FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Holden, WE Lewinsohn, DM Osborne, ML Griffin, C Spencer, A Duncan, C Deffebach, ME AF Holden, WE Lewinsohn, DM Osborne, ML Griffin, C Spencer, A Duncan, C Deffebach, ME TI Use of a clinical pathway to manage unsuspected radiographic findings SO CHEST LA English DT Article DE chest radiograph; clinical pathway; lung cancer; lung nodule; radiology; radiographic findings; radiology information systems ID SOLITARY PULMONARY NODULE; LUNG-CANCER; COMMUNICATION; CARCINOMA; PROJECT; CT AB Study objectives: To describe our 5-year experience with a clinical pathway used to ensure the timely communication and evaluation of unsuspected radiologic findings (URFs) noted on clinically requested chest imaging. Design: Prospective data collection on clinical practice. Setting: Academically affiliated Veterans Affairs medical center. Participants: Pulmonary physicians, nurses, and radiologists. Results: Over a period of 5 years, 1,629 URFs were referred to the pathway (from chest radiographs, 1,359 [83.4%]; from CT scans, 270 [16.6%]). Most URFs (78%) were nodules, with a specific diagnosis made in one third of URFs, and with a specific diagnosis thought to be clinically significant in another one third of URFs. The most common diagnosis was neoplasm, with over two thirds of these diagnoses being lung cancer. One third of lung cancers detected were either stage 1 or 2, with 1 in 17 of all URFs being stage IA lung cancer. The cost of the pathway was estimated at $28,600 per year. Conclusions: URFs noted on chest imaging are frequently clinically significant, and a systematic approach to managing URFs, such as a clinical pathway, can significantly improve care in a large teaching hospital. C1 Portland VA Med Ctr, Med Serv, Portland, OR 97201 USA. Portland VA Med Ctr, Pulm & Crit Care Sect, Portland, OR 97201 USA. Portland VA Med Ctr, Diagnost Radiol Serv, Portland, OR 97201 USA. RP Holden, WE (reprint author), Portland VA Med Ctr, Med Serv, P3-PULM,3710SW US Vet Hosp Rd, Portland, OR 97201 USA. EM william.holden@med.va.gov RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 12 TC 6 Z9 6 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2004 VL 125 IS 5 BP 1753 EP 1760 DI 10.1378/chest.125.5.1753 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 820ZM UT WOS:000221428700027 PM 15136387 ER PT J AU Taylor, SL Hefle, SL Bindslev-Jensen, C Atkins, FM Andre, C Bruijnzeel-Koomen, C Burks, AW Bush, RK Ebisawa, M Eigenmann, PA Host, A Hourihane, JO Isolauri, E Hill, DJ Knulst, A Lack, G Sampson, HA Moneret-Vautrin, DA Rance, F Vadas, PA Yunginger, JW Zeiger, RS Salminen, JW Madsen, C Abbott, P AF Taylor, SL Hefle, SL Bindslev-Jensen, C Atkins, FM Andre, C Bruijnzeel-Koomen, C Burks, AW Bush, RK Ebisawa, M Eigenmann, PA Host, A Hourihane, JO Isolauri, E Hill, DJ Knulst, A Lack, G Sampson, HA Moneret-Vautrin, DA Rance, F Vadas, PA Yunginger, JW Zeiger, RS Salminen, JW Madsen, C Abbott, P TI A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much? SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE allergy; clinical trial; DBPCFC; exposure; food; threshold; risk assessment ID CASEIN HYDROLYSATE FORMULA; DOUBLE-BLIND; IGE CONCENTRATIONS; ATOPIC-DERMATITIS; PEANUT ALLERGY; EGG ALLERGY; COW MILK; CHALLENGES; HYPERSENSITIVITY; IDENTIFICATION AB Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult. Objective A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods. Methods In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials. Results A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 mug of the allergenic food and would continue with doses of 100 mug and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose. Conclusion A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals. C1 Univ Nebraska, Food Allergy Res & Resource Program, Lincoln, NE 68583 USA. Odense Univ Hosp, Dept Dermatol, DK-5000 Odense, Denmark. Natl Jewish Med & Res Ctr, Denver, CO USA. Stallergenes, Antony, France. Univ Med Ctr, Dept Dermatol Allergol, Utrecht, Netherlands. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Natl Sagamihara Hosp, Kanagawa, Japan. Hop Enfants, Geneva, Switzerland. Odense Univ Hosp, Dept Pediat, DK-5000 Odense, Denmark. Univ Southampton, Southampton, Hants, England. Univ Turku, Dept Pediat, Turku, Finland. Royal Childrens Hosp, Parkville, Vic 3052, Australia. St Marys Hosp, London, England. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Hosp, Dept Internal Med Clin Immunol & Allergol, Nancy, France. Hop Enfants, Dept Allergol, Toulouse, France. Wellesley Cent Hosp, Toronto, ON, Canada. Mayo Clin, Rochester, MN USA. Kaiser Permanente Med Ctr, San Diego, CA USA. Hlth Prod & Foods Branch, Chem Hlth Hazard Assessment Div, Ottawa, ON, Canada. Danish Vet & Food Adm, Soborg, Denmark. Food Stand Australia New Zealand, Canberra, ACT, Australia. RP Taylor, SL (reprint author), Univ Nebraska, Food Allergy Res & Resource Program, 143 Food Ind Bldg, Lincoln, NE 68583 USA. EM staylor2@unl.edu RI Bindslev-Jensen, Carsten/H-1877-2011; Osborne, Nicholas/N-4915-2015; Eigenmann, Philippe/A-6569-2017 OI Bindslev-Jensen, Carsten/0000-0002-8940-038X; Osborne, Nicholas/0000-0002-6700-2284; Eigenmann, Philippe/0000-0003-1738-1826 NR 33 TC 116 Z9 119 U1 2 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD MAY PY 2004 VL 34 IS 5 BP 689 EP 695 DI 10.1111/j.1365-2222.2004.1886.x PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 820PN UT WOS:000221401900005 PM 15144458 ER PT J AU Kraeft, SK Ladanyi, A Galiger, K Herlitz, A Sher, AC Bergsrud, DE Even, G Brunelle, S Harris, L Salgia, R Dahl, T Kesterson, J Chen, LB AF Kraeft, SK Ladanyi, A Galiger, K Herlitz, A Sher, AC Bergsrud, DE Even, G Brunelle, S Harris, L Salgia, R Dahl, T Kesterson, J Chen, LB TI Reliable and sensitive identification of occult tumor cells using the improved rare event Imaging system SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER PATIENTS; BONE-MARROW; COLORECTAL-CANCER; PERIPHERAL-BLOOD; PROGNOSTIC FACTOR; LUNG-CANCER; CARCINOMA; DISEASE; QUANTIFICATION; HETEROGENEITY AB Purpose: The purpose of this study was to assess the feasibility of using rare event imaging system (REIS)-assisted analysis to detect occult tumor cells (OTCs) in peripheral blood (PB). The study also sought to determine whether REIS-assisted OTC detection presents a clinically viable alternative to manual microscopic detection to establish the true significance of OTC from solid epithelial tumors. Experimental Design: We recently demonstrated proof of concept using a fluorescence-based automated microscope system, REIS, for OTC detection from the PB. For this study, the prototype of the system was adopted for high-throughput and high-content cellular analysis. Results: The performance of the improved REIS was examined using normal blood (n = 10), normal blood added to cancer cells (n = 20), and blood samples obtained from cancer patients (n = 80). Data from the screening of 80 clinical slides from breast and lung cancer patients, by manual microscopy and by the REIS, revealed that as many as 14 of 35 positive slides (40%) were missed by manual screening but positively identified by REIS. In addition, REIS-assisted scanning reliably and reproducibly quantified the total number of cells analyzed in the assay and categorized positive cells based on their marker expression profile. Conclusions: REIS-assisted analysis provides excellent sensitivity and reproducibility for OTC detection. This approach may enable an improved method for screening of PB samples and for obtaining novel information about disease staging and about risk evaluation in cancer patients. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Vaytek Inc, Fairfield, IA USA. Synta Pharmaceut Corp, Lexington, MA USA. RP Chen, LB (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM drchen@shore.net FU NCI NIH HHS [1R43 CA094454-01] NR 35 TC 32 Z9 34 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2004 VL 10 IS 9 BP 3020 EP 3028 DI 10.1158/1078-0432.CCR-03-0361 PG 9 WC Oncology SC Oncology GA 818UN UT WOS:000221270100016 PM 15131038 ER PT J AU Mehrotra, J Vali, M McVeigh, M Kominsky, SL Fackler, MJ Lahti-Domenici, J Polyak, K Sacchi, N Garrett-Mayer, E Argani, P Sukumar, S AF Mehrotra, J Vali, M McVeigh, M Kominsky, SL Fackler, MJ Lahti-Domenici, J Polyak, K Sacchi, N Garrett-Mayer, E Argani, P Sukumar, S TI Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; METHYLATION-SPECIFIC PCR; DNA METHYLATION; SERIAL ANALYSIS; IN-SITU; EXPRESSION; RASSF1A; HIN-1; PROGRESSION; CARCINOMA AB Purpose: Most often it is not the primary tumor, but metastasis to distant organs that results in the death of breast cancer patients. To characterize molecular alterations in breast cancer metastasis, we investigated the frequency of hypermethylation of five genes (Cyclin D2, RAR-beta, Twist, RASSF1A, and HIN-1) in metastasis to four common sites: lymph node, bone, brain, and lung. Experimental Design: Methylation-specific PCR for the five genes was performed on DNA extracted from archival paraffin-embedded specimens of paired primary breast cancer and its lymph nodes (LN) metastasis (n = 25 each); in independent samples of metastasis to the bone (n = 12), brain (n = 8), and lung (n = 10); and in normal bone, brain, and lung (n = 22). Results: No hypermethylation was detected in the five genes in the normal host tissues. In paired samples, LN metastasis had a trend of higher prevalence of methylation compared with the primary breast carcinoma for all five genes with significance for HIN-1 (P = 0.04). Compared with the primary breast carcinomas, all five genes had higher methylation frequencies in the bone, brain, and lung metastasis, with HIN-1 and RAR-beta methylation being significantly higher (P < 0.01) in each group. Loss of expression of all five genes correlated, with a few exceptions, to hypermethylation of their promoter sequences in metastatic carcinoma cells microdissected from LNs. Conclusion: The frequent presence of hypermethylated genes in locoregional and distant metastasis could render them particularly susceptible to therapy targeted toward gene reactivation combining demethylating agents, histone deacetylase inhibitors, and/or differentiating agents. C1 Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Div Clin Trials & Biometry, Baltimore, MD 21231 USA. Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sukumar, S (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, BBCRB Room 410,1650 Orleans St, Baltimore, MD 21231 USA. EM saras@jhmi.edu FU NCI NIH HHS [P50 CA88843] NR 22 TC 80 Z9 85 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2004 VL 10 IS 9 BP 3104 EP 3109 DI 10.1158/1078-0432.CCR-03-0118 PG 6 WC Oncology SC Oncology GA 818UN UT WOS:000221270100028 PM 15131050 ER PT J AU Forrest, TJ Allen, DN Goldstein, G AF Forrest, TJ Allen, DN Goldstein, G TI Malingering indexes for the Halstead Category Test SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID PERFORMANCE; ATTORNEYS; DISSIMULATION; IMPAIRMENT; BATTERY; INJURY; FAKING AB Two studies were conducted to evaluate potential malingering indexes on the Halstead Category Test. The aim of the first study was that of documenting that groups of individuals with established cognitive impairment did not score positively on the proposed indexes. Of the indexes considered, it was found that these groups made very few errors on subtests I and II of the test and improved their performance on subtest VI relative to V. Subtests I and II are very simple and both subtest V and VI involve the same principle. It was proposed that malingerers would make excessive numbers of errors on subtests I and II, and would not show improvement on subtest VI over subtest V. The second study compared the performance of patients with brain damage to students who were either trained to malinger or encouraged to perform as well as they could on the Category Test. Comparisons were made on the malingering indexes among these groups showing that mean scores of the patients with brain damage on several of the indexes did not differ from those of the students encouraged to do well, but both of these groups did significantly better than the student malingerers. A discriminant analysis of the set of malingering indexes classified 20% of the student malingerers as brain damaged, and 3.4% of the patients with brain damage as malingerers. A stepwise analysis indicated that number of errors on subtests I and II and Total Errors were particularly sensitive to malingering. C1 Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA. VA Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA USA. RP Allen, DN (reprint author), Univ Nevada, Dept Psychol, 4505 Maryland Pkwy,Box 455030, Las Vegas, NV 89154 USA. EM dallen@ccmail.nevada.edu NR 29 TC 13 Z9 13 U1 2 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD MAY PY 2004 VL 18 IS 2 BP 334 EP 347 DI 10.1080/13854040490501673 PG 14 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 850HU UT WOS:000223602600012 PM 15587679 ER PT J AU Lhowe, DW Briggs, SM AF Lhowe, DW Briggs, SM TI Planning for mass civilian casualties overseas - IMSuRT-International medical/surgical response teams SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CITY; INJURIES; ATTACK AB The increased likelihood of mass casualties involving Americans living abroad has prompted the development of a mobile, civilian medical and surgical unit available for rapid deployment overseas. Using past experience derived from the National Disaster Medical Service, and from recent rescue efforts following the African embassy bombings in 1998, an International Medical-Surgical Response Team was developed. Organized under the Department of Homeland Security, it is staffed by civilian professionals from medical and bioengineering fields. Initial deployments to the World Trade Center (2001) and Guam (2002) have shown the ability to rapidly mobilize appropriate manpower and equipment to a mass casualty site, whether domestic or international. The goals of this organization are to work in cooperation with local authorities at the mass casualty site to provide rapid assessment and medical stabilization of injured persons. When the mass casualty is overseas, rapid evacuation of casualties is accomplished by the responding military air evacuation service. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lhowe, DW (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM DLHOWE@PARTNERS.ORG NR 10 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2004 IS 422 BP 109 EP 113 DI 10.1097/01.blo.0000131203.66160.b4 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 824XW UT WOS:000221721500017 PM 15187841 ER PT J AU Gilliam, M Knight, S McCarthy, M AF Gilliam, M Knight, S McCarthy, M TI Success with oral contraceptives: a pilot study SO CONTRACEPTION LA English DT Article DE oral contraceptives; self-efficacy; African-American; subsequent pregnancy; intervention ID REPEAT ADOLESCENT PREGNANCIES; TEENAGE MOTHERS; POSTPARTUM; PROGRAM; FAMILY; TRIAL AB The objective of this pilot study was to examine the effectiveness of a postpartum educational intervention aimed at increasing compliance with oral contraception (OCs) and decreasing repeat pregnancies in young, African American women in the year following an unplanned pregnancy. In this longitudinal study, 43 young, pregnant women attending Prentice Ambulatory Care, Northwestern Hospital, were enrolled and 33 were randomized to receive an antepartum, multicomponent intervention consisting of counseling, a videotape about OCs and written material or resident-physician counseling (usual care). Questionnaire data were collected at enrollment, immediately following the intervention, at 6 weeks, 6 months and 12 months. At 1 year, 25 women remained in the study. More women in the intervention group were not pregnant and still using contraception, and were able to successfully switch contraceptive methods compared to women in the control group. There was no decrease in repeat pregnancy in the intervention group at 1 year compared to the control group. Our intervention resulted in a sustained increase in knowledge of OCs throughout the study period. However, more is needed to promote postpartum contraceptive compliance and decrease repeat pregnancies in young, low-income African Americans with unintended pregnancies. (C) 2004 Elsevier Inc. All rights reserved. C1 Northwestern Univ, Sch Med, Mcgaw Med Ctr, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Gilliam, M (reprint author), Northwestern Univ, Sch Med, Mcgaw Med Ctr, Dept Obstet & Gynecol, 820 S Wood St,MC 808, Chicago, IL 60612 USA. EM mgilli2@uic.edu NR 24 TC 27 Z9 28 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD MAY PY 2004 VL 69 IS 5 BP 413 EP 418 DI 10.1016/j.contraception.2003.12.006 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 817KI UT WOS:000221176000012 PM 15105065 ER PT J AU Yosefy, C Cantor, A Reisin, L Efrati, S Ilia, R AF Yosefy, C Cantor, A Reisin, L Efrati, S Ilia, R TI The diagnostic value of QRS changes for prediction of coronary artery disease during exercise testing in women: false-positive rates SO CORONARY ARTERY DISEASE LA English DT Article DE women; exercise test; QRS width; false positive ID POSITRON EMISSION TOMOGRAPHY; MYOCARDIAL-ISCHEMIA; HEART-DISEASE; COMPUTERIZED METHOD; SENSITIVE MARKER; DURATION CHANGES; ANGINA-PECTORIS; PROLONGATION; SURGERY; ANGIOPLASTY AB Objectives The false positive rate of electrocardiographic exercise testing (ET) for coronary artery disease (CAD) in women ranges from 38 to 67%, using the ST-T changes (ST-T) criteria. The aim of this study was to compare the diagnostic accuracy of QRS duration change criteria with ST-T change criteria during ET. Methods We studied 234 women (mean age 58+/-17 years, range 27-83 years), of whom 160 were pre-menopausal (PrMW; mean age 41+/-9, range 27-56) and 4 were postmenopausal (PoMW; mean age 65+/-7, range 57-83). All participants underwent ET to rule out CAD, followed by thallium stress testing (TL). QRS duration, measured with a computerized optical scanner and ST-T changes at peak ET were compared with TL. An ischemic QRS response was defined as an exercise-induced prolongation of QRS duration >3 ms. Results The sensitivities of QRS duration changes for the entire study group, the PrMW group and the PoMW group in comparison with TL, were 93, 88 and 92%, respectively, while the corresponding rates of specificity were 91, 85 and 91%, respectively. The sensitivities of ET ST-T changes for the entire study group, for the PrMW group and for the PoMW group were 48, 46 and 54%, respectively, while the corresponding rates of specificity were 62, 75 and 79%, respectively. The false-positive rate was 20% for ischemic ST-T and 4% for ischemic QRS duration for the entire study population. Conclusions Computer-measured QRS duration changes during ET are more sensitive and specific than ST-T changes for the detection of ischemia in women. C1 Ben Gurion Univ Negev, Barzilai Med Ctr, Ashqelon, Israel. Ben Gurion Univ Negev, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. RP Yosefy, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Noninvas Cardiac Lab, Boston, MA 02115 USA. EM cyosefy@partners.org NR 31 TC 6 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD MAY PY 2004 VL 15 IS 3 BP 147 EP 154 DI 10.1097/01.mca.0000126140.36675.11 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 818TP UT WOS:000221267700003 PM 15096995 ER PT J AU Mitsiades, CS Mitsiades, N Koutsilieris, M AF Mitsiades, CS Mitsiades, N Koutsilieris, M TI The Akt pathway: Molecular targets for anti-cancer drug development SO CURRENT CANCER DRUG TARGETS LA English DT Review ID PROTEIN-KINASE-B; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR GENE; FORKHEAD TRANSCRIPTION FACTOR; BREAST-CANCER CELLS; NF-KAPPA-B; GLYCOGEN-SYNTHASE KINASE-3; NITRIC-OXIDE SYNTHASE; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; PACLITAXEL-MEDIATED CYTOTOXICITY AB The serine/threonine kinase Akt functions intracellularly as a cardinal nodal point for a constellation of converging upstream signaling pathways, which involve stimulation of receptor tyrosine kinases such as IGF-1R, HER2/Neu, VEGF-R, PDGF-R), and an assembly of membrane-localized complexes of receptor-PI-3K and activation of Akt through the second messenger PIP3. The integration of these intracellular signals at the level of Akt and its kinase activity, regulates the phosphorylation of its several downstream effectors, such as NF-kappaB, mTOR, Forkhead, Bad, GSK-3 and MDM-2. These phosphorylation events in turn mediate the effects of Akt on cell growth, proliferation, protection from pro-apoptotic stimuli, and stimulation of neoangiogenesis. Because Akt and its upstream regulators are deregulated in a wide range of solid tumors and hematologic malignancies, and in view of the aforementioned biologic sequelae of this pathway, the Akt pathway is considered a key determinant of biologic aggressiveness of these tumors, and a major potential target for novel anti-cancer therapies. This review focuses on ongoing translational efforts to therapeutically target Akt and its biologic sequelae, either at the level of Akt itself or at the levels of its upstream regulators and downstream effectors. Because Akt is also important for proliferative and anti-apoptotic signaling pathways critical for normal cells, particular emphasis is placed on the fine-tuning the targeting of individual components of this pathway to maximize the therapeutic index of anti-cancer strategies based on the PI-3K/Akt pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Athens, Sch Med, Dept Expt Physiol, GR-11527 Athens, Greece. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer Bldg,Room M555, Boston, MA 02115 USA. EM Constaritine_Mitsiades@dfci.harvard.edu NR 305 TC 163 Z9 179 U1 1 U2 15 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD MAY PY 2004 VL 4 IS 3 BP 235 EP 256 DI 10.2174/1568009043333032 PG 22 WC Oncology SC Oncology GA 833UD UT WOS:000222364200001 PM 15134532 ER PT J AU Dobs, AS Matsumoto, AM Wang, C Kipnes, MS AF Dobs, AS Matsumoto, AM Wang, C Kipnes, MS TI Short-term pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE AndroGel((R)); buccal mucoadhesive; hormone replacement therapy; hypogonadism; pharmacokinetics; striant((R)); testosterone ID HYPOGONADAL MEN; SERUM TESTOSTERONE; ELDERLY-MEN; THERAPY; DENSITY AB Objective: The primary objective of the study was to compare the percentage of men with mean serum total T (Cave(0-24)) within normal range during the 24-h pharmacokinetic (PK) sampling period on Days 14 and 15. Methods: Treatment with a new testosterone (T) buccal system, (Striant*), 30 mg twice daily was compared to a transdermal gel delivery system, (T-gel) [AndroGeldagger 5 g containing 1% (50 mg) T] daily for 14 days in T-deficient men. Safety parameters included laboratory assessments and collection of adverse events. Patients were otherwise healthy T-deficient men with total T less than or equal to 8.7 nmol/L (less than or equal to 2.5 ng/mL). Results: Twenty-six of the 28 patients enrolled completed the 24-h PK assessment. Of the evaluable patients, 92.3% of T buccal system and 83.3% of T-gel patients had Cave(0-24) within the normal range of 10.4-36.4 nmol/L (3.0-10.5 ng/mL). Mean total T values were not different in the T buccal system group ( C(ave(0-24))16.7 +/- 4.7 nmol/L; 4.8 +/- 1.4 ng/mL) compared to the T-gel group (C(ave(0-24))15.9 +/- 4.8 nmol/L; 4.6 +/- 1.4 ng/mL). All T values returned to baseline levels after the study drug was stopped. Serum LH and FSH levels decreased, and E, increased as expected following T administration. Differences in DHT concentrations between treatment groups were significant (p = 0.012) with mean DHT levels on Day 14 of 1.9 +/- 1.4 nmol/L (0.55 +/- 0.42 ng/mL) for the T buccal system and 3.2 +/- 1.3 nmol/L (0.93 +/- 0.38 ng/mL) for T-gel, which was greater than the upper level of normal (2.9 nmol/L; 0.85 ng/mL). Statistically significant differences were seen in the mean T/DHT ratio on Days 14 and 15 with the T buccal system (9.3) and T-gel (5.0) (normal 9-12) (Day 14, p < 0.00001; Day 15, p < 0.0001). All adverse events were mild to moderate in severity. Three of 12 adverse events were considered related to the study drug and included headache (11 for each of the T buccal system and T-gel), and breast pain (T-gel). Summary and conclusions: In this short-term study, the T buccal system produced steady-state T levels comparable to those with T-Gel without significant adverse effects in T-deficient men. The T buccal system provides an additional safe, effective and convenient option for testosterone replacement therapy in hypogonadal men. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA. Res & Educ Inst, Torrance, CA USA. Diabet & Glandular Dis Res Associates, San Antonio, TX USA. RP Dobs, AS (reprint author), Johns Hopkins Univ, Sch Med, 1830 Monument St, Baltimore, MD 21287 USA. EM adobs@jhu.edu FU NCRR NIH HHS [M01-RR0425] NR 18 TC 21 Z9 22 U1 0 U2 1 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, 26-32 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD MAY PY 2004 VL 20 IS 5 BP 729 EP 738 DI 10.1185/030079904125003494 PG 10 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 822VR UT WOS:000221569100021 PM 15140340 ER PT J AU Spate, U Schulze, PC AF Spate, U Schulze, PC TI Proinflammatory cytokines and skeletal muscle SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Article DE cytokines; growth factors; hormones; skeletal muscle ID CHRONIC HEART-FAILURE; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-I; NITRIC-OXIDE SYNTHASE; CAMP-RESPONSE ELEMENT; FACTOR-ALPHA; INFLAMMATORY CYTOKINES; KAPPA-B; EXERCISE INTOLERANCE; UBIQUITIN LIGASES AB Purpose of review Metabolic abnormalities leading to a catabolic syndrome with progressive muscular atrophy are a common final stage of various chronic diseases. Proinflammatory cytokines have been suggested both to induce and mediate local catabolic mechanisms. This review focuses on the role of proinflammatory cytokines in the development of muscular abnormalities resulting in a loss of muscle mass and function. In addition, the underlying molecular signaling pathways, their transcriptional regulation, and the cellular systems contributing to enhanced muscular protein breakdown are discussed. Recent findings Using transcriptional screening techniques, specific changes in gene expression have been identified that are characteristic of muscular wasting processes. Of particular interest is the atrophy-related and cytokine-inducible expression of a number of E3 ligases (e.g. atrogin-1, muscle ring finger protein 1), highly specific regulators of the ubiquitin-proteasome pathway, which target proteins for proteolytic breakdown by the proteasome. Furthermore, the activity of several transcription factors (e.g. nuclear factor kappa B) has been involved in specific transcriptional mechanisms of local inflammation and muscular atrophy. Finally, proinflammatory cytokines suppress the expression and function of the local anabolic growth factor insulin-like growth factor 1. Summary Pronounced catabolic effects of proinflammatory cytokines in various tissues contribute to local catabolism, with progressive atrophic alterations of the skeletal muscle in chronic disease states. Recent developments in this field have explored the underlying pathways of muscular wasting and have already resulted in the description of new molecular targets that might lead to new therapeutic options for the treatment of muscular atrophy. C1 Cardiovasc Res, Dept Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Univ Leipzig, Ctr Heart, Dept Cardiol, Leipzig, Germany. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA USA. RP Schulze, PC (reprint author), Cardiovasc Res, Dept Med, 65 Landsdowne St,Room 280, Cambridge, MA 02139 USA. EM pcschulze@dcs.bwh.harvard.edu NR 53 TC 92 Z9 99 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD MAY PY 2004 VL 7 IS 3 BP 265 EP 269 DI 10.1097/01.mco.0000126344.88494.de PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 819IM UT WOS:000221308600005 PM 15075917 ER PT J AU Brady, KT AF Brady, KT TI What treatment for which patient? SO CURRENT OPINION IN PSYCHIATRY LA English DT Editorial Material C1 Ralph H Johnson Vet Adm Med Ctr, CTN, MUSC, Dept Psychiat, Charleston, SC 29401 USA. RP Brady, KT (reprint author), Ralph H Johnson Vet Adm Med Ctr, CTN, MUSC, Dept Psychiat, 109 Bee St, Charleston, SC 29401 USA. EM bradyk@musc.edu 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 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2004 VL 17 IS 3 BP 159 EP 159 DI 10.1097/01.yco.0000126544.23545.c9 PG 1 WC Psychiatry SC Psychiatry GA 818GC UT WOS:000221232600001 ER PT J AU Barteneva, N Kim, M Luther, E Luo, K Chang, DC Carman, C Brochu, M Sumen, C Ketman, K Telford, WG AF Barteneva, N Kim, M Luther, E Luo, K Chang, DC Carman, C Brochu, M Sumen, C Ketman, K Telford, WG TI A novel approach to fluorescence resonance energy transfer (FRET)-analysis using biosensors and cytometers equipped with mercury ARC lamp or violet diode lasers SO CYTOMETRY PART A LA English DT Meeting Abstract CT 22nd Congress of the International-Society-for-Analytical-Cytology CY MAY 22-27, 2004 CL Montpellier, FRANCE SP Ins Soc Analyt Cytol C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. CompuCyte, Cambridge, MA USA. Hong Kong Univ Sci & Technol, Hong Kong, Hong Kong, Peoples R China. NPE Syst, Pembroke Pines, FL USA. NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD MAY PY 2004 VL 59A IS 1 BP 30 EP 31 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 819MV UT WOS:000221319900023 ER PT J AU Luther, E Barteneva, N Luo, K Chang, DC AF Luther, E Barteneva, N Luo, K Chang, DC TI Measurement of caspase 3 activation by CFP/YFP fluorescence resonance energy transfer (FRET) and laser scanning cytometry SO CYTOMETRY PART A LA English DT Meeting Abstract CT 22nd Congress of the International-Society-for-Analytical-Cytology CY MAY 22-27, 2004 CL Montpellier, FRANCE SP Ins Soc Analyt Cytol C1 CompuCyte, Cambridge, MA USA. CBR Inst Biomed Res, Boston, MA USA. Hong Kong Univ Sci & Technol, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD MAY PY 2004 VL 59A IS 1 BP 43 EP 43 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 819MV UT WOS:000221319900057 ER PT J AU Paietta, E Goloubeva, O Neuberg, D Bennett, JM Gallagher, R Racevskis, J Dewald, G Wiernik, PH Tallman, MS AF Paietta, E Goloubeva, O Neuberg, D Bennett, JM Gallagher, R Racevskis, J Dewald, G Wiernik, PH Tallman, MS CA Eastern Cooperative Oncology Grp TI A surrogate marker profile for PML/RAR alpha expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE surrogate immunophenotype; PML/RAR alpha; APL; multiparameter flow cytometry; transcript isoforms ID ACUTE MYELOID-LEUKEMIA; TRANS-RETINOIC ACID; PREVIOUSLY UNRECOGNIZED FORM; ACUTE MYELOBLASTIC-LEUKEMIA; FLOW-CYTOMETRIC ANALYSIS; PML GENE BREAKPOINT; CELL ACUTE-LEUKEMIA; CD2 EXPRESSION; BLAST CELLS; HLA-DR AB Background: The availability of genotype-specific therapy for PML/RARalpha(pos) acute promyelocytic leukemia (APL) requires that this disease he precisely diagnosed. Immunophenotypic characteristics heretofore proclaimed as reliably characterizing APL (HLA-DRlow, CD34(low), P-glycoprotein(low) myeloid phenotype) do not differentiate from APL-like immune profiles unassociated with the PML/RARalpha fusion transcript. Methods: To establish a surrogate marker profile for APL, we explored 19 potentially predictive markers compared with differentiated acute myeloid leukemia using the classification tree approach with recursive partitioning. Results: In a test group of 58 APL patients, the most predictive immune profile was HLA-DRlow, CD11a(low) (alpha(L) subunit of the leukocyte integrin LFA-1), CD18(low) (beta(2) subunit of LFA-1). APL cells always expressed CD117 (c-kit) but lacked the progenitor antigen CD133 and the more mature myeloid antigen, CD11b (alpha(M) leukocyte integrin). This antigen pattern was validated in 90 additional APL patients. M3v APLs (n = 30) had more leukemic promyelocytes expressing the T-cell antigen, CD2 (P < 0.0001) or the stem cell marker, CD34 (P = 0.0003) and demonstrated higher fluorescence intensity for the binding of antibody to the common leukocyte antigen, CD45 (P = 0.0008) than M3 (n = 102). S-form APL (n = 45) had a higher percent of cells expressing CD2 or CD34 (P < 0.0001 for both) or the neural cell adhesion molecule CD56 (P = 0.001) than L-form APL (n = 66). Conclusions: PML/RARalpha(pos) APL cells typically lack leukocyte integrins. HLA-DRlow, CD11a(low), CD18(low) is a reliable surrogate antigen expression profile for PML/RARalpha(pos) APL, irrespective of morphology and transcript isoform. (C) 2004 Wiley-Liss, Inc. C1 New York Med Coll, Our Lady Mercy Canc Ctr, Immunol Lab, Bronx, NY 10456 USA. Dana Farber Canc Inst, ECOG, Ctr Stat, Boston, MA 02115 USA. Univ Rochester, Rochester, NY USA. Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. RP Paietta, E (reprint author), New York Med Coll, Our Lady Mercy Canc Ctr, Immunol Lab, 600 E 233rd St, Bronx, NY 10456 USA. EM epaietta@earthlink.net NR 47 TC 52 Z9 54 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAY PY 2004 VL 59B IS 1 BP 1 EP 9 DI 10.1002/cyto.b.20001 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 818NT UT WOS:000221252500001 PM 15108165 ER PT J AU Marra, DE Schanbacher, CF Torres, A AF Marra, DE Schanbacher, CF Torres, A TI Mohs micrographic surgery of primary cutaneous mucinous carcinoma using immunohistochemistry for margin control SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID SWEAT GLAND ADENOCARCINOMA; ADENOCYSTIC CARCINOMA; ECCRINE CARCINOMA; SKIN AB BACKGROUND. Primary cutaneous mucinous carcinoma is a rare adnexal malignancy with a high recurrence rate following conventional excision and the potential for aggressive local invasion. OBJECTIVE. To enhance the microscopic detection of mucinous carcinoma in Mohs micrographic surgical sections by incorporating rapid immunohistochemical staining. METHODS. Standard Mohs micrographic surgical technique was used in conjunction with frozen section immunohistochemistry using an antibody to low-molecular-weight cytokeratin. RESULTS. Rapid immunoperoxidase staining using low-molecular-weight cytokeratin detected residual foci of mucinous carcinoma that were difficult to identify on routine frozen sections. Immunostaining was strongly positive in areas with clear evidence of tumor by routine histology, as well as in adjacent areas on a subsequent stage where frozen sections were equivocal or negative. Immunostaining was distinctly negative at the final surgical margin, which was shown by en face permanent sections to be free of tumor. The patient has been free of recurrence for 3 years. CONCLUSION. Immunoperoxidase-guided Mohs micrographic surgery using low-molecular-weight cytokeratin enhances the sensitivity for detection of mucinous carcinoma, and may help contribute to complete tumor removal. C1 Dana Farber Canc Inst, Mohs Surg Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Loma Linda Univ, Med Ctr, Dept Dermatol, Loma Linda, CA USA. RP Schanbacher, CF (reprint author), Dana Farber Canc Inst, Mohs Surg Ctr, 44 Binney St, Boston, MA 02115 USA. EM Carl_Schanbacher@dfci.harvard.edu NR 27 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 2004 VL 30 IS 5 BP 799 EP 802 DI 10.1111/j.1524-4725.2004.30223.