGIA; VAGOTOMY; DISORDERS; FAILURE AB Dysphagia after laparoscopic Nissen fundoplication (LNF) is commonly attributed to edema and/or improperly constructed wraps, and in some instances the cause can be difficult to identify. We report, for the first time, the development of secondary achalasia after LNF as a cause of late-onset postoperative dysphagia. A total of 250 consecutive patients undergoing LNF were analyzed for the development of postoperative dysphagia at a university hospital. Patients were considered to have secondary achalasia if they met the following four criteria: (1) preoperative manometry demonstrating normal peristalsis and normal lower esophageal sphincter (LES) relaxation; (2) lack of esophageal peristalsis on postoperative manometry or fluoroscopy with or without incomplete LES relaxation; (3) no mucosal lesions seen on endoscopy; and (4) dysphagia refractory to dilatation. The following three groups of patients were identified: patients who developed secondary achalasia (group A, n = 7); patients with persistent dysphagia requiring and responding to postoperative dilatation (group B, n 12 patients); and patients whose postoperative recovery was not complicated by dysphagia (group C, n = 2 3 1). The groups were comparable in terms of all preoperative variables except for age. Patients in group A were older than those in group B (57 years [range 27 to 66 years] vs. 36.5 years [range 27 to 63 years], P = 0.028) but were not significantly older than patients in group C (45 years [range 20 to 84 years], P = 0.42). The onset of severe dysphagia was later in group A than in group B (135 days [range 15 to 300 days] vs. 20 days [range 9 to 70 days], P = 0.002). The median weight loss in group A was also significantly greater than in Group B (15 pounds [range I I to 44 pounds] vs. 4 pounds [range 0 to 15 pounds], P = 0.0007). Two patients in group A who underwent reoperation failed to improve. Botulinum toxin injections were tried in two patients and Heller myotomy in one with good results. Nine patients in group B improved promptly after one dilatation, and three improved after two dilatations. Secondary achalasia should be considered as one of the causes of persistent dysphagia after an apparently successful antireflux operation. Secondary achalasia tends to occur in older patients and is characterized by a delayed onset of symptoms. Imaging studies are a reliable means of excluding mechanical obstruction as a cause of secondary achalasia, and a negative result should raise the suspicion of secondary achalasia. Esophageal motility studies are necessary to confirm the diagnosis. Failure to consider the diagnosis of secondary achalasia can lead to multiple fruitless attempts at dilatation or even inappropriate reoperations. C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. NR 38 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2002 VL 6 IS 3 BP 368 EP 376 AR PII S1091-255X(01)00019-7 DI 10.1016/S1091-255X(02)00019-7 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627EN UT WOS:000179920400025 PM 12022989 ER PT J AU Doble, MA Tola, VB Chamberlain, SA Cima, RR Van Hoek, A Soybel, DI AF Doble, MA Tola, VB Chamberlain, SA Cima, RR Van Hoek, A Soybel, DI TI Luminal regulation of Na+/H+ exchanger gene expression in rat ileal mucosa SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2001 CL ATLANTA, GEORGIA SP Soc Surg Alimentary Tract DE intestinal mucosa; ion transport; Na+; H+; glutamine ID ILEOSTOMY; NHE3; ISOFORM; COLON; WATER AB It is well recognized that ileostomy patients suffer from chronic depletion of Na+ through the stoma effluent. In this study we evaluated the effects of ileostomy on messenger RNA levels that encode different Na+/H+ exchanger isoforms (NHE-2 and NHE-3). Loop ileostomies were created in Sprague-Dawley rats. Segments of diverted ileum were harvested for quantitation of mRNA levels encoding these isoforms and the Na+/K+ ATPase in mucosal scrapings and for immunofluorescence microscopy, specifically of the NHE-3 protein. Our studies indicate that as early as 8 days after diversion, NHE-3 gene expression is selectively attenuated in poststomal ileal mucosa. Mucosal morphology remains undisturbed, and the distribution of protein expression along the crypt/villus axis is not altered. Infusion of Na+ or the enterocyte nutrient, glutamine, into the lumen of the diverted segment restores or even augments mRNA levels for NHE-3, again without altering the histologic appearance or distribution of the protein along the crypt/villus axis. These effects are specific because nonpolar osmolytes (mannitol) and related organic nutrients not specific for the enterocyte (i.e., butyrate) have no effect on mRNA levels of NHE-3. Further work is required to understand how the early changes in mRNA contribute to mucosal function and response to luminal diversion. C1 Brigham & Womens Hosp, Div Gen & Gastrointestinal Surg, Dept Surg, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA USA. RP Soybel, DI (reprint author), Brigham & Womens Hosp, Div Gen & Gastrointestinal Surg, Dept Surg, VA Boston Healthcare Syst, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [R01 DK 44571-11] NR 22 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2002 VL 6 IS 3 BP 387 EP 395 AR PII S1091-255X(01)00049-X DI 10.1016/S1091-255X(01)00049-X PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627EN UT WOS:000179920400029 PM 12022991 ER PT J AU Hinnebusch, BF Ma, Q Henderson, JW Siddique, A Archer, SY Hodin, RA AF Hinnebusch, BF Ma, Q Henderson, JW Siddique, A Archer, SY Hodin, RA TI Enterocyte response to ischemia is dependent on differentiation state SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2001 CL ATLANTA, GEORGIA SP Soc Surg Alimentary Tract DE small intestine; ischemia; apoptosis; differentiation ID INTESTINAL ADAPTATION; TRANSGENIC MICE; GENE-EXPRESSION; CELLS; CULTURE; ACID AB Enterocytes at the tips of microvilli are more sensitive to an ischemic insult than those cells residing in the crypts, an effect thought to be due to a relative lack of collateral flow. We speculated that this increased cellular sensitivity to ischemia might be an intrinsic feature of the cells related to their differentiated phenotype. To test this hypothesis, enterocyte response to ischemia was determined using both in vivo and in vitro models. For the in vivo studies, male Sprague-Dawley rats underwent laparotomy, and small intestinal ischemia was induced by clamping the superior mesenteric artery for 30 or 60 minutes, after which reperfusion was allowed for various time points up to 4 days. Injury was assessed histologically, as well as with Northern blots, probing for the enterocyte differentiation markers intestinal alkaline phosphatase and lactase, as well as the gut-epithelial marker villin. Mucosal changes consistent with ischemia/reperfusion injury were evident-that is, a rapid inflammatory response followed by progressive villus cell loss beginning at the tips and progressing to the crypts, depending on the degree of insult, with an eventual return to normal microanatomy. Intestinal alkaline phosphatase and lactase were lost immediately after ischemia and returned with reperfusion, confirming that the differentiated cells are particularly sensitive to ischemic injury. The in vitro studies employed two separate models of enterocyte differentiation: sodium butyrate-treated HT-29 cells and Caco-2 cells maintained for 7 days after confluence. In both models, undifferentiated and differentiated cells were subjected to treatment with 2-deoxyglucose and oligomycin-A (in vitro model of ischemia) and apoptosis was assessed by fluorescence-activated cell sorting analysis. Differentiation of both cell lines resulted in a significantly greater apoptotic response to ischemia compared to undifferentiated cells exposed to an identical insult. We conclude that differentiated enterocytes may be inherently more sensitive to ischemia-induced injury than their undifferentiated counterparts. These findings call into question the popularly held belief that villus tip cells are more susceptible to ischemia because of their location relative to the microvascular anatomy. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, 504 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK02527, DK47186, DK50623] NR 23 TC 31 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2002 VL 6 IS 3 BP 403 EP 409 AR PII S1091-255X(01)00076-2 DI 10.1016/S1091-255X(01)00076-2 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627EN UT WOS:000179920400031 PM 12022993 ER PT J AU Balcom, JH Keck, T Warshaw, AL Antoniu, B Lauwers, GY Fernandez-del Castillo, C AF Balcom, JH Keck, T Warshaw, AL Antoniu, B Lauwers, GY Fernandez-del Castillo, C TI Perioperative matrix metalloproteinase inhibition therapy does not impair wound or anastomotic healing SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2001 CL ATLANTA, GEORGIA SP Soc Surg Alimentary Tract DE matrix metalloproteinase; wound healing; anastomosis; collagen; surgical oncology ID DIFFERENTIAL EXPRESSION; COLONIC ANASTOMOSES; PANCREATIC-CANCER; STRENGTH; HYDROXYPROLINE; STROMELYSIN-2; ACTIVATION; REPAIR; MODEL; RATS AB Matrix metalloproteinases (MMP's) catalyze the degradation of collagen and extracellular matrix. They play a role in pathologic states including malignancy, in which they facilitate invasion and metastasis. MMP inhibition has been shown to block neoplastic invasion and improve survival in animal models of malignancy. Concern about the effects of NIMP inhibitors on wound and anastomotic healing may limit their potential use in the perioperative period to prevent local and systemic showering of cancer cells from surgical manipulation. We sought to assess the safety of perioperative administration of an MMP inhibitor (BB-94) with respect to skin and bowel healing in a rat model. Absorption of BB-94 was confirmed through high-pressure liquid chromatography and mass spectroscopy of sera from treated animals. Bowel bursting pressure in all animals increased almost 10-fold between 4 and 14 days. Two-way analysis of variance showed no significant difference in bowel bursting pressure between control and treatment animals over time. There was a significant increase in the collagen content of skin specimens of all animals combined between 4 and 28 days. Similarly, all animals showed an increase in bowel collagen between 4 and 28 days. There was no significant difference in skin or bowel collagen concentrations between control and treatment animals over time. Perioperative treatment with MMP inhibition does not impair wound or enteric healing in a rat model of laparotomy and small bowel resection. NIMP inhibitors are safe for use as adjuvant therapy after resection for cancer. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp WACC 336, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2002 VL 6 IS 3 BP 488 EP 495 AR PII S1091-255X(02)00015-X DI 10.1016/S1091-255X(02)00015-X PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627EN UT WOS:000179920400050 PM 12023004 ER PT J AU Sena-Esteves, M Hampl, JA Camp, SM Breakefield, XO AF Sena-Esteves, M Hampl, JA Camp, SM Breakefield, XO TI Generation of stable retrovirus packaging cell lines after transduction with herpes simplex virus hybrid amplicon vectors SO JOURNAL OF GENE MEDICINE LA English DT Article DE retroviral vectors; packaging lines; HSV amplicons; hybrid vectors; gene therapy ID MALIGNANT BRAIN-TUMORS; EPSTEIN-BARR VIRUS; HUMAN GLIOMA-CELLS; GENE-THERAPY; HIGH-TITER; RECOMBINANT RETROVIRUSES; PRODUCER CELLS; HELPER-FREE; THYMIDINE KINASE; HUMAN SERUM AB Background A number of properties have relegated the use of Moloney murine leukemia virus (Mo-MLV)-based retrovirus vectors primarily to ex vivo protocols. Direct implantation of retro-virus producer cells can bypass some of the limitations, and in situ vector production may result in a large number of gene transfer events. However, the fibroblast nature of most retrovirus packaging cells does not provide for an effective distribution of vector producing foci in vivo, especially in the brain. Effective development of new retrovirus producer cells with enhanced biologic properties may require the testing of a large number of different cell types, and a quick and efficient method to generate them is needed. Methods Moloney murine leukemia virus (Mo-MLV) gag-pol and env genes and retrovirus vector sequences carrying lacZ were cloned into different minimal HSV/AAV hybrid amplicons. Helper virus-free amplicon vectors were used to co-infect glioma cells in culture. Titers and stability of retrovirus vector production were assessed. Results Simultaneous infection of two glioma lines, Gli-36 (human) and J3T (dog), with both types of amplicon vectors, generated stable packaging populations that produced retrovirus titers of 0.5-1.2 x 10(5) and 3.1-7.1 x 10(3) tu/ml respectively. Alternatively, when cells were first infected with, retrovirus vectors followed by infection with HyRMOVAmpho amplicon vector, stable retrovirus packaging populations were obtained from Gli-36 and J3T cells producing retrovirus titers comparable to those obtained with a traditional retrovirus packaging cell line, PsiCRIPlacZ. Conclusions This amplicon vector system should facilitate generation of new types of retrovirus producer cells. Conversion of cells with migratory or tumor/tissue homing properties could result in expansion of the spatial distribution or targeting capacity, respectively, of gene delivery by retrovirus vectors in vivo. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Breakefield, XO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Mol Neurogenet Unit, CNY 6205,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 66 TC 17 Z9 18 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAY-JUN PY 2002 VL 4 IS 3 BP 229 EP 239 DI 10.1002/jgm.276 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 569TB UT WOS:000176617400001 PM 12112640 ER PT J AU Bradley, KA Epler, AJ Bush, KR Sporleder, JL Dunn, CW Cochran, NE Braddock, CH McDonell, MB Fihn, SD AF Bradley, KA Epler, AJ Bush, KR Sporleder, JL Dunn, CW Cochran, NE Braddock, CH McDonell, MB Fihn, SD TI Alcohol-related discussions during general medicine appointments of male VA patients who screen positive for at-risk drinking SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcohol; primary care; brief interventions; motivational interviewing ID RANDOMIZED CONTROLLED TRIAL; PRIMARY-CARE PHYSICIANS; BRIEF INTERVENTIONS; DRINKERS; CAGE; ABUSE; METAANALYSIS; PREVENTION; SERVICES; IMPACT AB OBJECTIVE: This study describes primary care discussions with patients who screened positive for at-risk drinking. In addition, discussions about alcohol use from 2 clinic firms, one with a provider-prompting intervention, are compared. DESIGN: Cross-sectional analyses of audiotaped appointments collected over 6 months. PARTICIPANTS AND SETTING: Male patients in a VA general medicine clinic were eligible if they screened positive for atrisk drinking and had a general medicine appointment with a consenting provider during the study period. Participating patients (N = 47) and providers (N = 17) were enrolled in 1 of 2 firms in the clinic (Intervention or Control) and were blinded to the study focus. INTERVENTION: Intervention providers received patient-specific results of positive alcohol-screening tests at each visit. MEASURES AND MAIN RESULTS: Of 68 visits taped, 39 (57.4%) included any mention of alcohol. Patient and provider utterances during discussions about alcohol use were coded using Motivational Interviewing Skills Codes. Providers contributed 58% of utterances during alcohol-related discussions with most coded as questions (24%), Information giving (23%), or facilitation (34%). Advice, reflective listening, and supportive or affirming statements occurred infrequently (5%, 3%, and 5%, of provider utterances respectively). Providers offered alcohol-related advice during 21% of visits. Sixteen percent of patient utterances reflected "resistance" to change and 12% reflected readiness to change. On average, Intervention providers were more likely to discuss alcohol use than Control providers (82.4% vs 39.6% of visits; P = .026). CONCLUSIONS: During discussions about alcohol, general medicine providers asked questions and offered information, but usually did not give explicit alcohol-related advice. Discussions about alcohol occurred more often when providers were prompted. C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv, Res & Dev Ctr Excellence, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Primary & Specilaty Med Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Res & Educ, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98104 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98104 USA. Univ Washington, Harborview Med Ctr, Harborview Injury Prevent & Res Ctr, Seattle, WA 98104 USA. White River Junct VA Hosp, White River Jct, VT USA. Dartmouth Coll Sch Med, Dept Med & Community & Family Med, White River Jct, VT USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv, Res & Dev Ctr Excellence, HSR&D 152,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [K23 AA000313, K23AA00313] NR 40 TC 37 Z9 38 U1 3 U2 5 PU BLACKWELL PUBLISHING 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 MAY PY 2002 VL 17 IS 5 BP 315 EP 326 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 556ZU UT WOS:000175882000001 PM 12047727 ER PT J AU Merrill, J Rhodes, LA Deyo, RA Marlott, GA Bradley, KA AF Merrill, J Rhodes, LA Deyo, RA Marlott, GA Bradley, KA TI Mutual mistrust in the medical care of drug users - The keys to the ''narc'' cabinet SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 23-25, 1998 CL CHICAGO, ILLINOIS SP Soc Gen Internal Med DE injection drug use; physician-patient relations; attitude of health personnel; trust; pain treatment; ethnography ID RANDOMIZED CONTROLLED TRIAL; METHADONE-MAINTENANCE; SUBSTANCE-ABUSE; PAIN; MANAGEMENT; DEPENDENCE; PHYSICIANS; OPIOIDS; ACCESS AB OBJECTIVE: Caring for patients who are active drug users is challenging. To better understand the often difficult relationships between Illicit drug-using patients and their physicians, we sought to identify major issues that emerge during their interactions in a teaching hospital. DESIGN: Exploratory qualitative analysis of data from direct observation of patient care interactions and interviews with drug-using patients and their physicians. SETTING: The inpatient internal medicine service of an urban public teaching hospital. PARTICIPANTS: Nineteen patients with recent active drug use, primarily opiate use, and their 8 physician teams. RESULTS: Four major themes emerged. First, physicians feared being deceived by drug-using patients. In particular, they questioned whether patients' requests for opiates to treat pain or withdrawal might result from addictive behavior rather than from "medically indicated" need. Second, they lacked a standard approach to commonly encountered clinical issues, especially the assessment and treatment of pain and opiate withdrawal. Because patients' subjective report of symptoms Is suspect, physicians struggled to find criteria for appropriate opiate prescription. Third, physicians avoided engaging patients regarding key complaints, and expressed discomfort and uncertainty in their approach to these patients. Fourth, drug-using patients were sensitive to the possibility of poor medical care, often interpreting physician inconsistency or hospital Inefficiency as signs of intentional mistreatment. CONCLUSION: Physicians and drug-using patients in the teaching hospital setting display mutual mistrust, especially concerning opiate prescription. Physicians' fear of deception, inconsistency and avoidance interacts with patients' concern that they are mistreated and stigmatized. Medical education should focus greater attention on addiction medicine and pain management. C1 Harborview Med Ctr, Div Gen Internal Med, Seattle, WA 98104 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv, Res & Dev Ctr Excellence, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. RP Merrill, J (reprint author), Harborview Med Ctr, Div Gen Internal Med, 325 9th Ave,Box 359780, Seattle, WA 98104 USA. NR 49 TC 90 Z9 90 U1 2 U2 6 PU BLACKWELL PUBLISHING 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 MAY PY 2002 VL 17 IS 5 BP 327 EP 333 DI 10.1046/j.1525-1497.2002.10625.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 556ZU UT WOS:000175882000002 PM 12047728 ER PT J AU Kraemer, KL Maisto, SA Conigliaro, J McNeil, M Gordon, AJ Kelley, ME AF Kraemer, KL Maisto, SA Conigliaro, J McNeil, M Gordon, AJ Kelley, ME TI Decreased alcohol consumption in outpatient drinkers is associated with improved quality of life and fewer alcohol-related consequences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-05, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Gen Internal Med DE alcohol drinking; alcohol dependence; alcohol abuse; quality of life; health status ID HEALTH SURVEY SF-36; BRIEF INTERVENTIONS; OF-LIFE; READINESS AB This study's objective was to determine whether changes in alcohol consumption are associated with changes in quality of life and alcohol-related consequences in an outpatient sample of drinkers. Two hundred thirteen subjects completed the Short Form 36-item (SF-36) Health Survey and the Short Inventory of Problems at baseline, 6 months, and 12 months. Subjects who sustained a 30% or greater decrease in drinks per month reported Improvement in SF-36 Physical Component Summary (P = .058) and Mental Component Summary (P = .037) scores and had fewer alcohol-related consequences (P < .001) when compared to those with a <30% decrease. These findings suggest another benefit of alcohol screening and intervention in the primary care setting. C1 Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Internal Med, MUH, Pittsburgh, PA 15213 USA. Syracuse Univ, Dept Psychol, Syracuse, NY USA. VA Pittsburgh Healtcare Syst, Ctr Hlth Serv Res, Pittsburgh, PA USA. RP Kraemer, KL (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Internal Med, MUH, E820,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NIAAA NIH HHS [AA1029, K23 AA00235, Z01 AA000235] NR 20 TC 30 Z9 33 U1 1 U2 5 PU BLACKWELL PUBLISHING 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 MAY PY 2002 VL 17 IS 5 BP 382 EP 386 DI 10.1046/j.1525-1497.2002.10613.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 556ZU UT WOS:000175882000011 PM 12047737 ER PT J AU Kweon, YO Goodman, ZD Dienstag, JL Schiff, ER Brown, NA Burchardt, ER Schoonhoven, R Brenner, DA Fried, MW AF Kweon, YO Goodman, ZD Dienstag, JL Schiff, ER Brown, NA Burchardt, ER Schoonhoven, R Brenner, DA Fried, MW TI Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B (vol 35, pg 749, 2001) SO JOURNAL OF HEPATOLOGY LA English DT Correction C1 Univ N Carolina, Chapel Hill, NC 27599 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Miami, Miami, FL 33152 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Bayer Pharmaceut, Leverkusen, Germany. RP Fried, MW (reprint author), Univ N Carolina, CB 7080,Room 708,Burnett Womack Bldg, Chapel Hill, NC 27599 USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAY PY 2002 VL 36 IS 5 BP 714 EP 714 AR PII S0168-8278(02)00116-2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 559FR UT WOS:000176015600024 ER PT J AU van's Gravesande, KS Layne, MD Ye, Q Le, L Baron, RM Perrella, MA Santambrogio, L Silverman, ES Riese, RJ AF van's Gravesande, KS Layne, MD Ye, Q Le, L Baron, RM Perrella, MA Santambrogio, L Silverman, ES Riese, RJ TI IFN regulatory factor-1 regulates IFN-gamma-dependent cathepsin S expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-II; INVARIANT CHAIN; INTERFERON-GAMMA; DENDRITIC CELLS; TRANSCRIPTIONAL ACTIVATOR; TRANSACTIVATOR CIITA; ANTIGEN PRESENTATION; EPITHELIAL-CELLS; IRF-2; GENES AB Cathepsin S is a cysteine protease with potent endoproteolytic activity and a broad pH profile. Cathepsin S activity is essential for complete processing of the MHC class II-associated invariant chain within B cells and dendritic cells, and may also be important in extracellular matrix degradation in atherosclerosis and emphysema. Unique among cysteine proteases, cathepsin S activity is up-regulated by IFN-gamma. Given its importance, we sought to elucidate the pathway by which IFN-gamma increases cathepsin S expression. Our data demonstrate that the cathepsin S promoter contains an IFN-stimulated response element (ISRE) that is critical for IFN-gamma-induced gene transcription in a cell line derived from type II alveolar epithelial (A549) cells. IFN response factor (IRF)-2 derived from A549 nuclear extracts associates with the ISRE oligonucleotide in gel shift assays, but is quickly replaced by IRF-1 following stimulation with IFN-gamma. The time course of IRF-1/ISRE complex formation correlates with increased levels of IRF-1 protein and cathepsin S mRNA. Overexpression of IRF-1, but not IRF-2, markedly augments cathepsin S promoter activity in A549 cells. Furthermore, overexpression of IRF-1 increases endogenous cathepsin S mRNA levels in 293T epithelial cells. Finally, freshly isolated bone marrow cells from IRF-1(-/-) mice fail to up-regulate cathepsin S activity in response to IFN-gamma. Thus, IRF-1 is the critical transcriptional mediator of IFN-gamma-dependent cathepsin S activation. These data elucidate a new pathway by which IRF-1 may affect MHC class II processing and presentation. C1 Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Riese, RJ (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, 75 Francis St Tower 4B, Boston, MA 02115 USA. NR 39 TC 32 Z9 32 U1 1 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 MAY 1 PY 2002 VL 168 IS 9 BP 4488 EP 4494 PG 7 WC Immunology SC Immunology GA 546FP UT WOS:000175263000031 ER PT J AU Yano, K Oura, H Detmar, M AF Yano, K Oura, H Detmar, M TI Targeted overexpression of the angiogenesis inhibitor thrombospondin-1 in the epidermis of transgenic mice prevents ultraviolet-B-induced angiogenesis and cutaneous photo-damage SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE VEGF; skin aging; endothelium ID ENDOTHELIAL GROWTH-FACTOR; HAIRLESS MOUSE SKIN; PERMEABILITY FACTOR VPF/VEGF; TOPICAL TRETINOIN; MOLECULAR REGULATION; RETINOIC ACID; EXPRESSION; CELLS; UVB; RADIATION AB Chronic ultraviolet-B irradiation of the skin results in epidermal hyperplasia, degradation of extracellular matrix molecules, and formation of wrinkles. To characterize the biologic role of the vascular system in the mediation of ultraviolet-B-induced skin damage, we performed quantitative analyses of cutaneous blood vessels of mice after 10 wk of ultraviolet-B irradiation. Skin vascularization was greatly increased after chronic ultraviolet-B exposure with a significant increase of both the number and the size of dermal blood vessels, associated with upregulation of vascular endothelial growth factor expression in the hyperplastic epidermis. To directly study whether inhibition of angiogenesis may diminish ultraviolet-B-induced cutaneous damage, wild-type and transgenic mice with skin-specific overexpression of the endogenous angiogenesis inhibitor thrombospondin-1 were subjected to the same ultraviolet-B irradiation regimen. Ultraviolet-B-irradiated thrombospondin-1 transgenic mice showed a significantly reduced skin vascularization, decreased endothelial cell proliferation, and increased endothelial cell apoptosis rates, compared with wild-type mice. Moreover, dermal photo-damage and wrinkle formation were greatly reduced in thrombospondin-1 transgenic mice. These results reveal an important role of the cutaneous vascular system in mediating ultraviolet-B-induced skin damage and suggest inhibition of angiogenesis as a potential new approach for the prevention of chronic cutaneous photo-damage. C1 Massachusetts Gen Hosp, Dept Dermatol, CBRC, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, CA86410] NR 45 TC 59 Z9 60 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2002 VL 118 IS 5 BP 800 EP 805 DI 10.1046/j.1523-1747.2002.01752.x PG 6 WC Dermatology SC Dermatology GA 549XJ UT WOS:000175472300008 PM 11982756 ER PT J AU Hussein, MRAE Wood, GS AF Hussein, MRAE Wood, GS TI Molecular aspects of melanocytic dysplastic nevi SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Review ID CUTANEOUS MALIGNANT-MELANOMA; TUMOR-SUPPRESSOR GENE; NONPOLYPOSIS COLON-CANCER; FIBROBLAST GROWTH-FACTOR; CELL-CYCLE CONTROL; WILD-TYPE P53; MISMATCH REPAIR GENES; CHROMOSOME ARM 1P; K MOLE SYNDROME; MICROSATELLITE INSTABILITY AB Melanocytic dysplastic nevi were first described in both patients and their relatives who had one or several cutaneous malignant melanomas. Most of these dysplastic lesions are biologically stable, but some of them have severe histological atypia and can progress further to melanomas. Although several studies have suggested the etiological importance of dysplastic nevi in the development of melanomas, comprehensive reviews of the molecular changes in these dysplastic lesions are stiff scarce. To remedy this issue, this article analyzes the available molecular information about dysplastic nevi and provides the current state of knowledge regarding the karyotypic abnormalities of the melanoma/dysplastic nevus trait and the involvement of allelic loss, tumor suppressor genes, mismatch repair proteins, microsatellite instability, oncogenes, extracellular matrix proteins, and growth factors in the genesis of these lesions. These studies suggest that although some of these lesions represent "genetic dead-ends," others represent intermediate lesional steps in the melanoma tumorigenesis pathway. C1 Univ Wisconsin, Dept Med Dermatol, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Med Dermatol, Madison, WI 53705 USA. FU NIAMS NIH HHS [AR 01326] NR 140 TC 26 Z9 27 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2002 VL 4 IS 2 BP 71 EP 80 DI 10.1016/S1525-1578(10)60684-8 PG 10 WC Pathology SC Pathology GA 549TM UT WOS:000175462900001 PM 11986397 ER PT J AU Fitzgerald, ML Moore, KJ Freeman, MW AF Fitzgerald, ML Moore, KJ Freeman, MW TI Nuclear hormone receptors and cholesterol trafficking: the orphans find a new home SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE orphan receptors; ABCA1; bile acids; liver X receptor; cholesterol absorption ID BINDING CASSETTE TRANSPORTER-1; DENSITY-LIPOPROTEIN DEFICIENCY; BILE-ACID BIOSYNTHESIS; MESSENGER-RNA LEVELS; APOLIPOPROTEIN-A-I; TANGIER-DISEASE; PPAR-GAMMA; LXR-ALPHA; CELLULAR CHOLESTEROL; ABC TRANSPORTERS AB There are many homeostatic mechanisms that contribute to the regulation of cellular and serum cholesterol levels in humans. Much of our understanding of this regulation arose from studies of the cellular pathways controlling cholesterol synthesis and the uptake and degradation of low-density lipoproteins. The physiology governing cholesterol disposition in whole animals, including the molecular mechanisms responsible for dietary uptake of cholesterol and its subsequent catabolism to bile acids, are only now being uncovered. This review summarizes recent studies that have used modern genetic techniques, as well as cell biological methods, to begin to elucidate the pathways responsible for cholesterol trafficking in vivo. This work has led to the realization that networks of nuclear hormone receptors, including the LXR, FXR, PPAR, and RXR proteins, play critical roles in lipid metabolism by virtue of their transcriptional regulation of the genes that control sterol metabolic pathways. Some of the major downstream targets of these regulatory networks involve members of the ABC transporter family, including ABCA1, ABCG1, ABCG5, ABCG8, MDR3/Mdr2, and SPGP/BSEP. These transporters contribute to the movement of sterols and biliary lipids across cellular membranes via mechanisms that have yet to be elucidated. The potential for manipulating these cholesterol trafficking pathways via drugs targeted to the nuclear hormone receptors has generated great interest in their biology and will undoubtedly lead to new therapeutic approaches to human disorders in the coming years. C1 Massachusetts Gen Hosp, Harvard Med Sch, Lipid Metab Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Lipid Metab Unit, Boston, MA 02114 USA. OI Moore, kathryn/0000-0003-2505-2547 NR 70 TC 56 Z9 58 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD MAY PY 2002 VL 80 IS 5 BP 271 EP 281 DI 10.1007/s00109-001-0318-y PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 560JC UT WOS:000176078100002 PM 12021839 ER PT J AU Baggio, R Burgstaller, P Hale, SP Putney, AR Lane, M Lipovsek, D Wright, MC Roberts, RW Liu, RH Szostak, JW Wagner, RW AF Baggio, R Burgstaller, P Hale, SP Putney, AR Lane, M Lipovsek, D Wright, MC Roberts, RW Liu, RH Szostak, JW Wagner, RW TI Identification of epitope-like consensus motifs using mRNA display SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Article DE molecular recognition; mRNA; protein; peptide; display; selection; 9E10; EETI-II; Myc; trypsin ID ELATERIUM TRYPSIN-INHIBITOR; AMINO-ACID-SEQUENCES; YEAST SURFACE DISPLAY; IN-VITRO SELECTION; PEPTIDE LIBRARIES; SQUASH FAMILY; PROTEIN; SEEDS; MICROPROTEINS; TECHNOLOGY AB The mRNA display approach to in vitro protein selection is based upon the puromycin-mediated formation of a covalent bond between an mRNA and its gene product. This technique can be used to identify peptide sequences involved in macromolecular recognition, including those identical or homologous to natural ligand epitopes. To demonstrate this approach, we determined the peptide sequences recognized by the trypsin active site, and by the anti-c-Myc antibody, 9E10. Here we describe the use of two peptide libraries of different diversities, one a constrained library based on the trypsin inhibitor EETI-II, where only the six residues in the first loop were randomized (6.4 x 10(7) possible sequences, 6.0 x 10(11) sequences in the library), the other a linear-peptide library with 27 randomized amino acids (1.3 x 10(35) possible sequences, 2 x 10(13) sequences in the library). The constrained library was screened against the natural target of wild-type EETI, bovine trypsin, and the linear library was screened against the anti-c-myc antibody, 9E10. The analysis of selected sequences revealed minimal consensus sequences of PR(LLV)L for the first loop of EETI-II and LISE for the 9E10 epitope. The wild-type sequences, PRILMR for the first loop of EETI-II and QKLISE for the 9E10 epitope, were selected with the highest frequency, and in each case the complete wildtype epitope was selected from the library. