FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Nahas, Z Kozel, FA Li, XB Anderson, B George, MS AF Nahas, Z Kozel, FA Li, XB Anderson, B George, MS TI Left prefrontal transcranial magnetic stimulation (TMS) treatment of depression in bipolar affective disorder: a pilot study of acute safety and efficacy SO BIPOLAR DISORDERS LA English DT Article DE bipolar affective disorder, repetitive transcranial magnetic stimulation-rTMS; TMS-transcranial magnetic stimulation ID DEXAMETHASONE SUPPRESSION TEST; RTMS IMPROVES MOOD; HUMAN MOTOR CORTEX; ELECTROCONVULSIVE-THERAPY; TRIAL; LAMOTRIGINE; THRESHOLD; ILLNESS; MANIA AB Objectives: Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve depressive symptoms. We designed and carried out the following left prefrontal rTMS study to determine the safety, feasibility, and potential efficacy of using TMS to treat the depressive symptoms of bipolar affective disorder (BPAD). Methods: We recruited and enrolled 23 depressed BPAD patients (12 BPI depressed state, nine BPII depressed state, two BPI mixed state). Patients were randomly assigned to receive either daily left prefrontal rTMS (5 Hz, 110% motor threshold, 8 sec on, 22 sec off, over 20 min) or placebo each weekday morning for 2 weeks. Motor threshold and subjective rating scales were obtained daily, and blinded Hamilton Rating Scale for Depression (HRSD) and Young Mania Rating Scales (YMRS) were obtained weekly. Results: Stimulation was well tolerated with no significant adverse events and with no induction of mania. We failed to find a statistically significant difference between the two groups in the number of antidepressant responders (>50% decline in HRSD or HRSD <10 - 4 active and 4 sham) or the mean HRSD change from baseline over the 2 weeks (t = -0.22, p=0.83). Active rTMS, compared with sham rTMS, produced a trend but not statistically significant greater improvement in daily subjective mood ratings post-treatment (t = 1.58, p=0.13). The motor threshold did not significantly change after 2 weeks of active treatment (t = 1.11, p=0.28). Conclusions: Daily left prefrontal rTMS appears safe in depressed BPAD subjects, and the risk of inducing mania in BPAD subjects on medications is small. We failed to find statistically significant TMS clinical antidepressant effects greater than sham. Further studies are needed to fully investigate the potential role, if any, of TMS in BPAD depression. C1 Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP Kozel, FA (reprint author), Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, 67 President St,POB 250861, Charleston, SC 29425 USA. RI Kozel, Frank/I-5366-2012 FU NIA NIH HHS [R01-AG40956] NR 48 TC 113 Z9 115 U1 1 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2003 VL 5 IS 1 BP 40 EP 47 DI 10.1034/j.1399-5618.2003.00011.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 645GF UT WOS:000180967300007 PM 12656937 ER PT J AU Gacci, M Bartoletti, R Figlioli, S Sarti, E Eisner, B Boddi, V Rizzo, M AF Gacci, M Bartoletti, R Figlioli, S Sarti, E Eisner, B Boddi, V Rizzo, M TI Urinary symptoms, quality of life and sexual function in patients with benign prostatic hypertrophy before and after prostatectomy: a prospective study SO BJU INTERNATIONAL LA English DT Article DE ICS-BPH; IPSS; IIEF; BPH; quality of life; erectile function; symptoms ID TRACT SYMPTOMS; ERECTILE DYSFUNCTION; ICS-BPH; COMMUNITY; INDEX; HYPERPLASIA AB OBJECTIVE To evaluate urinary symptoms, sexual dysfunction and quality of life in patients with benign prostatic hypertrophy (BPH) before and after open prostatectomy, using the International Prostate Symptom Score (IPSS), the International Continence Society (ICS)-'BPH' (ICS-male , ICS- sex and ICS-QoL) and International Index of Erectile Function (IIEF) questionnaires. PATIENTS AND METHODS Sixty men with BPH (mean age 68 years) underwent a digital rectal examination, transurethral ultrasonography, measurement of total prostatic specific antigen serum level and uroflowmetry. Their urinary symptoms, sexual function and quality of life were fully evaluated using the IPSS, ICS-'BPH' and IIEF before and 6 months after suprapubic prostatectomy. The body mass index (BMI) was also calculated for each patient. Univariate analysis was used to examine the relationship between symptom scores and age, tobacco use, alcohol intake and BMI. RESULTS In a univariate analysis, age was the most important prognostic factor for both urinary and sexual symptoms. Prostatectomy resulted in a significant improvement in obstructive (mean 9.68 to 3.38) and irritative symptom (6.70 to 3.06), and quality-of-life scores (3.41 to 1.34). ICS-male scores were both significantly decreased, the mean voiding score from 13.72 to 10.28 and the incontinence score from 10.43 to 7.81. There was also a significant decrease in the ICS- QoL symptom score (from 9.20 to 7.27). Comparative results between IIEF and ICS- sex showed no improvement in sexual scores after open surgery, but there was a significant increase in sexual desire and overall satisfaction (both P = 0.035). CONCLUSIONS The combined use of the IPSS, ICS-'BPH' and IIEF allows an evaluation of the relationship between age, prostatic symptoms and sexual dysfunction. Age may be considered both a direct and indirect (BPH-related) prognostic factor for sexual activity. Suprapubic prostatectomy resolves obstructive symptoms, and maintains sexual desire, overall sexual satisfaction and an improvement in quality of life. However, irritative symptoms, erection, orgasm and sexual intercourse satisfaction are not significantly altered. C1 Univ Florence, Dept Urol, I-50132 Florence, Italy. Univ Florence, Dept Stat, I-50132 Florence, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Cambridge, MA 02138 USA. RP Gacci, M (reprint author), Univ Florence, Dept Urol, V Masaccio N102, I-50132 Florence, Italy. OI Gacci, Mauro/0000-0001-7877-221X; Bartoletti, Riccardo/0000-0002-0021-0302 NR 17 TC 57 Z9 63 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2003 VL 91 IS 3 BP 196 EP 200 DI 10.1046/j.1464-4096.2003.04072.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 642PK UT WOS:000180812700009 PM 12581003 ER PT J AU Molrine, DC Antin, JH Guinan, EC Soiffer, RJ MacDonald, K Malley, R Malinoski, F Trocciola, S Wilson, M Ambrosino, DM AF Molrine, DC Antin, JH Guinan, EC Soiffer, RJ MacDonald, K Malley, R Malinoski, F Trocciola, S Wilson, M Ambrosino, DM TI Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; EPSTEIN-BARR-VIRUS; INFECTIONS; RECIPIENTS; POLYSACCHARIDE; IMMUNITY; IMMUNOGENICITY; ANTIGEN; GRAFT AB Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk for infections with Streptococcus pneumoniae and have long-lasting, impaired antibody responses to pneumococcal polysaccharide vaccines. We examined whether donor immunization With a heptavalent pneumococcal conjugate vaccine (PCV7) Would elicit protective antibody responses to additional doses of vaccine administered early after transplantation. Ninety-six patients scheduled to receive an allogeneic hematopoietic cell transplant were randomized with their donors to receive either a dose of PCV7 vaccine or no vaccine before transplantation. All patients received PCV7 at 3 months, 6 months, and 12 months following transplantation, and serotype-specific antibody concentrations were determined after each dose. Following HCT, geometric mean antibody concentrations of patients in the immunized donor group were significantly higher for 5 of the 7 vaccine serotypes after one dose P < .05) and for 4 of the 7 serotypes after 2 doses of vaccine. (P < .03). Sixty-seven percent of patients in the immunized donor group had presumed protective IgG concentrations more than or equal to 0.50 mug/mL to all 7 serotypes following the first dose of vaccine compared to 36% in the unimmunized donor group (P = .05). After the third dose of vaccine, both groups had more than 60% of patients with concentrations at least 0.50 mug/mL to all vaccine serotypes. Donor immunization enhances early antibody responses of patients undergoing HCT to pneumococcal conjugate vaccine. A 3-dose schedule of PCV7 vaccine at 3, 6, and 12 months is immunogenic in these patients regardless of donor immunization. (C) 2003 by The American Society of Hematology. C1 Univ Massachusetts, Sch Med, Massachusetts Biol Labs, Jamaica Plain, MA 02130 USA. Wyeth Pharmaceut, St Davids, PA USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol & Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Molrine, DC (reprint author), Univ Massachusetts, Sch Med, Massachusetts Biol Labs, 305 South St, Jamaica Plain, MA 02130 USA. FU NIAID NIH HHS [P01 AI 41584] NR 32 TC 57 Z9 59 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 831 EP 836 DI 10.1182/blood-2002-03-0832 PG 6 WC Hematology SC Hematology GA 640GG UT WOS:000180679700007 PM 12393732 ER PT J AU Park, H Shelley, CS Arnaout, MA AF Park, H Shelley, CS Arnaout, MA TI The zinc finger transcription factor ZBP-89 is a repressor of the human beta(2)-integrin CD11b gene SO BLOOD LA English DT Article ID DNA-BINDING PROTEINS; EVEN-SKIPPED PROTEIN; ADHESION MOLECULES; REGULATED EXPRESSION; NEGATIVE REGULATION; PROMOTER ACTIVITY; MYELOID CELLS; RECEPTOR GENE; ACTIVATION; DIFFERENTIATION AB Integrin CD11b is a differentiation marker of the myelomonocytic lineage and an important mediator of inflammation. Expression of the CD11b gene is transcriptionally induced as myeloid precursors differentiate into mature cells, then drops as monocytes further differentiate into macrophages. Previous studies have identified elements and factors involved in the transcriptional activation of the CD11b gene during myeloid differentiation, but no data exist regarding potential down-regulatory factors, especially in the later stages of differentiation. Using 2 copies of a GC-rich element (-141 to -110) in the CD11b promoter, we probed a cDNA expression library for interacting proteins. Three clones were identified among 9.1 million screened, all encoding the DNA-binding domain of the zinc finger factor ZBP-89. Overexpression of ZBP-89 in the monocyte precursor cell line U937 reduced CD11b promoter-driven luciferase activity when U937 cells were induced to differentiate into monocyte-like cells using phorbol esters. To identify the differentiation stage at which ZBP-89 repression of the CD11b gene is exerted, the protein level of ZBP-89 was correlated with that of CD11b mRNA in differentiating U937 as well as in normal human monocytes undergoing in vitro differentiation into macrophages. A clear inverse relationship was observed in the latter but not the former state, suggesting that ZBP-89 represses CD11b gene expression during the further differentiation of monocytes into macrophages. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Leukocyte Biol & Inflammat Program, Boston, MA USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK50779, DK50305] NR 60 TC 23 Z9 28 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 894 EP 902 DI 10.1182/blood-2002-03-0680 PG 9 WC Hematology SC Hematology GA 640GG UT WOS:000180679700016 PM 12393719 ER PT J AU Heck, S Ermakova, O Iwasaki, H Akashi, K Sun, CW Ryan, TM Townes, T Graf, T AF Heck, S Ermakova, O Iwasaki, H Akashi, K Sun, CW Ryan, TM Townes, T Graf, T TI Distinguishable live erythroid and myeloid cells in beta-globin ECFP x lysozyme EGFP mice SO BLOOD LA English DT Article ID FLUORESCENT PROTEIN; TRANSGENE; LINEAGE; PROGENITORS; STEM AB We previously described a mouse line that contains green myelomonocytic cells due to the knock-in of enhanced green fluorescence protein (EGFP) into the lysozyme M gene.(1) We have,now created a transgenic line with fluorescent erythroid cells using a beta-globin locus control region driving the enhanced cyan fluorescence protein (ECFP) gene. These mice exhibit cyan fluorescent cells specifically in the erythroid compartment and in megakaryocyte-erythroid progenitors. Crossing the animals with lysozyme EGFP mice yielded a line in which live erythroid and myeloid cells can readily be distinguished by fluorescence microscopy and by fluorescence-activated cell-sorter scanner. This cross allowed unambiguous identification of unstained mixed erythroid-myeloid colonies for the first time. The new mouse lines should become useful tools to dissect the branching between erythroid and myelomonocytic cells during in vitro differentiation of definitive multipotent progenitors. (C) 2003 by The American Society of Hematology. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol & Dev Biol, Bronx, NY 10461 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. RP Graf, T (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol & Dev Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Graf, Thomas/B-4252-2015; OI Graf, Thomas/0000-0003-2774-4117; Ermakova, Olga/0000-0001-8365-4904 FU NCI NIH HHS [R01 CA89590-01] NR 18 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 903 EP 906 DI 10.1182/blood-2002-06-1861 PG 4 WC Hematology SC Hematology GA 640GG UT WOS:000180679700017 PM 12393544 ER PT J AU Grader-Beck, T van Puijenbroek, AAFL Nadler, LM Boussiotis, VA AF Grader-Beck, T van Puijenbroek, AAFL Nadler, LM Boussiotis, VA TI cAMP inhibits both Ras and Rap1 activation in primary human T lymphocytes, but only Ras inhibition correlates with blockade of cell cycle progression SO BLOOD LA English DT Article ID PROTEIN-KINASE-A; DEPENDENT ACTIVATION; INTERLEUKIN-2 TRANSCRIPTION; GENE-EXPRESSION; PLASMA-MEMBRANE; MAP KINASE; IL-2 GENE; B-RAF; AMP; PATHWAY AB Cyclic adenosine monophosphate (cAMP) is a negative regulator of T-cell activation. However, the effects of cAMP on signaling pathways that regulate cytokine production and cell cycle progression remain unclear. Here, using primary human T lymphocytes in which endogenous cAMP was increased by the use of forskolin and 3-isobutyl-1-methylxanthine (IBMX), we show that increase of cAMP resulted in inhibition of T-cell receptor (TCR)/CD3 plus CD28-mediated T-cell activation and cytokine production and blockade of cell cycle progression at the G, phase. Increase of cAMP inhibited Ras activation and phosphorylation of mitogen-induced extracellular kinase (MEK) downstream targets extracellular signal-related kinase 1/2 (ERK1/2) and phosphatidylinositol-3-kinase (PI3K) downstream target protein kinase B (PKB; c-Akt). These functional and biochemical events were secondary to the impaired activation of ZAP-70 and phosphorylation of LAT and did not occur when cells were stimulated with phorbol ester, which bypasses the TCR proximal signaling events and activates Ras. Increase of cAMP also inhibited activation of Rap1 mediated by TCR/CD3 plus CD28. Importantly, inhibition of Rap1 activation by cAMP was also observed when cells were stimulated with phorbol ester, although under these conditions Ras was activated and cells progressed into the cell cycle. Thus, TCR plus CD28-mediated activation of ERK1/2 and PKB, cytokine production, and cell cycle progression, all of which are inhibited by cAMP, require activation of Ras but not Rap1. These results indicate that signals that regulate cAMP levels after encounter of T cells by antigen will likely determine the functional fate toward clonal expansion or repression of primary T-cell responses. (C) 003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer 547,44 Binney St, Boston, MA 02115 USA. EM vassiliki_boussiotis@dfci.harvard.edu FU NIAID NIH HHS [AI 43552, AI 46548] NR 56 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 998 EP 1006 DI 10.1182/blood-2002-06-1665 PG 9 WC Hematology SC Hematology GA 640GG UT WOS:000180679700032 PM 12393539 ER PT J AU Astier, AL Xu, RH Svoboda, M Hinds, E Munoz, O de Beaumont, R Crean, CD Gabig, T Freedman, AS AF Astier, AL Xu, RH Svoboda, M Hinds, E Munoz, O de Beaumont, R Crean, CD Gabig, T Freedman, AS TI Temporal gene expression profile of human precursor B leukemia cells induced by adhesion receptor: identification of pathways regulating B-cell survival SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FOCAL TYROSINE KINASE; STROMAL CELLS; SIGNALING PATHWAY; SHORT TRANSCRIPTS; DIRECT INHIBITOR; FAMILY PROTEINS; BINDING-PROTEIN; RT-PCR; APOPTOSIS AB The physical interactions between B cells and stromal cells from the lymphoid tissue microenvironment are critical to the survival of normal and malignant B cells. They are principally mediated by integrins expressed on B cells and counterreceptors on stromal cells. Specifically, alpha4beta1 integrin engagement rescues B cells from physiological or drug-induced apoptosis. Therefore, in order to understand the mechanisms by which integrins prevent apoptosis in leukemia B cells, we compared the temporal gene expression profiles induced by beta1-integrin ligation with fibronectin (Fn) or adhesion by poly-L-Lysine in serum-starved precursor B leukemia cells. Among the 38 selected differentially expressed genes, 6 genes involved in adhesion (VAV2, EPB41L1, CORO1A), proliferation (FRAP1, CCT4), and intercellular communication (GJB3) were validated by real-time quantitative polymerase chain reaction (RT-Q-PCR). Gene expression modulation could also be validated at the protein level for 5 other genes. We show that integrin stimulation up-regulated FBI-1 expression but inhibited CD79a, Requiem, c-Fos, and caspase 7 induction when the cells underwent apoptosis. We further demonstrate that Fn stimulation also inhibits caspase 3 activation but increases XIAP and survivin expression. Moreover, integrin stimulation also prevents caspase activation induced by doxorubicin. Therefore, we identified genes modulated by adhesion of human precursor B leukemia cells that regulate proliferation and apoptosis, highlighting new pathways that might provide insights into future therapy aiming at targeting apoptosis of leukemia cells. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46204 USA. Long Isl Jewish Hlth Syst, Biomed Res Inst, Manhasset, NY USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 FU NCI NIH HHS [CA06516, CA81494] NR 55 TC 25 Z9 28 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2003 VL 101 IS 3 BP 1118 EP 1127 DI 10.1182/blood-2002-05-1519 PG 10 WC Hematology SC Hematology GA 640GG UT WOS:000180679700047 PM 12393420 ER PT J AU Caplan, D Waters, G AF Caplan, D Waters, G TI On-line syntactic processing in aphasia: Studies with auditory moving window presentation SO BRAIN AND LANGUAGE LA English DT Article ID SENTENCE COMPREHENSION; LEXICAL DECISION; WORKING-MEMORY; LANGUAGE COMPREHENSION; INDIVIDUAL-DIFFERENCES; AMBIGUITY RESOLUTION; AGRAMMATISM; COMPLEXITY; TIME; DETERMINANTS AB Twenty-eight aphasic patients with left hemisphere strokes and matched control subjects were tested on an auditory moving windows task in which successive phrases of a sentence were presented in response to subjects' self-paced button presses and subjects made timed judgments regarding the plausibility of each sentence. Pairs of sentences were presented that differed in syntactic complexity. Patients made more errors and/or took longer in making the plausibility judgments than controls, and were more affected than controls by the syntactic complexity of a sentence in these judgments. Normal subjects showed effects of syntactic structure in self-paced listening. On-line syntactic effects differed in patients as a function of their comprehension level. High-performing patients showed the same effects as normal control subjects; low performing patients did not show the same effects of syntactic structure. On-line syntactic effects also differed in patients as a function of their clinical diagnosis. Broca's aphasic patients' on-line performances suggested that they were not processing complex syntactic structures on-line, while fluent aphasics' performances suggested that their comprehension impairment occurred after on-line processing was accomplished. The results indicate that many aphasic patients retain their ability to process syntactic structure on-line, and that different groups of patients with syntactic comprehension disorders show different patterns of on-line syntactic processing. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. NR 48 TC 32 Z9 33 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD FEB PY 2003 VL 84 IS 2 BP 222 EP 249 AR PII S0093-934X(02)00514-X DI 10.1016/S0093-934X(02)00514-X PG 28 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 651BH UT WOS:000181300000005 PM 12590913 ER PT J AU Sasaki, H Yu, CY Dai, MR Tam, C Loda, M Auclair, D Chen, LB Elias, A AF Sasaki, H Yu, CY Dai, MR Tam, C Loda, M Auclair, D Chen, LB Elias, A TI Elevated serum periostin levels in patients with bone metastases from breast but not lung cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE bone metastasis; cell adhesion; tumor invasion ID GROWTH-FACTOR-BETA; HORMONE-RELATED PROTEIN; METABOLIC MARKERS; PROGNOSTIC MARKER; SEQUENCE-ANALYSIS; FASCICLIN-I; EXPRESSION; ADHESION; SIALOPROTEIN; BETA-IG-H3 AB Periostin is a recently identified gene that is preferentially expressed in periosteum, indicating a potential role in bone formation and maintenance of structure. We independently identified and isolated periostin from cancer tissue, using the palindromic PCR-driven cDNA Differential Display technique. For the present work, we developed a novel sandwich chemiluminescence assay to detect serum periostin level using newly developed monoclonal and polyclonal antibodies. We investigated serum periostin levels in breast cancer and small cell lung cancer patients, especially in patients with bone metastasis. The study included 58 breast cancer and 44 small cell lung cancer patients. Serum periostin levels were elevated in breast cancer patients presenting with bone metastases (92.0 +/- 28.6 ng/ml) compared to similar breast cancer patients without evidence of bone metastasis (55.0 +/- 16.6 ng/ml, p = 0.04). No correlation was found between the serum periostin level and any other prognostic factors, such as clinical stage and lymph node metastasis in breast cancer. Serum periostin levels thus appear to serve as a marker of bone metastasis from breast cancer. In contrast, serum periostin levels were similar in samples from patients with small cell lung cancer who did or did not have bone metastasis. However, increasing T-stage and N-stage of patients with small cell lung cancer were correlated with higher periostin levels (T4, 126.5 +/- 29.7 ng/ml v.s. T2, 64.9 +/- 16.1 ng/ml, p = 0.03; and T4 v.s. T1, 36.3 +/- 7.5 ng/ml, p = 0.01; N3, 108.7 +/- 17.3 ng/ml v.s. N2, 49.7 +/- 10.9 ng/ml, p = 0.01). Periostin has a substantial homology with the insect cell adhesion molecule, fasciclin I. Thus, expression of periostin may facilitate tumor cell adhesion to the bone surface. In fact, we found by in situ RNA hybridization, that the periostin gene was highly expressed in the stromal cells immediately surrounding the tumor, but not within the breast cancer cells themselves. C1 Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Canc Biol, Cambridge, MA 02138 USA. RP Sasaki, H (reprint author), Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, 1 Kawasumi,Mizuho Cho, Nagoya, Aichi 4678601, Japan. NR 29 TC 92 Z9 95 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2003 VL 77 IS 3 BP 245 EP 252 DI 10.1023/A:1021899904332 PG 8 WC Oncology SC Oncology GA 631MD UT WOS:000180170800006 PM 12602924 ER PT J AU Santucci, M Pimpinelli, N Massi, D Kadin, ME Meijer, CJLM Muller-Hermelink, HK Paulli, M Wechsler, J Willemze, R Audring, H Bernengo, MG Cerroni, L Chimenti, S Chott, A Diaz-Perez, JL Dippel, E Duncan, LM Feller, AC Geerts, ML Hallermann, C Kempf, W Russell-Jones, R Sander, C Berti, E AF Santucci, M Pimpinelli, N Massi, D Kadin, ME Meijer, CJLM Muller-Hermelink, HK Paulli, M Wechsler, J Willemze, R Audring, H Bernengo, MG Cerroni, L Chimenti, S Chott, A Diaz-Perez, JL Dippel, E Duncan, LM Feller, AC Geerts, ML Hallermann, C Kempf, W Russell-Jones, R Sander, C Berti, E TI Cytotoxic/natural killer cell cutaneous lymphomas - Report of the EORTC Cutaneous Lymphoma Task Force Workshop SO CANCER LA English DT Review DE cytotoxic/NK cell lymphomas; skin; classification; CD56; TIA-1; prognosis; therapy ID CYTOPHAGIC HISTIOCYTIC PANNICULITIS; LARGE GRANULAR LYMPHOCYTES; INTRAVASCULAR MALIGNANT LYMPHOMATOSIS; RENAL-ALLOGRAFT RECIPIENT; MYCOSIS-FUNGOIDES; HEMOPHAGOCYTIC SYNDROME; PHENOTYPIC CHARACTERIZATION; CLINICOPATHOLOGICAL ENTITY; ANGIOTROPIC LYMPHOMA; SUBCUTANEOUS TISSUE AB BACKGROUND. Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS. This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS. Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS. Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded. Cancer 2003;97:610-27. (C) 2003 American Cancer Society. C1 Univ Florence, Sch Med, Dept Human Pathol & Oncol, I-50134 Florence, Italy. Univ Florence, Sch Med, Dept Dermatol Sci, Florence, Italy. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol,Sect Hematopathol, Boston, MA 02115 USA. Free Univ Amsterdam Hosp, Dept Pathol, Amsterdam, Netherlands. Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. IRCCS San Matteo Hosp, Dept Pathol, Pavia, Italy. Hop Henri Mondor, Dept Pathol, Paris, France. Leiden Univ, Dept Dermatol, Leiden, Netherlands. Humboldt Univ, Charite, Dept Dermatol, Berlin, Germany. Univ Turin, Dept Dermatol, Turin, Italy. Graz Univ, Dept Dermatol, Graz, Austria. Univ Roma Tor Vergata, Dept Dermatol, Rome, Italy. Univ Vienna, Inst Clin Pathol, Vienna, Austria. Univ Bilbao, Cruces Hosp, Dept Dermatol, Bilbao, Spain. Benjamin Franklin Univ Hosp, Dept Dermatol, Berlin, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02115 USA. Med Univ Lubeck, Inst Pathol, D-23538 Lubeck, Germany. State Univ Ghent Hosp, Dept Dermatol, B-9000 Ghent, Belgium. Univ Gottingen, Dept Dermatol, D-3400 Gottingen, Germany. Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. St Thomas Hosp, Skin Tumour Unit, St Johns Inst Dermatol, London, England. Univ Munich, Dept Dermatol, D-8000 Munich, Germany. Univ Milan, Inst Dermatol Sci, Milan, Italy. RP Santucci, M (reprint author), Univ Florence, Sch Med, Dept Human Pathol & Oncol, Viale GB Morgagni 85, I-50134 Florence, Italy. RI Berti, Emilio/F-5256-2012 NR 101 TC 133 Z9 148 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2003 VL 97 IS 3 BP 610 EP 627 DI 10.1002/cncr.11107 PG 18 WC Oncology SC Oncology GA 637WH UT WOS:000180536400011 PM 12548603 ER PT J AU Goggins, WB Tsao, H AF Goggins, WB Tsao, H TI A population-based analysis of risk factors for a second primary cutaneous melanoma among melanoma survivors SO CANCER LA English DT Article DE Surveillance, Epidemilogy, and End Results (SEER); second tumor; cutaneous melanoma; Cox proportional hazards model; epidemiology ID MULTIPLE PRIMARY MELANOMAS; MALIGNANT-MELANOMA; CDKN2A MUTATIONS; FAMILIES; CANCERS AB BACKGROUND. The results of several studies have provided evidence that patients diagnosed with cutaneous melanoma (CM) are at a higher risk of developing a second primary CM than the general population. In this study, the authors examined how the risk of a second primary tumor varied with time from diagnosis of CM and examined the patient- specific factors that modify a CM patient's risk of developing a second primary tumor. METHODS. Survival curves for time from first CM to second CM were calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to determine which demographic- and disease-related factors influence the risk of a second CM. RESULTS. Approximately 0.5% of Surveillance, Epidemiology, and End Results (SEER) CM patients were found to have synchronous second primaries. The estimated cumulative probability of having a second primary CM was 0.99% at 1 year after initial CM diagnosis, 2.06% at 5 years, 3.17% at 10 years, and 5.34% at 20 years. Risk was significantly greater for males; older patients; patients with first CM on the face, neck, or trunk; those from the Atlanta, Hawaii, or Connecticut registries; and more recently diagnosed patients. Risk was lower for patients from the Utah registry and those with Stage IV disease. CONCLUSIONS. The elevated risk for CM among CM survivors appears to be greatest in the first few months, and then subsequently declines. However, the risk for a second CM among CM survivors was found to remain substantially higher than the risk for a first CM in the general population throughout the observation period (> 20 years). Demographic- and disease-related factors substantially modify the risk of a second primary CM. Cancer 2003;97:639-43. (C) 2003 American Cancer Society. C1 Hong Kong Baptist Univ, Dept Math, Kowloon, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Dept Dermatol, MGH Melanoma Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Goggins, WB (reprint author), Hong Kong Baptist Univ, Dept Math, Kowloon, Hong Kong, Peoples R China. NR 15 TC 59 Z9 60 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2003 VL 97 IS 3 BP 639 EP 643 DI 10.1002/cncr.11116 PG 5 WC Oncology SC Oncology GA 637WH UT WOS:000180536400013 PM 12548605 ER PT J AU Smith, MR AF Smith, MR TI Diagnosis and management of treatment-related osteoporosis in men with prostate carcinoma SO CANCER LA English DT Article; Proceedings Paper CT 3rd North American Symposium on Skeletal Complications of Malignancy CY APR 25-27, 2002 CL BETHESDA, MARYLAND SP Paget Fdn DE androgen deprivation therapy; bicalutamide; bisphosphonate; fracture; gonadotropin-releasing hormone agonist; osteoporosis ID BONE-MINERAL DENSITY; ANDROGEN-DEPRIVATION THERAPY; X-RAY ABSORPTIOMETRY; OLDER MEN; HORMONE AGONISTS; AROMATASE DEFICIENCY; RANCHO BERNARDO; SEX STEROIDS; VITAMIN-D; CANCER AB Osteoporosis is a complication of androgen deprivation therapy in men with prostate carcinoma. Androgen deprivation therapy, caused by either bilateral orchiectomy or treatment with a gonadotropin-releasing hormone agonist, decreases bone mineral density and increases fracture risk. Other factors including diet and lifestyle may contribute to bone loss. There is limited information regarding the best strategy to prevent osteoporosis in men with prostate carcinoma. Lifestyle modification including smoking cessation, moderation of alcohol consumption, and regular weight-bearing exercise should be encouraged. Supplemental calcium and vitamin D are also recommended. Additional treatment may be warranted for men with osteoporosis, fractures, or high rates of bone loss during androgen deprivation therapy. Intravenous pamidronate, a second-generation bisphosphonate, prevents bone loss during androgen deprivation therapy. Zoledronic acid, a more potent third-generation bisphosphonate, not only prevents bone loss but also increases bone mineral density during androgen deprivation therapy. Other bisphosphonates may be effective although they have not been evaluated in this clinical setting. Treatment with estrogens or selective estrogen receptor modulators may also be effective. Monotherapy with bicalutamide or other antiandrogens may cause less bone loss than androgen deprivation therapy. (C) 2003 American Cancer Society. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 61 TC 47 Z9 48 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2003 VL 97 IS 3 SU S BP 789 EP 795 DI 10.1002/cncr.11149 PG 7 WC Oncology SC Oncology GA 640BK UT WOS:000180666300011 PM 12548577 ER PT J AU Anderson, KC AF Anderson, KC TI Moving disease biology from the lab to the clinic SO CANCER LA English DT Article; Proceedings Paper CT 3rd North American Symposium on Skeletal Complications of Malignancy CY APR 25-27, 2002 CL BETHESDA, MARYLAND SP Paget Fdn DE multiple myeloma; proteasome inhibitor; thalidomide; immunomodulatory derivative; NF-kappa B ID MULTIPLE-MYELOMA CELLS; INDUCED APOPTOSIS; DRUG-RESISTANCE; BONE-MARROW; INTERLEUKIN-6; THALIDOMIDE; GROWTH; TUMOR; EXPRESSION; ACTIVATION AB Multiple myeloma (MM) cells home to and adhere to extracellular matrix proteins and to bone marrow stromal cells (BMSCs); and in the BM microenvironment, grow, survive, resist drugs, and migrate under the influence of cytokines including interleukin-6, vascular endothelial growth factor, tumor necrosis factor a, and insulin-like growth factor (IGF)-1. Proliferation is via the Ras/Raf MAPK cascade, drug resistance via P13-K/Akt signaling, and migration via PKC dependent pathways. Novel therapies that target not only the MM cell, but also the BM microenvironment, can overcome drug resistance in vitro and in vivo in murine human MM models. For example, immunomodulatory derivatives of thalidomide (IMiDs) and the proteasome inhibitor PS-341 both induce apoptosis of MM cell lines and patient cells refractory to melphalan, doxorubicin, and dexamethasone; abrogate MM cell binding to fibronectin and BMSCs and related protection against immune- and drug-induced apoptosis; block production of cytokines which promote MM cell growth, survival, drug resistance, and migration; inhibit angiogenesis; and stimulate host anti-tumor immunity. In the setting of relapsed refractory MM, a Phase I trial of the IMiD CC5013 shows stable paraprotein or better in 20 of 24 (79%) patients, with a favorable toxicity profile. In this same patient population 85% of 54 patients treated in a Phase II trial of PS-341 achieved either paraprotein response (50%) or stable disease (35%). Cellular and gene microarray studies comparing PS-341 and an IkappaB kinase inhibitor, PS-1145, suggest that selective NF-kappaB blockade cannot account for all the anti-MM activity of PS-341. Finally, cellular and signaling studies provide the preclinical rationale for combining these novel agents with conventional therapies, or with each other, to enhance efficacy. These novel therapeutics therefore represent a new treatment paradigm in MM targeting the tumor cell in its microenvironment to overcome classical drug resistance and improve patient outcome. Future studies should define the utility of these agents as primary therapy, treatment for first relapse, and maintenance therapy. (C) 2003 American Cancer Society. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378, R0-1 50947] NR 29 TC 60 Z9 61 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 1 PY 2003 VL 97 IS 3 SU S BP 796 EP 801 DI 10.1002/cncr.11137 PG 6 WC Oncology SC Oncology GA 640BK UT WOS:000180666300012 PM 12548578 ER PT J AU Shannon, J Cook, LS Stanford, JL AF Shannon, J Cook, LS Stanford, JL TI Dietary intake and risk of postmenopausal breast cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE diet; food groups; postmenopausal breast cancer ID VITAMIN-D; PROSPECTIVE COHORT; FATTY-ACIDS; MAMMARY; CAROTENOIDS; CARCINOGENESIS; MUTAGENESIS; CONSUMPTION; PRODUCTS; HEALTH AB Objectives: While there is good evidence from cell-culture and animal studies to indicate that dietary intake impacts breast cancer risk, results of epidermologic studies have been inconsistent. Additionally, while the etiology of breast cancer in premenopausal versus postmenopausal women may be quite different, most studies have not chosen to focus solely on one group or the other. In this case-control Study, we evaluate the associations between red meat, fish, dairy products, and fruits and vegetables, and risk of breast cancer in postmenopausal women. Methods: A food-frequency questionnaire was completed by 441 women with in-situ or invasive breast cancer and 370 population controls. Cases were identified from the population-based Cancer Surveillance System (CSS) of western Washington and frequency age-matched controls identified by random-digit dialing (RDD). Unconditional logistic regression was used to model the association between each food grouping and breast cancer risk adjusting for age, number of pregnancies, and education. Results: Red meat intake was significantly associated with an increased breast cancer risk (p for trend = 0.002) and fish (including fried fish) and dairy product intake was inversely associated with breast cancer risk (l) for trend = 0.04 and 0.05, respectively). No significant associations were noted betwen fruit or vegetable intake and breast cancer risk. Conclusions: The findings from this study support the results of several larger cohort studies and contribute to the evidence for the development of dietary recommendations for breast cancer risk reduction specific to postmenopausal women. C1 Portland VA Med Ctr, Portland, OR 97201 USA. Univ Calgary, Dept Community Hlth Sci, Calgary, AB T2N 4N1, Canada. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. RP Shannon, J (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,P2-HSRD, Portland, OR 97201 USA. FU NCI NIH HHS [K07-CA01364, N01-CN-05230, R35-CA39779] NR 46 TC 40 Z9 40 U1 1 U2 10 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD FEB PY 2003 VL 14 IS 1 BP 19 EP 27 DI 10.1023/A:1022506507984 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 670KA UT WOS:000182405600003 PM 12708721 ER PT J AU Armstrong, SA Kung, AL Mabon, ME Silverman, LB Stam, RW Den Boer, ML Pieters, R Kersey, JH Sallan, SE Fletcher, JA Golub, TR Griffin, JD Korsmeyer, SJ AF Armstrong, SA Kung, AL Mabon, ME Silverman, LB Stam, RW Den Boer, ML Pieters, R Kersey, JH Sallan, SE Fletcher, JA Golub, TR Griffin, JD Korsmeyer, SJ TI Inhibition of FLT3 in MLL: Validation of a therapeutic target identified by gene expression based classification SO CANCER CELL LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; LYMPHOMA CELL-LINES; CHROMOSOMAL REARRANGEMENT; PHILADELPHIA-CHROMOSOME; RETROVIRAL VECTORS; BREAST-CANCER AB We recently found that MLL-rearranged acute lymphoblastic leukemias (MLL) have a unique gene expression profile including high level expression of the receptor tyrosine kinase FLT3. We hypothesized that FLT3 might be a therapeutic target in MLL and found that 5 of 30 MLLs contain mutations in the activation loop of FLT3 that result in constitutive activation. Three are a newly described deletion of 1836 and the others are D835 mutations. The recently described FLT3 inhibitor PKC412 proved cytotoxic to Ba/F3 cells dependent upon activated FLT3 containing either mutation. PKC412 is also differentially cytotoxic to leukemia cells with MLL translocations and FLT3 that is activated by either overexpression of the wild-type receptor or mutation. Finally, we developed a mouse model of MLL and used bioluminescent imaging to determine that PKC412 is active against MLL in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Sophia Childrens Univ Hosp, Rotterdam, Netherlands. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Whitehead Inst, Ctr Genome Res, Cambridge, MA 02142 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [P01 CA 68484, K08 CA 92551] NR 50 TC 265 Z9 274 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD FEB PY 2003 VL 3 IS 2 BP 173 EP 183 DI 10.1016/S1535-6108(03)00003-5 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650AL UT WOS:000181240100010 PM 12620411 ER PT J AU Paradis, AE Kantoff, PW Giovannucci, E Stampfer, MJ Ma, J AF Paradis, AE Kantoff, PW Giovannucci, E Stampfer, MJ Ma, J TI Association between the Met326Ile polymorphism of the p85 alpha regulatory subunit of phosphatidylinositol 3-kinase and prostate cancer risk: A prospective study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GLUCOSE DISAPPEARANCE CONSTANT; GROWTH-FACTOR-I; PHOSPHOINOSITIDE 3-KINASE; INSULIN SENSITIVITY; VARIANT C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Lank Ctr Genitourinary Oncol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Ma, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA-42182, CA78293, CA-57374, CA-58684] NR 10 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2003 VL 12 IS 2 BP 172 EP 173 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 644LG UT WOS:000180918800016 PM 12582030 ER PT J AU Su, L Liu, G Zhou, W Xu, LL Miller, DP Park, S Lynch, TJ Wain, JC Christiani, DC AF Su, L Liu, G Zhou, W Xu, LL Miller, DP Park, S Lynch, TJ Wain, JC Christiani, DC TI No association between the p21 codon 31 serine-arginine polymorphism and lung cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article C1 Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Canc Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thorac Surg Unit,Dept Surg, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES00002] NR 6 TC 22 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD FEB PY 2003 VL 12 IS 2 BP 174 EP 175 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 644LG UT WOS:000180918800017 PM 12582031 ER PT J AU Batra, RK Lin, A Sharma, S Dohadwala, M Luo, J Pold, M Dubinett, SM AF Batra, RK Lin, A Sharma, S Dohadwala, M Luo, J Pold, M Dubinett, SM TI Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism SO CANCER RESEARCH LA English DT Article ID PROSTAGLANDIN E(2); IMMUNE-SYSTEM; HUMAN TUMORS; IKK-BETA; PROTEINS; ALPHA; IL-10; PHOSPHORYLATION; TRANSCRIPTION; FAMILY AB T lymphocyte survival is critical for the development and maintenance of an effective host antitumor immune response; however, the tumor environment can negatively impact T-cell survival. Lymphocytes exposed to tumor supernatants (TSNs) were evaluated for apoptosis after mitogen stimulation. TSN was observed to significantly enhance phorbol 12myristate 13-acetate/ionomycin- and anti-CD3-stimulated lymphocyte apoptosis. Enhanced lymphocyte apoptosis was associated with an impairment of nuclear factor kappaB nuclear translocation and diminished IkappaBalpha degradation. In lymphocytes stimulated after exposure to TSNs, cytoplasmic IkappaBalpha persisted as a result of alterations in IkappaB kinase (IKK) activity. Accordingly, although there were no apparent differences in IKK component concentrations, lymphocytes preexposed to TSNs exhibited markedly reduced IKK activity. We conclude that non-small cell lung cancer-derived soluble factors promote apoptosis in activated lymphocytes by an IKK-dependent pathway. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Lung Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Lung Canc Res Program, 37-131 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [R01 CA078654-03, R01-CA78654, R01-CA71818]; PHS HHS [P50-90388] NR 45 TC 26 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 2003 VL 63 IS 3 BP 642 EP 646 PG 5 WC Oncology SC Oncology GA 640PT UT WOS:000180697700015 PM 12566308 ER PT J AU Sanchez, PL Rodriguez-Alemparte, M Colon-Hernandez, PJ Pomerantsev, E Inglessis, I Mahdi, NA Leinbach, RC Palacios, IF AF Sanchez, PL Rodriguez-Alemparte, M Colon-Hernandez, PJ Pomerantsev, E Inglessis, I Mahdi, NA Leinbach, RC Palacios, IF TI Directional coronary atherectomy vs. rotational atherectomy for the treatment of in-stent restenosis of native coronary arteries SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE stent; restenosis; atherectomy; rotablator; coronary ID BALLOON-EXPANDABLE-STENT; INTRAVASCULAR ULTRASOUND; ANGIOPLASTY; IMPLANTATION; MECHANISMS; DISEASE; PLACEMENT AB Management of in-stent restenosis has become a significant challenge in interventional cardiology. Since the mechanism of in-stent restenosis is predominantly intimal hyperplasia, debulking techniques have been used to treat, this condition. This study is a nonrandomized comparison of the immediate and long-term results of directional coronary atherectomy (DCA; n=58) vs. high-speed rotational atherectomy (ROTA; n=61) for the treatment of in-stent restenosis of native coronary arteries. There were no in-hospital deaths, Q-wave myocardial infarctions, or emergency coronary artery bypass surgery in either group. DCA resulted in a larger postprocedural minimal luminal diameter of (2.57+/-0.51 vs. 2.14+/-0.37 mm; P<0.0001) and a larger acute gain (1.83&PLUSMN;0.52 vs. 1.42&PLUSMN;0.48 mm; P<0.0001). Furthermore, 12-month clinically indicated target lesion revascularization (39% vs. 21%; P=0.02) and long-term follow-up MACE (44% vs. 28%; P=0.03) was greater in the ROTA group. The present study suggests that DCA appears to be superior to ROTA for the treatment of in-stent restenosis of native coronary arteries. Compared to ROTA, the debulking effect of DCA leads to a larger postprocedure minimal luminal diameter, and a lower incidence of subsequent target lesion revascularization and MACE. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, 55 Fruit St,Bulfinch 105, Boston, MA 02114 USA. OI Sanchez, Pedro L/0000-0002-4288-345X NR 29 TC 5 Z9 5 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 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2003 VL 58 IS 2 BP 155 EP 161 DI 10.1002/ccd.10399 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 677NN UT WOS:000182814600004 PM 12552536 ER PT J AU Kawase, Y Hayase, M Ito, S Ojio, S Tahara, H Ehara, M Kondo, H Ito, Y Suzuki, Y Ishihara, Y Suzuki, T AF Kawase, Y Hayase, M Ito, S Ojio, S Tahara, H Ehara, M Kondo, H Ito, Y Suzuki, Y Ishihara, Y Suzuki, T TI Compression of right ventricular out-flow due to localized hematoma after coronary perforation during PCI SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE tamponade; pericardiocentesis; coronary artery bypass graft ID RIGHT ATRIAL COMPRESSION; CARDIAC-TAMPONADE; DEVICE ERA; MANAGEMENT; RUPTURE; ECHOCARDIOGRAPHY; INTERVENTIONS; ANGIOPLASTY; SURGERY AB Although coronary perforation can cause tamponade during percutaneous coronary intervention (PCI), this is unusual for patients previously undergoing coronary artery bypass graft surgery (CABG) due to pericardial adhesions. We report here on a rare case of right ventricular out-flow obstruction complicating PCI in a patient with a previous CABG. C1 Toyohashi Heart Ctr, Div Cardiovasc Med, Toyohashi, Aichi, Japan. Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA 02114 USA. RP Kawase, Y (reprint author), 21-1 Gobudori,Oyama Cho, Toyohashi, Aichi 4418530, Japan. NR 14 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2003 VL 58 IS 2 BP 202 EP 206 DI 10.1002/ccd.10443 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 677NN UT WOS:000182814600013 PM 12552545 ER PT J AU Oesterle, SN Reifart, N Hayase, M Hauptmann, E Low, R Erbel, R Haude, M Dirsch, O Schuler, GC Virmani, R Yeung, AC AF Oesterle, SN Reifart, N Hayase, M Hauptmann, E Low, R Erbel, R Haude, M Dirsch, O Schuler, GC Virmani, R Yeung, AC TI Catheter-based coronary bypass: A development update SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE percutaneous bypass; retroperfusion; venous; coronary; revascularization AB Catheter-based coronary bypass has evolved since its origin in 1995. We present a status update of one version of catheter-based bypass, percutaneous in situ coronary venous arterialization (PICVA), its successes and failures, and the many questions and challenges that remain. Initial clinical experience with PICVA demonstrated promising mitigation of angina in no-option patients, but was complicated by a relatively low procedural completion rate and a high incidence of MACE. A great deal was learned in these initial cases. The system of devices is currently undergoing significant modification, and further clinical study is underway. C1 Stanford Univ, Med Ctr, Div Cardiol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Kardiol Inst, Div Cardiol, Bad Soden, Germany. Krankenhaus D Barmh Bruder, Div Cardiol, Trier, Germany. Univ Calif Davis, Div Cardiol, Davis, CA 95616 USA. Univ Essen Gesamthsch Klinikum, Div Cardiol, D-4300 Essen, Germany. Herzzentrum, Div Cardiol, Leipzig, Germany. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Yeung, AC (reprint author), Stanford Univ, Med Ctr, Div Cardiol, 300 Pastuer Dr, Stanford, CA 94305 USA. NR 5 TC 15 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD FEB PY 2003 VL 58 IS 2 BP 212 EP 218 DI 10.1002/ccd.10403 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 677NN UT WOS:000182814600015 PM 12552547 ER PT J AU Srinivasan, D Fisk, R Xu, H van den Heuvel, S AF Srinivasan, D Fisk, R Xu, H van den Heuvel, S TI Developmental control of mitotic spindle position and cleavage plane specification in C. elegans SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Meeting Abstract CT EMBO/EMBL Conference on Centrosomes and Spindle Pole Bodies CY SEP 13-17, 2002 CL HEIDELBERG, GERMANY C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RI van den Heuvel, Sander/B-8892-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD FEB PY 2003 VL 54 IS 2 MA 96 BP 187 EP 188 PG 2 WC Cell Biology SC Cell Biology GA 642GJ UT WOS:000180795600102 ER PT J AU Choudhury, GG Lenin, M Calhaun, C Zhang, JH Abboud, HE AF Choudhury, GG Lenin, M Calhaun, C Zhang, JH Abboud, HE TI PDGF inactivates forkhead family transcription factor by activation of Akt in glomerular mesangial cells SO CELLULAR SIGNALLING LA English DT Article DE mesangial cell; PDGF; Akt; FKHR; fas ligand ID PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; GROWTH-FACTOR; GENE-EXPRESSION; DNA-SYNTHESIS; FACTOR FKHR; C-FOS; PHOSPHORYLATION; INSULIN; SURVIVAL AB Regulation of the forkhead domain transcription factors by PDGF has not been studied. In this report, we investigated the role of PDGF-induced Akt in regulating forkhead domain protein FKHRL1 in glomerular mesangial cells. PDGF increased phosphorylation of FKHRL1 in a time- and PI 3 kinase-dependent manner. Expression of dominant negative Akt by adenovirus-mediated gene transfer blocked PDGF-induced FKHRL1 phosphorylation. PDGF inhibited transcription of a forkhead DNA binding element-driven reporter gene. This inhibition was mimicked by constitutively active myristoylated Akt. Moreover, FKHR1-mediated transcription of the reporter gene was completely attenuated by both PDGF and Myr-Akt. One of the targets of forkhead transcription factors is the proapoptotic Fas ligand (FasL) gene. PDGF, as well as Myr-Akt, inhibited transcription of FasL. In contrast, inhibition of PI 3 kinase and dominant negative Akt increased FasL gene transcription, suggesting that suppression of PI 3 kinase/Akt signalling may induce apoptosis in mesangial cells via upregulation of FasL expression. However, expression of dominant negative Akt by adenovirus did not induce apoptosis in mesangial cells, suggesting that Akt-independent antiapoptotic mechanisms also exist. Together, our data demonstrate for the first time that PDGF inactivates forkhead domain transcription factor by Akt-dependent phosphorylation and that suppression of Akt signalling is not sufficient to induce apoptosis in mesangial cells. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr,Mail Code 7882, San Antonio, TX 78229 USA. NR 56 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD FEB PY 2003 VL 15 IS 2 BP 161 EP 170 AR PII S0898-6568(02)00057-8 PG 10 WC Cell Biology SC Cell Biology GA 643XN UT WOS:000180888700003 ER PT J AU Bullmore, ET Suckling, J Zelaya, F Long, C Honey, G Reed, L Routledge, C Ng, V Fletcher, P Brown, J Williams, SCR AF Bullmore, ET Suckling, J Zelaya, F Long, C Honey, G Reed, L Routledge, C Ng, V Fletcher, P Brown, J Williams, SCR TI Practice and difficulty evoke anatomically and pharmacologically dissociable brain activation dynamics SO CEREBRAL CORTEX LA English DT Article ID FUNCTIONAL MAGNETIC-RESONANCE; EVENT-RELATED FMRI; ANTERIOR CINGULATE CORTEX; HUMAN WORKING-MEMORY; AGE-RELATED-CHANGES; PREFRONTAL CORTEX; CORTICAL ACTIVATION; MOTOR-PERFORMANCE; NEURAL MECHANISMS; TASK AB Brain activation is adaptive to task difficulty and practice. We used functional MRI to map brain systems activated by an object-location learning task in 24 healthy elderly volunteers each scanned following placebo and two of four active drugs studied. We distinguished a fronto-striatal system adaptive to difficulty from a posterior system adaptive to practice. Fronto-striatal response to increased cognitive load was significantly attenuated by scopolamine, sulpiride and methylphenidate; practice effects were not modulated by these drugs but were enhanced by diazepam. We also found enhancement by methylphenidate, and attenuation by sulpiride, of load response in premotor, cingulate and parietal regions comprising a spatial attention network. Difficulty and practice evoke anatomically and pharmacologically dissociable brain activation dynamics, which are probably mediated by different neurotransmitter systems in humans. C1 Univ Cambridge, Brain Mapping Unit, Dept Psychiat, Addenbrookes Hosp, Cambridge CB2 2QQ, England. Kings Coll London, Inst Psychiat, London SE5 8AF, England. Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. GlaxoSmithKline, Clin Res Unit, ACCI, Cambridge CB2 2GG, England. RP Bullmore, ET (reprint author), Univ Cambridge, Brain Mapping Unit, Dept Psychiat, Addenbrookes Hosp, Hills Rd, Cambridge CB2 2QQ, England. EM etb23@cam.ac.uk RI Williams, Steve/D-6979-2011; Zelaya, Fernando/I-3125-2012; Bullmore, Edward/C-1706-2012 OI Williams, Steve/0000-0003-4299-1941; Bullmore, Edward/0000-0002-8955-8283 FU Wellcome Trust [064351] NR 56 TC 32 Z9 34 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD FEB PY 2003 VL 13 IS 2 BP 144 EP 154 DI 10.1093/cercor/13.2.144 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 635GF UT WOS:000180390300004 PM 12507945 ER PT J AU Brown, ST Brett, I Almenoff, PL Lesser, M Terrin, M Teirstein, AS AF Brown, ST Brett, I Almenoff, PL Lesser, M Terrin, M Teirstein, AS CA ACCESS Research Group TI Recovery of cell wall-deficient organisms from blood does not distinguish between patients with sarcoidosis and control subjects SO CHEST LA English DT Article DE a case control etiologic study of sarcoidosis; cell wall-deficient forms; mycobacterium; sarcoidosis ID COMPLEX; FORMS AB Study objective: To determine if cell wall-deficient forms (CWDF) of mycobacteria can be grown in culture of blood from subjects with sarcoidosis. Design: A special multicenter study of sarcoidosis (A Case Control Etiologic Study of Sarcoidosis), supported by the National Heart, Lung, and Blood Institute. Patients and control subjects: Patients and control subjects were recruited at 10 institutions in the United States. Control subjects (controls) were of the same gender and race, and within 5 years of age as matching patients with sarcoidosis (cases). Results: Cultures were incubated from 347 blood specimens (197 cases, 150 controls). Two investigators trained to recognize CWDF mycobacteria examined material obtained from culture tubes after 3 weeks. Structures thought to be CWDF were seen with equal frequency in cases (38%) and controls (41%). Thirty-nine percent of cases and 37% of controls were read as negative for CWDF. Conclusion: This study fails to confirm earlier reports that CWDF mycobacteria can be grown from the blood of patients with sarcoidosis, but not from control subjects. C1 Bronx Vet Adm Med Ctr, Infect Dis Sect, Bronx, NY 10468 USA. Mt Sinai Med Ctr, Dept Internal Med, Bronx, NY USA. Clin Trials & Surveys Corp, Baltimore, MD USA. RP Brown, ST (reprint author), Bronx Vet Adm Med Ctr, Infect Dis Sect, 111F,130 W Kingsbridge Rd n, Bronx, NY 10468 USA. FU NHLBI NIH HHS [M01-HR-56065]; PHS HHS [56066, 56067, 56068, 56072, 56070, 56071, 56073, 56069, 56074, 56075] NR 23 TC 26 Z9 31 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD FEB PY 2003 VL 123 IS 2 BP 413 EP 417 DI 10.1378/chest.123.2.413 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 646XK UT WOS:000181061200021 PM 12576359 ER PT J AU Batchelor, TT Kolak, G Ciordia, R Foster, CS Henson, JW AF Batchelor, TT Kolak, G Ciordia, R Foster, CS Henson, JW TI High-dose methotrexate for intraocular lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RETICULUM-CELL SARCOMA; NERVOUS-SYSTEM LYMPHOMA; CLINICAL-FEATURES; PRIMARY CNS; B-CELL; CHEMOTHERAPY; MANAGEMENT; DIAGNOSIS AB Purpose: Intraocular lymphoma (IOL) frequently coexists with primary central nervous system lymphoma (PCNSL). We sought to determine the efficacy of high-dose methotrexate (MTX) alone in patients with IOL. We also sought to determine whether micromolar levels of MTX could be achieved in the aqueous and vitreous humor of the eye after i.v. administration of the drug. Experimental Design: Nine patients with concurrent PCNSL and IOL or isolated IOL were treated with MTX alone. All patients were treated with i.v. 8 g/m(2) MTX. MTX concentrations in serum, aqueous humor, and vitreous humor were obtained in seven of nine patients with IOL and in one additional patient with PCNSL but no evidence of IOL. Results: Micromolar concentrations of MTX were present in both ocular chambers 4 h after completion of the infusion in eight of eight patients. Levels of MTX were lower in the vitreous humor compared with the aqueous humor in five of six patients in whom both chambers were assayed. Initial response of IOL to MTX was demonstrated by seven of nine patients (six complete responses and one partial response), whereas two patients had persistent IOL despite achievement of micromolar concentrations of MTX. In the patients with concurrent PCNSL and IOL, seven of seven had complete responses in the brain after treatment with MTX. Three of seven patients with initial response of IOL experienced relapse in the eye requiring orbital radiation, and four of nine patients had sustained response of IOL to MTX. Conclusions: A subset of patients with IOL may experience sustained remission when treated with high-dose i.v. MTX alone. Although micromolar MTX concentrations are present in the eye 4 h after infusion, the lower concentration achieved in vitreous humor may contribute to persistence of IOL. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02108 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, 100 Blossom St,Cox 315, Boston, MA 02114 USA. NR 24 TC 85 Z9 87 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 FEB PY 2003 VL 9 IS 2 BP 711 EP 715 PG 5 WC Oncology SC Oncology GA 643AR UT WOS:000180840200025 PM 12576439 ER PT J AU Yang, R Sowers, R Mazza, B Healey, JH Huvos, A Grier, H Bernstein, M Beardsley, GP Krailo, MD Devidas, M Bertino, JR Meyers, PA Gorlick, R AF Yang, R Sowers, R Mazza, B Healey, JH Huvos, A Grier, H Bernstein, M Beardsley, GP Krailo, MD Devidas, M Bertino, JR Meyers, PA Gorlick, R TI Sequence alterations in the reduced folate carrier are observed in osteosarcoma tumor samples SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-DOSE METHOTREXATE; BREAST-CANCER CELLS; OSTEOGENIC-SARCOMA; PREOPERATIVE CHEMOTHERAPY; LEUKEMIA-CELLS; DIHYDROFOLATE-REDUCTASE; ANTIFOLATE RESISTANCE; TRANSMEMBRANE DOMAIN; TRANSPORT-PROPERTIES; FOLIC-ACID AB High-dose methotrexate is a standard component of therapy for high-grade osteosarcoma. Its effectiveness may be limited by intrinsic and acquired resistance. Decreased reduced folate carrier (RFC) expression has been shown in approximately half of osteosarcomas at diagnosis. Mutations and polymorphisms in the RFC gene have been reported in various cell lines. The purpose of this study was to investigate sequence alterations in the RFC gene in osteosarcoma tumor samples. The entire coding region of the RFC gene in samples from 162 osteosarcoma patients was screened by DNA single-stranded conformational polymorphism, followed by direct sequencing of any region with altered mobility. A previously identified polymorphism at cDNA position number 174 of RFC exon 2 was observed. Sixty-one samples (37.6%) were heterozygous with both A/G at this position (HiS(27)/Arg(27)), 52 samples (32.2%) were homozygous with G (Arg(27)), and 49 samples (30.2%) were homozygous with A (His(27)). Fifteen (9.2%) samples were identified with other RFC sequence variants. in exon 2, none of which have been reported. The sequence variants in exon 2 included a G to A substitution at cDNA position 231, a G to A substitution at cDNA position 155, a C to T substitution at cDNA position 114, and a T to C substitution at cDNA position 104, resulting in a serine to asparagine substitution at amino acid 46, a glutamate to lysine substitution at amino acid 21, an alanine to valine substitution at amino acid 7, and a serine to proline substitution at amino acid 4, respectively. A deletion of A at cDNA position 126 resulting in a frame-shift was also observed. Some of these variants were observed in multiple samples. Eight samples had altered single-stranded conformational polymorphism patterns in exon 3 that were associated with nucleotide changes that altered the amino acid sequence. All of these RFC sequence variants appeared to be heterozygous. Heterozygous C/T and homozygous C also were observed at RFC cDNA position 790 in exon 3, which does not alter the amino acid coding sequence. This study shows that RFC sequence alterations are frequent in samples from osteosarcoma patients. Additional studies are under way to determine the clinical significance of these sequence alterations and their effect on methotrexate transport and resistance. C1 Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Orthoped Surg, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop St Justine, Montreal, PQ, Canada. Yale Univ, Med Ctr, New Haven, CT USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. Childrens Oncol Grp Data Ctr, Gainesville, FL USA. RP Gorlick, R (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [R01 CA-83132] NR 39 TC 39 Z9 42 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 FEB PY 2003 VL 9 IS 2 BP 837 EP 844 PG 8 WC Oncology SC Oncology GA 643AR UT WOS:000180840200043 PM 12576457 ER PT J AU Suit, HD AF Suit, HD TI Protons to replace photons in external beam radiation therapy? SO CLINICAL ONCOLOGY LA English DT Article ID RADIOTHERAPY; MELANOMA AB Protons provide the basis for superior distribution of radiation dose due to the physical characteristics of protons. Proton beams used in radiation therapy can be designed to yield a uniform dose across the target and then virtually zero deep to the target and lower dose proximal to the target (for non-superficial lesions). Such beams can be employed in comparable number, direction, weighting, angulation, intensity modulation as is feasible for photon beams. The result is a smaller treatment volume, and hence a lower incidence and frequency of treatment-related morbidity. Importantly, the reduction in treatment volume permits a higher dose to the turnout. This means an improved tumour control probability and lower normal tissue complication probability. Clinical gains appear to have been realized in the treatment of patient with uveal melanoma, skull-base sarcoma, para-nasal sinus carcinomas, selected stages of lung carcinoma and hepatocellular carcinoma. There are now three proton therapy centres with gantry systems with seven more being built. Further, there are seven additional centres in active planning. At present, prospective clinical evaluations are in progress for tumours at many anatomical sites. (C) 2002 Published by Elsevier Science Ltd on behalf of The Royal College of Radiologists. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Suit, HD (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD FEB PY 2003 VL 15 IS 1 BP S29 EP S31 DI 10.1053/clon.2002.0171 PG 3 WC Oncology SC Oncology GA 640QW UT WOS:000180700300017 PM 12602561 ER PT J AU Albertson, TE Panacek, EA MacArthur, RD Johnson, SB Benjamin, E Matuschak, GM Zaloga, G Maki, D Silverstein, J Tobias, JK Haenftling, K Black, G Cowens, JW AF Albertson, TE Panacek, EA MacArthur, RD Johnson, SB Benjamin, E Matuschak, GM Zaloga, G Maki, D Silverstein, J Tobias, JK Haenftling, K Black, G Cowens, JW CA MAB-T88 Sepsis Study Grp TI Multicenter evaluation of a human monoclonal antibody to Enterobacteriaceae common antigen in patients with Gram-negative sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE sepsis; Gram-negative sepsis; septic shock; sepsis syndrome; monoclonal antibodies; Enterobacteriaceae; endotoxin ID PLACEBO-CONTROLLED TRIAL; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; INTENSIVE-CARE UNITS; SEPTIC SHOCK; DOUBLE-BLIND; CLINICAL-TRIALS; FUSION PROTEIN; FACTOR-ALPHA; ENDOTOXIN AB Objective: To evaluate in Gram-negative sepsis patients the human monoclonal immunoglobulin M antibody (MAB-T88) directed at the enterobacterial common antigen which is a specific surface antigen closely linked to lipopolysaccharide and shared by all members of the Enterobacteriaceae family of Gram-negative bacteria. Design: Prospective, randomized, double-blinded, placebo-controlled, multicenter trial. Setting: Thirty-three academic medical centers in the United States. Patients: Patients were entered with a clinical diagnosis of sepsis, the presence of either shock or multiple organ dysfunction, and presumptive evidence for Gram-negative infection. Interventions: Patients received a single intravenous infusion, over 30 mins, of either 300 mg of MAB-T88 formulated in albumin, or placebo (albumin). Measurements and Main Results: The primary analysis group was prospectively identified as those patients with documented evidence of an infection with bacteria of the family Enterobacteriaceae at any site. The primary end point was survival within the first 28 days. A total of 826 patients were enrolled with 55% (n = 455) in the primary analysis group. There were no significant differences between the intervention and control primary analysis group study groups for sites of infection, severity of illness, underlying medical conditions, adequacy of antibiotic or surgical treatment, or other baseline variables except for a higher frequency of chronic renal failure in the MAB-T88 group (4.4% vs. 1.3%, p = .051). The average Acute Physiology and Chronic Health Evaluation 11 scores were 26.8 +/- 8.6 (mean +/- SD) in the MAB-T88-treated group and 26.5 +/- 8.3 in the placebo-treated group (p = .72). There was no significant difference between MAB-T88- and placebo-treated groups during the first 28-day all-cause mortality in the primary analysis group (34.2% vs. 30.8%, p = .44) or in all 826 patients enrolled (37.0% vs. 34.0%, p =.36). On subset analysis, the use of MAB-T88 was not associated with significant mortality trends. More adverse events were seen with the use of MAB-T88 in the bacteremic enterobacterial common antigen group (p < .05). Conclusions: Use of the human monoclonal antibody, MAB-T88, did not improve the mortality in patients with presumed Gram-negative sepsis or in those patients with proven enterobacterial common antigen infections. No subset trends were identified that would support further investigation of this agent in sepsis. C1 Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. Med Coll Ohio, Toledo, OH 43699 USA. Univ Kentucky, Dept Surg, Lexington, KY 40506 USA. Mt Sinai Med Ctr, Dept Anesthesia, New York, NY 10029 USA. St Louis Univ Hosp, Dept Internal Med, St Louis, MO USA. Bowman Gray Sch Med, Winston Salem, NC USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Bronx Vet Adm Med Ctr, Dept Anesthesia, New York, NY USA. Chiron Corp, Emeryville, CA 94608 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Albertson, TE (reprint author), Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. NR 44 TC 29 Z9 31 U1 0 U2 2 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 FEB PY 2003 VL 31 IS 2 BP 419 EP 427 DI 10.1097/01.CCM.0000045564.51812.3F PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 644LQ UT WOS:000180919700011 PM 12576946 ER PT J AU Argaman, Z Young, VR Noviski, N Castillo-Rosas, L Lu, XM Zurakowski, D Cooper, M Davison, C Tharakan, JF Ajami, A Castillo, L AF Argaman, Z Young, VR Noviski, N Castillo-Rosas, L Lu, XM Zurakowski, D Cooper, M Davison, C Tharakan, JF Ajami, A Castillo, L TI Arginine and nitric oxide metabolism in critically ill septic pediatric patients SO CRITICAL CARE MEDICINE LA English DT Article DE pediatric sepsis; children; arginine; citrulline; leucine; nitric oxide; nitrate; stable isotopes; synthesis rate; oxidation; amino acid; kinetics; metabolism ID INFLAMMATORY RESPONSE SYNDROME; INTENSIVE-CARE UNIT; ORGAN FAILURE; ENTERAL DIET; SEPSIS; SHOCK; BALANCE; KINETICS; NITRATE; ACID AB Objective: To investigate whole body, in vivo arginine metabolism and nitric oxide synthesis rates in septic, critically ill pediatric patients. Design: Prospective study. Setting: Pediatric intensive care unit at a general hospital. Patients: Ten consecutive septic patients age 6-16 yrs. Interventions: Septic patients received an 8-hr primed, constant intravenous tracer infusion of L-[guanidino-N-15(2)]arginine, L-[1-C-13] leucine, and [C-13]urea. A 24-hr urine collection was obtained for determination of [N-15]nitrate enrichment ((15)N0(3)(-)) and urinary nitrogen. The next day they received an infusion of L-[5-C-13]arginine and L-[5-C-13-ureido, 5,5,H-2(2)]citrulline. Blood samples were obtained for determination of plasma isotopic enrichment of the tracers given and of derived [N-15]citrulline (nitric oxide synthesis), L-[C-13-guanidino 5,5, H-2(2)]arginine (M+3 arg) (arginine synthesis), and [N-15(2)]urea (urea formation). Data are compared with historic controls from studies in healthy young adults. Measurements and Main Results: Plasma arginine fluxes were 6 +/- 21 and 72 +/- 17 mumol.kg(-1).hr(-1), respectively, for the [N-15(2) guanidino] and the [13 C] arginine labels, which were not different from reported adult values. The rates of arginine oxidation were 22.9 +/- 10.8 mumol.kg(-1).hr(-1) and were higher than de novo arginine synthesis rates of 9.6 +/- 4.2 mumol.kg(-1).hr(-1) (p < .01); therefore, these patients were in a negative arginine balance. The rates of nitric oxide synthesis as estimated by the [N-15]citrulline method were 1.58 +/- 0.69 mumol.kg(-1).hr(-1) for septic patients and higher (p < .05) than values of 0.96 +/- 0.1 mumol.kg(-1).hr(-1) in healthy adults. Septic patients were in a negative protein (leucine) balance of about -1.00 +/- 0.40 g.kg(-1).day(-1). Conclusions: Homeostasis of plasma arginine in septic patients was impaired compared with reported adult values. The rates of arginine oxidation were increased whereas de novo net arginine synthesis was unchanged, leading to a negative arginine balance. The rates of nitric oxide synthesis and the fraction of plasma arginine used for nitric oxide and urea formation were increased. These findings suggest that under condition of sepsis, arginine becomes essential in critically ill children. C1 Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. MIT, Human Nutr Lab, Cambridge, MA 02139 USA. La Salle Univ, Sch Med, Mexico City, DF, Mexico. Shriners Burns Hosp, Boston, MA USA. MassTrace, Woburn, MA USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. RP Argaman, Z (reprint author), Shaare Zedek Med Ctr, Jerusalem, Israel. FU NCRR NIH HHS [M0-1RR02172]; NIDDK NIH HHS [DK15856, DK62363, P30-DK40561] NR 54 TC 69 Z9 72 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 FEB PY 2003 VL 31 IS 2 BP 591 EP 597 DI 10.1097/01.CCM.000050291.37714.74 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 644LQ UT WOS:000180919700036 PM 12576971 ER PT J AU Kim, W Kaelin, WG AF Kim, W Kaelin, WG TI The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; PROLYL HYDROXYLATION; GENE-PRODUCT; KINASE-C; REGULATE HIF; BETA-DOMAIN; VHL; GROWTH; FAMILY; HIF-1-ALPHA AB The von Hippel-Lindau tumor suppressor protein (pVHL) is the substrate-recognition module of an E3 ubiquitin ligase that targets the alpha subunits of hypoxia-inducible factor (HIF) for degradation in the presence of oxygen. Recognition of HIF by pVHL is linked to enzymatic hydroxylation of conserved prolyl residues in the HIF alpha subunits by members of the EGLN family. Dysregulation of HIF-target genes such as vascular endothelial growth factor and transforming growth factor a has been implicated in the pathogenesis of renal cell carcinomas and of hemangioblastomas, both of which frequently lack pVHL function. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kim, W (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. NR 60 TC 130 Z9 140 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD FEB PY 2003 VL 13 IS 1 BP 55 EP 60 DI 10.1016/S0959-437X(02)00010-2 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 645BR UT WOS:000180956800010 PM 12573436 ER PT J AU McCormick, BA AF McCormick, BA TI The use of transepithelial models to examine host-pathogen interactions SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID INTESTINAL EPITHELIAL MONOLAYERS; ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; CELLS; SALMONELLA; PROTEINS; TIGHT; RECEPTOR; MEMBRANE; INVASIN AB Many pathogens must overcome an epithelial barrier in order to establish an infection. Unsurprisingly, such pathogens have evolved different mechanisms to overcome this obstacle, targeting specific epithelial structures or functions. These include disruption of epithelial barrier function, transcytosing from the apical to the basolateral membrane domain or inducing cell movement such as neutrophil recruitment. When studying these processes in vivo, animal models often fail to mimic the disease observed in humans and present a complex system in which many variables cannot be controlled. Therefore, in vitro transepithelial models that permit the study of a relevant biological surface have been developed, to integrate not only interactions between bacteria and epithelial cells but also, under certain conditions, to integrate a third cell type, such as neutrophils or dendritic cells. Such models are particularly useful for studying the bacteria-host relationship as it would occur in the microenvironment of the human epithelium and have enhanced our understanding of the unique strategies by which pathogenic bacteria exploit host cells to overcome the initial epithelial hurdle. C1 Harvard Univ, Sch Med, CNY, Charlestown, MA 02129 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Div Mucosal Immunol, Dept Pediat Gastroenterol, 114 16th St 114-3503, Charlestown, MA 02129 USA. NR 26 TC 35 Z9 35 U1 3 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD FEB PY 2003 VL 6 IS 1 BP 77 EP 81 DI 10.1016/S1369-5274(02)00003-6 PG 5 WC Microbiology SC Microbiology GA 668NT UT WOS:000182300600013 PM 12615224 ER PT J AU Bandera, CA Ye, B Mok, SC AF Bandera, CA Ye, B Mok, SC TI New technologies for the identification of markers for early detection of ovarian cancer SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article DE ovarian cancer; early detection; biomarkers; microarray; proteomics AB Purpose of review. The ovarian cancer screening regimens in current use fail to identify disease at an early curable stage. Recent findings. New technologies are emerging that facilitate the identification of diagnostic tumor markers. In particular, high throughput techniques using microarray technology and proteomic screening have enriched the study of protein expression by ovarian cancer cells. Summary. Further evaluation of serum proteins associated with ovarian cancer holds promise for the development of a tumor marker panel that could aid in the early diagnosis of ovarian cancer, and save lives. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Obstet & Gynecol, Cambridge, MA 02138 USA. RP Bandera, CA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Obstet & Gynecol, 75 Francis St, Cambridge, MA 02138 USA. FU NCI NIH HHS [UO1CA86381]; NICHD NIH HHS [K12-HD01265] NR 16 TC 32 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD FEB PY 2003 VL 15 IS 1 BP 51 EP 55 DI 10.1097/01.gco.0000051556.77832.52 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 640HX UT WOS:000180683900008 PM 12544502 ER PT J AU Cohen, LE AF Cohen, LE TI Endocrine late effects of cancer treatment SO CURRENT OPINION IN PEDIATRICS LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GROWTH-HORMONE SECRETION; BONE-MARROW TRANSPLANTATION; CENTRAL PRECOCIOUS PUBERTY; CHILDHOOD BRAIN-TUMORS; CRANIAL IRRADIATION; GLUCOCORTICOID THERAPY; PITUITARY DYSFUNCTION; HODGKINS-DISEASE; THYROID-FUNCTION AB Endocrinopathies are significant consequences of childhood cancers and their treatments. The risk of developing these adverse events is related to the underlying disease and its treatment with cytotoxic drugs and radiation therapy. This article will explore the current literature about endocrine late effects of hypothalamic-pituitary, thyroid, and gonadal dysfunction, as well as osteoporosis and obesity. Curr Opin Pediatr 2003,15:3-9 (C) 2003 Lippincott Williams Wilkins, Inc. C1 Childrens Hosp, Dana Farber Canc Inst, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, LE (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. NR 53 TC 14 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD FEB PY 2003 VL 15 IS 1 BP 3 EP 9 DI 10.1097/00008480-200302000-00002 PG 7 WC Pediatrics SC Pediatrics GA 636BL UT WOS:000180434600002 PM 12544265 ER PT J AU Tatarkiewicz, K Lopez-Avalos, MD Yoon, KH Trivedi, N Quickel, RR Bonner-Weir, S Weir, GC AF Tatarkiewicz, K Lopez-Avalos, MD Yoon, KH Trivedi, N Quickel, RR Bonner-Weir, S Weir, GC TI Development and retroviral transduction of porcine neonatal pancreatic islet cells in monolayer culture SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE beta cells; duct cells; monolayer culture; pancreatic development; transplantation ID HUMAN-FETAL PANCREAS; HEPATOCYTE GROWTH-FACTOR; ENDOCRINE-CELLS; NUDE-MICE; DIABETES-MELLITUS; TISSUE-CULTURE; ORGAN-CULTURE; GENE-TRANSFER; B-CELLS; TRANSPLANTATION AB To learn more about the potential of neonatal porcine pancreatic duct and islet cells for xenotransplantation, the development of these cells when cultured as monolayers was evaluated. Immunostaining for islet hormones and cytokeratin-7 revealed that day eight monolayers consisted of approximately 70% duct cells and less than 10% beta cells. Using Ki-67 immunostaining as a proliferation marker, the fraction of beta cells in the cell cycle was shown to decrease from 20% at day three to 10% at day eight, and for duct cells from 36 to 19%. Insulin secretion increased 2.4-fold upon glucose stimulation, and 38-fold when 10 mm theophylline was added, showing the responsiveness of the neonatal beta cells. Reaggregated monolayers consisted mostly of duct cells, but 4 weeks after transplantation, grafts contained predominantly endocrine cells, with duct cells being almost absent, suggesting in vivo differentiation of duct cells to endocrine cells. Monolayer susceptibility to retroviral transduction was also investigated using a Moloney Murine Leukemia Virus-based vector. Approximately 60% of duct cells but less than 5% of beta cells expressed the transgene, indicating that precursor duct cells are better targets for transgene expression. These results show that porcine neonatal pancreatic cells can be cultured as monolayers in preparation for transplantation. Furthermore, in such a culture setting, precursor duct cells have a high rate of proliferation and are more efficiently transduced with a retrovirus-based reporter gene than are beta cells. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Lopez-Avalos, MD (reprint author), Univ Malaga, Fac Ciencias, Dept Biol Celular Genet & Fisiol, Campus Teatinos, E-29071 Malaga, Spain. FU NIDDK NIH HHS [DK-53087, DK-36836] NR 39 TC 9 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD FEB PY 2003 VL 45 IS 1 BP 39 EP 50 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 652TZ UT WOS:000181397500005 PM 12630945 ER PT J AU Gamer, LW Nove, J Rosen, V AF Gamer, LW Nove, J Rosen, V TI Return of the chalones SO DEVELOPMENTAL CELL LA English DT Editorial Material ID NEGATIVE REGULATOR; BETA SUPERFAMILY; FACTOR-11; MEMBER; GROWTH; LIMB AB Members of the TGFbeta superfamily play many roles in embryonic development and adult tissue homeostasis. Now recent work focused on growth and differentiation factors (GDFs) suggest that these TGFbeta-like molecules may also control organ size and may, in fact be the long sought after chalones, or negative growth regulators. C1 Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Forsyth Inst, Boston, MA 02115 USA. RP Gamer, LW (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. NR 10 TC 19 Z9 20 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD FEB PY 2003 VL 4 IS 2 BP 143 EP 144 DI 10.1016/S1534-5807(03)00027-3 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 645NN UT WOS:000180984600001 PM 12586054 ER PT J AU Niswender, KD Morrison, CD Clegg, DJ Olson, R Baskin, DG Myers, MG Seeley, RJ Schwartz, MW AF Niswender, KD Morrison, CD Clegg, DJ Olson, R Baskin, DG Myers, MG Seeley, RJ Schwartz, MW TI Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus - A key mediator of insulin-induced anorexia SO DIABETES LA English DT Article ID Y GENE-EXPRESSION; MESSENGER-RNA; LEPTIN RECEPTOR; BODY-WEIGHT; BRAIN; REPRODUCTION; OBESITY; MICE AB In peripheral tissues, insulin signaling involves activation of the insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase (PI3K) enzyme system. In the hypothalamus, insulin functions with leptin as an afferent adiposity signal important for the regulation of body fat stores and hepatic glucose metabolism. To test the hypothesis that hypothalamic insulin action involves intracellular PI3K signaling, we used histochemical and biochemical methods to determine the effect of insulin on hypothalamic IRS-PI3K activity. Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. Using an immunohistochemical technique to detect PI 3,4,5-triphosphate, the main product of PI3K activity, we further demonstrate that in the arcuate nucleus, insulin-induced PI3K activity occurs preferentially within cells that contain IRS-2. Finally, we show that the food intake-lowering effects of insulin are reversed by intracerebroventricular infusion of either of two PI3K inhibitors at doses that have no independent feeding effects. These findings support the hypothesis that the IRS-PI3K pathway is a mediator of insulin action in the arcuate nucleus and, combined with recent evidence that leptin activates PI3K signaling in the hypothalamus, provide a plausible mechanism for neuronal cross-talk between insulin and leptin signaling. C1 Harborview Med Ctr, Seattle, WA 98104 USA. Univ Washington, Div Metab Endocrinol & Nutr, Sch Med, Seattle, WA 98195 USA. Vet Affairs Med Ctr, Seattle, WA 98108 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. RP Schwartz, MW (reprint author), Harborview Med Ctr, Box 359757,325 9th Ave, Seattle, WA 98104 USA. RI Morrison, Christopher/A-6093-2010; Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK12829, DK17047, DK52989, DK54890, DK56731, T32 DK07247]; NINDS NIH HHS [NS32273] NR 25 TC 297 Z9 307 U1 1 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2003 VL 52 IS 2 BP 227 EP 231 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643YT UT WOS:000180891700001 PM 12540590 ER PT J AU Combs, TP Berg, AH Rajala, MW Klebanov, S Iyengar, P Jimenez-Chillaron, JC Patti, ME Klein, SL Weinstein, RS Scherer, PE AF Combs, TP Berg, AH Rajala, MW Klebanov, S Iyengar, P Jimenez-Chillaron, JC Patti, ME Klein, SL Weinstein, RS Scherer, PE TI Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin SO DIABETES LA English DT Article ID REVERSES INSULIN-RESISTANCE; ADIPOSE-SPECIFIC PROTEIN; GROWTH-HORMONE; RATS; OBESITY; METABOLISM; RECEPTORS; GLUCOSE; PIT-1; GENE AB Adiponectin or adipocyte complement-related protein of 30 kDa (Acrp30) is a circulating protein produced exclusively in adipocytes. Circulating Acrp30 levels have been associated with insulin sensitivity in adult mice and humans, yet the Acrp30 profile over the life-span and its hormonal regulation in vivo have not been previously described. Hence, we set forth to determine whether hormonal and metabolic changes associated with sexual maturation, reproduction, aging, and calorie restriction affect Acrp30. In mice, Acrp30 levels increase during sexual maturation by 4-fold in males and 10-fold in females. Neonatal castration (CX) allows Acrp30 of adults to reach female levels. CX in adults does not lead to female Acrp30 levels unless glucocorticoid exposure is elevated simultaneously by implant. Ovariectomy of infant mice does not interfere with the pubertal rise of Acrp30. However, ovariectomy in adults increases Acrp30. Estrogen suppressed Acrp30 in mice and 3T3-L1 adipocytes. In parallel to changes in estrogen action, Acrp30 decreased in late gestation but increased in both calorie-restricted and old (anovulatory) mice. The reduction of Acrp30 in lactating dams is consistent with a suppressive effect of prolactin and a stimulating effect of bromocriptine. In summary, Acrp30 levels in serum are under complex hormonal control and may play a key role in determining systemic insulin sensitivity under the respective conditions. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Ctr Diabet Res & Training, Bronx, NY 10467 USA. Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Internal Med, Ctr Osteoporosis & Metab Bone Dis, Div Endocrinol & Metab,Bone Morphometry Lab, Little Rock, AR 72205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Columbia Univ Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, Obes Res Ctr, New York, NY 10032 USA. RP Scherer, PE (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Jimenez-Chillaron, Josep/L-5854-2015 FU NIAMS NIH HHS [R01-AR46191]; NIDDK NIH HHS [1R01-DK55758, F32 DK61228, T32 DK 07513-15]; NIGMS NIH HHS [T32-GM07288] NR 50 TC 346 Z9 355 U1 4 U2 19 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2003 VL 52 IS 2 BP 268 EP 276 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643YT UT WOS:000180891700007 PM 12540596 ER PT J AU Berzins, SP Venanzi, ES Benoist, C Mathis, D AF Berzins, SP Venanzi, ES Benoist, C Mathis, D TI T-cell compartments of prediabetic NOD mice SO DIABETES LA English DT Article ID NONOBESE DIABETIC MICE; RECENT THYMIC EMIGRANTS; GENETIC-CONTROL; NKT CELLS; MOUSE; ABNORMALITIES; AUTOIMMUNITY; DEFICIENCY; REPERTOIRE; POOL AB Given the importance of the NOD mouse as a model of type 1 diabetes, there is a surprising lack of published information on the overall composition of the thymic and peripheral T-cell compartments. In this study, we revisited some earlier reports of T-cell abnormalities in this strain and examined a number of additional parameters to provide a global view of T-cells in prediabetic NOD mice. In some cases, we concur with past conclusions, but in other important areas, we find that NOD mice closely resemble nonautoimmune strains. Specifically, and contrary to published reports, the thymocyte subset distribution, the rate and composition of thymic export, and the composition of the peripheral T-cell pool, including the proportion of CD25(+)CD4(+) T-cells, are essentially normal in prediabetic NOD mice. These factors are therefore unlikely to be involved in the loss of tolerance that leads to autoimmunity within this strain. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA USA. RP Mathis, D (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [1R01DK59658-01] NR 52 TC 60 Z9 60 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 FEB PY 2003 VL 52 IS 2 BP 327 EP 334 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643YT UT WOS:000180891700015 PM 12540604 ER PT J AU Hull, RL Andrikopoulos, S Verchere, CB Vidal, J Wang, F Cnop, M Prigeon, RL Kahn, SE AF Hull, RL Andrikopoulos, S Verchere, CB Vidal, J Wang, F Cnop, M Prigeon, RL Kahn, SE TI Increased dietary fat promotes islet amyloid formation and beta-cell secretory dysfunction in a transgenic mouse model of islet amyloid SO DIABETES LA English DT Article ID TYPE-2 DIABETES-MELLITUS; POLYPEPTIDE AMYLIN; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; PANCREATIC-ISLETS; PERFUSED PANCREAS; C57BL/6J MICE; OBESITY; EXPRESSION; ACIDS AB Transgenic mice expressing the amyloidogenic human islet amyloid polypeptide (MAPP) in their islet R-cells are a model of islet amyloid formation as it occurs in type 2 diabetes. Our hIAPP transgenic mice developed islet amyloid when fed a breeder chow but not regular chow. Because the breeder chow contained increased amounts of fat, we hypothesized that increased dietary fat enhances islet amyloid formation. To test this hypothesis, we fed male MAPP transgenic and nontransgenic control mice diets containing 15% (low fat), 30% (medium fat), or 45% (high fat) of calories derived from fat for 12 months, and we measured islet amyloid, islet endocrine cell composition, and beta-cell function. Increased dietary fat in hLAPP transgenic mice was associated with a dose-dependent increase in both the prevalence (percentage of islets containing amyloid deposits; 34 +/- 8, 45 +/- 8, and 58 +/- 10%, P < 0.05) and severity (percentage of islet area occupied by amyloid; 0.8 +/- 0.5, 1.0 +/- 0.5, and 4.6 +/- 2.5%, P = 0.05) of islet amyloid. In addition, in these hLAPP transgenic mice, there was a dose-dependent decrease in the proportion of islet area comprising beta-cells, with no significant change in islet size. In contrast, nontransgenic mice adapted to diet-induced obesity by increasing their islet size more than twofold. Increased dietary fat was associated with impaired insulin secretion in hLAPP transgenic (P = 0.05) but not nontransgenic mice. In summary, dietary fat enhances both the prevalence and severity of islet amyloid and leads to beta-cell loss and impaired insulin secretion. Because both morphologic and functional defects are present in hIAPP transgenic mice, this would suggest that the effect of dietary fat to enhance islet amyloid formation might play a role in the pathogenesis of the islet lesion of type 2 diabetes in humans. C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 151,1660 S Columbian Way, Seattle, WA 98108 USA. OI Hull, Rebecca/0000-0001-9690-4087 FU NIDDK NIH HHS [DK-17047, DK-50703] NR 60 TC 68 Z9 70 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2003 VL 52 IS 2 BP 372 EP 379 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643YT UT WOS:000180891700021 PM 12540610 ER PT J AU Garvey, WT Kwon, S Zheng, D Shaughnessy, S Wallace, P Hutto, A Pugh, K Jenkins, AJ Klein, RL Liao, YL AF Garvey, WT Kwon, S Zheng, D Shaughnessy, S Wallace, P Hutto, A Pugh, K Jenkins, AJ Klein, RL Liao, YL TI Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance SO DIABETES LA English DT Article ID CORONARY-ARTERY DISEASE; LOW-DENSITY LIPOPROTEINS; HEART-DISEASE; RISK-FACTORS; TRIGLYCERIDE-METABOLISM; NONDIABETIC SUBJECTS; LDL; NIDDM; HYPERINSULINEMIA; ATHEROSCLEROSIS AB The insulin resistance syndrome (IRS) is associated with dyslipidemia and increased cardiovascular disease risk. A novel method for detailed analyses of lipoprotein subclass sizes and particle concentrations that uses nuclear magnetic resonance (NMR) of whole sera has become available. To define the effects of insulin resistance, we measured dyslipidemia using both NMR lipoprotein subclass analysis and conventional lipid panel, and insulin sensitivity as the maximal glucose disposal rate (GDR) during hyperinsulinemic clamps in 56 insulin sensitive (IS; mean +/- SD: GDR 15.8 +/- 2.0 mg. kg(-1). min(-1), fasting blood glucose [FBG] 4.7 +/- 0.3 mmol/l, BMI 26 +/- 5), 46 insulin resistant (IR; GDR 10.2 +/- 1.9, FBG 4.9 +/- 0.5, BMI 29 +/- 5), and 46 untreated subjects with type 2 diabetes (GDR 7.4 +/- 2.8, FBG 10.8 +/- 3.7, BMI 30 +/- 5). In the group as a whole, regression analyses with GDR showed that progressive insulin resistance was associated with an increase in VLDL size (r = -0.40) and an increase in large VLDL particle concentrations (r = -0.42), a decrease in LDL size (r = 0.42) as a result of a marked increase in small LDL particles (r = -0.34) and reduced large LDL (r = 0.34), an overall increase in the number of LDL particles (r = -0.44), and a decrease in HDL size (r = 0.41) as a result of depletion of large HDL particles (r = 0.38) and a modest increase in small HDL (r = -0.21; all P < 0.01). These correlations were also evident when only normoglycemic individuals were included in the analyses (i.e., IS + IR but no diabetes), and persisted in multiple regression analyses adjusting for age, BMI, sex, and race. Discontinuous analyses were also performed. When compared with IS, the IR and diabetes subgroups exhibited a two- to threefold increase in large VLDL particle concentrations (no change in medium or small VLDL), which produced an increase in serum triglycerides; a decrease in LDL size as a result of an increase in small and a reduction in large LDL subclasses, plus an increase in overall LDL particle concentration, which together led to no difference (IS versus IR) or a minimal difference (IS-versus diabetes) in LDL cholesterol; and a decrease in large cardioprotective HDL combined with an increase in the small HDL subclass such that there was no net significant difference in HDL cholesterol. We conclude that 1) insulin resistance had profound effects on lipoprotein size and subclass particle concentrations for VLDL, LDL, and HDL when measured by NMR; 2) in type 2 diabetes, the lipoprotein subclass alterations are moderately exacerbated but can be attributed primarily to the underlying insulin resistance; and 3) these insulin resistance-induced changes in the NMR lipoprotein subclass profile predictably increase risk of cardiovascular disease but were not fully apparent in the conventional lipid panel. It will be important to study whether NAIR lipoprotein subclass parameters can be used to manage risk more effectively and prevent cardiovascular disease in patients with the IRS. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Med Univ S Carolina, Div Endocrinol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Garvey, WT (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Biometry & Epidemiol, SB323,96 Jonathon Lucas St, Charleston, SC 29425 USA. FU NCRR NIH HHS [M01-RR-1070]; NHLBI NIH HHS [P01 HL-55782]; NIDDK NIH HHS [DK-38764] NR 50 TC 309 Z9 324 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 2003 VL 52 IS 2 BP 453 EP 462 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 643YT UT WOS:000180891700032 PM 12540621 ER PT J AU Young, BA Maynard, C Reiber, G Boyko, EJ AF Young, BA Maynard, C Reiber, G Boyko, EJ TI Effects of ethnicity and nephropathy on lower-extremity amputation risk among diabetic veterans SO DIABETES CARE LA English DT Article ID PERIPHERAL VASCULAR-DISEASE; LOWER-LIMB AMPUTATION; FOOT ULCER; POPULATION; MELLITUS; HEALTH; EPIDEMIOLOGY; MORTALITY; COMPLICATIONS; MINORITIES AB OBJECTIVE - To describe ethnic differences in the risk of amputation in diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS - A retrospective cohort study was conducted on a national cohort of diabetic patients who received primary care within the Veterans Affairs (VA) Health Care System. Hospitalizations for lower-limb amputations were established by ICD-9-CM procedure codes. Relative risk of amputation in diabetic patients with and without diabetic nephropathy was determined using Cox proportional hazard modeling for unadjusted and adjusted models. RESULTS - Of the 429,918 subjects identified with diabetes (mean age 64 +/- 11 years, 97.4% Male), 3,289 individuals were determined to have had a lower-limb amputation during the study period. Compared with diabetic patients without amputations, amputees were on average older, more likely to belong to a minority group, and were more likely to have received treatment for more comorbid conditions. Asians were more likely to have toe amputations compared with whites or other ethnicities, while Native Americans were more likely to have below-the-knee amputations. Native Americans had the highest risk of amputation (RR 1.74, 95% Cl 1.39-2.18), followed by African Americans (RR 1.41,95% Cl 1.34-1.48) and Hispanics (RR 1.28, 95% Cl 1.20-1.38) compared with whites. The presence of diabetic nephropathy increased the risk of amputation threefold in all groups. Asian subjects with diabetes had the lowest adjusted relative risk of amputation (RR 0.31, 95% CI 0.19-0.50). CONCLUSIONS - Among diabetic patients, certain ethnic minority individuals have an increased risk of lower-extremity amputation compared with whites. Presence of diabetic nephropathy further increases this risk. C1 VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Young, BA (reprint author), VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Dept Vet Affairs, 152-E,1660 S Columbian Way, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 38 TC 89 Z9 91 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2003 VL 26 IS 2 BP 495 EP 501 DI 10.2337/diacare.26.2.495 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UL UT WOS:000185505000043 PM 12547888 ER PT J AU Palmer, JP Hirsch, IB AF Palmer, JP Hirsch, IB TI What's in a name: LAtent autoimmune diabetes of adults, type 1.5, adult-onset, and type 1 diabetes SO DIABETES CARE LA English DT Editorial Material ID ISLET-CELL ANTIBODIES C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Palmer, JP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 14 TC 48 Z9 54 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 2003 VL 26 IS 2 BP 536 EP 538 DI 10.2337/diacare.26.2.536 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UL UT WOS:000185505000050 PM 12547896 ER PT J AU McGregor, DK Krishnan, B Green, L AF McGregor, DK Krishnan, B Green, L TI Fine-needle aspiration of adult rhabdomyoma: A case report with review of the literature SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Review DE rhabdomyoma; fine-needle aspiration; cytology ID CYTOLOGY AB The cytologic features of adult rhabdomyoma, a rare benign tumor of skeletal muscle origin, have been infrequently reported in the literature. We present here a case of a rhabdomyoma involving the floor of the mouth of a 78-year-old man initially diagnosed by v fine-needle aspiration cytology. Cytologic features seen on Papanicolaou-stained smear preparation included cohesive clusters of skeletal muscle cells having abundant eosinophilic cytoplasm and often peripherally located nuclei. Although cross-striations and elongated intracytoplasmic inclusions were not identified in the smears, they were noted in the cell block preparation of the aspirated specimen and in the touch preparation and histologic sections of the surgically resected specimen. The cytologic differential diagnosis of this tumor is discussed. (C) 2003 Wiley-Liss, Inc. C1 VA Med Ctr, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Green, L (reprint author), VA Med Ctr, Dept Pathol, 3A-220,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 9 TC 10 Z9 10 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD FEB PY 2003 VL 28 IS 2 BP 92 EP 95 DI 10.1002/dc.10241 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 641WL UT WOS:000180770000009 PM 12561029 ER PT J AU Brachtel, EF Pilch, BZ Khettry, U Zembowicz, A Faquin, WC AF Brachtel, EF Pilch, BZ Khettry, U Zembowicz, A Faquin, WC TI Fine-needle aspiration biopsy of a cystic pleomorphic adenoma with extensive adnexa-like differentiation: Differential diagnostic pitfall with mucoepidermoid carcinoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE pleomorphic adenoma; appendageal; squamous; mucoepidermoid carcinoma; FNAB ID SALIVARY-GLAND LESIONS; PAROTID-GLAND; TUMORS; CYTOLOGY; CYTODIAGNOSIS; APOCRINE AB Although fine-needle aspiration biopsy (FNAB) is a highly accurate tool for the diagnosis of pleomorphic adenomas, even this common salivary gland neoplasm can be diagnostically challenging and cause pitfalls in cytodiagnosis. In particular, the presence of either cystic degeneration or squamous and mucinous metaplasia can lead to a false positive diagnosis of malignancy. Here we present the case of a 16-year-old female who presented with a painless, slowly growing mass in the superficial lobe of the right parotid gland. Magnetic resonance imaging of the parotid demonstrated a mass with heterogeneous postcontrast enhancement and a central, nonenhancing area suggestive of necrosis. FNAB of the lesion yielded proteinaceous debris and numerous whorls of keratin, small cohesive clusters of basaloid and squamoid epithelial cells, and many vacuolated and,foamy cells. Initially and after consultation at an outside institution, the FNAB was reported as an "atypical neoplasm, cannot exclude mucoepidermoid carcinoma." A total, nerve-sparing parotidectomy and level II neck dissection revealed a pleomorphic adenoma with central cystic degeneration and extensive mixed appendageal differentiation. While foci of squamous metaplastic changes may occur in pleomorphic adenomas, the combination of cystic degeneration and extensive appendageal differentiation with numerous keratotic cysts is rare, and it presents the potential for misinterpretation of the FNAB as indicative of malignancy in general, and mucoepidermoid carcinoma in particular. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Lahey Clin Med Ctr, Dept Pathol, Burlington, MA 01803 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD FEB PY 2003 VL 28 IS 2 BP 100 EP 103 DI 10.1002/dc.10240 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 641WL UT WOS:000180770000011 PM 12561031 ER PT J AU Cooper, RA Boninger, ML Cooper, R Robertson, RN Baldini, FD AF Cooper, RA Boninger, ML Cooper, R Robertson, RN Baldini, FD TI Wheelchair racing efficiency SO DISABILITY AND REHABILITATION LA English DT Article ID PROPULSION TECHNIQUES; KINEMATIC ANALYSIS; PUSHING ECONOMY; EXERCISE; RACERS; RESPONSES; CAPACITY AB Purpose: For individuals with disabilities exercise, such as wheelchair racing, can be an important modality for community reintegration, as well as health promotion. The purpose of this study was to examine selected parameters during racing wheelchair propulsion among a sample of elite wheelchair racers. It was hypothesized that blood lactate accumulation and wheeling economy (i.e. oxygen consumed per minute) would increase with speed and that gross mechanical efficiency would reach an optimum for each athlete. Method: Twelve elite wheelchair racers with paraplegia participated in this study. Nine of the subjects were males and three were females. Each subject used his or her personal wheelchair during the experiments. A computer monitored wheelchair dynamometer was used during all testing. The method used was essentially a discontinuous economy protocol. Mixed model analysis of variance (ANOVA) was used to compare blood lactate concentration, economy (minute oxygen consumption), and gross mechanical efficiency across the stages. Results: The results of this study show that both economy and blood lactate concentration increase linearly with speed if resistance is held constant. The subjects in this study had gross mechanical efficiencies (gme) of about 18%, with the range going from 15.2-22.7%. The results indicate that at the higher speeds of propulsion, for example near race speeds, analysis of respiratory gases may not give a complete energy profile. Conclusion: While there is a good understanding of training methods to improve cardiovascular fitness for wheelchair racers, little is known about improving efficiency (e.g. technique, equipment), therefore methods need to be developed to determine efficiency while training or in race situations. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, Pittsburgh, PA USA. Calif State Univ Sacramento, Dept Kinesiol & Hlth Sci, Sacramento, CA 95819 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. OI Boninger, Michael/0000-0001-6966-919X NR 25 TC 4 Z9 4 U1 1 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1464-5165 J9 DISABIL REHABIL JI Disabil. Rehabil. PD FEB-MAR PY 2003 VL 25 IS 4-5 BP 207 EP 212 DI 10.1080/0963828021000030918 PG 6 WC Rehabilitation SC Rehabilitation GA 674VF UT WOS:000182657000006 PM 12623628 ER PT J AU Schlozman, SC AF Schlozman, SC TI Mental health specialists in schools SO EDUCATIONAL LEADERSHIP LA English DT Editorial Material ID CONSULTATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Grad Sch Educ, Boston, MA 02114 USA. RP Schlozman, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 2 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 FEB PY 2003 VL 60 IS 5 BP 80 EP 83 PG 4 WC Education & Educational Research SC Education & Educational Research GA 641FU UT WOS:000180735100017 ER PT J AU Puigserver, P Spiegelman, BM AF Puigserver, P Spiegelman, BM TI Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator SO ENDOCRINE REVIEWS LA English DT Review ID BROWN ADIPOSE-TISSUE; UNCOUPLING PROTEIN GENE; NUCLEAR RECEPTOR; THYROID-HORMONE; PPAR-GAMMA; SKELETAL-MUSCLE; MICE LACKING; MITOCHONDRIAL BIOGENESIS; HEPATIC GLUCONEOGENESIS; ADAPTIVE THERMOGENESIS AB Investigations of biological programs that are controlled by gene transcription have mainly studied the regulation of transcription factors. However, there are examples in which the primary focus of biological regulation is at the level of a transcriptional coactivator. We have reviewed here the molecular mechanisms and biological programs controlled by the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator la (PGC-1alpha). Key cellular signals that control energy and nutrient homeostasis, such as cAMP and cytokine pathways, strongly activate PGC-1alpha. Once PGC-1alpha is activated, it powerfully induces and coordinates gene expression that stimulates mitochondrial oxidative metabolism in brown fat, fiber-type switching in skeletal muscle, and multiple aspects of the fasted response in liver. The regulation of these metabolic and cell fate decisions by PGC-1alpha is achieved through specific interaction with a variety of transcription factors such as nuclear hormone receptors, nuclear respiratory factors, and muscle-specific transcription factors. PGC-1alpha therefore constitutes one of the first and clearest examples in which biological programs are chiefly regulated by a transcriptional coactivator in response to environmental stimuli. Finally, PGC-1alpha's control of energy homeostasis suggests that it could be a target for antiobesity or diabetes drugs. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way,Smith Bldg,Room 958, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK54477, R37DK31405] NR 76 TC 1109 Z9 1165 U1 24 U2 114 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD FEB PY 2003 VL 24 IS 1 BP 78 EP 90 DI 10.1210/er.2002-0012 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 645PU UT WOS:000180988200004 PM 12588810 ER PT J AU Takeoka, M Kim, F Caviness, VS Kennedy, DN Makris, N Holmes, GL AF Takeoka, M Kim, F Caviness, VS Kennedy, DN Makris, N Holmes, GL TI MRI volumetric analysis in Rasmussen encephalitis: A longitudinal study SO EPILEPSIA LA English DT Article DE Rasmussen encephalitis; volumetric analysis; longitudinal study; segmentation; parcellation ID MAGNETIC-RESONANCE; HUMAN BRAIN; HUMAN NEOCORTEX; DIASCHISIS AB Purpose: Rasmussen encephalitis is a progressive inflammatory process with difficult-to-control focal or lateralized seizure activity, leading to hemispheric dysfunction and atrophy in advanced stages. Anatomic changes of atrophy may be subtle in earlier phases of the disease, and progressive changes on serial scans may be difficult to detect. We report a case of early-stage Rasmussen encephalitis with a relatively stable clinical course in whom we performed magnetic resonance imaging (MRI)-based volumetric analysis over an interval of 1 year, to assess for volumetric changes. Methods: Volumetric analysis was performed on two successive MRI scans obtained at age 5 and 6 years, by using the CARDVIEWS program (J Cogn Neurosci, 1996). The images were segmented into gray- and white-matter structures according to signal intensity of their borders semiautomatically, with manual corrections. The cerebral cortex was further subdivided into smaller parcellation units according to anatomic landmarks identifiable on MRI. Results: Stable left cerebral hemispheric atrophy and progressive atrophy in the left precentral gyrus, left inferior frontal gyrus, and left cerebellar atrophy were detected over the 1-year interval. Conclusions: Volumetric analysis enables early detection and quantification of anatomic changes, identification of focal involvement, and assists in determining the severity of disease and timing for surgical interventions such as hemispherectomy. C1 Keio Univ, Sch Med, Dept Pediat, Child Neurol Serv,Chinjuku Ku, Tokyo 1608582, Japan. Massachusetts Gen Hosp, Childrens Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Childrens Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Childrens Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Childrens Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NW Univ, Med Sch, Childrens Mem Hosp, Dept Med Imaging, Chicago, IL USA. Dartmouth Coll Sch Med, Dept Neurol, Hanover, NH USA. RP Takeoka, M (reprint author), Keio Univ, Sch Med, Dept Pediat, Child Neurol Serv,Chinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. RI Kennedy, David/H-3627-2012 NR 12 TC 7 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD FEB PY 2003 VL 44 IS 2 BP 247 EP 251 DI 10.1046/j.1528-1157.2003.16202.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 644KT UT WOS:000180917100018 PM 12558582 ER PT J AU Larsson, T Zahradnik, R Lavigne, J Ljunggren, O Juppner, H Jonsson, KB AF Larsson, T Zahradnik, R Lavigne, J Ljunggren, O Juppner, H Jonsson, KB TI Immunohistochemical detection of FGF-23 protein in tumors that cause oncogenic osteomalacia SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; HYPOPHOSPHATEMIC RICKETS; MICE; GENE; SUBSTRATE; SERUM; FGF23; PHEX AB Objective: Oncogenic hypophosphatemic osteomalacia (OOM) is a rare disease characterized by hypophosphatemia, inappropriately low levels of circulating 1,2 5-dihydroxyvitamin D-3 and osteomalacia. The disease is most commonly caused by benign mesenchymal tumors that produce, among several other factors. fibroblast growth factor-23 (FGF-23). Current evidence thus suggests that this protein has an important role in the regulation of phosphate homeostasis. By producing polyclonal antibodies against human FGF-23 protein we wanted to determine the localization of FGF-23 protein in OOM tumors that express FGF-23 mRNA. Design and methods: Three polyclonal antibodies were raised in rabbits against three different peptides with sequences derived from human FGF-23: [Cys-70]FGF-23(51-69)amide, [Tyr-223]FGF-23(206-222)amide and [Tyr-224]FGF-23(225-244)amide. One of the resulting antisera was subsequently used for immunohistochemistry on sections from five different tumors causing OOM. FGF-23 mRNA expression was confirmed with in situ hybridization. Results: After affinity purification, two of three antisera detected recombinant human FGF-23 by Western blot analysis. Through immunohistochemical analysis using the anti-[Tyr-224]FGF-23(225-244)amide antibody and through in situ hybridization using full-length antisense FGF-23 cRNA as a probe, we showed that abundant amounts of FGF-23 protein and mRNA are present in certain tumor cells of Eve different OOM tumors. Conclusions: We conclude that OOM tumors express FGF-23 protein and that the immunohistochemical detection of FGF-23 in OOM tumors is feasible and may help in establishing the diagnosis of tumor-induced hypophosphatemia through analysis of biopsies or surgical specimens. C1 Univ Uppsala Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden. Immutop Inc, San Clemente, CA 92673 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jonsson, KB (reprint author), Univ Uppsala Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden. NR 22 TC 43 Z9 48 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA 16 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD FEB PY 2003 VL 148 IS 2 BP 269 EP 276 DI 10.1530/eje.0.1480269 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 648RH UT WOS:000181164000014 PM 12590648 ER PT J AU Sasada, T Yang, Y Lai, CC Touma, M Clayton, LK Liu, JH Parisini, E Wang, JH Reinherz, EL AF Sasada, T Yang, Y Lai, CC Touma, M Clayton, LK Liu, JH Parisini, E Wang, JH Reinherz, EL TI Disparate peptide-dependent thymic selection outcomes in beta 2M-deficient mice versus TAP-1-deficient mice: implications for repertoire formation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE thymus; T cell receptor; crystallography; selection; immune recognition ID T-CELL RECEPTOR; CLASS-I MOLECULES; POSITIVE SELECTION; NEGATIVE SELECTION; VIRAL PEPTIDE; COMPLEX; BINDING; ANTIGEN; LIGAND; IDENTIFICATION AB Fetal thymic organ cultures of N15-transgenic RAG-2(-/-) H-2(b) mice on normal, beta-2 microglobulin (beta2M)(-/-) or transporter associated with antigen processing (TAP-1)(-/-) MHCI-deficient backgrounds were used to examine differentiation of thymocytes bearing a TCR specific for a viral peptide bound to H-2K(b). Strong agonists mediate negative selection in all mice whereas weak agonists are positively selecting in beta2M(-/-) mice but negatively selecting on TAP-1(-/-) or normal backgrounds. Very weak agonists and very weak antagonists are generally without effect in beta2M(-/-) mice yet foster differentiation in TAP-1(-/-) animals. The 20-40-fold reduction in beta2M(-/-) thymic H-2Kb surface expression suggests that the avidity of the TCR for peptide-MHCI accounts for these differences, consistent with effects of TCR density and individual thymic-peptide abundance in peptide-MHC complexes. TCR-self-MHC interaction dominates K-b-based selection, subtly modulated by peptides as revealed by X-ray crystallography. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. NR 32 TC 2 Z9 2 U1 0 U2 3 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 FEB PY 2003 VL 33 IS 2 BP 368 EP 380 DI 10.1002/immu.200310011 PG 13 WC Immunology SC Immunology GA 645PT UT WOS:000180988100011 PM 12645934 ER PT J AU Chattopadhyay, M Goss, J Lacomis, D Goins, WC Glorioso, JC Mata, M Fink, DJ AF Chattopadhyay, M Goss, J Lacomis, D Goins, WC Glorioso, JC Mata, M Fink, DJ TI Protective effect of HSV-mediated gene transfer of nerve growth factor in pyridoxine neuropathy demonstrates functional activity of trkA receptors in large sensory neurons of adult animals SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE gene transfer; herpes simplex virus; nerve growth factors; polyneuropathies; receptor; trkA ID DORSAL-ROOT GANGLION; MESSENGER-RNA EXPRESSION; SIMPLEX VIRUS TYPE-1; NEUROTROPHIN RECEPTORS; SPINAL-CORD; DISTINCT PATTERNS; AXONAL-TRANSPORT; NGF BINDING; RAT; SYSTEM AB The distinct distribution of trkA receptors on small neurons and trkC receptors on large neurons in the dorsal root ganglion correlates with the dependence of these two classes of neurons on nerve growth factor and neurotrophin-3, respectively, for survival during development. In adult animals, the distribution of high affinity neurotrophin (trk) is complex and overlapping; neurotrophins are not required for cell survival, but may influence cell phenotype and the response to injury. In order to test the functional activity of trkA receptors in the sensory ganglia of adult animals in vivo , we examined the ability of a nerve growth factor-expressing recombinant replication-defective herpes simplex virus-based vector to prevent the selective degeneration of large sensory fibres caused by intoxication with pyridoxine. Transduction of dorsal root ganglion neurons in vivo by subcutaneous inoculation of the nerve growth factor-expressing vector prevented the development of pyridoxine-induced neuropathy measured by electrophysiological, morphological and behavioural measures. These results demonstrate a functional activity of trkA receptors expressed on large neurons in the dorsal root ganglion in mature animals; this observation has important implications for the choice of neurotrophic factors for treatment of peripheral nerve disease. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15213 USA. RP Fink, DJ (reprint author), S-520 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 42 TC 28 Z9 31 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD FEB PY 2003 VL 17 IS 4 BP 732 EP 740 DI 10.1046/j.1460-9568.2003.02500.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 649VY UT WOS:000181229700007 PM 12603263 ER PT J AU Bremer, C Ntziachristos, V Weissleder, R AF Bremer, C Ntziachristos, V Weissleder, R TI Optical-based molecular imaging: contrast agents and potential medical applications SO EUROPEAN RADIOLOGY LA English DT Review DE near infrared; in vivo; molecular imaging; fluorescence; optical contrast agents ID MATRIX-METALLOPROTEINASE INHIBITION; GREEN FLUORESCENT PROTEIN; TUMOR-ASSOCIATED LAMININ; CATHEPSIN-B EXPRESSION; BREAST-CANCER; LIVING MAMMALS; BIOLUMINESCENT REPORTER; TISSUE INHIBITOR; GENE-EXPRESSION; POOR-PROGNOSIS AB Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the. development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in "European Radiology" [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. C1 Univ Munster, Dept Clin Radiol, D-48129 Munster, Germany. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Bremer, C (reprint author), Univ Munster, Dept Clin Radiol, Albert Schweitzer Str 33, D-48129 Munster, Germany. NR 80 TC 193 Z9 199 U1 2 U2 29 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD FEB PY 2003 VL 13 IS 2 BP 231 EP 243 DI 10.1007/s00330-002-1610-0 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 647JJ UT WOS:000181089400002 PM 12598985 ER PT J AU Gajewski, CD Lin, MT Cudkowicz, ME Beal, MF Manfredi, G AF Gajewski, CD Lin, MT Cudkowicz, ME Beal, MF Manfredi, G TI Mitochondrial DNA from platelets of sporadic ALS patients restores normal respiratory functions in rho(0) cells SO EXPERIMENTAL NEUROLOGY LA English DT Article DE mtDNA; cybrids; ALS; mitochondria; respiratory chain; free radicals ID AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; ELDERLY PATIENTS; SKELETAL-MUSCLE; IN-VIVO; MTDNA; IMPAIRMENT; MUTATIONS; DEFECT AB Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, which affects the anterior horn cells of the spinal cord and cortical motor neurons. A pathophysiological role for mtDNA mutations was postulated based on the finding that cybrids obtained from mitochondria of sporadic ALS patients exhibited impaired respiratory chain activities, increased free radical scavenging enzymes, and altered calcium homeostasis. To date, however, no distinct mtDNA alterations associated with ALS have been reported. Therefore, we reexamined the hypotheses that mtDNA mutations accumulate in ALS and that cybrids generated from ALS patients' blood have impaired mitochondrial respiration. Cybrid cell lines were generated from 143B osteosarcoma rho(0) cells and platelet mitochondria of sporadic ALS patients or age-matched controls. We found no statistically significant differences in mitochondrial respiration between ALS and control cybrids, even when the electron transport chain was stressed with low concentrations of respiratory chain inhibitors. Mitochondrial respiratory chain enzyme activities were also normal in ALS cybrids, and there was no increase in free radical production. Therefore, we showed that mtDNA from platelets of ALS patients was able to restore normal respiratory function in rho(0) cells, suggesting that the presence of mtDNA mutations capable of affecting mitochondrial respiration was unlikely. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Neurol, Clin Trials Unit WACC 836, Boston, MA 02114 USA. RP Manfredi, G (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, 525 E 68th St,A-505, New York, NY 10021 USA. FU NIA NIH HHS [P01-AG12992, K08-AG00798] NR 25 TC 28 Z9 30 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 2003 VL 179 IS 2 BP 229 EP 235 DI 10.1016/S0014-4886(02)00022-5 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 653JM UT WOS:000181432100011 PM 12618129 ER PT J AU Rodriguez, A Doshi, RR AF Rodriguez, A Doshi, RR TI Potential therapeutic agents that raise high-density lipoprotein cholesterol levels SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE atherosclerosis; cholesterol; cholesterol ester transfer protein (CM); coronary artery disease; reverse cholesterol transport ID ESTER TRANSFER PROTEIN; CORONARY HEART-DISEASE; RECEPTOR CLASS-B; SCAVENGER RECEPTOR; SR-BI; TANGIER-DISEASE; ATHEROSCLEROSIS; ABCA1; METABOLISM; EFFLUX AB Cardiovascular disease remains one of the leading causes of death in westernised societies. A number of risk factors have been identified that accelerate the risk for cardiovascular disease (CVD), including family history for premature disease (first degree male relative with CVD onset before the age of 55; first degree female relative with CVD onset before the age of 65), hypertension (whether treated or not), age, smoking, diabetes mellitus and low high-density lipoprotein cholesterol (HDL-C) levels. One of the recent changes in the US Adult Treatment Panel guidelines was to increase the lower limit of desirable HDL-C levels (now raised to 40 mg/dL from 35 mg/dL). There have been a few clinical studies demonstrating the benefit of raising HDL-C levels but there are not many therapeutic options that easily accomplish this goal. Research into the understanding of HDL metabolism has yielded a number of potential therapeutic targets. HDL is thought to exert its cardioprotective effects by a number of mechanisms. The predominant one appears to be its participation in the process of reverse cholesterol transport, whereby excess cholesterol from peripheral cells is transported to the liver for disposal via bile acid production. The newer potential targets, among others, include peroxisomal proliferator-activated receptors (PPAR-alpha, -gamma and -delta), ATP-binding cassette (ABC) transporters, cholesterol ester transfer protein (CETP) and scavenger receptor class B Type I (SR-BI). Among this group, agonists; for PPAR-alpha and PPAR-gamma have been shown to increase HDL-C levels and are commonly used in the management of patients with Type 2 diabetes mellitus (fibrates and glitazones, respectively). The precise mechanism by which activation of PPAR-gamma leads to increased HDL-C is still not clearly defined but these agents have been shown to increase expression of ABC transporters and scavenger receptors both in animals and in vitro. An investigational agent, JTT-705, is a CETP inhibitor that has been shown to raise HDL-C levels 34% and without major side effects. The effect of the CETP inhibitor on clinical outcomes is unknown. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab,Bayview Med Ctr, Baltimore, MD 21224 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Rodriguez, A (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab,Bayview Med Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 57 TC 1 Z9 1 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD FEB PY 2003 VL 13 IS 2 BP 167 EP 175 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 657HK UT WOS:000181660200003 ER PT J AU Pollock, AS Turck, J Lovett, DH AF Pollock, AS Turck, J Lovett, DH TI The prodomain of interleukin 1 alpha interacts with elements of the RNA processing apparatus and induces apoptosis in malignant cells SO FASEB JOURNAL LA English DT Article DE IL-1 alpha; nuclear localization signal; RNA processing; Bcl-X ID PRE-MESSENGER-RNA; SPLICING FACTORS; SR PROTEINS; BCL-X; NUCLEAR SPECKLES; 2-HYBRID SYSTEM; PRECURSOR; SEQUENCE; GENE; TRANSCRIPTION AB Interleukin 1alpha (IL-1alpha), a 33 kDa precursor, is cleaved releasing the 17 kDa carboxyl-terminal cytokine IL-1alpha to which all of the biological properties of IL-1alpha have been attributed. We investigated the potential independent properties of the remaining 16 kDa IL-1alpha amino-terminal propiece by expression in human tumor and primary human cell lines. The IL-1alpha propiece produced apoptosis in malignant but not normal cell lines. A minimal fragment comprised of amino acids 55-108 was required for apoptosis. Deletion and mutation studies identified an extended nuclear localization sequence required for nuclear localization, induction of apoptosis and concentration of the IL-1alpha propiece in interchromatin granule clusters, concentrations of proteins in the RNA splicing and processing pathways. The IL-1alpha propiece interacted with five known components of the RNA splicing/processing pathway, suggesting that the mechanism of action may involve changes in RNA splicing or processing. Expression of the IL-1alpha propiece caused a shift in the ratio of Bcl-X-1/Bcl-X-s toward the apoptotic direction. Our findings indicate that the IL-1alpha propiece induces apoptosis in a range of tumor cells and likely operates through a mechanism involving the RNA processing apparatus and the alternate splicing of apoptosis regulatory proteins. C1 Univ Calif San Francisco, Vet Adm Med Ctr, No Calif Inst Res & Educ, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Pollock, AS (reprint author), San Francisco VAMC, Dept Med 111J, 4150 Clement St, San Francisco, CA 94121 USA. EM pollock.allan@maelstrom.ucsf.edu FU NCI NIH HHS [R55 CA91038]; NIDDK NIH HHS [R01DK39776, R01DK31398] NR 62 TC 39 Z9 40 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 FEB PY 2003 VL 17 IS 2 BP 203 EP 213 DI 10.1096/fj.02-0602com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 653VC UT WOS:000181456900045 PM 12554699 ER PT J AU Seifer, DB Lambert-Messerlian, G Schneyer, AL AF Seifer, DB Lambert-Messerlian, G Schneyer, AL TI Ovarian brain-derived neurotrophic factor is present in follicular fluid from normally cycling women SO FERTILITY AND STERILITY LA English DT Editorial Material C1 UMDNJ, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, Div Reprod Endocrinol & Infertil, New Brunswick, NJ 08901 USA. Women & Infants Hosp Rhode Isl, Dept Pathol & Lab Med, Providence, RI USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Reprod Endocrine Unit, Boston, MA USA. RP Seifer, DB (reprint author), UMDNJ, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, Div Reprod Endocrinol & Infertil, 303 George St,Suite 250, New Brunswick, NJ 08901 USA. OI Seifer, David/0000-0003-3950-9341 FU NIA NIH HHS [AG 15425]; NICHD NIH HHS [U54HD29164] NR 5 TC 28 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD FEB PY 2003 VL 79 IS 2 BP 451 EP 452 AR PII S0015-0282(02)04669-1 DI 10.1016/S0015-0282(02)04669-1 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 644CB UT WOS:000180899400039 PM 12568867 ER PT J AU Girnun, GD Spiegelman, BM AF Girnun, GD Spiegelman, BM TI PPAR gamma ligands: Taking Ppart in chemoprevention SO GASTROENTEROLOGY LA English DT Editorial Material ID ACTIVATED RECEPTOR-GAMMA; NUCLEAR HORMONE RECEPTORS; ABERRANT CRYPT FOCI; COLORECTAL-CANCER; DIABETES-MELLITUS; GENE-EXPRESSION; PROLIFERATOR; COLON; DIFFERENTIATION; INHIBITION C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 34 TC 20 Z9 22 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 FEB PY 2003 VL 124 IS 2 BP 564 EP 567 DI 10.1053/gast.2003.50070 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 641EP UT WOS:000180732100031 PM 12557160 ER PT J AU Jacobson, BC Pitman, MB Brugge, WR AF Jacobson, BC Pitman, MB Brugge, WR TI EUS-guided FNA for the diagnosis of gallbladder masses SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID FINE-NEEDLE ASPIRATION; ENDOSCOPIC ULTRASOUND EUS; PORCELAIN GALLBLADDER; CARCINOMA; LESIONS; CYTOLOGY; ULTRASONOGRAPHY; ENDOSONOGRAPHY; CANCER; BIOPSY AB Background: Gallbladder masses can be identified endosongraphically, but FNA for cytologic diagnosis is not routine. This is a review of our experience with EUS-guided FNA of gallbladder masses. Methods: Records of patients undergoing EUS were reviewed to identify cases in which FNA of the gallbladder was performed. Reports of EUS procedures, EUS images, cytology results, and clinical records were reviewed. Observations: Six cases were identified. The final diagnosis was gallbladder carcinoma in 5 and xanthogranulomatous cholecystitis in one. In each case, EUS revealed a hypoechoic mass within the gallbladder wall or gallbladder lumen. Gallbladder wall calcification was observed in 3 of the 5 cases of carcinoma. FNA yielded a specimen that was positive (n = 3) or raised a suspicion (n = 1) for adenocarcinoma in 4 of the 5 proven malignancies. FNA of regional lymph nodes demonstrated metastatic adenocarcinoma in 2 cases. FNA was negative for malignancy in the case of xanthogranulomatous cholecystitis and one case of proven carcinoma. There were no complications. Conclusions: EUS-guided FNA of gallbladder masses is safe and can provide a definitive diagnosis of malignancy. Gallbladder carcinoma appears endosonographically as a hypoechoic mass and may be associated with focal wall calcifications. C1 Boston Univ, Med Ctr, Gastroenterol Sect, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Jacobson, BC (reprint author), Boston Univ, Med Ctr, Gastroenterol Sect, 88 E Newton St,D408, Boston, MA 02118 USA. OI Jacobson, Brian/0000-0001-7064-2357 NR 32 TC 30 Z9 32 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD FEB PY 2003 VL 57 IS 2 BP 251 EP 254 DI 10.1067/mge.2003.86 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 641DV UT WOS:000180730000024 PM 12556797 ER PT J AU Boulis, A AF Boulis, A TI Medical careers and feminist agendas. SO GENDER & SOCIETY LA English DT Book Review C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Boulis, A (reprint author), Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-2432 J9 GENDER SOC JI Gend. Soc. PD FEB PY 2003 VL 17 IS 1 BP 143 EP 145 DI 10.1177/0891243202238992 PG 3 WC Sociology; Women's Studies SC Sociology; Women's Studies GA 637DZ UT WOS:000180497500013 ER PT J AU Gupta, VK Park, JO Kurihara, T Koons, A Mauceri, HJ Jaskowiak, NT Kufe, DW Weichselbaum, RR Posner, MC AF Gupta, VK Park, JO Kurihara, T Koons, A Mauceri, HJ Jaskowiak, NT Kufe, DW Weichselbaum, RR Posner, MC TI Selective gene expression using a DF3/MUC1 promoter in a human esophageal adenocarcinoma model SO GENE THERAPY LA English DT Article DE df3; muc1; gene therapy; radiation; esophageal cancer ID TUMOR-NECROSIS-FACTOR; REPLICATION-COMPETENT ADENOVIRUS; IONIZING-RADIATION; FACTOR-ALPHA; PROSTATE-CANCER; CELL-LINES; THERAPY; CARCINOMA; JUN; TRANSCRIPTION AB The efficacy of replication-deficient adenoviral vectors in gene therapy is confined to the number of tumor cells the vector infects. To focus and enhance the therapeutic efficacy, we employed a conditionally replication-competent adenoviral vector with a tissue-specific promoter, DF3/MUC1, in a human esophageal adenocarcinoma model. Our results demonstrate that Ad.DF3.E1A.CMV.TNF (Ad. DF3.TNF) specifically replicates in Bic-1 (DF3-producing cells) and mediates an enhanced biologic effect due to increased TNF-alpha in the same DF3-producing cells. We also show that the increased TNF-alpha interacts with ionizing radiation to produce greater tumor regression and a greater delay in tumor regrowth in Bic-1 (DF3-producing cells) compared to Seg-1 (DF3 non-producers). Tumor cell targeting using conditionally replication-competent adenoviral vectors with tumor-specific promoters to drive viral replication and deliver TNF-alpha provides a novel approach to enhancing tumor radiosensitivity. C1 Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Harvard Univ, Dana Farber Canc Inst, Div Pharmacol, Boston, MA 02115 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Posner, MC (reprint author), Univ Chicago, Dept Surg, 5841 S Maryland Ave,MC 5031, Chicago, IL 60637 USA. NR 39 TC 13 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD FEB PY 2003 VL 10 IS 3 BP 206 EP 212 DI 10.1038/sj.gt.3301867 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 638TX UT WOS:000180588000002 PM 12571627 ER PT J AU Ford, ME Havstad, SL Tilley, BC AF Ford, ME Havstad, SL Tilley, BC TI Recruiting older African American men to a cancer screening trial (the AAMEN Project) SO GERONTOLOGIST LA English DT Article DE recruitment; cancer screening; African American men; older adults ID PROSTATE-CANCER; CLINICAL-TRIALS; RACIAL-DIFFERENCES; COLORECTAL-CANCER; INFORMAL SUPPORT; ELDERLY BLACKS; WHITE MEN; PARTICIPATION; PREVENTION; RETENTION AB Purpose: This article describes the demographic characteristics of participants in a randomized trial (the AAMEN Project) designed to recruit older (aged 55+ years) African American men to a cancer screening trial. Design and Methods: The AAMEN Project is a recruitment trial developed for African American men aged 55+ years living in southeastern Michigan. Results: Of the 34,376 African American men in the study, 37.6% had low incomes and 62.4% had moderate-to-high incomes. The average age of the men was 63.3 years (SD = 5.9 years). Among men who were eligible and interested in participating, the proportion of men with low incomes was significantly greater than, the proportion of men with moderate-to-high incomes (p < .001). Implications: The AAMEN Project demonstrated success in recruiting a substantial proportion of men with low incomes as well as men with mode rate-to-high incomes. These findings may facilitate the development of future recruitment efforts involving older African American men. C1 Henry Ford Hlth Sci Ctr, Ctr Res Diverse Populat, Detroit, MI USA. Henry Ford Hlth Sci Ctr, Dept Biostat & Res Epidemiol, Detroit, MI USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. RP Ford, ME (reprint author), Baylor Coll Med, Vet Affairs Med Ctr 152, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [N01-CN-25512]; NIA NIH HHS [P 30 AG 5286] NR 62 TC 30 Z9 30 U1 2 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2003 VL 43 IS 1 BP 27 EP 35 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 644WP UT WOS:000180943600004 PM 12604743 ER PT J AU Kunik, ME Snow, AL Molinari, VA Menke, TJ Souchek, J Sullivan, G Ashton, CM AF Kunik, ME Snow, AL Molinari, VA Menke, TJ Souchek, J Sullivan, G Ashton, CM TI Health care utilization in dementia patients with psychiatric comorbidity SO GERONTOLOGIST LA English DT Article DE mental disorders; hospitalization; ambulatory care ID ALZHEIMERS-DISEASE; BEHAVIORAL DISTURBANCES; PSYCHOTIC SYMPTOMS; DEPRESSION; PREVALENCE; PREDICTORS; INPATIENTS; MORTALITY; DELUSIONS; SERVICES AB Purpose: The purpose of this research was to determine if differences in service use exist between dementia patients with and without psychiatric comorbidity. Design and Methods: A retrospective cohort study was conducted on all Veterans Affairs (VA) beneficiaries seen at the Houston Veterans Affairs Medical Center with a VA Outpatient Clinic File diagnosis of dementia in 1997. The primary dependent measure was amount of Houston VA health service use from study entry until the end of fiscal year 1999 or until death. Results: Of the 864 dementia patients in the identified cohort, two thirds had a comorbid psychiatric diagnosis. Examination of 2-year health service use revealed that, after adjusting for demographic and medical comorbidity differences, dementia patients with psychiatric comorbidity had increased medical and psychiatric inpatient days of care and more psychiatric outpatient visits compared with patients without psychiatric comorbidity. Implications: Further understanding of the current health service use of dementia patients with psychiatric comorbidity may help to establish a framework for considering change in the current system of care. A coordinated system of care with interdisciplinary teamwork may provide both cost-effective and optimal treatment for dementia patients. C1 Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Vet Affairs South Cent Mental Illness Res Educ &, Houston, TX USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Arkansas Med Sci, Dept Psychiat & Behav Sci, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Ctr Mental Hlth & Outcomes Res, Little Rock, AR USA. RP Kunik, ME (reprint author), VAMC, 2002 Holcombe HSR& D152, Houston, TX 77030 USA. NR 30 TC 23 Z9 23 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 2003 VL 43 IS 1 BP 86 EP 91 PG 6 WC Gerontology SC Geriatrics & Gerontology GA 644WP UT WOS:000180943600010 PM 12604749 ER PT J AU Wilhelmi, BJ Lee, WPA Pagensteert, GI May, JW AF Wilhelmi, BJ Lee, WPA Pagensteert, GI May, JW TI Replantation in the mutilated hand SO HAND CLINICS LA English DT Article ID DIGITAL REPLANTATION; UPPER EXTREMITY; ISCHEMIA TIME; COLD ISCHEMIA; EXPERIENCE; SURVIVAL; REVASCULARIZATION; INJURIES AB Since the first replantation 40 years ago, refinements in technique and advances in technology have enhanced survival rates and functional outcomes. The decision to attempt replantation and the techniques involved in replantation of amputated parts are often extremely difficult. The best survival and functional rates for replantation of amputated upper extremity parts are achieved with sharp amputations of the thumb, multiple fingers or at the level of the hand and wrist in younger patients. Preoperatively the patient must be prepared psychologically, to provide for realistic expectation for survival and return of function of the replanted part. Intraoperatively application of specialized techniques and optimal order for repairing of the various injured structures can improve operative times and survival rates. Post-replantation procedures such as tenolysis can be considered to optimize final outcome. Forty years after the first replant we recognize the ultimate goal not merely to preserve all living tissue through nonselective replantation but rather to preserve one's quality of life by improving their function and appearance. C1 So Illinois Univ, Sch Med, Plast Surg Inst, Springfield, IL 62794 USA. Univ Pittsburgh, Sch Med, Div Plast Surg Hand Surg, Pittsburgh, PA 15260 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA USA. RP Wilhelmi, BJ (reprint author), So Illinois Univ, Sch Med, Plast Surg Inst, 747 North Rutledge,3rd Floor, Springfield, IL 62794 USA. NR 80 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD FEB PY 2003 VL 19 IS 1 BP 89 EP + DI 10.1016/S0749-0712(02)00137-3 PG 34 WC Orthopedics SC Orthopedics GA 662PT UT WOS:000181956900009 PM 12683449 ER PT J AU Abroms, L Jorgensen, CM Southwell, BG Geller, AC Emmons, KM AF Abroms, L Jorgensen, CM Southwell, BG Geller, AC Emmons, KM TI Gender differences in young adults' beliefs about sunscreen use SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE gender differences; young adults; sun protection; sunscreen use ID SUN PROTECTION BEHAVIORS; SKIN-CANCER; EXPOSURE; KNOWLEDGE; ATTITUDES; ADOLESCENTS; POPULATION; INTENTIONS; TOUCH; RISK AB This study employs focus group methodology to explore gender differences in sunscreen use. Guided by the theory of reasoned action, males and females were found to differ on each of the following constructs: behavior, behavioral beliefs, and normative beliefs. Males and females differed in their sunscreen use, with females adopting a more preventive style of sunscreen use and males a more reactive style. Males and females differed in their salient beliefs that motivated their sunscreen use, many of which were related to traditional American gender roles. In addition, although males and females were aware of both positive and negative sources of normative beliefs regarding sunscreen use, females received more encouragement from their mothers and peers than males. Findings are discussed in terms of their implications for the design of future interventions. C1 Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. Boston Univ, Sch Med, Canc Prevent & Control Ctr, Boston, MA 02118 USA. Univ Minnesota, Sch Journalism & Mass Commun, Minneapolis, MN 55455 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Commun & Behav Sci Branch, Atlanta, GA 30341 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Jorgensen, CM (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Commun & Behav Sci Branch, MS K-48,4770 Bufford Hwy, Atlanta, GA 30341 USA. FU PHS HHS [T260] NR 29 TC 38 Z9 40 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD FEB PY 2003 VL 30 IS 1 BP 29 EP 43 DI 10.1177/1090198102239257 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 638JB UT WOS:000180566900002 PM 12564666 ER PT J AU Petersen, LA Normand, SLT Druss, BG Rosenheck, RA AF Petersen, LA Normand, SLT Druss, BG Rosenheck, RA TI Process of care and outcome after acute myocardial infarction for patients with mental illness in the VA health care system: Are there disparities? SO HEALTH SERVICES RESEARCH LA English DT Article DE acute myocardial infarction; mental disorders; outcome assessment (health care); health services accessibility; physicians' practice patterns ID COOPERATIVE CARDIOVASCULAR PROJECT; OF-VETERANS-AFFAIRS; CORONARY-ARTERY DISEASE; NEW-YORK-STATE; ELDERLY PATIENTS; RACIAL-DIFFERENCES; REVASCULARIZATION PROCEDURES; MEDICARE PATIENTS; CARDIAC-CATHETERIZATION; PSYCHIATRIC-PATIENTS AB Objective. To compare process of care and outcome after acute myocardial infarction, for patients with and without mental illness, cared for in die Veterans Health Administration (VA) health care system. Data Sources/Setting. Primary clinical data from 81 VA hospitals. Study Design. This was a retrospective cohort study of 4,340 veterans discharged with clinically confirmed acute myocardial infarction. Of these, 859 (19.8 percent) met the definition of mental illness. Measures were age-adjusted in-hospital and 90-day cardiac procedure use; age-adjusted relative risks (RR) of use of thrombolytic therapy, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, or aspirin at discharge; risk-adjusted 30-day and one-year mortality. Results. Patients with mental illness were marginally less likely than those without mental illness to undergo in-hospital angiography (age-adjusted RR 0.90 [95 percent confidence interval: 0.83, 0.98]), but there was no significant difference in the. age-adjusted RR of coronary artery bypass graft surgery in the 90 days after admission (0.85 [0.69,1.05]), or in the receipt of medications of known benefit. For example, ideal candidates with and without mental illness were equally likely to receive beta-blockers at the time of discharge (age-adjusted RR 0.92 [0.82, 1.02]). The risk-adjusted odds ratio (OR) for death in patients with mental illness versus those without mental illness within 30 days was 1.00 (0.75,1.32), and for death within one year was 1.25 (1.00,1.53). Conclusions. Veterans Health Administration patients with mental illness were marginally less likely than those without mental illness to receive diagnostic angiography, and no less likely to receive revascularization or medications of known benefit after acute myocardial infarction. Mortality at one year may have been higher, although this finding did not reach statistical significance. These findings are consistent with other studies showing reduced health care disparities in the VA for other vulnerable groups, and suggest that an integrated health care system with few financial barriers to health care access may attenuate some health care disparities. Further work should address how health care organizational features might narrow disparities in health care for vulnerable groups. C1 Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. Yale Univ, Dept Publ Hlth, New Haven, CT 06520 USA. RP Petersen, LA (reprint author), Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 72 TC 52 Z9 54 U1 4 U2 12 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2003 VL 38 IS 1 BP 41 EP 63 DI 10.1111/1475-6773.00104 PN 1 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 647RY UT WOS:000181108900003 PM 12650380 ER PT J AU Berlowitz, DR Young, GJ Hickey, EC Saliba, D Mittman, BS Czarnowski, E Simon, B Anderson, JJ Ash, AS Rubenstein, LV Moskowitz, MA AF Berlowitz, DR Young, GJ Hickey, EC Saliba, D Mittman, BS Czarnowski, E Simon, B Anderson, JJ Ash, AS Rubenstein, LV Moskowitz, MA TI Quality improvement implementation in the nursing home SO HEALTH SERVICES RESEARCH LA English DT Article DE quality improvement; quality of care; nursing homes; decubitus ulcers ID CLINICAL INDICATORS; CARE; MANAGEMENT; ADOPTION; CULTURE; TRIALS; IMPACT; TQM; VA AB Objective. To examine quality improvement (QI) implementation in nursing homes, its association with organizational culture, and its effects on-pressure ulcer care. Data Sources/Study Settings. Primary data were collected from staff at 35 nursing homes maintained by the Department of Veterans Affairs (VA) on measures related to QI implementation and organizational culture. These data were combined with information obtained from abstractions of medical records and analyses of an existing database., Study Design. A cross-sectional analysis of the association among the different measures was performed. Data Collection/Extraction Methods. Completed surveys containing information on QI implementation, organizational culture, employee satisfaction, and perceived adoption of guidelines were obtained from 1,065 nursing home staff. Adherence to best practices related to pressure ulcer prevention was abstracted from medical records. Risk-adjusted rates of pressure ulcer development were calculated from an administrative database. Principal Findings. Nursing homes differed significantly (p<.001) in their extent of QI implementation with scores on this I to 5 scale ranging from 2.98 to 4.08. Quality improvement implementation was greater in those nursing homes with an organizational culture that emphasizes innovation and teamwork. Employees of nursing homes with a greater degree of QI implementation were more satisfied with their jobs (a 1-point increase in QI score was associated with a 0.83 increase on the 5-point satisfaction scale, p <.001) and were more likely to report adoption of pressure ulcer clinical guidelines (a 1-point increase in QI score was associated with a 28 percent increase in number of staff reporting adoption, p<.001). No significant association was found, though, between QI implementation and either adherence to guideline recommendations as abstracted from records or the rate of pressure ulcer development. Conclusions. Quality improvement implementation is most likely to be successful in those VA nursing homes with an underlying culture that promotes innovation. While QI implementation may result in staff who are more satisfied with their jobs and who believe they are providing better; care, associations with improved care are uncertain. C1 Bedford VA Hosp, CHQOER, Bedford, MA 01730 USA. Edith Nourse Rogers Mem Vet Adm Hosp, CHQOER, Bedford, MA USA. Greater Boston VAMC, Management Decis & Res Ctr, Boston, MA USA. Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. RAND Corp, Santa Monica, CA USA. RP Berlowitz, DR (reprint author), Bedford VA Hosp, CHQOER, 200 Springs Rd, Bedford, MA 01730 USA. NR 31 TC 65 Z9 66 U1 2 U2 9 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD FEB PY 2003 VL 38 IS 1 BP 65 EP 83 DI 10.1111/1475-6773.00105 PN 1 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 647RY UT WOS:000181108900004 PM 12650381 ER PT J AU Rodriguez, A Alemparte, MR Baldi, J Navia, J Delacasa, A Vogel, D Oliveri, R Pereira, CF Bernardi, V O'Neill, W Palacios, IF AF Rodriguez, A Alemparte, MR Baldi, J Navia, J Delacasa, A Vogel, D Oliveri, R Pereira, CF Bernardi, V O'Neill, W Palacios, IF CA ERACI II Invest TI Coronary stenting versus coronary bypass surgery in patients with multiple vessel disease and significant proximal LAD stenosis: results from the ERACI II study SO HEART LA English DT Article ID GRAFT-SURGERY; BALLOON ANGIOPLASTY; RANDOMIZED TRIAL; ARTERY DISEASE; FOLLOW-UP; MULTIVESSEL DISEASE; SURVIVAL; IMPLANTATION; MORTALITY AB Purpose: To compare percutaneous coronary intervention (PCI) using stent implantation versus coronary artery bypass graft (CABG) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery (LAD). Methods: 230 patients with multiple vessel disease and severe stenosis of the proximal LAD (113 with PCI, 117 with CABG). They were a cohort of patients from the randomised ERACI (Argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease) II study. Results: Both groups had similar baseline characteristics. There were no significant differences in 30 day major adverse cardiac events (death, myocardial infarction, stroke, and repeat procedures) between the strategies (PCI 2.7% v CABG 7.6%, p = 0. 18). There were no significant differences in survival (PCI 96.4% v CABG 95%, p = 0.98) and survival with freedom from myocardial infarction (PCI 92% v CABG 89%, p = 0.94) at 41.5 (6) months' follow up. However, freedom from new revascularisation procedures (CABG 96.6% v PCI 73%, p = 0.0002) and frequency of angina (CABG 9.4% v PCI 22%, p = 0.025) were superior in the CABG group. Conclusion: Patients with multivessel disease and significant disease of the proximal LAD randomly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infarction at long term follow up. Repeat revascularisation procedures were higher in the PCI group. C1 Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Otamend Hosp, Buenos Aires, DF, Argentina. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA. NR 34 TC 43 Z9 45 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD FEB PY 2003 VL 89 IS 2 BP 184 EP 188 DI 10.1136/heart.89.2.184 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 639DE UT WOS:000180611700023 PM 12527674 ER PT J AU Spiegel, BMR Targownik, L Dulai, GS Karsan, HA Gralnek, IM AF Spiegel, BMR Targownik, L Dulai, GS Karsan, HA Gralnek, IM TI Endoscopic screening for esophageal varices in cirrhosis: Is it ever cost effective? SO HEPATOLOGY LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; TERM FOLLOW-UP; PROPHYLACTIC SCLEROTHERAPY; GASTROINTESTINAL ENDOSCOPY; PORTAL-HYPERTENSION; NATURAL-HISTORY; LIVER-CIRRHOSIS; UNITED-STATES; PREVENTION; HEMORRHAGE AB Current guidelines for the management of patients with compensated cirrhosis recommend universal screening endoscopy followed by prophylactic beta-blocker therapy to prevent initial hemorrhage in those found to have esophageal varices. However, the cost-effectiveness of this recommendation has not been established. Our objective was to determine whether screening endoscopy is cost-effective compared with empiric medical management in patients with compensated cirrhosis. Decision analysis with Markov modeling was used to calculate the cost-effectiveness of 6 competing strategies: (1) universal screening endoscopy (EGD) followed by beta-blocker (BB) therapy (EGD-->BB) if varices are present, (2) EGD followed by endoscopic band ligation (EBL) (EGD-->EBL) if varices are present, (3) selective screening endoscopy (sEGD) in high risk patients followed by BB therapy if varices are present (sEGD-->BB), (4) selective screening endoscopy followed by EBL (sEGD-->EBL) if varices are present, (5) empiric beta-blocker therapy in all patients, and (6) no prophylactic therapy ("Do Nothing"). Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per initial variceal hemorrhage prevented. The "Do Nothing" strategy was the least expensive yet least effective approach. Compared with the "Do Nothing" strategy, the empiric beta-blocker strategy cost an incremental $12,408 per additional variceal bleed prevented. Compared with the empiric beta-blocker strategy, in turn, both the EGD-->BB and the EGD-->EBL strategies cost over $175,000 more per additional bleed prevented. The sEGD-->BB and sEGD-->EBL strategies were more expensive and less effective than the empiric beta-blocker strategy. In conclusion, empiric beta-blocker therapy for the primary prophylaxis of variceal hemorrhage is a cost-effective measure, as the use of screening endoscopy to guide therapy adds significant cost with only marginal increase in effectiveness. C1 Univ Calif Los Angeles, Sch Med,CURE Digest Dis Res Ctr, Div Gastroenterol,Ctr Study Digest Healthcare, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, Sch Med,CURE Digest Dis Res Ctr, Div Gastroenterol,Ctr Study Digest Healthcare, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115 Rm 215B, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-07180]; PHS HHS [K23] NR 52 TC 84 Z9 87 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2003 VL 37 IS 2 BP 366 EP 377 DI 10.1053/jhep.2003.50050 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 640FQ UT WOS:000180678000018 PM 12540787 ER PT J AU Wheeler, VC Lebel, LA Vrbanac, V Teed, A Riele, HT MacDonald, ME AF Wheeler, VC Lebel, LA Vrbanac, V Teed, A Riele, HT MacDonald, ME TI Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSGENIC MOUSE MODELS; CAG REPEAT LENGTH; HUNTINGTONS-DISEASE; MUTANT HUNTINGTIN; SOMATIC INSTABILITY; INCREASES SURVIVAL; (CAG)(N) REPEAT; MICE; EXPANSION; EXPRESSION AB Somatic instability of expanded HD CAG repeats that enc ode the polyglutamine tract in mutant huntingtin has been implicated in the striatal selectivity of Huntington's disease (HD) pathology. Here in Hdh(Q111) mice, we have tested whether a genetic background deficient in Msh2, expected to eliminate the unstable behavior of the 109 CAG array inserted into the murine HD gene, would alter the timing or striatal specificity of a dominant disease phenotype that predicts late-onset neurodegeneration. Our analyses of Hdh(Q111/+):Msh2(+/+) and Hdh(Q111/+): Msh2(-/-) progeny revealed that, while inherited instability involved Msh2-dependent and -independent mechanisms, lack of Msh2 was sufficient to abrogate progressive HD CAG repeat expansion in striatum. The absence of Msh2 also eliminated striatal mutant huntingtin with somatically expanded glutamine tracts and caused an similar to5 month delay in nuclear mutant protein accumulation, but did not alter the striatal specificity of this early phenotype. Thus, somatic HD CAG instability appears to be a consequence of a striatal-selective disease process that accelerates the timing of an early disease phenotype, via expansion of the glutamine tract in mutant huntingtin. Therefore Msh2, as a striking modifier of early disease onset in a precise genetic HID mouse model, provides a novel target for the development of pharmacological agents that aim to slow pathogenesis in man. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands. RP Wheeler, VC (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS16367, NS32765] NR 50 TC 110 Z9 112 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB 1 PY 2003 VL 12 IS 3 BP 273 EP 281 DI 10.1093/hmg/ddg056 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 644JH UT WOS:000180913800007 PM 12554681 ER PT J AU Tan, DF Kirley, S Li, Q Ramnath, N Slocum, HK Brooks, JS Wu, CL Zukerberg, LR AF Tan, DF Kirley, S Li, Q Ramnath, N Slocum, HK Brooks, JS Wu, CL Zukerberg, LR TI Loss of cables protein expression in human non-small cell lung cancer: A tissue microarray study SO HUMAN PATHOLOGY LA English DT Article DE non-small cell lung cancer; Cables; immunohistochemistry ID 18Q; CARCINOMA; GENE; HETEROZYGOSITY; REGIONS; MICE AB Loss of heterozygosity (LOH) on chromosome 18q is common in lung cancer. The genes involved in LOH on 18q in lung cancer have not been well characterized. Cables, a cyclin-dependent kinase (cdk) interacting protein, has recently been identified and mapped to human chromosome 18q11-12. Cables inhibits cell growth and suppresses tumor formation in nude mice, making it a candidate gene for 18q LOH in lung cancer. Little is known regarding Cables protein expression in human non-small cell lung cancer (NSCLC). In this study we examined Cables expression in 163 NSCLC and nonneoplastic lung specimens using tissue microarrays. Strong nuclear staining was present in normal lung and bronchial tissue. We also evaluated the Cables protein expression pattern and its correlation with histopathologic features and with clinical course of NSCLC. The results of the present study demonstrate for the first time that numerous NSCLCs (45%) lose Cables expression. Furthermore, more adenocarcinomas show a loss of this novel protein than do squamous counterparts. The relationship between tumor histology type and Cables expression appears to be statistically significant (P = 0.028). Our results suggest that Cables may be involved in the pathogenesis of NSCLC. Copyright 2003, Elsevier Science (USA). All rights reserved. C1 SUNY Buffalo, Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP Tan, DF (reprint author), SUNY Buffalo, Roswell Pk Canc Inst, Dept Pathol, Elm & Carlton St, Buffalo, NY 14263 USA. FU NCI NIH HHS [CA16056] NR 28 TC 17 Z9 17 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD FEB PY 2003 VL 34 IS 2 BP 143 EP 149 DI 10.1053/hupa.2003.26 PG 7 WC Pathology SC Pathology GA 650QU UT WOS:000181275500007 PM 12612882 ER PT J AU Griffin, KA Abu-Amarah, I Picken, M Bidani, AK AF Griffin, KA Abu-Amarah, I Picken, M Bidani, AK TI Renoprotection by ACE inhibition or aldosterone blockade is blood pressure-dependent SO HYPERTENSION LA English DT Article DE hypertension, renal; rats, stroke-prone SHR; nephrosclerosis; autoregulation ID SPONTANEOUSLY HYPERTENSIVE RATS; REMNANT KIDNEY MODEL; RENIN-ANGIOTENSIN SYSTEM; CALCIUM-CHANNEL BLOCKERS; HEMORRHAGIC STROKE; GLOMERULAR INJURY; VASCULAR INJURY; RENAL ABLATION; ORGAN DAMAGE; SALT AB Renin-angiotensin-aldosterone system blockade has been shown to protect against renal damage in salt-supplemented, stroke-prone spontaneously hypertensive rats (SHRsp). Based on intermittent tail-cuff blood pressure (BP) measurements, it has been claimed that such protection is BP-independent and mediated by a blockade of the direct tissue-damaging effects of angiotensin and/or aldosterone. BP radiotelemetry was performed for 8 weeks in approximate to10-week-old male SHRsp who received a standard diet and either tap water (n=10) or 1% NaCl to drink. Saline-drinking SHRsp were either left untreated (n = 12), received enalapril (50 mg/L) in drinking fluid (n = 9), or had subcutaneous implantation of time-release 200-mg pellets of aldactone (n = 10). The average systolic BP (mean +/- SEM) during the final 3 weeks was significantly higher (P<0.05) in untreated saline-drinking (215 +/- 6 mm Hg) SHRsp but not aldactone-treated (198 +/- 4 mmHg) or enalapril-treated treated SHRsp (173 +/- 1 mmHg), as compared with tap water-drinking SHRsp (197 +/- 3 mm Hg). Histological renal damage scores at 8 weeks paralleled the BP in all groups, with an excellent correlation (r=0.8, P<0.001, n=41). Moreover, a renal damage score of >5 was only observed in SHRsp whose average systolic BP during the final 3 weeks exceeded 200 mm Hg, indicating a threshold relation with BP. These data show that protection by renin-angiotensin-aldosterone system blockade in this model is BP-dependent and mediated by preventing the severe increases in BP seen in untreated salt-supplemented SHRsp and further underscore the limitations of interpretations based on conventional tail-cuff BP measurements. C1 Loyola Univ, Med Ctr, Dept Internal Med, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Griffin, KA (reprint author), Loyola Univ, Med Ctr, Dept Internal Med, 2160 S 1st Ave, Maywood, IL 60153 USA. FU NHLBI NIH HHS [HL64807]; NIDDK NIH HHS [DK-40426] NR 49 TC 77 Z9 81 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 FEB PY 2003 VL 41 IS 2 BP 201 EP 206 DI 10.1161/01.HYP.0000049881.25304.73 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 645WQ UT WOS:000181003700004 PM 12574082 ER PT J AU Liu, YW Xiong, Y Naidenko, OV Liu, JH Zhang, R Joachimiak, A Kronenberg, M Cheroutre, H Reinherz, EL Wang, JH AF Liu, YW Xiong, Y Naidenko, OV Liu, JH Zhang, R Joachimiak, A Kronenberg, M Cheroutre, H Reinherz, EL Wang, JH TI The crystal structure of a TL/CD8 alpha alpha complex at 2.1 angstrom resolution: Implications for modulation of T cell activation and memory SO IMMUNITY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; THYMUS-LEUKEMIA ANTIGEN; CLASS-I MOLECULES; MHC-LIKE FOLD; NONCLASSICAL MHC; TRANSFERRIN RECEPTOR; MICE LACKING; MOUSE CD1; PEPTIDE; RECOGNITION AB TL is a nonclassical MHC class I molecule that modulates T cell activation through relatively high-affinity interaction with CD8alphaalpha. To investigate how the TL/CD8alphaalpha interaction influences TCR signaling, we characterized the structure of the TL/CD8alphaalpha complex using X-ray crystallography. Unlike antigen-presenting molecules, the TL antigen-binding groove is occluded by specific conformational changes. This feature eliminates antigen presentation, severely hampers direct TCR recognition, and prevents TL from participating in the TCR activation complex. At the same time, the TL/CD8alphaalpha interaction is strengthened through subtle structure changes in the TL alpha3 domain. Thus, TL functions to sequester and redirect CD8alphaalpha away from the TCR, modifying lck-dependent signaling. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. La Jolla Inst Allergy & Immunol, Div Dev Immunol, San Diego, CA 92121 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI45022, AI50263]; NIGMS NIH HHS [GM56008] NR 59 TC 68 Z9 69 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 2003 VL 18 IS 2 BP 205 EP 215 DI 10.1016/S1074-7613(03)00027-X PG 11 WC Immunology SC Immunology GA 648FC UT WOS:000181138100005 PM 12594948 ER PT J AU Bobbitt, KR Addo, MM Altfeld, M Filzen, T Onafuwa, AA Walker, BD Collins, KL AF Bobbitt, KR Addo, MM Altfeld, M Filzen, T Onafuwa, AA Walker, BD Collins, KL TI Rev activity determines sensitivity of HIV-1-infected primary T cells to CTL killing SO IMMUNITY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FULL-LENGTH CLONES; HEPATITIS-C VIRUS; CD8(+) LYMPHOCYTES; IMMUNE-RESPONSE; RNA EXPRESSION; HIV-1 REV; INFECTION; NEF; PROGRESSION AB The HIV Nef protein is thought to promote HIV immune evasion by downmodulating MHC-I and protecting infected cells from CTL killing. In addition, we demonstrated that Rev, an HIV regulatory protein needed for expression of the HIV late genes, can influence CTL killing. When Rev activity level was reduced by virtue of amino acid alterations in the Rev protein sequence, infected cells were more resistant to anti-Gag and anti-Env CTL killing. A screen of primary viral isolates revealed that viruses derived from asymptomatic, infected people had lower Rev activity, lower Gag levels, and greater resistance to anti-Gag CTL killing. Thus, rev alleles with low activity may have a selective advantage in infected people with effective immune responses. C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Ctr AIDS Res, Charlestown, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02114 USA. RP Collins, KL (reprint author), Univ Michigan, Dept Internal Med, 1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. FU NIAID NIH HHS [K08 AI01448, 5T32AI07528-03, R01 AI051192] NR 48 TC 29 Z9 30 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 2003 VL 18 IS 2 BP 289 EP 299 DI 10.1016/S1074-7613(03)00031-1 PG 11 WC Immunology SC Immunology GA 648FC UT WOS:000181138100012 PM 12594955 ER PT J AU von Boehmer, H Aifantis, I Gounari, F Azogui, O Haughn, L Apostolou, I Jaeckel, E Grassi, F Klein, L AF von Boehmer, H Aifantis, I Gounari, F Azogui, O Haughn, L Apostolou, I Jaeckel, E Grassi, F Klein, L TI Thymic selection revisited: how essential is it? SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL-RECEPTOR; NF-KAPPA-B; PROMISCUOUS GENE-EXPRESSION; FAMILY MEMBER BIM; MOUSE BONE-MARROW; MHC CLASS-II; ALPHA-BETA; POSITIVE SELECTION; GAMMA-DELTA; ALLELIC EXCLUSION AB Intrathymic T cell development represents one of the best studied paradigms of mammalian development. Lymphoid committed precursors enter the thymus and the Notch1 receptor plays an essential role in committing them to the T cell lineages. The pre-T cell receptor (TCR), as an autonomous cell signaling receptor, commits cells to the alphabeta lineage while its rival, the gammadeltaTCR, is involved in generating the gammadelta lineage of T cells. Positive and negative selection of immature alphabetaTCR-expressing cells are essential mechanisms for generating mature T cells, committing them to the CD4 and CD8 lineages and avoiding autoimmunity. Additional lineages of alphabetaT cells, such as the natural killer T cell lineage and the CD25(+) regulatory T cell lineage, are formed when the alphabetaTCR encounters specific ligands in suitable microenvironments. Thus, positive selection and receptor-instructed lineage commitment represent a hallmark of the thymus. Ectopically expressed organ-specific antigens contribute to thymic self-nonself discrimination, which represents an essential feature for the evolutionary fitness of mammalian species. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Pasteur, Paris, France. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Klein, Ludger/G-8785-2011 FU NIAID NIH HHS [AI45846, AI47281] NR 171 TC 137 Z9 140 U1 1 U2 8 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD FEB PY 2003 VL 191 IS 1 BP 62 EP 78 DI 10.1034/j.1600-065X.2003.00010.x PG 17 WC Immunology SC Immunology GA 652GY UT WOS:000181372500006 PM 12614352 ER PT J AU Swat, W Xavier, R Mizoguchi, A Mizoguchi, E Fredericks, J Fujikawa, K Bhan, AK Alt, FW AF Swat, W Xavier, R Mizoguchi, A Mizoguchi, E Fredericks, J Fujikawa, K Bhan, AK Alt, FW TI Essential role for Vav1 in activation, but not development, of gamma delta T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE antigen receptor; lymphocyte activation; lymphocyte development; intestinal epithelial lymphocyte; Vav1 ID ALPHA-BETA; MICE LACKING; THYMOCYTE DEVELOPMENT; RECEPTOR-GAMMA; INTRAEPITHELIAL LYMPHOCYTES; THYMIC DEVELOPMENT; GENE-EXPRESSION; DEFICIENT MICE; MUTANT MICE; PRE-TCR AB Vav1 is a guanine nucleotide exchange factor essential in the development and function of alphabeta lineage T cells. Here we report that in contrast to profound effects on pre-TCR- or alphabeta TCR-dependent events in thymocyte development, Vav1 deficiency has no detectable effect on the development of gammadelta T cells. Strikingly, however, these gammadelta T cells are markedly deficient in signaling through the gammadelta TCR, as evidenced by a lack of proliferation and cytokine production in response to stimulation with anti-gammadelta TCR antibodies. We propose that Vav1 has a unique and non-redundant role in the initiation of signaling downstream of the gammadelta TCR in lymphocytes. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol Med & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 320 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59561]; NIAID NIH HHS [AI01472]; NIDDK NIH HHS [DK47677] NR 46 TC 21 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD FEB PY 2003 VL 15 IS 2 BP 215 EP 221 DI 10.1093/intimm/dxg021 PG 7 WC Immunology SC Immunology GA 651DV UT WOS:000181306000008 PM 12578851 ER PT J AU Lavretsky, H Mistry, R Bastani, R Gould, R Gokhman, I Huang, D Maxwell, A McDermott, C Rosansky, J Jarvik, L AF Lavretsky, H Mistry, R Bastani, R Gould, R Gokhman, I Huang, D Maxwell, A McDermott, C Rosansky, J Jarvik, L CA UPBEAT Collaborative Grp TI Symptoms of depression and anxiety predict mortality in elderly veterans enrolled in the UPBEAT program SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Ctr Program Evaluat, Los Angeles, CA USA. Univ Calif Los Angeles, Str Comp Ctr, Los Angeles, CA USA. RP Lavretsky, H (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, 760 Westwood Pl,Room 37-425, Los Angeles, CA 90095 USA. RI Lavretsky, Helen/M-5711-2015 OI Lavretsky, Helen/0000-0001-9990-5085 FU NIMH NIH HHS [K23 MH 01948] NR 9 TC 8 Z9 8 U1 0 U2 0 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 FEB PY 2003 VL 18 IS 2 BP 183 EP 184 DI 10.1002/gps.706 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 648WT UT WOS:000181174500014 PM 12571829 ER PT J AU Balshi, TJ Wolfinger, GJ AF Balshi, TJ Wolfinger, GJ TI Immediate loading of dental implants in the edentulous maxilla: Case study of a unique protocol SO INTERNATIONAL JOURNAL OF PERIODONTICS & RESTORATIVE DENTISTRY LA English DT Article ID RETAINED MANDIBULAR OVERDENTURES AB Although immediate loading of dental implants is increasingly gaining recognition as an important option for certain categories of implant patients, the maxillary arch has historically posed difficulties that have limited the number of immediate loading applications. To address the needs of patients who cannot tolerate maxillary removable complete dentures, an immediate loading protocol we call "Teeth in a Day" uses a conversion prosthesis that has been expanded to include complete-arch maxillary reconstruction. Use of a large number of implants to prevent micromotion at the bone-to-implant interface is a critical element in this protocol. A patient treatment is reported. C1 Inst Facial Esthet, Ft Washington, PA 19034 USA. Harvard Univ, Sch Dent Med, Dept Prosthodont, Boston, MA 02115 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Balshi, TJ (reprint author), 467 Penn Ave 210, Ft Washington, PA 19034 USA. NR 18 TC 15 Z9 16 U1 0 U2 0 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0198-7569 J9 INT J PERIODONT REST JI Int. J. Periodontics Restor. Dent. PD FEB PY 2003 VL 23 IS 1 BP 37 EP 45 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 653FE UT WOS:000181423900005 PM 12617367 ER PT J AU Walss-Bass, C Kreisberg, JI Luduena, RF AF Walss-Bass, C Kreisberg, JI Luduena, RF TI Effect of the antitumor drug vinblastine on nuclear beta(II)-tubulin in cultured rat kidney mesangial cells SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE tubulin isotypes; micrombules; vinblastine; nuclear localization; DNA fragmentation ID MONOCLONAL-ANTIBODY; MITOTIC BLOCK; BETA-TUBULIN; MECHANISM; TAXOL; ISOTYPE; DEATH; PROLIFERATION; INHIBITION; DYNAMICS AB Tubulin, the main component of microtubules, is a major target for antitumor drugs such as vinblastine. We have recently discovered that the beta(II) isotype of tubulin is present in the nuclei of cultured rat kidney mesangial cells, smooth-muscle-like cells present in the renal glomerular mesangium (Walss C, Kreisberg JI, Luduena RF: Cell Motil Cytoskeleton 42: 274-284, 199). Here, we have investigated the effect of vinblastine on nuclear beta(II)-tubulin in these cells. We have found that, at concentrations of 15 nM and higher, vinblastine caused a reversible loss of beta(II)-tubulin from the nucleus. Our results raise the possibility that nuclear beta(II)-tubulin constitutes a population of tubulin that could be a novel target for antitumor drugs such as vinblastine. C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Dept Vet Affairs, Res & Dev Serv, San Antonio, TX 78229 USA. RP Luduena, RF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Biochem, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [CA26376] NR 25 TC 5 Z9 6 U1 0 U2 3 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 FEB PY 2003 VL 21 IS 1 BP 15 EP 20 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 660FJ UT WOS:000181822900002 PM 12795526 ER PT J AU Kaji, Y Amano, S Usui, T Oshika, T Yamashiro, K Ishida, S Suzuki, K Tanaka, S Adamis, AP Nagai, R Horiuchi, S AF Kaji, Y Amano, S Usui, T Oshika, T Yamashiro, K Ishida, S Suzuki, K Tanaka, S Adamis, AP Nagai, R Horiuchi, S TI Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GLUCOSE-MODIFIED PROTEINS; MAILLARD REACTION; OXIDANT STRESS; DIABETIC COMPLICATIONS; MACULAR DEGENERATION; ALZHEIMER-DISEASE; OXIDATIVE STRESS; BINDING-PROTEINS; GENE-EXPRESSION; AGE RECEPTORS AB PURPOSE. The corneal endothelium is a target of the aging process. This study was undertaken to reveal the relationship between corneal endothelial cell (CEC) death and the accumulation of advanced glycation end products (AGES), by investigating the possible mechanism of accumulation of AGE in CECs and its effects on CEC death. METHODS. First, the in vivo expression of the receptor was investigated for AGE (RAGE) and galectin-3, both receptors for AGE, at both the mRNA and protein levels. Second, AGES were added to the culture media of the cultured CECs, and the uptake of AGES, the generation of reactive oxygen species, and the induction of apoptosis were investigated. RESULTS. Immunohistochemistry and RT-PCR demonstrated that both RAGE and galectin-3 were expressed in bovine CECs. After administration of AGE-modified bovine serum albumin to the culture medium, uptake of AGE was observed in the cytoplasm of the cultured bovine CECs. In addition, with increasing concentration of AGES, the generation of reactive oxygen and the number of apoptotic cells also increased. CONCLUSIONS. These results show that the accumulation of AGES in CECs induced apoptosis, in part, by increasing cellular oxidative stress. The accumulation of AGES in the CECs of elderly patients may be involved in the loss of CECs during the aging process. C1 Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Bunkyo Ku, Tokyo 1138655, Japan. Kumamoto Univ, Sch Med, Dept Biochem 2, Kumamoto 860, Japan. Teikyo Univ, Ichihara Hosp, Dept Ophthalmol, Chiba, Japan. Univ Tsukuba, Inst Clin Med, Dept Ophthalmol, Tsukuba, Ibaraki 305, Japan. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Angiogenesis, Boston, MA USA. RP Kaji, Y (reprint author), Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Bunkyo Ku, Hongo 7-3-1, Tokyo 1138655, Japan. NR 53 TC 51 Z9 57 U1 1 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2003 VL 44 IS 2 BP 521 EP 528 DI 10.1167/iovs.02-0268 PG 8 WC Ophthalmology SC Ophthalmology GA 645GA UT WOS:000180966800011 PM 12556378 ER PT J AU Hamrah, P Liu, Y Zhang, Q Dana, MR AF Hamrah, P Liu, Y Zhang, Q Dana, MR TI The corneal stroma is endowed with a significant number of resident dendritic cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEMATOPOIETIC PROGENITOR CELLS; ANTIGEN-PRESENTING CELLS; LANGERHANS CELLS; RETINAL MICROGLIA; HLA-DR; EXPRESSION; PLASTICITY; EYE; TRANSPLANTATION AB PURPOSE. Dendritic cells (DCs) comprise a system of highly efficient antigen-presenting cells (APCs) that initiate immune responses. The purpose of this study was to examine the normal stroma for the presence of DCs and other bone marrow (BM)- derived cells. METHODS. Normal uninflamed corneas of BALB/c and other murine strains were excised, and immunofluorescence single- and double-staining for multiple markers was performed for examination by confocal microscopy. Corneal buttons were placed in culture and immunocytochemistry and flow cytometry performed. RESULTS. MHC class II(+)CD80(+)CD86(+) cells were found in the periphery of the anterior normal stroma. These cells were CD45(+), CD11c(+)CD11b(+) suggesting a BM-derived and monocytic DC lineage. In a surprising finding, significant numbers of MHC class II(-)CD80(-)CD86(-) cells were found in the center of the anterior stroma. These cells were also CD45(+)CD11c(+) CD11b(+) but CD3(-), GR-1(-), keratan sulfate(-), and CD8alpha(-), reflecting an immature precursor phenotype of myeloid DC. In addition to DC subsets in the anterior stroma, a CDIIc_ CD11b(+) population of BM-derived cells was found primarily in the posterior stroma, representing monocytes/macrophages. These cells were rarely present in the anterior third of the normal stroma. Further, CD14(+) precursor-type DCs were found throughout the stroma. These in vivo findings were not strain specific and were confirmed by immunocytochemistry and flow cytometry analyses of cells derived from corneal explants and by transmission electron microscopy. CONCLUSIONs. This study demonstrates that, in addition to the known Langerhans cells in the corneal epithelium, at least three BM-derived cell subsets reside in the normal corneal stroma. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [R01-EY12963] NR 61 TC 161 Z9 168 U1 2 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2003 VL 44 IS 2 BP 581 EP 589 DI 10.1167/iovs.02-0838 PG 9 WC Ophthalmology SC Ophthalmology GA 645GA UT WOS:000180966800019 PM 12556386 ER PT J AU Ambati, BK Anand, A Joussen, AA Kuziel, WA Adamis, AP Ambati, J AF Ambati, BK Anand, A Joussen, AA Kuziel, WA Adamis, AP Ambati, J TI Sustained inhibition of corneal neovascularization by genetic ablation of CCR5 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; FUNCTIONAL-RESPONSE; ALLOGRAFT-REJECTION; HUMAN MONOCYTES; EXPRESSION; INFLAMMATION; ANGIOGENESIS; MIP-1-ALPHA; KERATITIS; DIFFERENTIATION AB PURPOSE To determine whether genetic ablation of the CC chemokine receptor CCR5 (involved in leukocyte and endothelial chemotaxis) inhibits the development of corneal neo-vascularization. METHODS. Wild-type C57BL/6J mice and species-specific counterparts with targeted homozygous disruption of the CCR5 gene underwent chemical and mechanical denudation of corneal and limbal epithelium. Corneas were harvested 2 and 4 weeks after injury. Neovascularization was quantified by CD31 immunostaining. Expression of VEGF protein was quantified by ELSIA. RESULTS. The mean percentages of neovascularized corneal area in control mice and CCR5-deficient truce, 2 weeks after denudation were 58.3%. and 38.5% (P = 0.05), respectively, At 4 weeks after denudation, the corresponding percentages were 67.6% and 44.0% (P = 0.028). In CCR5-deficient mice, VEGF protein levels were reduced 51.1% at 2 weeks (P = 0.05) after injury and 37.3% at 4 weeks (P = 0.03) CONCLUSIONS. CCR5-deficient mice showed a persistent 34% to 35% inhibition of corneal neovascularization for tip to 4 weeks. This inhibition correlates with reduced expression of VEGF. These data implicate CCR5 as one essential component in the development of corneal neovascularization. C1 Eyetech Pharmaceut, Woburn, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. Univ Kentucky, Dept Ophthalmol, Lexington, KY 40536 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. RP Ambati, J (reprint author), Univ Kentucky, Dept Ophthalmol, 801 Rose St, Lexington, KY 40536 USA. NR 34 TC 50 Z9 54 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2003 VL 44 IS 2 BP 590 EP 593 DI 10.1167/iovs.02-0685 PG 4 WC Ophthalmology SC Ophthalmology GA 645GA UT WOS:000180966800020 PM 12556387 ER PT J AU Levinson, RD Park, MS Rikkers, SM Reed, EF Smith, JR Martin, TM Rosenbaum, JT Foster, CS Sherman, MD Holland, GN AF Levinson, RD Park, MS Rikkers, SM Reed, EF Smith, JR Martin, TM Rosenbaum, JT Foster, CS Sherman, MD Holland, GN TI Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID KOYANAGI-HARADA-SYNDROME; DISEASE AB PURPOSE. To identify genetic markers for the tubulointerstitial nephritis and uveitis (TINU) syndrome by using human leukocyte antigen (HLA) genotyping. METHODS. Eighteen patients who had TINU syndrome were evaluated at three institutions. Typing of class I and II genes was performed by using DNA-based techniques. RESULTS. Significant associations were found with HLA-B14 (6/18 patients, 33.3%; control subjects, 5.5%; P = 0.0003; relative risk [RR] = 8.5), HLA-DQA1*01 (17/18 patients, 94.4%; control subjects, 46.6%, P = 0.0001; RR = 19.5), HLA-DQA1*0101 (14/18 patients, 77.8%; control subjects 22.2%; P < 0.0001; RR = 12.2), HLA-DQB1*05 (14/18 patients, 77.8%; control subjects 17.7 %; P < 0.0001; RR = 16.3), HLA-DQB1*0501 (13/18 patients, 72.2%; control subjects 12.9%; P < 0.0001; RR = 17.6), HLA-DRB1*01 (14/18 patients, 77.8%; control subjects, 12.1%; P < 0.0001; RR = 25.5), and HLA-DRB1*0102 (13/18 patients, 72.2%; control subjects, 1.6%; P < 0.0001, RR = 167.1). The HLA haplotype most frequently identified in the study patients was HLA-DQA1*01/DQBl*05/ DRB1*01 (13/18 patients, 72.2%). CONCLUSIONS. TINU syndrome is strongly associated with HLA-DQA1*01, HLA-DQB1*05, and HLA-DRB1*01. The association with HLA-DRB1*0102 is one of the highest reported for any disease. Because these genes are in linkage disequilibrium, the role of the individual alleles is difficult to assess. Based on the results of the present study and on previously reported HLA associations in patients with TINU syndrome, the alphabeta dimer encoded by HLA-DQA1*01/DQB1*05 may be particularly important in conferring risk for development of this disease. C1 Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Immunogenet Ctr, Dept Ophthalmol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Immunogenet Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA USA. So Calif Permanente Med Grp, Uveitis Referral Serv, Orange, CA USA. RP Levinson, RD (reprint author), Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Ocular Inflammatory Dis Ctr, 100 Stein Plaza, Los Angeles, CA 90095 USA. NR 26 TC 59 Z9 69 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 2003 VL 44 IS 2 BP 653 EP 657 DI 10.1167/iovs.02-0376 PG 5 WC Ophthalmology SC Ophthalmology GA 645GA UT WOS:000180966800028 PM 12556395 ER PT J AU Freed, LH Gupta, R Hynes, C Miller, E AF Freed, LH Gupta, R Hynes, C Miller, E TI Detecting adolescent dating violence in the clinical setting SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Div Adolescent Med, Childrens Hosp Boston, Boston, MA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 2003 VL 32 IS 2 BP 151 EP 152 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 637XE UT WOS:000180538400066 ER PT J AU Yerevanian, BI Koek, RJ Mintz, J AF Yerevanian, BI Koek, RJ Mintz, J TI Lithium, anticonvulsants and suicidal behavior in bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; suicide; lithium; carbamazepine; valproic acid; longitudinal studies ID RISK; METAANALYSIS; MORTALITY AB Background: Lithium has been found to be effective in reducing suicide rates during long term treatment of patients with bipolar disorders. Data on the efficacy of anticonvulsant mood stabilizers in reducing suicide risk are sparse. Method: Charts of 140 bipolar patients treated continuously for a minimum of 6 months during a 23-year period of private practice by the senior author were extracted from nearly 4000 patient records. Data extracted from the charts were incidence of completed suicide, number of suicide attempts, and number of hospitalizations for suicidal ideation or behavior per 100 patient-years of either 'on' or 'off' lithium or anticonvulsant mood stabilizer monotherapy. Results: Only one completed suicide (during a period off of lithium) occurred in the patients studied. Incidence of non-lethal suicidal behavior was not different during treatment with lithium, compared with anticonvulsants. Being on a mood stabilizer significantly protected against suicidal behavior. The relative protective effect was more modest than in reports from other treatment settings. Limitations: This was a retrospective chart review study of naturalistically treated patients. Conclusions: Treatment of patients with bipolar disorder with either lithium or anticonvulsant mood stabilizers was associated with reduced risk of suicidal behavior. This study did not find evidence for a difference in the protective effect of the two types of mood stabilizing medications against non-lethal suicidal behavior in the naturalistic setting of private practice. (C) 2002 Published by Elsevier Science B.V. C1 VA Greater Los Angeles Healthcare Syst, Ctr Ambulatory Care, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. W Los Angeles VAMC, Biostat Consultat Unit, Los Angeles, CA USA. RP Yerevanian, BI (reprint author), 16111 Plummer St,116A, Sepulveda, CA 91343 USA. NR 20 TC 49 Z9 51 U1 1 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 FEB PY 2003 VL 73 IS 3 BP 223 EP 228 AR PII S0165-0327(02)00302-6 DI 10.1016/S0165-0327(02)00302-6 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 645QN UT WOS:000180990000002 PM 12547290 ER PT J AU Krupnick, AS Zhu, JL Nguyen, T Kreisel, D Balsara, KR Lankford, EB Clark, CC Levine, S Stedman, HH Shrager, JB AF Krupnick, AS Zhu, JL Nguyen, T Kreisel, D Balsara, KR Lankford, EB Clark, CC Levine, S Stedman, HH Shrager, JB TI Inspiratory loading does not accelerate dystrophy in mdx mouse diaphragm: implications for regenerative therapy SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE airway resistance; airway obstruction; regeneration; muscular dystrophies; dystrophin ID CONTRACTION-INDUCED INJURY; SKELETAL-MUSCLES; MUSCULAR-DYSTROPHY; MICE; SUSCEPTIBILITY; ADAPTATIONS; MYOFIBERS; DUCHENNE; FAILURE; FIBERS AB Since the finding that the mdx mouse diaphragm, in contrast to limb muscles, undergoes progressive degeneration analogous to that seen in Duchenne muscular dystrophy, the relationship between the workload on a muscle and the pathogenesis of dystrophy has remained controversial. We increased the work performed by the mdx mouse diaphragm in vivo by tracheal banding and evaluated the progression of dystrophic changes in that muscle. Despite the establishment of dramatically increased respiratory workload and accelerated myofiber damage documented by Evans blue dye, no change in the pace of progression of dystrophy was seen in banded animals vs. unbanded, sham-operated controls. At the completion of the study, more centrally nucleated fibers were evident in the diaphragms of banded mdx mice than in sham-operated mdx controls, indicating that myofiber regeneration increases to meet the demands of the work-induced damage. These data suggest that there is untapped regenerative capacity in dystrophin-deficient muscle and validates experimental efforts aimed at augmenting regeneration within skeletal muscle as a therapeutic strategy in the treatment of dystrophinopathies. C1 Univ Penn, Med Ctr, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Surg, Philadelphia, PA USA. Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. Thomas Jefferson Univ, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19107 USA. Univ Penn, Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biochem, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biophys, Philadelphia, PA 19104 USA. RP Shrager, JB (reprint author), Univ Penn, Med Ctr, Sch Med, Dept Surg, 4 Silverstein Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL-10251-ASK] NR 34 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2003 VL 94 IS 2 BP 411 EP 419 DI 10.1152/japplphysiol.00689.2002 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 636CU UT WOS:000180437600001 PM 12531909 ER PT J AU Conhaim, RL Watson, KE Heisey, DM Leverson, GE Harms, BA AF Conhaim, RL Watson, KE Heisey, DM Leverson, GE Harms, BA TI Perfusion heterogeneity in rat lungs assessed from the distribution of 4-mu m-diameter latex particles SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE alveolar perfusion; fluorescent microspheres; fractal analysis; pulmonary blood flow ID PULMONARY BLOOD-FLOW AB Pulmonary vascular perfusion has been shown to follow a fractal distribution down to a resolution of 0.5 cm 3 (5E11 mum(3)). We wanted to know whether this distribution continued down to tissue volumes equivalent to that of an alveolus (2E5 mum(3)). To investigate this, we used confocal microscopy to analyze the spatial distribution of 4-mum-diameter fluorescent latex particles trapped within rat lung microvessels. Particle distributions were analyzed in tissue volumes that ranged from 1.7E2 to 2.8E8 mum(3). The analysis resulted in fractal plots that consisted of two slopes. The left slope, encompassing tissue volumes less than 7E5 mum(3), had a fractal dimension of 1.50 +/- 0.03 (random distribution). The right slope, encompassing tissue volumes greater than 7E5 mum(3), had a fractal dimension of 1.29 +/- 0.04 (nonrandom distribution). The break point at 7E5 mum(3) corresponds closely to a tissue volume equivalent to that of one alveolus. We conclude that perfusion distribution is random at tissue volumes less than that of an alveolus and nonrandom at tissue volumes greater than that of an alveolus. C1 Univ Wisconsin, Sch Med, Dept Surg, Clin Sci Ctr H5 301, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Conhaim, RL (reprint author), Univ Wisconsin, Sch Med, Dept Surg, Clin Sci Ctr H5 301, 600 Highland Ave, Madison, WI 53792 USA. NR 16 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2003 VL 94 IS 2 BP 420 EP 428 DI 10.1152/japplphysiol.00700.2002 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 636CU UT WOS:000180437600002 PM 12391079 ER PT J AU Nielsen, JN Mustard, KJW Graham, DA Yu, HY MacDonald, CS Pilegaard, H Goodyear, LJ Hardie, DG Richter, EA Wojtaszewski, JFP AF Nielsen, JN Mustard, KJW Graham, DA Yu, HY MacDonald, CS Pilegaard, H Goodyear, LJ Hardie, DG Richter, EA Wojtaszewski, JFP TI 5 '-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE acetyl coenzyme A-carboxylase-beta phosphocreatine; adenine nucleotides; glycogen ID GLUCOSE-TRANSPORT; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBOSIDE; CHRONIC ACTIVATION; CREATINE-KINASE; GENE-EXPRESSION; GAMMA-SUBUNIT; ENERGY-CHARGE; BETA-SUBUNIT; RAT-LIVER; INSULIN AB 5'-AMP-activated protein kinase (AMPK) has been proposed to be a pivotal factor in cellular responses to both acute exercise and exercise training. To investigate whether protein levels and gene expression of catalytic (alpha(1), alpha(2)) and regulatory (beta(1), beta(2), gamma(1), gamma(2), gamma(3)) AMPK subunits and exercise-induced AMPK activity are influenced by exercise training status, muscle biopsies were obtained from seven endurance exercise-trained and seven sedentary young healthy men. The alpha(1)- and alpha(2)-AMPK mRNA contents in trained subjects were both 117 +/- 2% of that in sedentary subjects (not significant), whereas mRNA for gamma(3) was 61 +/- 1% of that in sedentary subjects (not significant). The level of alpha(1)- AMPK protein in trained subjects was 185 +/- 34% of that in sedentary subjects (P < 0.05), whereas the levels of the remaining subunits (α(2), β(1), β(2), γ(1), γ(2), γ(3)) were similar in trained and sedentary subjects. At the end of 20 min of cycle exercise at 80% of peak O-2 uptake, the increase in phosphorylation of α-AMPK (Thr(172)) was blunted in the trained group (138 +/- 38% above rest) compared with the sedentary group (353 +/- 63% above rest) (P < 0.05). Acetyl CoA-carboxylase beta-phosphorylation (Ser(221)), which is a marker for in vivo AMPK activity, was increased by exercise in both groups but to a lower level in trained subjects (32 +/- 5 arbitrary units) than in sedentary controls (45 +/- 1 arbitrary units) (P < 0.01). In conclusion, trained human skeletal muscle has increased α(1)-AMPK protein levels and blunted AMPK activation during exercise. C1 Univ Copenhagen, Copenhagen Muscle Res Ctr, Dept Human Physiol, August Krogh Inst, DK-2100 Copenhagen, Denmark. Univ Copenhagen, Inst Exercise & Sport Sci, DK-2100 Copenhagen, Denmark. Univ Dundee, Wellcone Trust Bioctr, Div Mol Physiol, Dundee DD1 4HN, Scotland. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Nielsen, JN (reprint author), Univ Copenhagen, Copenhagen Muscle Res Ctr, Dept Human Physiol, August Krogh Inst, 13 Univ Pk, DK-2100 Copenhagen, Denmark. RI Pilegaard, Henriette/M-2315-2014; Wojtaszewski, Jorgen /P-6583-2014; OI Pilegaard, Henriette/0000-0002-1071-0327; Wojtaszewski, Jorgen /0000-0001-9785-6830; Hardie, Grahame/0000-0002-8373-7379 NR 61 TC 95 Z9 99 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 2003 VL 94 IS 2 BP 631 EP 641 DI 10.1152/japplphysiol.00642.2002 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 636CU UT WOS:000180437600029 PM 12391032 ER PT J AU Tsatsanis, KD Dartnall, N Cicchetti, D Sparrow, SS Klin, A Volkmar, FR AF Tsatsanis, KD Dartnall, N Cicchetti, D Sparrow, SS Klin, A Volkmar, FR TI Concurrent validity and classification accuracy of the Leiter and Leiter-R in low-functioning children with autism SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE autism; Leiter International Performance Scale; Leiter-R; concurrent validity; nonverbal intelligence ID INTELLECTUAL ABILITIES; DISORDERS; CRITERIA; SCALE AB The concurrent validity of the Leiter International Performance Scale (Leiter) and Leiter International Performance Scale-Revised (Leiter-R) was examined in a sample of children with autism who could not be assessed with more traditional measures of intelligence (e. g., the Wechsler scales). The sample consisted of 26 children ranging in age from 4 to 16 years. The correlation between the Leiter scales was high (r = .87), and there was a difference of 3.7 points between the two mean scores, nonsignificant at both statistical and clinical levels. However, significant intraindividual discrepancies were present in 10 cases, 2 of which were both large (24 and 36 points) and clinically meaningful. The mean profile of performance on Leiter-R subtests is also presented for this sample of children with autism, to allow for comparison with other groups. Based on the results of this initial evaluation, together with the current normative data, good psychometric properties, and availability of global and subtest scores with the Leiter-R, the instrument is generally recommended for use with children with autism. However, because of changes in the design of the Leiter-R, there may be greater clinical success with the original Leiter for those children who are very low functioning and severely affected, particularly younger children. C1 Yale Univ, Yale Child Study Ctr, New Haven, CT 06520 USA. Connecticut Dept Mental Retardat, Hartford, CT USA. RP Tsatsanis, KD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 149 13th St,10th Floor, Charlestown, MA 02129 USA. NR 26 TC 32 Z9 32 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD FEB PY 2003 VL 33 IS 1 BP 23 EP 30 DI 10.1023/A:1022274219808 PG 8 WC Psychology, Developmental SC Psychology GA 642LK UT WOS:000180805700004 PM 12708577 ER PT J AU Kaufman, DR Patel, VL Hilliman, C Morin, PC Pevzner, J Weinstock, RS Goland, R Shea, S Starren, J AF Kaufman, DR Patel, VL Hilliman, C Morin, PC Pevzner, J Weinstock, RS Goland, R Shea, S Starren, J TI Usability in the real world: assessing medical information technologies in patients' homes SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE usability evaluation; field usability testing; cognitive methods; telemedicine; diabetes; chronic illness ID COLUMBIA-UNIVERSITY INFORMATICS; TELEMEDICINE IDEATEL PROJECT; DIABETES EDUCATION; CARE; INTERFACE; SYSTEM AB Objective: This paper presents an approach to usability evaluation of computer-based health care systems designed for patient use in their homes. Although such devices are becoming more prevalent, there is very little known about their usability. Design: The theoretical foundations for the methods are discussed. The approach incorporates a cognitive walkthrough usability evaluation and new methods for usability testing that can be conducted in patient's homes. The method was applied to the IDEATel intervention. a multi-institution randomized controlled trial of the feasibility, acceptability, and clinical utility of a home-based telemedicine system for diabetic Medicare population. The usability study was designed to assess barriers to optimal use of the system. The focus was both on dimensions of the interface and on dimensions of patient skills and competency. The usability field research involved testing 25 patients in their homes using the system. The analysis included a range of video-analytic methods of varying levels of granularity. Results: The usability evaluation revealed aspects of the interface that were sub-optimal and impeded the performance of certain tasks. It also found a range of patient-related factors such as numeracy and psychomotor skills that constituted barriers to productive use. Conclusions: A multifaceted usability approach provided important insight regarding use of technology by an elderly chronic-care patient population and more generally, for understanding how home health initiatives can more effectively use such technology. (C) 2003 Elsevier Inc. All rights reserved. C1 Columbia Univ, Dept Biomed Informat, Lab Decis Making & Cognit, New York, NY 10032 USA. SUNY Syracuse, Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Syracuse, Div Endocrinol Diabet & Metab, Upstate Med Univ, Syracuse, NY USA. VA Med Ctr, Syracuse, NY USA. Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Kaufman, DR (reprint author), Columbia Univ, Dept Biomed Informat, Lab Decis Making & Cognit, 622 W 168th St,VC-5, New York, NY 10032 USA. NR 28 TC 93 Z9 94 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD FEB-APR PY 2003 VL 36 IS 1-2 BP 45 EP 60 DI 10.1016/S1532-0464(03)0056-X PG 16 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 734RW UT WOS:000186072200005 PM 14552846 ER PT J AU Ring, D Jupiter, JB Gulotta, L AF Ring, D Jupiter, JB Gulotta, L TI Articular fractures of the distal part of the humerus SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: The purpose of this retrospective study was to identify the patterns of distal humeral articular fractures and to analyze the results of open reduction and internal fixation of these injuries. Methods: The cases of twenty-one patients with an articular fracture of the distal part of the humerus were reviewed at an average of forty months after the injury. Five components of the injury were identified: (1) the capitellum and the lateral aspect of the trochlea, (2) the lateral epicondyle, (3) the posterior aspect of the lateral column, (4) the posterior aspect of the trochlea, and (5) the medial epicondyle. All fractures were reduced and were stabilized with implants buried beneath the articular surface. Results: All fractures healed, and no patient had residual ulnohumeral instability or weakness. Ten patients required a second operation: six, for release of an elbow contracture; two, for treatment of ulnar neuropathy; one, for removal of hardware causing symptoms; and one, because of early loss of fixation. The average arc of ulnohumeral motion was 96degrees (range, 550 to 1400). The results according to the Mayo Elbow Performance Index were excellent in four patients, good in twelve, and fair in five. Conclusions: Apparent fractures of the capitellum are often more complex fractures of the articular surface of the distal part of the humerus. Treatment of these injuries with operative reduction and fixation with buried implants can result in satisfactory restoration of elbow function. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Intructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand Surg Serv, ACC 525,15 Parkman St, Boston, MA 02114 USA. NR 32 TC 85 Z9 100 U1 0 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2003 VL 85A IS 2 BP 232 EP 238 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 641BE UT WOS:000180723500008 PM 12571299 ER PT J AU Slice, LW Han, SK Simon, MI AF Slice, LW Han, SK Simon, MI TI G alpha(q) signaling is required for Rho-dependent transcriptional activation of the cyclooxygenase-2 promoter in fibroblasts SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PROSTAGLANDIN ENDOPEROXIDE SYNTHASE; NUCLEOTIDE EXCHANGE FACTOR; STRESS FIBER FORMATION; PROTEIN-KINASE-C; SWISS 3T3 CELLS; GENE-EXPRESSION; DIFFERENTIAL REGULATION; COLORECTAL ADENOMAS; RESPONSE ELEMENT; EPITHELIAL-CELLS AB Previously, we demonstrated that the gastrin releasing peptide (GRP) induces cyclooxygenase-2 (COX-2) expression through a Rho-dependent, protein kinase C (PKC)-independent signaling pathway in fibroblasts (Slice et al., 1999, J Biol Chem 274:27562-27566). However, the specific role of heterotrimeric guanine nucleotide binding regulatory proteins (G-proteins) that are coupled to the GRP receptor in Rho-dependent COX-2 expression has not been elucidated. In this report, we utilize embryonic fibroblasts from transgenic mice containing double gene knock-outs (DKO) for Galpha(q/11) and Galpha(12/13) to demonstrate that COX-2 promoter activation by GRP requires Galpha(q), Furthermore, we show that GRP-dependent COX-2 gene expression, as assessed by a COX-2 reporter luciferase assay, was induced in cells lacking Galpha(12/13) but was blocked in cells that did not express Galpha(q/11). GRP-dependent COX-2 promoter induction in Galpha(q/11) deficient cells was rescued by expression of wild type Gaq but blocked by inhibition of calcium signaling in calcium-free media or in cells treated with 2-aminoethoxydiphenylborate (2-APB). Co-stimulation of transfected Galpha(q/11) deficient cells with GRP and thapsigargin (TG) induced the COX-2 promoter. Activation of endogenous Rho by expression of Onco-lbc or expression of Rho A Q63L resulted in COX-2 promoter activation in Galpha(q/11) deficient cells. Inhibition of Rho by Clostridium botulinum C3 toxin blocked COX-2 promoter induction. Expression of Galpha(q) Q209L in the well-characterized fibroblast cell line, NIH3T3, induced the COX-2 promoter which was blocked by expression of C3 toxin. These results demonstrate that calcium signaling mediated by Gaq and Rho play critical roles in GRP-dependent COX-2 expression in fibroblasts. (C) 2002 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Slice, LW (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, Div Digest Dis,Dept Med, 900 Vet Ave, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [DK35740]; NIGMS NIH HHS [GM-34236] NR 71 TC 9 Z9 10 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 2003 VL 194 IS 2 BP 127 EP 138 DI 10.1002/jcp.10195 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 631WF UT WOS:000180189500004 PM 12494451 ER PT J AU Locascio, JJ Corkin, S Growdon, JH AF Locascio, JJ Corkin, S Growdon, JH TI Relation between clinical characteristics of Parkinson's disease and cognitive decline SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID RISK-FACTORS; DEMENTIA; MOTOR; ONSET; AGE; DEFICITS; MEMORY; PROGRESSION; IMPAIRMENT; DYSFUNCTION AB This study examined how cognitive impairments in Parkinson's disease (PD) are related to clinical characteristics such as age at testing, duration of illness, motor impairment, and especially age at disease onset. To address these issues, we administered 14 tests of memory, language, visuospatial, and frontal lobe capacities to 104 PD patients and 60 healthy volunteers of comparable age and education. The participants completed 1-9 test sessions over 1-10 years. Duration of PD was associated with deteriorating performance on most cognitive tests, independent of age-related decline. Severity of motor impairment, indexed by Hoehn and Yahr stages, was positively related to impairment on almost all cognitive tests, holding age and duration constant. For some tests, especially those that were motorically demanding and those that assessed language skills, cognitive deficits appeared earlier in the disease course for late-onset than for early-onset PD patients. These late onset deficits were synergistic effects beyond the additive contributions of disease duration and normal aging. These findings may assist physicians in advising PD patients and their families about the future course of the illness. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Locascio, JJ (reprint author), MIT, Dept Brain & Cognit Sci, NE20-352, Cambridge, MA 02139 USA. FU NIA NIH HHS [AG05134, AG08812, P50AG05134]; NINDS NIH HHS [P50NS37372] NR 63 TC 37 Z9 39 U1 1 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD FEB PY 2003 VL 25 IS 1 BP 94 EP 109 PG 16 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 666YD UT WOS:000182203300009 PM 12607175 ER PT J AU Hernandez, JM Coyle, FP Wright, CD Ballantyne, JC AF Hernandez, JM Coyle, FP Wright, CD Ballantyne, JC TI Epidural abscess after epidural anesthesia and continuous epidural analgesia in a patient with gastric lymphoma SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE abscess; epidural; analgesia; epidural; continuous; lymphoma; gastric ID COMPLICATIONS; CATHETERIZATION AB A case of spinal epidural abscess, a rare but possibly devastating complication of epidural instrumentation and catheterization, is described in an immunocompromised patient, which presented atypically and which resulted in the patient's death. (C) 2003 by Elsevier Science Inc. C1 Massachusetts Gen Hosp, Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Pain Management Ctr, Boston, MA 02114 USA. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Pain Ctr, 15 Parkman St,WACC 333, Boston, MA 02114 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD FEB PY 2003 VL 15 IS 1 BP 48 EP 51 DI 10.1016/S0952-8180(02)00481-6 PG 4 WC Anesthesiology SC Anesthesiology GA 663KG UT WOS:000182004300010 PM 12693415 ER PT J AU Kim, BW Daniels, GH Harrison, BJ Price, A Harney, JW Larsen, PR Weetman, AP AF Kim, BW Daniels, GH Harrison, BJ Price, A Harney, JW Larsen, PR Weetman, AP TI Overexpression of type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPERTHYROIDISM; TRIIODOTHYRONINE; THERAPY AB Thyroid function is normally undisturbed in patients with thyroid carcinoma. We have identified three patients with large or widely metastatic follicular thyroid carcinoma who had a persistently increased ratio of serum T(3) to T(4) in the absence of autonomous production of T(3) by the tumor. To investigate the possibility of tumor-mediated T(4) to T(3) conversion, we assayed types 1 and 2 iodothyronine selenodeiodinase (D1 and D2) activity in a 965-g follicular thyroid carcinoma resected from one of these patients. The V(max) for D2 was 8-fold higher than in normal human thyroid tissue. Resection of this tumor, leaving the left thyroid lobe intact, normalized the serum T3 to T4 ratio. In two other patients, treatment with sufficient levothyroxine to suppress TSH was associated with a high normal T(3) and a subnormal free T(4) index. In one, concomitant administration of the D1 inhibitors, propylthiouracil and propranolol, did not decrease the elevated serum T(3) to T(4) ratio. These data illustrate that increased T(4) to T(3) conversion in follicular thyroid carcinomas, probably by D2, can cause a significant perturbation in peripheral thyroid hormone concentrations. C1 Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Sheffield S5 7AU, S Yorkshire, England. Univ Sheffield, No Gen Hosp, Dept Surg, Sheffield S5 7AU, S Yorkshire, England. Univ Sheffield, No Gen Hosp, Dept Clin Chem, Sheffield S5 7AU, S Yorkshire, England. Brigham & Womens Hosp, Div Thyroid, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02108 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02108 USA. Harvard Univ, Sch Med, Boston, MA 02108 USA. RP Weetman, AP (reprint author), Univ Sheffield, No Gen Hosp, Ctr Clin Sci, Sheffield S5 7AU, S Yorkshire, England. EM k.f.watson@sheffield.ac.uk FU NIDDK NIH HHS [DK36256, DK07529] NR 14 TC 37 Z9 38 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 FEB PY 2003 VL 88 IS 2 BP 594 EP 598 DI 10.1210/jc.2002-020921 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 644JZ UT WOS:000180915300016 PM 12574186 ER PT J AU Misra, M MacLaughlin, DT Donahoe, PK Lee, MM AF Misra, M MacLaughlin, DT Donahoe, PK Lee, MM TI The role of Mullerian inhibiting substance in the evaluation of phenotypic female patients with mild degrees of virilization SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GRANULOSA-CELL TUMOR; TRUE HERMAPHRODITISM; DUCT SYNDROME; LEYDIG-CELLS; SERUM LEVELS; MOUSE OVARY; HORMONE; IMMUNOASSAY; INTERSEX; RECEPTORS AB Mullerian inhibiting substance (MIS) is a sexually dimorphic gonadal hormone with proven efficacy in the evaluation of boys with cryptorchidism and children with intersex conditions. We examined the role of MIS determination in the evaluation of 65 phenotypic females with mild virilization. Among the 28 subjects with MIS values elevated above the normal female range, all had abnormal gonadal tissue: ovotestes in 11, testes in 7, dysgenetic gonads in 7, and MIS-secreting ovarian tumors in 3. Among the 37 children with serum MIS in the normal female range, 19 had detectable MIS and 18 had unmeasurable MIS. In the former group with measurable but normal female MIS values, 16 subjects had ovaries, 1 had an ovotestis, and 1 had dysgenetic gonads containing testicular elements. Of 18 children with undetectable MIS values, 16 had ovaries and 2 had ovarian dysgenesis. In this study, elevation of serum MIS above the normal female range was consistently associated with the presence of testicular tissue or MIS-secreting tumors, mandating additional evaluation and surgical exploration. A value within the normal female range in a virilized patient did not exclude dysgenetic testicular tissue or ovotestis, whereas undetectable values were consistent with the absence of testicular tissue. C1 Duke Univ, Med Ctr, Pediat Endocrine Div, Durham, NC 27710 USA. MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. MassGen Hosp Children, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Duke Univ, Med Ctr, Pediat Endocrine Div, Durham, NC 27710 USA. RP Lee, MM (reprint author), Duke Univ, Med Ctr, Pediat Endocrine Div, Box 3080,308 Bell Bldg, Durham, NC 27710 USA. EM Lee00140@mc.duke.edu OI Lee, Mary/0000-0002-7204-4884 FU NCI NIH HHS [CA-17393]; NICHD NIH HHS [HD-10367, HD-31223, HD-36768]; NIDDK NIH HHS [DK-07703] NR 41 TC 9 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 2003 VL 88 IS 2 BP 787 EP 792 DI 10.1210/jc.2002-020889 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 644JZ UT WOS:000180915300044 PM 12574214 ER PT J AU Lieber, CS AF Lieber, CS TI Hepatitis C and alcohol SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Editorial Material ID LIVER FIBROSIS PROGRESSION; HEPATOCELLULAR-CARCINOMA; VIRUS-INFECTION; OXIDATIVE STRESS; CIRRHOSIS; RISK; CONSUMPTION; DISEASES C1 Bronx Vet Adm Med Ctr, Alcohol Res Ctr, Sect Liver Dis & Nutr, New York, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Lieber, CS (reprint author), Bronx Vet Adm Med Ctr, Alcohol Res Ctr, Sect Liver Dis & Nutr, New York, NY USA. NR 24 TC 7 Z9 8 U1 0 U2 0 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 FEB PY 2003 VL 36 IS 2 BP 100 EP 102 DI 10.1097/00004836-200302000-00003 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639JL UT WOS:000180624900003 PM 12544190 ER PT J AU Young, AB AF Young, AB TI Huntingtin in health and disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TRANSGENIC MOUSE MODEL; NEURONAL INTRANUCLEAR INCLUSIONS; STRIATAL PROJECTION NEURONS; D-ASPARTATE RECEPTORS; MUTANT HUNTINGTIN; WILD-TYPE; CAENORHABDITIS-ELEGANS; NEUROLOGICAL PHENOTYPE; GLUTAMINE REPEATS; BASAL GANGLIA C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Young, AB (reprint author), Massachusetts Gen Hosp, Neurol Serv, VBK-915,32 Fuit St, Boston, MA 02114 USA. FU NIA NIH HHS [AG13617, R01 AG013617, R37 AG013617]; NINDS NIH HHS [NS38106, R01 NS038106] NR 65 TC 67 Z9 68 U1 1 U2 4 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 FEB PY 2003 VL 111 IS 3 BP 299 EP 302 DI 10.1172/JCI200317742 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 642NX UT WOS:000180811400003 PM 12569151 ER PT J AU Garvey, WT AF Garvey, WT TI The role of uncoupling protein 3 in human physiology SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID MITOCHONDRIAL PROTON LEAK; SKELETAL-MUSCLE; EXPRESSION; MICE; OBESITY; HOMOLOG; TISSUE; UCP3 C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Garvey, WT (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Clin Sci Bldg 816,96 Jonathan Lucas St, Charleston, SC 29425 USA. NR 21 TC 8 Z9 10 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 FEB PY 2003 VL 111 IS 4 BP 438 EP 441 DI 10.1172/JC1200317835 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 646TK UT WOS:000181050200004 PM 12588880 ER PT J AU Fisher, SJ Kahn, CR AF Fisher, SJ Kahn, CR TI Insulin signaling is required for insulin's direct and indirect action on hepatic glucose production SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FREE FATTY-ACIDS; NUCLEAR-MAGNETIC-RESONANCE; PERIPHERAL INSULIN; DEPANCREATIZED DOGS; DIABETES-MELLITUS; CONSCIOUS DOG; GLUCONEOGENESIS; HUMANS; RESISTANCE; SUPPRESSION AB We and others have suggested that insulin predominantly acts indirectly to inhibit hepatic glucose production (HGP) via suppression of gluconeogenic precursors, FFAs, and glucagon. To test that hypothesis, we performed high-dose hyperinsulinemic-euglycemic clamps using [3-H-3]-glucose in liver-specific insulin receptor knockout (LIRKO) mice, LIRKO mice treated with streptozotocin (LIRKO+STZ), and controls. In LIRKO mice, fasted glucose was normal, but insulin levels were elevated tenfold. STZ treatment reduced insulinemia by 60% with resulting hyperglycemia. Interestingly, basal HGP was similar in all three groups. During the clamp, HGP was suppressed by 82 17% in controls, but was not suppressed in either LIRKO or LIRKO+STZ mice. Glucose infusion and utilization were impaired (similar to50%) in LIRKO and LIRKO+STZ mice versus controls. Insulin suppressed FFAs similarly in all groups (similar to46%). Glucagon was not significantly suppressed during the clamp. Thus, in LIRKO mice, (a) high-dose insulin fails to suppress HGP indicating that both direct and indirect effects of insulin require an intact insulin-signaling pathway in the liver; (b) primary hepatic insulin resistance leads to hyperinsulinemia and secondary extrahepatic insulin resistance; and (c) lowering insulin levels with STZ tended to improve extrahepatic insulin sensitivity but failed to reveal the previously postulated indirect role of insulin in suppressing HGP. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 705, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK 31036, R01 DK031036] NR 38 TC 117 Z9 130 U1 1 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 FEB PY 2003 VL 111 IS 4 BP 463 EP 468 DI 10.1172/JCI16426 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 646TK UT WOS:000181050200008 PM 12588884 ER PT J AU Mishra, N Reilly, CM Brown, DR Ruiz, P Gilkeson, GS AF Mishra, N Reilly, CM Brown, DR Ruiz, P Gilkeson, GS TI Histone deacetylase inhibitors modulate renal disease in the MRL-lpr/lpr mouse SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYTOKINE GENE-EXPRESSION; KAPPA-B-BETA; INTERFERON-GAMMA; TRICHOSTATIN-A; AUTOIMMUNE-DISEASE; LPR MICE; IN-VIVO; CELL DIFFERENTIATION; T-LYMPHOCYTES AB Studies in human systemic lupus erythematosus (SLE) suggest a possible role for histone deacetylases (HDACs) in skewed gene expression and disease pathogenesis. We used the MRL-lpr/lpr murine model of lupus to demonstrate that HDACs play a key role in the heightened levels of both Th1 and Th2 cytokine expression that contribute to disease. The availability of specific HDAC inhibitors (HDIs) such as trichostatin A (TSA) and suberonylanilide hydroxamic acid (SAHA) permits the study of the role of HDACs in gene regulation. Our results indicate that HDIs downregulate IL-12, IFN-gamma, IL-6, and IL-10 mRNA and protein levels in MRL-lpr/lpr splenocytes. This effect on gene transcription is associated with an increased accumulation of acetylated histories H3 and H4 in total cellular chromatin. To elucidate the in vivo effects of TSA on lupuslike disease, we treated MRL-lpr/lpr mice with TSA (0.5 mg/kg/d) for 5 weeks. Compared with vehicle-treated control mice, TSA-treated mice exhibited a significant reduction in proteinuria, glomerulonephritis, and spleen weight. Taken together, these findings suggest that increased expression of HDACs leading to an altered state of histone acetylation may be of pathologic significance in MRL-lpr/lpr mice. In addition, TSA or other HDIs may have therapeutic benefit in the treatment of SLE. C1 Wake Forest Univ, Sch Med, Sect Rheumatol & Clin Immunol, Dept Internal Med, Winston Salem, NC 27157 USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. Univ Miami, Med Ctr, Dept Immunopathol, Miami, FL 33152 USA. RP Mishra, N (reprint author), Wake Forest Univ, Sch Med, Sect Rheumatol & Clin Immunol, Dept Internal Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. OI Brown, Doris/0000-0001-8515-3759 FU NIAID NIH HHS [F32 AI010582, F32 AI10582]; NIAMS NIH HHS [AR 49153, R21 AR049153] NR 68 TC 224 Z9 237 U1 1 U2 8 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 FEB PY 2003 VL 111 IS 4 BP 539 EP 552 DI 10.1172/JC1200316153 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 646TK UT WOS:000181050200016 PM 12588892 ER PT J AU Kazor, CE Mitchell, PM Lee, AM Stokes, LN Loesche, WJ Dewhirst, FE Paster, BJ AF Kazor, CE Mitchell, PM Lee, AM Stokes, LN Loesche, WJ Dewhirst, FE Paster, BJ TI Diversity of bacterial Populations on the tongue dorsa of patients with halitosis and healthy patients SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ORAL MALODOR; SULFIDE MONITOR; PERIODONTITIS; PLAQUE; MICROFLORA; FLORA AB The primary purpose of the present study was to compare the microbial profiles of the tongue dorsa of healthy subjects and subjects with halitosis by using culture-independent molecular methods. Our overall goal was to determine the bacterial diversity on the surface of the tongue dorsum as part of our ongoing efforts to identify all cultivable and not-yet-cultivated species of the oral cavity. Tongue dorsum scrapings were analyzed from healthy subjects with no complaints of halitosis and subjects with halitosis, defined as an organoleptic score of 2 or more and volatile sulfur compound levels greater than 200 ppb. 16S rRNA genes from DNA isolated from tongue dorsum scrapings were amplified by PCR with universally conserved bacterial primers and cloned into Escherichia coli. Typically, 50 to 100 clones were analyzed from each subject. Fifty-one strains isolated from the tongue dorsa of healthy subjects were also analyzed. Partial sequences of approximately 500 bases of cloned inserts from the 16S rRNA genes of isolates were compared with sequences of known species or phylotypes to determine species identity or closest relatives. Nearly complete sequences of about 1,500 bases were obtained for potentially novel species or phylotypes. In an analysis of approximately 750 clones, 92 different bacterial species were identified. About half of the clones were identified as phylotypes, of which 29 were novel to the tongue microbiota. Fifty-one of the 92 species or phylotypes were detected in more than one subject. Those species most associated with healthy subjects were Streptococcus salivarius, Rothia mucilaginosa, and an uncharacterized species of Eubacterium (strain FTB41). Streptococcus salivarius was the predominant species in healthy subjects, as it represented 12 to 40% of the total clones analyzed from each healthy subject. Overall, the predominant microbiota on the tongue dorsa of healthy subjects was different from that on the tongue dorsa of subjects with halitosis. Those species most associated with halitosis were Atopobium parvulum, a phylotype (clone BS095) of Dialister, Eubacterium sulci, a phylotype (clone DR034) of the uncultivated phylum TM7, Solobacterium moorei, and a phylotype (clone BW009) of Streptococcus. On the basis of our ongoing efforts to obtain full 16S rRNA sequences for all cultivable and not-yet-cultivated species that colonize the oral cavity, there are now over 600 species. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Paster, BJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE11443, DE12465, R01 DE011443] NR 36 TC 244 Z9 266 U1 6 U2 43 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 FEB PY 2003 VL 41 IS 2 BP 558 EP 563 DI 10.1128/JCM.41.2.558-563.2003 PG 6 WC Microbiology SC Microbiology GA 643YM UT WOS:000180891200006 PM 12574246 ER PT J AU Redding, SW Kirkpatrick, WR Saville, S Coco, BJ White, W Fothergill, A Rinaldi, M Eng, T Patterson, TF Lopez-Ribot, J AF Redding, SW Kirkpatrick, WR Saville, S Coco, BJ White, W Fothergill, A Rinaldi, M Eng, T Patterson, TF Lopez-Ribot, J TI Multiple patterns of resistance to fluconazole in Candida glabrata isolates from a patient with oropharyngeal candidiasis receiving head and neck radiation SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AZOLE ANTIFUNGAL AGENTS; INFECTED PATIENTS; TRANSPORTER GENE; ALBICANS; COLONIZATION; SUSCEPTIBILITY; EPIDEMIOLOGY; STRAINS AB Candida glabrata has emerged in recent years as a significant cause of systemic fungal infection. We have previously reported on the first three patients receiving radiation for head and neck cancer to develop oropharyngeal candidiasis due to C. glabrata. The goal of this study was to track the development of increased fluconazole resistance in C. glabrata isolates and to evaluate previously described genetic mechanisms associated with this resistance from one of these three patients. The patient was a 52-year-old man with squamous cell carcinoma treated with radiation. At week 7 of his radiation, he developed oropharyngeal candidiasis, which was treated with 200 mg of fluconazole daily for 2 weeks. Serial cultures from this and three subsequent time points yielded C. glabrata. Isolates from these cultures were subjected to antifungal susceptibility testing, DNA karyotyping, and evaluation of the expression of genes previously associated with C. glabrata resistance to fluconazole, CgCDR1, CgCDR2, and CgERG11. Two strains (A and B) of C. glabrata were identified and found to display different patterns of resistance development and gene expression. Strain A developed resistance over a 2-week period and showed no overexpression of these genes. In contrast, strain B first showed resistance 6 weeks after fluconazole therapy was discontinued but showed overexpression of all three genes. In conclusion, development of resistance to fluconazole by C. glabrata is a highly varied process involving multiple molecular mechanisms. 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. RI Saville, Stephen/F-7668-2010; Lopez-Ribot, Jose/D-2048-2010 FU NIDCR NIH HHS [5-R01-DE11381-6, R01 DE011381] NR 23 TC 49 Z9 57 U1 0 U2 3 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 FEB PY 2003 VL 41 IS 2 BP 619 EP 622 DI 10.1128/JCM.41.2.619-622.2003 PG 4 WC Microbiology SC Microbiology GA 643YM UT WOS:000180891200016 PM 12574256 ER PT J AU Meyerkardt, JA Catalano, PJ Haller, DG Mayer, RJ Macdonald, JS Benson, AB Fuchs, CS AF Meyerkardt, JA Catalano, PJ Haller, DG Mayer, RJ Macdonald, JS Benson, AB Fuchs, CS TI Impact of diabetes mellitus on outcomes in patients with colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IGF-BINDING PROTEIN-3; GROWTH-FACTOR-I; COLORECTAL-CANCER; FACTOR (IGF)-I; BLOOD-GLUCOSE; PLASMA-LEVELS; RISK; INSULIN; COMORBIDITY; OLDER AB Purpose: To determine the influence of diabetes mellitus on long-term outcomes and treatment-related toxicity among patients with curatively resected colon cancer. Patients and Methods: This study was a cohort study within a large, randomized adjuvant chemotherapy trial of 3,759 patients with high-risk stage II and stage III colon cancer treated between 1988 and 1992 throughout the United States. In the cohort, 287 patients were identified as having diabetes mellitus. With a median follow-up of 9.4 years, we analyzed differences in overall survival (OS) and colon cancer recurrence as well as treatment-related toxicity between patients with diabetes and those without diabetes. Results: At 5 years, patients with diabetes mellitus, compared with patients without diabetes, experienced a significantly worse disease-free survival (DFS; 48% diabetics v 59% noncliabetics; P < .0001), OS (5 7% v 66%; P < .0001), and recurrence-free survival (RFS; 56% v 64%, P = .012). Median survival was 6.0 years and 11.3 years for diabetics and nondiabetics, respectively. Compared with patients without a history of diabetes, those with diabetes had a 42% increased risk of death from any cause (P < .0001) and 21% increased risk for recurrence (P = .05) after adjustment for other predictors of colon cancer outcome. Treatment-related toxicities were similar between the two groups, although patients with diabetes experienced an increase in treatment-related diarrhea. Conclusion: Patients with diabetes mellitus and high-risk stage II and stage III colon cancer experienced a significantly higher rate of overall mortality and cancer recurrence, even after adjustment for other predictors of colon cancer outcome. These results underscore the need for further research to understand the mechanism that underlies this relation. (C) 2003 by American Society of Clinical Oncology. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Stat Ctr, Dana Farber Canc Inst,Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. St Vincent Clin Canc Ctr, New York, NY USA. Northwestern Univ, Div Hematol, Chicago, IL 60611 USA. RP Meyerkardt, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 38 TC 182 Z9 194 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2003 VL 21 IS 3 BP 433 EP 440 DI 10.1200/JCO.2003.07.125 PG 8 WC Oncology SC Oncology GA 644QT UT WOS:000180930900010 PM 12560431 ER PT J AU Halabi, S Small, EJ Hayes, DF Vogelzong, NJ Kantoff, PW AF Halabi, S Small, EJ Hayes, DF Vogelzong, NJ Kantoff, PW TI Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in metastatic prostate cancer: A nested study within CALGB 9583 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARCINOMA; CELLS; RECURRENCE; ISSUES; BLOOD; ASSAY; STAGE; MEN AB Purpose : To determine whether reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating prostate-specific antigen (PSA)-positive cells is a prognostic factor for survival in hormone refractory prostate cancer and to validate the prognostic importance of this test in relation to other known prognostic factors. Patients and Methods: A single centralized laboratory received and analyzed whole blood for RT-PCR for PSA for a subset of patients enrolled on two Cancer and Leukemia Group B (CALGB) randomized trials (CALGB 9583 and CALGB 9480). Using 9583, a prognostic model was developed and an independent data set (CALGB 9480) was used to validate the fitted model. Results: Of 162 patients in 9583, 91 (56%) patients were negative for RT-PCR for PSA and 71 (44%) patients were positive. The median survival time was 21 months (95% confidence interval [CI], 18 to 27 months) for RT-PCR-negative patients compared with 11 months (95% CI, 8 to IS months) for RT-PCR-positive patients (P less than or equal to .001). In multivariable analysis, the hazard ratio (HR) for death was 1.7 (95% CI, 1.2 to 2.4; P = .006) for positive RT-PCR patients compared with negative RT-PCR patients. A fitted model that incorporated RT-PCR for PSA and other factors was used to classify patients from 9480 into one of two risk groups: low or high. We observed good agreement between the observed and predicted survival probabilities for the two risk groups. Conclusion: RT-PCR to detect PSA-positive circulating cells is confirmed to be a significant prognostic factor of survival in patients with hormone refractory prostate cancer. This model could be used to stratify patients in randomized phase III trials. C1 Duke Univ, Ctr Med, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Duke Univ, Ctr Med, CALGB Stat Ctr, Durham, NC 27710 USA. Univ Calif San Francisco, Urol Oncol Program, San Francisco, CA 94143 USA. Univ Michigan, Breast Oncol Program, Ann Arbor, MI 48109 USA. Univ Chicago, Ctr Canc Res, Chicago, IL 60637 USA. Univ Chicago, Sect Hematol & Oncol, Dept Med, Chicago, IL 60637 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. RP Halabi, S (reprint author), Duke Univ, Ctr Med, Dept Biostat & Bioinformat, Box 3958, Durham, NC 27710 USA. FU NCI NIH HHS [CA31946, CA36601, P30 CA14599] NR 17 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 1 PY 2003 VL 21 IS 3 BP 490 EP 495 DI 10.1200/JCO.2003.04.104 PG 6 WC Oncology SC Oncology GA 644QT UT WOS:000180930900019 PM 12560440 ER PT J AU Hamner, MB Deitsch, SE Brodrick, PS Ulmer, HG Lorberbaum, JP AF Hamner, MB Deitsch, SE Brodrick, PS Ulmer, HG Lorberbaum, JP TI Quetiapine treatment in patients with posttraumatic stress disorder: An open trial of adjunctive therapy SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ATYPICAL ANTIPSYCHOTIC-DRUGS; DOUBLE-BLIND; PSYCHOTIC FEATURES; PLACEBO; SCHIZOPHRENIA; RISPERIDONE; PTSD; MULTICENTER; SERTRALINE; OLANZAPINE AB In this 6-week, open-label trial, combat veterans meeting DSM-IV criteria for posttraurnatic stress disorder (PTSD) were treated with the atypical antipsychotic quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Primary outcome was measured using the Clinician Administered PT-SD Scale (CAPS). Secondary assessments of efficacy included the Positive and Negative Symptom Scale (PANSS), the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Safety and tolerability evaluations included neurologic ratings, vital signs, and assessment of treatment-emergent side effects. Eighteen of 20 patients enrolled in the study completed 6 weeks of open-label treatment. The dose range of quetiapine was 25 to 300 mg daily, with an average of 100 +/- 70 mg/d. There was significant improvement in CAPS scores, from 89.8 +/- 15.7 to 67.5 +/- 21.0 (t=4.863, df= 18, P<0.005), and composite PANSS ratings from baseline to endpoint. General psychopathology (PANSS) and depressive symptoms (HRSD) were also reduced at the 6-week end point. There were no serious adverse events and no clinically significant changes in vital signs or neurologic ratings. This preliminary open trial suggests that quetiapine is well tolerated and may have efficacy in reducing PTSD symptoms in patients who have not had an adequate response other medications. Studies utilizing a randomized, controlled trial design and larger sample sizes are needed to better define the potential role of quetiapine and other atypical antipsychotics in the treatment of PTSD. C1 Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv, 109 Bee St, Charleston, SC 29401 USA. EM hamnermb@musc.edu NR 37 TC 90 Z9 93 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2003 VL 23 IS 1 BP 15 EP 20 DI 10.1097/00004714-200302000-00003 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641UJ UT WOS:000180765000003 PM 12544370 ER PT J AU Frazier, JA Cohen, LG Jacobsen, L Grothe, D Flood, J Baldessarini, RJ Piscitelli, S Kim, GS Rapoport, JL AF Frazier, JA Cohen, LG Jacobsen, L Grothe, D Flood, J Baldessarini, RJ Piscitelli, S Kim, GS Rapoport, JL TI Clozapine pharmacokinetics in children and adolescents with childhood-onset schizophrenia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID MULTIPLE-DOSE PHARMACOKINETICS; PLASMA CLOZAPINE; CAFFEINE TEST; METABOLISM; SERUM; NORCLOZAPINE; CYP1A2 AB Clozapine (CLZ) dose-related adverse effects may be more common in children than adults, perhaps reflecting developmental pharmacokinetic (PK) differences. However, no pediatric CLZ PK data are available. Accordingly, we studied CLZ and its metabolites, norclozapine (NOR), and clozapine-N-oxide (NOX) in six youth, ages 9-16 years, with childhood onset schizophrenia (COS). At the time of the PK study, mean CLZ dose was 200 mg (3.4 mg/kg). Serum was collected during week 6 on CLZ before and 0.5-8 h after a morning dose. Serum concentrations were assayed by liquid chromatography/UV-detection. Mean concentration, area-under-the-curve (AUC), and clearance were calculated. CLZ clearance averaged 1.7 L/kg-h. NOR concentrations (410) exceeded CLZ (289) and NOX (63 ng/ml) and AUC(0-8h) of NOR (3,356) > CLZ (2,359) > NOX (559 ng/ml-h) [53, 38, and 9% of total analytes, respectively]. In adults, NOR serum concentrations on average are 10-25%.< CLZ, differing significantly from our sample. Dose normalized concentrations of CLZ (mg/kg-d) did not vary with age and were similar to reported adult values. Clinical improvement seen in. 5/6 patients correlated with serum CLZ concentrations. In addition, clinical response and total number of side effects correlated with NOR concentrations. NOR (a neuropharmacologically active metabolite) and free CLZ may contribute to the effectiveness and adverse effects in youth. C1 McLean Hosp, Pediat Psychot Disorders Program, Child Outpatient Serv, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Belmont, MA USA. Massachusetts Gen Hosp, Joint Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. NIH, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. NIH, Dept Pharm, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Clin Chem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Program Neurosci, Cambridge, MA 02138 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Frazier, JA (reprint author), McLean Hosp, Pediat Psychot Disorders Program, Child Outpatient Serv, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-47370]; PHS HHS [M-01573] NR 27 TC 43 Z9 44 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2003 VL 23 IS 1 BP 87 EP 91 DI 10.1097/00004714-200302000-00012 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641UJ UT WOS:000180765000012 PM 12544379 ER PT J AU Nierenberg, AA Papakostas, GI Petersen, T Montoya, HD Worthington, JJ Tedlow, J Alpert, JE Fava, M AF Nierenberg, AA Papakostas, GI Petersen, T Montoya, HD Worthington, JJ Tedlow, J Alpert, JE Fava, M TI Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; TRUE DRUG RESPONSE; MAJOR DEPRESSION; REFRACTORY DEPRESSION; DOUBLE-BLIND; PATTERN-ANALYSIS; CARBONATE AUGMENTATION; FLUOXETINE; ADJUNCT; DESIPRAMINE AB Lithium augmentation, the most studied augmentation strategy for depression, has not been evaluated in patients with a history of non-response to multiple antidepressants. The objective of this study was to assess the efficacy of lithium augmentation for patients with a history of treatment resistant depression who also failed a prospective trial of nortriptyline. We enrolled 92 subjects with treatment resistant depression. Treatment resistance was defined by at least one, but no more than five, adequate trials of antidepressants during the current episode. Subjects were treated with nortriptyline (NT) for 6 weeks. Those subjects who tolerated NT for 6 weeks and whose depression did not respond (n=35) were randomized to receive either lithium (n = 18) or placebo (N = 17) augmentation of nortriptyline for an additional 6 weeks. Response was defined as an equal to or greater than 50% decrease in HAM-D-17 scores. After 6 weeks of double-blind augmentation, 12.5 % of subjects responded to lithium and 20.0% to placebo. Our results revealed no significant difference between lithium and placebo augmentation. While lithium augmentation seems to be useful in depression refractory to a single medication in some studies, our data suggest limited usefulness of this option for patients refractory to multiple treatments. More definitive data await the outcome of the NIMH Sequential Treatment Alternatives to Relieve Depression (STAR*D) study. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R29 MH46952] NR 36 TC 58 Z9 61 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 2003 VL 23 IS 1 BP 92 EP 95 DI 10.1097/00004714-200302000-00013 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 641UJ UT WOS:000180765000013 PM 12544380 ER PT J AU Kuperberg, GR Holcomb, PJ Sitnikova, T Greve, D Dale, AM Caplan, D AF Kuperberg, GR Holcomb, PJ Sitnikova, T Greve, D Dale, AM Caplan, D TI Distinct patterns of neural modulation during the processing of conceptual and syntactic anomalies SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID EVENT-RELATED FMRI; POSITRON EMISSION TOMOGRAPHY; SURFACE-BASED ANALYSIS; MEDIAL TEMPORAL-LOBE; SENTENCE COMPREHENSION; BRAIN POTENTIALS; CORTICAL SURFACE; FUNCTIONAL MRI; CEREBRAL-CORTEX; BROCAS-AREA AB The aim of this study was to gain further insights into how the brain distinguishes between meaning and syntax during language comprehension. Participants read and made plausibility judgments on sentences that were plausible, morphosyntactically anomalous, or pragmatically anomalous. In an event-related potential (ERP) experiment, morphosyntactic and pragmatic violations elicited significant P600 and N400 effects, respectively, replicating previous ERP studies that have established qualitative differences in processing conceptually and syntactic anomalies. Our main focus was a functional magnetic resonance imaging (fMRI) study in which the same subjects read the same sentences presented in the same pseudorandomized sequence while performing the same task as in the ERP experiment. Rapid-presentation event-related fMRI methods allowed us to estimate the hemodynamic response at successive temporal windows as the sentences unfolded word by word, without assumptions about the shape of the underlying response function. Relative to nonviolated sentences, the pragmatic anomalies were associated with an increased hemodynamic response in left temporal and inferior frontal regions and a decreased response in the right medial parietal cortex. Relative to nonviolated sentences, the morphosyntactic anomalies were associated with an increased response in bilateral medial and lateral parietal regions and a decreased response in left temporal and inferior frontal regions. Thus, overlapping neural networks were modulated in opposite directions to the two types of anomaly. These fMRI findings document both qualitative and quantitative differences in how the brain distinguishes between these two types of anomalies. This suggests that morphosyntactic and pragmatic information can be processed in different ways but by the same neural systems. C1 Massachusetts Gen Hosp, MIT, HMS Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Tufts Univ, Medford, MA 02155 USA. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp E, CNY-9,Bldg 149, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NICHD NIH HHS [HD25889]; NIDCD NIH HHS [DC02146]; PHS HHS [K23 PA-00-004] NR 82 TC 145 Z9 149 U1 3 U2 13 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD FEB PY 2003 VL 15 IS 2 BP 272 EP 293 DI 10.1162/089892903321208204 PG 22 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 653TJ UT WOS:000181452900011 PM 12676064 ER PT J AU Dunlap, KD Larkins-Ford, J AF Dunlap, KD Larkins-Ford, J TI Diversity in the structure of electrocommunication signals within a genus of electric fish, Apteronotus SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE apteronotus; behavior; electrocommunication; electric fish ID CHIRPING BEHAVIOR; JAMMING AVOIDANCE; ORGAN DISCHARGE; LEPTORHYNCHUS; COMMUNICATION; MODULATIONS; EVOLUTION; BRAIN AB Some gymnotiform electric fish modulate their electric organ discharge for intraspecific communication. In Apteronotus leptorhynchus, chirps are usually rapid (10-30 ms) modulations that are activated through non-N-methyl-D-aspartate (non-NMDA) glutamate receptors in the hindbrain pacemaker nucleus. Males produce longer chirp types than females and chirp at higher rates. In Apteronotus albifrons, chirp rate is sexually monomorphic, but chirp structure (change in frequency and amplitude during a chirp) was unknown. To better understand the neural regulation and evolution of chirping behavior, we compared chirp structure in these two species under identical stimulus regimes. A. albifrons, like A. leptorhynchus, produced distinct types of chirps that varied, in part, by frequency excursion. However, unlike in A. leptorhynchus, chirp types in A. albifrons varied little in duration, and chirps were all longer (70200 ms) than those of A. leptorhynchus. Chirp type production was not sexually dimorphic in A. albifrons, but within two chirp types males produced longer chirps than females. We suggest that species differences in chirp duration might be attributable to differences in the relative proportions of fast-acting (non-NMDA) and slow-acting (NMDA) glutamate receptors in the pacemaker. Additionally, we map species difference onto a phylogeny and hypothesize an evolutionary sequence for the diversification of chirp structure. C1 Trinity Coll, Dept Biol, Hartford, CT 06106 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dunlap, KD (reprint author), Trinity Coll, Dept Biol, Hartford, CT 06106 USA. NR 21 TC 18 Z9 19 U1 2 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD FEB PY 2003 VL 189 IS 2 BP 153 EP 161 DI 10.1007/s00359-003-0393-3 PG 9 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 661NN UT WOS:000181896800009 PM 12607044 ER PT J AU Faraone, SV Monuteaux, MC Biederman, J Cohan, SL Mick, E AF Faraone, SV Monuteaux, MC Biederman, J Cohan, SL Mick, E TI Does parental ADHD bias maternal reports of ADHD symptoms in children? SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID ATTENTION-DEFICIT HYPERACTIVITY; CONTROLLED CLINICAL-TRIAL; DEFICIT/HYPERACTIVITY DISORDER; PSYCHIATRIC COMORBIDITY; CONDUCT DISORDER; FAMILIAL SUBTYPE; CHILDHOOD-ONSET; ADULTS; DEPRESSION; PATTERNS AB Within families, co-occurring attention-deficit/hyperactivity disorder (ADHD) in parents and children may be common. The authors evaluated the hypothesis that parental ADHD may lead to a reporting bias of ADHD symptoms in offspring. They combined 2 family case-controlled studies of ADHD using structured interviews. They compared rates of maternal reported ADHD symptoms among 3 groups of ADHD children: no parental ADHD (n = 231), mother with ADHD (n = 63), and father with ADHD (n = 57). With the exception of I symptom, the rates of reporting between groups did not differ. There was no evidence that the discrepancy between maternal reports and self-reports of symptoms differed by parental ADHD. Results were similar across child gender or referral status. These results do not support the notion that parental ADHD affects maternal reports of offspring ADHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat Psychipharmacol Unit ACC 725, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Biederman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat Psychipharmacol Unit ACC 725, 15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 55 TC 14 Z9 17 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD FEB PY 2003 VL 71 IS 1 BP 168 EP 175 DI 10.1037/0022-006X.71.1.168 PG 8 WC Psychology, Clinical SC Psychology GA 638VB UT WOS:000180591700019 PM 12602437 ER PT J AU Crowson, AN Mihm, MC Magro, C AF Crowson, AN Mihm, MC Magro, C TI Pyoderma gangrenosum: a review SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Review ID ERYTHEMA-ELEVATUM-DIUTINUM; SUPERFICIAL GRANULOMATOUS PYODERMA; BOWEL-BYPASS SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SUBCORNEAL PUSTULAR DERMATOSIS; COLONY-STIMULATING FACTOR; ULCERATIVE-COLITIS; BULLOUS PYODERMA; SWEETS-SYNDROME; NEUTROPHILIC DERMATOSIS AB Since its first description in 1930, the pathogenesis of pyoderma gangrenosum (PG) has remained obscure even as an ever-widening array of systemic diseases has been described in association with it. The histopathologic distinction of PG from other ulcerative processes with dermal neutrophilia is challenging and at times impossible. In consequence, when confronted with a biopsy from such a lesion, the pathologist has an obligation to obtain a full and detailed clinical history. In short, as a diagnosis of PG does not hinge exclusively upon the biopsy findings in isolation from other studies, a solid knowledge of the clinical features, the systemic disease associations and the differential diagnosis will help the pathologist to avoid diagnostic pitfalls or the generation of a report which is non-contributory to patient care. In this review, we describe in detail the different clinicopathologic forms of PG, summarize the diseases associated with this process in the literature and in our experience, and briefly review the treatment options. C1 St Johns Hosp, Reg Med Lab, Tulsa, OK USA. Univ Oklahoma, Dept Dermatol, Tulsa, OK USA. Univ Oklahoma, Dept Pathol, Tulsa, OK USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Ohio State Univ, Dept Pathol, Div Dermatopathol, Columbus, OH 43210 USA. RP Crowson, AN (reprint author), St Johns Hosp, Reg Med Lab, 1923 S Utica St, Tulsa, OK USA. NR 157 TC 101 Z9 107 U1 1 U2 3 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 FEB PY 2003 VL 30 IS 2 BP 97 EP 107 PG 11 WC Dermatology; Pathology SC Dermatology; Pathology GA 656WD UT WOS:000181633300001 PM 12641787 ER PT J AU Stewart, L Oesterle, AL Grifiss, JM Jarvis, GA Way, LW AF Stewart, L Oesterle, AL Grifiss, JM Jarvis, GA Way, LW TI Cholangitis: Bacterial virulence factors that facilitate cholangiovenous reflux and tumor necrosis factor-alpha production SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Surg Alimentary Tract DE cholangitis; cytokines; TNF; slime; biliary infections; gallstones ID SYSTEMIC INFLAMMATORY RESPONSE; CIRCULATING COMPLEMENT PROTEINS; TISSUE-INJURY; SEPSIS; BACTEREMIA; SHOCK; PATHOGENESIS; RESISTANCE; ACTIVATION; BILE AB In previous studies we noted that biliary bacteria produce slime and possess P1-fimbriae. The presence of gram-negative bacteria killed by complement correlated with serious biliary infections and induced more tumor necrosis factor-alpha (TNF-alpha) production in sera, suggesting a role for cytokine production and complement activation in biliary sepsis. This study examined bacterial virulence factors that facilitate cholangiovenous reflux (CVR) and TNT-alpha production in a rat model. Twenty-one biliary bacteria and two stool isolates were tested for slime production, sensitivity to complement killing, and hemolysin production. 10(7) Bacterial colony-forming units/ml (or saline control) were injected retrograde into the common bile ducts of Sprague-Dawley rat's at a pressure of 30 cm. H2O. Blood was obtained at 5 and 60 minutes after infusion for bacterial culture and TNF-alpha assay, respectively. The magnitude of slime production correlated inversely with the magnitude of bacterial CVR. Average bacterial colony-forming units were 1.4 X 10(5), 6.8 X 10(4), or 2.1 X 10(3) for bacteria with slime production 0 to 10 ! 11 to 99, or more than 100, respectively (P < 0.0001, analysis of variance). CVR was greater for serum-resistant bacteria (1.2 X 10(5) vs. 5.5 X 10(4) [P = 0.007, resistant vs. sensitive]), but TNF-alpha production was greater in serum-sensitive bacteria. TNF-alpha-production as a function of bacterial reflux followed a logarithmic curve (R-2 = 0.75) for serum-sensitive bacteria but was linear (R-2 = 0.60) for serum-resistant bacteria. These data show how specific virulence factors explain why some bacterial species colonize without causing illness, whereas others colonize and cause sepsis. Although slime production was necessary for colonization, too much slime inhibited CVR. Although complement killing cleared bacteria from the circulation, it was also associated with increased TNF-alpha production, which can lead to septic manifestations. The most virulent bacterial species (from patients with sepsis) were killed by complement, but they still had significant CVR and were associated with increased TNF-alpha production. (C) 2003 The Society for Surgery of the Alimentary Tract, Inc. C1 Univ Calif San Francisco, Dept Surg 112, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Surg Serv, San Francisco, CA USA. San Francisco VA Med Ctr, Ctr Immunochem, San Francisco, CA USA. RP Stewart, L (reprint author), Univ Calif San Francisco, Dept Surg 112, 4150 Clement St, San Francisco, CA 94121 USA. NR 32 TC 6 Z9 7 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 FEB PY 2003 VL 7 IS 2 BP 191 EP 198 AR PII S1091-255X(02)00133-6 DI 10.1016/S1091-255X(02)00133-6 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 649GA UT WOS:000181197800009 PM 12600443 ER PT J AU Hinnebusch, BF Henderson, JW Siddique, A Malo, MS Zhang, WY Abedrapo, MA Hodin, RA AF Hinnebusch, BF Henderson, JW Siddique, A Malo, MS Zhang, WY Abedrapo, MA Hodin, RA TI Transcriptional activation of the enterocyte differentiation marker intestinal alkaline phosphatase is associated with changes in the acetylation state of histone H3 at a specific site within its promoter region in vitro SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Surg Alimentary Tract DE small intestine; differentiation; histone acetylation; chromatin immunoprecipitation ID GENE-EXPRESSION; GROWTH; CELLS; HYPERACETYLATION; YEAST AB Enterocyte differentiation is thought to occur through the transcriptional regulation of a small subset of specific genes. A recent growing body of evidence indicates that post-translational modifications of chromatin proteins (histones) play an important role in the control of gene transcription. Previous work has demonstrated that one such modification, histone acetylation, occurs in an in vitro model of enterocyte differentiation, butyrate-treated HT-29 cells. In the present work, we sought to determine if the epigenetic signal of histone acetylation occurs in an identifiable pattern in association with the transcriptional activation of the enterocyte differentiation marker gene intestinal alkaline phosphatase (LkP). HT-29 cells were maintained under standard culture conditions and differentiated with sodium butyrate. The chromatin immunoprecipitation (ChIP) assay was used to compare the acetylation state of histones associated with specific regions of the IAP promoter in the two cell populations (undifferentiated vs. differentiated). Chromatin was extracted from cells and cleaved by sonication or enzymatic digestion to obtain fragments of approximately 200 to 600 base-pairs, as confirmed by polymerase chain reaction using primers designed to amplify the IAP segments of interest. The ChIP assay selects DNA sequences that are associated with acetylated histones by immunoprecipitation. Unbound segments represent DNA sequences whose histones are not acetylated. After immunoprecipitation, sequences were detected by radiolabeled polymerase chain reaction, and the relative intensity of the bands was quantified by densitometry. The relative acetylation state of histones at specific sites was determined by comparing the ratios of bound/unbound segments. We determined that in a segment of the IAP promoter between -378 and -303 basepairs upstream from the transcriptional start site, the acetylation state of histone H3 increased twofold in the differentiated, IAP expressing cells, whereas that of histone H4 remained essentially constant. Additionally, at a distant site, between -1378 and -1303 base-pairs, the acetylation state of H3 and H4 did not change appreciably between the undifferentiated and differentiated cells. We conclude that butyrate-induced differentiation is associated with specific and localized changes in the histone acetylation state within the UP promoter. These changes within the endogenous OAP gene may underlie its transcriptional activation in the context of the enterocyte differentiation program. (C) 2003 The Society for Surgery of the Alimentary Tract, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Gray Bigelow 504,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 50623, DK 47186] NR 17 TC 15 Z9 15 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 FEB PY 2003 VL 7 IS 2 BP 237 EP 244 AR PII S1091-255X(02)00140-3 DI 10.1016/S1091-255X(02)00140-3 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 649GA UT WOS:000181197800022 PM 12600448 ER PT J AU Stamm, K Williams, JW Noel, PH Rubin, R AF Stamm, K Williams, JW Noel, PH Rubin, R TI Helping journalists get it right - A physician's guide to improving health care reporting SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE journalism; medical; mass media; physician; communication; health education ID PREPUBLICATION RELEASE; INGELFINGER RULE; MEDIA COVERAGE; NEWS MEDIA; SCIENTISTS; EMBARGOES; ARTICLES; SMOKING; POLICY; PRESS AB News reports are the way that most people, including many physicians and scientists, first learn about new developments in medicine. Because these reports can raise awareness, influence behavior, and confer credibility, physicians should share responsibility with the media for accurate reporting. Physicians can work with reporters to avoid sensationalizing tentative findings, overstating benefits, and making inappropriate generalizations. This article includes pragmatic suggestions for crafting effective news releases and explaining numerical data. It details "rules of the road" for interviews. Working collaboratively with news reporters to improve the quality of medical stories in the lay press benefits patients and physicians alike. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Gen Med, San Antonio, TX 78229 USA. Dept Vet Affairs Med Ctr, HSR&D, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. S Texas Vet Hlth Care Syst, HSR&D Ctr Excellence, San Antonio, TX USA. S Texas Vet Hlth Care Syst, HSR&D Ctr Excellence, VERDICT, San Antonio, TX USA. USA TODAY, Arlington, VA 22229 USA. RP Stamm, K (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Gen Med, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 32 TC 12 Z9 14 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 FEB PY 2003 VL 18 IS 2 BP 138 EP 145 DI 10.1046/j.1525-1497.2003.20220.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 639AH UT WOS:000180605100009 PM 12542589 ER PT J AU Stone, VE AF Stone, VE TI Quality primary care for HIV/AIDS - How much HIV/AIDS experience is enough? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID IN-HOSPITAL MORTALITY; ANTIRETROVIRAL THERAPY; AIDS; CHOICE C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stone, VE (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 12 TC 3 Z9 3 U1 0 U2 1 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 FEB PY 2003 VL 18 IS 2 BP 157 EP 158 DI 10.1046/j.1525-1497.2003.21218.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 639AH UT WOS:000180605100013 PM 12542593 ER PT J AU Vauthey, JN Lauwers, GY AF Vauthey, JN Lauwers, GY TI Prognostic factors after resection of hepatocellular carcinoma: are there landmarks in the wild forest? SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID TRANSPLANTATION; HEPATITIS C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, 1515 Holcombe Blvd,Box 444, Houston, TX 77030 USA. NR 21 TC 5 Z9 9 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 FEB PY 2003 VL 38 IS 2 BP 237 EP 239 DI 10.1016/S0168-8278(02)00407-5 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 643ZF UT WOS:000180892900015 PM 12547414 ER PT J AU Ricono, JM Xu, YC Arar, M Jin, DC Barnes, JL Abboud, HE AF Ricono, JM Xu, YC Arar, M Jin, DC Barnes, JL Abboud, HE TI Morphological insights into the origin of glomerular endothelial and mesangial cells and their precursors SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE glomerulogenesis; development; kidney; microvasculature ID GROWTH-FACTOR; KIDNEY DEVELOPMENT; ADHESION MOLECULE; EMBRYONIC KIDNEY; PDGF-RECEPTOR; BETA-RECEPTOR; EXPRESSION; GLOMERULOGENESIS; DIFFERENTIATION; NEPHROGENESIS AB Glomerular endothelial and mesangial cells may originate from the metanephric mesenchyme. We used the MAb Thy1.1, a mesangial cell marker in the adult rat kidney, and rat endothelial cell markers MAb RECA-1, MAb PECAM-1 (CD31), and MAb Flk-1 as potential markers to characterize the spatial and temporal distribution of mesangial and endothelial cell precursors during nephrogenesis in the rat. At early stages of glomerulo-genesis, RECA-1- and Thy1.1-positive cells were detected in the metanephric blastema at 14 days post conception (dpc) embryos and 15 dpc, respectively, with Thy1.1 expression in cells surrounding the ureteric bud. At 17 and 18 dpc, both RECA-1- and Thy1.1-positive cells were found in the cleft of the S-shaped bodies and in the capillary loops of maturing glomeruli. Double staining for BrdU, a marker of proliferation, and for RECA-1 or BrdU and Thy1.1 also localize in the cleft of S-shaped bodies and in glomerular capillary loops at later stages of development. PDGFRbeta co-localizes in cells expressing endothelial or mesangial markers. The data suggest that endothelial and mesangial cell precursors share common markers during the course of glomerulogenesis and that full differentiation of these cells occurs at late stages of glomerular maturation. Thy1.1- and RECA-1-positive cells may be derived from the metanephric blastemal cells at early stages of kidney development. A subpopulation of these Thy1.1- or RECA-1-positive cells may be precursors that can migrate into the cleft of comma and S-shaped bodies and proliferate in situ to form glomerular capillary tufts. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Abboud, HE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,MC 7882, San Antonio, TX 78229 USA. FU NIDDK NIH HHS [DK-33665] NR 38 TC 30 Z9 32 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 2003 VL 51 IS 2 BP 141 EP 150 PG 10 WC Cell Biology SC Cell Biology GA 639LT UT WOS:000180631000002 PM 12533522 ER PT J AU Lee, JS Frevert, CW Thorning, DR Segerer, S Alpers, CE Cartron, JP Colin, Y Wong, VA Martin, TR Goodman, RB AF Lee, JS Frevert, CW Thorning, DR Segerer, S Alpers, CE Cartron, JP Colin, Y Wong, VA Martin, TR Goodman, RB TI Enhanced expression of Duffy antigen in the lungs during suppurative pneumonia SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE Duffy antigen; endothelial; chemokines; lungs; pneumonia ID ERYTHROCYTE CHEMOKINE RECEPTOR; RENAL-TRANSPLANT REJECTION; RED-BLOOD-CELLS; ENDOTHELIAL-CELLS; NEGATIVE INDIVIDUALS; GENE; ANTIGEN/RECEPTOR; PHENOTYPE; MUTATION; ARG89CYS AB Duffy antigen is a chemokine binding protein expressed on the surface of erythrocytes and postcapillary venular endothelial cells. It binds selective CXC and CC chemokines with high affinity. Although Duffy antigen is present in the normal pulmonary vascular bed, it is not known whether its expression is altered by innate inflammatory responses in the lungs. We studied Duffy antigen expression by immunohistochemistry in autopsy lung specimens from 16 cases of suppurative pneumonia, 11 cases of acute lung injury, and seven normal lungs. In lungs with suppurative pneumonia, Duffy antigen was expressed in higher numbers of pre- and postcapillary parenchymal vessels compared to normal specimens or specimens with acute lung injury (p<0.03 and p<0.02, respectively). Lungs with suppurative pneumonia also showed Duffy antigen expression on the alveolar septa, whereas this was a rare finding in normal specimens or in acute lung injury (p<0.02). Furthermore, Duffy antigen labeling of the alveolar septa localized to regions with airspace accumulation of neutrophil-rich exudates. In summary, Duffy antigen expression is increased in the vascular beds and alveolar septa of the lung parenchyma during suppurative pneumonia, suggesting that Duffy antigen may have a functional role in the lung parenchyma during inflammation. C1 VA Puget Sound Hlth Care Syst, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98108 USA. Inst Natl Transfus Sanguine, INSERM U76, F-75015 Paris, France. Univ Washington, Sch Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Pathol, Seattle, WA 98108 USA. RP Goodman, RB (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Pulm & Crit Care Med, 111B,1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL030542, HL10470, HL63652, HL69955, HL70178]; NIDDK NIH HHS [DK47659] NR 25 TC 27 Z9 30 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 2003 VL 51 IS 2 BP 159 EP 166 PG 8 WC Cell Biology SC Cell Biology GA 639LT UT WOS:000180631000004 PM 12533524 ER PT J AU Brown, JA Dorfman, DM Ma, FR Sullivan, EL Munoz, O Wood, CR Greenfield, EA Freeman, GJ AF Brown, JA Dorfman, DM Ma, FR Sullivan, EL Munoz, O Wood, CR Greenfield, EA Freeman, GJ TI Blockade of programmed death-1 Ligands on dendritic cells enhances T cell activation and cytokine production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL; COSTIMULATORY SIGNALS; INDUCED EXPRESSION; PD-1; GENE; IMMUNORECEPTOR; INHIBITION; RECEPTOR; ANTIGEN; MEMBER AB Programmed death-1 ligand (PD-L)1 and PD-L2 are ligands for programmed death-1 (PD-1), a member of the CD28/CTLA4 family expressed on activated lymphoid cells. PD-1 contains an immunoreceptor tyrosine-based inhibitory motif and mice deficient in PD-1 develop autoimmune disorders suggesting a defect in peripheral tolerance. Human PD-L1 and PD-L2 are expressed on immature dendritic cells (iDC) and mature dendritic cells (mDC), IFN-gamma-treated monocytes, and follicular dendritic cells. Using mAbs, we show that blockade of PD-L2 on dendritic cells results in enhanced T cell proliferation and cytokine production, including that of IFN-gamma and IL-10, while blockade of PD-L1 results in similar, more modest, effects. Blockade of both PD-L1 and PD-L2 showed an additive effect. Both whole mAb and Fab enhanced T cell activation, showing that PD-L1 and PD-L2 function to inhibit T cell activation. Enhancement of T cell activation was most pronounced with weak APC, such as iDCs and IL-10-pretreated mDCs, and less pronounced with strong APC such as mDCs. These data are consistent with the hypothesis that iDC have a balance of stimulatory vs inhibitory molecules that favors inhibition, and indicate that PD-L1 and PD-L2 contribute to the poor stimulatory capacity of iDC. PD-L1 expression differs from PD-L2 in that PD-L1 is expressed on activated T cells, placental trophoblasts, myocardial endothelium, and cortical thymic epithelial cells. In contrast, PD-L2 is expressed on placental endothelium and medullary thymic epithelial cells. PD-L1 is also highly expressed on most carcinomas but minimally expressed on adjacent normal tissue suggesting a role in attenuating antitumor immune responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Wyeth Ayerst Res, Cambridge, MA 02140 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA84500]; NIAID NIH HHS [AI39671, AI41584] NR 42 TC 463 Z9 502 U1 6 U2 29 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2003 VL 170 IS 3 BP 1257 EP 1266 PG 10 WC Immunology SC Immunology GA 639XM UT WOS:000180655500018 PM 12538684 ER PT J AU Thurman, JM Ljubanovic, D Edelstein, CL Gilkeson, GS Holers, VM AF Thurman, JM Ljubanovic, D Edelstein, CL Gilkeson, GS Holers, VM TI Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR-B; REPERFUSION INJURY; ENDOTHELIAL-CELLS; ANTIBODY; INHIBITOR; EXPRESSION; SELECTIN; NECROSIS; FRAGMENT; DISEASE AB Ischemia/reperfusion (I/R) injury of the kidney is a common cause of acute renal failure (ARF) and is associated with high morbidity and mortality in the intensive care unit. The mechanisms underlying I/R injury are complex. Studies have shown that complement activation contributes to the pathogenesis of I/R injury in the kidney, but the exact mechanisms of complement activation have not been defined. We hypothesized that complement activation in this setting occurs via the alternative pathway and that mice deficient in complement factor B, an essential component of the alternative pathway, would be protected from ischemic ARE Wild-type mice suffered from a decline in renal function and had significant tubular injury, particularly in the outer medulla, after I/R. We found that factor B-deficient mice (fB(-/-)) developed substantially less functional and morphologic renal injury after I/R. Furthermore, control wild-type mice had an increase in tubulointerstitial complement C3 deposition and neutrophil infiltration in the outer medulla after I/R, whereas fB(-/-) mice demonstrated virtually no C3 deposition or neutrophil infiltration. Our results demonstrate that complement activation in the kidney after I/R occurs exclusively via the alternative pathway, and that selective inhibition of this pathway provides protection to the kidneys from ischemic ARF. C1 Univ Colorado, Hlth Sci Ctr, Div Rheumatol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Nephrol & Hypertens, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29425 USA. RP Holers, VM (reprint author), Univ Colorado, Hlth Sci Ctr, Div Rheumatol, 4200 E 9th Ave,B-115, Denver, CO 80262 USA. FU NIAID NIH HHS [R0-1 AI31105, R0-1 AI47469]; NIDDK NIH HHS [5T32DK 07135] NR 34 TC 150 Z9 154 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2003 VL 170 IS 3 BP 1517 EP 1523 PG 7 WC Immunology SC Immunology GA 639XM UT WOS:000180655500050 PM 12538716 ER PT J AU Subramanian, S Matejuk, A Zamora, A Vandenbark, AA Offner, H AF Subramanian, S Matejuk, A Zamora, A Vandenbark, AA Offner, H TI Oral feeding with ethinyl estradiol. suppresses and treats experimental autoimmune encephalomyelitis in SJL mice and inhibits the recruitment of inflammatory cells into the central nervous system SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; MULTIPLE-SCLEROSIS; T-CELLS; IL-6-DEFICIENT MICE; IMMUNE-RESPONSE; GAMMA PROTECTS; INDUCTION; CHEMOKINE; MYELIN AB There is much interest in the possible ameliorating effects of estrogen on various autoimmunc diseases. We previously established the protective effects of 17beta-estradiol (E2) on experimental autoimmune encephalomyelitis (EAE). In the current study we investigated the effectiveness of oral treatment with ethinyl estradiol (EE) on EAE and the mechanisms involved. Ethinyl estradiol is a semisynthetic estrogen compound found in birth control pills, and its chemical structure allows this compound to retain activity when given orally. We found that oral EE, like E2, drastically suppressed EAE induced by proteolipid protein 139-151 peptide when given at initiation of EAE. However, unlike E2, EE reduced clinical severity when given after the onset of clinical signs. Treatment with EE significantly decreased the secretion of proinflammatory cytokines (IFN-gamma, TNF-alpha, and IL-6) by activated T cells as well as the expression of a key matrix metalloproteinase, disease-mediating chemokines/receptors, and IgG2a levels, but increased the expression of TGF-beta3 in the CNS. The absence of infiltrating lymphocytes together with the suppression of cytokines, matrix metalloproteinase, and chemokines/receptors suggests that EE, like E2, protects mice from EAE by inhibiting the recruitment of T cells and macrophages into the CNS. These results suggest that oral ethinyl estradiol might be a successful candidate as therapy for multiple sclerosis. The Journal of Immunology, 2003, 170: 1548-1555. C1 Portland Vet Affairs Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland Vet Affairs Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23444, NS23221] NR 51 TC 79 Z9 82 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 2003 VL 170 IS 3 BP 1548 EP 1555 PG 8 WC Immunology SC Immunology GA 639XM UT WOS:000180655500054 PM 12538720 ER PT J AU Coviello, AD Herbst, KL Amory, JK Anawalt, BD Jarow, JP Brown, T Wright, W Bremner, WJ Matsumoto, AM AF Coviello, AD Herbst, KL Amory, JK Anawalt, BD Jarow, JP Brown, T Wright, W Bremner, WJ Matsumoto, AM TI Intratesticular testosterone concentrations comparable to serum levels are not sufficient to maintain normal sperm production in men. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 365 BP S155 EP S155 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600371 ER PT J AU Cummings, DE Kletk, ML Frayo, DS Weigle, DS Purnell, JQ Chapelot, D Merriam, GR AF Cummings, DE Kletk, ML Frayo, DS Weigle, DS Purnell, JQ Chapelot, D Merriam, GR TI Evidence against an obligatory role for ghrelin in physiological growth hormone (GH) regulation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound HCS, Tacoma, WA USA. Univ Paris, Fac Xavier Bichat, F-75252 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 147 BP S116 EP S117 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600153 ER PT J AU Cummings, DE Kletke, ML Frayo, RS Weigle, DS Purnell, JQ Chapelot, D Merriam, GR AF Cummings, DE Kletke, ML Frayo, RS Weigle, DS Purnell, JQ Chapelot, D Merriam, GR TI Evidence against an obligatory role for ghrelin in physiological growth hormone (GH) regulation SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound HCS, Tacoma, WA USA. Univ Paris, Fac Xavier Bichat, F-75252 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 36 BP S97 EP S97 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600042 ER PT J AU Elias, FN Ledoux, WR Yuen, TJ Olson, SL Ching, RP Sangeorzan, BJ AF Elias, FN Ledoux, WR Yuen, TJ Olson, SL Ching, RP Sangeorzan, BJ TI Surgical intervention for the clawed hallux deformity. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 VA Puget Sound, RR&D Ctr Excellence, Seattle, WA USA. RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 246 BP S133 EP S133 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600252 ER PT J AU Furmanczyk, PS Quinn, LS AF Furmanczyk, PS Quinn, LS TI Interleukin-15 increases myosin heavy chain accumulation in primary human skeletal myogenic cultures SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 71 BP S103 EP S104 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600077 ER PT J AU Jensen, CC Shofer, JB Boyko, EJ Fujimoto, WY Kahn, SE AF Jensen, CC Shofer, JB Boyko, EJ Fujimoto, WY Kahn, SE CA ADA GENNID Study Grp TI Relationship of ethnicity and glucose tolerance to features of the metabolic syndrome. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 195 BP S125 EP S125 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600201 ER PT J AU Jensen, CC Shofer, JB Boyko, EJ Fujimoto, WY Kahn, SE AF Jensen, CC Shofer, JB Boyko, EJ Fujimoto, WY Kahn, SE CA ADA GENNID Study Grp TI Relationship of ethnicity and glucose tolerance to features of the metabolic syndrome SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 41 BP S98 EP S98 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600047 ER PT J AU Kiser, KM Prigeon, RL Kahn, SE AF Kiser, KM Prigeon, RL Kahn, SE TI Insulin sensitivity quantified with the minimal model is lower with the insulin-modified than the tolbutamide-modified frequently sampled intravenous glucose tolerance test SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res 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 B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 15 BP S94 EP S94 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600021 ER PT J AU Li, L Watson, L Merrell, M Selander, K Harris, KW AF Li, L Watson, L Merrell, M Selander, K Harris, KW TI Inhibition of cytokine receptor gp130 signaling in breast cancer cells results in decreased constitutive stat3 activation via inhibition of EGF receptor family members. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 175 BP S286 EP S286 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600703 ER PT J AU Nadeau, KI Draznin, B AF Nadeau, KI Draznin, B TI Insulin stimulates SREBP-1 expression in L6 muscle cells via the map kinase signaling pathway SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 189 BP S124 EP S124 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600195 ER PT J AU Phan, I Peterfy, M Reue, K AF Phan, I Peterfy, M Reue, K TI Lipin deficiency attenuates obesity and exacerbates diabetes in leptin deficient ob/ob mice. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 320 BP S147 EP S147 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600326 ER PT J AU Phan, J Peterfy, M Reue, K AF Phan, J Peterfy, M Reue, K TI Lipin deficiency attenuates obesity and exacerbates diabetes in leptin deficient ob/ob mice SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 84 BP S106 EP S106 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600090 ER PT J AU Rianthavorn, P Goodman, WG Salusky, IB Juppner, H Kuizon, BD AF Rianthavorn, P Goodman, WG Salusky, IB Juppner, H Kuizon, BD TI Impaired angiogenesis and osteoclastogenesis in nephrectomized (NX) rats given high calcium diet. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 346 BP S151 EP S152 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600352 ER PT J AU Saha, SK Barrington, R Zhang, M Carroll, MC AF Saha, SK Barrington, R Zhang, M Carroll, MC TI C3-deficient mice showenhanced follicular survival of antigen-specific B lymphocytes in a Fas-dependent manner SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Calif Los Angeles, David Geffen Sch Med, Med Sci Training Program, Los Angeles, CA 90024 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 381 BP S158 EP S158 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600387 ER PT J AU Senthil, D Choudhury, GG Kasinath, BS AF Senthil, D Choudhury, GG Kasinath, BS TI Vascular endothelial growth factor (VEGF) induces protein synthesis in mouse renal proximal tubular epithelial (MCT) cells: A potential role in diabetic nephropathy. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 223 BP S295 EP S295 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600751 ER PT J AU Utzschneider, K Carr, DB Barsness, SL Kahn, SE Schwartz, RS AF Utzschneider, K Carr, DB Barsness, SL Kahn, SE Schwartz, RS TI Weight loss is associated with improvements in insulin sensitivity and B-cell function in older subjects. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 198 BP S125 EP S125 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600204 ER PT J AU Wang, CCL Golovchenko, I Draznin, B AF Wang, CCL Golovchenko, I Draznin, B TI Vascular smooth muscle cell quiescence and migration are mediated differentially via phosphatidylinositol 3-kinase- and mitogen-activated kinase-dependent pathways SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 29-FEB 01, 2003 CL CARMEL, CALIFORNIA SP American Fed Med Res C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD FEB PY 2003 VL 51 SU 1 MA 403 BP S162 EP S162 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 638KF UT WOS:000180569600409 ER PT J AU Kluwe, L Mautner, V Heinrich, B Dezube, R Jacoby, LB Friedrich, RE MacCollin, M AF Kluwe, L Mautner, V Heinrich, B Dezube, R Jacoby, LB Friedrich, RE MacCollin, M TI Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; GERM-LINE MUTATIONS; TYPE-2 NEUROFIBROMATOSIS; NF2 GENE; DISEASE; SEVERITY; INDIVIDUALS; PHENOTYPES AB Neurofibromatosis 2 (NF2) is a severe autosomal dominant disorder that predisposes to multiple tumours of the nervous system. About half of all patients are founders with clinically unaffected parents. The purpose of the present study was to examine the extent to which mosaicism is present in NF2 founders. A total of 233 NF2 founders with bilateral vestibular schwannomas (BVS) were screened by exon scanning. NF2 mutations were detected in the blood samples of 122 patients (52%). In 10 of the 122 cases, the ratio of mutant to normal alleles was obviously less than 1, suggesting mosaicism. Tumour specimens were available from 35 of the 111 subjects in whom no mutation could be detected in blood specimens. Mutational analysis by exon scanning detected typical NF2 mutations in 21 of the 35 tumours. In nine subjects, the alterations found in tumours could be confirmed to be the constitutional mutation based on finding of identical mutations in pathologically and/or anatomically distinct second tumours. In six other subjects with only a single tumour available, allelic loss of the NF2 gene was found in addition to the mutation in each tumour, suggesting that either the mutation or the deletion of the NF2 gene is probably the constitutional genetic alteration. Our results suggest that failure to find constitutional mutations in blood specimen from these 15 patients was not because of the limitation of the applied screening technique, but the lack of the mutations in their leucocytes, best explained by mosaicism. Extrapolating the rate (15/35 = 43%) of mosaicism in these 35 cases to the 111 NF2 founders with no constitutional NF2 mutations found in their blood, we inferred 48 mosaic subjects (111 x 0.429). Adding the 10 mosaic cases detected directly in blood specimens, we estimate the rate of mosaicism to be 24.8% (58/233) in our cohort of 233 NF2 founders with bilateral vestibular schwannomos. C1 Univ Hosp Eppendorf, Dept Maxillofacial Surg, D-20246 Hamburg, Germany. Univ Hosp Eppendorf, Dept Neurosurg, Lab Brain Tumour Biol, Hamburg, Germany. Klinkum Nord Ochsenzoll, Dept Neurol, Hamburg, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kluwe, L (reprint author), Univ Hosp Eppendorf, Dept Maxillofacial Surg, Martinistr 52, D-20246 Hamburg, Germany. FU NINDS NIH HHS [R01NS40527] NR 28 TC 78 Z9 82 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD FEB PY 2003 VL 40 IS 2 BP 109 EP 114 DI 10.1136/jmg.40.2.109 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 645VG UT WOS:000180999900005 PM 12566519 ER PT J AU Weaver, KD Yeyeodu, S Cusack, JC Baldwin, AS Ewend, MG AF Weaver, KD Yeyeodu, S Cusack, JC Baldwin, AS Ewend, MG TI Potentiation of chemotherapeutic agents following antagonism of nuclear factor kappa B in human gliomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE apoptosis; chemotherapy; gene therapy; glioma; nuclear factor kappa B ID TUMOR-NECROSIS-FACTOR; MEDIATED GENE-TRANSFER; CANCER-CELLS; INDUCIBLE CHEMORESISTANCE; INDUCED APOPTOSIS; FACTOR-ALPHA; INHIBITION; ACTIVATION; PHOSPHORYLATION; REQUIREMENT AB Future success using chemotherapy against human gliomas may result from exploiting unique molecular vulnerabilities of these tumors. Chemotherapy frequently results in DNA damage. When such damage is sensed by the cell, programmed cell death, or apoptosis, may be initiated. However, chemotherapy-induced DNA damage may activate nuclear factor kappa B ( NF-kappaB) and block apoptosis. We inhibited NF-kappaB using a gene therapy approach to determine whether this would render human glioma cells more susceptible to chemotherapy. U87 and U251 glioma cell lines were infected with either treatment adenovirus containing the gene for a mutant non-degradable form of IkappaBalpha, which is an inhibitor of NF-kappaB nuclear translocation, or empty control virus. Following viral infection, cells were treated either with BCNU, carboplatin, tumor necrosis factor alpha (TNF-alpha), or SN-38. Chemotherapy resulted in a marked increase in active intranuclear NF-kappaB. This response was greatly decreased by insertion of the mutant repressor gene. Similarly, a significant increase in cell killing by all chemotherapy age was demonstrated following infection with treatment virus. Expression of the mutant repressor gene also resulted in increased apoptosis by TUNEL assay following chemotherapy. Numerous genes are responsible for glioma chemoresistance. DNA damage by chemotherapy may induce the antiapoptotic factor NF-kappaB and prevent programmed cell death. Insertion of a mutant inhibitor of NF-kappaB strips cells of this antiapoptotic defense and renders them more susceptible to killing by chemotherapy via increased apoptosis. C1 Univ N Carolina, Sch Med, Div Neurosurg, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Cell Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Ewend, MG (reprint author), Univ N Carolina, Sch Med, Div Neurosurg, 148 Burnett Womack,CB 7060, Chapel Hill, NC 27599 USA. NR 36 TC 72 Z9 78 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 FEB PY 2003 VL 61 IS 3 BP 187 EP 196 DI 10.1023/A:1022554824129 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 649JL UT WOS:000181204400001 PM 12675310 ER PT J AU Baehring, JM Longtine, J Hochberg, FH AF Baehring, JM Longtine, J Hochberg, FH TI A new approach to the diagnosis and treatment of intravascular lymphoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE intravascular lymphoma; methotrexate; IgH rearrangement ID LARGE-CELL LYMPHOMA; CENTRAL-NERVOUS-SYSTEM; POLYMERASE CHAIN-REACTION; HIGH-DOSE METHOTREXATE; MALIGNANT LYMPHOMATOSIS; NEUROLOGIC MANIFESTATIONS; INVOLVEMENT; TRANSPLANTATION; SYMPTOMS; ANGIOENDOTHELIOMATOSIS AB In intravascular lymphoma (IVL) tumor cells are initially restricted to vascular lumina. Neurological syndromes predominate and are caused by ischemia as well as tumor infiltration into the nervous system. Ante mortem diagnosis is challenging and frequently impossible. Chemotherapy is effective if started prior to ischemic damage. Over a three year period, we have diagnosed IVL in seven patients. Tissue diagnosis could be accomplished in only three cases. For those in whom tissue diagnosis failed we based our diagnosis on clinical presentation, typical magnetic resonance imaging findings, spinal fluid cytopathology, and molecular analyses. Six patients were treated with methotrexate chemotherapy alone or in combination with CHOP. Three patients are in complete remission 9-20 months after initial diagnosis. Another patient achieved a partial response. Two patients died due to progressive disease shortly after initiation of treatment. Grade III toxicity was observed in only 4 of 61 cycles. Based on a small retrospective series of patients, we conclude that methotrexate is a well tolerated and effective agent for the treatment of IVL. C1 Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Cox 315,100 Blossom St, Boston, MA 02114 USA. NR 47 TC 41 Z9 43 U1 0 U2 0 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 FEB PY 2003 VL 61 IS 3 BP 237 EP 248 DI 10.1023/A:1022588812415 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 649JL UT WOS:000181204400008 PM 12675317 ER PT J AU Seidberg, NA Clark, RSB Zhang, XP Lai, YC Chen, MZ Graham, SH Kochanek, PM Watkins, SC Marion, DW AF Seidberg, NA Clark, RSB Zhang, XP Lai, YC Chen, MZ Graham, SH Kochanek, PM Watkins, SC Marion, DW TI Alterations in inducible 72-kDa heat shock protein and the chaperone cofactor BAG-1 in human brain after head injury SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; Bcl-2; head injury; Hsc70; Hsp70; trauma ID OXIDE SYNTHASE EXPRESSION; CELL-DEATH; RAT-BRAIN; CULTURED NEURONS; STRESS-RESPONSE; HSP70; INDUCTION; GENE; HEAT-SHOCK-PROTEIN-70; FIBROBLASTS AB The stress response in injured brain is well characterized after experimental ischemic and traumatic brain injury (TBI); however, the induction and regulation of the stress response in humans after TBI remains largely undefined. Accordingly, we examined injured brain tissue from adult patients (n=8) that underwent emergent surgical decompression after TBI, for alterations in the inducible 72-kDa heat shock protein (Hsp70), the constitutive 73-kDa heat shock protein (Hsc70), and isoforms of the chaperone cofactor BAG-1. Control samples (n=6) were obtained postmortem from patients dying of causes unrelated to CNS trauma. Western blot analysis showed that Hsp70, but not Hsc70, was increased in patients after TBI versus controls. Both Hsp70 and Hsc70 coimmunoprecipitated with the cofactor BAG-1. The 33 and 46, but not the 50-kDa BAG-1 isoforms were increased in patients after TBI versus controls. The ratio of the 46/33-kDa isoforms was increased in TBI versus controls, suggesting negative modulation of Hsp70/Hsc70 protein refolding activity in injured brain. These data implicate induction of the stress response and its modulation by the chaperone cofactor and Bcl-2 family member BAG-1, after TBI in humans. C1 Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Anesthesiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Cell Biol & Physiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Clark, RSB (reprint author), Univ Pittsburgh, Safar Ctr Resuscitat Res, Dept Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [R01 NS38620, KO8 NS01946, P50 NS30318] NR 52 TC 23 Z9 23 U1 0 U2 0 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 FEB PY 2003 VL 84 IS 3 BP 514 EP 521 DI 10.1046/j.1471-4159.2003.01547.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 635UF UT WOS:000180417200011 PM 12558971 ER PT J AU Chen, RW Qin, ZH Ren, M Kanai, H Chalecka-Franaszek, E Leeds, P Chuang, DM AF Chen, RW Qin, ZH Ren, M Kanai, H Chalecka-Franaszek, E Leeds, P Chuang, DM TI Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AP-1; excitotoxicity; JNK; lithium neuroprotection; p38; p53 phosphorylation ID ACTIVATED PROTEIN-KINASE; NEUROBLASTOMA SH-SY5Y CELLS; CNS IN-VIVO; HUMAN P53; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; KAPPA-B; INDUCED INHIBITION; NERVOUS-SYSTEM; RAT-BRAIN AB In rat cerebellar granule cells, glutamate induced rapid activation of c-Jun N-terminal kinase (JNK) and p38 kinase to phosphorylate c-Jun (at Ser63) and p53 (at Ser15), respectively, and a subsequent marked increase in activator protein-1 (AP-1) binding that preceded apoptotic death. These glutamate-induced effects and apoptosis could largely be prevented by long-term (7 days) pretreatment with 0.5-2 mM lithium, an antibipolar drug. Glutamate's actions could also be prevented by known blockers of this pathway, MK-801 (an NMDA receptor blocker), SB 203580 (a p38 kinase inhibitor) and curcumin (an AP-1 binding inhibitor). The concentration- and time-dependent suppression of glutamate's effects by lithium and curcumin correlated well with their neuroprotective effects. These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity. Moreover, the neuroprotective effects of lithium are mediated, at least in part, by suppressing NMDA receptor-mediated activation of the mitogen-activated protein kinase pathway. C1 NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bldg 10-Rm 4C206,10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. NR 60 TC 83 Z9 104 U1 0 U2 2 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 FEB PY 2003 VL 84 IS 3 BP 566 EP 575 DI 10.1046/j.1471-4159.2003.01548.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 635UF UT WOS:000180417200016 PM 12558976 ER PT J AU Reifenberger, G Louis, DN AF Reifenberger, G Louis, DN TI Oligodendroglioma: Toward molecular definitions in diagnostic neuro-oncology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Review DE brain neoplasms; chemotherapy; molecular genetics; oligodendroglioma; prognostic factors; survival ID COMPARATIVE GENOMIC HYBRIDIZATION; GROWTH-FACTOR-RECEPTOR; TUMOR-SUPPRESSOR GENE; LOW-GRADE OLIGODENDROGLIOMA; ANAPLASTIC OLIGODENDROGLIOMAS; PROMOTER HYPERMETHYLATION; MUTATION ANALYSIS; CHROMOSOME 19Q; HUMAN GLIOMAS; ALLELIC LOSS AB Oligodendroglial tumors have attracted great interest in both basic and clinical neuro-oncology over the past decade. This interest is mainly due to the clinical observation that anaplastic oligodendrogliomas and anaplastic oligoastro-cytomas, in contrast to the vast majority of anaplastic astrocytomas and glioblastomas, frequently respond favorably to chemotherapy. In addition, oligodendroglial tumors are associated with longer survival times than the diffuse astrocytic gliomas. These differences in response to therapy and in prognosis have been associated with distinct genetic aberrations, in particular the frequent loss of alleles on chromosome arms 1p and 19q in oligodendroglial tumors. In addition, other genetic changes have been reported as indicators of poor response to therapy and short survival, including homozygous deletion of the CDKN2A gene at 9p21, mutation of the PTEN gene at 10q23, and amplification of the EGFR gene at 7p12. In this review we summarize the current state of the art concerning the molecular genetics of oligodendroglial tumors. A particular focus is placed on the role of molecular genetic findings in the diagnostic and prognostic assessment of these neoplasms. As a result of the recent advances in the field, we propose that clinical decisions in the management of patients with oligodendroglial tumors should be based on the combined assessment of clinical and neuroimaging features, histological classification and grading, as well as molecular genetic characteristics. C1 Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, C S Kubik Lab Neuropathol, Boston, MA 02129 USA. Univ Dusseldorf, Ctr Biol & Med Res, D-40225 Dusseldorf, Germany. RP Reifenberger, G (reprint author), Univ Dusseldorf, Dept Neuropathol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM reifenberger@med.uni-duesseldorf.de; dlouis@partners.org FU NCI NIH HHS [CA57683] NR 110 TC 212 Z9 221 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD FEB PY 2003 VL 62 IS 2 BP 111 EP 126 PG 16 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 643RT UT WOS:000180874800001 PM 12578221 ER PT J AU D'Amore, JD Kajdasz, ST McLellan, ME Bacskai, BJ Stern, EA Hyman, BT AF D'Amore, JD Kajdasz, ST McLellan, ME Bacskai, BJ Stern, EA Hyman, BT TI In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; amyloid-beta; in vivo imaging; multiphoton microscopy; senile plaque; transgenic mice ID AMYLOID PRECURSOR PROTEIN; NEUROPIL CHANGES; SENILE DEMENTIA; NEURONAL LOSS; PLAQUES; MICE; ABNORMALITIES; MICROSCOPY; DEPOSITION; DISRUPTION AB Postmortem analyses of senile plaques reveal numerous dystrophic processes in their vicinity. We used in vivo multiphoton microscopy of a transgenic model of Alzheimer disease (AD) to simultaneously image senile plaques and nearby neuronal processes. Plaques were labeled by immunofluorescent staining or thioflavine-S and neuronal processes were labeled with a fluorescent dextran conjugate. Imaging of 3-dimensional volumes in the vicinity of plaques revealed subtle changes in neurite geometry in or near diffuse plaques. By contrast, disruptions in neurite morphology, including dystrophic neurites immediately surrounding plaques as well as major alterations in neurite trajectories, were seen in association with thioflavine-S-positive plaques. Nearly half of all labeled processes that came within 50 mum of a thioflavine-S-positive plaque were altered, suggesting a fairly large "halo" of neuropil alterations that extend beyond the discrete border of a thioflavine-S plaque. These results support the hypothesis that compact thioflavine-S-positive plaques disrupt the neuropil in AD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Serv,Alzheimers Dis Res Unit,Dept Neurol, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Serv,Alzheimers Dis Res Unit,Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG08487, AG15453] NR 19 TC 57 Z9 57 U1 0 U2 2 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 FEB PY 2003 VL 62 IS 2 BP 137 EP 145 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 643RT UT WOS:000180874800003 PM 12578223 ER PT J AU Graf, CM Millar, S Feilteau, C Coakley, PJ Erickson, JI AF Graf, CM Millar, S Feilteau, C Coakley, PJ Erickson, JI TI Patients' needs for nursing care - Beyond staffing ratios SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID CALIFORNIA AB The current focus on staffing ratios as a means to assure appropriate care for patients ignores the very real differences among patients in their needs for nursing care. Implementing a system that identifies these needs provides a more accurate indication of staffing requirements. In addition, storing the raw data from the system at their most basic level provides opportunities for more extensive analyses and,informed, data-driven decision-making related to re-source allocation, performance improvement, and productivity enhancement. C1 Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. RP Millar, S (reprint author), Massachusetts Gen Hosp, Patient Care Serv, 55 Fruit St,GRB 015, Boston, MA 02114 USA. NR 9 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD FEB PY 2003 VL 33 IS 2 BP 76 EP 81 DI 10.1097/00005110-200302000-00003 PG 6 WC Nursing SC Nursing GA 651ZM UT WOS:000181354000003 PM 12584459 ER PT J AU Ponte, PR Conlin, G Conway, JR Grant, S Medeiros, C Nies, J Shulman, L Branowicki, P Conley, K AF Ponte, PR Conlin, G Conway, JR Grant, S Medeiros, C Nies, J Shulman, L Branowicki, P Conley, K TI Making patient-centered care come alive - Achieving full integration of the patient's perspective SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB A patient-centered model of care has profound implications for the way that care is planned, delivered, and evaluated. Although most leaders in healthcare organizations today embrace the basic tenets of a patient-centered philosophy, they often find that moving toward a patient-centered model requires an unanticipated level of commitment and significant adjustments in organizational structures. In this article, the authors describe how patients and families have been integrated into the care delivery model by involving them in planning, decision-making, and improvement processes at all levels of the organization. C1 Dana Farber Canc Inst, Nursing Serv, Boston, MA 02115 USA. Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. Dana Farber Canc Inst, Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. Dana Farber Canc Inst, Patient & Family Advisory Council, Boston, MA 02115 USA. Dana Farber Canc Inst, Clin Serv, Boston, MA 02115 USA. Dana Farber Canc Inst, Childrens Hosp, Med Patient Serv, Boston, MA 02115 USA. Northwestern Univ, Boston, MA USA. Brigham & Womens Hosp, Nursing Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Patient Care Serv, Boston, MA 02115 USA. Univ Washington, Med Ctr, Patient Care Serv, Seattle, WA 98195 USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, Nursing Serv, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 44 Z9 45 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD FEB PY 2003 VL 33 IS 2 BP 82 EP 90 DI 10.1097/00005110-200302000-00004 PG 9 WC Nursing SC Nursing GA 651ZM UT WOS:000181354000004 PM 12584460 ER PT J AU Erickson, JI Hamilton, GA Jones, DE Ditomassi, M AF Erickson, JI Hamilton, GA Jones, DE Ditomassi, M TI The value of collaborative governance/staff empowerment SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID NURSING WORK ENVIRONMENTS; TESTING KANTER THEORY; STRUCTURAL POWER; STAFF NURSES; ORGANIZATIONS; PERCEPTIONS; AUTONOMY; HEALTH AB Objective: Collaborative governance is the decision-making process that places the authority, responsibility, and accountability for patient care with the practicing clinician. Background: Collaborative governance was introduced as one of nine structures within the patient care services' professional practice model to facilitate communication and optimize staff participation in decision-making across disciplines. The concept of empowerment was used to evaluate the impact of the collaborative governance structure on members. Methods: The purpose of the current study was to compare empowerment and power scores for both members and nonmembers of collaborative governance over a 3-year period. Results: Initial survey data (baseline) from 136 staff from across disciplines was returned prior to beginning work on a committee. Study results were based on survey returns from 657 staff over a 3.5-year period. There were no significant differences between collaborative governance members and nonmembers on some demographic variables such as age, but there were significant differences on variables such as work status and education. All empowerment scores were significantly higher at the 2nd and 3rd measurement periods for collaborative governance members as compared to nonmembers. Conclusions: Findings suggest that membership on a collaborative governance committee increased staff sense of empowerment and fostered self-growth and organizational development. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Erickson, JI (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 230B, Boston, MA 02114 USA. NR 28 TC 20 Z9 20 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD FEB PY 2003 VL 33 IS 2 BP 96 EP 104 DI 10.1097/00005110-200302000-00006 PG 9 WC Nursing SC Nursing GA 651ZM UT WOS:000181354000006 PM 12584462 ER PT J AU Lee, BW London, L Paulauskis, J Myers, J Christiani, DC AF Lee, BW London, L Paulauskis, J Myers, J Christiani, DC TI Association between human paraoxonase gene polymorphism and chronic symptoms in pesticide-exposed workers SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SERUM PARAOXONASE; CHLORPYRIFOS-OXON; ORGANOPHOSPHATE; ARYLESTERASE; DNA AB Pesticides, such as parathion, are metabolized by cytochrome p-450 system to paraoxon, which is a potent cholinesterase inhibitor. Paraoxonase (PON) catalyzes the hydrolysis of these toxic metabolites and protects against pesticide toxicity. A glutamine/arginine (Gln/Arg) polymorphism at amino acid position 192 of PON has been described. The Arg/Arg genotype is associated with higher serum paraoxonase activity compared to Gln/Gln. The Arg/Gln genotype is associated with intermediate serum PON activity. The potential association between PON genotype and symptoms of chronic pesticide toxicity was examined among 100 farm workers. As part of a cross-sectional study of pesticide toxicity among mixed-race farm workers in the Western Cape, South Africa, 100 farm workers were genotyped for polymorphism of the paraoxonase gene at amino acid position 192. Subjects with two or more of the following symptoms were considered to have evidence of chronic toxicity: abdominal pain, nausea, rhinorrhea, dizziness, headache, somnolence, fatigue, gait disturbance, limb numbness, paresthesias, limb pain, or limb weakness : In multivariable logistic regression analysis, the independent predictors of chronic toxicity were previous history of head trauma resulting in loss of consciousness (OR 2.8, 95% Cl = 1.7-6.7), having worked as a pesticide applicator (OR 5.4, 95% Cl = 3.2- 8.9), and having one of the two "slow metabolism" (Gln/Gln or Gln/Arg) genotypes (OR 2.9, 95% Cl = 1.7-6.9). Furthermore, the prevalence of chronic toxicity increased in a stepwise fashion from 15% among pesticide nonapplicators with a "fast metabolism" (Arg/Arg) genotype, to 42.9% among pesticide nonapplicators with "slow metabolism" (Gln/Gln or Gln/Arg) genotypes, to 58.8% among pesticide applicators with "fast metabolism" genotype, and 75.0% among pesticide applicators with "slow metabolism" genotypes (P = 0.001). Age, number of years on the job, smoking history, alcohol history, education level, plasma or red blood cell cholinesterase level, or previous history of acute organophosphate poisoning were not statistically significant predictors of chronic toxicity. The PON genotype is an important determinant of a farmworker's susceptibility to chronic pesticide poisoning. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Hosp Ctr, Pulm & Crit Care Sect, Washington, DC 20010 USA. George Washington Univ, Sch Med, Washington, DC USA. Univ Cape Town, Dept Social Med, ZA-7700 Rondebosch, South Africa. RP Harvard Univ, Sch Publ Hlth, Dept Occupat Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI London, Leslie/G-6061-2011 FU NIEHS NIH HHS [ES00002] NR 22 TC 40 Z9 40 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 2003 VL 45 IS 2 BP 118 EP 122 DI 10.1097/01.jom.0000052953.59271e1 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 645FP UT WOS:000180965800002 PM 12625227 ER PT J AU Casarett, DJ Crowley, R Hirschman, KB AF Casarett, DJ Crowley, R Hirschman, KB TI Surveys to assess satisfaction with end-of-life care: Does timing matter? SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE hospice; satisfaction; surveys; grief; bereavement; research ethics ID ACCURACY AB The goals of this study were to determine whether post-death surveys of family members cause more distress if they are administered closer in time to the patient's death, and whether family members are less likely to respond to earlier surveys. Caregivers of hospice patients were randomly assigned to receive a survey at 2 weeks (n = 107) or at 6 weeks (n = 100) after the patient's death. Response rates and self-reported distress experienced in completing the survey were recorded. There were no differences in self-ratings of distress between 2- and 6-week surveys, and response rates were identical (2-week: 54 %; 6-week: 54 %). Distress and response rate do not appear to be influenced by the timing of data collection, even when surveys are administered very soon after death. J Pain Symptom Manage 2003;25:128-132. (C) 2003 U.S.Cancer Pain. Relief Committee. Published by Elsevier Allrights reserved. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Div Geriatr, Philadelphia, PA USA. Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), Inst Aging, 3615 St, Philadelphia, PA 19104 USA. NR 17 TC 31 Z9 31 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 2003 VL 25 IS 2 BP 128 EP 132 AR PII S0885-3924(02)00636-X DI 10.1016/S0885-3924(02)00636-X PG 5 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 649QW UT WOS:000181220300007 PM 12590028 ER PT J AU Kohler, T McCormick, BA Walker, WA AF Kohler, T McCormick, BA Walker, WA TI Bacterial-enterocyte crosstalk: Cellular mechanisms in health and disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review ID ENTEROPATHOGENIC ESCHERICHIA-COLI; MICROBIAL-MUCOSAL INTERACTIONS; INTESTINAL EPITHELIAL-CELLS; INVASIVE SHIGELLA-FLEXNERI; NUCLEOTIDE EXCHANGE FACTOR; PROTEIN SECRETION SYSTEM; INNATE IMMUNE-RESPONSE; TOLL-LIKE RECEPTORS; NF-KAPPA-B; SALMONELLA-TYPHIMURIUM C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Childrens Hosp, Dept Metab Dis Gastroenterol & Nutr, Dusseldorf, Germany. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. NR 105 TC 4 Z9 6 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD FEB PY 2003 VL 36 IS 2 BP 175 EP 185 PG 11 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 642BJ UT WOS:000180783800005 ER PT J AU Inagaki, K Krall, EA Fleet, JC Garcia, RI AF Inagaki, K Krall, EA Fleet, JC Garcia, RI TI Vitamin D receptor alleles, periodontal disease progression, and tooth loss in the VA dental longitudinal study SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE disease progression; longitudinal studies; periodontal; diseases; polymorphism; genetic; receptors; vitamin D; risk factors ID BONE-MINERAL DENSITY; INTERLEUKIN-1 GENE POLYMORPHISMS; POSTMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR; LUMBAR-SPINE; ASSOCIATION; POPULATION; TURNOVER; MASS; MEN AB Background: The relationship between the vitamin D receptor (VDR) genotype and periodontal disease is not known. This study compared periodontal disease progression among poly-morphisms of 2 VDR genes in men in the VA Dental Longitudinal Study. Methods: Subjects were 125 medically healthy, middle-aged men who had serial oral examinations over a mean 23-year period. Probing depth, gingival bleeding on probing, clinical attachment loss (CAL), and alveolar bone loss (ABL) from radiographs were measured at each examination. Progression of periodontal disease was defined as the percentage of teeth per decade that increased ABL by greater than or equal to40%, and the percentage of teeth per decade that developed CAL greater than or equal to5 mm. Apal and Taql polymorphisms were determined from buffy coat cells following polymerase chain reaction (PCR) amplification. Mean changes in oral status were adjusted for baseline values of smoking status, number of teeth present, and periodontal status by analysis of covariance. Results: Genotype distributions were 41 AA, 58 Aa, 26 aa; and 53 TT, 46 Tt, 26 tt. The AA genotype showed the highest rates of progression of ABL (5 +/- 1% versus 1 +/- 1% and 2 +/- 1% teeth in Aa and aa, respectively; P = 0.03), CAL (37 +/- 4% versus 17 +/- 4% and 27 +/- 6% teeth; P = 0.004), and tooth loss (2 +/- 0.3 versus 1 +/- 0.3 and 1 +/- 0.4 teeth; P= 0.04). When genotype combinations were examined, progression of ABL, CAL, and tooth loss was highest in the AATT and AATt genotypes. Conclusions: The Apal polymorphism of the VDR gene is associated with oral bone loss, clinical attachment loss, and tooth loss in older men. Analysis of the VDR alleles may prove useful for predicting periodontal disease. C1 Aichi Gakuin Univ, Sch Dent, Dept Periodontol, Chikusa Ku, Nagoya, Aichi 4648651, Japan. Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Inagaki, K (reprint author), Aichi Gakuin Univ, Sch Dent, Dept Periodontol, Chikusa Ku, 2-11 Suemoridori, Nagoya, Aichi 4648651, Japan. FU NIDCR NIH HHS [K24 DE00419, R03 DE12027]; NIDDK NIH HHS [R01 DK054111, R01 DK054111-07] NR 28 TC 28 Z9 29 U1 0 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD FEB PY 2003 VL 74 IS 2 BP 161 EP 167 DI 10.1902/jop.2003.74.2.161 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 754JZ UT WOS:000187314200003 PM 12666703 ER PT J AU Blais, MA Peterson, CA AF Blais, MA Peterson, CA TI Introduction to the book, software, and test reviews section SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 11, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 2003 VL 80 IS 1 BP 7 EP 7 DI 10.1207/S15327752JPA8001_04 PG 1 WC Psychology, Clinical; Psychology, Social SC Psychology GA 655NX UT WOS:000181559900004 ER PT J AU Mytilineou, C Walker, RH Jnobaptiste, R Olanow, CW AF Mytilineou, C Walker, RH Jnobaptiste, R Olanow, CW TI Levodopa is toxic to dopamine neurons in an in vitro but not an in vivo model of oxidative stress SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PARKINSONS-DISEASE; MESENCEPHALIC CULTURES; NIGROSTRIATAL LESIONS; ASCORBIC-ACID; RAT-BRAIN; GLUTATHIONE; CELLS; MECHANISMS; 6-HYDROXYDOPAMINE; CATECHOLAMINES AB Levodopa is the "gold standard" for the symptomatic treatment of Parkinson's disease (PD). There is a theoretical concern, however, that levodopa might accelerate the rate of nigral degeneration, because it undergoes oxidative metabolism and is toxic to cultured dopaminergic neurons. Most in vivo studies do not show evidence of levodopa toxicity; levodopa is not toxic to normal rodents, nonhuman primates, or humans and is not toxic to dopamine neurons in dopamine-lesioned rodents or nonhuman primates in most studies. However, the potential for levodopa to be toxic in vivo has not been tested under conditions of oxidative stress such as exist in PD. To assess whether levodopa is toxic under these circumstances, we have examined the effects of levodopa on dopamine neurons in mesencephalic cultures and rat pups in which glutathione synthesis has been inhibited by L-buthionine sulfoximine. Levodopa toxicity to cultured dopaminergic neurons was enhanced by glutathione depletion and diminished by antioxidants. In contrast, treatment of neonatal rats with levodopa, administered either alone or in combination with glutathione depletion, did not cause damage to the dopamine neurons of the substantia nigra or changes in striatal levels of dopamine and its metabolites. This study provides further evidence to support the notion that although levodopa can be toxic to dopamine neurons in vitro, it is not likely to be toxic to dopamine neurons in vivo and specifically in conditions such as PD. C1 Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. RP Olanow, CW (reprint author), Mt Sinai Sch Med, Dept Neurol, Box 1137, New York, NY 10029 USA. EM warren.olanow@mssm.edu NR 41 TC 65 Z9 72 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 2003 VL 304 IS 2 BP 792 EP 800 DI 10.1124/jpet.102.042267 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 637RL UT WOS:000180526600038 PM 12538835 ER PT J AU Fraser, PA Ding, WZ Mohseni, M Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Cooper, GS AF Fraser, PA Ding, WZ Mohseni, M Treadwell, EL Dooley, MA St Clair, EW Gilkeson, GS Cooper, GS TI Glutathione S-Transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: A possible gene-environment interaction for autoimmunity SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; glutathione S-transferase; metabolism; ultraviolet radiation ID CULTURED HUMAN-LYMPHOCYTES; INDUCED DNA-DAMAGE; REVISED CRITERIA; IN-VITRO; T-CELLS; POLYMORPHISMS; CANCER; UV; P1; CLASSIFICATION AB Objective. Multiple genetic factors modulate predisposition to systemic lupus erythematosus (SLE). The glutathione S-transferase (GST) genes GSTM1, GSTT1, and GSTP1 catalyze metabolic pathways for the excretion of reactive oxygen species that may be generated by cellular oxidative stress induced by ultraviolet radiation in sunlight. We hypothesized that risk of SLE associated with occupational sun exposure is modulated by GSTM1, GSTT1, and GSTP1 genotypes. Methods. DNA samples and occupational history were collected from 243 cases and 298 controls in the Carolina Lupus Study, a population based case-control study of patients with recently diagnosed SLE. Results. There was no independent association between SLE and presence of the homozygous null GSTM1 or GSTT1 genotype, the homozygous Val/Val or heterozygous Val/Ile GSTP1 genotype, or occupational sunlight exposure. The prevalence of Ro autoantibodies was significantly increased among Caucasians with the GSTM1 null genotype (OR 2.6, 95% CI 1.0, 6.8), but was somewhat weaker among African-Americans (OR 1.5, 95% CI 0.7, 3.5). In the combined analysis of occupational sunlight exposure and GSTM1 genotype, the effect of sun exposure among Caucasians varied depending on GSTM1 genotype. There was a 3-fold increased risk (OR 3.1, 95% CI 0.9, 10.8) of SLE associated with 24 or more months' occupational sun exposure among Caucasians with the GSTM1 null genotype, but sun exposure was not associated with risk among GSTM1 positive Caucasians (OR 0.6, 95% CI 0.3, 1.5). The interaction was statistically significant (p = 0.028). Conclusion. Our results suggest that GSTM1 homozygous null genotype may modify the effect of occupational sun exposure on the risk of SLE in caucasians. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Univ N Carolina, Div Rheumatol, Chapel Hill, NC USA. Duke Univ, Med Ctr, Div Rheumatol Allergy & Clin Immunol, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. NIEHS, Epidemiol Branch, Durham, NC USA. RP Fraser, PA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES10295] NR 37 TC 31 Z9 32 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD FEB PY 2003 VL 30 IS 2 BP 276 EP 282 PG 7 WC Rheumatology SC Rheumatology GA 640VY UT WOS:000180709700012 PM 12563680 ER PT J AU Madibally, SV Solomon, V Mitchell, RN Van De Water, L Yarmush, ML Toner, M AF Madibally, SV Solomon, V Mitchell, RN Van De Water, L Yarmush, ML Toner, M TI Influence of insulin therapy on burn wound healing in rats SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE burn injury; wound healing; insulin; polarization microscopy; muscle wasting ID MUSCLE PROTEIN BREAKDOWN; SKELETAL-MUSCLE; CYTOKINE PRODUCTION; INJURED RATS; SKIN; HYPERGLYCEMIA; OXANDROLONE; EXPRESSION; METABOLISM; INFUSION AB Background. Insulin is proposed as a therapy for suppressing muscle wasting after burn trauma although the long-term effects of this therapy on wound healing are not yet known. The present study was designed to investigate the effect of systemically administered insulin therapy on burn wound healing. Materials and methods. Young rats weighing 80-150 g were subjected to 15-20% total body surface area burn injury on their shaved dorsum. The insulin dosage was increased over the first 3 days in each rat from 0.25 U (Day 1), 0.5 U (Day 2), and 1.0 U (Day 3) per 100 g body wt. The rats were euthanized at the fourth or fifteenth day postinjury. Skin sections were analyzed by histochemistry and quantitative polarization microscopy. Results. Histology showed a decreased number of inflammatory cells and increased vasodilation in the insulin-treated animals at Day 4 relative to untreated rats; at Day 15 there was increased reepithelialization. Quantitative analysis using polarization microscopy and picrosirius red staining showed an increased collagen deposition in wounds by Day 4 in insulin-treated rats relative to untreated burn controls. Conclusion. These results indicate that insulin induces accelerated wound healing associated with diminished inflammation and increased collagen deposition. (C) 2003 Elsevier Science (USA). C1 Shriners Burns Hosp, Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol, Boston, MA 02115 USA. RP Toner, M (reprint author), Shriners Burns Hosp, Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org RI Xia, Xianfeng/F-9169-2011; Madihally, Sundararajan/D-9285-2012 OI Madihally, Sundararajan/0000-0001-7498-5760 FU NIGMS NIH HHS [R01 GM056442] NR 35 TC 36 Z9 50 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD FEB PY 2003 VL 109 IS 2 BP 92 EP 100 DI 10.1006/jsre.2003.6564 PG 9 WC Surgery SC Surgery GA 658CA UT WOS:000181703000004 PM 12643849 ER PT J AU Livingston, EH Liu, CY Glantz, G Li, ZP AF Livingston, EH Liu, CY Glantz, G Li, ZP TI Characteristics of bariatric surgery in an integrated VA health care system: Follow-up and outcomes SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID SURGICAL VOLUME; MORTALITY; OPERATIONS AB Background. Since the 1991 NIH consensus conference, obesity surgery has been increasingly accepted as a form of therapy for morbid obesity. Approximately 40% of Veteran patients are obese and would potentially benefit from the operations. Methods. Records were reviewed for all obesity operations performed at the Veterans Administration Greater Los Angeles Health Care System between January 1997 and April 2002. Morbidity, mortality, weight loss, and extent of follow-up were the outcomes measures assessed. Results. Forty-six [11 Female (24%), 35 Male (76%)] patients underwent Roux-Y gastric bypass during the 63-month period we reviewed. There was one death from pulmonary hypertension unexpectedly encountered in the operating room. There was a single major complication: an anastomotic leak successfully treated with intravenous antibiotics. The Computerized Patient Record System contained extensive weight loss information, with dozens of weight measurements for these patients before and after surgery. Weight loss was sustained in all but 2 patients during the follow-up period. The only patients lost to follow-up were those referred from medical centers outside the boundaries of our integrated health care system. Conclusion. (1) The VA population has the opposite male/female ratio of populations reported in most weight loss studies. Because the health risks attributable to obesity are greater in males, the VA represents an important population to study that may benefit significantly from weight loss surgery. (2) Extensive clinical information available in the computerized medical record combined with frequent accession of health care resources by our patients resulted in a database rich in follow-up data for a population where long-term outcomes are traditionally difficult to obtain. (3) There was very low surgical morbidity and mortality in a high-risk population. This contrasts with the results of most volume-outcome studies and occurred in a low-volume hospital by a high-volume surgical and medical team. (4) Distinct patterns of weight loss were observed. (C) 2003 Elsevier Science (USA). C1 Univ Calif Los Angeles, Sch Med, Bariatr Surg Program, Los Angeles, CA 90073 USA. Greater Los Angeles VA Hlth Care Syst, Surg & Res Serv, Los Angeles, CA 90073 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 11 TC 16 Z9 16 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 FEB PY 2003 VL 109 IS 2 BP 138 EP 143 DI 10.1006/jsre.2003.6589 PG 6 WC Surgery SC Surgery GA 658CA UT WOS:000181703000010 PM 12643855 ER PT J AU Da Silva, MS Sobel, M AF Da Silva, MS Sobel, M CA Surg S Assoc Vasc Surg TI Popliteal vascular injury during total knee arthroplasty SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE popliteal vascular injury; total knee arthroplasty; etiology; management; outcome ID ARTERIAL COMPLICATIONS; REPLACEMENT AB Background. Popliteal vascular injury during total knee arthroplasty (TKA) is rare. Although the etiology, management, and outcome of this injury have not been systematically studied, several anecdotal reviews and small case series have suggested a high morbidity, with tourniquet injury as a predominant etiology. Methods. We surveyed 190 members of a major regional vascular society concerning their experiences with popliteal vascular injuries sustained during TKA, specifically regarding the presentation, mechanisms of injury, diagnostic studies, surgical exposure and methods of repair, and outcomes. Results. Thirteen surgeons provided data (6.8% response rate) on 19 patients with TKA-related popliteal artery injuries. In contrast to the historical literature, sharp, direct trauma was the predominant etiology of vascular injury. Vascular reconstructive techniques varied, with arterial bypass being the most common. There was no mortality in this series. Eighty-four percent (16/19) of the patients had full recoveries. Limb loss occurred in 2 of the 19 patients (10.5%). Conclusion. Popliteal vascular injuries during TKA are primarily the result of direct trauma to the vessel. Prompt diagnosis, extensile vascular exposure through a medial knee surgical incision, and standard reconstructive techniques offer a good prognosis for this limb-threatening complication. (C) 2003 Elsevier Science (USA). C1 SUNY Upstate Med Univ, Dept Surg, Syracuse, NY 13210 USA. Vet Affairs Med Ctr, Syracuse, NY 13210 USA. Univ Washington, Sch Med, Dept Surg, Div Vasc Surg, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. RP Da Silva, MS (reprint author), SUNY Upstate Med Univ, Dept Surg, 750 E Adams St, Syracuse, NY 13210 USA. EM dasilvam@upstate.edu OI Hertzer, Norman/0000-0002-9698-1776 NR 13 TC 17 Z9 17 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 FEB PY 2003 VL 109 IS 2 BP 170 EP 174 DI 10.1006/jsre.2003.6592 PG 5 WC Surgery SC Surgery GA 658CA UT WOS:000181703000015 PM 12643860 ER PT J AU Monshizadeh, R Cohen, L Golkar, L Rubin, PAD AF Monshizadeh, R Cohen, L Golkar, L Rubin, PAD TI Perforating follicular hybrid cyst of the tarsus SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PILOMATRICOMA AB Follicular hybrid cysts are cutaneous tumours that arise from different portions of the hair follicle. We describe a follicular hybrid cyst of the tarsus that contained features of pilomatricoma and steatocystoma and perforated the palpebral conjunctiva. The unusual location and histopathologic features are discussed. C1 Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Div Dermatol, Gainesville, FL 32610 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cambridge, MA 02138 USA. RP Monshizadeh, R (reprint author), Univ Florida, Coll Med, Dept Ophthalmol, POB 100284, Gainesville, FL 32610 USA. NR 6 TC 9 Z9 9 U1 0 U2 0 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 FEB PY 2003 VL 48 IS 2 SU S BP S33 EP S34 DI 10.1067/mjd.2003.124 PG 2 WC Dermatology SC Dermatology GA 648TP UT WOS:000181166900013 PM 12582382 ER PT J AU Chen, C Botelho, C Cooper, A Hibberd, P Parsons, SK AF Chen, C Botelho, C Cooper, A Hibberd, P Parsons, SK TI Current practice patterns in the treatment of perforated appendicitis in children SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID COMPLICATED APPENDICITIS; MANAGEMENT AB BACKGROUND: The treatment of perforated appendicitis in children often involves a combination of surgical and medical therapy. The aim of this study was to document the degree of consensus in the current management of perforated appendicitis in children. STUDY DESIGN: A survey was sent to all practicing pediatric surgeons in North America in April 2000 who were members of the American Pediatric Surgical Association for 1999-2000. Survey questions pertained to preoperative, perioperative, and postoperative practice patterns, particularly those issues related to use of antibiotic therapy. RESULTS: Among eligible surgeons, 80.2% completed the survey. Although more than 80% of respondents practiced in an academic setting, only 17% of surgeons used a formal clinical practice guideline to direct care. Responses varied substantially in the duration of postoperative antibiotic therapy, the use of intravenous or oral agents or both, and the duration of hospitalization. A considerable number of patients are receiving a portion of their intravenous antibiotic therapy as outpatients. CONCLUSIONS: There is little apparent consensus in the,many aspects of perioperative and postoperative care of perforated appendicitis in children across North America. Only a fraction of surgeons currently uses a formal clinical practice guideline for treatment of perforated appendicitis, although increased pressures to develop more cost-effective therapeutic strategies can encourage development of additional guidelines. Definitive evidence to inform development of such guidelines and enhance consensus is lacking. Further studies are needed across institutions to better inform clinical decisions in light of a changing practice environment and treatment alternatives. (J Am Coll Surg 2003; 196:212-221. (C) 2003 by the American College of Surgeons). C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Clin Res Core Program Off, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Sch Med, Clin Res Inst, Boston, MA 02111 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Chen, C (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. RI Cooper, Andrew/C-1655-2010 OI Cooper, Andrew/0000-0001-6027-8272 NR 16 TC 70 Z9 71 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 2003 VL 196 IS 2 BP 212 EP 221 DI 10.1016/S1072-7515(02)01666-6 PG 10 WC Surgery SC Surgery GA 646LN UT WOS:000181036700008 PM 12595049 ER PT J AU Tavares, M Stultz, J Newman, M Smith, V Kent, R Carpino, E Goodson, JM AF Tavares, M Stultz, J Newman, M Smith, V Kent, R Carpino, E Goodson, JM TI Light augments tooth whitening with peroxide SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB Background. The authors tested the adjunctive use of light with a 15 percent peroxide gel as a single-visit, in-office tooth whitening system. Methods. Subjects (N = 87) with stained (> shade D4, Vita Zahn-fabrik, Bad Sackingen, Germany) anterior teeth were randomly assigned to test (peroxide and light), peroxide control (peroxide gel) or light control (placebo gel and light) groups and were tested for one hour. The researchers evaluated tooth shade, color and subject response at baseline and post-treatment and at three and six months posttreatment. Results. The initial shade unit reduction, of combined light and peroxide treatment (8.4) was greatest compared with that of peroxide alone (5.9) and of light alone (4.9). Approximately 88 percent of these effects persisted for six months. Lightness was increased and yellowness decreased to a significantly greater extent in the test group than in either control. These findings were corroborated by subject evaluation. One week after treatment, moderate to greatly increased tooth sensitivity occurred in 20 percent of test subjects, 21.7 percent of peroxide control subjects and non of the light control subjects. Neither tooth sensitivity nor gingival redness was present at the three- and six-month visits. Conclusions. Peroxide and light treatment significantly lightened the color of teeth to a greater extent than did peroxide or light alone, with a low and transient incidence of tooth sensitivity. Clinical Implications. Light can increase the tooth-whitening effect of peroxide, thereby increasing the effectiveness of tooth-whitening procedures. C1 Forsyth Inst, Boston, MA 02115 USA. RP Goodson, JM (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. NR 26 TC 57 Z9 64 U1 0 U2 2 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 FEB PY 2003 VL 134 IS 2 BP 167 EP 175 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 647NX UT WOS:000181100700012 PM 12636120 ER PT J AU Kassab, MM Cohen, RE AF Kassab, MM Cohen, RE TI The etiology and prevalence of gingival recession SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID GUIDED TISSUE REGENERATION; PERIODONTAL-DISEASE; NATURAL-HISTORY; AGE; TOOTHBRUSH; MEMBRANE; INCISORS; MONKEYS; ADULTS; GRAFT AB Background. Gingival recession in its localized or generalized form is an undesirable condition resulting in root exposure. The result often is not esthetic and may lead to sensitivity and root caries. Exposed root surfaces also are prone to abrasion. The purpose of this article is to describe the prevalence, etiology and factors associated with gingival recession. Types of Studies Reviewed. The authors reviewed cross-sectional epidemiologic studies of gingival recession and found that they correlated the prevalence of recession to trauma, sex, malpositioned teeth, inflammation and tobacco consumption. The recent surveys they reviewed revealed that 88 percent of people 65 years of age and older and 50 percent of people 18 to 64 years of age have one or more sites with recession. The presence and extent of gingival recession also increased with age. Results. More than 50 percent of the population has one or more sites with gingival recession was found in patients with both good and poor oral hygiene. It has been proposed that recession is multifactorial, with one type being associated with anatomical factors and another type with physiological or pathological factors. Recession has been found more frequently on buccal surfaces than on other aspects of the teeth. Clinical Implications. Dentists should be knowledgeable ab out the etiology, prevalence and associating factors of gingival recession, as well as treatment options, so that appropriate treatment modalities can be offered to patients. Treatments for gingival recession include gingival grafting, guided tissue regeneration and orthodontic therapy. Such treatments typically result in esthetic improvement, elimination of sensitivity and a decreased risk of developing root caries. C1 Forsyth Inst, Boston, MA 02115 USA. SUNY Buffalo, Dept Periodont & Endodont, Sch Dent Med, Buffalo, NY 14260 USA. RP Kassab, MM (reprint author), Forsyth Inst, 140 The Fenway, Boston, MA 02115 USA. RI Frade, Viviane/B-8653-2012 NR 44 TC 100 Z9 115 U1 1 U2 17 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 FEB PY 2003 VL 134 IS 2 BP 220 EP 225 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 647NX UT WOS:000181100700019 PM 12636127 ER PT J AU Alessi, CA Josephson, KR Harker, JO Pietruszka, FM Hoyl, MT Rubenstein, LZ AF Alessi, CA Josephson, KR Harker, JO Pietruszka, FM Hoyl, MT Rubenstein, LZ TI The yield, reliability, and validity of a postal survey for screening community-dwelling older people SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatric assessment; postal survey; screening ID RANDOMIZED CLINICAL-TRIAL; FUNCTIONAL DECLINE; ELDERLY PEOPLE; COGNITIVE IMPAIRMENT; URINARY-INCONTINENCE; GERIATRIC EVALUATION; PREDICTIVE-VALIDITY; GENERAL-PRACTICE; PRIMARY-CARE; QUESTIONNAIRE AB OBJECTIVES: To assess the yield, reliability, and validity of a postal survey developed to identify older persons in need of outpatient geriatric assessment and follow-up services. DESIGN: A longitudinal cohort study. SETTING: Outpatient primary care clinic at a Department of Veterans Affairs teaching ambulatory care center. PARTICIPANTS: Patients (N = 2,382) aged 65 and older who returned a Geriatric Postal Screening Survey (GPSS) that screened for common geriatric conditions (depression, cognitive impairment, urinary incontinence, falls, and functional status impairment). Validity and reliability testing was performed with subsamples of patients classified as high or lower risk based on responses to the GPSS. MEASUREMENTS: Test-retest reliability was measured by percentage agreement and kappa statistic. The diagnostic validity of the 10-item GPSS was tested by comparing single GPSS items to standardized geriatric assessment instruments for depression, mental status and functional status, as well as direct questions regarding falls, urinary incontinence, and use of medications. Validity was also tested against clinician evaluation of the specific geriatric conditions. Predictive validity was tested by comparing GPSS score with 1-year follow-up data on functional status, survival, and healthcare use. RESULTS: Respondents identified as high risk by the GPSS had scores that indicated significantly greater impairment on structured assessment instruments than those identified as lower risk by GPSS. The overall mean percentage agreement between the test and retest surveys was 88.3%, with a mean weighted kappa of 0.70. In comparison with a structured telephone interview and with a clinical assessment, individual items of the GPSS showed good accuracy (range 0.71-0.78) for identifying symptoms of depression, falls, and urinary incontinence. Over a 1-year follow-up period, the GPSS-identified high-risk group had significantly (P < .05) more hospital admissions, hospital days and nursing home admissions than the lower-risk group. CONCLUSION: A brief postal screening survey can successfully target patients for geriatric assessment services. In screening for symptoms of common geriatric conditions, the GPSS identified a subgroup of older outpatients with multiple geriatric syndromes who were at increased risk for hospital use and nursing home admission and who could potentially benefit from geriatric intervention. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Pontificia Univ Catolica Chile, Santiago, Chile. RP Alessi, CA (reprint author), VA Sepulveda Ambulatory Care Ctr, GRECC, 11E,16111 Plummer St, Sepulveda, CA 91343 USA. EM Cathy.Alessi@med.va.gov NR 33 TC 20 Z9 20 U1 1 U2 7 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 FEB PY 2003 VL 51 IS 2 BP 194 EP 202 DI 10.1046/j.1532-5415.2003.51058.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 639AL UT WOS:000180605400008 PM 12558716 ER PT J AU Carnes, M Howell, T Rosenberg, M Francis, J Hildebrand, C Knuppel, J AF Carnes, M Howell, T Rosenberg, M Francis, J Hildebrand, C Knuppel, J TI Physicians vary in approaches to the clinical management of delirium SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE benzodiazepine; delirium; haloperidol; hip fracture; restraint ID HOSPITALIZED OLDER PATIENTS; DOUBLE-BLIND; PSYCHOGERIATRIC PATIENTS; OPTIMIZING MANAGEMENT; ELDERLY PATIENTS; AIDS PATIENTS; HIP FRACTURE; HALOPERIDOL; CONFUSION; OUTCOMES AB OBJECTIVES: To ascertain the variation in strategies for managing delirium of physicians with expertise in geriatrics. DESIGN: Cross-sectional mail survey. SETTING: United States. PARTICIPANTS: A probability sample of physician members of the American Geriatrics Society. MEASUREMENTS: Management choices presented in a two-part case vignette of an older woman hospitalized with a hip fracture who develops mild and then severe delirium. RESULTS: One hundred twenty-two respondents (43%) selected the three answers constituting current "best practice," 50 (18%) selected an unnecessary diagnostic test (brain imaging, lumbar puncture, or electroencephalogram), and 47 (17%) selected unnecessary pharmacologic therapy for mild delirium. For severe delirium, 270 (96%) selected pharmacological therapy, of whom 180 chose haloperidol alone, 55 chose lorazepam alone, 23 chose lorazepam in combination with haloperidol, and 12 wrote in another drug. Thirty percent of the respondents made any selection of lorazepam, alone or in combination with haloperidol, for mild or severe delirium. Sixty-one percent of those selecting haloperidol for severe delirium chose a dose greater than that recommended for geriatric patients. Sex, date of graduation from medical school, clinical specialty, completion of a geriatric fellowship, or certification in geriatrics had no significant effect on responses. CONCLUSIONS: The common selection of lorazepam to treat delirium is troubling because benzodiazepines themselves are implicated in delirium. Selection of an initial dose of haloperidol higher than that recommended for geriatric patients by more than half of the respondents is also of concern. There is a paucity of sound clinical evidence to guide the choice of pharmacological agents for treating delirium in older hospitalized patients. C1 Univ Wisconsin, Dept Med, Madison, WI 53715 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53715 USA. Univ Wisconsin, Dept Biostat, Madison, WI 53715 USA. Univ Wisconsin, Ctr Womens Hlth & Womens Hlth Res, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. St Vincent Hosp & Hlth Syst, Indianapolis, IN USA. RP Carnes, M (reprint author), Univ Wisconsin, Dept Med, Ctr Womens Hlth & Womens Hlth Res, Meriter Hosp, 202 S Pk St, Madison, WI 53715 USA. FU NIA NIH HHS [K07AG00744] NR 44 TC 32 Z9 32 U1 0 U2 1 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 FEB PY 2003 VL 51 IS 2 BP 234 EP 239 DI 10.1046/j.1532-5415.2003.51063.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 639AL UT WOS:000180605400013 PM 12558721 ER PT J AU Tan, EJ Lui, LY Eng, C Jha, AK Covinsky, KE AF Tan, EJ Lui, LY Eng, C Jha, AK Covinsky, KE TI Differences in mortality of black and white patients enrolled in the program of all-inclusive care for the elderly SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY, 2001 CL CHICAGO, ILLINOIS SP Amer Geriatr Soc DE blacks; frail older people; health services research; long-term care; whites ID CONGESTIVE-HEART-FAILURE; ACUTE MYOCARDIAL-INFARCTION; OF-VETERANS-AFFAIRS; RACIAL-DIFFERENCES; OLDER BLACKS; RACE; SURVIVAL; GENDER; HOSPITALIZATION; EPIDEMIOLOGY AB OBJECTIVES: To examine the relationship between race and mortality in frail community-dwelling older people with access to a program providing comprehensive access and coordination of services. DESIGN: A longitudinal cohort study. SETTING: Twelve nationwide demonstration sites of the Program of All-Inclusive Care for the Elderly (PACE) from 1990 to 1996. PACE provides comprehensive medical and long-term care services for nursing home-eligible older people who live in the community. PARTICIPANTS: Two thousand two white patients and 859 black patients. MEASUREMENTS: Patients were followed after enrollment until death or the end of the follow-up period. Time from enrollment to death was measured with adjustment of the Cox proportional hazards model for comorbid conditions, functional status, site, and other demographic characteristics. RESULTS: Black patients were younger than white patients (mean age 77 vs 80, P < .001) but had worse functional status (mean activity of daily living (ADL) score 6.5 vs 7.2, P < .001) on enrollment. Survival for black and white patients was 88% and 86% at 1 year, 67% and 61% at 3 years, and 51% and 42% at 5 years, respectively (unadjusted hazard ratio (HR) for black patients = 0.77; 95% confidence interval (CI) = 0.67-0.89). After adjustment for baseline comorbid conditions, functional status, site, and demographic characteristics, black patients still had a lower mortality rate (HR = 0.77; 95% CI = .65-0.93). The survival advantage for black patients did not emerge until about 1 year after PACE enrollment (HR for first year after enrollment = 0.97; 95% CI = 0.72-1.31; HR after first year = 0.67; 95% CI = 0.54-0.85, P -value for time interaction < .001). During the first year of enrollment, black patients were more likely to improve and less likely to decline in ADL function than white patients (P < .001). CONCLUSION: In PACE, a system providing access to and coordination of comprehensive medical and long-term care services for frail older people, black patients have a lower mortality rate than white patients. This survival advantage, which emerges approximately 1 year after PACE enrollment, may be related to the comprehensive access and coordination of services provided by the PACE program. C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. VA Natl Qual Scholars Program, San Francisco, CA USA. On Lok Senior Hlth Serv, San Francisco, CA USA. RP Tan, EJ (reprint author), San Francisco Gen Hosp, 1001 Potrero Ave,5 H 22, San Francisco, CA 94110 USA. FU AHRQ HHS [K02HS00006-01] NR 39 TC 11 Z9 11 U1 7 U2 9 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 FEB PY 2003 VL 51 IS 2 BP 246 EP 251 DI 10.1046/j.1532-5415.2003.51065.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 639AL UT WOS:000180605400015 PM 12558723 ER PT J AU Go, AS Reed, GL Hylek, EM Phillips, KA Liu, L Henault, LE Selby, JV Singer, DE AF Go, AS Reed, GL Hylek, EM Phillips, KA Liu, L Henault, LE Selby, JV Singer, DE TI Factor V Leiden and risk of ischemic stroke in nonvalvular atrial fibrillation: The anticoagulation and risk factors in atrial fibrillation (ATRIA) study SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE atrial fibrillation; stroke; genetics; anticoagulants ID COAGULATION-FACTOR-V; ACTIVATED PROTEIN-C; SYSTEMIC EMBOLISM; MUTATION; PREVENTION; RESISTANCE; SCHEMES; GENE AB Background: Atrial fibrillation is a major cause of cardioembolic stroke. Since atrial and venous pressures are similar, genetic variants that promote venous thromboembolism may increase the risk of atrial thrombi and subsequent stroke in atrial fibrillation. Methods: We conducted a nested case-control study of the association between the presence of factor V Leiden polymorphism and incident ischemic stroke within a prospective cohort of 13,559 adult patients with diagnosed nonvalvular atrial fibrillation between July 1, 1996 and December 31, 1997. Incident cases with ischemic strokes were identified through August 31, 1999 and matching stroke-free controls were enrolled. Results: One hundred thirty-seven case patients with incident stroke and 214 controls were enrolled. Cases were older, more likely to be women, and more likely to have a prior stroke, heart failure, hypertension, diabetes, and coronary disease. The factor V Leiden polymorphism was present in 5.8% of cases and 3.7% of controls (P = 0.36). Among non-anticoagulated patients, 7/96 (7.3%) case patients and 3/81 (3.6%) control subjects were heterozygous for factor V Leiden (Odds Ratio 2.1 [95% CI: 0.5-8.4]). Adjustment for known stroke risk factors did not significantly change the observed association in non-anticoagulated patients (adjusted OR 1.9 [0.5-8.0]). Conclusions: Within a large nested case-control sample of patients with atrial fibrillation, factor V Leiden was not significantly associated with risk of stroke. However, given the suggestive nature of our findings, further study in even larger numbers of patients is needed to clarify the impact of factor V Leiden on stroke risk in atrial fibrillation. C1 Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Massachusetts Gen & Harvard Med Sch, Harvard Sch Publ Hlth, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Floor, Oakland, CA 94612 USA. FU NHLBI NIH HHS [R01 HL058496]; NIA NIH HHS [AG15487] NR 20 TC 17 Z9 19 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2003 VL 15 IS 1 BP 41 EP 46 DI 10.1023/A:1026192301848 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 732YH UT WOS:000185972800006 PM 14574075 ER PT J AU Wykrzykowska, JJ Kathiresan, S Jang, IK AF Wykrzykowska, JJ Kathiresan, S Jang, IK TI Clinician update: Direct thrombin inhibitors in acute coronary syndromes SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE direct thrombin inhibitors; hirudin; hirulog; argatroban ID ACUTE MYOCARDIAL-INFARCTION; HEPARIN-INDUCED THROMBOCYTOPENIA; GLYCOPROTEIN-IIB/IIIA BLOCKADE; RECOMBINANT HIRUDIN LEPIRUDIN; TISSUE-PLASMINOGEN ACTIVATOR; UNSTABLE ANGINA; RANDOMIZED-TRIAL; POSTINFARCTION ANGINA; EFEGATRAN SULFATE; ST-ELEVATION AB Antithrombotic therapy has become the cornerstone of the treatment for atherosclerotic cardiovascular disease. Unfractionated heparin (UFH) has been the thrombin inhibitor of choice for decades. UFH, however, has its deficiencies. To overcome these problems several direct thrombin inhibitors (DTIs) have been developed. These agents are capable of inactivating clot-bound thrombin more efficiently, and provide more predictable and safer anticoagulation in patients with of acute coronary syndromes (ACS). The initial studies of hirudin and bivalirudin in the clinical settings of acute myocardial infarction (AMI), unstable angina (UA) and percutaneous coronary interventions (PCI) conducted in the early 1990s proved to be disappointing. As the knowledge of more appropriate use of these drugs progressed, there is a renewed interest in DTIs. Herein we will review the clinical studies assessing hirudin, bivalirudin and argatroban in the settings of AMI, UA and PCI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Bigelow 800,55 Fruit St, Boston, MA 02114 USA. NR 47 TC 6 Z9 6 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2003 VL 15 IS 1 BP 47 EP 57 DI 10.1023/A:1026144518686 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 732YH UT WOS:000185972800007 PM 14574076 ER PT J AU Koenen, KC Goodwin, R Struening, E Hellman, F Guardino, M AF Koenen, KC Goodwin, R Struening, E Hellman, F Guardino, M TI Posttraumatic stress disorder and treatment seeking in a national screening sample SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE posttraumatic stress disorder; treatment seeking; comorbidity; anxiety disorders ID MENTAL-HEALTH-SERVICES; COMORBIDITY SURVEY; TRAUMATIC EVENTS; CARE UTILIZATION; UNITED-STATES; MEDICAL-CARE; COMMUNITY; FREQUENCY; ANXIETY; POPULATION AB The behavioral model of service use was employed to identify predictors of mental health treatment seeking and treatment readiness among individual with PTSD (N = 2,713) in data from the 1996 National Anxiety Disorders Screening Day (NADSD). This model examines the contribution of predisposing (age, sex, marital status, race/ethnicity, education), enabling (employment, geographic location), perceived need (interference of symptoms with daily life), and evaluated need (other diagnoses) factors to treatment seeking and treatment readiness for individuals with PTSD. Results indicate that although need factors (interference by anxiety symptoms with daily life, diagnosis of panic disorder) are related to both receiving and readiness for treatment, predisposing (age, marital status, minority race) factors influence which individuals receive treatment for PTSD. C1 Columbia Univ, Div Epidemiol, Joseph L Mailman Sch Publ Hlth, New York, NY USA. New York State Psychiat Inst & Hosp, Dept Epidemiol Mental Disorders, New York, NY 10032 USA. Freedom Fear, New York, NY USA. RP Koenen, KC (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B3, Natl Ctr PTSD, Boston, MA 02130 USA. RI Koenen, Karestan/K-5402-2014 OI Koenen, Karestan/0000-0003-3293-4281 FU NIMH NIH HHS [5T32MH13043] NR 46 TC 65 Z9 66 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2003 VL 16 IS 1 BP 5 EP 16 DI 10.1023/A:1022051009330 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 636JX UT WOS:000180453000002 PM 12602647 ER PT J AU Buckley, TC Galovski, T Blanchard, EB Hickling, EJ AF Buckley, TC Galovski, T Blanchard, EB Hickling, EJ TI Is the emotional Stroop paradigm sensitive to malingering? A between-groups study with professional actors and actual trauma survivors SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE malingering; Stroop; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT-RELATED PTSD; PSYCHOPHYSIOLOGICAL ASSESSMENT; RAPE VICTIMS; INFORMATION; THREAT; VETERANS; ANXIETY; SCALE AB Six professional actors, trained by psychologists and acting coaches to feign PTSD, were covertly enrolled into a treatment outcome study for PTSD with the aim of investigating malingering. During pretreatment assessment, individuals completed an emotional Stroop task. Vocal response latencies to different classes of stimuli were examined for sensitivity to malingering. Actor response latencies were compared to those of 6 nonlitigant PTSD patients and 6 nonanxiety controls. The actor/dissimulation group was able to feign an overall slowing of response latency across stimulus types, similar to the PTSD group. However, they were unable to modulate response latency as a function of stimulus content, a pattern that characterized the PTSD group. The use of information-processing paradigms to detect dissimulation is discussed. C1 VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, Boston, MA 02131 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. SUNY Albany, Ctr Stress & Anxiety Disorders, Albany, NY USA. RP Buckley, TC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02131 USA. FU NIMH NIH HHS [MH-48476] NR 38 TC 15 Z9 15 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2003 VL 16 IS 1 BP 59 EP 66 DI 10.1023/A:1022063412056 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 636JX UT WOS:000180453000008 PM 12602653 ER PT J AU Wagner, AW Roemer, L Orsillo, SM Litz, BT AF Wagner, AW Roemer, L Orsillo, SM Litz, BT TI Emotional experiencing in women with posttraumatic stress disorder: Congruence between facial expressivity and self-report SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT Annual Convention of the International-Society-for-Traumatic-Stress-Studies CY 1997 CL MONTREAL, CANADA SP International Soc Traumatic Stress Studies DE PTSD; facial expressivity; emotion; rape ID INDIVIDUAL-DIFFERENCES; EXPOSURE THERAPY; FEELINGS; BEHAVIOR; PTSD AB The congruence between facial expressivity and self-report of emotion was examined among 11 women with sexual assault-related PTSD and 8 women without PTSD, under both a neutral and a sexual assault prime condition. The PTSD group demonstrated some incongruities in emotional responding. Although the PTSD group was as facially expressive as the control group, they reported more arousal to the emotional stimuli. Further, an inverse relationship between negative facial expressivity and self-report to negative stimuli was found for some variables for the PTSD group only, such that the less expressions they showed facially, the more negative they reported feeling. However, the overall pattern of results suggests fewer significant relationships between expression and experience than predicted. C1 Boston VA Hlth Care Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. Boston VA Hlth Care Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. RP Wagner, AW (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Box 354694, Seattle, WA 98105 USA. OI Roemer, Lizabeth/0000-0002-2453-5435 NR 30 TC 19 Z9 19 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD FEB PY 2003 VL 16 IS 1 BP 67 EP 75 DI 10.1023/A:1022015528894 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 636JX UT WOS:000180453000009 PM 12602654 ER PT J AU Cheah, PY Liong, ML Yuen, KH Teh, CL Khor, T Yang, JR Yap, HW Krieger, JN AF Cheah, PY Liong, ML Yuen, KH Teh, CL Khor, T Yang, JR Yap, HW Krieger, JN TI Terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome: A randomized, placebo controlled trial SO JOURNAL OF UROLOGY LA English DT Article DE prostate; chronic disease; pelvic pain; prostatitis; drug therapy ID BLADDER OUTLET OBSTRUCTION; SYMPTOM INDEX; PROSTATODYNIA; MICTURITION; VALIDATION AB Purpose: We evaluate terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome. Materials and Methods: The study included 100, 20 to-50-year-old subjects who met the consensus criteria for chronic prostatitis/chronic pelvic pain syndrome and had not received previous alpha-blockers. Subjects were randomized to receive terazosin with dose escalation from I to 5 mg. daily or placebo for 14 weeks. The primary criterion for response was scoring 2 or less ("delighted-to-mostly satisfied") on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life item. The secondary criterion for response was greater than 50% reduction in NIH-CPSI pain score at 14 weeks. Other outcomes included total and NIH-CPSI domain scores, International Prostate Symptom Score, peak urinary flow rate, post-void residual urine and adverse effects. Results: Using the primary criterion 24 of 43 evaluable subjects (56%) responded in the terazosin group compared to 14 of 43 (36%) in the placebo group (p = 0.03). Using the secondary criterion 26 of 43 subjects (60%) responded in the terazosin group compared to 16 of 43 (37%) in the placebo group (p = 0.03). The terazosin group had greater reductions (p < 0.05) in NIH-CPSI total score, individual domain scores and International Prostate Symptom Score than the placebo group. There was no difference in peak urinary flow rate or post-void residual. In the terazosin group IS patients (42%) had side effects compared to 9 (21%) in the placebo group (p = 0.04). Conclusions: Terazosin proved superior to placebo for patients with chronic prostatitis/chronic pelvic pain syndrome who had not received a-blockers previously. C1 Univ Washington, Sch Med, Dept Urol Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Sci Malaysia, Sch Pharmaceut Sci, George Town, Malaysia. Lam Wah Ee Hosp, Dept Urol, George Town, Malaysia. Penang Adventist Hosp, Dept Urol, George Town, Malaysia. Penang Hosp, Dept Urol, George Town, Malaysia. Isl Hosp, Dept Urol, George Town, Malaysia. RP Krieger, JN (reprint author), Univ Washington, Sch Med, Dept Urol Surg, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Yuen, Kah Hay /F-9059-2010 NR 20 TC 78 Z9 97 U1 0 U2 6 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 FEB PY 2003 VL 169 IS 2 BP 592 EP 596 DI 10.1097/01.ju0000042927.45683.6c PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 636LY UT WOS:000180458500034 PM 12544314 ER PT J AU Clouse, WD Marone, LK Davison, JK Dorer, DJ Brewster, DC LaMuraglia, GM Cambria, RP AF Clouse, WD Marone, LK Davison, JK Dorer, DJ Brewster, DC LaMuraglia, GM Cambria, RP TI Late aortic and graft-related events after thoracoabdominal aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 09-11, 2002 CL BOSTON, MASSACHUSETTS SP Soc Vasc Surg ID LONG-TERM SURVIVAL; COMPLICATIONS; EXPERIENCE; DISSECTION; DISEASE AB Purpose: Unlike abdominal aortic aneurysm repair, little information exists regarding aortic-related morbidity (synchronous/metachronous aneurysm or graft-related complications) after thoracoabdominal aneurysm (TAA) repair. This study was performed to define such events and identify factors related to their development. Methods. Over a 15-year interval, 333 patients underwent TAA repair (type I, n = 90; 27%; type II, n = 59; 18%; type III, n = 118; 35%; and type IV, n = 66; 20%). Late aortic events were defined as aortic disease causing death or necessitating further intervention or graft-related complications (infection, pseudoaneurysm, branch occlusion) after hospital discharge. Variables were assessed for their association with aortic events with Cox proportional hazards regression. Results. In-hospital mortality occurred in 28 patients (8.4%), which left 305 available for follow-up (mean length of follow-up, 26 months; interquartile range, 2.7 to 38.4 months). After TAA repair, aneurysm remained in 60 patients (19.7%; ascending/arch, n = 41; 68.3%; discontinuous infrarenal, n = 12; 20%; contiguous descending, n = 7; 11.7%; contiguous abdominal, n 4; 6.7%). Events occurred in 33 individuals (10.8%) at 30 +/- 27 months after surgery. Twenty-four patients (73% of events; 7.9% of cohort) had aortic-related events, including another elective aneurysm repair (n = 16), urgent/emergent aneurysm operation (n = 5), acute dissection (n = 2), and atherothrombotic embolization (n = 1). Nine patients (27% of events; 2.9% of cohort) had graft-related incidents, including renovisceral occlusion (n = 5), visceral patch pseudoaneurysm (n = 2), graft infection (n = 2), and graft-esophageal fistula (n = 1). Variables independently predictive of events were female gender (odds ratio [OR], 2.3; P = .03), initial aneurysm rupture (OF, 4.8; P = .04), partial disease resection (OF, 4.2; P = .0008), and expansion of remaining aortic segments on imaging surveillance (OR, 2.5; P = .03). The event-free survival rates were 96% (95% CI, 93% to 98%) and 71% (95% CI, 60% to 83%) at I and 5 years. Conclusion: Late aortic events occur in at least 10% of patients after TAA repair and are usually the result of native aortic disease in remote (or noncontiguous) aortic segments. Graft-related complications, in particular, degeneration of inclusion anastamoses, are rare. Female gender, original presentation with rupture, and unresected disease identify those at highest risk. These findings verify the anatomic durability of TAA repair and suggest indefinite aortic surveillance is indicated for those at risk of events. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Aort Ctr, Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Aort Ctr, Anesthesia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Vasc Surg, Boston, MA USA. Harvard Univ, Sch Med, Div Vasc Anesthesia, Boston, MA USA. Harvard Univ, Sch Med, Thorac Aort Ctr, Surg Serv, Boston, MA USA. Harvard Univ, Sch Med, Thorac Aort Ctr, Anesthesia Serv, Boston, MA USA. Harvard Univ, Sch Med, Clin Res Ctr, Boston, MA USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 15 Parkman St WAC 458, Boston, MA 02114 USA. NR 32 TC 41 Z9 41 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD FEB PY 2003 VL 37 IS 2 BP 254 EP 260 DI 10.1067/mva.2003.62 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 643ZG UT WOS:000180893000002 PM 12563193 ER PT J AU Addo, MM Yu, XG Rathod, A Cohen, D Eldridge, RL Strick, D Johnston, MN Corcoran, C Wurcel, AG Fitzpatrick, CA Feeney, ME Rodriguez, WR Basgoz, N Draenert, R Stone, DR Brander, C Goulder, PJR Rosenberg, ES Altfeld, M Walker, BD AF Addo, MM Yu, XG Rathod, A Cohen, D Eldridge, RL Strick, D Johnston, MN Corcoran, C Wurcel, AG Fitzpatrick, CA Feeney, ME Rodriguez, WR Basgoz, N Draenert, R Stone, DR Brander, C Goulder, PJR Rosenberg, ES Altfeld, M Walker, BD TI Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHOCYTE RESPONSES; IMMUNE-RESPONSES; CD8(+) RESPONSES; INFECTION; VIREMIA; CTL; INDIVIDUALS; ESCAPE; AIDS; CD4(+) AB Cellular immune responses play a critical role in the control of human immunodeficiency virus type 1 (HIV-1); however, the breadth of these responses at the single-epitope level has not been comprehensively assessed. We therefore screened peripheral blood mononuclear cells (PBMC) from 57 individuals at different stages of HIV-1 infection for virus-specific T-cell responses using a matrix of 504 overlapping peptides spanning all expressed HIV-1 proteins in a gamma interferon-enzyme-linked immunospot (Elispot) assay. HIV-1-specific T-cell responses were detectable in all study subjects, with a median of 14 individual epitopic regions targeted per person (range, 2 to 42), and all 14 HIV-1 protein subunits were recognized. HIV-1 p24-Gag and Nef contained the highest epitope density and were also the most frequently recognized HIV-1 proteins. The total magnitude of the HIV-1-specific response ranged from 280 to 25,860 spot-forming cells (SFC)/10(6) PBMC (median, 4,245) among all study participants. However, the number of epitopic regions targeted, the protein subunits recognized, and the total magnitude of HIV-1-specific responses varied significantly among the tested individuals, with the strongest and broadest responses detectable in individuals with untreated chronic HIV-1 infection. Neither the breadth nor the magnitude of the total HIV-1-specific CD8(+)-T-cell responses correlated with plasma viral load. We conclude that a peptide matrix-based Elispot assay allows for rapid, sensitive, specific, and efficient assessment of cellular immune responses directed against the entire expressed HIV-1 genome. These data also suggest that the impact of T-cell responses on control of viral replication cannot be explained by the mere quantification of the magnitude and breadth of the CD8(+)-T-cell response, even if a comprehensive pan-genome screening approach is applied. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Fenway Community Hlth Ctr, Boston, MA USA. Lemuel Shattuck Hosp, Boston, MA USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford, England. RP Walker, BD (reprint author), MGH E, 149 13th St, Boston, MA 02129 USA. OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [R37 AI128568, P30 AI042851, P30AI42815, R01 AI030914, R01 AI044656, R01 AI050429, R01 AI30914, R01 AI44656, R01 AI50429] NR 51 TC 514 Z9 536 U1 3 U2 18 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 FEB PY 2003 VL 77 IS 3 BP 2081 EP 2092 DI 10.1128/JVI.77.3.2081-2092.2003 PG 12 WC Virology SC Virology GA 637AD UT WOS:000180488700045 PM 12525643 ER PT J AU Streblow, DN Kreklywich, C Yin, Q De La Melena, VT Corless, CL Smith, PA Brakebill, C Cook, JW Vink, C Bruggeman, CA Nelson, JA Orloff, SL AF Streblow, DN Kreklywich, C Yin, Q De La Melena, VT Corless, CL Smith, PA Brakebill, C Cook, JW Vink, C Bruggeman, CA Nelson, JA Orloff, SL TI Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants SO JOURNAL OF VIROLOGY LA English DT Article ID GRANULOCYTE-MACROPHAGE PROGENITORS; CARDIAC ALLOGRAFT VASCULOPATHY; ENDOTHELIAL-CELLS; VIRUS INFECTION; MARROW TRANSPLANTATION; AORTIC ALLOGRAFTS; DHPG PROPHYLAXIS; DIRECT INDUCTION; RECEPTOR CXCR3; CLASS-II AB Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression. C1 Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Gene Therapy Inst, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Univ Maastricht, Dept Microbiol, Maastricht, Netherlands. RP Orloff, SL (reprint author), Oregon Hlth Sci Univ, Dept Surg, Mc L590,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NHLBI NIH HHS [HL 65754, HL 66238-01, R01 HL066238, R01 HL065754]; NIAID NIH HHS [AI 21640, R01 AI021640] NR 57 TC 65 Z9 68 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 FEB PY 2003 VL 77 IS 3 BP 2182 EP 2194 DI 10.1128/JVI.77.3.2182-2194.2003 PG 13 WC Virology SC Virology GA 637AD UT WOS:000180488700055 PM 12525653 ER PT J AU Evans, DT Chen, LM Gillis, J Lin, KC Harty, B Mazzara, GP Donis, RO Mansfield, KG Lifson, JD Desrosiers, RC Galan, JE Johnson, PR AF Evans, DT Chen, LM Gillis, J Lin, KC Harty, B Mazzara, GP Donis, RO Mansfield, KG Lifson, JD Desrosiers, RC Galan, JE Johnson, PR TI Mucosal priming of simian immunodeficiency virus-specific cytotoxic T-lymphocyte responses in rhesus macaques by the Salmonella type III secretion antigen delivery system SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINE PROTECTION; SIV INFECTION; IN-VIVO; RECOMBINANT; AIDS; IMMUNIZATION; CELLS; TYPHIMURIUM; INDUCTION; CHALLENGE AB Nearly all human immunodeficiency virus (HIV) infections are acquired mucosally, and the gut-associated lymphoid tissues are important sites for early virus replication. Thus, vaccine strategies designed to prime virus-specific cytotoxic T lymphocyte (CTL) responses that home to mucosal compartments may be particularly effective at preventing or containing HIV infection. The Salmonella type III secretion system has been shown to be an effective approach for stimulating mucosal CTL responses in mice. We therefore tested DeltaphoP-phoQ attenuated strains of Salmonella enterica serovar Typhimurium and S. enterica serovar Typhi expressing fragments of the simian immunodeficiency virus (SIV) Gag protein fused to the type III-secreted SopE protein for the ability to prime virus-specific CTL responses in rhesus macaques. Mamu-A*01(+) macaques were inoculated with three oral doses of recombinant Salmonella, followed by a peripheral boost with modified vaccinia virus Ankara expressing SIV Gag (MVA Gag). Transient low-level CTL responses to the Mamu-A*01 Gag(181-189) epitope were detected following each dose of Salmonella. After boosting with MVA Gag, strong Gag-specific CTL responses were consistently detected, and tetramer staining revealed the expansion of Gag(181-189)-specific CD8(+) T-cell responses in peripheral blood. A significant percentage of the Gag(181-189)-specific T-cell population in each animal also expressed the intestinal homing receptor alpha4beta7. Additionally, Gag(181-189)-specific CD8(+) T cells were detected in lymphocytes isolated from the colon. Yet, despite these responses, Salmonella-primed/MVA-boosted animals did not exhibit improved control of virus replication following a rectal challenge with SIVmac239. Nevertheless, this study demonstrates the potential of mucosal priming by the Salmonella type III secretion system to direct SIV-specific cellular immune responses to the gastrointestinal mucosa in a primate model. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA. Therion Biol Corp, Cambridge, MA 02142 USA. Univ Nebraska, Dept Vet & Biomed Sci, Lincoln, NE 68583 USA. NCI Frederick, Retroviral Pathogenesis lab, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02115 USA. RP Johnson, PR (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCI NIH HHS [N01CO12400, N01 CO 12400]; NCRR NIH HHS [K26 RR000168, RR 00168, P51 RR000168]; NIAID NIH HHS [AI 35365, R01 AI046953, AI 45314, AI 10464, AI 46953, F32 AI010464, P01 AI035365, U01 AI035365] NR 43 TC 73 Z9 77 U1 1 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 FEB PY 2003 VL 77 IS 4 BP 2400 EP 2409 DI 10.1128/JVI.77.4.2400-2409.2003 PG 10 WC Virology SC Virology GA 640WZ UT WOS:000180712700011 PM 12551977 ER PT J AU de la Monte, SM Chiche, JD von dem Bussche, A Sanyal, S Lahousse, SA Janssens, SP Bloch, KD AF de la Monte, SM Chiche, JD von dem Bussche, A Sanyal, S Lahousse, SA Janssens, SP Bloch, KD TI Nitric oxide synthase-3 overexpression causes apoptosis and impairs neuronal mitochondrial function: Relevance to Alzheimer's-type neurodegeneration SO LABORATORY INVESTIGATION LA English DT Article ID BAX PROTEIN EXPRESSION; DNA-DAMAGE; PERMEABILITY TRANSITION; ABERRANT EXPRESSION; CELL-DEATH; DISEASE; BRAIN; BCL-2; HIPPOCAMPUS; MECHANISMS AB Dementia in Alzheimer's disease (AD) is correlated with cell loss that is mediated by apoptosis, mitochondrial (Mt) dysfunction, and possibly necrosis. Previous studies demonstrated increased expression of the nitric oxide synthase 3 (NOS3) gene in degenerating neurons of AD brains. For investigating the role of NOS3 overexpression as a mediator of neuronal loss, human PNET2 central nervous system-derived neuronal cells were infected with recombinant adenovirus vectors that expressed either human NOS3 or green fluorescent protein cDNA under the control of a CMV promoter. NOS3 overexpression resulted in apoptosis accompanied by increased levels of p53, p21/Waf1, Bax, and CD95. In addition, NOS3 overexpression impaired neuronal Mt function as demonstrated by the reduced levels of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and nicotinamide adenine dinucleotide (reduced form)-tetrazolium reductase activities and MitoTracker Red fluorescence. These adverse effects of NOS3 were associated with increased cellular levels of reactive oxygen species and impaired membrane integrity and were not produced in cells that were transfected with a cDNA encoding catalytically inactive NOS3. Importantly, modest elevations in NOS3 expression, achieved by infection with low multiplicities of adenovirus-NOS3 infection, did not cause apoptosis but rendered the cells more sensitive to oxidative injury by H2O2 or diethyldithiocarbamate. In contrast, treatment with NO donors did not enhance neuronal sensitivity to oxidative injury. These results suggest that NOS3-induced neuronal death is mediated by Mt dysfunction, oxidative injury, and impaired membrane integrity, rather than by NO production, and that neuroprotection from these adverse effects of NOS3 may be achieved by modulating intracellular levels of oxidative stress. C1 Brown Univ, Sch Med, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Pathol, Providence, RI 02903 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. Flanders Interuniv, Inst Biotechnol, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Cardiac Unit, Louvain, Belgium. RP de la Monte, SM (reprint author), Brown Univ, Sch Med, Rhode Isl Hosp, Dept Med, 55 Claverick St,Room 419, Providence, RI 02903 USA. NR 57 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 2003 VL 83 IS 2 BP 287 EP 298 DI 10.1097/01.LAB.0000056995.07053.C0 PG 12 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 652QE UT WOS:000181389200013 PM 12594242 ER PT J AU McGibbon, CA Bencardino, J Palmer, WE AF McGibbon, CA Bencardino, J Palmer, WE TI Subchondral bone and cartilage thickness from MRI: effects of chemical-shift artifact SO MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE LA English DT Article DE subchondral bone; articular cartilage; chemical-shift artifact; thickness; magnetic resonance imaging ID KNEE HYALINE CARTILAGE; IN-VIVO MEASUREMENTS; ARTICULAR-CARTILAGE; GRADIENT-ECHO; SPIN-ECHO; EXPERIMENTAL OSTEOARTHRITIS; INTERLEAVED WATER; FAT-SUPPRESSION; TRABECULAR BONE; DIXON TECHNIQUE AB Magnetic resonance imaging (MRI) is the modality of choice for visualizing and quantifying articular cartilage thickness. However, difficulties persist in MRI of subchondral bone using spoiled gradient-echo (SPGR) and other gradient-echo sequences, primarily due to the effects of chemical-shift artifact. Fat-suppression techniques are often used to reduce these artifacts, but they prevent measurement of bone thickness. In this report, we assess the magnitude of chemical-shift effects (phase-cancellation and misregistration artifacts) on subchondral bone and cartilage thickness measurements in human femoral heads using a variety of pulse sequence parameters. Phase-cancellation effects were quantified by comparing measurements from in-phase images (TE = 13.5 ms) to out-of-phase images (TE = 15.8 ms). We also tested the assumption of the optimal in-phase TE by comparing thickness measures at small variations on TE (13.0, 13.5 and 14.0 ms). Misregistration effects were quantified by comparing measurements from water+fat images (water-only+fat-only images) to the measurements from in-phase (TE = 13.5) images. A correction algorithm was developed and applied to the in-phase measurements and then compared to measurements from water+fat images. We also compared thickness measurements at different image resolutions. Results showed that both phase-cancellation artifact and misregistration artifact were significant for bone thickness measurement, but not for cartilage thickness measurement. Using an in-phase TE and correction algorithm for misregistration artifact, the errors in bone thickness relative to water+fat images were non-significant. This information may be useful for developing pulse sequences for optimal imaging of both cartilage and subchondral bone. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Ruth Sleeper Hall 010,40 Parkman St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR45278] NR 49 TC 26 Z9 26 U1 2 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0968-5243 J9 MAGN RESON MATER PHY JI Magn. Reson. Mat. Phys. Biol. Med. PD FEB PY 2003 VL 16 IS 1 BP 1 EP 9 DI 10.1007/s10334-003-0001-0 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 685GH UT WOS:000183253600001 PM 12695880 ER PT J AU Chen, XL Mele, J Giese, H Van Remmen, H Dolle, MET Steinhelper, M Richardson, A Vijg, J AF Chen, XL Mele, J Giese, H Van Remmen, H Dolle, MET Steinhelper, M Richardson, A Vijg, J TI A strategy for the ubiquitous overexpression of human catalase and CuZn superoxide dismutase genes in transgenic mice SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE catalase; CuZnSOD; transgenic mice ID LONG-LIVED STRAIN; HUMAN RENIN GENE; LIFE-SPAN; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; OXIDATIVE DAMAGE; EXPRESSION; LONGEVITY; RESISTANCE; MOUSE AB In the present study, we generated transgenic mice that overexpress catalase or CuZn superoxide dismutase (CuZnSOD) in all tissues using large genomic DNA fragments. An 80 kb human genomic DNA, containing the 33 kb human CAT gene as well as the 41 kb of 5' and the 6 kb of 3' flanking regions, was obtained by screening a human PI library and was used to produce transgenic mice Tg(CAT). Transgenic mice Tg(SOD1) were produced by a similar strategy using a 64 kb human genomic DNA containing the 10 kb human SOD1 gene and the 27 kb of both 5' and 3' flanking regions. Catalase mRNA levels were 2-6- fold higher and catalase activity levels were 2-4- fold higher in the various tissues of the hemizygous Tg(CAT) mice compared with wild type mice. The mRNA levels for CuZnSOD were 2-12- fold higher and the CuZnSOD activity levels were 2-5- fold higher in the hemizygous Tg(SOD1) mice compared with wild type mice. In summary, our study demonstrates that a strategy of using large genomic DNA containing either the entire human CAT or SOD1 gene with large flanking regions gives ubiquitous increased expression of CuZnSOD and catalase. In addition, the expression of catalase closely reflects the tissue specific pattern found in the endogenous gene. These transgenic mice will be useful in studying the role of oxidative stress/damage in aging and age-related pathologies. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78229 USA. Sam & Ann Barshop Ctr Longev & Aging Studies, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. FU NIA NIH HHS [P01AG14674, P01AG17242, P03 AG13319] NR 37 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD FEB PY 2003 VL 124 IS 2 BP 219 EP 227 AR PII S0047-6374(02)00161-6 DI 10.1016/S0047-6374(02)00161-6 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 665BM UT WOS:000182099800010 PM 12633942 ER PT J AU Culver, JP Choe, R Holboke, MJ Zubkov, L Durduran, T Slemp, A Ntziachristos, V Chance, B Yodh, AG AF Culver, JP Choe, R Holboke, MJ Zubkov, L Durduran, T Slemp, A Ntziachristos, V Chance, B Yodh, AG TI Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: Evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging SO MEDICAL PHYSICS LA English DT Article DE optical tomography; NIR spectroscopy; breast imaging; clinical system ID HETEROGENEOUS TURBID MEDIA; IN-VIVO; TISSUE; SPECTROSCOPY; MAMMOGRAPHY; SCATTERING; CONTRAST; PHANTOM; RECONSTRUCTION; CALIBRATION AB Three-dimensional diffuse optical tomography (DOT) of breast requires large data sets for even modest resolution (1 cm). We present a hybrid DOT system that combines a limited number of frequency domain (FD) measurements with a large set of continuous wave (cw) measurements. The FD measurements are used to quantitatively determine tissue averaged absorption and scattering coefficients. The larger cw data sets (105 measurements) collected with a lens coupled CCD, permit 3D DOT reconstructions of a 1-liter tissue volume. To address the computational complexity of large data sets and 3D volumes we employ finite difference based reconstructions computed in parallel. Tissue phantom measurements evaluate imaging performance. The tests include the following: point spread function measures of resolution, characterization of the size and contrast of single objects, field of view measurements and spectral characterization of constituent concentrations. We also report in vivo measurements. Average tissue optical properties of a healthy breast are used to deduce oxy- and deoxy-hemoglobin concentrations. Differential imaging with a tumor simulating target adhered to the surface of a healthy breast evaluates the influence of physiologic fluctuations on image noise. This tomography system provides robust, quantitative, full 3D image reconstructions with the advantages of high data throughput, single detector-tissue coupling path, and large (1L) imaging domains. In addition, we find that point spread function measurements provide a useful and comprehensive representation of system performance. (C) 2003 American Association of Physicists in Medicine. C1 Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Culver, JP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RI Durduran, Turgut/N-7768-2015 OI Durduran, Turgut/0000-0001-5838-1027 FU NCI NIH HHS [R01-CA75124-04] NR 46 TC 198 Z9 198 U1 3 U2 16 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 FEB PY 2003 VL 30 IS 2 BP 235 EP 247 DI 10.1118/1.1534109 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 645NH UT WOS:000180984100016 PM 12607841 ER PT J AU Moore, ME Butler, PF Hendee, WR AF Moore, ME Butler, PF Hendee, WR TI Reference values are de facto regulatory limits for patient exposures SO MEDICAL PHYSICS LA English DT Editorial Material C1 Philadelphia VA Med Ctr, Radiat Safety Off, Philadelphia, PA 19104 USA. Amer Coll Radiol, Breast Imaging Accreditat Programs, Reston, VA 20191 USA. RP Moore, ME (reprint author), Philadelphia VA Med Ctr, Radiat Safety Off, Philadelphia, PA 19104 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 2003 VL 30 IS 2 BP 273 EP 275 DI 10.1118/1.1538613 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 645NH UT WOS:000180984100020 PM 12607845 ER PT J AU Caballero, AE Saouaf, R Lim, SC Hamdy, O Abou-Elenin, K O'Connor, C LoGerfo, FW Horton, ES Veves, A AF Caballero, AE Saouaf, R Lim, SC Hamdy, O Abou-Elenin, K O'Connor, C LoGerfo, FW Horton, ES Veves, A TI The effects of troglitazone, an insulin-sensitizing agent, on the endothelial function in early and late type 2 diabetes: A placebo-controlled randomized clinical trial SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID RECEPTOR-GAMMA ACTIVATORS; CORONARY HEART-DISEASE; OBESITY/INSULIN-RESISTANCE; BRACHIAL-ARTERY; IN-VIVO; CELLS; ATHEROSCLEROSIS; DYSFUNCTION; MORTALITY; MELLITUS AB Activation of the peroxisome proliferator-activator receptor gamma (PPARgamma) improves insulin resistance and glycemic control in patients with diabetes. As PPARgamma is expressed in the endothelial cell, we have investigated the effect of troglitazone, a PPARgamma activator, on the endothelial function in people with type 2 diabetes in a 12-week, prospective, randomized, double-blinded clinical trial. We studied 87 type 2 diabetic patients who were divided into 3 groups. Group A consisted of 27 patients with recently diagnosed diabetes and no clinical manifestations of macrovascular disease; group 13, 29 patients with long-term diabetes and no clinically evident macrovascular disease; and group C, 31 diabetic patients with documented macrovascular disease (cardiovascular, cerebrovascular, or peripheral vascular disease). High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD, endothelium-dependent) and nitroglycerin-induced dilation (NID, endothelium-independent) in the brachial artery. Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (Ach, endothelium-dependent) and 1% sodium nitroprusside (NaNP, endothelium-independent). The plasma concentrations of von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The FMD improved in the troglitazone-treated patients in group A (7.72 +/- 3.4 v 5.27 +/- 2.0, P < .05 [exit visit v baseline, percent of increase in brachial artery diameter, mean +/- SD]). The fasting insulin level also improved in this group (15.6 +/- 10 v 19.7 +/- 10, P < .05) and was strongly correlated to changes in FMD (r = -.73, P < .01). No changes were found in the FMD or the fasting insulin levels in the troglitazone-treated patients in groups B or C. The NID was not changed by troglitazone treatment in any of the 3 groups. Also, no differences were found in the microcirculation reactivity measurements or in the biochemical markers of endothelial dysfunction in all 3 groups. A small, but significant, improvement of the FMD was found in placebo-treated patients in group 13, probably related to the low FMD levels at baseline in the patients (5.40 +/- 3.0 v 4.36 +/- 2.4, P < .05). We concluded that troglitazone treatment for 12 weeks improved endothelial function in the macrocirculation of patients with recently diagnosed type 2 diabetes and no clinical evidence of macrovascular disease. This improvement was strongly associated with the improvement of fasting plasma insulin concentrations. Copyright 2003, Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Joslin Diabet Ctr,Med Sch, Microcirculat Lab, Div Vasc Surg,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Columbia Univ, Sch Med, Dept Radiol, Columbia Presbyterian Med Ctr, New York, NY USA. RP Veves, A (reprint author), Harvard Univ, Joslin Diabet Ctr,Med Sch, Microcirculat Lab, Div Vasc Surg,Beth Israel Deaconess Med Ctr, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. FU NCRR NIH HHS [RR 01032] NR 27 TC 90 Z9 98 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD FEB PY 2003 VL 52 IS 2 BP 173 EP 180 DI 10.1053/meta.2003.50023 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 644MH UT WOS:000180921500009 PM 12601628 ER PT J AU Yamagoe, S Kanno, T Kanno, Y Sasaki, S Siegel, RM Lenardo, MJ Humphrey, G Wang, YH Nakatani, Y Howard, BH Ozato, K AF Yamagoe, S Kanno, T Kanno, Y Sasaki, S Siegel, RM Lenardo, MJ Humphrey, G Wang, YH Nakatani, Y Howard, BH Ozato, K TI Interaction of histone Acetylases and deacetylases in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; N-COR; TRANSCRIPTIONAL REPRESSION; DNA METHYLATION; ENERGY-TRANSFER; COMPLEX; PCAF; YEAST; COACTIVATOR; PROTEIN AB Having opposing enzymatic activities, histone acetylases (HATs) and deacetylases affect chromatin and regulate transcription. The activities of the two enzymes are thought to be balanced in the cell by an unknown mechanism that may involve their direct interaction. Using fluorescence resonance energy transfer analysis, we demonstrated that the acetylase PCAF and histone deacetylase 1 (HDAC1) are in close spatial proximity in living cells, compatible with their physical interaction. In agreement, coimmunoprecipitation assays demonstrated that endogenous HDACs are associated with PCAF and another acetylase, GCN5, in HeLa cells. We found by glycerol gradient sedimentation analysis that HATs are integrated into a large multiprotein HDAC complex that is distinct from the previously described HDAC complexes containing mSin3A, Mi-2/NRD, or CoREST. This HDAC-HAT association is partly accounted for by a direct protein-protein interaction observed in vitro. The HDAC-HAT complex may play a role in establishing a dynamic equilibrium of the two enzymes in vivo. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 2A01, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009; Kanno, Yuka/B-5802-2013; OI Siegel, Richard/0000-0001-5953-9893; Kanno, Yuka/0000-0001-5668-9319 NR 46 TC 58 Z9 60 U1 0 U2 3 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 FEB PY 2003 VL 23 IS 3 BP 1025 EP 1033 DI 10.1128/MCB.23.3.1025-1033.2003 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 640DY UT WOS:000180673600024 PM 12529406 ER PT J AU Jin, XW von Gall, C Pieschl, RL Gribkoff, VK Stehle, JH Reppert, SM Weaver, DR AF Jin, XW von Gall, C Pieschl, RL Gribkoff, VK Stehle, JH Reppert, SM Weaver, DR TI Targeted disruption of the mouse Mel(1b) melatonin receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAT SUPRACHIASMATIC NUCLEUS; CIRCADIAN ACTIVITY RHYTHMS; PHASE RESPONSE CURVE; SYRIAN-HAMSTERS; PINEAL-GLAND; LIGHT; CLOCK; SUBTYPES; CLONING; CREB AB Two high-affinity, G protein-coupled melatonin receptor subtypes have been identified in mammals. Targeted disruption of the Mel(1a) melatonin receptor prevents some, but not all, responses to the hormone, suggesting functional redundancy among receptor subtypes (Liu et al., Neuron 19:91-102, 1997). In the present work, the mouse Mel(1a) melatonin receptor cDNA was isolated and characterized, and the gene has been disrupted. The cDNA encodes a receptor with high affinity for melatonin and a pharmacological profile consistent with its assignment as encoding a melatonin receptor. Mice with targeted disruption of the Mel(1b) receptor have no obvious circadian phenotype. Melatonin suppressed multiunit electrical activity in the suprachiasmatic nucleus (SCN) in Mel(1b) receptor-deficient mice as effectively as in wild-type controls. The neuropeptide, pituitary adenylyl cyclase activating peptide, increases the level of phosphorylated cyclic AMP response element binding protein (CREB) in SCN slices, and melatonin reduces this effect. The Mel(1a) receptor subtype mediates this inhibitory response at moderate ligand concentrations (1 nM). A residual response apparent in Mel(1a) receptor-deficient C3H mice at higher melatonin concentrations (100 nM) is absent in Mel(1a)-Mel(1a) double-mutant mice, indicating that the Mel(1b) receptor mediates this effect of melatonin. These data indicate that there is a limited functional redundancy between the receptor subtypes in the SCN. Mice with targeted disruption of melatonin receptor subtypes will allow molecular dissection of other melatonin receptor-mediated responses. C1 Univ Massachusetts, Sch Med, Dept Neurobiol, Worcester, MA 01605 USA. Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Frankfurt, Anat Inst 2, D-60590 Frankfurt, Germany. Bristol Myers Squibb Co, Pharmaceut Res Inst, Neurosci Drug Discovery, Wallingford, CT 06492 USA. RP Weaver, DR (reprint author), Univ Massachusetts, Sch Med, Dept Neurobiol, Lazare Res Bldg,Room 723,364 Plantat St, Worcester, MA 01605 USA. OI Weaver, David/0000-0001-7941-6719 FU NIA NIH HHS [AG09975, P01 AG009975]; NIDDK NIH HHS [DK42125]; NIMH NIH HHS [F32 MH012067, F32 MH12067] NR 47 TC 158 Z9 163 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 FEB PY 2003 VL 23 IS 3 BP 1054 EP 1060 DI 10.1128/MCB.23.3.1054-1060.2003 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 640DY UT WOS:000180673600027 PM 12529409 ER PT J AU Kumar, S Mishra, N Raina, D Saxena, S Kufe, D AF Kumar, S Mishra, N Raina, D Saxena, S Kufe, D TI Abrogation of the cell death response to oxidative stress by the c-Abl tyrosine kinase inhibitor STI571 SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-DAMAGE; BCR-ABL; APOPTOTIC RESPONSE; ACTIVATION; NUCLEAR; GROWTH; TRANSCRIPTION; MITOCHONDRIA; REPAIR AB Normal aerobic metabolism is associated with the production of reactive oxygen species (ROS) and, consequently, the induction of apoptosis and necrosis. The cell death response to oxidative stress is thought to contribute to aging, neurological degeneration, and other disorders. ROS-induced apoptosis and necrosis involves activation of the cytoplasmic c-Abl tyrosine kinase and thereby signaling to mitochondria. Herein, we show that STI571, an inhibitor of Bcr-Abl in chronic myelogenous leukemia, blocks activation of c-Abl in the response of mouse embryo fibroblasts and human U-937 myeloid leukemia cells to hydrogen peroxide (H2O2). Immunofluorescence microscopy and subcellular fractionation studies demonstrate that STI571 decreases H2O2-induced targeting of c-Abl to mitochondria in the two cell types by 59 to 85%. The results also show that STI571 attenuates H2O2-induced loss of the mitochondrial transmembrane potential. In concert with these effects, STI571 inhibits the death response to H2O2 exposure by 40 to 80% depending on the cell type. These findings indicate that inhibition of c-Abl signaling by STI571 attenuates mitochondrial dysfunction and cell death in the cellular response to oxidative stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Lovelace Resp Res Inst, Albuquerque, NM USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802, CA49639] NR 34 TC 38 Z9 38 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 2003 VL 63 IS 2 BP 276 EP 282 DI 10.1124/mol.63.2.276 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 635JK UT WOS:000180395600003 PM 12527798 ER PT J AU Chan, B Lanyi, A Song, HK Griesbach, J Simarro-Grande, M Poy, F Howie, D Sumegi, J Terhorst, C Eck, MJ AF Chan, B Lanyi, A Song, HK Griesbach, J Simarro-Grande, M Poy, F Howie, D Sumegi, J Terhorst, C Eck, MJ TI SAP couples Fyn to SLAM immune receptors SO NATURE CELL BIOLOGY LA English DT Article ID LINKED LYMPHOPROLIFERATIVE-DISEASE; GENE-PRODUCT SAP; HUMAN B-LYMPHOCYTES; HEMATOPOIETIC-CELLS; CRYSTAL-STRUCTURE; ENCODING GENE; SH3 DOMAIN; ACTIVATION; MUTATIONS; SURFACE AB SAP (SLAM-associated protein) is a small lymphocyte-specific signalling molecule that is defective or absent in patients with X-linked lymphoproliferative syndrome (XLP)(1-3). Consistent with its single src homology 2 (SH2) domain architecture and unusually high affinity for SLAM (also called CD150), SAP has been suggested to function by blocking binding of SHP-2 or other SH2-containing signalling proteins to SLAM receptors(1,4). Additionally, SAP has recently been shown to be required for recruitment and activation of the Src-family kinase FynT after SLAM ligation(5). This signalling 'adaptor' function has been difficult to conceptualize, because unlike typical SH2-adaptor proteins, SAP contains only a single SH2 domain and lacks other recognized protein interaction domains or motifs. Here, we show that the SAP SH2 domain binds to the SH3 domain of FynT and directly couples FynT to SLAM. The crystal structure of a ternary SLAM-SAP-Fyn-SH3 complex reveals that SAP binds the FynT SH3 domain through a surface-surface interaction that does not involve canonical SH3 or SH2 binding interactions. The observed mode of binding to the Fyn-SH3 domain is expected to preclude the auto-inhibited conformation of Fyn, thereby promoting activation of the kinase after recruitment. These findings broaden our understanding of the functional repertoire of SH3 and SH2 domains. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. RI Simarro, Maria/M-3947-2015; Song, Hyun Kyu/D-6763-2016 OI Simarro, Maria/0000-0001-8917-7328; Song, Hyun Kyu/0000-0001-5684-4059 NR 30 TC 224 Z9 235 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD FEB PY 2003 VL 5 IS 2 BP 155 EP 160 DI 10.1038/ncb920 PG 6 WC Cell Biology SC Cell Biology GA 642KF UT WOS:000180802100016 PM 12545174 ER PT J AU Hieronymus, H Silver, PA AF Hieronymus, H Silver, PA TI Genome-wide analysis of RNA-protein interactions illustrates specificity of the mRNA export machinery SO NATURE GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; BINDING-FACTOR; YEAST; MEX67P; YRA1P; SUB2P AB Nuclear export of mRNA is mediated by a complex machinery of RNA-binding proteins that recognizes and routes mRNAs through a messenger ribonucleoprotein (mRNP) network. The full spectrum of mRNA cargoes for any dedicated mRNA export factor is unknown. We identified the mRNAs that bind two conserved yeast mRNA export factors, Yra1 (refs. 1-5) and Mex67 (refs. 6,7), on a genome-wide scale and determined their level of binding. Yra1 and Mex67 bind approximately 1,000 and 1,150 mRNAs, respectively, corresponding to almost 20% of the yeast genome and roughly 36% of all transcriptional events each. The binding level of Yra1 targets is related to their transcriptional frequency, but that of Mex67 targets is not. Yra1-bound transcripts are enriched in mRNAs that are regulated by a number of transcription factors. Yra1- and Mex67-bound populations also show enrichment of mRNAs encoding distinct functional classes of proteins, some of which are regulated by these transcription factors. We determined that one such transcription factor, Abf1 (refs. 8-10), associates with Yra1. These results indicate a previously unidentified specificity of mRNA export factors, which coordinates the export of transcriptionally co-regulated, functional classes of transcripts, perhaps through interactions with the transcriptional machinery. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 30 TC 148 Z9 150 U1 1 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 FEB PY 2003 VL 33 IS 2 BP 155 EP 161 DI 10.1038/ng1080 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 641YB UT WOS:000180773700012 PM 12524544 ER PT J AU Tonon, G Modi, S Wu, LZ Kubo, A Coxon, AB Komiya, T O'Neil, K Stover, K El-Naggar, A Griffin, JD Kirsch, IR Kaye, FJ AF Tonon, G Modi, S Wu, LZ Kubo, A Coxon, AB Komiya, T O'Neil, K Stover, K El-Naggar, A Griffin, JD Kirsch, IR Kaye, FJ TI t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway SO NATURE GENETICS LA English DT Article ID MINOR SALIVARY-GLAND; NEOPLASTIC TRANSFORMATION; CHROMOSOMAL TRANSLOCATIONS; HUMAN HOMOLOG; GENE; TUMOR; ACTIVATION; EXPRESSION; MASTERMIND; RECEPTORS AB Truncation of Notch1 has been shown to cause a subtype of acute leukemia(1), and activation of Notch4 has been associated with mammary and salivary gland carcinomas of mice(2). Here we identify a new mechanism for disrupting Notch signaling in human tumorigenesis, characterized by altered function of a new ortholog of the Drosophila melanogaster Notch co-activator molecule Mastermind. We cloned the t(11;19) translocation that underlies the most common type of human malignant salivary gland tumor. This rearrangement fuses exon 1 from a novel gene of unknown function at 19p13, termed mucoepidermoid carcinoma translocated 1 (MECT1), with exons 2-5 of a novel member of the Mastermind-like gene family (MAML2) at 11q21 (ref. 3). Similar to D. melanogaster Mastermind and MAML1 (refs. 4,5), full-length MAML2 functioned as a CSL (CBF-1, suppressor of hairless and Lag-1)-dependent transcriptional co-activator for ligand-stimulated Notch. In contrast, MECT1-MAML2 activated transcription of the Notch target gene HES1 independently of both Notch ligand and CSL binding sites. MECT1-MAML2 induced foci formation in RK3E epithelial cells, confirming a biological effect for the fusion product. These data suggest a new mechanism to disrupt the function of a Notch co-activator in a common type of malignant salivary gland tumor. C1 Natl Canc Inst, Genet Branch, Ctr Canc Res, Bethesda, MD 20889 USA. Natl Naval Med Res Inst, Bethesda, MD 20889 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Natl Naval Med Res Inst, Dept Med, Div Pulm, Bethesda, MD 20889 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Kaye, FJ (reprint author), Natl Canc Inst, Genet Branch, Ctr Canc Res, Bethesda, MD 20889 USA. EM fkaye@helix.nih.gov RI kaye, frederic/E-2437-2011 NR 30 TC 217 Z9 235 U1 4 U2 11 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 FEB PY 2003 VL 33 IS 2 BP 208 EP 213 DI 10.1038/ng1083 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 641YB UT WOS:000180773700022 PM 12539049 ER PT J AU Fan, ZS Beresford, PJ Zhang, D Xu, Z Novina, CD Yoshida, A Pommier, Y Lieberman, J AF Fan, ZS Beresford, PJ Zhang, D Xu, Z Novina, CD Yoshida, A Pommier, Y Lieberman, J TI Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A SO NATURE IMMUNOLOGY LA English DT Article ID HUMAN APURINIC ENDONUCLEASE; BASE EXCISION-REPAIR; APURINIC/APYRIMIDINIC ENDONUCLEASE; POLY(ADP-RIBOSE) POLYMERASE; REDOX REGULATION; MAMMALIAN-CELLS; DNA-BINDING; IN-VIVO; EXPRESSION; REF-1 AB The cytolytic T lymphocyte protease granzyme A (GzmA) initiates a caspase-independent cell death pathway. Here we report that the rate-limiting enzyme of DNA base excision repair, apurinic endonuclease-1 (Ape1), which is also known as redox factor-1 (Ref-1), binds to GzmA and is contained in the SET complex, a macromolecular complex of 270-420 kDa that is associated with the endoplasmic reticulum and is targeted by GzmA during cell-mediated death. GzmA cleaves Ape1 after Lys31 and destroys its known oxidative repair functions. In so doing, GzmA may block cellular repair and force apoptosis. In support of this, cells with silenced Ape1 expression are more sensitive, whereas cells overexpressing noncleavable Ape1 are more resistant, to GzmA-mediated death. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 43 TC 172 Z9 178 U1 2 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 FEB PY 2003 VL 4 IS 2 BP 145 EP 153 DI 10.1038/ni885 PG 9 WC Immunology SC Immunology GA 640JW UT WOS:000180686500014 PM 12524539 ER PT J AU Freeman, MW Moore, KJ AF Freeman, MW Moore, KJ TI eLiXiRs for restraining inflammation SO NATURE MEDICINE LA English DT Editorial Material ID CHOLESTEROL EFFLUX; LXR-ALPHA; GENE; EXPRESSION; RECEPTORS C1 Massachusetts Gen Hosp, Dept Med, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Dept Med, Lipid Metab Unit, Boston, MA 02114 USA. OI Moore, kathryn/0000-0003-2505-2547 NR 14 TC 7 Z9 9 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 FEB PY 2003 VL 9 IS 2 BP 168 EP 169 DI 10.1038/nm0203-168 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 642KD UT WOS:000180801900018 PM 12563335 ER PT J AU Rudin, M Weissleder, R AF Rudin, M Weissleder, R TI Molecular imaging in drug discovery and development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; GENE-EXPRESSION; PHARMACEUTICAL RESEARCH; CONTRAST AGENTS; CLINICAL-TRIALS; PET; SPECTROSCOPY; TUMORS; CANCER AB Imaging sciences have grown exponentially during the past three decades, and many techniques, such as magnetic resonance imaging, nuclear tomographic imaging and X-ray computed tomography, have become indispensable in clinical use. Advances in imaging technologies and imaging probes for humans and for small animals are now extending the applications of imaging further into drug discovery and development, and have the potential to considerably accelerate the process. This review summarizes some of the recent developments in conventional and molecular imaging, and highlights their impact on drug discovery. C1 Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. RI Rudin, Markus/F-2417-2010 NR 79 TC 452 Z9 471 U1 6 U2 101 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD FEB PY 2003 VL 2 IS 2 BP 123 EP 131 DI 10.1038/nrd1007 PG 9 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 641GV UT WOS:000180737800014 PM 12563303 ER PT J AU Inal, JM Pascual, M Lesavre, P Schifferli, JA AF Inal, JM Pascual, M Lesavre, P Schifferli, JA TI Complement inhibition in renal diseases SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Editorial Material DE complement; glomerulonephritis; ischaemia/reperfusion injury ID ACUTE HUMORAL REJECTION; INJURY; MICE; CLEARANCE; CLUSTERIN; NEPHRITIS; CELLS C1 Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Transplantat Unit, Boston, MA 02114 USA. Hop Necker Enfants Malad, Serv Nephrol, INSERM U507, Paris, France. RP Inal, JM (reprint author), Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland. RI Inal, Jameel/G-2995-2010 OI Inal, Jameel/0000-0002-7200-0363 NR 29 TC 9 Z9 10 U1 1 U2 2 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 FEB PY 2003 VL 18 IS 2 BP 237 EP 240 DI 10.1093/ndt/18.2.237 PG 4 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 644CW UT WOS:000180901200001 PM 12543873 ER PT J AU Nguyen, DP Frank, LM Brown, EN AF Nguyen, DP Frank, LM Brown, EN TI An application of reversible-jump Markov chain Monte Carlo to spike classification of multi-unit extracellular recordings SO NETWORK-COMPUTATION IN NEURAL SYSTEMS LA English DT Article ID INFERENCE; MIXTURES; SIGNALS; CORTEX; MODELS AB Multi-electrode recordings in neural. tissue contain the action potential waveforms of many closely spaced neurons. While we can observe the action potential waveforms, we cannot observe which neuron is the source for which waveform nor how many source neurons are being recorded. Current spike-sorting algorithms solve this problem by assuming a fixed number of source neurons and assigning the action potentials given this fixed number. We model the spike waveforms as an anisotropic Gaussian mixture model and present, as an alternative, a reversible-jump Markov chain Monte Carlo (MCMC) algorithm to simultaneously estimate the number of source neurons and to assign each action potential to a source. We derive this MCMC algorithm and illustrate its application using simulated three-dimensional data and real four-dimensional feature vectors extracted from tetrode recordings of rat entorhinal cortex neurons. In the analysis of the simulated data our algorithm finds the correct number of mixture components (sources) and classifies the action potential waveforms with minimal error. In the analysis of real data, our algorithm identifies clusters closely. resembling those previously identified by a user-dependent graphical clustering procedure. Our findings suggest that a reversible-jump MCMC algorithm could offer a new strategy for designing automated spike-sorting algorithms. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,MIT,Div Hlth Sci & Technol, Dept Anesthesia & Crit Care,Neurosci Stat Res Lab, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, RIKEN MIT Neurosci Res Ctr, Picower Ctr Learning & Memory, Cambridge, MA 02139 USA. RP Nguyen, DP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,MIT,Div Hlth Sci & Technol, Dept Anesthesia & Crit Care,Neurosci Stat Res Lab, Boston, MA 02114 USA. OI Frank, Loren/0000-0002-1752-5677 FU NIDA NIH HHS [DA015644]; NIMH NIH HHS [MH59733, MH61637, MH65102] NR 26 TC 12 Z9 12 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0954-898X J9 NETWORK-COMP NEURAL JI Netw.-Comput. Neural Syst. PD FEB PY 2003 VL 14 IS 1 BP 61 EP 82 AR PII S0954-898X(03)57776-4 DI 10.1088/0954-898X/14/1/304 PG 22 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Neurosciences SC Computer Science; Engineering; Neurosciences & Neurology GA 653AG UT WOS:000181412600005 PM 12617059 ER PT J AU Rostasy, K Augood, SJ Hewett, JW Leung, JCO Sasaki, H Ozelius, LJ Ramesh, V Standaert, DG Breakefield, XO Hedreen, JC AF Rostasy, K Augood, SJ Hewett, JW Leung, JCO Sasaki, H Ozelius, LJ Ramesh, V Standaert, DG Breakefield, XO Hedreen, JC TI TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion SO NEUROBIOLOGY OF DISEASE LA English DT Article DE torsin; dystonia; human brain; substantia nigra ID DOPA-RESPONSIVE DYSTONIA; HUMAN BRAIN; SUBSTANTIA-NIGRA; ASHKENAZI JEWS; PARKINSONS-DISEASE; MUTANT TORSINA; LEWY BODIES; GENE DYT1; RAT-BRAIN; MECHANISM AB Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. Most cases are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A (DYT1) gene, which is widely expressed in human brain and encodes the protein-torsinA. This study compares neuropathology and torsinA expression in the normal human brain with that in dystonia cases with and without the GAG deletion. TorsinA-like protein was expressed in neuronal cytoplasm throughout the human brain, including cerebellum, substantia nigra, hippocampus, and neostriatum, with higher levels in specific neurons. This immunostaining pattern was not discernibly different in dystonia and normal brains in midbrain and neostriatal regions. However, nigral dopaminergic neurons appeared to be larger in both GAG-deletion and non-GAG-deletion dystonia brains compared to normal, and may be more closely spaced in GAG-deletion brains. Beyond these apparent changes in neuronal size and spacing in dystonia brains, there was no indication of neuron loss, inflammation, DNA strand breaks, or altered distribution of torsin-like immunoreactivity, supporting a functional rather than degenerative etiology of early onset torsion dystonia. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Tufts Univ, New England Med Ctr, Dept Psychiat 1007, Boston, MA 02111 USA. Pediat Neurol Floating Hosp, Boston, MA USA. Univ Gottingen, Dept Pediat Neurol, D-3400 Gottingen, Germany. Massachusetts Gen Hosp, Neurodegenerat Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurooncol Lab, Charlestown, MA USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Harvard Univ, McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP Hedreen, JC (reprint author), Tufts Univ, New England Med Ctr, Dept Psychiat 1007, 750 Washington St, Boston, MA 02111 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS37409] NR 48 TC 97 Z9 100 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2003 VL 12 IS 1 BP 11 EP 24 DI 10.1016/S0969-9961(02)00010-4 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 652ZM UT WOS:000181410800002 PM 12609485 ER PT J AU Kesari, S Batchelor, TT AF Kesari, S Batchelor, TT TI Leptomeningeal metastases SO NEUROLOGIC CLINICS LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; CELL LUNG-CANCER; CEREBROSPINAL-FLUID CYTOLOGY; HUMAN NEOPLASTIC MENINGITIS; NON-HODGKINS-LYMPHOMA; INTRATHECALLY ADMINISTERED CHEMOTHERAPY; RADIOLABELED MONOCLONAL-ANTIBODIES; CEREBELLAR PILOCYTIC ASTROCYTOMA AB Metastases to the nervous system are an increasingly common complication of cancer, and can involve the brain parenchyma, dura, skull, epidural space, peripheral nerves, and leptomeninges (pia and arachnoid membranes). Leptomeningeal metastasis (LM) is defined as the appearance of tumor cells in the leptomeninges or cerebrospinal fluid (CSF) distant from the site of a primary tumor [1]. LM is also know as carcinomatous meningitis, neoplastic meningitis, neoplastic meningosis, leukemic meningitis (for leukemia), lymphomatous meningitis (for lymphoma), and meningeal carcinomatosis (for carcinoma) [2-11]. LM was first described in 1870 in a patient with lung cancer, and was thought to be a rare condition, usually diagnosed at autopsy [12]. By the 1970s, the condition was increasingly diagnosed due to increased suspicion and improved diagnostic tests [8,13]. As treatments for systemic cancers improve and as patients live longer, there is a higher risk of central nervous system (CNS) metastases, including LM. LM has a devastating impact on the prognosis and quality of life for affected patients. Neurologic dysfunction may severely impair the ability of a patient to function independently. Advances in diagnostics, chemotherapy, radiotherapy, and surgery have made it possible to partially alleviate symptoms and to improve the quality of life. Further advances in modalities that may allow earlier diagnosis of LM and the development of more effective therapeutics may offer future patients with LM an improved quality of life and longer duration of survival. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Cox 315,100 Blossom St, Boston, MA 02114 USA. RI Kesari, Santosh/E-8461-2013 NR 305 TC 66 Z9 76 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 2003 VL 21 IS 1 BP 25 EP + AR PII S0733-8619(02)00032-4 DI 10.1016/S0733-8619(02)00032-4 PG 43 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 641EK UT WOS:000180731700003 PM 12690644 ER PT J AU Wen, PY Schiff, D AF Wen, PY Schiff, D TI Neurologic complications of solid tumors SO NEUROLOGIC CLINICS LA English DT Review ID SPINAL-CORD COMPRESSION; CELL LUNG-CANCER; PARANEOPLASTIC CEREBELLAR DEGENERATION; GAMMA-KNIFE RADIOSURGERY; SINGLE BRAIN METASTASIS; MALIGNANT-MELANOMA; BREAST-CANCER; LIMBIC ENCEPHALITIS; RADIATION-THERAPY; NECK-CANCER AB In this article the authors review the neurologic complications of the more common solid tumors. The conditions that are considered primarily are those resulting from direct infiltration of neural structures by the tumors themselves or metastatic disease or as a result of paraneoplastic syndromes. Many of these neurologic complications are discussed in greater detail in other articles in this issue and in several texts [1-3]. Treatment-related toxicities caused by surgery, radiation therapy, and chemotherapy are also common in patients with solid tumors. A comprehensive discussion of these complications is beyond the scope of this article. They are discussed in depth in the articles by Cross and Glantz and Plotkin and Wen elsewhere in this issue and are considered only briefly here. In addition, cancer patients frequently develop toxic and metabolic encephalopathies as a result of medications, metabolic derangements, infections, and nutritional deficiencies. The evaluation of encephalopathies in cancer patients is reviewed elsewhere [4] and is not discussed here. C1 Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Univ Virginia, Med Ctr, Neurooncol Ctr, Charlottesville, VA 22908 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, 75 Francis St, Boston, MA 02115 USA. NR 150 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 2003 VL 21 IS 1 BP 107 EP + AR PII S0733-8619(02)00029-4 DI 10.1016/S0733-8619(02)00029-4 PG 35 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 641EK UT WOS:000180731700006 PM 12690647 ER PT J AU Plotkin, SR Wen, PY AF Plotkin, SR Wen, PY TI Neurologic complications of cancer therapy SO NEUROLOGIC CLINICS LA English DT Review ID NERVOUS-SYSTEM TOXICITY; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; INTRATHECAL METHOTREXATE OVERDOSE; TRANS-RETINOIC ACID; PHASE-II TRIAL; MULTIFOCAL INFLAMMATORY LEUKOENCEPHALOPATHY; PERIPHERAL SENSORY NEUROPATHY; CISPLATIN-BASED CHEMOTHERAPY AB Patients with cancer often take multiple medications. These medications may be directed at underlying neoplasms (eg, chemotherapy, hormonal agents, biologic modifiers) or at secondary symptoms such as cerebral edema or seizures (eg, corticosteroids, anticonvulsants). Given that chemotherapeutic agents are active against rapidly dividing cells and that they are frequently excluded from the central nervous system (CNS) by the blood-brain barrier (BBB), it is surprising that many medications have adverse effects on the nervous system. The various mechanisms underlying neurotoxicity are an area of active investigation in neuro-oncology. The pace of drug development has progressed rapidly during the past decade. When a patient with cancer presents with new neurologic symptoms, one must consider neurotoxicity related to cancer treatment. The goal of this review is to describe the neurotoxicity associated with established chemotherapeutic agents and with some of newer medications used in the treatment of cancer (Table 1). A number of excellent reviews have been published previously [1-9]. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02446 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02446 USA. NR 240 TC 37 Z9 38 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 2003 VL 21 IS 1 BP 279 EP + AR PII S0733-8619(02)00034-8 DI 10.1016/S0733-8619(02)00034-8 PG 41 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 641EK UT WOS:000180731700012 PM 12690653 ER PT J AU Smith, ER Chapman, PH Ogilvy, CS AF Smith, ER Chapman, PH Ogilvy, CS TI Far posterior subtemporal approach to the dorsolateral brainstem and tentorial ring: Technique and clinical experience SO NEUROSURGERY LA English DT Article DE approach; brainstem; cavernous malformation; subtemporal ID INFRATENTORIAL SUPRACEREBELLAR APPROACH; SKULL BASE; LESIONS; ANATOMY AB OBJECTIVE: Surgical access to the posterolateral mesencephalon or tentorial ring,can be problematic, depending on the angle of the tentorium and associated venous structures. A far posterior subtemporal approach was developed that uses the wide opening of the tentorium and the option of supratentorial retraction of the cerebellum to provide an excellent angle of approach to this region. Details of this, technique and a series of eight patients with lesions treated by this approach are presented. METHODS: Seven cavernous malformations and one dural arteriovenous malformation were approached in eight patients. In this far posterior subtemporal approach, a horseshoe incision is centered slightly behind the ear, with the caudal extent of the craniotomy defined by the temporal fossa floor. The entry of the vein of Labbe into transverse sinus is identified intradurally. If the vein enters anteriorly in the exposure, it is mobilized. Retractors are then placed, and the tentorium is visualized and opened laterally, avoiding the trochlear nerve. A thin, tapered retractor can be used to retract the cerebellum posterolaterally away from the brainstem. RESULTS: This approach was used to treat eight patients, and their lesions were successfully resected. Seven patients experienced good outcomes, and one patient! who presented with Hunt-Hess Grade IV subarachnoid hemorrhage from a dural-arteriovenous malformation, experienced a fair outcome. CONCLUSION: The far posterior subtemporal approach is effective for approaching carefully selected lesions of the posterolateral mesencephalon and tentorial ring. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, VBK 710,Fruit St, Boston, MA 02114 USA. NR 12 TC 25 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2003 VL 52 IS 2 BP 364 EP 368 DI 10.1227/01.NEU.0000043939.24784.31 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 644DA UT WOS:000180901600023 PM 12535365 ER PT J AU Liu, CD Glantz, GJ Livingston, EH AF Liu, CD Glantz, GJ Livingston, EH TI Fibrin glue as a sealant for high-risk anastomosis in surgery for morbid obesity SO OBESITY SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Society-of-Bariatric-Surgery CY JUN 24-29, 2002 CL LAS VEGAS, NEVADA SP Amer Soc Bariatr Surg DE fibrin sealant; gastric bypass; enteric leaks; bariatric surgery; morbid obesity ID BOWEL ANASTOMOSES; COMPLICATIONS AB Background: Fibrin sealants promote hemostasis and wound healing. Complex revisional surgery is performed for morbid obesity, and high-risk patients undergo weight loss surgery routinely. Fibrin sealant, Tisseel(TM), Was used by one surgeon on 120 consecutive patients at the gastrojejunal anastomosis in Roux-en-Y gastric bypass (RYGBP). We hypothesized that the application of fibrin sealant would decrease anastomotic leaks. Methods: One surgeon (Surgeon A) used fibrin sealant for 120 consecutive patients, while two other surgeons (Surgeons B & C) served as controls and did not use fibrin glue for their last 120 patients. Surgeon A did not use fibrin glue in 120 patients to serve as an internal control. All 480 patients underwent a RYGBP. Fibrin glue was applied at the gastrojejunal anastomosis. Results: The fibrin sealant group did not have any documented leaks on the previous 120 patients, while 5 patients with Surgeon B, 2 patients with Surgeon C and 1 patient with Surgeon A without fibrin sealant experienced enteric leaks requiring re-operation, drainage, or long-term total parenteral nutrition (N=480 total patients). Conclusions: Fibrin sealant may be useful in preventing leaks and promoting healing, of the "high risk" anastomosis during complex gastrointestinal surgery. While the cost of fibrin glue is to be considered, re-operation and management of subsequent enterocutanous fistulas or anastomotic strictures may be more costly than routine use for high-risk morbidly obese patients. C1 Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90024 USA. Greater Los Angeles VA Med Ctr, Dept Surg, Los Angeles, CA USA. RP Liu, CD (reprint author), Univ Calif Los Angeles, Sch Med, Dept Surg, 10833 LeConte Ave,72-215CHS, Los Angeles, CA 90024 USA. NR 10 TC 62 Z9 66 U1 0 U2 1 PU F D-COMMUNICATIONS INC PI TORONTO PA 3100 BAYVIEW AVE, UNIT 4, TORONTO, ONTARIO M2N 5L3, CANADA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD FEB PY 2003 VL 13 IS 1 BP 45 EP 48 DI 10.1381/096089203321136575 PG 4 WC Surgery SC Surgery GA 651ZX UT WOS:000181355100007 PM 12630612 ER PT J AU Solomon, DH Connelly, MT Rosen, CJ Dawson-Hughes, B Kiel, DP Greenspan, SL Leib, ES Holick, M Miguel, AH Finkelstein, JS AF Solomon, DH Connelly, MT Rosen, CJ Dawson-Hughes, B Kiel, DP Greenspan, SL Leib, ES Holick, M Miguel, AH Finkelstein, JS TI Factors related to the use of bone densitometry: survey responses of 494 primary care physicians in New England SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE bone mineral densitometry; primary care; osteoporosis ID HORMONE REPLACEMENT THERAPY; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; OSTEOPOROTIC FRACTURES; VERTEBRAL FRACTURES; INFORMATION; MANAGEMENT; BEHAVIORS; DECISIONS AB Large population-based surveys have shown that approximately 30% of people over age 65 years have osteoporosis and that 17% of the population over 65 years will sustain a fracture during their lifetime. Many people with osteoporosis are never being evaluated even though effective treatments are available. We examined why primary care physicians order few bone mineral density scans. We conducted a cross-sectional survey of primary care physicians practicing in any of the six New England states. Target physician specialties included internal medicine, general practitioners/family physicians, and obstetrician-gynecologists who had a facsimile number listed with the American Medical Association. Demographics, practice characteristics, use of bone densitometry, and attitudes regarding osteoporosis, bone densitometry and health maintenance were assessed by questionnaire. Twelve percent (n=494) of the physicians responded to the questionnaire. Respondents were similar to non-respondents with respect to years of practice, training and geographical state, though they were more likely to be female (pless than or equal to0.05). Respondents had a mean age of 51 years, and 51% were trained in internal medicine, 25% in general practice/family practice and 24% in obstetrics-gynecology. The mean number of self-reported bone densitometry referrals per month was 10+/-11, and 25% of respondents reported that they referred fewer than 4 patients per month. In adjusted logistic models, factors significantly associated with referring fewer than 4 patients per month were: training in internal medicine (odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9) or general practice/family practice (OR 2.6, 95% CI 1.3-5.2) versus obstetrics-gynecology; practicing in an urban setting (OR 2.5, 95% CI 1.3-4.9) or rural/small town setting (OR 2.2, 95% CI 1.2-4.1) versus a suburban setting; spending less than 50% of professional time in patient care (OR 4.0, 95% CI 1.7-9.5); seeing the lowest proportion of postmenopausal women (OR 2.5., 95% CI 1.2-5.3); the belief that calcium and vitamin D are adequate to treat osteoporosis (OR 2.1, 95% CI 1.0-4.5); and the belief that osteoporosis treatment should not be based on bone density results (OR 3.2, 95% CI 1.7-6.1). Potentially modifiable physician beliefs and a number of practice characteristics are associated with low referral rates for bone densitometry. Educational strategies aimed at improving the use of bone density testing should consider these factors. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Maine Osteoporosis Ctr, Bangor, ME USA. Tufts Univ, USDA, Nutr Ctr, Boston, MA 02111 USA. Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Univ Pittsburgh, Div Endocrinol, Pittsburgh, PA USA. Univ Vermont, Div Rheumatol, Burlington, VT 05405 USA. Boston Univ, Med Ctr, Div Endocrinol, Boston, MA USA. Procter Gamble Pharmaceut Inc, Cincinnati, OH 45202 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 221 Longwood Ave,Suite 341, Boston, MA 02115 USA. OI Holick, Michael/0000-0001-6023-9062; Kiel, Douglas/0000-0001-8474-0310 FU NIAMS NIH HHS [K23-AR48616]; NIDDK NIH HHS [K24-DK02759] NR 31 TC 22 Z9 22 U1 0 U2 2 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD FEB PY 2003 VL 14 IS 2 BP 123 EP 129 DI 10.1007/s00198-002-1326-7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 740JX UT WOS:000186400200006 PM 12730780 ER PT J AU Krebs, DE Gill-Body, KM Parker, SW Ramirez, JV Wernick-Robinson, M AF Krebs, DE Gill-Body, KM Parker, SW Ramirez, JV Wernick-Robinson, M TI Vestibular rehabilitation: Useful but not universally so SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID VESTIBULOOCULAR REFLEX; LOCOMOTOR ACTIVITIES; BALANCE; POSTUROGRAPHY; DYSFUNCTION; STABILITY; THERAPY; HYPOFUNCTION; HABITUATION; KINEMATICS AB OBJECTIVE: Although vestibular rehabilitation (VR) is gaining popularity, few data support its utility in improving locomotor stability, and no good predictors exist of whom will benefit most. STUDY DESIGN AND SETTING: A double-blind, placebo-controlled randomized trial of vestibular rehabilitation was conducted at a large tertiary care hospital on 124 patients (59 18 years old) with unilateral (n = 51) or bilateral (n = 73) vestibular hypofunction, of whom 86 completed a 12-week intervention. Of these 86, 27 returned for long-term (1-year) follow-up testing. The primary outcome measure was locomotor stability. RESULTS: Group A (6 weeks of VR) significantly (P < 0.01) increased their gait velocity and stability compared with group B (6 weeks of strengthening exercise), but there was a smaller difference (P = 0.05) between groups at 12 weeks, when both had had VR; there were no group differences at 1 year. Of the 86 who completed the intervention, 52 (61%) had clear locomotor gains. CONCLUSION AND SIGNIFICANCE: VR is helpful for most patients in providing locomotor stability, but further work is needed to determine the factors that prevent VR from being effective for all patients with vestibulopathy. C1 MGH Inst Hlth Profess, Boston, MA 02129 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Krebs, DE (reprint author), MGH Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. FU NCCIH NIH HHS [R21-AT-000553]; NIA NIH HHS [R01-AG-11255] NR 34 TC 53 Z9 55 U1 0 U2 6 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 FEB PY 2003 VL 128 IS 2 BP 240 EP 250 DI 10.1067/mhn.2003.72 PG 11 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 651GJ UT WOS:000181311900013 PM 12601321 ER PT J AU Nagasako, EM Oaklander, AL Dworkin, RH AF Nagasako, EM Oaklander, AL Dworkin, RH TI Congenital insensitivity to pain: an update SO PAIN LA English DT Review DE pain; congenital insensitivity; congenital indifference; hereditary sensory and autonomic neuropathy ID HEREDITARY SENSORY NEUROPATHY; FAMILIAL DYSAUTONOMIA; AUTONOMIC NEUROPATHY; INDIFFERENCE; ANHIDROSIS C1 Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. Washington Univ, Sch Med, St Louis, MO USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nerve Injury Unit,Dept Anesthesiol Neurol & Patho, Boston, MA USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.edu FU NIMH NIH HHS [MH 51791]; NINDS NIH HHS [NS 42866] NR 40 TC 111 Z9 120 U1 0 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD FEB PY 2003 VL 101 IS 3 BP 213 EP 219 DI 10.1016/S0304-3959(02)00482-7 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 648AF UT WOS:000181125700001 PM 12583863 ER PT J AU Shah, U Dickinson, BL Blumberg, RS Simister, NE Lencer, WI Walker, WA AF Shah, U Dickinson, BL Blumberg, RS Simister, NE Lencer, WI Walker, WA TI Distribution of the IgG Fc receptor, FcRn, in the human fetal intestine SO PEDIATRIC RESEARCH LA English DT Article ID I-RELATED RECEPTOR; IMMUNOGLOBULIN-G; HUMAN PLACENTA; CELL-LINE; EXPRESSION; TRANSPORT; GENE; BINDING; SYSTEM; KIDNEY AB The intestinal Fc receptor, FcRn, functions in the maternofetal transfer of gamma globulin (IgG) in the neonatal rodent. In humans, most of this transfer is presumed to occur in utero via the placenta. Although the fetus swallows amniotic fluid that contains immunoglobulin, it is unknown whether this transfer also occurs via the fetal intestine. A human FcRn has been identified in the syncytiotrophoblast that mediates the maternofetal transfer of antibody. It has also been identified in human fetal intestine and is postulated to function in IgG transport. We hypothesize that the human fetal intestinal FcRn may play a role in IgG transport from the amniotic fluid into the fetal circulation. The aim of this study was to characterize the distribution of the FcRn along the human fetal intestine. Lysates prepared from human fetal intestine and from a nonmalignant human fetal intestinal epithelial cell line (H4) were subjected to Western blot analysis and probed using anti-FcRn antibodies. A 42-kD band, detected along the human fetal intestine and in H4 cells. Expression of the human FcRn was confirmed with immunohistochemistry. Our study demonstrates the expression of FcRn along the human fetal intestine and in a human nonmalignant fetal intestinal epithelial cell line (H4), which by location indicates that FcRn could play a role in the uptake and transport of IgG in the human fetus. C1 Massachusetts Gen Hosp, Musosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Childrens Hosp, Sch Med, Intestinal Cell Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Brandeis Univ, WM Keck Inst Cellular Visualizat, Rosentiel Ctr Basic Biomed Sci, Waltham, MA 02254 USA. Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Musosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, 114,16th St 114-3503, Charlestown, MA 02129 USA. FU NICHD NIH HHS [R01 HD031852, R37-HD12437, R37 HD012437-20, R01 HD031852-06, R01-HD 31852, R37 HD012437]; NIDDK NIH HHS [T32 DK007477, P30 DK040561, P30 DK040561-06, P30-DK40561, P01-DK 33506, P01 DK033506-140001, P01 DK033506, T32 DK007477-15, T32-DK07477] NR 27 TC 64 Z9 65 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD FEB PY 2003 VL 53 IS 2 BP 295 EP 301 DI 10.1203/01.PDR.0000047663.81816.E3 PG 7 WC Pediatrics SC Pediatrics GA 637KW UT WOS:000180511100015 PM 12538789 ER PT J AU Co, JPT Ferris, TG Marino, BL Homer, CJ Perrin, JM AF Co, JPT Ferris, TG Marino, BL Homer, CJ Perrin, JM TI Are hospital characteristics associated with parental views of pediatric inpatient care quality? SO PEDIATRICS LA English DT Article DE quality of care; children; patient experience; academic health centers; hospital characteristics ID PATIENT SATISFACTION; ADVERSE EVENTS; MORTALITY AB Objective. Patient assessments of care are increasingly being considered an important dimension of quality of care. Few studies have examined the types and extent of problems identified by parents in the care of hospitalized children and whether hospital characteristics are associated with some of these problems. The objective of this study was to describe the quality of pediatric inpatient care as perceived by parents of hospitalized children and test whether hospital characteristics (academic status, market competition, freestanding children's hospital) are associated with variations in quality. Methods. We performed a cross-sectional analysis of surveys from 6030 parents of children who were discharged for a medical condition from 38 hospitals that used the Picker Institute's Pediatric Inpatient Survey. The Pediatric Inpatient Survey measures 7 dimensions of inpatient care quality: partnership, coordination, information to parent, information to child, physical comfort, confidence and trust, and continuity and transition. Our main outcome measures included an overall quality of care rating (1=poor, 5=excellent), as well as overall and dimension-specific problem scores (0=no problems, 100=problems with 100% of processes asked about in the survey). We used Pearson correlation to determine the strength of association between the overall quality of care rating and dimension problem scores. We tested for associations between hospital characteristics and problem scores using linear regression models, controlling for patient health status and other socioeconomic status variables. Results. Parents on average rated their child's care as very good (mean: 4.2) but reported problems with 27% of the survey's hospital process measures. Information to the child (33%) and coordination of care (30%) had the highest problem rates. Parent communication problems correlated most strongly with overall quality of care ratings (r = -0.49). Parents of children who were hospitalized at academic health centers (AHCs) reported 4% more problems overall (29.8% vs 25.5%) and almost 9% more problems with coordination of care (34.1% vs 25.6%) compared with those at non-AHCs. Parents in more competitive markets reported almost 3% more problems than those in the less competitive ones (28.9% vs 26.3%). The freestanding children's hospital classification was not associated with overall problem scores. We found wide variation in problem scores by hospital, even among AHCs. Hospital and patient characteristics explained only 6% of the variance in problem scores. Conclusions. Despite high subjective ratings of quality of care, measures of specific processes of care reveal significant variations among hospitals and identify areas with opportunities for improvement. Improving the quality of communication with the parent of a hospitalized child may have the most positive impact on a hospital's overall quality of care rating. AHCs and hospitals in more competitive markets may be more prone to problems. With wide variation in parental perceptions of hospital quality of care, a systems analysis of individual hospitals may provide strategies for hospitals to deliver higher quality care. C1 Harvard Univ, Sch Med, Dept Pediat, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02115 USA. PHT Corp, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Co, JPT (reprint author), MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Ste 901, Boston, MA 02114 USA. FU AHRQ HHS [T32HS00063] NR 30 TC 47 Z9 48 U1 1 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2003 VL 111 IS 2 BP 308 EP 314 DI 10.1542/peds.111.2.308 PG 7 WC Pediatrics SC Pediatrics GA 640VR UT WOS:000180709100029 PM 12563056 ER PT J AU Furukawa, O Hirokawa, M Guth, PH Engel, E Kaunitz, JD AF Furukawa, O Hirokawa, M Guth, PH Engel, E Kaunitz, JD TI Role of protein kinases on acid-induced duodenal bicarbonate secretion in rats SO PHARMACOLOGY LA English DT Article DE bicarbonate; duodenum; epithelial cells; protein kinase A; protein kinase C; tyrosine kinase; PMA; acid ID GASTRODUODENAL HCO3 TRANSPORT; GUINEA-PIG; CHOLINERGIC REGULATION; MUCOSAL PROTECTION; ALKALINE RESPONSE; RECEPTOR; CELLS; PROSTAGLANDINS; COTRANSPORTER; STIMULATION AB We examined the effect of several protein kinase inhibitors, such as staurosporine for protein kinase C (PKC), H-89 for protein kinase A (PKA) and genistein for tyrosine kinase (TK) on acid-induced duodenal bicarbonate secretion (DBS) in rats. HCO3- secretion was measured using the pH-stat method. Mucosal acidification was performed by perfusing the duodenal loop for 10 min with pH 2.2 HCl. Indomethacin, staurosporine and genistein were added to acidified saline and then perfused, respectively. In some cases, genistein and phorbol 12-myristate 13-acetate (PMA) were added to the luminal solution to examine the effect on basal duodenal HCO3- secretion. PGE(2) (PKA pathway) and PMA (PKC pathway) stimulate basal DBS. Indomethacin, H-89, staurosporine and genistein inhibit acid-induced DBS, indicating involvement of the cyclooxygenase, PKA, PKC and TK pathways. Copyright (C) 2003 S. Karger AG, Basel. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. CURE Digest Dis Res Ctr, 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. NR 33 TC 3 Z9 3 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 J9 PHARMACOLOGY JI Pharmacology PD FEB PY 2003 VL 67 IS 2 BP 99 EP 105 DI 10.1159/000067740 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641KN UT WOS:000180744100007 PM 12566854 ER PT J AU Konradi, C Heckers, S AF Konradi, C Heckers, S TI Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE schizophrenia; glutamate; neuroplasticity; neurotoxicity; antipsychotic drugs; neuropathology ID METHYL-D-ASPARTATE; LONG-TERM-MEMORY; ATYPICAL ANTIPSYCHOTIC-DRUGS; D-2 RECEPTOR OCCUPANCY; CEREBRAL VENTRICULAR ENLARGEMENT; CHRONIC HALOPERIDOL TREATMENT; EXCITATORY AMINO-ACIDS; MEDIAL TEMPORAL-LOBE; PROTEIN-KINASE-II; TREATMENT-RESISTANT SCHIZOPHRENIA AB The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system. (C) 2002 Elsevier Science Inc. All rights reserved. C1 McLean Hosp, Charles D Baker Lab Neuroplast, Mailman Res Ctr, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Konradi, C (reprint author), McLean Hosp, Charles D Baker Lab Neuroplast, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIDA NIH HHS [DA07134, R01 DA007134, R01 DA007134-14] NR 369 TC 198 Z9 209 U1 5 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD FEB PY 2003 VL 97 IS 2 BP 153 EP 179 DI 10.1016/S0163-7258(02)00328-5 PG 27 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 644ZT UT WOS:000180952300004 PM 12559388 ER PT J AU Ouedraogo, GD Redmond, RW AF Ouedraogo, GD Redmond, RW TI Secondary reactive oxygen species extend the range of photosensitization effects in cells: DNA damage produced via initial membrane photosensitization SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Society-for-Photobiology CY JUL, 2002 CL QUEBEC CITY, CANADA SP Amer Soc Photobiol ID INDUCED LIPID-PEROXIDATION; HUMAN SKIN FIBROBLASTS; PHOTODYNAMIC THERAPY; SINGLET OXYGEN; COMET ASSAY; SUBCELLULAR-LOCALIZATION; CELLULAR UPTAKE; STRAND BREAKS; PHOTOFRIN-II; REPAIR AB The type-II photosensitization process is mediated by the formation of singlet oxygen (O-2[(1)Delta(g)]). The short lifetime of this species dictates that chemical reactions with biological substrates can only occur when O-2((1)Delta(g)) is in very close proximity to the photosensitizer itself. In this study, deuteroporphyrin, a type-II, membrane-localized photosensitizer, was used to generate O-2((1)Delta(g)) in human lymphoblast WTK-1 cells, and the range of influence was determined by a variety of biological assays. Surprisingly, the initial membrane-confined events were shown, by comet assay, to induce DNA damage in these cells. DNA damage was inhibited both by membrane-localized (alpha-tocopherol acetate) and by cytoplasmic (trolox) free radical scavengers. Comet formation also was inhibited by treatment at low temperature. DNA fragmentation was not influenced by treatment with the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, showing that apoptosis was not responsible for fragmentation. Taken together, these results show that primary photosensitization reactions involving O-2((1)Delta(g)), even when tightly confined in extranuclear locations, leads to the production of secondary reactive oxygen species, probably as a result of lipid peroxidation, that can act at greater distances from the photosensitizer itself. These experiments were carried out under conditions where cell survival was significant and raise questions regarding DNA damage and mutagenesis pathways, even when extranuclear O-2((1)Delta(g))-generating compounds are used. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, W-224, Boston, MA 02114 USA. FU NCI NIH HHS [5 R01 CA68524-04] NR 70 TC 52 Z9 54 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD FEB PY 2003 VL 77 IS 2 BP 192 EP 203 DI 10.1562/0031-8655(2003)077<0192:SROSET>2.0.CO;2 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 644NK UT WOS:000180924200012 PM 12785059 ER PT J AU Rudkin, GH Carlsen, BT Miller, TA AF Rudkin, GH Carlsen, BT Miller, TA TI Nasolabial flap reconstruction of large defects of the lower lip SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID LONGUS FREE-FLAP; ADVANCEMENT FLAP; CHIN C1 Univ Calif Los Angeles, Sch Med, Div Plast & Reconstruct Surg, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Miller, TA (reprint author), Univ Calif Los Angeles, Sch Med, Div Plast & Reconstruct Surg, 200 Med Plaza,Suite 465, Los Angeles, CA 90024 USA. NR 28 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2003 VL 111 IS 2 BP 810 EP 817 DI 10.1097/01.PRS.0000040468.61171.30 PG 8 WC Surgery SC Surgery GA 642HR UT WOS:000180798600049 PM 12560704 ER PT J AU Goldstein, MG Niaura, R Willey, C Kazura, A Rakowski, W DePue, J Park, E AF Goldstein, MG Niaura, R Willey, C Kazura, A Rakowski, W DePue, J Park, E TI An academic detailing intervention to disseminate physician-delivered smoking cessation counseling: smoking cessation outcomes of the Physicians Counseling Smokers Project SO PREVENTIVE MEDICINE LA English DT Article DE tobacco use disorder; smoking cessation; practice guidelines; primary health care; physicians; education; professional education; family practice; general practice ID EXPERT-SYSTEM INTERVENTION; PRIMARY-CARE PHYSICIANS; POPULATION-BASED SURVEY; RANDOMIZED-TRIAL; PREVENTIVE CARE; TRAINING PHYSICIANS; PRIVATE PRACTICES; HEALTH PROMOTION; PROGRAM; QUIT AB Background. Little is known about the effectiveness of interventions to disseminate smoking cessation interventions among a population of primary care physicians. This study's objective was to determine the effect of a community-based academic detailing intervention on the quit rates of a population-based sample of smokers. Methods. This community-based, quasi-experimental study involved representative samples of 259 primary care physicians and 4295 adult smokers. An academic detailing intervention was delivered to physicians in intervention areas over a period of 15 months. Analyses were performed on the data from the 2346 subjects who reported at least one physician visit over 24 months. Multivariate regression analyses were conducted to determine the impact of the intervention on self-reported smoking quit rates, reported by adjusted odds ratios. Results. Among smokers reporting a physician visit during the study period, there was a borderline significant effect for those residing in intervention areas versus control areas (OR = 1.35; 95% CI .99-1.83; P = 0.057). Among a subgroup of 819 smokers who reported a visit with an enrolled physician, we observed a significant effect for those residing in intervention areas (OR = 1.80; 95% CI 1.16-2.75; P = 0.008). Conclusion. An academic detailing intervention to enhance physician delivered smoking cessation counseling is an effective strategy for disseminating smoking cessation interventions among community-based practices. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 Bayer Inst Hlth Care Commun, West Haven, CT 06516 USA. Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI USA. Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI USA. Univ Rhode Isl, Coll Pharm, Kingston, RI 02881 USA. Rhode Isl Hosp, Div Child & Adolescent Psychiat, Providence, RI 02903 USA. Brown Univ, Sch Med, Dept Community Hlth, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Goldstein, MG (reprint author), Bayer Inst Hlth Care Commun, 400 Morgan Lane, West Haven, CT 06516 USA. EM michael.goldstein.b@bayer.com FU NCI NIH HHS [P01 CA 50087] NR 54 TC 35 Z9 35 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD FEB PY 2003 VL 36 IS 2 BP 185 EP 196 DI 10.1016/S0091-7435(02)00018-X PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 650KD UT WOS:000181261700008 PM 12590994 ER PT J AU Dobscha, SK Anderson, TA Hoffman, WF Winterbottom, SM Turner, EH Snodgrass, LS Hauser, P AF Dobscha, SK Anderson, TA Hoffman, WF Winterbottom, SM Turner, EH Snodgrass, LS Hauser, P TI Strategies to decrease costs of prescribing selective serotonin reuptake inhibitors at a VA medical center SO PSYCHIATRIC SERVICES LA English DT Article ID OF-VETERANS-AFFAIRS; HEALTH-CARE COSTS; DEPRESSION; ANTIDEPRESSANTS; DISORDERS; SAVINGS AB Objective: The authors examined the efficacy of a multifaceted intervention designed to contain the cost of prescribing selective serotonin reuptake inhibitors (SSRIs) to inpatients and outpatients served by a Veterans Affairs (VA) medical center. Methods: Elements of the intervention included identification of a preferred agent, tablet splitting, education and feedback for prescribers, and an electronic record and ordering system to facilitate changes in prescriber behaviors. VA databases were searched for information on use and costs of antidepressants. Results: Over 35 months the number of patients treated with SSRIs and the amount spent on SSRIs increased. However, the mean monthly cost per patient decreased from $57.12 to $42.19. The projected cost savings over the 35 months was approximately $700,000; one-fourth of the savings was due to tablet splitting and three-fourths to changes in the proportions of the various SSRIs prescribed. A survey of the top 75 antidepressant prescribers showed that after the educational interventions, 91 percent were aware that citalopram was the medical center's preferred antidepressant, and 59 percent identified it as their own preferred first-line treatment. Discussion and conclusions: The results suggest that multifaceted interventions can influence antidepressant costs through provider education and changes in pharmacy and computerized information processes, resulting in substantial cost savings for institutions. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Behav Hlth & Clin Neurosci Div, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Hosp & Specialty Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland Ctr Evaluat Clin Serv, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, POB 1034,P3MHDC, Portland, OR 97207 USA. EM dobschas@ohsu.edu OI Turner, Erick/0000-0002-3522-3357 NR 25 TC 10 Z9 10 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD FEB PY 2003 VL 54 IS 2 BP 195 EP 200 DI 10.1176/appi.ps.54.2.195 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BH UT WOS:000222757800011 PM 12556600 ER PT J AU Davis, TM Bush, KR Kivlahan, DR Dobie, DJ Bradley, KA AF Davis, TM Bush, KR Kivlahan, DR Dobie, DJ Bradley, KA TI Screening for substance abuse and psychiatric disorders among women patients in a VA health care system SO PSYCHIATRIC SERVICES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ALCOHOL-USE DISORDERS; PROBLEM DRINKING; FEMALE VETERANS; HEAVY DRINKING; PREVALENCE; POPULATION; SYMPTOMS; SMOKING; IDENTIFICATION AB Objective: This study of women Veterans Affairs (VA) health care patients screened for the prevalence of past-year smoking, hazardous and problem drinking, other drug abuse, and psychiatric disorders. Methods. A survey was mailed to women veterans who had received care from VA Puget Sound Health Care System between October 1, 19965 and January 1, 1998. Screening measures included questions about cigarettes; questions from the Alcohol Use Disorders Identification Test about consumption (hazardous drinking); the TWEAK test (problem drinking); a drug abuse screen; the Patient Health Questionnaire (psychiatric conditions); and the PTSD (posttramnatic stress disorder) Checklist. Results: Of eligible patients, 1,257 (65 percent) returned surveys with complete substance use data. Patients reported a relatively high rate of past-year smoking (29.1 percent) and hazardous drinking, problem drinking, or both (31.1 percent). The rate of past-year drug use was much lower (4.9 percent). Younger age was strongly associated with greater substance abuse: 59 percent of women under age 35 screened positive for smoking, hazardous or problem drinking, or drug abuse. Screening positive for a psychiatric condition (N=504) was also associated with substance abuse: The rate of past-year drug abuse among women screening positive for a psychiatric condition (9.7 percent) was double the rate for the entire sample; Of the women who screened positive for depression, PTSD, eating disorders, or panic disorders, 57 percent screened positive for substance abuse (including smoking). Conclusions: Substance abuse is common among women VA patients and is associated with younger age and with screening positive for other psychiatric conditions. Providers are expected to follow up on positive screening tests, and these data indicate, substantial provider burden. C1 Univ Washington, Ctr Excellence Subst Abuse Treatment, Seattle, WA 98195 USA. Univ Washington, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98195 USA. Univ Washington, Hlth Serv Res & Dev Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Davis, TM (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, S116ATC,1660 S Columbian Way, Seattle, WA 98108 USA. EM tania.davis@med.va.gov FU NIAAA NIH HHS [K23AA00313] NR 43 TC 45 Z9 45 U1 6 U2 10 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD FEB PY 2003 VL 54 IS 2 BP 214 EP 218 DI 10.1176/appi.ps.54.2.214 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BH UT WOS:000222757800014 PM 12556603 ER PT J AU Curtin, HD AF Curtin, HD TI Superior semicircular canal dehiscence syndrome and multi-detector row CT SO RADIOLOGY LA English DT Editorial Material DE computed tomography; multi-detector row; computed tomography; thin-section; ear, abnormalities; editorials; temporal bone, abnormalities; temporal bone ID PRESSURE-INDUCED VERTIGO; TULLIO PHENOMENON; SOUND; SYMPTOMS C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Curtin, HD (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. EM hugh_curtin@med.harvard.edu NR 12 TC 35 Z9 36 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 FEB PY 2003 VL 226 IS 2 BP 312 EP 314 DI 10.1148/radiol.2262021327 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 639YC UT WOS:000180657000005 PM 12563121 ER PT J AU Gervais, DA McGovern, F Arellano, RS McDougal, WS Mueller, PR AF Gervais, DA McGovern, F Arellano, RS McDougal, WS Mueller, PR TI Renal cell carcinoma: Clinical experience and technical success with radio-frequency ablation of 42 tumors SO RADIOLOGY LA English DT Article DE computed tomography (CT) guidance; kidney, interventional procedures; kidney neoplasms, therapy; radiofrequency (RF) ablation; ultrasound (US), guidance ID RADIOFREQUENCY TISSUE ABLATION; INTERSTITIAL THERMAL ABLATION; HEPATOCELLULAR-CARCINOMA; COAGULATION NECROSIS; LIVER METASTASES; CANCER; ELECTRODE; MALIGNANCIES; LESIONS; TRIAL AB PURPOSE: To evaluate clinical experience with percutaneous image-guided radio-frequency (RF) ablation of renal cell carcinoma (RCC) and to assess factors that may influence technical success. MATERIALS AND METHODS: Thirty-four patients who underwent RF ablation of 42 RCC tumors during a 3.5-year period were evaluated. Overlapping ablations were performed on the basis of tumor size and geometry. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. With the exception of those patients with renal insufficiency, who were followed up with unenhanced and gadolinium-enhanced magnetic resonance imaging, patients were followed up with unenhanced and contrast material-enhanced computed tomography. Univariate analysis of the results was performed with the Fisher exact test to assess the effect of tumor size and location on technical success. P less than or equal to .05 was considered to represent a significant difference. Complications and the management and outcomes of the complications were recorded. RESULTS: All 29 exophytic tumors (mean size, 3.2 cm; size range, 1.1-5.0 cm) were completely ablated, as were two parenchymal tumors. The remaining 11 tumors had a component in the renal sinus. For large (>3.0 cm) tumors, presence of a tumor component in the renal sinus was a significant negative predictor of technical success (P = .004); only five of these 11 tumors were completely treated, compared with 11 of 11 tumors without a renal sinus component. A similar analysis was not possible for small tumors because no small tumors involved the renal sinus. Four complications occurred in a total of 54 ablation sessions: one minor hemorrhage, two major hemorrhages, and one ureteral stricture. CONCLUSION: RF ablation of RCC can be successful in exophytic RCC tumors up to 5.0 cm in size. Tumors larger than 3.0 cm with a component in the renal sinus are more difficult to treat but can be ablated successfully. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. NR 28 TC 264 Z9 275 U1 1 U2 8 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 FEB PY 2003 VL 226 IS 2 BP 417 EP 424 DI 10.1148/radiol.2262012062 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 639YC UT WOS:000180657000019 PM 12563135 ER PT J AU Livraghi, T Solbiati, L Meloni, MF Gazelle, GS Halpern, EF Goldberg, SN AF Livraghi, T Solbiati, L Meloni, MF Gazelle, GS Halpern, EF Goldberg, SN CA Collaborative Italian Grp Cooltip TI Treatment of focal liver tumors with percutaneous radio-frequency ablation: Complications encountered in a multicenter study SO RADIOLOGY LA English DT Article DE liver neoplasms, CT; liver neoplasms, MR; liver neoplasms, therapy; liver neoplasms, US; radiofrequency (RF) ablation ID RADIOFREQUENCY TISSUE ABLATION; QUALITY IMPROVEMENT GUIDELINES; SMALL HEPATOCELLULAR-CARCINOMA; ETHANOL INJECTION; COAGULATION NECROSIS; HEPATIC METASTASES; ELECTRODE; CIRRHOSIS; CANCER AB PURPOSE: To report complications encountered by members of a collaborative group who performed radio-frequency (RF) ablation in patients with focal liver cancer. MATERIALS AND METHODS: Members of 41 Italian centers that were part of a collaborative group used a percutaneous internally cooled RF ablation technique and a standardized protocol for follow-up. They completed a questionnaire regarding number of deaths, presumed cause of death, and likelihood of its relationship to the RF procedure; number and types of major complications; and types of minor complications and side effects. Enrollment included 2,320 patients with 3,SS4 lesions (size, 3.1 cm +/- 1.1 [SD] in diameter): 1,610 had hepatocellular carcinoma with chronic liver disease; 693 had metastases, predominantly from colorectal cancer (n = 501); and 17 had cholangiocellular carcinoma. Number and characteristics of complications (ie, deaths and major and minor complications) attributed to the procedure were reported. Data were subsequently analyzed with analysis of variance to determine whether the major complication rate was related to tumor size, number of ablation sessions, or electrode type (single or cluster). RESULTS: In total, 3,554 lesions were treated. Six deaths (0.3%) were noted, including two caused by multiorgan failure following intestinal perforation; one case each of septic shock following Staphylococcus aureus-caused peritonitis, massive hemorrhage following tumor rupture, liver failure following stenosis of right bile duct; and one case of sudden death of unknown cause 3 days after the procedure. Fifty (2.2%) patients had additional major complications. The most frequent of these were peritoneal hemorrhage, neoplastic seeding, intrahepatic abscesses, and intestinal perforation. An increased number of RF sessions were related to a higher rate of major complications (P < .01), whereas the number of complications was not significantly different when tumor size or electrode type were compared. Minor complications were observed in less than 5% of patients. CONCLUSION: Results of this study confirm that RF ablation is a relatively low-risk procedure for the treatment of focal liver tumors. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Osped Civile, Dept Radiol, Vimercate, Italy. Osped Gen, Dept Ultrasound & Intervent, Busto Arsizio, Italy. Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. OI meloni, maria franca/0000-0001-7485-7400; Solbiati, Luigi/0000-0002-3109-1449 NR 29 TC 699 Z9 774 U1 3 U2 41 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 FEB PY 2003 VL 226 IS 2 BP 441 EP 451 DI 10.1148/radiol.2262012198 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 639YC UT WOS:000180657000022 PM 12563138 ER PT J AU Benjamin, MS Drucker, EA McLoud, TC Shepard, JAO AF Benjamin, MS Drucker, EA McLoud, TC Shepard, JAO TI Small pulmonary nodules: Detection at chest CT and outcome SO RADIOLOGY LA English DT Article DE lung, CT; lung, nodule; lung neoplasms ID LUNG-CANCER AB PURPOSE: To determine the outcome of pulmonary nodules less than 1 cm in diameter detected at chest computed tomography (CT). MATERIALS AND METHODS: Reports of chest CT performed during 6 months were reviewed to find patients with pulmonary nodules smaller than I cm in long axis for which repeat CT was recommended. Records were studied to determine whether follow-up had been performed, the initial nodules had changed in size, or nodules had been resected. RESULTS: A total of 3,446 chest CT examinations were performed, with 334 patients meeting inclusion criteria. Three patients underwent nodule resection and had pathologic examination results positive for cancer; 185 underwent follow-up, of whom 13 had results excluded as indeterminate. In the remaining 172 patients, 88 had incomplete characterization because of follow-up of less than 2 years, which left 84 with nodule characterization at follow-up. When these 84 patients were combined with the three patients with nodule resection, the number yielded was 87 patients. Seventy-seven of 87 had benign nodules because of resolution or 2-year stability, and 10 of 87 had malignant nodules because of growth or positive histologic examination results. Nine of 10 with malignant nodules had a known primary neoplasm. CONCLUSION: CT commonly helped identify small nodules. Increase in size occurred infrequently and almost exclusively in patients with a known malignancy. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Benjamin, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders House 2-202B, Boston, MA 02114 USA. NR 12 TC 55 Z9 56 U1 0 U2 3 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 FEB PY 2003 VL 226 IS 2 BP 489 EP 493 DI 10.1148/radiol.2262010556 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 639YC UT WOS:000180657000028 PM 12563144 ER PT J AU Hershey, JC Asch, DA Jepson, C Baron, J Ubel, PA AF Hershey, JC Asch, DA Jepson, C Baron, J Ubel, PA TI Incremental and average cost-effectiveness ratios: Will physicians make a distinction? SO RISK ANALYSIS LA English DT Article DE cost-effectiveness analysis; incremental cost effectiveness; average cost effectiveness; medical screening; medical decision making ID MAIL SURVEYS; CANCER AB Physicians are increasingly asked to use cost-effectiveness information when evaluating alternative health care interventions. Little is known about how the way such information is presented can influence medical decision making. We presented physicians with hypothetical screening scenarios with multiple options, varying the type of cost-effectiveness ratios provided as well as whether the scenarios described cancer screening settings that were familiar or unfamiliar. Half the scenarios used average cost-effectiveness ratios, as commonly reported, calculating benefits and costs relative to a no-screening option. The other half used the preferred incremental cost-effectiveness ratios, with each option's benefits and costs calculated relative to the next best alternative. Relative to average cost-effectiveness ratios, incremental cost-effectiveness information significantly reduced preference for the most expensive screening strategies in two of three unfamiliar scenarios. No such difference was found for familiar scenarios, for which physicians likely have established practice patterns. These results suggest that, in unfamiliar settings, average cost-effectiveness ratios as reported in many analyses reported in the literature can hide the often high price for achieving incremental health care goals, potentially causing physicians to choose interventions with poor cost effectiveness. C1 Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ann Arbor, MI 48109 USA. VAMC, Program Improving Hlth Care Decis, Ann Arbor, MI USA. RP Hershey, JC (reprint author), Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. FU NCI NIH HHS [R01-CA78052-01] NR 19 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 2003 VL 23 IS 1 BP 81 EP 89 DI 10.1111/1539-6924.00291 PG 9 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 679AN UT WOS:000182899000007 PM 12635724 ER PT J AU Gregory, RC Taniguchi, T D'Andrea, AD AF Gregory, RC Taniguchi, T D'Andrea, AD TI Regulation of the Fanconi anemia pathway by monoubiquitination SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE Fanconi anemia; monoubiquitin; DNA repair; ataxia telangiectasia ID DNA-DAMAGE RESPONSE; NUCLEAR-COMPLEX; LIGASE ACTIVITY; S-PHASE; BRCA1; PROTEINS; PHOSPHORYLATION; REPAIR; CANCER; UBIQUITINATION AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome characterized by multiple congenital anomalies. bone marrow failure, and cellular sensitivity to mitomycin C (MMC). To date, six FA genes have been cloned, and the encoded proteins function in a novel pathway. The FA pathway is required for the normal cellular response to DNA damage. Following DNA damage. the pathway is activated, leading to monoubiquitination of the FA protein. FANCD2, and its targeting to subnuclear foci. Disruption of the FA pathway results in the absence of FANCD2 nuclear foci, leading to the cellular and clinical abnormalities of FA. Here, we review the recent studies describing the regulated monoubiquitination of the FANCD2 protein and discuss the interaction of the FA pathway with other DNA damage response pathways. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. NR 41 TC 47 Z9 48 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD FEB PY 2003 VL 13 IS 1 BP 77 EP 82 AR PII S1044-579X(02)00102-5 DI 10.1016/S1044-579X(02)00102-5 PG 6 WC Oncology SC Oncology GA 639EC UT WOS:000180613800009 PM 12507559 ER PT J AU Sattler, M Salgia, R AF Sattler, M Salgia, R TI Molecular and cellular biology of small cell lung cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; GASTRIN-RELEASING PEPTIDE; C-KIT PROTOONCOGENE; PROTEIN-KINASE-C; PHOSPHOINOSITIDE 3-KINASE INHIBITION; SUSCEPTIBILITY GENE-PRODUCT; FACTOR SCATTER FACTOR; IN-VIVO ALTERATIONS; MET PROTOONCOGENE; TUMOR-SUPPRESSOR C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med Oncol, Dana Farber Canc Inst,Div Thorac Oncol Program, Boston, MA 02115 USA. RP Sattler, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana 730B,44 Binney St, Boston, MA 02115 USA. NR 156 TC 43 Z9 49 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 2003 VL 30 IS 1 BP 57 EP 71 DI 10.1053/sonc.50019 PG 15 WC Oncology SC Oncology GA 673VX UT WOS:000182601900007 PM 12635090 ER PT J AU Hajduk, IA Strollo, PJ Jasani, RR Atwood, CW Houck, PR Sanders, MH AF Hajduk, IA Strollo, PJ Jasani, RR Atwood, CW Houck, PR Sanders, MH TI Prevalence and predictors of nocturia in obstructive sleep apnea-hypopnea syndrome - a retrospective study SO SLEEP LA English DT Article DE nocturia; obstructive sleep apnea-hypopnea syndrome; sleep disorders ID POSITIVE AIRWAY PRESSURE; ATRIAL-NATRIURETIC-PEPTIDE; POPULATION-BASED SURVEY; URINARY-INCONTINENCE; MEN; SYMPTOMS; AGE; COMMUNITY; HYPERTENSION; ASSOCIATION AB Objective: To determine the prevalence and predictors of pathological nocturia (PN) in patients with OSAHS. Methods: Retrospective review of clinical and polysomnographic data obtained from patients evaluated at the Pulmonary Sleep Evaluation Center of the University of Pittsburgh Medical Center between November 1998 and September 1999. PN was defined as two or more urination events per night. OSAHS was defined as Apnea-Hypopnea Index (AHI)greater than or equal to5. Group t-tests and Chi-square test were used to examine differences in subjects with and without PN. A multivariate approach utilizing logistic regression was performed to examine the relationships between polysomnographic variables [Arousal Index (ARI), AHI, Apnea-Hypopnea Time/Total Sleep Time x 100(%) (AHT/TST), % Total Sleep Time (TST)<90% Oxyhemoglobin Saturation (SpO(2)), nadir SpO(2), Desaturation Event Frequency (average number of desaturations > 4% per hour sleep) (DEF)] and the presence of PN, while controlling for medical co-morbidities. Data are expressed as mean + SD unless otherwise specified. Statistical significance was assessed at p < 0.05. Results: Study population: n = 138 (50 females, 88 males), age: 49.7 +/- 12.3 years, BMI [Body Mass Index (kg/m(2))]: 37.7 +/- 11.3. The overall prevalence of PN was 47.8%. The prevalence of PN was greater in females (60% vs. 40.9% in males). OSAHS patients with PN had a higher prevalence of peripheral edema, higher BMI, a greater %TST <90% SpO(2), lower nadir SpO(2) and greater DEF. The logistic regression model indicated that age, ARI, AHI, AHT/TST, %TST <90%, DEF were significant predictors of PN independent of BMI, neck circumference and medical co-morbidities. Conclusions: Our data confirm that PN is common in OSAHS patients. The strongest predictors are age and selected polysomnographic variables reflecting OSAHS severity. C1 Univ Pittsburgh, Med Ctr, Pulm Sleep Evaluat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Sleep & Chronobiol Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Pulm Sleep Disorders Program, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pulm Sect, Pittsburgh, PA USA. RP Sanders, MH (reprint author), Montefiore Univ Hosp, Div Pulm Allergy & Crit Care Med, NW 628,3459 5th Ave, Pittsburgh, PA 15213 USA. EM sandersmh@msx.upmc.edu NR 43 TC 32 Z9 32 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD FEB 1 PY 2003 VL 26 IS 1 BP 61 EP 64 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 658MM UT WOS:000181724800013 PM 12627734 ER PT J AU Moskowitz, MA Lo, EH AF Moskowitz, MA Lo, EH TI Neurogenesis and apoptotic cell death SO STROKE LA English DT Editorial Material DE apoptosis; caspases; growth factors; neurogenesis; stem cells ID BRAIN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprot Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprot Res Lab, 149 13th St,Rm 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [5 R01 NS374141, NS10828, R01 NS37074, R01 NS38731, R01 NS40529] NR 25 TC 37 Z9 44 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2003 VL 34 IS 2 BP 324 EP 326 DI 10.1161/01.STR.0000054047.14853.AD PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 645AT UT WOS:000180954600002 PM 12574524 ER PT J AU Fox, CS Polak, JF Chazaro, I Cupples, A Wolf, PA D'Agostino, RA O'Donnell, CJ AF Fox, CS Polak, JF Chazaro, I Cupples, A Wolf, PA D'Agostino, RA O'Donnell, CJ TI Genetic and environmental contributions to atherosclerosis phenotypes in men and women - Heritability of carotid intima-media thickness in the Framingham Heart Study SO STROKE LA English DT Article DE epidemiology; genetics; intima-media thickness ID WALL SHEAR-STRESS; CONVERTING-ENZYME GENOTYPES; NHLBI FAMILY HEART; RISK-FACTORS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR HEALTH; OLDER ADULTS; GENOME SCAN; ARTERY; DISEASE AB Background and Purpose-Carotid intima-media thickness (IMT) is a quantitative measure of subclinical atherosclerosis that is predictive of subsequent myocardial infarction and stroke. There is controversy regarding the proportion of variability in IMT explained by genetic factors. Thus, it is uncertain whether carotid IMT is a heritable trait that can be used in genetic studies. Methods-From 1996 to 1998, we measured carotid IMT in 906 men (mean age, 56.7 years) and 980 women (mean age, 57.4 years) from 586 extended families (1630 sib pairs) in the Framingham Offspring cohort. B-mode carotid ultrasonography was used to define mean and maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA). Correlation coefficients were calculated in pairs of siblings. Variance component methods were used to estimate heritability with crude, age-and sex-adjusted, and multivariable-adjusted normalized deviates. Results-Multivariable-adjusted correlation coefficients for mean CCA and ICA IMT were 0.16 and 0.16, respectively. Crude, age-and sex-adjusted, and multivariable-adjusted heritabilities were 0.67, 0.44, and 0.38 for the mean CCA IMT (all P<0.001) and 0.43, 0.37, and 0.35 for the mean ICA IMT (all P<0.001). For CCA IMT, 27% of the overall variance was due to measured covariates; 38% was due to heritable factors. Conclusions-These data suggest that a substantial proportion of the variability in carotid IMT is explained by genetic factors. Further studies of genetic linkage and candidate gene association are warranted to identify specific genetic variants predisposing to subclinical atherosclerosis and stroke. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Dept Biostat & Epidemiol, Boston, MA 02215 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-25195]; NINDS NIH HHS [5R01-NS17950-20] NR 44 TC 134 Z9 136 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2003 VL 34 IS 2 BP 397 EP 401 DI 10.1161/01.STR.0000048214.56981.6F PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 645AT UT WOS:000180954600031 PM 12574549 ER PT J AU Barker, CR Warshaw, A AF Barker, CR Warshaw, A TI Jonathan E. Rhoads, 1907-2002 SO SURGERY LA English DT Article C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Barker, CR (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT 506, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 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 FEB PY 2003 VL 133 IS 2 BP 133 EP 134 DI 10.1067/msy.2003.81 PG 2 WC Surgery SC Surgery GA 651QR UT WOS:000181332500002 PM 12605172 ER PT J AU Liu, V Mihm, MC AF Liu, V Mihm, MC TI Pathology of malignant melanoma SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID PRIMARY CUTANEOUS MELANOMA; INTERCELLULAR-ADHESION MOLECULE-1; TUMOR-INFILTRATING LYMPHOCYTES; POLYMERASE CHAIN-REACTION; EPITHELIOID CELL NEVUS; SENTINEL LYMPH-NODES; EARLY-STAGE MELANOMA; SPITZ-NEVUS; PROGNOSTIC-SIGNIFICANCE; MICROSCOPIC SATELLITES AB Understanding the fundamental aspects of the pathology of melanoma is crucial for the surgeon to deliver optimal care to the patient with melanoma. Pathology provides diagnostic data, offers prognostic information, and, to a large extent, directs management. This article reviews several aspects of the pathology of melanoma, with special relevance to the surgeon, including benign clinicopathologic simulators of melanoma, fundamental concepts of the pathology of melanoma, histopathologic prognostic factors of melanoma, approach to lymph nodes, and implications of the revised staging system. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. RP Liu, V (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Warren 829,55 Fruit St, Boston, MA 02114 USA. NR 94 TC 16 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2003 VL 83 IS 1 BP 31 EP + DI 10.1016/S0039-6109(03)00003-3 PG 31 WC Surgery SC Surgery GA 661YN UT WOS:000181917900003 PM 12691449 ER PT J AU Stylopoulos, N Gazelle, GS Rattner, DW AF Stylopoulos, N Gazelle, GS Rattner, DW TI A cost-utility analysis of treatment options for inguinal hernia in 1,513,008 adult patients SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE inguinal hernia; laparoscopy; mortality; treatment; decision analysis; Markov model ID RANDOMIZED CONTROLLED TRIAL; TENSION-FREE HERNIOPLASTY; DAY SURGICAL-PROCEDURE; POSTOPERATIVE PAIN; SHOULDICE REPAIR; CLINICAL-TRIAL; TRANSABDOMINAL PREPERITONEAL; LAPAROSCOPIC HERNIOPLASTY; MULTICENTER TRIAL; HEALTH OUTCOMES AB Background: The controversial issue of the cost-effectiveness of laparoscopic inguinal hernia repair is examined, employing a decision analytic method. Materials and methods: The NSAS, NHDS (National Center for Health Statistics), HCUP-NIS (Agency for Healthcare Research and Quality) databases and 51 randomized controlled trials were analyzed. The study group constituted of a total of 1,513,008 hernia repairs. Projection of the clinical, economic, and quality-of-life outcomes expected from the different treatment options was done by using a Markov Monte Carlo decision model. Two logistic regression models were used to predict the probability of hospital admission after an ambulatory procedure and the probability of death after inguinal hernia repair. Four treatment strategies were modeled: (1) laparoscopic repair (LR), (2) open mesh (OM), (3) open non-mesh (ONM), and (4) expectant management. Costs were expressed in US dollars and effectiveness in quality-adjusted life years (QALYs). The main outcome measures were the average and the incremental cost-effectiveness (ICER) ratios. Results: Compared to the expectant management, the incremental cost per QALY gained was $605 ($4086, 9.04 QALYs) for LR, $697 ($4290, 8.975 QALYs) for OM, and $1711 ($6200, 8.546 QALYs) for ONM. In sensitivity analysis the two major components that affect the cost-effectiveness ratio of the different types of repair were the ambulatory facility cost and the recurrence rate. At a LR ambulatory facility cost of $5526 the ICER of LR compared to OM surpasses the threshold of $50,000/QALY. Conclusions: On the basis of our assumptions this mathematical model shows that from a societal perspective laparoscopic approach can be a cost-effective treatment option for inguinal hernia repair. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 75 TC 40 Z9 41 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD FEB PY 2003 VL 17 IS 2 BP 180 EP 189 DI 10.1007/s00464-002-8849-z PG 10 WC Surgery SC Surgery GA 644RF UT WOS:000180932600002 PM 12415334 ER PT J AU Lee, CR Grodzinsky, AJ Spector, M AF Lee, CR Grodzinsky, AJ Spector, M TI Modulation of the contractile and Biosynthetic activity of chondrocytes seeded in collagen-glycosaminoglycan matrices SO TISSUE ENGINEERING LA English DT Article ID SMOOTH-MUSCLE ACTIN; HUMAN ARTICULAR CHONDROCYTES; IN-VITRO; DIHYDROCYTOCHALASIN-B; CARTILAGE DIFFERENTIATION; CANINE CHONDROCYTES; RETINOIC ACID; STROMAL CELLS; CROSS-LINKING; STAUROSPORINE AB Studies have demonstrated that articular chondrocytes can express the gene for alpha-smooth muscle actin (SMA) and can contract porous polymeric matrices employed for tissue engineering, thereby altering the pore structure and distorting the shape of the scaffold. The objectives of this study were to determine whether an agent known to disrupt microfilament organization in chondrocytes could reduce this contractility and to assess whether there was an association between the contractile behavior of chondrocytes and their biosynthetic activity. Staurosporine, an antibiotic known to inhibit protein kinase C and disrupt cytoskeletal structure, was used as the agent to modulate the chondrocytic phenotype and contractile and biosynthetic activity of serially passaged adult canine chondrocytes seeded in type 1 collagen-glycosaminoglycan scaffolds. Cells in monolayer culture treated with as little as 3 nM staurosporine for 4 days contained type II procollagen, whereas few cells in the untreated control cultures demonstrated type II procollagen synthesis. Treatment with staurosporine also led to a decrease in the amount of SMA synthesized by the cells. Consistent with this decreased expression of the contractile actin isoform, cells cultured in the collagen-glycosaminoglycan scaffolds and treated with 5 nM staurosporine contracted the scaffold significantly less than untreated cells (15% diameter contraction by treated cells, compared with more than 50% contraction by untreated cells). The staurosporine-treated cells were biosynthetically active, displaying higher rates of protein and glycosaminoglycan synthesis, as indicated by rates of incorporation of [H-3] proline and [S-35] sulfate, respectively, compared with untreated cells. The long-held notion that changes in cytoskeletal structure influence phenotypic characteristics of cultured chondrocytes may now be extended to relate expression of a specific muscle actin isoform to certain cell processes. Moreover, the finding that chondrocytes with a lower level of expression of SMA and reduced contractility display higher rates of biosynthesis warrants further study. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Dept Elect Engn, Cambridge, England. VA Boston Healthcare Syst, Tissue Engn, Boston, MA USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, 75 Francis St,MRB 106, Boston, MA 02115 USA. NR 43 TC 29 Z9 30 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD FEB PY 2003 VL 9 IS 1 BP 27 EP 36 DI 10.1089/107632703762687500 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 646RM UT WOS:000181048100003 PM 12625951 ER PT J AU Lewandrowski, KU Hile, DD Thompson, BMJ Wise, DL Tomford, WW Trantolo, DJ AF Lewandrowski, KU Hile, DD Thompson, BMJ Wise, DL Tomford, WW Trantolo, DJ TI Quantitative measures of osteoinductivity of a porous poly(propylene fumarate) bone graft extender SO TISSUE ENGINEERING LA English DT Article ID CEMENT; HYDROXYAPATITE; SUBSTITUTE; CULTURE; DEFECTS; FOAMS; RATS AB Bioresorbable bone graft substitutes could alleviate disadvantages associated with the use of autografts, allografts, and other synthetic materials. However, little is known about the minimum autograft/ extender ratio for a given material at which a sufficient osteoinductive effect is still seen. Therefore, we investigated a bioresorbable bone graft substitute made from the unsaturated polyester poly( propylene fumarate), PPF, at various mixing ratios with autograft. The bone graft extender is cross-linked in the presence of a hydroxylapatite filler and effervescent foaming agents citric acid and sodium bicarbonate. The porous bone graft extender material develops porosity in vivo by generating carbon dioxide during the effervescent reaction, resulting in foam formation and expansion with respective pore sizes of 50 to 1000 mm. In an attempt to determine how much cancellous autograft bone could be extended with the poly( propylene fumarate) material and at which ratio the autograft/ extender combination remained supportive of the overall structural integrity of the repairing defect site, we studied the amount of new bone formation on implantation of the materials in 3-mm holes made in the anteromedial tibial metaphysis of Sprague-Dawley rats. The extender formulation was analyzed at high autograft/ extender (75% autograft/ 25% extender) and low autograft/ extender (25% autograft/ 75% extender) mixing ratios and compared with negative (extender alone) and positive (autograft alone) controls. Animals from each of the formulations were killed in groups of eight at 6 weeks postoperatively. Hence, a total of 32 animals were included in this study. Histologic analysis of the healing process revealed enhanced in vivo osteoinduction with the bone graft extender regardless of the autograft loading. Histomorphometry did not show any statistically significant difference between the high and low autograft/ extender ratios. All formulations maintained implant integrity and did not provoke sustained inflammatory responses. This study suggested that the presence of even a small amount of autograft within the polymer-based bone graft extender results in significant enhancement of osteoinduction. This finding has immediate applicability to the development of bone graft extender formulations for clinical use. C1 Massachusetts Gen Hosp, Orthoped Res Labs, Boston, MA 02114 USA. Albany Med Coll, Albany, NY 12208 USA. Cambridge Sci Inc, Cambridge, MA 02138 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [1 R43 AR46970, AR 45062] NR 23 TC 8 Z9 8 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD FEB PY 2003 VL 9 IS 1 BP 85 EP 93 DI 10.1089/107632703762687564 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 646RM UT WOS:000181048100009 PM 12625957 ER PT J AU Afting, M Stock, UA Nasseri, B Pomerantseva, I Seed, B Vacanti, JP AF Afting, M Stock, UA Nasseri, B Pomerantseva, I Seed, B Vacanti, JP TI Efficient and stable retroviral transfection of ovine endothelial cells with green fluorescent protein for cardiovascular tissue engineering SO TISSUE ENGINEERING LA English DT Article ID PULMONARY-ARTERY; LONG-TERM; TRANSPLANTATION; ORIGIN AB To determine whether cellular components of tissue-engineered cardiovascular structures are derived from cells harvested and seeded onto an acellular scaffold, or from cells originating from surrounding tissue (e.g., proximal and distal anastomosis), cellular retroviral transfection with green fluorescent protein (GFP) was used. Ovine endothelial cells (ECs) were transfected with a Moloney murine leukemia virus (Mo-MuLV)-based retroviral vector expressing GFP. Transfection was evaluated by fluorescence microscopy and fluorescence-activated cell sorting. The rate of transfection of the primary cells was 33.4% for ECs, 48 hours after transfection. Stable transfection could be observed for at least 25 subsequent passages. Retroviral transfection with GFP enables stable and reliable long-term labeling of ovine ECs. This approach might offer an attractive pathway to study tissue development, with emphasis on distinguishing between cellular components initially seeded onto a construct and those occurring as a result of cell ingrowth from surrounding tissue. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Lab Tissue Engn & Organ Fabricat, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-97-005] NR 15 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD FEB PY 2003 VL 9 IS 1 BP 137 EP 141 DI 10.1089/107632703762687618 PG 5 WC Cell & Tissue Engineering SC Cell Biology GA 646RM UT WOS:000181048100014 PM 12625962 ER PT J AU Marty-Roix, R Bartlett, JD Spector, M AF Marty-Roix, R Bartlett, JD Spector, M TI Growth of porcine enamel-, dentin-, and cementum-derived cells in collagen-glycosaminoglycan matrices in vitro: expression of alpha-smooth muscle actin and contraction SO TISSUE ENGINEERING LA English DT Article ID BIOSYNTHETIC ACTIVITY; CROSS-LINKING; IN-VITRO; REGENERATION; CHONDROCYTES; FIBROBLASTS AB The objective of the study was to investigate the behavior of porcine enamel, dentin, and cementum cells, isolated from tissue digests and growing out from explants, in monolayer culture and in a collagen-glycosaminoglycan (GAG) matrix for tissue engineering. A notable finding of the study was the expression of a contractile muscle actin isoform, alpha-smooth muscle actin (SMA), by each cell type and their contraction of the collagen-GAG scaffold. Of importance was the immunohistochemical demonstration that the majority of ameloblasts and odontoblasts in vivo contained SMA. Western blot analysis demonstrated the presence of SMA in all of the cell types. A large amount of SMA was found in the odontoblasts after the first passage. SMA expression in the enamel- and cementum-derived cells appeared to increase with time in culture and with passage number. The implications of this finding for tissue engineering and the possible roles for SMA in dental tissue cells are discussed. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Harvard Univ, Sch Dent Med, Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Tissue Engn, Boston, MA USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, MRB 106,75 Francis St, Boston, MA 02115 USA. FU NIDCR NIH HHS [P01 DE013237] NR 23 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD FEB PY 2003 VL 9 IS 1 BP 175 EP 186 DI 10.1089/107632703762687654 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 646RM UT WOS:000181048100018 PM 12625966 ER PT J AU Stipp, CS Kolesnikova, TV Hemler, ME AF Stipp, CS Kolesnikova, TV Hemler, ME TI Functional domains in tetraspanin proteins SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID EXTRACELLULAR DOMAIN; CD9-DEFICIENT MICE; PLASMA-MEMBRANE; GAMETE FUSION; CELL MOTILITY; GROWTH-FACTOR; MAJOR CD9; INTEGRIN; CD81; ASSOCIATION AB Exciting new findings have emerged about the structure, function and biochemistry of tetraspanin proteins. Five distinct tetraspanin regions have now been delineated linking structural features to specific functions. Within the large extracellular loop of tetraspanins, there is a variable region that mediates specific interactions with other proteins, as well as a more highly conserved region that has been suggested to mediate homodimerization. Within the transmembrane region, the four tetraspanin transmembrane domains are probable sites of both intra- and inter-molecular interactions that are crucial during biosynthesis and assembly of the network of tetraspanin-linked membrane proteins known as the 'tetraspanin web'. In the intracellular juxtamembrane region, palmitoylation of cysteine residues also contributes to tetraspanin web assembly, and the C-terminal cytoplasmic tail region could provide specific functional links to cytoskeletal or signaling proteins. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. NR 56 TC 256 Z9 264 U1 4 U2 22 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 2003 VL 28 IS 2 BP 106 EP 112 AR PII S0968-0004(02)00014-2 DI 10.1016/S0968-0004(02)00014-2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648MK UT WOS:000181155000010 PM 12575999 ER PT J AU Freedland, SJ Sutter, ME Dorey, F Aronson, WJ AF Freedland, SJ Sutter, ME Dorey, F Aronson, WJ TI Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy SO UROLOGY LA English DT Article ID BIOCHEMICAL RECURRENCE; RADIATION-THERAPY; CANCER RECURRENCE; RADIOTHERAPY; RISK; PROGRESSION; BIOPSY; RACE AB Objectives. To determine the ideal cutpoint for defining prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Although various cutpoints have been used, a recent study suggested that 0.4 ng/mL may be the most appropriate. Methods. A retrospective survey of 358 men undergoing RP at the West Los Angeles Veterans Affairs Medical Center between 1991 and 2001 was undertaken. The 3-year and 5-year risk of PSA recurrence was estimated by Kaplan-Meier analyses using various cutpoints of postoperative PSA to define recurrence: greater than 0.1, greater than 0.2, greater than 0.3, greater than 0.4, and greater than 0.5 ng/mL. The 1 and 3-year risk of PSA progression after a detectable PSA level (PSA rising to a higher cutpoint) was evaluated for each definition of PSA recurrence using Kaplan-Meier analyses. Multivariate analysis using a Cox proportional hazards model was used to determine the clinical variables that were significant independent predictors of PSA recurrence at each cutpoint. Results. For patients with a detectable postoperative PSA value from 0.11 to 0.2 ng/mL, the 1 and 3-year risk of PSA progression was 64% (95% confidence interval [CI] 46% to 82%) and 93% (95% CI 74% to 99%), respectively. For patients with a PSA value from 0.21 to 0.3 ng/mL, the I and 3-year risk of PSA progression was 86% (95% CI 69% to 97%) and 100% (95% CI 87% to 100%), respectively. The use of higher PSA cutpoints to define recurrence resulted in a lower 5-year risk of PSA recurrence. The 5-year risk of PSA recurrence using a greater than 0.1 ng/mL cutpoint resulted in a 43% (95% Cl 36% to 50%) risk of recurrence compared with only 23% (95% CI 18% to 30%) for a greater than 0.5 ng/mL cutpoint. In multivariate analysis, PSA and biopsy Gleason score were significant independent predictors of biochemical recurrence, regardless of the definition of PSA recurrence used (P less than or equal to 0.002). Conclusions. PSA and biopsy Gleason score were significant predictors of biochemical failure, regardless of the definition of failure used. However, the definition of PSA recurrence dramatically affected the perceived success of therapy. Patients with a postoperative PSA value greater than 0.2 ng/mL are at very high risk of developing an additional rise in PSA. On the basis of this finding, a PSA value greater than 0.2 ng/mL is an appropriate cutpoint to define PSA recurrence after RP. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA USA. Univ Calif Davis, Sch Med, Dept Emergency Med, Davis, CA 95616 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. NR 19 TC 152 Z9 160 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2003 VL 61 IS 2 BP 365 EP 369 DI 10.1016/S0090-4295(02)02268-9 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 648NN UT WOS:000181157600023 PM 12597949 ER PT J AU Addona, GH Sandermann, H Kloczewiak, MA Miller, KW AF Addona, GH Sandermann, H Kloczewiak, MA Miller, KW TI Low chemical specificity of the nicotinic acetylcholine receptor sterol activation site SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE acetylcholine receptor; reconstitution; gating; cholesterol; steroid specificity ID MEMBRANE LIPID-COMPOSITION; BINDING-SITES; CHOLESTEROL; PERMEABILITY; MODULATION; PROBE AB The nicotinic acetylcholine receptor (nAcChoR) has an absolute requirement for cholesterol if agonist-stimulated channel opening is to occur [Biochemistry 25 (1986) 830]. Certain non-polar analogs could replace cholesterol in vectorial vesicle permeability assays. Using a stopped-flow fluorescence assay to avoid the limitations of permeability assays imposed by vesicle morphology, it was shown that polar conjugates of cholesterol could also satisfy the sterol requirement [Biochim. Biophys. Acta 1370 (1998) 299]. Here this assay is used to explore the chemical specificity of sterols. Affinity-purified nAcChoRs from Torpedo were reconstituted into bilayers at mole ratios of 58:12:30 [1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dioleoyl-sn-glycero-3-phosphate (DOPA)/steroid]. When the enantiomer of cholesterol was used, or when the stereochemistry at the 3-hydroxy group was changed from beta to alpha by substituting epicholesterol for cholesterol, activation was still supported. The importance of cholesterol's planar ring structure was tested by comparing planar cholestanol (5alpha-cholestan-3beta-ol) with nonplanar coprostanol (5beta-cholestan-3beta-ol). Both supported activation. Thus, these steroids support activation independent of structural features known to be important for modulation of lipid bilayer properties. This provides indirect support for a steroid binding site possessing very lax structural requirements. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Biochem Pflanzenpathol, D-85764 Neuherberg, Germany. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Edwards 505,Blossom St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM 58448] NR 26 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JAN 31 PY 2003 VL 1609 IS 2 BP 177 EP 182 DI 10.1016/S0005-2736(02)00685-5 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 640MW UT WOS:000180693400007 PM 12543379 ER PT J AU Tritos, NA Mastaitis, JW Kokkotoua, EG Puigserver, P Spiegelman, BM Maratos-Flier, E AF Tritos, NA Mastaitis, JW Kokkotoua, EG Puigserver, P Spiegelman, BM Maratos-Flier, E TI Characterization of the peroxisome proliferator activated receptor coactivator 1 alpha (PGC 1 alpha) expression in the murine brain SO BRAIN RESEARCH LA English DT Article DE peroxisome proliferator activated receptor coactivator 1 alpha (PGC-1 alpha); adaptive thermogenesis; mitochondria; brain; in situ hybridization; leptin ID PPAR-GAMMA COACTIVATOR-1; MITOCHONDRIAL BIOGENESIS; HEPATIC GLUCONEOGENESIS; ADAPTIVE THERMOGENESIS; TRANSCRIPTION; ATTENTION; PEPTIDES AB The peroxisome proliferator activated receptor coactivator 1 alpha (PGC-1alpha) is a nuclear transcriptional coactivator that is expressed in brown adipose tissue, brain, heart and kidney as well as cold-exposed skeletal muscle. In liver, white and brown adipose tissue, PGC-1alpha expression is regulated in a manner suggesting a role in energy homeostasis. To characterize PGC-1alpha expression in the rodent brain and to determine brain PGC-1alpha regulation, we used in situ hybridization histochemistry in C57B1/6J mice and Sprague-Dawley rats. We found that PGC-1alpha is widely expressed in brain areas, including in the olfactory bulb, cerebral cortex, the diagonal band of Broca, the medial septal nucleus, reticular thalamic nucleus, the striatum and globus pallidus, the hippocampus, the substantia nigra, the mesencephalic nucleus of the trigeminal nerve, the cochlear nucleus and the superior olivary complex. In contrast, PGC-1alpha expression was absent in the hypothalamus. To evaluate PGC-1alpha expression under different physiologic states in these various brain areas, we examined expression with fasting, leptin treatment and cold exposure (4 h at 4 degreesC) and found no change, nor was expression changed in the brain of the leptin-deficient ob/ob mice and the hyperleptinemic UCP-DTA mice. Hence, PGC-1alpha is widely expressed in the rodent brain, but is not regulated by states of caloric deficiency, leptin, obesity or cold exposure. Its functional role in the brain requires further study. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02215 USA. RP Tritos, NA (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. FU NIDDK NIH HHS [5R01DK53978, 5R01DK56113] NR 23 TC 24 Z9 25 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 JAN 31 PY 2003 VL 961 IS 2 BP 255 EP 260 AR PII S0006-8993(02)03961-6 DI 10.1016/S0006-8993(02)03961-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 641QL UT WOS:000180756800008 PM 12531492 ER PT J AU Longas, MO Garg, HG Trinkle-Pereira, JM Hales, CA AF Longas, MO Garg, HG Trinkle-Pereira, JM Hales, CA TI Heparin antiproliferative activity on bovine pulmonary artery smooth muscle cells requires both N-acetylation and N-sulfonation SO CARBOHYDRATE RESEARCH LA English DT Article ID STRUCTURAL DETERMINANTS; PROLIFERATION; GLYCOSAMINOGLYCANS; CAPACITY; INHIBIT AB The antiproliferative activity of Heparin (HP) on bovine pulmonary artery smooth muscle cells (BPASMC) in vitro requires both N-acetylation and N-sulfonation. This was demonstrated by quantifying the relative N-acetylation of three commercial heparins of known antiproliferative activities, using their Fourier-transform infrared (FTIR) band areas at 1381-1378 and 1320-1317 cm(-1), which combined resulted in 1.0, 1.0 and 1.3 cm(2) for Choay, Elkins-Sinn and Upjohn HP, respectively. These results show that Upjohn HP, which is at least 44% more antiproliferative than the other two, is 30% more N-acetylated. Upjohn HP was also N-desulfonated chemically, and its antiproliferative activity was determined. Its total sulfonate (-SO3-) content (O-and N-sulfonate) was quantified using the FTIR band area at 1260-1200 cm(-1) for the S=O stretching; a drop in sulfonate content from 21.87% (w/w) before N-desulfonation to 16.51% (w/w) after N-desulfonation, resulted in a 67% decrease in its inhibitory potency. In addition to the requirement that similar to24% of the sulfonate content be bonded to N, the data show a direct correlation between the extent of Upjohn HP N-acetylation and its antiproliferative activity on BPASMC. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Purdue Univ Calumet, Dept Chem & Phys, Hammond, IN 46323 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA. RP Longas, MO (reprint author), Purdue Univ Calumet, Dept Chem & Phys, Hammond, IN 46323 USA. FU NHLBI NIH HHS [HL 39150] NR 12 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JAN 31 PY 2003 VL 338 IS 3 BP 251 EP 256 AR PII S0008-6215(02)00441-X DI 10.1016/S0008-6215(02)00441-X PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 643PG UT WOS:000180869200005 PM 12543557 ER PT J AU Lee, YH Giraud, J Davis, RJ White, MF AF Lee, YH Giraud, J Davis, RJ White, MF TI c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASE; RECEPTOR SUBSTRATE-1 IRS-1; NH2-TERMINAL KINASE; TYROSINE PHOSPHORYLATION; GLUCOSE-TRANSPORT; MICE LACKING; FACTOR-ALPHA; RESISTANCE; OBESITY AB Activation of the c-Jun N-terminal kinase (JNK) by proinflammatory cytokines inhibits insulin signaling, at least in part, by stimulating phosphorylation of rat/mouse insulin receptor substrate 1 (Irs1) at Ser(307) (Ser(312) in human IRS1). Here we show that JNK mediated feedback inhibition of the insulin signal in mouse embryo fibroblasts, 3T3-L1 adipocytes, and 32D(IR) Cells. Insulin stimulation of JNK activity required phosphatidylinositol 3-kinase and Grb2 signaling. Moreover, activation of JNK by insulin was inhibited by a cell-permeable peptide that disrupted the interaction of JNK with cellular proteins. However, the direct binding of JNK to Irs1 was not required for its activation by insulin, whereas direct binding was required for Ser(307) phosphorylation of Irs1. Insulin-stimulated Ser(307) phosphorylation was reduced 80% in cells lacking JNK1 and JNK2 or in cells expressing a mutant Irs1 protein lacking the JNK binding site. Reduced Ser(307) phosphorylation was directly related to increased insulin-stimulated tyrosine phosphorylation, Akt phosphorylation, and glucose uptake. These results support the hypothesis that JNK is a negative feedback regulator of insulin action by phosphorylating Ser(307) in Irs1. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Howard Hughes Med Inst,Program Mol Med, Worcester, MA 01605 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK32520, DK38712, DK63368] NR 65 TC 242 Z9 253 U1 0 U2 11 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 JAN 31 PY 2003 VL 278 IS 5 BP 2896 EP 2902 DI 10.1074/jbc.M208359200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 644JW UT WOS:000180915000018 PM 12417588 ER PT J AU Curtain, CC Ali, FE Smith, DG Bush, AI Masters, CL Barnham, KJ AF Curtain, CC Ali, FE Smith, DG Bush, AI Masters, CL Barnham, KJ TI Metal ions, pH, and cholesterol regulate the interactions of Alzheimer's disease amyloid-beta peptide with membrane lipid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID A-BETA; PROTEIN; ZINC; PHOSPHOLIPIDS; AGGREGATION; VESICLES; NEUROTOXICITY; PRESENILIN-1; COMPLEXES; CHANNELS AB The interaction of Abeta peptides with the lipid matrix of neuronal cell membranes plays an important role in the pathogenesis of Alzheimer's disease. By using EPR and CD spectroscopy, we found that in the presence of Cu2+ or Zn2+, pH, cholesterol, and the length of the peptide chain influenced the interaction of these peptides with lipid bilayers. In the presence of Zn2+, Abeta40 and Abeta42 both inserted into the bilayer over the pH range 5.5-7.5, as did Abeta42 in the presence of Cu2+. However, Abeta40 only penetrated the lipid bilayer in the presence of Cu2+ at pH 5.5-6.5; at higher pH there was a change in the Cu2+ coordination sphere that inhibited membrane insertion. In the absence of the metals, insertion of both peptides only occurred at pH < 5.5. Raising cholesterol to 0.2 mol fraction of the total lipid inhibited insertion of both peptides under all conditions investigated. Membrane insertion was accompanied by the formation of alpha-helical structures. The nature of these structures was the same irrespective of the conditions used, indicating a single low energy structure for Abeta in membranes. Peptides that did not insert into the membrane formed beta-sheet structures on the surface of the lipid. C1 Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Int Victoria, Parkville, Vic 3052, Australia. Monash Univ, Sch Phys & Mat Engn, Clayton, Vic 3800, Australia. Univ Melbourne, Sch Chem, Parkville, Vic 3010, Australia. Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Lab Oxidat Biol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. RP Barnham, KJ (reprint author), Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RI Bush, Ashley/A-1186-2007; OI Bush, Ashley/0000-0001-8259-9069; Curtain, Cyril/0000-0001-6955-320X FU NIA NIH HHS [2R01AG12686] NR 44 TC 140 Z9 145 U1 3 U2 24 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 JAN 31 PY 2003 VL 278 IS 5 BP 2977 EP 2982 DI 10.1074/jbc.M205455200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 644JW UT WOS:000180915000028 PM 12435742 ER PT J AU Laybutt, DR Glandt, M Xu, G Ahn, YB Trivedi, N Bonner-Weir, S Weir, GC AF Laybutt, DR Glandt, M Xu, G Ahn, YB Trivedi, N Bonner-Weir, S Weir, GC TI Critical reduction in beta-cell mass results in two distinct outcomes over time - Adaptation with impaired glucose tolerance or decompensated diabetes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED INSULIN-SECRETION; FREE FATTY-ACIDS; LACTATE-DEHYDROGENASE; CHRONIC HYPERGLYCEMIA; INTRAVENOUS GLUCOSE; PANCREATIC-ISLETS; GENE-EXPRESSION; C-MYC; RAT; HOMEOBOX AB We have proposed that hyperglycemia-induced dedifferentiation of beta-cells is a critical factor for the loss of insulin secretory function in diabetes. Here we examined the effects of the duration of hyperglycemia on gene expression in islets of partially pancreatectomized (Px) rats. Islets were isolated, and mRNA was extracted from rats 4 and 14 weeks after Px or sham Px surgery. Px rats developed different degrees of hyperglycemia; low hyperglycemia was assigned to Px rats with fed blood glucose levels less than 150 mg/dl, and high hyperglycemia was assigned above 150 mg/dl. beta-Cell hypertrophy was present at both 4 and 14 weeks. At the same time points, high hyperglycemia rats showed a global alteration in gene expression with decreased mRNA for insulin, IAPP, islet-associated transcription factors (pancreatic and duodenal homeobox-1, BETA2/NeuroD, Nkx6.1, and hepatocyte nuclear factor 1alpha), beta-cell metabolic enzymes (glucose transporter 2, glucokinase, mitochondrial glycerol phosphate dehydrogenase, and pyruvate carboxylase), and ion channels/pumps (Kir6.2, VDCCbeta, and sarcoplasmic reticulum. Ca2+-ATPase 3). Conversely, genes normally suppressed in beta-cells, such as lactate dehydrogenase-A, hexokinase 1, glucose-6-phosphatase, stress genes (heme oxygenase-1, A20, and Fas), and the transcription factor c-Myc, were markedly increased. In contrast, gene expression in low hyperglycemia rats was only minimally changed at 4 weeks but significantly changed at 14 weeks, indicating that even low levels of hyperglycemia induce beta-cell dedifferentiation over time. In addition, whereas 2 weeks of correction of hyperglycemia completely reverses the changes in gene expression of Px rats at 4 weeks, the changes at 14 weeks were only partially reversed, indicating that the phenotype becomes resistant to reversal in the long term. In conclusion, chronic hyperglycemia induces a progressive loss of beta-cell phenotype with decreased expression of beta-cell-associated genes and increased expression of normally suppressed genes, these changes being present with even minimal levels of hyperglycemia. Thus, both the severity and duration of hyperglycemia appear to contribute to the deterioration of the beta-cell phenotype found in diabetes. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NCRR NIH HHS [2U42 RR16606-02]; NIDDK NIH HHS [DK-35449]; PHS HHS [36836] NR 51 TC 112 Z9 118 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 2003 VL 278 IS 5 BP 2997 EP 3005 DI 10.1074/jbc.M210581200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 644JW UT WOS:000180915000031 PM 12438314 ER PT J AU Babcock, GJ Farzan, M Sodroski, J AF Babcock, GJ Farzan, M Sodroski, J TI Ligand-independent dimerization of CXCR4, a principal HIV-1 coreceptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-COUPLED RECEPTORS; CHEMOKINE RECEPTORS; PARAMAGNETIC PROTEOLIPOSOMES; MEMBRANE-PROTEINS; CRYSTAL-STRUCTURE; PRIMARY INFECTION; FACTOR-I; TYPE-1; BINDING AB CXCR4, a member of the G protein-coupled receptor family of proteins, is the receptor for stromal cell-derived factor (SDF-1alpha) and is a principal coreceptor for human immunodeficiency virus type 1 (HIV-1). CXCR4 has also been implicated in breast cancer metastasis. We examined the ability of CXCR4 to homomultimerize in detergent-solubilized cell lysates and in the membranes of intact cells. CXCR4 was found to multimerize in cell lysates containing the detergents CHAPSO or Cymal-7 but not other detergents that have been shown to disrupt the native conformation of CXCR4. CXCR4 expression levels did not affect the observed multimerization and differentially tagged CXCR4 molecules associated only when coexpressed in the same cell. CXCR4 did not interact with CCR5, the other principal HIV-1 coreceptor, when the two proteins were coexpressed. Using bioluminescence resonance energy transfer (BRET2), we demonstrated that CXCR4 multimers are found naturally in the intact cell membrane, in both the presence and absence of multiple CXCR4 ligands. Ligand binding did not significantly alter the observed BRET2 signal, suggesting that CXCR4 exists as a constitutive oligomer. In cell lysates prepared with non-denaturing detergents, CXCR4 sedimented in a manner consistent with a dimer, whereas CCR5 sedimented as a monomer under these conditions. The stable, constitutive dimerization of CXCR4 may contribute to its biological functions in chemokine binding, signaling, and HIV-1 entry. 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. 