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 813XV UT WOS:000220940700021 PM 15099329 ER PT J AU Bulgakov, OV Eggenschwiler, JT Hong, DH Anderson, KV Li, TS AF Bulgakov, OV Eggenschwiler, JT Hong, DH Anderson, KV Li, TS TI FKBP8 is a negative regulator of mouse sonic hedgehog signaling in neural tissues SO DEVELOPMENT LA English DT Article DE FKBP8; FKBP38; sonic hedgehog; neural tube patterning; signaling; mouse ID CENTRAL-NERVOUS-SYSTEM; DEVELOPING SPINAL-CORD; PROTEIN-KINASE-A; CUBITUS INTERRUPTUS; FLOOR PLATE; NEURONAL SPECIFICATION; BINDING-PROTEIN; TUBE DEFECTS; OPEN BRAIN; CELL FATE AB Sonic hedgehog (SHH) is a secreted morphogen that regulates the patterning and growth of many tissues in the developing mouse embryo, including the central nervous system (CNS). We show that a member of the FK506-binding protein family, FKBP8, is an essential antagonist of SHH signaling in CNS development. Loss of FKBP8 causes ectopic and ligand-independent activation of the Shh pathway, leading to expansion of ventral cell fates in the posterior neural tube and suppression of eye development. Although it is expressed broadly, FKBP8 is required to antagonize SHH signaling primarily in neural tissues, suggesting that hedgehog signal transduction is subject to cell-type specific modulation during mammalian development. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Sloan Kettering Inst, Dev Biol Program, New York, NY 10021 USA. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. EM tli@meei.harvard.edu OI Anderson, Kathryn/0000-0003-1657-2161 FU NEI NIH HHS [EY10309]; NINDS NIH HHS [NS044385] NR 69 TC 69 Z9 71 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2004 VL 131 IS 9 BP 2149 EP 2159 DI 10.1242/dev.01122 PG 11 WC Developmental Biology SC Developmental Biology GA 824DE UT WOS:000221663600023 PM 15105374 ER PT J AU Zelzer, E Mamluk, R Ferrara, N Johnson, RS Schipani, E Olsen, BR AF Zelzer, E Mamluk, R Ferrara, N Johnson, RS Schipani, E Olsen, BR TI VEGFA is necessary for chondrocyte survival during bone development SO DEVELOPMENT LA English DT Article DE conditional knockout mice; VEGFA; chondrocyte survival; bone development; angiogenesis; HIF1; HIF1 alpha; VEGF ID ENDOTHELIAL GROWTH-FACTOR; INDUCIBLE FACTOR-I; EXTRACELLULAR-MATRIX; MICE LACKING; HIF-ALPHA; HYPOXIA; EXPRESSION; ANGIOGENESIS; CELLS; DIFFERENTIATION AB To directly examine the role of vascular endothelial growth factor (VEGFA) in cartilage development, we conditionally knocked out Vegfa in chondrocytes, using the Col2a1 promoter to drive expression of Cre recombinase. Our study of Vegfa conditional knockout (CKO) mice provides new in-vivo evidence for two important functions of VEGFA in bone formation. First, VEGFA plays a significant role in both early and late stages of cartilage vascularization, since Vegfa CKO mice showed delayed invasion of blood vessels into primary ossification centers and delayed removal of terminal hypertrophic chondrocytes. Second, VEGFA is crucial for chondrocyte survival, since massive cell death was seen in joint and epiphyseal regions of Vegfa CKO endochondral bones. Chondrocytes in these regions were found to upregulate expression of Vegfa in wild-type mice at the time when massive cell death occurred in the Vegfa CKO mice. The expression of the VEGFA receptors Npr1 and Npr2 in epiphyseal chondrocytes and lack of blood vessel reduction in the vicinity of the cartilaginous elements in the Vegfa CKO mice raise the possibility that the observed cell death is the result of a direct involvement of VEGFA in chondrocyte survival. Interestingly, the extensive cell death seen in Vegfa CKO null bones had a striking similarity to the cell death phenotype observed when hypoxia-inducible factor 1alpha (Hif1a) expression was abolished in developing cartilage. This similarity of cell death phenotypes and the deficient VEGFA production in Hif1a null epiphyseal chondrocytes demonstrate that HIF1alpha and VEGFA are components of a key pathway to support chondrocyte survival during embryonic bone development. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg Res, Boston, MA 02115 USA. Genentech Inc, Dept Mol Oncol, San Francisco, CA 94080 USA. Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Olsen, BR (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM bjorn_olsen@hms.harvard.edu OI Johnson, Randall/0000-0002-4084-6639 FU NIAMS NIH HHS [AR36820, AR36819] NR 47 TC 212 Z9 230 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2004 VL 131 IS 9 BP 2161 EP 2171 DI 10.1242/dev.01053 PG 11 WC Developmental Biology SC Developmental Biology GA 824DE UT WOS:000221663600024 PM 15073147 ER PT J AU Pfander, D Kobayashi, T Knight, MC Zelzer, E Chan, DA Olsen, BR Giaccia, AJ Johnson, RS Haase, VH Schipani, E AF Pfander, D Kobayashi, T Knight, MC Zelzer, E Chan, DA Olsen, BR Giaccia, AJ Johnson, RS Haase, VH Schipani, E TI Deletion of Vhlh in chondrocytes reduces cell proliferation and increases matrix deposition during growth plate development SO DEVELOPMENT LA English DT Article DE von Hippel-Lindau tumor suppressor protein; cartilage development; HIFI alpha ID LINDAU TUMOR-SUPPRESSOR; ENDOCHONDRAL BONE-FORMATION; HORMONE-RELATED PEPTIDE; RENAL-CARCINOMA CELLS; PROLYL HYDROXYLATION; EMBRYONIC LETHALITY; PARATHYROID-HORMONE; MOUSE DEVELOPMENT; MICE LACKING; FACTOR VEGF AB The von Hippel Lindau tumor suppressor protein (pVHL) is a component of a ubiquitin ligase that promotes proteolysis of the transcription factor hypoxia-inducible-factor 1alpha (HIF1alpha), the key molecule in the hypoxic response. We have used conditional inactivation of murine VHL (Vhlh) in all cartilaginous elements to investigate its role in endochondral bone development. Mice lacking Vhlh in cartilage are viable, but grow slower than control littermates and develop a severe dwarfism. Morphologically, Vhlh null growth plates display a significantly reduced chondrocyte proliferation rate, increased extracellular matrix, and presence of atypical large cells within the resting zone. Furthermore, stabilization of the transcription factor HIF1alpha leads to increased expression levels of HIF1alpha target genes in Vhlh null growth plates. Lastly, newborns lacking both Vhlh and Hif1alpha genes in growth plate chondrocytes display essentially the same phenotype as Hif1a null single mutant mice suggesting that the Vhlh null phenotype could result, at least in part, from increased activity of accumulated HIF1alpha. This is the first study reporting the novel and intriguing findings that pVHL has a crucial role in endochondral bone development and is necessary for normal chondrocyte proliferation in vivo. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Orthoped Surg, Div Orthoped Rheumatol, D-91054 Erlangen, Germany. Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Stanford Univ, Dept Radiat Oncol, Program Canc Biol, Stanford, CA 94305 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu RI Haase, Volker Hans/A-6758-2013; OI Haase, Volker Hans/0000-0002-7051-8994; Johnson, Randall/0000-0002-4084-6639 FU NIAMS NIH HHS [AR048191]; NIDDK NIH HHS [K08 DK002668] NR 59 TC 81 Z9 83 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 2004 VL 131 IS 10 BP 2497 EP 2508 DI 10.1242/dev.01138 PG 12 WC Developmental Biology SC Developmental Biology GA 830MY UT WOS:000222127700025 PM 15128677 ER PT J AU Sassa, Y Hata, Y Aiello, LP Taniguchi, Y Kohno, K Ishibashi, T AF Sassa, Y Hata, Y Aiello, LP Taniguchi, Y Kohno, K Ishibashi, T TI Bifunctional properties of peroxisome proliferator-activated receptor gamma 1 in KDR gene regulation mediated via interaction with both Sp1 and Sp3 SO DIABETES LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; SMOOTH-MUSCLE-CELLS; TYROSINE KINASE; FACTOR EXPRESSION; PROGENITOR CELLS; RETINOIC ACID; GAMMA; NEOVASCULARIZATION; TRANSCRIPTION; ANGIOGENESIS AB Vascular endothelial growth factor receptor 2 (KDR) plays a critical role in mediating a variety of vasculogenic and angiogenic processes, including diabetic retinopathy. We previously demonstrated that the promoter activity of the KDR gene in retinal capillary endothelial cells (RCECs) was regulated in part by the relative concentration of positive/negative transcription factors Sp1/Sp3. We also reported that the peroxisome proliferator-activated receptor (PPAR)gamma ligand could inhibit intraocular angiogenesis. In the present study, the role of PPAR-gamma in KDR gene regulation in RCECs was examined. PPARgamma1 protein physically interacted with both Sp1 and Sp3. Transactivation and electrophoretic mobility shift assays clearly demonstrated novel findings that PPAR-gamma1 increased KDR promoter activity by enhancing the interaction between Sp1, but not Sp3, and KDR promoter region without its ligand in RCECs. The ligand-binding site but not the DNA binding site of PPARgamma1 enhanced the interaction between Sp1 and KDR promoter region. Conversely, PPARgamma1 ligand 15-deoxy Delta (12,14)-prostaglandin J2 dose-dependently suppressed the binding of KDR promoter region with both Sp1 and Sp3, resulting an inhibition of KDR gene expression. In conclusion, PPAR-gamma1 has bifunctional properties in the regulation of KDR gene expression mediated via interaction with both Sp1 and Sp3. C1 Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Kyoto Univ, Grad Sch Agr, Dept Anim Breeding & Genet, Kyoto, Japan. Univ Occupat & Environm Hlth, Sch Med, Dept Mol Biol, Kitakyushu, Fukuoka 807, Japan. RP Ishibashi, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM ishi@med.kyushu-u.ac.jp RI Sassa, Yukio/H-6339-2012; U-ID, Kyushu/C-5291-2016 NR 35 TC 43 Z9 45 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2004 VL 53 IS 5 BP 1222 EP 1229 DI 10.2337/diabetes.53.5.1222 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 817DD UT WOS:000221157300007 PM 15111490 ER PT J AU Florez, JC Burtt, N de Bakker, PIW Almgren, P Tuomi, T Holmkvist, J Gaudet, D Hudson, TJ Schaffner, SF Daly, MJ Hirschhorn, JN Groop, L Altshuler, D AF Florez, JC Burtt, N de Bakker, PIW Almgren, P Tuomi, T Holmkvist, J Gaudet, D Hudson, TJ Schaffner, SF Daly, MJ Hirschhorn, JN Groop, L Altshuler, D TI Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region SO DIABETES LA English DT Article ID TYPE-2 DIABETES-MELLITUS; BETA-CELL FUNCTION; INSULIN-SECRETION; SEQUENCE VARIANTS; K+ CHANNEL; FRENCH CAUCASIANS; GLUCOSE-TOLERANCE; E23K VARIANT; HUMAN GENOME; KIR6.2 AB The genes for the sulfonylurea receptor (SUR1; encoded by ABCC8) and its associated islet ATP-sensitive potassium channel (Kir6.2; encoded by KCNJ11) are adjacent to one another on human chromosome 11. Multiple studies have reported association of the E23K variant of Kir6.2 with risk of type 2 diabetes. Whether and how E23K itself-or other variant(s) in either of these two closely linked genes-influences type 2 diabetes remains to be fully determined. To better understand genotype-phenotype correlation at this important candidate gene locus, we 1) characterized haplotype structures across the gene region by typing 77 working, high-frequency markers spanning 207 kb and both genes; 2) performed association studies of E23K and nearby markers in >3,400 patients (type 2 diabetes and control) not previously reported in the literature; and 3) analyzed the resulting data for measures of insulin secretion. These data independently replicate the association of E23K with type 2 diabetes with an odds ratio (OR) in the new data of 1.17 (P = 0.003) as compared with an OR of 1.14 provided by meta-analysis of previously published, nonoverlapping data (P = 0.0002). We find that the E23K variant in Kir6.2 demonstrates very strong allelic association with a coding variant (A1369S) in the neighboring SUR1 gene (r(2) > 0.9) across a range of population samples, making it difficult to distinguish which gene and polymorphism in this region are most likely responsible for the reported association. We show that E23K is also associated with decreased insulin secretion in glucose-tolerant control subjects, supporting a mechanism whereby beta-cell dysfunction contributes to the common form of type 2 diabetes. Like peroxisome proliferator-activated receptor gamma, the SUR1/Kir6.2 gene region both contributes to the inherited risk of type 2 diabetes and encodes proteins that are targets for hypoglycemic medications, providing an intriguing link between the underlying mechanism of disease and validated targets for pharmacological treatment. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Lund Univ, Univ Hosp MAS, Dept Endocrinol, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Folkhalsan Res Inst, Helsinki, Finland. Univ Montreal, Chicoutimi Hosp, Community Genom Ctr, Quebec City, PQ, Canada. McGill Univ, Montreal, PQ, Canada. Genome Quebec Innovat Ctr, Montreal, PQ, Canada. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Groop, L (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM leif.groop@endo.mas.lu.se RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 FU NIDDK NIH HHS [5T32 DK 07028-28] NR 37 TC 199 Z9 205 U1 2 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2004 VL 53 IS 5 BP 1360 EP 1368 DI 10.2337/diabetes.53.5.1360 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 817DD UT WOS:000221157300024 PM 15111507 ER PT J AU Kim, SH Ma, XW Weremowicz, S Ercolino, T Powers, C Mlynarski, W Bashan, KA Warram, JH Mychaleckyj, J Rich, SS Krolewski, AS Doria, A AF Kim, SH Ma, XW Weremowicz, S Ercolino, T Powers, C Mlynarski, W Bashan, KA Warram, JH Mychaleckyj, J Rich, SS Krolewski, AS Doria, A TI Identification of a locus for maturity-onset diabetes of the young on chromosome 8p23 SO DIABETES LA English DT Article ID MULTIPOINT LINKAGE ANALYSIS; GENOME-WIDE SEARCH; I ALPHA-GENE; SUSCEPTIBILITY LOCUS; LOD SCORES; INDEPENDENT REPLICATION; COMMON-CAUSE; MUTATIONS; MELLITUS; HETEROGENEITY AB Maturity-onset diabetes of the young (MODY) is a subtype of diabetes defined by an autosomal dominant inheritance and a young onset. Six MODY genes have been discovered to date. To identify additional MODY loci, we conducted a genome scan in 21 extended U.S. families (15 white and 6 from minorities, for a total of 237 individuals) in which MODY was not caused by known MODY genes. Seven chromosomal regions (1q42, 2q24, 2q37, 4p13, 8p23, 11p15, and 19q12) had a parametric heterogeneity logarithm of odds (HLOD) greater than or equal to1.00 or a nonparametric logarithm of odds (LOD) greater than or equal to 0.59 (P less than or equal to 0.05) in the initial screen. After typing additional markers at these loci to reduce the spacing to 2-3 cM, significant linkage was detected on 8p23 (HLOD = 3.37 at D8S1130 and nonparametric LOD = 3.66; P = 2 X 10(-5) at D8S265), where a 4.7-Mb inversion polymorphism is located. Thirty percent of the families (6 of 21) were linked with this region. Another linkage peak on chromosome 2q37 with an HLOD of 1.96 at D2S345/ D2S2968 accounted for diabetes in an additional 25% of families (5 of 21). All 6 minority families were among the 11 families linked to these loci. None of the other loci followed up had an HLOD exceeding 1.50. In summary, we have identified a MODY locus on 8p23 that accounts for diabetes in a substantial proportion of MODY cases unlinked to known MODY genes. Another novel MODY locus may be present on 2q37. Cloning these new MODY genes may offer insights to disease pathways that are relevant to the cause of common type 2 diabetes. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Cytogenet Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu FU NIDDK NIH HHS [DK 36836, DK 55523, DK 60837, DK 47475] NR 55 TC 25 Z9 26 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2004 VL 53 IS 5 BP 1375 EP 1384 DI 10.2337/diabetes.53.5.1375 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 817DD UT WOS:000221157300026 PM 15111509 ER PT J AU Maciejewski, ML Maynard, C AF Maciejewski, ML Maynard, C TI Diabetesm related utilization and costs for inpatient and outpatient services in the veterans administration SO DIABETES CARE LA English DT Article ID AFFAIRS; SYSTEM AB OBJECTIVE - The purpose of this study was to calculate the total number of inpatient hospitalizations, outpatient clinic visits, and total direct health care costs associated with veterans with diabetes receiving care in Veterans Administration (VA) facilities. RESEARCH DESIGN AND METHODS - The number of inpatient hospitalizations is tracked for years 1994-1998, and outpatient clime visits are tracked for years 1997 and 1998. Trends in utilization across different age and racial groups, as well as total direct inpatient and outpatient costs for 1998, are presented. RESULTS - Between 1.994 and 1998, hospitalization rates decreased from 1.68 to 1.61. The average number of outpatient visits was 4.5 in 1997 and 4.6 in 1998. VA incurred $214.8 million in outpatient expenditures and $1.45 billion in inpatient expenditures for veterans with diabetes receiving VA care. CONCLUSIONS - Health care delivery systems and payers track the cost and utilization of services by specific patient groups to Support disease management, quality improvement, external reporting, and cost containment. Tracking the utilization and cost of diabetes care is necessary to understand the financial impact of diabetes on health care systems and the overall burden of diabetes on individuals. C1 VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. RP Maciejewski, ML (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM mlmaciej@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 11 TC 37 Z9 39 U1 0 U2 0 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 MAY PY 2004 VL 27 SU 2 BP B69 EP B73 DI 10.2337/diacare.27.suppl_2.B69 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800012 PM 15113786 ER PT J AU Mayfield, JA Reiber, GE Maynard, C Czerniecki, J Sangeorzan, B AF Mayfield, JA Reiber, GE Maynard, C Czerniecki, J Sangeorzan, B TI The epidemiology of lower extremity disease in veterans with diabetes SO DIABETES CARE LA English DT Article AB OBJECTIVE - To describe the epidemiology of lower-extremity complications of diabetes in veterans who are users of the Department of Veterans Affairs (VA). RESEARCH DESIGN AND METHODS - Hospital discharge records for care provided in all VA hospitals in 1998 were obtained. All hospitalizations for lower-extremity ulceration, peripheral vascular procedures, and amputation were analyzed using frequency tables. A diabetes denominator was defined as a veteran with at least three ambulatory care visits with at least one diabetes diagnosis code. Age-specific and total age-adiusted rates of discharge with ulceration, vascular procedures, and amputation were calculated. RESULTS - Veterans with diabetes comprised over half of all hospitalizations for lower-extremity ulceration, one-third of all hospitalizations for peripheral vascular procedures, and two-thirds of all hospitalizations for amputation. The age-specific discharge rate per 1,000 diabetic persons for age 0-64 years, 65-74 years, and 75 years and older for ulceration were 28.4, 31.0, and 37.9; for vascular procedures, the rates were 3.5, 4.4, and 4.41 and for amputation, the rates were 7.3, 9.0, and 1.0.0, respectively. CONCLUSIONS - Veterans With diabetes comprise a significant proportion of hospitalizations for lower-extremity ulceration, peripheral vascular bypass, and amputation. Age-specific rates of diabetic amputation in Veterans are lower than U.S. rates. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Ctr Excellence Amputat Prosthet & Limb Loss Preve, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Orthoped Surg, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, 152,1660 S Columbin Way, Seattle, WA 98108 USA. EM greiber@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 9 TC 18 Z9 18 U1 0 U2 4 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 MAY PY 2004 VL 27 SU 2 BP B39 EP B44 DI 10.2337/diacare.27.suppl_2.B39 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800007 PM 15113781 ER PT J AU Maynard, C Chapko, MK AF Maynard, C Chapko, MK TI Data resources in the Department of Veterans Affairs SO DIABETES CARE LA English DT Article ID MEDICAL-CARE SYSTEM; HOSPITALS; FILES AB OBJECTIVE - To provide an overview of databases that are maintained by the Department of Veterans Affairs (VA) and are of relevance to investigators involved in epidemiologic, clinical, and health services research. RESEARCH DESIGN AND METHODS - We reviewed both national and local VA databases and identified their strengths and limitations. We also referenced specific studies that have assessed the validity and reliability of VA databases. RESULTS - There are numerous national databases housed at the Austin Automation Center in Austin, Texas. These include the Patient Treatment File (hospital abstracts), the Outpatient Care File, the Beneficiary Identification Record Locator System death file for assessing vital status, and the Decision Support System, which provides integrated clinical and financial information for managerial decision making. The major limitation of these databases is that clinical detail below the level of ICD-9-CM diagnosis and procedure codes is not uniformly available nationally. These databases offer an excellent opportunity to monitor the health of veterans over time because they track all inpatient and outpatient utilization in the VA. However, at the local or medical center level, the Veterans Health information and Systems and Technology Architecture contains extensive clinical information, but has fewer patients, varies in format across medical centers, and poses difficulties with data extraction for statistical analysis. CONCLUSIONS - Both local and national VA databases are valuable resources for investigators who have interests in a wide array of research topics, including diabetes. The potential for investigating important scientific questions with VA databases becomes greater as communications and database management technologies improve. C1 VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Maynard, C (reprint author), VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM cmaynard@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 11 TC 68 Z9 69 U1 2 U2 4 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 MAY PY 2004 VL 27 SU 2 BP B22 EP B26 DI 10.2337/diacare.27.suppl_2.B22 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800004 PM 15113778 ER PT J AU Orcutt, J Avakian, A Koepsell, TD Maynard, C AF Orcutt, J Avakian, A Koepsell, TD Maynard, C TI Eye disease in veterans with diabetes SO DIABETES CARE LA English DT Article ID RETINOPATHY; MELLITUS; CARE AB OBJECTIVE - To describe the screening, prevalence, and management of eye disease in veterans cared for by the Veterans Affairs (VA) System. RESEARCH DESIGN AND METHODS - Eye examinations, treatments, and diseases were identified in veterans with diabetes who received care in inpatient and outpatient VA settings during FY1998. Analysis was conducted to characterize the patient population and screened population and to compare them to the total VA patient population with diabetes. Logistic regression was performed to predict eye screening. RESULTS - Overall 48% of veterans with diabetes had an eye examination in FY1998. One-third of all veterans had an eye condition and 8.6% of veterans had ophthalmic manifestations of diabetes. In addition 11% reported glaucoma and 17.8% reported cataract surgery. Approximately 11,500 (2.7%) veterans were blind. CONCLUSIONS - Visual impairment is a common complication of diabetes. Half of this population of veterans had a visual examination recorded in VA. The VA is testing a more targeted screening and treatment approach for diabetic eye disease in order to prevent the serious eye complications. C1 VA Paget Sound Hlth Care Syst, Dept Opthalmol, Seattle, WA 98108 USA. Univ Washington, Dept Opthamol, Seattle, WA 98195 USA. Seattle ERIC, VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Orcutt, J (reprint author), VA Paget Sound Hlth Care Syst, Dept Opthalmol, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jorcutt@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 12 TC 7 Z9 7 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 MAY PY 2004 VL 27 SU 2 BP B50 EP B53 DI 10.2337/diacare.27.suppl_2.B50 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800009 PM 15113783 ER PT J AU Reiber, GE Boyko, EJ AF Reiber, GE Boyko, EJ TI Diabetes research in the department of veterans affairs SO DIABETES CARE LA English DT Article ID TRIAL AB OBJECTIVE - To provide an overview of the Department of Veterans Affairs (VA) research activities, highlighting diabetes-related research. RESEARCH DESIGN AND METHODS - Diabetes is an important component of the VA research portfolio. All four VA research services support aspects of diabetes research. VA diabetes research projects and funding were examined from 1998 to 2003. RESULTS - VA scientists are conducting research on diabetes genetics, etiology, diagnosis, therapy, epidemiology, health services, and rehabilitation. VA research funding is available to answer important veteran-relevant questions through peer review, Center of Excellence activities, and multisite trial mechanisms. Many VA scientists also receive research support from nonfederal sources, including private corporations and nonprofit foundations. The VA Office of Research and Development actively supports training the next generation of researchers through their career development awards and the VA health profession training programs. CONCLUSIONS - The VA's diabetes research portfolio is extensive and includes many investigators, trainees, and fellows. There is substantial leveraging of VA diabetes research with support from other federal and nonfederal funding agencies, foundations, and private corporations. VA diabetes research findings benefit the global diabetes care community. C1 VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. HSR&D Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM greiber@u.washington.edu NR 4 TC 6 Z9 6 U1 0 U2 0 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 MAY PY 2004 VL 27 SU 2 BP B95 EP B98 DI 10.2337/diacare.27.suppl_2.B95 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800016 PM 15113790 ER PT J AU Reiber, GE Au, D McDonell, M Fihn, SD AF Reiber, GE Au, D McDonell, M Fihn, SD TI Diabetes quality improvement in department of veterans affairs - Ambulatory care clinics - A group-randomized clinical trial SO DIABETES CARE LA English DT Article ID MANAGEMENT; GUIDELINES; SYSTEM AB OBJECTIVE - To conduct a group-randomized clinical trial to determine whether regular feedback to primary care providers of synthesized information on patients' health, function, and satisfaction would demonstrate improved outcomes for their patients with diabetes. RESEARCH DESIGN AND METHODS - Patients in General Internal Medicine Clinics Department of Veterans Affairs (VA) Medical Centers were randomized into seven intervention or control firms. Patient self-reported information was collected by mail on general health, diabetes, and up to five other chronic conditions. Patients with diabetes received the Seattle Diabetes Questionnaire, the 36-item Medical Outcomes Study short form (SF-36), and a validated patient Satisfaction questionnaire at regular intervals. Data from self-report, clinical, Pharmacy, and laboratory sources were synthesized into patient-specific feedback reports that intervention providers received before patients visits. RESULTS - The timely delivery to primary care providers of state-of-the-art patient-feedback reports that identified patient issues and areas for improvement did not result in significant improvements in patient outcomes between the intervention and control firms. CONCLUSIONS - Outcomes in diabetic patients whose providers received synthesized patient data before visits were no better than in those receiving care from control firms. Future studies may benefit from substantial involvement in patients discussing, problem solving, and goal setting in addition to use of timely synthesized patient data. C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Seattle, WA 98108 USA. Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Seattle, WA 98108 USA. EM greiber@u.washington.edu NR 18 TC 9 Z9 9 U1 0 U2 0 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 MAY PY 2004 VL 27 SU 2 BP B61 EP B68 DI 10.2337/diacare.27.suppl_2.B61 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800011 PM 15113785 ER PT J AU Reiber, GE Koepsell, TD Maynard, C Haas, LB Boyko, EJ AF Reiber, GE Koepsell, TD Maynard, C Haas, LB Boyko, EJ TI Diabetes in nonveterans, veterans, and veterans receiving Department of Veterans Affairs health care SO DIABETES CARE LA English DT Article ID DISEASE AB \OBJECTIVE - To compare behavioral risk factors and health and disease characteristics among three groups of adults with diabetes: nonveterans, veterans not receiving Department of Veterans Affairs (VA) health care, and veterans using VA services. RESEARCH DESIGN AND METHODS - Two data sources were used to describe the veteran population. First, the 2000 Behavioral Risk Factor Surveillance System (BRFSS) characterized the U.S. adult population by preventive health practices and risk behaviors linked to chronic and preventable diseases. New to the 2000 survey were questions on veteran status, which were administered in all states. Second, VA administrative and veterans benefits data were analyzed to describe comorbidity, education services, and veterans benefits. RESULTS - The estimated prevalence of diabetes in male veterans receiving VA care was 16%. Male veterans with diabetes using VA care were more likely to be nonwhite, not employed, have lower income, lower health status, and more activity limitations than male veterans not using these services. Computerized records indicate VA users with diabetes also had high concurrent comorbidity. Frequency of VA diabetes and preventive care services, as measured by selected quality indicators, was equivalent to or higher than the levels reported by veterans not receiving VA care and nonveterans. in addition to health care, nearly one-fourth of veterans with diabetes also received monthly awards for compensation and pension. CONCLUSIONS - Males receiving VA care with self-reported diabetes indicated receiving preventive care services at equivalent or higher levels than their counterparts receiving care outside the VA and nonveterans. C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Veterans Affairs Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM greiber@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 21 TC 39 Z9 39 U1 0 U2 0 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 MAY PY 2004 VL 27 SU 2 BP B3 EP B9 DI 10.2337/diacare.27.suppl_2.B3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800002 PM 15113776 ER PT J AU Reiber, GE Boyko, EJ Maynard, C Koepsell, TD Pogach, LM AF Reiber, GE Boyko, EJ Maynard, C Koepsell, TD Pogach, LM TI Diabetes in the Department of Veterans Affairs SO DIABETES CARE LA English DT Article ID HEALTH-CARE-SYSTEM C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Veterans Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA New Jersey Hlth Care Syst, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM greiber@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 6 TC 5 Z9 5 U1 0 U2 0 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 MAY PY 2004 VL 27 SU 2 BP B1 EP B2 DI 10.2337/diacare.27.suppl_2.B1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800001 PM 15113775 ER PT J AU Smith, NL Maynard, C AF Smith, NL Maynard, C TI The burden of diabetes-associated cardiovascular hospitalizations in veterans administration (VA) and non-VA medical facilities SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; IMPAIRED FASTING GLUCOSE; MICROVASCULAR COMPLICATIONS; MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; INSULIN; EVENTS; RISK; PRAVASTATIN AB OBJECTIVE - This study examines the relative burden of cardiovascular disease in diabetic and nondiabetic admissions to Veterans Administration (VA) and non-VA hospitals. RESEARCH DESIGN AND METHODS - Calendar year 1997 hospitalization data were collected from the VA Patient Treatment File and the National Hospital Discharge Survey, National Center for Health Statistics. Discharge diagnoses based on ICD-9 codes were used to classify cardiovascular events and procedures and diabetes. Proportionate hospitalization ratios (PHRs) were calculated based on the number of cardiovascular hospitalizations from among all hospitalizations. RESULTS - We identified 119,653 VA hospitalizations (19.1%) and 3,765,696 non-VA hospitalizations (16.8%) that coded diabetes among the discharge diagnoses. Cardiovascular hospitalizations, primarily coronary in origin, accounted for nearly 50% of all hospitalizations of persons with diabetes within VA and non-VA medical care systems. Coronary events and procedures (PHR = 1.85 and 1.68) and, to a lesser extent, cerebrovascular events and procedures (PHR = 1.55 and 1.33) were more common in VA hospitalizations where diabetes was listed as a comorbidity than in VA hospitalizations where diabetes was not listed. The burden of coronary hospitalizations was larger in VA than non-VA facilities for men (PHR = 1.82 vs. 1.66) and smaller in VA than non-VA facilities for women (PHR = 3.11 vs. 3.44) in age and race-standardized analyses. The burden of coronary hospitalization was higher for whites and blacks in VA facilities (PHR = 1.83 and 2.01) when compared with non-VA facilities (PHR = 1.68 and 1.84). CONCLUSIONS - The burden of cardiovascular hospitalizations is not equally borne across hospitalizations with and without diabetes and across VA and non-VA facilities. C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA USA. RP Smith, NL (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle Div, 1660 S Columbian Way,Mailstop 152E, Seattle, WA 98108 USA. EM nlsmith@u.washington.