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Phylos Inc, Lexington, MA 02421 USA. Noxxon Pharma AG, D-13355 Berlin, Germany. CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Baggio, R (reprint author), Phylos Inc, 128 Spring St, Lexington, MA 02421 USA. NR 36 TC 50 Z9 57 U1 2 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD MAY-JUN PY 2002 VL 15 IS 3 BP 126 EP 134 DI 10.1002/jmr.567 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 580UL UT WOS:000177254200002 PM 12203838 ER PT J AU Jaeckle, KA Batchelor, T O'Day, SJ Phuphanich, S New, P Lesser, G Cohn, A Gilbert, M Aiken, R Heros, D Rogers, L Wong, E Fulton, D Gutheil, JC Baidas, S Kennedy, JM Mason, W Moots, P Russell, C Swinnen, LJ Howell, SB AF Jaeckle, KA Batchelor, T O'Day, SJ Phuphanich, S New, P Lesser, G Cohn, A Gilbert, M Aiken, R Heros, D Rogers, L Wong, E Fulton, D Gutheil, JC Baidas, S Kennedy, JM Mason, W Moots, P Russell, C Swinnen, LJ Howell, SB TI An open label trial of sustained-release cytarabine (DepoCyt (TM)) for the intrathecal treatment of solid tumor neoplastic meningitis SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE neoplastic meningitis; intrathecal; cytarabine; liposome; cerebrospinal fluid ID CEREBROSPINAL-FLUID; MENINGEAL CARCINOMATOSIS; RANDOMIZED TRIAL; BREAST-CANCER; SLOW-RELEASE; METHOTREXATE; CHEMOTHERAPY; EXPOSURE; LUNG AB Drugs currently available for intrathecal administration are cleared rapidly from the CSF. DepoCyt is a slow-release formulation of cytarabine that maintains cytotoxic concentrations of free cytarabine in the CSF for > 14 days following a single injection. DepoCyt was administered to 110 patients with a diagnosis of neoplastic meningitis based on either a positive CSF cytology (76) or neurologic and CT or MRI scan findings sufficient to document neoplastic meningitis (34). Patients were treated with DepoCyt 50 mg every 2 weeks for 1 month of induction therapy by either lumbar puncture (LP) or intraventricular (IVT) injection. Patients without neurologic progression were candidates to receive an additional 3 months of consolidation therapy. All patients received dexamethasone 4 mg BID on days 1-5 of each cycle. Median time to neurologic progression was 55 days; median overall survival was 95 days. Among the 76 patients with a positive CSF cytology at baseline, 70 were evaluable for response, and of this group 19 (27%) attained the criteria for response (cytologic response in the absence of neurologic progression). The most important adverse events were headache and arachnoiditis. When drug-related, these were largely low grade, transient, and reversible. Drug-related grade 3 headache occurred on 4% of cycles; grade 3 or 4 arachnoiditis occurred on 6% of cycles. No cumulative toxicity was observed. DepoCyt injected once every 2 weeks produced a response-rate comparable to that previously reported for methotrexate given twice a week. The once in every 2-week-dosing interval offers an advantage over conventional schedules (2-3 doses/week) used for other agents available for intrathecal injection. C1 Mayo Clin, Jacksonville, FL 32224 USA. Massachusetts Gen Hosp, Dept Neuro Oncol, Boston, MA 02114 USA. John Wayne Canc Inst, Santa Monica, CA USA. Moffitt Canc Ctr, Dept Neuro Oncol, Tampa, FL USA. Univ Texas, Dept Med, San Antonio, TX 78285 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Univ Colorado, Med Ctr, Denver, CO 80202 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Mt Sinai Comprehens Canc Ctr, Miami Beach, FL USA. Wayne State Univ, Ctr Hlth, Detroit, MI USA. Beth Israel Deaconess Med Ctr, Brookline, MA USA. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Sidney Kimmel Canc Ctr, San Diego, CA USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Frankford Hosp, Ctr Canc, Philadelphia, PA USA. Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Norris Canc Ctr, Los Angeles, CA USA. Loyola Univ, Maywood, IL 60153 USA. RP Howell, SB (reprint author), Univ Calif San Diego, Dept Med 0058, La Jolla, CA 92093 USA. NR 19 TC 71 Z9 74 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2002 VL 57 IS 3 BP 231 EP 239 DI 10.1023/A:1015752331041 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 571TD UT WOS:000176734500008 PM 12125986 ER PT J AU Thom, SR Bhopale, V Fisher, D Manevich, Y Huang, PL Buerk, DG AF Thom, SR Bhopale, V Fisher, D Manevich, Y Huang, PL Buerk, DG TI FAST TRACK - Stimulation of nitric oxide synthase in cerebral cortex due to elevated partial pressures of oxygen: An oxidative stress response SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE heat shock protein 90; hyperbaric oxygen; cerebral blood flow; MK 801 ID HYPERBARIC-OXYGEN; BLOOD-FLOW; SUPEROXIDE-DISMUTASE; ARGININE METABOLISM; ENDOTHELIAL-CELLS; RAT-BRAIN; TOXICITY; ACTIVATION; RECEPTOR; PHOSPHORYLATION AB The purpose of this investigation was to determine the impact of elevated partial pressures of 0, on the steady state concentration of nitric oxide (NO) in the cerebral cortex. Rodents with implanted O-2- and NO-specific microelectrodes were exposed to O-2 at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA) for up to 45 min. Elevations in NO concentration occurred with all partial pressures above that of ambient air. In rats exposed to 2.8 ATA 0, the increase was 692 +/- 73 nM (S.E., n = 5) over control. Changes were not associated with alterations in concentrations of nitric oxide synthase (NOS) enzymes. Based on studies with knock-out mice lacking genes for neuronal NOS (nNOS) or endothelial NOS (eNOS), nNOS activity contributed over 90% to total NO elevation due to hyperoxia. Immunoprecipitation studies indicated that hyperoxia doubles the amount of nNOS associated with the molecular chaperone, heat shock protein 90 (Hsp90). Both NO elevations and the association between nNOS and Rsp90 were inhibited in rats infused with superoxide dismutase. Elevations of NO were also inhibited by treatment with the relatively specific nNOS inhibitor, 7 nitroindazole, by the ansamycin antibiotics herbimycin and geldanamycin, by the antioxidant N-acetylcysteine, by the calcium channel blocker nimodipine, and by the N-Methyl-D-aspartate inhibitor, MK 801. Hyperoxia did not alter eNOS association with Hsp90, nor did it modify nNOS or eNOS associations with calmodulin, the magnitude of eNOS tyrosine phosphorylation, or nNOS phosphorylation via calmodulin kinase. Cerebral cortex blood flow, measured by laser Doppler flow probe, increased during hyperoxia and may be causally related to elevations of steady state NO concentration. We conclude that hyperoxia causes an increase in NO synthesis as part of a response to oxidative stress. Mechanisms for nNOS activation include augmentation in the association with Rsp90 and intracellular entry of calcium. (C) 2002 Wiley Periodicals, Inc. C1 Univ Penn, Med Ctr, Dept Emergency Med, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Inst Environm Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Penn, Med Ctr, Dept Physiol, Philadelphia, PA 19104 USA. RP Thom, SR (reprint author), Univ Penn, Med Ctr, Dept Emergency Med, Philadelphia, PA 19104 USA. RI Buerk, Donald/F-6888-2014 FU NCCIH NIH HHS [AT-00428]; NIEHS NIH HHS [ES-05211]; NINDS NIH HHS [NS-33335] NR 44 TC 67 Z9 70 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAY PY 2002 VL 51 IS 2 BP 85 EP 100 DI 10.1002/neu.10044 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 542AK UT WOS:000175020300001 PM 11932951 ER PT J AU Carvelli, L Moron, JA Kahlig, KM Ferrer, JV Sen, N Lechleiter, JD Leeb-Lundberg, LMF Merrill, G Lafer, EM Ballou, LM Shippenberg, TS Javitch, JA Lin, RZ Galli, A AF Carvelli, L Moron, JA Kahlig, KM Ferrer, JV Sen, N Lechleiter, JD Leeb-Lundberg, LMF Merrill, G Lafer, EM Ballou, LM Shippenberg, TS Javitch, JA Lin, RZ Galli, A TI PI 3-kinase regulation of dopamine uptake SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amphetamine; dopamin transporter; insulin; P13-kinase ID PROTEIN-KINASE-C; CELL-SURFACE EXPRESSION; N-SH CELLS; FUNCTIONAL REGULATION; NEUROTRANSMITTER TRANSPORTERS; NOREPINEPHRINE TRANSPORT; RECEPTOR INTERNALIZATION; SEROTONIN TRANSPORTERS; MEMBRANE TRAFFICKING; INSULIN-RECEPTORS AB The magnitude and duration of dopamine (DA) signaling is defined by the amount of vesicular release, DA receptor sensitivity, and the efficiency of DA clearance, which is largely determined by the DA transporter (DAT). DAT uptake capacity is determined by the number of functional transporters on the cell surface as well as by their turnover rate. Here we show that inhibition of phosphatidylinositol (PI) 3-kinase with LY294002 induces internalization of the human DAT (hDAT), thereby reducing transport capacity. Acute treatment with LY294002 reduced the maximal rate of [H-3]DA uptake in rat striatal synaptosomes and in human embryonic kidney (HEK) 293 cells stably expressing the hDAT (hDAT cells). In addition, LY294002 caused a significant redistribution of the hDAT from the plasma membrane to the cytosol. Conversely, insulin, which activates PI 3-kinase, increased [H-3]DA uptake and blocked the amphetamine-induced hDAT intracellular accumulation, as did transient expression of constitutively active PI 3-kinase. The LY294002-induced reduction in [H-3]DA uptake and hDAT cell surface expression was inhibited by expression of a dominant negative mutant of dynamin I, indicating that dynamin-dependent trafficking can modulate transport capacity. These data implicate DAT trafficking in the hormonal regulation of dopaminergic signaling, and suggest that a state of chronic hypoinsulinemia, such as in diabetes, may alter synaptic DA signaling by reducing the available cell surface DATs. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. NIDA, Integrat Neurosci Sect, IRP, Baltimore, MD USA. Columbia Univ, Coll Phys & Surg, Ctr Mol Recognit, New York, NY USA. Brooke Army Med Ctr, Dept Clin Invest, Ft Sam Houston, TX 78234 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Galli, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Mail Code 7764,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Lin, Richard/J-1754-2014 OI Lin, Richard/0000-0002-3473-7276 FU NIDA NIH HHS [DA 13975, DA 11495, DA 14684]; NIMH NIH HHS [MH 57324]; NINDS NIH HHS [R01 NS029051] NR 52 TC 126 Z9 130 U1 2 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2002 VL 81 IS 4 BP 859 EP 869 DI 10.1046/j.1471-4159.2002.00892.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 549YL UT WOS:000175475100020 PM 12065645 ER PT J AU de la Monte, SM Chiche, JD Janssens, SP Bloch, KD AF de la Monte, SM Chiche, JD Janssens, SP Bloch, KD TI Nitric oxide synthase-3 over-expression causes apoptosis and impairs neuronal mitochondrial function: Relevance to Alzheimer type neurodegeneration. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Brown Univ, Mem Hosp Rhode Isl, Sch Med, Providence, RI 02912 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Hosp Gasthuisberg VIB, Ctr Transgen Technol & Gene Therapy, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 22 BP 447 EP 447 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500029 ER PT J AU Delalle, I Newell, K Hedley-Whyte, ET AF Delalle, I Newell, K Hedley-Whyte, ET TI Incidence of cotton wool plaques in Alzheimer disease brains in the Massachusetts Alzheimer disease Research Center Brain Bank. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 50 BP 454 EP 454 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500057 ER PT J AU Newell, KL Dawson, TP AF Newell, KL Dawson, TP TI Tau-immunohistochemical evaluation of septi pellucidi and adjacent areas in brains from former boxers. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Alzheimer Dis Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. Royal Preston Hosp, Dept Neuropathol, Preston, Lancs, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 117 BP 471 EP 471 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500123 ER PT J AU Forman, MS Giasson, BI Duda, JE Miller, B Lee, VM Trojanowski, JQ AF Forman, MS Giasson, BI Duda, JE Miller, B Lee, VM Trojanowski, JQ TI Convergence of tau and alpha-synuclein pathology in dementia patients. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Univ Penn, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Dept Neurol, Philadelphia, PA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2002 VL 61 IS 5 MA 169 BP 484 EP 484 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 554FR UT WOS:000175724500175 ER PT J AU Qiu, JH Whalen, MJ Lowenstein, P Fiskum, G Fahy, B Darwish, R Aarabi, B Yuan, JY Moskowitz, MA AF Qiu, JH Whalen, MJ Lowenstein, P Fiskum, G Fahy, B Darwish, R Aarabi, B Yuan, JY Moskowitz, MA TI Upregulation of the Fas receptor death-inducing signaling complex after traumatic brain injury in mice and humans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE traumatic brain injury; Fas; death-inducing signaling complex; caspases; human; adenoviral vectors ID NEURONAL CELL-DEATH; PC12 CELLS; SYMPATHETIC NEURONS; INDUCED APOPTOSIS; CORTICAL IMPACT; TRANSGENIC MICE; CD95; EXPRESSION; CASPASE-3; PROTEIN AB Recent studies have implicated Fas in the pathogenesis of inflammatory, ischemic, and traumatic brain injury (TBI); however, a direct link between Fas activation and caspase-mediated cell death has not been established in injured brain. We detected Fas-Fas ligand binding and assembly of death-inducing signaling complexes (DISCs) [Fas, Fas-associated protein with death domain, and procaspase-8 or procaspase-10; receptor interacting protein (RIP)-RIP-associated interleukin-1beta converting enzyme and CED-3 homolog-1/Ced 3 homologous protein with a death domain-procaspase-2] by immunoprecipitation and immunoblotting within mouse parietal cortex after controlled cortical impact. At the time of DISC assembly, procaspase-8 was cleaved and the cleavage product appeared at 48 hr in terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive neurons. Cleavage of caspase-8 was accompanied by caspase-3 processing detected at 48 hr by immunohistochemistry, and by caspase-specific cleavage of poly( ADP-ribose) polymerase at 12 hr. Fas pathways were also stimulated by TBI in human brain, because Fas expression plus Fas-procaspase-8 interaction were robust in contused cortical tissue samples surgically removed between 2 and 30 hr after injury. To address whether Fas functions as a death receptor in brain cells, cultured embryonic day 17 cortical neurons were transfected with an adenoviral vector containing the gene encoding Fas ligand. After 48 hr in culture, Fas ligand expression and Fas-procaspase-8 DISC assembly increased, and by 72 hr, cell death was pronounced. Cell death was decreased by similar to50% after pan-caspase inhibition (Z-Val-ALa-Asp(Ome)-fluoromethylketone). These data suggest that Fas-associated DISCs assemble in neurons overexpressing Fas ligand as well as within mouse and human contused brain after TBI. Therefore, Fas may function as a death receptor after brain injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Charlestown, MA 02129 USA. Cedars Sinai Med Ctr, Gene Therapeut Res Inst, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90048 USA. Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [2 R01 NS34152, 2 RO1 NS34152, KO8 NS41969-01] NR 52 TC 84 Z9 91 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2002 VL 22 IS 9 BP 3504 EP 3511 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 546VN UT WOS:000175296200028 PM 11978827 ER PT J AU Frank, LM Eden, UT Solo, V Wilson, MA Brown, EN AF Frank, LM Eden, UT Solo, V Wilson, MA Brown, EN TI Contrasting patterns of receptive field plasticity in the hippocampus and the entorhinal cortex: An adaptive filtering approach SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; CA1; entorhinal cortex; plasticity; receptive field; adaptive filtering; place field; spatial; coding ID VISUAL RECOGNITION MEMORY; INFERIOR TEMPORAL CORTEX; SPATIAL FIRING PATTERNS; FREELY-MOVING RAT; PLACE CELLS; NEURONAL-ACTIVITY; UNIT-ACTIVITY; THETA-RHYTHM; BEHAVING RAT; SHARP WAVES AB Neural receptive fields are frequently plastic: a neural response to a stimulus can change over time as a result of experience. We developed an adaptive point process filtering algorithm that allowed us to estimate the dynamics of both the spatial receptive field (spatial intensity function) and the interspike interval structure (temporal intensity function) of neural spike trains on a millisecond time scale without binning over time or space. We applied this algorithm to both simulated data and recordings of putative excitatory neurons from the CA1 region of the hippocampus and the deep layers of the entorhinal cortex (EC) of awake, behaving rats. Our simulation results demonstrate that the algorithm accurately tracks simultaneous changes in the spatial and temporal structure of the spike train. When we applied the algorithm to experimental data, we found consistent patterns of plasticity in the spatial and temporal intensity functions of both CA1 and deep EC neurons. These patterns tended to be opposite in sign, in that the spatial intensity functions of CA1 neurons showed a consistent increase over time, whereas those of deep EC neurons tended to decrease, and the temporal intensity functions of CA1 neurons showed a consistent increase only in the "theta" (75-150 msec) region, whereas those of deep EC neurons decreased in the region between 20 and 75 msec. In addition, the minority of deep EC neurons whose spatial intensity functions increased in area over time fired in a significantly more spatially specific manner than non-increasing deep EC neurons. We hypothesize that this subset of deep EC neurons may receive more direct input from CA1 and may be part of a neural circuit that transmits information about the animal's location to the neocortex. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02114 USA. Univ New S Wales, Sch Elect Engn & Telecommun, Sydney, NSW, Australia. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RIKEN MIT Neurosci Res Ctr, Ctr Learning & Memory, Cambridge, MA 02139 USA. RP Frank, LM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3, Neurosci Stat Res Lab, 55 Fruit St, Boston, MA 02114 USA. OI Frank, Loren/0000-0002-1752-5677 FU NIMH NIH HHS [K02 MH061637, MH59733, MH61637, R01 MH059733] NR 45 TC 39 Z9 40 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 2002 VL 22 IS 9 BP 3817 EP 3830 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 546VN UT WOS:000175296200058 PM 11978857 ER PT J AU Rockhill, RL Daly, FJ MacNeil, MA Brown, SP Masland, RH AF Rockhill, RL Daly, FJ MacNeil, MA Brown, SP Masland, RH TI The diversity of ganglion cells in a mammalian retina SO JOURNAL OF NEUROSCIENCE LA English DT Article DE anatomy; green fluorescent protein; photofill; gene gun; neuron; photochemistry ID INDOLEAMINE-ACCUMULATING NEURONS; ACCESSORY OPTIC-SYSTEM; RABBIT RETINA; CAT RETINA; RECEPTIVE-FIELDS; PRIMATE RETINA; AMACRINE CELLS; DENDRITIC STRUCTURE; BIPOLAR CELLS; MORPHOLOGIES AB We report a survey of the population of ganglion cells in the rabbit retina. A random sample of 301 neurons in the ganglion cell layer was targeted for photofilling, a method in which the arbors of the chosen neurons are revealed by diffusion of a photochemically induced fluorescent product from their somas. An additional 129 cells were labeled by microinjection of Lucifer yellow. One hundred and thirty-eight cells were visualized by expression of the gene encoding a green fluorescent protein, introduced by particle-mediated gene transfer. One hundred and sixty-six cells were labeled by particle-mediated introduction of Dil. In the total population of 734 neurons, we could identify 11 types of retinal ganglion cell. An analysis based on retinal coverage shows that this number of ganglion cell types would not exceed the available total number of ganglion cells. Although some uncertainties remain, this sample appears to account for the majority of the ganglion cells present in the rabbit retina. Some known physiological types could easily be mapped onto structural types, but half of them could not; a large set of poorly known codings of the visual input is transmitted to the brain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Wellman 429,50 Blossom St, Boston, MA 02114 USA. RI Brown, Solange/H-1615-2012 NR 73 TC 189 Z9 197 U1 1 U2 9 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 MAY 1 PY 2002 VL 22 IS 9 BP 3831 EP 3843 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 546VN UT WOS:000175296200059 PM 11978858 ER PT J AU Teter, B Xu, PT Gilbert, JR Roses, AD Galasko, D Cole, GM AF Teter, B Xu, PT Gilbert, JR Roses, AD Galasko, D Cole, GM TI Defective neuronal sprouting by human apolipoprotein E4 is a gain-of-negative function SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE apolipoprotein E; neurite sprouting; transgenic mice; Alzheimer's disease ID ORGANOTYPIC SLICE CULTURES; RECEPTOR-RELATED PROTEIN; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; TRANSGENIC MICE; E ISOFORMS; IN-VITRO; APOE; ESTROGEN AB The apolipoprotein E (apoE) epsilon 4 allele (apoE4) is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A role for apoE in regeneration of synaptic circuitry after neural injury has been shown in several in vitro studies in which apoE3 supports neuronal sprouting better than apoE4. We evaluated sprouting in an in vitro mouse organotypic hippocampal slice culture system derived from transgenic mice expressing apoE3 or apoE4, in which apoE-dependent granule cell mossy fiber sprouting in the presence of apoE4 is only 51% of the level of apoE3. Sprouting supported by apoE4 had a dose response opposite that by supported by apoE3: although increasing E3 expression increased sprouting, increasing E4 expression decreased sprouting, suggesting that the defect in E4 in supporting neuronal sprouting is a gain-of-negative activity. These results may have important pharmacogenomic implications for AD therapies that modulate apoE expression levels. (C) 2002 Wiley-Liss, Inc. C1 Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Sepulveda, CA 91343 USA. Duke Univ, Durham, NC USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Teter, B (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, 16111 Plummer St MC151, Sepulveda, CA 91343 USA. FU NIA NIH HHS [K01 AG000962, AG16570] NR 55 TC 46 Z9 48 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 1 PY 2002 VL 68 IS 3 BP 331 EP 336 DI 10.1002/jnr.10221 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 548XX UT WOS:000175416100009 PM 12111863 ER PT J AU Wang, XY Mori, T Jung, JC Fini, ME Lo, EH AF Wang, XY Mori, T Jung, JC Fini, ME Lo, EH TI Secretion of matrix metalloproteinase-2 and-9 after mechanical trauma injury in rat cortical cultures and involvement of MAP kinase SO JOURNAL OF NEUROTRAUMA LA English DT Article DE MAP kinase; mechanical injury; MMP; neuroprotection; primary cortical cultures; rats ID ACTIVATED PROTEIN-KINASE; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; TRANSIENT FOREBRAIN ISCHEMIA; GENE KNOCK-OUT; BRAIN INJURY; MATRIX-METALLOPROTEINASE-9 EXPRESSION; INHIBITION; PATHWAYS; NEURONS AB Matrix metalloproteinases (MMP) are involved in the pathophysiology of brain injury. We recently showed that knockout mice deficient in MMP-9 expression were protected against traumatic brain injury. However, the cellular sources of MMP activity after trauma remain to be fully defined. In this study, we investigated the hypothesis that resident brain cells secrete MMP after mechanical trauma injury in vitro, and mitogen-activated protein (MAP) kinase signal transduction pathways are involved in this response. Rat primary cortical neurons, astrocytes, and co-cultures were subjected to needle scratch mechanical injury, and levels of MMP-2 and MMP-9 in conditioned media were assayed by zymography. MMP-2 and MMP-9 were increased in cortical astrocytes and co-cultures, whereas only MMP-2 was increased in neurons. Western blots showed that phosphorylated extracellular signal regulated kinase (ERK1/2) and p38 were rapidly upregulated in co-cultures after mechanical injury. No change in phosphorylated c-jun N-terminal kinase (JNK) was observed. In-gel kinase assays confirmed this lack of response in the JNK pathway. Treatment with either 10 muM of U0126 (a MAP kinase/ERK1/2 kinase inhibitor) or 10 muM of SB203580 (a p38 inhibitor) had no detectable effect on MMP-2 and MMP-9 levels after mechanical injury. However, combination treatment with both inhibitors significantly reduced secretion of MMP-9. Herein, we demonstrate that (1) resident brain cells secrete MMP after mechanical injury, (2) astrocytes are the main source of MMP-9 activity, and (3) ERK and p38 MAP kinases are upregulated after mechanical injury, and mediate the secretion of MMP-9. C1 Harvard Univ, Med Sch, Det Neurol, Neuroprot Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprot Res Lab, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Med Sch, Program Neurosci, Charlestown, MA USA. Tufts Univ, Sch Med, New England Eye Ctr, Vis Res Labs, Boston, MA USA. Massachusetts Gen Hosp, Neuroprot Res Lab, Dept Neurol, Boston, MA 02114 USA. RP Wang, XY (reprint author), Harvard Univ, Med Sch, Det Neurol, Neuroprot Res Lab, MGH East 149-2322, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01-NS40529, R01-NS37074, R01-NS38731] NR 54 TC 77 Z9 84 U1 0 U2 6 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 MAY PY 2002 VL 19 IS 5 BP 615 EP 625 DI 10.1089/089771502753754082 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 557PA UT WOS:000175915900006 PM 12042096 ER PT J AU Tawakol, A Elmaleh, D Fischman, AJ Muller, J Gewirtz, H Daghighian, F AF Tawakol, A Elmaleh, D Fischman, AJ Muller, J Gewirtz, H Daghighian, F TI Intravascular characterization of atherosclerotic lesions with F-18-FDG and a novel intravascular beta probe. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. IntraMed Imaging, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 9 BP 3P EP 4P AR UNSP 200965 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800010 ER PT J AU Tawakol, A Muller, J Gewirtz, H Fischman, AJ AF Tawakol, A Muller, J Gewirtz, H Fischman, AJ TI Non-invasive characterization of atherosclerotic plaques with F-18-FDG. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 24 BP 8P EP 8P AR UNSP 201249 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800025 ER PT J AU Van den Abbeele, AD Friedberg, JW Fischman, A Neuberg, D Kim, H Takvorian, T Mauch, P Canellos, GP AF Van den Abbeele, AD Friedberg, JW Fischman, A Neuberg, D Kim, H Takvorian, T Mauch, P Canellos, GP TI FDG-PET is superior to Ga-67 scintigraphy in the staging and follow-up of patients with Hodgkin disease: A prospective, blinded comparison. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 109 BP 30P EP 31P AR UNSP 200371 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800110 ER PT J AU Brownell, AL Chen, YI Canales, K Powers, B Jenkins, BG AF Brownell, AL Chen, YI Canales, K Powers, B Jenkins, BG TI Neural degeneration in a transgenic HD mouse model - An ultra high resolution PET study with comparison to MRI/MRS. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 220 BP 61P EP 61P AR UNSP 202010 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800221 ER PT J AU El Fakhri, G Kijewski, MF Zimmerman, RE Syrkin, G Jones, K Johnson, KA Killiany, R Albert, MS AF El Fakhri, G Kijewski, MF Zimmerman, RE Syrkin, G Jones, K Johnson, KA Killiany, R Albert, MS TI Relative importance of individual brain structure SPECT perfusion measures for preclinical prediction of Alzheimer's disease. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 232 BP 64P EP 64P AR UNSP 202473 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800233 ER PT J AU Van den Abbeele, AD Burrell, SC Spangler, TA McCollum, AD Haddad, RI Norris, CM Tishler, RB Posner, MR AF Van den Abbeele, AD Burrell, SC Spangler, TA McCollum, AD Haddad, RI Norris, CM Tishler, RB Posner, MR TI The role of FDG-PET in patients with squamous cell cancer of the head and neck (SCCHN) after sequential induction chemotherapy and definitive chemoradiotherapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 264 BP 73P EP 73P AR UNSP 200956 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800265 ER PT J AU Rajendran, JG Muzi, M Peterson, LM Diaz, AZ Spence, AM Schwartz, DL Krohn, KA AF Rajendran, JG Muzi, M Peterson, LM Diaz, AZ Spence, AM Schwartz, DL Krohn, KA TI Analyzing the results of (FMISO)-F-18 PET hypoxia imaging: What is the best way to quantify hypoxia? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 367 BP 102P EP 102P AR UNSP 200797 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800368 ER PT J AU Blankenberg, F Mari, C Karabiyikoglu, M Tait, J Strauss, HW Yenari, M AF Blankenberg, F Mari, C Karabiyikoglu, M Tait, J Strauss, HW Yenari, M TI Radionuclide imaging of post-ischemic inflammation using radiolabeled monocyte chemotactic peptide (MCP-1) and annexin V. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 396 BP 110P EP 110P AR UNSP 201289 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800397 ER PT J AU Brownell, A Canales, K Chen, YI Owen, C Powers, R Kozikowski, A Elmaleh, D Yu, M AF Brownell, A Canales, K Chen, YI Owen, C Powers, R Kozikowski, A Elmaleh, D Yu, M TI Metabotropic glutamate receptors - New targets for neuroimaging. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 397 BP 110P EP 111P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800398 ER PT J AU Zervos, G Tokareva, E Barrow, S Bruce, A Stubbs, J Graham-Coco, W Goodbody, A Babich, J AF Zervos, G Tokareva, E Barrow, S Bruce, A Stubbs, J Graham-Coco, W Goodbody, A Babich, J TI A phase I study to determine the dosimetry, distribution and safety of I-123-BMIPP. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Radiat Dosimetry Syst Inc, Alpharetta, GA USA. Biostream Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 517 BP 142P EP 143P AR UNSP 200799 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800518 ER PT J AU Yu, M Livni, E Nagren, K Canales, K Powers, R Elmaleh, D Kozikowski, A Brownell, AL AF Yu, M Livni, E Nagren, K Canales, K Powers, R Elmaleh, D Kozikowski, A Brownell, AL TI C-11 labelling of methyl 2-(methoxycarbonyl)-2-(methylamino) bicycle (2.1.1)-hexane-5-carboxylate, a potent neuroprotective drug. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Turku PET Ctr, Turku, Finland. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 609 BP 167P EP 168P AR UNSP 201330 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800610 ER PT J AU Sarda-Mantel, L Nazneen, L Peker, C Michel, JB Loiseau, P Martel, G Meulemans, A Ensing, G Vrigneaud, JM Khaw, BA Le Guludec, D AF Sarda-Mantel, L Nazneen, L Peker, C Michel, JB Loiseau, P Martel, G Meulemans, A Ensing, G Vrigneaud, JM Khaw, BA Le Guludec, D TI Comparison of Tc-99m-annexin V and In-111-antimyosin-antibody myocardial uptake in experimental acute myocardial infarction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 CEA, Serv Hosp Frederic Joliot, F-91406 Orsay, France. Fac Bichat Claude Bernard, INSERM, U460, Paris, France. Mallinckrodt, Petten, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 703 BP 168P EP 168P AR UNSP 201591 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800613 ER PT J AU Alpert, NM Elahi, D Minaker, K Tompkins, R Fischman, A AF Alpert, NM Elahi, D Minaker, K Tompkins, R Fischman, A TI Measurement of myocardial protein synthesis in human subjects. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 711 BP 170P EP 171P AR UNSP 200683 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800621 ER PT J AU Bonab, AA Alpert, NM Livni, E Fischman, AJ AF Bonab, AA Alpert, NM Livni, E Fischman, AJ TI Development of a bolus-infusion technique for evaluation of dopamine transporter (DAT) density by PET or SPECT with altropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 836 BP 203P EP 204P AR UNSP 200933 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800746 ER PT J AU Bonab, AA Madras, BK Barrow, SA Fischman, AJ AF Bonab, AA Madras, BK Barrow, SA Fischman, AJ TI Test-retest reliability of I-123-Altropane binding potential in monkeys. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 854 BP 208P EP 208P AR UNSP 201815 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800764 ER PT J AU Canales, K Brownell, A AF Canales, K Brownell, A TI New approaches in parametric imaging - Use of direct algorithm. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 859 BP 209P EP 210P AR UNSP 202189 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800769 ER PT J AU Li, Z Link, JM Stratton, JR Caldwell, JH AF Li, Z Link, JM Stratton, JR Caldwell, JH TI Modeling of neuronal uptake and vesicular transport of C-11-meta-hydroxyephedrine (mHED) in PET studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 858 BP 209P EP 209P AR UNSP 202129 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800768 ER PT J AU El Fakhri, G Kijewski, MF Moore, SC Zimmerman, RE Jones, K Syrkin, G Johnson, KA Becker, JA Killiany, R Albert, MS AF El Fakhri, G Kijewski, MF Moore, SC Zimmerman, RE Jones, K Syrkin, G Johnson, KA Becker, JA Killiany, R Albert, MS TI Comparison of reconstruction and correction algorithms based on performance in diagnosis of preclinical Alzheimer's disease (AD). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 880 BP 215P EP 215P AR UNSP 202123 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800793 ER PT J AU Madras, BK Meltzer, PC Bonab, AA Livni, F Fischman, AJ AF Madras, BK Meltzer, PC Bonab, AA Livni, F Fischman, AJ TI Dopamine transporter occupancy by candidate cocaine medications. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 948 BP 232P EP 233P AR UNSP 201376 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800858 ER PT J AU Fischman, AJ Bonab, AA Livni, E Meltzer, PC Barrow, SA Madras, BK AF Fischman, AJ Bonab, AA Livni, E Meltzer, PC Barrow, SA Madras, BK TI Evaluation of dopamine transporter (DAT) density in patients with Parkinsons disease (PD) by PET with I-127,C-11 Altropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 952 BP 233P EP 234P AR UNSP 200387 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800861 ER PT J AU Madras, BK Bonab, AA Livni, E Fischman, AJ AF Madras, BK Bonab, AA Livni, E Fischman, AJ TI PET imaging of the dopamine transporter (DAT): Evidence for compensatory DAT down-regulation with sustained improvement in activity of Parkinsonian monkey. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 949 BP 233P EP 233P AR UNSP 202318 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800859 ER PT J AU Dougherty, DD Cosgrove, GR Weiss, AP Alpert, NM Cassem, EH Niereneberg, AA Price, BH Mayberg, HS Fischman, AJ Rauch, SL AF Dougherty, DD Cosgrove, GR Weiss, AP Alpert, NM Cassem, EH Niereneberg, AA Price, BH Mayberg, HS Fischman, AJ Rauch, SL TI Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for major depressive disorder. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Rotman Res Inst, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1053 BP 260P EP 260P AR UNSP 200439 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800963 ER PT J AU Carter, EA McKuster, K Syed, S Tompkins, RG Fischman, AJ AF Carter, EA McKuster, K Syed, S Tompkins, RG Fischman, AJ TI Comparison of (FLT)-F-18 with (18)FDG for differntiation between tumor and focal sites of infection in rats. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1074 BP 266P EP 266P AR UNSP 200390 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800984 ER PT J AU Carter, EA McCusker, C Syed, S Tompkins, RG Fischman, AJ AF Carter, EA McCusker, C Syed, S Tompkins, RG Fischman, AJ TI Effect of prolonged fasting and refeeding on hepatic apoptosis in rats evaluated with radiolabeled annexin V. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McCusker, Catherine/G-2795-2010 OI McCusker, Catherine/0000-0001-9580-3612 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1335 BP 332P EP 332P AR UNSP 202574 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801246 ER PT J AU Yatin, M Burker, M McCusker, C Syed, S Hillier, S Carter, EA Fischman, AJ AF Yatin, M Burker, M McCusker, C Syed, S Hillier, S Carter, EA Fischman, AJ TI Synthesis and pharmacokinetic evaluation of a novel I-125 spermine analog as a potential tracer for infection imaging. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McCusker, Catherine/G-2795-2010 OI McCusker, Catherine/0000-0001-9580-3612 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1512 BP 376P EP 376P AR UNSP 200839 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801423 ER PT J AU Papisov, MI Yurkovetskiy, A Yin, M Hiller, A Fischman, AJ AF Papisov, MI Yurkovetskiy, A Yin, M Hiller, A Fischman, AJ TI Fully biodegradable hydrophilic polyacetals for macromolecular radiopharmaceuticals. SO JOURNAL OF NUCLEAR MEDICINE 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 SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2002 VL 43 IS 5 SU S MA 1514 BP 377P EP 377P AR UNSP 202372 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801425 ER PT J AU Hinnebusch, BF Meng, SF Wu, JT Archer, SY Hodin, RA AF Hinnebusch, BF Meng, SF Wu, JT Archer, SY Hodin, RA TI The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation SO JOURNAL OF NUTRITION LA English DT Article DE fatty acids; histone hyperacetylation; cyclin-dependent kinase inhibitor; intestinal alkaline phosphatase; histone deacetylase ID LARGE-BOWEL CANCER; CYCLIN B1; GROWTH-INHIBITION; SODIUM-BUTYRATE; GENE-EXPRESSION; DIETARY FIBER; HT-29 CELLS; DEACETYLASE; APOPTOSIS; DIFFERENTIATION AB The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial fermentation within the colon and is thought to be protective in regard to colon carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA, a variety of other SCFA also exist in the colonic lumen. Butyrate is thought to exert its cellular effects through the induction of histone hyperacetylation. We sought to determine the effects of a variety of the SCFA on colon carcinoma cell growth, differentiation and apoptosis. HT-29 or HCT-116 (wild-type and p21-deleted) cells were treated with physiologically relevant concentrations of various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel electrophoresis and immunoblotting. Growth and apoptotic effects were studied by flow cytometry, and differentiation effects were assessed using transient transfections and Northern blotting. Propionate (C3) and valerate (C5) caused growth arrest and differentiation in human colon carcinoma cells. The magnitude of their effects was associated with a lesser degree of histone hyperacetylation compared with butyrate. Acetate (C2) and caproate (C6), in contrast, did not cause histone hyperacetylation and also had no appreciable effects on cell growth or differentiation. SCFA-induced transactivation of the differentiation marker gene, intestinal alkaline phosphatase (IAP), was blocked by histone deacetylase (HDAC), further supporting the critical link between SCFA and histones. Butyrate also significantly increased apoptosis, whereas the other SCFA studied did not. The growth arrest induced by the SCFA was characterized by an increase in the expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1 (CB1). In p21-deleted HCT-116 colon cancer cells, the SCFA did not alter the rate of proliferation. These data suggest that the anti proliferative, apoptotic and differentiating properties of the various SCFA are linked to the degree of induced histone hyperacetylation. Furthermore, SCFA-mediated growth arrest in colon carcinoma cells requires the p21 gene. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 02527, DK 47186, DK 50623] NR 40 TC 211 Z9 224 U1 2 U2 19 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2002 VL 132 IS 5 BP 1012 EP 1017 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 550DQ UT WOS:000175488700024 PM 11983830 ER PT J AU Fuselier, JC Ellis, EE Dodson, TB AF Fuselier, JC Ellis, EE Dodson, TB TI Do mandibular third molars alter the risk of angle fracture? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID 3RD MOLARS AB Purpose: In this study, we measured the relationship between the presence of mandibular third molars (M3s) and angle fractures. In addition, the study examined the relationship between M3 impaction level and angle fracture susceptibility, Patients and Methods: We used a multicenter retrospective cohort study design and a sample composed of patients treated for mandibular fractures. The predictor variables were 1) the presence of an M3 and 2) the position of an M3 classified according to the Pell and Gregory system. The outcome variable was the presence or absence of an angle fracture. Results: The study sample was composed of 1,210 patients. Patients with M3s present had a 2.1 times greater chance of an angle fracture than did patients without M3s (P < .001). There was a statistically significant variation in the risk for an angle fracture depending on M3 position (P < .001), Conclusions: In patients who sustain a mandible fracture, the presence of M3s significantly, increases the likelihood of an angle fracture. In addition, the risk for an angle fracture depends on M3 position. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Austin Oral & Maxillofacial Surg Associates, Austin, TX 78705 USA. Univ Texas, SW Med Ctr, Div Oral & Maxillofacial Surg, Dallas, TX USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Fuselier, JC (reprint author), Austin Oral & Maxillofacial Surg Associates, 711 W 38th St,Suite A-1, Austin, TX 78705 USA. FU NIDCR NIH HHS [K24-DE00448] NR 12 TC 33 Z9 35 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2002 VL 60 IS 5 BP 514 EP 518 DI 10.1053/joms.2002.31847 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 548UF UT WOS:000175407700009 PM 11988927 ER PT J AU Bourgeois, SL Alvarez, CM AF Bourgeois, SL Alvarez, CM TI Use of vinyl polysiloxane impression material as an extraoral obturator for orocutaneous fistulas SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article C1 Univ Texas, Hlth Sci Ctr, Dept Oral & Maxillofacial Surg, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Div Oral & Maxillofacial Surg, Audie L Murphy Div, San Antonio, TX USA. RP Bourgeois, SL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Oral & Maxillofacial Surg, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 11 TC 1 Z9 1 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2002 VL 60 IS 5 BP 597 EP 599 DI 10.1053/joms.2002.31864 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 548UF UT WOS:000175407700027 PM 11988945 ER PT J AU Pappo, AS Grier, HE AF Pappo, AS Grier, HE TI A tribute to Dr. Charles Pratt SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Biographical-Item C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pappo, AS (reprint author), Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAY PY 2002 VL 24 IS 4 BP 242 EP 243 DI 10.1097/00043426-200205000-00002 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 550AP UT WOS:000175481200002 ER PT J AU Martinez, V Wang, LX Rivier, JE Vale, W Tache, Y AF Martinez, V Wang, LX Rivier, JE Vale, W Tache, Y TI Differential actions of peripheral corticotropin-releasing factor (CRF), urocortin II, and urocortin III on gastric emptying and colonic transit in mice: Role of CRF receptor subtypes 1 and 2 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BINDING-PROTEIN; GUINEA-PIG; ANTAGONIST; HORMONE; STRESS; ASTRESSIN; MOTILITY; POTENT; RATS AB Peripheral CRF inhibits gastric emptying and stimulates colonic motor function in rats. We investigated the role of CRF1 and CRF2 receptors in i.p. CRF-induced alterations of gut transit in conscious mice using selective CRF1 and CRF2 ligands injected i.p. Gastric emptying 2 h after ingestion of a solid chow meal and colonic transit (time to expel a bead inserted into the distal colon) were determined simultaneously. Rat/human (r/h)CRF, which has CRF1 > CRF2 binding affinity, decreased distal colonic transit time at lower doses (6-12 mug/kg) than those inhibiting gastric emptying (20-60 mug/kg). Ovine CRF, a preferential CRF1 receptor agonist (6-60 mug/kg), reduced significantly the colonic transit time without altering gastric emptying, whereas the selective CRF2 receptor agonists mouse urocortin II (20-60 mug/kg) and urocortin III (120 mug/kg) inhibited significantly gastric emptying without modifying colonic transit. The CRF1/CRF2 receptor antagonist, astressin (30-120 mug/kg), dose dependently prevented r/hCRF (20 mug/kg)-induced inhibition of gastric emptying and reduction of colonic transit time. The selective CRF1 receptor antagonists, NBI-27914 (C18H20Cl4N4C7H8O3S) and CP-154,526 (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-yl]ethylamine) (5-30 mg/kg), dose dependently blocked r/hCRF action on the colon without influencing the gastric response, whereas the CRF2 receptor antagonist, antisauvagine-30 (30-100 mug/kg), dose dependently abolished r/hCRF-induced delayed gastric emptying and had no effect on colonic response. These data show that i.p. r/hCRF-induced opposite actions on upper and lower gut transit in conscious mice are mediated by different CRF receptor subtypes: the activation of CRF1 receptors stimulates colonic propulsive activity, whereas activation of CRF2 receptors inhibits gastric emptying. C1 Univ Calif Los Angeles, Dept Med, Div Digest Dis, VA Greater Los Angeles Healthcare Syst,CURE,DDRC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, Dept Med, Div Digest Dis, VA Greater Los Angeles Healthcare Syst,CURE,DDRC, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-26741, DK-57238, DK-41301] NR 43 TC 124 Z9 133 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2002 VL 301 IS 2 BP 611 EP 617 DI 10.1124/jpet.301.2.611 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 543ZB UT WOS:000175132800028 PM 11961064 ER PT J AU Mazumdar, S Houck, PR Liu, KS Mulsant, BH Pollock, BG Dew, MA Reynolds, CF AF Mazumdar, S Houck, PR Liu, KS Mulsant, BH Pollock, BG Dew, MA Reynolds, CF TI Intent-to-treat analysis for clinical trials: use of data collected after termination of treatment protocol SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE pragmatic analysis; explanatory analysis; mixture models ID RATING-SCALE; DOUBLE-BLIND; DEPRESSION; NORTRIPTYLINE; PAROXETINE; ILLNESS; MODELS AB Following patients for a period of time alter termination of treatment protocols is a common practice in clinical trials of drug treatments. After termination of the protocol treatment. patients are usually provided with medical care as deemed appropriate. e.g, different doses of the same drug, augmentation with other drugs, or different drugs. Data collected on patients when they are not in the treatment protocol are termed "off-treatment" data to be differentiated from "on-treatment" data that are collected while patients arc in the treatment protocol. The purpose of the present paper is to describe some recent statistical methodological advances in the use of "off-treatment" data for intent-to-treat (IT) analysis using mixture models [Biometrics 52 (1996) 1002]. T so-piece spline models conditional on the protocol treatment dropout time are developed first. The two pieces of the spline model represent the on-treatment and off-treatment segments of data and are joined at the dropout time. The weighted average of the two-piece conditional models across realizations of the dropout times provides the mixture model for the pragmatic IT analysis. The weights are the estimates of tire probabilities of the dropout tunes. The mixture model is amenable to an explanatory analysis which assumes that the patients remain on their assigned treatments. The model allows the parameters of the splines to depend on the dropout time. Statistical inference is based on bootstrap sampling procedures. We have illustrated this methodology using data from a drug trial comparing nortriptyline and paroxetine in the treatment of major depression in older patients. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15213 USA. RP Mazumdar, S (reprint author), Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. FU NIMH NIH HHS [MH52247, R37 MH43832, R01 MH37869, K05 MH00295, K01 MH01613] NR 17 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAY-JUN PY 2002 VL 36 IS 3 BP 153 EP 164 AR PII S0022-3956(01)00057-7 DI 10.1016/S0022-3956(01)00057-7 PG 12 WC Psychiatry SC Psychiatry GA 552WP UT WOS:000175643300006 PM 11886693 ER PT J AU Czerniecki, J AF Czerniecki, J TI Presentation highlights: patient perspectives SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article; Proceedings Paper CT Roundtable Meeting on VA/NIH Prosthetics CY JUN 25, 2001 CL ROCKVILLE, MARYLAND C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Czerniecki, J (reprint author), Univ Washington, Seattle, WA 98195 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2002 VL 39 IS 3 SU S BP 13 EP 14 PG 2 WC Rehabilitation SC Rehabilitation GA 577AP UT WOS:000177039600009 ER PT J AU Cooper, RA DiGiovine, CP Boninger, ML Shimada, SD Koontz, AM Baldwin, MA AF Cooper, RA DiGiovine, CP Boninger, ML Shimada, SD Koontz, AM Baldwin, MA TI Filter frequency selection for manual wheelchair biomechanics SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE filtering; frequency; motion analysis; noise reduction; wheelchairs ID SPINAL-CORD INJURY; 3-DIMENSIONAL KINEMATICS; PROPULSION EFFICIENCY; FORCE APPLICATION; GAIT; ERGOMETER; CHILDREN; ADULTS; SPEEDS AB Wheelchair locomotion is an important form of mobility for many individuals with spinal cord injury. However, manual wheelchair propulsion can lead to upper-limb pain and can be very inefficient. This has led investigators to apply biomechanics to the study of wheelchair use. The objectives of this study were (1) to determine the frequency content of the motion of both hands during two speeds of wheelchair propulsion, (2) to obtain the filter frequencies necessary to remove noise from wheelchair motion data, and (3) to provide signal-to-noise ratio data for wheelchair kinematics. The participants in this study were a random sample of manual wheelchair users with paraplegia caused by spinal cord injury. Subjects propelled their personal wheelchairs on a computer-controlled dynamometer at speeds of 0.9 m/s and 1.8 m/s. Motion data were collected at 60 Hz with the use of a commercial infrared marker-based system. The main outcome measures were arm motions and noise frequency spectra, filter cutoff frequencies, and signal-to-noise ratio. Our results indicate that there is no useful signal power above 6 Hz during manual wheelchair propulsion at the speeds that we analyzed. In many cases, there was no useful signal power above 4 Hz. This would indicate that the frequency content of manual wheelchair propulsion is similar to that of human gait. The mean signal-to-noise ratio varied from a high of 91 dB to a low of 2 1.8 dB. The signal-to-noise ratio was greatest in the x direction (along the line of progression) and lowest in the x direction (medial-lateral). Manual wheelchair propulsion kinematic data should be low-pass filtered at approximately 6 Hz for speeds at or below 1.8 m/s. The data presented in the archival literature appear to have been filtered at an appropriate frequency. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Human Engn Res Labs, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI DiGiovine, Carmen/E-2982-2011; OI Boninger, Michael/0000-0001-6966-919X FU NICHD NIH HHS [P01 HD33989-01]; PHS HHS [PA-93-082] NR 33 TC 38 Z9 38 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2002 VL 39 IS 3 BP 323 EP 336 PG 14 WC Rehabilitation SC Rehabilitation GA 575NY UT WOS:000176955300004 PM 12173753 ER PT J AU Camacho, DLA Ledoux, WR Rohr, ES Sangeorzan, BJ Ching, RP AF Camacho, DLA Ledoux, WR Rohr, ES Sangeorzan, BJ Ching, RP TI A three-dimensional, anatomically detailed foot model: A foundation for a finite element simulation and means of quantifying foot-bone position SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE anatomic models; computerized topography; computer models; foot; structural models ID TIBIAL TENDON INSUFFICIENCY; LONGITUDINAL ARCH; STRESSES; HEIGHT; PLANUS; INDEX; FEET AB We generated an anatomically detailed, three-dimensional (3-D) reconstruction of a human foot from 286 computerized topographic (CT) images. For each bone, 2-D cross-sectional data were obtained and aligned to form a stacked image model. We calculated the inertial matrix of each bone from the stacked image model and used it to determine the principal axes. Relative angles between the principal axes of the bones were employed to describe the shape of the foot, i.e., the relationships between the bones of the foot. A 3-D surface model was generated from the stacked image models and a detailed 3-D mesh for each bone was created. Additionally, the representative geometry of the plantar soft tissue was obtained from the CT scans, while the geometries of the cartilage between bones were obtained from the 3-D surface bone models. This model served dual purposes: it formed the anatomical foundation for a future finite element model of the human foot and we used it to objectively quantify foot shape using the relationships between the principal axes of the foot bones. C1 Dept Vet Affairs Rehabil Res, Seattle, WA USA. Dev Ctr Excellence Limb Loss Prevent, Seattle, WA USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 34 TC 42 Z9 45 U1 0 U2 10 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2002 VL 39 IS 3 BP 401 EP 410 PG 10 WC Rehabilitation SC Rehabilitation GA 575NY UT WOS:000176955300011 PM 12173760 ER PT J AU Feltmate, CM Genest, DR Goldstein, DP Berkowitz, RS AF Feltmate, CM Genest, DR Goldstein, DP Berkowitz, RS TI Advances in the understanding of placental site trophoblastic tumor SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE trophoblastic neoplasms; placental site trophoblastic disease ID INTERMEDIATE TROPHOBLAST; DISEASE-CENTER; MR APPEARANCE; PSEUDOTUMOR; EXPERIENCE; NEOPLASM AB Placental site trophoblastic tumor (PSTT) is the least common form of gestational trophoblastic disease. The tumor represents a neoplastic transformation of intermediate trophoblastic cells that normally play a critical role in implantation. PSTT can occur after a normal pregnancy, spontaneous abortion, termination of pregnancy, ectopic pregnancy or molar pregnancy. It displays a wide spectrum of behavior, and when metastatic, can be difficult to control even with surgery and chemotherapy. Because of PSTT's rarity, limited information is known about its natural history. Several recent studies have indicated that milotic index is an important prognostic indicator. Advances in chemotherapeutic regimens have also improved clinical response in metastatic disease. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Div Gynecol Oncol,Dept O, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,New England Trophoblast Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med,Gillette Ctr Womens Canc, Brigham & Womens Hosp,Dept Pathol, Dana Farber Canc Inst,Trophoblast Tumor Registry, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Div Gynecol Oncol,Dept O, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 26 Z9 29 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 2002 VL 47 IS 5 BP 337 EP 341 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 555RE UT WOS:000175806400002 PM 12063871 ER PT J AU Garrett, AP Garner, EO Goldstein, DP Berkowitz, RS AF Garrett, AP Garner, EO Goldstein, DP Berkowitz, RS TI Methotrexate infusion and folinic acid as primary therapy for nonmetastatic and low-risk metastatic gestational trophoblastic tumors - 15 years of experience SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE trophoblastic tumor; methotrexate; folinic acid ID WEEKLY INTRAMUSCULAR METHOTREXATE; DISEASE; MANAGEMENT; AGENT AB OBJECTIVE: To investigate the efficacy and toxicity of methotrexate (MTX) given intravenously (IV) at a dose of 100 mg/m(2) IV bolus and 200 mg/m(2) infusion over 12 hours followed by folinic acid in the primary treatment Of gestational trophoblastic tumors (GTTs). STUDY DESIGN: We reviewed the records of patients at the New England Trophoblastic Disease Center who had received MTX infusion at 17 dose Of 100 mg/m(2) IV bolus and 200 mg/m(2) infusion over 12 hours followed by folinic acid as primary therapy for GTTs that did not resolve with uterine evacuation alone. Data on the patients' age, gravity and parity, disease stage (by FIGO and WHO criteria), antecedent pregnancy, presenting level of hCG, metastatic status, courses of chemotherapy required to achieve remission, toxicity related to chemotherapy treatments and time to normalization of hCG were recorded. RESULTS: One hundred ninety-two patients with persistent GTTs were treated with the MTX infusion protocol between December 1985 and December 2000. One hundred twenty-four patients (64.6%) achieved complete remission with the MTX infusion protocol. Complete remission was induced in 108 (87.1%) with a single course of chemotherapy; 12 others achieved remission with a single additional course of MTX. All patients found to be resistant to MTX therapy later achieved remission with other chemotherapy. Minimal toxicity was experienced during MTX treatment. CONCLUSION: MTX infusion with folic acid is effective mid well tolerated as primary single-agent therapy for nonmetastatic and low-risk metastatic GTT. C1 Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Trophoblast Tumor Registry, Boston, MA 02115 USA. Harvard Univ, Sch Med,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Gillette Ctr Womens Canc,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, New England Trophoblast Dis Ctr, 75 Francis St, Boston, MA 02115 USA. NR 34 TC 34 Z9 44 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 2002 VL 47 IS 5 BP 355 EP 362 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 555RE UT WOS:000175806400005 PM 12063874 ER PT J AU Genest, DR Ruiz, RE Weremowicz, S Berkowitz, RS Goldstein, DP Dorfman, DM AF Genest, DR Ruiz, RE Weremowicz, S Berkowitz, RS Goldstein, DP Dorfman, DM TI Do nontriploid partial hydatidiform moles exist? A histologic and flow cytometric reevaluation of nontriploid specimens SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE hydatidiform mole; ploidies; histology; flow cytometry ID BECKWITH-WIEDEMANN SYNDROME; DNA-PLOIDY; HISTOPATHOLOGY; DIAGNOSIS; PLACENTAS; FEATURES; HYDROPS; ORIGIN AB OBJECTIVE: To Study whether nontriploid partial hydatidiform moles truly exist. STUDY DESIGN: We conducted a reevaluation of pathology and ploidy in 19 putative nontriploid partial hydatidiform moles using standardized histologic diagnostic criteria and repeat flow cytometric testing by the Hedley technique. RESULTS: On review of the 19 moles, 53% (10/19) were diploid nonpartial Moles (initially pathologically misclassified ), and 37% (7/19) were triploid partial moles (initial ploidy misclassifications). One additional case (5%) was a diploid early complete mole (initially pathologically misclassified). CONCLUSION: Nontriploid partial moles probably do not exist: careful reevaluation of putative specimens will probably recover pathologic or ploidy errors in almost all cases. C1 Brigham & Womens Hosp, Dept Pathol, Cytogenet & Hematol Lab, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Womens Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Perinatal Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, New England Trophoblast Dis Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Genest, DR (reprint author), Brigham & Womens Hosp, Dept Pathol, Cytogenet & Hematol Lab, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 33 TC 23 Z9 24 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 2002 VL 47 IS 5 BP 363 EP 368 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 555RE UT WOS:000175806400006 PM 12068831 ER PT J AU Garner, EIO Lipson, E Bernstein, MR Goldstein, DP Berkowitz, RS AF Garner, EIO Lipson, E Bernstein, MR Goldstein, DP Berkowitz, RS TI Subsequent pregnancy experience in patients with molar pregnancy and gestational trophoblastic tumor SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article ID IN-VITRO FERTILIZATION; PARTIAL HYDATIDIFORM MOLE; PROPHYLACTIC CHEMOTHERAPY; REPRODUCTIVE EXPERIENCE; FOLLOW-UP; DISEASE; RECURRENT; RISK; DIAGNOSIS; ENTITIES AB Modern therapy for molar pregnancy and gestational trophoblastic tumors has resulted in high cure rates and preservation of fertility, even in the setting of metastatic disease requiring chemotherapy. Patients and their partners facing future pregancy after treatment for gestational trophoblastic disease express fear related to risk of disease recurrence and outcome of subsequent pregnancies. Data from the New England Trophoblastic Disease Center on later pregnancies following complete and partial mole as well as persistent gestational trophoblastic tumor show that patients, in general, can anticipate normal subsequent pregnancy outcomes. C1 Brigham & Womens Hosp, Div Gynecol Oncol,Dept Obstet Gynecol & Reprod Bi, Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA 02115 USA. Gillette Ctr Womens Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol,Dept Obstet Gynecol & Reprod Bi, Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, 75 Francis St, Boston, MA 02115 USA. NR 49 TC 22 Z9 23 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 2002 VL 47 IS 5 BP 380 EP 386 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 555RE UT WOS:000175806400008 PM 12063876 ER PT J AU Wenzel, L Berkowitz, RS Newlands, E Hancock, B Goldstein, DP Seckl, MJ Habbal, R Bernstein, M Kluhsman, B Kulchak-Rahm, A Strickland, S Higgins, J AF Wenzel, L Berkowitz, RS Newlands, E Hancock, B Goldstein, DP Seckl, MJ Habbal, R Bernstein, M Kluhsman, B Kulchak-Rahm, A Strickland, S Higgins, J TI Quality of life after gestational trophoblastic disease SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE trophoblastic cancer; trophoblastic tumor; molar pregnancy; quality of life ID OF-LIFE; IMPACT; CANCER AB OBJECTIVE: To describe the quality of life (QoL) and long-term psychosocial sequelae in women diagnosed with gestational trophoblastic tumor (GTT) 5-10 years earlier. STUDY DESIGN: Utilizing a cross-sectional descriptive design, 111 survivors completed a comprehensive QoL interview. RESULTS: Participants were predominantly married women and non-Hispanic white, with a mean age of diagnosis of 30 years and a current mean age of 37 years.disease-free sample enjoys a good QoL, with physical, social and emotional functioning comparable to or better than comparative norms. However, certain psychological survivorship sequelae persist. Additionally, a sizable number of survivors currently experience significant reproductive concerns. Participants reporting good QoL were less likely to report ongoing coping efforts related to having had this illness, more likely to report greater social support (P <.0001), greater sexual pleasure (P = .0063), and less GTT-specific distress (P <.0001). Fifty-one percent of respondents expressed that they would likely participate in a counseling program today to discuss psychosocial issues raised by having had GTT, and 74% stated that they would have attended a support group program during the initial treatment if it had been offered. CONCLUSION: This information provides insight into the complex survivorship relationships between QoL and sequelae of GTT. C1 Univ Calif Irvine, Coll Med, Dept Obstet & Gynecol, Irvine, CA 92697 USA. Brigham & Womens Hosp, Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Div Gynecol Oncol,Dept Obstet Gynecol & Reprod Bi, Boston, MA 02115 USA. Gillette Ctr Womens Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. AMC Canc Res Ctr, Denver, CO USA. Charing Cross Hosp, Dept Med Oncol, London W6 8RF, England. Weston Pk Hosp, Dept Genomic Med, Sheffield, S Yorkshire, England. RP Wenzel, L (reprint author), Univ Calif Irvine, Coll Med, Dept Obstet & Gynecol, 224 Irvine Hall, Irvine, CA 92697 USA. FU NCI NIH HHS [3 P30 CA46934-10S2P30] NR 16 TC 28 Z9 29 U1 3 U2 4 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 2002 VL 47 IS 5 BP 387 EP 394 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 555RE UT WOS:000175806400009 PM 12063877 ER PT J AU Ausiello, JC Stafford, RS AF Ausiello, JC Stafford, RS TI Trends in medication use for osteoarthritis treatment SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE osteoarthritis; nonsteroidal antiinflammatory drug; acetaminophen; time trends ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; GASTROINTESTINAL COMPLICATIONS; THERAPEUTIC STRATEGIES; RISK; DISEASE; ULCERS; NSAID; KNEE; ACETAMINOPHEN AB Objective. To investigate recent national trends in nonsteroidal antiinflammatory drug (NSAID) and acetaminophen use for osteoarthritis (OA). Methods. Using data from the 1989-98 National Ambulatory Medical Care Survey, a representative sample of US office based physician visits, we assessed 4471 visits by patients 45 years of older with a diagnosis of OA. We examined cross sectional and longitudinal patterns of OA pharmacotherapy, The independent effects of patient and physician characteristics on NSAID and acetaminophen use were examined using multiple logistic regression analysis. Results. Pharmacological treatment for OA (either NSAID, acetaminophen, or both) has steadily decreased from 49% of visits (1989-91) to 46% (1992-94) to 40% (1995-98) (p = 0.001). Reduced NSAID use over this time period (46% to 33%; p = 0.001) was partially offset by a modest increase in acetaminophen use (5% to 10%; p = 0,001). Among individual NSAID, ibuprofen (5.7% of OA visits), nabumetone (4.9%,), naproxen (4.6%), and aspirin (4.4%) were the most frequently reported in 1995-98. For patient visits in 1995-98, 45 to 59-year-olds (38%) received NSAID more often than 60 to 74-year-olds (34%) or patients older than 75 (28%; p = 0.029). Other possible predictors of OA therapy included patient race and physician specialty, Conclusion. The decline in the use of NSAID from 1989 to 1998, especially among elderly patients, and the frequent selection of safer medications may reflect awareness of the literature citing the risks of nonsteroidals for OA. However, variations in prescribing patterns among different patient populations and the modest use of acetaminophen. despite evidence supporting its efficacy, suggest that better assimilation of the literature into medical practice is needed to optimize OA therapy. C1 Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA. RP Stafford, RS (reprint author), Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. FU AHRQ HHS [HS07892]; NHLBI NIH HHS [K08-HL03548] NR 49 TC 21 Z9 21 U1 1 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 MAY PY 2002 VL 29 IS 5 BP 999 EP 1005 PG 7 WC Rheumatology SC Rheumatology GA 549DW UT WOS:000175430100024 PM 12022364 ER PT J AU Berger, DH AF Berger, DH TI The Association for Academic Surgery, an idea whose time has come? SO JOURNAL OF SURGICAL RESEARCH LA English DT Editorial Material C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Berger, DH (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 1 PY 2002 VL 104 IS 1 BP 1 EP 7 DI 10.1006/jsre.2002.6375 PG 7 WC Surgery SC Surgery GA 549EJ UT WOS:000175431300001 PM 11971670 ER PT J AU Awad, SS Liscum, KR Aoki, N Awad, SH Berger, DH AF Awad, SS Liscum, KR Aoki, N Awad, SH Berger, DH TI Does the subjective evaluation of medical student surgical knowledge correlate with written and oral exam performance? SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Association-for-Academic-Surgery CY NOV 15-17, 2001 CL MILWAUKEE, WISCONSIN SP Assoc Acad Surg DE subjective; objective; evaluation; surgical fund of knowledge; correlation; medical students; grades ID SURGERY CLERKSHIP; EXPERIENCE AB Background. Medical student performance evaluations have historically contained a significant subjective component. Multiple tools are used to assess fund of knowledge including subjective evaluation by faculty and residents as well as objective evaluations through standardized written and oral exams. We hypothesized that subjective evaluation of medical student knowledge would correlate with objective evaluation through written and oral exams. Methods. Records of consecutive medical students assigned to the surgery clerkship from January 1999 and March 2001 were reviewed. The core surgical rotation consisted of two 4-week blocks on a private, county, or VA hospital service. Surgical knowledge was assessed subjectively by both faculty (FES) and senior residents (RES) using a 10-point scale with verbal anchors. Objective measures of student surgical knowledge included the National Board shelf exam (WE) and a semistructured oral exam (OE). Data are reported as mean +/- SEM. Spearman rank correlation coefficient (r) was used to assess relationships between groups (r greater than or equal to 0.5 --> positive correlation). Results. A total of 354 students were evaluated. The mean FES was 7.8 +/- 0.05 (median = 7.75, range 4.75 to 9.75). The mean RES was 7.7 +/- 0.06 (median = 8.0, range 3.5 to 10.0). There was poor correlation between the subjective perception and objective measures of surgical knowledge (Table 1). Comparison of the FES and RES also showed poor correlation (r = 0.38). Conclusions. Subjective evaluation of surgical knowledge by faculty and residents correlates poorly with performance measured objectively. These results question whether subjective evaluation of surgical C1 Baylor Coll Med, Dept Informat Res & Planning, Houston, TX 77030 USA. UT Hlth Sci Ctr, Dept Emergency Med, Houston, TX USA. Baylor Coll Med, Houston VAMC, Surg Serv, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. RP Awad, SS (reprint author), Baylor Coll Med, Houston VAMC, Surg Serv, Michael E DeBakey Dept Surg, 112,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 10 TC 19 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 1 PY 2002 VL 104 IS 1 BP 36 EP 39 DI 10.1006/jsre.2002.6401 PG 4 WC Surgery SC Surgery GA 549EJ UT WOS:000175431300006 PM 11971675 ER PT J AU Parada, HJ Bostic, JQ AF Parada, HJ Bostic, JQ TI School violence: Assessment, management, prevention. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Parada, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2002 VL 41 IS 5 BP 626 EP 627 DI 10.1097/00004583-200205000-00023 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 544YF UT WOS:000175188900023 ER PT J AU Trehan, M Taylor, CR AF Trehan, M Taylor, CR TI High-dose 308-nm excimer laser for the treatment of psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PUVA; PHOTOTHERAPY; RADIATION AB Background: The excimer laser can deliver high-intensity. ultraviolet B (UVB) energy at 308 nm, a wavelength similar to that Used in narrow-band UVB phototherapy. Objective: The goal of this investigation was to evaluate the role of high-close single treatments with the excimer 308-nm laser in stable plaque-type psoriasis. Methods: Eighteen volunteers were enrolled in the study. Two plaques were selected and half of each plaque was held as a control while the other half was treated with a single dose of either 8 or 16 times the minimal erythema close. Results: Sixteen subjects completed the Study, Two patients signed up but never actually participated because of Scheduling problems. Eleven showed significant improvement within 1 month, and 5 still demonstrated persistent areas of clearing at 4 months. Conclusion: As little as one high-close excimer laser treatment can be effective for localized plaque-type psoriasis. Multiple treatments or other irradiation schedules With this innovative device may prove even more efficacious. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Gange Photomed Res Ctr,Wellman Labs Photomed, Boston, MA 02114 USA. RP Trehan, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Gange Photomed Res Ctr,Wellman Labs Photomed, 55 Fruit St,Bartlett 622, Boston, MA 02114 USA. NR 11 TC 59 Z9 62 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2002 VL 46 IS 5 BP 732 EP 737 DI 10.1067/mjd.2002.120538 PG 6 WC Dermatology SC Dermatology GA 557NN UT WOS:000175914800015 PM 12004316 ER PT J AU Januzzi, JL Lewandrowski, K MacGillivray, TE Newell, JB Kathiresan, S Servoss, SJ Lee-Lewandrowski, E AF Januzzi, JL Lewandrowski, K MacGillivray, TE Newell, JB Kathiresan, S Servoss, SJ Lee-Lewandrowski, E TI A comparison of cardiac troponin T and creatine kinase-MB for patient evaluation after cardiac surgery SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PERIOPERATIVE MYOCARDIAL-INFARCTION; ARTERY BYPASS-SURGERY; DAMAGE; MARKER; DIAGNOSIS; ISCHEMIA; PREDICT; RELEASE; VALUES; RISK AB OBJECTIVES The aim of this study was to assess the role of serum markers of myocardial necrosis after cardiac surgery. BACKGROUND The role of serum troponin T (TnT) and creatine kinase-MB (CK-MB) for the risk stratification of patients after cardiac surgery remains undefined. METHODS Serum levels of TnT and CK-MB were measured from 224 patients every 8 h after cardiac surgery. The results of serum cardiac marker testing were correlated with adverse events, including new myocardial infarction (MI), cardiogenic shock or death, Univariable analysis identified factors predictive of complications, while stepwise logistic regression identified independent predictors of postoperative complications. RESULTS Cardiac marker elevation was universal after cardiac surgery. At all time points measured, compared with those patients without complications, the TnT levels from patients with complications were more significantly elevated (all: p < 0.0005). In contrast, among identically timed specimens, the levels of CK-MB from complicated patients were less reliably discriminatory. Multivariable analysis suggested that a TnT level in the highest quintile (greater than or equal to1.58 ng/ml was the strongest predictor of complications, including death (post-op, odds ratio [OR] = 31.0, 9506 confidence interval [CI] 3.67 to 263.1, p = 0.002) or shock I post-op: OR = 18.9, 95% Cl = 2.29 to 156.1, p 0.006 18 h to 24 h: OR = 30.7, 95% CI = 3.75 to 250.7, p = 0.0011), as well as the composite end points of death/MI (18 h to 24 h: OR = 60.1, 95% CI 7.34 to 492.1, p < 0.0005) shock\MI (post-op: OR = 23.3, 95% Cl = 2.82 to 191.4, p = 0.003; 18 h to 24 h: OR = 37.8, 95% Cl = 4.66 to 307.3, p = 0.001) or death/shock/MI (post-op: OR = 20.0, 9506 CI = 2.81 to 142.0, p = 0.003; 18 h to 24 h: OR = 67.4, 95% Cl = 6.96 to 652.3, p < 0.0005). In contrast, in the presence of TnT, the results of CK-MB measurement added no independent prognostic information. CONCLUSIONS Troponin T is superior to CK-MB for the prediction of impending complications after cardiac surgical procedures. (C) 2002 by the American College of Cardiology Foundation. C1 Massachusetts Gen Hosp, Clin Chem Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. RP Lee-Lewandrowski, E (reprint author), Massachusetts Gen Hosp, Clin Chem Labs, Gray Bigelow 5,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 87 Z9 91 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 1 PY 2002 VL 39 IS 9 BP 1518 EP 1523 AR PII S0735-1097(02)01789-8 DI 10.1016/S0735-1097(02)01789-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 545PW UT WOS:000175227200018 PM 11985917 ER PT J AU Friedlander, AH Marder, SR AF Friedlander, AH Marder, SR TI The psychopathology, medical management and dental implications of schizophrenia SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID ANTIPSYCHOTIC MEDICATIONS; MENTAL-HEALTH; RISPERIDONE; CLOZAPINE; DIMENSIONS; SYMPTOMS; AGENTS; MEMORY AB Background. Schizophrenia is a psychiatric illness characterized by thought disturbances, bizarre behaviors and cognitive impairments that may diminish a person's abilities in the areas of social relations, school or work and self-care. The onset of the disorder typically occurs between the late teens and mid-30s. Advanced dental disease is seen frequently in patients with schizophrenia for several reasons: the disease impairs these patients' ability to plan and perform oral hygiene procedures; some of the antipsychotic medications they take have adverse orofacial effects such as xerostomia; and these patients sometimes have limited access to treatment because of a paucity of financial resources and adequate number of dentists comfortable in providing care. The recent Introduction of more effective medications has permitted the majority of patients to receive their psychiatric care from community-based providers rather than in the hospital. Consequently, dentists in the private sector also are being called on more frequently to care for these people. Conclusions. Dentists cognizant of the signs and symptoms of schizophrenia are likely to feel more secure in treating patients schizophrenia and more confident when obtaining consultative advice from the patients' psychiatrists. Dentists usually can provide a full range of services to such patients, can enhance these patients' self-esteem and can contribute to the psycho-therapeutic aspect of management. Clinical implications. To effectively provide treatment to patients with schizophrenia, dentists must be familiar with the disease process so that they can communicate effectively with the patient, treating psychiatrist and family members who serve as caregivers. In addition, treatment may need to be modified because of the patients impaired ability to think logically, the local and systemic effects psychiatric medications, and adverse interactions between these drugs medications used in dentistry. C1 VA Greater Los Angeles Healthcare Syst 14, Dept Vet Affairs VISN 22 Mental Illness Res Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Med, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst 14, Clin Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst 14, Dept Vet Affairs VISN 22 Mental Illness Res Educ, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 59 TC 44 Z9 44 U1 6 U2 10 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2002 VL 133 IS 5 BP 603 EP 610 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 552YQ UT WOS:000175648200021 PM 12036166 ER PT J AU Oslin, DW Datto, CJ Kallan, MJ Katz, IR Edell, WS TenHave, T AF Oslin, DW Datto, CJ Kallan, MJ Katz, IR Edell, WS TenHave, T TI Association between medical comorbidity and treatment outcomes in late-life depression SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression; older treatment; medical illness ID COGNITIVE IMPAIRMENT; POSTSTROKE DEPRESSION; GERIATRIC DEPRESSION; MAJOR DEPRESSION; OLDER-PEOPLE; PRIMARY-CARE; DISABILITY; SYMPTOMS; MORTALITY; IMPACT AB OBJECTIVES: Previous studies have demonstrated an association between major depression and physical disability in late life. The objectives of this study were to examine the relationship between specific medical illnesses and the outcomes of treatment for late-fife depression. DESIGN: The study was a longitudinal assessment of medical illness, depression, and disability. Patients were assessed during an initial inpatient psychiatric hospitalization and 3 months postdischarge. SETTING: All patients were initially evaluated after admission to one of 71 inpatient psychiatric treatment facilities. PARTICIPANTS: A sample of 671 older patients who received inpatient treatment for depression was evaluated at entry into the hospital and 3 months after discharge. MEASUREMENTS: Depressive symptoms were measured using the Geriatric Depression Scale. Disability was measured using the instrumental activities of daily living scale and the Medical Outcomes Study 36-item short form. Medical illness was assessed using the medical illness checklist. RESULTS: As previously reported, physical disability and the total number of medical illnesses were significantly related to change in depressive symptoms. In this study, we find that arthritis, circulatory problems, a speech disorder, or a skin problem, but not other general medical conditions, were related to a worse outcome with respect to depression symptoms. The effect of these problems was statistically and clinically significant. After controlling for pretreatment disability, arthritis and skin problems continued to predict a worse outcome. However, the apparent effect of each of these conditions was mediated by the residual disability after treatment. CONCLUSION: The results of this study support the hypothesis that certain somatic disorders play a role in the treatment response of late-life depression and suggest that the effect of specific illnesses on depression may be mediated by the presence of functional disability. C1 Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Mental Hlth Outcomes, Lewisville, TX USA. RP Oslin, DW (reprint author), Univ Penn, Sect Geriatr Psychiat, 3600 Chestnut St,Room 790, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [1K08 MH01599-01, 2P30 ,MH 52129-05] NR 34 TC 45 Z9 46 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2002 VL 50 IS 5 BP 823 EP 828 DI 10.1046/j.1532-5415.2002.50206.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 549GE UT WOS:000175435500006 PM 12028167 ER PT J AU Weyman, AE Davidoff, R Gardin, J Ryan, T Sutton, MSJ Weissman, NJ AF Weyman, AE Davidoff, R Gardin, J Ryan, T Sutton, MSJ Weissman, NJ TI Echocardiographic evaluation of pulmonary artery pressure with clinical correlates in predominantly obese adults SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID DOPPLER ULTRASOUND; TRICUSPID REGURGITATION; NONINVASIVE ESTIMATION; VALVE ABNORMALITIES; SYSTOLIC PRESSURE; DEXFENFLURAMINE; HEART AB Pulmonary artery systolic pressure (PASP) was examined in relationship to age, body mass index (BMI), the effects of comorbid disease, and standard echocardiographic measurements of cardiac chamber size, left ventricular filling patterns, and left ventricular systolic function in 5 large cohorts presenting with a primary problem of obesity. For subjects with a measurable PASP, means (+/- SD) across cohorts for age ranged from 46.0 +/- 11.2 to 54.1 +/- 12.8 years, for BMI from 26.0 +/- 4.4 to 37.2 +/- 6.1 kg/m(2), and PASP (n = 1515) from 29.9 +/- 7.7 to 33.8 +/- 7.8 mm Hg. PASP 30 mm Hg or greater occurred in 46% to 66% of subjects and 35 mm Hg or greater in 16% to 36%. Age and BMI were the most significant correlates of PASP. Increased PASP was also significantly associated with systemic hypertension and a history of cardiovascular disease. The mean PASP in obese individuals is higher than previously reported with nearly one third having a PASP of 35 mm Hg or greater. Clinical interpretation of PASP should include BMI, age, blood pressure, and presence of cardiovascular disease. C1 Boston Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Irvine, Med Ctr, Irvine, CA USA. Duke Univ, Med Ctr, Raleigh, NC USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Cardiovasc Res Fdn, Washington, DC USA. RP Weyman, AE (reprint author), Boston Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. OI Davidoff, Ravin/0000-0002-3797-5325 NR 28 TC 12 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2002 VL 15 IS 5 BP 454 EP 462 DI 10.1067/mje.2002.114912 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 558EN UT WOS:000175953500010 PM 12019429 ER PT J AU Hinkin, CH Hardy, DJ Mason, KI Catellon, SA Lam, MN Stefaniak, M Zolnikov, B AF Hinkin, CH Hardy, DJ Mason, KI Catellon, SA Lam, MN Stefaniak, M Zolnikov, B TI Verbal and spatial working memory performance among HIV-infected adults SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the International-Neuropsychological-Society CY FEB, 2000 CL DENVER, COLORADO SP Int Neuropsychol Soc DE working memory; HIV infection; executive functions ID AIDS DEMENTIA COMPLEX; MAGNETIC-RESONANCE SPECTROSCOPY; PREFRONTAL CORTEX; FRONTAL-CORTEX; PET; INDIVIDUALS; DEFICITS; THERAPY; DISEASE; SYSTEM AB Subtypes of working memory performance were examined in a cohort of 50 HIV-infected adults and 23 uninfected controls using an it-back paradigm (2-back) in which alphabetic stimuli were quasi-randomly presented to a quadrant of a computer monitor. In the verbal working memory condition, participants determined whether each successive letter matched the letter that appeared two previously in the series. regardless of spatial location. In the spatial working memory condition, participants determined whether each letter matched the spatial location of the letter that had appeared two previously, regardless of letter identity. The dependent variable was percent accuracy in each condition. Results of mixed model ANOVA revealed that the HIV-infected participants performed significantly worse than controls on both the verbal and spatial working memory tasks. A significant main effect for working memory condition was also present with both participant groups performing better on the spatial working memory task. These results, the first study of HIV-infected adults to directly compare verbal versus spatial working memory performance using the identical test stimuli across task conditions, suggests that HIV infection is associated with a decrement in working memory efficiency that is equally apparent for both verbal and spatial processing. These findings implicate central executive dysfunction as a likely substrate and provide the basis for hypothesizing that decline in working memory may contribute to other HIV-associated neuropsychological deficits. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Hinkin, CH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, Neuropsychiat Inst & Hosp, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [R01 MH058552, R01 MH58552] NR 42 TC 26 Z9 28 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2002 VL 8 IS 4 BP 532 EP 538 DI 10.1007/S1355617701020276 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 550TN UT WOS:000175519500002 PM 12030306 ER PT J AU Partridge, AH Avorn, J Wang, PS Winer, EP AF Partridge, AH Avorn, J Wang, PS Winer, EP TI Adherence to therapy with oral antineoplastic agents SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; CANCER PREVENTION TRIALS; BREAST-CANCER; PATIENT COMPLIANCE; LYMPHOBLASTIC-LEUKEMIA; MEDICATION COMPLIANCE; DRUG-COMPLIANCE; PILL COUNTS; ANTIHYPERTENSIVE THERAPY; ADJUVANT CHEMOTHERAPY AB With the rise in availability and increasing use of oral anticancer agents, concerns about adherence to prescribed regimens will become an increasingly important issue in oncology. Few published studies have focused on adherence to oral antineoplastic therapy, in part because the vast majority of chemotherapy is delivered intravenously in physicians' offices or hospitals. In this article, we review current knowledge of adherence behavior with regard to oral medications in general, including factors associated with adherence and methods for measuring adherence. We also review published studies of adherence to oral antineoplastic agents in adult and pediatric populations and adherence issues in cancer prevention. The available evidence reveals that patient adherence to oral chemotherapy recommendations is variable and not easily predicted. Adherence rates ranging from less than 20% to 100% have been reported, and certain populations, such as adolescents, pose particular challenges. Future efforts should focus on improving measurement and prediction of adherence and on developing interventions to improve adherence for both patients in clinical trials and patients being treated outside of the research setting. Assessment of adherence among individuals with cancer and implementation of interventions in situations of poor adherence should improve clinical outcomes. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, Binney St, Boston, MA 02115 USA. NR 109 TC 264 Z9 275 U1 1 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 1 PY 2002 VL 94 IS 9 BP 652 EP 661 PG 10 WC Oncology SC Oncology GA 547QN UT WOS:000175343400006 PM 11983753 ER PT J AU Moon, TD AF Moon, TD TI Editorial: Ureteral stenting - An obsolete procedure? SO JOURNAL OF UROLOGY LA English DT Editorial Material ID URETEROSCOPY C1 Univ Wisconsin, Div Urol, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Moon, TD (reprint author), Univ Wisconsin, Div Urol, Madison, WI 53706 USA. NR 5 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2002 VL 167 IS 5 BP 1984 EP 1984 AR UNSP 0022-5347/02/1675-1984/0 DI 10.1016/S0022-5347(05)65068-9 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 541AW UT WOS:000174963900009 PM 11956423 ER PT J AU D'Amico, AV Chen, MH Malkowicz, SB Whittington, R Renshaw, AA Tomaszewski, JE Samofalov, Y Wein, A Richie, JP AF D'Amico, AV Chen, MH Malkowicz, SB Whittington, R Renshaw, AA Tomaszewski, JE Samofalov, Y Wein, A Richie, JP TI Lower prostate specific antigen outcome than expected following radical prostatectomy in patients with high grade prostate cancer and a prostatic specific antigen level of 4 ng./ml. or less SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; testosterone; treatment outcome ID RECURRENCE; NOMOGRAM AB Purpose: We report the estimates of 10-year prostate specific antigen (PSA) outcome following radical prostatectomy in patients with or without grade 4 or 5 disease in the needle biopsy or prostatectomy specimen stratified by the presenting PSA level. Materials and Methods: From 1989 to 2001, 2,254 patients treated with radical prostatectomy for clinically localized prostate cancer comprised the study cohort. PSA outcome was estimated using the actuarial method of Kaplan and Meier, and was stratified by the presenting PSA level and needle biopsy and prostatectomy Gleason score. Results: The 10-year estimates of PSA outcome declined significantly (p less than or equal to 0.002) for patients with biopsy or prostatectomy Gleason score 6 or less as the presenting PSA level increased. This trend was observed for biopsy and prostatectomy Gleason score 7 or higher except for the PSA 4 or less group which did significantly worse (46% versus 62%, p = 0.03) compared to the PSA greater than 4 to 10 ng./ml. group. This finding may be explained by a low serum free testosterone level and the presence of a significantly higher proportion of prostatectomy Gleason score 8 to 10 disease (25% versus 16%, p = 0.03) in the PSA 4 or less versus greater than 4 to 10 ng./ml. group. Conclusions: Patients with Gleason grade 4 or 5 disease in the radical prostatectomy specimen and a presenting PSA of 4 ng./ml. or less may be androgen deficient and have a significantly lower estimate of 10-year PSA outcome then expected based on the presenting PSA level. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math, Worcester, MA 01609 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 16 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2002 VL 167 IS 5 BP 2025 EP 2030 AR UNSP 0022-5347/02/1675-2025/0 DI 10.1016/S0022-5347(05)65076-8 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 541AW UT WOS:000174963900019 PM 11956431 ER PT J AU Matsumoto, AM Tenover, L McClung, M Mobley, D Geller, J Sullivan, M Grayhack, J Wessells, H Kadmon, D Flanagan, M Zhang, GK Schmidt, J Taylor, AM Lee, M Waldstreicher, J AF Matsumoto, AM Tenover, L McClung, M Mobley, D Geller, J Sullivan, M Grayhack, J Wessells, H Kadmon, D Flanagan, M Zhang, GK Schmidt, J Taylor, AM Lee, M Waldstreicher, J CA PLESS Study Grp TI The long-term effect of specific type II 5 alpha-reductase inhibition with finasteride on bone mineral density in men: Results of a 4-year placebo controlled trial SO JOURNAL OF UROLOGY LA English DT Article DE prostatic hyperplasia; bone density; stanolone; finasteride ID BENIGN PROSTATIC HYPERPLASIA; MALE PSEUDOHERMAPHRODITISM; OSTEOPOROSIS; ANDROGENS; TESTOSTERONE; DEFICIENCY; THERAPY; CANCER; MASS AB Purpose: We determine the effect of long-term suppression of dihydrotestosterone with finasteride, a specific type II 5alpha-reductase inhibitor, on bone mineral density. Materials and Methods: As part of a large (3,040 cases) 4-year, double-blind, placebo controlled trial designed to assess the long-term effects of finasteride in men with benign prostatic hyperplasia, 157 men 46 to 76 years old who were randomized to receive either 5 mg. finasteride or placebo underwent dual energy x-ray absorptiometry of the lumbar spine at baseline and at years 2, 3 and 4. Results: Of 117 patients who had a baseline measurement and at least 1 additional measurement during the study baseline mean plus or minus standard deviation bone mineral density values were 1.12 +/- 0.17 gm./cm.(2) in the finasteride group (63) and 1.10 +/- 0.17 gm./cm.(2) in the placebo group (54). After 4 years bone mineral density was not different between treatment groups (finasteride 1.14 +/- 0.17 gm./cm.(2) and placebo 1.13 +/- 0.18 gm./cm.(2)). Similar results were obtained for the 33 finasteride and 25 placebo treated patients who completed the study with year 4 bone mineral density measurements. Conclusions: These data demonstrate that long-term inhibition of type II 5alpha-reductase with finasteride does not adversely affect bone mineral density. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Emory Univ, Atlanta, GA 30322 USA. Oregon Osteoporosis Ctr, Portland, OR USA. Res Hlth Inc, Houston, TX USA. Mercy Res Clin, San Diego, CA USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Arizona, Tucson, AZ USA. Baylor Coll Med, Houston, TX 77030 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Pk Nicollet Clin, Minneapolis, MN USA. Univ Calif San Diego, San Diego, CA 92103 USA. Merck & Co Inc, Rahway, NJ 07065 USA. RP Matsumoto, AM (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 20 TC 34 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2002 VL 167 IS 5 BP 2105 EP 2108 AR UNSP 0022-5347/02/1675-2105/0 DI 10.1016/S0022-5347(05)65095-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 541AW UT WOS:000174963900044 PM 11956450 ER PT J AU Yang, XZ Lee, J Mahony, EM Kwong, PD Wyatt, R Sodroski, J AF Yang, XZ Lee, J Mahony, EM Kwong, PD Wyatt, R Sodroski, J TI Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; HIV-1 GP41; NEUTRALIZING ANTIBODIES; GP120 GLYCOPROTEIN; IMMUNE-RESPONSES; ATOMIC-STRUCTURE; RECEPTOR; PROTEIN; DOMAIN; IMMUNIZATION AB The envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) function as a trimer composed of three gp120 exterior glycoproteins and three gp41 transmembrane proteins. Soluble gp140 glycoproteins composed of the uncleaved ectodomains of gp120 and gp41 form unstable, heterogeneous oligomers, but soluble gp140 trimers can be stabilized by fusion with a C-terminal, trimeric GCN4 motif (X. Yang et al., J. Virol 74:5716-5725, 2000). To understand the influence of the C-terminal trimerization domain on the properties of soluble HIV-1 envelope glycoprotein trimers, uncleaved, soluble gp140 glycoproteins were stabilized by fusion with another trimeric motif derived from T4 bacteriophage fibritin. The fibritin construct was more stable to heat and reducing conditions than the GCN4 construct. Both GCN4- and fibritin-stabilized soluble gp140 glycoproteins exhibited patterns of neutralizing and nonneutralizing antibody binding expected for the functional envelope gIycoprotein spike. Of note, two potently neutralizing antibodies, immunoglobulin G1b12 and 2G12, exhibited the greatest recognition of the stabilized, soluble trimers, relative to recognition of the gp120 monomer. The observed similarities between the GCN4 and fibritin constructs indicate that the HIV-1 envelope glycoprotein ectodomains dictate many of the antigenic and structural features of these fusion proteins. The melting temperatures and ligand recognition properties of the GCN4- and fibritin-stabilized soluble gp140 glycoproteins suggest that these molecules assume conformations distinct from that of the fusion-active, six-helix bundle. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. NIAID, Struct Biol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Lab Struct Virol, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St JFB824, Boston, MA 02115 USA. FU NIAID NIH HHS [P30 AI028691, AI24755, AI28691, AI31783, AI39420, R01 AI031783, R01 AI039420, R37 AI024755] NR 52 TC 203 Z9 208 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4634 EP 4642 DI 10.1128/JVI.76.9.4634-4642.2002 PG 9 WC Virology SC Virology GA 541CB UT WOS:000174966700050 PM 11932429 ER PT J AU Mueller, NJ Barth, RN Yamamoto, S Kitamura, H Patience, C Yamada, K Cooper, DKC Sachs, DH Kaur, A Fishman, JA AF Mueller, NJ Barth, RN Yamamoto, S Kitamura, H Patience, C Yamada, K Cooper, DKC Sachs, DH Kaur, A Fishman, JA TI Activation of cytomegalovirus in pig-to-primate organ xenotransplantation SO JOURNAL OF VIROLOGY LA English DT Article ID BABOON CYTOMEGALOVIRUS; THYMIC TRANSPLANTATION; MINIATURE SWINE; IN-VITRO; INFECTION; TOLERANCE; RECIPIENTS; LYMPHOCYTES; BARRIER; RISK AB Xenotransplantation of porcine organs carries the risk of reactivation of latent virus in donor and recipient tissues as well as transmission of viruses between species. We have investigated the activation of baboon cytomegalovirus (BCMV) and porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. tissues originating from a series of six swine-to-baboon composite thymokidney xenotransplants were investigated. Four immunosuppressed baboons died (survival range, 7 to 27 days) with the graft in situ. Increases in BCMV DNA copy numbers occurred in three (75%) of these baboons and was thought to be responsible for pneumonitis and the death of one animal. In two baboons, disseminated intravascular coagulation was successfully treated by graftectomy and discontinuation. of immunosuppression. PCMV was upregulated in five of six xenografts (83%). PCMV infection was associated with ureteric necrosis in one xenograft. Although significantly increased in native tissues, low levels of BCMV and PCMV were also detected in tissues other than that of the native viral host species. The cross-species presence of CMV did not appear to cause clinical or histological signs of invasive disease. Thus, viral infections with clinical disease were restricted to tissues of the native species of each virus. Intensive immune suppression currently required for xenotransplantation results in a significant risk of reactivation of latent infections by BCMV an PCMV. It is not yet known whether viral DNA detected across species lines represents cellular microchimerism, ongoing viral infection, or uptake of free virus. The observation of graft injury by PCMV demonstrates that CMV will be an important pathogen in immunosuppressed xenograft recipients. Strategies must be developed to exclude CMV from porcine organ donors. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Immerge BioTherapeut Inc, Charlestown, MA USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. RI Barth, Rolf/B-2542-2014; Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 FU NIAID NIH HHS [R01-AI43890, 5T32-AI07529-04, P01 AI045897, P01-AI45897, R01 AI043890, T32 AI007529] NR 25 TC 62 Z9 64 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 4734 EP 4740 DI 10.1128/JVI.76.10.4734-4740.2002 PG 7 WC Virology SC Virology GA 546DK UT WOS:000175256500006 PM 11967290 ER PT J AU Chen, SH Lee, LY Garber, DA Schaffer, PA Knipe, DM Coen, DM AF Chen, SH Lee, LY Garber, DA Schaffer, PA Knipe, DM Coen, DM TI Neither LAT nor open reading frame P mutations increase expression of spliced or intron-containing ICP0 transcripts in mouse ganglia latently infected with herpes simplex virus SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; GENE MESSENGER-RNA; TRIGEMINAL GANGLIA; GAMMA(1)34.5 GENE; STABLE INTRON; IN-VITRO; TYPE-1; REACTIVATION; MUTANTS; PROTEIN AB Latent infections by herpes simplex virus are characterized by repression of productive-cycle gene expression. Several hypotheses to explain this repression involve inhibition of expression of the immediate-early gene activator ICP0 during latency. To address these hypotheses, we developed quantitative reverse transcriptase-PCR assays that detected spliced and intron-containing ICP0 transcripts in mouse ganglia latently infected with wild-type virus. In these ganglia, the numbers of spliced ICP0 transcripts correlated better with the numbers of transcripts from the immediate-early gene encoding ICP4 than with those from the early gene encoding thymidine kinase. There were fewer spliced than intron-containing ICP0 transcripts on average, with considerable ganglion-to-ganglion variation. We then investigated whether ICP0 expression in latently infected ganglia is reduced by the latency-associated transcripts (LATs) and whether splicing of ICP0 transcripts is inhibited by the product of open reading frame (01117) P. A LAT deletion mutation which essentially eliminates expression of the major LATs did not appreciably increase levels of ICP0 transcripts. LAT deletion mutants did, however, appear to express reduced levels of intron-containing ICP0 transcripts. ORF P mutations did not alter levels of ICP0 transcripts in a manner consistent with inhibition of ICP0 splicing by ORF P. Although these results argue against antisense inhibition of ICP0 expression by LATs or inhibition of ICP0 splicing by ORF P, they are consistent with the possibilities of a block between immediate-early and early gene expression and regulation of spliced versus intron-containing ICP0 transcripts in latently infected ganglia. C1 Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, SH (reprint author), Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan. FU NINDS NIH HHS [P01 NS035138, P01NS35138] NR 51 TC 39 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 4764 EP 4772 DI 10.1128/JVI.76.10.4764-4772.2002 PG 9 WC Virology SC Virology GA 546DK UT WOS:000175256500009 PM 11967293 ER PT J AU Mascola, JR Louder, MK Winter, C Prabhakara, R De Rosa, SC Douek, DC Hill, BJ Gabuzda, D Roederer, M AF Mascola, JR Louder, MK Winter, C Prabhakara, R De Rosa, SC Douek, DC Hill, BJ Gabuzda, D Roederer, M TI Human immunodeficiency virus type 1 neutralization measured by flow cytometric quantitation of single-round infection of primary human T cells SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1/SIV CHIMERIC VIRUS; BLOOD MONONUCLEAR-CELLS; HIV-INFECTION; ENVELOPE GLYCOPROTEINS; MONOCLONAL-ANTIBODIES; REPLICATIVE CAPACITY; ANTIGEN-DETECTION; P24 ANTIGEN; IN-VITRO; ASSAYS AB There is currently intensive research on the design of novel human immunodeficiency virus type I (HIV-1) vaccine immunogens that can elicit potent neutralizing antibodies. A prerequisite for comparing and optimizing these strategies is the ability to precisely measure neutralizing antibody responses. To this end, we sought to develop an assay that directly quantifies single-round HIV-1 infection of peripheral blood mononuclear cells (PBMC). Initial experiments demonstrated that essentially all productively infected PBMC could be identified by flow cytometric detection of intracellular p24 antigen (p24-Ag). After infection of PBMC with HIV-1, p24(+) lymphocytes could be distinguished beginning 1 day postinfection, and the majority of CD8(-) T cells were p24-Ag positive by 3 to 4 days postinfection. To directly quantify first-round infection, we included a protease inhibitor in PBMC cultures. The resulting 2-day assay was highly sensitive and specific for the detection of HIV-1-infected PBMC. Serial dilutions of virus stocks demonstrated that the number of target cells infected was directly related to the amount of infectious virus input into the assay. In neutralization assays, the flow cytometric enumeration of first-round infection of PBMC provided quantitative data on the number of target calls infected and on the inactivation of infectious virus due to reaction with antibody. We also used this single-round assay to compare the percentage of cells expressing p24-Ag to the number of copies of HIV-1 gag per 100 PBMC. The precision and reproducibility of this assay will facilitate the measurement of HIV-1 neutralization, particularly incrementally improved neutralizing antibody responses generated by new candidate vaccines. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. RI Roederer, Mario/G-1887-2011 FU NINDS NIH HHS [NS37277, R01 NS037277] NR 78 TC 93 Z9 99 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 4810 EP 4821 DI 10.1128/JVI.76.10.4810-4821.2002 PG 12 WC Virology SC Virology GA 546DK UT WOS:000175256500014 PM 11967298 ER PT J AU Hofmann-Lehmann, R Vlasak, J Chenine, AL Li, PL Baba, TW Montefiori, DC McClure, HM Anderson, DC Ruprecht, RM AF Hofmann-Lehmann, R Vlasak, J Chenine, AL Li, PL Baba, TW Montefiori, DC McClure, HM Anderson, DC Ruprecht, RM TI Molecular evolution of human immunodeficiency virus env in humans and monkeys: Similar patterns occur during natural disease progression or rapid virus passage SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODIES; TYPE-1 ENVELOPE GLYCOPROTEINS; PIG-TAILED MACAQUES; RHESUS-MONKEYS; IN-VIVO; V3 DOMAIN; PERSISTENT INFECTION; VARIABLE REGION; CHAIN-REACTION; GP120 AB Neonatal rhesus macaque 95-3 was inoculated with nonpassaged simian-human immunodeficiency virus strain SHIV-vpu(+), which encodes env of the laboratory-adapted human immunodeficiency virus (HIV) strain IIIB and is considered nonpathogenic. CD4(+) T-cell counts dropped to <200 cells/mul within 4.6 years, and monkey 95-3 died with opportunistic infections 5.9 years postinoculation. Transfer of blood from 95-3 to two naive adult macaques resulted in high peak viral loads and rapid, persistent T-cell depletion. Progeny virus evolved in 95-3 despite high SHIV-vpu(+) neutralizing antibody titers and still used CXCR4 but, in contrast to parental SHIV-vpu(+), productively infected macrophages and resisted neutralization. Sequence analysis revealed three new potential glycosylation sites in gp120; another two were lost. Strikingly similar mutations were detected in a laboratory worker who progressed to AIDS after accidental HIV-IIIB infection (T. Beaumont et al., J. Virol. 75:2246-2252, 2001), thus supporting the SHIV-v-pu(+)/rhesus macaque system as a relevant model. Similar mutations were also described after rapid passage of chimeric viruses encoding IIIB env in rhesus and pig-tailed macaques (M. Cayabyab et al., J. Virol. 73:976-984, 1999; Z. Q. Liu et al., Virology 260:295-307, 1999; S. V. Narayan et al., Virology 256:54-63, 1999; R. Raghavan et al., Brain Pathol. 7:851-861, 1997; E. B. Stephens et al., Virology 231:313-321, 1997). Thus, HIV-IIIB env evolved similarly in three different species; this selection occurred in chronically infected individuals during disease progression as well as after rapid virus passage. We postulate that evolutionary pressure led to the outgrowth of more aggressive viral variants in all three species. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Div Newborn Med, Boston, MA 02111 USA. Duke Univ, Med Ctr, Dept Surg, Ctr AIDS Res, Durham, NC 27710 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB809, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 FU NCRR NIH HHS [R01 RR014180, RR14180, P51 RR000165, RR00165]; NIAID NIH HHS [R01 AI034266, R01 AI34266, AI85343]; NIDCR NIH HHS [R01 DE012937, DE12937]; PHS HHS [5 K08-A101327] NR 50 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 10 BP 5278 EP 5284 DI 10.1128/JVI.76.10.5278-5284.2002 PG 7 WC Virology SC Virology GA 546DK UT WOS:000175256500059 PM 11967343 ER PT J AU Yoshida, T Kurella, M Beato, F Min, H Ingelfinger, JR Stears, RL Swinford, RD Gullans, SR Tang, SS AF Yoshida, T Kurella, M Beato, F Min, H Ingelfinger, JR Stears, RL Swinford, RD Gullans, SR Tang, SS TI Monitoring changes in gene expression in renal ischemia-reperfusion in the rat SO KIDNEY INTERNATIONAL LA English DT Article DE microarray; ischemia-reperfusion; gene expression ID SURFACE-MEMBRANE POLARITY; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; HEME OXYGENASE; MESSENGER-RNA; EPITHELIAL POLARITY; OXIDANT STRESS; CELL-DEATH; INJURY; INDUCTION AB Background. Although acute renal failure (ARF) is a relatively common disorder with major morbidity and mortality, its molecular basis remains incompletely defined. The present study examined global gene expression in the well-characterized ischemia-reperfusion model of ARF using DNA microarray technology. Methods. Male Wistar rats underwent bilateral renal ischemia (30 min) or sham operation, followed by reperfusion for 1, 2, 3 or 4 clays. Plasma creatinine increased approximately fivefold over baseline, peaking on day 1. Renal total RNA was used to probe cDNA microarrays. Results. Alterations in expression of IS genes were identified by microarray analysis. Nine genes were up-regulated (ADAM2, HO-1, UCP-2, and thymosin beta4 in the early phase and clusterin, vanin1, fibronectin, heat-responsive protein 12 and FK506 binding protein in the established phase), whereas another nine were down-regulated (glutamine synthetase, cytochrome p450 IId6, and cyp 2d9 in the early phase and cyp 4a14, Xist gene, PPARgamma, alpha-albumin, uromodulin, and ADH B2 in the established phase). The identities of these IS genes were sequence-verified. Changes in gene expression of ADAM2, cyp2d6, fibronectin, HO-1 and PPARgamma were confirmed by quantitative real-time polymerase chain reaction (PCR). ADAM2, cyp2d6, and PPARgamma have not previously been known to be involved in ARF. Conclusion. Using DNA microarray technology, we identified changes in expression of IS genes during renal ischemia-reperfusion injury in the rat. We confirmed changes in five genes (fibronectin, ADAM2, cyp 2d6, HO-1 and PPARgamma) by quantitative real-time PCR. Several genes, not previously been identified as playing a role in ischemic ARF, may have importance in this disease. C1 Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. Univ Texas, Med Ctr, Div Pediat, Nephrol Unit, Houston, TX USA. RP Tang, SS (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, 55 Fruit St,BHX 410, Boston, MA 02114 USA. RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU NHLBI NIH HHS [HL 48455]; NIDDK NIH HHS [DK 58950, DK 50836, DK 51606, DK-36031, DK58849] NR 56 TC 96 Z9 104 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2002 VL 61 IS 5 BP 1646 EP 1654 DI 10.1046/j.1523-1755.2002.00341.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 542PV UT WOS:000175054200009 PM 11967014 ER PT J AU Shimizu, A Yamada, K Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Sachs, DH Colvin, RB TI Persistent rejection of peritubular capillaries and tubules is associated with progressive interstitial fibrosis SO KIDNEY INTERNATIONAL LA English DT Article DE acute rejection; organ rejection; interstitial fibrosis; peritubular capillary; tubular basement membrane; tubulitis ID RENAL-ALLOGRAFT REJECTION; MINIATURE SWINE; CLASS-I; TUBULOINTERSTITIAL FIBROSIS; TRANSPLANTATION TOLERANCE; GLOMERULAR-DISEASES; STABLE INDUCTION; CELL-DEATH; INJURY; TRANSDIFFERENTIATION AB Background. We have reported that a 12-day course of high dose cyclosporine A treatment in thymectomized miniature swine with major histocompatibility complex (MHC class I-mismatched renal allografts results in transient acute rejection followed by either in chronic rejection (progression group) or graft acceptance (recovery group). Here, we examined the differential features between both groups in the peritubular capillaries (PTCs) and tubules to clarify the pathogenesis of the progressive interstitial fibrosis in chronic rejection. Methods. Morphometric and immunohistochemical studies were performed on serial renal biopsies (days 0 to 100) obtained from both groups, focusing on the cellular infiltrate, rejection of PTCs and tubules, myofibroblast accumulation, and progressive interstitial fibrosis. Results. In the progression group, acute rejection occurred by day 8 and progressed to chronic rejection by day 100, with the development of interstitial fibrosis. PTC endothelial cell and tubular epithelial cell death associated with CD3+ cell infiltration was evident, confirmed by nick end-labeling (TUNEL), commencing by day 8 and continuing thereafter. In acute rejection, destruction of PTCs and tubules accompanied by disruption of basement membrane (BM) occurred with capillaritis or tubulitis in areas with a severe cellular infiltrate. During the development of chronic rejection, capillaritis of PTCs and tubulitis continued by day 100, accompanied by persistent T cell infiltration, and the remaining PTCs and tubules exhibited progressive atrophy with thickening and/or lamination of BM. On day 100, identifiable PTCs and tubules were lost in areas of interstitial fibrosis. Proliferating (PCNA+) alpha-actin+ myofibroblasts accumulated around PTCs, tubules and in interstitium, and widespread interstitial fibrosis developed by day 100. In contrast, in the recovery group, injured PTCs and tubules recovered by day 100 based on the resolution of acute rejection, and minimal loss of PTCs and tubules was evident by day 100 with minimal interstitial fibrosis. Conclusions. Persistent rejection directed at PTCs and tubules, and proliferation of myofibroblasts are prominent features in the progressive interstitial fibrosis in chronic rejection, and are probably key events in its pathogenesis. C1 Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Nippon Med Coll, Dept Pathol, Tokyo 113, Japan. RP Colvin, RB (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,WRN 225, Boston, MA 02114 USA. FU NHLBI NIH HHS [P0P1-HL 18646]; NIAID NIH HHS [R01-AI 31046]; PHS HHS [P01-H218646] NR 46 TC 41 Z9 41 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2002 VL 61 IS 5 BP 1867 EP 1879 DI 10.1046/j.1523-1755.2002.00309.x PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 542PV UT WOS:000175054200034 PM 11967039 ER PT J AU Dember, LA Holmberg, EF Kaufman, JS AF Dember, LA Holmberg, EF Kaufman, JS TI Value of static venous pressure for predicting arteriovenous graft thrombosis SO KIDNEY INTERNATIONAL LA English DT Article DE AV graft; thrombosis; stenosis; vascular access; hemodialysis; end-stage renal disease ID INTRA-ACCESS PRESSURE; VASCULAR ACCESS; HEMODIALYSIS ACCESS; PHARMACOMECHANICAL THROMBOLYSIS; STENOSES AB Background. Static venous pressure elevation has been shown to have both high sensitivity and high specificity for hemodialysis arteriovenous (AV) graft venous anastomosis stenosis. However, it is not known how well static venous pressure elevation predicts subsequent AV graft thrombosis. Methods. Monthly static venous pressure measurements were made during two consecutive dialysis sessions in all patients with a functioning upper extremity AV graft in two hemodialysis units during a 16-month period. Static venous pressure was normalized to systolic blood pressure and corrected for the height difference between the AV graft and the dialysis machine pressure transducer to yield the static venous pressure ratio (SVPR). Results. Fifty-four patients (38%) had a thrombotic event during the study period and thus were labeled as clotters. Among the clotters, SVPR just prior to thrombosis was 0.51 +/- 0.16 (mean +/- SD), and mean time to thrombosis following an elevated SVPR (greater than or equal to0.4) was 118 +/- 106 days. Receiver operating characteristic (ROC) curves were generated using the sensitivities and specificities of a range of SVPR values for access thrombosis within one, two, three and four months. The areas under the curve (AUCs) for the ROC curves ranged from 0.557 to 0.638, reflecting the absence of SVPR values with both high sensitivity and high specificity for access thrombosis. An increase in SVPR over time was not a better predictor of access thrombosis than absolute SVPR. Conclusion. Static venous pressure measurement is not an optimal screening test for identifying AV grafts at risk for thrombosis. C1 Boston Univ, Med Ctr, Renal Sect, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Dember, LA (reprint author), Boston Univ, Med Ctr, Renal Sect, Sch Med, EBRC 504,650 Albany St, Boston, MA 02118 USA. NR 18 TC 27 Z9 27 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2002 VL 61 IS 5 BP 1899 EP 1904 DI 10.1046/j.1523-1755.2002.00337.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 542PV UT WOS:000175054200038 PM 11967043 ER PT J AU Lacayo, NJ Lum, BL Becton, DL Weinstein, H Ravindranath, Y Chang, MN Bomgaars, L Lauer, SJ Sikic, BI Dahl, GV AF Lacayo, NJ Lum, BL Becton, DL Weinstein, H Ravindranath, Y Chang, MN Bomgaars, L Lauer, SJ Sikic, BI Dahl, GV TI Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in children with acute myeloid leukemia SO LEUKEMIA LA English DT Article DE multidrug resistance; P-glycoprotein; cyclosporine; pharmacokinetics; etoposide; mitoxantrone; acute myeloid leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; P-GLYCOPROTEIN EXPRESSION; CHILDHOOD ACUTE-LEUKEMIA; MULTIDRUG-RESISTANCE; CLINICAL PHARMACODYNAMICS; DRUG-RESISTANCE; CANCER GROUP; CHEMOTHERAPY; TOXICITY; TUMORS AB The purpose of this study was to assess the effect of the multidrug resistance modulator cyclosporine (CsA) on the pharmacokinetics of etoposide and mitoxantrone in children with de novo acute myeloid leukemia (AML). Serial blood samples for pharmacokinetic studies were obtained In 38 children over a 24-h period following cytotoxin treatment with or without CsA on days 1 and 4. Drug concentrations were quantitated using validated HPLC methods, and pharmacokinetic parameters were determined using compartmental modeling with an Iterative two-stage approach, Implemented on ADAPT II software. Etoposide displayed a greater degree of Interindividual variability In clearance and systemic exposure than mitoxantrone. With CsA treatment, etoposide and mitoxantrone mean clearance declined by 71% and 42%, respectively. These effects on clearance, in combination with the empiric 40% dose reduction for either cytotoxin, resulted in a 47% and 12% increases In the mean AUC for etoposide and mitoxantrone, respectively. There were no differences in the rates of stomatitis or infection between the two groups. CsA treatment resulted In an increased Incidence of hyperbilrubinemia, which rapidly reversed upon conclusion of drug therapy. The variability observed in clearance, combined with the empiric 40% dose reduction of the cytotoxins, resulted in statistically similar systemic exposure and similar toxicity. C1 Stanford Univ, Sch Med, Div Pediat Hematol Oncol, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Div Med Oncol, Palo Alto, CA 94304 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. Univ Gainesville, Pediat Oncol Grp Stat Off, Gainesville, FL USA. Baylor Coll Med, Houston, TX 77030 USA. Emory Univ, Sch Med, Atlanta, GA USA. Pediat Oncol Grp, Chicago, IL USA. RP Dahl, GV (reprint author), POB 60012, Arcadia, CA 91066 USA. FU NCI NIH HHS [CA 69177, CA 33603, CA 69428, CA 20543, R01 CA 52168, CA 25408, CA 32053, CA 41573, CA 03161, CA 11233, CA 28383, CA 29293, CA 30969, CA 15898, CA 29691, CA 33587, CA 05587, CA 15525, CA 29139, CA 31566, CA 07431, CA 33625, CA 28439, CA 28473]; NCRR NIH HHS [M01 RR 00070] NR 51 TC 23 Z9 25 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2002 VL 16 IS 5 BP 920 EP 927 DI 10.1038/sj/leu/2402455 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 552QN UT WOS:000175631200020 PM 11986955 ER PT J AU Stone, ME AF Stone, ME TI The Oxford companion to the body. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 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 MAY 1 PY 2002 VL 127 IS 8 BP 92 EP 92 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 547NJ UT WOS:000175338400034 ER PT J AU Young, GD Winokur, TS Cerfolio, RJ Van Tine, BA Chow, LT Okoh, V Garver, RI AF Young, GD Winokur, TS Cerfolio, RJ Van Tine, BA Chow, LT Okoh, V Garver, RI TI Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes SO LUNG CANCER LA English DT Article DE lung neoplasms; intermediate filaments; desmosomes ID INTERMEDIATE FILAMENTS; DESMOSOMAL PLAQUE; ADENOSQUAMOUS CARCINOMA; DNA-SYNTHESIS; CANCER; PHOSPHORYLATION; ADENOCARCINOMA; JUNCTIONS AB Adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the lung are morphologically distinguished in part by cyto-architectural features. However, little is known about the relative expression and distribution of cyto-architectural proteins among AC, SCC and ASC. Initial microarray analysis revealed significant differences in expression of two cyto-architectural genes in AC, SCC and ASC. Desmoplakin (DP) 1 and 2, which link desmosomes to intermediate filaments, was strongly expressed in SCC relative to AC and ASC. Cytokeratin 18 (CK18), an intermediate filament that is commonly linked to desmoplakin, was strongly expressed in AC and ASC relative to SCC. Western blot analysis demonstrated that AC and ASC had abundant CK18 protein, whereas CK18 was weakly detected in SCC. DP 1 and 2 are strongly expressed in SCC and minimally expressed in AC and ASC. However, the ratio of one to the other is the same in SCC and AC, but DP2 is lost in ASC. Microscopic analysis with fluorescence-labeled antibodies for CK18 and DP I and 2 revealed abundant membrane localization of DP and minimal perinuclear localization of CK18 in SCC. In contrast, in both AC and ASC, the CK18 protein was diffusely distributed within the cytoplasm, and DP showed both membranous and cytoplasmic localization. In conclusion, the data here shows that AC, SCC and ASC each have specific patterns of DP I and 2 and CK18 gene expression, protein content and biodistribution. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. Univ Alabama, Med Sci Training Program, Birmingham, AL 35294 USA. RP Garver, RI (reprint author), Univ Alabama, Dept Med, 701 S 19th St,LHRB 339, Birmingham, AL 35294 USA. OI Winokur, Thomas/0000-0002-6785-2991 NR 29 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAY PY 2002 VL 36 IS 2 BP 133 EP 141 AR PII S0169-5002(01)00486-X DI 10.1016/S0169-5002(01)00486-X PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 560QL UT WOS:000176092700003 PM 11955647 ER PT J AU Johri, M Paltiel, AD Goldie, SJ Freedberg, KA AF Johri, M Paltiel, AD Goldie, SJ Freedberg, KA TI State AIDS drug assistance programs - Equity and efficiency in an era of rapidly changing treatment standards SO MEDICAL CARE LA English DT Article DE acquired immunodeficiency syndrome; economics; cost-benefit analysis; antiviral agents; health services accessibility ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; CD4 CELL COUNTS; COST-EFFECTIVENESS; UNITED-STATES; SERVICES UTILIZATION; CUBIC MILLIMETER; PLUS INDINAVIR; ADULTS AB BACKGROUND. The 54 state AIDS Drug Assistance Programs (ADAP) provide medications to HIV-infected persons with limited resources. Eligibility and coverage vary, raising concerns about health inequities. OBJECTIVE. To compare the relative clinical and economic performance of ADAP programs. RESEARCH DESIGN. A state-transition simulation model of HIV disease was used to explore the clinical consequences and lifetime costs associated with selected state policies. Clinical data came from the Multicenter AIDS Cohort Study, AIDS Clinical Trials Group Protocol 320, and other published randomized trials. Cost data came from the national AIDS Cost and Services Utilization Survey, and the 1999 Red Book. ADAP data came from National Association of State and Territorial AIDS Directors reports and interviews. MEASURES. Projected life expectancy, quality-adjusted life expectancy, total lifetime direct medical costs, cost-effectiveness in dollars per quality-adjusted life year (QALY) gained. RESULTS. ADAPs vary considerably in terms of formulary policies, health outcomes, expected costs, and cost-efficiency. Conservative projections, based on a cohort with starting mean CD4 count of 250 cells/muL, yield life expectancies ranging from 5.36 to 6.81 life years (4.69-6.01 quality-adjusted life years [QALYs]). Total per person lifetime direct medical costs range from $81,200 to $112,700, higher costs reflect increased spending on medications. Expected costs per QALY gained range from $7000 to $28,000. Under pessimistic assumptions regarding initial CD4 counts, drug efficacy, and discounting, the most comprehensive policy remains below $33,000/QALY. CONCLUSIONS. Even the most comprehensive ADAPs constitute a cost-effective use of HIV care resources. A uniform, national ADAP formulary warrants consideration. C1 Univ Montreal, Fac Med, Dept Hlth Adm, Montreal, PQ H3C 3J7, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Clin Epidemiol & Community Studies, Montreal, PQ H3T 1E2, Canada. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Johri, M (reprint author), Univ Montreal, Fac Med, Dept Hlth Adm, CP 6128,Succ Ctr Ville, Montreal, PQ H3C 3J7, Canada. OI Johri, Mira/0000-0001-5642-787X FU NIAID NIH HHS [R01 AI042006, 1P30AI4285101A2, P30 AI042851, R01-AI42006, U01 AI38838]; NIDA NIH HHS [DA 09531]; NIMH NIH HHS [MH56826, P01 MH056826]; ODCDC CDC HHS [U64/CCU 114927] NR 54 TC 19 Z9 19 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2002 VL 40 IS 5 BP 429 EP 441 DI 10.1097/00005650-200205000-00008 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 548EJ UT WOS:000175375400008 PM 11961477 ER PT J AU Roman, GC AF Roman, GC TI Vascular dementia revisited: Diagnosis, pathogenesis, treatment, and prevention SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID AUTOSOMAL-DOMINANT ARTERIOPATHY; FRONTAL-SUBCORTICAL CIRCUITS; POSITRON EMISSION TOMOGRAPHY; FAMILIAL BRITISH DEMENTIA; CONGESTIVE-HEART-FAILURE; BASE-LINE FREQUENCY; CEREBRAL BLOOD-FLOW; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; DOUBLE-BLIND AB Vascular dementia is an etiologic category that includes clinical forms of dementia caused by ischemic or hemorrhagic cerebrovascular disease, or by ischemic-hypoxic brain lesions of cardiovascular origin. This article describes recent developments in the research on vascular dementia: the recognition of the adjuvant role of vascular factors in Alzheimer's, the recent identification of genetic forms of vascular dementia, progress in the understanding of pathogenetic mechanisms, and new possibilities of early diagnosis, treatment, and prevention. C1 Univ Texas, Hlth Sci Ctr, Dept Med Neurol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Neurol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 153 TC 88 Z9 104 U1 2 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2002 VL 86 IS 3 BP 477 EP + AR PII S0025-7125(02)00008-1 DI 10.1016/S0025-7125(02)00008-1 PG 24 WC Medicine, General & Internal SC General & Internal Medicine GA 578TN UT WOS:000177136100003 PM 12168556 ER PT J AU Tsuang, DW Bird, TD AF Tsuang, DW Bird, TD TI Genetics of dementia SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID FAMILIAL ALZHEIMERS-DISEASE; PRION PROTEIN GENE; TRINUCLEOTIDE REPEAT EXPANSION; GERSTMANN-STRAUSSLER-SCHEINKER; FRONTAL-LOBE DEGENERATION; AMYLOID PRECURSOR PROTEIN; LEWY BODIES DLB; APOLIPOPROTEIN-E; FRONTOTEMPORAL DEMENTIA; HUNTINGTONS-DISEASE AB The past decade has seen a tremendous explosion of new information on the genetics of a variety of dementing disorders. This article focuses on seven of the most prominent examples of dementing disorders for which genes have been identified. The clinical, epidemiologic, and molecular genetic findings of these disorders are summarized. The goal is to bring together a succinct description of the latest genetic findings in these important disorders so that practitioners can more effectively diagnose and manage these conditions in their patients. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Clin & Educ Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Alzheimers Dis Res Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med Genet, Seattle, WA 98195 USA. RP Tsuang, DW (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Clin & Educ Ctr, 116MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 NR 112 TC 13 Z9 14 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2002 VL 86 IS 3 BP 591 EP + AR PII S0025-7125(02)00003-2 DI 10.1016/S0025-7125(02)00003-2 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA 578TN UT WOS:000177136100009 PM 12171060 ER PT J AU Bonner, LT Peskind, ER AF Bonner, LT Peskind, ER TI Pharmacologic treatments of dementia SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; PLACEBO-CONTROLLED TRIAL; LEWY BODY DEMENTIA; SEVERE ALZHEIMERS-DISEASE; DOUBLE-BLIND; SENILE DEMENTIA; ALPHA-TOCOPHEROL; ACETYLCHOLINESTERASE INHIBITION; SELECTIVE-INHIBITION; VASCULAR DEMENTIA AB Alzheimer's disease and other forms of dementia affect millions worldwide. Is it estimated that Alzheimer's, the most common cause of dementia, accounts for nearly 70% of dementias. Dementia with Lewy Bodies and Vascular/Multi-Infarct Dementia are probably the second and third most common forms of dementia. This article discusses current pharmacologic treatment options for dementia diseases, as well as effective nonpharmacologic approaches to treatment. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Bonner, LT (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136, AG18644] NR 80 TC 40 Z9 43 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2002 VL 86 IS 3 BP 657 EP + AR PII S0025-7125(02)00007-X DI 10.1016/S0025-7125(02)00007-X PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 578TN UT WOS:000177136100013 PM 12171061 ER PT J AU Thieke, C Nill, S Oelfke, U Bortfeld, T AF Thieke, C Nill, S Oelfke, U Bortfeld, T TI Acceleration of intensity-modulated radiotherapy dose calculation by importance sampling of the calculation matrices SO MEDICAL PHYSICS LA English DT Article DE dose calculation; inverse planning; pencil beam; random sampling; IMRT ID TREATMENT PLANS AB In inverse planning for intensity-modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look-up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low-dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well-known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan. (C) 2002 American Association of Physicists in Medicine. C1 Deutsch Krebsforschungszentrum, Dept Med Phys, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thieke, C (reprint author), Deutsch Krebsforschungszentrum, Dept Med Phys, D-69120 Heidelberg, Germany. NR 10 TC 14 Z9 16 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2002 VL 29 IS 5 BP 676 EP 681 DI 10.1118/1.1469633 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 553KU UT WOS:000175675000004 PM 12033562 ER PT J AU Ntziachristos, V Weissleder, R AF Ntziachristos, V Weissleder, R TI Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media SO MEDICAL PHYSICS LA English DT Article DE fluorescence; imaging; tomography; fluorescent probes; contrast agents ID RESOLVED OPTICAL TOMOGRAPHY; IMAGE-RECONSTRUCTION; CONTRAST AGENTS; TUMORS; SPECTROSCOPY; LIFETIME; BREAST; LIGHT AB We present a novel tomographer for three-dimensional reconstructions of fluorochromes in diffuse media. Photon detection is based on charge-coupled device technology that allows the implementation of a large parallel array of detection channels with high sensitivity. Using this instrument we studied the response and detection limits of near-infrared fluorochromes in diffuse media as a function of light intensity and for a wide range of biologically relevant concentrations. We further examined the resolution of the scanner and the reconstruction linearity achieved. We demonstrate that the instrument attains better than 3 mm resolution, is linear within more than two orders of magnitude of fluorochrome concentration, and can detect fluorescent objects at femto-mole quantities in small animal-like geometries. These measurements delineate detection and reconstruction characteristics associated with imaging of novel classes of fluorescent probes developed for in vivo molecular and functional probing of tissues. (C) 2002 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 30 TC 119 Z9 125 U1 1 U2 10 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2002 VL 29 IS 5 BP 803 EP 809 DI 10.1118/1.1470209 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 553KU UT WOS:000175675000018 PM 12033576 ER PT J AU Hunt, SC Richardson, RD Engel, CC AF Hunt, SC Richardson, RD Engel, CC TI Clinical management of Gulf War veterans with medically unexplained physical symptoms SO MILITARY MEDICINE LA English DT Article ID ILLNESS; PATIENT; CARE; ATTRIBUTIONS; PREVALENCE; POPULATION; HEALTH; PAIN AB Veterans of the Persian Gulf War have increased rates of medically unexplained physical symptoms (MUPS). This article describes a model for the clinical management of MUPS in Gulf War veterans. Predisposing, precipitating, and perpetuating factors contribute to the emergence and clinical course of MUPS. Predisposing factors include biologically and psychosocially determined vulnerabilities that render individuals more susceptible to MUPS and related morbidity. Precipitating factors promote the onset of MUPS. These factors are triggering events that serve to initiate episodes of MUPS. Perpetuating factors sustain illness. They maintain, exacerbate, or prolong MUPS and associated distress and disability. Intervention involves identifying and addressing all relevant predisposing, precipitating, and perpetuating factors. A representative patient vignette is presented to illustrate the clinical utility of the model for a Gulf War veteran with MUPS. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA. RP Hunt, SC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. NR 32 TC 8 Z9 8 U1 2 U2 2 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAY PY 2002 VL 167 IS 5 BP 414 EP 420 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 653DU UT WOS:000181420600010 PM 12053851 ER PT J AU Nasseri, BA Vacanti, JP AF Nasseri, BA Vacanti, JP TI Cell transplantation for heart failure, and tissue engineering of cardiovascular structures SO MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES LA English DT Article DE cell transplantation; stem cells; tissue engineering; heart failure; myogenic progenitor cells ID EMBRYONIC STEM-CELLS; GROWN IN-VITRO; MYOBLAST TRANSPLANTATION; HUMAN BLASTOCYSTS; BLOOD-VESSEL; CARDIOMYOCYTES; VALVES; DIFFERENTIATION; MYOCARDIUM; REGENERATION AB The emergence of selective cell transplantation and tissue engineering has opened up new alternatives for the treatment of heart failure. These involve the use of stem and progenitor cells, as well as new biodegradable polymer scaffolds. The last two decades have seen a dramatic increase in our knowledge of how to fabricate a wide array of tissues, including cardiovascular structures. This article reviews current trends in selective cell transplantation and tissue engineering, and summarises recent achievements and remaining questions in constructing functional cardiac tissue. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 32 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1364-5706 J9 MINIM INVASIV THER JI Minim. Invasive Ther. Allied Technol. PD MAY 1 PY 2002 VL 11 IS 3 BP 117 EP 121 DI 10.1080/136457002320174186 PG 5 WC Surgery SC Surgery GA 577JW UT WOS:000177058600007 ER PT J AU Adsay, NV Hasteh, F Cheng, JD Bejarano, PA Lauwers, GY Batts, KP Kloppel, G Klimstra, DS AF Adsay, NV Hasteh, F Cheng, JD Bejarano, PA Lauwers, GY Batts, KP Kloppel, G Klimstra, DS TI Lymphoepithelial cysts of the pancreas: a report of 12 cases and a review of the literature SO MODERN PATHOLOGY LA English DT Article DE cysts; lymphoepithelial; pancreas ID FINE-NEEDLE ASPIRATION; INTRAPANCREATIC ACCESSORY SPLEEN; ONCOCYTIC PAPILLARY NEOPLASMS; DERMOID CYST; EPIDERMOID CYST; DIFFERENTIAL-DIAGNOSIS; MUCINOUS CYSTADENOCARCINOMA; SEBACEOUS DIFFERENTIATION; FLUID ANALYSIS; CT AB Lymphoepithelial cyst (LEC) of the pancreas is a rare lesion of undetermined pathogenesis that had been documented almost exclusively in males. The literature on this entity is limited to reports of single or small numbers of cases. Here is presented a clinicopathologic analysis of 12 patients with LEC, 4 of whom were female. The mean age of the patients was 56 years. Four patients presented with abdominal pain and nausea, but in two patients, the cysts were detected incidentally. Only one patient had a history of chronic pancreatitis, and another had a family member with pancreatic, cancer. In one patient, a clinical diagnosis of pseudocyst was rendered, and the remaining patients were clinically thought to have cystic neoplasms. None of the patients had any identifiable immunosuppression, HIV positivity, autoimmune disorder (such as Siogren syndrome) or lymphoma. Seven cysts were located in the head of the pancreas, and 5 were in the tail. The mean size was 4.8 cm (range, 1.2-17 cm). Five LECs were multilocular, three were unflocular; in others, the number of locull was not recorded. All were "macrocystic" lesions. Two patients had two separate lesions, both in the tail of the pancreas. Histologically, all cases were characterized by cysts, some containing keratin, and lined by mature stratified squamous epithelium surrounded by dense lymphoid tissue, often with prominent follicles. In some areas, the lining epithelium had more cuboidal, flattened, or transitional appearance. Mucinous goblet-like cells were seen in one case. Acute inflammation was not seen. Four cases contained solid lymphoepithelial islands, a feature not previously described in LECs. No squamous metaplasia was identified in the uninvolved pancreatic tissue and no epithelial elements were identified in peripancreatic lymph nodes. In summary, LEC of the pancreas is a rare but distinctive lesion that may be seen in the tail of the organ where most cystic pancreatic neoplasms are encountered. In contrast to the impression from the literature, LECs may also develop in females and, therefore, should be considered in the clinical differential diagnosis of mucinous cystic neoplasms that affect a similar age group. LECs are not associated with the clinical syndromes that are seen with their analogues in the salivary glands. C1 Karmanos Canc Inst, Dept Pathol, Detroit, MI USA. Wayne State Univ, Sch Med, Detroit, MI USA. Providence Hosp, Dept Pathol, Detroit, MI USA. Miami Univ, Dept Pathol, Miami, FL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mayo Clin, Dept Pathol, Rochester, MN USA. Univ Kiel, Dept Pathol, D-2300 Kiel, Germany. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Adsay, NV (reprint author), Harper Grace Hosp, Dept Pathol, 3990 John R St, Detroit, MI 48201 USA. NR 98 TC 66 Z9 68 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2002 VL 15 IS 5 BP 492 EP 501 DI 10.1038/modpathol.3880553 PG 10 WC Pathology SC Pathology GA 553FN UT WOS:000175665300003 PM 12011254 ER PT J AU Yang, H Williams, BO Hinds, PW Shih, TS Jacks, T Bronson, RT Livingston, DM AF Yang, H Williams, BO Hinds, PW Shih, TS Jacks, T Bronson, RT Livingston, DM TI Tumor suppression by a severely truncated species of retinoblastoma protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID UBIQUITIN-PROTEASOME PATHWAY; CELL-CYCLE ARREST; GENE-PRODUCT; GROWTH SUPPRESSION; FUNCTIONAL INTERACTIONS; REPRESS TRANSCRIPTION; HISTONE DEACETYLASE; FAMILY PROTEINS; CHIMERIC MICE; RB PROTEIN AB Rb+/+:Rb-/- chimeric mice are healthy until early in adulthood when they develop lethal pituitary tumors composed solely of Rb-/- cells. In an effort to delineate the minimal structures of the retinoblastoma protein necessary for RB tumor suppression function, chimeric animals derived from stably transfected RB-/- embryonic stem (ES) cells were generated. One such ES cell transfectant expressed a human RB allele encoding a stable, truncated nuclear derivative lacking residues 1 to 378 (Delta1-378). Others encoded either wild-type human RB or an internally deleted derivative of the Delta1-378 mutant. All gave rise to viable chimeric animals with comparable degrees of chimerism. However, unlike control mice derived, in part, from naive Rb-/- ES cells or from ES cells transformed by the double RB mutant, Delta1-378/Deltaexon22, animals derived from either wild-type RB- or Delta1-378 RB-producing ES cells failed to develop pituitary tumors. Thus, in this setting, a substantial fraction of the RB sequence is unnecessary for RB-mediated tumor suppression. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Williams, Bart/A-3539-2013 OI Williams, Bart/0000-0002-5261-5301 NR 54 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 9 BP 3103 EP 3110 DI 10.1128/MCB.9.3103-3110.2002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541EQ UT WOS:000174972600021 PM 11940667 ER PT J AU Katz, SG Cantor, AB Orkin, SH AF Katz, SG Cantor, AB Orkin, SH TI Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; CELLULAR PHOSPHOPROTEIN; NEGATIVE MODULATION; HEMATOPOIETIC-CELLS; E1A PROTEIN; CTBP; COFACTOR; REPRESSION; DOMAIN AB The hematopoietic, zinc-finger protein FOG-1 is essential for the development of the erythroid and megakaryocytic lineages. FOG-1's function in hematopoiesis is dependent on its ability to interact with the transcription factor GATA-1. FOG-1 has also been observed to interact with the corepressor molecule C-terminal binding protein (CtBP) through a peptide motif shared by all FOG family members. In this study, we confirmed that FOG-1 and CtBP interact by coimmunoprecipitation. We further demonstrate that a FOG-1 mutant unable to interact with CtBP has increased erythropoietic (but not megakaryocytic) rescue (relative to the wild type) of a FOG-1(-/-) cell line. To analyze further the physiological role of the FOG-1-CtBP interaction, we generated knock-in mice that express a FOG-1 variant unable to bind CtBP. Surprisingly, these mice are normal and fertile. Furthermore, erythropoiesis at all stages of development is normal in these mice. Erythrocyte production is similar in mutant and wild-type mice even under conditions of erythropoietic stress stimulated by either exogenously added erythropoietin or phenylhydrazine-induced anemia. Thus, despite conservation of the FOG-CtBP interaction site, the in vivo function of FOG-1 in erythroid development is not affected by its inability to interact with the corepressor CtBP. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Med Ctr, Div Hematol, 320 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [5K08CA82175] NR 37 TC 52 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 9 BP 3121 EP 3128 DI 10.1128/MCB.22.9.3121-3128.2002 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 541EQ UT WOS:000174972600023 PM 11940669 ER PT J AU Yoshida, K Komatsu, K Wang, HG Kufe, D AF Yoshida, K Komatsu, K Wang, HG Kufe, D TI c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SCHIZOSACCHAROMYCES-POMBE RAD1(+); APOPTOTIC RESPONSE; FISSION YEAST; HUMAN HOMOLOG; FUNCTIONAL INTERACTION; IONIZING-RADIATION; CELLULAR-RESPONSE; DEATH AGONIST; CONTROL GENE; BH3 DOMAIN AB The ubiquitously expressed c-Abl tyrosine kinase is activated in the apoptotic response of cells to DNA damage. The mechanisms by which c-Abl signals the induction of apoptosis are not understood. Here we show that c-Abl binds constitutively to the mammalian homolog of the Schizosaccharomyces pombe Rad9 cell cycle checkpoint protein. The SH3 domain of c-Abl interacts directly with the C-terminal region of Rad9. c-Abl phosphorylates the Rad9 Bcl-2 homology 3 domain (Tyr-28) in vitro and in cells exposed to DNA-damaging agents. The results also demonstrate that c-Abl-mediated phosphorylation of Rad9 induces binding of Rad9 to the antipototic Bcl-x(L) protein. The regulation of Rad9 by c-Abl in the DNA damage response is further supported by the demonstration that the interaction between c-Abl and Rad9 contributes to DNA damage-induced apoptosis. These findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Wang, Hong-Gang/A-3018-2015 FU NCI NIH HHS [CA29431, CA55241] NR 60 TC 59 Z9 64 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3292 EP 3300 DI 10.1128/MCB.22.10.3292-3300.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900009 PM 11971963 ER PT J AU Shao, WL Halachmi, S Brown, M AF Shao, WL Halachmi, S Brown, M TI ERAP140, a conserved tissue-specific nuclear receptor coactivator SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATION FUNCTION AF-2; RNA-POLYMERASE-II; ESTROGEN-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; HISTONE ACETYLTRANSFERASE; GLUCOCORTICOID RECEPTOR; PROTEIN; COMPLEX; BINDING; SRC-1 AB We report here the identification and characterization of a novel nuclear receptor coactivator, ERAP140. ERAP140 was isolated in a screen for ERalpha-interacting proteins using the ERalpha ligand binding domain as a probe. The ERAP140 protein shares no sequence and has little structural homology with other nuclear receptor cofactors. However, homologues of ERAP140 have been identified in mouse, Drosophila, and Caenorhabditis elegans. The expression of ERAP140 is cell and tissue type specific and is most abundant in the brain, where its expression is restricted to neurons. In addition to interacting with ERalpha, ERAP140 also binds ERbeta, TRbeta, PRARgamma, and RARalpha. ERAP140 interacts with ERalpha via a noncanonical interaction motif. The ERalpha-ERAP140 association can be competed by coactivator NR boxes, indicating ERAP140 binds ERalpha on a surface similar to that of other coactivators. ERAP140 can enhance the transcriptional activities of nuclear receptors with which it interacts. In vivo, ERAP140 is recruited by estrogen-bound ERalpha to the promoter region of endogenous ERalpha target genes. Furthermore, the E-2-induced recruitment of ERAP140 to the promoter follows a cyclic pattern similar to that of other coactivators. Our results suggest that ERAP140 represents a distinct class of nuclear receptor coactivators that mediates receptor signaling in specific target tissues. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [R01-CA57374] NR 52 TC 55 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3358 EP 3372 DI 10.1128/MCB.22.10.3358-3372.2002 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900015 PM 11971969 ER PT J AU Hahn, WC Dessain, SK Brooks, MW King, JE Elenbaas, B Sabatini, DM DeCaprio, JA Weinberg, RA AF Hahn, WC Dessain, SK Brooks, MW King, JE Elenbaas, B Sabatini, DM DeCaprio, JA Weinberg, RA TI Enumeration of the simian virus 40 early region elements necessary for human cell transformation (vol 22, pg 2111, 2002) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Hahn, WC (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. NR 1 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2002 VL 22 IS 10 BP 3562 EP 3562 DI 10.1128/MCB.22.10.3562.2002 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 547GD UT WOS:000175323900032 ER PT J AU Hideshima, T Chauhan, D Hayashi, T Podar, K Akiyama, M Gupta, D Richardson, P Munshi, N Anderson, KC AF Hideshima, T Chauhan, D Hayashi, T Podar, K Akiyama, M Gupta, D Richardson, P Munshi, N Anderson, KC TI The biological sequelae of stromal cell-derived factor-1 alpha in multiple myeloma SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NF-KAPPA-B; HEMATOPOIETIC PROGENITOR CELLS; ENDOTHELIAL GROWTH-FACTOR; FOCAL ADHESION PROTEINS; CHEMOKINE SDF-1; DRUG-RESISTANCE; TYROSINE PHOSPHORYLATION; FACTOR-I; APOPTOSIS; INTERLEUKIN-6 AB Stromal cell-derived factor (SDF)-1alpha mediates migration of normal hematopoietic stem cells, but its role in hematological malignancies is undefined. In this study, we detected SDF-1alpha in bone marrow (BM) plasma from 10 patients with MM (multiple myeloma; 2.6 +/- 1.5 ng/ml) and BM stromal cell culture supernatants from 5 patients with MM (0.6 +/- 0.2 ng/ml). We show that SDF-1alpha promotes proliferation, induces migration, and protects against dexamethasone-induced apoptosis in MM cells, but these effects are only modest. In MM cell lines and patient MM cells, SDF-1alpha induces phosphorylation of p42/44 mitogen-activated protein kinase, as well as Akt and its downstream target Bad, and also activates nuclear factor-kappaB. In the BM milieu, SDF-1alpha upregulates secretion of interleukin 6 and vascular endothelial growth factor in BM stromal cells, which promote tumor cell growth, survival, and migration. These data demonstrate that SDF-1alpha promotes growth, migration and drug resistance of MM cells in the BM microenvironment, but these effects are only modest, SDF-1alpha therefore does not represent a target for novel therapeutics in this disease. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378] NR 37 TC 114 Z9 117 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2002 VL 1 IS 7 BP 539 EP 544 PG 6 WC Oncology SC Oncology GA 607BK UT WOS:000178770400011 PM 12479272 ER PT J AU Hussein, MR Sun, M Roggero, E Sudilovsky, EC Tuthill, RJ Wood, GS Sudilovsky, O AF Hussein, MR Sun, M Roggero, E Sudilovsky, EC Tuthill, RJ Wood, GS Sudilovsky, O TI Loss of heterozygosity, microsatellite instability, and mismatch repair protein alterations in the radial growth phase of cutaneous malignant melanomas SO MOLECULAR CARCINOGENESIS LA English DT Article DE tumor suppressor genes; polymerase chain reaction; microsatellite stable ID COLORECTAL-CANCER; ENDOMETRIAL CARCINOMAS; GENETIC ALTERATIONS; ALTERED EXPRESSION; TUMOR PROGRESSION; HMLH1 EXPRESSION; DYSPLASTIC NEVI; ALLELIC LOSSES; DNA; HMSH2 AB Little is known about genomic alterations during development of the radial growth phase (RGP) of cutaneous malignant melanomas (CMMs). In this investigation polymerase chain reaction-based microsatellite assays were applied to analyze 13 RGP-CMMs with 18 microsatellite markers at SIX chromosomal regions: 1p, 3p, 4q, 6q, 9p, and 10q. Loss of heterozygosity (LOH) was found in eight cases (62%), at 9p22, 1p36, and 10q11, suggesting the presence of tumor-suppressor genes at these regions. LOH was encountered frequently at the interferon-alpha (31%) and D10S249 loci (15%). Low-level microsatellite instability (MSI) (11 - 16% of investigated loci unstable) was noted in three cases (23%). Two MSI banding patterns were seen: band shift and the presence of additional bands. To investigate the underlying mechanisms of the low-level MSI pattern, we analyzed the lesions for expression of mismatch repair (MMR) proteins with immunoperoxidase methods and mouse monoclonal antibodies. The average percentages of positively stained cells for human MutL homolog 1 (hMLHI), human MutS homolog 2 (hMSH2), and human MutS homolog 6 (hMSH6) in RGP-CMM (75.6 +/- 3.4%, 67.20 +/- 7.71%, and 76.6 +/- 2.1%, respectively) were reduced compared with benign nevi. No statistically significant differences in MMR protein expression were found between microsatellite-stable and low-level MSI lesions (P=0.173, P=0.458, and P=0.385 for hMLH1, hMSH2, and hMSH6, respectively). There was a direct correlation between values for percentages of positively stained cells for hMSH2 and hMSH6 (r= +0.9, P=0.03), suggesting that common mechanisms regulate their expression. In conclusion, LOH, MSI, and reduced MMR protein expression appear to be present in at least some RGP-CMMs and may play a role in their pathogenesis. Further studies are necessary to support these finding and to determine their diagnostic and prognostic significance. (C) 2002 Wiley-Liss, Inc. C1 Univ Wisconsin, Dept Med Dermatol, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53715 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Inst Histopatol, Rosario, Santa Fe, Argentina. Cleveland Clin Fdn, Dept Anatom Pathol, Cleveland, OH 44195 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Med Dermatol, 1 S Pk,7th Floor, Madison, WI 53715 USA. FU NIAMS NIH HHS [AR02136] NR 58 TC 38 Z9 39 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 2002 VL 34 IS 1 BP 35 EP 44 DI 10.1002/mc.10047 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 549LZ UT WOS:000175446600005 PM 12112321 ER PT J AU Wang, JH Reinherz, EL AF Wang, JH Reinherz, EL TI Structural basis of T cell recognition of peptides bound to MHC molecules SO MOLECULAR IMMUNOLOGY LA English DT Review DE T cell receptor; alloreactivity; MHC class II; structure; thymic selection ID ANTIGEN RECEPTOR TCR; CRYSTAL-STRUCTURE; CLASS-I; POSITIVE SELECTION; HUMAN CD4; THYMIC SELECTION; ECTODOMAIN FRAGMENT; FUNCTIONAL-ANALYSIS; TCR/CD3 COMPLEX; SELF-PEPTIDE AB Helper T lymphocytes play a critical role in immune system activation following recognition of MHC class II-bound peptide ligands (pMHCII). These CD4 T cells stimulate B cell antibody production and cytolytic T cell generation. Until recently. the structural basis of coordinate T cell receptor (TCR) and CD4 co-receptor interaction with a given was unknown. Here we review current structural data on specific pMHCII recognition by T cells and compare TCR and co-receptor docking to pMHCI versus pMHCII ligands. The implications of these findings for thymic selection. helper versus cytoltic T cell recognition and alloreactivity are discussed. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Wang, JH (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI19807]; NIGMS NIH HHS [GM56008] NR 70 TC 63 Z9 72 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 2002 VL 38 IS 14 SI SI BP 1039 EP 1049 AR PII S0161-5890(02)00033-0 DI 10.1016/S0161-5890(02)00033-0 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 558VC UT WOS:000175986600005 PM 11955596 ER PT J AU Sehnert, AJ Huq, A Weinstein, BM Walker, C Fishman, M Stainier, DYR AF Sehnert, AJ Huq, A Weinstein, BM Walker, C Fishman, M Stainier, DYR TI Cardiac troponin T is essential in sarcomere assembly and cardiac contractility SO NATURE GENETICS LA English DT Article ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; SUDDEN-DEATH; CARDIOVASCULAR-SYSTEM; MUTATIONS; ZEBRAFISH; TROPOMYOSIN; DISEASE; CHAIN; GENES AB Mutations of the gene (TNNT2) encoding the thin-filament contractile protein cardiac troponin T are responsible for 15% of all cases of familial hypertrophic cardiomyopathy, the leading cause of sudden death in young athletes(1,2). Mutant proteins are thought to act through a dominant-negative mode that impairs function of heart muscle(3). TNNT2 mutations can also lead to dilated cardiomyopathy, a leading cause of heart failure(4). Despite the importance of cardiac troponin T in human disease, its loss-of-function phenotype has not been described. We show that the zebrafish silent heart (sih) mutation affects the gene tnnt2. We characterize two mutated alleles of sih that severely reduce tnnt2 expression: one affects mRNA splicing, and the other affects gene transcription. Tnnt2, together with alpha-tropomyosin (Tpma) and cardiac troponins C and I (Tnni3), forms a calcium-sensitive regulatory complex within sarcomeres(5). Unexpectedly, in addition to loss of Tnnt2 expression in sih mutant hearts, we observed a significant reduction in Tpma and Tnni3, and consequently, severe sarcomere defects. This interdependence of thin-filament protein expression led us to postulate that some mutations in tnnt2 may trigger misregulation of thin-filament protein expression, resulting in sarcomere loss and myocyte disarray, the life-threatening hallmarks of TNNT2 mutations in mice and humans(6,7). C1 Univ Calif San Francisco, Dept Biochem & Biophys, Program Dev Biol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, Genet Program, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, Program Human Genet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Stainier, DYR (reprint author), Univ Calif San Francisco, Dept Biochem & Biophys, Program Dev Biol, 513 Parnassus Ave,Box 0448, San Francisco, CA 94143 USA. NR 25 TC 307 Z9 314 U1 0 U2 25 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 MAY PY 2002 VL 31 IS 1 BP 106 EP 110 DI 10.1038/ng875 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 547ZF UT WOS:000175362500024 PM 11967535 ER PT J AU Kulkarni, RN Holzenberger, M Shih, DQ Ozcan, U Stoffel, M Magnuson, MA Kahn, CR AF Kulkarni, RN Holzenberger, M Shih, DQ Ozcan, U Stoffel, M Magnuson, MA Kahn, CR TI beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass SO NATURE GENETICS LA English DT Article ID GROWTH-FACTOR-I; INSULIN-RECEPTOR; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; MICE CAUSES; DIFFERENTIATION; TRANSCRIPTION; SECRETION; PANCREAS; REPLICATION AB Regulation of glucose homeostasis by insulin depends on the maintenance of normal beta-cell mass and function. Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function(1,2), but the factors controlling this process are poorly understood. Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on beta-cells(3-6). Igf1 has been shown to influence beta-cell apoptosis(7), and both Igf1 and Igf2 increase islet growth(8,9); Igf2 does so in a manner additive with fibroblast growth factor 2 (ref. 10). When mice deficient for the Igf1 receptor (Igf1r(+/-)) are bred with mice lacking insulin receptor substrate 2 (Irs2(-/-)), the resulting compound knockout mice show a reduction in mass of beta-cells(11) similar to that observed in pancreas of Igf1r(-/-) mice (ref. 11), suggesting a role for Igf1r in growth of beta-cells. It is possible, however, that the effects in these mice occur secondary to changes in vascular endothelium(12) or in the pancreatic ductal cells, or because of a decrease in the effects of other hormones implicated in islet growth. To directly define the role of Igf1, we have created a mouse with a beta-cell-specific knockout of Igf1r (Igf1r(-/-)). These mice show normal growth and development of beta-cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in beta-cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance. Thus, Igf1r is not crucial for islet beta-cell development, but participates in control of differentiated function. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. Hop St Antoine, INSERM, U515, F-75571 Paris, France. Rockefeller Univ, Lab Metab Dis, New York, NY 10021 USA. Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. RI Magnuson, Mark/B-1335-2009 OI Magnuson, Mark/0000-0002-8824-6499 NR 29 TC 242 Z9 250 U1 2 U2 5 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 MAY PY 2002 VL 31 IS 1 BP 111 EP 115 DI 10.1038/ng872 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 547ZF UT WOS:000175362500025 PM 11923875 ER PT J AU Inlay, M Alt, FW Baltimore, D Xu, Y AF Inlay, M Alt, FW Baltimore, D Xu, Y TI Essential roles of the kappa light chain intronic enhancer and 3 ' enhancer in kappa rearrangement and demethylation SO NATURE IMMUNOLOGY LA English DT Article ID CELL-SPECIFIC DEMETHYLATION; MARROW B-CELLS; IG-KAPPA; GENE REARRANGEMENT; REGION; LOCUS; LYMPHOCYTES; REPERTOIRE; DOWNSTREAM; TOLERANCE AB The kappa intronic (MiE(kappa)) and 3' (3'E-kappa) enhancers are both quantitatively important to, but not essential for, immunoglobulin kappa rearrangement. To determine the functional redundancy between these two enhancers, B cells derived from mutant embryonic stem cells-in which both MiE(kappa) and 3'E-kappa were deleted on both kappa alleles-were analyzed for kappa rearrangement. Our findings indicate that these double-mutant B cells have essentially no kappa rearrangement but do rearrange and express lambda. Therefore, these two kappa enhancers share essential roles in activatingV(kappa)J(kappa) rearrangement. Our findings also indicate that the two kappa enhancers play overlapping and distinct roles in the demethylation of kappa in B cells. C1 Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Xu, Y (reprint author), Univ Calif San Diego, Div Biol, Mol Biol Sect, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIAID NIH HHS [AI44838] NR 26 TC 75 Z9 75 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2002 VL 3 IS 5 BP 463 EP 468 DI 10.1038/ni790 PG 6 WC Immunology SC Immunology GA 548VU UT WOS:000175411200015 PM 11967540 ER PT J AU Aifantis, I Borowski, C Gounari, F Lacorazza, HD Nikolich-Zugich, J von Boehmer, H AF Aifantis, I Borowski, C Gounari, F Lacorazza, HD Nikolich-Zugich, J von Boehmer, H TI A critical role for the cytoplasmic tail of pT alpha in T lymphocyte development SO NATURE IMMUNOLOGY LA English DT Article ID BETA GENE-EXPRESSION; CELL-RECEPTOR; PRE-TCR; ACTIVATION; DOMAIN; COSTIMULATION; CD2; LCK AB Signals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the alphabeta T cell lineage. In contrast to the gammadelta TCR, the pre-TCR localizes cellautonomously to membrane rafts, where it appears to signal in a constitutive and ligand-independent manner.We addressed here the role played by structural features specific to the cytoplasmic domain of the pre-TCRalpha chain (pTalpha). More specifically, we examined a COON-terminal proline-rich sequence that might play a role in signal transduction and a juxtamembrane cysteine residue that could be a target for palmitoylation, thus allowing spontaneous raft localization. Expression of pTalpha mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pTalpha cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pTalpha juxtamembrane cysteine appeared to be dispensable for pre-TCR function. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Lab Mol Aspects Hematopoiesis, New York, NY 10021 USA. Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. OI Nikolich-Zugich, Janko/0000-0001-5830-5323 FU NIAID NIH HHS [AI45846, AI47281] NR 27 TC 65 Z9 65 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2002 VL 3 IS 5 BP 483 EP 488 DI 10.1038/ni779 PG 6 WC Immunology SC Immunology GA 548VU UT WOS:000175411200018 PM 11927911 ER PT J AU Gounari, F Aifantis, I Martin, C Fehling, HJ Hoeflinger, S Leder, P von Boehmer, H Reizis, B AF Gounari, F Aifantis, I Martin, C Fehling, HJ Hoeflinger, S Leder, P von Boehmer, H Reizis, B TI Tracing lymphopoiesis with the aid of a pT alpha-controlled reporter gene SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; HEMATOPOIETIC STEM-CELLS; MURINE FETAL THYMUS; B-CELL; BONE-MARROW; LYMPHOID DIFFERENTIATION; COORDINATE REGULATION; LINEAGE COMMITMENT; PRECURSOR CELLS; EXPRESSION AB A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor alpha (pTalpha) promoter, was used to identify lymphoid precursors that expressed pTalpha intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of lymphocytes but not myeloid cells. The earliest intrathymic precursors were CD4(lo)CD8(-)CD25(-)CD44(+)c-Kit(+) cells that expressed elevated levels of Notch-I mRNA. Clonogenic assays showed that the extrathymic precursors were common lymphoid progenitors (CLPs) that included CD19(-), B220(+), ThyI(+) and CD4(+) cells. Thus, the pTalpha reporter can be used to trace lymphopoiesis between CLPs and alphabeta T ceIIs.The slower extinction of the hCD25 reporter compared to pTa enabled us to define points at which pTalpha(-) lineages branched off. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Univ Clin Ulm, Fac Med, Dept Immunol, D-89070 Ulm, Germany. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. OI Reizis, Boris/0000-0003-1140-7853 FU NIAID NIH HHS [R01AI47281, R01AI 45846] NR 42 TC 81 Z9 82 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2002 VL 3 IS 5 BP 489 EP 496 DI 10.1038/ni778 PG 8 WC Immunology SC Immunology GA 548VU UT WOS:000175411200019 PM 11927910 ER PT J AU Gray, ML Bonventre, JV AF Gray, ML Bonventre, JV TI Training PhD researchers to translate science to clinical medicine: Closing the gap from the other side SO NATURE MEDICINE LA English DT Editorial Material ID PHYSICIAN-SCIENTISTS; TECHNOLOGY C1 MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gray, ML (reprint author), MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. NR 9 TC 19 Z9 20 U1 0 U2 3 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 MAY PY 2002 VL 8 IS 5 BP 433 EP 436 DI 10.1038/nm0502-433 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 547ZW UT WOS:000175336800014 PM 11984576 ER PT J AU Wucherpfennig, KW AF Wucherpfennig, KW TI Infectious triggers for inflammatory neurological diseases SO NATURE MEDICINE LA English DT Editorial Material ID I-ASSOCIATED MYELOPATHY; MYELIN BASIC-PROTEIN; T-CELL CLONES; MOLECULAR MIMICRY; VIRUS; AUTOIMMUNITY AB Do autoimmune diseases develop 'spontaneously' or are they induced by environmental triggers, such as infectious agents? This is a central- and challenging-question in the autoimmunity field. A new study in this issue provides strong evidence for a virus-induced autoimmune process in a human neurological disease. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 12 TC 16 Z9 16 U1 0 U2 0 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 MAY PY 2002 VL 8 IS 5 BP 455 EP 457 DI 10.1038/nm0502-455 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 547ZW UT WOS:000175336800023 PM 11984586 ER PT J AU Crone, SA Zhao, YY Fan, L Gu, YS Minamisawa, S Liu, Y Peterson, KL Chen, J Kahn, R Condorelli, G Ross, J Chien, KR Lee, KF AF Crone, SA Zhao, YY Fan, L Gu, YS Minamisawa, S Liu, Y Peterson, KL Chen, J Kahn, R Condorelli, G Ross, J Chien, KR Lee, KF TI ErbB2 is essential in the prevention of dilated cardiomyopathy SO NATURE MEDICINE LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; DEFICIENT MICE; HEART-FAILURE; TRASTUZUMAB HERCEPTIN; CARDIAC DEVELOPMENT; SIGNALING NETWORK; REQUIREMENT; EXPRESSION; RECEPTORS; CANCER AB Amplification of the gene encoding the ErbB2 (Her2/neu) receptor tyrosine kinase is critical for the progression of several forms of breast cancer. In a large-scale clinical trial, treatment with Herceptin (trastuzumab), a humanized blocking antibody against ErbB2, led to marked improvement in survival. However, cardiomyopathy was uncovered as a mitigating side effect, thereby suggesting an important role for ErbB2 signaling as a modifier of human heart failure. To investigate the physiological role of ErbB2 signaling in the adult heart, we generated mice with a ventricular-restricted deletion of Erbb2. These ErbB2-deficient conditional mutant mice were viable and displayed no overt phenotype. However, physiological analysis revealed the onset of multiple independent parameters of dilated cardiomyopathy, including chamber dilation, wall thinning and decreased contractility. Additionally, cardiomyocytes isolated from these conditional mutants were more susceptible to anthracycline toxicity. ErbB2 signaling in cardiomyocytes is therefore essential for the prevention of dilated cardiomyopathy. C1 Salk Inst Biol Studies, La Jolla, CA 92037 USA. Univ Calif San Diego, UCSD Salk Program Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Lee, KF (reprint author), Salk Inst Biol Studies, La Jolla, CA 92037 USA. RI Chen, Ju/E-5579-2011; OI Condorelli, Gianluigi/0000-0003-0481-6843 NR 37 TC 465 Z9 481 U1 3 U2 18 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 MAY PY 2002 VL 8 IS 5 BP 459 EP 465 DI 10.1038/nm0502-459 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 547ZW UT WOS:000175336800030 PM 11984589 ER PT J AU Hafezi-Moghadam, A Simoncini, T Yang, ZQ Limbourg, FP Plumier, JC Rebsamen, MC Hsieh, CM Chui, DS Thomas, KL Prorock, AJ Laubach, VE Moskowitz, MA French, BA Ley, K Liao, JK AF Hafezi-Moghadam, A Simoncini, T Yang, ZQ Limbourg, FP Plumier, JC Rebsamen, MC Hsieh, CM Chui, DS Thomas, KL Prorock, AJ Laubach, VE Moskowitz, MA French, BA Ley, K Liao, JK TI Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase SO NATURE MEDICINE LA English DT Article ID PROTEIN-KINASE-B; GLUCOCORTICOID RECEPTOR; LEUKOCYTE ADHESION; DNA-BINDING; CELLS; AKT; DEFICIENCY; INHIBITION; INDUCTION; HORMONE AB Corticosteroids have been shown to exert beneficial effects in the treatment of acute myocardial infarction, but the precise mechanisms underlying their protective effects are unknown. Here we show that high-dose corticosteroids exert cardiovascular protection through a novel mechanism involving the rapid, non-transcriptional activation of endothelial nitric oxide synthase (eNOS). Binding of corticosteroids to the glucocorticoid receptor (GR) stimulated phosphatidylinositol 3-kinase and protein kinase Akt, leading to eNOS activation and nitric oxide-dependent vasorelaxation. Acute administration of pharmacological concentrations of corticosteroids in mice led to decreased vascular inflammation and reduced myocardial infarct size following ischemia and reperfusion injury. These beneficial effects of corticosteroids were abolished by GR antagonists or eNOS inhibitors in wild-type mice and were completely absent in eNOS-deficient (Nos3(-/-)) mice. The rapid activation of eNOS by the non-nuclear actions of GR, therefore, represents an important cardiovascular protective effect of acute high-dose corticosteroid therapy. C1 Brigham & Womens Hosp, Dept Med, Vasc Med Res Unit, 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. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. Univ Virginia, Dept Surg, Charlottesville, VA USA. Univ Pisa, Dept Reprod Med & Child Dev, Pisa, Italy. RP Liao, JK (reprint author), Brigham & Womens Hosp, Dept Med, Vasc Med Res Unit, 75 Francis St, Boston, MA 02115 USA. RI Moskowitz, Michael/D-9916-2011; Laubach, Victor/E-8818-2015; OI Laubach, Victor/0000-0001-9673-5383; Hafezi-Moghadam, Ali/0000-0002-5336-0697; Simoncini, Tommaso/0000-0002-2971-0079 FU NHLBI NIH HHS [HL58582, F32 HL067574, HL48743, HL54136, HL62602, HL65754, HL70274, P01 HL048743, P01 HL048743-080008, P01 HL048743-090008, P01 HL048743-100008, R01 HL052233, R01 HL052233-05, R01 HL052233-06, R01 HL052233-07, R01 HL058582, R01 HL070274] NR 44 TC 346 Z9 359 U1 3 U2 20 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 MAY PY 2002 VL 8 IS 5 BP 473 EP 479 DI 10.1038/nm0502-473 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 547ZW UT WOS:000175336800032 PM 11984591 ER PT J AU Hahn, WC Weinberg, RA AF Hahn, WC Weinberg, RA TI Modelling the molecular circuitry of cancer SO NATURE REVIEWS CANCER LA English DT Review ID LARGE T-ANTIGEN; MAMMARY EPITHELIAL-CELLS; TUMOR-SUPPRESSOR GENE; EMBRYONIC CELLULAR PROLIFERATION; TRANSFORMED HUMAN-CELLS; REPLICATIVE LIFE-SPAN; TELOMERASE ACTIVITY; HUMAN-FIBROBLASTS; RAS ONCOGENE; PROTEIN PHOSPHATASE-2A AB Cancer arises from a stepwise accumulation of genetic changes that liberates neoplastic cells from the homeostatic mechanisms that govern normal cell proliferation. In humans, at least four to six mutations are required to reach this state, but fewer seem to be required in mice. By rationalizing the shared and unique elements of human and mouse models of cancer, we should be able to identify the molecular circuits that function differently in humans and mice, and use this knowledge to improve existing models of cancer. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Dept Med, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Hahn, WC (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 157 TC 634 Z9 666 U1 2 U2 38 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2002 VL 2 IS 5 BP 331 EP 341 DI 10.1038/nrc795 PG 11 WC Oncology SC Oncology GA 636GQ UT WOS:000180446600011 PM 12044009 ER PT J AU Seelan, RS Irwin, M van der Stoop, P Qian, CP Kaelin, WG Liu, WG AF Seelan, RS Irwin, M van der Stoop, P Qian, CP Kaelin, WG Liu, WG TI The human p73 promoter: Characterization and identification of functional E217 binding sites SO NEOPLASIA LA English DT Article DE p73; E2F1; promoter analysis; gene regulation; cancer ID HUMAN BLADDER-CANCER; KINASE C-ABL; P53-RELATED PROTEIN; APOPTOTIC RESPONSE; INDUCE APOPTOSIS; LUNG-CANCER; CELL-LINES; DNA-DAMAGE; P53; GENE AB p73, a member of the p53 family, is overexpressed in many cancers. To understand the mechanism(s) underlying this overexpression, we have undertaken a detailed characterization of the human p73 promoter. The promoter is strongly activated in cells expressing exogenous E2F1 and suppressed by exogenous Rb. At least three functional E2F binding sites, located immediately upstream of exon 1 (at -284, -155 and -132) mediate this induction. 