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 [AI28691, AI41851, AI46725] NR 53 TC 146 Z9 153 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 31 PY 2003 VL 278 IS 5 BP 3378 EP 3385 DI 10.1074/jbc.M210140200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 644JW UT WOS:000180915000078 PM 12433920 ER PT J AU Heinrich, MC Corless, CL Duensing, A McGreevey, L Chen, CJ Joseph, N Singer, S Griffith, DJ Haley, A Town, A Demetri, GD Fletcher, CDM Fletcher, JA AF Heinrich, MC Corless, CL Duensing, A McGreevey, L Chen, CJ Joseph, N Singer, S Griffith, DJ Haley, A Town, A Demetri, GD Fletcher, CDM Fletcher, JA TI PDGFRA activating mutations in gastrointestinal stromal tumors SO SCIENCE LA English DT Article ID C-KIT; IDENTIFICATION; CELLS AB Most gastrointestinal stromal tumors (GISTS) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTS respond well to Gleevec, which inhibits KIT kinase activity. Here we show that similar to35% (14 of 40) of GISTS lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, plate let-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Med, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Pathol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Heinrich, MC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. OI Duensing, Anette/0000-0002-0168-4067 NR 17 TC 1271 Z9 1399 U1 3 U2 32 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 JAN 31 PY 2003 VL 299 IS 5607 BP 708 EP 710 DI 10.1126/science.1079666 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 640KH UT WOS:000180687700047 PM 12522257 ER PT J AU Fischer, H Wright, CI Whalen, PJ McInerney, SC Shin, LM Rauch, SL AF Fischer, H Wright, CI Whalen, PJ McInerney, SC Shin, LM Rauch, SL TI Brain habituation during repeated exposure to fearful and neutral faces: A functional MRI study SO BRAIN RESEARCH BULLETIN LA English DT Article DE amygdala; emotion; facial expressions; hippocampus; human; neuroimaging ID HUMAN AMYGDALA; MEMORY; ATTENTION; STIMULUS; CORTEX; PET AB Central nervous system habituation in humans was studied using functional magnetic resonance imaging and repeated presentations of single fearful and neutral faces. Habituation of blood-oxygenation-level-dependent (BOLD) signal during exposure to face stimuli, collapsed over fearful and neutral expressions, was evident in the right amygdala and hippocampus, as well as in the medial/inferior temporal cortex bilaterally. In the hippocampus, significantly greater habituation was evident on the right as compared to the left side, which could reflect the visual nature of the stimuli. There were no time by expression interaction effects in these regions, suggesting similar neural attenuation rates to fearful and neutral face stimuli. These results indicate that brain regions involved in novelty detection and memory processing habituate at similar rates regardless of whether the face in focus displays an aversive emotional expression or not. (C) 2002 Published by Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Bldg 149,13th St,9th Floor, Charlestown, MA 02129 USA. RI Frank, David/E-8213-2012 FU NIMH NIH HHS [MH-60219] NR 27 TC 145 Z9 148 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JAN 30 PY 2003 VL 59 IS 5 BP 387 EP 392 AR PII S0361-9230(02)00940-1 DI 10.1016/S0361-9230(02)00940-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 635YR UT WOS:000180428200008 PM 12507690 ER PT J AU Mikkola, HKA Klintman, J Yang, HD Hock, H Schlaeger, TM Fujiwara, Y Orkin, SH AF Mikkola, HKA Klintman, J Yang, HD Hock, H Schlaeger, TM Fujiwara, Y Orkin, SH TI Haematopoietic stem cells retain long-term repopulating activity and multipotency in the absence of stem-cell leukaemia SCL/tal-1 gene SO NATURE LA English DT Article ID TRANSCRIPTION FACTOR SCL; HEMATOPOIETIC LINEAGES; MICE; PROGENITOR; ERYTHROPOIESIS; MESODERM; PROTEINS; BINDING AB The production of blood cells is sustained throughout the lifetime of an individual by haematopoietic stem cells (HSCs)(1). Specification of HSCs from mesoderm during embryonic development requires the stem cell leukaemia SCL/tal-1 gene product(2-6). Forced expression of SCL/tal-1 strongly induces blood formation in embryos, indicating that this gene has a dominant role in commitment to haematopoiesis(7,8). In the adult haematopoietic system, expression of SCL/tal-1 is enriched in HSCs and multipotent progenitors, and in erythroid and megakaryocytic lineages(9-11), consistent with roles for this factor in adult haematopoiesis. Here we assess by conditional gene targeting whether SCL/tal-1 is required continuously for the identity and function of HSCs. We find that SCL/tal-1 is dispensable for HSC engraftment, self-renewal and differentiation into myeloid and lymphoid lineages; however, the proper differentiation of erythroid and megakaryocytic precursors is dependent on SCL/tal-1. Thus, SCL/tal-1 is essential for the genesis of HSCs, but its continued expression is not essential for HSC functions. These findings contrast with lineage choice mechanisms, in which the identity of haematopoietic lineages requires continuous transcription factor expression(12,13). C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. NR 24 TC 268 Z9 272 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 30 PY 2003 VL 421 IS 6922 BP 547 EP 551 DI 10.1038/nature01345 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 640DB UT WOS:000180670600049 PM 12540851 ER PT J AU Baden, LR Elliott, DD Miseljic, S Ryan, ET Wain, JC AF Baden, LR Elliott, DD Miseljic, S Ryan, ET Wain, JC TI Case 4-2003: A 42-year-old woman with cough, fever, and abnormalities on thoracoabdominal computed tomography - Echinococcus granulosus infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PULMONARY HYDATID-DISEASE; SURGICAL-TREATMENT; PERCUTANEOUS TREATMENT; SEROLOGICAL TESTS; ALBENDAZOLE; DIAGNOSIS; CYSTS; LUNG; LIVER; CT C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Baden, LR (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 39 TC 5 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 30 PY 2003 VL 348 IS 5 BP 447 EP 455 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 639RU UT WOS:000180643800012 PM 12556547 ER PT J AU Chaput, JC Ichida, JK Szostak, JW AF Chaput, JC Ichida, JK Szostak, JW TI DNA polymerase-mediated DNA synthesis on a TNA template SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEIC-ACID STRUCTURE; IN-VITRO SELECTION; CHEMICAL ETIOLOGY; CRYSTAL-STRUCTURE; LARGE FRAGMENT; REPLICATION; MOLECULES; COMPLEX; LIGANDS C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 20 TC 64 Z9 65 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 29 PY 2003 VL 125 IS 4 BP 856 EP 857 DI 10.1021/ja028589k PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 638PN UT WOS:000180579600002 PM 12537469 ER PT J AU Rutter, MK Parise, H Benjamin, EJ Levy, D Larson, MG Meigs, JB Nesto, RW Wilson, PWF Vasan, RS AF Rutter, MK Parise, H Benjamin, EJ Levy, D Larson, MG Meigs, JB Nesto, RW Wilson, PWF Vasan, RS TI Impact of glucose intolerance and insulin resistance on cardiac structure and function - Sex-related differences in the Framingham Heart Study SO CIRCULATION LA English DT Article DE insulin; echocardiography; ventricle, left; hypertrophy, ventricular ID LEFT-VENTRICULAR MASS; DIABETES-MELLITUS; ELDERLY MEN; HYPERTENSION; CARDIOMYOPATHY; TOLERANCE; GEOMETRY; HYPERTROPHY; OBESITY; DISEASE AB Background-Although insulin resistance has been implicated in the pathogenesis of left ventricular (LV) hypertrophy, previous studies have yielded inconsistent results and are limited by referral bias. Methods and Results-We examined the relations between echocardiographic LV measurements and glucose tolerance status in 2623 Framingham Study subjects (1514 women, mean age 53 years) free of myocardial infarction and heart failure. We also evaluated the relations of insulin resistance (homeostasis model, HOMA-IR) and LV and left atrial (LA) measures within the normal and abnormal glucose tolerance categories (the latter included impaired glucose tolerance, impaired fasting glucose, and newly diagnosed diabetes). LV mass (adjusted for age, height, heart rate, and systolic blood pressure) increased across categories of worsening glucose tolerance; the trend was more striking in women (P<0.001) compared with men (P=0.054). In subjects with normal (n=2022) and abnormal glucose tolerance (n=327), covariate-adjusted LV mass and LV wall thickness increased across HOMA-IR quartiles in women (P<0.001) but not men. In contrast, covariate-adjusted LA size increased with worsening glucose tolerance and across HOMA-IR quartiles in the normal and abnormal glucose tolerance groups in both sexes. Adjustment for body mass index considerably attenuated the relations of LV/LA measures and HOMA-IR, rendering them statistically nonsignificant in the normal glucose tolerance group. Conclusions-In our large community-based sample, LV mass and wall thickness increased with worsening glucose intolerance, an effect that was more striking in women compared with men. Insulin resistance was associated with increased LV mass in women alone, but this relation was largely accounted for by obesity. C1 Lahey Clin Fdn, Burlington, MA USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Clin Epidemiol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. OI Larson, Martin/0000-0002-9631-1254; Rutter, Martin/0000-0001-6380-539X; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1K24 HL04334, N01-HC-25195]; NINDS NIH HHS [5R01-NS-17950] NR 26 TC 273 Z9 289 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 28 PY 2003 VL 107 IS 3 BP 448 EP 454 DI 10.1161/01.CIR.0000045671.62860.98 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 642CE UT WOS:000180786100033 PM 12551870 ER PT J AU Kelly, PJ Furie, KL Kistler, JP Barron, M Picard, EH Mandell, R Shih, VE AF Kelly, PJ Furie, KL Kistler, JP Barron, M Picard, EH Mandell, R Shih, VE TI Stroke in young patients with hyperhomocysteinemia due to cystathionine beta-synthase deficiency SO NEUROLOGY LA English DT Article ID FACTOR-V LEIDEN; RISK FACTOR; VASCULAR-DISEASE; NATURAL-HISTORY; HOMOCYSTINURIA; HOMOCYSTEINE; MUTATION; THROMBOSIS; DISSECTION; GENE AB Background: Although hyperhomocyst(e)inemia (Hyper-Hcy) may predispose to atherosclerosis and venous thrombosis, the mechanisms of stroke associated with Hyper-Hcy are not defined. Methods: Clinical and biochemical phenotypes and genetic features of three unrelated patients with premature stroke and severe Hyper-Hcy due to cystathionine beta-synthase (CBS) deficiency are described. Plasma Hey and amino acids were measured by fluorescence polarization immune assay and ion exchange chromatography. Analysis of the CBS and methylenetetrahydrofolate reductase genes was performed by restriction enzyme digestion and sequence analysis. Results: Two of the three index cases had no known diagnosis of homocystinuria and initially presented with embolic cerebral and retinal infarction in mid-adulthood. Mechanisms of cerebrovascular disease were carotid intraluminal thrombosis, arterial dissection, and possible cardiac embolism. Family screening revealed additional members with clinically silent homocystinuria and severe Hyper-Hcy. Excluding tall stature in two individuals, all had mild phenotypes, without classic findings of CBS deficiency. Plasma total and free Hey, methionine, and urine Hey were elevated. Genotyping revealed heterozygous CBS mutations (1278T, D444N, G307S) in affected individuals. Conclusion: Artery-to-artery embolism and dissection may cause stroke in young adults with homocystinuria. The results also support a rationale for screening for Hyper-Hcy in young adults with stroke without a phenotype suggestive of classic homocystinuria. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kelly, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK 802,Fruit St, Boston, MA 02114 USA. NR 23 TC 39 Z9 46 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 28 PY 2003 VL 60 IS 2 BP 275 EP 279 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 639ET UT WOS:000180615200022 PM 12552044 ER PT J AU Caselli, A Rich, J Hanane, T Uccioli, L Veves, A AF Caselli, A Rich, J Hanane, T Uccioli, L Veves, A TI Role of C-nociceptive fibers in the nerve axon reflex-related vasodilation in diabetes SO NEUROLOGY LA English DT Article ID ENDOTHELIAL DYSFUNCTION; SKIN MICROCIRCULATION; PERIPHERAL NEUROPATHY; INSULIN-RESISTANCE; FOOT ULCERATION; RISK AB Objective: To evaluate the role of the C-nociceptive nerve fibers in nerve axon reflex-related vasodilation. Methods: Skin vascular reactivity, in response to iontophoresis of acetylcholine and sodium nitroprusside, was evaluated at both the forearm and the foot levels in 13 diabetic neuropathic (DN),11 nonneuropathic (D), and 9 healthy control (C) subjects. The total and nerve axon reflex-related vasodilation were measured by two single-point laser probes. A topical anesthetic was applied on the contralateral forearm and foot, and all the measurements were repeated. Results: Dermal anesthesia resulted in a reduction of the nerve axon reflex-related vasodilation at the forearm in all three groups (C 70.7 +/- 12%, D 59.7 +/- 7%, and DN 73.5 +/- 14%; percentage of reduction over preanesthesia response, mean +/- SEM; p < 0.001) and at the foot in the two nonneuropathic groups (C 74 +/- 10% and D 68.9 +/- 9%; p < 0.001 versus before anesthesia). This reduction was absent at the foot of the neuropathic patients (DN -4 +/- 21%; p = NS versus before anesthesia). A correlation was found between the nerve axon reflex-related response and measurements of nerve function (neuropathy disability score, r = -0.425, p < 0.017; vibration perception threshold, r = -0.527, p < 0.002; Semmes-Weinstein monofilament perception, r = -0.619, p < 0.001). Conclusion: The nerve axon reflex-related vasodilation is directly related to the function of the C-nociceptive fibers and is significantly associated with other nerve function measurements. As this is an objective measurement, it has the potential to be used as an alternative to currently employed techniques to evaluate small-fiber function. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Microcirlat Lab, Dept Surg,Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Microcirlat Lab, Dept Surg,Joslin Beth Israel Deaconess Foot Ctr, Palmer 317,West Campus,1 Deaconess Rd, Boston, MA 02215 USA. NR 19 TC 40 Z9 40 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 28 PY 2003 VL 60 IS 2 BP 297 EP 300 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 639ET UT WOS:000180615200026 PM 12552048 ER PT J AU Lee, MS Lessell, S AF Lee, MS Lessell, S TI Lithium-induced periodic alternating nystagmus SO NEUROLOGY LA English DT Editorial Material C1 Cleveland Clin Fdn, Cole Eye Inst I32, Cleveland, OH 44195 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Neuroophthalmol Unit, Boston, MA 02115 USA. RP Lee, MS (reprint author), Cleveland Clin Fdn, Cole Eye Inst I32, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 6 TC 11 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 28 PY 2003 VL 60 IS 2 BP 344 EP 344 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 639ET UT WOS:000180615200039 PM 12552061 ER PT J AU Gerling, IC Solomon, SS Bryer-Ash, M AF Gerling, IC Solomon, SS Bryer-Ash, M TI Genomes, transcriptomes, and proteomes - Molecular medicine and its impact on medical practice SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GENE-EXPRESSION; OLD DISEASE; INSULIN; OBESITY; PHARMACOGENETICS; COMPLICATIONS; PATHOGENESIS; DEFICIENCY; TOLERANCE AB The human genome project and the technological breakthroughs it has produced have moved the field of molecular medicine forward with breathtaking speed. This will impact not only the advance of scientific discoveries and the way science is conducted but also the clinical practice of medicine. In this review we explain the basic principles of these new technologies. Their potential use and impact are demonstrated by using diabetes mellitus as an example of a common and serious medical disorder. Finally, several potentially adverse consequences of "excessive" knowledge are discussed. C1 Univ Tennessee, Hlth Sci Ctr, VAMC Res 151, Div Endocrinol,Dept Med, Memphis, TN 38104 USA. Univ Tennessee, Hlth Sci Ctr, Dept Pharmacol, Memphis, TN 38104 USA. Vet Affairs Med Ctr, Res Serv, Memphis, TN USA. Vet Affairs Med Ctr, Med Serv, Memphis, TN USA. Univ Calif Los Angeles, Gonda Diabet Ctr, Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Gerling, IC (reprint author), Univ Tennessee, Hlth Sci Ctr, VAMC Res 151, Div Endocrinol,Dept Med, 1030 Jefferson Ave, Memphis, TN 38104 USA. EM igerling@utmem.edu NR 60 TC 13 Z9 17 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 27 PY 2003 VL 163 IS 2 BP 190 EP 198 DI 10.1001/archinte.163.2.190 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 638YZ UT WOS:000180601900006 PM 12546609 ER PT J AU Pitris, C Bouma, BE Shiskov, M Tearney, GJ AF Pitris, C Bouma, BE Shiskov, M Tearney, GJ TI A GRISM-based probe for spectrally encoded confocal microscopy SO OPTICS EXPRESS LA English DT Article ID HUMAN SKIN AB Spectrally encoded confocal microscopy (SECM) is a novel approach for obtaining high resolution, depth-sectioned images of microstructure within turbid samples. By encoding one spatial dimension in wavelength, imaging probes can be greatly simplified compared to standard scanning confocal microscopes, potentially enabling endoscopic implementation. The use of a diffraction grating for spectral encoding, however, skews the optical axis through the probe, thus complicating the design of narrow diameter instruments. In this Letter, we describe a novel use of a single-optical-axis element based on high index-of-refraction prisms and a transmission holographic grating for the design of narrow diameter SECM devices. Confocal images obtained with a 10.0 mm probe demonstrate a transverse resolution of 1.1 mum and a field of view of 650 mum. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. RP Pitris, C (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. EM tearney@helix.mgh.harvard.edu OI Pitris, Costas/0000-0002-5559-1050 NR 7 TC 25 Z9 26 U1 1 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JAN 27 PY 2003 VL 11 IS 2 BP 120 EP 124 DI 10.1364/OE.11.000120 PG 5 WC Optics SC Optics GA 639NV UT WOS:000180636900006 PM 19461714 ER PT J AU Tavakkolizadeh, A Berger, UV Stephen, AE Kim, BS Mooney, D Hediger, MA Ashley, SW Vacanti, JP Whang, EE AF Tavakkolizadeh, A Berger, UV Stephen, AE Kim, BS Mooney, D Hediger, MA Ashley, SW Vacanti, JP Whang, EE TI Tissue-engineered neomucosa: Morphology, enterocyte dynamics, and SGLT1 expression topography SO TRANSPLANTATION LA English DT Article ID SMALL-BOWEL; INTESTINAL TRANSPLANTATION; CELLS; DIFFERENTIATION; NUTRITION; GROWTH AB Background. The standard therapy for short bowel syndrome is total parenteral nutrition, which is expensive and associated with significant morbidity and mortality. New therapeutic approaches for this disorder are needed. We have applied the techniques of tissue engineering to develop, a prototype neointestine. We hypothesized that anastomosis of this neointestine to the native bowel would result in regeneration of mucosal morphology and enterocyte dynamics. Methods. Biodegradable polymers seeded with neonatal rat intestinal organoid units were implanted into, the omenta of adult rats to form neointestinal cysts. Five weeks after implantation, side-to side cyst-jejunal anastomoses were fashioned in one cohort of rats. Tissues were harvested from all, rats at 5 months after implantation. Native jejunal (J) and non-anastomosed (N-N) and anastomosed (A-N) neointestinal tissues were assessed for morphology, epithelial cell proliferation (5-bromo-2-deoxyuridine immunohistochemistry), apoptotic rates (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay), and SGLT1 in situ hybridization. Results. Mucosal morphology, rates and topography of enterocyte proliferation, and transporter expression in A-N neointestine recapitulated those of native jejunum. Each of these features was rudimentary in N-N neointestine. Conclusions. These results suggest that the tissue-engineered neomucosa can develop structural and dynamic features of the normal jejulnum. Anastomosis to the native intestine is an essential step for neomucosal development. Tissue engineering offers promise as a novel approach to the treatment of patients suffering from short bowel syndrome. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, In Situ Hybridizat Core Facil, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Membrane Biol Program, Boston, MA 02115 USA. RP Whang, EE (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. RI Kim, Byung-Soo/O-2352-2013 FU NHLBI NIH HHS [HL60424]; NIDDK NIH HHS [DK47326, DK02786] NR 24 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 2003 VL 75 IS 2 BP 181 EP 185 DI 10.1097/01.TP.0000044101.03656.9F PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 644EV UT WOS:000180905700003 PM 12548119 ER PT J AU Hagengimana, A Hinton, D Bird, B Pollack, M Pitman, RK AF Hagengimana, A Hinton, D Bird, B Pollack, M Pitman, RK TI Somatic panic-attack equivalents in a community sample of Rwandan widows who survived the 1994 genocide SO PSYCHIATRY RESEARCH LA English DT Article DE panic disorder; stress disorders; post-traumatic; depression; Rwanda; holocaust ID POSTTRAUMATIC-STRESS-DISORDER; ATAQUES-DE-NERVIOS; BHUTANESE REFUGEES; PTSD CHECKLIST; PUERTO-RICO; PREVALENCE; TRAUMA; SYMPTOMS; DISASTER; COMORBIDITY AB The present study is the first to attempt to determine rates of panic attacks, especially 'somatically focused' panic attacks, panic disorder, symptoms of post-traumatic stress disorder (PTSD), and depression levels in a population of Rwandans traumatized by the 1994 genocide. The following measures were utilized: the Rwandan Panic-Disorder Survey (RPDS); the Beck Depression Inventory (BDI); the Harvard Trauma Questionnaire (HTQ); and the PTSD Checklist (PCL). Forty of 100 Rwandan widows suffered somatically focused panic attacks during the previous 4 weeks. Thirty-five (87%) of those having panic attacks suffered panic disorder, making the rate of panic disorder for the entire sample 35%. Rwandan widows with panic attacks had greater psychopathology on all measures. Somatically focused panic-attack subtypes seem to constitute a key response to trauma in the Rwandan population. Future studies of traumatized non-Western populations should carefully assess not only somatoform disorder but also somatically focused panic attacks. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Hinton, D (reprint author), Revere Counseling Ctr, 265 Beach St, Revere, MA 02151 USA. FU NIMH NIH HHS [K23 MH066253-05, K23 MH066253, R01 MH094312] NR 52 TC 17 Z9 17 U1 1 U2 2 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 JAN 25 PY 2003 VL 117 IS 1 BP 1 EP 9 AR PII S0165-1781(02)00301-3 DI 10.1016/S0165-1781(02)00301-3 PG 9 WC Psychiatry SC Psychiatry GA 653NZ UT WOS:000181444000001 PM 12581815 ER PT J AU Hofmann-Lehmann, R Vlasak, J Williams, AL Chenine, AL McClure, HM Anderson, DC O'Neil, S Ruprecht, RM AF Hofmann-Lehmann, R Vlasak, J Williams, AL Chenine, AL McClure, HM Anderson, DC O'Neil, S Ruprecht, RM TI Live attenuated, nef-deleted SIV is pathogenic in most adult macaques after prolonged observation SO AIDS LA English DT Article DE live attenuated SIV; pathogenicity; AIDS vaccine; primate model; HIV ID SIMIAN IMMUNODEFICIENCY VIRUS; POLYMERASE CHAIN-REACTION; PIG-TAILED MACAQUES; RHESUS MACAQUES; IMMUNE-RESPONSES; HIV VACCINES; CAUSES AIDS; IN-VIVO; BIOLOGICAL CHARACTERIZATION; MUCOSAL INFECTION AB Objective: A live attenuated SIV vaccine strain, termed SIVmac239Delta3 and containing large deletions in nef, vpr and the negative regulatory element, was previously shown to cause AIDS mostly in monkeys vaccinated as infants. In the present study, we demonstrate that SIVmac239Delta3 is pathogenic in most vaccinated adult monkeys, given enough time. Methods: Eleven rhesus macaques vaccinated as adults with SIVmac239Delta3 were followed for extended periods (up to 6.8 years). Results: We found signs of immune dysregulation in all 11 adult vaccinees. All animals developed persistently inverted CD4:CD8 T -cellratios, seven (64%) had persistent recurrent viremia, and six (55%) had decreased CD4 T-cell counts (<500x10(6) cells/l). Further signs included low CD4CD29 lymphocyte subsets, loss of anti-Gag antibodies, anemia, thrombocytopenia, wasting, and opportunistic infections. Two adult vaccinees (18%) subsequently developed AIDS. Development of chronic, recurrent viremia with plasma viral RNA loads &GE;10(3) copies/ml and cytoviremia was a poor prognostic sign. Conclusion: Our data demonstrate that with time, a live attenuated, multiply deleted SIV vaccine can cause immune dysregulation in most vaccine recipients, even in initially immune competent, healthy adults. Immune dysfunction can progress to full AIDS. However, pathogenic effects became evident only several years after vaccination. Thus, mass vaccination of humans with similarly constructed live attenuated HIV vaccines, recently suggested for countries with high HIV-1 transmission rates, seems contraindicated. (C) 2003 Lippincott Williams & Wilkins. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Res Resources, Atlanta, GA 30322 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 FU NCRR NIH HHS [R01 RR14180] NR 66 TC 84 Z9 88 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 24 PY 2003 VL 17 IS 2 BP 157 EP 166 DI 10.1097/01.aids.0000042942.55529.01 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 643HN UT WOS:000180856000002 PM 12545074 ER PT J AU Bluher, M Kahn, BB Kahn, CR AF Bluher, M Kahn, BB Kahn, CR TI Extended longevity in mice lacking the insulin receptor in adipose tissue SO SCIENCE LA English DT Article ID LIFE-SPAN; FOOD RESTRICTION; CALORIC RESTRICTION; GENE; ELEGANS; MUTANT; LEPRECHAUNISM; PARAMETERS; EXTENSION; MUTATIONS AB Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals. In some organisms, this has been associated with a decreased fat mass and alterations in insulin/insulin-like growth factor 1 (IGF-1) pathways. To further explore these associations with enhanced longevity, we studied mice with a fat-specific insulin receptor knockout (FIRKO). These animals have reduced fat mass and are protected against age-related obesity and its subsequent metabolic abnormalities, although their food intake is normal. Both male and female FIRKO mice were found to have an increase in mean life-span of similar to134 days (18%), with parallel increases in median and maximum life-spans. Thus, a reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 43051, DK 30136, DK 56116] NR 33 TC 771 Z9 792 U1 5 U2 42 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 JAN 24 PY 2003 VL 299 IS 5606 BP 572 EP 574 DI 10.1126/science.1078223 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 638EZ UT WOS:000180559800052 PM 12543978 ER PT J AU Greene, MF AF Greene, MF TI Magnesium sulfate for preeclampsia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ECLAMPSIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 16 Z9 16 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 23 PY 2003 VL 348 IS 4 BP 275 EP 276 DI 10.1056/NEJMp020166 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 637JD UT WOS:000180507200001 PM 12540639 ER PT J AU Coblyn, JS McCluskey, RT King, ME Costenbader, KH AF Coblyn, JS McCluskey, RT King, ME Costenbader, KH TI Case 3-2003: A 36-year-old man with renal failure, hypertension, and neurologic abnormalities - Classic polyarteritis nodosa associated with hepatitis B infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RHEUMATOLOGY 1990 CRITERIA; MICROSCOPIC POLYANGIITIS; MIXED CRYOGLOBULINEMIA; CLINICAL ASPECTS; VASCULITIS; CLASSIFICATION; INVOLVEMENT; ARTERITIS C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Coblyn, JS (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol, 75 Francis St, Boston, MA 02115 USA. NR 20 TC 2 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 23 PY 2003 VL 348 IS 4 BP 333 EP 342 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 637JD UT WOS:000180507200009 PM 12540647 ER PT J AU Snapper, SB Rosen, FS AF Snapper, SB Rosen, FS TI A family of WASPs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACTIN C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, J706,55 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL59561]; NIAID NIH HHS [AI50950] NR 5 TC 21 Z9 22 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 23 PY 2003 VL 348 IS 4 BP 350 EP 351 DI 10.1056/NEJMcibr001155 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 637JD UT WOS:000180507200013 PM 12540651 ER PT J AU Landon, BE Reschovsky, J Blumenthal, D AF Landon, BE Reschovsky, J Blumenthal, D TI Changes in career satisfaction among primary care and specialist physicians, 1997-2001 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MANAGED CARE; JOB-SATISFACTION; HEALTH-CARE; UNITED-STATES; MEDICAL-CARE; QUALITY; ORGANIZATIONS; WORKLIFE AB Context A number of forces have changed the practice of medicine in the past decade. Evidence suggests that physicians are becoming less satisfied in this environment. Objectives To describe changes in career satisfaction in a large, nationally representative sample of physicians and to examine market and practice factors associated with changes in physician satisfaction. Design and Setting Data were collected from the first 3 rounds of the Community Tracking Study (CTS) Physician Survey, a series of nationally representative telephone surveys of physicians in 60 US sites conducted in 1996-1997 (round 1: 12385 respondents; 65% response rate), 1998-1999 (round 2: 12 280 respondents; 61% response rate), and 2000-2001 (round 3: 12 389 respondents; 59% response rate) for the Center for Studying Health System Change. The second and third rounds of the survey included physicians sampled in the previous round, as well as new physicians. Participants Primary care and specialist physicians who spent at least 20 hours per week in direct patient care activities. Main Outcome Measures Changes in physicians' overall satisfaction with their career and the proportion of dissatisfied physicians in particular sites. Results Physician satisfaction levels declined marginally between 1997 and 2001, with most of the decline occurring between 1997 and 1999. Among primary care physicians, 42.4% were very satisfied in 1997, as were 433% of specialists, compared with 38.5% and 41.4%, respectively, in 2001. There were nearly equal increases in those who reported that they were somewhat satisfied. Overall means mask significant differences across the 60 sites. Among 12 sites randomly selected for more intensive study, the proportion of respondents who were somewhat or very dissatisfied ranged from 8.8% of physicians in Lansing, Mich (1999), to 34.2% in Miami, Fla (1997). Between 1997 and 1999, 25.6% of primary care physicians reported decreased satisfaction and 18.1% reported improved satisfaction, while approximately equal percentages reported increased (19.8%) and decreased (20.4%) satisfaction between 1999-2001. Findings were similar for specialist physicians. In multivariable models, the strongest and most consistent predictors of change in satisfaction were changes in measures of clinical autonomy, including increases in hours worked and physicians' ability to obtain services for their patients. Changes in exposure to managed care were weakly related to changes in satisfaction. Conclusions Our findings demonstrate that overall physician satisfaction levels over this time period did not change dramatically. in addition, satisfaction and changes in satisfaction vary greatly among sites. Rather than declining income, threats to physicians autonomy, to their ability to manage their day-to-day patient interactions and their time, and to their ability to provide high-quality care are most strongly associated with changes in satisfaction. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp Partners Healthcare Syst, Inst Hlth Care Policy, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Ctr Studying Hlth Syst Change, Washington, DC USA. RP Landon, BE (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU AHRQ HHS [P01-HS-10803] NR 34 TC 165 Z9 170 U1 0 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 22 PY 2003 VL 289 IS 4 BP 442 EP 449 DI 10.1001/jama.289.4.442 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 636TD UT WOS:000180472300025 PM 12533123 ER PT J AU Metlay, JP Fine, MJ AF Metlay, JP Fine, MJ TI Testing strategies in the initial management of patients with community-acquired pneumonia SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID INTENSIVE-CARE TREATMENT; C-REACTIVE PROTEIN; PROGNOSTIC FACTORS; PNEUMOCOCCAL PNEUMONIA; ELDERLY PATIENTS; PREDICTION RULE; REQUIRING HOSPITALIZATION; LEGIONNAIRES-DISEASE; DIAGNOSING PNEUMONIA; PHYSICAL-EXAMINATION AB The initial management of patients suspected of having community-acquired pneumonia is challenging because of the broad range of clinical presentations, potential life-threatening nature of the illness, and associated high costs of care. The initial testing strategies should accurately establish a diagnosis and prognosis in order to determine the optimal treatment strategy. The diagnosis is important in determining the need for antibiotic therapy, and the prognosis is important in determining the site of care. This paper reviews the test characteristics of the history, physical examination, and laboratory findings, individually and in combination, in diagnosing community-acquired pneumonia and predicting short-term risk for death from the infection. In addition, we consider the implications of these test characteristics from the perspective of decision thresholds. The history and physical examination cannot provide a high level of certainty in the diagnosis of community-acquired pneumonia, but the absence of vital sign abnormalities substantially reduces the probability of the infection. Chest radiography is considered the gold standard for pneumonia diagnosis; however, we do not know its sensitivity and specificity, and we have limited data on the costs of false-positive and false-negative results. In the absence of empirical evidence, the decision to order a chest radiograph needs to rely on expert opinion in seeking strategies to optimize the balance between harms and benefits. Once community-acquired pneumonia is diagnosed, a combination of history, physical examination, and laboratory items can help estimate the short-term risk for death and, along with the patient's psychosocial characteristics, determine the appropriate site of treatment. C1 Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Metlay, JP (reprint author), Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, 9th Floor,Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU AHRQ HHS [R01 HS06468] NR 104 TC 117 Z9 124 U1 2 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 21 PY 2003 VL 138 IS 2 BP 109 EP 118 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 646CY UT WOS:000181018300005 PM 12529093 ER PT J AU Picard, MH Davidoff, R Sleeper, LA Mendes, LA Thompson, CR Dzavik, V Steingart, R Gin, K White, HD Hochman, JS AF Picard, MH Davidoff, R Sleeper, LA Mendes, LA Thompson, CR Dzavik, V Steingart, R Gin, K White, HD Hochman, JS CA SHOCK Trial TI Echocardiographic predictors of survival and response to early revascularization in cardiogenic shock SO CIRCULATION LA English DT Article DE shock; echocardiography; myocardial infarction; regurgitation ID ACUTE MYOCARDIAL-INFARCTION; ISCHEMIC MITRAL REGURGITATION; PAPILLARY-MUSCLE DYSFUNCTION; RIGHT-VENTRICULAR-FUNCTION; THROMBOLYSIS; MORTALITY; MECHANISM; RECOVERY AB Background-Although echocardiography is used in diagnosis and management of myocardial infarction, it has not been established whether specific features of cardiac structure or function early in the course of cardiogenic shock provide prognostic value. The purposes of this substudy of the SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK (SHOCK) trial were to describe the echocardiographic features of cardiogenic shock, identify findings on early echocardiograms associated with outcome, examine the interaction of such features with treatment, and determine whether these features could provide insights into the survival benefit observed with early revascularization and guide selection of patients for this strategy. Methods and Results-One hundred seventy-five echocardiograms performed within 24 hours of randomization to the early revascularization (ERV) or initial medical stabilization (IMS) arms of the trial were submitted for quantitative assessment, and 169 were suitable for analysis. The 2 groups were similar in terms of clinical and early echocardiographic characteristics. Mean left ventricular ejection fraction (LVEF) was 31%, and moderate or greater mitral regurgitation (MR) was noted in 39.1%. On multivariate analysis; the only independent predictors of survival were MR severity and LVER A survival benefit for the ERV strategy was observed at all levels of LVEF and MR. Conclusions-A wide range of cardiac structural and functional abnormalities exists in patients presenting with acute cardiogenic shock. Both short- and long-term mortality appear to be associated with initial left ventricular systolic function and MR as assessed by echocardiography, and a benefit of ERV is noted regardless of baseline LVEF or MR. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Med Ctr, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Univ Alberta Hosp, Edmonton, AB T6G 2B7, Canada. Winthrop Univ Hosp, Mineola, NY 11501 USA. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. Green Lane Hosp, Auckland 3, New Zealand. St Lukes Roosevelt Hosp, New York, NY USA. Columbia Univ, New York, NY USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, VBK508,55 Fruit St, Boston, MA 02114 USA. RI Thompson, Christopher/F-3967-2010; OI Thompson, Christopher/0000-0001-9206-376X; Davidoff, Ravin/0000-0002-3797-5325; Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [R01-HL-50020, R01-HL-49970] NR 27 TC 67 Z9 76 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 21 PY 2003 VL 107 IS 2 BP 279 EP 284 DI 10.1161/01.CIR.0000045667.11911.F6 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 642CA UT WOS:000180785700014 PM 12538428 ER PT J AU Goldfine, AB Goldfine, HL AF Goldfine, AB Goldfine, HL TI Cardiovascular disease in the diabetic patient SO CIRCULATION LA English DT Article C1 Joslin Diabet Ctr, Boston, MA 02215 USA. MetroWest Med Ctr, Framingham, MA USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 3 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 21 PY 2003 VL 107 IS 2 BP E14 EP E16 DI 10.1161/01.CIR.0000041764.06760.B9 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 642CA UT WOS:000180785700001 PM 12538441 ER PT J AU Llacer, J Deasy, JO Bortfeld, TR Solberg, TD Promberger, C AF Llacer, J Deasy, JO Bortfeld, TR Solberg, TD Promberger, C TI Absence of multiple local minima effects in intensity modulated optimization with dose-volume constraints SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOTHERAPY OPTIMIZATION AB This paper reports on the analysis of intensity modulated radiation treatment optimization problems in the presence of non-convex feasible parameter spaces caused by the specification of dose-volume constraints for the organs-at-risk (OARs). The main aim was to determine whether the presence of those non-convex spaces affects the optimization of clinical cases in any significant way. This was done in two phases: (1) Using a carefully designed two-dimensional mathematical phantom that exhibits two controllable minima and with randomly initialized beamlet weights, we developed a methodology for exploring the nature of the convergence characteristics of quadratic cost function optimizations (deterministic or stochastic). The methodology is based on observing the statistical behaviour of the residual cost at the end of optimizations in which the stopping criterion is progressively more demanding and carrying out those optimizations to very small error changes per iteration. (2) Seven clinical cases were then analysed with dose-volume constraints that are stronger than originally used in the clinic. The clinical cases are two prostate cases differently posed, a meningioma case, two head-and-neck cases, a spleen case and a spine case. Of the 14 different sets of optimizations (with and without the specification of maximum doses allowed for the OARs), 12 fail to show any effect due to the existence of non-convex feasible spaces. The remaining two sets of optimizations show evidence of multiple minima in the solutions, but those minima are very close to each other in cost and the resulting treatment plans are practically identical, as measured by the quality of the dose-volume histograms (DVHs). We discuss the differences between fluence maps resulting from those similar treatment plans. We provide a possible reason for the observed results and conclude that, although the study is necessarily limited, the annealing characteristics of a simulated annealing method may not be justified in clinical optimization in the presence of dose-volume constraints. The results of optimizations by the Newton gradient (NG) method with a quadratic cost function are reported in detail. An adaptive simulated annealing method, optimizing the same function, and the dynamically penalized likelihood method, optimizing a log likelihood function, have also been used in the Study. The results of the latter two methods have only been discussed briefly, as they yielded the same conclusions as the NG method. C1 EC Engn Cosultants, Los Gatos, CA 95032 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90095 USA. BrainLAB AG, D-85551 Heimstetten, Germany. RP Llacer, J (reprint author), EC Engn Cosultants, LLC 130,Forest Hill Dr, Los Gatos, CA 95032 USA. OI Deasy, Joseph/0000-0002-9437-266X NR 11 TC 41 Z9 42 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2003 VL 48 IS 2 BP 183 EP 210 AR PII S0031-9155(03)53457-1 DI 10.1088/0031-9155/48/2/304 PG 28 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 647ZZ UT WOS:000181125100004 PM 12587904 ER PT J AU Wolf, K Mazo, I Leung, H Engelke, K von Andrian, UH Deryugina, EI Strongin, AY Brocker, EB Friedl, P AF Wolf, K Mazo, I Leung, H Engelke, K von Andrian, UH Deryugina, EI Strongin, AY Brocker, EB Friedl, P TI Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis SO JOURNAL OF CELL BIOLOGY LA English DT Article DE cell migration; invasion; fibrosarcoma cells; carcinoma cells; matrix proteases ID 3-DIMENSIONAL COLLAGEN LATTICES; ACTIVATED MATRIX METALLOPROTEINASE-2; EXTRACELLULAR-MATRIX; I COLLAGEN; MELANOMA-CELLS; CANCER; LOCOMOTION; MEMBRANE; ADHESION; INVASION AB Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor-based treatment, suggesting the existence of migratory compensation strategies. in three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma and MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including the coclustering of beta1 integrins and MT1-matrix metalloproteinase (MMP) at fiber bindings sites and the generation of tube-like proteolytic degradation tracks. Near-total inhibition of MMPs, serine proteases, cathepsins, and other proteases, however, induced a conversion toward spherical morphology at near undiminished migration rates. Sustained protease-independent migration resulted from a flexible amoeba-like shape change, i.e., propulsive squeezing through preexisting matrix gaps and formation of constriction rings in the absence of matrix degradation, concomitant loss of clustered beta1 integrins and MT1-MMP from fiber binding sites, and a diffuse cortical distribution of the actin cytoskeleton. Acquisition of protease-independent amoeboid dissemination was confirmed for HT-1080 cells injected into the mouse dermis monitored by intravital multiphoton microscopy. In conclusion, the transition from proteolytic mesenchymal toward nonproteolytic amoeboid movement highlights a supramolecular plasticity mechanism in cell migration and further represents a putative escape mechanism in tumor cell dissemination after abrogation of pericellular proteolysis. C1 Univ Wurzburg, Dept Dermatol, D-97080 Wurzburg, Germany. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Friedl, P (reprint author), Univ Wurzburg, Dept Dermatol, Josef Schneider Str 2, D-97080 Wurzburg, Germany. RI Wolf, Katarina/A-7787-2010; Peng, Chunwei/F-6788-2010; von Andrian, Ulrich/A-5775-2008; Friedl, Peter/A-8961-2010; OI Strongin, Alex/0000-0003-3765-3016 FU NCI NIH HHS [CA77470, CA83017, R01 CA077470, R01 CA083017]; NHLBI NIH HHS [HL56949, HL54936, P01 HL056949, R01 HL054936] NR 57 TC 825 Z9 848 U1 11 U2 109 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 20 PY 2003 VL 160 IS 2 BP 267 EP 277 DI 10.1083/jcb.200209006 PG 11 WC Cell Biology SC Cell Biology GA 649EN UT WOS:000181194100013 PM 12527751 ER PT J AU Haverkamp, S Ghosh, KK Hirano, AA Wassle, H AF Haverkamp, S Ghosh, KK Hirano, AA Wassle, H TI Immunocytochemical description of five bipolar cell types of the mouse retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE mouse retina; bipolar cells; CaB5; NK3R; CaB1; recoverin; glutamate receptors ID MACAQUE MONKEY RETINA; GLUTAMATE-RECEPTOR SUBUNITS; PROTEIN-KINASE-C; CALCIUM-BINDING PROTEIN; RAT RETINA; MAMMALIAN RETINA; PRIMATE RETINA; CAT RETINA; ROD PHOTORECEPTORS; KAINATE RECEPTORS AB With the ever-growing number of transgenic mice being used in vision research, a precise knowledge of the cellular organization of the mouse retina is required. As with the cat, rabbit, rat, and primate retinae, as many as 10 cone bipolar types and one rod bipolar type can be expected to exist in the mouse retina; however, they still have to be defined. In the current study, several immunocytochemical markers were applied to sections of mouse retina, and the labeling of bipolar cells was studied using confocal microscopy and electron microscopy. By using antibodies against the neurokinin-3 receptor NK3R; the plasma membrane calcium ATPase1 (PMCA1); and the calcium (Ca)-binding proteins CaB1, CaB5, caldendrin, and recoverin, three different OFF-cone bipolar cells could be identified. One type of ON-cone bipolar cell was identified through its immunoreactivity for CaB5 and PMCA1. Rod bipolar cells, comparable in morphology to those of other mammalian retinae, expressed protein kinase Ca and CaB5. It was also shown that putative OFF-cone bipolar cells receive light signals through flat contacts at the cone pedicle base, whereas ON-cone bipolar signaling involves invaginating contacts. The distribution of the kainate receptor subunit GluR5 was studied by confocal and electron microscopy. GluR5 was expressed at flat bipolar cell contacts; however, it appears to be involved with only certain types of OFF-cone bipolar cells. This suggests that different bipolar cell types receive their light signals through different sets of glutamate receptors. C1 Max Planck Inst Hirnforsch, D-60528 Frankfurt, Germany. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Wassle, H (reprint author), Max Planck Inst Hirnforsch, Deutschordenstr 46, D-60528 Frankfurt, Germany. FU NEI NIH HHS [EY 07026, R01 EY004067, R01 EY004067-23, R01 EY015573, T32 EY007026] NR 68 TC 141 Z9 141 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 20 PY 2003 VL 455 IS 4 BP 463 EP 476 DI 10.1002/cne.10491 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 630QD UT WOS:000180118800004 PM 12508320 ER PT J AU Rauch, SL Phillips, KA Segal, E Makris, N Shin, LM Whalen, PJ Jenike, MA Caviness, VS Kennedy, DN AF Rauch, SL Phillips, KA Segal, E Makris, N Shin, LM Whalen, PJ Jenike, MA Caviness, VS Kennedy, DN TI A preliminary morphometric magnetic resonance imaging study of regional brain volumes in body dysmorphic disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE segmentation; caudate nucleus; striatum; hippocampus; white matter; obsessive-compulsive disorder; dysmorphophobia ID OBSESSIVE-COMPULSIVE DISORDER; STRUCTURED CLINICAL INTERVIEW; RECURRENT MAJOR DEPRESSION; BASAL GANGLIA VOLUMES; TOURETTES-SYNDROME; MRI; RELIABILITY; ABNORMALITIES; SEVERITY; CAUDATE AB Morphometric magnetic resonance imaging (MRI) was used to compare regional brain volumes in eight women with body dysmorphic disorder (BDD) and eight healthy comparison subjects. The BDD group exhibited a relative leftward shift in caudate asymmetry and greater total white matter vs. the comparison group. Findings with respect to the caudate nucleus are consistent with both the conceptualization of BDD as an obsessive-compulsive spectrum disorder, and the 'striatal topography model' of obsessive-compulsive disorders. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Butler Hosp, Providence, RI 02906 USA. Brown Med Sch Providence, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA 02129 USA. Tufts Univ, Dept Psychol, Boston, MA 02115 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,139th St,9th Floor, Charlestown, MA 02129 USA. RI Kennedy, David/H-3627-2012 FU NIMH NIH HHS [R01MH50275, R01MH60219, K24 MH063975, R29MH54841] NR 34 TC 51 Z9 53 U1 5 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JAN 20 PY 2003 VL 122 IS 1 BP 13 EP 19 AR PII S0925-4927(02)00117-8 DI 10.1016/S0925-4927(02)00117-8 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 653NY UT WOS:000181443900002 PM 12589879 ER PT J AU Bai, JR Sui, JH Zhu, RY Tallarico, AS Gennari, F Zhang, DS Marasco, WA AF Bai, JR Sui, JH Zhu, RY Tallarico, AS Gennari, F Zhang, DS Marasco, WA TI Inhibition of Tat-mediated transactivation and HIV-1 replication by human anti-hCyclinT1 intrabodies SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SCID-HU MOUSE; PHAGE DISPLAY TECHNOLOGY; IN-VITRO; ANTI-TAT; T-CELLS; P-TEFB; PROTEIN; RNA; MODEL AB Human immunodeficiency virus, type 1 (HIV-1) replication requires the interaction of Tat protein with the human cyclinT1 (hCyclinT1) subunit of the positive transcription elongation factor (P-TEFb) complex, which then cooperatively binds to transactivation response element (TAR) RNA to transactivate HIV transcription. In this report, a non-immune human single-chain antibody (sFv) phage display library was used to isolate anti-hCyclinT1 sFvs that could disrupt hCyclinT1-Tat interactions. The N-terminal 272 residues of hCyclinT1, including the entire cyclin domains and the Tat-TAR recognition motif (TRM), that fully support Tat transactivation was used for panning, and of the five unique anti-hCyclinT1 sFvs that were obtained, three bound to the cyclin box domains and two bound to TRM. All sFvs could be expressed as intrabodies at high levels in transiently transfected 293T and in stable Jurkat and SupT1 transfectants and could specifically co-immuno-precipitate co-expressed hCyclinT1 in 293T cells with varying efficacy without disrupting hCyclinT1-Cdk9 interactions. In addition, two sFv clones (3R6-1 and 2R6-21) that mapped to the cyclin box domains markedly inhibited Tat-mediated transactivation in several transiently transfected cell lines without inhibiting basal transcription or inducing apoptosis. When HIV-1 challenge studies were performed on stable 3R6-1-expressing Jurkat T cells, near complete inhibition of viral replication was obtained at a low challenge dose, and 74-88% inhibition to HIV-1 replication was achieved at a high infection dose in SupT1 cells. These results provide proof-in-principle that anti-hCyclinT1 intrabodies can be designed to block HIV-1 replication without causing cellular toxicity, and as a result, they may be useful agents for "intracellular immunization"-based gene therapy strategies for HIV-1 infection/AIDS. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 824,44 Binney St, Boston, MA 02115 USA. OI SUI, JIANHUA/0000-0002-1272-9662 FU NCRR NIH HHS [5R01-RR14447]; NIAID NIH HHS [2R01-AI28785] NR 37 TC 60 Z9 66 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 JAN 17 PY 2003 VL 278 IS 3 BP 1433 EP 1442 DI 10.1074/jbc.M208297200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636NK UT WOS:000180462200010 PM 12401780 ER PT J AU Xu, GM Gonzalez-Perrett, S Essafi, M Timpanaro, GA Montalbetti, N Arnaout, MA Cantiello, HF AF Xu, GM Gonzalez-Perrett, S Essafi, M Timpanaro, GA Montalbetti, N Arnaout, MA Cantiello, HF TI Polycystin-1 activates and stabilizes the polycystin-2 channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KIDNEY-DISEASE; CATION CHANNEL; PROTEIN; PKD2; GENE; INTERACTS AB Autosomal dominant polycystic kidney disease (AD-PKD) is a prevalent genetic disorder largely caused by mutations in the PKD1 and PKD2 genes that encode the transmembrane proteins polycystin-1 and -2, respectively. Both proteins appear to be involved in the regulation of cell growth and maturation, but the precise mechanisms are not yet well defined. Polycystin-2 has recently been shown to function as a Ca2+-permeable, non-selective cation channel. Polycystin-2 interacts through its cytoplasmic carboxyl-terminal region with a coiled-coil motif in the cytoplasmic tail of polycystin-1 (P1CC). The functional consequences of this interaction on its channel activity, however, are unknown. In this report, we show that P1CC enhanced the channel activity of polycystin-2. R742X, a disease-causing polycystin-2 mutant lacking the polycystin-1 interacting region, fails to respond to P1CC. Also, P1CC containing a disease-causing mutation in its coiled-coil motif loses its stimulatory effect on wild-type polycystin-2 channel activity. The modulation of polycystin-2 channel activity by polycystin-1 may be important for the various biological processes mediated by this molecular complex. C1 Massachusetts Gen Hosp, Renal Unit, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Fac Farm & Bioquim, Fac Fisioquim & Quim Anal, RA-1113 Buenos Aires, DF, Argentina. Fac Med, Dept Fisiol, RA-1121 Buenos Aires, DF, Argentina. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Med, 149 13th St, Charlestown, MA 02129 USA. OI Montalbetti, Nicolas/0000-0003-2897-9540 FU NIDDK NIH HHS [DK54711] NR 19 TC 74 Z9 79 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 JAN 17 PY 2003 VL 278 IS 3 BP 1457 EP 1462 DI 10.1074/jbc.M209996200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636NK UT WOS:000180462200013 PM 12407099 ER PT J AU Geiben-Lynn, R Kursar, M Brown, NV Addo, MM Shau, H Lieberman, J Luster, AD Walker, BD AF Geiben-Lynn, R Kursar, M Brown, NV Addo, MM Shau, H Lieberman, J Luster, AD Walker, BD TI HIV-1 antiviral activity of recombinant natural killer cell enhancing factors, NKEF-A and NKEF-B, members of the peroxiredoxin family SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; OXIDATIVE STRESS; GENE-EXPRESSION; NONCYTOLYTIC INHIBITION; THIOREDOXIN PEROXIDASE; ANTIOXIDANT PROPERTIES; REVERSE TRANSCRIPTION; CHEMOKINE RECEPTORS; PRIMARY MACROPHAGES AB CD8(+) T-cells are a major source for the production of non-cytolytic factors that inhibit HIV-1 replication. In order to characterize further these factors, we analyzed gene expression profiles of activated CD8(+) T-cells using a human cDNA expression array containing 588 human cDNAs. mRNA for the chemokine I-309 (CCL1), the cytokines granulocyte-macrophage colony-stimulating factor and interleukin-13, and natural killer cell enhancing factors (NKEF) -A and -B were up-regulated in bulk CD8(+) T-cells from HIV-1 seropositive individuals compared with seronegative individuals. Recombinant NKEF-A and NKEF-B inhibited HIV-1 replication when exogenously added to acutely infected T-cells at an ID50 (dose inhibiting HIV-1 replication by 50%) of similar to130 nm (3 mug/ml). Additionally, inhibition against dual-tropic simian immunodeficiency virus and dual-tropic simian-human immunodeficiency virus was found. T-cells transfected with NKEF-A or NKEF-B cDNA were able to inhibit 80-98% HIV-1 replication in vitro. Elevated plasma levels of both NKEF-A and NKEF-B proteins were detected in 23% of HIV-infected non-treated individuals but not in persons treated with highly active antiviral therapy or uninfected persons. These results indicate that the peroxiredoxin family members NKEF-A and NKEF-B are up-regulated in activated CD8(+) T-cells in HIV infection, and suggest that these antioxidant proteins contribute to the antiviral activity of CD8(+) T-cells. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Hillsborough 02129, North Ireland. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Hillsborough 02129, North Ireland. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Hillsborough 02129, North Ireland. Harvard Univ, Sch Med, Hillsborough 02129, North Ireland. Univ Calif Los Angeles, Sch Med, Div Surg Oncol, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Geiben-Lynn, R (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Bldg 149,13th St, Hillsborough 02129, North Ireland. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI28568, AI30914, AI46999] NR 61 TC 57 Z9 61 U1 3 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 17 PY 2003 VL 278 IS 3 BP 1569 EP 1574 DI 10.1074/jbc.M209964200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636NK UT WOS:000180462200027 PM 12421812 ER PT J AU Ashrafi, K Chang, FY Watts, JL Fraser, AG Kamath, RS Ahringer, J Ruvkun, G AF Ashrafi, K Chang, FY Watts, JL Fraser, AG Kamath, RS Ahringer, J Ruvkun, G TI Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes SO NATURE LA English DT Article ID LIFE-SPAN; NERVOUS-SYSTEM; RECEPTORS; LONGEVITY; PATHWAY; DAF-16; FOOD AB Regulation of body fat storage involves signalling between centres that regulate feeding in the brain and sites of fat storage and use in the body(1,2). Here we describe an assay for analysing fat storage and mobilization in living Caenorhabditis elegans. By using RNA-mediated interference (RNAi)(3,4) to disrupt the expression of each of the 16,757 worm genes, we have systematically screened the C. elegans genome for genes necessary for normal fat storage. We identify 305 gene inactivations that cause reduced body fat and 112 gene inactivations that cause increased fat storage. Analysis of the fat-reducing gene inactivations in insulin, serotonin and tubby signalling mutants of C. elegans, which have increased body fat, identifies a core set of fat regulatory genes as well as pathway-specific fat regulators. Many of the newly identified worm fat regulatory genes have mammalian homologues, some of which are known to function in fat regulation. Other C. elegans fat regulatory genes that are conserved across animal phylogeny, but have not previously been implicated in fat storage, may point to ancient and universal features of fat storage regulation, and identify targets for treating obesity and its associated diseases. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA. Univ Cambridge, Wellcome Canc Res UK Inst, Cambridge CB2 1QR, England. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Fraser, Andrew/0000-0001-9939-6014 FU Wellcome Trust [054523] NR 29 TC 610 Z9 661 U1 7 U2 59 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 16 PY 2003 VL 421 IS 6920 BP 268 EP 272 DI 10.1038/nature01279 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 635KG UT WOS:000180397600047 PM 12529643 ER PT J AU Yurchak, PM Deshpande, V Holmvang, G Playford, D Mark, EJ Rubenstein, MH Hourigan, L Hilgenberg, AD Deshpande, V AF Yurchak, PM Deshpande, V Holmvang, G Playford, D Mark, EJ Rubenstein, MH Hourigan, L Hilgenberg, AD Deshpande, V TI Case 2-2003: A 60-year-old man with mild congestive heart failure of uncertain cause - Rheumatoid arthritis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EVIDENT CARDIOVASCULAR-DISEASE; DIASTOLIC FUNCTION; CONSTRICTIVE PERICARDITIS; ABNORMALITIES; DURATION C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Yurchak, PM (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 16 PY 2003 VL 348 IS 3 BP 243 EP 249 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 635GJ UT WOS:000180390600010 PM 12529466 ER PT J AU Neidel, EM Tornow, W Trotter, DEG Howell, CR Crowell, AS Macri, RA Walter, RL Weisel, GJ Esterline, J Witala, H Crowe, BJ Pedroni, RS Markoff, DM AF Neidel, EM Tornow, W Trotter, DEG Howell, CR Crowell, AS Macri, RA Walter, RL Weisel, GJ Esterline, J Witala, H Crowe, BJ Pedroni, RS Markoff, DM TI A new twist to the long-standing three-nucleon analyzing power puzzle SO PHYSICS LETTERS B LA English DT Article ID POLARIZATION OBSERVABLES; POTENTIAL MODELS; D SCATTERING; A(Y) PUZZLE; P-D; FORCE AB New results for the neutron-deuteron analyzing power A(y)(theta) at E-n = 1.2 and 1.9 MeV and their comparison to proton-deuteron data reveal a sizeable and unexpected difference which increases with decreasing center-of-mass energy. This finding calls for the theoretical treatment of a subtle electromagnetic effect presently not incorporated in rigorous three-nucleon scattering calculations, before it is justified to invoke charge-dependent three-nucleon forces and/or other new physics. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Duke Univ, Dept Phys, Durham, NC 27706 USA. Triangle Univ Nucl Lab, Durham, NC 27708 USA. Penn State Altoona, Dept Phys, Altoona, PA 16601 USA. Guilford Coll, Greensboro, NC 27410 USA. Jagiellonian Univ, Inst Phys, PL-30059 Krakow, Poland. N Carolina Cent Univ, Dept Phys, Durham, NC 27707 USA. N Carolina A&T & State Univ, Dept Phys, Greensboro, NC 27411 USA. N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. RP Neidel, EM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 19 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0370-2693 J9 PHYS LETT B JI Phys. Lett. B PD JAN 16 PY 2003 VL 552 IS 1-2 BP 29 EP 34 DI 10.1016/S0370-2693(02)03106-4 PG 6 WC Astronomy & Astrophysics; Physics, Nuclear; Physics, Particles & Fields SC Astronomy & Astrophysics; Physics GA 635PR UT WOS:000180408500005 ER PT J AU Danias, PG Tritos, NA Stuber, M Botnar, RM Kissinger, KV Manning, WJ AF Danias, PG Tritos, NA Stuber, M Botnar, RM Kissinger, KV Manning, WJ TI Comparison of aortic elasticity determined by cardiovascular magnetic resonance imaging in obese versus lean adults SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ESSENTIAL-HYPERTENSION; DISTENSIBILITY; ARTERIAL AB The vascular properties of large vessels in the obese have not been adequately studied. We used cardiovascular magnetic resonance imaging to quantify the cross-sectional area and elastic properties of the ascending thoracic and abdominal aorta in 21 clinically healthy obese young adult men and 25 men who were age-matched lean controls. Obese subjects had greater maximal cross-sectional area of the ascending thoracic aorta (984 +/- 252 vs 786 +/- 109 mm(2), p <0.01) and of the abdominal aorta (415 +/- 71 vs 374 +/- 51 mm(2), p <0.05). When indexed for height the differences persisted, but when indexed for body surface area, a significant difference between groups was found only for the maximal abdominal aortic cross-sectional area. The obese subjects also had decreased abdominal aortic elasticity, characterized by 24% lower compliance (0.0017 +/- 0.0004 vs 0.0021 +/- 0.0005 mm(2)/kPa/mm, p <0.01), 22% higher stiffness index β (6.0 +/- 1.5 vs 4.9 +/- 0.7, p <0.005), and 41% greater pressure-strain-elastic modulus (72 +/- 25 vs 51 +/- 9, p <0.005). At the ascending thoracic aorta, only the pressure-strain elastic modulus was different between obese and lean subjects (85 +/- 42 vs 65 +/- 26 kPa, respectively; p <0.05), corresponding to a 31% difference-but arterial compliance and stiffness index were not significantly different between groups. in clinically healthy young adult obese men, obesity is associated with increased cross-sectional aortic area and decreased aortic elasticity. (C) 2003 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Danias, PG (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, 330 Brookline Ave, Boston, MA 02215 USA. RI Stuber, Matthias/B-2949-2010; Botnar, Rene/E-6875-2012 OI Stuber, Matthias/0000-0001-9843-2028; Botnar, Rene/0000-0003-2811-2509 FU NCRR NIH HHS [RR01032] NR 12 TC 51 Z9 54 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2003 VL 91 IS 2 BP 195 EP 199 AR PII S0002-9149(02)03109-0 DI 10.1016/S0002-9149(02)03109-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 635PX UT WOS:000180409000015 PM 12521634 ER PT J AU Michelson, D Adler, L Spencer, T Reimherr, FW West, SA Allen, AJ Kelsey, D Wernicke, J Dietrich, A Milton, D AF Michelson, D Adler, L Spencer, T Reimherr, FW West, SA Allen, AJ Kelsey, D Wernicke, J Dietrich, A Milton, D TI Atomoxetine in adults with ADHD: Two randomized, placebo-controlled studies SO BIOLOGICAL PSYCHIATRY LA English DT Article DE atomoxetine; ADHD; adults; nonstimulant ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; FOLLOW-UP; BUPROPION; CHILDREN; METHYLPHENIDATE; DESIPRAMINE; STIMULANTS AB Background: Attention-deficit/hyperactivity disorder (ADHD) has been less studied in adults than in children, and the treatment studies reported to date have been small, single-center trials. To assess the efficacy of atomoxetine, a new, and highly selective inhibitor of the norepinephrine transporter, we conducted two large, multicenter treatment trials. Methods: Two identical studies using randomized, double-blind, placebo-controlled designs and a 10-week treatment period were conducted in adults with DSM-IV-defined ADHD as assessed by clinical history and confirmed by a structured interview (study I, n = 280; study II, n = 256). The primary outcome measure was a comparison of atomoxetine and placebo using repeated measures mixed model analysis of postbaseline values of the Conners' Adult ADHD Rating Scale. Results: In each study, atomoxetine was statistically superior to placebo in reducing both inattentive and hyperactive and impulsive symptoms as assessed by primary and secondary measures. Discontinuations for adverse events among atomoxetine patients were tinder 10% in both studies. Conclusions: Atomoxetine appears to be an efficacious treatment for adult ADHD. Its lack of abuse potential may be an advantage for many patients. (C) 2003 Society of Biological Psychiatry. C1 Lilly Res Labs, Indianapolis, IN 46285 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. NYU, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Salt Lake City, UT USA. Psyciat Inst Florida, Orlando, FL USA. Neuropsychiat Associates, Woodstock, VT USA. RP Michelson, D (reprint author), Lilly Res Labs, DC 6026, Indianapolis, IN 46285 USA. NR 42 TC 364 Z9 370 U1 7 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2003 VL 53 IS 2 BP 112 EP 120 DI 10.1016/S0006-3223(02)01671-2 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 637NM UT WOS:000180518900002 PM 12547466 ER PT J AU Tsatsanis, KD Rourke, BP Klin, A Volkmar, FR Cicchetti, D Schultz, RT AF Tsatsanis, KD Rourke, BP Klin, A Volkmar, FR Cicchetti, D Schultz, RT TI Reduced thalamic volume in high-functioning individuals with autism SO BIOLOGICAL PSYCHIATRY LA English DT Article DE thalamus; autism; neuroimaging; brain; magnetic resonance imaging ID SHORT-TERM PLASTICITY; THALAMOCORTICAL INNERVATION; AUGMENTING RESPONSES; INFANTILE-AUTISM; CHILDHOOD AUTISM; BRAIN; CORTEX; ATTENTION; SYSTEMS; MEMORY AB Background: In this study,specific consideration is given to a role for the thalamus in autism. Methods: A volumetric analysis of the thalamus was conducted using magnetic resonance imaging, based on segmentation of continuous 1.2 mm(3) coronal images. The sample consisted of 12 high-functioning individuals with autism, mean age of 21.0 years (SD = 10.4) and mean IQ of 106.4 (SD = 18.3). Normal control subjects were selected to match this group; the mean age was 18.1 years (SD = 6.3); mean IQ was 108.8 (SD = 15.6). Results: Unadjusted mean thalamic volume was not significantly different; however, there were significant differences in the relationship between thalamic volume and total brain volume (TBV). The correlation was strong and positive in the control group but statistically nonsignificant in the autism group. Group differences were found when adjustments were made for TBV, achieved by grouping subjects' measurements on this variable using a split median procedure. Mean thalamic volume was significantly reduced in the autism group relative to normal control subjects, specifically within the high TBV group. Conclusions: The increase in thalamic volume with increase in TBV was not seen in autism, suggesting under-developed connections between cortical and subcortical regions and indicating a need to examine this structure further. (C) 2003 Society of Biological Psychiatry. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Yale Univ, Yale Child Study Ctr, New Haven, CT USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Windsor, Windsor, ON N9B 3P4, Canada. RP Tsatsanis, KD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 149 3th St,10th Floor, Charlestown, MA 02129 USA. FU NCRR NIH HHS [M01-RR06022]; NICHD NIH HHS [01-HD03008] NR 77 TC 102 Z9 105 U1 5 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2003 VL 53 IS 2 BP 121 EP 129 DI 10.1016/S0006-3223(02)01530-5 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 637NM UT WOS:000180518900003 PM 12547467 ER PT J AU Akashi, K He, X Chen, J Iwasaki, H Niu, C Steenhard, B Zhang, JW Haug, J Li, LH AF Akashi, K He, X Chen, J Iwasaki, H Niu, C Steenhard, B Zhang, JW Haug, J Li, LH TI Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis SO BLOOD LA English DT Article ID STEM-CELLS; BONE-MARROW; EXPRESSION; PROLIFERATION; SPECIFICATION; PROGENITORS; ENGRAFTMENT; COMMITMENT; PATTERNS; PROTEIN AB Hematopoietic stem cells (HSCs) maintain hernatopoiesis by giving rise to all types of blood cells. Recent reports suggest that HSCs also possess the potential to generate nonhematopoietic tissues. To evaluate the underlying mechanisms in the commitment of HSCs into multitissue and multilhematopoietic lineages, we performed oligonucleotide array analyses targeting for prospectively purified HSCs, multipotent progenitors (MPPs), common lymphold progenitors (CLPs), and common myeloid progenitors (CMPs). Here we show that HSCs coexpress multiple nonhematopoletic genes as well as hematopoietic genes; MPPs coexpress myeloid and lymphold genes; CMPs,coexpress myeloerythroid, but not lymphoid genes, whereas CLPs coexpress T-, B-, and natural killer-lymphoid, but not myeloid, genes. Thus, the stepwise decrease in transcriptional accessibility for multilineage-affiliated genes may represent progressive restriction of developmental potentials in early hematopoiesis. These data support the hypothesis that stem cells possess a wide-open chromatin structure to maintain their multipotentiality, which is progressively quenched as they go down a particular pathway of differentiation. (Blood. 2003;101:383-390) (C) 2003 by The American Society of Hematology C1 Stowers Inst Med Res, Kansas City, MO 64110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Missouri, Dept Math & Stat, Kansas City, MO 64110 USA. RP Li, LH (reprint author), Stowers Inst Med Res, 1000 E 50th St, Kansas City, MO 64110 USA. NR 56 TC 273 Z9 279 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2003 VL 101 IS 2 BP 383 EP 390 DI 10.1182/blood-2002-06-1780 PG 8 WC Hematology SC Hematology GA 635EG UT WOS:000180384800002 PM 12393558 ER PT J AU Mikkola, HKA Fujiwara, Y Schlaeger, TM Traver, D Orkin, SH AF Mikkola, HKA Fujiwara, Y Schlaeger, TM Traver, D Orkin, SH TI Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo SO BLOOD LA English DT Article ID GLYCOPROTEIN-IIB-IIIA; MURINE YOLK-SAC; STEM-CELLS; ENDOTHELIAL-CELLS; FETAL LIVER; MYELOID PROGENITORS; COMMON PRECURSOR; IN-VITRO; SCL GENE; VASCULOGENESIS AB Murine hematopoietic stem cells (HSCs) originate from mesoderm in a process that requires the transcription factor SCL/Tal1. To define steps in the commitment to blood cell fate, we compared wild-type and SCL-/- embryonic stem cell differentiation in vitro and identified CD41 (GpIlb) as the earliest surface marker missing from SCL-/- embryoid bodies (EBs). Culture of fluorescence-activated cell sorter (FACS) purified cells from EBs showed that definitive hematopoietic progenitors were highly enriched in the CD41(+) fraction, whereas endothelial cells developed from CD41(-) cells. In the mouse embryo, expression of CD41 was detected in yolk sac blood islands and in fetal liver. In yolk sac and EBs, the panhematopoietic marker CD45 appeared in a subpopulation of CD41+ cells. However, multilineage hematopoietic colonies developed not only from CD45(+)CD41(+) cells but also from CD45(-)CD41(+) cells, suggesting that CD41 rather than CD45 marks the definitive culture colony-forming unit (CFU-C) at the embryonic stage. In contrast, fetal liver CFU-C was CD45(+), and only a sub-fraction expressed CD41, demonstrating down-regulation of CD41 by the fetal liver stage. In yolk sac and EBs, CD41 was coexpressed with embryonic HSC markers c-kit and CD34. Sorting for CD41 and c-kit expression resulted in enrichment of definitive hematopoietic progenitors. Furthermore, the CD41(+) c-kit(+) population was missing from runx1/AML1(-/-) EBs that lack definitive hematopoiesis. These results suggest that the expression of CD41, a candidate target gene of SCL/Tal1, and c-kit define the divergence of definitive hematopoiesis from endothelial cells during development. Although CD41 is commonly referred to as megakaryocyte-platelet integrin in adult hematopoiesis, these results implicate a wider role for CD41 during murine ontogeny. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol & Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 55 TC 250 Z9 254 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 JAN 15 PY 2003 VL 101 IS 2 BP 508 EP 516 DI 10.1182/blood-2002-06-1699 PG 9 WC Hematology SC Hematology GA 635EG UT WOS:000180384800022 PM 12393529 ER PT J AU Oura, H Bertoncini, J Velasco, P Brown, LF Carmeliet, P Detmar, M AF Oura, H Bertoncini, J Velasco, P Brown, LF Carmeliet, P Detmar, M TI A critical role of placental growth factor in the induction of inflammation and edema formation SO BLOOD LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; TRANSGENIC MICE; OVEREXPRESSING ANGIOPOIETIN-1; DELAYED-HYPERSENSITIVITY; FACTOR VPF/VEGF; ANGIOGENESIS; EXPRESSION; SKIN; PSORIASIS; RECEPTORS AB Angiogenesis is a prominent feature of a number of inflammatory human diseases, including rheumatoid arthritis, psoriasis, and cutaneous delayed-type hypersensitivity (DTH) reactions. Up-regulation of placental growth factor (PIGF), a member of the vascular endothelial growth factor (VEGF) family, has been found in several conditions associated with pathologic angiogenesis; however, its distinct role in the control of angiogenesis has remained unclear. To directly investigate the biologic function of PIGF in cutaneous inflammation and angiogenesis, DTH reactions were investigated in the ear skin of wild-type mice, of PIGF-deficient mice, and of transgenic mice with targeted overexpression of human PIGF-2 in epidermal keratinocytes, driven by a keratin 14 promoter expression construct. Chronic transgenic delivery of PIGF-2 to murine epidermis resulted in a significantly increased inflammatory response, associated with more pronounced vascular enlargement, edema, and inflammatory cell infiltration than seen in wild-type mice. Conversely, PIGF deficiency resulted in a diminished and abbreviated inflammatory response, together with a reduction of inflammatory angiogenesis and edema formation. VEGF expression was up-regulated at a comparable level in the inflamed skin of all genotypes. These findings reveal that placental growth factor plays a critical role in the control of cutaneous inflammation, and they suggest inhibition of PIGF bioactivity as a potential new approach for anti-inflammatory therapy. (C) 2003 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Dept Dermatol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Katholieke Univ Leuven, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, CA86410, CA91861] NR 47 TC 113 Z9 118 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 JAN 15 PY 2003 VL 101 IS 2 BP 560 EP 567 DI 10.1182/blood-2002-05-1516 PG 8 WC Hematology SC Hematology GA 635EG UT WOS:000180384800029 PM 12393422 ER PT J AU Dimitroff, CJ Bernacki, RJ Sackstein, R AF Dimitroff, CJ Bernacki, RJ Sackstein, R TI Glycosylation-dependent inhibition of cutaneous lymphocyte-associated antigen expression: implications in modulating lymphocyte migration to skin SO BLOOD LA English DT Article ID SELECTIN GLYCOPROTEIN LIGAND-1; T-CELL LYMPHOMA; P-SELECTIN; FUCOSYL-TRANSFERASE; FUCT-VII; LEUKOCYTE ADHESION; HECA-452 EPITOPE; SPECIALIZED FORM; HOMING RECEPTOR; BINDING AB Constitutive E-selectin expression on dermal microvascular endothelial cells plays a critical role in mediating rolling adhesive interactions of human skin-homing T cells and in pathologic accumulation of lymphocytes in skin. The major E-selectin ligand on human skin-homing T cells is cutaneous lymphocyte-associated antigen (CLA), a specialized glycoform of P-selectin glycoprotein ligand-1 (PSGL-1) defined by monoclonal antibody HECA-452. Since HECA-452 reactivity, and not PSGL-1 polypeptide itself, confers the specificity of human T cells to enter dermal tissue, inhibition of HECA-452 expression is a potential strategy for modulating lymphocyte migration to skin. In this study, we examined the efficacy of several well-characterized metabolic inhibitors of glycosylation and of a novel fluorinated analog of N-acetylglucosamine (2-acetamido-1,3,6-tri-O-acetyl-4-deoxy-4- fluoro-D-glucopyranose [4-F-GlcNAc]) to alter HECA-452 expression on human CLA(+) T cells and prevent cell tethering and rolling on selectins under shear stress. At concentrations that did not affect PSGL-1 expression, we found that swainsonine (inhibitor of complex-type N-glycan synthesis) had no effect on HECA-452 expression or selectin ligand activity, whereas benzyl-O-N-acetylgalactosamide (BAG; inhibitor of O-glycan biosynthesis) ablated HECA-452 expression on PSGL-1 and significantly lowered selectin ligand activity. We found that 4-F-GlcNAc (putative inhibitor of poly-N-acetyllactosamine biosynthesis) was more potent than BAG at lowering HECA-452 expression and selectin binding. In addition, we show that 4-F-GlcNAc was directly incorporated into native CLA expressed on T cells, indicating direct inhibition on poly-N-acetyllactosamine elongation and selectin-binding determinants on PSGL-1 0-glycans. These observations establish a potential treatment approach for targeting pathologic lymphocyte trafficking to skin and indicate that 4-F-GlcNAc may be a promising agent for treatment of dermal tropism associated With malignancies and inflammatory disorders. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Skin Dis Res Ctr, Boston, MA 02115 USA. Roswell Pk Canc Inst, Grace Canc Drug Ctr, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sackstein, R (reprint author), Harvard Univ, Inst Med, Room 671,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NCI NIH HHS [CA91780-01, R01 CA84156, R01 CA73872, CA16056]; NHLBI NIH HHS [R01 HL60528]; NIAMS NIH HHS [P30AR42689] NR 51 TC 50 Z9 52 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2003 VL 101 IS 2 BP 602 EP 610 DI 10.1182/blood-2002-06-1736 PG 9 WC Hematology SC Hematology GA 635EG UT WOS:000180384800034 PM 12393521 ER PT J AU Hideshima, T Akiyama, M Hayashi, T Richardson, P Schlossman, R Chauhan, D Anderson, KC AF Hideshima, T Akiyama, M Hayashi, T Richardson, P Schlossman, R Chauhan, D Anderson, KC TI Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; FACTOR-ALPHA; DRUG-RESISTANCE; STROMAL CELLS; INTERLEUKIN-6; KINASE; EXPRESSION; APOPTOSIS; ACTIVATION AB p38 mitogen-activated protein kinase (MAPK) is a member of the MAPK family which is activated by cytokines and growth factors, but its role in pathogenesis of multiple myeloma (MM) is unknown. In this study, we demonstrate that the specific p38 MAPK inhibitor VX-745 inhibits interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) secretion in bone marrow stromal cells (BMSCs), without affecting their viability. Tumor necrosis factor alpha (TNF-alpha)induced IL-6 secretion in BMSCs is also inhibited by VX-745. Importantly, VX-745 inhibits both MM cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that it can inhibit paracrine MM cell growth in the BM milieu and overcome cell adhesion-related drug resistance. These studies therefore identify p38 MAPK as a novel therapeutic target to overcome drug resistance and improve patient outcome in MM. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, M557,44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378, R0-1 50947] NR 22 TC 81 Z9 89 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2003 VL 101 IS 2 BP 703 EP 705 DI 10.1182/blood-2002-06-1874 PG 3 WC Hematology SC Hematology GA 635EG UT WOS:000180384800047 PM 12393542 ER PT J AU Sackstein, R Messina, JL Elfenbein, GJ AF Sackstein, R Messina, JL Elfenbein, GJ TI In vitro adherence of lymphocytes to dennal endothelium under shear stress: implications in pathobiology and steroid therapy of acute cutaneous GVHD SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; PSORIATIC DERMAL ENDOTHELIUM; RECEPTOR LIGAND INTERACTION; INVITRO PREDICTIVE TEST; TOTAL-BODY IRRADIATION; ACUTE GRAFT; T-CELLS; ADHESION MOLECULES; SELECTIN LIGAND AB The extravasation of leukocytes at sites of inflammation critically depends on initial shear-resistant adhesive interactions between leukocytes in blood flow and target tissue endothelium. Dermal lymphocytic infiltrates are a hallmark feature of acute cutaneous graft-versus-host disease (acGVHD) following allogeneic hematopoietic stem cell (allo-HSC) transplantation. These infiltrates occur commonly during periods of profound lymphopenia, suggesting that the dermal endothelial adhesive mechanism(s) promoting lymphocyte emigration in acGVHD are highly efficient. To examine this issue, we performed Stamper-Woodruff assays on frozen sections of biopsy specimens of cutaneous lesions occurring within 100 days of HSC transplantation in 22 autologous hernatopoietic stem cell transplant (auto-HSCT) and 25 allo-HSCT recipients. By using this shear-based assay, we observed lymphocyte adherence to papillary dermal vascular structures in all punch biopsy specimens of allo-HSCT recipients who had clinicohistologic evidence of acGVHD and who were not receiving steroids, whereas no lymphocyte adherence was observed within skin specimens from allo-HSCT recipients who did not develop acGVHD. Within the group of auto-HSCT recipients, 2 of 22 skin biopsies demonstrated lymphocyte binding to dermal vessels. Among allo-HSCT patients receiving steroid therapy for acGVHD, lymphocyte binding to dermal endothelium was abrogated prior to resolution of rash in those who responded, yet binding was persistent in skin from one patient whose rash did not respond to steroid therapy. Collectively, these data indicate that the papillary endothelium of skin in acGVHD displays heightened capacity to support lymphocyte adhesion under shear stress conditions and suggest that down-modulation of this endothelial adhesive capability may be one mechanism by which steroids abrogate acGVHD reactions. (C) 2003 by The American Society of Hematology. C1 Roger Williams Gen Hosp, Dept Oncol, Providence, RI 02908 USA. Univ S Florida, Coll Med, Dept Pathol & Lab Med, Tampa, FL USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol,Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur,Rm 671, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA84156] NR 53 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2003 VL 101 IS 2 BP 771 EP 778 DI 10.1182/blood-2002-05-1452 PG 8 WC Hematology SC Hematology GA 635EG UT WOS:000180384800057 PM 12393384 ER PT J AU Haddad, R Colevas, AD Tishler, R Busse, P Goguen, L Sullivan, C Norris, CM Lake-Willcutt, B Case, MA Costello, R Posner, M AF Haddad, R Colevas, AD Tishler, R Busse, P Goguen, L Sullivan, C Norris, CM Lake-Willcutt, B Case, MA Costello, R Posner, M TI Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck - The Dana Farber Cancer Institute experience SO CANCER LA English DT Article DE head and neck carcinoma; induction chemotherapy; docetaxel; cisplatin; 5-fluorouracil; hyperfractionated radiotherapy ID PHASE-III TRIAL; RADIATION-THERAPY; RANDOMIZED TRIAL; FLUOROURACIL; LEUCOVORIN AB BACKGROUND. The authors conducted a series of four Phase I-II trials of high-dose and intermediate-dose docetaxel, cisplatin, and 5-fluorouracil (TPF)-based induction chemotherapy for patients with advanced squamous cell carcinoma of the head and neck (SCCHN). The chemotherapy regimens and response rates for each trial were published previously. In the current analysis, the authors report the data on long-term survival, patterns of failure, and morbidity among the patients who were treated at their institution. METHODS. A total of 101 patients with Previously untreated, locally advanced, curable SCCHN were entered onto the studies. Overall, 68 patients (67%) had N2-N3 disease, and 86 patients (85%) had Stage IV disease. Patients were treated with combinations of TPF with or without leucovorin. Cycles were repeated every 21-28 days for a total of 3 cycles followed by hyperfractionated radiotherapy. RESULTS. After a median follow-up of 49 months, 65 patients (64%) remain alive with no evidence of disease (NED), and 3 patients remain alive with disease, for an overall survival rate of 67% (68 patients). Twenty-six patients had locoregional recurrences (LRR), and 5 patients had both LRR and distant metastasis (DM). Only five patients had DM as the sole site of failure. Four patients underwent salvage surgery at the primary site and remain alive with NED. Excluding 17 patients with nasopharyngeal carcinoma, of 84 patients, 55 patients remain alive with NED (65%). Notably, 43 of 84 patients (51%) had oropharyngeal primary tumors, and 30 of those patients remain alive with NED (70%). Significant morbidity was low, with two treatment-related deaths. All but two of the surviving patients are able to swallow and had their feeding tubes removed. CONCLUSIONS. These data suggest that docetaxel adds incrementally to the efficacy of cisplatin and fluorouracil. Local-regional failures continue to be the major impediment to cure in these patients. Given the increase in local-regional dose intensity with chemoradiation, sequential treatment plans that integrate induction chemotherapy and chemoradiotherapy seem to be the logical next step. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, CTEP, Invest Drug Branch, Rockville, MD USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Haddad, R (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, SW430G,44 Binney St, Boston, MA 02115 USA. NR 20 TC 67 Z9 67 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 2003 VL 97 IS 2 BP 412 EP 418 DI 10.1002/cncr.11063 PG 7 WC Oncology SC Oncology GA 635LW UT WOS:000180401600009 PM 12518365 ER PT J AU Biswas, DK Martin, KJ McAlister, C Cruz, AP Graner, E Dai, SC Pardee, AB AF Biswas, DK Martin, KJ McAlister, C Cruz, AP Graner, E Dai, SC Pardee, AB TI Apoptosis caused by chemotherapeutic inhibition of nuclear factor-kappa B activation SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; TRANSCRIPTION FACTORS; GENE-EXPRESSION; PROGRESSION; PROTEINS; TARGET AB Both the protein kinase C (alpha/beta) inhibitor Go6976 and expression of dominant-negative nuclear factor (NF)-kappaB inhibitor kinase mutants: (a) blocked the growth and caused regression of a mammary tumor in syngeneic mice; (b) inhibited epidermal growth factor (EGF)-induced activation, nuclear translocation, and DNA-binding activity of NF-kappaB; and (c) caused apoptosis of EGF-stimulated cultured mammary tumor cells. cDNA microarray analysis revealed that these treatments reversed the expression changes of a subset of genes altered by EGF treatment. These included: up-regulation of proapoptotic genes of the tumor necrosis factor (TNF) pathway, death-associated protein (DAP) kinase, p53, and p21/Waf1; and down-regulation of inhibitors of apoptosis: inhibitor of apoptosis (IAP)-1 and X-IAP, TNF receptor-associated factor (TRAF)-2, and factors OX40 and 4-1BB. These results and our previous studies suggest the practicality of a target-directed chemotherapy for EGF-responsive breast cancers, by blocking NF-kappaB activation and thereby reinstating apoptosis. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Room Smith 822,44 Binney St, Boston, MA 02115 USA. RI Graner, Edgard/K-4411-2012 NR 25 TC 65 Z9 72 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2003 VL 63 IS 2 BP 290 EP 295 PG 6 WC Oncology SC Oncology GA 640PQ UT WOS:000180697500005 PM 12543776 ER PT J AU French, CA Miyoshi, I Kubonishi, I Grier, HE Perez-Atayde, AR Fletcher, JA AF French, CA Miyoshi, I Kubonishi, I Grier, HE Perez-Atayde, AR Fletcher, JA TI BRD4-NUT fusion oncogene: A novel mechanism in aggressive carcinoma SO CANCER RESEARCH LA English DT Article ID TRANSLOCATION; BROMODOMAIN AB The poorly differentiated carcinoma with t(15;19)(q13, p13.1) is characterized by its highly aggressive, invariably lethal clinical course. The chromosome 19 translocation breakpoint targets the BRD4 double bromodomain-containing gene, which functions in regulation of cell cycle progression. Herein we demonstrate that BRD4 is fused with nearly the entire transcript of the novel 15q13 gene, NUT (nuclear protein in testis), forming a 6.4-kb fusion oncogene, BRD4-NUT. NUT, like BRD4, is predicted to encode a nuclear protein but, unlike the ubiquitous BRD4 transcript, is expressed only in testis. These findings establish a model to elucidate the oncogenic consequences of unscheduled NUT expression and altered BRD4 function. Very few fusion oncogenes have been identified in epithelial tumors, and BRD4-NUT is the first fusion oncogene mechanism identified in a highly lethal form of carcinoma. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Kochi Med Sch, Nanko Ku, Kochi 7838505, Japan. RP French, CA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [1 K08 CA92158-01]; NHLBI NIH HHS [T32-HL07627] NR 16 TC 160 Z9 167 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2003 VL 63 IS 2 BP 304 EP 307 PG 4 WC Oncology SC Oncology GA 640PQ UT WOS:000180697500008 PM 12543779 ER PT J AU Okada, Y Hurwitz, EE Esposito, JM Brower, MA Nutt, CL Louis, DN AF Okada, Y Hurwitz, EE Esposito, JM Brower, MA Nutt, CL Louis, DN TI Selection pressures of TP53 mutation and microenvironmental location influence epidermal growth factor receptor gene amplification in human glioblastomas SO CANCER RESEARCH LA English DT Article ID EGFR AMPLIFICATION; MULTIFORME; GLIOMA; P53; EXPRESSION; INVASION AB Epidermal growth factor receptor (EGFR) gene amplification occurs in glioblastomas as so-called double minutes. Because double minutes are extrachromosomal fragments, selection pressures must operate to maintain high EGFR copy number over multiple cell divisions. In analyses of glioblastoma lysates, EGFR amplification has been observed almost exclusively in glioblastomas harboring wild-type TP53 genes, which raises the alternative hypotheses that TP53 mutation either prevents amplification or selects against maintenance of EGFR-amplified cells. To address these possibilities at the cellular level, we studied 14 glioblastomas for TP53 mutation and EGFR gene amplification status, using fluorescence in situ hybridization (FISH), for the latter. Remarkably, four of the six cases with TP53 mutation had isolated EGFR-amplified cells in different regions, demonstrating that EGFR amplification occurs frequently at the cellular level in TP53-mutant glioblastomas. Thus, TP53 mutation does not prevent EGFR amplification but does not facilitate selection of EGFR-amplified cells. Of the eight cases without TP53 mutation, five had widespread EGFR amplification. In four of these five cases, multiple regions of the tumor were available for examination; FISH demonstrated a gradation of EGFR amplification, with highly amplified cells, primarily at the invading edges rather than the relatively solid tumor centers, suggesting that EGFR overexpression, when selected for in vivo, may be related to tumor invasion. C1 Massachusetts Gen Hosp, Mol Pathol Lab, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Pathol Lab, Dept Pathol, CNT7,149 13th St, Charlestown, MA 02129 USA. NR 23 TC 76 Z9 81 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2003 VL 63 IS 2 BP 413 EP 416 PG 4 WC Oncology SC Oncology GA 640PQ UT WOS:000180697500025 PM 12543796 ER PT J AU Kau, TR Silver, PA AF Kau, TR Silver, PA TI Nuclear transport as a target for cell growth SO DRUG DISCOVERY TODAY LA English DT Review ID NF-KAPPA-B; PROTEIN-KINASE-B; FORKHEAD TRANSCRIPTION FACTOR; ORDER CHROMOSOME STRUCTURE; TUMOR-SUPPRESSOR PROTEIN; RING-FINGER DOMAIN; LEPTOMYCIN-B; CAENORHABDITIS-ELEGANS; PEPTIDE APTAMERS; EXPORT SIGNAL AB The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor kappaB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a potential therapeutic target, only two nuclear transport inhibitors have been reported. Here, we explore the roles of small-molecule inhibitors that cause target proteins to sequester in either the nucleus or cytoplasm. Methods of artificially targeting proteins to the nucleus or cytoplasm using peptide aptamer technology are also discussed. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Kau, TR (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 74 TC 48 Z9 49 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JAN 15 PY 2003 VL 8 IS 2 BP 78 EP 85 AR PII S1359-6446(02)02562-X DI 10.1016/S1359-6446(02)02562-X PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 636BF UT WOS:000180434100008 PM 12565010 ER PT J AU Zinkel, SS Ong, CC Ferguson, DO Iwasaki, H Akashi, K Bronson, RT Kutok, JL Alt, FW Korsmeyer, SJ AF Zinkel, SS Ong, CC Ferguson, DO Iwasaki, H Akashi, K Bronson, RT Kutok, JL Alt, FW Korsmeyer, SJ TI Proapoptotic BID is required for myeloid homeostasis and tumor suppression SO GENES & DEVELOPMENT LA English DT Article DE BID; BCL-2; myeloid; cancer; apoptosis; Fas ID BCL-2 FAMILY MEMBERS; HEMATOPOIETIC STEM-CELLS; CYTOCHROME-C RELEASE; LYMPHOID HYPERPLASIA; DEFICIENT MICE; DEATH AGONIST; IN-VIVO; APOPTOSIS; BAX; SURVIVAL AB The proper expansion and contraction of hematopoietic cells requires tight regulation of cell death. BID, a "BH3-only" molecule, amplifies death receptor signals connecting the extrinsic to intrinsic pathways by triggering the mitochondrial pathway of apoptosis. Bid-deficient mice, as they age, spontaneously develop a myeloproliferative disorder, which progresses from myeloid hyperplasia to a fatal, clonal malignancy closely resembling chronic myelomonocytic leukemia (CMML). Thus, an apoptotic defect can result in myeloid leukemogenesis. Premalignant Bid-/- myeloid precursor cells are resistant to death receptor-induced apoptosis. Furthermore, a competitive reconstitution assay demonstrates that Bid-deficient long-term repopulating cells give rise to expanded myelomortocytic cells in vivo. Surprisingly, a single BH3-only molecule operating in the extrinsic death receptor pathway proved essential in vivo for physiologic cell death required to maintain myeloid homeostasis. Moreover, progression to CMML indicates that an upstream BH3-only molecule, BID, is required to suppress tumorigenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med,Dept Genet, Howard Hughes Med Inst,Ctr Blood Res, Div Immunol,Boston Childrens Hosp, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Howard Hughes Med Inst, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA50239] NR 45 TC 125 Z9 126 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2003 VL 17 IS 2 BP 229 EP 239 DI 10.1101/gad.1045603 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 637DP UT WOS:000180496600007 PM 12533511 ER PT J AU Shibata, S Lee, JT AF Shibata, S Lee, JT TI Characterization and quantitation of differential Tsix transcripts: implications for Tsix function SO HUMAN MOLECULAR GENETICS LA English DT Article ID X-CHROMOSOME INACTIVATION; MOUSE XIST GENE; BECKWITH-WIEDEMANN-SYNDROME; DOUBLE-STRANDED-RNA; EXPRESSED TRANSCRIPT; IMPRINTED GENES; CPG ISLAND; ANTISENSE; REGION; LOCUS AB In dosage compensation of female mammals, the accumulation of Xist RNA initiates silencing of one X-chromosome. Xist action is repressed by the antisense gene, Tsix, whose full-length RNA product is complementary to Xist RNA in mice. While previous work showed that Tsix transcription blocks the accumulation of Xist RNA, it is still unclear whether this repression requires the antisense RNA product or whether the antisense transcriptional movement is sufficient. A better understanding of potential mechanisms requires elucidation of Tsix RNA structure and determination of Tsix RNA copy number relative to that of Xist RNA. Previous work indicated that at least some of murine Tsix is spliced and that human TSIX truncates within the 3' end of XIST. Here, further characterization and quantitation of murine Tsix RNA reveal three new findings: first, in undifferentiated embryonic stem cells, Tsix RNA is present at 10-100-fold molar excess over Xist RNA. Second, only 30-60% of Tsix RNA is spliced at known exon-intron junctions. The nearly equal abundance of spliced and unspliced species leaves open possible roles for both isoforms. Finally, Tsix is spliced heterogeneously at the 5' end and most detectable splice variants exhibit only a 1.9 kb region of complementarity between sense and antisense RNAs. Implications for Tsix's possible mechanisms of action are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01GM58835] NR 45 TC 60 Z9 63 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN 15 PY 2003 VL 12 IS 2 BP 125 EP 136 DI 10.1093/hmg/ddg010 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 636PD UT WOS:000180464200004 PM 12499393 ER PT J AU Wong, GC Giugliano, RP Antman, EM AF Wong, GC Giugliano, RP Antman, EM TI Use of low-molecular-weight heparins in the management of acute coronary artery syndromes and percutaneous coronary intervention SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; FACTOR PATHWAY INHIBITOR; DIRECT THROMBIN INHIBITOR; UNSTABLE ANGINA-PECTORIS; UNFRACTIONATED HEPARIN; TISSUE FACTOR; PLATELET ACTIVATION; THERAPEUTIC CONCENTRATIONS; SUBCUTANEOUS ENOXAPARIN; PLASMINOGEN-ACTIVATOR AB Context Low-molecular-weight heparins (LMWHs) possess several potential pharmacological advantages over unfractionated heparin as an antithrombotic agent. Objective To systematically summarize the clinical data on the efficacy and safety of LMWHs compared with unfractionated heparin across the spectrum of acute coronary syndromes (ACSs), and as an adjunct to percutaneous coronary intervention (PCI). Data Sources We searched MEDLINE for articles from 1990 to 2002 using the index terms heparin, enoxaparin, dalteparin, nadroparin, tinzaparin, low molecular weight heparin, myocardial infarction, unstable angina, coronary angiography, coronary angioplasty, thrombolytic therapy, reperfusion, and drug therapy, combination. Additional data sources included bibliographies of articles identified on MEDLINE, inquiry of experts and pharmaceutical companies, and data presented at recent national and international cardiology conferences. Study Selection We selected for review randomized trials comparing LMWHs against either unfractionated heparin or placebo for treatment of ACS, as well as trials and registries examining clinical outcomes, pharmacokinetics, and/or phamacodynamics of LMWHs in the setting of PCI. Of 39 studies identified, 31 fulfilled criteria for analysis. Data Extraction Data quality was determined by publication in the peer-reviewed literature or presentation at an official cardiology society-sponsored meeting. Data Synthesis The LMWHs are recommended by the American Heart Association and the American College of Cardiology for treatment of unstable angina/non-ST-elevation myocardial infarction. Clinical trials have demonstrated similar safety with LMWHs compared with unfractionated heparin in the setting of PCI and in conjunction with glycoprotein IIb/IIIa inhibitors. Finally, LMWHs show promise as an. antithrombotic agent for the treatment of ST-elevation myocardial infarction. Conclusions The LMWHs could potentially replace unfractionated heparin as the antithrombotic agent of choice across the spectrum of ACSs. In addition, they show promise as a safe and efficacious antithrombotic agent for PCI. However, further study is warranted to define the benefit of LMWHs in certain high-risk subgroups before their use can be universally recommended. C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. NR 95 TC 56 Z9 63 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 15 PY 2003 VL 289 IS 3 BP 331 EP 342 DI 10.1001/jama.289.3.331 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 634MV UT WOS:000180345100028 PM 12525234 ER PT J AU Emmons, KM Butterfield, RM Puleo, E Park, ER Mertens, A Gritz, ER Lahti, M Li, FP AF Emmons, KM Butterfield, RM Puleo, E Park, ER Mertens, A Gritz, ER Lahti, M Li, FP TI Smoking among participants in the childhood cancer survivors cohort: The partnership for health study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SELF-EFFICACY; PSYCHOLOGICAL DISTRESS; TRANSTHEORETICAL MODEL; NICOTINE DEPENDENCE; CESSATION; BEHAVIORS; PREDICTORS; BUPROPION AB Purpose: This article describes baseline data collection and the intervention design of Partnership for Health, a smoking cessation intervention for smokers in the Childhood Cancer Survivors Study. The purpose of this article is to evaluate demographic, psychosocial, and cancer-related factors that are associated with smoking behavior and mediators of smoking cessation. Patients and Methods: This study includes 796 smokers from the Childhood Cancer Survivors Study database who were diagnosed with cancer before the age of 21, had survived at least 5 years, and were at least 18 years of age at the time of the baseline survey. Correlates of smoking behaviors included smoking rate, number of recent quit attempts, and nicotine dependence; two key mediators of smoking cessation, readiness to quit smoking and self-efficacy, were also assessed. Results: Participants smoked, on average, 14 cigarettes/day; 53.2% were nicotine dependent, and 58% had made at least one quit attempt in the past year. Smoking behaviors were primarily associated with demographic variables; mediators of cessation were primarily associated with age at cancer diagnosis and perceived vulnerability to smoking-related illnesses. Severity of psychologic symptoms was associated with increased smoking rate, high nicotine dependence, and low self-efficacy. Support for quitting was related to smoking rate, number of quit attempts, readiness to quit smoking, and self-efficacy. Conclusion: These findings indicate that many cancer survivors who smoke are receptive to smoking cessation interventions. factors related to mediators of smoking cessation might be particularly good targets for intervention. (C) 2003 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA77780, U24-CA55727] NR 47 TC 58 Z9 58 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 15 PY 2003 VL 21 IS 2 BP 189 EP 196 DI 10.1200/JCO.2003.06.130 PG 8 WC Oncology SC Oncology GA 685UG UT WOS:000183281200004 PM 12525509 ER PT J AU Schnoll, RA Zhang, B Rue, M Krook, JE Spears, WT Marcus, AC Engstrom, PF AF Schnoll, RA Zhang, B Rue, M Krook, JE Spears, WT Marcus, AC Engstrom, PF TI Brief physician-initiated quit-smoking strategies for clinical oncology settings: A trial coordinated by the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; NECK-CANCER; TOBACCO USE; HOSPITALIZED SMOKERS; CESSATION; HEAD; INTERVENTION; DEPENDENCE; PREDICTORS; SURVIVAL AB Purpose : Although tobacco use by cancer patients increases the risk of relapse, diminishes treatment efficacy, and worsens quality of life, about one third of patients who smoked before their diagnosis continue to smoke. Because patients have regular contact with oncologists, the efficacy of a physician-based smoking cessation treatment was evaluated. Methods: Cancer patients (n = 432) were randomly assigned to either usual care or a National Institutes of Health (NIH) physician-based smoking intervention. The primary outcome was 7-day point prevalence abstinence at 6 and 12 months after study entry. Results: At the 6-month follow-up, there was no significant difference in quit rates between the usual care (11.9%) and intervention (14.4%) groups, and there was no significant difference between the usual care (13.6%) and intervention (13.3%) groups at the 12-month follow-up. Patients were more likely to have quit smoking at 6 months if they had head and neck or lung cancer, began smoking after the age of 16, reported at baseline using a cessation self-help guide or treatment in the last 6 months, and showed greater baseline desire to quit. Patients were more likely to have quit smoking at 12 months if they smoked 15 or fewer cigarettes per day, had head and neck or lung cancer, tried a group cessation program, and showed greater baseline desire to quit. Finally, there was greater adherence among physicians to the NIH model for physician smoking treatment for patients in the intervention versus the usual care group. Conclusion: While training physicians to provide smoking cessation treatment to cancer patients can enhance physician adherence to clinical practice guidelines, physician smoking cessation interventions fail to yield significant gains in long-term quit rates among cancer patients. (C) 2003 by American Society of Clinical Oncology. C1 Fox Chase Canc Ctr, Psychosocial & Behav Med Program, Cheltenham, PA 19012 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duluth Clin, Duluth, MN USA. Pk Nicollet Hlth Serv, St Louis Pk, MN USA. AMC Res Ctr, Denver, CO USA. RP Schnoll, RA (reprint author), Fox Chase Canc Ctr, Psychosocial & Behav Med Program, 510 Township Line Rd, Cheltenham, PA 19012 USA. RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [CA13650, CA21115, CA23318, CA27525, CA66636] NR 57 TC 73 Z9 76 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 15 PY 2003 VL 21 IS 2 BP 355 EP 365 DI 10.1200/JCO.2003.04.122 PG 11 WC Oncology SC Oncology GA 685UG UT WOS:000183281200025 PM 12525530 ER PT J AU Parhami-Seren, B Seavey, M Krudysz, J Tsantili, P AF Parhami-Seren, B Seavey, M Krudysz, J Tsantili, P TI Structural correlates of a functional streptokinase antigenic epitope: serine 138 is an essential residue for antibody binding SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE streptokinase; streptokinase variants; streptokinase-plasminogen activator complex; anti-streptokinase monoclonal antibodies; site-directed mutagenesis; plasminogen activation ID GROUP-A STREPTOCOCCI; AMINO-ACID-SEQUENCE; HUMAN-PLASMINOGEN; NUCLEOTIDE-SEQUENCE; CRYSTAL-STRUCTURE; ACTIVATION; GENE; DOMAIN; REGION; SUBSTRATE AB We determined the pattern of cross-reactivity of a panel of anti-streptokinase (SK) monoclonal antibodies (mAbs) with SK variants in order to map the antigenic and functional epitope of SK. Comparison of the pattern of cross-reactivity of the anti-SK mAb A4.3 with SK variants and sequence alignments of SK variants and native (n) SK suggested that mutation of Ser 13 8 to Lys results in loss of binding of mAb A4.3 to SK variants. However, this mutation does not affect formation of activator complex by these proteins. The epitope specificity of the mAb A4.3 was further confirmed by mutating Ser 138 to Lys in n SK. 2 Monoclonal Ab A4.3 did not bind to mutant SK (Ser138Lys)(2). Activator activity of mutant SK (Ser138Lys) was indistinguishable from that of n SK and recombinant n SK. Since addition of A4.3 mAb to an equimolar mixture of SK and human plasminogen inhibits activator complex fort-nation, the sequences spanning position 138 are likely important for formation of streptokinase-plasminogen activator complex or processing of the plasminogen substrate. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Parhami-Seren, B (reprint author), Univ Vermont, Coll Med, Dept Biochem, Given Bldg,89 Beaumont St, Burlington, VT 05405 USA. NR 34 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 15 PY 2003 VL 272 IS 1-2 BP 93 EP 105 AR PII S0022-1759(02)00435-0 DI 10.1016/S0022-1759(02)00435-0 PG 13 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 635RR UT WOS:000180413400009 PM 12505715 ER PT J AU Reddy, J Bettelli, E Nicholson, L Waldner, H Jang, MH Wucherpfennig, KW Kuchroo, VK AF Reddy, J Bettelli, E Nicholson, L Waldner, H Jang, MH Wucherpfennig, KW Kuchroo, VK TI Detection of autoreactive myelin proteolipid protein 139-151-specific T cells by using MHC II (IA(s)) tetramers SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED DEMYELINATING DISEASE; SUSCEPTIBLE SJL/J MICE; THYMIC SELECTION; ENCEPHALITOGENIC DETERMINANT; PEPTIDE; MOLECULES; EPITOPE; ENCEPHALOMYELITIS; IDENTIFICATION; RESPONSES AB Detection of autoreactive T cells using MHC II tetramers is difficult because of the low affinity of their TCR. We have generated a class II tetramer using the IA(s) class II molecule combined with an autoantigenic peptide from myelin proteolipid protein (PLP; PLP139-151) and used it to analyze myelin PLP139-151-reactive T cells. Using monomers and multimerized complexes labeled with PE, we confirmed the specificity of the reagent by bioassay and flow cytometry. The IA(s) tetramers stimulated and stained the PLP139-151-specific 5B6 TCR transgenic T cells and a polyclonal cell line specific for PLP139-151, but not a control T cell line specific for PLP178-191. We used this reagent to optimize conditions to detect low affinity autoreactive T cells. We found that high pH (similar to8.0) and neuraminidase treatment enhances the staining capacity of PLP139-151 tetramer without compromising specificity. Furthermore, we found that induction of calcium fluxing by tetramers in T cells may be used as a sensitive measure to detect autoreactive T cells with a low affinity. Taken together, the data show that the tetrameric reagent binds and stimulates PLP139-151-reactive T cells with specificity. This tetrameric reagent will be useful in studying the evolution of PLP139-151-specific repertoire in naive mice and its expansion during the autoimmune disease experimental autoimmune encephalomyelitis. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Harvard Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kuchroo, VK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Harvard Inst Med, Rm 706, Boston, MA 02115 USA. RI Reddy, Jay/K-7200-2014 OI Reddy, Jay/0000-0003-4082-9254 NR 33 TC 50 Z9 50 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2003 VL 170 IS 2 BP 870 EP 877 PG 8 WC Immunology SC Immunology GA 633QQ UT WOS:000180294300027 PM 12517952 ER PT J AU Valdez, H Mitsuyasu, R Landay, A Sevin, AD Chan, ES Spritzler, J Kalams, SA Pollard, RB Fahey, J Fox, L Namkung, A Estep, S Moss, R Sahner, D Lederman, MM AF Valdez, H Mitsuyasu, R Landay, A Sevin, AD Chan, ES Spritzler, J Kalams, SA Pollard, RB Fahey, J Fox, L Namkung, A Estep, S Moss, R Sahner, D Lederman, MM TI Interleukin-2 increases CD4(+) lymphocyte numbers but does not enhance responses to immunization: Results of A5046s SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN ID IMMUNODEFICIENCY-VIRUS INFECTION; ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; VACCINATION; RECALL AB To ascertain whether CD4(+) lymphocyte increases induced by interleukin (IL)-2 enhanced in vivo immune responses, 38 human immunodeficiency virus (HIV)-infected patients who had received highly active antiretroviral therapy (HAART) or HAART and IL-2 for at least 60 weeks were immunized with tetanus toxoid, inactivated glycoprotein 120-depleted HIV-1, and hepatitis A and B vaccines. Despite dramatic increases in CD4(+) lymphocyte counts, IL-2 did not enhance immunization responses. C1 Univ Hosp Cleveland, AIDS Clin Trials Unit, Div Infect Dis, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Immune Response Corp, Carlsbad, CA USA. Chiron Corp, Emeryville, CA 94608 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Texas, Galveston, TX 77555 USA. NIH, Div AIDS, Bethesda, MD 20892 USA. AIDS Clin Trials Grp Operat Ctr, Silver Spring, MD USA. RP Valdez, H (reprint author), Univ Hosp Cleveland, AIDS Clin Trials Unit, Div Infect Dis, 2061 Cornell Rd,Rm 401B, Cleveland, OH 44106 USA. FU NCRR NIH HHS [RR00080]; NIAID NIH HHS [AI-50501-01, AI-25879, AI-38855, AI-38858, AI-36219] NR 15 TC 40 Z9 40 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2003 VL 187 IS 2 BP 320 EP 325 DI 10.1086/346056 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 632MF UT WOS:000180226500019 PM 12552459 ER PT J AU Monnard, PA AF Monnard, PA TI Liposome-entrapped polymerases as models for microscale/nanoscale bioreactors SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review DE amphiphile vesicles; liposomes; entrapped polymerases; bioreactors; artificial cell ID SELF-REPRODUCING VESICLES; FATTY-ACID MEMBRANES; CATIONIC LIPOSOMES; LIPID VESICLES; PHOSPHOLIPID-VESICLES; GENE-TRANSFER; AMINO-ACIDS; DNA; BILAYERS; SIZE C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Monnard, PA (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Wellman 9,50 Blossom St, Boston, MA 02114 USA. NR 63 TC 57 Z9 57 U1 1 U2 15 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JAN 15 PY 2003 VL 191 IS 2 BP 87 EP 97 DI 10.1007/s00232-002-1046-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 642RC UT WOS:000180817300001 PM 12533776 ER PT J AU Dijkhuizen, RM Singhal, AB Mandeville, JB Wu, O Halpern, EF Finklestein, SP Rosen, BR Lo, EH AF Dijkhuizen, RM Singhal, AB Mandeville, JB Wu, O Halpern, EF Finklestein, SP Rosen, BR Lo, EH TI Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats: A functional magnetic resonance imaging study SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain ischemia; neuronal plasticity; recovery of function; hemodynamics; magnetic resonance imaging; rats ID ARTERY OCCLUSION; VASOGENIC EDEMA; WATER DIFFUSION; BLOOD-VOLUME; ADULT-RATS; STROKE; RECOVERY; MRI; PLASTICITY; INFARCTION AB The pattern and role of brain plasticity in stroke recovery has been incompletely characterized. Both ipsilesional and contralesional changes have been described, but it remains unclear how these relate to functional recovery. Our goal was to correlate brain activation patterns with tissue damage, hemodynamics, and neurologic status after temporary stroke, using functional magnetic resonance imaging (fMRI). Transverse relaxation time (T-2)-weighted, diffusion-weighted, and perfusion MRI were performed at days 1 (n = 7),3 (n = 7), and 14 (n = 7) after 2 hr unilateral middle cerebral artery occlusion in rats. Functional activation and cerebrovascular reactivity maps were generated from contrast-enhanced fMRI during forelimb stimulation and hypercapnia, respectively. Before MRI, rats were examined neurologically. We detected loss of activation responses in the ipsilesional sensorimotor cortex, which was related to T-2 lesion size (r= -0.858 on day 3, r= -0.979 on day 14; p < 0.05). Significant activation responses in the contralesional hemisphere were detected at days 1 and 3. The degree of shift in balance of activation between the ipsilesional and contralesional hemispheres, characterized by the laterality index, was linked to the T(c)ontralesional forelimb region of the primary somatosensory cortex and primary motor cortex at day 1 (r= -0.807 and 0.782, respectively; p < 0.05) and day 14 (r= -0.898 and -0.970, respectively; p < 0.05). There was no correlation between activation parameters and perfusion status or cerebrovascular reactivity. Finally, we found that the laterality index and neurologic status changed in parallel over time after stroke, so that when all time points were grouped together, neurologic status was inversely correlated with the laterality index (r= -0.571; p = 0.016). This study suggests that the degree of shift of activation balance toward the contralesional hemisphere early after stroke increases with the extent of tissue injury and that functional recovery is associated mainly with preservation or restoration of activation in the ipsilesional hemisphere. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Athinoula A Martinos Ctr Biopmed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Data Anal Grp, Boston, MA 02114 USA. ViaCell Neurosci Inc, Worcester, MA 01605 USA. RP Univ Med Ctr Utrecht, Image Sci Inst, Bolognalaan 50, NL-3584 CJ Utrecht, Netherlands. EM rick@invivonmr.uu.nl RI Dijkhuizen, Richard/A-6506-2008 FU NCI NIH HHS [P01-CA48729]; NCRR NIH HHS [P41-RR14075]; NHLBI NIH HHS [R01-HL39810]; NINDS NIH HHS [R01-NS38731, P50-NS10828, R01-NS37074, R01-NS38477] NR 48 TC 169 Z9 180 U1 1 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 15 PY 2003 VL 23 IS 2 BP 510 EP 517 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 637QC UT WOS:000180523000017 PM 12533611 ER PT J AU Bozkurt, B Agoston, I Knowlton, AA AF Bozkurt, B Agoston, I Knowlton, AA TI Complications of inappropriate use of spiroholactone in heart failure: When an old medicine spirals out of new guidelines SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONVERTING ENZYME-INHIBITORS; SPIRONOLACTONE; OUTCOMES AB Objectives This study was designed to investigate the appropriateness and complications of the use of spironolactone for heart failure (HF) in clinical practice. Background Spironolactone was reported by one prospective randomized trial to decrease morbidity and mortality in patients with New York Heart Association (NYHA) class III and IV HF. With this report (Randomized Spironolactone Evaluation Study [RALES] trial), we noted a marked increase in widespread use of spironolactone in patients with HF. Long-term outcome data with respect to safety and utilization of this medication in HF are not available. Methods To investigate the use of spironolactone for HF in a clinical setting, we analyzed the application of the RALES trial protocol to the care of 104 patients, whom we identified as being started on spironolactone for HF after prerelease of the RALES trial. Results We found broader use, less intensive follow-up, and increased complications with spironolactone treatment compared with the RALES trial. Cardiologists provided more appropriate care than did primary care providers. Conclusions These data suggest that spironolactone is being used widely in HF without consideration of the NYHA class and ejection fraction, and without optimization of background treatment with angiotensin-converting enzyme inhibitors and beta-blockers. Clinical follow-up does not adhere to the RALES trial guidelines, resulting in higher complications. We conclude that long-term studies with further safety and efficacy data are needed. C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. RP Knowlton, AA (reprint author), Univ Calif Davis, Div Cardiovasc, TB172,1 Shields Ave, Davis, CA 95616 USA. NR 13 TC 130 Z9 134 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 JAN 15 PY 2003 VL 41 IS 2 BP 211 EP 214 AR PII S0735-1097(02)02694-3 DI 10.1016/S0735-1097(02)02694-3 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 634VQ UT WOS:000180362800007 PM 12535810 ER PT J AU Abernethy, WB Choo, JK Hutter, AM AF Abernethy, WB Choo, JK Hutter, AM TI Echocardiographic characteristics of professional football players SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ATHLETES HEART; HYPERTROPHIC CARDIOMYOPATHY; BLOOD-PRESSURE; DIMENSIONS AB Objectives We examined the echocardiographic characteristics of highly trained American football players. Background Intense physical training is associated with morphologic and physiologic cardiac changes often referred to as the "athlete's heart." Echocardiographic features peculiar to elite football players have not been described. Methods We studied cardiac morphology and function as assessed by rest and stress echocardiography in 156 asymptomatic National Football League players. Resting and stress ejection fraction (EF), wall thickness, and diastolic left ventricular internal diameter (LVID) were measured. Left ventricular (LV) mass was calculated, as was relative wall thickness (RWT) defined as septal and posterior wall thickness divided by LVID. Control data were obtained from published studies. Results The mean LVID (53+/-0.5 mm) and maximal wall thickness (11.2+/-0.2 mm) were increased over normal reported control subjects. There was a correlation between LVID and body weight (p=0.01) and body surface area (BSA) (p=0.01). The average LVID indexed to BSA was 23+/-2 mm/M-2. There was also a correlation between maximal wall thickness and body weight (p=0.01) and BSA (p=0.01). The average wall thickness indexed to BSA was 5.05+/-0.88 mm/M-2. Of the players, 23% had evidence of LV hypertrophy. Two players had an increased septal-to-posterior-wall-thickness ratio (greater than or equal to1.3), although no player had an outflow gradient. The RWT for the players was 0.424 (+/-0.1). The mean resting EF was 58% (+/-4.4%), and every player undergoing exercise testing had an appropriate hyperdynamic response in cardiac function. Conclusions Both wall thickness and LVID of elite American football players are increased and correlate with body size. There is a high R W, reflecting an emphasis on strength training. The LV EF was normal and not supranormal, as is sometimes believed. Regardless of the resting EF, all players had hyperdynamic cardiac responses with exercise. C1 ACC 467 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Hutter, AM (reprint author), ACC 467 Massachusetts Gen Hosp, Cardiac Unit, 14 Parkman St, Boston, MA 02114 USA. NR 15 TC 50 Z9 50 U1 0 U2 3 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 JAN 15 PY 2003 VL 41 IS 2 BP 280 EP 284 AR PII S0735-1097(02)02633-5 DI 10.1016/S0735-1097(02)02633-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 634VQ UT WOS:000180362800020 PM 12535823 ER PT J AU Okura, Y Dec, GW Hare, JM Kodama, M Berry, GJ Tazelaar, HD Bailey, KR Cooper, LT AF Okura, Y Dec, GW Hare, JM Kodama, M Berry, GJ Tazelaar, HD Bailey, KR Cooper, LT TI A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LONG-TERM SURVIVAL; EXPRESSION; CYTOKINE; DISEASE; ENTITY AB Objectives The goal of this study was to determine the prognostic value of clinical data available at presentation and histology in cardiac sarcoidosis (CS) and idiopathic giant cell myocarditis (IGCM). Background The prognosis of patients with nonischemic cardiomyopathy is partly dependent on the histologic diagnosis. Survival in IGCM is poor. The prognosis of a histologically related entity, cardiac sarcoidosis (CS), is less well established, and the prognostic value of the distinction between CS and IGCM on endomyocardial biopsy (EMB) is unknown. Methods We identified 115 patients from the Multicenter IGCM Registry with CS (n=42) and IGCM (n=73). We compared the clinical data for these two groups using Cox proportional-hazards models to assess the association between histologic diagnosis and survival. In order to determine whether histologic features could reliably diffierentiate these two entities, two cardiac pathologists semiquantitatively graded the inflammatory infiltrate components and compared the results between groups. Results Black race was more frequent in the CS group (31% vs. 4%, p<0.0001). Syncope and atrioventricular block were also more frequently observed in CS than IGCM (31% vs. 5%, p=0.0002 and 50% vs. 15%, p<0.0001, respectively). Left-sided heart failure was more common in IGCM (40% vs. 64%, p=0.013). In CS patients diagnosed by EMB, the five-year transplant-free survival after diagnosis was 69.8% versus 21.9% for IGCM (p<0.0001, log-rank test). In multivariate models, presentation with heart failure predicted IGCM, and presentation with heart block or more than nine weeks of symptoms predicted CS. Eosinophils, myocyte damage, and foci of lymphocytic myocarditis were more frequent in IGCM, while granulomas and fibrosis were more frequent in CS. Conclusions Transplant-free survival is better for patients with CS than for IGCM diagnosed by EMB. Presentation with heart failure predicted IGCM, and presentation with heart block or more than nine weeks of symptoms predicted CS. C1 Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Anat Pathol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Biostat, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. Johns Hopkins Univ Hosp, Div Cardiovasc, Baltimore, MD 21287 USA. Niigata Univ, Sch Med, Dept Internal Med 1, Niigata, Japan. Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. RP Cooper, LT (reprint author), Mayo Clin & Mayo Fdn, Div Cardiovasc, Mayo E 16B, Rochester, MN 55905 USA. NR 22 TC 89 Z9 94 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 JAN 15 PY 2003 VL 41 IS 2 BP 322 EP 328 AR PII S0735-1097(02)02715-8 DI 10.1016/S0735-1097(02)02715-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 634VQ UT WOS:000180362800026 PM 12535829 ER PT J AU Bronikowski, AM Carter, PA Morgan, TJ Garland, T Ung, N Pugh, TD Weindruch, R Prolla, TA AF Bronikowski, AM Carter, PA Morgan, TJ Garland, T Ung, N Pugh, TD Weindruch, R Prolla, TA TI Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart SO PHYSIOLOGICAL GENOMICS LA English DT Article DE aging; artificial selection; exercise; microarray; Mus domesticus; stress/inflammation response ID DIETARY RESTRICTION; STRESS RESISTANCE; PHYSICAL-ACTIVITY; APOLIPOPROTEIN-D; DEFICIENT MICE; HOUSE MICE; LONGEVITY; SPAN; RATS; PROTEIN AB We present the first quantitative gene expression analysis of cardiac aging under conditions of sedentary and active lifestyles using high-density oligonucleotide arrays representing 11,904 cDNAs and expressed sequence tags (ESTs). With these data, we test the hypothesis that exercise attenuates the gene expression changes that normally occur in the aging heart. Male mice (Mus domesticus) were sampled from the 16th generation of selective breeding for high voluntary exercise. For the selective breeding protocol, breeders were chosen based on the maximum number of wheel revolutions run on days 5 and 6 of a test at 8 wk of age. For the colony sampled herein, mice were housed individually over their entire lifetimes (from weaning) either with or without access to running wheels. The hearts of these two treatment groups (active and sedentary) were assayed at middle age (20 mo) and old age (33 mo). Genes significantly affected by age in the hearts of the sedentary population by at least a 50% expression change (n = 137) were distributed across several major categories, including inflammatory response, stress response, signal transduction, and energy metabolism. Genes significantly affected by age in the active population were fewer (n = 62). Of the 42 changes in gene expression that were common to both treatment groups, 32 (72%) displayed smaller fold changes as a result of exercise. Thus exercise offset many age-related gene expression changes observed in the hearts of the sedentary animals. These results suggest that adaptive physiological mechanisms that are induced by exercise can retard many effects of aging on heart muscle at the transcriptional level. C1 Iowa State Univ Sci & Technol, Dept Zool & Genet, Ames, IA 50011 USA. Washington State Univ, Sch Biol Sci, Pullman, WA 99164 USA. Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53706 USA. Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Zool, Madison, WI 53706 USA. RP Bronikowski, AM (reprint author), Iowa State Univ Sci & Technol, Dept Zool & Genet, Ames, IA 50011 USA. OI Bronikowski, Anne/0000-0001-6432-298X FU NIA NIH HHS [AG-18922, AG-05784] NR 50 TC 48 Z9 50 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JAN 15 PY 2003 VL 12 IS 2 BP 129 EP 138 DI 10.1152/physiolgenomics.00082.2002 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 635LJ UT WOS:000180400100007 PM 12429864 ER PT J AU Mathes, DW Randolph, MA Solari, MG Nazzal, JA Nielsen, GP Arn, JS Sachs, DH Lee, WPA AF Mathes, DW Randolph, MA Solari, MG Nazzal, JA Nielsen, GP Arn, JS Sachs, DH Lee, WPA TI Split tolerance to a composite tissue allograft in a swine model SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; RENAL-ALLOGRAFTS; CLASS-I; TRANSPLANTATION; ANTIGEN; INDUCTION; REJECTION; CELLS AB Background. The antigenicity of skin is a major obstacle to expanding human composite tissue transplantation. For example, multiple rejection episodes of the skin have been noted in clinical hand transplant patients. We have previously demonstrated tolerance to vascularized musculoskeletal allografts in major histocompatibility complex (MHC)-matched miniature swine treated with 12 days of cyclosporine. This regimen did not reproducibly lead to tolerance to subsequent frozen donor skin grafts. However, such skin grafts did not have a primary vascular supply. The aim of this study was to determine if tolerance to limb allografts with a vascularized skin component could be achieved with MHC matching and a 12-day course of immunosuppression. Methods. Hind limb grafts harvested with a 100 cm(2) cutaneous paddle were transplanted heterotopically into six MHC-matched, minor antigen-mismatched miniature swine. All animals received a 12-day course of cyclosporine. One control animal was not immuno-suppressed. Grafts were evaluated with biweekly biopsies and tissue viability determined by histologic analysis. To test for sensitization, frozen donor skin grafts were applied to all animals that survived to postoperative day 100. Results. All treated animals (n=6) were tolerant to their musculoskeletal allografts at the time of necropsy (>100 days) regardless of the status of the epidermis. One animal demonstrated tolerance to the skin for more than 180 days. The other five animals demonstrated prolonged survival of the epidermal portion of the graft. The control animal rejected the graft epidermis at 10 days postoperatively. Frozen donor skin grafts demonstrated accelerated rejection (<10 days) in three of the animals and led to simultaneous rejection of both the epidermis of the allograft and the skin graft in the long-term tolerant animal. The rejection of the skin grafts did not break tolerance to the musculoskeletal portion in any of the animals. Conclusions. All animals exhibited indefinite survival of the musculoskeletal portion of their allografts but only prolonged survival of the epidermis. The loss of the graft skin appears to be the result of an isolated immune reaction to the skin, and, in particular, the epidermis. This observation is further substantiated by the accelerated rejection of secondarily placed frozen donor skin grafts. C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA USA. RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Div Plast Surg, WAC 453, Boston, MA 02114 USA. OI Mathes, David/0000-0003-4388-1373 FU NCI NIH HHS [1R01 CA79988-01A1]; NHLBI NIH HHS [5R01 HL63430-02] NR 31 TC 91 Z9 94 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 JAN 15 PY 2003 VL 75 IS 1 BP 25 EP 31 DI 10.1097/01.TP.0000035881.03116.E3 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 639FW UT WOS:000180617800005 PM 12544866 ER PT J AU Street, VA Bennett, CL Goldy, JD Shirk, AJ Kleopa, KA Tempel, BL Lipe, HP Scherer, SS Bird, TD Chance, PF AF Street, VA Bennett, CL Goldy, JD Shirk, AJ Kleopa, KA Tempel, BL Lipe, HP Scherer, SS Bird, TD Chance, PF TI Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C SO NEUROLOGY LA English DT Article ID PERIPHERAL MYELIN PROTEIN-22; TYPE-1A; DUPLICATION; LIPOPOLYSACCHARIDE; PMP-22; IDENTIFICATION; EXPRESSION; APOPTOSIS; MOUSE; 1A AB Background: Charcot-Marie-Tooth (CMT) neuropathy is a heterogeneous group of inherited disorders of the peripheral nervous system. The authors recently mapped an autosomal dominant demyelinating form of CMT type I (CMT1C) to chromosome 16p13.1-p12.3. Objective: To find the gene mutations underlying CMT1C. Methods: The authors used a combination of standard positional cloning and candidate gene approaches to identify the causal gene for CMT1C. Western blot analysis was used to determine relative protein levels in patient and control lymphocyte extracts. Northern blotting was used to characterize gene expression in 1) multiple tissues; 2) developing sciatic nerve; and 3) nerve-crush and nerve-transection experiments. Results: The authors identified missense mutations (G112S, T115N, W116G) in the LITAF gene (lipopolysaccharide-induced tumor necrosis factor-ut factor) in three CMT1C pedigrees. LITAF, which is also referred to as SIMPLE, is a widely expressed gene encoding a 161-amino acid protein that may play a role in protein degradation pathways. The mutations associated with CMT1C were found to cluster, defining a domain of the LITAF protein having a critical role in peripheral nerve function. Western blot analysis suggested that the T115N and W116G mutations do not alter the level of LITAF protein in peripheral blood lymphocytes. The LITAF transcript is expressed in sciatic nerve, but its level of expression is not altered during development or in response to nerve injury. This finding is in stark contrast to that seen for other known genes that cause CMT1. Conclusions: Mutations in LITAF may account for a significant proportion of CMT1 patients with previously unknown molecular diagnosis and may define a new mechanism of peripheral nerve perturbation leading to demyelinating neuropathy. C1 Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, VM Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. RP Chance, PF (reprint author), Univ Washington, Dept Pediat, Box 356320, Seattle, WA 98195 USA. FU NIA NIH HHS [AG00057]; NICHD NIH HHS [HD02274]; NIDCD NIH HHS [DC02739]; NINDS NIH HHS [NS2878, NS38181] NR 31 TC 117 Z9 129 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 14 PY 2003 VL 60 IS 1 BP 22 EP 26 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 633ZU UT WOS:000180316000006 PM 12525712 ER PT J AU Posner, MR Lefebvre, JL AF Posner, MR Lefebvre, JL TI Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck SO BRITISH JOURNAL OF CANCER LA English DT Review DE docetaxel; induction; PF regimens; squamous cell carcinoma of the head and neck ID PHASE-III TRIAL; HIGH-DOSE LEUCOVORIN; FRACTIONATED RADIOTHERAPY; ACTIVE-DRUG; CANCER; CHEMOTHERAPY; CISPLATIN; FLUOROURACIL; RECURRENT; CHEMORADIOTHERAPY AB Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are often treated with induction chemotherapy or chemoradiotherapy, but to date without major impact on survival. The combination of cisplatin-5-fluorouracil (5-FU) (PF) has been used as standard induction therapy; however, poor patient survival has stimulated investigation into new agents with potential activity in SCCHN. Docetaxel has significant single-agent activity in SCCHN and has been investigated in combination with PF regimens as induction therapy. The results of six phase II studies of docetaxel-PF regimens (TPF) as induction in locally advanced SCCHN patients are reviewed and reported. Consistently, high 2-year survival rates and over-all response rates were demonstrated across the phase II trials in the range 42 - 82 and 71 - 100%, respectively. The toxicity profile seen with TPF-based regimens was acceptable. The primary toxicity was neutropenia, which together with gastrointestinal complaints accounted for the majority of adverse events. Given the encouraging phase II experience with TPF-based regimens, two large-scale phase III studies comparing TPF-based regimens with standard PF regimens are underway. The results have significant potential for validating the findings of the phase II studies, demonstrating improved survival and over-all response of patients treated with docetaxel-based induction chemotherapy. (C) 2003 Cancer Research UK. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Ctr Oscar Lambret, F-59020 Lille, France. RP Posner, MR (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, SW430H,44 Binney St, Boston, MA 02115 USA. NR 49 TC 21 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 13 PY 2003 VL 88 IS 1 BP 11 EP 17 DI 10.1038/sj.bjc.6600685 PG 7 WC Oncology SC Oncology GA 647EF UT WOS:000181078900003 PM 12556952 ER PT J AU Schernhammer, ES Leitzmann, MF Michaud, DS Speizer, FE Giovannucci, E Colditz, GA Fuchs, CS AF Schernhammer, ES Leitzmann, MF Michaud, DS Speizer, FE Giovannucci, E Colditz, GA Fuchs, CS TI Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas SO BRITISH JOURNAL OF CANCER LA English DT Article DE colon cancer; colon adenomas; gallstones; cholecystectomy; risk factors ID COLON CANCER; METAANALYSIS; COHORT; CARCINOMA; WOMEN; FAT AB Earlier work describes a modest association between cholecystectomy and the risk of colorectal cancer. We conducted a prospective study of 85 184 women, 36-61 year's old, who had no history of cancer to evaluate whether known risk factor's for colorectal cancer, including dietary history, that have not been controlled for in previous analyses can help explain the observed association. During 16 years of follow-up, 877 cases of colorectal cancer were documented and 1452 women who underwent endoscopy during the follow-up time were diagnosed with distal adenomas. After adjustment for age and other known or suspected risk factors, we found a significant, positive association between cholecystectomy and the risk of colorectal cancer (multivariate relative risk RR 1.21, 95% Cl 1.01-1.46). The risk was highest for cancers of the proximal colon (RR 1.34, 95% Cl 0.97-1.88) and the rectum (RR 1.58, 95% Cl 1.05-2.36). However, we did not observe a significant association between cholecystectomy and distal colorectal adenomas. In this large prospective cohort study, a history of cholecystectomy appears to increase modestly the risk of colorectal cancer, even after adjustment for other colorectal cancer risk factors. (C) 2003 Cancer Research UK. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Nutr Epidemiol Branch, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Ctr Canc Prevent, Boston, MA USA. Dana Faber Harvard Canc Ctr, Program Epidemiol, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [R01 CA086102, CA 40356, CA 55075, CA 86102, CA/ES62984, CA87969, P01 CA055075, P01 CA087969, R01 CA040356] NR 23 TC 33 Z9 45 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN 13 PY 2003 VL 88 IS 1 BP 79 EP 83 DI 10.1038/sj.bjc.6600661 PG 5 WC Oncology SC Oncology GA 647EF UT WOS:000181078900014 PM 12556963 ER PT J AU Maison, SF Adams, JC Liberman, MC AF Maison, SF Adams, JC Liberman, MC TI Olivocochlear innervation in the mouse: Immunocytochemical maps, crossed versus uncrossed contributions, and transmitter colocalization SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cochlea; efferents; hair cells; acetylcholine; gamma-aminobutyric acid; calcitonin generelated peptide ID GAMMA-AMINOBUTYRIC-ACID; GENE-RELATED PEPTIDE; GUINEA-PIG COCHLEA; ENKEPHALIN-LIKE IMMUNOREACTIVITY; SELECTIVE RETROGRADE TRANSPORT; GABA-LIKE IMMUNOREACTIVITY; SUPERIOR OLIVARY COMPLEX; BRAIN-STEM; CHOLINE-ACETYLTRANSFERASE; GLUTAMATE-DECARBOXYLASE AB To further understand the roles and origins of gamma-aminobutyric acid (GABA) and calcitonin gene-related peptide (CGRP) in the efferent innervation of the cochlea, we first produced in the mouse an immunocytochemical map of the efferent terminals that contain acetylcholine (ACh), CGRP, and GABA. Olivocochlear (OC) terminals in inner and outer hair cell (THC and OHC) regions were analyzed quantitatively along the cochlear spiral via light-microscopic observation of cochlear wholemounts immunostained with antibodies to glutamic acid decarboxylase (GAD), vesicular acetylcholine transporter (VAT), or the peptide CGRP. Further immunochemical characterization was performed in mice with chronic OC transection at the floor of the fourth ventricle to distinguish crossed from uncrossed contributions and, indirectly, the contributions of lateral versus medial components of the OC system. The results in mouse showed that (1) there are prominent GABAergic, cholinergic, and CGRPergic innervations in the OHC and IHC regions, (2) GABA and CGRP are extensively colocalized with ACh in all OC terminals in the IHC and OHC areas, (3) the longitudinal gradient of OC innervation peaks roughly at the 10-kHz region in the OHC area and is more uniform along the cochlear spiral in the IHC area, (4) in contrast to other mammalian species there is no radial gradient of OC innervation of the OHCs, and (5) all OHC efferent terminals arise from the medial OC system and terminals in the IHC area arise from the lateral OC system. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM sfna@epl.meei.harvard.edu FU NIDCD NIH HHS [P30 DC005209, R01 DC-0188, R01 DC-03929, R01 DC000188, R01 DC003929] NR 50 TC 87 Z9 88 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 13 PY 2003 VL 455 IS 3 BP 406 EP 416 DI 10.1002/cne.10490 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 627ZJ UT WOS:000179966800011 PM 12483691 ER PT J AU Okafor, CC Saunders, L Li, XP Ito, T Dixon, M Stepenek, A Hajjar, RJ Wood, JR Doye, AA Gwathmey, JK AF Okafor, CC Saunders, L Li, XP Ito, T Dixon, M Stepenek, A Hajjar, RJ Wood, JR Doye, AA Gwathmey, JK TI Myofibrillar responsiveness to cAMP, PKA, and caffeine in an animal model of heart failure SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE calcium; cardiomyopathy; contractile function; troponin T; thin myofilament; heart failure; ventricular function ID HUMAN VENTRICULAR MYOCARDIUM; HUMAN DILATED CARDIOMYOPATHY; HYPERTROPHIED FERRET HEARTS; ADULT CARDIAC MYOCYTES; INTRACELLULAR CALCIUM; SARCOPLASMIC-RETICULUM; TENSION DEVELOPMENT; PRESSURE-OVERLOAD; ISOMETRIC TENSION; DPI 201-106 AB We investigated whether an alteration of myofilament calcium responsiveness and contractile activation may in part contribute to heart failure. A control group of Broad Breasted White turkey poults was given regular feed without additive, whereas the experimental group was given the control ration with 700 ppm of furazolidone at 1 week of age for 3 weeks (DCM). At 4 weeks of age, left ventricular trabeculae carneae were isolated from hearts and calcium-force relationships studied. No differences in calcium-activation between fibers from control or failing hearts were noted under standard experimental conditions. Also failing hearts demonstrated no significant shift in the population of troponin T isoforms but we did observe a significant 4-fold decrease in TnT content in failing hearts compared to non-failing hearts. Addition of caffeine, however, resulted in a greater leftward shift on the calcium axis in fibers from failing hearts. At pCa 6, caffeine increased force by 26 +/- 2.1% in control fibers and 44.5 +/- 8.7% in myopathic fibers. Cyclic AMP resulted in a greater rightward shift on the calcium axis in failing myocardium. In control muscles, the frequency of minimum stiffness (f(min)) was higher than in muscles from failing hearts. cAMP and caffeine both shifted f(min) to higher frequencies in control fibers whereas in fibers from failing hearts both caused a greater shift. These results lead us to conclude that heart failure exerts differential effects on cAMP and caffeine responsiveness. Our data suggest that changes tit the level of the thin myofilaments may alter myofilament calcium responsiveness and contribute to the contractile dysfunction seen in heart failure. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Boston Univ, Med Ctr, Boston, MA 02118 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Smith Coll, Dept Biol, Northampton, MA 01063 USA. Gwathmey Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arizona, Tucson, AZ 85721 USA. RP Boston Univ, Med Ctr, 715 Albany St, Boston, MA 02118 USA. EM gwathmey@earthlink.net FU NHLBI NIH HHS [HL 49574] NR 47 TC 2 Z9 3 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 EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 10 PY 2003 VL 300 IS 2 BP 592 EP 599 DI 10.1016/S0006-291X(02)02885-1 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 639BD UT WOS:000180607000050 PM 12504124 ER PT J AU Kodama, T Doukas, AG Hamblin, MR AF Kodama, T Doukas, AG Hamblin, MR TI Delivery of ribosome-inactivating protein toxin into cancer cells with shock waves SO CANCER LETTERS LA English DT Article DE shock tube; saporin; cancer; ribosome-inactivating protein; cytoplasmic delivery ID PHOTOCHEMICAL INTERNALIZATION; PLASMA-MEMBRANE; THERAPY; PERMEABILIZATION; IMMUNOTOXINS; LEUKEMIA; SAPORIN; ASSAY; P53 AB We report on the use of shock waves delivered by a shock-tube to permeabilize cancer cells and potentiate the cytotoxicity of the type-1 ribosome-inactivating protein, saporin. We studied human colorectal cancer HT29 and ovarian cancer OVCAR-5 cells, and used two different cytotoxicity assays, colony formation and loss of mitochondrial activity. A single shock wave and saporin (10(-9) M) produced significant toxicity not seen with either shock wave or drug alone. Increasing the number of shock waves up to five further increased cytotoxicity. Higher toxicity was seen with the clonogenic assay compared to MTT assay. Shock waves may have applications in promoting cytoplasmic delivery of toxins into cancer cells after intratumoral injection. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, WEL224, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, WEL224, 55 Fruit St, Boston, MA 02114 USA. OI kodama, tetsuya/0000-0003-4727-9558; Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA/AI838801, R01 CA083882]; NIAID NIH HHS [R01 AI050875] NR 25 TC 19 Z9 19 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 10 PY 2003 VL 189 IS 1 BP 69 EP 75 AR PII S0340-3835(02)00503-7 DI 10.1016/S0304-3835(02)00503-7 PG 7 WC Oncology SC Oncology GA 625FU UT WOS:000179807100009 PM 12445679 ER PT J AU Hoffmeister, KM Felbinger, TW Falet, H Denis, CV Bergmeier, W Mayadas, TN von Andrian, UH Wagner, DD Stossel, TP Hartwig, JH AF Hoffmeister, KM Felbinger, TW Falet, H Denis, CV Bergmeier, W Mayadas, TN von Andrian, UH Wagner, DD Stossel, TP Hartwig, JH TI The clearance mechanism of chilled blood platelets SO CELL LA English DT Article ID GLYCOPROTEIN IB-ALPHA; VON-WILLEBRAND-FACTOR; P-SELECTIN; BACTERIAL-CONTAMINATION; GPIB-IX; ACTIVATION; INTEGRIN; CD11B/CD18; EXPRESSION; MEMBRANE AB Platelet transfusion is a very common lifesaving medical procedure. Not widely known is the fact that platelets, unlike other blood cells, rapidly leave the circulation if refrigerated prior to transfusion. This peculiarity requires blood services to store platelets at room temperature, limiting platelet supplies for clinical needs. Here, we describe the mechanism of this clearance system, a longstanding mystery. Chilling platelets clusters their von Willebrand (vWf) receptors, eliciting recognition of mouse and human platelets by hepatic macrophage complement type 3 (CR3) receptors. CR3-expressing but not CR3-deficient mice exposed to cold rapidly decrease platelet counts. Cooling primes platelets for activation. We propose that platelets are thermosensors, primed at peripheral sites where most injuries occurred throughout evolution. Clearance prevents pathologic thrombosis by primed platelets. Chilled platelets bind vWf and function normally in vitro and ex vivo after transfusion into CR3-deficient mice. Therefore, GPIb modification might permit cold platelet storage. C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hoffmeister, KM (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008; Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [HL19429, HL36028, HL56949, P01 HL056949] NR 43 TC 203 Z9 212 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 2003 VL 112 IS 1 BP 87 EP 97 DI 10.1016/S0092-8674(02)01253-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 649DK UT WOS:000181191500009 PM 12526796 ER PT J AU Shimaoka, M Xiao, T Liu, JH Yang, YT Dong, YC Jun, CD McCormack, A Zhang, RG Joachimiak, A Takagi, J Wang, JH Springer, TA AF Shimaoka, M Xiao, T Liu, JH Yang, YT Dong, YC Jun, CD McCormack, A Zhang, RG Joachimiak, A Takagi, J Wang, JH Springer, TA TI Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation SO CELL LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; FUNCTION-ASSOCIATED ANTIGEN-1; CRYSTAL-STRUCTURE; LIGAND-BINDING; A-DOMAIN; CONFORMATIONAL-CHANGES; MONOCLONAL-ANTIBODY; INSERTED DOMAIN; T-CELLS; LFA-1 AB The structure of the I domain of integrin alphaLbeta2 bound to the Ig superfamily ligand ICAM-1 reveals the open ligand binding conformation and the first example of an integrin-IgSF interface. The I domain Mg2+ directly coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241 enables a critical salt bridge. Liganded and unliganded structures for both high- and intermediate-affinity mutant I domains reveal that ligand binding can induce conformational change in the alphaL I domain and that allosteric signals can convert the closed conformation to intermediate or open conformations without ligand binding. Pulling down on the C-terminal alpha7 helix with introduced disulfide bonds ratchets the beta6-alpha7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, 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. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu; springer@cbr.med.harvard.edu RI Xiao, Tsan/A-8590-2010; Xiao, Tsan/I-7616-2013 OI Xiao, Tsan/0000-0001-9688-475X FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798]; NHLBI NIH HHS [HL48675, P01 HL048675] NR 58 TC 335 Z9 347 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 2003 VL 112 IS 1 BP 99 EP 111 DI 10.1016/S0092-8674(02)01257-6 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 649DK UT WOS:000181191500010 PM 12526797 ER PT J AU van Balkom, BWM van Raak, M Breton, S Pastor-Soler, N Bouley, R van der Sluijs, P Brown, D Deen, PMT AF van Balkom, BWM van Raak, M Breton, S Pastor-Soler, N Bouley, R van der Sluijs, P Brown, D Deen, PMT TI Hypertonicity is involved in redirecting the aquaporin-2 water channel into the basolateral, instead of the apical, plasma membrane of renal epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; DARBY CANINE KIDNEY; RAT-KIDNEY; BRATTLEBORO RATS; COLLECTING DUCT; MDCK CELLS; EXPRESSION; VASOPRESSIN; TRAFFICKING; RECEPTOR AB In renal collecting ducts, vasopressin increases the expression of and redistributes aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical membrane, leading to urine concentration. However, basolateral membrane expression of AQP2, in addition to AQP3 and AQP4, is often detected in inner medullary principal cells in vivo. Here, potential mechanisms that regulate apical versus basolateral targeting of AQP2 were examined. The lack of,AQP2-4 association into heterotetramers and the complete apical expression of AQP2 when highly expressed in Madin-Darby canine kidney cells indicated that neither heterotetramerization of AQP2 with AQP3 and/or AQP4, nor high expression levels of AQP2 explained the basolateral AQP2 localization. However, long term hypertonicity, a feature of the inner medullary interstitium, resulted in an insertion of AQP2 into the basolateral membrane of Madin-Darby canine kidney cells after acute forskolin stimulation. Similarly, a marked insertion of AQP2 into the basolateral membrane of principal cells was observed in the distal inner medulla from normal rats and Brattleboro rats after acute vasopressin treatment of tissue slices that had been chronically treated with vasopressin to increase interstitial osmolality in the medulla, but not in tissues from vasopressin-deficient Brattleboro rats. These data reveal for the first time that chronic hypertonicity can program cells in vitro and in vivo to change the insertion of a protein into the basolateral membrane instead of the apical membrane. C1 UMC St Radbound Nijmegen, Dept Cell Physiol, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands. Massachusetts Gen Hosp, Program Membrane Biol & Renal Unit, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. RP Deen, PMT (reprint author), UMC St Radbound Nijmegen, Dept Cell Physiol, Nijmegen Ctr Mol Life Sci, POB 9101,160, NL-6500 HB Nijmegen, Netherlands. RI Deen, P.M.T./H-8023-2014 OI Deen, P.M.T./0000-0002-7868-4655 FU NICHD NIH HHS [HD08684]; NIDDK NIH HHS [DK38452] NR 56 TC 54 Z9 55 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 JAN 10 PY 2003 VL 278 IS 2 BP 1101 EP 1107 DI 10.1074/jbc.M207339200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 634CF UT WOS:000180321900054 PM 12374804 ER PT J AU Jain, RK Padera, TP AF Jain, RK Padera, TP TI Lymphatics make the break SO SCIENCE LA English DT Editorial Material ID MICE LACKING; SYK C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. NR 10 TC 33 Z9 34 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 10 PY 2003 VL 299 IS 5604 BP 209 EP 210 DI 10.1126/science.1081345 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 633LD UT WOS:000180284000023 PM 12522236 ER PT J AU Mukamal, KJ Conigrave, KM Mittleman, MA Camargo, CAJ Stampfer, MJ Willett, WC Rimm, EB AF Mukamal, KJ Conigrave, KM Mittleman, MA Camargo, CAJ Stampfer, MJ Willett, WC Rimm, EB TI Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; REGULAR DRINKERS; CONTROLLED TRIAL; BRITISH MEN; CONSUMPTION; RISK; WINE; BEER; MORTALITY AB BACKGROUND: Although moderate drinking confers a decreased risk of myocardial infarction, the roles of the drinking pattern and type of beverage remain unclear. METHODS: We studied the association of alcohol consumption with the risk of myocardial infarction among 38,077 male health professionals who were free of cardiovascular disease and cancer at base line. We assessed the consumption of beer, red wine, white wine, and liquor individually every four years using validated food-frequency questionnaires. We documented cases of nonfatal myocardial infarction and fatal coronary heart disease from 1986 to 1998. RESULTS: During 12 years of follow-up, there were 1418 cases of myocardial infarction. As compared with men who consumed alcohol less than once per week, men who consumed alcohol three to four or five to seven days per week had decreased risks of myocardial infarction (multivariate relative risk, 0.68 [95 percent confidence interval, 0.55 to 0.84] and 0.63 [95 percent confidence interval, 0.54 to 0.74], respectively). The risk was similar among men who consumed less than 10 g of alcohol per drinking day and those who consumed 30 g or more. No single type of beverage conferred additional benefit, nor did consumption with meals. A 12.5-g increase in daily alcohol consumption over a four-year follow-up period was associated with a relative risk of myocardial infarction of 0.78 (95 percent confidence interval, 0.62 to 0.99). CONCLUSIONS: Among men, consumption of alcohol at least three to four days per week was inversely associated with the risk of myocardial infarction. Neither the type of beverage nor the proportion consumed with meals substantially altered this association. Men who increased their alcohol consumption by a moderate amount during follow-up had a decreased risk of myocardial infarction. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Univ Sydney, Dept Publ Hlth & Community Med, Sydney, NSW 2006, Australia. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,LY-303, Boston, MA 02215 USA. OI Conigrave, Katherine/0000-0002-6428-1441 FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464]; NIAAA NIH HHS [AA11181, AA00299] NR 37 TC 440 Z9 459 U1 6 U2 35 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 2003 VL 348 IS 2 BP 109 EP 118 DI 10.1056/NEJMoa022095 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 633DL UT WOS:000180263900003 PM 12519921 ER PT J AU Tanoue, LT Mark, EJ AF Tanoue, LT Mark, EJ TI A 43-year-old man with fever and night sweats. Mycobacterium tuberculosis infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MILIARY TUBERCULOSIS; PULMONARY TUBERCULOSIS; RAPID DIAGNOSIS; UNITED-STATES; VITAMIN-D; EPIDEMIOLOGY; HYPOPITUITARISM; BRUCELLOSIS; MENINGITIS; DISEASE C1 Yale Univ, Sch Med, Pulm & Crit Care Med Sect, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tanoue, LT (reprint author), Yale Univ, Sch Med, Pulm & Crit Care Med Sect, 333 Cedar St, New Haven, CT 06510 USA. NR 40 TC 3 Z9 3 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 2003 VL 348 IS 2 BP 151 EP 161 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 633DL UT WOS:000180263900008 PM 12519926 ER PT J AU Aballay, A Drenkard, E Hilbun, LR Ausubel, FM AF Aballay, A Drenkard, E Hilbun, LR Ausubel, FM TI Caenorhabditis elegans innate immune response triggered by Salmonella enterica requires intact LPS and is mediated by a MAPK signaling pathway SO CURRENT BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; ESCHERICHIA-COLI; INDUCED APOPTOSIS; KINASE CASCADE; TYPHIMURIUM; LIPOPOLYSACCHARIDE; PHOSPHORYLATION; INTERFERENCE; ATTACHMENT; INFECTION AB Compared to mammals, insects, and plants, relatively little is known about innate immune responses in the nematode Caenorhabditis elegans. Previous work showed that Salmonella enterica serovars cause a persistent infection in the C. elegans intestine [1, 2] that triggers gonadal programmed cell death (PCD) and that C. elegans cell death (ced) mutants are more susceptible to Salmonella-mediated killing [3]. To further dissect the role of PCD in C. elegans innate immunity, we identified both C. elegans and S. enterica factors that affect the elicitation of Salmonella-induced PCD. Salmonella-elicited PCD was shown to require the C. elegans homolog of the mammalian p38 mitogen-activated protein kinase (MAPK) encoded by the pmk-1 gene. Inactivation of pmk-1 by RNAi blocked Salmonella-elicited PCD, and epistasis analysis showed that CED-9 lies downstream of PMK-1. Wild-type Salmonella lipopolysaccharide (LPS) was also shown to be required for the elicitation of PCD, as well as for persistence of Salmonella in the C. elegans intestine. However, a presumptive C. elegans TOLL signaling pathway did not appear to be required for the PCD response to Salmonella. These results establish a PMK-1-dependant PCD pathway as a C. elegans innate immune response to Salmonella. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. RP Aballay, A (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM48707] NR 31 TC 100 Z9 114 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 8 PY 2003 VL 13 IS 1 BP 47 EP 52 AR PII S0960-9822(02)01396-9 DI 10.1016/S0960-9822(02)01396-9 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 644KC UT WOS:000180915600021 PM 12526744 ER PT J AU Trinh, NH Hoblyn, J Mohanty, SU Yaffe, K AF Trinh, NH Hoblyn, J Mohanty, SU Yaffe, K TI Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease - A meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PLACEBO-CONTROLLED TRIAL; CONTROLLED-RELEASE PHYSOSTIGMINE; QUALITY-OF-LIFE; LONG-TERM-CARE; DOUBLE-BLIND; PSYCHIATRIC-SYMPTOMS; DRUG TRIALS; DEMENTIA; METRIFONATE; MULTICENTER AB Context Cholinesterase inhibitors are the primary treatment for the cognitive symptoms of Alzheimer disease (AD). Cholinergic dysfunction is also associated with neuropsychiatric and functional deficits, but results from randomized controlled trials of cholinesterase inhibitors are conflicting. Objective To conduct a systematic review and meta-analysis to quantify the efficacy of cholinesterase inhibitors for neuropsychiatric and functional outcomes in patients with mild to moderate AD. Data Sources We performed a literature search of trials using MEDLINE (January 1966-December 2001), Dissertations Abstracts On-line, PSYCHINFO, BIOSIS, PubMed, and the Cochrane Controlled Trials Register. We retrieved English- and non-English-language articles for review and collected references from bibliographies of reviews, original research articles, and other articles of interest. We searched for both published and unpublished trials, contacting researchers and pharmaceutical companies. Study Selection We included 29 parallel-group or crossover randomized, double-blind, placebo-controlled trials of outpatients who were diagnosed as having mild to moderate probable AD and were treated for at least 1 month with a cholinesterase inhibitor. Sixteen trials included neuropsychiatric and 18 included functional measures. Data Extraction Two investigators (N.H.T. and J.H.) independently extracted study methods, sources of bias, and outcomes. Neuropsychiatric outcomes were measured with the Neuropsychiatric Inventory (NPI, 0-120 points) and the Alzheimer Disease Assessment Scale, noncognitive (ADAS-noncog, 0-50 points) and were analyzed with the weighted mean difference method. Functional outcomes were measured with several activities of daily living (ADL) and instrumental activities of daily living (IADL) scales and analyzed with the standardized mean difference method. Data Synthesis For neuropsychiatric outcomes, 10 trials included the ADAS-noncog and 6 included the NPI. Compared with placebo, patients randomized to cholinesterase inhibitors improved 1.72 points on the NPI (95% confidence interval [CI], 0.87-2.57 points), and 0.03 points on the ADAS-noncog (95% CI, 0.00-0.05 points). For functional outcomes, 14 trials used ADL and 13 trials used IADL scales. Compared with placebo, patients randomized to cholinesterase inhibitors improved 0.1 SDs on ADL scales (95% CI, 0.00-0.19 SDs), and 0.09 SDs on IADL scales (95% CI, 0.01 to 0.17 SDs). There was no difference in efficacy among various cholinesterase inhibitors. Conclusions These results indicate that cholinesterase inhibitors have a modest beneficial impact on neuropsychiatric and functional outcomes for patients with AD. Future research should focus on how such improvements translate into long-term outcomes such as patient quality of life, institutionalization, and caregiver burden. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA. Harvard Univ, Ctr Astrophys, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Psychiat, Box 111G,4150 Clement St, San Francisco, CA 94121 USA. EM kyaffe@itsa.ucsf.edu FU NIA NIH HHS [K23-AG00888] NR 64 TC 279 Z9 293 U1 3 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 8 PY 2003 VL 289 IS 2 BP 210 EP 216 DI 10.1001/jama.289.2.210 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 632ME UT WOS:000180226400032 PM 12517232 ER PT J AU Shlipak, MG Fried, LF Crump, C Bleyer, AJ Manolio, TA Tracy, RP Furberg, CD Psaty, BM AF Shlipak, MG Fried, LF Crump, C Bleyer, AJ Manolio, TA Tracy, RP Furberg, CD Psaty, BM TI Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency SO CIRCULATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Heart-Associations-Epidemiology-Council CY APR 24, 2002 CL HONOLULU, HAWAII SP Amer Heart Assoc Epidemiol Council DE inflammation; coagulation; kidney; coronary disease ID C-REACTIVE PROTEIN; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; CREATININE CLEARANCE; SERUM CREATININE; FACTOR-VII; D-DIMER; FIBRINOGEN; RISK AB Background-Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease. Methods and Results-The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged greater than or equal to65 years. C-reactive protein. fibrinogen, factor VIII, and factor VIIIc levels were treasured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dither levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level greater than or equal to1.3 mg/dL in women and greater than or equal to1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 617 (11%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIII, factor VIIIc, plasmin-antiplasmin complex, and D-dieter were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar. Conclusion-Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease. C1 Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. RP Shlipak, MG (reprint author), Vet Affairs Med Ctr, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R03 HL68099-01] NR 30 TC 441 Z9 463 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 7 PY 2003 VL 107 IS 1 BP 87 EP 92 DI 10.1161/01.CIR.0000042700.48769.59 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634WZ UT WOS:000180366600030 PM 12515748 ER PT J AU Tearney, GJ Yabushita, H Houser, SL Aretz, HT Jang, IK Schlendorf, KH Kauffman, CR Shishkov, M Halpern, EF Bouma, BE AF Tearney, GJ Yabushita, H Houser, SL Aretz, HT Jang, IK Schlendorf, KH Kauffman, CR Shishkov, M Halpern, EF Bouma, BE TI Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography SO CIRCULATION LA English DT Article DE atherosclerosis; catheters; imaging; tomography; plaque ID IN-VIVO; RUPTURE; THROMBOSIS; CATHETER; BIOPSY; TISSUE AB Background-Macrophage degradation of fibrous cap matrix is an important contributor to atherosclerotic plaque instability. An imaging technology capable of identifying macrophages in patients could provide valuable information for assessing plaque vulnerability. Optical coherence tomography (OCT) is a new intravascular imaging modality that allows cross-sectional imaging of tissue with a resolution of approximate to10 mum. The aim of this study was to investigate the use of OCT for identifying macrophages in fibrous caps. Methods and Results-OCT images of 26 lipid-rich atherosclerotic arterial segments obtained at autopsy were correlated with histology. Cap macrophage density was quantified morphometrically by immunoperoxidase staining with CD68 and smooth muscle actin and compared with the standard deviation of the OCT signal intensity at corresponding locations. There was a high degree of positive correlation between OCT and histological measurements of fibrous cap macrophage density (r=0.84, P<0.0001) and a negative correlation between OCT and histological measurements of smooth muscle actin density (r=-0.56, P<0.005). A range of OCT signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity and specificity for identifying caps containing >10% CD68 staining. Conclusions-The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. The unique capabilities of OCT for fibrous cap characterization suggest that this technology may be well suited for identifying vulnerable plaques in patients. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kinki Univ, Sch Med, Dept Internal Med 1, Osaka 589, Japan. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 40 Blossom St,BAR 703, Boston, MA 02114 USA. NR 25 TC 333 Z9 351 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 7 PY 2003 VL 107 IS 1 BP 113 EP 119 DI 10.1161/01.CIR.0000044384.41037.43 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634WZ UT WOS:000180366600034 PM 12515752 ER PT J AU Chan, C Berthiaume, F Lee, K Yarmush, ML AF Chan, C Berthiaume, F Lee, K Yarmush, ML TI Metabolic flux analysis of cultured hepatocytes exposed to plasma SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE metabolic flux analysis; plasma; preconditioning; bioartificial liver; lipid metabolism ID PEROXISOMAL BETA-OXIDATION; ACUTE LIVER-FAILURE; HIGH-FAT DIETS; RAT-LIVER; AMINO-ACID; GLYCOGEN-SYNTHESIS; KREBS CYCLE; CELLS; GLUCOSE; INDUCTION AB Hepatic metabolism can be investigated using metabolic flux analysis (MFA), which provides a comprehensive overview of the intracellular metabolic flux distribution. The characterization of intermediary metabolism in hepatocytes is important for all biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. During BAL operation, hepatocytes are exposed to plasma or blood from the patient, at which time they are prone to accumulate intracellular lipids and exhibit poor liver-specific functions. In a prior study, we found that preconditioning the primary rat hepatocytes in culture medium containing physiological levels of insulin, as opposed to the typical supraphysiological levels found in standard hepatocyte culture media, reduced lipid accumulation during subsequent plasma exposure. Furthermore, supplementing the plasma with amino acids restored hepatospecific functions. In the current study, we used MFA to quantify the changes in intracellular pathway fluxes of primary rat hepatocytes in response to low-insulin preconditioning and amino acid supplementation. We found that culturing hepatocytes in medium containing lower physiological levels of insulin decreased the clearance of glucose and glycerol with a concomitant decrease in glycolysis. These findings are consistent with the general notion that low insulin, especially in the presence of high glucagon levels, downregulates glycolysis in favor of gluco neogenesis in hepatocytes. The MFA model shows that, during subsequent plasma exposure, low-insulin preconditioning upregulated gluconeogenesis, with lactate as the primary precursor in unsupplemented plasma, with a greater contribution from deaminated amino acids in amino acid-supplemented plasma. Concomitantly, low-insulin preconditioning increased fatty acid oxidation, an effect that was further enhanced by amino acid supplementation to the plasma. The increase in fatty acid oxidation reduced intracellular triglyceride accumulation. Overall, these findings are consistent with the notion that the insulin level in medium culture presets the metabolic machinery of hepatocytes such that it directly impacts on their metabolic behavior during subsequent plasma culture. (C) 2002 Wiley Periodicals, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, GRB 1401,55 Fruit St, Boston, MA USA. RI Lee, Kyongbum/D-9230-2013 FU NIDDK NIH HHS [R01 DK41709]; NIGMS NIH HHS [R01 GM07035] NR 43 TC 72 Z9 75 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JAN 5 PY 2003 VL 81 IS 1 BP 33 EP 49 DI 10.1002/bit.10453 PG 17 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 625MB UT WOS:000179819300005 PM 12432579 ER PT J AU Anton, PA Mitsuyasu, RT Deeks, SG Scadden, DT Wagner, B Huang, C Macken, C Richman, DD Christopherson, C Borellini, F Lazar, R Hege, KM AF Anton, PA Mitsuyasu, RT Deeks, SG Scadden, DT Wagner, B Huang, C Macken, C Richman, DD Christopherson, C Borellini, F Lazar, R Hege, KM TI Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects SO AIDS LA English DT Article DE HIV-1; quantitative; reservoirs; mucosa; tissue; gastrointestinal-associated lymphoid tissue; viral load; clinical trials; assay correlation; assay variability ID IMMUNODEFICIENCY-VIRUS INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; T-CELLS; MONONUCLEAR-CELLS; LATENT RESERVOIR; LYMPHOID-TISSUE; PLASMA; RNA; LYMPHOCYTES; REPLICATION AB Objectives: To determine the levels of residual HIV DNA and RNA in blood and gut reservoirs in aviremic patients, assess correlations among compartmental measurements of HIV burden, and evaluate association with clinical parameters. Design: Cross-sectional analysis of baseline data only, on 40 patients enrolled in phase 11 study evaluating efficacy of autologous gene-modified CD4+ and CD8+ T cells. All patients were on stable antiretroviral regimen with undetectable plasma HIV RNA (< 50 copies/ml). Methods: Measurements repeatedly performed over 8-12 weeks pre-intervention: blood HIV DNA, analysis of rectal mucosa-associated lymphoid tissue for both HIV RNA and HIV DNA, and quantitative co-culture of HIV from CD8-depleted peripheral blood mononuclear cells (PBMC). Results: Quantifiable levels of HIV detected in compartments despite undetectable levels of plasma HIV RNA: HIV co-culture of PBMC (88%), blood HIV DNA (95%), rectal biopsy HIV DNA (95%), rectal biopsy HIV RNA (65%). A significant correlation existed among various measures of HIV burden (HIV co-culture, blood HIV DNA, rectal biopsy HIV RNA and DNA) but not between assays and clinical parameters [duration of highly active antiretroviral therapy (HAART), type of HAART]. All assays had comparable or less variability than in plasma viral load assays; HIV co-culture had the highest coefficient of variability whereas the blood HIV DNA assay had the lowest and was considered the most reliable assay. Conclusions: The data support safety, feasibility and high compliance of quantifying reservoirs of residual HIV in treated subjects with undetectable plasma HIV RNA. Lack of correlation between levels of HIV in residual reservoirs and duration of HAART suggests treatment-mediated viral suppression alone does not lead to reproducible decay in HIV reservoirs. (C) 2003 Lippincott Williams & Wilkins. C1 Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90095 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. ViRx Inc, San Francisco, CA USA. Adv Res Associates, Mt View, CA USA. Los Alamos Natl Lab, Los Alamos, NM USA. Univ Calif San Diego, San Diego, CA 92103 USA. Roche Mol Syst, Alameda, CA USA. Cell Genesys Inc, Foster City, CA USA. RP Anton, PA (reprint author), Univ Calif Los Angeles, AIDS Inst, MRL 2734,675 Charles E Young Dr S, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [5-MO1-RR00083-37, RR-00051, RR-00865]; NIAID NIH HHS [AI28697, AI01610] NR 25 TC 55 Z9 56 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 JAN 3 PY 2003 VL 17 IS 1 BP 53 EP 63 DI 10.1097/00002030-200301030-00008 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 634YF UT WOS:000180369500008 PM 12478069 ER PT J AU Zhou, YL Mehta, KR Choi, AP Scolavino, S Zhang, X AF Zhou, YL Mehta, KR Choi, AP Scolavino, S Zhang, X TI DNA damage-induced inhibition of securin expression is mediated by p53 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-TRANSFORMING GENE; SISTER-CHROMATID SEPARATION; DEPENDENT PROTEIN-KINASE; NF-Y; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; CHROMOSOMAL STABILITY; ANAPHASE INHIBITOR; HSP70 PROMOTER; FISSION YEAST AB Tumor suppressor p53 induces the cellular response to DNA damage mainly by regulating expression of its downstream target genes. The human securin is an anaphase inhibitor, preventing premature chromosome separation through inhibition of separase activity. It is also known as the product of the human pituitary tumor-transforming gene, pttg, a proto-oncogene. Here we report that the expression of human securin is suppressed in cells treated with the DNA-damaging drugs doxorubicin and bleomycin. This suppression requires functional p53. Analysis of the human securin promoter reveals that DNA-binding sites for Sp1 and NF-Y are both required for activation of securin expression; however, only the NF-Y site is essential for the suppression by p53. Our study indicates that securin is a p53 target gene and may play a role in p53-mediated cellular response to DNA damage. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhang, X (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. FU NCI NIH HHS [5 F32 CA88519-02] NR 65 TC 65 Z9 66 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 JAN 3 PY 2003 VL 278 IS 1 BP 462 EP 470 DI 10.1074/jbc.M203793200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 632ZX UT WOS:000180255700061 PM 12403781 ER PT J AU Rosowsky, A Chen, H Fu, HM Queener, SF AF Rosowsky, A Chen, H Fu, HM Queener, SF TI Synthesis of new 2,4-diaminopyrido[2,3-d]pyrimidine and 2,4-diaminopyrrolo[2,3-d]pyrimidine inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductase SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID POTENTIAL ANTIPNEUMOCYSTIS; OPPORTUNISTIC INFECTIONS; SELECTIVE INHIBITORS; ANTITUMOR AGENTS; ANTIFOLATE AB A concise new route allowing easy access to five previously unreported 2,4-diamino-6-(substituted benzyl)pyrido[2,3-d]pyrimidines (2a-e) was developed, involving condensation of 2,4-dipivaloylamino-5-bromopyrido[2,3-d]pyrimidine (6) with an organozinc halide in the presence of a catalytic amount of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)(CH2Cl2)-C-., followed by removal of the pivaloyl groups with base. Also prepared via a scheme based on the Taylor ring expansion/ring annulation synthesis were three heretofore undescribed 2,4-diamino-5-(substituted benzyl)-7H-pyrrolo[2,3-d]pyrimidines (3b-c). Standard spectrophotometric assays were used to compare the ability of 2a-e and 3b-c to inhibit dihydrofolate reductase (DHFR) from Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium, three examples of opportunistic pathogens to which AIDS patients are highly vulnerable because of their immunocompromised state. For comparison, 13 previously untested 2,4-diamino-6-(substituted benzyl)quinazolines (17a-m) were also evaluated as inhibitors of these enzymes, as well as the enzyme from rat liver. None of the quinazolines or pyridopyrimidines tested was more potent against the P. carinii enzyme than the structurally related reference compound piritrexim (1), and none showed selectivity for the P. carinii enzyme over the rat enzyme. One of the pyridopyrimidines (2c) showed 10-fold selectivity for T. gondii versus rat DHFR, and two of them (2b, 2c) showed selectivity for the M. avium enzyme. However, this gain in species selectivity was achieved at the cost of decreased in potency, as has been noted with many other lipophilic DHFR inhibitors. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [R01-AI29904] NR 21 TC 75 Z9 77 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 2 PY 2003 VL 11 IS 1 BP 59 EP 67 AR PII S0968-0896(02)00325-5 DI 10.1016/S0968-0896(02)00325-5 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 626WX UT WOS:000179897800007 PM 12467708 ER PT J AU Cook, DL Schwindt, PC Grande, LA Spain, WJ AF Cook, DL Schwindt, PC Grande, LA Spain, WJ TI Synaptic depression in the localization of sound SO NATURE LA English DT Article ID INTERAURAL TIME DIFFERENCES; NUCLEUS LAMINARIS NEURONS; STEM AUDITORY NUCLEI; COINCIDENCE DETECTION; COCHLEAR NUCLEUS; BRAIN-STEM; RELEASE PROBABILITY; PHASE-LOCKING; BARN OWL; CHICK AB Short-term synaptic plasticity, which is common in the central nervous system, may contribute to the signal processing functions of both temporal integration and coincidence detection(1-3). For temporal integrators, whose output firng rate depends on a running average of recent synaptic inputs, plasticity modulates input synaptic strength and thus may directly control signalling gain(2) and the function of neural networks(1-4). But the firing probability of an ideal coincidence detector would depend on the temporal coincidence of events rather than on the average frequency of synaptic events. Here we have examined a specific case of how synaptic plasticity can affect temporal coincidence detection, by experimentally characterizing synaptic depression at the synapse between neurons in the nucleus magnocellularis and coincidence detection neurons in the nucleus laminaris in the chick auditory brainstem(5). We combine an empirical description of this depression with a biophysical model of signalling in the nucleus laminaris. The resulting model predicts that synaptic depression provides an adaptive mechanism for preserving interaural time-delay information (a proxy for the location of sound in space) despite the confounding effects of sound-intensity-related information. This mechanism may help nucleus laminaris neurons to pass specific sound localization information to higher processing centres. C1 Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA. Univ Washington, Dept Neurol, Seattle, WA 98105 USA. Univ Washington, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98105 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Spain, WJ (reprint author), Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA. FU BLRD VA [I01 BX000386] NR 30 TC 106 Z9 106 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 2 PY 2003 VL 421 IS 6918 BP 66 EP 70 DI 10.1038/nature01248 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 631JY UT WOS:000180165500038 PM 12511955 ER PT J AU von Andrian, UH Engelhardt, B AF von Andrian, UH Engelhardt, B TI alpha(4) integrins as therapeutic targets in autoimmune disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ENCEPHALOMYELITIS; ANTIBODIES; MADCAM-1; COLITIS; VCAM-1; CELLS; FLOW; MICE C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Max Planck Inst Vasc Biol, Munster, Germany. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 17 TC 187 Z9 193 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 2003 VL 348 IS 1 BP 68 EP 72 DI 10.1056/NEJMe020157 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 630WY UT WOS:000180134400012 PM 12510047 ER PT S AU Correia, JA Burnham, CA Kaufman, D Brownell, AL Fischman, AJ AF Correia, JA Burnham, CA Kaufman, D Brownell, AL Fischman, AJ BE Metzler, S TI Performance evaluation of a second generation small animal PET. SO 2002 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC) CY NOV 10-16, 2002 CL NORFOLK, VA SP IEEE, Nucl & Plasma Sci Soc AB We have completed construction of a second-generation, single-plane small-animal PET instrument based on LSO detectors. The second-generation design addresses some of the limitations in the first-generation. The purpose of the work reported here was to characterize the physical performance of this instrument. Physical measurements presented include measurements of spatial resolution, sensitivity, linearity, scatter fraction and count-rate performance as well as the imaging of extended objects. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Correia, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-7636-6 J9 IEEE NUCL SCI CONF R PY 2003 BP 802 EP 806 PG 5 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BX56R UT WOS:000185702500174 ER PT S AU Badawi, RD Domigan, P Johnson, O Kemp, B Kudrolli, H Rempel, T Rohatgi, R Romanov, LV Surti, S Worstell, WA Zimmerman, RE AF Badawi, RD Domigan, P Johnson, O Kemp, B Kudrolli, H Rempel, T Rohatgi, R Romanov, LV Surti, S Worstell, WA Zimmerman, RE BE Metzler, S TI Count-rate dependent event mispositioning and NEC in PET SO 2002 IEEE NUCLEAR SCIENCE SYMPOSIUM, CONFERENCE RECORD, VOLS 1-3 SE IEEE NUCLEAR SCIENCE SYMPOSIUM - CONFERENCE RECORD LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC) CY NOV 10-16, 2002 CL NORFOLK, VA SP IEEE, Nucl & Plasma Sci Soc ID DETECTORS AB Most current PET detector designs suffer from event mispositioning at high count rates, as scintillation light from nearby and nearly simultaneous gamma ray conversions becomes mixed. We have used the NEMA NU 2-2001 70 cm test phantom and a Na-22 point source to quantify this effect as a function of activity on two block-detector tomographs (the Siemens/CTI HR+ and the General Electric Discovery LS), and two Anger-type PET tomographs (the Siemens ECAM DUET and the Philips CPET+). After accounting for event losses due to dead time, we find that the number of counts on LORs passing through a cylinder of diameter and height equal to the point-source full width at tenth-maximum measured at low rate surrounding the point source decreases by between 9% (HR+) and 35% (CPET+) at the activity giving rise to peak Noise Equivalent Count (NEC) rate. Mispositioned events act to reduce signal-to-noise ratio, both by reducing apparent activity at the originating location and by increasing the signal background. We have reformulated the conventional expression for NEC rate to account for this phenomenon. The new formulation of NEC, which we call NEC*, results in a lower peak value which in turn occurs at a lower activity concentration than for the conventional formulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Nucl Med, Boston, MA 02115 USA. RP Badawi, RD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Nucl Med, 44 Binney St, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 0-7803-7636-6 J9 IEEE NUCL SCI CONF R PY 2003 BP 1182 EP 1187 PG 6 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BX56R UT WOS:000185702500259 ER PT B AU Aksan, A Toner, M AF Aksan, A Toner, M GP ASME TI Glass formation during room temperature, isothermal drying SO 2003 ADVANCES IN BIOENGINEERING LA English DT Proceedings Paper CT ASME International Mechanical Engineering Congress CY NOV 15-21, 2003 CL Washington, DC SP ASME, Fluid Power Syst & Technol Div, ASME, Micro Elect Mech Syst Div, ASME, Fluids Engn Div, ASME, Bioengn Div, ASME, Appl Mech Div, ASME, Elect & Photon Packaging Div, ASME, Mfg Engn Div, ASME, Adv Energy Syst Div, ASME, Aerosp Div AB Isothermal drying and glass transition of solutions and films have drawn considerable attention from many industries. We here explore the feasibility of modifying the isothermal drying and vitrification kinetics of carbohydrate solutions in order to ensure the stability and quality of their ingredients. Modulated Differential Scanning Calorimetry experiments with isothermally dried trehalose and trehalose/dextran solutions were performed and the glass transition kinetics have been determined. Three distinct drying regimes were observed. With isothermal, isobaric drying at 0%RH, it was indeed possible to reach the glassy state for a trehalose and a trehalose-dextran system. With the addition of high molecular weight sugars, the glass transitions of isothermally dried carbohydrate solutions can be accelerated as a function of dextran mass ratio in the sample. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Aksan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RI Aksan, Alptekin/C-1579-2014 OI Aksan, Alptekin/0000-0001-9891-1715 NR 4 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 0-7918-3710-6 PY 2003 BP 7 EP 8 PG 2 WC Biophysics; Engineering, Biomedical; Mechanics; Medicine, Research & Experimental SC Biophysics; Engineering; Mechanics; Research & Experimental Medicine GA BAL07 UT WOS:000222660500003 ER PT B AU Elliott, GD Azadivar, J Toner, M AF Elliott, GD Azadivar, J Toner, M GP ASME TI Microscale resolution of moisture content in dried sugar matrices SO 2003 ADVANCES IN BIOENGINEERING LA English DT Proceedings Paper CT ASME International Mechanical Engineering Congress CY NOV 15-21, 2003 CL Washington, DC SP ASME, Fluid Power Syst & Technol Div, ASME, Micro Elect Mech Syst Div, ASME, Fluids Engn Div, ASME, Bioengn Div, ASME, Appl Mech Div, ASME, Elect & Photon Packaging Div, ASME, Mfg Engn Div, ASME, Adv Energy Syst Div, ASME, Aerosp Div ID PYRANINE; PROBE AB Currently many methods of drying are under investigation for the anhydrous preservation of mammalian cells, including convective drying (Bhowmick et al., 2003), vacuum drying (Elliott et al., 2002), room temperature desiccation cabinet drying (Acker et al., 2002), and freeze-drying (Wolkers et al., 2001). Independent of the drying method, cells are typically in an aqueous suspension at the onset. Generally the change in 'system' weight (cells and extracellular solution) is measured gravimetrically and this moisture loss in the system is assumed to equate to the loss of moisture within the suspended cells. This approach assumes that the intra- and extracellular water contents are equivalent and that the dried sample is homogenous. These assumptions are not always valid. Oftentimes cells are seen to pool towards the middle of a droplet and macroscopic heterogeneities of moisture content within the droplet are sometimes visible by eye. Although important advances in mammalian cell preservation have been made using this approach, a convenient method of determining localized water content within such samples would advance the state-of-the-art in drying technologies. Because sugars are a common excipient used in drying, the current study investigates the spatial distribution of moisture content in dried sugar matrices using pyranine as a fluorescent probe of the local water environment. The pyranine molecule has two fluorescent states, emitting at 511 nm (green) and 440 nm (blue). Using calibration curves based on ratiometric measurements of blue to green pyranine fluorescence emissions the effect of drying substrate on moisture content uniformity is explored in pyranine-doped sucrose solutions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. RP Elliott, GD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 0-7918-3710-6 PY 2003 BP 15 EP 16 PG 2 WC Biophysics; Engineering, Biomedical; Mechanics; Medicine, Research & Experimental SC Biophysics; Engineering; Mechanics; Research & Experimental Medicine GA BAL07 UT WOS:000222660500007 ER PT B AU Most, E Li, G Rubash, HE AF Most, E Li, G Rubash, HE GP ASME TI Tibiofemoral contact after conventional and high-flexion posterior cruciate-retaining total knee arthroplasty SO 2003 ADVANCES IN BIOENGINEERING LA English DT Proceedings Paper CT ASME International Mechanical Engineering Congress CY NOV 15-21, 2003 CL Washington, DC SP ASME, Fluid Power Syst & Technol Div, ASME, Micro Elect Mech Syst Div, ASME, Fluids Engn Div, ASME, Bioengn Div, ASME, Appl Mech Div, ASME, Elect & Photon Packaging Div, ASME, Mfg Engn Div, ASME, Adv Energy Syst Div, ASME, Aerosp Div ID MOTION; JOINT AB The human knee is capable of flexing up to 160degrees, yet most patients do not achieve more than 120degrees after total knee arthroplasty (TKA). The translation of the tibiofemoral contact points with flexion is important in the overall understanding of knee kinematics and knee stability, particularly in high flexion. In this study, cadaveric knees were used in conjunction with a robotic testing system and TekScan(R) film to quantify the tibiofemoral contact between 0degrees-150degrees for two TKA designs. We found that, for both TKAs, with increasing knee flexion, the peak contact point moved posteriorly and that the contact area decreased with increasing knee flexion. C1 Massachusetts Gen Hosp, Dept Orthopaed, Bioengn Lab, Boston, MA 02114 USA. RP Most, E (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Bioengn Lab, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 5 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 0-7918-3710-6 PY 2003 BP 299 EP 300 PG 2 WC Biophysics; Engineering, Biomedical; Mechanics; Medicine, Research & Experimental SC Biophysics; Engineering; Mechanics; Research & Experimental Medicine GA BAL07 UT WOS:000222660500137 ER PT B AU Tsourkas, A Josephson, L Weissleder, R AF Tsourkas, A Josephson, L Weissleder, R GP ASME TI The development of non-radiative probes for in vivo applications SO 2003 ADVANCES IN BIOENGINEERING LA English DT Proceedings Paper CT ASME International Mechanical Engineering Congress CY NOV 15-21, 2003 CL Washington, DC SP ASME, Fluid Power Syst & Technol Div, ASME, Micro Elect Mech Syst Div, ASME, Fluids Engn Div, ASME, Bioengn Div, ASME, Appl Mech Div, ASME, Elect & Photon Packaging Div, ASME, Mfg Engn Div, ASME, Adv Energy Syst Div, ASME, Aerosp Div DE nanoparticle; probe; imaging; magnetic AB Recently, the field of activatable probes has been extended from fluorescence to magnetic resonance (MR). Magnetic relaxation switches take advantage of the change in T2 relaxation time that occurs upon binding of multiple bioconjugated superparamagnetic iron-oxide nanoparticles to a target. Here, we use a model system to detect biotinilated BSA using switchable magnetic particles. The presence of the biotinilated BSA results in the aggregation of nanoparticles and leads to a substantial decrease in the T2 relaxation time. Magnetic relaxation switches show great promise for clinical in vitro diagnostics and in vivo imaging since changes in T2 are independent of the sample medium. Tests can be performed in turbid solutions without loss of sensitivity, unlike with fluorescence measurements. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tsourkas, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Tsourkas, Andrew/0000-0001-7758-1753 NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 0-7918-3710-6 PY 2003 BP 351 EP 352 PG 2 WC Biophysics; Engineering, Biomedical; Mechanics; Medicine, Research & Experimental SC Biophysics; Engineering; Mechanics; Research & Experimental Medicine GA BAL07 UT WOS:000222660500163 ER PT B AU Cascio, EW Sisterson, JM Flanz, JB Wagner, MS AF Cascio, EW Sisterson, JM Flanz, JB Wagner, MS GP IEEE TI The proton irradiation program at the Northeast Proton Therapy Center SO 2003 IEEE RADIATION EFFECTS DATA WORKSHOP RECORD LA English DT Proceedings Paper CT IEEE Radiation Effects Data Workshop held in Conjunction with IEEE Nuclear and Space Radiation Effects Conference CY JUL 21-25, 2003 CL MONTEREY, CA SP IEEE Nucl & Plasma Sci Soc, Inst Elect & Elect Engineers Inc AB The Harvard Cyclotron Laboratory (HCL) was closed on 1 July 2002. The successful transfer of the research and radiation effects testing program from HCL to the Northeast Proton Therapy Center is described. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Cascio, EW (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-8127-0 PY 2003 BP 141 EP 144 DI 10.1109/REDW.2003.1281365 PG 4 WC Engineering, Aerospace; Computer Science, Hardware & Architecture; Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Computer Science; Physics GA BY48Z UT WOS:000189348100022 ER PT J AU Sahani, D Prasad, SR Tannabe, KK Hahn, PF Mueller, PR Saini, S AF Sahani, D Prasad, SR Tannabe, KK Hahn, PF Mueller, PR Saini, S TI Thorotrast-induced cholangiocarcinoma: case report SO ABDOMINAL IMAGING LA English DT Article DE thorotrast; liver; cholangiocarcinoma; magnetic resonance; computed tomography ID INTRAHEPATIC PERIPHERAL CHOLANGIOCARCINOMA; MRI; CT AB Thorotrast, a contrast medium used extensively before being banned in 1950s, delivers a densely ionizing, high linear energy transfer type of radiation that predisposes to malignancies. We report a case of peripheral cholangiocarcinoma and describe its computed tomographic and magnetic resonance imaging features in a patient who developed it 48 years after exposure to Thorotrast. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 8 TC 15 Z9 16 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD JAN-FEB PY 2003 VL 28 IS 1 BP 72 EP 74 DI 10.1007/s00261-001-0148-y PG 3 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 632CX UT WOS:000180207100016 PM 12483389 ER PT J AU Langdale, LA Schaad, D Wipf, J Marshall, S Vontver, L Scott, CS AF Langdale, LA Schaad, D Wipf, J Marshall, S Vontver, L Scott, CS TI Preparing graduates for the first year of residency: Are medical schools meeting the need? SO ACADEMIC MEDICINE LA English DT Article ID CLERKSHIP AB Purpose. Changes in graduate medical education associated with full implementation of the Balanced Budget Act of 1997 have required medical schools to review and revise their curricula. As limited funding increases pressures to streamline training, residencies will potentially expect an entry level of skill and competence that is greater than that which schools are currently providing. To determine whether medical school curricular requirements correlate with residency needs, this multidisciplinary pilot study investigated expectations and prerequisites for postgraduate specialty training, Method. A questionnaire about 100 skills and competencies expected of new first-year residents was sent to 50 U.S. residency directors from surgery, internal medicine, family medicine, pediatrics, and obstetrics-gynecology programs. Each director was asked to state expectations of a first-year resident's competence in each skill at entry to residency and after three months of training. Skills deemed most appropriately acquired in residency were also identified. Competencies included diagnosis, management, triage, interpretation of data, informatics and technology, record keeping, interpersonal communications, and manual skills. Results. A total of 39 residency directors responded, including seven surgery, nine medicine, seven family medicine, eight pediatrics, and eight obstetrics -gynecology. In addition to physical examination skills, 13 competencies achieved more than 70% agreement as being entry, level skills. There was wide variability as to the relative importance of the remaining skills, with residency directors expecting to devote significant resources and time in early training to ensure competence. Conclusions. Medical schools should consider the expectations of their students' future residency directors when developing new curricula. Assuring students' competencies through focused curricular change should save both time and resources during residency. C1 Univ Washington, Sch Med, Dept Surg, VA Puget Sound Hlth Care, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med Educ, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98108 USA. RP Langdale, LA (reprint author), Univ Washington, Sch Med, Dept Surg, VA Puget Sound Hlth Care, Bldg 1,Room 314,1660 S Columbian Way, Seattle, WA 98108 USA. NR 8 TC 54 Z9 54 U1 0 U2 5 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2003 VL 78 IS 1 BP 39 EP 44 DI 10.1097/00001888-200301000-00009 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 636CD UT WOS:000180436200009 PM 12525408 ER PT J AU Kiely, SC Russo, KS Orav, EJ McMahon, K Shannon, RP O'Donnell, WJ AF Kiely, SC Russo, KS Orav, EJ McMahon, K Shannon, RP O'Donnell, WJ TI The effect of a teaching hospital's financial crisis and reorganization on a group of residents SO ACADEMIC MEDICINE LA English DT Article ID SATISFACTION; PERCEPTIONS; PROGRAMS; QUALITY; HOUSE; FALL AB Purpose. Allegheny General Hospital (AGH) in Pittsburgh, Pennsylvania, was part of a statewide health care system that underwent a financial crisis and operational reorganization between 1998 and 2000. This study assessed internal medicine (IM) residents' perceptions of the effects of AGH's financial crisis on their residencies Method. A confidential, program-based questionnaire was distributed to 75 IM residents at AGH in spring 2000 and included questions on demographic information, inpatient and outpatient medical education, and the hospital's financial crisis. Residents were asked to assess the effects of the financial crisis on their residencies, personal experiences, and attitudes toward health care systems. Outcomes included consideration of transfer, recommendation of the program to a medical student, concerns about fellowship opportunities, opinions about large health care systems, and medicine as a career recommendation. Results. A total of 71 residents (95%) responded to the questionnaire. Fifty-five (79%) had experienced effects on their residencies due to the financial crisis, but perceptions differed widely. Eighteen (25%) considered transferring from the program, but 44 of 59 (75%) would have recommended the program to a medical student. Because of the financial crisis, respondents reported significant changes in concerns about fellowship opportunities (P < .001), opinions about large health care systems (p < .001), and opinions about recommending medicine as a career (P < .001). Conclusion. This study highlights the fact that residents serve as program ambassadors and their experiences may influence recruitment and retention. Thus, programs should consider ways to assess and address residents concerns during any system crisis or reorganization. C1 Allegheny Gen Hosp, Dept Med, Pittsburgh, PA 15212 USA. Drexel Univ, Sch Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Sect Clin Epidemiol, Boston, MA USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Kiely, SC (reprint author), Allegheny Gen Hosp, Dept Med, Suite 295 ST,320 East North Ave, Pittsburgh, PA 15212 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2003 VL 78 IS 1 BP 45 EP 53 DI 10.1097/00001888-200301000-00010 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 636CD UT WOS:000180436200010 PM 12525409 ER PT J AU Patten, C Horak, FB Krebs, DE AF Patten, C Horak, FB Krebs, DE TI Head and body center of gravity control strategies: Adaptations following vestibular rehabilitation SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE adaptation; coordination; kinematics; orientation; vestibular ID LOCOMOTOR TASKS; MOVEMENTS; BALANCE; HUMANS; REFLEX; STABILIZATION; PATTERNS; TRUNK; NECK AB Objective-We present for the first time evidence that vestibulopathy impairs coordination of the head with the body center of gravity (CG) during free speed gait over ground, Vestibulopathic individuals demonstrate uncoordinated movement and gait due, at least in part, to impaired head stability and visual fixation. Vestibular rehabilitation increases speed and stability during gait and stair climbing, although the underlying mechanisms are poorly understood. Material and methods-To determine whether these locomotor improvements are due to reorganized coordination of the head with whole body CG, three-dimensional kinematics were obtained from 10 vestibulopathic individuals before and after vestibular rehabilitation and from 10 matched healthy control subjects during unconstrained, paced and in-place gait. Head control patterns were characterized using both qualitative pattern analysis and quantification of coherence between head and body CG displacements. Results-Patterns of head-CG coordination differ between normal and vestibulopathic individuals in all three directions of head rotation-pitch, roll and yaw-before rehabilitation. Following vestibular rehabilitation, subjects with vestibulepathy demonstrate more normal patterns in pitch and improvements toward normal in roll and yaw. Conclusion-These data strongly suggest that compensatory mechanisms, obtained during vestibular rehabilitation, mediate head-CG coordination. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomot Lab, Boston, MA USA. RP Krebs, DE (reprint author), MGH Inst Hlth Profess, MGH Biomot Lab, 36 1st Ave,223, Boston, MA 02129 USA. EM krebs@helix.mgh.harvard.edu RI Patten, Carolynn/B-4804-2009 OI Patten, Carolynn/0000-0002-9948-0045 FU NIA NIH HHS [R01 AG11255] NR 25 TC 13 Z9 14 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0001-6489 EI 1651-2251 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PY 2003 VL 123 IS 1 BP 32 EP 40 DI 10.1080/003655402/000028036 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 651DF UT WOS:000181304600006 PM 12625570 ER PT B AU Monga, T AF Monga, T BE Sorkoker, N Ring, H TI Sexuality and disability SO ADVANCES IN PHYSICAL AND REHABILITATION MEDICINE LA English DT Proceedings Paper CT 2nd World Congress of the International-Society-of-Physical-and-Rehabilitation-Medicine (ISPRM) CY MAY 18-23, 2003 CL Prague, CZECH REPUBLIC SP Int Soc Phys & Rehabilitat Med ID SPINAL-CORD-INJURY; TRAUMATIC BRAIN INJURY; IN-VITRO FERTILIZATION; ERECTILE DYSFUNCTION; SILDENAFIL CITRATE; MALE-INFERTILITY; STROKE PATIENTS; CHRONIC PAIN; WOMEN; ELECTROEJACULATION AB Although the philosophy and practice of rehabilitation medicine has been well defined, little emphasis has been placed on dealing with problems related to sexual functioning in people with disabilities. While the problems with sexual functioning are reported to be common, the question of sexual functioning is often not discussed during rehabilitation and the sexual needs of physically challenged people arc still being ignored. The exact magnitude of the problem is not known as the information gathered is based upon self-reports. Many patients experience arousal and orgasmic problems. Sexual function and sexual adjustment within the functional limitations of a disability have not been studied systematically. Cultural differences and personal preferences have not been incorporated in study designs. Treatment interventions have not been systematically investigated. Future research should address the fundamental questions of intimate relationships, pregnancy, labor, parenting, ethical and legal issues regarding sexuality in people with physical disabilities. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Rehabil Care Line, Houston, TX 77030 USA. RP Monga, T (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Rehabil Care Line, Houston, TX 77030 USA. NR 81 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-3122-5 PY 2003 BP 345 EP 354 PG 10 WC Clinical Neurology; Orthopedics; Rehabilitation SC Neurosciences & Neurology; Orthopedics; Rehabilitation GA BX05W UT WOS:000184146600042 ER PT J AU Shulman, DG AF Shulman, DG TI Two mast cell stabilizers, pemirolast potassium 0.1% and nedocromil sodium 2%, in the treatment of seasonal allergic conjunctivitis: A comparative study SO ADVANCES IN THERAPY LA English DT Article DE seasonal allergic conjunctivitis; allergen challenge; pemirolast; nedocromil; comfort ID CHALLENGE; TILAVIST AB This randomized, double-masked, active-control, parallel-group trial compared the mast cell stabilizers pemirolast potassium 0.1% and nedocromil sodium 2% in the treatment of seasonal allergic conjunctivitis. Pemirolast is currently indicated for four-times-daily-administration, nedocromil, for twice-daily dosing. Both ophthalmic solutions were instilled bilaterally twice a day for 8 weeks. The study involved four office visits and two telephone contacts. Participants evaluated their symptoms daily in take-home diaries (itching was the primary efficacy variable) and completed questionnaires to assess comfort. Of a total enrollment of 80, 78 patients completed the study. No significant differences were found between pemirolast and nedocromil on any signs or symptoms of allergic conjunctivitis (redness, chemosis, itching, eyelid swelling). At each visit, pemirolast was rated significantly more comfortable than nedocromil. A significantly higher percentage of the pemirolast group experienced no signs or symptoms at work or school (58% vs 28%; P=.005). The number of adverse events did not differ significantly between groups. Twice-daily administration of pemirolast potassium was as efficacious and safe as twice-daily nedocromil sodium in the 8-week treatment of ragweed allergic conjunctivitis and was superior to nedocromil in comfort. Increased comfort with pemirolast may increase patient satisfaction and compliance with therapy. C1 Univ Texas Hlth Ctr, Audie L Murphy Vet Adm Hosp, Dept Ophthalmol, San Antonio, TX USA. RP Shulman, DG (reprint author), 999 E Basse Rd,Suite 127, San Antonio, TX 78209 USA. NR 16 TC 2 Z9 3 U1 1 U2 1 PU HEALTH COMMUNICATIONS INC PI EDISON PA 292 FERNWOOD AVE, EDISON, NJ 08837 USA SN 0741-238X J9 ADV THER JI Adv. Ther. PD JAN-FEB PY 2003 VL 20 IS 1 BP 31 EP 40 DI 10.1007/BF02850117 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 676VL UT WOS:000182773200004 PM 12772816 ER PT J AU Roelofs, CF Barbeau, EM Ellenbecker, MJ Moure-Eraso, R AF Roelofs, CF Barbeau, EM Ellenbecker, MJ Moure-Eraso, R TI Prevention strategies in industrial hygiene: A critical literature review SO AIHA JOURNAL LA English DT Review DE controls; industrial hygiene; literature review; prevention ID INTERVENTION RESEARCH; OCCUPATIONAL-SAFETY; HEALTH; EXPOSURE AB Little is known of the extent of use of industrial hygiene prevention and control strategies in actual workplaces. The recent occupational safety and health literature was identified as a potential source for identifying which strategies are being utilized and evaluated as a means of controlling or preventing chemical hazards. Using preestablished selection criteria, the peer-reviewed industrial hygiene literature 1994-1999 was searched for articles describing prevention and control strategies for chemical hazards in actual workplaces. Ninety-two articles were found and categorized by the type of strategy discussed, whether strategies were implemented and evaluated, and by several other categories. Almost three-quarters discussed engineering control strategies, mostly local exhaust ventilation. Administrative strategies, including housekeeping, personal hygiene, and medical surveillance, appeared in about half the articles. Personal protective equipment was considered in one-third of the articles, and primary prevention strategies, such as material substitution, were considered in one-quarter. Intervention effectiveness was not consistently evaluated in these articles. In response to these findings, recommendations are made to improve the evaluation and promotion of effective prevention and control strategies. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 01854 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 01854 USA. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. RP Roelofs, CF (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 01854 USA. FU NCI NIH HHS [5-R25-CA57711-10] NR 22 TC 19 Z9 20 U1 1 U2 10 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 1529-8663 J9 AIHA J JI AIHA J. PD JAN-FEB PY 2003 VL 64 IS 1 BP 62 EP 67 DI 10.1080/15428110308984788 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 644CM UT WOS:000180900400010 PM 12570397 ER PT J AU Oscar-Berman, M Marinkovic, K AF Oscar-Berman, M Marinkovic, K TI Alcoholism and the brain: An overview SO ALCOHOL RESEARCH & HEALTH LA English DT Review DE neurobehavioral theory of AODU (alcohol and other drug use); alcoholic brain syndrome; brain atrophy; neuropsychological assessment; neurotransmission; risk factors; comorbidity; disease susceptibility; neuroimaging; treatment factors; survey of research ID POSITRON-EMISSION-TOMOGRAPHY; EVENT-RELATED POTENTIALS; NEUROBIOLOGY; ABSTINENT; DAMAGE AB Alcoholism can affect the brain and behavior in a variety of ways, and multiple factors can influence these effects. A person's susceptibility to alcoholism-related brain damage may be associated with his or her age, gender, drinking history, and nutrition, as well as with the vulnerability of specific brain regions. Investigators use a variety of methods to study alcoholism-related brain damage, including examining brains of deceased patients as well as neuroimaging, a technique that enables researchers to test and observe the living brain and to evaluate structural damage in the brain. C1 Boston Univ, Dept Anat & Neurobiol, Sch Med, Boston, MA 02215 USA. Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA. Boston Univ, Dept Neurol, Sch Med, Boston, MA 02215 USA. US Dept Vet Affairs, Healthcare Syst, Jamaica Plain Div, Boston, MA USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oscar-Berman, M (reprint author), Boston Univ, Dept Anat & Neurobiol, Sch Med, Boston, MA 02215 USA. FU NIAAA NIH HHS [K01 AA013402, K01-AA-13402, K05-AA-00219, R37-AA-07112] NR 28 TC 104 Z9 107 U1 1 U2 16 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2003 VL 27 IS 2 BP 125 EP 133 PG 9 WC Substance Abuse SC Substance Abuse GA 853BG UT WOS:000223800500001 PM 15303622 ER PT J AU McNamara, ME Burnham, DC Smith, C Carroll, DL AF McNamara, ME Burnham, DC Smith, C Carroll, DL TI The effects of back massage before diagnostic cardiac catheterization SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Article ID HEART-RATE-VARIABILITY; CORONARY-CARE UNIT; RELAXATION; THERAPY; ANXIETY; DISEASE; MUSIC; RUB AB Context Admission to the hospital for a diagnostic cardiac catheterization can he perceived as a threat to one's health status. Autonomic nervous system arousal, particularly the sympathetic division, can elicit negative physiological and psychological human responses as a reaction to this threat. Objective The purpose of this study was to measure the effects of a 20-minute hack massage on the physiological and psychological human responses of patients admitted for a diagnostic cardiac catheterization. Design A randomized clinical trial design was used. Data were compared in a repeated measures design before massage (T1), immediately following the hack massage or standard care (T2), and 10 minutes later (T3). Setting A large urban academic medical center. Participants Forty-six subjects admitted from home for a diagnostic cardiac catheterization. Main Outcome Measures Heart rate, heart rate variability, blood pressure, respiration, peripheral skin temperature, pain perception, and psychological state. Intervention A 20-minute hack massage. Results e There was a significant difference between subject effect for group, with a reduction in systolic blood pressure in the treatment group (F = 8.6, P < .05). In addition, main effects were noted for time for diastolic blood pressure (F = 5.44; P < .006), respiration (F = 10.6; P < .005), total Profile of Mood States score (F = 5.9; P < .001) and pain perception (F = 4.09; P < .04) in both groups. Conclusions A 20-minute hack massage appeared to reduce systolic blood pressure in patients awaiting a diagnostic cardiac catheterization, while preparatory time in the cardiac catheterization laboratory appeared to reduce diastolic blood pressure, respiration, perceived psychological distress, and pain. C1 Massachusetts Gen Hosp, Knight Ctr Cardiovasc Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Knight Ctr Cardiovasc Therapy, Boston, MA 02114 USA. RP McNamara, ME (reprint author), Massachusetts Gen Hosp, Knight Ctr Cardiovasc Therapy, Boston, MA 02114 USA. NR 32 TC 12 Z9 12 U1 0 U2 4 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD JAN-FEB PY 2003 VL 9 IS 1 BP 50 EP 57 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 636TJ UT WOS:000180472800012 PM 12564351 ER PT J AU Copeland, MP Daly, E Hines, V Mastromauro, C Zaitchik, D Gunther, J Albert, M AF Copeland, MP Daly, E Hines, V Mastromauro, C Zaitchik, D Gunther, J Albert, M TI Psychiatric symptomatology and prodromal Alzheimer's disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer's disease; psychiatric symptoms; depression; personality change; prodromal AD ID DEPRESSIVE SYMPTOMS; PERSONALITY CHANGES; COGNITIVE DECLINE; COMMUNITY SAMPLE; DEMENTIA; AD AB The aim of this study was to determine the prevalence of psychiatric symptoms among nondemented individuals with memory changes and whether such symptoms predict progression of functional decline or diagnosis of Alzheimer disease (AD). A semi-structured interview was administered at baseline to controls (n = 32) and to nondemented subjects with memory changes (n = 112) and to each subject's collateral source. The interview assessed the impact of cognition on functional abilities in daily life and a variety of psychiatric symptoms, including symptoms of psychosis, depression, and personality change. Participants were followed annually for 3 years to determine who had progressive functional decline and who progressed to meet clinical criteria for AD. Those diagnosed with AD on follow-up had more symptoms of personality change, such as agitation and passivity, at baseline than those who did not progress to meet clinical criteria for AD. Mild depressive symptoms were also more common among individuals at baseline who subsequently 'converted' to AD. Symptoms of personality change were associated with a more rapid increase in functional difficulty over time, whereas depressive symptoms were not. Changes in personality are more common among subjects with memory changes who go on to develop AD. Particular types of personality change, such as agitation and passivity, are related to progression of functional difficulty over time. Depressive symptoms, although common in prodromal AD, are not associated with a more rapid functional decline. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Copeland, MP (reprint author), Massachusetts Gen Hosp East, 149-9124,149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01-AG04953] NR 31 TC 79 Z9 82 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2003 VL 17 IS 1 BP 1 EP 8 DI 10.1097/00002093-200301000-00001 PG 8 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 653MC UT WOS:000181439300001 PM 12621314 ER PT J AU Leape, LL Weissman, JS Schneider, EC Piana, RN Gatsonis, C Epstein, AM AF Leape, LL Weissman, JS Schneider, EC Piana, RN Gatsonis, C Epstein, AM TI Outcomes, health policy, and managed care - Adherence to practice guidelines: The role of specialty society guidelines SO AMERICAN HEART JOURNAL LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; BYPASS GRAFT-SURGERY; NEW-YORK-STATE; TRANSLUMINAL CORONARY ANGIOPLASTY; ASSOCIATION TASK-FORCE; PHYSICIAN COMPLIANCE; APPROPRIATENESS; PROGRAM; OVERUSE AB Background Physician adherence to guidelines is often poor, but the reasons have not been completely studied. We investigated whether physician adherence to guidelines for percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) varied by source, development methods, or the extent of their evidence-base. Methods and Results We assessed adherence to guidelines developed by the American College of Cardiology/American Heart Association (ACC/AHA) for PTCA (1988 and 1993) and for CABG (1990) and guidelines developed by RAND for PTCA and CABG in 1990. We randomly sampled patients on Medicare who were undergoing coronary angiography in 5 states in 1991 and 1992, extracting clinical and laboratory data from medical records and using computer programs to classify the appropriateness of each procedure. A total of 543 PTCA and 676 CABG procedures were studied. By use of the 1988 ACC/AHA guidelines, 30% of PTCAs were rated class III (inappropriate), whereas 24% were class III by use of the 1993 guidelines. Only 1.5% of CABG procedures were class III with ACC/AHA guidelines. By use of RAND guidelines, 12% of PTCA and 9% of CABG procedures were classified as inappropriate. Conclusions Adherence to guidelines is higher when the recommendations are supported by evidence from randomized clinical trials (CABG). The credibility of the source and familiarity with the guidelines do not ensure compliance. When evidence is lacking, as with PTCA at the time of this study, guideline recommendations may lag behind appropriate changes in clinical practice. More frequent revisions coupled with on-line access have the potential to make guidelines more useful. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brown Univ, Dept Stat, Providence, RI 02912 USA. Vanderbilt Univ, Med Ctr, Div Cardiol, Nashville, TN USA. Brigham & Womens Hosp, Div Gen Internal Med, Sect Hlth Serv & Policy Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Hlth Policy, Boston, MA 02114 USA. RP Leape, LL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. OI Schneider, Eric/0000-0002-1132-5084 FU AHRQ HHS [5 R0 HS07098-02S1] NR 23 TC 62 Z9 64 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2003 VL 145 IS 1 BP 19 EP 26 DI 10.1067/mhj.2003.35 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 632CA UT WOS:000180205000005 PM 12514650 ER PT J AU Bahit, MC Cannon, CP Antman, EM Murphy, SA Gibson, CM McCabe, CH Braunwald, E AF Bahit, MC Cannon, CP Antman, EM Murphy, SA Gibson, CM McCabe, CH Braunwald, E TI Direct comparison of characteristics, treatment, and outcomes of patients enrolled versus patients not enrolled in a clinical trial at centers participating in the TIMI 9 trial and TIMI 9 registry SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; COOPERATIVE CARDIOVASCULAR PROJECT; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; THROMBOLYTIC THERAPY; THROMBIN INHIBITION; REPERFUSION THERAPY; ACC/AHA GUIDELINES; MORTALITY; EXPERIENCE AB Background Questions about the generalizability of randomized trial results to clinical practice have arisen because the overall mortality rate is generally lower in trials, potentially because patients who are at lower risk are enrolled. However, little is known about the characteristics of patients included in clinical trials versus those who are not included. Methods The Thrombolysis In Myocardial Infarction (TIMI) 9 Registry prospectively evaluated patients with ST-elevation myocardial infarction at 20 hospitals during the TIMI 9 trial, which compared hirudin versus heparin with fibrinolysis. We compared the characteristics, treatment, and outcomes of patients enrolled in TIMI 9B (n = 3002) with other fibrinolytic-eligible patients not enrolled in TIMI 9B (n = 296) and with those not eligible for fibrinolysis by American College of Cardiology/American Heart Association criteria, at the same centers (n = 282), with the latter groups divided by use of reperfusion therapy. Results Across the groups, ranging from those in the TIMI 9 trial to those ineligible for fibrinolysis, we observed a gradient of higher-risk baseline characteristics, lower use of reperfusion therapy, and higher mortality rates (P <.001). In addition, comparing fibrinolytic-eligible patients in TIMI 913 versus those not enrolled in the trial, the use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors was significantly higher in the TIMI 913 trial. Ineligible patients not treated with reperfusion therapy had much lower rates of use of these medications and the highest inhospital mortality rate (24%, adjusted odds ratio 2.8, P <.0001) Conclusions In this prospective registry, patients not enrolled in a clinical trial had higher risk characteristics and worse outcomes; however, they also were treated less frequently with guideline-recommended medications, which may have contributed to their higher mortality rates. C1 Brigham & Womens Hosp, Div Cardiol, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Clin Res Inst, Boston, MA USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiol, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 25 TC 43 Z9 43 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2003 VL 145 IS 1 BP 109 EP 117 DI 10.1067/mhj.2003.43 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 632CA UT WOS:000180205000017 PM 12514662 ER PT J AU Graf, LL Welsh, CH Qamar, Z Marlar, RA AF Graf, LL Welsh, CH Qamar, Z Marlar, RA TI Activated protein C resistance assay detects thrombotic risk factors other than factor V Leiden SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE activated protein C resistance; case-control study; factor V Leiden; factor VIII; HR2 haplotype; venous thromboembolism ID POOR ANTICOAGULANT RESPONSE; VENOUS THROMBOSIS; HR2 HAPLOTYPE; MUTATION; THROMBOEMBOLISM; THROMBOPHILIA; SENSITIVITY; R506Q; GENE; DNA AB Activated protein C (APC) resistance is a common risk factor for venous thromboembolism (VTE) attributed to various mechanisms, including factor V Leiden (FVL) polymorphism. FVL is considered responsible for up to 95% of APC resistance; however, other factor V polymorphisms and elevated factor VIII levels also have been implicated. We assessed whether additional mechanisms contribute to APC resistance in a blinded case-control study of 65 subjects by measuring APC resistance using 3 methods: 2 activated partial thromboplastin time-based methods with and without dilution in factor V-deficient plasma and I Russell viper venom-based assay (RVV). Without factor V-deficient plasma, 24 subjects were APC resistant; with factor V-deficient plasma, the assay identified fewer APC-resistant subjects, as did RVV All assays detected the 7 heterozygous FVL subjects. Thirteen subjects had factor VIII levels above 150% (1.50). After excluding subjects with FVL or elevated factor VIII levels, 4 subjects still had APC resistance. VTE risk trended higher for subjects with APC resistance in the absence of FVL. Measurement of APC resistance without dilution in factor V-deficient plasma is needed to assess for potentially important, thrombotic risk factors other than FVL. C1 Denver Vet Affairs Med Ctr, Pathol Res Lab, Res Serv, Denver, CO USA. Denver Vet Affairs Med Ctr, Div Pulm & Crit Care Med, Med Serv, Denver, CO USA. Denver Vet Affairs Med Ctr, Pathol Res Lab, Pathol & Lab Med Serv, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem, Denver, CO 80262 USA. Aga Khan Univ, Sch Med, Karachi, Pakistan. RP Marlar, RA (reprint author), Denver Vet Affairs Med Ctr, Lab Serv 113, 1055 Clermont St, Denver, CO 80220 USA. NR 39 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2003 VL 119 IS 1 BP 52 EP 60 DI 10.1092/LX9E6Y043P58YVCL PG 9 WC Pathology SC Pathology GA 630VN UT WOS:000180131000007 PM 12520697 ER PT J AU Refaai, MA Laposata, M Van Cott, EM AF Refaai, MA Laposata, M Van Cott, EM TI Clinical significance of a borderline titer in a negative ELISA test for heparin-induced thrombocytopenia SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE heparin; heparin-induced thrombocytopenia; platelet count; thrombosis; thrombocytopenia; ELISA; HIT titer ID ANTIBODIES; THROMBOSIS; DIAGNOSIS; HIT AB We studied the usefulness of repeated enzyme-linked immunosorbent assay testing for heparin-induced thrombocytopenia (HIT) when the initial test result was negative and sought to determine whether the titer of the initial negative result correlated with the likelihood of obtaining a positive test result in repeated testing. We divided 150 patients who underwent HIT testing into 3 groups (50 patients each): (1) very low titer negative (0.0%-33.3% of the threshold for a positive test); (2) low titer negative (33.4%-66.6% of the threshold); and (3) high titer negative (66.7%-99.9% of the threshold). Among the patients who underwent a repeat test, 5% (1/20) of group 1 patients, 13% (4/32) of group 2 patients, and 43% (13.30) of group 3 patients tested positive in the repeat test (P = .0026). Thus, nearly half of patients with initially negative HIT test results had positive results in the repeat test if the negative titer was 66.7% or more of the threshold. If laboratories report the HIT titer, rather than just negative or positive, the titer might help clinicians predict which patients have HIT despite a negative initial test, and the overall sensitivity for diagnosing HIT might be improved. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Coagulat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Coagulat Lab, Room 235,Gray Bldg, Boston, MA 02114 USA. NR 20 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2003 VL 119 IS 1 BP 61 EP 65 DI 10.1092/4TH2FXGADTTF2K5X PG 5 WC Pathology SC Pathology GA 630VN UT WOS:000180131000008 PM 12520698 ER PT J AU Hu, Y Shahidi, A Park, S Guilfoyle, D Hirshfield, I AF Hu, Y Shahidi, A Park, S Guilfoyle, D Hirshfield, I TI Detection of extrahepatic hepatitis C virus replication by a novel, highly sensitive, single-tube nested polymerase chain reaction SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE hepatitis C virus; lymphocyte; complementary DNA; PCR; polymerase chain reaction; nested PCR; DNA sequencing ID BLOOD MONONUCLEAR-CELLS; FOLLOW-UP; RNA; INFECTION; STRAND; LINE; PCR; ASSAY; LIVER AB We established a cell culture system for the replication of hepatitis C virus (HCV) by using human T and B leukemia cell lines. These 2 cell lines were infected in vitro by using HCV-positive pooled patient serum samples. HCV RNA was extracted from infected cell lines at different times after infection, and a sequence of the virus 5' untranslated region was analyzed. Hepatitis C minus-strand RNA was detected in the infected cell lines by highly strand-specific rTth (recombinant Thermus thermophilus DNA polymerase)based reverse transcription followed by a novel, highly sensitive, single-tube nested polymerase chain reaction (PCR) method. PCR products were analyzed by direct DNA sequencing. These results indicate that the HCV can replicate in T and B lymphocytes. This model should represent a valuable tool for the detailed study of the initial steps of the HCV replication cycle and for the evaluation of antiviral molecules. C1 US FDA, Microbiol Sci Branch, NE Reg Lab, Jamaica, NY 11433 USA. US Dept Vet Affairs, Med Ctr, Clin Microbiol Lab, Bronx, NY USA. St Johns Univ, Dept Biol Sci, Jamaica, NY 11439 USA. RP Hu, Y (reprint author), US FDA, Microbiol Sci Branch, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 33 TC 29 Z9 30 U1 1 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2003 VL 119 IS 1 BP 95 EP 100 DI 10.1092/MG0L7NK6P9WE37RJ PG 6 WC Pathology SC Pathology GA 630VN UT WOS:000180131000013 PM 12520703 ER PT J AU Karlsgodt, KH Lukas, SE Elman, I AF Karlsgodt, KH Lukas, SE Elman, I TI Psychosocial stress and the duration of cocaine use in non-treatment seeking individuals with cocaine dependence SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE POMS; STAI; HRSD; craving ID CORTICOTROPIN-RELEASING FACTOR; PSYCHOLOGICAL STRESS; DRUG-ADDICTION; DEPRESSIVE SYMPTOMATOLOGY; INDUCED RELAPSE; RATS; ABUSE; ALCOHOL; DYSREGULATION; ANXIETY AB The aim of this study was to explore a potential link between psychosocial stress and cocaine dependence among 36 non-treatment-seeking individuals enrolled in a brain imaging protocol. Stress was assessed using computerized multidimensional instruments, including the Profile of Mood States (POMS) and Speilberger State-Trait Anxiety Inventory (STAI). Additional clinical assessments employed were the Addiction Severity Index and the Hamilton Rating Scale for Depression (HRSD). Based on the median POMS' tension-anxiety scale score the entire sample was divided into two groups, those with high and low levels of stress. The two groups (n = 16 and 20) were similar in terms of age, gender distribution, and severity of addiction. Compared with the low stress group, high-stress individuals displayed significantly longer duration of cocaine use, greater POMS, STAI-state, STAI-Trait, and HRSD scores. Our results replicate those of prior reports implicating stress in the course of cocaine dependence and extend these prior findings by 1) including a new subject population of non-treatment-seekers and 2) by suggesting that the stress-cocaine link may be generalizable to psychosocial stress and negative affective states defined by POMS, STAI, and HRSD scores. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, McLean Hosp, Boston, MA 02114 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St,WACC-812, Boston, MA 02114 USA. RI Karlsgodt, Katherine/H-2964-2013 OI Karlsgodt, Katherine/0000-0003-3332-4231 FU NIDA NIH HHS [DA 09467, DA 14410] NR 58 TC 26 Z9 26 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2003 VL 29 IS 3 BP 539 EP 551 DI 10.1081/ADA-120023457 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 720PH UT WOS:000185268800003 PM 14510039 ER PT J AU Provenzale, D Ofman, J Gralnek, I Rabeneck, L Koff, R McCrory, D AF Provenzale, D Ofman, J Gralnek, I Rabeneck, L Koff, R McCrory, D TI Gastroenterologist specialist care and care provided by generalists - An evaluation of effectiveness and efficiency SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID HELICOBACTER-PYLORI; PHYSICIAN SPECIALTY; COLORECTAL-CANCER; MANAGEMENT; OUTCOMES; KNOWLEDGE; INFECTION; PATTERNS; THERAPY; FAILURE AB OBJECTIVE In this era of cost containment, gastroenterologists must demonstrate that they provide effective and efficient care. The aim of this study was to evaluate the process and outcomes of care provided by gastroenterologists and generalist physicians (internists, family physicians, general surgeons) for GI conditions. METHODS: We conducted a systematic literature review using a MEDLINE search of English language articles (January 1980 to September 1998). A total of 2157 articles were identified; 10 met inclusion criteria for systematic review. In addition, there were nine articles that described the results of physician surveys, and examined the process of care among gastroenterologists and generalist physicians. RESULTS: Care provided by gastroenterologists for GI bleeding and diverticulitis resulted in significantly shorter length of hospital stay. Gastroenterologists diagnosed celiac disease more accurately than generalists, and more adequately diagnosed colorectal cancer and prescribed antimicrobials for peptic ulcer disease. There was no difference between gastroenterologists and generalists in terms of colonoscopy procedure time, and family physicians detected a greater number of cancers. Furthermore, there was no difference in the outcomes of gastroesophageal reflux disease therapy in patients seen by gastroenterologists, versus those educated by nurses. The survey articles suggested that gastroenterologists were more likely to test and treat for Helicobacter pylori in patients with peptic ulcer disease, and were more likely recommended for medical versus surgical therapy. Gastroenterologists had a lower threshold for ordering ERCP before cholecystectomy than surgeons, but had similar responses regarding indications for surgery in inflammatory bowel disease. Finally, primary care physicians were less likely to associate symptoms of profuse watery diarrhea with cryptosporidium infection compared with gastroenterologists and infectious disease specialists. CONCLUSIONS: We reached the following conclusions: 1) The results suggest that gastroenterologists deliver effective and efficient care for GI bleeding and diverticulitis and provide more effective diagnosis in certain disorders. 2) Studies are limited by retrospective design, small sample size, and lack of control groups. 3) To fully evaluate care by gastroenterologists, prospective comparisons with greater attention to methodology are needed. (C) 2003 by Am. Coll. of Gastroenterology. C1 Duke Univ, Med Ctr, Div Gastroenterol, GI Outcomes Res Grp, Durham, NC 27710 USA. Durham VA Med Ctr, Div Gastroenterol, Durham, NC USA. Cedars Sinai Hlth Syst, Beverly Hills, CA USA. VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90024 USA. CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Study Disgest Healthcare Qual & Outcomes, CURE, Los Angeles, CA USA. VA Med Ctr, Houston, TX USA. Univ Massachusetts, Worcester, MA 01605 USA. Duke Univ, Evidence Based Med Ctr, Durham, NC USA. Ctr Hlth Policy Res, Durham, NC USA. RP Provenzale, D (reprint author), Duke Univ, Med Ctr, Div Gastroenterol, GI Outcomes Res Grp, Box 3515, Durham, NC 27710 USA. FU NCI NIH HHS [1 K24 CA83885-01] NR 33 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2003 VL 98 IS 1 BP 21 EP 28 AR PII S0002-9270(02)05876-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639NQ UT WOS:000180636400006 PM 12526931 ER PT J AU Jacobson, BC Ferris, TG Shea, TL Mahlis, EM Lee, TH Wang, TC AF Jacobson, BC Ferris, TG Shea, TL Mahlis, EM Lee, TH Wang, TC TI Who is using chronic acid suppression therapy and why? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; FUNCTIONAL DYSPEPSIA; GENERAL-PRACTICE; PRIMARY-CARE; DIAGNOSIS; GUIDELINES; DRUGS; SYMPTOMS AB OBJECTIVES: Acid suppression medications have become one of the most commonly prescribed classes of therapeutic agents. Because little data exists describing the chronic use of these agents among a general population, we sought to determine the patterns of use of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs) in clinical practice, as well as the distribution and severity of symptoms in patients prescribed these therapies. METHODS: Pharmacy billing data from two insurers were used to identify all patients on chronic (> 90 days) PPIs and H2RAs within a large, eastern Massachusetts provider network. Patient demographics, diagnoses, frequency of office visits, and information about diagnostic testing were obtained from billing databases. A questionnaire addressing recent upper GI symptoms, over-the-counter medication use, and gastroenterologist consultations was mailed to a 1,139 patient subset (35%) of eligible patients. We compared the diagnoses of patients on chronic therapy with those of the general population of the network. We also compared the frequency of symptoms and diagnostic testing between those prescribed H2RAs and PPIs. RESULTS: From a total population of 168,727 adult patients, we identified 4,684 (2.8%) prescribed chronic acid suppression therapy, with 47% taking H2RAs and 57% taking PPIs (4% filled prescriptions for both simultaneously). A relevant GI diagnosis was found using billing data for only 61% of patients, mainly for gastroesophageal reflux disease (38%) and dyspepsia (42%), with many patients carrying both diagnoses. Our survey (response rate 59%) revealed that more than 30% of responders experienced heartburn or reflux more than twice a week, and more than half experienced symptoms of dyspepsia at least once a week. Diagnostic testing was uncommon, with only 19% having undergone esophagogastroduodenoscopy within the prior 2 yr. CONCLUSIONS: Acid suppression medications were used chronically by a large number of patients within this population. A significant proportion of patients on chronic PPI or H2RA lacked definitive upper GI diagnoses in their billing data. The high symptom burden and low use of diagnostic testing indicates opportunities for improvement in the care of patients on chronic acid suppression therapy. (C) 2003 by Am. Coll. of Gastroenterology. C1 Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Inst Hlth Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Community HealthCare Inc, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Merck Medco, Franklin Lakes, NJ USA. RP Jacobson, BC (reprint author), Boston Univ, Med Ctr, Gastroenterol Sect, 88 E Newton St,D408, Boston, MA 02118 USA. NR 31 TC 76 Z9 81 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2003 VL 98 IS 1 BP 51 EP 58 AR PII S0002-9270(02)05854-9 DI 10.1111/j.1572-0241.2003.07186.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639NQ UT WOS:000180636400011 PM 12526936 ER PT J AU Spiegel, BMR Ofman, JJ Woods, K Vakil, NB AF Spiegel, BMR Ofman, JJ Woods, K Vakil, NB TI Minimizing recurrent peptic ulcer hemorrhage after endoscopic hemostasis: The cost-effectiveness of competing strategies SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/Annual Meeting of the American-Gastroenterology-Association CY MAY 19-23, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Gastroenterol Assoc ID PROSPECTIVE RANDOMIZED TRIAL; HEATER PROBE THERMOCOAGULATION; HYPERTONIC SALINE-EPINEPHRINE; NONBLEEDING VISIBLE VESSEL; ACTIVELY BLEEDING ULCERS; INJECTION THERAPY; ADRENALINE INJECTION; FIBRIN GLUE; LASER PHOTOCOAGULATION; ETHANOLAMINE OLEATE AB OBJECTIVES: Controversy exists regarding the optimal strategy to minimize recurrent ulcer hemorrhage after successful endoscopic hemostasis. Our objective was to evaluate the cost-effectiveness of competing strategies for the posthemostasis management of patients with high risk ulcer stigmata. METHODS: Through decision analysis, we calculated the cost-effectiveness of four strategies: 1) follow patients clinically after hemostasis and repeat endoscopy only in patients with evidence of rebleeding (usual care); 2) administer intravenous proton pump inhibitors (i.v. PPIs) after hemostasis and repeat endoscopy only in patients with clinical signs of rebleeding; 3) perform second look endoscopy at 24 h in all patients with successful endoscopic hemostasis; and 4) perform selective second look endoscopy at 24 h only in patients at high risk for rebleeding as identified by the prospectively validated Baylor Bleeding Score. Probability estimates were derived from a systematic review of the medical literature. Cost estimates were based on Medicare reimbursement. Effectiveness was defined as the proportion of patients with rebleeding, surgery, or death prevented. RESULTS: The selective second look endoscopy strategy was the most effective and least expensive of the four competing strategies, and therefore dominated the analysis. The i.v. PPI strategy required 50% fewer endoscopies than the competing strategies, and became the dominant strategy when the rebleed rate with i.v. PPIs fell below 9% and when the cost of i.v. PPIs fell below $10/day. CONCLUSIONS: Compared with the usual practice of "watchful waiting," performing selective second look endoscopy in high risk patients may prevent more cases of rebleeding, surgery, or death at a lower overall cost. However, i.v. PPIs are likely to reduce the need for second look endoscopy and may be preferred overall if the rebleed rate and cost of i.v. PPIs remains low. (C) 2003 by Am. Coll. of Gastroenterology. C1 Univ Wisconsin, Sch Med, Aurora Sinai Med Ctr, Dept Gastroenterol, Milwaukee, WI 53233 USA. Univ Calif Los Angeles, Sch Med, Dept Digest Dis, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA USA. Cedars Sinai Med Ctr, Div Gastroenterol & Hlth Serv Res, Los Angeles, CA 90048 USA. Zynx Hlth Inc, Los Angeles, CA USA. Baylor Coll Med, Div Gastroenterol, Houston, TX 77030 USA. RP Vakil, NB (reprint author), Univ Wisconsin, Sch Med, Aurora Sinai Med Ctr, Dept Gastroenterol, 945 N 12th St,Room 4040, Milwaukee, WI 53233 USA. NR 52 TC 62 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2003 VL 98 IS 1 BP 86 EP 97 AR PII S0002-9270(02)05831-8 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639NQ UT WOS:000180636400017 PM 12526942 ER PT J AU El-Serag, HB Anand, B Richardson, P Rabeneck, L AF El-Serag, HB Anand, B Richardson, P Rabeneck, L TI Association between hepatitis C infection and other infectious diseases: A case for targeted screening? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID OF-VETERANS-AFFAIRS; VIRUS-INFECTION; BACTERIAL-INFECTIONS; MONONUCLEAR-CELLS; LIVER-DISEASE; CIRRHOSIS; SYSTEM; HIV; RECIPIENTS; RECORDS AB OBJECTIVE: Hepatitis C virus (HCV) shares risk factors and routes of transmission with several other infectious agents. However, the prevalence of comorbid infectious disorders among HCV-infected patients remains unknown. To analyze the association between HCV and several categories of infectious disorders, we carried out a case-control study using information from 172 hospitals contained in the computerized databases of the Department of Veterans Affairs. METHODS: We identified all HCV-infected patients who were hospitalized during 1992-1999. For each case, four control subjects without HCV were randomly chosen from hospitalized patients and were matched with cases on the year of admission. The frequencies of several predefined infectious disease diagnoses were compared between cases and control subjects, and the strength of these associations were assessed in multivariable logistic regression analyses. RESULTS: We identified 34,204 HCV-infected patients (cases) and 136,816 control subjects without HCV. Patients in the case group were younger (48.4 yr vs 59.8 yr), were more frequently nonwhite (38.5% vs 26.5%), and were more likely to have served in Vietnam (68.1% vs 33.0%); all p < 0.0001. Compared with control subjects, patients with HCV had a significantly higher prevalence of other blood-borne virus infections, including HIV (14.1% vs 3.0%) and hepatitis B (22.4% vs 0.7%); immunodeficiency-related infections, including cytomegalovirus (0.6% vs 0.2%), toxoplasmosis (0.3% vs 0.1%), cryptococcosis (0.4% vs 0.1%), and tuberculosis (3.3% vs 1.3%); sexually transmitted diseases, including gonococcus (0.5% vs 0.1%), chlamydia (1.6% vs 0.7%), syphilis (2.0% vs 0.6%), and genital herpes (1.0% vs 0.3%); and bacterial infection, including peritonitis, sepsis, endocarditis, cellulitis, and carbuncles (all p < 0.0001). After excluding potentially immunocompromised patients, including those with HIV, organ transplant, and cirrhosis, HCV remained significantly associated with CMV, cryptococcus, tuberculosis, and sexually transmitted diseases. Similar results were obtained when the analyses were restricted to Vietnam-era veterans. CONCLUSIONS: Several infectious diseases are more common among HCV-infected patients compared with those without HCV infection. These findings support an approach of targeted screening for HCV among patients with these infectious diseases. (Am J Gastroenterol 2003;98:167-174. (C) 2003 by Am. Coll. of Gastroenterology). C1 Houston Vet Affairs Med Ctr, HSR&D 152, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, HSR&D 152, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIDDK NIH HHS [1 K24 DK 59318-01] NR 25 TC 50 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2003 VL 98 IS 1 BP 167 EP 174 AR PII S0002-9270(02)05844-6 DI 10.1016/S0002-9270(02)05844-6 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639NQ UT WOS:000180636400028 PM 12526953 ER PT J AU Yang, H Shi, MJ VanRemmen, H Chen, XL Vijg, J Richardson, A Guo, ZM AF Yang, H Shi, MJ VanRemmen, H Chen, XL Vijg, J Richardson, A Guo, ZM TI Reduction of pressor response to vasoconstrictor agents by overexpression of catalase in mice SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE catalase; hydrogen peroxide; transgenic mouse; blood pressure ID MUSCLE CELL-PROLIFERATION; ARTERIAL SMOOTH-MUSCLE; HYDROGEN-PEROXIDE; ANGIOTENSIN-II; OXIDATIVE STRESS; RAT AORTA; ESSENTIAL-HYPERTENSION; SUPEROXIDE PRODUCTION; BLOOD-PRESSURE; CONTRACTION AB Background: Hydrogen peroxide (H2O2) has been shown to induce vascular smooth muscle cell contraction in vitro. In this study, the effect of endogenously produced H2O2 on blood pressure (BP) was examined using a transgenic mouse model (hCatTg(+/0)) in which catalase is overexpressed. Methods: The hCatTg(+/0) and wild-type mice received a bolus injection of norepinephrine (NE; 1 mug/g) or angiotensin II (Ang II 0.5 mug/g), or an osmotic minipump infusion of NE (2.5 mug/g/day) or Ang II (0.5 mug/g/day) for 7 days. Systolic BP (SBP) was measured using a tail-cuff apparatus. H2O2 release from mouse aortas was measured using an H2O2 assay kit. Results: The hCatTg(+/0) and wild-type mice showed similar basal levels of systolic BP (SBP) and H2O2 release from the aorta. A bolus injection of NE or Ang II increased SBP 31 +/- 5 and 37 +/- 6 mm Hg, respectively, in wild-type mice. In contrast, same doses of NE and Ang II increased SBP only 15 +/- 3 and 17 +/- 4 min Hg, respectively, in hCatTg(+/0) mice. Osmotic minipump infusion of NE or Ang II increased SBP by approximately 30 mm Hg in wild-type mice, but only by about 10 mm Hg in hCatTg(+/0) mice. The addition of NE or Ang II to the incubation media significantly increased H2O2 release from the aortic segment of wild-type mice but did not alter H2O2 release from the aortic segment of hCatTg(+/0) mice. Conclusion: Overexpression of catalase diminishes the pressor response to NE and Ang II by reducing H2O2 production in the arterial wall. C1 Meharry Med Coll, Dept Physiol & Anat, Nashville, TN 37208 USA. Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Guo, ZM (reprint author), Meharry Med Coll, Dept Physiol & Anat, Nashville, TN 37208 USA. FU NIA NIH HHS [P30 AG013319, P01 AG020591, P01 AG13319, P03 AG13319, AG 16998] NR 30 TC 17 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2003 VL 16 IS 1 BP 1 EP 5 AR PII S0895-7061(02)03086-8 DI 10.1016/S0895-7061(02)03086-8 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634EE UT WOS:000180326400001 PM 12517675 ER PT J AU Ng, DPK Warram, JH Krolewski, AS AF Ng, DPK Warram, JH Krolewski, AS TI TGF-beta 1 as a genetic susceptibility locus for advanced diabetic nephropathy in type 1 diabetes mellitus: An investigation of multiple known DNA sequence variants SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE cytokine; polymorphism; glomerulosclerosis ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1 GENE; MESANGIAL CELLS; FACTOR-BETA-1 GENE; GLUCOSE TRANSPORTERS; II RECEPTOR; TGF-BETA; EXPRESSION; ACTIVATION; PROMOTER AB Background: Transforming growth factor-beta1 (TGF-beta1) is a profibrotic cytokine suspected to be a crucial factor underlying glomerulosclerosis in advanced diabetic nephropathy. However, its potential role as a susceptibility gene for the development of this microvascular complication is unresolved. Methods: We examined whether DNA sequence variants in the TGF-beta1 gene are associated with advanced diabetic nephropathy among Caucasians with type 1 diabetes mellitus. These variants included three coding (Leu10Pro, Arg25Pro, and Thr263Ile) and two noncoding single-nucleotide polymorphisms (-800 and -509), as well as an insertion/deletion of a cytosine residue in intron 4. A large case-control study design was used in which cases were patients with type 1 diabetes with advanced diabetic nephropathy (presence of persistent proteinuria or end-stage renal disease [ESRD]; n = 298) and controls were patients who remained normoalbuminuric despite greater than 15 years of type 1 diabetes (n = 263). Results: Genotype frequencies for all polymorphisms were in Hardy-Weinberg equilibrium. Genotype distributions of all six DNA sequence variants were very similar between cases and controls (P = not significant). There was no significant difference in genotype distributions among cases regardless of whether these individuals with diabetes were proteinuric at the time of examination or had already developed ESRD secondary to diabetic nephropathy. Stratified analyses according to diabetes duration and glycemic control likewise did not detect an association between DNA sequence variants and advanced diabetic nephropathy. Conclusion: Genetic variation at the TGF-beta1 locus is unlikely to confer significant susceptibility to advanced diabetic nephropathy in patients with type 1 diabetes mellitus. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK53534, DK41526] NR 33 TC 27 Z9 27 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2003 VL 41 IS 1 BP 22 EP 28 DI 10.1053/ajkd.2003.50011 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 631HB UT WOS:000180161100003 PM 12500218 ER PT J AU Watnick, S Kirwin, P Mahnensmith, R Concato, J AF Watnick, S Kirwin, P Mahnensmith, R Concato, J TI The prevalence and treatment of depression among patients starting dialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE depression; end-stage renal disease (ESRD); dialysis; prevalence; Beck Depression Inventory (BDI) ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; HEMODIALYSIS-PATIENTS; PERITONEAL-DIALYSIS; BEHAVIORAL COMPLIANCE; MAJOR DEPRESSION; ILLNESS; EVENTS; PERCEPTION; MORTALITY AB Background: Depression is common in patients with end-stage renal disease (ESRD) and is associated with increased mortality, but little is known about depression in patients just after they start dialysis therapy. We sought to assess the prevalence of depressive symptoms in patients with ESRD starting dialysis therapy, identify patient characteristics associated with depression, and determine whether patients with serious depressive symptoms were receiving treatment. Methods: We implemented a multicenter prospective cohort study at 14 dialysis centers in Connecticut. Patients with ESRD who were 18 years and older were interviewed within 10 days of initiating dialysis therapy between November 2000 and July 2001. The Beck Depression Inventory (BDI) was used to assess depressive symptoms. Chi-square tests were used to evaluate associations between several patient characteristics and depression, and multivariable logistic regression models were used to determine odds ratios (ORs) for depression, with adjustment for baseline variables. Results: Among 123 patients, 44% (54 of 123 patients) had scores above the validated cutoff value in the BDI for depression. In logistic regression analysis, depression was statistically significantly associated with Caucasian race (OR, 3.4; P = 0.02), lower self-rated quality of life (OR, 2.2; P = 0.003), and no previous acquaintances on dialysis therapy (OR, 10.2; P = 0.03). Only 16% (9 of 54 patients) of depressed patients were being treated at enrollment; 13% (5 of 38 patients) of those with mild symptoms and 25% (4 of 16 patients) with more severe symptoms were being treated. Conclusion: Our results show that depressive symptoms are very common at the start of dialysis therapy, and specific characteristics are associated with a greater burden of depressive symptoms. Despite a high prevalence, treatment rates are low, even among patients with moderate to severe symptoms of depression. C1 Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Vet Affairs Connecticut Healthcare Syst, Dept Psychiat, West Haven, CT USA. Vet Affairs Connecticut Healthcare Syst, Clin Epidemiol Unit, West Haven, CT USA. RP Watnick, S (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,P3NEPH, Portland, OR 97207 USA. NR 33 TC 184 Z9 191 U1 3 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2003 VL 41 IS 1 BP 105 EP 110 DI 10.1053/ajkd.2003.50029 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 631HB UT WOS:000180161100012 PM 12500227 ER PT J AU O'Hare, AM Bacchetti, P Segal, M Hsu, CY Johansen, KL AF O'Hare, AM Bacchetti, P Segal, M Hsu, CY Johansen, KL TI Factors associated with future amputation among patients undergoing hemodialysis: Results from the dialysis morbidity and mortality study waves 3 and 4 SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE amputation; dialysis; risk factors; phosphorus; peripheral vascular disease (PVD); diabetes; prevention; screening ID LOWER-EXTREMITY AMPUTATIONS; STAGE RENAL-DISEASE; RISK-FACTORS; POPULATION AB Background: Amputation is more common in hemodialysis patients than in the general population, but risk factors for amputation in this population have not been studied extensively. Methods: We used the US Renal Data System Dialysis Morbidity and Mortality Study Waves 3 and 4 in combination with Medicare discharge data to identify factors associated with lower-extremity amputation (excluding toe amputations) in hemodialysis patients. We used stepwise multivariable logistic regression analysis to identify variables most strongly associated with amputation within 2 years of the study start date. Results: Male sex, diabetes, previous diagnosis of peripheral vascular disease (PVD), mean systolic blood pressure, and elevated serum phosphorus level were associated with the outcome of amputation within 2 years of the study start date. Among patients without diabetes, a previous diagnosis of cardiac disease, longer time from initiation of dialysis therapy (vintage), and previous hospitalization for limb ischemia were associated with increased risk for future amputation. Conclusion: The importance of preventing amputation in this population cannot be overemphasized. The strength of the association of amputation with PVD makes a strong case for screening all dialysis patients for this disease. The association of amputation with serum phosphorus level reported here should be explored further because this may offer an avenue for future intervention to reduce amputation rates. C1 Univ Calif San Francisco, Div Nephrol, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA USA. RP O'Hare, AM (reprint author), Univ Calif San Francisco, Div Nephrol, Dept Med, 400 Parnassus Ave,672 HSE,Box 532, San Francisco, CA 94143 USA. NR 24 TC 32 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2003 VL 41 IS 1 BP 162 EP 170 DI 10.1053/ajkd.2003.50000 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 631HB UT WOS:000180161100018 PM 12500233 ER PT J AU Johansen, KL Sakkas, GK Doyle, J Shubert, T Dudley, RA AF Johansen, KL Sakkas, GK Doyle, J Shubert, T Dudley, RA TI Exercise counseling practices among nephrologists caring for patients on dialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE exercise; counseling; preventive services; physical activity ID PHYSICAL-ACTIVITY; PRIMARY-CARE; INTERNISTS; PRACTITIONERS; HEMODIALYSIS; PROMOTION; DELIVERY AB Background: Patients on dialysis therapy are inactive, are at high risk for conditions that can be prevented or ameliorated by exercise, and often receive most of their care from their nephrologist. Exercise counseling by physicians can increase patients' levels of physical activity. The aim of the study is to determine the frequency of exercise assessment and counseling among practicing nephrologists, characteristics of nephrologists who provide exercise counseling to their dialysis patients, and barriers to exercise counseling perceived by nephrologists. Methods: A 25-item survey regarding exercise counseling was administered to nephrologists attending the World Congress of Nephrology meeting in 2001. Results: Five hundred five nephrologists completed the survey. Overall, 38% reported "almost always" or "often" assessing patient level of physical activity and counseling inactive patients to increase activity. Older (P < 0.0001), more active (P = 0.033), and women (P = 0.018) nephrologists, as well as those who provided primary care to more of their patients (P = 0.007), were more likely to provide exercise counseling. Nephrologists who do not provide routine counseling were more likely to endorse lack of time (P < 0.0001), lack of confidence in their ability to counsel patients (P < 0.0001), and lack of conviction that patients will respond as barriers to counseling (P = 0.01). In addition, noncounseling nephrologists were more likely to believe that other medical issues were more important than exercise (P = 0.01). Conclusion: Rates of exercise counseling among nephrologists are low, although dialysis patients are a high-risk group unlikely to receive advice about exercise from other health care providers. The low rates of counseling, particularly among younger nephrologists, could be addressed by including information about counseling in fellowship training and/or practice guidelines for the care of patients on dialysis therapy. C1 San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Inst Hlth Policy Studies, San Francisco, CA 94143 USA. No Calif Inst Res & Educ, San Francisco, CA USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Dept Med, Nephrol Sect 111J,4150 Clement St, San Francisco, CA 94121 USA. OI Sakkas, Giorgos/0000-0002-2462-995X FU NIDDK NIH HHS [R01-DK-56182] NR 31 TC 60 Z9 62 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2003 VL 41 IS 1 BP 171 EP 178 DI 10.1053/ajkd.2003.50001 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 631HB UT WOS:000180161100019 PM 12500234 ER PT J AU Leckman, JF Pauls, DL Zhang, HP Rosario-Campos, MC Katsovich, L Kidd, KK Pakstis, AJ Alsobrook, JP Robertson, MM McMahon, WM Walkup, JT van de Wetering, BJM King, RA Cohen, DJ AF Leckman, JF Pauls, DL Zhang, HP Rosario-Campos, MC Katsovich, L Kidd, KK Pakstis, AJ Alsobrook, JP Robertson, MM McMahon, WM Walkup, JT van de Wetering, BJM King, RA Cohen, DJ CA Tourette Syndrome Assoc Int Conso TI Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Gilles de la Tourette syndrome; obsessive-compulsive disorder; quantitative traits; segregation analyses ID AUTOSOMAL-DOMINANT TRANSMISSION; SIB PAIRS; SEGREGATION ANALYSIS; TREATMENT RESPONSE; LINKAGE ANALYSIS; YOUNG-CHILDREN; FOLLOW-UP; DISORDER; FAMILY; BEHAVIOR AB Obsessive-compulsive disorder (OCD) is an etiologically heterogeneous disorder. Recent factor analyses have consistently identified several symptom dimensions, two of which are associated with increased familial risk for OCD; aggressive, sexual, and religious obsessions and checking compulsions (FACTOR 1) and symmetry and ordering obsessions and compulsions (FACTOR 2). Both of these symptom dimensions are also frequently seen in association with Gilles de la Tourette syndrome (GTS). The purpose of this study was to determine whether these obsessive-compulsive (OC) symptom dimensions are correlated within families (between sibs and between parent-child pairs). Using data collected by the Tourette Syndrome Association International Consortium for Genetics Affected Sibling Pair Study, the authors selected all available GTS sib pairs and their parents for which these OC symptom dimensions (factor scores) could be generated. This group included 128 full sibs and their mothers (54) and fathers (54). Four OC symptom dimension scores were computed for each family member using an algorithm derived from item endorsements from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) symptom checklist. In addition to a series of univariate analyses, complex segregation analyses were also completed using these quantitative OC symptom dimension scores. FACTOR 1 and FACTOR 2 scores were significantly correlated in sib pairs concordant for GTS. The mother-child correlations, but not father-child correlations, were also significant for these two factors. Segregation analyses were consistent with dominant major gene effects for both FACTOR 1 and FACTOR 2. We conclude that familial factors contribute significantly to OC symptom dimension phenotypes in GTS families. This familial contribution could be genetic or environmental. (C) 2003 Wiley-Liss, Inc. C1 Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Curagen Corp, Branford, CT USA. UCL, Dept Psychiat & Behav Sci, London WC1E 6BT, England. Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84112 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Erasmus Univ, Dept Psychiat, Rotterdam, Netherlands. RP Leckman, JF (reprint author), Yale Univ, Sch Med, Ctr Child Study, 230 S Frontage Rd, New Haven, CT 06520 USA. EM james.leckman@yale.edu RI do Rosario, Maria Conceicao/E-5213-2012 OI do Rosario, Maria Conceicao/0000-0002-9687-0072 FU NCRR NIH HHS [RR-00125, RR-00044]; NIAAA NIH HHS [AA-12044]; NIDA NIH HHS [DA-12468]; NIMH NIH HHS [MH-493515, MH-00508, MH-30929]; NINDS NIH HHS [NS-07338, NS-16648, NS-40024-01] NR 42 TC 100 Z9 101 U1 5 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 1 PY 2003 VL 116B IS 1 BP 60 EP 68 DI 10.1002/ajmg.b.10001 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 670GU UT WOS:000182399800012 PM 12497616 ER PT J AU Zimmerman, RK Santibanez, TA Janosky, JE Fine, MJ Raymund, M Wilson, SA Bardella, IJ Medsger, AR Nowalk, MP AF Zimmerman, RK Santibanez, TA Janosky, JE Fine, MJ Raymund, M Wilson, SA Bardella, IJ Medsger, AR Nowalk, MP TI What affects influenza vaccination rates among older patients? An analysis from inner-city, suburban, rural, and Veterans Affairs practices SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID RISK; BEHAVIOR; PREVENTION; MODEL; QUESTIONNAIRE; OUTPATIENTS; VALIDATION; ADULTS; COST AB BACKGROUND: Despite strong evidence of the effectiveness of influenza vaccination, immunization rates have reached a plateau that is below the 20 10 national goals. Our objective was to identify facilitators of, and barriers to, vaccination in diverse groups of older patients. METHODS: A survey was conducted in 2000 by computer-assisted telephone interviewing of patients from inner-city health centers, Veterans Affairs (VA) outpatient clinics, rural practices, and suburban practices. The inclusion criteria were age greater than or equal to66 years and an office visit after September 30, 1998. RESULTS: Overall, 1007 (73%) interviews were completed among 1383 patients. Influenza vaccination rates were 91% at VA clinics, 79% at rural practices, 79% at suburban practices, and 67% at inner-city.health centers. There was substantial variability in vaccination rates among practices, except at the VA. Nearly all persons who were vaccinated reported that their physician recommended influenza vaccinations, compared with 63% of unvaccinated patients (P <0.001). Thirty-eight percent of unvaccinated patients were concerned that they would get influenza from the vaccine, compared with only 6% of vaccinated persons (P <0.001). Sixty-three percent of those vaccinated, in contrast with 22% of unvaccinated persons, thought that an unvaccinated person would probably contract influenza (P <0.001). CONCLUSION: Older patients need intentional messages from physicians that recommend vaccination. Furthermore, more patient education is needed to counter myths about adverse reactions. (C) 2003 by Excerpta Medica Inc. C1 Univ Pittsburgh, Sch Med, Dept Clin Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Serv Adm, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, St Margaret Family Practice Residency, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Div Gen Internal Med, Pittsburgh, PA USA. Vet Affairs Ctr Study Hlth Dispar, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Family Med, Pittsburgh, PA USA. RP Zimmerman, RK (reprint author), Univ Pittsburgh, Sch Med, Dept Family Med & Clin Epidemiol, 3518 5th Ave, Pittsburgh, PA 15261 USA. OI Zimmerman, Richard/0000-0001-5941-6092 FU AHRQ HHS [HS09874] NR 40 TC 125 Z9 129 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2003 VL 114 IS 1 BP 31 EP 38 DI 10.1016/S0002-9343(02)01421-3 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 638PL UT WOS:000180579400007 PM 12543287 ER PT J AU Steere, AC Dhar, A Hernandez, J Fischer, PA Sikand, VK Schoen, RT Nowakowski, J McHugh, G Persing, DH AF Steere, AC Dhar, A Hernandez, J Fischer, PA Sikand, VK Schoen, RT Nowakowski, J McHugh, G Persing, DH TI Systemic symptoms without erythema migrans as the presenting picture of early Lyme disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID HUMAN GRANULOCYTIC EHRLICHIOSIS; BORRELIA-BURGDORFERI; NANTUCKET-ISLAND; HUMAN BABESIOSIS; SERODIAGNOSIS; DOXYCYCLINE; INFECTION; ILLNESS; AGENT C1 Tufts Univ, Sch Med, New England Med Ctr, Div Rheumatol Immunol, Boston, MA 02111 USA. Yale Univ, Sch Med, New Haven, CT USA. New York Med Coll, Div Infect Dis, Valhalla, NY 10595 USA. Mayo Clin & Mayo Fdn, Clin Microbiol Sect, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Infect Dis Sect, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Expt Pathol Sect, Rochester, MN 55905 USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8301, Charlestown, MA 02129 USA. FU ODCDC CDC HHS [CCU110291] NR 26 TC 28 Z9 29 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2003 VL 114 IS 1 BP 58 EP 62 DI 10.1016/S0002-9343(02)01440-7 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 638PL UT WOS:000180579400012 PM 12543291 ER PT J AU Selinger, RRE Norman, S Dominitz, JA AF Selinger, RRE Norman, S Dominitz, JA TI Failure of health care professionals to interpret fecal occult blood tests accurately SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID COLORECTAL-CANCER C1 VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Gastroenterol, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Sch Med, Dept Pathol & Lab Med, Seattle, WA USA. Univ Washington, Sch Med, Gastroenterol Sect, Seattle, WA USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, 111-S Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 14 TC 23 Z9 23 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2003 VL 114 IS 1 BP 64 EP 67 DI 10.1016/S0002-9343(02)01350-5 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 638PL UT WOS:000180579400014 PM 12543293 ER PT J AU Goodman, DN Hoh, BL Rabinov, JD Pryor, JC AF Goodman, DN Hoh, BL Rabinov, JD Pryor, JC TI CT angiography before emholization for hemorrhage in head and neck cancer SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID EMBOLIZATION AB We present a patient with advanced head and neck carcinoma and a bleeding pseudoaneurysm diagnosed by means of CT angiography; this was not apparent on conventional digital subtraction angiograms. The information provided by CT angiography facilitated rapid identification of the pseudoaneurysm and treatment with embolization. CT angiography may be helpful before embolization in cases of hemorrhage in head and neck cancer. C1 Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol, 55 Fruit St,GRB 289, Boston, MA 02114 USA. NR 6 TC 7 Z9 7 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 JAN PY 2003 VL 24 IS 1 BP 140 EP 142 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 645EC UT WOS:000180962400028 PM 12533343 ER PT J AU Gee, MS Procopio, WN Makonnen, S Feldman, MD Yeilding, NM Lee, WMF AF Gee, MS Procopio, WN Makonnen, S Feldman, MD Yeilding, NM Lee, WMF TI Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL-CELL SURVIVAL; MALIGNANT-MELANOMA; PDGF-B; ANGIOGENESIS; INHIBITION; PERICYTE; RESISTANCE; CANCER; VEGF; MICE AB The effect of anti-vascular agents on the growth of experimental tumors is well studied. Their impact on tumor vasculature, the primary therapeutic target of these agents, is not as well characterized, even though this primarily determines treatment outcome. Hypothesizing that the response of vessels to therapy is influenced by their stage of maturation, we studied vascular development and the vascular effects of therapy in several transplanted murine tumor models. Based on size, perfusion, endothelial cell (EC) proliferation, and the presence of pericytes, tumor vessels segregated into three categories. Least mature were highly proliferative, nonperfused EC sprouts emanating from functional vessels. intermediate were small, perfused vessels which, like the angiogenic sprouts, were not covered by pericytes. Most mature were larger vessels, which were predominantly pericyte-covered with quiescent ECs and few associated sprouts. Thus, a developmental order, similar to that described during physiological neovascularization, was evident among vessels in growing rumors. This order markedly influenced tumor vessel response to anti-vascular therapy with recombinant interleukin-12. Therapy reduced tumor vessel density, which was attributable to a decrease in angiogenic sprouts and induction of EC apoptosis in pericyte-negative vessels. Although the great majority of vessels in growing tumors lacked pericyte coverage, selective loss of less mature vessels with therapy significantly increased the fraction of pericyte-positive vessels after therapy. These data indicate that the therapeutic susceptibility of tumor vasculature to recombinant murine IL-12 and, potentially, other anti-vascular agents is limited by its level of maturation. An implication is that tumor susceptibility is similarly limited, making pericyte coverage of tumor vasculature a potential indicator of tumor responsiveness. C1 Univ Penn, Biomed Grad Program, Dept Med, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lee, WMF (reprint author), BRB 2-3,Room 312,421 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [R01 CA077851, CA 83042, R01 CA 77851]; NIDDK NIH HHS [P30 DK050306] NR 30 TC 143 Z9 156 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2003 VL 162 IS 1 BP 183 EP 193 DI 10.1016/S0002-9440(10)63809-6 PG 11 WC Pathology SC Pathology GA 628RG UT WOS:000180009800019 PM 12507901 ER PT J AU Cook, DG Leverenz, JB McMillan, PJ Kulstad, JJ Ericksen, S Roth, RA Schellenberg, GD Jin, LW Kovacina, KS Craft, S AF Cook, DG Leverenz, JB McMillan, PJ Kulstad, JJ Ericksen, S Roth, RA Schellenberg, GD Jin, LW Kovacina, KS Craft, S TI Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon 4 allele SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; BETA-PROTEIN; EXTRACELLULAR LEVELS; DIABETES-MELLITUS; E GENOTYPE; DEGRADATION; BRAIN; NEPRILYSIN; DEMENTIA; CHROMOSOME-10 AB A,6 is the major component of amyloid plaques characterizing Alzheimer's disease (AD). Abeta accumulation can be affected by numerous factors including increased rates of production and/or impaired clearance. Insulin-degrading enzyme (IDE) has been implicated as a candidate enzyme responsible for the degradation and clearance of Abeta in the brain. We have previously shown that AD patients exhibit abnormalities in insulin metabolism that are associated with apoliprotein E (APOE) status. The possible association of IDE with AD, as well as the link between APOE status and insulin metabolism, led us to examine the expression of IDE in AD. We report that hippocampal IDE protein is reduced by approximately 50% in epsilon4+ AD patients compared to epsilon4- patients and controls. The allele-specific decrease of IDE in epsilon4+ AD patients is not associated with neuronal loss since neuronspecific enolase levels were comparable between the AD groups, regardless of APOE status. Hippocampal IDE mRNA levels were also reduced in AD patients with the epsilon4 allele compared to AD and normal subjects without the epsilon4 allele. These findings show that reduced IDE expression is associated with a significant risk factor for AD and suggest that IDE may interact with APOE status to affect Abeta metabolism. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychol, Seattle, WA USA. Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA. RP Craft, S (reprint author), VA Puget Sound Hlth Care Syst, GRECC S-182,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136, P50 AG005136] NR 36 TC 201 Z9 214 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2003 VL 162 IS 1 BP 313 EP 319 DI 10.1016/S0002-9440(10)63822-9 PG 7 WC Pathology SC Pathology GA 628RG UT WOS:000180009800032 PM 12507914 ER PT J AU Isnard-Bagnis, C Da Silva, N Beaulieu, V Yu, ASL Brown, D Breton, S AF Isnard-Bagnis, C Da Silva, N Beaulieu, V Yu, ASL Brown, D Breton, S TI Detection of ClC-3 and ClC-5 in epididymal epithelium: immunofluorescence and RT-PCR after LCM SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE chloride channels, vacuolar H+-ATPase, principal cells, clear cells; laser capture microdissection ID MALE REPRODUCTIVE-TRACT; CHLORIDE CHANNEL; RAT EPIDIDYMIS; DENTS-DISEASE; COLLECTING DUCT; CYSTIC-FIBROSIS; H+-ATPASE; CELLS; KIDNEY; EXPRESSION AB Epithelial cells of the epididymis and vas deferens establish an optimum luminal environment in which spermatozoa mature and are stored. This is achieved by active transepithelial transport of various ions including Cl- and H+. We investigated the localization of three closely related members of the ClC family, ClC-3, ClC-4, and ClC-5, in the epididymis and vas deferens. RT-PCR using mRNA isolated by laser capture microdissection (LCM)-detected ClC-3 and ClC-5 transcripts but did not detect any ClC-4-specific transcript. Western blot and immunofluorescence analysis demonstrated that ClC-3 and ClC-5 proteins are present in all regions of the epididymis and in the vas deferens. ClC-5 is expressed exclusively in H+-ATPase-rich cells (narrow and clear cells). Confocal microscopy showed that ClC-5 partially colocalizes with the H+-ATPase in the subapical pole of clear cells. ClC-3 is strongly expressed in the apical membrane of principal cells of the caput epididymidis and the vas deferens and is less abundant in principal cells of the body and cauda epididymidis. These findings are consistent with a potential role for ClC-3 in transepithelial chloride transport by principal cells and for ClC-5 in the acidification of H+-ATPase-containing vesicles in narrow and clear cells. ClC-5 might facilitate endosome trafficking in the epididymis, as has been proposed in the kidney. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. OI isnard bagnis, corinne/0000-0002-1048-6636 FU NICHD NIH HHS [HD 40793]; NIDDK NIH HHS [DK 38452, DK 43351, DK 57521] NR 56 TC 25 Z9 25 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JAN PY 2003 VL 284 IS 1 BP C220 EP C232 DI 10.1152/ajpcell.00374.2001 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 624BH UT WOS:000179739500024 PM 12475763 ER PT J AU Voland, P Weeks, DL Marcus, EA Prinz, C Sachs, G Scott, D AF Voland, P Weeks, DL Marcus, EA Prinz, C Sachs, G Scott, D TI Interactions among the seven Helicobacter pylori proteins encoded by the urease gene cluster SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE yeast two-hybrid; urease assembly; protein interactions ID KLEBSIELLA-AEROGENES UREASE; IN-VIVO; APOPROTEIN COMPLEXES; GNOTOBIOTIC PIGLETS; FUNCTIONAL-ANALYSIS; ACID RESISTANCE; 2-HYBRID; PH; ACTIVATION; GASTRITIS AB Survival of Helicobacter pylori in acid depends on intrabacterial urease. This urease is a Ni2+-containing oligomeric heterodimer. Regulation of its activity and assembly is important for gastric habitation by this neutralophile. The gene complex encodes catalytic subunits (ureA/B), an acid-gated urea channel (ureI), and accessory assembly proteins (ureE-H). With the use of yeast two-hybrid analysis for determining protein-protein interactions, UreF as bait identified four interacting sequences encoding UreH, whereas UreG as bait detected five UreE sequences. These results were confirmed by coimmunoprecipitation and beta-galactosidase assays. Native PAGE immunoblotting of H. pylori inner membranes showed interaction of UreA/B with UreI, whereas UreI deletion mutants lacked this protein interaction. Deletion of ureE-H did not affect this interaction with UreI. Hence, the accessory proteins UreE/G and UreF/H form dimeric complexes and UreA/B form a membrane complex with UreI, perhaps enabling assembly of the urease apoenzyme at the membrane surface and immediate urea access to intrabacterial urease to allow rapid periplasmic neutralization. C1 Tech Univ Munich, Dept Med 2, D-81675 Munich, Germany. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Hlth Syst, Los Angeles, CA 90073 USA. RP Voland, P (reprint author), Tech Univ Munich, Dept Med 2, Ismaningerstr 22,Bau 520,Rm 20-01-12, D-81675 Munich, Germany. FU NIDDK NIH HHS [DK-53462, DK-41301, DK-46917] NR 39 TC 63 Z9 66 U1 1 U2 8 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 JAN PY 2003 VL 284 IS 1 BP G96 EP G106 DI 10.1152/ajpgi.00160.2002 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 626JU UT WOS:000179868800011 PM 12388207 ER PT J AU Baicu, CF Stroud, JD Livesay, VA Hapke, E Holder, J Spinale, FG Zile, MR AF Baicu, CF Stroud, JD Livesay, VA Hapke, E Holder, J Spinale, FG Zile, MR TI Changes in extracellular collagen matrix alter myocardial systolic performance SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertrophy; matrix metalloproteinases; heart failure; muscle; plasmin ID LEFT-VENTRICULAR DILATATION; HYPERTENSIVE HEART-DISEASE; AORTIC-VALVE DISEASE; PERFUSED RAT HEARTS; METALLOPROTEINASE INHIBITION; HYPERTROPHIED MYOCARDIUM; CONTRACTILE DYSFUNCTION; DILATED CARDIOMYOPATHY; FIBRILLAR COLLAGEN; FAILURE AB The purpose of this study was to test the hypothesis that acute disruption of fibrillar collagen will decrease myocardial systolic performance without changing cardiomyocyte contractility. Isolated papillary muscles were treated either with plasmin (0.64 U/ml, 240 min) or untreated and served as same animal control. Plasmin treatment caused matrix metalloproteinase activation and collagen degradation as measured by gelatin zymography, hydroxyproline assays, and scanning electron microscopy. Plasmin caused a significant decrease in myocardial systolic performance. Isotonic shortening extent and isometric developed tension decreased from 0.17 +/- 0.01 muscle length (ML) and 45 +/- 4 mN/mm(2) in untreated muscles to 0.09 +/- 0.01 ML and 36 +/- 3 mN/mm(2) in treated muscles (P < 0.05). However, plasmin treatment (0.64 U/ml, 240 min) did not alter shortening extent or velocity in isolated cardiomyocytes. Acute disruption of the fibrillar collagen network caused a decrease in myocardial systolic performance without changing cardiomyocyte contractility. These data support the hypothesis that fibrillar collagen facilitates transduction of cardiomyocyte contraction into myocardial force development and helps to maintain normal myocardial systolic performance. C1 Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg, Charleston, SC 29425 USA. RP Zile, MR (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, 96 Jonathan Lucas St,Suite 816,POB 250623, Charleston, SC 29425 USA. FU NHLBI NIH HHS [P01-HL-48788, R01-HL-59165-05, R01-HL-55444-03] NR 41 TC 62 Z9 62 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2003 VL 284 IS 1 BP H122 EP H132 DI 10.1152/ajpheart.00233.2002 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 626DW UT WOS:000179857900016 PM 12485818 ER PT J AU Prorock, AJ Hafezi-Moghdam, A Laubach, VE Liao, JK Ley, K AF Prorock, AJ Hafezi-Moghdam, A Laubach, VE Liao, JK Ley, K TI Vascular protection by estrogen in ischemia-reperfusion injury requires endothelial nitric oxide synthase SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE leukocyte adhesion; rolling; P-selectin; microcirculation; inflammation ID PLATELET-ACTIVATING-FACTOR; P-SELECTIN EXPRESSION; PROTEIN-KINASE-B; CREMASTER MUSCLE; MICE LACKING; IN-VIVO; INTERCELLULAR-ADHESION; LEUKOCYTE RECRUITMENT; CELL-INTERACTION; OXYGEN RADICALS AB Estrogen increases nitric oxide (NO) production by inducing the activity of endothelial NO synthase (eNOS) (Simoncini et al. Nature 407: 538, 2000). Ischemia (30 min) and reperfusion (I/R) increased the number of adherent leukocytes and decreased their rolling velocities in mouse cremaster muscle venules with a strong dependence on wall shear rate. Minimum rolling velocity at similar to5 min after the onset of reperfusion was accompanied by increased P-selectin expression. This preceded the peak in leukocyte adhesion (at 10-15 min). In untreated wild-type mice, I/R caused a decrease of leukocyte rolling velocity from 37 to 26 mum/s and a 2.0-fold increase in leukocyte adhesion. Both were completely abolished by 0.25 mg ip estrogen 1 h before surgery. In eNOS(-/-) mice, the decrease of leukocyte rolling velocity and increase in adhesion were similar but were only marginally improved by estrogen. We conclude that the protective effect of estrogen, as measured by leukocyte rolling and adhesion, is significantly reduced in eNOS(-/-) mice, suggesting that induction of eNOS activity is the major mechanism of vasoprotection by estrogen in this model. C1 Univ Virginia, Hlth Sci Ctr, Dept Biomed Engn, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Surg, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. RP Ley, K (reprint author), Hlth Syst Dept Biomed Engn, POB 800759, Charlottesville, VA 22908 USA. RI Laubach, Victor/E-8818-2015; OI Laubach, Victor/0000-0001-9673-5383; Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NHLBI NIH HHS [HL-70274, HL-48242, HL-64381, HL-52233] NR 50 TC 25 Z9 26 U1 0 U2 3 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 JAN PY 2003 VL 284 IS 1 BP H133 EP H140 DI 10.1152/ajpheart.00957.2001 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 626DW UT WOS:000179857900017 PM 12388253 ER PT J AU Evans, SB Wilkinson, CW Gronbeck, P Bennett, JL Taborsky, GJ Figlewicz, DP AF Evans, SB Wilkinson, CW Gronbeck, P Bennett, JL Taborsky, GJ Figlewicz, DP TI Inactivation of the PVN during hypoglycemia partially simulates hypoglycemia-associated autonomic failure SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE paraventricular nucleus; hypothalamus; stress; rat; lidocaine ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; SYMPATHETIC PREGANGLIONIC NEURONS; CORTICOTROPIN-RELEASING FACTOR; INCREASED GLUCAGON-SECRETION; INSULIN-INDUCED HYPOGLYCEMIA; ANTECEDENT HYPOGLYCEMIA; NERVE ACTIVITY; ADRENAL RESPONSES; EFFECTIVE SPREAD; CONSCIOUS RATS AB The anatomic connections of the paraventricular nucleus of the hypothalamus (PVN) are such that it is ideally situated to modulate and/or control autonomic responses to a variety of stressors, including hypoglycemia. In our experimental model of hypoglycemia-associated autonomic failure (HAAF), a syndrome in which the counterregulatory response to hypoglycemia is partially compromised via unknown mechanisms, activation of the PVN is blunted (15). We hypothesized that this blunted PVN activation during HAAF may be sufficient to cause the impaired counterregulatory response. To test this hypothesis, we anesthetized the PVN with lidocaine during insulin-induced hypoglycemia in rats and measured counterregulatory hormone levels. PVN inactivation decreased indexes of the sympathoadrenal response (plasma epinephrine and norepinephrine) and the hypothalamic-pituitary axis response (ACTH). Inactivation decreased the peak epinephrine response to hypoglycemia by almost half (-42 +/- 6% from control; P = 0.04) and the peak norepinephrine response by 34 +/- 5% (P = 0.01). The peak plasma ACTH levels attained were suppressed by 35 +/- 6% (P = 0.02). Adrenal corticosterone and pancreatic glucagon responses were not impaired. This pattern of neuroendocrine response is unlike that previously seen with our HAAF model. Control infusions of lidocaine greater than or equal to1 mm anterior or posterior to the PVN did not simulate this neuroendocrine pattern. Thus it appears that decreased PVN activation, as occurs with HAAF, may be involved in specific components of HAAF (i.e., blunting the sympathoadrenal and hypothalamic-pituitary-adrenocortical axis response), but not in others (i.e., blunting the glucagon response). C1 Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Puget Sound Hlth Care Syst, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. RP Evans, SB (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM ngevans@u.washington.edu FU NIDDK NIH HHS [R01-DK-40,963, R01-DK-50,154] NR 59 TC 21 Z9 21 U1 0 U2 1 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 JAN PY 2003 VL 284 IS 1 BP R57 EP R65 DI 10.1152/ajpregu.00439.2002 PG 9 WC Physiology SC Physiology GA 625YF UT WOS:000179842600007 PM 12388440 ER PT J AU Gooch, JL Barnes, JL Garcia, S Abboud, HE AF Gooch, JL Barnes, JL Garcia, S Abboud, HE TI Calcineurin is activated in diabetes and is required for glomerular hypertrophy and ECM accumulation SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE extracellular matrix; kidney; cyclosporin A; mesangial cells ID GROWTH-FACTOR-I; CARDIAC-HYPERTROPHY; MESANGIAL CELLS; MESSENGER-RNAS; CYCLOSPORINE-A; HEART-FAILURE; FACTOR-BETA; EXPRESSION; INHIBITION; PATHWAY AB Diabetic nephropathy is characterized by the rapid onset of hypertrophy and ECM expansion. Previously, we showed that calcineurin phosphatase is required for hypertrophy and ECM synthesis in cultured mesangial cells. Therefore, we examined the effect of calcineurin inhibition on renal hypertrophy and ECM accumulation in streptozotocin-induced diabetic rats. After 2 wk of diabetes, calcineurin protein was increased in whole cortex and glomeruli in conjunction with increased phosphatase activity. Daily administration of cyclosporin A blocked accumulation of both calcineurin protein and calcineurin activity. Also associated with calcineurin upregulation was nuclear localization of the calcineurin substrate NFATc1. Inhibition of calcineurin reduced whole kidney hypertrophy and abolished glomerular hypertrophy in diabetic rats. Furthermore, calcineurin inhibition substantially reduced ECM accumulation in diabetic glomeruli but not in cortical tissue, suggesting a differential effect of calcineurin inhibition in glomerular vs. extraglomerular tissue. Corresponding increases in fibronectin mRNA and transforming growth factor-beta mRNA were observed in tubulointerstitium but not in glomeruli. In summary, calcineurin plays an important role in glomerular hypertrophy and ECM accumulation in diabetic nephropathy. C1 Univ Texas, Hlth Sci Ctr, Div Renal, San Antonio, TX 78284 USA. Audie Murphy Mem Hosp, S Texas Vet Hlth Care Adm, San Antonio, TX 78284 USA. RP Gooch, JL (reprint author), Univ Texas, Hlth Sci Ctr, Div Renal, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM Gooch@UTHSCSA.edu NR 39 TC 44 Z9 49 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2003 VL 284 IS 1 BP F144 EP F154 DI 10.1152/ajprenal.00158.2002 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 623NK UT WOS:000179709600016 PM 12388427 ER PT J AU Eastwood, JD Lev, MH Provenzale, JM AF Eastwood, JD Lev, MH Provenzale, JM TI Perfusion CT with iodinated contrast material SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID CEREBRAL BLOOD-FLOW; 3-DIMENSIONAL FUNCTIONAL CT; ACUTE HEMISPHERIC STROKE; ACUTE ISCHEMIC STROKE; HUMAN BRAIN-TUMORS; DYNAMIC CT; INTRAARTERIAL THROMBOLYSIS; MICROVASCULAR PERMEABILITY; QUANTITATIVE ASSESSMENT; COMPUTED-TOMOGRAPHY C1 Duke Univ, Med Ctr, Dept Radiol, Div Neuroradiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. RP Eastwood, JD (reprint author), Duke Univ, Med Ctr, Dept Radiol, Div Neuroradiol, Box 3808, Durham, NC 27710 USA. NR 52 TC 63 Z9 73 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2003 VL 180 IS 1 BP 3 EP 12 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 628EJ UT WOS:000179979400002 PM 12490467 ER PT J AU Kopans, DB AF Kopans, DB TI The most recent breast cancer screening controversy about whether mammographic screening benefits women at any age: Nonsense and nonscience SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID CARCINOMA MORTALITY; TRIALS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 33 TC 25 Z9 25 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2003 VL 180 IS 1 BP 21 EP 26 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 628EJ UT WOS:000179979400005 PM 12490471 ER PT J AU Gill, TJ Zarins, B AF Gill, TJ Zarins, B TI Open repairs for the treatment of anterior shoulder instability SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article ID INFERIOR GLENOHUMERAL LIGAMENT; RECURRENT DISLOCATION; BANKART PROCEDURE; CAPSULAR SHIFT; MAGNUSON-STACK; RECONSTRUCTION; BRISTOW; JOINT; STABILIZATION; SUBLUXATION AB Successful treatment of anterior instability of the shoulder requires a balance between restoring joint stability and minimizing loss of glenohumeral motion. The choice of treatment should be individualized on the basis of the patient's occupation and level of participation in sports, as well as on the degree of instability of the shoulder. Despite discussions to the contrary, there is no single "essential lesion," as proposed by Bankart, that is responsible for recurrent anterior shoulder instability, although the Bankart lesion is by far the most important. The choice of operative treatment must be tailored to correct the abnormality that is identified at the time of surgery. A variety of promising arthroscopic techniques have been developed for the treatment of anterior shoulder instability; however, open stabilization remains the standard, especially for severe instabilities, revision procedures, and for athletes who participate in contact sports. This article will review the open surgical techniques used for treatment of anterior instability of the shoulder. Both current and historical operations will be discussed. Regardless of which procedure is chosen by a surgeon, the treatment should follow the guidelines taught by Rowe: anatomic dissection at the time of surgery, identification and repair of the lesions responsible for the instability, returning tissues to their anatomic locations, and early postoperative range of motion. By following these guidelines, the results of treatment of anterior instability of the shoulder can be optimized. (C) 2003 American Orthopaedic Society for Sports Medicine. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Sport Med Serv, Boston, MA 02114 USA. RP Zarins, B (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sport Med Serv, Ambulatory Care Suite 514, Boston, MA 02114 USA. NR 97 TC 37 Z9 40 U1 0 U2 1 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JAN-FEB PY 2003 VL 31 IS 1 BP 142 EP 153 PG 12 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 636TP UT WOS:000180473300024 PM 12531772 ER PT J AU Parker, DC Folpe, AL Bell, J Oliva, E Young, RH Cohen, C Amin, MB AF Parker, DC Folpe, AL Bell, J Oliva, E Young, RH Cohen, C Amin, MB TI Potential utility of uroplakin III, thrombomodulin, high molecular weight cytokeratin, and cytokeratin 20 in noninvasive, invasive, and metastatic urothelial (transitional cell) carcinomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE urothelial carcinoma; uroplakin III; thrombomodulin; high molecular weight cytokeratin; cytokeratin 20; tissue microarray analysis; WHO/ISUP grade ID MALIGNANT PLEURAL MESOTHELIOMA; INTERMEDIATE FILAMENT PROTEINS; PULMONARY ADENOCARCINOMA; IMMUNOHISTOCHEMICAL MARKER; MONOCLONAL-ANTIBODIES; TISSUE MICROARRAYS; MEMBRANE-PROTEINS; EXPRESSION; DIAGNOSIS; TUMORS AB The morphology of urothelial carcinomas, particularly when poorly differentiated or in metastatic sites, is not distinctive and overlaps significantly with other poorly differentiated nonurothelial carcinomas. Currently, there is no widely used single marker or panel of markers to confirm urothelial origin. We evaluated a panel consisting of antibodies to uroplakin III (UROIII), thrombomodulin (THR), high molecular weight cytokeratin (HMWCK), and cytokeratin 20 (CK20) in a wide range of urothelial tumors. Immunohistochemistry was performed on 112 paraffin-embedded urothelial neoplasms: 14 low malignant potential, 16 low-grade noninvasive, 16 high-grade noninvasive, 36 invasive, and 25 metastatic and 5 small cell carcinomas of the urinary bladder. Tissue microarray analysis was used to examine 498 tissue cores of nonurothelial tumors and normal tissue using antibodies to UROIII, THR, and HMWCK. Overall positive staining results in all urothelial tumors are as follows: UROIII, 64 of 112 (57.1%); THR, 77 of 112 (68.8%); HMWCK, 88 of 110 (80%); and CK20,53 of 110 (48.2%). The expression of the four markers varied with tumor grade and stage. All small cell carcinomas were negative for all markers. Variant morphologic subtypes showed similar staining as conventional urothelial carcinomas. Tissue microarray analysis showed no UROIII immunoreactivity in tissue cores of nonurothelial tumors. THR was expressed by a limited number of nonurothelial cores (10 of 37 [27%] non-small cell lung carcinomas, 2 of 36 [5.6%] lymphomas). HMWCK was expressed by 43.8% of non-small cell lung carcinomas and essentially absent in other nonurothelial tumor cores. Based on the results of the study, the expression of UROIII in a tumor is essentially diagnostic of urothelial origin; however, it is expressed in only slightly more than half of urothelial tumors. The coexpression of THR, HMWCK, and CK20 strongly suggests urothelial origin. The coexpression of two of three non-UROIII markers (THR, HMWCK, CK20) suggests urothelial origin but requires clinicopathologic correlation. The results of the study indicate a role for an antibody panel that includes UROIII, THR, HMWCK, and CK20 in the diagnosis of urothelial tumors. C1 Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Amin, MB (reprint author), Emory Univ Hosp, G-167,1364 Clifton Rd NE, Atlanta, GA 30322 USA. NR 42 TC 112 Z9 116 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 JAN PY 2003 VL 27 IS 1 BP 1 EP 10 DI 10.1097/00000478-200301000-00001 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 631AH UT WOS:000180144000001 PM 12502922 ER PT J AU Yamada, A Laufer, TM Gerth, AJ Chase, CM Colvin, RB Russell, PS Sayegh, MH Auchincloss, H AF Yamada, A Laufer, TM Gerth, AJ Chase, CM Colvin, RB Russell, PS Sayegh, MH Auchincloss, H TI Further analysis of the T-cell subsets and pathways of murine cardiac allograft rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE rejection; indirect pathway; CD4+; CD8+; T cells ID II-DEFICIENT MICE; SKIN-GRAFTS; MONOCLONAL-ANTIBODIES; INDIRECT RECOGNITION; EFFECTOR-CELLS; ANTIGENS; SURVIVAL; INVIVO; MHC; LYMPHOCYTES AB The present study examined the role of CD4(+) and CD8(+) T cells in cardiac allograft rejection when either the direct or indirect pathway was eliminated for the CD4(+) portion of the response. To study the pathways in vivo, we used genetically altered mouse strains that lack class II antigens as either the donors or recipients for cardiac transplantation. In contrast to earlier published studies, which used different strain combinations, we found that either CD4 or CD8-depletion prolonged cardiac allograft survival moderately, but not indefinitely, in an MHC-mismatched, minor-matched combination. When the CD4(+) indirect pathway was eliminated, rapid graft rejection occurred when both T-cell subsets were present and when either CD4(+) or CD8(+) T cells were depleted. When the CD4(+) direct pathway was eliminated, rapid graft rejection occurred when both T-cell subsets were present, there was slow rejection when CD4(+) T cells were eliminated, and no rejection was seen for more than 100 days when CD8(+) T cells were eliminated. However, the long-surviving allografts on the recipients with only CD4+ cells and an indirect pathway did show evidence of chronic vasculopathy. Thus, either CD4(+) or CD8(+) T cells can mediate acute cardiac allograft rejection in these experiments when both pathways are available. In addition, CD4(+) T cells can provide help for acute rejection through either the direct or indirect pathway. Finally, recipients who have only CD4(+) cells and an indirect pathway do not demonstrate acute rejection, but do show evidence of chronic rejection. C1 Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL43340, HL-58675]; NIAID NIH HHS [AI-38397, AI-34965] NR 23 TC 31 Z9 33 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2003 VL 3 IS 1 BP 23 EP 27 DI 10.1034/j.1600-6143.2003.30105.x PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 632LR UT WOS:000180225200005 PM 12492706 ER PT J AU Baid, S Tolkoff-Rubin, N Saidman, S Chung, R Williams, WW Auchincloss, H Colvin, RB Delmonico, FL Cosimi, AB Pascual, M AF Baid, S Tolkoff-Rubin, N Saidman, S Chung, R Williams, WW Auchincloss, H Colvin, RB Delmonico, FL Cosimi, AB Pascual, M TI Acute humoral rejection in hepatitis C-infected transplant recipients receiving antiviral therapy SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE acute humoral rejection; HCV; interferon ID INTERFERON-ALPHA TREATMENT; RENAL-ALLOGRAFT REJECTION; PATHOLOGICAL FEATURES; ANTIBODY; KIDNEY AB The use of interferon-alpha (IFN) in hepatitis C (HCV)infected renal recipients has been associated with acute rejection and graft loss. We reviewed our recent experience in HCV (+) renal recipients treated with antiviral therapy for biopsy proven chronic hepatitis C. Twelve HCV (+) recipients who recently received antiviral therapy were analyzed. Post-treatment sera were tested for donor-specific human leukocyte antigen (HLA) antibodies (DSA). Within 6 months of initiating antiviral therapy, two of 12 patients (17%) developed acute rejection, which was characterized as acute humoral rejection (de novo DSA in serum and C4d deposits in peritubular capillaries). Both progressed to graft failure. Nine of the remaining 10 patients tested did not have DSA. The use of IFN was associated with severe acute humoral rejection (C4d +, DSA +). The recognition of IFN-associated acute humoral rejection in this series may explain the high rate of graft loss reported previously in renal recipients receiving IFN. C1 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, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA 02114 USA. NR 20 TC 79 Z9 81 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2003 VL 3 IS 1 BP 74 EP 78 DI 10.1034/j.1600-6143.2003.30113.x PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 632LR UT WOS:000180225200013 PM 12492714 ER PT J AU Metzger, RA Delmonico, FL Feng, S Port, FK Wynne, JJ Merion, RM AF Metzger, RA Delmonico, FL Feng, S Port, FK Wynne, JJ Merion, RM TI Expanded criteria donors for kidney transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE deceased donors; expanded criteria; graft survival; kidney transplantation; OPTN; organ allocation; SRTR; waiting list ID RENAL-ALLOGRAFTS; MARGINAL DONORS; RECIPIENTS; SURVIVAL; GLOMERULOSCLEROSIS; AGE C1 URREA, SRTR, Ann Arbor, MI USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Michigan, SRTR, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. TransLife Florida Hosp Med Ctr, Orlando, FL USA. RP Port, FK (reprint author), URREA, SRTR, Ann Arbor, MI USA. FU PHS HHS [231-00-0116] NR 19 TC 282 Z9 294 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2003 VL 3 SU 4 BP 114 EP 125 DI 10.1034/j.1600-6143.3.s4.11.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 683PY UT WOS:000183159300012 PM 12694055 ER PT J AU Woody, GE AF Woody, GE TI Research findings on psychotherapy of addictive disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT Conference on Whats New in Addiction Psychiatry CY APR, 2002 CL SILVER HILL HOSP, NEW CANAAN, CONNECTICUT HO SILVER HILL HOSP ID SUBSTANCE-ABUSE TREATMENT; COCAINE DEPENDENCE AB Psychoanalytically trained physicians working in methadone programs in the 1980s theorized that adding psychotherapy to addiction treatment would improve outcomes. Since then, a number of clinical studies have evaluated the effect of psychotherapy, drug counseling, and twelve-step intervention on treatment outcomes in methadone maintenance or cocaine and alcohol addiction programs. These studies have shown consistently that psychosocial treatments are helpful for patients with addictive disorders, with an effect size that ranges from mild to moderate. Major studies of psychotherapy in the treatment of addictive disorders are reviewed, and background information on psychotherapy and drug counseling is presented. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Woody, GE (reprint author), Vet Affairs Med Ctr, Addict Treatment & Res Ctr, Dept Psychiat, 600 Publ Ledger Bldg,150 S Independence Mall W, Philadelphia, PA 19106 USA. NR 12 TC 11 Z9 11 U1 6 U2 9 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2003 VL 12 SU 2 BP S19 EP S26 DI 10.1080/10550490390210236 PG 8 WC Substance Abuse SC Substance Abuse GA 710LT UT WOS:000184682200003 PM 12857660 ER PT J AU Maggard, MA Thompson, JE Ko, CY AF Maggard, MA Thompson, JE Ko, CY TI Why do breast cancer mortality rates vary across states? SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 18-20, 2002 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surgeons, SO Calif Chapter ID OLDER WOMEN; MAMMOGRAPHY; SURVIVAL; OUTCOMES; PROJECT AB In 2001 approximately 40,000 deaths from breast cancer will occur in the United States. Although some estimates suggest possible state-to-state variations in breast cancer mortality rates the reasons for such differences remain unknown. Our objective was to confirm whether breast cancer mortality rates are significantly different by state and to identify predictors for such variation. Administrative data from the National Center for Health Statistics (NCHS) report were used to determine statewide death rates. Analyses were similarly performed with the Surveillance, Epidemiology, and End Results (SEER) cancer database to determine predictors of high versus low mortality rates. State-level variation in breast cancer mortality rates was demonstrated in the NCHS database. A subsequent analysis of high versus low mortality states in the SEER cancer registry demonstrates that stage at presentation was a significant predictor of mortality, as "high" mortality states had more patients presenting with later-stage disease. We conclude that variations in the breast cancer mortality rates exist between states. A nearly 50 per cent increase is observed between the states with the highest and lowest mortality rates. Adjusted analyses demonstrate that stage at presentation is a more important predictor of mortality variation than treatment differences. As such breast cancer mortality rates may be best improved by targeting screening and access-to-care issues rather than treatment. C1 Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. W Los Angeles VA, Los Angeles, CA USA. Olive View UCLA Med Ctr, Dept Surg, Sylmar, CA 91342 USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Gen Surg, CHS,Room 72-228,10833 Le Conte Ave, Los Angeles, CA 90024 USA. NR 13 TC 8 Z9 9 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD JAN PY 2003 VL 69 IS 1 BP 59 EP 62 PG 4 WC Surgery SC Surgery GA 639UC UT WOS:000180646900013 PM 12575783 ER PT S AU Rauch, SL Shin, LM Wright, CI AF Rauch, SL Shin, LM Wright, CI BE ShinnickGallagher, P Pitkanen, A Shekhar, A Cahill, L TI Neuroimaging studies of amygdala function in anxiety disorders SO AMYGDALA IN BRAIN FUNCTION: BACIC AND CLINICAL APPROACHES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Amygdala in Brain Function CY JUN 24-26, 2002 CL GALVESTON, TEXAS SP Univ Texas Med Branch, NY Acad Sci, NIH, RW Johnson Pharmaceut Inst, NIA, Natl Inst Neurol Dis & Stroke DE functional magnetic resonance imaging; positron emission tomography; posttraumatic stress disorder; phobias; obsessive-compulsive disorder; panic disorder ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; GLUCOSE METABOLIC RATES; CHILDHOOD SEXUAL ABUSE; SCRIPT-DRIVEN IMAGERY; PANIC DISORDER; SOCIAL PHOBIA; HIPPOCAMPAL VOLUME AB Neuroimaging research has helped to advance neurobiological models of anxiety disorders. The amygdala is known to play an important role in normal fear conditioning and is implicated in the pathophysiology of anxiety disorders. The amygdala may also be a target for the beneficial effects of cognitive-behavioral and medication treatments for anxiety disorders. In the current paper, we review neuroimaging research pertaining to the role of the amygdala in anxiety disorders and their treatment. Moreover, we discuss the development of new neuroimaging paradigms for measuring aspects of amygdala function, as well as the function of related brain regions. We conclude that such tools hold great promise for facilitating progress in relevant basic neuroscience as well as clinical research domains. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Harvard Med Sch, Dept Psychiat, Boston, MA USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, Bldg 149,Room 9130,13th St, Charlestown, MA 02129 USA. NR 118 TC 245 Z9 255 U1 14 U2 32 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-404-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 985 BP 389 EP 410 PG 22 WC Multidisciplinary Sciences; Neurosciences; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BW71H UT WOS:000182918800030 PM 12724173 ER PT S AU Siegle, GJ Konecky, RO Thase, ME Carter, CS AF Siegle, GJ Konecky, RO Thase, ME Carter, CS BE ShinnickGallagher, P Pitkanen, A Shekhar, A Cahill, L TI Relationships between amygdala volume and activity during emotional information processing tasks in depressed and never-depressed individuals - An fMRI investigation SO AMYGDALA IN BRAIN FUNCTION: BACIC AND CLINICAL APPROACHES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Amygdala in Brain Function CY JUN 24-26, 2002 CL GALVESTON, TEXAS SP Univ Texas Med Branch, NY Acad Sci, NIH, RW Johnson Pharmaceut Inst, NIA, Natl Inst Neurol Dis & Stroke DE fMRI; amygdala; depression; emotion; information processing C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Siegle, GJ (reprint author), UPMC Hlth Syst, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH30915, MH01306, MH16804, MH60473] NR 3 TC 52 Z9 52 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-404-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 985 BP 481 EP 484 PG 4 WC Multidisciplinary Sciences; Neurosciences; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BW71H UT WOS:000182918800039 PM 12724182 ER PT J AU Raines, DE Claycomb, RJ Forman, SA AF Raines, DE Claycomb, RJ Forman, SA TI Modulation of GABA(A) receptor function by nonhalogenated alkane anesthetics: The effects on agonist enhancement, direct activation, and inhibition SO ANESTHESIA AND ANALGESIA LA English DT Article ID GATED ION CHANNELS; NICOTINIC ACETYLCHOLINE-RECEPTOR; RAT HIPPOCAMPAL-NEURONS; VOLATILE ANESTHETICS; INHALED ANESTHETICS; POTENTIATION; CURRENTS; COMPLEX; STOICHIOMETRY; MECHANISMS AB At clinically relevant concentrations, ethers, alcohols, and halogenated alkanes enhance agonist action on the gamma-aminobutyric acid(A) (GABA(A)) receptor, whereas non-halogenated alkanes do not. Many anesthetics also directly activate and/or inhibit GABA(A) receptors, actions that may produce important behavioral effects; although, the effects of nonhalogenated alkane anesthetics on GABA(A) receptor direct activation and inhibition have not been studied. In this study, we assessed the abilities of two representative nonhalogenated alkanes, cyclopropane and butane, to enhance agonist action, directly activate, and inhibit currents mediated by expressed alpha(1)beta(2)gamma(2L) GABA(A) receptors using electrophysiological techniques. Our studies reveal that cyclopropane and butane enhance agonist action on the GABA(A) receptor at concentrations that exceed those required to produce anesthesia. Neither nonhalogenated alkane directly activated nor inhibited GABAA receptors, even at concentrations that approach their aqueous saturated solubilities. These results strongly suggest that the behavioral actions of nonhalogenated alkane anesthetics do not result from their abilities to enhance agonist actions, directly activate, or inhibit alpha(1) beta(2) gamma(2L) GABA(A) receptors and are consistent with the hypothesis that electrostatic interactions between anesthetics and their protein binding sites modulate GAB(A) receptor potency. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01-GM61927] NR 28 TC 19 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2003 VL 96 IS 1 BP 112 EP 118 DI 10.1213/01.ANE.0000039317.51505.40 PG 7 WC Anesthesiology SC Anesthesiology GA 631LR UT WOS:000180169700024 PM 12505935 ER PT J AU Zhao, M Josephson, L Tang, Y Weissleder, R AF Zhao, M Josephson, L Tang, Y Weissleder, R TI Magnetic sensors for protease assays SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE biosensors; biotin; enzymes; magnetic properties; proteases ID RESONANCE ENERGY-TRANSFER; MATRIX METALLOPROTEINASES; TAT PEPTIDE; EXPRESSION; INHIBITORS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. NR 23 TC 166 Z9 167 U1 2 U2 29 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2003 VL 42 IS 12 BP 1375 EP 1378 DI 10.1002/anie.200390352 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 664ZT UT WOS:000182095700010 PM 12671972 ER PT J AU Bertucci, C Hook, P Haynes, C Macaruso, P Bickley, C AF Bertucci, C Hook, P Haynes, C Macaruso, P Bickley, C TI Vowel perception and production in adolescents with reading disabilities SO ANNALS OF DYSLEXIA LA English DT Article ID LESS-SKILLED READERS; SPEECH-PERCEPTION; DEVELOPMENTAL DYSLEXIA; POOR READERS; CHILDREN; DEFICITS; DISCRIMINATION; ABILITY; IDENTIFICATION; INSTRUCTION AB Perception and production of the vowels /I/, /epsilon/, /ae/ in the words pit, pet and pat were investigated in two groups of adolescents who differed significantly on measures of reading and phonological awareness. Perception performance was assessed using slope measurements between vowel categories. Duration measurements and a rating system based on first and second formant (F1 and F2) values were used to analyze production performance. As a group, the students with reading disabilities not only perceived but also produced less well-defined vowel categories than the control group of age-matched good readers. Perception and production performance, however, were not correlated. Results suggest that the speech processing difficulties of the students with reading disabilities include weak phonological coding for vowel sounds with similar phonetic characteristics. The implications of these findings for intervention are addressed. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02129 USA. Lexington Publ Sch, Lexington, MA USA. Community Coll Rhode Isl, Providence, RI USA. Haskins Labs Inc, New Haven, CT 06511 USA. MIT, Cambridge, MA 02139 USA. RP Hook, P (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Charlestown Navy Yard,36 1st Ave, Boston, MA 02129 USA. NR 58 TC 2 Z9 2 U1 3 U2 4 PU INT DYSLEXIA ASSOC PI BALTIMORE PA CHESTER BUILDING, STE 382, 8600 LA SALLE RD, BALTIMORE, MD 21286-2044 USA SN 0736-9387 J9 ANN DYSLEXIA JI Ann. Dyslexia PY 2003 VL 53 BP 174 EP 200 DI 10.1007/s11881-003-0009-1 PG 27 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 751YD UT WOS:000187117300009 ER PT J AU Lambe, S Washington, DL Fink, A Laouri, M Liu, HH Fosse, JS Brook, RH Asch, SM AF Lambe, S Washington, DL Fink, A Laouri, M Liu, HH Fosse, JS Brook, RH Asch, SM TI Waiting times in California's emergency departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Robert-Wood-Johnson-Foundation-Clinical-Scholars CY NOV, 2001 CL FT LAUDERDALE, FLORIDA SP Robert Wood Johnson Fdn Clin Scholars ID HEALTH AB Study objective: Many perceive emergency department crowding as a significant problem that is getting worse. A national survey of ED directors defined crowding, in part, as waiting more than 1 hour to see a physician, a wait considered likely to result in adverse outcomes. Yet few data are available on ED waiting times among a heterogeneous group of hospitals serving a distinct geographic region. Methods: We observed a random sample of 1,798 patients visiting 30 California EDs between December 15, 2000, and May 15, 2001. We defined waiting time as the interval from ED arrival to first contact with a physician or midlevel provider. Results: Patients waited an average of 56 minutes (95% confidence interval [CI] 52 to 61 minutes; median 38 minutes); 42% waited longer than 60 minutes. Ordinary least squares regression analysis revealed that waiting times were significantly longer at hospitals in poorer neighborhoods; for every $10,000 decline in per capita income, patients waited 10.1 minutes longer (95% CI 1.8 to 18.4 minutes; P=.02) after adjusting for hospital ownership, teaching status, trauma status, proximity to a recently closed ED, ED volume, patient severity, and age. Lower ratios of physicians and triage nurses to waiting room patient were also associated with longer waits. Conclusion: Waiting times often exceeded the threshold set by a survey of ED directors. Further study is required to examine factors that lead to longer waiting times at hospitals in low-income areas. Physician and nurse staffing should be investigated as a means of reducing waiting times. C1 Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med & Publ Hlth, Los Angeles, CA 90024 USA. Calif HealtCare Fdn, Oakland, CA USA. Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med & Hlth Serv, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. RP Lambe, S (reprint author), Univ Calif San Francisco, Div Emergency Med, Box 0208,505 Parnassus St, San Francisco, CA 94143 USA. NR 27 TC 50 Z9 50 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 2003 VL 41 IS 1 BP 35 EP 44 DI 10.1067/mem.2003.2 PG 10 WC Emergency Medicine SC Emergency Medicine GA 634YC UT WOS:000180369200006 PM 12514681 ER PT J AU Janne, PA AF Janne, PA TI The role of epidermal growth advanced non-small cell lung factor receptor in carcinoma SO ANNALS OF MEDICINE LA English DT Article DE chemotherapy; epidermal growth factor receptor; lung carcinoma; non-small cell; receptor tyrosine kinase ID TYROSINE KINASE INHIBITOR; QUALITY-OF-LIFE; PLATINUM-BASED CHEMOTHERAPY; PHASE-III TRIAL; RANDOMIZED-TRIAL; SUPPORTIVE CARE; CANCER-THERAPY; ZD1839 IRESSA; EXPRESSION; SURVIVAL AB Chemotherapy is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Over the past 20 years, advances in chemotherapy have shown minimal incremental improvement in the survival outcomes of patients with advanced NSCLC. With the identification of molecular and genetic alterations in lung cancer, several new potential rationally designed therapeutic targets have emerged. One of these is the epidermal growth factor receptor (EGFR) and member of the ErbB family of receptor tyrosine kinases. Several inhibitors, both antibodies directed at the extra-cellular portion of the receptor, and small molecule inhibitors directed at the tyrosine kinase domain of EGFR are in clinical development in lung cancer. This article will review the pre-clinical rationale and the clinical studies of EGFR inhibitors alone and/or in combination with chemotherapy that have been performed to date in advanced NSCLC. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St,D1234, Boston, MA 02115 USA. NR 46 TC 2 Z9 2 U1 0 U2 1 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2003 VL 35 IS 7 BP 450 EP 457 DI 10.1080/07853890310010889 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 744CJ UT WOS:000186610100001 PM 14649327 ER PT J AU Hartnick, CJ Brigger, MT Cotton, RT Willging, JP Myer, CM AF Hartnick, CJ Brigger, MT Cotton, RT Willging, JP Myer, CM TI Surgery for pediatric vocal cord paralysis: A retrospective review SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY MAY 11-12, 2002 CL BOCA RATON, FLORIDA SP Amer Broncho Esophagol Assoc DE bilateral pediatric vocal cord paralysis; decannulation; partial arytenoidectomy; vocal cord lateralization ID ENDOSCOPIC LASER ARYTENOIDECTOMY; FOLD PARALYSIS; CHILDREN; YOUNGER; INFANTS; AGE AB To determine the outcome of surgical procedures for bilateral vocal cord paralysis in children, we performed a retrospective review of children under 18 years of age with bilateral vocal cord paralysis and a previous tracheotomy who underwent a primary procedure at a single tertiary care institution with an aim of decannulation. The primary outcome measure was the operation-specific decannulation rate (OSDR). The overall decannulation rates, as well as morbidity rates, were also recorded. Fifty-two children met the inclusion criteria (mean age at time of primary surgery, 6.2 years; SD, 5 years). Vocal cord lateralization procedures combined with a partial arytenoidectomy achieved the highest OSDR (17/24 or 71%). This OSDR was statistically higher than the OSDRs for CO2 laser cordotomy or arytenoidectomy procedures (OSDR, 5/17 or 29%, p = .008), for isolated arytenoidopexy procedures (OSDR, 1/4 or 25%, p = .000004), or for posterior costal cartilage graft procedures (OSDR, 3/5 or 60%, p = .0004). Neither of the 2 children who underwent isolated arytenoidectomy achieved primary decannulation. The incidence of aspiration following posterior cartilage graft procedures was 15% (2/15). Subanalysis by age failed to reveal differences in OSDR. We conclude that vocal cord lateralization procedures with partial arytenoidectomy afford the highest OSDR among primary procedures for pediatric vocal cord paralysis. The CO2 laser procedures, while having limited success as a primary procedure, are effective for revision. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Natl Naval Med Res Inst, Dept Surg, Bethesda, MD USA. Childrens Hosp, Med Ctr, Dept Pediat Otolaryngol, Cincinnati, OH 45229 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 25 Z9 25 U1 1 U2 4 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2003 VL 112 IS 1 BP 1 EP 6 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 636EV UT WOS:000180442300001 PM 12537049 ER PT J AU Wang, PC Chu, CC Tai, CJ Liang, SC Gliklich, RE AF Wang, PC Chu, CC Tai, CJ Liang, SC Gliklich, RE TI Validation assessment of the Chinese-version chronic ear survey: A comparison between data from English and Chinese versions SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE chronic suppurative otitis media; health status; outcome; treatment effectiveness ID HEALTH SURVEY SF-36; OTITIS-MEDIA AB The Chronic Ear Survey (CES) is a valid, disease-specific measure for the evaluation of health status and treatment effectiveness for adults with chronic suppurative otitis media (CSOM). This study compares the validation properties of the English and Chinese versions of the CES. The CES was translated into Mandarin Chinese by means of a parallel model. The Chinese version of the CES (CCES) was administered to 103 patients in a prospective manner, then was validated according to established criteria for reliability, validity, and longitudinal sensitivity. The CCES demonstrated good test-retest reliability and internal consistency (Cronbach's alpha = 0.81). The CCES significantly correlated with the Mandarin Chinese (Taiwan) version of the generic 36-Item Short-Form Health Survey (TSF-36). The standardized response mean for the CCES total-score was 2.1, indicating excellent sensitivity to clinical change. This validation study demonstrated that the performance characteristics of the CCES were equivalent to those of the English-version CES. The CCES is a valid tool for evaluation of adults with CSOM among the Chinese-speaking population. C1 Cathay Gen Hosp, Dept Otolaryngol, Taipei 106, Taiwan. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Clin Outcome Res Unit, Boston, MA 02114 USA. China Med Coll Hosp, Dept Otolaryngol, Taichung, Taiwan. China Med Coll, Dept Publ Hlth, Taichung, Taiwan. Dept Hlth, Taipei, Taiwan. RP Wang, PC (reprint author), Cathay Gen Hosp, Dept Otolaryngol, 280,Sec 4,Jen Ai Rd, Taipei 106, Taiwan. NR 11 TC 5 Z9 9 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2003 VL 112 IS 1 BP 85 EP 90 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 636EV UT WOS:000180442300016 PM 12537064 ER PT J AU Petit, F Minns, AB Dubernard, JM Hettiaratchy, S Lee, WPA AF Petit, F Minns, AB Dubernard, JM Hettiaratchy, S Lee, WPA TI Composite tissue allotransplantation and reconstructive surgery - First clinical applications SO ANNALS OF SURGERY LA English DT Review ID PERIPHERAL-NERVE REGENERATION; KNEE-JOINT TRANSPLANTATION; HAND TRANSPLANTATION; FOLLOW-UP; LARYNGEAL TRANSPLANTATION; ALLOGRAFT; REPLANTATION; EXPERIENCE; STRATEGIES; THERAPY AB Objective To review the first clinical cases of composite tissue allotransplantation (CTA) for reconstructive surgery and to discuss the outcome of and indications for these procedures in the context of chronic immunosuppression. Summary Background Data The first human hand transplant was performed in 1998. This procedure, as well as other composite tissue transplants, offers the potential for correcting untreatable large tissue defects. However, concerns remain regarding obligatory chronic immunosuppression and long-term functional results. Methods All the CTAs performed in humans that have been published or documented were reviewed. The preexisting clinical conditions and surgical procedures and the immunosuppressive therapy are described. The functional results and the complications or side effects of the treatment are detailed. Results Vascularized tendons (two cases), vascularized femoral diaphyses (three cases), knees (five cases), hands (four bilateral and seven unilateral cases), larynx (one case), and nonvascularized peripheral nerves (seven cases) have been transplanted in humans in the past decade. Rejection was prevented in most cases without difficulty. Early results are encouraging, particularly for hand and larynx transplants, but will need to be evaluated in the long term and in a larger number of patients. Conclusions CTA holds great potential for reconstructive surgery but is at present restricted by the risks of chronic immunosuppression and uncertain long-term results. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Plast Surg Res Lab, Boston, MA 02114 USA. Univ Paris 12, Hop Henri Mondor, Dept Plast Reconstruct & Aesthet Surg, F-94010 Creteil, France. Univ Lyon 1, Hop Edouard Herriot, Dept Transplantat Surg, F-69365 Lyon, France. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Plast Surg Res Lab, WAC-453,15 Parkman St, Boston, MA 02114 USA. NR 45 TC 54 Z9 58 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 2003 VL 237 IS 1 BP 19 EP 25 DI 10.1097/00000658-200301000-00004 PG 7 WC Surgery SC Surgery GA 730MC UT WOS:000185833700004 PM 12496526 ER PT J AU Lim, JE Chien, MW Earle, CC AF Lim, JE Chien, MW Earle, CC TI Prognostic factors following curative resection for pancreatic adenocarcinoma - A population-based, linked database analysis of 396 patients SO ANNALS OF SURGERY LA English DT Article ID FACTORS INFLUENCING SURVIVAL; ADJUVANT COMBINED RADIATION; AMERICAN JOINT COMMITTEE; DUCTAL ADENOCARCINOMA; COMBINATION THERAPY; OPERATIVE MORTALITY; COMORBIDITY INDEX; PROGRESS REPORT; CANCER; PANCREATICODUODENECTOMY AB Objective To analyze prognostic factors influencing pancreatic cancer survival following curative resection, using prospectively collected, population-based data. Summary Background Data Several studies have analyzed the determinants of long-term survival in postresection pancreatic cancer patients, but the majority of these have been single-institutional chart reviews yielding inconsistent results. Methods This retrospective cohort study examined 396 Medicare-eligible patients over age 65 who were diagnosed with nonmetastatic pancreatic adenocarcinoma and who underwent surgical resection with curative intent while residing in one of the 11 Survival, Epidemiology, and End Results (SEER) registries between January 1991 and December 1996. Linked Medicare data provided information on treatment and comorbidity, while linked census tract data supplied sociodemographic characteristics. Results Median survival for the overall study population was 17.6 months, with 1- and 3-year survival rates of 60.1% and 34.3%, respectively. Survival appears to be gradually improving over time, concomitant with a rise in the proportion of patients undergoing surgery in teaching centers. Prognostic variables significantly diminishing survival on univariate analysis included African American race, treatment not in a teaching hospital, lack of adjuvant chemoradiation therapy, as well as histopathologic factors that included tumor size larger than 2 cm in diameter, moderate to poor histologic grade, and positive lymph node metastases. Higher socioeconomic status was associated both with an increased likelihood of receiving adjuvant therapy and improved overall survival. Multivariate analyses indicated the strongest predictors of survival were adjuvant combined chemoradiotherapy, small tumors (<2 cm in diameter), negative lymph nodes, well-differentiated histology, undergoing surgery in a teaching hospital, and high socioeconomic status. Conclusions Although biologic characteristics remain important predictors of survival for patients with resected pancreatic cancer, the most powerful determinant is postoperative adjuvant chemoradiation therapy. An interesting finding that warrants further investigation is the effect of socioeconomic status on both the likelihood of receiving adjuvant treatment and subsequent survival, indicating a possible relationship between the quality of care delivered and outcomes. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Earle, CC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA009001, T32-CA09001-25] NR 57 TC 318 Z9 331 U1 1 U2 9 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 JAN PY 2003 VL 237 IS 1 BP 74 EP 85 DI 10.1097/00000658-200301000-00011 PG 12 WC Surgery SC Surgery GA 730MC UT WOS:000185833700011 PM 12496533 ER PT J AU Arnoletti, JP Pan, ZZ Fletcher, J Favorova, O Von Mehren, M Eisenberg, BL Godwin, AK AF Arnoletti, JP Pan, ZZ Fletcher, J Favorova, O Von Mehren, M Eisenberg, BL Godwin, AK TI Sprouty4A, a novel genetic marker of response to imatinib mesylate in gastrointestinal stromal tumors (GIST) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 56th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 05-09, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol C1 Univ Alabama, Birmingham, AL USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Russian State Med Univ, Moscow 117437, Russia. 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2003 VL 10 IS 1 SU S MA 3 BP S8 EP S8 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 706AK UT WOS:000184429300004 ER PT J AU Donahue, JM Nakamura, H Mullen, JT Kasuya, H Kawasaki, H Soundararajalu, C Tanabe, KK AF Donahue, JM Nakamura, H Mullen, JT Kasuya, H Kawasaki, H Soundararajalu, C Tanabe, KK TI Viral oncolysis: magnitude of viral replication correlates with antineoplastic efficacy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 56th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 05-09, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kasuya, hideki/I-7278-2014 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2003 VL 10 IS 1 SU S MA P3 BP S42 EP S42 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 706AK UT WOS:000184429300105 ER PT J AU Flannery, JV Xia, L Liu, R Adams, J Elliott, P Cusack, JC AF Flannery, JV Xia, L Liu, R Adams, J Elliott, P Cusack, JC TI Proteasome inhibition enhances response to combination gemcitabine and CPT-11 treatment in pancreatic xenografts SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 56th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 05-09, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2003 VL 10 IS 1 SU S MA 49 BP S22 EP S23 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 706AK UT WOS:000184429300050 ER PT J AU Ott, MJ Zeegen, EN Matthews, HM Delaney, TF Harmon, DC Gebhardt, MC Mankin, HJ Hornicek, FJ AF Ott, MJ Zeegen, EN Matthews, HM Delaney, TF Harmon, DC Gebhardt, MC Mankin, HJ Hornicek, FJ TI A prospective evaluation of sentinel node mapping for synovial cell, epithelioid, and clear cell sarcoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 56th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 05-09, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol C1 Latter Day St Hosp, Salt Lake City, UT 84143 USA. 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 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2003 VL 10 IS 1 SU S MA 88 BP S35 EP S36 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 706AK UT WOS:000184429300089 ER PT J AU Pierie, JP Muzikansky, A Tanabe, KK Ott, MJ AF Pierie, JP Muzikansky, A Tanabe, KK Ott, MJ TI The outcome of surgical resection versus assignment to the liver transplantation waitlist for hepatocellular carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 56th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 05-09, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol C1 Latter Day St Hosp, Salt Lake City, UT 84143 USA. Med Ctr Leeuwarden, Leeuwarden, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2003 VL 10 IS 1 SU S MA 71 BP S30 EP S30 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 706AK UT WOS:000184429300072 ER PT J AU Wargo, JA Ribas, A Butterfield, L Dissette, V Glaspy, JA McBride, W Economou, J AF Wargo, JA Ribas, A Butterfield, L Dissette, V Glaspy, JA McBride, W Economou, J TI Genetic immunotherapy using melanoma antigen engineered dendritic cells generates potent immunity in MHC class 1-knock out mice SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 56th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 05-09, 2003 CL LOS ANGELES, CALIFORNIA SP Soc Surg Oncol C1 Univ Calif Los Angeles, Div Surg Oncol, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Div Med Oncol, Los Angeles, CA USA. Univ Calif Los Angeles, Div Expt Radiat Oncol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2003 VL 10 IS 1 SU S MA 56 BP S25 EP S25 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 706AK UT WOS:000184429300057 ER PT J AU Bailey, SH Bull, DA Harpole, DH Rentz, JJ Neumayer, LA Pappas, TN Daley, J Henderson, WG Krasnicka, B Khuri, SF AF Bailey, SH Bull, DA Harpole, DH Rentz, JJ Neumayer, LA Pappas, TN Daley, J Henderson, WG Krasnicka, B Khuri, SF TI Outcomes after esophagectomy: A ten-year prospective cohort SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 28-30, 2002 CL FT LAUDERDALE, FLORIDA SP Soc Thorac Surgeons ID AFFAIRS SURGICAL RISK; LEWIS,IVOR ESOPHAGOGASTRECTOMY; POSTOPERATIVE MORTALITY; CARCINOMA; CANCER; CARE; SURVIVAL; THERAPY; SURGERY; QUALITY AB Background. The Department of Veterans Affairs National Surgical Quality Improvement Program is a unique resource to prospectively analyze surgical outcomes from a cross-section of surgical services nationally. We used this database to assess risk factors for morbidity and mortality after esophagectomy in Veterans Affairs Medical Centers from 1991 to 2001. Methods. A total of 1,777 patients underwent an esophagectomy at 109 Veterans Affairs hospitals with complete in-hospital and 30-day outcomes recorded. Bivariate and multivariable analyses were completed. Results. Thirty-day mortality was 9.8% (174/1,777) and the incidence of one or more of 20 predefined complications was 49.5% (880/1,777). The most frequent postoperative complications were pneumonia in 21% (380/1,777), respiratory failure in 16% (288/1,777), and ventilator support more than 48 hours in 22% (387/1,777). Preoperative predictors of mortality based on multivariable analysis included neoadjuvant therapy, blood urea nitrogen level of more than 40 mg/dL, alkaline phosphatase level of more than 125 U/L, diabetes mellitus, alcohol abuse, decreased functional status, ascites, and increasing age. Preoperative factors impacting morbidity were increasing age, dyspnea, diabetes mellitus, chronic obstructive pulmonary disease, alkaline phosphatase level of more than 125 U/L, lower serum albumin concentration, increased complexity score, and decreased functional status. Intraoperative risk factors for mortality included the need for transfusion; intraoperative risk factors for morbidity included the need for transfusion and longer operative time. Conclusions. These data constitute the largest prospective outcomes cohort in the literature and document a near 50% morbidity rate and 10% mortality rate after esophagectomy. Data from this study can be used to better stratify patients before esophagectomy. (C) 2003 by The Society of Thoracic Surgeons. C1 Univ Utah, Div Cardiothorac Surg, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Vet Affairs Med Ctr, Salt Lake City, UT USA. Duke Univ, Sch Med, Vet Affairs Med Ctr, Durham, NC USA. Harvard Univ, Sch Med, Inst Hlth Policy, Massachusetts Gen Hosp,Partners Healthcare Syst &, Boston, MA USA. Harvard Univ, Sch Med, Vet Affairs Med Ctr, W Roxburg, MA USA. Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. RP Bull, DA (reprint author), Univ Utah, Div Cardiothorac Surg, 50 N Med Dr,Rm 3C127, Salt Lake City, UT 84132 USA. NR 24 TC 240 Z9 260 U1 0 U2 3 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 JAN PY 2003 VL 75 IS 1 BP 217 EP 222 AR PII S0003-4975(02)04368-0 DI 10.1016/S0003-4975(02)04368-0 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 636MB UT WOS:000180458900052 PM 12537219 ER PT J AU Yarmush, ML Banta, S AF Yarmush, ML Banta, S TI Metabolic engineering: Advances in modeling and intervention in health and disease SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING LA English DT Review DE metabolic pathways; metabolic modeling; metabolic flux; human disease; diabetes ID HAMSTER OVARY CELLS; STIMULATED INSULIN-SECRETION; GTP-CYCLOHYDROLASE-I; BIOCHEMICAL SYSTEMS-THEORY; PENTOSE-PHOSPHATE PATHWAY; TRICARBOXYLIC-ACID CYCLE; C-13 NMR-SPECTROSCOPY; PANCREATIC BETA-CELL; RED-BLOOD-CELLS; EXPRESSING TYROSINE-HYDROXYLASE AB The field of metabolic engineering encompasses a powerful set of tools that can be divided into (a) methods to model complex metabolic pathways and (b) techniques to manipulate these pathways for a desired metabolic outcome. These tools have recently seen increased utility in the medical arena, and this paper aims to review significant accomplishments made using these approaches. The modeling of metabolic pathways has been applied to better understand disease-state physiology in a variety of cellar, subcellular, and organ systems, including the liver, heart, mitochondria, and cancerous cells. Metabolic pathway engineering has been used to generate cells with novel biochemical functions for therapeutic use, and specific examples are provided in the areas of glycosylation engineering and dopan-line-replacement therapy. In order to document the potential of applying both metabolic modeling and pathway manipulation, we describe pertinent advances in the field of diabetes research. Undoubtedly, as the field of metabolic engineering matures and is applied to a wider array of problems, new advances and therapeutic strategies will follow. C1 Massachusetts Gen Hosp, Shriners Burns Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Shriners Burns Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 59766-A01A1, DK43371-09A1]; NIGMS NIH HHS [GM058125-04] NR 211 TC 25 Z9 29 U1 0 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1523-9829 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2003 VL 5 BP 349 EP 381 DI 10.1146/annurev.bioeng.5.031003.163247 PG 35 WC Engineering, Biomedical SC Engineering GA 742AV UT WOS:000186493800012 PM 14527316 ER PT J AU Hemler, ME AF Hemler, ME TI Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain SO ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY LA English DT Review DE palmitoylation; uroplakin; peripherin; lipid raft; fertilization; integrins; EWI-2; EWI-F; CD9; CD81; CD151; exosomes ID DIPHTHERIA-TOXIN SENSITIVITY; TRANSMEMBRANE 4 SUPERFAMILY; UROTHELIAL PLAQUE PARTICLE; LARGE EXTRACELLULAR LOOP; GROWTH-FACTOR; ANTIPROLIFERATIVE ANTIBODY; MONOCLONAL-ANTIBODIES; B-LYMPHOCYTES; EGF RECEPTOR; LIPID RAFTS AB This review summarizes key aspects of tetraspanin proteins, with a focus on the functional relevance and structural features of these proteins and how they are organized into a novel type of membrane microdomain. Despite the size of the tetraspanin family and their abundance and wide distribution over many cell types, most have not been studied. However, from studies of prototype tetraspanins, information regarding functions, cell biology, and structural organization has begun to emerge. Genetic evidence points to critical roles for tetraspanins on oocytes during fertilization, in fungi during leaf invasion, in Drosophila embryos during neuromuscular synapse formation, during T and B lymphocyte activation, in brain function, and in retinal degeneration. From structure and mutagenesis studies, we are beginning to understand functional subregions within tetraspanins, as well as the levels of connections among tetraspanins and their many associated proteins. Tetraspanin-enriched microdomains (TEMs) are emerging as entities physically and functionally distinct from lipid rafts. These microdomains now provide a context in which to evaluate tetraspanins in the regulation of growth factor signaling and in the modulation of integrin-mediated post-cell adhesion events. Finally, the enrichment of tetraspanins within secreted vesicles called exosomes, coupled with hints that tetraspanins may regulate vesicle fusion and/or fission, suggests exciting new directions for future research. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA42368, CA86712]; NIGMS NIH HHS [GM38903] NR 149 TC 448 Z9 462 U1 4 U2 43 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1081-0706 J9 ANNU REV CELL DEV BI JI Annu. Rev. Cell Dev. Biol. PY 2003 VL 19 BP 397 EP 422 DI 10.1146/annurev.cellbio.19.111301.153609 PG 30 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 749LP UT WOS:000186922500016 PM 14570575 ER PT J AU Florez, JC Hirschhorn, J Altshuler, D AF Florez, JC Hirschhorn, J Altshuler, D TI The inheritebasis odiabetes mellitus: Implications for the genetic analysis of complex traits SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS LA English DT Review ID DEPENDENT DIABETES-MELLITUS; GENOME-WIDE SEARCH; PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA-2; HUMAN INSULIN GENE; HL-A ANTIGENS; IMPAIRED GLUCOSE-TOLERANCE; AMINO-ACID POLYMORPHISMS; SENSITIVE K-CHANNEL; BODY-MASS INDEX; SUSCEPTIBILITY LOCUS AB Diabetes encompasses a heterogeneous group of diseases, each with a substantial genetic component. We review the division of diabetes into different subtypes based on clinical phenotype, the fruitful pursuit of genes underlying monogenic forms of the disease, the successes and drawbacks of whole-genome linkage scans in type 1 and type 2 diabetes, and the recent identification of several diabetes genes by large association studies. We use the lessons learned from this extensive body of evidence to illustrate general implications for the genetic analysis of complex traits. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Whitehead MIT Ctr Genome Res, Program Med & Populat Genet, Cambridge, MA 02139 USA. Childrens Hosp, Div Genet, Boston, MA 02114 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM jcflorez@partners.org; joel.hirschhorn@tch.harvard.edu; altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 196 TC 181 Z9 191 U1 0 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2003 VL 4 BP 257 EP 291 DI 10.1146/annurev.genom.4.070802.110436 PG 35 WC Genetics & Heredity SC Genetics & Heredity GA 836UG UT WOS:000222580700010 PM 14527304 ER PT J AU Cummings, DE Merriam, GR AF Cummings, DE Merriam, GR TI Growth hormone therapy in adults SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE aging; ghrelin; growth hormone deficiency; insulin-like growth factor-I; somatotropin ID PLACEBO-CONTROLLED TRIAL; GH-DEFICIENT ADULTS; HEALTHY AGED WOMEN; QUALITY-OF-LIFE; FACTOR-I; BODY-COMPOSITION; HYPOPITUITARY ADULTS; REPLACEMENT THERAPY; ELDERLY-MEN; OLDER MEN AB Growth hormone (GH) is classically linked with linear growth in childhood but continues to have important metabolic actions throughout life. GH deficiency in adulthood causes a distinct syndrome with significant morbidities. These include increased total and visceral fat, decreased muscle mass and aerobic capacity, affective disturbances, abnormal lipids, and increased vascular mortality, all of which are ameliorated with GH replacement. The possibility of adult GH deficiency (AGHD) should always be considered in individuals with a history of childhood GH deficiency or significant hypothalamic-pituitary damage, and the diagnosis should then be confirmed by biochemical testing. Adult GH dosing is much lower than that in pediatric practice, as appropriate for physiologic reconstitution. Hormonal side effects are minimized by stepwise dose titration. Lingering concerns remain regarding the possibility of increased cancer risk with long-term treatment, but this hazard has not been unequivocally demonstrated. Compared with AGHD, there is much less information about GH replacement in other diseases or in normal aging, or about the use of supraphysiologic GH doses to treat catabolic states. In critical illness, high-dose GH therapy has proven clearly harmful, and the balance of risks and benefits of GH administration in most adult contexts other than AGHD has not been defined. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. EM davidec@u.washington.edu; merriam@u.washington.edu NR 93 TC 56 Z9 57 U1 2 U2 3 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2003 VL 54 BP 513 EP 533 DI 10.1146/annurev.med.54.101601.152147 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 670WV UT WOS:000182433600030 PM 12471175 ER PT J AU Abrahm, JL AF Abrahm, JL TI Update in palliative medicine and end-of-life care SO ANNUAL REVIEW OF MEDICINE-SELECTED TOPICS IN THE CLINICAL SCIENCES LA English DT Review DE communication; pain; depression; delirium; bereavement ID TERMINALLY ILL PATIENTS; CANCER-PATIENTS; TREATMENT PREFERENCES; BREAKTHROUGH PAIN; EDUCATION; MANAGEMENT; DEPRESSION; OPPORTUNITIES; RESUSCITATION; COMMUNICATION AB Palliative medicine includes clinical palliative care, education, and research that focus on the quality of life of patients with advanced disease and their families. The domain of palliative medicine is the relief of suffering: physical, psychological, social, and spiritual. Palliative medicine and care for patients at the end of life and their families include the following key components: compassionate communication; exploration of patient and family values and goals of care; expert attention to relief of suffering; management of pain, depression, delirium, and other symptoms; awareness of the manifestations of grief, and sensitivity to the concerns of bereaved survivors. C1 Dana Farber Canc Inst, Pain & Palliat Care Program, Boston, MA 02115 USA. RP Abrahm, JL (reprint author), Dana Farber Canc Inst, Pain & Palliat Care Program, 44 Binney St, Boston, MA 02115 USA. NR 92 TC 10 Z9 10 U1 0 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2003 VL 54 BP 53 EP 72 DI 10.1146/annurev.med.54.101601.152218 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 670WV UT WOS:000182433600004 PM 12525669 ER PT J AU Scadden, DT AF Scadden, DT TI AIDS-related malignancies SO ANNUAL REVIEW OF MEDICINE-SELECTED TOPICS IN THE CLINICAL SCIENCES LA English DT Review DE Kaposi's sarcoma; non-Hodgkin's lymphoma; Epstein-Barr virus; human herpesvirus-8; human immunodeficiency ID NON-HODGKINS-LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; BONE-MARROW TRANSPLANTATION; IMMUNE-DEFICIENCY SYNDROME; PEGYLATED-LIPOSOMAL DOXORUBICIN; INTERFERON REGULATORY FACTOR; COLONY-STIMULATING FACTOR AB Immunodeficiency alters the risk of cancer. Specific types of immune dysfunction are associated with different tumor risks, but most tumors are related to oncogenic viruses. In acquired immunodeficiency due to the human immunodeficiency virus (HIV), HIV itself rarely directly causes cancer; rather, it provides the immunologic background against which other viruses can escape immune control and induce tumors. The most common malignancies are Kaposi's sarcoma and non-Hodgkin's lymphoma. This chapter discusses the pathophysiologic background of these tumors, how they have been affected by the use of anti-HIV medications, and their clinical management. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. NR 134 TC 22 Z9 24 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2003 VL 54 BP 285 EP 303 DI 10.1146/annurev.med.54.101601.152143 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 670WV UT WOS:000182433600018 PM 12525676 ER PT J AU Cummings, DE Schwartz, MW AF Cummings, DE Schwartz, MW TI Genetics and pathophysiology of human obesity SO ANNUAL REVIEW OF MEDICINE-SELECTED TOPICS IN THE CLINICAL SCIENCES LA English DT Review DE energy homeostasis; leptin; melanocortins; ghrelin; body-weight regulation ID PLASMA GHRELIN LEVELS; CENTRAL MELANOCORTIN RECEPTORS; MELANIN-CONCENTRATING HORMONE; REVERSES INSULIN-RESISTANCE; BODY-MASS INDEX; FOOD-INTAKE; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; MICE LACKING; DIABETIC HYPERPHAGIA AB Obesity has become a leading public health concern. Over 1 billion people are now overweight or obese, and the prevalence of these conditions is rising rapidly. Remarkable new insights into the mechanisms that control body weight are providing an increasingly detailed framework for a better understanding of obesity pathogenesis. Key peripheral signals, such as leptin, insulin, and ghrelin, have been linked to hypothalamic neuropeptide systems, and the anatomic and functional networks that integrate these systems have begun to be elucidated. This article highlights some of these recent findings and their implications for the future of obesity treatment. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Harborview Med Ctr, Seattle, WA 98195 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RI Schwartz, Michael/H-9950-2012 NR 110 TC 214 Z9 223 U1 1 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 2003 VL 54 BP 453 EP 471 DI 10.1146/annurev.med.54.101601.152403 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 670WV UT WOS:000182433600027 PM 12414915 ER PT J AU Segal, RA AF Segal, RA TI Selectivity inneurotrophin signaling: Theme and variations SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE NGF; BDNF; Erk 5; retrograde; anterograde; synapse ID NERVE GROWTH-FACTOR; PHOSPHOLIPASE C-GAMMA; PROTEIN-KINASE-B; RECEPTOR TYROSINE KINASE; NF-KAPPA-B; FORKHEAD TRANSCRIPTION FACTOR; GLYCOGEN-SYNTHASE KINASE-3; TRK PROTOONCOGENE PRODUCT; CLATHRIN-COATED VESICLES; FAMILY-BASED ASSOCIATION AB (N)eurotrophins are a family of growth factors critical for the development and functioning of the nervous system. Although originally identified as neuronal survival factors, neurotrophins elicit many biological effects, ranging from proliferation to synaptic modulation to axonal pathfinding. Recent data indicate that the nature of the signaling cascades activated by neurotrophins, and the biological responses that ensue, are specified not only by the ligand itself but also by the temporal pattern and spatial location of stimulation. Studies on neurotrophin signaling have revealed variations in the Ras/MAP kinase, PI3 kinase, and phospholipase C pathways, which transmit spatial and temporal information. The anatomy of neurons makes them particularly appropriate for studying how the location and tempo of stimulation determine the signal cascades that are activated by receptor tyrosine kinases such as the Trk receptors. These signaling variations may represent a general mechanism eliciting specificity in growth factor responses. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Segal, RA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 44 Binney St, Boston, MA 02115 USA. EM Rosalind_segal@dfci.harvard.edu FU NINDS NIH HHS [NS 37757, NS 35148] NR 208 TC 250 Z9 262 U1 2 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2003 VL 26 BP 299 EP 330 DI 10.1146/annurev.neuro.26.041002.131421 PG 32 WC Neurosciences SC Neurosciences & Neurology GA 717MJ UT WOS:000185093200012 PM 12598680 ER PT J AU Mann, DL AF Mann, DL TI Stress-activated cytokines and the heart: From adaptation to maladaptation SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE TNF; IL-6; IL-1; contractility; stress; homeostasis ID TUMOR-NECROSIS-FACTOR; ACUTE MYOCARDIAL-INFARCTION; RAT CARDIAC MYOCYTES; NF-KAPPA-B; LEFT-VENTRICULAR DYSFUNCTION; ISCHEMIA-REPERFUSION INJURY; ADULT FELINE MYOCARDIUM; GROWTH-FACTOR-BETA; FACTOR-ALPHA GENE; NITRIC-OXIDE AB The ability of the myocardium to successfully compensate for and adapt to environmental stress ultimately determines whether the heart will decompensate and fail or maintain preserved function. Despite the importance of the myocardial response to environmental stress, very little is known with respect to the biochemical mechanisms that are responsible for mediating and integrating the stress response in the heart. In the present review we summarize recent experimental material suggesting that the cytokines expressed within the myocardium in response to environmental injury, namely tumor necrosis factor (TNF), interleukin-1 (IL-1), and the interleukin-6 (IL-6) family, play an important role in initiating and integrating homeostatic responses. However, these stress-activated cytokines all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. Accordingly, the theme to emerge from this review is that the short-term expression of stress-activated cytokines within the heart may be an adaptive response to stress, whereas long-term expression of these molecules may be frankly maladaptive by producing cardiac decompensation. C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX 77030 USA. RP Mann, DL (reprint author), Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R01 HL61543, HL-42250-10/10, P50 HL-O6H, R01 HL58081] NR 101 TC 170 Z9 187 U1 2 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2003 VL 65 BP 81 EP 101 DI 10.1146/annurev.physiol.65.092101.142249 PG 23 WC Physiology SC Physiology GA 672MD UT WOS:000182523700005 PM 12500970 ER PT J AU Kitamura, T Kahn, CR Accili, E AF Kitamura, T Kahn, CR Accili, E TI Insulin receptor knockout mice SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE diabetes; genetics; signal transduction; beta-cell; animal models ID GROWTH-FACTOR-I; HOMOZYGOUS NONSENSE MUTATION; PANCREATIC BETA-CELLS; DEPENDENT DIABETES-MELLITUS; RABSON-MENDENHALL-SYNDROME; BROWN ADIPOSE-TISSUE; CAENORHABDITIS-ELEGANS; TARGETED DISRUPTION; GLUCOSE-TRANSPORT; TYROSINE KINASE AB To examine the role of the insulin receptor in fuel homeostasis, we and others have carried out genetic ablation studies in mice. Mice lacking insulin receptors are born. with normal features, but develop early postnatal diabetes and die of ketoacidosis. In contrast, mice lacking insulin receptors in specific cell types as a result of conditional mutagenesis develop mild metabolic and reproductive abnormalities. These experiments have uncovered novel functions of insulin receptors in tissues such as brain and pancreatic beta-cells. Combined knockout studies of insulin and Igf1 receptors indicate that the insulin receptor also promotes embryonic growth. Experimental crosses of mice with insulin receptor haploinsufficiency have been instrumental to the genetic analysis of insulin action by enabling us to assign specific roles to different insulin receptor substrates and identify novel elements in insulin signaling. C1 Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, Dept Med, New York, NY 10032 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kitamura, T (reprint author), Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, Dept Med, New York, NY 10032 USA. NR 129 TC 125 Z9 136 U1 0 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2003 VL 65 BP 313 EP 332 DI 10.1146/annurev.physiol.65.092101.142540 PG 22 WC Physiology SC Physiology GA 672MD UT WOS:000182523700013 PM 12471165 ER PT J AU Mays, VM Ponce, NA Washington, DL Cochran, SD AF Mays, VM Ponce, NA Washington, DL Cochran, SD TI Classification of race and ethnicity: Implications for public health SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE classification bias; public health statistics; cultural competence ID BLACK-AND-WHITE; UNITED-STATES; MANAGED CARE; 2000 CENSUS; RESIDENTIAL SEGREGATION; MEDICAID BENEFICIARIES; MINORITY POPULATIONS; INTERRACIAL MARRIAGE; DIABETES EDUCATION; RACIAL DISPARITIES AB Emerging methods in the measurement of race and ethnicity have important implications for the field of public health. Traditionally, information on race and/or ethnicity has been integral to our understanding of the health issues affecting the U.S. population. We review some of the complexities created by new classification approaches made possible by the inclusion of multiple-race assessment in the U.S. Census and large health surveys. We discuss the importance of these classification decisions in understanding racial/ethnic health and health care access disparities. The trend toward increasing racial and ethnic diversity in the United States will put further pressure on the public health industry to develop consistent and useful approaches to racial/ethnic classifications. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. RP Mays, VM (reprint author), Univ Calif Los Angeles, Dept Psychol, Box 951563, Los Angeles, CA 90095 USA. EM mays@ucla.edu; nponce@ucla.edu; donna.washington@med.va.gov; cochran@ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NIDA NIH HHS [DA 045539, R01 DA015539]; NIMH NIH HHS [R01 MH061774, MH 61774, R01 MH044345] NR 133 TC 119 Z9 120 U1 5 U2 20 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 2003 VL 24 BP 83 EP 110 DI 10.1146/annurev.publhealth.24.100901.140927 PG 28 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 717MX UT WOS:000185094600006 PM 12668755 ER PT J AU Ma, PC Blaszkowsky, L Bharti, A Ladanyi, A Kraeft, SK Bruno, A Skarin, AT Chen, LB Salgia, R AF Ma, PC Blaszkowsky, L Bharti, A Ladanyi, A Kraeft, SK Bruno, A Skarin, AT Chen, LB Salgia, R TI Circulating tumor cells and serum tumor biomarkers in small cell lung cancer SO ANTICANCER RESEARCH LA English DT Review DE small cell lung cancer; tumor biomarkers; circulating tumor cells ID HEPATOCYTE GROWTH-FACTOR; POLYMERASE-CHAIN-REACTION; NEURON-SPECIFIC ENOLASE; HUMAN DIGESTIVE SYSTEM; FACTOR SCATTER FACTOR; BONE-MARROW; PROGNOSTIC-SIGNIFICANCE; C-KIT; CARCINOEMBRYONIC ANTIGEN; REVERSE-TRANSCRIPTASE AB Lung cancer accounts for approximately 30% of all cancer mortalities in the United States. Small cell lung cancer (SCLC), which is an aggressive malignancy with frequent and early metastases, accounts for about 15% of all of the lung cancer cases with a dismal 5-year survival rate of <5% with current standard therapies. Early detection of SCLC is challenging, in pail due to the lack of adequate serum tumor markers. The goal of this review is to summarize the current knowledge of circulating tumor cells and serum biomarkers in small cell lung cancer. The role of circulating tumor cells in prognostication is controversial, but may be better defined with advancing technologies of detection of such cells with higher precision, and improved clinico-pathological correlations. The current knowledge on the known. serum cytokines and tumor biomarkers of SCLC, such as CEA, chromogranin A and neuron-specific enolase will be presented. Serum cytokines, such as vascular endothelial growth factor (VEGF), stem cell factor (SCF) and hepatocyte growth factor/scatter factor (HGF/SF) are also discussed New findings in the search for novel diagnostic and therapeutic molecular markers using the emerging genomics and proteomics technologies are emphasized It is our hope that validation of these new research platforms and technologies will result in improved early detection, prognostication and finally treatment of SCLC with potential novel molecularly-targeted therapeutics. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Dept Hematol Oncol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 1234B,44 Binney St, Boston, MA 02115 USA. EM ravi_salgia@dfci.harvard.edu NR 125 TC 30 Z9 37 U1 0 U2 8 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 2003 VL 23 IS 1A BP 49 EP 62 PG 14 WC Oncology SC Oncology GA 657LQ UT WOS:000181669000009 PM 12683352 ER PT J AU Lamendola, DE Duan, ZF Penson, RT Oliva, E Seiden, MV AF Lamendola, DE Duan, ZF Penson, RT Oliva, E Seiden, MV TI beta tubulin mutations are rare in human ovarian carcinoma SO ANTICANCER RESEARCH LA English DT Article DE paclitaxel; pseudogenes; drug resistance ID CANCER-CELLS; GENOMIC INSTABILITY; TAXOL RESISTANCE; LUNG-CANCER; P53 GENE; PACLITAXEL; CONFORMATION; MECHANISMS; EXPRESSION; IDENTIFICATION AB Background: The interaction between paclitaxel and its target, beta tubulin, is essential for effective cytotoxicity. Alterations or mutation of beta tubulin have the potential to alter paclitaxel binding and confer a drug resistant phenotype. Materials and Methods: Twenty-nine paired tumor samples from women with ovarian cancer were examined to evaluate the incidence of exon four mutations in tumors with evolving paclitaxel resistance. Tissue was dissected from five-micron paraffin slices and analyzed for mutations in exon four of human beta tubulin by PCR-SSCP. Nested PCR primers generated three partially overlapping or neighboring fragments corresponding to exon four of beta tubulin. P-32 labeled PCR fragments were then subjected to SSCP analysis polyacrylamide gel electrophoresis. Results: PCR-SSCP analysis demonstrated no mutations in the twenty-nine paired tumor samples studied. Conclusion: This result suggests that mutations within exon four of human beta tubulin are rare in newly-diagnosed and recurrent paclitaxel resistant human ovarian cancer. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640, Boston, MA 02114 USA. NR 33 TC 20 Z9 22 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN-FEB PY 2003 VL 23 IS 1B BP 681 EP 686 PG 6 WC Oncology SC Oncology GA 657LR UT WOS:000181669100029 PM 12680167 ER PT J AU Ince, D Zhang, XM Silver, LC Hooper, DC AF Ince, D Zhang, XM Silver, LC Hooper, DC TI Topoisomerase targeting with and resistance to gemifloxacin in Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO ACTIVITY; DNA GYRASE; STREPTOCOCCUS-PNEUMONIAE; QUINOLONE RESISTANCE; FLUOROQUINOLONE RESISTANCE; NONFLUORINATED QUINOLONES; ANTIMICROBIAL ACTIVITY; MULTIDRUG-RESISTANCE; COUMARIN ACTIVITY; ESCHERICHIA-COLI AB Gemifloxacin, a novel quinolone with potent activity against Staphylococcus aureus, was 8- to 16-fold more active against wild-type S. aureus than ciprofloxacin. The two- to fourfold increase in the MIC of gemifloxacin in genetically defined grlBA mutants and the twofold increase in a single gyrA mutant, supported by the low frequency of selection of resistant mutants at twice the MIC (7.4 X 10(-11) to 1.1 X 10(-10)), suggested similar targeting of the two enzymes by gemifloxacin. Dual mutations in both gyrase and topoisomerase IV caused a 64- to 128-fold increase in the MIC of gemifloxacin, similar to that seen with ciprofloxacin. Gemifloxacin also had similar activity in vitro against topoisomerase IV and gyrase purified from S. aureus (50% inhibitory concentrations of 0.25 and 0.31 mug/ml, respectively). This activity was 10- to 20-fold higher than that of ciprofloxacin for topoisomerase IV and 33-fold higher than that for gyrase. In contrast to the in vitro findings, only topoisomerase IV mutants were selected in first-step mutants. Overexpression of the NorA efflux pump had a minimal effect on resistance to gemifloxacin, and a mutation in the promoter region of the gene for NorA was selected only in the sixth step of serial selection of mutants. Our data show that although gemifloxacin targets purified topoisomerase IV and gyrase similarly in vitro, topoisomerase IV is the preferred target in the bacteria. Selection of novel resistance mutations in grlA requires further expansion of quinolone-resistance-determining regions, and their study may provide increased insight into enzyme-quinolone interactions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis & Med Serv, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI023988, R01 AI23988] NR 52 TC 21 Z9 22 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2003 VL 47 IS 1 BP 274 EP 282 DI 10.1128/AAC.47.1.274-282.2003 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 631CL UT WOS:000180149600042 PM 12499202 ER PT J AU Sazani, P Astriab-Fischer, A Kole, R AF Sazani, P Astriab-Fischer, A Kole, R TI Effects of base modifications on antisense properties of 2 '-O-methoxyethyl and PNA oligonucleotides SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID CATIONIC LIPIDS; CYTOSINE ANALOG; NUCLEIC-ACIDS; PHOSPHOROTHIOATE; OLIGODEOXYNUCLEOTIDES; DELIVERY; BINDING; CONJUGATION; EXPRESSION; OLIGOMERS AB A recently developed antisense splicing assay was used to determine the relative activities of 2'-O-methoxyethoxy (2'-MOE) phosphorothioate oligonucleotides containing base modifications. In the assay, RNase H-inactive oligonucleotides are used to block aberrant splicing and restore correct splicing of an Enhanced Green Fluorescence Protein (EGFP) reporter pre-mRNA stably expressed in HeLa cells. Thus, the extent of EGFP upregulation is proportional to the antisense activity of the tested molecule. The base modifications included C-5 propynyl analogs of uridine and cytidine and phenoxazine and G-clamp analogs of cytosine. Base-modified 2'-MOE oligonucleotides were delivered to the HeLa EGFP-654 test cells by cationic lipid transfection or scrape-loading or without any delivery method (free uptake). When delivered with a cationic lipid, the G-clamp and phenoxazine oligomers showed increases in activity over the unmodified 2'-MOE parent compound. However, when delivered by scrape-loading or without a delivery method, the unmodified oligomer performed best. The results suggest that base modifications do not enhance the free uptake activity of RNase H inactive 2-MOE oligomers. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. RP Sazani, P (reprint author), Massachusetts Gen Hosp, Wellman 9, Boston, MA 02114 USA. FU PHS HHS [P01-59299] NR 30 TC 21 Z9 21 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PY 2003 VL 13 IS 3 BP 119 EP 128 DI 10.1089/108729003768247583 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 711CT UT WOS:000184722400001 PM 12954112 ER PT S AU Sisterson, JM AF Sisterson, JM BE Duggan, JL Morgan, IL TI Status of ion beam therapy in 2002 SO APPLICATION OF ACCELERATORS IN RESEARCH AND INDUSTRY SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 17th International Conference on the Application of Accelerators in Research and Industry CY NOV 12-16, 2002 CL UNIV N TEXAS, DENTON, TX SP Natl Sci Fdn, US DOE HO UNIV N TEXAS ID PROTON AB Dose distributions produced by using proton and ion beams in radiation therapy conform closely to the target volume maximizing the sparing of adjacent normal tissues and sensitive structures. Worldwide, through 2001, over 30.000 patients have been treated with proton beams and over 3,500 with ion beams. In 2002, there are 21 operating proton therapy facilities, including several hospital-based dedicated facilities. Seven of these facilities are limited to treating eye tumors only. Carbon ions are available at two facilities in Japan and one in Germany. All existing centers use either a cyclotron or a synchrotron and several facilities have one gantry or more to provide beams at any angle to the patient. For several treatment sites, there are good long-term follow-up results, increasing the interest worldwide in having proton or ion beams more readily available. As a result many new facilities are under construction or being planned and some existing facilities are being upgraded. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Sisterson, JM (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0149-7 J9 AIP CONF PROC PY 2003 VL 680 BP 1077 EP 1080 PG 4 WC Nuclear Science & Technology; Physics, Applied; Physics, Atomic, Molecular & Chemical SC Nuclear Science & Technology; Physics GA BX88G UT WOS:000186713800243 ER PT J AU Fu, W Cockerell, CJ AF Fu, W Cockerell, CJ TI The actinic (solar) keratosis - A 21st-century perspective SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; INTRAEPITHELIAL NEOPLASIA; NATURAL-HISTORY C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Cockerell, CJ (reprint author), 2330 Butler St,Suite 115, Dallas, TX 75235 USA. NR 24 TC 71 Z9 75 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2003 VL 139 IS 1 BP 66 EP 70 DI 10.1001/archderm.139.1.66 PG 5 WC Dermatology SC Dermatology GA 636LE UT WOS:000180456700012 PM 12533168 ER PT J AU Anderson, RR AF Anderson, RR TI Dermatologic history of the ruby laser - The long story of short pulses SO ARCHIVES OF DERMATOLOGY LA English DT Article ID PORT-WINE STAIN; DYE-LASER; HAIR REMOVAL; TATTOOS; DAMAGE; TEMPERATURE; THERAPY; TERM C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St,MGH BHX 630, Boston, MA 02114 USA. NR 34 TC 15 Z9 15 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2003 VL 139 IS 1 BP 70 EP 74 DI 10.1001/archderm.139.1.70 PG 5 WC Dermatology SC Dermatology GA 636LE UT WOS:000180456700013 PM 12533169 ER PT J AU Wang, XR Pan, LD Zhang, HX Sun, BX Dai, HL Christiani, DC AF Wang, XR Pan, LD Zhang, HX Sun, BX Dai, HL Christiani, DC TI Lung function, airway reactivity, and atopy in newly hired female cotton textile workers SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article DE atopy; cotton dust; endotoxin; occupational lung disease; pulmonary function; respiratory symptoms; textile workers ID ACROSS-SHIFT DROP; PULMONARY-FUNCTION; DUST EXPOSURE; BRONCHIAL REACTIVITY; LONGITUDINAL CHANGES; FEV(1); RESPONSIVENESS; ENDOTOXIN AB To assess changes in lung function and airway reactivity resulting from exposure to cotton dust, and the role of atopic status in these changes, the authors observed a group of 225 newly hired Chinese textile workers for 1 yr. All workers were female, lifelong nonsmokers, and none of them had been exposed previously to cotton or other occupational dust. Atopic status was determined at baseline. Spirometry, response to methacholine challenge, and total serum immunoglobulin E level were examined at baseline and again after subjects began work in the cotton mills. Obvious cross-shift drops in forced expiratory volume in 1 sec (FEV1.0), and declines in forced vital capacity and FEV1.0 over 1 yr, were observed. Atopic workers had a significantly greater acute drop in FEV1.0 than did nonatopic workers. Both atopic and nonatopic workers had slightly increased airway reactivity at 1 yr, compared with baseline values. The results suggest that exposure to cotton dust is responsible for acute and longitudinal declines in lung function, as well as for slightly increased airway reactivity. Atopy may interact with cotton dust to accentuate the acute lung function response. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02215 USA. First Hosp Shanghai Text Bur, Shanghai, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02215 USA. RI Lin, Sihao/A-8412-2012 FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OH02421] NR 30 TC 9 Z9 10 U1 0 U2 0 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 JAN PY 2003 VL 58 IS 1 BP 6 EP 13 DI 10.3200/AEOH.58.1.6-13 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 674CR UT WOS:000182619700001 PM 12747513 ER PT J AU Harlow, BL Wise, LA Otto, MW Soares, CN Cohen, LS AF Harlow, BL Wise, LA Otto, MW Soares, CN Cohen, LS TI Depression and its influence on reproductive endocrine and menstrual cycle markers associated with perimenopause - The Harvard Study of Moods and Cycles SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENOPAUSE; WOMEN; PREVALENCE; SYMPTOMS; AGE; TRANSITION AB Background: Few studies have determined the impact of a lifetime history of major depression on an early transition to menopause. Methods: Reproductive and psychiatric interviews and early follicular-phase blood specimens were obtained at study enrollment and every 6 months during 36 months of follow-up from 332 women with and 644 women without a history of major depression, 36 to 45 years of age. We used menstrual cycle markers to determine inception of perimenopause, defined as time from study enrollment to a follow-up interview with: (1) 7-day or more change in menstrual cycle length; (2) a change in menstrual flow amount or duration; or (3) amenorrhea lasting at least 3 months. Results: Women with a history of depression had 1.2 times the rate of perimenopause of women with no such history (95% confidence interval, 0.9-1.6). Compared with nondepressed women, depressed women with more pronounced depressive symptoms at study enrollment (Hamilton Rating Scale for Depression scores >8) had twice the risk of an earlier perimenopausal transition. Among the women with greater depressive symptoms (Hamilton scores >8), those who also reported use of antidepressants had nearly 3 times the risk of an earlier perimenopausal transition (hazard ratio, 2.7; 95% confidence interval, 1.5-4.8) of nondepressed women. Women with a lifetime history of depression also had higher follicle-stimulating hormone and luteinizing hormone levels and lower estradiol levels at study enrollment and during the follow-up period after adjustment for covariates. Conclusion: A lifetime history of major depression may be associated with an early decline in ovarian function. C1 Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. RP Harlow, BL (reprint author), Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. FU NIMH NIH HHS [R01-MH-50013] NR 31 TC 121 Z9 132 U1 1 U2 9 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 JAN PY 2003 VL 60 IS 1 BP 29 EP 36 PG 8 WC Psychiatry SC Psychiatry GA 633MJ UT WOS:000180286800004 PM 12511170 ER PT J AU Li, WJ Gragoudas, ES Egan, KM AF Li, WJ Gragoudas, ES Egan, KM TI Tumor basal area and metastatic death after proton beam irradiation for choroidal melanoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CILIARY BODY MELANOMA; UVEAL MELANOMA; PROGNOSTIC FACTORS; SURVIVAL; MICROCIRCULATION; ENUCLEATION; REGRESSION; RATES AB Background: Tumor dimension is an established prognostic factor for metastasis-related death after radiotherapy for uveal melanoma. Objective: To compare various methods of modeling the relationship between tumor dimension and metastatic death. Patients and Methods: The analyses were based on a consecutive series of 1204 patients with primary choroidal melanoma treated with proton beam irradiation (70 cobalt-gray equivalent in 5 fractions) at the Harvard Cyclotron Laboratory, Boston, Mass, between January 1985 and December 1998. Largest basal diameter and largest perpendicular basal diameter were recorded at the time of surgical placement of tantalum rings used for tumor localization during proton treatment. The height of the tumor and the axial diameter of the eye were measured by ultrasonography prior to treatment. Using proportional hazards regression, we compared the prognostic influence of different indices of tumor size with estimated risk ratios and death rates according to tumor basal area and largest basal diameter. All estimates were adjusted for other established prognostic factors. Results: Patients were followed up annually through June 30, 2000. Of the 1204 patients analyzed, 193 died of melanoma metastasis. The median follow-up among survivors was 7.9 years. The 5- and 10-year metastatic death rates were 12.8% and 20.7%, respectively. Among various approaches for modeling tumor dimension, the logarithm of tumor basal area had the highest log-likelihood and performed better than other approaches in 85% of the simulations. Based on this model, the covariate-adjusted rate ratio for any doubling in tumor basal area was 1.92 (95% confidence interval, 1.62-2.28). Conclusion: Tumor basal area is a better prognostic indicator than largest tumor diameter and tumor volume in the prediction of metastatic death after proton beam irradiation for uveal melanoma. C1 Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. Tufts New England Med Ctr, Div Clin Care Res, Biostat Res Ctr, Boston, MA USA. RP Egan, KM (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Med Ctr E,Suite 6000, Nashville, TN 37232 USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 35 TC 12 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2003 VL 121 IS 1 BP 68 EP 72 PG 5 WC Ophthalmology SC Ophthalmology GA 633WD UT WOS:000180306800008 PM 12523887 ER PT J AU Yueh, B Weaver, EM Bradley, EH Krumholz, HM Heagerty, P Conley, A Sasaki, CT AF Yueh, B Weaver, EM Bradley, EH Krumholz, HM Heagerty, P Conley, A Sasaki, CT TI A critical evaluation of critical pathways in head and neck cancer SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Head-and-Neck-Society CY MAY 11, 2002 CL BOCA RATON, FLORIDA SP Amer Head Neck Surg ID ACUTE MYOCARDIAL-INFARCTION; CONTROLLED TRIAL; HOSPITAL STAY; CARE; MANAGEMENT; QUALITY; IMPLEMENTATION; LARYNGECTOMY; PROTOCOLS; EFFICACY AB Background: Critical pathways have been purported to decrease resource utilization in the management of head and neck cancer. Prior reports have documented shorter lengths of stay (LOS) for pathway patients than for historical cohorts. Objective: To critically evaluate the impact of critical pathways on LOS after laryngectomy. Design: Length-of-stay trends of 2 concurrent observational cohorts of laryngectomy patients (September 1992 to February 1999) were compared, I at each of 2 medical centers. One center instituted a critical pathway for laryngectomy patients in February 1997; the other never used such pathways. In addition, we examined the independent impact of the critical path way at the pathway institution after controlling for date of laryngectomy (which reflected temporal trends) and other confounding variables. Results: Both centers experienced reductions in LOS after February 1997, but there was no statistically significant difference between the reductions (1.9 days at the pathway center vs 1.5 days at the nonpathway center; P>.05). Multivariable linear and linear spline regression models demonstrated that the use of critical pathways at the pathway institution had no statistically significant impact on LOS after controlling for the date of laryngectomy. Conclusions: Pathway implementation has a limited direct impact on LOS in relatively low-volume procedures such as laryngectomy. Although pathways may influence utilization trends, their impact is likely mediated by the development and educational process that accompanies pathway adoption rather than implementation of the pathway itself. The inclusion of temporal trends and contemporary cohorts provides substantial insight into the effectiveness of critical pathways. C1 Vet Affairs Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Yale Univ, Div Hlth Policy & Adm, Dept Epidemiol, New Haven, CT USA. Yale Univ, Div Hlth Policy & Adm, Dept Publ Hlth, New Haven, CT USA. Yale Univ, Med Sect Cardiol, New Haven, CT USA. Yale Univ, Dept Surg, Otolaryngol Sect, New Haven, CT USA. Yale Univ, Ctr Outcomes Res & Evaluat, New Haven, CT USA. RP Yueh, B (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, 112OTO,1660 S Columbian Way, Seattle, WA 98108 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 28 TC 7 Z9 8 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 JAN PY 2003 VL 129 IS 1 BP 89 EP 95 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 634DU UT WOS:000180325400014 PM 12525201 ER PT J AU Roth, SI Faquin, WC AF Roth, SI Faquin, WC TI The pathologist's intraoperative role during parathyroid surgery SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roth, SI (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. NR 2 TC 6 Z9 6 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 JAN PY 2003 VL 127 IS 1 BP 15 EP 15 PG 1 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 639MZ UT WOS:000180634500001 PM 12562272 ER PT J AU Jellinek, MS AF Jellinek, MS TI Mirror, mirror on the wall - Are we prescribing the right psychotropic medications to the right children using the right treatment plan? SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material ID MANAGED CARE; HEALTH C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Bulfinch 351, Boston, MA 02114 USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JAN PY 2003 VL 157 IS 1 BP 14 EP 16 PG 3 WC Pediatrics SC Pediatrics GA 632NP UT WOS:000180229600001 PM 12517189 ER PT J AU Doctor, JN Wolfson, AM McKnight, P Burns, SP AF Doctor, JN Wolfson, AM McKnight, P Burns, SP TI The effect of inaccurate FIM instrument ratings on prospective payment: A study of clinician expertise and FIM rating difficulty as contributing to inaccuracy SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE outcome assessment (health care); prospective payment system; rehabilitation ID FUNCTIONAL INDEPENDENCE MEASURE; JUDGMENTS; SYSTEM AB Objective: To test whether clinician expertise and FIM(TM) instrument rating difficulty explain clinician overconfidence in FIM rating accuracy. Design: Participants answered 60 true/false FIM questions and, for each question. completed a 6-category scale to assess confidence in the accuracy of their responses. Experts and novices, as well as hard and easy items, Were identified through a Rasch analysis, The relation between confidence and accuracy was examined for these different groups. Setting: Three urban medical centers. Participants: Fifty medical rehabilitation professionals, including physical therapists, occupational therapists, rehabilitation psychologists, speech pathologists, and rehabilitation nurses. Interventions: Not applicable. Main Outcome Measures: Observed proportion of correct responses to 60 true/false questions and responses from the 6-category confidence scale. Results: The amount of overconfidence was mediated by the difficulty of the FIM task and the level of expertise of the clinical,judge. Conclusions: Decreasing the level of overconfidence in FIM scoring is a promising avenue for improving the accuracy of functional assessment. Accurate assessment of functional status for case-mix group classification will be of even greater importance under the recently initiated Medicare prospective payment system. C1 Univ Washington, Dept Med Educ, Div Biomed & Hlth Informat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. Rehabil Psychol Associates LLC, New Orleans, LA USA. Univ Arizona, Dept Psychol, Evaluat Grp Anal Data, Tucson, AZ 85721 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Doctor, JN (reprint author), Univ Washington, Dept Med Educ, Div Biomed & Hlth Informat, Box 357240, Seattle, WA 98195 USA. FU NICHD NIH HHS [K01HD01221] NR 17 TC 2 Z9 2 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2003 VL 84 IS 1 BP 46 EP 50 DI 10.1053/apmr.2003.50063 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 634YM UT WOS:000180370100007 PM 12589619 ER PT J AU Cooper, RA Wolf, E Fitzgerald, SG Boninger, ML Ulerich, R Ammer, WA AF Cooper, RA Wolf, E Fitzgerald, SG Boninger, ML Ulerich, R Ammer, WA TI Seat and footrest shocks and vibrations in manual wheelchairs with and without suspension SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE cumulative trauma disorders; rehabilitation; vibration; wheelchairs ID WHOLE-BODY VIBRATION; APPARENT MASS; BIOMECHANICS; SUBJECT; POSTURE; IMPACT; DESIGN; MODEL; PAIN AB Objective: To examine differences in the shock and vibration transmitted to an occupant of a manual wheelchair with and Without suspension caster forks and with and without rear-suspension systems. Design: Repeated-measures engineering testing, Setting: Rehabilitation engineering center With a wheelchair standards test laboratory. Specimens: Six manual wheelchairs. Interventions: An American National Standards Institute/Rehabilitation Engineering and Assistive Technology Society of North America wheelchair test dummy and a Hybrid III test dummy were used to test shock and vibration transmission in wheelchairs equipped with original equipment manufacturer (OEM) caster forks and suspension caster forks. Ultralight wheelchairs, half of which had factory-equipped rear-suspension systems, were tested. Testing was conducted on a double-drum wheelchair test machine. Main Outcome Measures: Shocks were examined by using peak acceleration and the frequency at which peak acceleration occurs for the seat and footrest. Vibration was characterized by the acceleration power per octave for the seat and footrest, Results: Significant differences were found in the peak accelerations at the seat (P=.0004) and footrest (P=.0007) between the Wheelchairs with the OEM caster forks and those with the suspension casters, The wheelchairs with suspension had significantly different frequencies at which the peak accelerations occurred for both the seat (P=.01) and footrest (P=.0001). The wheelchairs with suspension caster forks had a lower total power per octave than the wheelchairs with the OEM caster forks. For the footrest vibrations, significant differences Were found between the types of caster forks for all octaves except those associated with frequencies more than 78.75Hz. There were significant differences for wheelchairs with and without rear suspension for total power per octave of seat vibrations in the octaves between 7,81 and 9.84Hz (P=.01) and 12.40 and 15,63Hz (P=.008). Conclusions: Suspension caster forks reduce the shock and vibration exposure to the user of a manual wheelchair, Rear-suspension systems reduce some of the factors related to shock and vibration exposure, but they are not clearly superior to traditional designs. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Lab, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Lab, 151 R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper+@pitt.edu OI Wolf, Erik/0000-0002-6353-7978; Boninger, Michael/0000-0001-6966-919X NR 31 TC 21 Z9 21 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2003 VL 84 IS 1 BP 96 EP 102 DI 10.1053/apmr.2003.50069 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 634YM UT WOS:000180370100016 PM 12589628 ER PT J AU Cassens, U Lewinski, G Samraj, AK von Bernuth, H Baust, H Khazaie, K Los, M AF Cassens, U Lewinski, G Samraj, AK von Bernuth, H Baust, H Khazaie, K Los, M TI Viral modulation of cell death by inhibition of caspases SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE CrmA; IAP; p35; caspase; granzyme B ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; BACULOVIRUS P35 PROTEIN; GAMMA-INDUCING FACTOR; SWINE FEVER VIRUS; COWPOX VIRUS; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; INDUCED APOPTOSIS; CYTOCHROME-C; SERPIN CRMA AB Caspases are key effectors of the apoptotic process. Some of them play important roles in the immune system, being involved in the proteolytic maturation of the key cytokines, including interleukin 1beta (IL-1beta) and IL-18. The latter directs the production of interferon gamma (IFN-gamma). Among pathogens, particularly viruses express various modulators of caspases that inhibit their activity by direct binding. By evading the apoptotic process, viruses can better control their production in the infected cell and avoid the attack of the immune system. Targeting the maturation of the key cytokines involved in the initiation of (antiviral) immune response helps to avoid recognition and eradication by the immune system. The three main classes of caspase inhibitors frequently found among viruses include serine proteinase inhibitors (serpins: CrmA/SPI-2), viral IAPs (vIAPs) and p35. Their molecular mechanisms of action, structures and overall influence on cellular physiology are discussed in the review below. C1 Univ Munster, Inst Expt Dermatol, D-48149 Munster, Germany. Univ Munster, Inst Transfus Med, D-48149 Munster, Germany. Municipal Hosp, Surg Unit, PL-38300 Gorlice, Poland. Univ Dusseldorf, Inst Mol Med, D-40225 Dusseldorf, Germany. Childrens Univ Clin, Lab Clin Res, D-01307 Dresden, Germany. Univ Ulm, Dept Radiotherapy, D-89070 Ulm, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. RP Los, M (reprint author), Univ Munster, Inst Expt Dermatol, Roentgenstr 21, D-48149 Munster, Germany. OI Los, Marek/0000-0001-9518-1411 NR 93 TC 21 Z9 24 U1 0 U2 1 PU INST IMMUNOLOGY & EXPERIMENTAL THERAPY PI WROCLAW PA POLISH ACADEMY OF SCIENCES CZERSKA 12, 53-114 WROCLAW, POLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PY 2003 VL 51 IS 1 BP 19 EP 27 PG 9 WC Immunology SC Immunology GA 650KB UT WOS:000181261500003 PM 12691301 ER PT J AU Matejuk, A Dwyer, J Hopke, C Vandenbark, AA Offner, H AF Matejuk, A Dwyer, J Hopke, C Vandenbark, AA Offner, H TI 17 beta-estradiol treatment profoundly down-regulates gene expression in spinal cord tissue in mice protected from experimental autoimmune encephalomyelitis SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Article DE 17 beta estradiol; EAE; microarray; spinal cord ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; INTERFERON-GAMMA; BINDING-PROTEIN; NERVOUS-SYSTEM; RECEPTOR; CYTOKINE; CELLS; RATS; IDENTIFICATION AB It is now well documented that experimental autoimmune encephalomyeltitis (EAE) can be effectively prevented by estrogen therapy. Previously, we identified a limited set of genes that were altered in spleens of mice protected from EAE by 17beta-estradiol (E2) treatment. As a continuation of these studies, we present here transcriptional changes in genes expressed in spinal cord tissue. The Affymetrix microarray system was used to screen more than 12,000 genes from E2-treated double transgenic (BV8S2 and AV4) female mice protected from EAE vs. control mice with severe EAE. We found that estrogen therapy had a profound inhibitory effect on the expressions of many immune-related genes in spinal cords. Estrogen significantly affected the transcription of 315 genes, 302 of which were down-regulated and only 13 that were up-regulated by greater than or equal to2.4 fold. A number of genes encoding the histocompatibility complex, cytokines/receptors, chemokines, adhesion molecules, and signal transduction proteins were strongly down-regulated (>20 fold) in estrogen-treated mice to levels similar to those of the spinal cord tissue from unmanipulated mice. The identification of genes with altered expression patterns in the spinal cords of estrogen-treated mice provides unique insight into the process that ultimately results in protection against EAE. C1 Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. NR 36 TC 15 Z9 18 U1 0 U2 2 PU INST IMMUNOLOGY & EXPERIMENTAL THERAPY PI WROCLAW PA POLISH ACADEMY OF SCIENCES CZERSKA 12, 53-114 WROCLAW, POLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PY 2003 VL 51 IS 3 BP 185 EP 193 PG 9 WC Immunology SC Immunology GA 693RZ UT WOS:000183733300006 PM 12894873 ER PT J AU Chen, JQ Kuhlencordt, P Urano, F Ichinose, H Astern, J Huang, PL AF Chen, JQ Kuhlencordt, P Urano, F Ichinose, H Astern, J Huang, PL TI Effects of chronic treatment with L-arginine on atherosclerosis in ApoE knockout and ApoE/inducible NO synthase double-knockout mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; arginine; apolipoprotein E; nitric oxide ID NITRIC-OXIDE SYNTHASE; DIETARY L-ARGININE; E-DEFICIENT MICE; ENDOTHELIAL DYSFUNCTION; SUPEROXIDE GENERATION; HYPERCHOLESTEROLEMIC RABBITS; DEPENDENT VASODILATION; HEART-DISEASE; RAT AORTA; TETRAHYDROBIOPTERIN AB Objective-L-Arginine serves as a substrate for the formation of NO by the NO synthase (NOS) enzymes. In some studies, dietary supplementation Of L-arginine reduces atherosclerosis through the restoration of NO release and improvement in endothelial function. In the present study, we investigate the effect Of L-arginine supplementation on the development of atherosclerosis in a mouse model. Methods and Results-Apolipoprotein E (apoE) knockout (ko) and apoE/inducible NOS (iNOS) double-ko mice were fed a western-type diet with or without L-arginine supplementation in the drinking water (25 g/L). L-Arginine did not affect the lesion area after 16 weeks or 24 weeks in apoE ko mice. However, L-arginine negates the protective effect of iNOS gene deficiency. In contrast to apoE/iNOS dko mice without arginine supplementation, lesion areas were increased in apoE/iNOS double-ko mice with arginine supplementation at 24 weeks. This was associated with an increase in thiobarbituric acid-reactive malondialdehyde adducts, nitrotyrosine staining within lesions, and a decrease in the ratio of reduced tetrahydrobiopterin to total biopterins. Conclusions-Although L-arginine supplementation does not affect lesion formation in the western-type diet-fed apoE ko mice, it negates the protective effect of iNOS gene deficiency in this model. This raises the possibility that L-arginine supplementation may paradoxically contribute to, rather than reduce, lesion formation by mechanisms that involve lipid oxidation, peroxynitrite formation, and NOS uncoupling. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Fujita Hlth Univ, Div Mol Genet, Inst Comprehens Med Sci, Toyoake, Aichi, Japan. RP Huang, PL (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. RI Ichinose, Hiroshi/D-8986-2015 OI Ichinose, Hiroshi/0000-0001-6008-6860 FU NHLBI NIH HHS [HL-57818]; NINDS NIH HHS [NS-33335] NR 29 TC 69 Z9 70 U1 0 U2 2 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 JAN PY 2003 VL 23 IS 1 BP 97 EP 103 DI 10.1161/01.ATV.0000040223.74255.5A PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 634XB UT WOS:000180366800021 PM 12524231 ER PT J AU Blake, GJ Ostfeld, RJ Yucel, EK Varo, N Schonbeck, U Blake, MA Gerhard, M Ridker, PM Libby, P Lee, RT AF Blake, GJ Ostfeld, RJ Yucel, EK Varo, N Schonbeck, U Blake, MA Gerhard, M Ridker, PM Libby, P Lee, RT TI Soluble CD40 ligand levels indicate lipid accumulation in carotid atheroma - An in vivo study with high-resolution MRI SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE CD40 ligand; atherosclerosis; lipid pool; MRI ID SMOOTH-MUSCLE CELLS; IN-VIVO; ATHEROSCLEROTIC PLAQUE; TISSUE FACTOR; EXPRESSION; CHEMOKINES; INDUCTION; LIGATION; ACCURACY; VITRO AB Objective-The CD40/CD40 ligand pathway mediates inflammatory processes important in atherogenesis and the formation of the intraplaque lipid pool. We tested the hypothesis that plasma levels of soluble CD40 ligand are elevated in patients with evidence of a lipid pool on high-resolution magnetic resonance imaging (MRI) of carotid stenoses. Methods and Results-We recruited 49 patients with evidence of carotid atherosclerosis on ultrasonography; 3 patients could not undergo carotid MRI because of claustrophobia. The remaining 46 patients underwent high-resolution MRI of the carotid arteries. Two radiologists blinded to all other data determined the presence or absence of an intraplaque lipid pool based on the loss of signal between the 20-ms echo time (TE20) and the fat-suppressed TE55 fast spin-echo images. Plasma levels of soluble CD40 ligand were determined by ELISA. Baseline levels of soluble CD40 ligand were higher among patients with evidence of intraplaque lipid (n=14) than among those without it (n=32; median, 2.54 ng/mL; interquartile range [IQR], 1.85 to 3.52 vs median, 1.58 ng/mL; IQR, 1.21 to 2.39; P=0.02). In contrast, soluble CD40 ligand levels were not correlated with percent diameter stenosis (r=-0.19; P=0.21). The relative risk for intraplaque lipid associated with soluble CD40 ligand levels above the median was 6.0 (95% confidence interval, 1.15 to 31.23; P=0.03). The magnitude of this predictive effect did not substantially change after adjustment for traditional cardiovascular risk factors (relative risk, 5.12; 95% confidence interval, 0.78 to 33.73; P=0.09). Conclusions-Plasma levels of soluble CD40 ligand may predict patients with features of high-risk atherosclerotic lesions. These data provide novel insight into the mechanism through which elevated levels of soluble CD40 ligand may reflect cardiovascular risk in humans and illustrate the potential value of interfacing high-resolution MRI with studies of vascular inflammation. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Leducq Ctr Cardiovasc Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Lee, RT (reprint author), 65 Landsdowne St,Room 279, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [HL-48743] NR 16 TC 51 Z9 57 U1 0 U2 2 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 JAN PY 2003 VL 23 IS 1 BP E11 EP E14 DI 10.1161/01.ATV.0000050143.22910.62 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 634XB UT WOS:000180366800017 PM 12524242 ER PT J AU Montesinos, MC Desai, A Delano, D Chen, JF Fink, JS Jacobson, MA Cronstein, BN AF Montesinos, MC Desai, A Delano, D Chen, JF Fink, JS Jacobson, MA Cronstein, BN TI Adenosine A(2A) or A(3) receptors are required for inhibition of inflammation by methotrexate and its analog MX-68 SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LOW-DOSE METHOTREXATE; PLACEBO-CONTROLLED TRIAL; PROTEIN-KINASE-C; RHEUMATOID-ARTHRITIS; FOLINIC ACID; TNF-ALPHA; POLYMORPHONUCLEAR LEUKOCYTES; IMMUNOSUPPRESSIVE PROPERTIES; ANTIINFLAMMATORY MECHANISM; INDEPENDENT MECHANISMS AB Objective. Low-dose weekly methotrexate therapy remains a mainstay in the treatment of inflammatory arthritis. Results of previous studies demonstrated that adenosine, acting at one or more of its receptors, mediates the antiinflammatory effects of methotrexate in animal models of both acute and chronic inflammation. We therefore sought to establish which receptor(s) is involved in the modulation of acute inflammation by methotrexate and its nonpolyglutamated analog MX-68 (N-[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H-1,4-benzothiazin-7-yl]-carbonyl]-L-homoglutamic acid). Methods. We studied the effects of low-dose methotrexate (0.75 mg/kg intraperitoneally [IP] every week for 5 weeks), MX-68 (2 mg/kg IP 2 days and 1 hour before induction of inflammation), dexamethasone (1.5 mg/kg IP 1 hour before induction of inflammation), or vehicle control on acute inflammation in an air-pouch model in A(2A) and A(3) receptor knockout mice. Results. Low-dose weekly methotrexate treatment increased the adenosine concentration in the exudates of all mice studied and reduced leukocyte and tumor necrosis factor alpha accumulation in the exudates of wildtype mice, but not in those of A(2A) or A(3) receptor knockout mice. Dexamethasone, an agent that-suppresses inflammation by a different mechanism, was equally effective at suppressing leukocyte accumulation in A(2A) knockout, A(3) knockout, and wild-type mice, indicating that the lack of response was specific for methotrexate and MX-68. Conclusion. These findings confirm that adenosine, acting at A(2A) and A(3) receptors, is a potent regulator of inflammation. Moreover, these results provide strong evidence that adenosine, acting at either or both of these receptors, mediates the antiinflammatory effects of methotrexate and its analog MX-68. C1 NYU, Sch Med, Dept Med, New York, NY 10016 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Merck Res Lab, W Point, PA USA. RP Cronstein, BN (reprint author), NYU, Sch Med, Dept Med, 550 1st Ave, New York, NY 10016 USA. RI Montesinos, M. Carmen/G-8852-2015 OI Montesinos, M. Carmen/0000-0003-1801-311X FU NCRR NIH HHS [M01-RR-00096]; NIAMS NIH HHS [AR-41911]; NIGMS NIH HHS [GM-56268] NR 58 TC 113 Z9 121 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JAN PY 2003 VL 48 IS 1 BP 240 EP 247 DI 10.1002/art.10712 PG 8 WC Rheumatology SC Rheumatology GA 635UT UT WOS:000180418500029 PM 12528125 ER PT J AU Krane, SM AF Krane, SM TI Elucidation of the potential roles of matrix metalloproteinases in skeletal biology SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE arthritis; bone remodeling; collagenases; collagens; skeletal development ID MULTICENTRIC OSTEOLYSIS; COLLAGENASE CLEAVAGE; BONE-RESORPTION; I COLLAGEN; MICE; ARTHRITIS; GENE; DEFICIENT; MUTATION; DISEASE AB Irreversible destruction of joint structures is a major feature of osteoarthritis and rheumatoid arthritis. Fibrillar collagens in bone, cartilage and other soft tissues are critical for optimal joint form and function. Several approaches can be used to ascertain the role of collagenases, matrix metalloproteinases, in proteolysis of joint collagens in arthritis. These approaches include identifying spontaneous genetic disorders of the enzymes and substrates in humans and animals, as well as engineering mutations in the genes that encode these proteins in mice. Insights gained from such studies can be used to design new therapies to interrupt these catabolic events. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Krane, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Ctr Immunol & Inflammatory Dis, Bldg 149,13th St, Charlestown, MA 02129 USA. EM krane.stephen@mgh.harvard.edu FU NIAMS NIH HHS [AR-44815, AR-03564, AR-07258, R01 AR044815, T32 AR007258] NR 22 TC 13 Z9 13 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2003 VL 5 IS 1 BP 2 EP 4 DI 10.1186/ar600 PG 3 WC Rheumatology SC Rheumatology GA 660BG UT WOS:000181813600001 PM 12716440 ER PT J AU Costenbader, KH Liang, MH AF Costenbader, KH Liang, MH TI SLE - Practical and theoretical barriers to the prevention of accelerated atherosclerosis in systemic lupus erythematosus SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE atherosclerosis; cardiac risk factor; coronary artery disease; systemic lupus erythematosus ID CORONARY-ARTERY DISEASE; RISK-FACTORS; NECROPSY PATIENTS; WOMEN; MANAGEMENT; PREVALENCE; HEART AB Accelerated atherosclerotic vascular disease (ASVD) is a major cause of death in systemic lupus erythematosus (SLE). Although many authorities are calling for aggressive assessment and management of cardiac risk factors in patients with SLE, both theoretical and practical barriers to this approach exist. It seems that SLE and/or its treatment are themselves strong risk factors for the development of ASVD and it is unclear how much this risk can be decreased by the control of traditional risk factors. Studies from several centers have shown that suboptimal risk factor management and barriers to acceptance of these measures must also be studied further. C1 Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Brigham & Womens Hosp, Robert B Brigham Arthritis & Musculoskeletal Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Costenbader, KH (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM kcostenbader@partners.org FU NIAMS NIH HHS [P60 AR047782, P60 AR47782] NR 19 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2003 VL 5 IS 4 BP 178 EP 179 DI 10.1186/ar773 PG 2 WC Rheumatology SC Rheumatology GA 688JU UT WOS:000183431600012 PM 12823848 ER PT J AU Peters, JH Carsons, S Yoshida, M Ko, F McDougall, S Loredo, GA Hahn, TJ AF Peters, JH Carsons, S Yoshida, M Ko, F McDougall, S Loredo, GA Hahn, TJ TI Electrophoretic characterization of species of fibronectin bearing sequences from the N-terminal heparin-binding domain in synovial fluid samples from patients with osteoarthritis and rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article DE chondrocytes; fibronectin; osteoarthritis; rheumatoid arthritis; synovial fluid ID HUMAN ARTICULAR CHONDROCYTES; CARTILAGE CHONDROLYSIS; INCREASED EXPRESSION; INTEGRIN EXPRESSION; FRAGMENTS; MATRIX; PROTEINS; SURVIVAL; RECEPTOR; CULTURE AB Fragments of fibronectin (FN) corresponding to the N-terminal heparin-binding domain have been observed to promote catabolic chondrocytic gene expression and chondrolysis. We therefore characterized FN species that include sequences from this domain in samples of arthritic synovial fluid using one- and two-dimensional (1D and 2D) Western blot analysis. We detected similar assortments of species, ranging from similar to 47 to greater than 200 kDa, in samples obtained from patients with osteoarthritis (n= 9) versus rheumatoid arthritis (n= 10). One of the predominant forms, with an apparent molecular weight of similar to 170 kDa, typically resolved in 2D electrophoresis into a cluster of subspecies. These exhibited reduced binding to gelatin in comparison with a more prevalent species of similar to200+ kDa and were also recognized by a monoclonal antibody to the central cell-binding domain (CBD). When considered together with our previous analyses of synovial fluid FN species containing the alternatively spliced EIIIA segment, these observations indicate that the similar to 170-kDa species includes sequences from four FN domains that have previously, in isolation, been observed to promote catabolic responses by chondrocytes in vitro: the N-terminal heparin-binding domain, the gelatin-binding domain, the central CBD, and the EIIIA segment. The similar to 170-kDa N-terminal species of FN may therefore be both a participant in joint destructive processes and a biomarker with which to gauge activity of the arthritic process. C1 Sacramento VA Med Ctr, VA No Calif Hlth Care Syst, Mather, CA 95655 USA. Univ Calif Davis, Sch Med, Dept Internal Med, Davis, CA 95616 USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. W Los Angeles VA Med Ctr, VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Peters, JH (reprint author), Sacramento VA Med Ctr, VA No Calif Hlth Care Syst, 151-SMC,10535 Hosp Way, Mather, CA 95655 USA. EM John.Peters3@med.va.gov FU NIA NIH HHS [P60 AG010415, P60 AG10415] NR 36 TC 14 Z9 14 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2003 VL 5 IS 6 BP R329 EP R339 DI 10.1186/ar1001 PG 11 WC Rheumatology SC Rheumatology GA 736BT UT WOS:000186151000009 PM 14680507 ER PT J AU Ho, IC Pai, SY Truitt, ML AF Ho, IC Pai, SY Truitt, ML TI Novel function of GATA-3, revealed by conditional deficient mice SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT 3rd World Congress of the Global-Arthritis-Research-Network (GARN) CY SEP 14-17, 2003 CL Miyakazi, JAPAN C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2003 VL 5 SU 3 MA 80 BP S26 EP S26 DI 10.1186/ar881 PG 1 WC Rheumatology SC Rheumatology GA 801SX UT WOS:000220116700082 ER PT J AU Lee, D Brenner, M Gerard, C Benoist, C Mathis, D Watts, G AF Lee, D Brenner, M Gerard, C Benoist, C Mathis, D Watts, G TI Synovial mast cells require C5a receptor (CD88) for arthritis induction SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT 3rd World Congress of the Global-Arthritis-Research-Network (GARN) CY SEP 14-17, 2003 CL Miyakazi, JAPAN C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2003 VL 5 SU 3 MA 8 BP S3 EP S4 DI 10.1186/ar809 PG 2 WC Rheumatology SC Rheumatology GA 801SX UT WOS:000220116700010 ER PT J AU Fishman, JA AF Fishman, JA TI Xenotransplantation - a model for surveillance of unknown pathogens SO ASM NEWS LA English DT Article ID ENDOGENOUS RETROVIRUS AB Despite potential benefits, assessing of infectious risks of xenotransplants will be central to their acceptance. C1 Massachusetts Gen Hosp, Transplantat Infect Dis & Compromised Host Progra, Infect Dis Unit, Boston, MA USA. Massachusetts Gen Hosp, Transplantat Infect Dis & Compromised Host Progra, Transplantat Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD JAN PY 2003 VL 69 IS 1 BP 18 EP 24 PG 7 WC Microbiology SC Microbiology GA 636DA UT WOS:000180438200012 ER PT S AU Singh, BN Sarma, JSM AF Singh, BN Sarma, JSM BE Papp, JG Straub, M Ziegler, D TI Mechanisms of antiarrhythmic actions in the maintenance of sinus rhythm in patients with atrial fibrillation: Clinical and experimental correlations SO ATRIAL FIBRILLATION: NEW THERAPEUTIC CONCEPTS SE SOLVAY PHARMACEUTICALS CONFERENCES LA English DT Proceedings Paper CT 2nd Solvay-Pharmaceuticals Conference CY NOV 28-30, 2001 CL Budapest, HUNGARY SP Solvay Pharmaceut DE class III antiarrhythmic actions; rate-dependent property; atrial-specific antifibrillatory effects; pure class III antiarrhythmic agents ID CONGESTIVE-HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; LOW-DOSE AMIODARONE; TORSADE-DE-POINTES; ELECTRICAL CARDIOVERSION; QUINIDINE; CONVERSION; TEDISAMIL; THERAPY; FLUTTER AB Atrial fibrillation (AF) is now the commonest arrhythmia in clinical practice. It is associated with an increased mortality by a factor of two-fold, with significant morbidity, and impaired quality of life. It has not yielded uniformly well to the use of implantable atrial defibrillators or ablative techniques. Restoration and maintenance of sinus rhythm long-term by the use of antifibrillatory drugs therefore remain a desirable therapeutic goal. The ideal antiarrhythmic compound is a compound that is at least in part atrial-specific and blocks AV nodal conduction. AF occurs more frequently in patients with shorter atrial action potentials (APDs) and effective refractory periods (ERPs) than in those with longer ones. This has formed the basis for the use of class III drug actions in the control of AF. Studies of a range of class III compounds from the simplest (pure class IIIs such as dofetilide and azimilide) to the most complex ones (amiodarone and dronedarone), and those with an intermediate degree of complexity (such as dl-sotalol and tedisamil) have provided insights into the actions of antiarrhythmic drugs for use in AF. The electrophysiological property that appears to be of major clinical interest is the rate-dependent effect of the compounds on the APD and ERP. Drugs that exert the classical reverse rate dependency (dofetilide, quinidine, and dl-sotalol) appear to exhibit a similar ceiling of efficacy and a similar propensity for inducing torsades de pointes (TDP). In contrast, the actions of amiodarone and those of dronedarone are similar, as under the action of these drugs, the ERP increases in a parallel fashion over a wide range of frequencies, a phenomenon also noted in the case of azimilide. The efficacy for maintaining stability of sinus rhythm appears to be the highest in the case of amiodarone and is associated with the lowest incidence of TDP. Of much importance also is the fact that in the case of flecainide (presumably also propafenone) the atrial ER-P and APD both prolong APD and ERP (a class III action) as the cardiac frequency increases. In such a setting the drug is more effective in AF than in flutter. Such an atrial-specific action is of much theoretical and clinical importance for the synthesis and characterization of future compounds. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. RP Singh, BN (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 67 TC 13 Z9 13 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1566-7685 BN 1-58603-387-5 J9 SOLVAY PHARMACEUT PY 2003 VL 2 BP 41 EP 55 PG 15 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA BY95G UT WOS:000189503200004 ER PT S AU Bauman, ML Kemper, TL AF Bauman, Margaret L. Kemper, Thomas L. BE Bock, G Goode, J TI The neuropathology of the autism spectrum disorders: what have we learned? SO AUTISM: NEURAL BASIS AND TREATMENT POSSIBILITIES SE NOVARTIS FOUNDATION SYMPOSIUM LA English DT Article; Proceedings Paper CT Symposium on Autism - Neural Basis and Treatment Possibilities CY JUN 18-20, 2002 CL Novartis Fdn, London, ENGLAND HO Novartis Fdn ID DEFICIT HYPERACTIVITY DISORDER; DEVELOPMENTAL DYSLEXIA; CEREBELLAR CORTEX; INFANTILE-AUTISM; BRAIN; CHILDREN; LIFE; IDENTIFICATION; ABNORMALITIES; MODEL AB Autism is a behaviourally defined disorder, initially described by, Kanner in 1943. By definition, symptoms are manifested by 36 months of age and are characterized by delayed and disordered language, impaired social interaction, abnormal responses to sensory stimuli, events and objects, poor eye contact, an insistence on sameness, an unusual capacity for rote memory, repetitive and stereotypic behaviour and a normal physical appearance. Relatively few neuropathological studies have been performed on the brains of autistic subjects. Of those reported, abnormalities have been described in the cerebral cortex, the brainstem, the limbic system and the cerebellum. Although those with the disorder present with a specific set of core characteristics, each individual patient is somewhat different from another. Thus, it should not be surprising that the brains of these subjects should show a wide range of abnormalities. However, it is important to delineate the anatomic features, which are common to all cases, regardless of age, sex and IQ, in order to begin to understand the central neurobiological profile of this disorder. The results of our systematic studies indicate that the anatomic features that are consistently, abnormal in all cases include reduced numbers of Purkinje cells in the cerebellum, and small tightly packed neurons in the entothinal cortex and in the medially placed nuclei of the amygdala. It is known that the limbic system is important for learning and memory, and that the amygdala plays a role in emotion and behaviour. Research in the cerebellum indicates that this structure is important as a modulator of a variety of brain functions and impacts on language processing, anticipatory and motor planning, mental imagery and timed sequencing. Defining the differences and similarities in brain anatomy in autism and correlating these observations with detailed clinical descriptions of the patient may allow us greater insight into the underlying neurobiology of this disorder. C1 Massachusetts Gen Hosp, Childs Neurol Serv, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. RP Bauman, ML (reprint author), Massachusetts Gen Hosp, Childs Neurol Serv, 55 Fruit St, Boston, MA 02114 USA. NR 47 TC 44 Z9 45 U1 8 U2 15 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND SN 1528-2511 BN 978-0-470-85099-2 J9 NOVART FDN SYMP PY 2003 VL 251 BP 112 EP 128 PG 17 WC Medicine, General & Internal; Neurosciences; Psychiatry SC General & Internal Medicine; Neurosciences & Neurology; Psychiatry GA BGN65 UT WOS:000248830100007 PM 14521190 ER PT J AU Sanford, LD Tang, XD Ross, RJ Morrison, AR AF Sanford, LD Tang, XD Ross, RJ Morrison, AR TI Influence of shock training and explicit fear-conditioned cues on sleep architecture in mice: Strain comparison SO BEHAVIOR GENETICS LA English DT Article DE anxiety; conditioning; fear; mouse strains; rapid eye movement sleep; sleep ID INBRED MOUSE STRAINS; EYE-MOVEMENT SLEEP; CONTEXTUAL FEAR; POTENTIATED STARTLE; ANXIETY DISORDERS; C57BL/6 MICE; AMYGDALA; STATES; WAKEFULNESS; INHIBITION AB Fear conditioning is thought to model anticipatory anxiety. Inbred mouse strains exhibit different levels of reactivity to aversive environmental stimuli, which may reflect anxiety. We examined the effects of fear conditioning on sleep in mouse strains that differ on behavioral measures of anxiety. Mice (BALB/cJ [C], C57BL/6J [B6], CB6F1/J [CB6], n = 7-10 per strain) were implanted with transmitters for recording sleep by telemetry. Baseline sleep was recorded, and the mice were trained to associate a cue (tone) with footshock (15 cue-shock pairings on 4 consecutive days). Sleep was recorded after shock training and again 4 to 5 days later after presentation of the cue alone. Shock training produced a relatively selective suppression of rapid eye movement sleep (REM) that was greater in the C strain compared to the B6 and CB6 mice. Post-training exposure to the cue alone suppressed REM in all strains. The C strain exhibited a relatively greater immediate suppression of REM, and the CB6 hybrid mice showed the greatest overall suppression of REM. These data demonstrate that stimuli associated with an aversive event can alter sleep and suppress REM in much the same way as exposure to the event itself. Fear conditioning may provide a model for examining genetic and neural mechanisms underlying the influence of anxiety on sleep. C1 Eastern Virginia Med Sch, Dept Anat & Pathol, Sleep Res Lab, Norfolk, VA 23501 USA. Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Sanford, LD (reprint author), Eastern Virginia Med Sch, Dept Anat & Pathol, Sleep Res Lab, POB 1980, Norfolk, VA 23501 USA. FU NIMH NIH HHS [MH61716, MH64827]; NINDS NIH HHS [NS36694] NR 36 TC 66 Z9 69 U1 3 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JAN PY 2003 VL 33 IS 1 BP 43 EP 58 DI 10.1023/A:1021051516829 PG 16 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 614QR UT WOS:000179201400006 PM 12645821 ER PT J AU Lewandrowski, KU Bondre, SP Wise, DL Trantolo, DJ AF Lewandrowski, KU Bondre, SP Wise, DL Trantolo, DJ TI Enhanced bioactivity of a poly(propylene fumarate) bone graft substitute by augmentation with nano-hydroxyapatite SO BIO-MEDICAL MATERIALS AND ENGINEERING LA English DT Article DE bioactivity; nanohydroxyapatite; bioresorbable; bone graft substitute ID CEMENT; POLYMER AB The bioactivity of a nano-hydroxyapatite-augmented, bioresorbable bone graft substitute made from the unsaturated polyester, poly(propylene fumarate), was analyzed by evaluating biocompatibility and osteointegration of implants placed into a rat tibial defect. Three groups of eight animals each were evaluated by grouting bone graft substitutes into 3-mm holes that were made into the anteromedial tibial metaphysis of rats. Thus, a total of 24 animals was included in this study. Two different formulations varying as to the type of hydroxyapatite were used: Group 1-nano-hydroxyapatite, Group 2-micron-hydroxyapatite, with a Group 3 control defect remaining unfilled. Animals of each of the three groups were sacrificed in groups of eight at postoperative week three. Histologic analysis revealed best superior biocompatibility and osteointegration of bone graft substitutes when nanohydroxyapatite was employed. At three weeks, there was more reactive new bone formation in this group when compared to the micron-hydroxyapatite group. The control group showed incomplete closure of the defect. This study suggested that nano-hydroxyapatite may improve upon the bioactivity of bone implant and repair materials. The model scaffold used in this study, poly(propylene fumarate), appeared to provide an osteoconductive pathway by which bone will grow in faster. Clinical implications of the use potential advantages of nano-hydroxyapatite on bone repair and orthopaedic implant design are discussed. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. EM dtrantolo@aol.com FU NIAMS NIH HHS [AR 45062]; NIDCR NIH HHS [1 R43 DE13881-02] NR 18 TC 42 Z9 54 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0959-2989 J9 BIO-MED MATER ENG JI Bio-Med. Mater. Eng. PY 2003 VL 13 IS 2 BP 115 EP 124 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 681YJ UT WOS:000183062900002 PM 12775902 ER PT J AU Zhang, JH Carey, V Gentleman, R AF Zhang, JH Carey, V Gentleman, R TI An extensible application for assembling annotation for genomic data SO BIOINFORMATICS LA English DT Article AB AnnBuilder is an R package for assembling genomic annotation data. The system currently provides parsers to process annotation data from LocusLink, Gene Ontology Consortium, and Human Gene Project and can be extended to new data sources via user defined parsers. AnnBuilder differs from other existing systems in that it provides users with unlimited ability to assemble data from user selected sources. The products of AnnBuilder are files in XML format that can be easily used by different systems. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Channing Labs, Boston, MA USA. RP Zhang, JH (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. NR 3 TC 31 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN PY 2003 VL 19 IS 1 BP 155 EP 156 DI 10.1093/bioinformatics/19.1.155 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 636PA UT WOS:000180463900024 PM 12499308 ER PT J AU Weiss, AP Schacter, DL Goff, DC Rauch, SL Alpert, NM Fischman, AJ Heckers, S AF Weiss, AP Schacter, DL Goff, DC Rauch, SL Alpert, NM Fischman, AJ Heckers, S TI Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; memory; hippocampus; positron emission tomography; functional neuroimaging; cognitive remediation ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; CONSCIOUS RECOLLECTION; RECOGNITION MEMORY; DECLARATIVE MEMORY; PREFRONTAL CORTEX; EPISODIC MEMORY; FRONTAL-CORTEX; RETRIEVAL; PET AB Background: Patients with schizophrenia demonstrate poor verbal memory, ascribed to impaired prefrontal and hippocampal function. Healthy adults can increase recall accuracy following encoding interventions, such as item repetition and the formation of semantic associations. We examined the effects of these interventions on both memory performance and retrieval-related hippocampal activity in healthy adults and patients with schizophrenia. Methods: Twelve patients with schizophrenia and twelve healthy control subjects participated. During study, subjects counted either the number of meanings or T-junctions in words seen only once or repeated four times. At test, O-15-positron emission tomography scans were acquired while subjects completed word-stems with previously studied items. Results: Control subjects recalled more words overall, but both groups demonstrated similar performance benefits following deeper encoding. Both item repetition and the use of a semantic encoding task were associated with memory retrieval-related hippocampal recruitment in control but not schizophrenic participants. Patients with schizophrenia demonstrated greater activation of prefrontal cortical areas during word retrieval. Conclusions: Despite a lack of hippocampal recruitment, patients with schizophrenia showed intact modulation of memory performance following both encoding interventions. Impaired hippocampal recruitment, in concert with greater prefrontal activation, may reflect a specific deficit in conscious recollection in schizophrenia. (C) 2003 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY 9112,13th St, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH60941, MH01 763-01, MH57915] NR 50 TC 101 Z9 101 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2003 VL 53 IS 1 BP 48 EP 55 AR PII S0006-3223(02)01541-X DI 10.1016/S0006-3223(02)01541-X PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 637ME UT WOS:000180515000006 PM 12513944 ER PT J AU Braaten, EB Beiderman, J Monuteaux, MC Mick, E Calhoun, E Cattan, G Faraone, SV AF Braaten, EB Beiderman, J Monuteaux, MC Mick, E Calhoun, E Cattan, G Faraone, SV TI Revisiting the association between attention-deficit hyperactivity disorder and anxiety disorders: A familial risk analysis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; anxiety disorders; first-degree relatives; boys; girls ID CONDUCT DISORDER; PANIC DISORDER; CHILDREN; ADHD; COMORBIDITY; DEPRESSION; BEHAVIOR; PATTERNS; PARENTS; ADULTS AB Background: This study tested competing hypotheses about patterns of familial association between attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders using familial risk analysis methodology. Methods: The risk for ADHD and anxiety disorders in first-degree relatives was examined after stratifying ADHD probands by the presence or absence of comorbid anxiety disorders. The presence of anxiety disorders in probands and relatives was defined as meeting DSM-III-R diagnostic criteria for greater than or equal to2 anxiety syndromes in the same subject. Results: Familial risk analyses revealed that 1) the risk for anxiety disorders was significantly higher in ADHD probands and their relatives than in control probands and their relatives; 2) the risk for anxiety disorders among the relatives of ADHD probands was limited to those families in which the proband had a diagnosis of ADHD; 3) the riskfor anxiety disorders was significantly higher among the relatives of ADHD probands with anxiety disorders than in relatives of ADHD probands without anxiety disorders, but these two groups did not differ in the familial risk for ADHD; and 4) ADHD and anxiety disorders did not cosegregate within families, and there was no evidence for nonrandom (assortative) mating. Conclusions: These findings are most consistent with the hypothesis that ADHD and anxiety disorders segregate independently in families. (C) 2003 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Beiderman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 41314-07] NR 29 TC 19 Z9 20 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2003 VL 53 IS 1 BP 93 EP 99 AR PII S0006-3223(02)01434-8 DI 10.1016/S0006-3223(02)01434-8 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 637ME UT WOS:000180515000011 PM 12513949 ER PT S AU Whitcomb, DC AF Whitcomb, DC BE Ogawa, M Yamamoto, T Hirota, M TI Molecular and genetic mechanisms of acute and chronic pancreatitis SO BIOLOGICAL RESPONSE TO PLANNED AND UNPLANNED INJURIES: CELLULAR, MOLECULAR AND GENETIC ASPECTS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 19th Kumamoto Medical Bioscience Symposium CY NOV 07-08, 2002 CL KUMAMOTO, JAPAN DE pancreatitis; trypsin; CFTR; pancreatic secretory trypsin inhibitor; SPINK1 ID CATIONIC TRYPSINOGEN GENE; HEREDITARY PANCREATITIS; STELLATE CELLS; CALCIUM-CARBONATE; RAT PANCREAS; MUTATIONS; ACTIVATION; CLASSIFICATION; PROTEIN; IDENTIFICATION AB Hereditary pancreatitis is a rare, autosomal dominant disorder characterized by acute pancreatitis, chronic pancreatitis and a very high risk for pancreatic cancer. Over 300 families have been identified, with the majority originating in Europe. The cause of most of the cases is from mutations in the cationic trypsinogen gene, or PRSS1. The three most common mutations are R122H, N291 and R122C. The mutations are thought to cause gain-of-function mutations so that typsinogen is either more easily activated, or active trypsin has delayed degradation. Research focused on the amino acids mutated in hereditary pancreatitis teach us about the central role of trypsin in the initiation of acute pancreatitis, and how the pancreas is normally protected from trypsin. The link between SPINK1 and trypsin activation further supports these concepts. Hereditary pancreatitis also teaches us about chronic pancreatitis. In this case, chronic pancreatitis develops in patients with recurrent acute pancreatitis. The unifying sentinel acute pancreatitis event (SAPE) model is reviewed. There are several major unanswered questions. First, how are 20% of the individuals who inherit the hereditary pancreatitis gene protected from ever getting an attack of pancreatitis? Secondly, what is the cause of the pancreatitis in the 35-40% of patients who do not have trypsinogen mutations? Third, what determines the severity of pancreatitis in those who develop pancreatitis? Finally, with knowledge of the mechanisms leading to pancreatitis, what can be done to limit or prevent damage from this disease? (C) 2003 Published by Elsevier B.V. C1 Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Dept Med Cell Biol & Physiol, Pittsburgh, PA 15213 USA. RP Whitcomb, DC (reprint author), UPMC Presbyterian, M2,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 56 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-51259-4 J9 INT CONGR SER PY 2003 VL 1255 BP 49 EP 60 DI 10.1016/S0531-5131(03)00674-5 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BX83V UT WOS:000186622700008 ER PT J AU Hahn, T Wingard, JR Anderson, KC Bensinger, WI Berenson, JR Brozeit, G Carver, JR Kyle, RA McCarthy, PL AF Hahn, T Wingard, JR Anderson, KC Bensinger, WI Berenson, JR Brozeit, G Carver, JR Kyle, RA McCarthy, PL TI The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of multiple myeloma: An evidence-based review SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE multiple myeloma; systematic review; stem cell transplantation ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE THERAPY; MINIMAL RESIDUAL DISEASE; DONOR LYMPHOCYTE INFUSIONS; PROGRESSION-FREE SURVIVAL; POLYMERASE-CHAIN-REACTION; CIRCULATING TUMOR-CELLS; FIRST-LINE TREATMENT; TERM FOLLOW-UP; PHASE-II TRIAL AB Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of multiple myeloma (MM) is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published medical literature and for grading the quality of the evidence, the strength of the evidence, and the strength of the treatment recommendations. Treatment recommendations based on the evidence presented in the review were made unanimously by a panel of MM experts. Recommendations for SCT as an effective therapy for MM include the following: SCT is preferred to standard chemotherapy as de novo therapy; SCT is preferred as de novo rather than salvage therapy; autologous peripheral blood stem cell transplantation (PBSCT) is preferred to bone marrow transplantation (BMT); and melphalan is preferred to melphalan plus total body irradiation as the conditioning regimen for autologous SCT. Recommendations that SCT is not effective include the following: current purging techniques of bone marrow. Recommendations of equivalence include the following: PBSCT using CD34+ selected or unselected stem cells. No recommendation is made for indications or trunsplantation techniques that have not been adequately studied, including the following: SCT versus standard chemotherapy as salvage therapy, tandem autologous SCT, autologous or allogeneic SCT as a high-dose sequential regimen, allogeneic BMT versus PBSCT, a preferred allogeneic myeloablative or non-myeloablative conditioning regimen, and maintenance therapy post-autologous SCT with interferon alpha post-SCT. The priority area of needed future research is maintenance therapy posttransplantation with nothing versus interferon alpha versus other agents such as corticosteroids or thalidomide or its derivatives. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Univ Florida, Coll Med, Gainesville, FL USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Int Myeloma Fdn, N Hollywood, CA USA. Univ Penn, Canc Res Inst, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MN USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton Sts, Buffalo, NY 14263 USA. NR 198 TC 52 Z9 54 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2003 VL 9 IS 1 BP 4 EP 37 DI 10.1053/bbmt.2003.50002 PG 34 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 645PC UT WOS:000180986500002 PM 12533739 ER PT J AU Rueda, BR Littell, RD Luo, HW Kirley, SD Pru, JK Zukerberg, LR AF Rueda, BR Littell, RD Luo, HW Kirley, SD Pru, JK Zukerberg, LR TI Determining the role of cables in female reproduction utilizing mutant mice. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 10 BP 115 EP 116 PG 2 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400066 ER PT J AU Pavlik, JA Hou, XY Townson, DH Rueda, BR Davis, JS AF Pavlik, JA Hou, XY Townson, DH Rueda, BR Davis, JS TI Inflammatory cytokines enhance expression of interferon regulatory factor-1 in bovine corpus luteum microvascular endothelial cells SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Univ Nebraska, Ctr Med, Dept Obstet & Gynecol, Olson Ctr Womens Hlth, Omaha, NE 68198 USA. Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH 03824 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA USA. VA Med Ctr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 45 BP 130 EP 130 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400101 ER PT J AU Liptak, AR Sullivan, BT Henkes, L Davis, JS Rueda, BR Townson, DH AF Liptak, AR Sullivan, BT Henkes, L Davis, JS Rueda, BR Townson, DH TI Cooperative expression of monocyte chemoattractant protein-1 MCP-1) within the bovine corpus luteum: Immune cell-endothelial cell interactions in a co-culture system SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH 03824 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA USA. Univ Nebraska, Ctr Med, Dept Obstet & Gynecol, Omaha, NE 68198 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 74 BP 143 EP 143 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400130 ER PT J AU Wilson-Rawls, J Hahn, K Johnson, J AF Wilson-Rawls, J Hahn, K Johnson, J TI Lunatic fringe (Lfng) null female mice are infertile due to a meiotic defect. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Arizona State Univ, Sch Life Sci, Tempe, AZ USA. Arizona State Univ, Grad Program Mol & Cellular Biol, Tempe, AZ USA. Harvard Univ, Sch Med, Vincent Ctr Reprod Biol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 263 BP 220 EP 221 PG 2 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400318 ER PT J AU Henkes, LE Lynch, MP Rueda, BR AF Henkes, LE Lynch, MP Rueda, BR TI Defining the apoptotic potential of specific members of the sphingomyelin pathway in murine luteinized granulosa cells. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 288 BP 231 EP 231 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400343 ER PT J AU Kaneko, T Ge, RL Kolesnick, RN Pru, JK AF Kaneko, T Ge, RL Kolesnick, RN Pru, JK TI Sphingolipid signaling coordinates decldual cell cox-2 expression. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 312 BP 241 EP 241 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400367 ER PT J AU Pru, JK Kollara, A Johnson, J Brown, TJ AF Pru, JK Kollara, A Johnson, J Brown, TJ TI Pharmacologic ligands of the aryl hydrocarbon receptor repress cell cycle regulatory genes in the decidua of early pregnancy. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Div Reprod Sci, Toronto, ON M5G 1X5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 314 BP 241 EP 242 PG 2 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400369 ER PT J AU Styer, AK Pru, JK Lynch, MP Rueda, BR AF Styer, AK Pru, JK Lynch, MP Rueda, BR TI Gene array comparison of survivin expression between preovulatory granulosa cells and corpora lutea of mid and late pregnancy. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 469 BP 305 EP 305 PG 1 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400523 ER PT J AU Hou, XY Arvisais, E Hansen, TR Rueda, BR Davis, JS AF Hou, XY Arvisais, E Hansen, TR Rueda, BR Davis, JS TI Evidence for cytokine-mediated gene expression in PGF(2 alpha)-induced corpus luteum regression. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 36th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 19-22, 2003 CL CINCINNATI, OHIO SP Soc Study Reproduct C1 Univ Nebraska, Ctr Med, Olson Ctr Womens Hlth, Omaha, NE 68182 USA. VA Med Ctr, Omaha, NE USA. Univ Wyoming, Laramie, WY 82071 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2003 VL 68 SU 1 MA 473 BP 306 EP 307 PG 2 WC Reproductive Biology SC Reproductive Biology GA 695FX UT WOS:000183821400527 ER PT B AU Guinan, JJ Cooper, NP AF Guinan, JJ Cooper, NP BE Gummer, AW TI Fast effects of efferent stimulation on basilar membrane motion SO BIOPHYSICS OF THE COCHLEA: FROM MOLECULES TO MODELS LA English DT Proceedings Paper CT Conference on Biophysics of the Cochlea - Molecules to Models CY JUL 27-AUG 07, 2002 CL TITISEE, GERMANY ID GUINEA-PIG COCHLEA; FREQUENCY TONES; DISPLACEMENT; RESPONSES AB To aid in understanding the mechanisms by which medial olivocochlear efferents produce their effects, we measured basilar membrane (BM) motion in response to tones in the basal turn of guinea pigs, with and without electrical stimulation of efferents, using a paradigm that selected only efferent fast effects. As previously reported, efferents produced (1) a reduction in BM motion for low-level tones near the charactristic frequency (CF), (2) an enhancement of BM motion for high-level tones above-CF, and (3) at most small effects for tones an octave or more below CF. In addition, we found consistent changes in BM phase: (1) a phase lead at CF increasing to about 45 degrees above CF, and (2) below CF, small phase lags at low levels, sometimes becoming phase leads at high levels. We hypothesize that the efferent enhancement of BM motion is due to the reduction of one of two out-of-phase components of BM motion. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Eaton Peabody Lab, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu; nigel.cooper@bristol.ac.uk NR 10 TC 8 Z9 8 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-238-304-2 PY 2003 BP 245 EP 251 DI 10.1142/9789812704931_0035 PG 7 WC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology SC Acoustics; Biophysics; Cell Biology; Otorhinolaryngology GA BCM39 UT WOS:000229998300035 ER PT J AU Tung, CH Zeng, Q Ho, NH Weissleder, R AF Tung, CH Zeng, Q Ho, NH Weissleder, R TI In vivo imaging of thrombosis-associated enzymes using fluorescence peptide probes SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA O69 BP 300 EP 300 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800110 ER PT J AU Pham, W Weissleder, R Tung, CH AF Pham, W Weissleder, R Tung, CH TI Peptide-based optical probes specific for matrix metalloproteinases activity detection SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P003 BP 306 EP 306 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800128 ER PT J AU Ho, NH Weissleder, R Tung, CH AF Ho, NH Weissleder, R Tung, CH TI New approach for peptide ligation SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P167 BP 341 EP 341 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800290 ER PT J AU Remmer, HA Ambulos, NP Bonewald, LF Dougherty, JJ Eisenstein, E Fowler, E Johnson, J Khatri, A Lively, MO Ritter, N Weintraub, ST AF Remmer, HA Ambulos, NP Bonewald, LF Dougherty, JJ Eisenstein, E Fowler, E Johnson, J Khatri, A Lively, MO Ritter, N Weintraub, ST TI Synthetic peptides as certified analytical standards SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Missouri, Kansas City, MO 64108 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. Texas A&M Univ, College Stn, TX 77843 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Wake Forest Univ, Winston Salem, NC 27157 USA. NMRbiotech, Germantown, MD 20874 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P233 BP 354 EP 354 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800356 ER PT J AU Khatri, A Huang, XC Shimizu, N Gardella, TJ AF Khatri, A Huang, XC Shimizu, N Gardella, TJ TI Synthesis of conformationally constrained PTH(1-14) analogs SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P385 BP 386 EP 387 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800507 ER PT J AU Huang, Z Kumar, S Dong, CZ Liu, D Tian, S Choi, WT Wang, Y Stepensky, V Li, Y An, J Madani, N Cayabyab, M Sodroski, JG AF Huang, Z Kumar, S Dong, CZ Liu, D Tian, S Choi, WT Wang, Y Stepensky, V Li, Y An, J Madani, N Cayabyab, M Sodroski, JG TI Synthetic unnatural chemokines: Probes of receptor-ligand interactions and inhibitors of HIV-1 entry SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. Univ Illinois, Dept Chem, Urbana, IL 61801 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P393 BP 388 EP 388 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800515 ER PT J AU Zurawski, JA Cocklin, S Bajgier, J Sodroski, J Chaiken, IM AF Zurawski, JA Cocklin, S Bajgier, J Sodroski, J Chaiken, IM TI A novel biosensor assay for screening peptide antagonism of the interaction between HIV-1 envelope, CD4 and membrane-embedded CCR5. SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Drexel Univ, Coll Med, Dept Biochem, Philadelphia, PA 19102 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P395 BP 388 EP 389 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800517 ER PT J AU Quinti, L Weissleder, R Tung, CH AF Quinti, L Weissleder, R Tung, CH TI Novel fluorescent ruthenium complexes for peptide labeling SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P480 BP 406 EP 406 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800602 ER PT J AU Tung, CH Zeng, Q Ho, NH Weissleder, R AF Tung, CH Zeng, Q Ho, NH Weissleder, R TI In vivo imaging of thrombosis-associated enzymes using fluorescence peptide probes SO BIOPOLYMERS LA English DT Meeting Abstract CT 18th American Peptide Symposium CY JUL 19-23, 2003 CL BOSTON, MASSACHUSETTS C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2003 VL 71 IS 3 MA P479 BP 406 EP 406 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 696GG UT WOS:000183878800601 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 LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; CD34(+) HEMATOPOIETIC PROGENITORS; BONE-MARROW; PERIPHERAL-BLOOD; NOD/SCID MICE; TRANSENDOTHELIAL MIGRATION; TYROSINE PHOSPHORYLATION; IMMUNE RECONSTITUTION; ENDOTHELIAL-CELLS; IN-VITRO AB T-lymphocyte depletion of bone marrow grafts compromises engraftment, suggesting a facilitating mechanisim provided by the T cells that has been shown to associate with CD8(+) but not CD4(+) T cells. Explanations for this phenomenon have focused on immune targeting of residual host cells or cytokine production. We provide evidence for an alternative e mechanism based on cooperative effects on cell motility. We observed that engraftment of CD34(+) cells in a beta(2)-microglobulin-deficient nonobase diabetic/severe combined immunodeficiency (beta(2)m-/- NOD/SCID) mouse model paralled clinical observations in humans, with an enhancing effect noted from the addition of CD8(+) cells but not CD4(+) cells. This correlated with CD8(+) augmentation of CD34(+) cell homing to the bone marrow in vivo and CD8(+) cell-associated increases of CD34(+) cell transmigration through a bone marrow endothelial cell line in vitro. The cooperative interaction was not sensitive to brefeldin A inhibition of protein secretion. However, cytochalasin D-induced inhibition of CD8(+) cytoskeletal rearrangements abrogated CD34(+) transendothelial migration and impaired CD34(+) cell homing in vivo. CD8(+) cells did not migrate in tandem with CD34(+) cells or alter endothelial barrier integrity; rather, they affected phosphotyrosine-mediated signaling in CD34+ cells in response to the chemokine stromal derived factor-lot (SDF-1alpha). These data demonstrate cell-cell cooperativity between different cell types in mediating chemotactic events and provide one potential explanation for the clinically observed effect of CD8(+) cells on bone marrow transplantation. This modification of cell migration by neighboring cells provides broad possibilities for combinatorial effects between cells of different types to influence cell localization. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Indiana Univ, Sch Med, Inst Canc Res, Indianapolis, IN USA. RP Adams, GB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Bldg 149,13th St,Room 5212, Boston, MA 02129 USA. OI Foxall, Russell/0000-0001-9821-0708 NR 38 TC 33 Z9 36 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2003 VL 101 IS 1 BP 45 EP 51 DI 10.1182/blood-2002-02-0486 PG 7 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500007 PM 12393569 ER PT J AU Cristillo, AD Macri, MJ Bierer, BE AF Cristillo, AD Macri, MJ Bierer, BE TI Differential chemokine expression profiles in human peripheral blood T lymphocytes: dependence on T-cell coreceptor and calcineurin signaling SO BLOOD LA English DT Article ID CYCLOSPORINE-A; CHEMOTACTIC RESPONSIVENESS; TYROSINE PHOSPHORYLATION; PROTEIN PHOSPHATASE; RECEPTOR EXPRESSION; MOLECULAR-CLONING; IMMUNE-RESPONSES; IL-2 PRODUCTION; C ACTIVATION; TRANSCRIPTION AB The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein-coupled receptors is necessary for primary immune responses and for homing of leukocytes; to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1alpha at and MIP-1beta, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. RP Bierer, BE (reprint author), Dana Farber Canc Inst, Dana 810,44 Binney St, Boston, MA 02115 USA. NR 68 TC 15 Z9 17 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2003 VL 101 IS 1 BP 216 EP 225 DI 10.1182/blood-2002-03-0697 PG 10 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500033 PM 12393716 ER PT J AU Zhang, D Shankar, P Xu, Z Harnisch, B Chen, G Lange, C Lee, SJ Valdez, H Lederman, MM Lieberman, J AF Zhang, D Shankar, P Xu, Z Harnisch, B Chen, G Lange, C Lee, SJ Valdez, H Lederman, MM Lieberman, J TI Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPSTEIN-BARR-VIRUS; CELLULAR IMMUNE-RESPONSES; TOXIC LYMPHOCYTES-T; HIV-INFECTION; REVERSE-TRANSCRIPTASE; DIRECT VISUALIZATION; SIGNALING MOLECULES; TRANSPLANT PATIENTS; EFFECTOR FUNCTION AB Despite the frequency of HIV-specific CD8 T cells, most HIV-infected patients do not control viral replication without antiviral drugs. Although CD8 T cells are important in containing acute HIV and simian immunodeficiency virus (SIV) infection, CD8 T-cell functions are compromised in chronic infection. To investigate whether functional deficits are specific to HIV, the phenotypic and functional properties of HIV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV)-specific CD8 T cells, labeled with HILA A2.1 or B8 tetramers, were compared in 35 HIV-infected and 9 healthy donors. Cytotoxic T lymphocytes express the cytolytic molecules perforin and granzymes, and are thought to be CD45RA(+)CD27(-). Although most HIV-specific cells are antigen experienced and express granzyme A (median, 85%), few express high levels of perforin (median, 10%) or CD45RA (median, 14%) or have down-modulated CD27 (median, 12%). Perforin expression by HIV-specific cells is not significantly different from that of EBV- or CMV-specific cells in the same donors or in healthy donors. EBV- and CMV-specific cells, like HIV-specific cells, are often not cytotoxic when tested directly ex vivo. HIV-specific T-cell expression of other phenotypic markers is similar to that of EBV- and CMV-specific CD8 T cells in healthy donors. However, CMV-specific cells (and, to a lesser extent, EBV-specific cells) in HIV-infected donors are more likely to be CD27(-), CD45RA(+), and GzmA(+). These results suggest that the chance to eradicate an infection by T-cell-mediated lysis may be undermined once an infection becomes chronic. Impaired antiviral cytotoxicity during chronic infection is not specific to HIV but likely represents the immune response to chronic antigenic exposure. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Ctr AIDS Res, Cleveland, OH 44106 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pediat, 800 Huntington Ave, Boston, MA 02115 USA. RI Lange, Christoph/J-6289-2012; Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI-42519, AI-45406, AI28691, AI36219] NR 54 TC 126 Z9 133 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2003 VL 101 IS 1 BP 226 EP 235 DI 10.1182/blood-2002-03-0791 PG 10 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500034 PM 12393740 ER PT J AU Hochberg, EP Miklos, DB Neuberg, D Eichner, DA McLaughlin, SF Mattes-Ritz, A Alyea, EP Antin, JH Soiffer, RJ Ritz, J AF Hochberg, EP Miklos, DB Neuberg, D Eichner, DA McLaughlin, SF Mattes-Ritz, A Alyea, EP Antin, JH Soiffer, RJ Ritz, J TI A novel rapid single nucleotide polymorphism (SNP)-based method for assessment of hematopoietic chimerism after allogeneic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGEN; POLYMERASE-CHAIN-REACTION; VERSUS-HOST DISEASE; MIXED CHIMERISM; HEMATOLOGIC MALIGNANCIES; PARKINSONS-DISEASE; DIALLELIC GENE; GRAFT FAILURE; HUMAN GENOME AB A major end point of nonmyeloablative hematopoietic stem cell transplantation is the attainment of either mixed chimerism or full donor hematopoiesis. Because the majority of human genetic disparity is generated. by single nucleotide polymorphisms (SNPs), direct measurement of SNPs should provide a robust tool for the detection and quantitation of chimerism. Using pyrosequencing, a rapid quantitative sequencing technology, we developed a SNP-based assay for hematopoietic chimerism. Based on 14 SNPS with high allele frequencies,we were able to identify at least 1 informative SNP locus in 55 patients with HLA-identical donors. The median number of informative SNPs in related pairs was 5 and in unrelated pairs was 8 (P <.0001). Assessment of hematopoietic chimerism in posttransplantation DNA Was shown to be quantitative, accurate, and highly reproducible. The presence of 5% donor cells was reliably detected in replicate assays. Compared with current measures of engraftment based on identification of short tandem repeats (STRs), variable number of tandem repeats (VNTRs), or microsatellite, polymorphisms, this SNP-based method provides 6 more rapid and quantitative assessment of chimerism. A large panel of SNPs enhances the ability to identify an informative marker in almost all patient/donor pairs and also facilitates the simultaneous use of multiple markers to improve the statistical validity of chimerism measurements. The inclusion of SNPS that encode minor histocompatibility antigens or other genetic polymorphisms that may influence graft-versus-host disease or other transplantation outcomes can provide additional clinically relevant data. SNP-based assessment of chimerism is a promising technique that will assist in the analysis of outcomes following transplantation. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 45 TC 48 Z9 52 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2003 VL 101 IS 1 BP 363 EP 369 DI 10.1182/blood-2002-05-1365 PG 7 WC Hematology SC Hematology GA 630ZT UT WOS:000180142500056 PM 12393452 ER PT J AU Cuajungco, MP Faget, KY AF Cuajungco, MP Faget, KY TI Zinc takes the center stage: its paradoxical role in Alzheimer's disease SO BRAIN RESEARCH REVIEWS LA English DT Review DE Alzheimer's disease; zinc; copper; oxidative stress ID AMYLOID PRECURSOR PROTEIN; RAPID CELLULAR DEGENERATION; A-BETA; HYDROGEN-PEROXIDE; NEUROFIBRILLARY TANGLES; CEREBROSPINAL-FLUID; TRANSGENIC MICE; BINDING-SITE; IN-VIVO; INDUCED AGGREGATION AB There is compelling evidence that the etiology of Alzheimer's disease (AD) involves characteristic amyloid-beta (Abeta) deposition, oxidative stress, and anomalous metal-Abeta protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer's disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-beta plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Abeta, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Abeta cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer's diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Charlestown, MA 02129 USA. Bryn Mawr Coll, Bryn Mawr, PA 19010 USA. RP Cuajungco, MP (reprint author), Harvard Inst Human Genet, HIM Bldg,Rm 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 NR 154 TC 154 Z9 160 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD JAN PY 2003 VL 41 IS 1 BP 44 EP 56 AR PII S0165-0173(02)00219-9 DI 10.1016/S0165-0173(02)00219-9 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 638KT UT WOS:000180570700004 PM 12505647 ER PT J AU Rossi, S Loda, M AF Rossi, S Loda, M TI The role of the ubiquitination-proteasome pathway in breast cancer - Use of mouse models for analyzing ubiquitination processes SO BREAST CANCER RESEARCH LA English DT Review DE beta-catenin; E6-AP; mdm2; mouse models; p27; Skp 2; ubiquitin; Wnt-1 ID MAMMARY-GLAND DEVELOPMENT; PROTEIN-KINASE CK2; BETA-CATENIN; S-PHASE; ANGELMAN-SYNDROME; MICE LACKING; CYCLIN D1; APC GENE; C-MYC; P53 AB Turnover of several regulatory proteins results from targeted destruction via ubiquitination and subsequent degradation through the proteosome. The timely and irreversible degradation of critical regulators is essential for normal cellular function. The precise biochemical mechanisms that are involved in protein turnover by ubiquitin-mediated degradation have been elucidated using in vitro assays and cell culture systems. However, pathways that lead to ubiquitination of critical regulatory proteins in vivo are more complex, and have both temporal and tissue-specific differences. In vivo models will allow identification of substrates and enzymes of the ubiquitin-proteosome pathway that play important roles in selected tissues and diseases. In addition, assessment of the therapeutic efficacy of drugs designed to inhibit or enhance protein turnover by ubiquitination requires in vivo models. In the present review we describe selected examples of transgenic and knockout models of proteins that are known either to be regulated by ubiquitin-mediated degradation or to have a catalytic function in this process, and to play an important role in breast cancer. We outline the functions of these proteins in vivo and focus on knowledge gained in the comparison of in vivo behavior predicted from cell-free in vitro data or from experiments conducted in cell culture systems. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D740,44 Binney St, Boston, MA 02115 USA. OI Rossi, Sabrina/0000-0001-9122-1308 FU NCI NIH HHS [R01CA-81755] NR 56 TC 13 Z9 13 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2003 VL 5 IS 1 BP 16 EP 22 DI 10.1186/bcr542 PG 7 WC Oncology SC Oncology GA 629JN UT WOS:000180046700006 PM 12559040 ER PT J AU Varley, J Haber, DA AF Varley, J Haber, DA TI Familial breast cancer and the hCHK2 1100delC mutation: assessing cancer risk SO BREAST CANCER RESEARCH LA English DT Review DE breast; familial; hCHK2; Li -Fraumeni; penetrance ID LI-FRAUMENI-SYNDROME; DNA-DAMAGE; CHK2; P53 AB Germline mutations in the human checkpoint gene, hCHK2, were first identified in 1999 in cases of Li-Fraumeni syndrome. Recent studies have demonstrated that the hCHK2 1100delC mutation acts as a low-penetrance tumour suppressor gene in familial breast cancer not associated with mutations in BRCA1 or BRCA2. The present article describes the published studies on hCHK2 1100delC and addresses some of the key questions raised. C1 Paterson Inst Canc Res, CR UK, Dept Canc Genet, Manchester M20 4BX, Lancs, England. Massachusetts Gen Hosp, Ctr Risk Anal, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Varley, J (reprint author), Paterson Inst Canc Res, CR UK, Dept Canc Genet, Wilmslow Rd, Manchester M20 4BX, Lancs, England. NR 12 TC 10 Z9 10 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2003 VL 5 IS 3 BP 123 EP 125 DI 10.1186/bcr582 PG 3 WC Oncology SC Oncology GA 688ML UT WOS:000183439400005 PM 12793891 ER PT J AU Burstein, HJ Lieberman, G Slamon, DJ Winer, EP Klein, R AF Burstein, HJ Lieberman, G Slamon, DJ Winer, EP Klein, R TI Isolated central nervous system metastases in patients with HER2 overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 226 BP S50 EP S51 PG 2 WC Oncology SC Oncology GA 747AN UT WOS:000186783100156 ER PT J AU Harris, LN Witkiewicz, A Friedman, P Kamma, M Winer, EP Iglehart, JD Schnitt, S AF Harris, LN Witkiewicz, A Friedman, P Kamma, M Winer, EP Iglehart, JD Schnitt, S TI Response to herceptin and chemotherapy in herceptin-naive patients with HER2 3+/FISH+ breast cancer is modified by pattern of expression of insulin-like growth factor-I receptor (IGF-IR) but not epidermal growth factor receptor (EGFR) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Abbott Labs, Chicago, IL USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 316 BP S73 EP S73 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100227 ER PT J AU Lesnikoski, BA Pollard, K Eltzschig, HK Posner, M Iglehart, JD AF Lesnikoski, BA Pollard, K Eltzschig, HK Posner, M Iglehart, JD TI For outpatient breast surgery patients, paravertebral blockade improves pain control, shortens length of stay, and has a high degree of patient satisfaction when compared with current general anesthetic techniques. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 448 BP S108 EP S108 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100341 ER PT J AU Partridge, AH Gelber, S Knudsen, K Laufer, M Rosenberg, R Michele, P Rein, A Winer, EP AF Partridge, AH Gelber, S Knudsen, K Laufer, M Rosenberg, R Michele, P Rein, A Winer, EP TI A web-based survey of fertility issues in young women with breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Brigham & Womens Hosp, Young Survival Coalit, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 31 BP S15 EP S16 PG 2 WC Oncology SC Oncology GA 747AN UT WOS:000186783100044 ER PT J AU Pierce, L Levin, A Rebbeck, T Kardia, S BenDavid, M Harris, E Solin, L Haffty, B Wynen, E Gaffney, D Narod, S Metcalfe, K Dawson, L Eisen, A Whelan, T Olivotto, I Galinski, D Meirovitz, A Olopade, O Garber, J Nixon, A Merajver, S Isaacs, C Weber, B AF Pierce, L Levin, A Rebbeck, T Kardia, S BenDavid, M Harris, E Solin, L Haffty, B Wynen, E Gaffney, D Narod, S Metcalfe, K Dawson, L Eisen, A Whelan, T Olivotto, I Galinski, D Meirovitz, A Olopade, O Garber, J Nixon, A Merajver, S Isaacs, C Weber, B TI Ten-year outcome of breast-conserving surgery (BCS) and radiotherapy (RT) in women with breast cancer (BC) and germline BRCA 1/2 mutations: results from an international collaboration SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Georgetown Univ, Washington, DC USA. Dana Farber, Boston, MA USA. Univ Chicago, Chicago, IL 60637 USA. Hadassah Med Ctr, IL-91120 Jerusalem, Israel. Univ Toronto, Toronto, ON, Canada. Univ Utah, Salt Lake City, UT USA. Yale Univ, New Haven, CT USA. Chaim Sheba Med Ctr, Ramat Gan, Israel. Univ Penn, Philadelphia, PA 19104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RI Whelan, Timothy/D-3185-2017 NR 0 TC 3 Z9 3 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 5 BP S7 EP S7 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100018 ER PT J AU Pories, SE Lamb, CC Lewis, G Zurakowski, D Lotz, MM Raza, S Scheib, RG Lenahan, C Borges, V Yee, BH Moses, MA AF Pories, SE Lamb, CC Lewis, G Zurakowski, D Lotz, MM Raza, S Scheib, RG Lenahan, C Borges, V Yee, BH Moses, MA TI Urinary MMPs: potential predictors of breast cancer stage and progression. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Auburn Hosp, Cambridge, MA 02238 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 403 BP S94 EP S94 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100296 ER PT J AU Roberts, LA Dias, CCC Ngo, T Friedman, P Harris, L Solomon, N AF Roberts, LA Dias, CCC Ngo, T Friedman, P Harris, L Solomon, N TI Low-level expression of HER2 and CK19 in normal peripheral blood leukocytes SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Abbott Labs, Abbott Pk, IL 60064 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 405 BP S95 EP S95 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100298 ER PT J AU Thomas, E Bunnell, CA Vahdat, LT Schwartsberg, LS Gralow, JR Whitaker, LM Peck, R AF Thomas, E Bunnell, CA Vahdat, LT Schwartsberg, LS Gralow, JR Whitaker, LM Peck, R TI A phase I study of BMS-247550 in combination with capecitabine in patients with metastatic breast cancer previously treated with a taxane and an anthracycline SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, NY Presbyterian Hosp, New York, NY 10021 USA. W Canc Clin, Memphis, TN USA. Univ Washington, Seattle, WA 98195 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 350 BP S83 EP S83 PG 1 WC Oncology SC Oncology GA 747AN UT WOS:000186783100261 ER PT J AU Wong, ZW Isaacs, C Harris, L Ellis, MJ AF Wong, ZW Isaacs, C Harris, L Ellis, MJ TI A phase II trial of letrozole and trastuzumab for ER and/or PgR and HER2 positive metastatic breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TEXAS C1 Duke Univ, Med Ctr, Durham, NC USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 82 SU 1 MA 444 BP S106 EP S107 PG 2 WC Oncology SC Oncology GA 747AN UT WOS:000186783100337 ER PT J AU Beslija, S Bonneterre, J Burstein, HJ Gnant, M Goodwin, P Heinemann, V Jassem, J Kostler, W Krainer, M Menard, S Miles, D Petruzelka, L Possinger, K Schmid, P Stadtmauer, E Stockler, M Van Belle, S Vogel, C Wilcken, N Wiltschke, C Zielinski, CC Zwierzina, H AF Beslija, S Bonneterre, J Burstein, HJ Gnant, M Goodwin, P Heinemann, V Jassem, J Kostler, W Krainer, M Menard, S Miles, D Petruzelka, L Possinger, K Schmid, P Stadtmauer, E Stockler, M Van Belle, S Vogel, C Wilcken, N Wiltschke, C Zielinski, CC Zwierzina, H TI Consensus on medical treatment of metastatic breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Editorial Material C1 Univ Hosp Vienna, Univ Klin Innere Med 1, Dept Med 1, Klin Abt Onkol, A-1090 Vienna, Austria. Inst Oncol, Sarajevo, Bosnia & Herceg. Ctr Oscar Lambret, F-59020 Lille, France. Univ Hosp Vienna, Dept Surg, A-1090 Vienna, Austria. Univ Innsbruck Hosp, Dept Med, A-6020 Innsbruck, Austria. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. Charite, Med Klin, Berlin, Germany. Dept Radiotherapy & Oncol, Gdansk, Poland. Ist Nazl Tumori, I-20133 Milan, Italy. Guys & St Thomas Hosp, London SE1 9RT, England. Charles Univ, Dept Oncol, Prague, Czech Republic. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA. Royal Prince Alfred Hosp, Dept Med, Sydney Canc Ctr RPAH & CRGH, Camperdown, NSW 2050, Australia. Westmead Hosp, Dept Med Oncol & Palliat Care, Sydney, NSW, Australia. Univ Ziekenhuis, Ctr Oncol, Ghent, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zielinski, CC (reprint author), Univ Hosp Vienna, Univ Klin Innere Med 1, Dept Med 1, Klin Abt Onkol, 18-20 Waehringer Guertel, A-1090 Vienna, Austria. RI Goodwin, Pamela/K-1477-2013; Stockler, Martin/N-3859-2016; Petruzelka, Lubos/A-2750-2017 OI Stockler, Martin/0000-0003-3793-8724; Petruzelka, Lubos/0000-0002-4397-0635 NR 0 TC 7 Z9 7 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 81 SU 1 BP S1 EP S7 PG 7 WC Oncology SC Oncology GA 750RR UT WOS:000187012100001 ER PT J AU Burstein, HJ AF Burstein, HJ TI Hormone replacement therapy after breast cancer? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT Concensus Development Conference on the Medical Treatment of Metastatic Breast Cancer CY JAN 24-25, 2003 CL VIENNA, AUSTRIA ID POSTMENOPAUSAL WOMEN; ESTROGEN; SURVIVORS; CARCINOMA; DIAGNOSIS; MORTALITY; HISTORY; RISK C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St,Dana Bldg D1210, Boston, MA 02115 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 81 SU 1 BP S99 EP S101 PG 3 WC Oncology SC Oncology GA 750RR UT WOS:000187012100019 ER PT J AU Burstein, HJ AF Burstein, HJ TI Trastuzumab in combination with chemotherapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT Concensus Development Conference on the Medical Treatment of Metastatic Breast Cancer CY JAN 24-25, 2003 CL VIENNA, AUSTRIA DE breast cancer; chemotherapy; HER2; taxane; trastuzumab; vinorelbine ID METASTATIC BREAST-CANCER; PHASE-II; MONOCLONAL-ANTIBODY; HER2; PACLITAXEL; PLUS AB Trastuzumab has been widely studied in combination with chemotherapy. Efficacy and safety data have been established for several combination regimens. Because trastuzumab in combination with chemotherapy has been shown to improve survival for women with HER2-overexpressing metastatic breast cancer when compared to treatment with chemotherapy alone, the use of combination therapy is the preferred initial treatment for such patients. Comparative studies of combination therapy versus single agent trastuzumab therapy have not been done. The optimal trastuzumab/chemotherapy combination is not known, nor is the optimal time of initiation of trastuzumab nor the optimal duration of therapy established. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Evaluat Ctr, 44 Binney St,Dana Bldg D1210, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2003 VL 81 SU 1 BP S69 EP S72 PG 4 WC Oncology SC Oncology GA 750RR UT WOS:000187012100014 ER PT J AU Feuerhake, F Sigg, W Hofter, EA Unterberger, P Welsch, U AF Feuerhake, F Sigg, W Hofter, EA Unterberger, P Welsch, U TI Cell proliferation, apoptosis, and expression of Bcl-2 and Bax in non-lactating human breast epithelium in relation to the menstrual cycle and reproductive history SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE apoptosis; Bax; Bcl-2; human; Ki-67; resting mammary gland; TUNEL ID RESTING HUMAN-BREAST; CANCER RISK; IN-VIVO; AGE; PREGNANCY; TURNOVER; CARCINOGENESIS; DEATH; FASL AB Cell proliferation, apoptosis, and the expression of Bcl-2 and Bax were investigated in breast tissue of healthy premenopausal women in order to study the effect of the menstrual cycle and reproductive history on the cell turnover in the non-lactating mammary gland epithelium. Immunohistochemistry was used to detect the proliferation-associated antigen Ki-67, as well as Bcl-2 and Bax. Apoptotic cells were identified by enzymatic labelling of fragmentized DNA (TUNEL-technique) and morphologic analysis. Consistent with published data, the proliferative activity and the frequency of apoptotic events as detected by morphologic analysis was higher in the luteal than in the follicular phase of the menstrual cycle. Parity, lactation, and age correlated with lower proliferative activity, whereas the frequency of apoptosis was not significantly influenced by the reproductive history. Staining patterns for Bax and Bcl-2 showed characteristic changes due to the menstrual cycle with a maximum of immunoreactivity for Bcl-2 in the follicular phase and for Bax in the luteal phase. However, there was no statistically significant association between Bcl-2/Bax immunoreactivity and menstrual cycle or reproductive parameters. We conclude that other molecular pathways than the Bax/Bcl-2 antagonism may additionally be involved in the regulation of apoptotic cell death in the breast epithelium. Knowledge of the entire complexity of apoptosis regulation is necessary to understand the observed effects of parity and lactation on mammary epithelial biology, and possibly to be able to influence pathological processes caused by an imbalance between cell renewal and elimination. C1 Univ Freiburg, Neuroctr, Dept Neuropathol, D-7800 Freiburg, Germany. Univ Munich, Anat Anstalt, D-80539 Munich, Germany. City Hosp, Dept Plast Surg, Munich, Germany. RP Feuerhake, F (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 33 TC 20 Z9 22 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2003 VL 77 IS 1 BP 37 EP 48 DI 10.1023/A:1021119830269 PG 12 WC Oncology SC Oncology GA 617BX UT WOS:000179341300005 PM 12602903 ER PT J AU Hayashi, T Hideshima, T Anderson, KC AF Hayashi, T Hideshima, T Anderson, KC TI Novel therapies for multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE bone marrow microenvironment; thalidomide; proteasome inhibitor; NF-kappa B inhibitor ID ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; MARROW STROMAL CELLS; NF-KAPPA-B; DEXAMETHASONE-INDUCED APOPTOSIS; ARSENIC TRIOXIDE AS2O3; RESISTANCE CAM-DR; DENDRITIC CELLS; KINASE PATHWAY; TUMOR-GROWTH C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-178378] NR 80 TC 56 Z9 57 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2003 VL 120 IS 1 BP 10 EP 17 DI 10.1046/j.1365-2141.2003.03929.x PG 8 WC Hematology SC Hematology GA 627RJ UT WOS:000179948000004 PM 12492571 ER PT J AU Feinstein, LC Sandmaier, BM Hegenbart, U McSweeney, PA Maloney, DG Gooley, TA Maris, MB Chauncey, TR Bruno, B Appelbaum, FR Niederwieser, DW Storb, RF AF Feinstein, LC Sandmaier, BM Hegenbart, U McSweeney, PA Maloney, DG Gooley, TA Maris, MB Chauncey, TR Bruno, B Appelbaum, FR Niederwieser, DW Storb, RF TI Non-myeloablative allografting from human leucocyte antigen-identical sibling donors for treatment of acute myeloid leukaemia in first complete remission SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE AML; first remission; non-myeloablative; transplant ID BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; SOUTHWEST-ONCOLOGY-GROUP; COUNCIL AML11 TRIAL; VERSUS-HOST DISEASE; ELDERLY PATIENTS; DOUBLE-BLIND; INTENSIVE CHEMOTHERAPY; POSTREMISSION THERAPY AB Many patients with acute myeloid leukaemia (AML) in first complete remission (CR1) are ineligible for allogeneic transplantation as a result of age or medical problems other than leukaemia. Eighteen patients (median age 59 years, range 36-73 years) with de novo (n = 13) and secondary (n = 5) AML in morphological CR1, who were not candidates for conventional allografting, received non-myeloablative peripheral blood stem cell transplants from human leucocyte antigen identical sibling donors after conditioning with 2 Gy total body irradiation (TBI; n = 10) or 2 Gy TBI and 90 mg/m(2) of fludarabine (n = 8). Postgrafting immunosuppression was with cyclosporine and mycophenolate mofetil. Two rejections were observed in patients not given fludarabine and one died with relapse. Overall, 10 patients died between 77 and 841 d, seven from relapse and three from non-relapse mortality (NRM). Day +100 NRM was 0% with a 1-year estimated NRM of 17%[95% confidence interval (CI) 0-35%]. The median follow-up among the eight survivors was 766 d (range, 188-1141 d). Seven of these eight survivors remain in complete remission (CR). One-year estimates of overall and progression-free survivals were 54% (95% CI 31-78%) and 42% (95% CI 19-66%) respectively. While follow-up is short, this analysis demonstrates that the procedure is sufficiently safe to be studied in a wider group of patients. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Seattle, WA 98195 USA. Univ Leipzig, Leipzig, Germany. Univ Colorado, Denver, CO 80202 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Turin, Turin, Italy. RP Storb, RF (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM rstorb@fhcrc.org FU NCI NIH HHS [P01 CA078902, CA15704, CA18221, CA78902, K23CA92058]; NHLBI NIH HHS [HL36444] NR 37 TC 75 Z9 77 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2003 VL 120 IS 2 BP 281 EP 288 DI 10.1046/j.1365-2141.2003.04057.x PG 8 WC Hematology SC Hematology GA 638XW UT WOS:000180598900017 PM 12542488 ER PT J AU Arroyo, JG Postel, EA Stone, T McCuen, BW Egan, KM AF Arroyo, JG Postel, EA Stone, T McCuen, BW Egan, KM TI A matched study of primary scleral buckle placement during repair of posterior segment open globe injuries SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SEVERE OCULAR TRAUMA AB Aims: To compare the visual and anatomical outcomes of patients who underwent primary scleral buckle (SB) placement during posterior segment open globe repair with matched control patients who did not undergo primary SB placement. Methods: Patients who underwent open globe repair alone or with SB placement at Duke University Eye Center (November 1994-September 1997) and the Massachusetts Eye and Ear Infirmary (July 1993-July 1997) were identified. 19 open globe patients who received primary SB placement were matched with control patients who did not receive a primary SB based on three important prognostic factors: (1) visual grade; (2) zone of injury; and (3) mechanism of injury. The outcomes of interest were: (1) visual outcome; (2) anatomical outcome; (3) subsequent retinal detachment (RD); and (4) number of subsequent surgeries. Results: Baseline characteristics between the groups were similar. Patients who received primary SB placement had a better final visual grade (p=0.02), logMAR vision (p=0.007), and anatomical grade (p=0.01) compared with control patients. Primary SB patients had an average final vision of 20/270, whereas control patients had an average final vision of hand movement, Primary SB placement also resulted in fewer subsequent RDs (26% versus 53%), but this difference did not reach statistical significance (p=0.10). There were no complications associated with primary SB placement. Conclusion: Primary SB placement during posterior segment open globe repair may decrease the risk of subsequent RD and improve final visual and anatomical outcome. C1 Harvard Univ, Brigham & Womens Hosp,Sch Med, Beth Israel Deaconess Med Ctr, Massachusetts Eye & Ear Infirm, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Duke Univ, Ctr Eye, Durham, NC USA. RP Arroyo, JG (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Retina Serv, 12th Floor,243 Charles St, Boston, MA 02114 USA. FU PHS HHS [K23] NR 15 TC 23 Z9 24 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2003 VL 87 IS 1 BP 75 EP 78 DI 10.1136/bjo.87.1.75 PG 4 WC Ophthalmology SC Ophthalmology GA 631RN UT WOS:000180180700018 PM 12488267 ER PT J AU Thomas, SH Silen, W AF Thomas, SH Silen, W TI Effect on diagnostic efficiency of analgesia for undifferentiated abdominal pain SO BRITISH JOURNAL OF SURGERY LA English DT Review ID ACUTE ABDOMEN; RELIEF AB Background: The question of whether it is safe to provide analgesia for patients with undifferentiated acute abdominal pain is marked by longstanding controversy over the possible masking of physical findings. The goal of this review is to assess the pertinent studies. Method: A Medline search was performed in April 2002, using the terms 'analgesia', 'abdominal pain', 'acute abdomen' and 'morphine'. Other articles were identified using the bibliographies of papers found through Medline. All articles reporting clinical trials of analgesia and its effects on diagnosis or physical examination were reviewed. Results: A total of eight trials (one reported only as an abstract) were identified. Because of significant disparity in trial design, no formal analysis such as meta-analysis was performed. However, detailed review of the trials revealed a striking consistency in results. In no study was there an association between analgesia and diagnostic impairment or dangerous masking of the findings of physical examination. Conclusion: The literature addressing early pain relief for abdominal pain is characterized by weaknesses, but there is a common theme suggesting that analgesia is safe. Pending further research, which should address some of the shortcomings of extant studies, a practice of judicious provision of analgesia appears safe, reasonable and in the best interests of patients in pain. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Room 115,Clin Bldg, Boston, MA 02114 USA. NR 12 TC 28 Z9 28 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD JAN PY 2003 VL 90 IS 1 BP 5 EP 9 DI 10.1002/bjs.4009 PG 5 WC Surgery SC Surgery GA 639LF UT WOS:000180629700003 PM 12520567 ER PT J AU Meyer, GS AF Meyer, GS TI Building the bridge across the quality chasm SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material ID CARE C1 Massachusetts Gen Phys Org, Boston, MA 02114 USA. RP Meyer, GS (reprint author), Massachusetts Gen Phys Org, Bulfinch 205,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2003 VL 81 IS 5 BP 313 EP 313 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 684BC UT WOS:000183184700001 PM 12856046 ER PT J AU Walsh, NE Walsh, WS AF Walsh, NE Walsh, WS TI Rehabilitation of landmine victims - the ultimate challenge SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Article DE blast injuries/rehabilitation/complications; artifical limbs; health services accessibilty; health care costs; costs of illness; socioeconomic factors ID MINES; MOZAMBIQUE; INJURIES AB Antipersonnel landmines are often used indiscriminately and frequently result in injury or death of non-combatants. In the last 65 years, over 110 million mines have been spread throughout the world into an estimated 70 countries. Landmine victims use a disproportionately high amount of medical resoures; the vast majority of incidents occur in regions and countries without a sophisticated medical infrastructure and with limited resources, where rehabilitation is difficult in the best of circumstances. It is suggested that only a quarter of the patients with amputation secondary to landmines receive appropriate care. C1 Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Syst, Phys Med & Rehabil Serv, San Antonio, TX USA. Univ Hlth Syst, San Antonio, TX USA. RP Walsh, NE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, 7703 Floyd Curl Dr,Mail Code 7872, San Antonio, TX 78229 USA. NR 29 TC 24 Z9 25 U1 1 U2 5 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 2003 VL 81 IS 9 BP 665 EP 670 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731GQ UT WOS:000185876300008 PM 14710508 ER PT J AU D'Amico, AV Cote, K Loffredo, M Renshaw, AA Chen, MH AF D'Amico, AV Cote, K Loffredo, M Renshaw, AA Chen, MH TI Advanced age at diagnosis is an independent predictor of time to death from prostate carcinoma for patients undergoing external beam radiation therapy for clinically localized prostate carcinoma SO CANCER LA English DT Article DE prostatic neoplasms; prognostic factor; age; radiation therapy; andropause ID RADICAL PROSTATECTOMY; CANCER; GRADE; MEN; BIOPSIES; ANTIGEN; TESTOSTERONE; RECURRENCE; NOMOGRAM; DISEASE AB BACKGROUND. Whether age at diagnosis is predictive of time to prostate carcinoma specific death after external beam radiation therapy (RT) for patients who are diagnosed with clinically localized prostate carcinoma during the prostate specific antigen (PSA) era has not been investigated previously. METHODS. A multivariate Cox regression analysis was used to evaluate the ability of pretreatment risk group and age at diagnosis to predict time to all causes of death and time to death from prostate carcinoma for 381 patients who underwent RT for clinically localized prostate carcinoma. RESULTS. Age at diagnosis, as a continuous variable (P-continuous = 0.04) and risk group (P-categorical = 0.02) were independent predictors of time to death from prostate carcinoma, whereas only age at diagnosis (P-cotinuous = 0.01) was a predictor of time to all causes of death. When analyzed as a categorical variable, beginning at age 73 years, age at diagnosis was an independent predictor (P-categorical < 0.04) of time to death from prostate carcinoma. Upon further analysis, this finding was limited to high-risk patients. For example, age &GE; 75 years at diagnosis predicted for a shorter median time to death from prostate carcinoma (6.3 years vs. 9.7 years; P = 0.002) in high-risk patients. CONCLUSIONS. Patients with clinically localized, high-risk prostate carcinoma who were diagnosed at age &GE; 73 years and were treated with RT had a worse prognosis compared with patients who were diagnosed age < 73 years, raising the possibility that a more aggressive prostate carcinoma biology may develop during andropause. C1 Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Connecticut, Dept Biostat, Storrs, CT USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Therapy, 75 Francis St,L-2 Level, Boston, MA 02115 USA. NR 20 TC 15 Z9 15 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2003 VL 97 IS 1 BP 56 EP 62 DI 10.1002/cncr.11053 PG 7 WC Oncology SC Oncology GA 634BE UT WOS:000180319500007 PM 12491505 ER PT J AU Michaelson, MD Ryan, DP Fuchs, CS Supko, JG Garcia-Carbonero, R Eder, JP Clark, JW AF Michaelson, MD Ryan, DP Fuchs, CS Supko, JG Garcia-Carbonero, R Eder, JP Clark, JW TI A phase I study of 9-nitrocamptothecin given concurrently with capecitabine in patients with refractory, metastatic solid tumors SO CANCER LA English DT Article DE capecitabine; 5-fluorouracil; Phase I trial; camptothecin; DNA topoisomerase I; chemotherapy ID FLUOROURACIL PLUS LEUCOVORIN; FIRST-LINE TREATMENT; COLORECTAL-CANCER; TOPOISOMERASE-I; ORAL 9-NITROCAMPTOTHECIN; ANTITUMOR-ACTIVITY; CAMPTOTHECIN; MULTICENTER AB BACKGROUND. 9-Nitrocamptothecin (9-NC) is an orally available camptothecin analog with antineoplastic activity that results from the inhibition of DNA topoisomerase I. Previous studies have suggested that it has significant clinical efficacy. The primary toxicities of 9-NC include gastrointestinal upset, cystitis, and myelosuppression at the maximum tolerated dose (MTD) of 1.5 mg/m(2) per day. Capecitabine is a prodrug of 5-fluorouracil that is approved for use in patients with metastatic breast carcinoma and colorectal carcinoma, and it offers the convenience of oral administration. This trial examined the combination of these two oral agents in patients with metastatic solid tumors. METHODS. Capecitabine was administered twice daily at a total daily dose of 1300 mg/m(2) per day for 14 days followed by a 1-week break. 9-NC was taken daily 5 days per week for 2 weeks in a dose-escalation scheme. The starting dose was 0.5 mg/m(2) per day, and cohorts of 3 patients were enrolled until the dose level reached 1.25 mg/m(2) per day. RESULTS. Twenty-one patients were evaluable for toxicity and response, and nausea and emesis were the dose-limiting toxicities. Despite antiemetic prophylaxis with 5-hydroxytryptamine-3 antagonists, 2 of 3 patients at the 1.0 mg/m(2) per day dose level had Grade 2-3 nausea; while at the MTD of 0.75 mg/m(2) per day, 3 of 14 patients had Grade 2 nausea. The incidence of hand-foot syndrome, stomatitis, diarrhea, and myelosuppression did not exceed that expected with capecitabine alone, suggesting that 9-NC does not exacerbate these side effects. No objective responses were seen. Stable disease was observed in 9 patients (43%) with a median duration of 11 weeks, including 3 patients with responses that lasted from 20 weeks to 40 weeks. CONCLUSIONS. The combination of 9-NC and capecitabine with the current schedule was limited in dose by nausea and had minimal clinical efficacy in a group of patients with refractory solid tumors. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox Bldg,Room 640,100 Blossom St, Boston, MA 02114 USA. NR 19 TC 6 Z9 8 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 2003 VL 97 IS 1 BP 148 EP 154 DI 10.1002/cncr.11038 PG 7 WC Oncology SC Oncology GA 634BE UT WOS:000180319500018 PM 12491516 ER PT J AU Daley, GQ AF Daley, GQ TI Dodging the magic bullet - Understanding imatinib resistance SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE STI571; imatinib; Gleevec; BCR-ABL; chronic myeloid leukemia; drug resistance ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE; BCR-ABL; CELLS; PROGENITORS; INHIBITOR; STI571 C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. NR 11 TC 9 Z9 10 U1 1 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN-FEB PY 2003 VL 2 IS 1 BP 109 EP 110 PG 2 WC Oncology SC Oncology GA 685RD UT WOS:000183276300022 PM 12673130 ER PT J AU Maser, RS DePinho, RA AF Maser, RS DePinho, RA TI Take care of your chromosomes lest cancer takes care of you SO CANCER CELL LA English DT Article ID STRAND BREAK REPAIR; TELOMERE DYSFUNCTION; TRANSLOCATIONS AB The analysis of compound mouse mutants for nonhomologous end-joining DNA double-strand break repair and those deficient for the p53 checkpoint pathway has provided a fascinating look at the carcinogenic consequences of the failure to properly repair DNA damage and to elicit appropriate checkpoints. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Maser, RS (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Maser, Richard/B-2970-2012 NR 15 TC 26 Z9 27 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2003 VL 3 IS 1 BP 4 EP 6 DI 10.1016/S1535-6108(02)00243-X PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 639LQ UT WOS:000180630600002 PM 12559169 ER PT J AU Breakefield, XO Grandi, P Sena-Esteves, M Shah, K Kumar, S Krasnykh, V Curiel, D Tung, C Weissleder, R AF Breakefield, XO Grandi, P Sena-Esteves, M Shah, K Kumar, S Krasnykh, V Curiel, D Tung, C Weissleder, R TI HSV vectors for targeting, regulation and imaging of tumor death SO CANCER GENE THERAPY LA English DT Meeting Abstract CT 11th International Conference on Gene Therapy of Cancer CY DEC 12-14, 2002 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. Univ Alabama, Gene Therapy Ctr, Tuscaloosa, AL 35487 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2003 VL 10 SU 1 MA 41 BP S16 EP S16 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 642VT UT WOS:000180826700040 ER PT J AU Lopez, CA Park, JO Brown, CK Mauceri, HJ Darga, TE Manan, A Posner, MC Kufe, DW Weichselbaum, RR AF Lopez, CA Park, JO Brown, CK Mauceri, HJ Darga, TE Manan, A Posner, MC Kufe, DW Weichselbaum, RR TI Transcriptional control of viral gene therapy by chemotherapy SO CANCER GENE THERAPY LA English DT Meeting Abstract CT 11th International Conference on Gene Therapy of Cancer CY DEC 12-14, 2002 CL SAN DIEGO, CALIFORNIA C1 Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN PY 2003 VL 10 SU 1 MA 79 BP S29 EP S29 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 642VT UT WOS:000180826700076 ER PT J AU Skeel, RT Huang, J Manola, J Wilding, G Dreicer, R Walker, P Muggia, F Crawford, ED Dutcher, JP Loehrer, PJ AF Skeel, RT Huang, J Manola, J Wilding, G Dreicer, R Walker, P Muggia, F Crawford, ED Dutcher, JP Loehrer, PJ TI A phase II study of 13-cis retinoic acid plus interferon alpha-2a in advanced stage penile carcinoma: An eastern cooperative oncology group study (E3893) SO CANCER INVESTIGATION LA English DT Article DE penile neoplasms; interferon alpha-2a; tretinoin; clinical trials ID SQUAMOUS-CELL CARCINOMA; 13-CIS-RETINOIC ACID; CANCER-THERAPY; CISPLATIN; CERVIX; METHOTREXATE; COMBINATION; BLEOMYCIN; 5-FLUOROURACIL; CHEMOTHERAPY AB Purpose. Combined biological therapy with 13-cis-retinoic acid (13-cRA) and interferon alpha-2a (IFN alpha-2a) was reported to be highly effective in squamous cell carcinoma of the cervix and skin, Squamous cell carcinoma of the penis is rare in the United States, accounting for less than 1/2% of all male malignancies. Because of the association of infection with human papillomavirus with both carcinomas of the cervix and penis and their shared squamous cell histology, we carried out a phase II Study of 13-cRA and IFN alpha-2a in carcinoma of the penis. Materials and Method. Eighteen ambulatory patients with surgically unresectable. recurrent. and/or metastatic squamous cell carcinoma of the penis were treated with IFN alpha-2a. 3 MU/day administered subcutaneously and 13-cRA, 1 mg/kg orally daily for at least eight weeks. unless intolerable toxicity occurred. Results. One patient vas ineligible; one patient withdrew prior to treatment, Among the 16 eligible. treated patients. there was one complete response. Fourteen patients had progressive disease as their only treatment effect, Two patients were unevaluable for tumours response because they had no follow-up tumor measurements. No unexpected treatment-related toxicities were found on study. The only common form of grade 3 toxicity was hypertriglyceridemia found in eight of the 17 patients (47%). No toxicities above grade 3 were observed. Conclusion. In contrast to its benefit in squamous cell carcinomas of the cervix and skin, the combination of 13-cRA and IFN alpha-2a has low efficacy in advanced carcinoma of the penis. C1 Med Coll Ohio, Toledo, OH 43699 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Ball Mem Hosp, Muncie, IN 47303 USA. NYU Med Ctr, New York, NY 10016 USA. Univ Colorado, Denver, CO 80202 USA. New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. Indiana Univ, Hosp Med, Indianapolis, IN 46204 USA. RP Skeel, RT (reprint author), Med Coll Ohio, Toledo, OH 43699 USA. FU NCI NIH HHS [CA14958, CA21115, CA23318, CA32102, CA42777, CA49883, CA58882, CA66636, CACA21076] NR 23 TC 12 Z9 12 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 1 BP 41 EP 46 DI 10.1081/CNV-120016402 PG 6 WC Oncology SC Oncology GA 654CG UT WOS:000181475600006 PM 12643008 ER PT J AU Poiesz, BJ Poiesz, MJ Choi, D AF Poiesz, BJ Poiesz, MJ Choi, D TI The human T-cell lymphoma/leukemia viruses SO CANCER INVESTIGATION LA English DT Review ID TYPE-1 TAX PROTEIN; LEUKEMIA-LYMPHOMA VIRUS; DNA-BINDING ACTIVITY; HTLV-I TAX; POLYMERASE-CHAIN-REACTION; NF-KAPPA-B; COMPLETE NUCLEOTIDE-SEQUENCE; ENZYME-LINKED IMMUNOSORBENT; COMPLETE GENOMIC SEQUENCE; LONG TERMINAL REPEATS AB The primate T-cell lymphoma/leukemia viruses belong to an oncogenic genus of complex retroviruses. Members of this genus have been shown to be pathogenic in man. The human T-cell lymphoma/leukemia virus (HTLV) type I has been linked in the etiology of T-cell malignancies and "autoimmune-like" neurologic and rheumatic disorders; a related virus, HTLV-II, is becoming increasingly associated with similar disorders. Cell transformation is thought to be caused predominantly by the effects of the viral regulatory protein, Tax. An additional induced host cell molecule, adult T-cell lymphoma-derived factor, may contribute to cell immortalization. Like the DNA tumor viruses, HTLV activates transcription of cellular proto-oncogenes and inhibits cellular mechanisms of tumor suppression, cell cycle arrest, and apoptosis. However, individuals who are able to mount a strong cell-mediated immune response and limit viral entry into uninfected cells do not develop associated malignancies. Unfortunately, HTLV-induced malignancies are difficult to treat with conventional chemotherapy, and disease progression is often rapid with a median survival of less than 2 years. There are, however, some novel approaches that have yet to be fully tested that may have greater efficacy in the treatment of HTLV-induced diseases. In the future, better screening and detection methods, along with new vaccines and therapies, may contribute to the increased prevention and control of HTLV infection and its associated diseases. C1 SUNY Syracuse, Upstate Med Univ, Dept Med, New York, NY 13120 USA. Beth Israel New England Deaconess Med Ctr, Dept Neurol, Boston, MA USA. RP Poiesz, BJ (reprint author), SUNY Syracuse, Upstate Med Univ, Dept Med, New York, NY 13120 USA. EM poieszb@upstate.edu NR 149 TC 23 Z9 28 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 2 BP 253 EP 277 DI 10.1081/CNV-120016422 PG 25 WC Oncology SC Oncology GA 674YL UT WOS:000182665200011 PM 12743991 ER PT J AU Aghi, M Chiocca, EA AF Aghi, M Chiocca, EA TI Genetically engineered herpes simplex viral vectors in the treatment of brain tumors: A review SO CANCER INVESTIGATION LA English DT Article DE herpes simplex virus type one; gene therapy; brain tumor; review article ID VIRUS THYMIDINE KINASE; LONG-TERM SURVIVAL; GENE-THERAPY; IONIZING-RADIATION; MALIGNANT GLIOMA; RIBONUCLEOTIDE REDUCTASE; ONCOLYTIC VIRUS; INVIVO BEHAVIOR; CANCER-THERAPY; HSV-1 VECTOR C1 Harvard Univ, Neurosurg Serv, Mol Neurooncol Labs, Sch Med,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Chiocca, EA (reprint author), Harvard Univ, Neurosurg Serv, Mol Neurooncol Labs, Sch Med,Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 55 TC 6 Z9 6 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 2 BP 278 EP 292 DI 10.1081/CNV-120016423 PG 15 WC Oncology SC Oncology GA 674YL UT WOS:000182665200012 PM 12743992 ER PT J AU Zhu, AX AF Zhu, AX TI Hepatocellular carcinoma: Are we making progress? SO CANCER INVESTIGATION LA English DT Article DE heptocellular carcinoma; hepatitis; treatment; prevention ID HEPATITIS-B-VIRUS; RANDOMIZED CONTROLLED TRIAL; PERCUTANEOUS ETHANOL INJECTION; POLYMERASE CHAIN-REACTION; ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; LIVER-TRANSPLANTATION; CIRRHOTIC-PATIENTS; P53 GENE; ARTERIAL CHEMOEMBOLIZATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 96 TC 39 Z9 40 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 3 BP 418 EP 428 DI 10.1081/CNV-120018233 PG 11 WC Oncology SC Oncology GA 705WF UT WOS:000184418400011 PM 12901288 ER PT J AU Oh, WK AF Oh, WK TI Predicting outcome in localized prostate cancer: How far have we come? SO CANCER INVESTIGATION LA English DT Editorial Material ID RADICAL PROSTATECTOMY C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 5 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 3 BP 487 EP 488 DI 10.1081/CNV-120018656 PG 2 WC Oncology SC Oncology GA 705WF UT WOS:000184418400020 PM 12901296 ER PT J AU Ryan, DP Clark, JW Kulke, MH Fuchs, CS Earle, CC Enzinger, PC Stuart, K Catarius, KJ Winkelmann, J Mayer, RJ AF Ryan, DP Clark, JW Kulke, MH Fuchs, CS Earle, CC Enzinger, PC Stuart, K Catarius, KJ Winkelmann, J Mayer, RJ TI A phase II study of modified deGramont 5-fluorouracil, leucovorin, and oxaliplatin in previously treated patients with metastatic colorectal cancer SO CANCER INVESTIGATION LA English DT Article ID MULTICENTER RANDOMIZED-TRIAL; HIGH-DOSE LEUCOVORIN; FLUOROURACIL FAILURE; CONTINUOUS-INFUSION; 1ST-LINE TREATMENT; IRINOTECAN; CHEMOTHERAPY; CARCINOMA; RESISTANT; REGIMEN AB Purpose: To evaluate the toxicity and efficacy of a modified deGramont regimen of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin in patients with advanced colorectal cancer who have progressed on at least one but not more than two prior chemotherapy regimens. Patients and Methods: Patients with stage 4 colorectal cancer were treated with oxaliplatin 85 mg/m(2) by a 2-hour intravenous infusion, followed by leucovorin 500 mg/m(2) by a 2-hour intravenous infusion, followed by 5-FU 400 mg/m(2) by bolus injection, followed by 5-FU 2.4 g/m(2) administered by a 46-hour continuous infusion. Cycles were administered every 2 weeks. Results: Seventy patients were treated and 68 patients had previously received irinotecan. Eleven percent of patients had a partial response, 33% of CEA-evaluable patients had a greater than or equal to 50% drop in their CEA level. The median time to progression was 6.2 months, and the median overall survival was 8.7 months. Toxicity was mild to moderate, as 14% of patients experienced grade 3 or 4 neutropenia and 3% of patients experienced grade 3 neuropathy. Conclusion: The modified deGramont regimen of 5-FU, leucovorin, and oxaliplatin is tolerable and is associated with a modest degree of antitumor activity in patients who have progressed on both 5-FU and irinotecan. C1 Brigham & Womens Hosp, Dana Farber Partners Canc Care Gastrointestinal C, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dana Farber Partners Canc Care Gastrointestinal C, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Dana Farber Partners Canc Care Gastrointestinal C, Boston, MA 02115 USA. RP Ryan, DP (reprint author), MGH Canc Ctr, Box 640, Boston, MA 02114 USA. NR 19 TC 5 Z9 5 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 4 BP 505 EP 511 DI 10.1081/CNV-120022359 PG 7 WC Oncology SC Oncology GA 726HQ UT WOS:000185593300003 PM 14533439 ER PT J AU Cella, D Paul, D Yount, S Winn, R Chang, CH Banik, D Weeks, J AF Cella, D Paul, D Yount, S Winn, R Chang, CH Banik, D Weeks, J TI What are the most important symptom targets when treating advanced cancer? A survey of providers in the National Comprehensive Cancer Network (NCCN) SO CANCER INVESTIGATION LA English DT Article DE cancer; symptoms; assessment; quality of life ID QUALITY-OF-LIFE; METASTATIC BREAST-CANCER; FUNCTIONAL ASSESSMENT; CLINICAL-TRIALS; PROSTATE-CANCER; NECK-CANCER; THERAPY; INSTRUMENT; VALIDITY; RELIABILITY AB We derived a set of brief, clinically relevant symptom indices for assessing symptomatic response to chemotherapy for advanced bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreas, lung, ovarian, and prostate cancers. Questions were extracted from a multidimensional cancer quality of life (QOL) measurement system, the Functional Assessment of Cancer Therapy (FACT). Surveys of disease-related symptoms were presented to expert physicians and nurses at 17 National Comprehensive Cancer Network (NCCN) member institutions. In a two-step procedure, each expert narrowed the list to no more than five of the very most important to attend to when assessing the value of drug treatment for advanced disease. Symptoms endorsed at a frequency greater than chance probability were retained for the nine symptom indices. The resulting NCCN/FACT symptom indices are comprised of 6-15 items, depending on disease. Fatigue, pain, nausea, weight loss, worry about worsening condition, and contentment with current QOL were consistently selected by experts as priority symptoms across tumor sites. These nine tumor-specific symptom indices indicate the most important clinician-rated targets of chemotherapy for many advanced cancers. These results await validation in patient populations and examination of the extent to which changes in symptomatology translate into meaningful improvement to the patient. C1 Evanston Northwestern Hlth Care, Ctr Outcomes Res & Educ, Evanston, IL 60201 USA. Northwestern Univ, Evanston, IL USA. Natl Comprehens Canc Network, Rockledge, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cella, D (reprint author), Evanston Northwestern Hlth Care, Ctr Outcomes Res & Educ, 1001 Univ Pl,Suite 100, Evanston, IL 60201 USA. NR 39 TC 62 Z9 62 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 4 BP 526 EP 535 DI 10.1081/CNV-120022366 PG 10 WC Oncology SC Oncology GA 726HQ UT WOS:000185593300006 PM 14533442 ER PT J AU Abrahm, JL AF Abrahm, JL TI Waiting for the platelet count to rise: Negotiating care at the end of life SO CANCER INVESTIGATION LA English DT Article DE prognosis; palliative care; advance care planning; hospice ID TERMINALLY ILL PATIENTS; TREATMENT PREFERENCES; CANCER-PATIENTS AB Oncologists play a crucial role in enabling patients at the end of life and their families to decide whether the burden of chemotherapy is worth the benefit. Using language that displays their concern for providing ongoing care and that does not mistakenly imply withholding of effective therapies can ease the transition off chemotherapy. Providing accurate, timely prognostic information; exploring patients' hopes, goals, and values; helping them resume meaningful activities; meeting their health care proxies and discussing the advance care plan with them can all enhance the relationship with patients at the end of life and case fears of abandonment. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Abrahm, JL (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 22 TC 3 Z9 3 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2003 VL 21 IS 5 BP 772 EP 781 DI 10.1081/CNV-120023775 PG 10 WC Oncology SC Oncology GA 742ET UT WOS:000186504300012 PM 14628435 ER PT J AU Akiyama, M Hideshima, T Hayashi, T Tai, YT Mitsiades, CS Mitsiades, N Chauhan, D Richardson, P Munshi, NC Anderson, KC AF Akiyama, M Hideshima, T Hayashi, T Tai, YT Mitsiades, CS Mitsiades, N Chauhan, D Richardson, P Munshi, NC Anderson, KC TI Nuclear factor-kappa B p65 mediates tumor necrosis factor alpha-induced nuclear translocation of telomerase reverse transcriptase protein SO CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA CELLS; PHOSPHORYLATION; INHIBITION AB Sustained proliferation of cancer cells requires telomerase to maintain telomeres that regulate chromosomal stability and cellular mitosis. Expression of human telomerase reverse transcriptase (hTERT) catalytic subunit, which modulates telomerase activity, is regulated at both the transcriptional level and via phosphorylation by Akt kinase. Moreover, nuclear localization of hTERT is required to promote elongation of telomere sequences. In this study, we show for the first time that hTERT protein interacts directly with nuclear factor (NF)kappaB p65 in MM.1S cells. Importantly, tumor necrosis factor alpha (TNFalpha) modulates telomerase activity by inducing translocation from the cytoplasm to the nucleus of hTERT protein bound to NF-kappaB p65. Conversely, a specific IkappaB kinase (IKK) inhibitor PS-1145, and a specific NF-kappaB nuclear translocation inhibitor SN-50, both block TNFalpha-induced hTERT nuclear translocation. These studies suggest that NF-kappaB p65 plays a pivotal role in regulating telomerase by modulating its nuclear translocation. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Vet Adm Boston Healthcare Syst, W Roxbury, MA 02132 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378, R0-1 50947] NR 21 TC 145 Z9 159 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2003 VL 63 IS 1 BP 18 EP 21 PG 4 WC Oncology SC Oncology GA 633NZ UT WOS:000180290500004 PM 12517770 ER PT J AU Trasler, J Deng, LY Melnyk, S Pogribny, I Hiou-Tim, F Sibani, S Oakes, C Li, E James, SJ Rozen, R AF Trasler, J Deng, LY Melnyk, S Pogribny, I Hiou-Tim, F Sibani, S Oakes, C Li, E James, SJ Rozen, R TI Impact of Dnmt1 deficiency, with and without low folate diets, on tumor numbers and DNA methylation in Min mice SO CARCINOGENESIS LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; NESTED CASE-CONTROL; PLASMA HOMOCYSTEINE; COLORECTAL-CANCER; GENE-EXPRESSION; SUPPRESSOR GENE; COLON-CANCER; P53 GENE; HYPOMETHYLATION; RISK AB Although a number of studies have suggested that diets with low intake of folate, an important methyl donor, are associated with increased risks of colon cancer and its precursor the adenomatous polyp, the underlying mechanisms are poorly understood. Dysregulation and instability of DNA methylation and alterations in the levels of the predominant DNA methylating enzyme, DNA (cytosine-5)methyltransferase 1 (Dnmt1), have also been linked to tumorigenesis. We have used a combination of genetic and dietary manipulation to assess the effects of reduced Dnmt1 expression with and without folate deficiency on tumor induction in the Apc(Min) mouse. Apc(Min) mice with a reduction in Dnmt1 expression (Apc(Min/+) /Dnmt1(C/+)) had significantly lower tumor numbers than Ape(Min) mice with normal Dnmt1 (Apc(Min/+) /Dnmt1(+/+)). Dietary folate deficiency from weaning to 13 weeks of age did not affect tumor number or size in Apc(Min/+) /Dnmt(+/+) mice. However, in Apc(Min/+) /Dnmt1(C/+) mice with high baseline tumor numbers (41 4), folate deficiency was associated with a decreased absolute number of tumors (27 3), but a higher proportion of larger tumors as compared with mice on the control diet. In the repeat experiment, Apc(Min/+) / Dnmt1(C/+) mice had low baseline tumor numbers (20 +/- 2) and folate deficiency did not affect tumor number (23 +/- 4) or size as compared with the same mice on the control diet. These results suggest that, in the presence of Dnmt1 deficiency, the effects of folate deficiency on tumor number and size may depend on the stage of adenoma development when folate deficiency is initiated. We also show that folate deficiency with or without reductions in Dnmt1 did not affect overall genomic DNA methylation or the methylation levels of two candidate genes, E-cadherin or p53, in normal or neoplastic intestinal tissue. In conclusion, genetic deficiency in Dnmt1 with or without folate deficiency decreases tumor number in the Apc(Min) mouse model, but this effect may not be mediated by changes in SAM or SAH levels, nor by alterations in global methylation in the pre-neoplastic intestinal tissue. C1 McGill Univ, Dept Pediat, Montreal Childrens Hosp, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Dept Human Genet, Montreal Childrens Hosp, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Med Sch, Boston, MA USA. RP Rozen, R (reprint author), McGill Univ, Dept Pediat, Montreal Childrens Hosp, 4060 St Catherine St W, Montreal, PQ H3Z 2Z3, Canada. RI Oakes, Christopher/H-7288-2014 NR 38 TC 43 Z9 46 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2003 VL 24 IS 1 BP 39 EP 45 DI 10.1093/carcin/24.1.39 PG 7 WC Oncology SC Oncology GA 644AP UT WOS:000180896000006 PM 12538347 ER PT J AU Pirraglia, PA Peterson, JC Williams-Russo, P Charlson, ME AF Pirraglia, PA Peterson, JC Williams-Russo, P Charlson, ME TI Assessment of decline in health-related quality of life among angina-free patients undergoing coronary artery bypass graft surgery SO CARDIOLOGY LA English DT Article DE coronary artery bypass; quality of life; postoperative complications ID TRIAL; INTERVENTION; ANGIOPLASTY; VALIDATION; OUTCOMES; SYMPTOMS AB Purpose: Coronary artery bypass graft (CABG) surgery generally decreases symptoms and improves quality of life, but for those patients without angina, prolongation of life takes precedence. We used the SF-36 to assess changes in health-related quality of life (HRQOL) among patients who were angina free prior to CABG compared to those reporting angina. Methods: We combined data from two randomized trials of hemodynamic management during surgery. Prior to CABG, demographic, clinical and SF-36 data were obtained. Patients were re-evaluated at a 6-month follow-up. Patients with a decline of ! 15 points from baseline to follow-up for individual SF-36 domains and >5 points for summary components were classified as having a decline. We used logistic regression models that controlled for baseline SF-36 score and other baseline characteristics to assess HRQOL decline with respect to angina status. Results: Of 590 patients, 28% were angina free at baseline. A third of the patients angina free at baseline had a postoperative decline in physical function. Patients who were angina free at baseline were three times more likely to suffer a decline in physical function than those with angina (odds ratio 3.29, 95% confidence interval 1.86-5.82). This finding remained after addition of adverse outcomes to the model. Baseline angina status was not related to any other SF-36 domain or to physical or mental summary component scores. Major adverse outcomes did not differ between angina-free patients and those with angina. Conclusions: The incidence of patients reporting a decline in physical function after CABG was greater in patients without angina preoperatively, even when adjusting for baseline score. Given the substantial risk of decreased physical functioning, employing interventions to maintain HRQOL in this population should be considered. Copyright (C) 2003 S. Karger AG, Basel. C1 Cornell Univ, NY Presbyterian Hosp, Weill Med Coll, Dept Med, New York, NY 10021 USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit, Boston, MA USA. RP Peterson, JC (reprint author), Weill Med Coll, Div Gen Internal Med, 525 E 68th St,Box 46, New York, NY 10021 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2003 VL 99 IS 3 BP 115 EP 120 DI 10.1159/000070667 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 698LE UT WOS:000184000400001 PM 12824718 ER EF