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 16 TC 10 Z9 10 U1 1 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 MAY PY 2004 VL 27 SU 2 BP B27 EP B32 DI 10.2337/diacare.27.suppl_2.B27 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800005 PM 15113779 ER PT J AU Smith, NL Chen, L Au, DH McDonell, M Fihn, SD AF Smith, NL Chen, L Au, DH McDonell, M Fihn, SD TI Cardiovascular risk factor control among veterans with diabetes - The ambulatory care quality improvement project SO DIABETES CARE LA English DT Article ID BLOOD-PRESSURE; PROGRAM; DISEASE AB OBJECTIVE - To describe the extent to which hyperglycemia, hypertension, and dyslipidemia are currently detected, treated, and controlled in U.S. veterans with diabetes with and Without ischemic heart disease (IHD). RESEARCH DESIGN AND METHODS - A cohort of 3,769 veterans who self-reported diabetes and who received all health care from the Veterans Administration (VA) medical centers were selected from subjects enrolled in the Ambulatory Care Quality Improvement Project, a randomized health services intervention at seven VA primary care clinics. IHD was defined by a self-reported history of myocardial ischemia, infarction, or revascularization. Mean values of HbA(1c), blood pressure, and cholesterol subfractions were collected from computerized laboratory databases. Medication data were collected from computerized pharmacy databases. RESULTS - Mean HbA(1c) and optimal control (HbA(1c) <7%) did not differ for those without and with IHD: 8.1 vs. 8.0%, and 26 vs. 24%, respectively. Veterans with IHD were more likely to have hypertension (73 vs. 64%), to be treated (88 vs. 78%), and to have optimal blood pressure control (19 vs. 10%) compared with veterans without IHD (all P values <0.01). Veterans with IHD were more likely to have dyslipidemia (81 vs. 53%), were equally likely to be treated (54 vs. 50%), and were more likely to have optimal LDL levels (30 vs. 16%) compared with veterans without IHD, all P values <0.01. CONCLUSIONS - Optimal cardiovascular risk factor control was the exception in this cohort of diabetic veterans attending primary care clinics. More aggressive management of cardiovascular risk factors in veterans with diabetes may be warranted, especially among those without prevalent (IHD). C1 VA Puget Sound Hlth Care System, Seattle Epidemiol Res & Informat Ctr, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Rochester, Ctr Med, Cardiol Unit, Rochester, NY USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Smith, NL (reprint author), VA Puget Sound Hlth Care System, Seattle Epidemiol Res & Informat Ctr, Seattle Div, 1660 S Columbian Way,Mailstop 152E, Seattle, WA 98108 USA. EM nlsmith@u.washington.edu NR 14 TC 7 Z9 7 U1 0 U2 0 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 MAY PY 2004 VL 27 SU 2 BP B33 EP B38 DI 10.2337/diacare.27.suppl_2.B33 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800006 PM 15113780 ER PT J AU Young, BA Pugh, JA Maynard, C Reiber, G AF Young, BA Pugh, JA Maynard, C Reiber, G TI Diabetes and renal disease in veterans SO DIABETES CARE LA English DT Article ID PIMA-INDIANS; GROSS PROTEINURIA; MELLITUS; MICROALBUMINURIA; NEPHROPATHY; MORTALITY; DETERMINANTS; PREVALENCE; SURVIVAL; NIDDM AB OBJECTIVE - To describe the frequency and sequelae of diabetic renal disease in veterans who receive health care from the Veterans Administration (VA). RESEARCH DESIGN AND METHODS - Veterans With a diagnosis of diabetes, diabetic nephropathy, other kidney diseases, and end-stage renal disease (ESRD) were identified by diagnosis codes from national VA databases for FY1998. Data were obtained and analyzed for prevalence of renal disease, comorbid conditions, and 1-year mortality. RESULTS - A total of 44,671 (10.7%) of the 415,910 veterans with diabetes had a concomitant diagnosis of any renal disease. The average age was 67 years; 98% were male and 60% were white. The prevalence of diabetic nephropathy was 6.0% (n = 25,263). ESPD secondary to diabetes was present in 4.2% (17,636) of subjects. The age-standardized prevalence of diabetes and any renal disease was 72.6/1,000 persons and differed by race (white 76.1/1,000, black 103.4/1,000 persons). Diabetes-associated ESRD prevalence was higher among black versus white veterans and male versus female veterans. One-year age-standardized mortality was 10.7%. CONCLUSIONS - Nephropathy is prevalent in veterans with diabetes. Greater mortality is observed among those with renal disease compared with those without renal disease. Additional surveillance is needed to identify persons likely to progress to diabetic nephropathy and to plan for appropriate and timely health care for these individuals. C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Seattle, WA 98108 USA. Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Rs & Dev, Seattle, WA USA. Puget Sound Hlth Care Syst, Dept Vet Affairs, Dept Med, Div Gen Med, Seattle, WA USA. NW Kidney Ctr, Seattle, WA USA. Dept Vet Affairs, VERDICT Hlth Serv Res & Dev Ctr Excellence, S Texas Vet Hlth Ctr, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, Dept Med, Div Gen Internal Med, San Antonio, TX 78285 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Young, BA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, 152E,1660 S Columbian Way, Seattle, WA 98108 USA. EM youngb@u.washmgton.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 32 TC 19 Z9 19 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 MAY PY 2004 VL 27 SU 2 BP B45 EP B49 DI 10.2337/diacare.27.suppl_2.B45 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 819MU UT WOS:000221319800008 PM 15113782 ER PT J AU Marynluk, MD Bronzini, BM Lorenzl, GM AF Marynluk, MD Bronzini, BM Lorenzl, GM TI Quality diabetes self-management education: Achieving and maintaining ADA education program recognition SO DIABETES EDUCATOR LA English DT Article AB PURPOSE The purpose of this article is to describe the ADA Education Recognition Program Review Criteria for the National standards for DSME and to help ADA-Recognized programs be prepared in the event of a random audit. METHODS A multidisciplinary committee defined the Review Criteria and Indicators to demonstrate implementation of the 10 National Standards. Tips for completing the application as well as the 2 types of audits, random paper and onsite, are described. RESULTS Five percent of all ADA-Recognized education programs will receive an onsite review conducted by 2 trained auditors. Detailed steps (based on over 100 audits that have been conducted) are outlined describing what happens prior to and during an audit so education program can more fully understand the process and be prepared. The most common reasons that applications and/or audits fail are described. CONCLUSIONS The Education Recognition Program of the ADA aims to ensure that diabetes education programs that meet quality standards will reach as many patients as possible. The lessons learned from other program applications and audits help to strengthen all diabetes education services to ensure that educators are doing the best for their patients. C1 Joslin Diabet Ctr, Affiliated Programs, Boston, MA 02215 USA. Amer Diabet Assoc, Recognit Program, Alexandria, VA USA. Univ Calif San Francisco, Dept Med, La Jolla, CA USA. RP Marynluk, MD (reprint author), 367 W Chicago Ave, Chicago, IL 60610 USA. EM Melinda.maryniuk@joslin.harvard.edu NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2004 VL 30 IS 3 BP 467 EP 475 DI 10.1177/014572170403000318 PG 9 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 852EN UT WOS:000223738100010 PM 15208844 ER PT J AU Lipsky, BA AF Lipsky, BA TI A report from the international consensus on diagnosing and treating the infected diabetic foot SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 4th International Symposium on the Diabetic Foot CY MAY 22-24, 2003 CL Noordwijkerhout, NETHERLANDS DE diabetic foot infections; osteomyelitis; antibiotic therapy; wound cultures; guidelines; foot complications ID COLONY-STIMULATING FACTOR; RESISTANT STAPHYLOCOCCUS-AUREUS; CONTROLLED TRIAL; ANTIBIOTIC-THERAPY; LIMB; OSTEOMYELITIS; MELLITUS; PENETRATION; MANAGEMENT; AMPICILLIN/SULBACTAM AB in persons with diabetes, foot infection, that is, invasion and multiplication of microorganisms in tissues accompanied by tissue destruction or a host usually begins with skin trauma or ulceration inflammatory response, [1]. While most foot infections remain superficial, they can spread to subcutaneous tissues, including muscle, joints, and bone. Many diabetic foot ulcers eventuate in an amputation; infection plays a role in approximately 60% of cases [2-4]. Neuropathy is the main factor leading to skin breaks, while arterial perfusion largely affects infection outcome. Among the factors predisposing diabetic patients to foot infections are ill-defined immunological perturbations [5,6]; foot anatomy may foster proximal spread of infection and ischemic necrosis [7,8]. Published in 2004 by John Wiley Sons, Ltd. RP Lipsky, BA (reprint author), VA Puget Sound HCS, S-111 GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Benjamin.Lipsky@med.va.gov OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 64 TC 121 Z9 124 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2004 VL 20 SU 1 BP S68 EP S77 DI 10.1002/dmrr.453 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 826GD UT WOS:000221816400016 PM 15150818 ER PT J AU Aldhahi, W Mun, E Goldfine, AB AF Aldhahi, W Mun, E Goldfine, AB TI Portal and peripheral cortisol in obese humans SO DIABETOLOGIA LA English DT Article DE cortisol; human; 11 beta hydroxysteroid dehydrogenase; obesity; portal blood ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; HEPATIC INSULIN SENSITIVITY; ADIPOSE-TISSUE; THERAPEUTIC TARGET; CARBENOXOLONE; DISEASE AB Aims/hypothesis. Excess total body and visceral fat has been associated with insulin resistance, diabetes and the metabolic syndrome. Excess glucocorticoids produce both central obesity and diabetes. However, systemic glucocorticoid levels are normal in typical Type 2 diabetes and persons with idiopathic obesity. Glucocorticoids can be produced locally through the enzyme 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1). Transgenic mice with selective overexpression in adipose tissue of 11beta HSD-1 to levels seen in humans develop visceral obesity, hyperlipidaemia and insulin-resistant diabetes associated with a 2.7-fold increase in corticosterone levels in portal compared to peripheral circulation. To examine whether the liver is exposed to higher levels of glucocorticoids, which may undergo metabolic degradation prior to measurement in the systemic circulation, we assessed concentrations of cortisol in the portal and peripheral circulation in morbidly obese humans. Methods. Portal and peripheral blood samples were obtained simultaneously from six morbidly obese humans with and without diabetes during bariatric abdominal surgery. The samples were assessed for serum cortisol to determine whether an increase in the portal to peripheral circulation is found in obese humans. Insulin, which undergoes metabolic clearance in the liver, and thyroxin (free T-4), which does not, were also assessed. Results. Levels of serum cortisol (698.8+/-200.4 vs 696.3+/-232.4 nmol/l, portal vs peripheral, p=0.9) and free T-4 (22.0+/-7.8 vs 20.6+/-8.1 pmol/l, portal vs peripheral, p=0.3) were not significantly different in portal compared to peripheral circulation. Portal insulins were significantly higher than peripheral levels (466.7+/-302.9 vs 78.5+/-50.9 pmol/l, portal vs peripheral, p=0.03). Conclusions/interpretation. These observations suggest that in morbidly obese humans the liver is not exposed to excess glucocorticoids. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Allison.Goldfine@Joslin.Harvard.Edu FU NCRR NIH HHS [M01 RR 01032]; NIDDK NIH HHS [K09-DK02604]; PHS HHS [K23-02795] NR 18 TC 20 Z9 20 U1 1 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2004 VL 47 IS 5 BP 833 EP 836 DI 10.1007/s00125-004-1389-4 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 825BQ UT WOS:000221731400008 PM 15095041 ER PT J AU Deng, XY Wood, PG Eagon, PK Whitcomb, DC AF Deng, XY Wood, PG Eagon, PK Whitcomb, DC TI Chronic alcohol-induced alterations in the pancreatic secretory control mechanisms SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE pancreatic secretion; chronic alcoholics; CCK; 2-DG; meal; rat ID CERULEIN-INDUCED PANCREATITIS; CHRONIC ETHANOL-CONSUMPTION; ACINAR CELL-FUNCTION; EXOCRINE SECRETION; PROTEIN-SYNTHESIS; ENZYME-SECRETION; HEAVY DRINKERS; AREA POSTREMA; ANIMAL-MODELS; RAT PANCREAS AB Chronic alcohol ingestion appears to increase susceptibility of the pancreas to pancreatitis through multiple mechanisms. The aim of the current study was to determine the effect of chronic low- and high-dose alcohol consumption on the neurohormonal control of the exocrine pancreas in rats. Male Wistar rats were fed Lieber DeCarli liquid control-, low-, and high-dose alcohol diets for 3 months. Pancreatic exocrine secretion was measured under basal and 2-deoxy-D-glucose (2-DG)-, CCK-, bethanechol-, or meal-stimulated conditions while on chronic alcohol diets and after 2-DG or CCK stimulation during alcohol withdrawal in awake rats. Chronic alcohol ingestion was associated with a dose-related inhibition of basal pancreatic protein secretion, which was reversed upon alcohol withdrawal. Low-dose alcohol feeding had no effect on bethanechol- stimulated pancreatic secretion but altered 2-DG-stimulated pancreatic secretion. In chronic high-dose alcohol rats, meal- and bethanechol- stimulated protein secretion was significantly potentiated during early and late phases. The response to CCK appeared to be disinhibited, whereas the response to 2-DG was uniformly blunted. Upon withdrawal of low- dose alcohol, the response to 2-DG was potentiated, whereas with the withdrawal of high-dose alcohol, the response to CCK was potentiated. Adaptation to chronic alcohol consumption differs depending on the alcohol dose. The most significant effects were seen after high-dose alcohol withdrawal, with apparent loss of central inhibitory regulation combined with exaggerated response at the acinar cell level. This combination of factors could increase susceptibility to acute alcoholic pancreatitis through a hyperstimulation mechanism. C1 Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutrit, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutrit, Room 571,Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM whitcomb@pitt.edu FU NIAAA NIH HHS [R01-AA10855]; NIDDK NIH HHS [R01 DK 50236, R29 DK45781] NR 57 TC 22 Z9 23 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2004 VL 49 IS 5 BP 805 EP 819 DI 10.1023/B:DDAS.0000030093.25897.61 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 826RU UT WOS:000221847000017 PM 15259503 ER PT J AU Partridge, SK Hodin, RA AF Partridge, SK Hodin, RA TI Small bowel adenocarcinoma at a strictureplasty site in a patient with Crohn's disease: Report of a case SO DISEASES OF THE COLON & RECTUM LA English DT Article ID CARCINOMA; CANCER C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 504, Boston, MA 02114 USA. EM rhodin@partners.org NR 12 TC 34 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD MAY PY 2004 VL 47 IS 5 BP 778 EP 781 DI 10.1007/s10350-003-0101-y PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 818NV UT WOS:000221252700023 PM 15037927 ER PT J AU Gatewood, MO Zane, RD AF Gatewood, MO Zane, RD TI Lightning injuries SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article ID REFLEX SYMPATHETIC DYSTROPHY; ELECTRICAL INJURIES; SYSTEM; DEATH; MANAGEMENT; STRIKES AB Lightning is persistently one of the leading causes of death caused by environmental or natural disaster. To understand the pathophysiology and treatment of lightning injuries one must first discount the innumerable myths, superstitions, and misconceptions surrounding lightning. The fundamental difference between high-voltage electrical injury and lightning is the duration of exposure to current. Reverse triage should be instituted in lightning strike victims because victims in cardiopulmonary arrest might gain the greatest benefit from resuscitation efforts, although there is no good evidence suggesting that lightning strike victims might benefit from longer than usual resuscitation times. Many of the injuries suffered by lightning strike victims are unique to lightning, and long-term sequelae should be anticipated and addressed in the lightning victim. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Zane, RD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. EM rzane@partners.org NR 74 TC 27 Z9 29 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD MAY PY 2004 VL 22 IS 2 BP 369 EP + DI 10.1016/j.emc.2004.02.002 PG 37 WC Emergency Medicine SC Emergency Medicine GA 829LS UT WOS:000222050500008 PM 15163573 ER PT J AU Kim, JY Mukherjee, S Ngo, L Christiani, DC AF Kim, JY Mukherjee, S Ngo, L Christiani, DC TI Urinary 8-hydroxy-2 '-deoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to fine particulates SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; epidemiology; occupational; oxidative DNA damage; particulate matter ID FUEL-OIL ASH; EXPIRED NITRIC-OXIDE; LEAD BATTERY PLANTS; LUNG-CANCER; FLY-ASH; NICKEL REFINERY; CELLULAR DNA; 8-HYDROXYDEOXYGUANOSINE; ASSOCIATION; METALS AB Residual oil fly ash (ROFA) is a chemically complex mixture of compounds, including metals that are potentially carcinogenic because of their ability to cause oxidative injury. In this study, we investigated the association between exposure to particulate matter with an aerodynamic mass median diameter less than or equal to 2.5 mum (PM2.5) and oxidative DNA damage and repair, as indicated by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, in a group of boilermakers exposed to ROFA and metal fumes. Twenty workers (50% smokers) were monitored for 5 days during an overhaul of oil-fired boilers. The median occupational PM2.5 8-hr time-weighted average was 0.44 mg/m(3) (25th-75th percentile, 0.29-0.76). The mean +/- SE creatinine-adjusted 8-OHdG levels were 13.26 +/- 1.04 mug/g in urine samples collected pre-workshift and 15.22 +/- 0.99 mu/g in the post-workshift samples. The urinary 8-OHdG levels were significantly greater in the post-workshift samples than in the pre-workshift samples (p = 0.02), after adjusting for urinary cotinine levels, chronic bronchitis status, and age. Linear mixed models indicated a significant exposure-response association between PM2.5 exposure and urinary 8-OHdG levels (p = 0.03). Each 1-mg/m(3) incremental increase in PM2.5 exposure was associated with an increase of 1.67 mug/g (95% confidence interval, 0.21-3-14) in 8-OHdG levels. PM2.5 vanadium, manganese, nickel, and lead exposures also were positively associated with 8-OHdG levels (p less than or equal to 0.05). This study suggests that a relatively young and healthy cohort of boilermakers may experience an increased risk of developing oxidative DNA injury after exposure to high levels of metal-containing particulate matter. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. 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,Bldg I,Room 1402, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu FU NCI NIH HHS [CA94715]; NIEHS NIH HHS [T32 ES07069, ES00002, ES09860]; PHS HHS [T42110421] NR 52 TC 96 Z9 101 U1 3 U2 13 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2004 VL 112 IS 6 BP 666 EP 671 DI 10.1289/ehp.6827 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 822DD UT WOS:000221514400031 PM 15121508 ER PT J AU Hauser, R Duty, S Godfrey-Bailey, L Calafat, AM AF Hauser, R Duty, S Godfrey-Bailey, L Calafat, AM TI Medications as a source of human exposure to phthalates SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; environmental health; medications; phthalates; reproductive health ID MALE REPRODUCTIVE DEVELOPMENT; DI(N-BUTYL) PHTHALATE; DI(2-ETHYLHEXYL) PHTHALATE; QUANTITATIVE DETECTION; DELIVERY SYSTEMS; LATE-GESTATION; RATS; METABOLITES; PLASTICIZERS; GONOCYTES AB Phthalates are a group of multifunctional chemicals used in consumer and personal care products, plastics, and medical devices. Laboratory studies show that some plathalates are reproductive and developmental toxicants. Recently, human studies have shown measurable levels of several phthalates in most of the U.S. general population. Despite their widespread use and the consistent toxicologic data on phthalates, information is limited on sources and pathways of human exposure to phthalates. One potential source of exposure is medications. The need for site-specific dosage medications has led to the use of enteric coatings that allow the release of the active ingredients into the small intestine or in the colon. The enteric coatings generally consist of various polymers that contain plasticizers, including triethyl citrate, dibutyl sebacate, and phthalates such as diethyl phthalate (DEP) and dibutyl plathalate (DBP). In this article we report on medications as a potential source of exposure to DBP in a man who took Asacol [active ingredient mesalamine (mesalazine)] for the treatment of ulcerative colitis. In a spot urine sample from this man collected 3 months after he started taking Asacol, the concentration of monobutyl phthalate, a DBP metabolite, was 16,868 ng/mL (6,180 mug/g creatinine). This concentration was more than two orders of magnitude higher than the 95th percentile for males reported in the 1999-2000 National Health and Nutrition Examination Survey (NHANES). The patient's urinary concentrations of monoethyl phthalate (443.7 ng/mL, 162.6 mug/g creatinine), mono-2-ethythexyl plathalate (3.0 ng/mL, 1.1 mug/g creatinine), and monobenzyl phthalate (9.3 ng/mL, 3.4 mug/g creatinine) were unremarkable compared with the NHANES 1999-2000 values. Before this report, the highest estimated human exposure to DBP was more than two orders of magnitude lower than the no observable adverse effect level from animal studies. Further research is necessary to determine the proportional contribution of medications, as well as personal care and consumer products, to a person's total phthalate burden. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1405, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu FU NIEHS NIH HHS [ES00002, ES09718] NR 34 TC 120 Z9 121 U1 2 U2 27 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2004 VL 112 IS 6 BP 751 EP 753 DI 10.1289/ehp.6804 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 822DD UT WOS:000221514400042 PM 15121520 ER PT J AU Marr, LC Grogan, LA Wohrnschimmel, H Molina, LT Molina, MJ Smith, TJ Garshick, E AF Marr, LC Grogan, LA Wohrnschimmel, H Molina, LT Molina, MJ Smith, TJ Garshick, E TI Vehicle traffic as a source of particulate polycyclic aromatic hydrocarbon exposure in the Mexico City metropolitan area SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID VOLATILE ORGANIC-COMPOUNDS; ATMOSPHERIC PARTICLES; COMBUSTION AEROSOLS; IN-SITU; EMISSIONS; AIR; ULTRAFINE; MATTER; MASSACHUSETTS; PHOTOEMISSION AB Surface properties of aerosols in the Mexico City metropolitan area have been measured in a variety of exposure scenarios related to vehicle emissions in 2002, using continuous, real-time instruments. The objective of these experiments is to describe ambient and occupational particulate polycyclic aromatic hydrocarbon (PAH) concentrations associated with vehicular traffic and facilities using diesel vehicles. Median total particulate PAH concentrations along Mexico City's roadways range from 60 to 910 ng m(-3), averaged over a minimum of 1 h. These levels are approximately 5 times higher than concentrations measured in the United States and among the highest measured ambient values reported in the literature. The ratio of particulate PAH concentration to aerosol active surface area is much higher along roadways and in other areas of fresh vehicle emissions, compared to ratios measured at sites influenced more by aged emissions or noncombustion sources. For particles freshly emitted by vehicles, PAH and elemental carbon (EC) concentrations are correlated because they both originate during the combustion process. Comparison of PAH versus EC and active surface area concentrations at different locations suggests that surface PAH concentrations may diminish with particle aging. These results indicate that exposure to vehicle-related PAH emissions on Mexico City's roadways may present an important public health risk. C1 MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA 02132 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. RP MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. EM mmolina@mit.edu RI Marr, Linsey/C-9698-2010; Lucas, Elizabeth/E-2733-2010 OI Marr, Linsey/0000-0003-3628-6891; FU NCI NIH HHS [R01 CA090792, CA90792] NR 41 TC 71 Z9 75 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X EI 1520-5851 J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD MAY 1 PY 2004 VL 38 IS 9 BP 2584 EP 2592 DI 10.1021/es034962s PG 9 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 817PR UT WOS:000221189900023 PM 15180054 ER PT J AU Extermann, M Bonetti, M Sledge, GW O'Dwyer, PJ Bonomi, P Benson, AB AF Extermann, M Bonetti, M Sledge, GW O'Dwyer, PJ Bonomi, P Benson, AB TI MAX2 - a convenient index to estimate the average per patient risk for chemotherapy toxicity: validation in ECOG trials SO EUROPEAN JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 3rd Meeting of SIOG held at the 7th International Conference on Geriatric Oncology CY SEP 27-28, 2002 CL BOSTON, MA SP SIOG DE chemotherapy toxicity; aged; aged > 80 years; predictive factors ID CELL LUNG-CANCER; GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-II; MULTICENTER TRIAL; COLORECTAL-CANCER; BREAST-CANCER; SINGLE-AGENT; GEMCITABINE; PACLITAXEL; CISPLATIN AB Cancer patients, especially the elderly, present with a highly variable susceptibility to toxicity from chemotherapy. To estimate correctly a patient's risk for toxicity, both the average toxicity of a chemotherapy regimen and patient-related variables need to be assessed. However, treatment toxicities are typically reported item by item, not summarised per patient. We tested an index derived from a pilot study, the MAX2, on the ECOG database. Studies including 20 or more patients aged 70 years and older per arm were selected. Four studies were identified, representing 2526 patients, 410 (16%) being elderly. The association of the MAX2 index with the per patient incidence of grade 4 haematological and/or grade 3 or 4 non-haematological toxicity was highly significant, both for the overall group and for the elderly subgroup. The MAX2 index is a convenient and reproducible way of comparing the average per patient risk for toxicity from chemotherapy across several regimens. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Med Ctr, Bloomington, IN 47405 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. RP Extermann, M (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. EM extermann@moffitt.usf.edu OI Bonetti, Marco/0000-0003-2304-4180 NR 20 TC 32 Z9 32 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 2004 VL 40 IS 8 BP 1193 EP 1198 DI 10.1016/j.ejca.2004.01.028 PG 6 WC Oncology SC Oncology GA 821ZF UT WOS:000221501400025 PM 15110883 ER PT J AU Bruder, D Probst-Kepper, M Westendorf, AM Geffers, R Beissert, S Loser, K von Boehmer, H Buer, J Hansen, W AF Bruder, D Probst-Kepper, M Westendorf, AM Geffers, R Beissert, S Loser, K von Boehmer, H Buer, J Hansen, W TI Neuropilin-1: a surface marker of regulatory T cells (vol 34, pg 623, 2004) SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Correction C1 German Res Ctr Biotechnol, Dept Cell Biol & Immunol, Braunschweig, Germany. Hannover Med Sch, Dept Visceral & Transplant Surg, D-3000 Hannover, Germany. Univ Munster, Dept Dermatol, D-4400 Munster, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hannover Med Sch, Inst Med Microbiol, D-3000 Hannover, Germany. RP Bruder, D (reprint author), German Res Ctr Biotechnol, Dept Cell Biol & Immunol, Braunschweig, Germany. NR 1 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2004 VL 34 IS 5 BP 1498 EP 1498 DI 10.1002/eji.200490008 PG 1 WC Immunology SC Immunology GA 820YZ UT WOS:000221427400029 ER PT J AU Catapano, LA Arlotta, P Cage, TA Macklis, JD AF Catapano, LA Arlotta, P Cage, TA Macklis, JD TI Stage-specific and opposing roles of BDNF, NT-3 and bFGF in differentiation of purified callosal projection neurons toward cellular repair of complex circuitry SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE growth factors; mouse; neocortex; neurotrophins; regeneration ID FIBROBLAST-GROWTH-FACTOR; RAT HIPPOCAMPAL-NEURONS; ADULT-MOUSE NEOCORTEX; NEURAL STEM-CELLS; CORPUS-CALLOSUM; DENDRITIC GROWTH; IN-VITRO; NEUROTROPHIC FACTOR; CEREBRAL-CORTEX; EMBRYONIC NEURONS AB Cellular repair of neuronal circuitry affected by neurodegenerative disease or injury may be approached in the adult neocortex via transplantation of neural precursors ("neural stem cells") or via molecular manipulation and recruitment of new neurons from endogenous precursors in situ. A major challenge for potential future approaches to neuronal replacement will be to specifically direct and control progressive differentiation, axonal projection and connectivity of neural precursors along a specific neuronal lineage. This goal will require a progressively more detailed understanding of the molecular controls over morphologic differentiation of specific neuronal lineages, including neurite outgrowth and elongation, in order to accurately permit and direct proper neuronal integration and connectivity. Here, we investigate controls over the morphologic differentiation of a specific prototypical lineage of cortical neurons: callosal projection neurons (CPN). We highly enriched CPN to an essentially pure population, and cultured them at three distinct stages of development from embryonic and postnatal mouse cortex by retrograde fluorescence labelling, followed by fluorescence-activated cell sorting. We find that specific peptide growth factors exert direct stage-specific positive and negative effects over the morphologic differentiation and process outgrowth of CPN. These effects are distinct from the effects of these growth factors on CPN survival [Catapano et al. (2001) J. Neurosci., 21, 8863-8872]. These data may be critical for the future goal of directing lineage-specific neuronal differentiation of transplanted or endogenous precursors/"stem cells" toward cellular repair of complex cortical circuitry. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nervous Syst Repair,Dept Neurosurg, Edwards 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu FU NICHD NIH HHS [HD18655, HD28478]; NINDS NIH HHS [NS45523, NS41590] NR 67 TC 17 Z9 17 U1 1 U2 2 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 MAY PY 2004 VL 19 IS 9 BP 2421 EP 2434 DI 10.1111/j.1460-9568.2004.03303.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 816RJ UT WOS:000221126700008 PM 15128396 ER PT J AU Spires, TL Grote, HE Garry, S Cordery, PM Van Dellen, A Blakemore, C Hannan, AJ AF Spires, TL Grote, HE Garry, S Cordery, PM Van Dellen, A Blakemore, C Hannan, AJ TI Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE environmental enrichment; medium spiny neurons; neurodegeneration; single-section Golgi ID DEGENERATIVE CHANGES; SYNAPTIC PLASTICITY; MOUSE MODELS; NEURONS; GENE; ABNORMALITIES; STRIATUM; SYNAPSES; MUTATION; DEMENTIA AB Huntington's disease (HD) is a fatal neurodegenerative disease caused by a CAG repeat expansion coding for an expanded polyglutamine tract in the huntingtin protein. Dendritic abnormalities occur in human HD patients and in several transgenic mouse models of the disease. In this study, we examine, for the first time, dendrite and spine pathology in the R6/1 mouse model of HD, which mimics neurodegeneration seen in human HD. Enriching the environment of HD transgenic mice delays the onset of symptoms, so we also examine the effects of enrichment on dendrite pathology. Golgi-impregnated tissue from symptomatic R6/1 HD mice reveals a decrease in dendritic spine density and dendritic spine length in striatal medium spiny neurons and cortical pyramidal neurons. HD also causes a specific reduction in the proportion of bifurcated dendritic spines on basal dendrites of cortical pyramidal neurons. No differences in soma size, recurving distal dendrites, or dendritic branching were observed. Although home-cage environmental enrichment from 1 to 8 months of age increases spine density in wild-type mice, it has no effect on the spine pathology in HD mice. These results show that dendritic spine pathology in R6/1 HD mice resembles degenerative changes seen in human HD and in other transgenic mouse models of the disease. We thus provide further evidence that the HD mutation disrupts the connectivity in both neostriatum and cerebral cortex, which will contribute to motor and cognitive disease symptoms. Furthermore, we demonstrate that Huntington's disease pathology interferes with the normal plastic response of dendritic spines to environmental enrichment. C1 Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. RP Spires, TL (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Bldg 114,16th St,Room 2021, Charlestown, MA 02129 USA. EM tspires@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 NR 34 TC 106 Z9 108 U1 0 U2 1 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 MAY PY 2004 VL 19 IS 10 BP 2799 EP 2807 DI 10.1111/j.1460-9568.2004.03374.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 821VR UT WOS:000221491600019 PM 15147313 ER PT J AU Lapointe, N Bulte, J Owen, M Gross, R Chen, IY Yu, M Wang, X Owen, C Cicchetti, F Brownell, AL AF Lapointe, N Bulte, J Owen, M Gross, R Chen, IY Yu, M Wang, X Owen, C Cicchetti, F Brownell, AL TI Monitoring the migration of transplanted progenitor cells with pet and MRI. SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 11th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY MAY 06-09, 2004 CL Clearwater, FL SP Amer Soc Neural Transplantat & Repair C1 CHUL, Ctr Rech Neurosci, St Foy, PQ G1V 4G2, Canada. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Simmons Coll, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2004 VL 187 IS 1 BP 212 EP 212 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 813FE UT WOS:000220892200055 ER PT J AU Hong, YK Lange-Asschenfeldt, B Velasco, P Hirakawa, S Kunstfeld, R Brown, LF Bohlen, P Senger, DR Detmar, M AF Hong, YK Lange-Asschenfeldt, B Velasco, P Hirakawa, S Kunstfeld, R Brown, LF Bohlen, P Senger, DR Detmar, M TI VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha 1 beta 1 and alpha 2 beta 1 integrins SO FASEB JOURNAL LA English DT Article DE VEGF; lymphangiogenesis; wound healing; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; TRANSGENIC MICE; ANGIOGENESIS; LYMPHANGIOGENESIS; MECHANISMS; SKIN; KERATINOCYTES; VASCULATURE; EXPRESSION; DELIVERY AB Vascular endothelial growth factor-A (VEGF-A) is strongly up-regulated in wounded cutaneous tissue and promotes repair-associated angiogenesis. However, little is known about its role in lymphatic regeneration of the healing skin. We studied wound healing in transgenic mice that overexpress VEGF-A specifically in the epidermis and in wild-type mice in the absence or presence of inhibitors of VEGF-A signaling. Surprisingly, transgenic overexpression of VEGF-A in the skin promoted lymphangiogenesis at the wound healing site, whereas systemic blockade of VEGFR-2 prevented lymphatic vessel formation. Studies in cultured lymphatic endothelial cells revealed that VEGF-A induced expression of the alpha1 and alpha2 integrins, which promoted their in vitro tube formation and their haptotactic migration toward type I collagen. VEGF-A-induced lymphatic endothelial cord formation and haptotactic migration were suppressed by anti-alpha1 and anti-alpha2 integrin blocking antibodies, and systemic blockade of the alpha1 and alpha2 integrins inhibited VEGF-A-driven lymphangiogenesis in vivo. We propose that VEGF-A promotes lymphatic vasculature formation via activation of VEGFR-2 and that lineage-specific differences of integrin receptor expression contribute to the distinct dynamics of wound-associated angiogenesis and lymphangiogenesis. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. ImClone Syst Inc, New York, NY USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM michael.detmar@cbrc2.mgh.harvard.edu FU NCI NIH HHS [CA69184, CA77357, CA86410, CA92644] NR 31 TC 191 Z9 209 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2004 VL 18 IS 7 BP 1111 EP + DI 10.1096/fj.03-1179fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 827EZ UT WOS:000221883200026 PM 15132990 ER PT J AU Theodore, GH Buch, M Amendola, A Bachmann, C Fleming, LL Zingas, C AF Theodore, GH Buch, M Amendola, A Bachmann, C Fleming, LL Zingas, C TI Extracorporeal shock wave therapy for the treatment of plantar fasciitis SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE heel pain; plantar fasciitis; shock wave ID PAINFUL HEEL SYNDROME; FASCIOTOMY; RELEASE AB One hundred fifty patients were enrolled in a multicenter, randomized, placebo-controlled, prospective, double-blind study to assess the clinical safety and effectiveness of extracorporeal shock wave therapy (ESWT) using the Dornier Epos Ultra for the treatment of plantar fasciitis. The Active Group was treated with electromagnetically generated shocks using ultrasound guidance during a single therapy session. The Control Group received a sham treatment under similar clinical conditions. The groups were demographically similar with respect to age, height, and weight. The average duration of symptoms was nearly 2 years in both groups. All patients were evaluated by the visual analog scale for pain, American Orthopaedic Foot and Ankle Society scores, Roles and Maudsley Score, SF-12 health status questionnaire, and physical examination. The Active Group reported 56% success at 3 months and 94% success at 12 months posttreatment. The Control Group reported 47% success at 3 months posttreatment. Twelve-month data were not collected for the Control Group as they were unblinded at 3 months and offered treatment. ESWT represents a safe treatment option for chronic proximal plantar fasciitis. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Othopaed Klin Kassel, Kassel, Germany. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Henry Ford Hlth Syst, Dept Orthoped, Detroit, MI USA. RP Theodore, GH (reprint author), Massachusetts Gen Hosp, 101 Merrimac St, Boston, MA 02114 USA. EM GTheodore@Partners.org NR 31 TC 41 Z9 51 U1 0 U2 6 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAY PY 2004 VL 25 IS 5 BP 290 EP 297 PG 8 WC Orthopedics SC Orthopedics GA 854FD UT WOS:000223885800003 PM 15134608 ER PT J AU Zeytoonjian, T Mankin, HJ Gebhardt, MC Hornicek, FJ AF Zeytoonjian, T Mankin, HJ Gebhardt, MC Hornicek, FJ TI Distal lower extremity sarcomas: Frequency of occurrence and patient survival rate SO FOOT & ANKLE INTERNATIONAL LA English DT Article DE foot; frequency; outcomes; sarcoma ID METASTATIC TUMORS; SOFT-TISSUE; FOOT; BONE; CHONDROSARCOMA; SYSTEM; ANKLE AB Background: Primary sarcomas in the distal leg, tibia, fibula, ankle, and foot are uncommon and are believed to be less malignant than those that arise in other sites, but only limited information is available to support this contention. Methods: Using a computerized system containing extensive information regarding over 14,000 patients, mostly with tumors treated by our center over a 25-year period, 175 sarcomatous lesions with MSTS stage I, II, and III were located in the distal lower extremity. These were compared with 2367 lesions of similar diagnoses in other body parts. The principal studies included diagnostic distribution and outcome (recorded as death as a result of disease). Data were compared for diagnosis, gender, age, Musculoskeletal Tumor Society (MSTS) stage, anatomic site, and treatment methods and evaluated statistically by chi-square methods. Results: The most frequent distal lower limb tumors were synovial cell sarcoma, osteosarcoma, and Ewing's tumor and the percentage distribution of the various tumors for that site as compared with the rest of the body was quite different. Of even more importance was the remarkable difference in outcome with the death rate for the lower limb tumors set at 10%, while the same tumors at other sites had a death rate of 27% (p <.000002). Furthermore, gender, stage, age, and the type of operative procedure showed highly significant differences between the tumors of the lower leg and those of the remainder of the body. Conclusions: On the basis of these data, it is evident that far fewer sarcomas occur in the lower leg, tibia, fibula, ankle, and foot than in other body sites and that their diagnostic distribution is different. Of perhaps greater interest is the fact that the rate of metastasis and death is markedly reduced for this site as compared with others. The authors speculate on the causes of this remarkable alteration in numbers and outcome. C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Serv, Orthopaed Serv Gray 604, Boston, MA 02114 USA. EM hmankin@partners.org NR 42 TC 38 Z9 45 U1 0 U2 1 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAY PY 2004 VL 25 IS 5 BP 325 EP 330 PG 6 WC Orthopedics SC Orthopedics GA 854FD UT WOS:000223885800009 PM 15134614 ER PT J AU Snow, KJ AF Snow, KJ TI Erectile dysfunction: A review and update SO FORMULARY LA English DT Review ID DOUBLE-BLIND; CONTROLLED-TRIAL; PENILE ERECTION; PDE5 INHIBITOR; CLINICAL-TRIAL; MEN; VARDENAFIL; SILDENAFIL; IMPOTENCE; PLACEBO AB Erectile dysfunction (ED) is now recognized as a common problem in men. Several medical problems, including diabetes mellitus, coronary artery disease, hypertension, and hyperlipidemia are known to increase the likelihood of developing ED. Diagnosis depends on an adequate history and physical examination. Several therapies are now available for the treatment of ED. With the advent of the phosphodiesterase type 5 (PDE5) inhibitors, therapy for ED has become more acceptable for many men. Oral therapy is usually the first-line treatment due to the ease of use and the effectiveness of this therapy. For men who do not respond to or have a contraindication to PDE5 therapy, intrapenile injection therapy, intraurethral therapy, and vacuum devices are effective alternatives. C1 Joslin Clin, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Snow, KJ (reprint author), Joslin Clin, Boston, MA USA. EM kenneth.snow@joslin.harvard.edu NR 43 TC 3 Z9 3 U1 1 U2 2 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1082-801X J9 FORMULARY JI Formulary PD MAY PY 2004 VL 39 IS 5 BP 261 EP 268 PG 12 GA 823TB UT WOS:000221635000014 ER PT J AU Zaccagni, H Fried, J Cornell, J Padilla, P Brey, RL AF Zaccagni, H Fried, J Cornell, J Padilla, P Brey, RL TI Soluble adhesion molecule levels, neuropsychiatric lupus and lupus-related damage SO FRONTIERS IN BIOSCIENCE LA English DT Article DE systemic lupus erythematosus; adhesion molecules; neuropsychiatric disease ID CENTRAL-NERVOUS-SYSTEM; ENDOTHELIAL-CELL ADHESION; DISEASE-ACTIVITY; E-SELECTIN; ANTIPHOSPHOLIPID ANTIBODIES; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; UP-REGULATION; IN-VITRO; ERYTHEMATOSUS AB Nervous system dysfunction may occur in as many as 80% of patients with Systemic Lupus Erythematous (SLE) at some point in their disease course. Upregulation of adhesion molecules has been linked to acute SLE-related disease activity and chronic damage. We evaluated the relationship between soluble adhesion molecule levels and neuropsychiatric lupus (NPSLE) manifestations using the American College of Rheumatology (ACR) case definitions to investigate for evidence of a link between upregulation of adhesion molecules and NPSLE manifestations. Sera from the initial study visit of 133 SLE patients enrolled in the San Antonio Lupus Study of Neuropsychiatric Disease (SALUD) and 40 controls were evaluated for soluble adhesion molecule levels (VCAM-1, ICAM-1 and E-selectin) and antiphospholipid antibodies. A subset of 57 SLE patients were evaluated for soluble adhesion molecule levels and antiphospholipid antibodies on two subsequent study visits, as well. NPSLE manifestations at the time of sera ascertainment were recorded using ACR case definitions and SLE-related acute activity and damage were measured. Elevated levels of all three soluble adhesion molecules were seen in SLE patients compared to normal control values. Soluble VCAM-1 levels correlated with measures of current disease activity, NPSLE manifestations and deep venous thrombosis. Persistently positive levels of ICAM-1 and VCAM-1, but not E-selectin were association with increased SLE-related damage. Elevated levels of all soluble adhesion molecule levels correlated with abnormal levels of antiphospholipid antibodies, which are associated with some NPSLE manifestations and have been shown to upregulate adhesion molecule expression. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Neurol,Dept Med, VERDICT Ctr Excellence, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. RP Brey, RL (reprint author), Dept Med, Div Neurol 7883, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM brey@uthscsa.edu FU NCRR NIH HHS [M01RR 01346-19]; NINDS NIH HHS [R01 NS35477] NR 41 TC 21 Z9 25 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2004 VL 9 BP 1654 EP 1659 DI 10.2741/1273 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 779ZA UT WOS:000189333700052 PM 14977576 ER PT J AU Freeman, JW DeArmond, D Lake, M Huang, WQ Venkatasubbarao, K Zhao, SJ AF Freeman, JW DeArmond, D Lake, M Huang, WQ Venkatasubbarao, K Zhao, SJ TI Alterations of cell signaling pathways in pancreatic cancer SO FRONTIERS IN BIOSCIENCE LA English DT Article DE pancreatic cancer; cell signaling; growth factors; growth factor receptors; TGF beta; review ID GROWTH-FACTOR-BETA; LINE MIA PACA-2; II RECEPTOR EXPRESSION; TUMOR-SUPPRESSOR GENE; MYC DOWN-REGULATION; TGF-BETA; BREAST-CANCER; C-MYC; CYCLIN D1; FACTOR INDEPENDENCE AB Pancreatic ductal adenocarcinomas continue to have the worst prognosis of any adult malignancy with a five-year survival rate of less than 4%. One approach to improve patient survival from pancreatic cancer is to identify new biological targets that contribute to the aggressive pathogenecity of this disease and to develop reagents that will interfere with the function of these targets. Apart from the identification of the genetic profile of pancreatic cancer, a number of studies have focused on aberrant cell signaling pathways and their role in pancreatic cancer biology and response to therapy. This review, although not comprehensive, will discuss the salient features of several of these pathways. These include the roles of TGFbeta signaling in both tumor suppression and tumor promotion and the effects of deregulation of phosphotyrosine kinase receptor signaling pathways in pancreatic cancer. C1 Univ Texas, Hlth Sci Ctr, Div Med Oncol, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev, San Antonio, TX 78229 USA. RP Freeman, JW (reprint author), Univ Texas, Hlth Sci Ctr, Div Med Oncol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freemanjw@uthscsa.edu RI Huang, Weiqi/E-4341-2010 FU NCI NIH HHS [CA96122] NR 87 TC 12 Z9 14 U1 3 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2004 VL 9 BP 1889 EP 1898 DI 10.2741/1388 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 779ZA UT WOS:000189333700071 PM 14977595 ER PT J AU Ioannou, GN Dominitz, JA Weiss, NS Heagerty, PJ Kowdley, KV AF Ioannou, GN Dominitz, JA Weiss, NS Heagerty, PJ Kowdley, KV TI The effect of alcohol consumption on the prevalence of iron overload, iron deficiency, and iron deficiency anemia SO GASTROENTEROLOGY LA English DT Article ID SERUM FERRITIN; UNITED-STATES; HEREDITARY HEMOCHROMATOSIS; LIVER DISEASE; ABSORPTION; CIRRHOSIS; MEN; STORES; POPULATION; DIAGNOSIS AB Background & Aims: Our aim was to investigate the relationship between alcohol consumption and iron overload, iron deficiency, or iron deficiency anemia in the U.S. population. Methods: Adult participants of the Third National Health and Nutrition Examination Survey who did not consume alcohol (n = 8839) were compared with participants who consumed less than or equal to1 (n = 4976), >1 to less than or equal to2 (n = 1153), or >2 (n = 915) alcoholic drinks/day during the preceding 12 months. We examined the following markers of iron overload: elevated serum transferrin-iron saturation (TS) level (>45%, >50%, and >60%), elevated serum ferritin level (>300, >400, >500, and >600 ng/mL), and combinations of both elevated serum TS and ferritin levels. Iron deficiency was defined as the presence of at least 2 of the following: serum ferritin level <12 ng/mL, serum TS level <15%, and erythrocyte protoporphyrin level >1.24 mumol/L. Iron deficiency anemia was defined as the presence of both iron deficiency and anemia. Results: Compared with nondrinkers, the prevalence of all markers of iron overload was significantly elevated among those who consumed >2 alcoholic drinks/day after adjusting for potential confounders. Consumption of any amount of alcohol was associated with a 40% reduction in the risk of iron deficiency anemia. Conclusions: Consumption of up to 2 alcoholic drinks/day seems to be associated with reduced risk of iron deficiency and iron deficiency anemia without a concomitant increase in the risk of iron overload. Consumption of >2 alcoholic drinks/day is associated with a significant elevation in the risk of iron overload. C1 Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Div Gastroenterol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Adm Med Ctr, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu OI Dominitz, Jason/0000-0002-8070-7086 FU NIDDK NIH HHS [K24 DK 02957] NR 52 TC 73 Z9 79 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2004 VL 126 IS 5 BP 1293 EP 1301 DI 10.1053/j.gastro.2004.01.020 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 818AD UT WOS:000221217100011 PM 15131790 ER PT J AU Brugge, WR Lewandrowski, K Lee-Lewandrowski, E Centeno, BA Szydlo, T Regan, S del Castillo, CF Warshaw, AL AF Brugge, WR Lewandrowski, K Lee-Lewandrowski, E Centeno, BA Szydlo, T Regan, S del Castillo, CF Warshaw, AL CA Investigators CPC Study TI Diagnosis of pancreatic cystic neoplasms: A report of the cooperative pancreatic cyst study SO GASTROENTEROLOGY LA English DT Article ID FLUID ANALYSIS; DIFFERENTIAL-DIAGNOSIS; PATHOLOGICAL OBSERVATIONS; CARCINOEMBRYONIC ANTIGEN; LESIONS; TUMORS; EUS; PSEUDOCYSTS; PROGNOSIS; ACCURACY AB Background & Aims: Cysts of the pancreas display a wide spectrum of histology, including inflammatory (pseudocysts), benign (serous), premalignant (mucinous), and malignant (mucinous) lesions. Endoscopic ultrasonography (EUS) may offer a diagnostic tool through the combination of imaging and guided, fine-needle aspiration (FNA). The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cystic lesions. Methods: The results of EUS imaging, cyst fluid cytology, and cyst fluid tumor markers (CEA, CA 72-4, CA 125, CA 19-9, and CA 15-3) were prospectively collected and compared in a multicenter study using histology as the final diagnostic standard. Results: Three hundred forty-one (34:1) patients underwent EUS and FNA of a pancreatic cystic lesion; 1:12 of these patients underwent surgical resection, providing a histologic diagnosis of the cystic lesion (68 mucinous, 7 serous, 27 inflammatory, 5 endocrine, and 5 other). Receiver operator curve analysis of the tumor markers demonstrated that cyst fluid CEA (optimal cutoff of 192 ng/mL) demonstrated the greatest area under the curve (0.79) for differentiating mucinous vs. nonmucinous cystic lesions. The accuracy of CEA (88 of 111, 79%) was significantly greater than the accuracy of EUS morphology (57 of 112, 51%) or cytology (64 of 109, 59%) (P < 0.05). There was no combination of tests that provided greater accuracy than CEA alone (P < 0.0001). Conclusions: Of tested markers, cyst fluid CEA is the most accurate test available for the diagnosis of mucinous cystic lesions of the pancreas. C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33620 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Pathol, Tampa, FL 33620 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM Wbrugge@partners.org OI Regan, Susan/0000-0003-0940-2017 NR 30 TC 611 Z9 629 U1 1 U2 14 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2004 VL 126 IS 5 BP 1330 EP 1336 DI 10.1053/j.gastro.2004.02.013 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 818AD UT WOS:000221217100015 PM 15131794 ER PT J AU Shammas, MA Koley, H Beer, DG Li, C Goyal, RK Munshi, NC AF Shammas, MA Koley, H Beer, DG Li, C Goyal, RK Munshi, NC TI Growth arrest, apoptosis, and telomere shortening of Barrett's-associated adenocarcinoma cells by a telomerase inhibitor SO GASTROENTEROLOGY LA English DT Article ID HUMAN TUMOR-CELLS; HUMAN FIBROBLASTS; HEPATOCELLULAR-CARCINOMA; GASTRIC-CARCINOMA; CANCER-CELLS; DNA; ESOPHAGEAL; PROGRESSION; EXPRESSION; IMMORTALIZATION AB Background & Aims: Barrett's esophageal adenocarcinoma (BEAC) is a complication of gastroesophageal reflux disease, with no effective chemotherapy and poor prognosis. BEAC cells, like many other types of cancers, may reactivate telomerase to achieve unlimited proliferative potential, making telomerase a unique therapeutic target. The purpose of this study was to evaluate effects of telomerase inhibition on BEAC. Methods: We examined the effect of a selective G-quadruplex intercalating telomerase inhibitor, 2,6-bis[3-{N-Piperidino} propionamido]anthracene-9,10-dione (PPA), on telomerase activity, telomere length, colony size distribution, and proliferative potential in 2 BEAC cell lines, BIC-1 and SEG-1. Results: Telomerase activity was >10-fold and >600-fold elevated in the adenocarcinoma cells as compared with normal gastric/intestinal cells and normal diploid fibroblasts, respectively. Telomeres were short, being less than 4 kilobase pair in both tumor cell lines. Exposure to PPA effectively inhibited telomerase activity and shortened telomeres. PPA also arrested cell proliferation and reduced colony number and size after a lag period of about 10 cell generations, consistent with the attrition of telomeres. The growth arrest was not due to senescence but was due to apoptosis. Expression analysis of the cells following PPA treatment did not show significant change in the expression of genes involved in cell-cycle proliferation and apoptosis. Exposure to PPA had no effect on proliferative potential of normal intestinal cells. Conclusions: We conclude that telomerase inhibition by PPA induces cell growth arrest in BEAC cells and demonstrate the potential of telomerase inhibitors in chemoprevention and treatment of Barrett's-associated esophageal adenocarcinoma. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. VA Boston Hlth Care Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu FU NCI NIH HHS [P50 CA 10070]; NIDDK NIH HHS [DK 031092]; PHS HHS [P01 78378] NR 53 TC 37 Z9 42 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2004 VL 126 IS 5 BP 1337 EP 1346 DI 10.1053/j.gastro.2004.01.026 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 818AD UT WOS:000221217100016 PM 15131795 ER PT J AU Sands, BE AF Sands, BE TI From symptom to diagnosis: Clinical distinctions among various forms of intestinal inflammation SO GASTROENTEROLOGY LA English DT Review ID POUCH-ANAL ANASTOMOSIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; SELF-LIMITED COLITIS; TERM-FOLLOW-UP; NON-RELAPSING COLITIS; BOWEL-DISEASE; CROHNS-DISEASE; ULCERATIVE-COLITIS; COLLAGENOUS COLITIS; DIVERSION COLITIS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study IBD, Boston, MA 02114 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM bsands@partners.org FU NIDDK NIH HHS [5K23DK002850] NR 115 TC 151 Z9 164 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2004 VL 126 IS 6 BP 1518 EP 1532 DI 10.1053/j.gastro.2004.02.072 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 823VR UT WOS:000221642200003 PM 15168364 ER PT J AU Brugge, WR AF Brugge, WR TI Evaluation of pancreatic cystic lesions with EUS SO GASTROINTESTINAL ENDOSCOPY LA English DT Review ID FINE-NEEDLE-ASPIRATION; DIFFERENTIAL-DIAGNOSIS; SEROUS CYSTADENOMA; FLUID ANALYSIS; PATHOLOGICAL CORRELATION; TUMORS; NEOPLASMS; CT; ULTRASOUND; FEATURES C1 Massachusetts Gen Hosp, Endoscopy Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), GI Endoscopy Unit, Blake 452C,55 Fruit St, Boston, MA 02114 USA. NR 36 TC 76 Z9 79 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 MAY PY 2004 VL 59 IS 6 BP 698 EP 707 DI 10.1016/S0016-5107(04)00175-0 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 820HI UT WOS:000221377800020 PM 15114319 ER PT J AU Nath, SK Namjou, B Garriott, CP Frank, S Joslin, PA Kilpatrick, J Kelly, JA Harley, JB AF Nath, SK Namjou, B Garriott, CP Frank, S Joslin, PA Kilpatrick, J Kelly, JA Harley, JB TI Linkage analysis of SLE susceptibility: confirmation of SLER1 at 5p15.3 SO GENES AND IMMUNITY LA English DT Article DE systemic lupus erythematosus; rheumatoid arthritis; linkage; genome scan ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SIB-PAIR FAMILIES; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; TELOMERASE ACTIVITY; REVISED CRITERIA; GENOME SCAN; COMPLEX; GENES; GENETICS AB We detected a novel susceptibility gene, SLER1, for systemic lupus erythematosus (SLE) at 5p15.3.(1) This finding was based on a selected subgroup of SLE families, where two or more family members have had alleged rheumatoid arthritis (SLE-RA). The main objective of this study was to replicate the linkage at 5p15.3 based on an independent data set of 88 SLE-RA families. Heterogeneity in the genetic model led us to use a nonparametric allele-sharing method. Since our a priori hypothesis of linkage at 5p15.3 was fixed, we genotyped six markers at the linked region. Our new results replicate the initial linkage at 5p15.3 (Zlr = 2.58, P<0.005, LOD = 1.45). Moreover, evidence of linkage was sustained when analysis was restricted to the subset of SLE families who had 3 or more individuals with alleged RA ( Zlr = 3.32, P = 0.008, LOD = 2.40) The results of our previous findings, together with these new results, confirm the SLER1 linkage at 5p15.3. Our results also demonstrate the utility of clinically defined subgroup analysis for detecting susceptibility loci for complex genetic diseases, such as SLE. C1 Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. Arthrit & Immunol Res Program, Oklahoma City, OK USA. Cardiol Clin Muskogee, Muskogee, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Nath, SK (reprint author), Oklahoma Med Res Fdn, Genet Epidemiol Unit, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM swapan-nath@omrf.ouhsc.edu OI Frank, Summer/0000-0003-0779-4926 FU NIAID NIH HHS [AI24717, AI31584]; NIAMS NIH HHS [AR048928, AR048940, AR049084, AR12253, AR15577, AR42460] NR 32 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD MAY PY 2004 VL 5 IS 3 BP 209 EP 214 DI 10.1038/sj.gene.6364060 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 814CC UT WOS:000220951800009 PM 15014430 ER PT J AU Hallsson, JH Haflidadottir, BS Stivers, C Odenwald, W Arnheiter, H Pignoni, F Steingrimsson, E AF Hallsson, JH Haflidadottir, BS Stivers, C Odenwald, W Arnheiter, H Pignoni, F Steingrimsson, E TI The basic helix-loop-helix leucine zipper transcription factor Mitf is conserved in Drosophila and functions in eye development SO GENETICS LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; MOUSE MICROPHTHALMIA LOCUS; NEURAL-CREST; PERIPODIAL CELLS; IMAGINAL DISCS; FACTOR FAMILY; EYELESS GENE; EXPRESSION; DIFFERENTIATION; PROTEIN AB The MITF protein is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3, TFEC, and TFEB proteins. In the mouse, MITF is required for the development of several different cell types, including the retinal pigment epithelial (RPE) cells of the eye. In Mitf mutant mice, the presumptive RPE cells hyperproliferate, abnormally express the retinal transcriptional regulator Pax6, and form an ectopic neural retina. Here we report the structure of the Mitf gene in Drosophila and demonstrate expression during embryonic development and in the eye-antennal imaginal disc. In vitro, transcriptional regulation by Drosophila Mitf, like its mouse counterpart, is modified by the Eyeless (Drosophila Pax6) transcription factor. In vivo, targeted expression of wild-type or dominant-negative Drosophila Mitf results in developmental abnormalities reminiscent of Mitf function in mouse eye development. Our results suggest that the Mitf gene is the original member of the Mitf-Tfe subfamily of bHLH-Zip proteins and that its developmental function is at least partially conserved between vertebrates and invertebrates. These findings further support the common origin of the vertebrate and invertebrate eyes. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. NINDS, Lab Dev Neurogenet, NIH, Bethesda, MD 20892 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. RP Harvard Univ, Sch Med, Dept Ophthalmol, 507,243 Charles St, Boston, MA 02114 USA. EM francesca_pignoni@meei.harvard.edu OI Hallsson, Jon/0000-0002-9127-2137 FU NEI NIH HHS [R01 EY013167, R01 EY13167] NR 51 TC 30 Z9 32 U1 0 U2 2 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD MAY PY 2004 VL 167 IS 1 BP 233 EP 241 DI 10.1534/genetics.167.1.233 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 826TF UT WOS:000221851100019 PM 15166150 ER PT J AU Suzuki, Y Jezewski, PA Machida, J Watanabe, Y Shi, M Cooper, ME Viet, LT Tin, NTD Hai, H Natsume, N Shimozato, K Marazita, ML Murray, JC AF Suzuki, Y Jezewski, PA Machida, J Watanabe, Y Shi, M Cooper, ME Viet, LT Tin, NTD Hai, H Natsume, N Shimozato, K Marazita, ML Murray, JC TI In a Vietnamese population, MSX1 variants contribute to cleft lip and palate SO GENETICS IN MEDICINE LA English DT Article DE cleft lip; cleft palate; MSX1; TGFA; TGFB3 ID CANDIDATE GENES; ORAL CLEFTS; OROFACIAL CLEFTS; AND/OR PALATE; ASSOCIATION; TGFB3; MUTATION; HUMANS; MICE AB Purpose: To identify causes of nonsyndromic cleft lip and palate in a Vietnamese population. Methods: In this study, 175 families with at least one case of cleft lip and/or palate were studied using the candidate genes TGFA, MSX1, and TGFB3. Results: Transmission distortion for alleles of MSX1 were demonstrated for the whole population and two missense mutations were identified, including one (P147Q) that is found in approximately 2% of the population. The P147Q appears to arise from a founder individual based on shared haplotypes in unrelated families. Conclusions: MSX1 contributes to nonsyndromic clefting in a Vietnamese population, and consistent with other studies, identifiable mutations in this gene cause about 2% of cases of nonsyndromic clefting. C1 Univ Iowa, Dept Pediat, Div Neonatol, Iowa City, IA 52242 USA. Aichi Gakuin Univ, Sch Dent, Dept Oral & Maxillofacial Surg 2, Nagoya, Aichi 464, Japan. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Toyohashi Municipal Hosp, Div Oral & Maxillofacial Surg, Toyohashi, Aichi, Japan. Univ Pittsburgh, Ctr Craniofacial & Dent Genet, Sch Dent Med, Pittsburgh, PA USA. Odonto Maxillo Facial Ctr, Ho Chi Minh City, Vietnam. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Sch Dent Med,Dept Oral & Maxillofacial Surg, Pittsburgh, PA USA. RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, Div Neonatol, 2182 ML, Iowa City, IA 52242 USA. FU NIDCR NIH HHS [DE10876, DE13076, R01 DE016148, DE08559] NR 27 TC 71 Z9 75 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD MAY-JUN PY 2004 VL 6 IS 3 BP 117 EP 125 DI 10.1097/01.GIM.0000127275.52925.05 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 821XF UT WOS:000221495900002 PM 15354328 ER PT J AU Lawrence, R Kuberan, B Beeler, DL Rosenberg, RD AF Lawrence, R Kuberan, B Beeler, DL Rosenberg, RD TI Mapping critical biological motifs and biosynthetic pathways of heparan sulfate SO GLYCOBIOLOGY LA English DT Article DE glycosaminoglycans; capillary liquid chromatography; mass spectrometry; stable isotope labeling; biosynthetic mechanisms; critical groups ID HERPES-SIMPLEX-VIRUS; D-GLUCOSAMINYL 3-O-SULFOTRANSFERASE; ANTITHROMBIN-III; MASS-SPECTROMETRY; MOLECULAR-CLONING; BINDING SITE; EXPRESSION; RESIDUES; OLIGOSACCHARIDES; PENTASACCHARIDE AB Heparan sulfate (HS) interacts with numerous proteins at the cell surface and orchestrates myriad biological events. Unraveling the mechanisms of these events at the molecular level calls for the structural analysis of these negatively charged and highly heterogeneous biopolymers. However, HS is often available only in small quantities, and the task of structural analysis necessitates the use of ultra-sensitive methods, such as mass spectrometry. Sequence heterogeneity within HS chains required us to identify critical functional groups and their spacing to determine structure-function relationships for HS. We carried out structural analysis of HS isolated from wild type, 3-OST-1, 3-OST-3A, or 3-OST-5 sulfotransferase-transduced Chinese hamster ovary cells and also from various tissues. In the context of tissue-specific HS, the data allowed us to map the biosynthetic pathways responsible for the placement of critical groups. As a means of determining the distance between critical groups within a motif, we determined the spacing of the rare GlcNAc-GlcA disaccharide sequence in the completely desulfated re-N-sulfated porcine intestinal heparin. These disaccharides are biosynthetic regulatory markers for 3-OST-1 modification and the partial structure of the antithrombin III binding site. They occur only at the distance of hexasaccharide, octasaccharide, decasaccharide, or dodecasaccharide. Thus this approach allowed us to map both the biosynthetic pathways for generating critical functional groups and their spacing within HS. Our new strategy removes two obstacles to rapid progress in this field of research. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, BIDMC, Div Mol & Vasc Med, Boston, MA 02215 USA. RP Rosenberg, RD (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rdrrosen@mit.edu FU NHLBI NIH HHS [5R01HL 59479, 1PO1 HL 66105] NR 31 TC 20 Z9 20 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD MAY PY 2004 VL 14 IS 5 BP 467 EP 479 DI 10.1093/glycob/cwh057 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 816XI UT WOS:000221142200011 PM 15033939 ER PT J AU Brakora, KA Lee, H Yusuf, R Sullivan, L Harris, A Colella, T Seiden, MV AF Brakora, KA Lee, H Yusuf, R Sullivan, L Harris, A Colella, T Seiden, MV TI Utility of osteopontin as a biomarker in recurrent epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; osteopontin; tumor markers; CA125 ID TUMOR-MARKERS; IDENTIFICATION AB Objective. Osteopontin (OPN) is overexpressed in tumors and serum of ovarian cancer patients and may serve as a biomarker. To evaluate the utility of serum osteopontin in monitoring disease status, we evaluated 234 serum samples from post-oophorectomy patients with ovarian cancer and 38 samples from healthy controls. Methods. Serum samples were collected from 203 women with recurrent ovarian cancer and 31 newly diagnosed women participating in an experimental chemotherapeutic clinical trial. Controls included I I young healthy women and 27 peri- or postmenopausal women without ovarian cancer. Samples were assayed for osteopontin using an enzyme-linked immunosorbent assay (ELISA) kit. Statistical analyses for group comparisons of biomarker distribution used the nonparametric Wilcoxon's rank sum test for two-group comparisons and the Kruskal-Wallis test for three-group comparisons. Results. Osteopontin values ranged from 25 to 1463 ng/ml for patients and 25 to 617 ng/ml for controls. Mean patient levels were lower than mean control levels (74 ng/ml vs. 147 ng/ml, respectively, P = 0.0006). Serum osteopontin levels correlated with recurrent disease versus remission (68 ng/ml vs. 34 ng/ml, P = 0.0034), presence of ascites versus absence (71 ng/ml vs. 53 ng/ml, P = 0.0002), and bulky disease vs. nonbulky disease (75 ng/ml vs. 38 ng/ml, P = 0.0005). CA-125 values yielded the same trends with greater statistical difference. Conclusions. These results demonstrate that serum osteopontin concentrations in post-oophorectomy patients with recurrent ovarian cancer are not greater than in healthy controls. Nevertheless, within this heterogeneous patient population, the values do correlate with bulk of disease. The potential utility of this assay in monitoring women with CA-125 negative disease is worthy of exploration. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM mseiden@partners.org OI Harris, Adrian/0000-0003-1376-8409 NR 13 TC 32 Z9 39 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2004 VL 93 IS 2 BP 361 EP 365 DI 10.1016/j.ygyno.2004.01.050 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 816OZ UT WOS:000221120500014 PM 15099946 ER PT J AU Birnbaum, RJ AF Birnbaum, RJ TI Borderline, bipolar, or both? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID PERSONALITY-DISORDER; DIAGNOSIS C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Birnbaum, RJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 12 TC 2 Z9 3 U1 0 U2 0 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2004 VL 12 IS 3 BP 146 EP 149 DI 10.1080/10673220490472391 PG 4 WC Psychiatry SC Psychiatry GA 836IW UT WOS:000222550100003 PM 15371069 ER PT J AU Brendel, RW Bryan, E AF Brendel, RW Bryan, E TI HIPAA for psychiatrists SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE confidentiality; Health Insurance Portability and Accountability Act of 1996 (HIPAA); medical privacy; patient access; psychiatric records; psychotherapy notes C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brendel, RW (reprint author), Massachusetts Gen Hosp, Warren 605,55 Fruit St, Boston, MA 02114 USA. EM rbrendel@partners.org NR 8 TC 5 Z9 5 U1 0 U2 2 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2004 VL 12 IS 3 BP 177 EP 183 DI 10.1080/10673220490472436 PG 7 WC Psychiatry SC Psychiatry GA 836IW UT WOS:000222550100007 PM 15371073 ER PT J AU Schwartz, SR McDowell, J Yueh, B AF Schwartz, SR McDowell, J Yueh, B TI Numeracy and the shortcomings of utility assessment in head and neck cancer patients SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article; Proceedings Paper CT Meeting of the Western-Section of the Triological-Society CY FEB 01, 2003 CL Indian Wells, CA SP Triolog Soc, W Sect DE utility; numeracy; head and neck cancer; quality of life; function ID QUALITY-OF-LIFE; HEALTH LITERACY; PERFORMANCE; VALIDITY; SCALE AB Background. Because survival differences between surgical and nonsurgical treatment for head and neck cancer (HNC) are hard to detect, increasing focus has been placed on quality of life (QOL) differences after treatment. Utility assessment provides insight into COL. Evidence suggests that a patient's comfort with numerical concepts ("numeracy") may influence utility measures. We hypothesize that patients who are nonnumerate provide inconsistent utility data in COIL studies. Methods. New HNC (n = 18) patients were recruited to participate. Patients completed a numeracy questionnaire, a utility assessment, and a global COIL questionnaire. Higher scores reflect better function. Interviewers rated the functional level of each patient. For both numerate and nonnumerate patients, utility scores were compared with global QOL (good vs poor) and observer-rated function. Results. Half of the patients were numerate. Numerate patients who rated their COIL as good had significantly higher utility scores than did patients with poor global COIL (0.95 vs 0.43, p =.03). In contrast, nonnumerate patients with good COIL had lower utility scores than did patients with poor COIL (0.45 vs 0.77 NS). Utility scores for numerate patients correlated well with observer-rated function (r= 0.41 to r= 0.57), whereas those of nonnumerate patients did not (r = -0.16 to r = 0.06). Conclusions. QOL evaluation through utility assessment may provide inaccurate and contradictory data about patient functioning for nonnumerate patients. This may confound COIL assessment when interpreting utility data. (C) 2004 Wiley Periodicals, Inc.* C1 Univ Washington, Med Ctr, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. RP Schwartz, SR (reprint author), Univ Washington, Med Ctr, Dept Otolaryngol Head & Neck Surg, 1959 NE Pacific St,Box 356515, Seattle, WA 98195 USA. EM schwarsr@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 NR 17 TC 24 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAY PY 2004 VL 26 IS 5 BP 401 EP 407 DI 10.1002/hed.10383 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 818HQ UT WOS:000221236600003 PM 15122656 ER PT J AU Chapman, RH Berger, M Weinstein, MC Weeks, JC Goldie, S Neumann, PJ AF Chapman, RH Berger, M Weinstein, MC Weeks, JC Goldie, S Neumann, PJ TI When does quality-adjusting life-years matter in cost-effectiveness analysis? SO HEALTH ECONOMICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Medicial-Decision-Making CY SEP 26, 2000 CL Cincinnati, OH SP Soc Med Decis Making DE quality-adjusted life-years; preference weights; utilities; cost-utility analysis; cost-effectiveness analysis ID UTILITY ANALYSES AB Purpose: This paper investigates the impact of quality-of-life adjustment on cost-effectiveness analyses, by comparing ratios from published studies that have reported both incremental costs per (unadjusted) life-year and per quality-adjusted life-year for the same intervention. Methods: A systematic literature search identified 228 original cost-utility analyses published prior to 1998. Sixty-three of these analyses (173 ratio pairs) reported both cost/LY and cost/QALY ratios for the same intervention, from which we calculated medians and means, the difference between ratios (cost/LY minus cost/ QALY) and between reciprocals of the ratios, and cost/LY as a percentage of the corresponding cost/QALY ratio. We also compared the ratios using rank-order correlation, and assessed the frequency with which quality-adjustment resulted in a ratio crossing the widely used cost-effectiveness thresholds of $20000, $50000, and $100000/QALY or LY. Results: The mean ratios were $69100/LY and $103100/QALY, with corresponding medians of $24600/LY and $20400/QALY. The mean difference between ratios was approximately -$34300 (median difference: $1300), with 60% of ratio pairs differing by $10000/year or less. Mean difference between reciprocals was 59 (QA)LYs per million dollars (median: 2.1). The Spearman rank-order correlation between ratio types was 0.86 (p<0.001). Quality-adjustment led to a ratio moving either above or below $50000/LY (or QALY) in 8% of ratio pairs, and across 100000 in 6% of cases. Conclusions: In a sizable fraction of cost utility analyses, quality adjusting did not substantially alter the estimated cost-effectiveness of an intervention, suggesting that sensitivity analyses using ad hoc adjustments or 'off-the-shelf' utility weights may be sufficient for many analyses. The collection of preference weight data should be subjected to the same scrutiny as other data inputs to cost-effectiveness analyses, and should only be undertaken if the value of this information is likely to be greater than the cost of obtaining it. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Program Econ Evaluat Med Technol, Boston, MA 02115 USA. Merck & Co Inc, W Point, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chapman, RH (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Program Econ Evaluat Med Technol, 718 Huntington Ave, Boston, MA 02115 USA. EM pneumann@hsph.harvard.edu NR 15 TC 50 Z9 51 U1 2 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD MAY PY 2004 VL 13 IS 5 BP 429 EP 436 DI 10.1002/hec.853 PG 8 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 821WU UT WOS:000221494800004 PM 15127423 ER PT J AU Contrada, RJ Idler, EL Goyal, TM Cather, C Rafalson, L Krause, TJ AF Contrada, RJ Idler, EL Goyal, TM Cather, C Rafalson, L Krause, TJ TI Why not find out whether religious beliefs predict surgical outcomes? If they do, why not find out why? Reply to Freedland (2004) SO HEALTH PSYCHOLOGY LA English DT Article DE religion; surgery; health; biopsychosocial model ID CORONARY-ARTERY-BYPASS; LENGTH-OF-STAY; INTERCESSORY PRAYER; ATRIAL-FIBRILLATION; CARE UNIT; SURGERY; HEALTH; MORTALITY; MODEL AB In this reply to K. E. Freedland's (2004) comments on R. J. Contrada et al. (2004), it is shown that the statistical issues he raised, and his preferred interpretation of the findings, were adequately addressed in the original article. It is argued that methodological limitations also were fully characterized and do not differ in kind from those of biomedical studies. Other issues discussed include the merits of focusing on distal versus proximal causation, plausibility of explanatory mechanisms for health effects of religious involvement, and potential practical applications that do not require manipulation of religious involvement. The article is concluded by commenting on subtle aspects of discourse that may unnecessarily polarize discussions of possible physical health effects of religious involvement. C1 Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Sociol, Piscataway, NJ 08854 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Contrada, RJ (reprint author), Rutgers State Univ, Dept Psychol, 53 Ave E, Piscataway, NJ 08854 USA. EM contrada@rci.rutgers.edu FU NIA NIH HHS [AG16750] NR 23 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2004 VL 23 IS 3 BP 243 EP 246 DI 10.1037/0278-6133.23.3.243 PG 4 WC Psychology, Clinical; Psychology SC Psychology GA 816PC UT WOS:000221120800003 PM 15099164 ER PT J AU Polgreen, P Flutz, SL Justice, AC Wagner, JH Diekema, DJ Rabeneck, L Weissman, S Stapleton, JT AF Polgreen, P Flutz, SL Justice, AC Wagner, JH Diekema, DJ Rabeneck, L Weissman, S Stapleton, JT TI Association of hypocholesterolaemia with hepatitis C virus infection in HIV-infected people SO HIV MEDICINE LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN DE cholesterol; HCV; hepatitis C; HIV; lipids ID HUMAN-IMMUNODEFICIENCY-VIRUS; DENSITY-LIPOPROTEIN RECEPTOR; CLINICAL-TRIALS GROUP; ANTIRETROVIRAL THERAPY; SERUM-CHOLESTEROL; VERY-LOW; PARTICLES; LIPIDS; PREVALENCE; CIRRHOSIS AB Objective To study the impact of hepatitis C virus (HCV) status on serum cholesterol levels in HIV-infected patients. Methods We retrospectively analysed data front the 881 participants of the Veterans Ageing Cohort 3 Site Study. Four different models were constructed using total cholesterol, low-density lipid (LDL) cholesterol, high-density lipid (HDL) cholesterol and triglycerides as dependent variables. The relevant covariates included HCV antibody status, HIV medication class, CD4 count, HIV viral load, glucose level, lipid-lowering drug use, gender, race, age, liver function test results, ethanol use, drug use, and HIV exposure category. Variables excluded from the final model included niacin use, gender, race, age, current ethanol use, and HIV exposure category. Results Of the 881 HIV-positive patients enrolled in the study, 700 (79%) were screened for HCV antibody, with 300 (42.8%) HCV antibody positive and 400 (57.2%) HCV antibody negative. A positive HCV antibody status was independently associated with lower total cholesterol levels (P = 0.001) and LDL cholesterol levels (P< 0.00 1) but not with lower HDL cholesterol or triglyceride levels. HCV-positive patients had predicted LDL levels 19 mg/dL lower than those of HCV-negative subjects. HCV infection was also associated with a decreased use of lipid-lowering medication, and protease inhibitor use was associated with increased LDL and total cholesterol levels. Conclusions HCV infection has been associated with lower cholesterol levels in HIV-negative individuals, and the same appears to be true with HIV-infected patients. This is an interesting finding given that HCV particles bind to LDL receptors in vitro and also because HCV-lipid interactions appear to be important in the HCV replication cycle. C1 Iowa City Vet Adm, Med Ctr, Iowa City, IA USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Pittsburgh, Ctr Hlth Equ Res & Promot, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Hosp St Raphael, New Haven, CT USA. RP Stapleton, JT (reprint author), UIHC, Dept Internal Med, SW34-P,GH,200 Hawkins Dr, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu OI Diekema, Daniel/0000-0003-1273-0724 FU NIA NIH HHS [K23 AG 00826]; NIAAA NIH HHS [AA 12671, AA 13566] NR 31 TC 35 Z9 36 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD MAY PY 2004 VL 5 IS 3 BP 144 EP 150 DI 10.1111/j.1468-1293.2004.00202.x PG 7 WC Infectious Diseases SC Infectious Diseases GA 822KZ UT WOS:000221539600004 PM 15139979 ER PT J AU Thadhani, R Ecker, JL Mutter, WP Wolf, M Smirnakis, KV Sukhatme, VP Levine, RJ Karumanchi, SA AF Thadhani, R Ecker, JL Mutter, WP Wolf, M Smirnakis, KV Sukhatme, VP Levine, RJ Karumanchi, SA TI Insulin resistance and alterations in angiogenesis - Additive insults that may lead to preeclampsia SO HYPERTENSION LA English DT Article DE pregnancy; insulin resistance; preeclampsia; clinical trials ID HORMONE-BINDING GLOBULIN; ENDOTHELIAL GROWTH-FACTOR; GESTATIONAL DIABETES-MELLITUS; POSTMENOPAUSAL WOMEN; SIGNAL-TRANSDUCTION; GLUCOSE-TOLERANCE; TYROSINE KINASE-1; PREGNANCY; RISK; HYPERTENSION AB Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule). Compared with controls, women who developed preeclampsia had lower serum levels of SHBG (208+/-116 versus 256+/-101 nmol/L, P=0.05) and PlGF (16+/-14 versus 67+/-150 pg/mL, P<0.001), and in multivariable analysis, women with serum levels of PlGF&LE;20 pg/mL had an increased risk of developing preeclampsia (odds ratio [OR] 7.6, 95% CI 1.4 to 38.4). Stratified by levels of serum SHBG (&LE;175 versus >175 mg/dL), women with low levels of SHBG and PlGF had a 25.5-fold increased risk of developing preeclampsia (P=0.10), compared with 1.8 (P=0.38) among women with high levels of SHBG and low levels of PlGF. Formal testing for interaction (PlGF x SHBG) was significant (P=0.02). In a model with 3 (n-1) interaction terms (high PlGF and high SHBG, reference), the risk for developing preeclampsia was as follows: low PlGF and low SHBG, OR 15.1, 95% CI 1.7 to 134.9; high PlGF and low SHBG, OR 4.1, 95% CI 0.45 to 38.2; low PlGF and high SHBG, OR 8.7, 95% CI 1.2 to 60.3. Altered angiogenesis and insulin resistance are additive insults that lead to preeclampsia. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Hosp, Renal Unit, Boston, MA USA. NIDDK, NIH, Bethesda, MD USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Renal Unit, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NICHD NIH HHS [HD39223]; NIDDK NIH HHS [DK02825, DK64255] NR 36 TC 65 Z9 68 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2004 VL 43 IS 5 BP 988 EP 992 DI 10.1161/01.HYP.0000124460.67539.1d PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816ME UT WOS:000221113200018 PM 15023932 ER PT J AU Mathis, D Benoist, C AF Mathis, D Benoist, C TI Back to central tolerance SO IMMUNITY LA English DT Review ID NONOBESE DIABETIC MICE; T-CELL TOLERANCE; THYMIC EPITHELIAL-CELLS; PROMISCUOUS GENE-EXPRESSION; AUTOIMMUNE REGULATOR AIRE; NOD MICE; NEGATIVE SELECTION; TRANSPLANTATION TOLERANCE; PERIPHERAL TOLERANCE; APOPTOSIS RESISTANCE AB The establishment and maintenance of immunological tolerance entails both central and peripheral mechanisms. The latter have been highlighted in the past several years, mostly because of great interest in the activities of regulatory T cells. However, an important role for central tolerance mechanisms has been reemphasized by recent results on human autoimmune diseases, including APECED and type 1 diabetes. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu NR 87 TC 136 Z9 140 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2004 VL 20 IS 5 BP 509 EP 516 DI 10.1016/S1074-7613(04)00111-6 PG 8 WC Immunology SC Immunology GA 823RX UT WOS:000221631900002 PM 15142520 ER PT J AU Vijayakrishnan, L Slavik, JM Illes, Z Greenwald, RJ Rainbow, D Greve, B Peterson, LB Hafler, DA Freeman, GJ Sharpe, AH Wicker, LS Kuchroo, VK AF Vijayakrishnan, L Slavik, JM Illes, Z Greenwald, RJ Rainbow, D Greve, B Peterson, LB Hafler, DA Freeman, GJ Sharpe, AH Wicker, LS Kuchroo, VK TI An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells SO IMMUNITY LA English DT Article ID ANTIGEN 4 CTLA-4; REGULATORY CELLS; ACTIVATION; SUSCEPTIBILITY; GENE; LYMPHOCYTES; ENGAGEMENT; EXPRESSION; MICE; LOCI AB Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a critical role in downregulating T cell responses. A number of autoimmune diseases have shown genetic linkage to the CTLA-4 locus. We have cloned and expressed an alternatively spliced form of CTLA-4 that has genetic linkage with type I diabetes in the NOD mice. This splice variant of CTLA-4, named ligand-independent CTLA-4 (liCTLA-4), lacks exon2 including the MYPPPY motif essential for binding to the costimulatory ligands B7-1 and B7-2. Here we show that liCTLA-4 is expressed as a protein in primary T cells and strongly inhibits T cell responses by binding and dephosphorylating the TcRzeta chain. Expression of liCTLA-4, but not full-length CTLA-4 (fICTLA-4), was higher in memory/regulatory T cells from diabetes-resistant NOD congenic mice compared to susceptible NOD mice. These data suggest that increased expression and negative signaling delivered by the liCTLA-4 may regulate development of T cell-mediated autoimmune diseases. C1 Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Cambridge, Cambridge Inst Med Res, Diabet & Inflammat Lab, Juvenille Diabet Res Fdn,Wellcome Trust, Cambridge CB2 2XY, England. Merck Res Labs, Dept Pharmacol, Rahway, NJ 07065 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. EM wicker@cimr.cam.ac.uk; vkuchroo@rics.bwh.harvard.edu RI Wicker, Linda/F-7384-2010 FU NIAID NIH HHS [P01 AI 39671, R01 AI4480]; NINDS NIH HHS [NS35685] NR 32 TC 146 Z9 151 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2004 VL 20 IS 5 BP 563 EP 575 DI 10.1016/S1074-7613(04)00110-4 PG 13 WC Immunology SC Immunology GA 823RX UT WOS:000221631900007 PM 15142525 ER PT J AU Siffledeen, JS Fedorak, RN Siminoski, K Jen, H Vaudan, E Abraham, N Seinhart, H Greenberg, G AF Siffledeen, JS Fedorak, RN Siminoski, K Jen, H Vaudan, E Abraham, N Seinhart, H Greenberg, G TI Bones and Crohn's - Risk factors associated with low bone mineral density in patients with Crohn's disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE bone mineral density; Crohn's disease; inflammatory bowel disease; osteopenia; osteoporosis ID INFLAMMATORY-BOWEL-DISEASE; POPULATION-BASED COHORT; ULCERATIVE-COLITIS; FRACTURE RISK; HIP FRACTURE; I COLLAGEN; OSTEOPOROSIS; METABOLISM; DIAGNOSIS; WOMEN AB Previous studies have confirmed that the prevalence of decreased bone mineral density is elevated in patients with inflammatory bowel disease. The objective of the current study was to determine the prevalence of osteopenia and osteoporosis in a cross-sectional outpatient population of 242 adult patients with Crohn's disease and to determine which clinical characteristics and serum and urine biochemical factors might be predictive of bone loss. Thirty-seven percent had normal bone density, 50.0% were osteopenic, and 12.9% were osteoporotic. Among the sites used to diagnose low bone mineral density, the femoral neck demonstrated the highest prevalence of osteopenia and the ultra-distal radius the highest prevalence of osteoporosis. However, low bone mineral density at one site was always predictive of low bone mineral density at the other. Corticosteroid use during the year before assessment was found to be consistently predictive of low bone mineral density in males but not in females. In contrast, low body mass index and high platelet counts were consistently predictive of low bone mineral density in females but not in males. Disease location, smoking, and age were not predictive of changes in bone mineral density. C1 Univ Alberta, Div Gastroenterol, Edmonton, AB T6G 2C1, Canada. Univ Alberta, Div Endocrinol, Edmonton, AB T6G 2C1, Canada. Univ Toronto, Div Gastroenterol, Toronto, ON, Canada. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Fedorak, RN (reprint author), Univ Alberta, Div Gastroenterol, Edmonton, AB T6G 2C1, Canada. EM Richard.fedorak@ualberta.ca RI Greenberg, Gordon/C-4620-2015; OI Fedorak, Richard/0000-0002-7382-0080 NR 49 TC 58 Z9 59 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2004 VL 10 IS 3 BP 220 EP 228 DI 10.1097/00054725-200405000-00007 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 817NM UT WOS:000221184200007 PM 15290915 ER PT J AU Carlet, J Thijs, LG Antonelli, M Cassell, J Cox, P Hill, N Hinds, C Pimentel, JM Reinhart, K Thompson, BT AF Carlet, J Thijs, LG Antonelli, M Cassell, J Cox, P Hill, N Hinds, C Pimentel, JM Reinhart, K Thompson, BT TI Challenges in end-of-life care in the ICU - Statement of the 5th International Consensus Conference in Critical Care: Brussels, Belgium, April 2003 SO INTENSIVE CARE MEDICINE LA English DT Article DE end-of-life care; ICU; terminal illness ID SELF-REPORTED PRACTICES; INTENSIVE-CARE; SUSTAINING TREATMENT; DECISION-MAKING; ILL PATIENTS; CONTROLLED TRIAL; ETHICAL QUESTIONNAIRE; TREATMENT PREFERENCES; RESOURCE UTILIZATION; PATIENT PREFERENCES AB The jurors identified numerous problems with end of life in the ICU including variability in practice, inadequate predictive models for death, elusive knowledge of patient preferences, poor communication between staff and surrogates, insufficient or absent training of health-care providers, the use of imprecise and insensitive terminology, and incomplete documentation in the medical records. The jury strongly recommends that research be conducted to improve end-of-life care. The jury advocates a "shared" approach to end-of-life decision-making involving the caregiver team and patient surrogates. Respect for patient autonomy and the intention to honour decisions to decline unwanted treatments should be conveyed to the family. The process is one of negotiation, and the outcome will be determined by the personalities and beliefs of the participants. Ultimately, it is the attending physician's responsibility, as leader of the health-care team, to decide on the reasonableness of the planned action. In the event of conflict, the ICU team may agree to continue support for a predetermined time. Most conflicts can be resolved. If the conflict persists, however, an ethics consultation may be helpful. Nurses must be involved in the process. The patient must be assured of a pain-free death. The jury of the Consensus Conference subscribes to the moral and legal principles that prohibit administering treatments specifically designed to hasten death. The patient must be given sufficient analgesia to alleviate pain and distress; if such analgesia hastens death, this "double effect" should not detract from the primary aim to ensure comfort. C1 Fdn Hop St Joseph, F-75674 Paris 14, France. Univ Sacred Heart, Policl Gemelli, Dept Anesthesiol Intens Care, I-00168 Rome, Italy. Washington Univ, Sch Med, St Louis, MO 63110 USA. Hosp Sick Children, Dept Crit Care Med, Toronto, ON M5G 1X8, Canada. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. St Bartholomews Hosp, Dept Intens Care, London EC1A 7BE, England. Univ Jena Klinikum, Klinikum Anasthesiol & Intens Therapie, D-07740 Jena, Germany. Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. RP Carlet, J (reprint author), Fdn Hop St Joseph, 185 Rue Raymond Losserand, F-75674 Paris 14, France. EM jcarlet@hopital-saint-joseph.org RI Antonelli, Massimo/F-9848-2010; OI Antonelli, Massimo/0000-0003-3007-1670 NR 73 TC 255 Z9 268 U1 2 U2 19 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAY PY 2004 VL 30 IS 5 BP 770 EP 784 DI 10.1007/s00134-004-2241-5 PG 15 WC Critical Care Medicine SC General & Internal Medicine GA 817BW UT WOS:000221154000008 PM 15098087 ER PT J AU Simarro, M Lanyi, A Howie, D Poy, F Bruggeman, J Choi, M Sumegi, J Eck, MJ Terhorst, C AF Simarro, M Lanyi, A Howie, D Poy, F Bruggeman, J Choi, M Sumegi, J Eck, MJ Terhorst, C TI SAP increases FynT kinase activity and is required for phosphorylation of SLAM and Ly9 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE signal transduction; Src; T-lymphocyte; X-linked lymphoproliferative disease ID LINKED LYMPHOPROLIFERATIVE-DISEASE; ACTIVATION MOLECULE SLAM; GENE-PRODUCT SAP; NATURAL-KILLER-CELLS; SH2 DOMAIN; CUTTING EDGE; SIGNAL-TRANSDUCTION; SURFACE RECEPTORS; IMMUNE RECEPTORS; GAMMA PRODUCTION AB The free Src homology 2 (SH2) domain protein SAP, encoded by the X-linked lymphoproliferative disease gene SH2D1A, controls signal transduction initiated by engagement of the SLAM-related receptors in T and NK cells. Here we demonstrate that SAP is required for phosphorylation of both SLAM and Ly9 in thymocytes and peripheral T cells. Furthermore, in vitro protein interaction studies and yeast two-hybrid analyses indicated that SAP binds directly to FynT and Lck. While SAP bound to both the SH3 domain and to the kinase domain of FynT, SAP bound solely to the kinase domain of Lck. The existence of a strong interaction between SAP and the SH3 domain of FynT prompted us to study the role of SAP in modulating the activity of FynT. In vitro addition of SAP to the autoinhibited form of FynT caused a large increase in FynT catalytic activity. By contrast, the SAP mutant R78E, which is unable to bind to the FynT SH3 domain, did not increase FynT activity and also displayed a reduced adaptor function upon transfection into T cells. Our results demonstrate that SAP is an adaptor that bridges SLAM and Ly9 with Src-like protein tyrosine kinases (PTKs), and has the ability to activate FynT. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Div Hematol & Oncol, Cincinnati, OH 45229 USA. RP Simarro, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. EM msimarro@rics.bwh.harvard.edu; terhorst@caregroup.harvard.edu RI Simarro, Maria/M-3947-2015 OI Simarro, Maria/0000-0001-8917-7328 FU NIAID NIH HHS [AI-035714, AI-15066] NR 52 TC 40 Z9 41 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 MAY PY 2004 VL 16 IS 5 BP 727 EP 736 DI 10.1093/intimm/dxh074 PG 10 WC Immunology SC Immunology GA 819DY UT WOS:000221295100011 PM 15096483 ER PT J AU Keel, PK Dorer, D Heatherton, TF AF Keel, PK Dorer, D Heatherton, TF TI Decreasing rates of bulimia nervosa among college students SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Univ Iowa, Iowa City, IA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Coll, Hanover, NH 03755 USA. RI Heatherton, Todd/H-5478-2011 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 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 042 BP 392 EP 392 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900043 ER PT J AU Franko, DL Dorer, DJ Jackson, SC Keel, PK Herzog, DB AF Franko, DL Dorer, DJ Jackson, SC Keel, PK Herzog, DB TI Predictors of onset and recovery for alcohol abuse in eating disorders SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Northeastern Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Univ Iowa, Iowa City, IA USA. Harvard Univ, Sch Med, Boston, MA 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 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 102 BP 427 EP 427 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900102 ER PT J AU Abidi, SC Dorer, DJ Franko, DL Manzo, MP Keel, PK Herzog, DB AF Abidi, SC Dorer, DJ Franko, DL Manzo, MP Keel, PK Herzog, DB TI Diagnostic migration in restricting anorexia nervosa SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northeastern Univ, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA 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 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 200 BP 454 EP 454 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900149 ER PT J AU Franko, DL Dorer, DJ Manzo, MP Jackson, SC Keel, PK Herzog, DB AF Franko, DL Dorer, DJ Manzo, MP Jackson, SC Keel, PK Herzog, DB TI Alcohol abuse symptom clusters in eating disorders SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Northeastern Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Iowa, Iowa City, IA USA. Harvard Univ, Sch Med, Boston, MA 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 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 202 BP 455 EP 455 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900151 ER PT J AU Pratt, EM Najavits, LM AF Pratt, EM Najavits, LM TI Eating disorder symptomatology in a treatment-seeking sample of women with substance use disorder and posttraumatic stress disorder: Description, effect on outcome, and response to treatment SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Boston VAHCS, Natl Ctr PTSD, Boston, MA USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 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 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 204 BP 456 EP 456 PG 1 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900153 ER PT J AU Delinsky, SS Hildebrandt, TB Dorer, DJ Franko, DL Jackson, SC Manzo, MP Herzog, DB AF Delinsky, SS Hildebrandt, TB Dorer, DJ Franko, DL Jackson, SC Manzo, MP Herzog, DB TI Patterns of purging among women with eating disorders SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Rutgers State Univ, Piscataway, NJ USA. Massachusetts Gen Hosp, 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 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 210 BP 459 EP 460 PG 2 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900159 ER PT J AU Miller, KK Grinspoon, SK Grieco, KA Ciampa, J Herzog, DB Klibanski, A AF Miller, KK Grinspoon, SK Grieco, KA Ciampa, J Herzog, DB Klibanski, A TI Preservation of menstrual function in women who fulfill criteria for anorexia nervosa SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Neuroendocrine Unit, 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 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 MA 286 BP 502 EP 503 PG 2 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900235 ER PT J AU Agras, WS Brandt, HA Bulik, CM Dolan-Sewell, R Fairburn, CG Halmi, KA Herzog, DB Jimerson, DC Kaplan, AS Kaye, WH le Grange, D Lock, J Mitchell, JE Rudorfer, MV Street, LL Striegel-Moore, R Vitousek, KM Walsh, BT Wilfley, DE AF Agras, WS Brandt, HA Bulik, CM Dolan-Sewell, R Fairburn, CG Halmi, KA Herzog, DB Jimerson, DC Kaplan, AS Kaye, WH le Grange, D Lock, J Mitchell, JE Rudorfer, MV Street, LL Striegel-Moore, R Vitousek, KM Walsh, BT Wilfley, DE TI Report of the National Institutes of Health Workshop on Overcoming Barriers to Treatment Research in Anorexia Nervosa SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE National Institutes of Health; National Institute of Mental Health; workshop; anorexia nervosa; treatment ID EATING-DISORDERS; BULIMIA-NERVOSA; INDIVIDUAL THERAPY; CONTROLLED TRIAL; FOLLOW-UP; FAMILY; ADOLESCENT; RECOVERY; PREDICTORS; RELAPSE AB Objective: Anorexia nervosa (AN) is associated with serious medical morbidity and has the highest mortality rate of all psychiatric disorders. The National Institutes of Health (NIH) Workshop on Overcoming Barriers to Treatment Research in Anorexia Nervosa convened on September 26-27, 2002 to address the dearth of treatment research in this area. The goals of this workshop were to discuss the stages of illness and illness severity, pharmacologic interventions, psychological interventions, and methodologic considerations. Method: The program consisted of a series of brief presentations by moderators, each followed by a discussion of the topic by workshop participants, facilitated by the session chair. Results: This report summarizes the major discussions of these sessions and concludes with a set of recommendations related to the development of treatment research in AN based on these findings. Discussion: It is crucial that treatment research in this area be prioritized. (C) 2004 by Wiley Periodicals, Inc. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychol, St Louis, MO 63110 USA. Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. St Joseph Med Ctr, Ctr Eating Disorders, Baltimore, MD USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. NIMH, Div Mental Disorders Behav Res & AIDS, Bethesda, MD 20892 USA. Univ Oxford, Dept Psychiat, Oxford, England. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp Westchester, White Plains, NY USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Toronto, Toronto Gen Hosp, Dept Psychiat, Toronto, ON M5G 1L7, Canada. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Neuropsychiat Res Inst, Fargo, ND USA. Univ N Dakota, Sch Med & Hlth Sci, Dept Neurosci, Fargo, ND USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Wesleyan Univ, Dept Psychol, Middletown, CT USA. Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Wilfley, DE (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid,Campus Box 8134, St Louis, MO 63110 USA. EM wilfleyd@psychiatry.wustl.edu RI Le Grange, Daniel/A-2649-2011 NR 35 TC 77 Z9 78 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2004 VL 35 IS 4 BP 509 EP 521 DI 10.1002/eat.10261 PG 13 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 816PD UT WOS:000221120900237 PM 15101067 ER PT J AU Demidova, TN Hamblin, MR AF Demidova, TN Hamblin, MR TI Macrophage-targeted photodynamic therapy SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Review DE macrophages; photosensitizer conjugate; cancer; inflammation; atherosclerosis ID TUMOR-ASSOCIATED MACROPHAGES; HOST-CELL POPULATIONS; SCAVENGER-RECEPTOR; PLAQUE RUPTURE; GROWTH-FACTOR; ATHEROSCLEROTIC PLAQUES; PHOTOFRIN ACCUMULATION; CANCER; PARADIGM; THROMBOSIS AB Photodynamic therapy (PDT) uses light activatable molecules that after illumination produce reactive oxygen species and unwanted tissue destruction. PDT has dual selectivity due to control of light delivery and to some extent selective photosensitizer (PS) accumulation in tumors or other diseased tissue, additional targeted selectivity of PS for disease is necessary. The delivery of drugs to selected lesions can be enhanced by the preparation of targeted macromolecular conjugates that employ cell type specific targeting by ligand-receptor recognition. Macrophages and monocytes express a scavenger-receptor that is a high-capacity route for delivering molecules into endocytic compartments in a cell-type specific manner. We have shown that by attaching PS to scavenger-receptor ligands it is possible to get three logs of selective cell killing in macrophages while leaving non-macrophage cells unharmed. The capability to selectively kill macrophages has applications in treating cancer and in the detection and therapy of vulnerable atherosclerotic plaque and possibly for autoimmune disease and some infections. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Demidova, TN (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882, R01 CA083882-01A2, R01 CA083882-02, R01-CA/AI838801]; NIAID NIH HHS [R01-AI050875, R01 AI050875] NR 45 TC 41 Z9 46 U1 0 U2 3 PU BIOLIFE SAS PI SILVA MARINA (TE) PA VIA S STEFANO 39 BIS, 64029 SILVA MARINA (TE), ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD MAY-AUG PY 2004 VL 17 IS 2 BP 117 EP 126 PG 10 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA 841YH UT WOS:000222968000003 PM 15171812 ER PT J AU Mehta, RP Faquin, WC Cunningham, MJ AF Mehta, RP Faquin, WC Cunningham, MJ TI Cervical bronchogenic cysts: a consideration in the differential diagnosis of pediatric cervical cystic masses SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE bronchogenic cyst; bronchial cyst; cervical cyst; neck mass ID NECK AB Objective: To discuss the clinical and histopathologic features of cervical. bronchogenic cysts. Methods: Retrospective case series. Results: A 22-year pathology database search identified 24 patients 18 years of age and younger with bronchial/bronchogenic cysts, four of which presented in the cervical region. Conclusion: Cervical bronchogenic cysts are rare in the pediatric population but deserve inclusion in the differential diagnosis of cystic neck masses. Such cysts result from abnormal tracheobronchial tree development with characteristic pathology including respiratory-type epithelium, mural cartilage, smooth muscle, and seromucinous glands. Definitive treatment requires surgical excision. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM michael_cunningham@meei.harvard.edu NR 4 TC 18 Z9 20 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD MAY PY 2004 VL 68 IS 5 BP 563 EP 568 DI 10.1016/j.ijporl.2003.12.015 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 817GY UT WOS:000221167200006 PM 15081229 ER PT J AU Thurman, SA Schnitt, SJ Connolly, JL Gelman, R Silver, R Harris, JR Recht, A AF Thurman, SA Schnitt, SJ Connolly, JL Gelman, R Silver, R Harris, JR Recht, A TI Outcome after breast-conserving therapy for patients with stage I or II mucinous, medullary, or tubular breast carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LA SP Amer Soc Therapeut Radiol & Oncol DE radiotherapy; tubular; medullary; mucinous; breast cancer ID 20-YEAR FOLLOW-UP; CANCER; SURGERY; MASTECTOMY; SURVIVAL; CONSERVATION; RADIOTHERAPY; IRRADIATION; RECURRENCE AB Purpose: To evaluate the site of first failure of patients with early-stage tubular, mucinous, and medullary breast carcinoma after breast-conserving therapy and compare their results with those of patients with infiltrating ductal carcinoma (IDC). Methods and Materials: Twenty clinical Stage I and II patients with mucinous carcinoma, 27 with medullary carcinoma, 28 with tubular carcinoma, and 1055 with IDC were identified. The minimal potential follow-up was 10 years. Results: No statistically significant difference (p = 0.15) was seen in the site of first failure between the four histologic types within the first 10 years after treatment. When the IDC tumors were omitted from the comparison, the failure patterns of the remaining three histologic types were not significantly different (P = 0.31). In a polychotomous logistic model, histologic type was not significantly associated with the site of first failure (all p > 0.17). Local failure was significantly associated with age < 50 years (p = 0.04), positive surgical margins (p = 0.007), lymphovascular invasion (p = 0.04), and tumors with an extensive intraductal component (p < 0.001). Regional/distant/opposite breast failure was significantly associated with clinical Stage T2 tumors (p < 0.001), four or more positive lymph nodes (p = 0.004), and lymphovascular invasion-positive tumors (p < 0.001). Second malignancy or death was significantly associated with age at diagnosis >60 years (p < 0.001) and lymphovascular invasion-positive tumors (p = 0.03). Conclusion: No statistically significant difference was noted in the site of first failure between patients with medullary, mucinous, or tubular carcinoma and patients with IDC. Although not statistically significant, we did note a trend toward a lower long-term rate of disease-free survival in patients with IDC. (C) 2004 Elsevier Inc. C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Thurman, SA (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, 330 Brookline Ave,Finard Basement, Boston, MA 02215 USA. EM sthurman@caregroup.harvard.edu NR 18 TC 19 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2004 VL 59 IS 1 BP 152 EP 159 DI 10.1016/j.ijrobp.2003.10.029 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 815MX UT WOS:000221047500021 PM 15093911 ER PT J AU Jagsi, R Chronowski, GM Buck, DA Kang, S Palermo, J AF Jagsi, R Chronowski, GM Buck, DA Kang, S Palermo, J CA ARRO Executive Committee TI Special report: Results of the 2000-2002 Association of Residents in Radiation Oncology (ARRO) surveys SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 06-10, 2002 CL NEW ORLEANS, LA SP Amer Soc Therapeut Radiol & Oncol DE Association of Residents in Radiation Oncology; ARRO; radiation oncology residency; resident training; survey ID TRAINING-PROGRAMS AB Between 2000 and 2002, the Association of Residents in Radiation Oncology (ARRO) conducted its 18th, 19th, and 20th annual surveys of all residents training in radiation oncology in the United States. This report summarizes these results. The demographic characteristics of residents in training between 2000 and 2002 are detailed, as are issues regarding the quality of training and career choices of residents entering practice. (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Coll Med, Richmond, VA USA. Duke Univ, Raleigh, NC USA. Wake Forest Univ, Winston Salem, NC 27109 USA. RP Jagsi, R (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. OI Jagsi, Reshma/0000-0001-6562-1228 NR 13 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2004 VL 59 IS 1 BP 313 EP 318 DI 10.1016/j.ijrobp.2003.12.025 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 815MX UT WOS:000221047500038 PM 15093928 ER PT J AU Lewinsohn, DA Gennaro, ML Scholvinck, L Lewinsohn, DM AF Lewinsohn, DA Gennaro, ML Scholvinck, L Lewinsohn, DM TI Tuberculosis immunology in children: diagnostic and therapeutic challenges and opportunities SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Review DE tuberculosis; child; infant; immunity; cellular; dendritic cells ID T-CELL RESPONSES; GROWTH-FACTOR-BETA; ACTIVE PULMONARY TUBERCULOSIS; NECROSIS-FACTOR-ALPHA; HUMAN DENDRITIC CELLS; RESPIRATORY SYNCYTIAL VIRUS; CALMETTE-GUERIN VACCINATION; ACELLULAR PERTUSSIS-VACCINE; INTERFERON-GAMMA PRODUCTION; HEALTHY HOUSEHOLD CONTACTS AB Tuberculosis (TB) is one of the most important causes of infectious morbidity and mortality worldwide. Young children are more likely to develop severe disease from the causative agent Mycobacterium tuberculosis. These clinical observations likely reflect fundamental differences in the immune systems of young children and adults. Essential to effective TB immunity are functioning macrophages, dendritic cells, strong Th1-type T-cell immunity and a relative absence of Th2-type T-cell immunity. Critical differences between adults and children relevant to TB immunity include deficiencies in macrophage and dendritic cell function, deficiencies in the development of Th1-type T-cells in response to pathogens, and the propensity for infants and young children to develop Th2-type CD4(+) T-cells in response to immunogens. In this article, knowledge about the requisite components of protective immunity, differences between the immune systems of children and adults relevant to pediatric tuberculosis, M. tuberculosis-specific T-cell immunity in children, and potential application to immunodiagnostics and vaccine development will be reviewed. C1 Oregon Hlth Sci Univ, Dept Pediat, CDRCP, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Publ Hlth Res Inst, Dept Pediat, Newark, NJ USA. Univ London Imperial Coll Sci Technol & Med, St Marys, London SW7 2AZ, England. Portland VA Med Ctr, Portland, OR USA. RP Lewinsohn, DA (reprint author), Oregon Hlth Sci Univ, Dept Pediat, CDRCP, 707 SW Gaines Rd, Portland, OR 97239 USA. EM lewinsde@ohsu.edu RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 NR 229 TC 70 Z9 71 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD MAY PY 2004 VL 8 IS 5 BP 658 EP 674 PG 17 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 818PF UT WOS:000221256300028 PM 15137550 ER PT J AU Gatinel, D Malet, J Hoang-Xuan, T Azar, DT AF Gatinel, D Malet, J Hoang-Xuan, T Azar, DT TI Corneal asphericity change after excimer laser hyperopic surgery: Theoretical effects on corneal profiles and corresponding Zernike expansions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID IN-SITU KERATOMILEUSIS; ORDER WAVE-ABERRATION; PHOTOREFRACTIVE KERATECTOMY; HUMAN-EYE; SPHERICAL-ABERRATION; MONOCHROMATIC ABERRATIONS; OPTICAL ABERRATIONS; REFRACTIVE SURGERY; MATHEMATICAL-MODEL; ABLATION PROFILES AB PURPOSE. To determine the theoretical relationships between the changes in corneal paraxial power, asphericity, and the corresponding Zernike polynomial expansion after conventional and customized excimer laser correction of hyperopia. METHODS. The initial corneal profile was modeled as a conic section of apical radius of curvature R-1 and asphericity Q(1). The theoretical value of the postoperative apical radius of curvature R-2 was computed by using a paraxial formula from the value of R-1 and hyperopic defocus D. The postoperative asphericity Q(2) of the corneal surface was computed within the optical zone of diameter S after the delivery of a Munnerlyn-based profile of ablation for hyperopia using conic section-fitting and minimization of the squared residuals. These calculations were repeated for different values of defocus, initial apical radius of curvature, and asphericity. Taylor series expansions were also used to provide an approximation aimed at predicting change in asphericity. The coefficients of a Zernike polynomial expansion of the rotationally symmetrical corneal profile (defocus C-2(o), spherical aberration C-4(o), secondary spherical aberration C-6(o)) were also computed, by using scalar products applied to the considered corneal profile modeled as a conic section and were expressed as a function of both its apical radius and asphericity. This allowed approximation of the variations of the Zernike polynomial expansion of the corneal profiles by subtracting the postoperative coefficient weighting a particular aberration from that of the preoperative one in different theoretical situations, after both conventional and customized hyperopia treatments aimed at controlling the postoperative corneal asphericity and delivered over a normalized pupil diameter. RESULTS. Conical least-squares fitting was unambiguous, allowing approximation of the postoperative corneal profile as a conic section of apical radius R-2. After a Munnerlyn-based hyperopia treatment, the sign of the asphericity of this profile remains theoretically unchanged, but its value decreased for initially oblate and increased for initially prolate corneas, respectively. A similar trend was noted with the approximation obtained by the Taylor series expansion. The alteration of the apical radius and/or of the asphericity of the corneal surface resulted in variations of both the corneal profile Zernike coefficients C-2(o) and C-4(o). The former was essentially dependent on the variation of the apical radius and the latter essentially on the variation of both apical radius and asphericity. CONCLUSIONS. Conventional and customized profiles of ablation for hyperopia alter the postoperative corneal asphericity and the Zernike coefficients of the corneal profile. The results of this study may be useful in the interpretation of the postoperative variations of the corneal profile and their impact on corneal wavefront expansion variations after both conventional and customized profiles of ablation. C1 Harvard Univ, External Dis & Refract Surg Serv, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Univ Paris, Rothschild Fdn, F-75252 Paris, France. Univ Paris 06, Inst Stat, Paris, France. RP Azar, DT (reprint author), Harvard Univ, External Dis & Refract Surg Serv, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu FU NEI NIH HHS [EY10101] NR 39 TC 20 Z9 20 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2004 VL 45 IS 5 BP 1349 EP 1359 DI 10.1167/iovs.03-0753 PG 11 WC Ophthalmology SC Ophthalmology GA 816BF UT WOS:000221084700012 PM 15111588 ER PT J AU Huang, W Wang, L Yuan, M Ma, JX Hui, YN AF Huang, W Wang, L Yuan, M Ma, JX Hui, YN TI Adrenomedullin affects two signal transduction pathways and the migration in retinal pigment epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MONOCYTE CHEMOTACTIC PROTEIN-1; NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR; CYCLIC-AMP; MESSENGER-RNA; PROLIFERATIVE VITREORETINOPATHY; SMOOTH-MUSCLE; RPE CELLS; PHEOCHROMOCYTOMA; EXPRESSION AB Purpose. Adrenomedullin is a multifunctional regulatory peptide known to inhibit the migration of smooth muscle cells. In vitro studies were performed to identify whether adrenomedullin (ADM) also inhibits the migration of RPE cells. The aberrant behavior of these cells is an early event in proliferative vitreoretinopathy, and these studies were designed to determine how ADM acts on RPE cells at the second-messenger level. Methods. Migration of cultured human RPE cells was determined by the Boyden chamber method, using 10% fetal calf serum (FCS) as a chemotactic factor. The attachment assay was performed on fibronectin, laminin, or poly-D-lysine-coated 96-well plates. RPE cells were incubated in PBS buffer with or without ADM for 15 minutes. Intracellular CAMP and cGMP changes were then measured by enzyme immunoassay (EIA). To determine the cytoplasmic free Ca2+ concentration ([Ca2+](i)) response to ADM, fluo-3 AM-loaded RPE cells were imaged with a laser scanning confocal microscope, after stimulation with ADM (10(-12)-10(-7) M). Results. ADM exhibited a concentration-dependent inhibition of FCS-stimulated RPE cell migration. The maximum inhibitory effect of ADM, observed at 10(-7) M, on basal and FCS-induced RPE cell migration was approximately 53.8% and 43.8% of the control, respectively. Exogenously added ADM (10(-9)-10(-7) M) had no significant effect on RPE cell attachment on all tested substrates. ADM increased intracellular CAMP and decreased intracellular cGMP levels dose dependently (10(-10)-10(-7) M) in RPE. The maximum effect was observed at 10(-7) M. ADM also induced a [Ca2+](i) decrease in a dose-dependent manner (10(-12)-10(-7) M). The maximum effect was observed at 0.1 muM, at which point the level declined to 42.9% of the control. Conclusions. ADM inhibits the migration of RPE cells in vitro by a mechanism that involves the reciprocal upregulation of cAMP and downregulation of cGMP, in association with reductions in [Ca2+](i). ADM-mediated fluctuations in [Ca2+](i), which are well known to be involved in cell migration, appear to be regulated in part by mechanisms involving cAMP synthase. Thus, it appears that ADM acts as a constitutive regulatory system to control aberrant RPE cell behavior and specific migration in response to inflammatory mediators. C1 Fourth Mil Med Univ, Xijing Hosp, Inst Ophthalmol, Xian, Peoples R China. Fourth Mil Med Univ, Xijing Hosp, Inst Cardiol, Xian, Peoples R China. RP Huang, W (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM wei_huang@meei.harvard.edu NR 38 TC 9 Z9 9 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2004 VL 45 IS 5 BP 1507 EP 1513 DI 10.1167/iovs-03-0731 PG 7 WC Ophthalmology SC Ophthalmology GA 816BF UT WOS:000221084700033 PM 15111609 ER PT J AU Kuritzkes, DR Bassett, RL Hazelwood, JD Barrett, H Rhodes, RA Young, RK Johnson, VA AF Kuritzkes, DR Bassett, RL Hazelwood, JD Barrett, H Rhodes, RA Young, RK Johnson, VA CA Adult ACTG Protocol 306 and 370 Te TI Rate of thymidine analogue resistance mutation accumulation with zidovudine- or stavudine-based regimens SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 11th International Workshop on HIV Drug Resistance and Treatment Strategies CY JUL 02-05, 2002 CL SEVILLE, SPAIN DE zidovudine; stavudine; drug resistance; thymidine analogues ID IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE; LAMIVUDINE; THERAPY; TRIAL; COMBINATION; DIDANOSINE; INFECTION; PATTERNS AB Zidovudine (ZDV) and stavudine (d4T) select for the same set of thymidine analogue resistance mutations (TAMs). To compare the rate at which TAMs emerge, genotypic analysis of HIV-1 was performed on serial plasma samples from treatment-naive subjects randomly assigned to receive ZDV or d4T in combination with lamivudine. After 72 weeks of follow-up, TAMs were detected in samples from 50% of ZDV-treated subjects and 45% of d4T-treated subjects (P = 0.79). The frequency of K70R and T215Y or F mutations was similar in both groups, although M41L was observed more frequently in samples from ZDV-treated subjects. This randomized study shows that TAMs accumulate at similar rates during treatment with ZDV or d4T, but the specific pattern of mutations may differ somewhat in patients treated with these thymidine analogues. C1 Univ Colorado, Ctr Hlth Sci, Denver, CO 80202 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Med Sch Birmingham, Birmingham, AL USA. RP Kuritzkes, DR (reprint author), Brigham & Womens Hosp, Sect Retroviral Therapeut, 65 Landsdowne St,Room 449, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org FU NCRR NIH HHS [RR00051, RR16482]; NIAID NIH HHS [AI 32775, AI32770, AI38855, AI38858, AI40876, AI42567] NR 19 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2004 VL 36 IS 1 BP 600 EP 603 DI 10.1097/00126334-200405010-00008 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 817KX UT WOS:000221177500008 PM 15097303 ER PT J AU Metzger, LJ Paige, SR Carson, MA Lasko, NB Paulus, LA Pitman, RK Orr, SP AF Metzger, LJ Paige, SR Carson, MA Lasko, NB Paulus, LA Pitman, RK Orr, SP TI PTSD arousal and depression symptoms associated with increased right-sided parietal EEG asymmetry SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; REGIONAL BRAIN ACTIVITY; VIETNAM NURSE VETERANS; MAJOR DEPRESSION; PERCEPTUAL ASYMMETRY; ANXIETY DISORDER; COMORBIDITY; PATTERNS; EMOTION AB Researchers have proposed that depression and particular types of Anxiety are associated with unique patterns of regional brain activation. The authors examined the relationship among posttraumatic stress disorder (PTSD), anxiety, and depressive symptoms and frontal, temporal, and parietal EEG alpha asymmetry in female Vietnam War nurse veterans. The results indicate that PTSD arousal symptoms are associated with increased right-sided parietal activation. However, the combination of arousal, depression, and their interaction explain more than twice the variance in parietal asymmetry compared with arousal alone. The results support the contention that the association between anxiety and right-sided posterior activation is specific to the anxious arousal subtype. These findings underscore the importance of isolating, both theoretically and statistically, emotional subcomponents in studies of regional brain activation. C1 Vet Affairs Med Ctr, Res Serv 151, Manchester, NH 03104 USA. Univ Nebraska, Omaha, NE 68182 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. St Anselm Coll, Manchester, NH 03102 USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Metzger, LJ (reprint author), Vet Affairs Med Ctr, Res Serv 151, 718 Smyth Rd, Manchester, NH 03104 USA. EM linda_metzger@hms.harvard.edu FU NIMH NIH HHS [R03MH57386] NR 29 TC 61 Z9 63 U1 4 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2004 VL 113 IS 2 BP 324 EP 329 DI 10.1037/0021-843X.113.2.324 PG 6 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 816MI UT WOS:000221113600016 PM 15122952 ER PT J AU Brogan, TV Robertson, HT Lamm, WJE Souders, JE Swenson, ER AF Brogan, TV Robertson, HT Lamm, WJE Souders, JE Swenson, ER TI Carbon dioxide added late in inspiration reduces ventilation-perfusion heterogeneity without causing respiratory acidosis SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE hypercapnia; respiratory acidosis; oxygen; dog; multiple inert-gas elimination technique ID BLOOD-FLOW DISTRIBUTION; TRACHEAL SMOOTH-MUSCLE; INTRACELLULAR PH; PULMONARY VASOCONSTRICTION; LUNG; CO2; HYPERCAPNIA; AIRWAY; GAS; HYPOCAPNIA AB We have shown previously that inspired CO2 (3-5%) improves ventilation-perfusion ((V)over dotA/(Q)over dot)matching but with the consequence of mild arterial hypercapnia and respiratory acidosis. We hypothesized that adding CO2 only late in inspiration to limit its effects to the conducting airways would enhance (V)over dotA/(Q)over dot matching and improve oxygenation without arterial hypercapnia. CO2 was added in the latter half of inspiration in a volume aimed to reach a concentration of 5% in the conducting airways throughout the respiratory cycle. Ten mixed-breed dogs were anesthetized and, in a randomized order, ventilated with room air, 5% CO2 throughout inspiration, and CO2 added only to the latter half of inspiration. The multiple inert-gas elimination technique was used to assess (V)over dotA/(Q)over dot heterogeneity. Late-inspired CO2 produced only very small changes in arterial pH (7.38 vs. 7.40) and arterial CO2 (40.6 vs. 39.4 Torr). Compared with baseline, late-inspired CO2 significantly improved arterial oxygenation (97.5 vs. 94.2 Torr), decreased the alveolar-arterial PO2 difference (10.4 vs. 15.7 Torr) and decreased the multiple inert-gas elimination technique-derived arterial-alveolar inert gas area difference, a global measurement of (V)over dotA/(Q)over dot heterogeneity(0.36 vs. 0.22). These changes were equal to those with 5% CO2 throughout inspiration (arterial PO2, 102.5 Torr; alveolar-arterial PO2 difference, 10.1 Torr; and arterial-alveolar inert gas area difference, 0.21). In conclusion, we have established that the majority of the improvement in gas exchange efficiency with inspired CO2 can be achieved by limiting its application to the conducting airways and does not require systemic acidosis. C1 Childrens Hosp & Reg Med Ctr, Dept Pediat, Seattle, WA 98105 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA 98105 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98105 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA. Univ Washington, Dept Med, Seattle, WA 98105 USA. RP Brogan, TV (reprint author), Childrens Hosp & Reg Med Ctr, Dept Pediat, 4800 Sand Point Way NE,CH-05, Seattle, WA 98105 USA. EM botcho@u.washington.edu FU NHLBI NIH HHS [HL-03796, HL-45591] NR 32 TC 22 Z9 22 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY 1 PY 2004 VL 96 IS 5 BP 1894 EP 1898 DI 10.1152/japplphysiol.00160.2003 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 810XM UT WOS:000220737000042 PM 14660515 ER PT J AU Haake, DA Suchard, MA Kelley, MM Dundoo, M Alt, DP Zuerner, RL AF Haake, DA Suchard, MA Kelley, MM Dundoo, M Alt, DP Zuerner, RL TI Molecular evolution and mosaicism of leptospiral outer membrane proteins involves horizontal DNA transfer SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SURFACE-EXPOSED LIPOPROTEIN; LATERAL GENE EXCHANGE; PATHOGENIC LEPTOSPIRA; BAYESIAN-INFERENCE; SEQUENCE-ANALYSIS; NEISSERIA-MENINGITIDIS; NUCLEOTIDE-SEQUENCES; MAMMALIAN INFECTION; INTERROGANS; SELECTION AB Leptospires belong to a genus of parasitic bacterial spirochetes that have adapted to a broad range of mammalian hosts. Mechanisms of leptospiral molecular evolution were explored by sequence analysis of four genes shared by 38 strains belonging to the core group of pathogenic Leptospira species: L. interrogans, L. kirschneri, L. noguchii, L. borgpetersenii, L. santarosai, and L. weilii. The 16S rRNA and lipL32 genes were highly conserved, and the lipL41 and ompL1 genes were significantly more variable. Synonymous substitutions are distributed throughout the ompL1 gene, whereas nonsynonymous substitutions are clustered in four variable regions encoding surface loops. While phylogenetic trees for the 16S, lipL32, and lipL41 genes were relatively stable, 8 of 38 (20%) ompL1 sequences had mosaic compositions consistent with horizontal transfer of DNA between related bacterial species. A novel Bayesian multiple change point model was used to identify the most likely sites of recombination and to determine the phylogenetic relatedness of the segments of the mosaic ompL1 genes. Segments of the mosaic oinpL1 genes encoding two of the surface-exposed loops were likely acquired by horizontal transfer from a peregrine allele of unknown ancestry. Identification of the most likely sites of recombination with the Bayesian multiple change point model, an approach which has not previously been applied to prokaryotic gene sequence analysis, serves as a model for future studies of recombination in molecular evolution of genes. C1 VA Greater LA Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA USA. USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. RP Haake, DA (reprint author), VA Greater LA Healthcare Syst, Div Infect Dis, 111F,10021 Wilshire Blvd, Los Angeles, CA 90073 USA. EM dhaake@ucia.edu FU NCI NIH HHS [CA 16042, P30 CA016042]; NIAID NIH HHS [R01 AI034431-07, AI 34431, R01 AI034431, R21 AI034431, R29 AI034431]; NIGMS NIH HHS [GM 068955, R01 GM068955] NR 52 TC 79 Z9 93 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2004 VL 186 IS 9 BP 2818 EP 2828 DI 10.1128/JB.186.9.2818-2828.2004 PG 11 WC Microbiology SC Microbiology GA 816DR UT WOS:000221091100036 PM 15090524 ER PT J AU Li, G Most, E DeFrate, LE Suggs, JF Gill, TJ Rubash, HE AF Li, G Most, E DeFrate, LE Suggs, JF Gill, TJ Rubash, HE TI Effect of the posterior cruciate ligament on posterior stability of the knee in high flexion SO JOURNAL OF BIOMECHANICS LA English DT Article DE PCL; high flexion; knee kinematics; posterior soft tissues ID IN-SITU FORCES; ANTERIOR-POSTERIOR; MUSCLE LOADS; REPLACEMENT; QUADRICEPS; INTACT; GRAFT AB Most biomechanical studies of the knee have focused on knee flexion angles between 0degrees and 120degrees. The posterior cruciate ligament (PCL) has been shown to constrain posterior laxity of the knee ill this range of flexion. However, little is known about PCL function in higher flexion angles (greater than 120degrees). This in vitro study examined knee kinematics before and after cutting the PCL at high flexion under a posterior tibial load and various muscle loads. The results demonstrated that although the PCL plays in important role in constraining posterior tibial translation at low flexion angles, the PCL had little effect in constraining tibial translation at 150degrees of flexion under the applied loads. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Biomech Lab, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 19 TC 25 Z9 26 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD MAY PY 2004 VL 37 IS 5 BP 779 EP 783 DI 10.1016/j.jbiomech.2003.09.031 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 811OQ UT WOS:000220781600021 PM 15047008 ER PT J AU Hallstrom, BR Golladay, GJ Vittetoe, DA Harris, WH AF Hallstrom, BR Golladay, GJ Vittetoe, DA Harris, WH TI Cementless acetabular revision with the Harris-Galante Porous prosthesis - Results after a minimum of ten years of follow-up SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL HIP-ARTHROPLASTY; COMPONENT; CLASSIFICATION; REPLACEMENT; OSTEOLYSIS; PLACEMENT; SCREWS; SCORE; WEAR AB Background: Revisions of the acetabular component of a total hip arthroplasty have a higher rate of complications, particularly loosening and dislocation, than do primary procedures. The purpose of this study, in which the results of a consecutive series of revisions performed with the Harris-Galante Porous acetabular component by a single surgeon were evaluated at an average of twelve years, was to quantify the complications and outcomes of acetabular revision. Methods: Clinical and radiographic results were evaluated to assess loosening, lysis, radiolucencies, and trochanteric union in 188 hips (170 patients) treated between 1984 and 1990. One hundred and twenty-two hips in 110 patients were followed for at least ten years, which was required for inclusion in the study. Thirty-one patients (thirty-six hips) died less than ten years postoperatively, and twenty-nine patients (thirty hips) were lost to or refused to return for follow-up. Results: The average Harris hip score was 78 points at an average of 12.5 years after revisioi, which was a 29-point improvement compared with the preoperative score. The rate of repeat revision because of aseptic loosening of the acetabular shell was 4% (five of 122). The rate of repeat revision of the shell for any reason was 15% (eighteen of 122). Eight unrevised sockets were loose radiographically, for a total rate of aseptic loosening of 11% (thirteen of 122). Conclusions: This study demonstrated that most acetabular revisions with this cementless hemispherical socket were successful. Few structural grafts and no cages were used. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hallstrom, BR (reprint author), Orthopaed Surg Associates, 5315 Elliott Dr,Suite 301, Ypsilanti, MI 48197 USA. EM wharris.obbl@partners.org NR 20 TC 32 Z9 35 U1 0 U2 0 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 MAY PY 2004 VL 86A IS 5 BP 1007 EP 1011 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 818SJ UT WOS:000221264500018 PM 15118045 ER PT J AU Kha, HT Basseri, B Shouhed, D Richardson, J Tetradis, S Hahn, TJ Parhami, F AF Kha, HT Basseri, B Shouhed, D Richardson, J Tetradis, S Hahn, TJ Parhami, F TI Oxysterols regulate differentiation of mesenchymal stem cells: Pro-bone and anti-fat SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE oxysterols; stein cells; osteogenesis; adipogenesis; bone morphogenetic protein ID MARROW STROMAL CELLS; CHOLESTEROL BIOSYNTHETIC-PATHWAY; ACTIVATED PROTEIN-KINASE; ARACHIDONIC-ACID RELEASE; OSTEOBLASTIC DIFFERENTIATION; NONHEMATOPOIETIC TISSUES; OSTEOGENESIS IMPERFECTA; MORPHOGENETIC PROTEIN-2; NRK-49F CELLS; GLA PROTEIN AB Pluripotent mesenchymal stem cells can undergo lineage-specific differentiation in adult organisms. However, understanding of the factors and mechanisms that drive this differentiation is limited. We show the novel ability of specific oxysterols to regulate lineage-specific differentiation of mesenchymal stem cells into osteogenic cells while inhibiting their adipogenic differentiation. Such effects may have important implications for intervention with osteoporosis. C1 Univ Calif Los Angeles, Sch Dent, Hlth Sci Ctr, Dept Cardiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Parhami, F (reprint author), Univ Calif Los Angeles, Sch Dent, Hlth Sci Ctr, Dept Cardiol, Room 47-123 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM fparhami@mednet.ucla.edu NR 64 TC 111 Z9 124 U1 3 U2 9 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2004 VL 19 IS 5 BP 830 EP 840 DI 10.1359/JBMR.040115 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 814GB UT WOS:000220962100018 PM 15068507 ER PT J AU Kadilak, PR Vanasse, S Sheridan, RL AF Kadilak, PR Vanasse, S Sheridan, RL TI Favorable short-and long-term outcomes of prolonged translaryngeal intubation in critically ill children SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID INTENSIVE-CARE-UNIT; MECHANICAL VENTILATION; RESPIRATORY-FAILURE; BURNED CHILDREN; TRACHEOSTOMY; TRACHEOTOMY; PATIENT AB In those children who require protracted mechanical ventilation, we use long-term intubation in order to avoid the consequences of tracheostomy in young children. A retrospective 9-year review was performed to document the efficacy and safety of this practice. A retrospective review of children admitted from January 1, 1991, to December 31, 1998, who required mechanical ventilatory support for at least 7 consecutive days was performed. Data are presented as mean +/- standard deviation. There were 98 children, ventilated for a total of 1967 days, who satisfied review criteria. They had an average age of 6.1 +/- 5.3 years (range, 3 months to 17 years) a total body surface area burn of 53 +/- 25% (range, 0-100%), and 71 of 98 (72%) had suffered an inhalation injury. They were ventilated for 19.7 +/- 16.8 days (range, 7-92 days) and were hospitalized for 67.8 +/- 48.9 days (range, 9-211 days). Ninety-three percent (91 of 98) of the patients were maintained on morphine infusions at a mean hourly rate of 0.35 +/- 0.33 mg/kg/hr (range, 0.01-4.38) and 78% (76 of 98) on midazolam infusions at a mean hourly rate of 0.14 +/- 0.17 mg/kg/hr (range, 0.01-1.82). Neuromuscular blocking agents were administered in 39% (38 of 98) of patients during all or part of 355 (18%) of the 1967 ventilator days. Patients were ventilated with an oral endotracheal (ET) tube in 82% of ventilator days and nasal ET tube in 18% of ventilator days. Two patients (2%) required tracheostomies for long-term management, and five patients (5.1%) died during the study period unrelated to airway issues. There were five unplanned extubation events, for an incidence rate of 2.54 per 1000 ventilator days. All patients were reintubated successfully. Thirteen ET tubes needed to be changed for issues such as leaking cuffs. Patients were followed up for a mean of 2.99 +/- 2.24 years (range, 1 month to 8 years). Possible sequelae related to prolonged intubation were noted in follow-up visits in 8 patients, including sinusitis (one; resolved without treatment), subglottic stenosis (one; required reconstructive surgery), persistent cough (three; all resolved spontaneously), occipital breakdown because of ET ties (one; healed after 1 month), soft voice (two; resolved spontaneously), and decreased pharyngeal sensation (one; resolved without treatment). Translaryngeal intubation is a safe and effective method to provide long-term ventilatory support in children. C1 Shriners Hosp Children, Boston Burn Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. RP Kadilak, PR (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. NR 20 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD MAY-JUN PY 2004 VL 25 IS 3 BP 262 EP 265 DI 10.1097/01.BCR.0000124786.68570.7C PG 4 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 820ZL UT WOS:000221428600008 PM 15273467 ER PT J AU Raitt, MH Kusumoto, W Giraud, G McAnulty, JH AF Raitt, MH Kusumoto, W Giraud, G McAnulty, JH TI Reversal of electrical remodeling after cardioversion of persistent atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; cardioversion; refractory period; conduction velocity; signal averaging ID SINUS NODE FUNCTION; AVERAGED P-WAVE; DURATION; REFRACTORINESS; RECURRENCE; VULNERABILITY; PREDICTION; MECHANISMS; RECOVERY; HUMANS AB Reverse Atrial Electrical Remodeling. Introduction: In animals, atrial fibrillation results in reversible atrial electrical remodeling manifested as shortening of the atrial effective refractory period, slowing of intra-atrial conduction, and prolongation of sinus node recovery time. There is limited information on changes in these parameters after cardioversion in patients with persistent atrial fibrillation. Methods and Results: Thirty-eight patients who had been in atrial fibrillation for 1 to 12 months underwent electrophysiologic testing 10 minutes and 1 hour after cardioversion. At 1 week, 19 patients still in sinus rhythm returned for repeat testing. Reverse remodeling of the effective refractory period was not uniform across the three atrial sites tested. At the lateral right atrium, there was a highly significant increase in the effective refractory period between 10 minutes and 1 hour after cardioversion (drive cycle length 400 ms: 204+/-17 ms vs 211+/-20 ms, drive cycle length 550 ms: 213+/-18 ms vs 219+/-23 ms, P<0.001). The effective refractory period at the coronary sinus and distal coronary sinus did not change in the first hour but had increased by 1 week. The corrected sinus node recovery time did not change in the first hour but was shorter at 1 week (606+/-311 ms vs 408+/-160 ms, P=0.009). P wave duration also was shorter at 1 week (135+/-18 ms vs 129+/-13 ms, P=0.04) consistent with increasing atrial conduction velocity. Conclusion: The atrial effective refractory period increases, sinus node function improves, and atrial conduction velocity goes up in the first week after cardioversion of long-standing atrial fibrillation in humans. Reverse electrical remodeling of the effective refractory period occurs at different rates in different regions of the atrium. C1 Portland VA Med Ctr, Div Cardiol, Portland, OR USA. Oregon Hlth Sci Univ, Div Cardiol, Portland, OR 97201 USA. Colorado Permanente & St Josephs Hosp, Denver, CO USA. RP Raitt, MH (reprint author), P-3-CARD,3710 SW US Vet Rd, Portland, OR 97239 USA. EM merritt.raitt@med.va.gov NR 27 TC 43 Z9 44 U1 0 U2 3 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2004 VL 15 IS 5 BP 507 EP 512 DI 10.1046/j.1540-8167.2004.03217.