5' serially deleted promoter constructs and constructs harboring mutated E2F sites were analyzed for their response to exogenously expressed E2F1 or Rb to establish functionality of these sites. Authenticity of E2F sites was further confirmed by electrophoretic mobility shift assay (EMSA) using E2F1/DP1 heterodimers synthesized in vitro, followed by competition assays with unlabeled wild-type or mutant oligonucleotides and supershift analysis using anti-E2F1 antibodies. In vivo binding of E2F1 to the p73 promoter was demonstrated using nuclear extracts prepared from E2F1-inducible Saos2 cells. The region conferring the highest promoter activity was found to reside between -113 to -217 of the p73 gene. Two of the three functional E2F sites(at -155 and -132) reside within this region. Our results suggest that regulation of p73 expression is primarily mediated through binding of E2F1 to target sites at -155 and -132. C1 Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Div Expt Pathol, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Liu, WG (reprint author), Mayo Clin & Mayo Fdn, Dept Lab Med & Expt Pathol, 200 1st St SW, Rochester, MN 55905 USA. NR 46 TC 37 Z9 38 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2002 VL 4 IS 3 BP 195 EP 203 DI 10.1038/sj/neo/7900237 PG 9 WC Oncology SC Oncology GA 550WR UT WOS:000175528000003 PM 11988839 ER PT J AU Bogdanov, AA Lin, CP Simonova, M Matuszewski, L Weissleder, R AF Bogdanov, AA Lin, CP Simonova, M Matuszewski, L Weissleder, R TI Cellular activation of the self-quenched fluorescent reporter probe in tumor microenvironment SO NEOPLASIA LA English DT Article DE tumor; cathepsin; microscopy confocal; fluorescent probe; indocyanine ID NEAR-INFRARED FLUORESCENCE; IN-VIVO CHARACTERIZATION; MATRIX METALLOPROTEINASES; CONTRAST AGENTS; CANCER INVASION; SOLID TUMORS; DELIVERY; MODEL; PROGRESSION; PROTEASES AB The effect of intralysosomal proteolysis of near-infrared fluorescent (NIRF) self-quenched macromolecular probe (PGC-Cy5.5) has been previously reported and used for tumor imaging. Here we demonstrate that proteolysis can be detected noninvasively in vivo at the cellular level. A codetection of GFP fluorescence (using two-photon excitation) and NIRF was performed in tumor-bearing animals injected with PGC-Cy5.5. In vivo microscopy of tumor cells in subdermal tissue layers (up to 160 mum) showed a strong Cy5.5 dequenching effect in GFP-negative cells. This observation was corroborated by flow cytometry, sorting, and reverse transcription polymerase chain reaction analysis of tumor-isolated cells. Both GFP-positive (81% total) and GFP-negative (19% total) populations contained Cy5.5-positive cells. The GIFP-negative cells were confirmed to be host mouse cells by the absence of rat cathepsin mRNA signal. The subfraction of GFP-negative cells (2.5-3.0%) had seven times higher NIRF intensity than the majority of GFP-positive or GFP-negative cells (372 and 55 AU, respectively). Highly NIRF-positive, FP-negative cells were CD45- and MAC3-positive. Our results indicate that: 1) intracellular proteolysis can be imaged in vivo at the cellular level using cathepsin-sensitive probes; 2) tumor-recruited cells of hematopoetic origin participate most actively in uptake and degradation of long-circulating macromolecular probes. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Charlestown, MA 02129 USA. RP Bogdanov, AA (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Room 5420,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 54 TC 43 Z9 46 U1 1 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2002 VL 4 IS 3 BP 228 EP 236 DI 10.1038/sj/neo/7900238 PG 9 WC Oncology SC Oncology GA 550WR UT WOS:000175528000006 PM 11988842 ER PT J AU Jara, A Chacon, C Felsenfeld, AJ AF Jara, A Chacon, C Felsenfeld, AJ TI How dietary phosphate, renal failure and calcitriol administration affect the serum calcium-phosphate relationship in the rat SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcitriol; calcium; hyperparathyroidism; parathyroid hormone; phosphate; renal failure ID PARATHYROID-HORMONE; CALCEMIC RESPONSE; VITAMIN-D; PHOSPHORUS; METABOLISM AB Background. The effect of hyperphosphataemia on serum calcium regulation in renal failure has not been well Studied in a setting in which hypercalcaemia is not parathyroid hormone (PTH) mediated. In azotemic rats with a normal serum calcium concentration, in increased dietary phosphate burden affects serum calcium regulation because of its effects on skeletal resistance to PTH, calcitriol production, and possibly intestinal calcium absorption. Our goal was to determine how hyperphosphataemia affected the development of hypercalcaemia during calcitriol-induced hypercalcaemia and PTH suppression in azotemic rats with established hyperparathyroidism. Methods. Rats underwent a two-stage 5/6 nephrectomy or corresponding sham operations. After surgery, rats were given a high phosphate diet (P 1.2%) for 4 weeks to exacerbate hyperparathyroidism and were then changed to a normal diet (P 0.6%) for 2 weeks to normalize serum calcium values in the azotemic rats. At week 7, rats were divided into five groups and sacrificed after receiving three intraperitoneal doses of calcitriol (CTR, 500 pmol/100 g) or vehicle at 24 h intervals. The five groups and dietary phosphate content were: group 1, normal renal function (NRF) + 0.6% P+vehicle group 2, NRF + 0.6%, P + CTR; group 3, renal failure (RF)+ 0.6% P+vehicle; group group 5, RF + 0.6% P + 4 RF + 1.2% P + CTR; and CTR. Both the 0.6% and 1.2% phosphate diets contained 0.6%, calcium. Results. Serum creatinine values were increased (P < 0.05) in 5/6 nephrectomized rats (groups 3, 4 and 5), as were serum calcium values (P < 0.05) in CTR-treated rats (groups 2, 4 and 5) and serum phosphate values (P < 0.05) in CTR-treated azotemic rats (groups 4 and 5). Serum PTH values were suppressed (P < 0.05) in CTR-treated hypercalcemic rats (groups 2, 4 and 5) and increased (P < 0.05) in azotemic rats not given CTR (group 3). In the azotemic groups (groups 3, 4 and 5), an inverse correlation was present between serum calcium and phosphate in each group, despite a wide variation in serum calcium values. The slope of the inverse relationship between serum calcium and phosphate was steeper in CTR-treated azotemic rats on a 1.2% phosphate (group 4) diet than on a 0.6% phosphate (group 5) diet (P = 0.02). Thus, for a similar increase in the serum phosphate concentration, serum calcium values decreased more in group 4 than in group 5. The independent effect of dietary phosphate on serum calcium values was also confirmed by analysis of covariance. Finally, the serum calcium concentration was shown to be greater for any given serum phosphate value in CTR-treated rats than in those not on CTR. Conclusions. In azotemic rats with calcitriol-induced hypercalcaemia, the magnitude of hypercalcaemia is affected by: (i) the serum phosphate concentration; and (ii) differences in dietary phosphate content. Calcitriol administration also acts to shift upwards the relationship between serum calcium and phosphate so that a higher serum calcium concentration can be maintained for any given serum phosphate value. C1 Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Pontificia Univ Catolica Chile, Dept Nephrol, Santiago, Chile. RP Jara, A (reprint author), Pontificia Univ Catolica Chile, Hosp Clin, Dept Nephrol, Marcoleta 345, Santiago, Chile. NR 20 TC 4 Z9 4 U1 0 U2 3 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 MAY PY 2002 VL 17 IS 5 BP 765 EP 771 DI 10.1093/ndt/17.5.765 PG 7 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 551GC UT WOS:000175550800013 PM 11981061 ER PT J AU Chee, MWL Hon, NHH Caplan, D Lee, HL Goh, J AF Chee, MWL Hon, NHH Caplan, D Lee, HL Goh, J TI Frequency of concrete words modulates prefrontal activation during semantic judgments SO NEUROIMAGE LA English DT Article DE fMRI; semantic memory; word frequency; processing ID LEXICAL ACCESS; CORTEX; TASK; RETRIEVAL; LANGUAGE; ANATOMY; MEMORY; SOUND AB The effect of word frequency on semantic processing was characterized by studying two groups of right-handed participants using fMRI. Stimuli were presented in blocks of either high frequency or low frequency word triplets where a sample word appeared above a pair of test words. One group (n = 8) made semantic judgments by selecting the word from the test pair that was more closely associated with the sample. Stimulus triplets were designed such that relatedness between sample and "correct" items was obvious. The other group (n = 8) read the words silently without making any semantic decision and pressed a button on completing the reading of each triplet. Semantic judgments while no less accurate, were associated with greater left prefrontal BOLD signal change when they involved low frequency words, whereas there was no reliable effect of word frequency in the reading condition. These findings suggest that retrieval effort modulates left prefrontal activity when deliberate access to semantics is required. (C) 2002 Elsevier Science (USA). C1 Singapore Gen Hosp, Cognit Neurosci Lab, Singapore 169856, Singapore. Natl Univ Singapore, Dept Social Work & Psychol, Singapore 119260, Singapore. Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. RP Chee, MWL (reprint author), Singapore Gen Hosp, Cognit Neurosci Lab, Singapore 169856, Singapore. RI GOH, JOSHUA/C-8063-2016; OI GOH, JOSHUA/0000-0001-7808-5452; Chee, Michael/0000-0002-6087-0548 FU NIDCD NIH HHS [DC02146] NR 26 TC 59 Z9 62 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2002 VL 16 IS 1 BP 259 EP 268 DI 10.1006/nimg.2002.1061 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 569WD UT WOS:000176624700022 PM 11969333 ER PT J AU Zhang, KH Tarazi, FI Davids, E Baldessarini, RJ AF Zhang, KH Tarazi, FI Davids, E Baldessarini, RJ TI Plasticity of dopamine D-4 receptors in rat forebrain: Temporal association with motor hyperactivity following neonatal 6-hydroxydopamine lesioning SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE attention deficit hyperactivity disorder (ADHD); development; dopamine D-4 receptors; 6-hydroxydopamine; motor hyperactivity; neonatal lesions ID ATTENTION-DEFICIT DISORDER; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; BEHAVIORAL-RESPONSES; EXCITOTOXIC LESIONS; D-4-LIKE RECEPTORS; LOCOMOTOR-ACTIVITY; NOVELTY SEEKING; PRIMATE BRAIN; DRD4 GENE AB Genetic studies suggest that dopamine D receptor polymorphism is associated with attention deficit hyperactivity disorder (ADHD). We recently reported that motor hyperactivity in juvenile male rats with neonatal 6-hydroxydopamine lesions of the central dopamine system can be reversed by dopamine D-4 receptor-selective antagonists. In this study, effects of such lesions on D-4 as well as other dopamine receptors (D-1 and D-2) were autoradiographically quantified of selected developmental stages. Neonatal lesions resulted in motor hyperactivity at postnatal day (PD) 25, but not at PD 37 or 60. Correspondingly, D-4 receptor levels in lesioned rats were substantially increased in caudate-putamen and decreased in nucleus accumbens at PD 25, but not at PD 37 or 60. Neonatal lesions also led to relatively minor changes in D-1 and D-2 receptor binding in various forebrain regions. However, the time-course of lesion-induced motor hyperactivity correlated only with changes in D-4 but not D-1 and D-2 receptors. These results further support the hypothesis that D-4 receptors may play a pivotal role in lesion-induced hyperactivity, and possibly in clinical ADHD. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Zhang, KH (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47270, MH034006] NR 55 TC 26 Z9 30 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2002 VL 26 IS 5 BP 625 EP 633 AR PII S0893-133X(01)00404-3 DI 10.1016/S0893-133X(01)00404-3 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 538AJ UT WOS:000174791600007 PM 11927187 ER PT J AU Montoya, A Weiss, AP Price, BH Cassem, EH Dougherty, DD Nierenberg, AA Rauch, SL Cosgrove, GR AF Montoya, A Weiss, AP Price, BH Cassem, EH Dougherty, DD Nierenberg, AA Rauch, SL Cosgrove, GR TI Magnetic resonance imaging-guided stereotactic limbic leukotomy for treatment of intractable psychiatric disease SO NEUROSURGERY LA English DT Article DE anterior cingulate gyrus; functional neurosurgery; limbic leukotomy; major depression; obsessive-compulsive disorder; psychosurgery; subcaudate tractotomy ID OBSESSIVE-COMPULSIVE DISORDER; TERM FOLLOW-UP; CINGULOTOMY; PSYCHOSURGERY AB OBJECTIVE: To assess the efficacy and complication rates of magnetic resonance imaging-guided stereotactic limbic leukotomy for the treatment of intractable major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). METHODS: We conducted preoperative evaluations and postoperative follow-up assessments of efficacy and complications for 21 patients who underwent limbic leukotomy. Efficacy was based on physician- and patient-rated global assessments of functioning, as well as evaluations using disease-specific rating scales commonly used in studies of MDD and OCD. RESULTS: The mean time from limbic leukotomy to follow-up assessment was 26 months. On the basis of standard outcome measures, 36 to 50% of patients were considered to be treatment responders. Although permanent surgical morbidity was rare, there were reports of postoperative sequelae, including apathy, urinary incontinence, and memory complaints, which occurred in a substantial minority of cases. CONCLUSION: For this cohort of 21 patients with chronic severe MDD or OCD, who had experienced failure with an exhaustive array of previous treatments, limbic leukotomy was associated with substantial benefit for 36 to 50%. This rate is comparable to those of previous studies of limbic system surgery and indicates that limbic leukotomy is a feasible treatment option for severe, treatment-refractory MDD or OCD. Adverse consequences associated with the procedure included affective, cognitive, and visceromotor sequelae, which were generally transient. C1 Massachusetts Gen Hosp, Dept Neurosurg, Wang ACC 331, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. Natl Inst Neurol & Neurosurg, Dept Neuropsychiat, Mexico City, DF, Mexico. RP Cosgrove, GR (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Wang ACC 331, 15 Parkman St, Boston, MA 02114 USA. NR 20 TC 45 Z9 47 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2002 VL 50 IS 5 BP 1043 EP 1049 DI 10.1097/00006123-200205000-00018 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 548CC UT WOS:000175370100025 PM 11950407 ER PT J AU Ng, AK Mauch, PM AF Ng, AK Mauch, PM TI Controversies in early-stage Hodgkin's disease SO ONCOLOGY-NEW YORK LA English DT Article ID EXTENDED-FIELD RADIOTHERAPY; SUBTOTAL LYMPHOID IRRADIATION; CONTROLLED CLINICAL-TRIALS; PROGNOSTIC FACTORS; RANDOMIZED TRIAL; MEDIASTINAL INVOLVEMENT; MOPP CHEMOTHERAPY; RADIATION-THERAPY; PLUS RADIOTHERAPY; GALLIUM SCANS AB Early-stage Hodgkin's disease accounts for approximately 60% of all cases of the illness. Because of its excellent care rate (80% to 90%) and high salvage rate, it is difficult to demonstrate survival advantages for different management options. Currently, there is no consensus as to the optimal staging and treatment strategy for early-stage Hodgkin's disease. With the increasing recognition of the late consequences of Hodgkin's disease therapy, the focus of recent clinical trials has been on exploring treatment modifications to reduce these late effects. Areas of controversy that are being explored include extent of staging workup, radiation field size and dose (and as part of combined-modality therapy), optimal chemotherapy regimen, number of cycles of chemotherapy, and limited- vs extended-field radiation therapy and dose. In addition, several studies are investigating the feasibility of chemotherapy alone in early-stage patients. Along with the evaluation of modified treatments, long-term follow-up efforts should continue in patients who are cured in order to confirm the long-term safety of such therapies. C1 Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. RP Mauch, PM (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, 75 Francis St, Boston, MA 02115 USA. NR 52 TC 8 Z9 8 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 MAY PY 2002 VL 16 IS 5 BP 588 EP + PG 9 WC Oncology SC Oncology GA 554HR UT WOS:000175730200008 PM 12108888 ER PT J AU Sonis, ST Fey, EG AF Sonis, ST Fey, EG TI Oral complications of cancer therapy SO ONCOLOGY-NEW YORK LA English DT Article ID BONE-MARROW TRANSPLANTATION; CHEMOTHERAPY-INDUCED MUCOSITIS; TRANSFORMING GROWTH FACTOR-BETA-3; RANDOMIZED CLINICAL-TRIAL; DOUBLE-BLIND; NECK-CANCER; PHARMACOLOGICAL PROPERTIES; NEUTROPENIC PATIENTS; PHASE-I; PREVENTION AB The month is a frequent site of complications arising from drug or radiation cancer therapy, with mucositis, xerostomia, osteoradionecrosis, and local infections being the most common. Front the standpoint of dose limitation, treatment breaks, quality of life, and health economic outcomes, mucositis is the most significant acute oral toxicity. Xerostomia, a chronic side effect of radiation, involves the salivary gland tissue, and results in changes in taste, tissue resilience, and an increased risk of caries and periodontal disease, While the incidence of osteoradionecrosis seems to be decreasing, the chronicity and symptoms of this festering bony condition are especially difficult for patients. Local oral infections resulting from the overgrowth of opportunistic organisms or the activation of latent viruses are so common as to warrant a prophylactic approach in many cases. A surge of investigational interest has been directed at understanding the mechanisms of these stomatotoxicities and at developing treatment strategies to combat them. C1 Harvard Univ, Brigham & Womens Hosp, Dept Oral Med & Diagnost Sci, Sch Dent Med,Dana Farber Canc Inst, Boston, MA 02115 USA. Biomodels LLC, Boston, MA USA. RP Sonis, ST (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Oral Med & Diagnost Sci, Sch Dent Med,Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 67 TC 72 Z9 75 U1 0 U2 6 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 MAY PY 2002 VL 16 IS 5 BP 680 EP 686 PG 7 WC Oncology SC Oncology GA 554HR UT WOS:000175730200025 PM 12108892 ER PT J AU Samson, CM Nduaguba, C Baltatzis, S Foster, CS AF Samson, CM Nduaguba, C Baltatzis, S Foster, CS TI Limbal stem cell transplantation in chronic inflammatory eye disease SO OPHTHALMOLOGY LA English DT Article ID OCULAR-SURFACE DISORDERS; RECONSTRUCTION AB Objective: The goal of this study was to describe the outcome of limbal stem cell transplantation (LSCT) in patients with severe ocular surface disease caused by underlying chronic inflammatory eye disease. Design: Retrospective noncomparative case series. Participants: Nine patients with limbal stem cell deficiency caused by an underlying ocular inflammatory disease who underwent LSCT. Methods: The authors reviewed the records of 11 eyes of 9 patients with immunologically mediated ocular surface disease that underwent LSCT. Main Outcome Measures: The main outcome measures were reepithelialization of the corneal surface, restoration of corneal surface, and improvement in visual acuity. Results: A total of 11 eyes underwent either autologous (n = 1) or HLA-matched living related donor (n 10) LSCT for ocular surface disease secondary to inflammatory disease. Reepithelialization of the corneal surface in the immediate postoperative period occurred in 10 eyes (91%) within an average of 10 days (range, 3-21 days). Long-term restoration of the corneal surface was achieved in six (55%) eyes, Visual acuity improved in six eyes (55%). Reasons for poor outcomes included microbial infection, limbal stem cell graft rejection, and corneal ulceration. No donor eyes had complications. Conclusions: Patients with underlying immunologically mediated diseases, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or ocular cicatricial pemphigoid, who undergo LSCT have lower success rates than do those patients with noninflammatory ocular surface diseases. Ophthalmology 2002;109:862-868 (C) 2002 by the American Academy of Ophthalmology. C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Dept Ophthalmol, Boston, MA 02114 USA. Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 60 Z9 66 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2002 VL 109 IS 5 BP 862 EP 868 AR PII S0161-6420(02)00994-6 DI 10.1016/S0161-6420(02)00994-6 PG 7 WC Ophthalmology SC Ophthalmology GA 549YG UT WOS:000175474400035 PM 11986089 ER PT J AU Luepongsak, N Amin, S Krebs, DE McGibbon, CA Felson, D AF Luepongsak, N Amin, S Krebs, DE McGibbon, CA Felson, D TI The contribution of type of daily activity to loading across the hip and knee joints in the elderly SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE knee; hip; biomechanics; osteoarthritis ID OCCUPATIONAL ACTIVITY; OSTEOARTHRITIS; KINEMATICS; EXERCISE; MOMENTS; LEVEL; GAIT; OPTIMIZATION; BIOMECHANICS; PRESSURE AB Objective: In the elderly, we evaluated loading across the hip or knee joints during different daily activities. Methods: Elderly people drawn from the community entering an exercise study underwent a full kinetic and kinematics analysis of five different activities, standing, walking, arising from a chair, going downstairs and bending over. Inverse dynamic equations were used to compute forces and torques across the knees and hips during all of these activities. Results: 132 elderly people, mean age 75, participated. Compressive forces across the knees and hips were, by far, the greatest vector forces and were highest during stair descent and, to a lesser extent, during walking. Compressive forces were lowest during standing. The highest moments were flexion and adduction moments, and these were maximal during stair descent. Conclusion: Of the five activities we studied, descending stairs was associated with the highest calculated forces and torques across the knees and hips, and that may account for its tendency to cause joint symptoms and for its possible association with osteoarthritis incidence. (C) 2002 Published by Elsevier Science Ltd on behalf of OsteoArthritis Research Society International. C1 Boston Univ, Multipurpose Arthrit & Musculoskeletal Dis Ctr, Boston, MA 02118 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Boston Med Ctr, Dept Med, Boston, MA USA. MGH Inst Hlth Profess, Boston, MA USA. RP Felson, D (reprint author), Boston Univ, Arthrit Ctr, 715 Albany St,A203, Boston, MA 02118 USA. OI Felson, David/0000-0002-2668-2447 FU NIA NIH HHS [R01 AG12561]; NIAMS NIH HHS [AR20613] NR 40 TC 21 Z9 23 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD MAY PY 2002 VL 10 IS 5 BP 353 EP 359 DI 10.1053/joca.2000.0511 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 563AT UT WOS:000176231800003 PM 12027536 ER PT J AU Chung, JH Cosenza, MJ Rahbar, R Metson, RB AF Chung, JH Cosenza, MJ Rahbar, R Metson, RB TI Mitomycin C for the prevention of adhesion formation after endoscopic sinus surgery: A randomized, controlled study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 09-14, 2001 CL DENVER, COLORADO SP Amer Acad Otolaryngol Head & Neck Surg ID STENOSIS; COMPLICATIONS; EXPOSURES AB OBJECTIVE. Mitomycin C (MMC) is an antineoplastic agent that has been shown to decrease scar tissue after ophthalmologic surgery. Our goal was to determine whether the application of MMC at the conclusion of sinus surgery decreases the incidence of postoperative adhesion formation. METHODS: At the completion of endoscopic sinus surgery in 55 patients, a cotton pledget saturated with 1 mL of 0.4 mg/mL MMC was placed for 4 minutes in the right or left middle meatus and a similar saline-soaked pledget was placed on the opposite side. Patients were examined postoperatively by a masked observer for the presence of synechiae and mucosal changes. RESULTS: Postoperative adhesions were observed in 16 patients (29%) with a mean follow-up of 4.1 months. These adhesions were bilateral in 6 patients (10.9%) and unilateral in 10 patients (18%). Unilateral adhesions were observed on only 2 sides (3.6%) treated with MMC and 8 controls (14.5%) (P = 0.058). No adverse effects were observed. CONCLUSIONS. MMC was found to be safe to use during sinus surgery; and it may reduce the incidence of postoperative adhesions at the dosage used in this study. SIGNIFICANCE: Because of the observed trend toward decreased synechiae formation with MMC application, further trials using higher concentrations and application times are warranted. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp, Dept Otolaryngol & Commun Disorders, Boston, MA 02115 USA. RP Metson, RB (reprint author), Zero Emerson Pl,Suite 2D, Boston, MA 02114 USA. NR 20 TC 80 Z9 82 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2002 VL 126 IS 5 BP 468 EP 474 DI 10.1067/mhn.2002.124705 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 564HK UT WOS:000176308800003 PM 12075219 ER PT J AU Adams, JC AF Adams, JC TI Clinical implications of inflammatory cytokines in the cochlea: A technical note SO OTOLOGY & NEUROTOLOGY LA English DT Article DE cytokine; interleukin-1; spiral ligament; tumor necrosis factor ID NF-KAPPA-B; GAP JUNCTIONAL COMMUNICATION; NECROSIS-FACTOR-ALPHA; INNER-EAR DISEASE; HEARING-LOSS; MUTATIONS; EXPRESSION; ACTIVATION; CELLS; GLUCOCORTICOIDS AB Hypothesis: Establishing the presence of critical cellular stress response components in cochlear cells can contribute to a better understanding of cochlear cell biology and pathology. Background: Inflammatory cytokines and related proteins play critical roles in a variety of cellular processes, but to date, little is known about the identity and cellular localization of these compounds within the ear. Cytokines are autocrine, which means that cells that produce them have corresponding surface receptors. The presence of these receptors makes the cells vulnerable to disruption by circulating or local sources of cytokines and related ligands. Such disruptions may explain previously poorly understood cochlear pathologies. Methods: The messenger RNA precursors that encode inflammatory cytokines and related proteins are identified in the inner ear by using reverse transcriptase-polymerase chain reaction. Cochlear cells that contain the corresponding proteins are identified by immunostaining. Results: Messenger RNA for interleukin-la, tumor necrosis factor alpha, NFkappaB P65 and P50, and IkappaBalpha was found in cochlear tissue. Cells that immunostained most conspicuously for cytokine production are Type I ribrocytes and root cells located within the spiral ligament, Conclusion: Production of inflammatory cytokines by the above-mentioncd cells indicates that they are vulnerable to disruption by extra-cochlear sources of cytokines and associated ligands. These cells play critical roles in cochlear function, and their disruption could induce hearing loss. These findings suggest that systemic or local production of inflammatory ligands may play roles in a number of causes of deafness, including immune mediated hearing loss, sudden hearing loss, and sensorineural hearing loss associated with otosclerosis, otitis media, and bacterial meningitis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Adams, JC (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC 03929] NR 40 TC 74 Z9 80 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2002 VL 23 IS 3 BP 316 EP 322 DI 10.1097/00129492-200205000-00015 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 548YM UT WOS:000175417500015 PM 11981388 ER PT J AU Megerian, CA Haynes, DS Poe, DS Choo, DI Keriakas, TJ Glasscock, ME AF Megerian, CA Haynes, DS Poe, DS Choo, DI Keriakas, TJ Glasscock, ME TI Hearing preservation surgery for small endolymphatic sac tumors in patients with von Hippel-Lindau syndrome SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Neurotology-Society CY MAY 12-13, 2001 CL PALM SPRINGS, CALIFORNIA SP Amer Neurotol Soc DE endolymphatic sac tumor; hearing preservation surgery; von Hippel-Lindau syndrome ID TEMPORAL BONE; MIDDLE-EAR; PAPILLARY CYSTADENOMA; DISEASE; ADENOMA; ADENOCARCINOMA; GENE; NEOPLASM; ORIGIN AB Objective: To determine the incidence of bilateral endolymphatic sac tumors in von Hippel-Lindau syndrome and to describe the technique and results of hearing preservation surgery for small endolymphatic sac tumors in a series of patients with von Hippel-Lindau syndrome. Study Design: Analysis of the literature to determine the incidence of bilateral endolymphatic sac tumors and a retrospective case review of hearing preservation surgery for removal of small endolymphatic sac tumors in four patients with von Hippel-Lindau syndrome. Setting: Tertiary care academic medical centers. Patients: Four patients with von Hippel-Lindau syndrome (three with bilateral endolymphatic sac tumors) and progressive sensorineural hearing loss in which preoperative imaging studies revealed in situ or small endolymphatic sac tumors without ipsilateral labyrinthine destruction. Intervention: All four patients had complete surgical excisions of the endolymphatic sac tumor via one of three surgical approaches with the goal of hearing preservation. One patient had bilateral surgery. Main Outcome Measures: Audiometric and radiographic. Results: Nearly one-third (30.2%) of patients with von Hippel-Lindau syndrome and endolymphatic sac tumors have bilateral disease. All four patients (five cars) maintained serviceable hearing postoperatively after surgical excision of the endolymphatic sac tumor via a variety of approach options. Conclusion: The discovery of a small or in situ endolymphatic sac tumor affords the patient the option of surgical removal with hearing preservation. This is critical in the patient with von Hippel-Lindau syndrome who is at risk for bilateral disease and complete bilateral anacusis if tumor growth progresses. C1 Univ Massachusetts, Sch Med, Dept Otolaryngol, Worcester, MA USA. Vanderbilt Univ, Sch Med, Dept Otolaryngol, Nashville, TN 37212 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Univ Cincinnati, Sch Med, Dept Otolaryngol, Cincinnati, OH USA. RP Megerian, CA (reprint author), Univ Massachusetts, Med Ctr, Dept Otolaryngol Head & Neck Surg, 55 Lake Ave,Room S2-861, Worcester, MA 01655 USA. NR 33 TC 44 Z9 47 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2002 VL 23 IS 3 BP 378 EP 387 DI 10.1097/00129492-200205000-00026 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 548YM UT WOS:000175417500026 PM 11981399 ER PT J AU Rider, EA Perrin, JM AF Rider, EA Perrin, JM TI Performance profiles: The influence of patient satisfaction data on physicians' practice SO PEDIATRICS LA English DT Article DE performance profiles; patient satisfaction; physician report cards ID HEALTH-CARE; CARDIAC-SURGERY; MEDICAL-CARE; QUALITY; PARTICIPATION; INTERVENTION; FEEDBACK AB Objective. Health maintenance organizations and other payers increasingly use patient satisfaction data to profile physician performance. Little is known about physicians' use of patient satisfaction information or how profiles affect individual physician behaviors. The objective of this study was to examine primary care physicians' perceptions of performance profiles based on patient satisfaction data, whether physicians use profiles to change practice behaviors, and which profile components physicians think are important for assessing quality of care. Methods. A written survey was conducted in 1998 in Massachusetts with 810 primary care physicians (304 pediatricians, 201 family practitioners, 305 internists) who had at least 100 patients in a large managed care plan and had received 1 or more profiles based on patient satisfaction data. Physicians in training were excluded. Physicians' perceptions of profiles and their reported use to change practice behaviors were measured. Results. The response rate was 68%. Twenty-three percent reported that profiles were very or extremely useful for improving care. Only 7% reported using profiles often or always to change care. Although specific profile components related to interpersonal aspects of care were rated more useful, <11% reported using profiles often or always to make changes on any individual component. A majority, 67% to 89%, reported making no or minor changes on profile components. Responses did not vary by specialty, demographics, or practice characteristics. Physicians rated interpersonal factors (eg, ability to communicate with patients, ability to show caring and empathy) as the most important indicators of quality of care; they report having the most control over these factors. Office factors (eg, staying on schedule, ease of scheduling appointments) were ranked as least important for assessing quality of care. Conclusion. Although health maintenance organizations and other payers increasingly use patient satisfaction reports to profile individual physicians and guide physician compensation and health plan participation, <25% of primary care physicians find profiles useful for improving patient care and even fewer report using profiles to change practice. Profiles likely have limited influence on behavior changes. Payers who invest in profiles may find it advantageous to focus on health plans and practice facilities rather than on individual physicians. C1 Harvard Univ, Sch Med, Off Educ Dev, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. MassGen Hosp Children, Div Gen Pediat, Boston, MA USA. RP Rider, EA (reprint author), Harvard Univ, Sch Med, Off Educ Dev, 260 Longwood Ave,MEC 384, Boston, MA 02115 USA. NR 39 TC 17 Z9 17 U1 0 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 MAY PY 2002 VL 109 IS 5 BP 752 EP 757 DI 10.1542/peds.109.5.752 PG 6 WC Pediatrics SC Pediatrics GA 547EZ UT WOS:000175321200021 PM 11986432 ER PT J AU Mischoulon, D AF Mischoulon, D TI Potential pitfalls to the therapeutic relationship arising from disability claims SO PSYCHIATRIC ANNALS LA English DT Article ID PSYCHIATRIC DISABILITY; SUBSTANCE-ABUSE; MENTAL-ILLNESS; PAYMENTS; DEPENDENCE; PATIENT; COCAINE; INCOME AB Potential Pitfalls to the Therapeutic Relationship Arising From Disability Claims. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAY PY 2002 VL 32 IS 5 BP 299 EP + PG 5 WC Psychiatry SC Psychiatry GA 550MH UT WOS:000175506500005 ER PT J AU Babb, SM Wald, LL Cohen, BM Villafuerte, RA Gruber, SA Yurgelun-Todd, DA Renshaw, PF AF Babb, SM Wald, LL Cohen, BM Villafuerte, RA Gruber, SA Yurgelun-Todd, DA Renshaw, PF TI Chronic citicoline increases phosphodiesters in the brains of healthy older subjects: an in vivo phosphorus magnetic resonance spectroscopy study SO PSYCHOPHARMACOLOGY LA English DT Article DE 5 '-cytidine diphosphate choline; choline; phosphatidylcholine; aging; brain; magnetic resonance spectroscopy ID CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; MEMBRANE PHOSPHOLIPID-METABOLISM; ALZHEIMERS-DISEASE; IN-VIVO; PREFRONTAL CORTEX; CDP-CHOLINE; P-31 MRS; INVIVO; HYPOTHESIS; MECHANISMS AB Rationale: Phosphatidylcholine (PtdCho) in brain cell membranes decreases with age. Evidence from both animal and in vitro studies indicates that CDP-choline (citicoline) administration may increase phosphatidylcholine (PtdCho) synthesis and might reverse PtdCho loss. Objectives: We investigated whether oral citicoline can increase PtdCho synthesis in the brains of older subjects by measuring levels of phosphorus-containing metabolites using proton-decoupled phosphorus magnetic resonance spectroscopy (P-31-MRS) before and after citicoline treatment. Methods: All subjects took 500 mg citicoline once orally each day for 6 weeks, then took either citicoline or placebo once orally per day for a second 6-week period. Subjects underwent a 31P-MRS scan at baseline and following 6 and 12 weeks of treatment. Results: Treatment with citicoline for 6 weeks was associated with a 7.3% increase from baseline levels in brain phosphodiesters (P=0.008), including an 11.6% increase in glycerophosphoethanolamine (P=0.002) and a 5.1% increase in glycerophosphocholine (P=0.137). Subjects who continued to take citicoline for the second 6-week period did not show significant additional increases in the levels of these metabolites. No changes were seen in other phosphorus-containing metabolites. There was a correlation between improvement on the California Verbal Learning Test and increase in phosphodiesters. Conclusions: The increases in phosphodiesters seen in this study indicate that phospholipid synthesis and turnover were stimulated by 6 weeks of oral citicoline. These results in humans support previous in vitro and animal studies and suggest that the administration of oral citicoline may be of use in reversing age-related changes in the brain. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. RP Babb, SM (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. RI Wald, Lawrence/D-4151-2009 FU NIDA NIH HHS [DA 09448]; NIMH NIH HHS [MH 57520-01A1] NR 49 TC 22 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2002 VL 161 IS 3 BP 248 EP 254 DI 10.1007/s00213-002-1045-y PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 562JG UT WOS:000176193200004 PM 12021827 ER PT J AU Silver, MH Newell, K Brady, C Hedley-White, ET Perls, TT AF Silver, MH Newell, K Brady, C Hedley-White, ET Perls, TT TI Distinguishing between neurodegenerative disease and disease-free aging: Correlating neuropsychological evaluations and neuropathological studies in centenarians SO PSYCHOSOMATIC MEDICINE LA English DT Article DE Alzheimer's; centenarians; cognition; dementia; neuropathology; neuropsychology ID ALZHEIMERS-DISEASE; OLDEST-OLD; CLINICAL EXPRESSION; AGE; DEMENTIA; PREVALENCE; CONSORTIUM; ESTABLISH; VALIDITY; REGISTRY AB Objective: In an examination of disease-free aging and neurodegenerative disease in 100-year-olds, the New England Centenarian Study compared data from neuropsychological evaluations with postmortem brain studies of fourteen 100-year-olds to ascertain if the presence or absence of Alzheimer disease changes correlated with measured cognitive abilities. Methods: Fourteen of 74 centenarians who underwent annual extensive neuropsychological evaluation proceeded to postmortem neuropathological examination. CERAD criteria, emphasizing neuritic amyloid plaques and Braak and Braak staging of neurofibrillary tangles were used to assess the 14 brains. Results: Neuropsychological and neuropathological findings correlated well for four subjects with no dementia on testing (CDR = 0) and for six subjects with CDR scores in the dementia range (CDR = 1-5). In the latter group, Alzheimer's disease was diagnosed in four brains; Pick's disease was an etiological factor in the fifth and hippocampal sclerosis in the sixth. Correlation was low for four subjects: two subjects with no dementia on neuropsychological testing met CERAD neuropathological criteria for possible AD; two subjects with dementia on testing did not meet CERAD criteria for definite Alzheimer's disease and had otherwise minimal changes to correlate with the cognitive findings. Conclusions: Lack of correlation between level of cognitive functioning and brain pathology in two subjects with no dementia raised the question of whether a functional reserve delayed the functional expression of pathological changes. For two subjects with dementia on testing, there appeared to be no sufficient pathological explanation for the extent of the cognitive changes: depression and such factors as environment, sensory impairment, and medical illness may all have played a role. There may also have been neuropathologic changes not detected by current methods. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Aging, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Silver, MH (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Aging, 1 Deaconess Rd,CC105, Boston, MA 02215 USA. FU NIA NIH HHS [AG05134, 2R21AG16916, 1R01AG18721] NR 56 TC 51 Z9 51 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 2002 VL 64 IS 3 BP 493 EP 501 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 555JV UT WOS:000175791700014 PM 12021423 ER PT J AU Hazuda, HP Gerety, MB Lee, S Mulrow, CD Lichtenstein, MJ AF Hazuda, HP Gerety, MB Lee, S Mulrow, CD Lichtenstein, MJ TI Measuring subclinical disability in older Mexican Americans SO PSYCHOSOMATIC MEDICINE LA English DT Article DE activities of daily living; adaptation; disability; elderly; Mexican Americans; methods ID DISABLEMENT PROCESS; SCALE; MOBILITY AB Objective: The purpose of this study was to develop a comprehensive list of adaptive strategies to prevent disability and use this information to devise a preliminary measure of subclinical disability (state of sustained independence in the presence of latent or manifest functional limitations) suitable for older Mexican Americans. Method: Semistructured interviews were conducted with 24 community-dwelling Mexican American elders ( greater than or equal to65 years old) to elicit information about adaptations in performance of daily living tasks (eg, walking, dressing, and shopping) that may indicate presence of subclinical disability. This information was used to construct a quantitative self-report measure of subclinical disability administered to 207 older Mexican Americans. Item and factor analyses were performed to reduce the number of items and establish their underlying structure. Construct and discriminant validity of the reduced instrument was determined. Results: A framework comprised of nine categories of daily living tasks, three functional levels, and five adaptation types was generated from the qualitative data. The initial 133-item measure (named the ADAPT) was reduced to a 44-item scale with three subscales (physical, household, and social). ADAPT scores correlated significantly in the expected direction with standard functional status measures, but the shared variance was modest, indicating that the ADAPT captured substantial, unique variance. Mean ADAPT scores differed significantly and were monotonically lower across subgroups classified as independent, subclinically disabled, and disabled, respectively. Conclusions: The ADAPT seems to have construct and discriminant validity as a measure of subclinical disability. Additional research is required to determine sensitivity to change and clinically significant cut points for varying risk of frank disability. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. Aging Res & Educ Ctr, Div Geriatr & Gerontol, San Antonio, TX USA. Aging Res & Educ Ctr, Div Gen Med & Gerontol, San Antonio, TX USA. GRECC, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Med Res Serv, Dept Vet Affairs, San Antonio, TX USA. RP Hazuda, HP (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, MC 7873,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCRR NIH HHS [M01RR01346-19]; NIA NIH HHS [1 P20 AG12044]; PHS HHS [1 R01 10444, 1 R01 16518] NR 22 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 2002 VL 64 IS 3 BP 520 EP 530 PG 11 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 555JV UT WOS:000175791700017 PM 12021426 ER PT J AU Okereke, OI AF Okereke, OI TI Neuropsychiatric complications associated with interferon-alpha-2b treatment of malignant melanoma SO PSYCHOSOMATICS LA English DT Article ID ADJUVANT THERAPY; ALPHA THERAPY; HEPATITIS-C; MOOD C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Okereke, OI (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang Bldg,Suite 812, Boston, MA 02114 USA. RI Okereke, Olivia/R-9934-2016 NR 16 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2002 VL 43 IS 3 BP 237 EP 240 DI 10.1176/appi.psy.43.3.237 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 553RM UT WOS:000175689300010 PM 12075040 ER PT J AU Bankier, B Littman, AB AF Bankier, B Littman, AB TI Psychiatric disorders and coronary heart disease in women - A still neglected topic: Review of the literature from 1971 to 2000 SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Editorial Material DE psychiatric disorder; coronary heart disease; women; review ID ACUTE MYOCARDIAL-INFARCTION; ANOREXIA-NERVOSA; RISK-FACTORS; ARTERY DISEASE; YOUNG-WOMEN; CHEST PAIN; CARDIAC REHABILITATION; PSYCHOSOCIAL VARIABLES; REPLACEMENT THERAPY; PANIC DISORDER AB Background. Coronary heart disease (CHID) is the leading cause of death in women aged over 40 years in the United States, for whom it conveys a worse prognosis than for men. Recently, psychosocial factors have been understood to represent significant risk factors for developing CHID, as well as having a worse outcome with established CHID. However, these factors are often overlooked, in particular comorbid psychiatric disorders and psychiatric symptoms. To summarize the current knowledge in this interdisciplinary field, the authors conducted a review of CHD in women, taking into account psychosocial aspects, in particular psychiatric disorders. Methods: Medline searches using the keywords 'psychiatric disorder' and 'coronary heart disease' and 'women', and 'psychiatric disorder' and 'cardiac disease' and 'women', were performed, covering the time span from the beginning of the Medline database until January 1, 2001. Results: Quoted items included depression, panic disorder, generalized anxiety disorder, mitral valve prolapse, chest pain, anorexia nervosa, menopause, alcohol abuse, cocaine use, sleep disorder, sexual dysfunction, hostility and type A behavior, as well as other psychosocial aspects. There is accumulating evidence of significant associations between psychosocial factors, in particular psychiatric disorders and psychiatric symptoms, and the development and recurrence of CHID in women. Conclusions: However, in summary, the topic still seems to be neglected. Future research into psychiatric disorders and psychiatric symptoms and CHID in women is strongly required, and the focus on women exclusively is underlined, Copyright (C) 2002 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Behav Med Prevent Cardiol, Div Psychiat, Boston, MA 02114 USA. RP Bankier, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Behav Med Prevent Cardiol, Div Psychiat, RSHB-090,40 Parkman St, Boston, MA 02114 USA. NR 71 TC 33 Z9 33 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD MAY-JUN PY 2002 VL 71 IS 3 BP 133 EP 140 DI 10.1159/000056280 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 551XV UT WOS:000175590000002 PM 12021555 ER PT J AU Naughton, MJ Herndon, JE Shumaker, SA Miller, AA Kornblith, AB Chao, D Holland, J AF Naughton, MJ Herndon, JE Shumaker, SA Miller, AA Kornblith, AB Chao, D Holland, J TI The health-related quality of life and survival of small-cell lung cancer patients: Results of a companion study to CALGB 9033 SO QUALITY OF LIFE RESEARCH LA English DT Article DE chemotherapy; quality of life; small cell lung cancer; survival ID ETOPOSIDE CYCLOPHOSPHAMIDE METHOTREXATE; RESEARCH-CAMPAIGN TRIAL; RANDOMIZED PHASE-III; DAILY DIARY CARD; OF-LIFE; ORAL ETOPOSIDE; PROGNOSTIC FACTORS; WEEKLY CARBOPLATIN; LIMITED DISEASE; 6 COURSES AB The purposes of this study were 2-fold: to evaluate the impact of the schedule dependency of etoposide (3-day IV short course vs. a 21-day oral prolonged course) with cisplatin on the quality of life of small-cell lung cancer (SCLC) patients; and to examine the effect of baseline quality of life variables on long-term survival, after adjustment for known demographic and clinical prognostic factors. Participants were 70 patients enrolled in the cancer and leukemia group B (CALGB) protocol 9033. Quality of life was assessed at baseline, 6 and 12 weeks by: the EORTC QLQ-30, the Centers for epidemiology studies - Depression short form, the medical outcomes study (MOS) social support questionnaire, and a scale of sleep quality. Contrary to expectations, study results suggested no significant differences in the patients' life quality and treatment response based on whether they received etoposide in a 3-day IV vs. a 21-day oral regimen. The use of the baseline variables in predicting overall survival indicated that patients who were non-white and with liver involvement had decreased survival. Brain involvement, being male, and higher depressive symptoms were also found to be borderline significant in predicting decreased survival in this patient population. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. CALGB Stat Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Naughton, MJ (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NCI NIH HHS [CA33601, CA47555, CA03927] NR 43 TC 33 Z9 33 U1 2 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAY PY 2002 VL 11 IS 3 BP 235 EP 248 DI 10.1023/A:1015257121369 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 545GW UT WOS:000175209700004 PM 12074261 ER PT J AU Epperly, MW Sikora, CA DeFilippi, SJ Gretton, JA Zhan, QM Kufe, DW Greenberger, JS AF Epperly, MW Sikora, CA DeFilippi, SJ Gretton, JA Zhan, QM Kufe, DW Greenberger, JS TI Manganese superoxide dismutase (SOD2) inhibits radiation-induced apoptosis by stabilization of the mitochondrial membrane SO RADIATION RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; DEPRIVATION-INDUCED CYTOTOXICITY; METABOLIC OXIDATIVE STRESS; DEPENDENT ANION CHANNEL; CYTOCHROME-C RELEASE; CELL-DEATH; IONIZING-RADIATION; GLUCOSE DEPRIVATION; MITOTIC CATASTROPHE; MAP-KINASE AB To define the molecular pathways involved in radiation-induced apoptosis and the role of the mitochondria, 32D cl 3 hematopoietic cells and subclones overexpressing either the human manganese superoxide dismutase (SOD2) transgene (1F2 and 2C6) or BCL2L1 (also known as Bcl-xl) transgene (32D-Bcl-xl) were compared for their response to radiation at the subcellular level, comparing nuclear to mitochondrial localized pathways. All cell lines showed complete detectable DNA repair by 30 min after irradiation, and clearly delayed migration of BAX and active stress-activated protein (SAP) kinases MAPK1 (also known as p38) and MAPK8 (also known as JNK1) to the mitochondria at 3 h. Radioresistant clonal lines 1172, 2C6 and 32D-Bcl-xl showed significant decreases in mitochondrial membrane permeability, cytochrome C release, caspase 3 and poly(adenosine diphosphate-ribose) polymerase (PARP) activation at 6-12 h, and in apoptosis at 24 h. Since the nuclear-to-cytoplasm events preceding the release of cytochrome C were similar in all cell lines, and increased expression of either the SOD2 or the BCL2L1 transgene provided radiation protection, we conclude that events at the level of the mitochondria are critically involved in radiation-induced apoptosis. (C) 2002 by Radiation Research Society. C1 Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Inst Canc, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Epperly, MW (reprint author), Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Inst Canc, 200 Lothrop St,Room B346-PUH, Pittsburgh, PA 15213 USA. FU NHLBI NIH HHS [R01-HL60132] NR 42 TC 97 Z9 98 U1 1 U2 6 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 2002 VL 157 IS 5 BP 568 EP 577 DI 10.1667/0033-7587(2002)157[0568:MSDSIR]2.0.CO;2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 549PE UT WOS:000175452500010 PM 11966323 ER PT J AU Delille, JP Slanetz, PJ Yeh, ED Kopans, DB Garrido, L AF Delille, JP Slanetz, PJ Yeh, ED Kopans, DB Garrido, L TI Breast cancer: Regional blood flow and blood volume measured with magnetic susceptibility-based MR imaging - Initial results SO RADIOLOGY LA English DT Article DE breast neoplasms, diagnosis; breast neoplasms, MR; magnetic resonance (MR), perfusion study ID POSITRON EMISSION TOMOGRAPHY; CONTRAST AGENTS; SOLID TUMORS; GD-DTPA; PERMEABILITY; LESIONS; ANGIOGENESIS; EXPERIENCE; CARCINOMA; KINETICS AB The purpose of this study was to quantify microcirculation in breast neoplasms with magnetic susceptibility-based contrast material-enhanced magnetic resonance imaging. With this imaging method for invasive cancers, the mean values of the ratios of tumor to normal blood flow and blood volume were significantly higher (P < .002) than those for benign or normal tissue. The method allows independent measurement of regional blood flow and blood volume in breast cancers. (C) RSNA, 2002. C1 CSIC, Inst Ciencia & Tecnol Polimeros, Madrid 28006, Spain. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Ctr, Boston, MA 02114 USA. RP Garrido, L (reprint author), CSIC, Inst Ciencia & Tecnol Polimeros, Juan Cierva 3, Madrid 28006, Spain. RI Garrido, Leoncio/K-3092-2014; OI Garrido, Leoncio/0000-0002-7587-1260; Slanetz, Priscilla/0000-0003-1248-5116 NR 36 TC 39 Z9 42 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2002 VL 223 IS 2 BP 558 EP 565 DI 10.1148/radiol.2232010428 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 546JB UT WOS:000175270000041 PM 11997568 ER PT J AU Barkhuizen, A AF Barkhuizen, A TI Rational and targeted pharmacologic treatment of fibromyalgia SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID IRRITABLE-BOWEL-SYNDROME; PLACEBO-CONTROLLED TRIAL; CHRONIC-FATIGUE-SYNDROME; RESTLESS LEGS SYNDROME; CHRONIC NONMALIGNANT PAIN; DOUBLE-BLIND CROSSOVER; MULTIPLE CHEMICAL SENSITIVITIES; RANDOMIZED CONTROLLED TRIAL; MYOFASCIAL TRIGGER POINT; FEMALE URETHRAL SYNDROME AB Despite disappointing results when subjected to randomized clinical trials, pharmacologic agents remain an important component of fibromyalgia (FM) management. Addressing the main symptoms of pain, disturbed sleep, mood disturbances, fatigue and associated conditions are essential to improve patient functioning and enhanced quality of life. However, much work remains to design clinical trials that address the complexity of FM, while satisfying evidence-based medicine paradigms. C1 Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Barkhuizen, A (reprint author), Oregon Hlth & Sci Univ, Dept Med, OP09,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 168 TC 31 Z9 34 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 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 2002 VL 28 IS 2 BP 261 EP + AR PII S0889-857X(01)00011-4 DI 10.1016/S0889-857X(01)00011-4 PG 31 WC Rheumatology SC Rheumatology GA 569LK UT WOS:000176603700006 PM 12122917 ER PT J AU Harris, JG Young, DA Rojas, DC Cajade-Law, A Scherzinger, A Nawroz, S Adler, LE Cullum, CM Simon, J Freedman, R AF Harris, JG Young, DA Rojas, DC Cajade-Law, A Scherzinger, A Nawroz, S Adler, LE Cullum, CM Simon, J Freedman, R TI Increased hippocampal volume in schizophrenics' parents with ancestral history of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article ID STRUCTURAL BRAIN ABNORMALITIES; CEREBRAL VENTRICULAR SIZE; TWINS DISCORDANT; REDUCTION; DYSFUNCTION; PATHOLOGY; SIBLINGS; BIRTH AB Objective: Decreased hippocampal volume is one of the hypothesized pathological features of schizophrenia, but it is not known if this abnormality is familially transmitted. The aim of this study was to measure the hippocampal volume of the parents of schizophrenic probands. in relationship to the apparent transmission of genetic risk. Method: Eighteen subjects from families consisting of a schizophrenic proband and two clinically unaffected parents were studied. Probands were compared to six control subjects, matched for age, sex, and educational level. The six families were selected so that only one parent had an ancestral family history of schizophrenia. The volumes of both hippocampi were measured by magnetic resonance imaging and adjusted for age and whole brain volume. Results: The total hippocampal volumes of the parents with ancestral family history of schizophrenia were significantly larger than those of their schizophrenic offspring. Conclusions: This study suggests that decreased hippocampal volume in schizophrenia is not a familially transmitted abnormality. Rather, it appears that clinically unaffected parents who transmit apparent genetic risk for schizophrenia may have increased hippocampal volume, which may be a protective factor against the illness. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Radiol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Aurora Community Mental Hlth Ctr, Aurora, CO 80014 USA. RP Harris, JG (reprint author), Univ Colorado, Sch Med, Dept Psychiat, C268-71,4200 E 9th Ave, Denver, CO 80262 USA. RI Rojas, Don/F-4296-2012; OI Rojas, Don/0000-0001-6560-9616 NR 34 TC 15 Z9 15 U1 4 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY 1 PY 2002 VL 55 IS 1-2 BP 11 EP 17 AR PII S0920-9964(01)00272-9 DI 10.1016/S0920-9964(01)00272-9 PG 7 WC Psychiatry SC Psychiatry GA 546ZQ UT WOS:000175307500002 PM 11955959 ER PT J AU Christou, H Serdy, S Mantzoros, CS AF Christou, H Serdy, S Mantzoros, CS TI Leptin in relation to growth and developmental processes in the fetus SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE leptin; fetus; growth ID CORD-BLOOD LEPTIN; POLYCYSTIC OVARIAN SYNDROME; PLACENTAL LEPTIN; FETAL GROWTH; GESTATIONAL PROFILE; INTRAUTERINE GROWTH; LUTEINIZING-HORMONE; RECOMBINANT LEPTIN; MISSENSE MUTATION; MATERNAL SMOKING AB Leptin, a 16-kilodalton protein secreted by the adipose tissue in proportion to the amount of energy stored in adipose tissue, conveys to the hypothalamus information on energy homeostasis and regulates reproductive function. In addition, there is accumulating evidence that leptin produced by placental or fetal tissues acts through specific leptin receptors to regulate fetal growth and development. Although leptin levels are correlated with insulin and insulin-like growth factor (IGF)-1 levels, observational studies in humans indicate that its effects on fetal growth are independent of these axes and of adiposity. The extent to which leptin per se mediates the fetal growth and developmental abnormalities associated with disease states such as diabetes, hypoxia, or preeclampsia remains to be fully clarified by future studies in humans. It is hoped that clarification of these mechanisms may provide novel therapeutic approaches. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Deaconess Med Ctr, Div Endocrinol,Dept Internal Med, Boston, MA USA. RP Mantzoros, CS (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, RN 325,99 Brookline Ave, Boston, MA 02215 USA. NR 66 TC 18 Z9 18 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD MAY PY 2002 VL 20 IS 2 BP 123 EP 129 DI 10.1055/s-2002-32503 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 570CL UT WOS:000176640600007 PM 12087497 ER PT J AU Beltran, J Bencardino, J Padron, M Shankman, S Beltran, L Ozkarahan, G AF Beltran, J Bencardino, J Padron, M Shankman, S Beltran, L Ozkarahan, G TI The middle glenohumeral ligament: normal anatomy, variants and pathology SO SKELETAL RADIOLOGY LA English DT Review DE glenohumeral ligaments; MRI; MR arthrography; shoulder MRI; middle glenohumeral ligament ID MR ARTHROGRAPHY; CAPSULAR MECHANISM; GLENOID LABRUM; BICEPS TENDON; ROTATOR CUFF; SLAP LESIONS; SHOULDER; COMPLEX; JOINT; DISLOCATION AB The middle glenohumeral ligament frequently presents variations of the normal anatomy and it is often injured in patients suffering trauma to the glenohumeral joint. The purpose of this pictorial assay is to illustrate the normal anatomy, biomechanics, normal variants and pathology of the middle glenohumeral ligament, as shown on MRI and MR arthrography of the shoulder. C1 Maimonides Hosp, Dept Radiol, Brooklyn, NY 11219 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Dept Radiol, Clin CEMTRO, Madrid, Spain. New York Med Coll, Valhalla, NY 10595 USA. RP Beltran, J (reprint author), Maimonides Hosp, Dept Radiol, Brooklyn, NY 11219 USA. OI Beltran, Luis/0000-0003-3627-4575 NR 34 TC 27 Z9 28 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD MAY PY 2002 VL 31 IS 5 BP 253 EP 262 DI 10.1007/s00256-002-0492-1 PG 10 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 557EF UT WOS:000175894600001 PM 11981601 ER PT J AU Hug, EB Muenter, MW Adams, JA de Vries, A Rosenberg, AE Munzenrider, JE AF Hug, EB Muenter, MW Adams, JA de Vries, A Rosenberg, AE Munzenrider, JE TI 3-D-conformal radiation therapy for pediatric giant cell tumors of the skull base SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Review DE giant cell tumor; base of skull neoplasms; protons; charged particle therapy; pediatric neoplasm ID SPHENOID BONE; PROTON THERAPY; RADIOTHERAPY; IRRADIATION; CHORDOMAS; CHONDROSARCOMAS; BRAIN AB Background: Giant cell tumors (GCT) of the base of skull are rare neoplasms. This report reviews the treatment of four pediatric patients presenting with aggressive giant cell tumor, using fractionated and combined, conformal proton and photon radiation therapy at Massachusetts General Hospital and Harvard Cyclotron Laboratory. Patients and Methods: Three female patients and one adolescent male, ages 10-15 years, had undergone prior, extensive surgical resection(s) and were treated for either primary (two patients) or recurrent (two patients) disease. Gross residual tumor was evident in three patients and microscopic disease suspected in one patient. Combined proton and photon radiation therapy was based on three-dimensional (3-D) planning, consisting of fractionated treatment, one fraction per day at 1.8 CGE (cobalt-gray equivalent) to total target doses of 57.6, 57.6, 59.4, and 61.2 Gy/CGE. Results: With observation times of 3.1 years, 3.3, 5.3, and 5.8 years, all four patients were alive and well and remained locally controlled without evidence of recurrent disease. Except for one patient with partial pituitary insufficiency following radiotherapy for sellar recurrent disease, thus far no late effects attributable to radiation therapy have been observed. Conclusions: 3-D-conformal radiation therapy offers a realistic chance of tumor control for aggressive giant cell tumor in the skull base, either postoperatively or at time of recurrence. Conformal treatment techniques allow the safe delivery of relatively high radiation doses in the pediatric patient without apparent increase of side effects. C1 Dartmouth Coll, Hitchcock Med Ctr, Sect Radiat Oncol, Lebanon, NH 03756 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Cyclotron Lab, Cambridge, MA USA. RP Hug, EB (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Sect Radiat Oncol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. NR 40 TC 13 Z9 14 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2002 VL 178 IS 5 BP 239 EP 244 DI 10.1007/s00066-002-0931-x PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 556QT UT WOS:000175861000001 PM 12082682 ER PT J AU Rosand, J Greenberg, SM AF Rosand, J Greenberg, SM TI Beyond hypertension: Unraveling the causes of intracerebral Hemorrhage SO STROKE LA English DT Editorial Material ID RECURRENT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Boston, MA USA. RP Rosand, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Crit Care Unit, Boston, MA 02114 USA. NR 4 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2002 VL 33 IS 5 BP 1195 EP 1196 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 549ML UT WOS:000175447900014 PM 12532961 ER PT J AU Singhal, AB Topcuoglu, MA Buonanno, FS AF Singhal, AB Topcuoglu, MA Buonanno, FS TI Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis - A diffusion-weighted magnetic resonance imaging study SO STROKE LA English DT Article DE brain infarction; diffusion; endocarditis; infection; magnetic resonance imaging; neoplasm; stroke, embolic ID NEUROLOGIC COMPLICATIONS; BACTERIAL-ENDOCARDITIS; ARTERIAL TERRITORIES; BRAIN EMBOLISM; TIME-COURSE; ECHOCARDIOGRAPHY; DIAGNOSIS; VEGETATIONS; INFARCTION; DISEASE AB Background and Purpose-Although infective endocarditis (IE) and nonbacterial thrombotic endocarditis (NBTE) are associated with cardioembolic stroke, differences in the nature of these conditions may result in differences in associated stroke patterns. We compared patterns of acute and recurrent ischemic stroke in IE and NBTE, using diffusion-weighted MRI (DWI). Methods-Using ICD-9 diagnostic codes and medical record review, we identified 362 patients (387 episodes) with IE and 14 patients with NBTE. Thirty-five patients (with 27 episodes of IE, 9 NBTE) who underwent 36 initial and 29 follow-up DWI scans were selected for this study. DWI lesion size, number, and location were compared between groups and correlated with stroke syndromes and endocarditis features. Results-DWI was abnormal in all but 2 patients. Four acute stroke patterns were identified: (1) single lesion, (2) territorial infarction, (3) disseminated punctate lesions, and (4) numerous small (<10 mm) and medium (10 to 30 mm) or large (>30 mm) lesions in multiple territories. All patients with NBTE exhibited pattern 4, whereas those with IE exhibited patterns 1, 2, 3, and 4 (6, 2, 8 and 9 episodes, respectively). Seventy-five percent of patients with pattern 3 exhibited the clinical syndrome of embolic encephalopathy. Vegetation size, valve, and organisms had no correlation with stroke patterns. Conclusion-DWI has utility in differentiating between IE and NBTE. Patients with NBTE uniformly have multiple, widely distributed, small and large strokes, whereas patients with IE exhibit a panoply of stroke patterns. C1 Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, VBK-802,55 Fruit St, Boston, MA 02114 USA. NR 36 TC 70 Z9 75 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2002 VL 33 IS 5 BP 1267 EP 1273 DI 10.1161/01.STR.0000015029.91577.36 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 549ML UT WOS:000175447900027 PM 11988602 ER PT J AU Grossmann, EM Longo, WE Virgo, KS Johnson, FE Oprian, CA Henderson, W Daley, J Khuri, SF AF Grossmann, EM Longo, WE Virgo, KS Johnson, FE Oprian, CA Henderson, W Daley, J Khuri, SF TI Morbidity and mortality of gastrectomy for cancer in department of Veterans Affairs Medical Centers SO SURGERY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the Society-of-University-Surgeons CY FEB 10-12, 2000 CL TORONTO, CANADA SP Soc Univ Surgeons ID POSITIVE GASTRIC-CARCINOMA; SURGICAL CARE; CURATIVE GASTRECTOMY; OPERATIVE MORTALITY; RISK ADJUSTMENT; QUALITY; SURVIVAL; D2; LYMPHADENECTOMY; ASCERTAINMENT AB Background. The purpose of this study was to define risk factors that predict 30-day morbidity and mortality after gastrectomy for cancer in Veterans Affairs (VA) Medical Centers. Methods. The VA National Surgical Quality Improvement Program prospectively collected data on 708 patients undergoing gastrectomy for cancer in 123 participating VA medical centers from 1991 to 1998. Independent variables included 68 preoperative patient characteristics and 12 intraoperative variables; the dependent variables were 21 defined adverse outcomes and death. Predictive models for 30-day morbidity and mortality were constructed by using stepwise logistic regression analysis. Results. The 30-day marbidity rate was 33.3% (236 of 708). The overall 30-day mortality rate was 7.6% (54 of 708). Significant positive predictors of morbidity (P < .05) included current pneumonia, American Society of Anesthesiologists class IV (threat to life), partially dependent functional status, dyspnea on minimal exertion, preoperative transfusion, extended operative time, and increasing age. Significant positive predictors of mortality (P < .05) included do not resuscitate status, prior stroke, intraoperative transfusion, preoperative weight loss, preaperative transfusion, and elevated preoperative alkaline phosphatase level. Conclusions. Risk factors predicting morbidity and mortality rates at VA hospitals after gastrectomy for gastric cancer are reported 1, using a prospectively collected, multi-institutional database. Assigning relative weights to factors associated with adverse outcomes may help improve patient care. C1 St Louis Univ, Med Ctr, Dept Surg, Sch Med, St Louis, MO 63110 USA. St Louis VA Med Ctr, St Louis, MO USA. Harvard Univ, Sch Med, Inst Hlth Policy, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Partners Healthcare Syst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA USA. RP Longo, WE (reprint author), St Louis Univ, Med Ctr, Dept Surg, Sch Med, 3635 Vista Ave, St Louis, MO 63110 USA. NR 29 TC 41 Z9 44 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2002 VL 131 IS 5 BP 484 EP 490 DI 10.1067/msy.2002.123806 PG 7 WC Surgery SC Surgery GA 550PU UT WOS:000175512100002 PM 12019399 ER PT J AU Thayer, SP Fernandez-del Castillo, C Balcom, JH Warshaw, AL AF Thayer, SP Fernandez-del Castillo, C Balcom, JH Warshaw, AL TI Complete dorsal pancreatectomy with preservation of the ventral pancreas: A new surgical technique SO SURGERY LA English DT Article ID HEAD C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thayer, SP (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 9 TC 23 Z9 24 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2002 VL 131 IS 5 BP 577 EP 580 DI 10.1067/msy.2002.123010 PG 4 WC Surgery SC Surgery GA 550PU UT WOS:000175512100018 PM 12019413 ER EF