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 821IC UT WOS:000221452600001 PM 15149416 ER PT J AU Mansour, M AF Mansour, M TI Learning while burning: Further evidence for drivers and fibrillatory conduction as a mechanism for atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material ID ISOLATED SHEEP HEART C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 20 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2004 VL 15 IS 5 BP 522 EP 523 DI 10.1046/j.1540-8167.2004.03173.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 821IC UT WOS:000221452600004 PM 15149419 ER PT J AU Mansour, M Ruskin, J Keane, D AF Mansour, M Ruskin, J Keane, D TI Efficacy and safety of segmental ostial versus circumferential extra-ostial pulmonary vein isolation for atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; pulmonary vein isolation; electroanatomic mapping ID ISOLATED SHEEP HEART; CATHETER ABLATION; ANATOMIC APPROACH; COMPLICATIONS; MECHANISM AB Pulmonary Vein Isolation for AF. Introduction: Pulmonary vein (PV) isolation for atrial fibrillation (AF) can be performed using a segmental ostial or a circumferential extra-ostial approach. The relative merits and potential limitations of each approach are currently debated. Here we report our early experience with each of these approaches, including their relative efficacy and safety. Methods and Results: Forty patients with drug-refractory AF underwent segmental ostial PV isolation and were compared to 40 consecutive patients who underwent PV isolation using a circumferential extraostial approach. The latter approach described here is novel in two aspects: (1) the endpoint for ablation was PV isolation and not only delay in left atrial to PV conduction time, and (2) isolation of the right and left PVs was achieved by a single encirclement of ipsilateral veins. At follow-up, 60% of the patients in the segmental group were free of AF compared to 75% of the patients in the circumferential group. There was one thromboembolic cerebrovascular complication during the ablation procedure in each group. Conclusion: PV isolation using a circumferential extra-ostial approach, where the ipsilateral PVs are isolated together by one encircling line of block using electroanatomic mapping, is a technically feasible procedure. This approach is at least as effective and safe as the more established segmental ostial approach for AF ablation. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Keane, D (reprint author), St James Hosp, Cardiac Arrhythmia Serv, Dublin 8, Ireland. EM dkeane@stjames.ie NR 22 TC 67 Z9 72 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2004 VL 15 IS 5 BP 532 EP 537 DI 10.1046/j.1540-8167.2004.03503.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 821IC UT WOS:000221452600006 PM 15149421 ER PT J AU Armoundas, AA Albert, CM Cohen, RJ Mela, T AF Armoundas, AA Albert, CM Cohen, RJ Mela, T CA TOVA Investigators TI Utility of implantable cardioverter defibrillator electrograms to estimate repolarization alternans preceding a tachyarrhythmic event SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE ventricular arrhythmias; electrocardiology; alternans; primary prevention ID T-WAVE ALTERNANS; SIGNAL-AVERAGED ELECTROCARDIOGRAPHY; VENTRICULAR-ARRHYTHMIAS; ELECTRICAL ALTERNANS; HEART-FAILURE; SUDDEN-DEATH; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; RISK STRATIFICATION; FIBRILLATION AB Repolarization Alternans Estimates from ICD Electrograms. Electrical alternans is a pattern of variation in the shape of the ECG waveform that appears on an every-other-beat basis. In humans, alternation in ventricular repolarization, namely, repolarization alternans, has been associated with increased vulnerability to ventricular tachycardia/ventricular fibrillation and sudden cardiac death. This study investigates the utility of implantable cardioverter defibrillator electrograms to estimate repolarization alternans preceding a tachyarrhythmic event. It is demonstrated that microvolt-level repolarization alternans is present prior to an arrhythmic event, and one can record low-amplitude-noise signals that can be used to obtain reliable estimates of repolarization alternans. This study eventually may lead to new methods that would prevent the onset of malignant tachyarrhythmias. C1 MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. Johns Hopkins Univ, Div Mol Cardiobiol, Baltimore, MD USA. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM aarmoundas@partners.org NR 32 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD MAY PY 2004 VL 15 IS 5 BP 594 EP 597 DI 10.1046/j.1540-8167.03411.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 821IC UT WOS:000221452600017 PM 15149432 ER PT J AU Frolov, MV Dyson, NJ AF Frolov, MV Dyson, NJ TI Molecular mechanisms of E2F-dependent activation and pRB-mediated repression SO JOURNAL OF CELL SCIENCE LA English DT Article DE Rb/E2F; cell cycle; transcription repression; histone acetylation; histone methylation ID DEPENDENT TRANSCRIPTIONAL REPRESSION; HISTONE LYSINE METHYLATION; TUMOR-SUPPRESSOR PROTEIN; CELL-CYCLE ARREST; RETINOBLASTOMA PROTEIN; GROWTH ARREST; CHROMATIN-STRUCTURE; C/EBP-ALPHA; E2F FAMILY; GENE-PRODUCT AB Alterations in transcription of genes regulated by members of the E2F family of transcription factors can be viewed as a measure of the ebb and flow in a constantly evolving battle between repressor and activator complexes. Various chromatin regulatory complexes have been linked to Rb/E2F proteins, and changes in histone modifications correlate with states of E2F-dependent transcription. E2F has traditionally been viewed in the context of cell-cycle control. However, several recent studies have revealed a new aspect of E2F function in which pRB/E2F-family proteins confer stable repression of transcription. Such repression is evident in both actively proliferating cells and in cells that have withdrawn from the cell cycle. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NCI NIH HHS [CA64402]; NIGMS NIH HHS [GM53203] NR 81 TC 261 Z9 265 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2004 VL 117 IS 11 BP 2173 EP 2181 DI 10.1242/jcs.01227 PG 9 WC Cell Biology SC Cell Biology GA 830DQ UT WOS:000222102200002 PM 15126619 ER PT J AU Binder, LM Campbell, KA AF Binder, LM Campbell, KA TI Medically unexplained symptoms and neuropsychological assessment SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Review ID CHRONIC-FATIGUE-SYNDROME; POSTTRAUMATIC-STRESS-DISORDER; MULTIPLE CHEMICAL-SENSITIVITY; GULF-WAR VETERANS; CEREBRAL BLOOD-FLOW; IDIOPATHIC ENVIRONMENTAL INTOLERANCES; BORDERLINE PERSONALITY-DISORDER; FUNCTIONAL SOMATIC SYNDROMES; CONNECTIVE-TISSUE DISEASES; SILICONE BREAST IMPLANTS AB Several illnesses expressed somatically that do not have clearly demonstrated pathophysiological origin and that are associated with neuropsychological complaints are reviewed. Among them are nonepileptic seizures, fibromyalgia, chronic fatigue syndrome, Persian Gulf War unexplained illnesses, toxic mold and sick building syndrome, and silicone breast implant disease. Some of these illnesses may be associated with objective cognitive abnormalities, but it is not likely that these abnormalities are caused by traditionally defined neurological disease. Instead, the cognitive abnormalities may be caused by a complex interaction between biological and psychological factors. Nonepileptic seizures serve as an excellent model of medically unexplained symptoms. Although nonepileptic seizures clearly are associated with objective cognitive abnormalities, they are not of neurological origin. There is evidence that severe stressors and PTSD are associated with immune system problems, neurochemical changes, and various diseases; these data blur the distinctions between psychological and organic etiologies. Diagnostic problems are intensified by the fact that many patients are poor historians. Patients are prone to omit history of severe stressors and psychiatric problems, and the inability to talk about stressors increases the likelihood of suffering from physiological forms of stress. C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. RP Binder, LM (reprint author), 4900 SW Griffith Dr Suite 244, Beaverton, OR 97005 USA. EM pdxlarry@aol.com NR 177 TC 31 Z9 32 U1 3 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD MAY PY 2004 VL 26 IS 3 BP 369 EP 392 DI 10.1080/13803390490510095 PG 24 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 859GP UT WOS:000224251700006 PM 15512927 ER PT J AU Hoffman, AR Kuntze, JE Baptista, J Baum, HBA Baumann, GP Biller, BMK Clark, RV Cook, D Inzucchi, SE Kleinberg, D Klibanski, A Phillips, LS Ridgway, EC Robbins, RJ Schlechte, J Sharma, M Thorner, MO Vance, ML AF Hoffman, AR Kuntze, JE Baptista, J Baum, HBA Baumann, GP Biller, BMK Clark, RV Cook, D Inzucchi, SE Kleinberg, D Klibanski, A Phillips, LS Ridgway, EC Robbins, RJ Schlechte, J Sharma, M Thorner, MO Vance, ML TI Growth hormone (GH) replacement therapy in adult-onset GH deficiency: Effects on body composition in men and women in a double-blind, randomized, placebo-controlled trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; RECOMBINANT HUMAN GH; QUALITY-OF-LIFE; FACTOR-I; CARDIOVASCULAR-DISEASE; MUSCLE STRENGTH; GENDER; MASS; METABOLISM; HYPOPITUITARISM AB Adult GH deficiency (AGHD) is characterized by an altered body composition, an atherogenic lipid profile, decreased exercise capacity, and diminished quality of life. We performed a randomized, double-blind, placebo-controlled, multicenter study in 166 subjects with AGHD to assess the effects of GH on these outcomes. GH was initiated at 0.0125 mg/kg.d, increased to 0.025 mg/kg.d as tolerated, or decreased to 0.00625 mg/kg.d for 12 months. Primary measures of efficacy included body composition, strength and endurance, and quality of life. Additional parameters included serum IGF-I concentrations, serum lipids, and bone mineral density. After 12 months, 79% of subjects remained on GH 0.0125 mg/kg.d, whereas 21% received 0.00625 mg/kg.d. GH-treated men and women demonstrated significant decreases in total body and trunk fat and increases in lean body mass over base-line. In GH-treated men, mean IGF-I SD scores exceeded age-adjusted normal ranges, whereas similar doses produced a smaller response in women. GH treatment was associated with significant improvements in total cholesterol and low-density lipoprotein (P < 0.05 for all). No significant treatment effects were observed in strength and endurance, quality of life, or bone mineral density. GH treatment was generally well tolerated. Subjects with AGHD should receive individualized GH therapy to maintain IGF-I between the mean value and +2 SD and improve body composition and cardiovascular risk factors. C1 Vet Affairs Palo Alto Hlth Care Syst, Med Serv, Palo Alto, CA 94304 USA. Stanford Univ, Palo Alto, CA 94304 USA. Genentech Inc, Med Affairs, San Francisco, CA 94080 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. NYU, Med Ctr, New York, NY 10010 USA. Vet Affairs Med Ctr, New York, NY 10010 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Iowa, Iowa City, IA 52242 USA. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Hoffman, AR (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Med Serv, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM arhoffman@stanford.edu NR 50 TC 94 Z9 102 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2004 VL 89 IS 5 BP 2048 EP 2056 DI 10.1210/jc.2003-030346 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100011 PM 15126520 ER PT J AU Wang, C Cunningham, G Dobs, A Iranmanesh, A Matsumoto, AM Snyder, PJ Weber, T Berman, N Hull, L Swerdloff, RS AF Wang, C Cunningham, G Dobs, A Iranmanesh, A Matsumoto, AM Snyder, PJ Weber, T Berman, N Hull, L Swerdloff, RS TI Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the Endocrine-Society CY JUN 19-22, 2002 CL SAN FRANCISCO, CA SP Endocrine Soc ID CLINICAL-RESEARCH-CENTER; TRANSDERMAL TESTOSTERONE; BODY-COMPOSITION; AROMATASE DEFICIENCY; MUSCLE STRENGTH; OLDER MEN; REPLACEMENT; GENE; AGE; PHARMACOKINETICS AB Transdermal testosterone ( T) delivery represents an effective alternative to injectable androgens. We studied 163 hypogonadal men who applied 5, 7.5, or 10 g AndroGel (T gel) 1% CIII per day for up to 42 months. Efficacy data were presented in 123 subjects considered evaluable. Continuous AndroGel treatment normalized mean serum T and free T levels. Mean serum 5alpha-dihydrotestosterone concentrations and 5alpha-dihydrotestosterone/T ratio slightly increased, mean serum estradiol/T ratio doubled, and mean serum FSH and LH levels were suppressed by T replacement. Sexual function and mood parameters improved rapidly and were maintained throughout T treatment. Lean body mass increased (P = 0.0001) and fat mass decreased (P = 0.0001), and these changes were maintained with treatment but were not accompanied by significant increases in muscle strength. Increases in serum bone markers suggestive of increased bone formation were followed by gradual and progressive increases in bone mineral density more in the spine (P = 0.0001) than the hip (P = 0.0004). Mild local skin irritation occurred in 12 subjects, resulting in discontinuation in only one subject. Except for the anticipated increase in hematocrit and hemoglobin, there were no clinically significant changes in blood counts or biochemistry. In three subjects with elevated serum prostate-specific antigen, prostate biopsies showed cancer. We conclude that continued application of AndroGel resulted in beneficial effects similar to those with injectables and other transdermal preparations. This study was neither placebo controlled nor powered to determine the effects of T treatment on prostate cancer risk. Thus, monitoring for prostatic disease and assessment for erythrocytosis are strongly advised to reduce the risk of adverse events with T treatment of hypogonadal men. C1 Harbor UCLA Med Ctr, Gen Clin Res Ctr, Dept Med Pediat, Div Endocrinol, Torrance, CA 90509 USA. Harbor UCLA Res & Educ Inst, Dept Med Pediat, Div Endocrinol, Torrance, CA 90509 USA. Baylor Coll Med, Vet Affairs Med Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Baltimore, MD 21287 USA. Vet Affairs Med Ctr, Salem, VA 24153 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Duke Univ, Med Ctr, Durham, NC 27705 USA. RP Wang, C (reprint author), Harbor UCLA Med Ctr, Gen Clin Res Ctr, Dept Med Pediat, Div Endocrinol, 1000 W Carson St, Torrance, CA 90509 USA. EM wang@gcrc.rei.edu FU NCRR NIH HHS [M01-RR-00425, M01-RR-0030] NR 38 TC 343 Z9 352 U1 1 U2 15 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2004 VL 89 IS 5 BP 2085 EP 2098 DI 10.1210/jc.2003-032006 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100016 PM 15126525 ER PT J AU Driscoll, SD Meininger, GE Ljungquist, K Hadigan, C Torriani, M Klibanski, A Frontera, WR Grinspoon, S AF Driscoll, SD Meininger, GE Ljungquist, K Hadigan, C Torriani, M Klibanski, A Frontera, WR Grinspoon, S TI Differential effects of metformin and exercise on muscle adiposity and metabolic indices in human immunodeficiency virus-infected patients SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE; MIDDLE-AGED MEN; INSULIN-RESISTANCE; ANTIRETROVIRAL THERAPY; COMPUTED-TOMOGRAPHY; ABDOMINAL-FAT; HIV-LIPODYSTROPHY AB The HIV-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance (IR). The mechanisms and treatment strategies for IR in HIV-lipodystrophy are unclear, but data suggest that intramuscular lipids contribute to IR in this population. We previously showed that metformin and exercise improve hyperinsulinemia more than metformin alone in HIV-lipodystrophy. Now we investigate the effects of these treatment strategies on thigh muscle adiposity measured by computed tomography and additional body composition measures. Twenty-five HIV-infected patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution participated in a prospective, randomized, 3-month study of metformin alone or metformin and resistance training three times a week. Thigh muscle adiposity decreased significantly more as shown by increased muscle attenuation [2.0 (range, 0.5-5.0) vs.-1.0 (-3.5-0), P = 0.04] and sc leg fat tended to decrease more [-3.3 (-7.5-4.3) vs. 0.8 (-2.1-9.5), P = 0.06] in the combined treatment group in comparison with metformin alone. In multivariate analysis, change in thigh muscle adiposity remained a significant predictor of change in insulin (P = 0.04), controlling for changes in other body composition measurements. These data suggest that muscle adiposity, in addition to other fat depots, is an important determinant of hyperinsulinemia and that exercise has complex effects on regional fat depots in HIV-infected patients. Reduction in muscle adiposity may be an important mechanism by which exercise improves hyperinsulinemia in this population. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02144 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [RR01066, RR300088]; NIDDK NIH HHS [DK49302] NR 70 TC 35 Z9 36 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2004 VL 89 IS 5 BP 2171 EP 2178 DI 10.1210/jc.2003-031858 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 818BH UT WOS:000221220100029 PM 15126538 ER PT J AU Bausell, RB Lee, WL Soeken, KL Li, YF Berman, BM AF Bausell, RB Lee, WL Soeken, KL Li, YF Berman, BM TI Larger effect sizes were associated with higher quality ratings in complementary and alternative medicine randomized controlled trials SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE randomized controlled trials; complementary and alternative medicine; trial quality; effect sizes ID ACUTE MYOCARDIAL-INFARCTION; DESIGN AFFECTS OUTCOMES; CLINICAL-TRIALS; METHODOLOGICAL QUALITY; METAANALYSIS; PLACEBO; BIAS; HOMEOPATHY; EFFICACY; DISCREPANCIES AB Objective: To determine if the quality of, complementary and alternative medicine (CAM) placebo controlled randomized controlled trials (RCTs) is related to the effect sizes they produce when the type of interventions and outcome variables are controlled. Study Design and Setting: A sample of 25 CAM meta-analyses was identified from MEDLINE and hand searches containing published effect sizes for at least three efficacy trials employing placebo control groups. From these 25 reviews, 26 pairs of trials were selected: the one reporting the largest effect size and the matching trial reporting the smallest effect size. Quality and publication characteristics were then abstracted from each trial. Results: Unlike the preponderance of past evidence examining the relationship between quality and effect size, the present study found that trials possessing the largest effect sizes within a meta-analysis were also associated with higher quality ratings than their counterparts possessing the lowest effect sizes (P = .019). Conclusions: Possible theoretical reasons for this unexpected positive relationship include (a) sampling error, (b) reduced within group variation, (c) fraudulent reporting, and (d) the restriction of the analyses to placebo controlled trial. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. Univ Maryland, Kernan Hosp Mans, Sch Med, Complementary Med Program, Baltimore, MD 21207 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Bausell, RB (reprint author), Univ Maryland, Sch Nursing, 655 W Lombard St, Baltimore, MD 21201 USA. EM bbausell@compmed.umm.edu NR 52 TC 6 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2004 VL 57 IS 5 BP 438 EP 446 DI 10.1016/j.jclinepi.2003.11.001 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 832OM UT WOS:000222276800002 PM 15196613 ER PT J AU Andrews, NC AF Andrews, NC TI Anemia of inflammation: the cytokine-hepcidin link SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID ANTIMICROBIAL PEPTIDE HEPCIDIN; CHRONIC DISEASE; IRON OVERLOAD; EXPRESSION; GENE; HEMOCHROMATOSIS; PROTEIN; LIVER; MICE AB The anemia of inflammation, commonly observed in patients with chronic infections, malignancy, trauma, and inflammatory disorders, is a well-known clinical entity. Until recently, we understood little about its pathogenesis. It now appears that the inflammatory cytokine IL-6 induces production of hepcidin, an iron-regulatory hormone that may be responsible for most or all of the features of this disorder (see the related article beginning on page 1271). C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM nandrews@enders.tch.harvard.edu OI Andrews, Nancy/0000-0003-0243-4462 NR 18 TC 190 Z9 216 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2004 VL 113 IS 9 BP 1251 EP 1253 DI 10.1172/JCI200421441 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818MP UT WOS:000221249500004 PM 15124013 ER PT J AU Iinuma, T Homma, S Noda, T Kufe, D Ohno, T Toda, G AF Iinuma, T Homma, S Noda, T Kufe, D Ohno, T Toda, G TI Prevention of gastrointentional tumors based on adenomatous polyposis coli gene mutation by dendrite cell vaccine SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; CYTOTOXIC T-LYMPHOCYTES; MOUSE BONE-MARROW; ANTITUMOR IMMUNITY; CARCINOMA-CELLS; ANTIGEN PRESENTATION; APC GENE; FUSIONS; INTERLEUKIN-12; IMMUNIZATION AB Here we describe the effect of immunization with dendritic cells loaded with syngeneic tumor cells (DC/Ts) by polyethylene glycol treatment, on tumor development in adenomatous polyposis coli (APC) gene mutant mouse models, APC1309 and APC(Min-/+), in which adenomatous polyps of the gastrointestinal tracts develop with a high incidence. Treatment with DC/Ts prevented the development of gastrointestinal tumors, and coadministration of DC/Ts and IL-12 caused a further reduction in tumor incidence. Splenocytes from APC1309 mice treated with DC/Ts and IL-12 showed no cytotoxic activity toward the tumor cells, but serum antibody specific to them was detected. IgG from the treated mice exhibited cytotoxic activity against the tumor cells in vitro. Predominance of Th2 cell response over Th1 response was also suggested by ELISPOT assays in the treated mice. Depletion in vivo of CD4(+) T cells, not CD8(+) T cells, by the intraperitoneal administration of corresponding mAb's decreased the antitumor effect of DC/T inoculation. Immunofluorescence microscopic studies showed that Ig was attached to tumor cells in mice treated with DC/Ts and IL-12. These findings indicate that DC/T vaccination prevents tumor development through APC gene mutation and that its preventive effects are mediated by Immoral antitumor immunity. C1 Jikei Univ, Sch Med, Inst DNA Med, Dept Oncol,Minato Ku, Tokyo, Japan. Inst Canc Res, Dept Cell Biol, Toshima Ku, Tokyo, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Minato Ku, Tokyo, Japan. RP Iinuma, T (reprint author), 3-25-8 Nishi Shimbashi,Minato Ku, Tokyo 1058461, Japan. EM t.iinuma@jikei.ac.jp RI Noda, Tetsuo/B-1667-2016 NR 47 TC 33 Z9 35 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2004 VL 113 IS 9 BP 1307 EP 1317 DI 10.1172/JCI200417323 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818MP UT WOS:000221249500013 PM 15124022 ER PT J AU MacLean, HE Guo, J Knight, MC Zhang, PM Cobrinik, D Kronenberg, HM AF MacLean, HE Guo, J Knight, MC Zhang, PM Cobrinik, D Kronenberg, HM TI the cyclin-dependent kinase inhibitor p57(Kip2) mediates proliferative actions of PTHrP in chrondrocytes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-DEVELOPMENT; PARATHYROID-HORMONE; INDIAN-HEDGEHOG; MICE LACKING; CHONDROCYTE DIFFERENTIATION; TERMINAL DIFFERENTIATION; HYPERTROPHIC DIFFERENTIATION; PTH/PTHRP RECEPTOR; GROWTH-PLATE AB Parathyroid hormone-related peptide (PTHrP) is a positive regulator of chondrocyte proliferation during bone development. In embryonic mice lacking PTHrP, chondrocytes stop proliferating prematurely, with accelerated differentiation. Because the bone phenotype of mice lacking the cyclin-dependent kinase inhibitor p57(Kip2) is the opposite of the PTHrP-null phenotype, we hypothesized that PTHrP's proliferative actions in chondrocytes might be mediated by opposing p57. We generated p57/PTHrP-null embryos, which showed partial rescue of the PTHrP-null phenotype. There was reversal of the loss of proliferative chondrocytes in most bones, with reversal of the accelerated differentiation that occurs in the PTHrP-null phenotype. p57 mRNA and protein were upregulated in proliferative chondrocytes in the absence of PTHrP. Metatarsal culture studies confirmed the action of pTHrP to decrease p57 mRNA and protein levels in a model in which parathyroid hormone (PTH), used as an analog of PTHrP, increased chondrocyte proliferation rate and the length of the proliferative domain. PTH treatment of p57-null metatarsals had no effect on proliferation rate in round proliferative chondrocytes but still stimulated proliferation in columnar chondrocytes. These studies suggest that the effects of PTHrP on both the rate and extent of chondrocyte proliferation are mediated, at least in part, through suppression of p57 expression. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu FU NIDDK NIH HHS [DK-56246, P01 DK056246] NR 44 TC 62 Z9 63 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2004 VL 113 IS 9 BP 1334 EP 1343 DI 10.1172/JCI200421252 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818MP UT WOS:000221249500016 PM 15124025 ER PT J AU Iglesias, A Murga, M Laresgoiti, U Skoudy, A Bernales, I Fullaondo, A Moreno, B Lloreta, J Field, SJ Real, FX Zubiaga, AM AF Iglesias, A Murga, M Laresgoiti, U Skoudy, A Bernales, I Fullaondo, A Moreno, B Lloreta, J Field, SJ Real, FX Zubiaga, AM TI Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID THYMIC NEGATIVE SELECTION; E2F TRANSCRIPTION FACTORS; CELLULAR PROLIFERATION; FAMILY-MEMBERS; TARGET GENES; IN-VIVO; S-PHASE; CELLS; EXPRESSION; INDUCTION AB E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop non-autoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult. C1 Univ Basque Country, Fac Sci, Dept Genet Phys Anthropol & Anim Physiol, E-48080 Bilbao, Spain. Univ Pompeu Fabra, Inst Municipal Invest Med, Unitat Biol Cellular Mol, Barcelona, Spain. Basque Inst Agrarian Res & Dev, NEIKER, Derio, Spain. Hosp del Mar, Serv Patol, Barcelona, Spain. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Endocrinol, Boston, MA 02215 USA. RP Zubiaga, AM (reprint author), Univ Basque Country, Fac Sci, Dept Genet Phys Anthropol & Anim Physiol, Apartado 644, E-48080 Bilbao, Spain. EM ggpzuela@lg.ehu.es RI Fullaondo, Asier/C-5176-2011; Lloreta, J/I-2112-2014; Iglesias, Ainhoa/H-3021-2015; Laresgoiti-Servitje, Estibalitz/B-7658-2014; Real, Francisco X/H-5275-2015 OI Lloreta, J/0000-0003-1644-9470; Laresgoiti-Servitje, Estibalitz/0000-0002-3271-9955; Real, Francisco X/0000-0001-9501-498X NR 46 TC 63 Z9 65 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2004 VL 113 IS 10 BP 1398 EP 1407 DI 10.1172/JCI200418879 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 822IA UT WOS:000221531200007 PM 15146237 ER PT J AU Gursoy-Ozdemir, Y Qiu, JH Matsuoka, N Bolay, H Bermpohl, D Jin, HW Wang, XY Rosenberg, GA Lo, EH Moskowitz, MA AF Gursoy-Ozdemir, Y Qiu, JH Matsuoka, N Bolay, H Bermpohl, D Jin, HW Wang, XY Rosenberg, GA Lo, EH Moskowitz, MA TI Cortical spreading depression activates and upregulates MMP-9 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BLOOD-BRAIN-BARRIER; FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE-CELLS; MATRIX METALLOPROTEINASES; RAT-BRAIN; MATRIX-METALLOPROTEINASE-9 EXPRESSION; REPERFUSION INJURY; ARTERY OCCLUSION AB Cortical spreading depression (CSD) is a propagating wave of neuronal and glial depolarization and has been implicated in disorders of neurovascular regulation such as stroke, head trauma, and migraine. In this study, we found that CSD alters blood-brain barrier (BBB) permeability by activating brain MMPs. Beginning at 3-6 hours, MMP-9 levels increased within cortex ipsilateral to the CSD, reaching a maximum at 24 hours and persisting for at least 48 hours. Gelatinolytic activity was detected earliest within the matrix of cortical blood vessels and later within neurons and pia arachnoid ( 3 hours), particularly within piriform cortex; this activity was suppressed by injection of the metalloprotease inhibitor GM6001 or in vitro by the addition of a zinc chelator (1,10-phenanthroline). At 3-24 hours, immunoreactive laminin, endothelial barrier antigen, and zona occludens-1 diminished in the ipsilateral cortex, suggesting that CSD altered proteins critical to the integrity of the BBB. At 3 hours after CSD, plasma protein leakage and brain edema developed contemporaneously. Albumin leakage was suppressed by the administration of GM6001. Protein leakage was not detected in MMP-9-null mice, implicating the MMP-9 isoform in barrier disruption. We conclude that intense neuronal and glial. depolarization initiates a cascade that disrupts the BBB via an MMP-9-dependent mechanism. C1 Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Neurol, Charlestown, MA 02129 USA. Gazi Univ, Fac Med, Dept Neurol, Ankara, Turkey. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA. Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM moskowitz@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [R01 NS21169-11, F32 NS010828, NS10828, P01 NS010828, P50 NS010828] NR 57 TC 246 Z9 254 U1 1 U2 18 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2004 VL 113 IS 10 BP 1447 EP 1455 DI 10.1172/JCI200421227 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 822IA UT WOS:000221531200012 PM 15146242 ER PT J AU Henderson, DC Daley, TB Kunkel, L Rodrigues-Scott, M Koul, P Hayden, D AF Henderson, DC Daley, TB Kunkel, L Rodrigues-Scott, M Koul, P Hayden, D TI Clozapine and hypertension: A chart review of 82 patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID WEIGHT-GAIN AB Objective: Clozapine has been linked to significant weight gain and increase in serum lipids and appears to negatively impact glucose metabolism. In this retrospective chart review study, we examine changes in systolic and diastolic blood pressure and treatment for hypertension in clozapine-treated patients. Method: Data on demographics and systolic and diastolic blood pressure were examined for up to 5 years (September 1987 to September 1992) in 82 patients treated with clozapine. Rates of hypertension treatment in clozapine-treated patients were compared with patients receiving conventional antipsychotics (N = 56) and other atypical antipsychotic agents (N = 102). Results: The mean age of the 82 patients at the time of clozapine initiation was 36.4 +/- 7.8 years, with 22 (27%) female, 75 (91%) white, 3 (4%) black, 3 (4%) Hispanic, and I (1%) Asian. The baseline weight was 175.5 +/- 34.0 lb (79.0 +/- 15.3 kg) and baseline body mass index was 26.9 +/- 5.0 kg/m(2). There was a significant increase in systolic blood pressure (p = .0004) and diastolic blood pressure (p = .0001). Overall, 22 patients (27%) received treatment for hypertension following clozapine initiation. Only 2 (4%) of 56 patients in the conventional antipsychotic group and 9 (9%) of 102 patients in the other atypical antipsychotic group (olanzapine, N = 6; risperidone, N = 3) received treatment for hypertension. Conclusion: Our findings suggest that long-term clozapine treatment is associated with increased rates of hypertension, which may have a significant impact on medical morbidity and mortality. C1 Harvard Univ, Sch Med, Schizophrenia Program, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, MGH Biostat Program, Boston, MA 02114 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org NR 11 TC 40 Z9 42 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2004 VL 65 IS 5 BP 686 EP 689 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 827GG UT WOS:000221887100014 PM 15163256 ER PT J AU Mani, A Napel, S Paik, DS Jeffrey, RB Yee, J Olcott, EW Prokesch, R Davila, M Schraedley-Desmond, P Beaulieu, CF AF Mani, A Napel, S Paik, DS Jeffrey, RB Yee, J Olcott, EW Prokesch, R Davila, M Schraedley-Desmond, P Beaulieu, CF TI Computed tomography colonography - Feasibility of computer-aided polyp detection in a "First reader" paradigm SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article; Proceedings Paper CT 88th Scientific Assembly and Annual Meeting of the Radiologic-Society-of-North-America CY DEC 01-06, 2002 CL Chicago, IL SP Radiol Soc N Amer DE colon; polyps; computed tomography colonography; virtual colonoscopy; computer-aided diagnosis; interpretation accuracy; interpretation efficiency ID SPIRAL CT COLONOGRAPHY; VIRTUAL COLONOSCOPY; COLORECTAL POLYPS; COLONIC POLYPS; CONVENTIONAL COLONOSCOPY; DIAGNOSTIC PERFORMANCE; DATA-ACQUISITION; COLOGRAPHY; SUPINE; PRONE AB Objective: To determine the feasibility of a computer-aided detection (CAD) algorithm as the "first reader" in computed tomography colonography (CTC). Methods: In phase 1 of a 2-part blind trial, we measured the performance of 3 radiologists reading 41 CTC studies without CAD. In phase 2, readers interpreted the same cases using a CAD list of 30 potential polyps. Results: Unassisted readers detected, on average, 63% of polyps greater than or equal to10 mm in diameter. Using CAD, the sensitivity was 74% (not statistically different). Per-patient analysis showed a trend toward increased sensitivity for polyps greater than or equal to10mm in diameter, from 73% to 90% with CAD (not significant) without decreasing specificity. Computer-aided detection significantly decreased interobserver variability (P = 0.017). Average time to detection of the first polyp decreased significantly with CAD, whereas total reading case reading time was unchanged. Conclusion: Computer-aided detection as a first reader in CTC was associated with similar per-polyp and per-patient detection sensitivity to unassisted reading. Computer-aided detection decreased interobserver variability and reduced the time required to detect the first polyp. C1 Stanford Univ, Med Ctr, Dept Radiol, Stanford, CA 94305 USA. Stanford Med Sch, Stanford, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Univ Vienna, Dept Radiol, Vienna, Austria. Stanford Univ, Ctr Med, Dept Med, Stanford, CA USA. RP Beaulieu, CF (reprint author), Stanford Univ, Med Ctr, Dept Radiol, MC 5105,300 Pasteur Dr, Stanford, CA 94305 USA. EM beaulieu@stanford.edu FU NCI NIH HHS [1R01 CA72023]; NCRR NIH HHS [1P41 RR09784-01] NR 60 TC 53 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2004 VL 28 IS 3 BP 318 EP 326 DI 10.1097/00004728-200405000-00003 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 818GV UT WOS:000221234500003 PM 15100534 ER PT J AU Armstrong, AW Fazeli, A Yeh, SW Mackool, BT Liu, V AF Armstrong, AW Fazeli, A Yeh, SW Mackool, BT Liu, V TI Vancomycin-induced linear IgA disease manifesting as bullous erythema multiforme SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID DERMATOSIS AB Background: Vancomycin-induced linear immunoglobulin A (IgA) disease, an autoimmune, blistering disease in response to vancomycin administration, is characterized by a subepidermal, vesiculobullous eruption and linear IgA deposition along the basement membrane zone on direct immunofluorescence. Case report: We report the case of an 81-year-old man treated with vancomycin who developed diffuse erythema multiforme and tense bullae involving the palmoplantar surfaces. Discontinuation of vancomycin therapy resulted in complete resolution of this patient's cutaneous eruption. Results: Biopsy of a representative skin lesion demonstrated lichenoid interface dermatitis with focal subepidermal clefting, dyskeratosis, and prominent eosinophils. Direct immunofluorescence showed linear basement membrane staining With immunoreactants to IgA; indirect immunofluorescence demonstrated the presence of circulating IgG antibodies binding in an intercellular pattern. Immunoprecipitation studies using the patient's serum revealed 210, 130, and 83 kDa target antigens. Conclusions: Presenting with an initial clinical picture, suggestive of bullous erythema multiforme, this patient's subsequent clinical course and direct immunofluorescence confirm the diagnosis of linear IgA bullous disease (LABD). His indirect immunofluorescence findings and immunoprecipitation results suggest that circulating non-IgA antibodies may represent a newly recognized immunopathologic feature of vancomycin-induced linear IgA disease, underscoring the variable and unpredictable manifestations of this drug-induced cutaneous disease. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Liu, V (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, 55 Fruit St,Warren 827, Boston, MA 02114 USA. EM april_armstrong@student.hms.harvard.edu; vliu@partners.org NR 12 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2004 VL 31 IS 5 BP 393 EP 397 DI 10.1111/j.0303-6987.2004.00190.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 815RE UT WOS:000221058600008 PM 15059226 ER PT J AU Thomas, SH Andruszkiewicz, LM AF Thomas, SH Andruszkiewicz, LM TI Ongoing visual analog score display improves Emergency Department pain care SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE acute pain management; visual analog scale; pain assessment; ED analgesia ID 5TH VITAL SIGN; INADEQUATE EMERGENCY; ABDOMINAL-PAIN; RISK FACTOR; ANALGESIA; SCALE; OLIGOANALGESIA; SEVERITY; AGE; STATISTICS AB The study purpose was to test two methods of pain assessment and display: ongoing (11 times over 2 h) visual analog scale (VAS) determination with data tabulation in the ED chart (Tabulation group), and similar VAS assessments with display of the information at the head of the ED bed (Graph group). A Control group had initial and 2-h VAS ascertainments charted (not graphed). Tertiary-care university-affiliated ED patients were randomized into the three groups and pain care outcomes assessed. Compared to Controls, those in the Graph group had the following findings (p < 0.05): 1) treating physicians more likely aware of initial and final VAS scores, 2) earlier analgesia, 3) likelier perception (by patients and physicians) that VAS was useful and likelier patient perception that pain care was adequate. Tabulation group results were intermediate to those of Control and Graph patients. The data support further investigation of VAS display as a means of improving ED pain assessment. (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Wellesley Coll, Wellesley, MA 02181 USA. RP Thomas, SH (reprint author), MGH Clin Bldg,Room 155,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2004 VL 26 IS 4 BP 389 EP 394 DI 10.1016/j.jemermed.2003.11.020 PG 6 WC Emergency Medicine SC Emergency Medicine GA 813XC UT WOS:000220938800001 PM 15093842 ER PT J AU Osborne, DW Brown, DFM Nadel, ES AF Osborne, DW Brown, DFM Nadel, ES TI Chest pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID CORONARY-ARTERY-DISEASE; EXERCISE PROTOCOL; ANGINA-PECTORIS; SPECT C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2004 VL 26 IS 4 BP 447 EP 450 DI 10.1016/j.jemermed.2004.01.011 PG 4 WC Emergency Medicine SC Emergency Medicine GA 813XC UT WOS:000220938800012 PM 15093853 ER PT J AU Chiu, HK Palmer, JP AF Chiu, HK Palmer, JP TI Autoimmune diabetes: More than just one flavor? SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Editorial Material DE Type 1 diabetes; latent autoimmune diabetes in adults; Type 1.5 diabetes ID GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL ANTIBODIES; CLINICAL-DIAGNOSIS; INSULIN THERAPY; ADULT-ONSET; MELLITUS; TYPE-1; AUTOANTIBODIES; IDDM; GAD C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Chiu, HK (reprint author), 1660 S Columbian Way,Endo 111, Seattle, WA 98108 USA. EM chiuh@u.washington.edu FU NIDDK NIH HHS [P30DK17047] NR 60 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0391-4097 EI 1720-8386 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD MAY PY 2004 VL 27 IS 5 BP 480 EP 484 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 832DB UT WOS:000222246300016 PM 15279084 ER PT J AU Gill, TM McDermott, MM Ibrahim, SA Petersen, LA Doebbeling, BN AF Gill, TM McDermott, MM Ibrahim, SA Petersen, LA Doebbeling, BN TI Getting funded - Career development awards for aspiring clinical investigators SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE career development; academic medicine; research training ID GENERAL INTERNAL-MEDICINE; PERSPECTIVE AB For aspiring clinical investigators, career development awards provide a primary mechanism for "getting funded." The objective of this article is to provide information that will facilitate a successful application for a research career development award. Specifically, we discuss important issues that cut across the diverse array of awards, and we highlight the most common sources of funding, including the unique opportunities that are available for underrepresented minorities. The target audience includes junior faculty and fellows who are pursuing or considering a research career in academic medicine, as well as their mentors and program directors. C1 Yale Univ, Sch Med, Dorothy Adler Geriatr Assessment Ctr, Dept Internal Med, New Haven, CT 06504 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. VA Pittsburgh Healthcare Syst, VA Ctr Excellence Hlth Equ Res & Prom, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Regenstrief Inst Hlth Care Res, Indianapolis, IN USA. RP Gill, TM (reprint author), Yale Univ, Sch Med, Dorothy Adler Geriatr Assessment Ctr, Dept Internal Med, 20 York St, New Haven, CT 06504 USA. EM gill@ynhh.org FU NIA NIH HHS [K24 AG021507]; NIOSH CDC HHS [K01 OH00131] NR 6 TC 8 Z9 8 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2004 VL 19 IS 5 BP 472 EP 478 DI 10.1111/j.1525-1497.2004.30293.x PN 1 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 816VR UT WOS:000221137900012 PM 15109347 ER PT J AU Houston, TK Connors, RL Cutler, N Nidiry, MA AF Houston, TK Connors, RL Cutler, N Nidiry, MA TI A primary care musculoskeletal clinic for residents - Success and sustainability SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE musculoskeletal; housestaff; primary care ID EDUCATION; MEDICINE; FACULTY; IMPACT AB Musculoskeletal complaints are common, but are often under-emphasized in residency training. We evaluated the experience of residents (12) in 4 sessions of an innovative concentrated ambulatory, community-based musculoskeletal (MS) clinic precepted by general internists with additional training in teaching MS medicine. Compared with the yearlong longitudinal house staff (HS) clinic experience, the mean number of musculoskeletal diagnoses per resident seen in MS clinic was higher (13.9 [standard deviation 4.0] vs 5.4 [standard deviation 4.0]; P < .01). Common diagnoses in MS clinic included shoulder, hip, and knee tendonitis/bursitis, and the majority of diagnoses in HS clinic were nonspecific arthralgia (66%). Fifty-two injections were performed in MS clinic over the year, compared with one in HS clinic. C1 Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. RP Houston, TK (reprint author), Univ Alabama, Div Gen Internal Med, Birmingham Vet Affairs Med Ctr,Dept Med, Deep S Effectiveness Targeted Res Enhancement Pro, 1813 6th Ave S,MEB 621, Birmingham, AL 35294 USA. EM tkhouston@uabmc.edu RI Houston, Thomas/F-2469-2013 NR 16 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2004 VL 19 IS 5 BP 524 EP 529 DI 10.1111/j.1525-1497.2004.30173.x PN 2 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 821IB UT WOS:000221452500009 PM 15109317 ER PT J AU Harness, N Ring, D Jupiter, JB AF Harness, N Ring, D Jupiter, JB TI Volar Barton's fractures with concomitant dorsal fracture in older patients SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Barton; classification; malunion; radius; shearing; fracture ID INTRAARTICULAR FRACTURES; DISTAL END; RADIUS; FIXATION AB Purpose: To describe a variant of Barton's volar articular shearing fracture of the distal radial articular surface with a subtle concomitant fracture of the dorsal metaphyseal cortex. Methods: This fracture pattern was observed in 6 women and 2 men with an average age of 67 years (range, 58-76 years). All 8 patients were treated with a volar plate and screws. The dorsal metaphyseal fracture was not recognized in 5 patients and a volar buttress plating technique using an intentionally undercontoured volar plate was used. In 3 patients the dorsal fracture line was identified before surgery and the plate was contoured to fit the volar surface of the distal radius. Results: All 5 patients treated with an undercontoured plate had loss of the normal palmar tilt of the distal radius (average, -9.4degrees; range, 0degrees to-22degrees) and dorsal translation of the distal radial articular fragments. For the entire group the palmar tilt averaged-5.9degrees (range, 0.0degrees to-22degrees), the ulnar inclination 19degrees(range, 10degrees-23degrees), and the ulnar variance-0.9 mm (range, 0.0 to-3.0 mm). All patients attained forearm suppination of 80degrees and the average pronation was 75degrees (range, 45degrees-80degrees). According to Sarmiento's modification of the system of Gartland and Werley there were 1 excellent, 6 good, and 1 fair results. The average Patient-Rated Wrist Evaluation score was 16 (range, 0-35). Conclusion: Some fractures with an oblique volar marginal articular fracture of the distal radius and volar radiocarpal subluxation (known as Barton's fracture) may also have a fracture through the dorsal metaphyseal cortex. Failure to identify this fracture line can lead to dorsal translation and angulation of the distal radius articular surface, particularly when an undercontoured volar plate is used for internal fixation. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Combined Orthopaed Residency, Boston, MA 02115 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Serv,Dept Orthopaed Surg, 15 Parkman St,ACC 525, Boston, MA 02114 USA. NR 20 TC 8 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2004 VL 29A IS 3 BP 439 EP 445 DI 10.1016/j.jhsa.2003.12.009 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 822QO UT WOS:000221555100017 PM 15140487 ER PT J AU Ring, D Hannouche, D Jupiter, JB AF Ring, D Hannouche, D Jupiter, JB TI Surgical treatment of persistent dislocation or subluxation of the ulnohumeral joint after fracture-dislocation of the elbow SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE fracture; dislocation; elbow; instability; external fixation ID POSTEROLATERAL ROTATORY INSTABILITY; DISTRACTION ARTHROPLASTY; INTRAARTICULAR FRACTURES; RADIAL HEAD; RECONSTRUCTION; NONUNION AB Purpose: To review the results of surgical reconstruction of posttraumatic elbow instability in the setting of either intact or repaired olecranon process using a protocol incorporating hinged elbow fixation. Methods: Thirteen consecutive patients with ulnohumeral instability after a fracture-dislocation of the elbow, adequate articular surfaces, and adequate, stable alignment of the olecranon were treated with temporary hinged external fixation, preservation, or reconstruction of both the coronoid process and radiocapitelllar contact and with repair or reconstruction of the lateral collateral ligament complex. There were 9 men and 4 women with an average age of 45 years. Seven patients had a terrible triad pattern injury and 6 had a posterior Monteggia pattern injury. All 13 patients had fracture of the radial head and 10 patients had fracture of the coronoid process. Results: At an average follow-up period of 57 months stability was restored in every patient. The average Disabilities of the Arm, Shoulder, and Hand questionnaire score was 15 and the average Mayo score was 84, with 6 excellent, 4 good, and 3 fair results. The average arc of ulnohumeral motion was 99degrees. Sic patients had radiographic signs of arthrosis including 5 of 6 patients with olecranon fracture-dislocations. Conclusions: A stable, functional elbow can be restored in most patients with persistent instability after fracture-dislocation of the elbow using a treatment protocol incorporating hinged external fixation. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 15 Parkman St,ACC 525, Boston, MA 02114 USA. NR 31 TC 44 Z9 49 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 2004 VL 29A IS 3 BP 470 EP 480 DI 10.1016/j.jhsa.2004.01.005 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 822QO UT WOS:000221555100022 PM 15140492 ER PT J AU Rudd, RE Kaphingst, K Colton, T Gregoire, J Hyde, J AF Rudd, RE Kaphingst, K Colton, T Gregoire, J Hyde, J TI Rewriting public health information in plain language SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID READABILITY FORMULA AB Public health materials are often designed to inform and rally the public to spur action and maintain vigilance on important issues to family, work, community, and public policy. Limited access to public health information certainly curtails knowledge and awareness but may also hamper action and civic involvement. A growth in published assessments of health materials indicates an increased interest in the mismatch between the reading level of most health materials and the reading ability of the average adult. However, while several guidebooks offer suggestions for developing new materials, little attention has been given to the process of rewriting materials and grappling with bureaucratic language. We describe, in this case study, a process we used to assess and then rewrite a federally mandated report to consumers about the quality of their water. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pathfinder Int, Watertown, MA USA. Massachusetts Water Resources Author, Boston, MA USA. Tufts Univ, Sch Med, Dept Family Med & Community Hlth, Boston, MA 02111 USA. RP Rudd, RE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM rrudd@hsph.harvard.edu NR 21 TC 18 Z9 18 U1 2 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD MAY-JUN PY 2004 VL 9 IS 3 BP 195 EP 206 DI 10.1080/10810730490447039 PG 12 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 831GS UT WOS:000222183500003 PM 15360033 ER PT J AU Knosalla, C Muller, J Moran, K Wallukat, G Hetzer, R Cooper, DKC AF Knosalla, C Muller, J Moran, K Wallukat, G Hetzer, R Cooper, DKC TI Non-specific removal of antibodies in patients with idiopathic dilated cardiomyopathy: Implications for xenotransplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID NATURAL ANTIBODIES; HUMANS; SERA AB We assessed the efficiency of non-specific extracorporeal immunoadsorption (EIA), using polyclonal anti-human immunoglobulin antibodies, in depleting the serum of anti-galactosealpha1,3galactose (Gal) antibody and in decreasing serum cytotoxicity in 5 patients with idiopathic dilated cardiomyopathy. The mean concentrations of, anti-Gal immunoglobulin (Ig)M and IgG before EIA were 74 mug/ml and 159 mug/ml, respectively. After EIA, these anti concentrations decreased by 86% and 88%, respectively. Both anti-Gal IgM and IgG returned to pre-EIA concentrations within I month, without rebound to greater than baseline concentrations. After EIA, mean serum cytotoxicity also decreased from 90% to 17%, with recovery by 1 month. Extracorporeal immunoadsorption proved safe in patients with heart failure and was effective in depleting anti-Gal antibody and in decreasing serum cytotoxicity to pig cells. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Immerge BioTherapeut, Charlestown, MA USA. Deutsch Herzzentrum Berlin, Dept Cardiothorac & Vasc Surg, Berlin, Germany. Max Delbruck Ctr Mol Biol, Berlin, Germany. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E Bldg 149-9019,13th St, Boston, MA 02129 USA. EM David.Cooper@tbrc.mgh.harvard.edu FU NIAID NIH HHS [1P01 AI45897] NR 10 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAY PY 2004 VL 23 IS 5 BP 623 EP 626 DI 10.1016/S1053-2498(03)00229-8 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 820MO UT WOS:000221393700017 PM 15135381 ER PT J AU Miura, K Acierno, JS Seminara, SB AF Miura, K Acierno, JS Seminara, SB TI Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH) SO JOURNAL OF HUMAN GENETICS LA English DT Article DE human nasal embryonic LHRH factor gene; GnRH cell migration; alternatively spliced variants; expression pattern; polymorphism ID KALLMANN-SYNDROME; HORMONE DEFICIENCY; OLFACTORY PLACODE; MIGRATION; NEURONS; CELLS AB As the mouse nasal embryonic LHRH factor gene (Nelf) encodes a guidance molecule for the migration of the olfactory axon and gonadotropin-releasing hormone neurons, its human homolog, NELF, is a candidate gene for Kallmann syndrome, a disease of idiopathic hypogonadotropic hypogonadism (IHH) with anosmia or hyposmia. We report here characterization of NELF and results of mutation analysis in 65 IHH patients. Assembling EST clones, RACE, and sequencing showed that NELF mapped to 9q34.3 is composed of 16 exons and 15 introns with a 1,590-bp ORF encoding 530 amino acids. RT-PCR on a fetal brain cDNA library revealed five alternatively spliced variants. Among them, NELF-v1 has 93-94% identity at the amino acid level to mouse/rat Nelf, and four other transcripts are also highly conserved among the three species. A 3.0-kb transcript is expressed most highly in the adult and fetal brain, testis, and kidney, indicating that NELF plays a role in the function of these tissues. Mutation screening detected in a patient with IHH one novel heterozygous missense mutation (1438A>G, T480A) at the donor-splice site in exon 15 of NELF. As this mutation was not found in 100 normal control individuals, T480A may be associated with IHH. Four other novel SNPs (102C>T and 1029C>T within the coding region, and two IVS14+47C>T and IVS15+41G>A) were also identified in NELF. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Miura, K (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Obstet & Gynecol, 1-7-1 Sakamoto, Nagasaki 8528501, Japan. EM kiyonori@net.nagasaki-u.ac.jp FU NICHD NIH HHS [R01 HD043341] NR 14 TC 70 Z9 73 U1 0 U2 2 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1435-232X J9 J HUM GENET JI J. Hum. Genet. PD MAY PY 2004 VL 49 IS 5 BP 265 EP 268 DI 10.1007/s10038-004-0137-4 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 821FS UT WOS:000221446400005 PM 15362570 ER PT J AU Gauduin, MC Kaur, A Ahmad, S Yilma, T Lifson, JD Johnson, RP AF Gauduin, MC Kaur, A Ahmad, S Yilma, T Lifson, JD Johnson, RP TI Optimization of intracellular cytokine staining for the quantitation of antigen-specific CD4(+) T cell responses in rhesus macaques SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CD4(+) T cell-responses; antigen-specific activation; intracellular cytokine staining; SIV/macaque model ID SIMIAN-IMMUNODEFICIENCY VIRUS; FLOW CYTOMETRIC DETERMINATION; INTERFERON-GAMMA; WHOLE-BLOOD; IFN-GAMMA; ENVELOPE GLYCOPROTEIN; LYMPHOCYTE RESPONSES; ELISPOT ASSAY; SIV VACCINE; EXPRESSION AB Standard proliferation assays used for analysis of CD4(+) T cell function have significant shortcomings, including limited sensitivity, lack of truly quantitative readouts and significant variability. We have optimized an intracellular cytokine staining (ICS) assay in rhesus macaques which allows us to identify virus-specific CD4(+) T cells at the single-cell level with high sensitivity while reducing background staining to a minimum. A variety of parameters were tested to determine the optimal experimental conditions necessary for the detection of antigen-specific CD4(+) T cells in macaques. Central to our optimized protocol was the addition of cross-linked costimulatory anti-CD28 and anti-CD49d Mabs, a modification which resulted in up to threefold enhancement of the frequency of TNF-alpha-secreting CD4(+) T cells following superantigen- or antigen-specific stimulation. The ICS protocol was also optimized with respect to antigen concentration and duration of antigerric stimulation. These modifications resulted in a convenient and highly reproducible assay with intra- and inter-assay variability of less than 10%. Although cryopreservation of PBMC generally led to a 40% to 80% decrease in the frequency of antigen-specific CD4(+) T cells detected by ICS using stimulation with viral proteins, the use of overlapping peptide pools minimized the effects of cryopreservation on ICS responses. The use of more sensitive techniques such as ICS permits delineation of antigen-specific cells at the single cell level and should provide new insights into pathogen-specific immune responses in the rhesus macaque model. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Univ Calif Davis, VM Pathol Microbiol & Immunol, ILMB, Davis, CA 95616 USA. SAIC Frederick Inc, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Infect Dis Unit, Boston, MA 02115 USA. RP Gauduin, MC (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. EM marie-claire_gauduin@hms.harvard.edu FU NCI NIH HHS [N01-CO-12400]; NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI43890, AI45314] NR 53 TC 27 Z9 28 U1 0 U2 1 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 MAY PY 2004 VL 288 IS 1-2 BP 61 EP 79 DI 10.1016/j.jim.2004.02.007 PG 19 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 831TH UT WOS:000222218500007 PM 15183086 ER PT J AU Mueller, NJ Livingston, C Knosalla, C Barth, RN Yamamoto, S Gollackner, B Dor, FJMF Buhler, L Sachs, DH Yamada, K Cooper, DKC Fishman, JA AF Mueller, NJ Livingston, C Knosalla, C Barth, RN Yamamoto, S Gollackner, B Dor, FJMF Buhler, L Sachs, DH Yamada, K Cooper, DKC Fishman, JA TI Activation of porcine cytomegalovirus, but not porcine lymphotropic herpesvirus, in pig-to-baboon xenotransplantation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DNA-POLYMERASE LOCI; LYMPHOPROLIFERATIVE DISEASE; MINIATURE SWINE; TRANSPLANTATION; SIMILARITY; RECIPIENTS; TOLERANCE AB Tissue-invasive disease due to porcine cytomegalovirus (PCMV) has been demonstrated after pig-to-baboon solid-organ xenotransplantation. Porcine lymphotropic herpesvirus (PLHV)-1 is associated with B cell proliferation and posttransplant lymphoproliferative disorder after allogeneic bone marrow transplantation in swine but has not been observed in pig-to-primate xenotransplantation. Activation of PCMV and PLHV-1 was investigated in 22 pig-to-baboon xenotransplants by use of quantitative polymerase chain reaction. PCMV was found in all xenografts; increased viral replication occurred in 68% of xenografts during immunosuppression. PLHV-1 was found in 12 xenografts (55%); no increases in viral replication occurred during immunosuppression. Control immunosuppressed swine coinfected with PCMV and PLHV-1 had activation of PCMV but. not PLHV-1. PCMV, but not PLHV-1, is activated in solid-organ xenotransplantation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org RI Dor, Frank/E-1032-2013; Barth, Rolf/B-2542-2014; Mueller, Nicolas/B-6864-2013 OI Dor, Frank/0000-0001-7845-3075; Mueller, Nicolas/0000-0002-1059-3191 FU NIAID NIH HHS [5T32-AI07529-04, R01-AI43890, P01-AI45897] NR 18 TC 32 Z9 33 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 MAY 1 PY 2004 VL 189 IS 9 BP 1628 EP 1633 DI 10.1086/383351 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 814BX UT WOS:000220951300011 PM 15116299 ER PT J AU Tyler, KL Barton, ES Ibach, ML Robinson, C Campbell, JA O'Donnell, SM Valyi-Nagy, T Clarke, P Wetzel, JD Dermody, TS AF Tyler, KL Barton, ES Ibach, ML Robinson, C Campbell, JA O'Donnell, SM Valyi-Nagy, T Clarke, P Wetzel, JD Dermody, TS TI Isolation and molecular characterization of a novel type 3 reovirus from a child with meningitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ATTACHMENT PROTEIN SIGMA-1; JUNCTION ADHESION MOLECULE; INDUCED APOPTOSIS; SIALIC-ACID; MONOCLONAL-ANTIBODIES; MAMMALIAN REOVIRUSES; SEQUENCE DIVERSITY; INFECTION; PATHOGENESIS AB Mammalian reoviruses are nonenveloped viruses that contain a segmented, double-stranded RNA genome. Reoviruses infect most mammalian species, although infection with these viruses in humans is usually asymptomatic. We report the isolation of a novel reovirus strain from a 6.5-week-old child with meningitis. Hemagglutination and neutralization assays indicated that the isolate is a serotype 3 strain, leading to the designation T3/Human/Colorado/1996 (T3C/96). Sequence analysis of the T3C/96 S1 gene segment, which encodes the viral attachment protein, sigmal, confirmed the serotype assignment for this strain and indicated that T3C/96 is a novel reovirus isolate. T3C/96 is capable of systemic spread in newborn mice after peroral inoculation and produces lethal encephalitis. These results suggest that serotype 3 reoviruses can cause meningitis in humans. C1 Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Childrens Hosp, Dept Pathol, Denver, CO 80218 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. RP Dermody, TS (reprint author), Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, D7235 MCN, Nashville, TN 37232 USA. EM ken.tyler@uchsc.edu; terry.dermody@vanderbilt.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NCI NIH HHS [T32 CA09385]; NIAID NIH HHS [R01 AI38296, T32 AI07474] NR 70 TC 37 Z9 44 U1 1 U2 4 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 MAY 1 PY 2004 VL 189 IS 9 BP 1664 EP 1675 DI 10.1086/383129 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 814BX UT WOS:000220951300015 PM 15116303 ER PT J AU Sackstein, R AF Sackstein, R TI The bone marrow is akin to skin: HCELL and the biology of hematopoietic stem cell homing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Montagna Symposium on Biology of Skin CY JUN 13-17, 2003 CL Snowmass Village, CO DE adult stem cell; hematopoietic stem cell; homing; regenerative therapy; selectin ID L-SELECTIN LIGAND; CUTANEOUS LYMPHOCYTE ANTIGEN; P-SELECTIN; PROGENITOR CELLS; T-CELLS; GLYCOPROTEIN LIGAND-1; ADHESION MOLECULE-1; IN-VIVO; LEUKOCYTE ADHESION; ENDOTHELIAL-CELLS AB The recent findings that adult stem cells are capable of generating new blood vessels and parenchymal cells within tissues they have colonized has raised immense optimism that these cells may provide functional recovery of damaged organs. The use of adult stem cells for regenerative therapy poses the challenging task of getting these cells into the requisite sites with minimum morbidity and maximum efficiency. Ideally, tissue-specific colonization could be achieved by introducing the stem cells intravascularly and exploiting the native physiologic processes governing cell trafficking. Critical to the success of this approach is the use of stem cells bearing appropriate membrane molecules that mediate homing from vascular to tissue compartments. Hematopoietic stem cells (HSC) express a novel glycoform of CD44 known as hematopoietic cell E-/L-selectin ligand (HCELL). This molecule is the most potent E-selectin ligand natively expressed on any human cell. This article reviews our current understanding of the molecular basis of HSC homing and will describe the fundamental "roll" of HCELL in opening the avenues for efficient HSC trafficking to the bone marrow, the skin and other extramedullary sites. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,HArvard Skin Dis Res Ctr, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,HArvard Skin Dis Res Ctr, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Harvard Univ, Inst Med, 77 Ave Louis Pasteur,Room 671, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu FU NCI NIH HHS [R01-CA84156]; NHLBI NIH HHS [R01-HL60528, R01-HL73714] NR 129 TC 38 Z9 38 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2004 VL 122 IS 5 BP 1061 EP 1069 DI 10.1111/j.0022-202X.2004.09301.x PG 9 WC Dermatology SC Dermatology GA 819FU UT WOS:000221301000006 PM 15140204 ER PT J AU Reusch, JEB AF Reusch, JEB TI Time management in academic medicine SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. RP Reusch, JEB (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Endocrinol 111-H,1055 Clermont St, Denver, CO 80220 USA. EM Jane.Reusch@uchsc.edu NR 0 TC 1 Z9 1 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 MAY PY 2004 VL 52 IS 4 BP 259 EP 261 DI 10.2310/6650.2004.00015 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 860ST UT WOS:000224364200022 PM 15521549 ER PT J AU Vielma, SA Mironova, M Ku, JR Lopes-Virella, MF AF Vielma, SA Mironova, M Ku, JR Lopes-Virella, MF TI Oxidized LDL further enhances expression of adhesion molecules in Chlamydophila pneumoniae-infected endothelial cells SO JOURNAL OF LIPID RESEARCH LA English DT Article DE intracellular adhesion molecule-1; E-selectin; vascular cell adhesion molecule-1; oxidized low density lipoprotein; cell adhesion molecules ID LOW-DENSITY-LIPOPROTEIN; CIRCULATING IMMUNE-COMPLEXES; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; FACTOR-KAPPA-B; CHLAMYDIA-PNEUMONIAE; HEART-DISEASE; E-SELECTIN; ATHEROSCLEROSIS; INFLAMMATION AB Chlamydophila pneumoniae is a common respiratory pathogen that has been shown to be associated with coronary, artery disease. Recent studies have shown that one of the possible mechanisms of the atherogenicity of C. pneumioniae is overexpression of cell adhesion molecules (CAMs) in infected endothelial cells. We investigated whether exposure of C. pneumoniae-infected endothelial cells to oxidized LDL (oxLDL) leads to further upregulation of CAMs. Flow cytometry and immunoblot analysis of human aortic endothelial cells (HAECs) was performed for intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. ICAM-1 was expressed in 78.7% of C. pneumoniae-infected HAECs. The addition of oxLDL (100 mug/ml) to infected HAECs increased the proportion of ICAM-1-positive cells to 92%. VCAM-I was only observed in 9.3% of infected HAECs, and the addition of oxLDL had no further effect on the surface expression of VCAM-1. C. pneumoniae also upregulated the surface expression of E-selectin on 52.2% of the cells, and incubation with oxLDL further increased the proportion of positive cells to 63.64%.jlr; In conclusion, C. pneumoniae upregulated the expression of the adhesion molecules ICAM-1, VCAM-1. and E-selectin on HAECs. The addition of oxLDL to the infected cells further enhanced the surface expression of ICAM-1 and E-selectin.-Vielma, S. A. M. Mironova,a, J-R. Ku. and M. F. Lopes-Virella. Oxidized LDL further enhances expression of adhesion molecules in Chlamydophila pneumoniae-infected endothelial cells. J. Lipid Res. 2004. 45: 873-880. C1 Med Univ S Carolina, Div Metab Endocrinol & Nutr, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Div Metab Endocrinol & Nutr, Dept Med, Charleston, SC 29425 USA. EM virellam@musc.edu FU NHLBI NIH HHS [R01 HL-46815, P01 HL-55782] NR 43 TC 10 Z9 10 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2004 VL 45 IS 5 BP 873 EP 880 DI 10.1194/jlr.M300456-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 814TS UT WOS:000220997600010 PM 14967815 ER PT J AU Ogino, S Wilson, RB Grody, WW AF Ogino, S Wilson, RB Grody, WW TI Bayesian risk assessment for autosomal recessive diseases: fetal echogenic bowel with one or no detectable CFTR mutation SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CYSTIC-FIBROSIS MUTATION; PRENATAL-DIAGNOSIS; PREGNANCIES; MANAGEMENT; FETUS C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM sogino@partners.org NR 20 TC 12 Z9 13 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1468-6244 J9 J MED GENET JI J. Med. Genet. PD MAY PY 2004 VL 41 IS 5 AR e70 DI 10.1136/jmg.2003.015065 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 817GI UT WOS:000221165600030 PM 15121798 ER PT J AU Roberts, PS Dabora, S Thiele, EA Franz, DN Jozwiak, S Kwiatkowski, DJ AF Roberts, PS Dabora, S Thiele, EA Franz, DN Jozwiak, S Kwiatkowski, DJ TI Somatic mosaicism is rare in unaffected parents of patients with sporadic tuberous sclerosis SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID GERM-LINE MOSAICISM; TSC1; GENE; IDENTIFICATION; DISEASE; COMPLEX; COMMON; 9Q34 C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Hematol Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat & Neurol, Boston, MA 02114 USA. Childrens Hosp, Dept Pediat & Neurol, Cincinnati, OH 45229 USA. Childrens Hosp, Dept Child Neurol, Warsaw, Poland. RP Kwiatkowski, DJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Hematol Div, 221 Longwood Ave,LMRC 302, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu FU PHS HHS [31535, 24279] NR 21 TC 11 Z9 11 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD MAY PY 2004 VL 41 IS 5 AR e69 DI 10.1136/jmg.2003.014126 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 817GI UT WOS:000221165600029 PM 15121797 ER PT J AU Su, YH Wang, MJ Brenner, DE Ng, A Melkonyan, H Umansky, S Syngal, S Block, TM AF Su, YH Wang, MJ Brenner, DE Ng, A Melkonyan, H Umansky, S Syngal, S Block, TM TI Human urine contains small, 150 to 250 nucleotide-sized, soluble DNA derived from the circulation and may be useful in the detection of colorectal cancer SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID K-RAS MUTATIONS; TUMOR-RELATED ALTERATIONS; PLASMA DNA; LUNG-CANCER; CELL-DEATH; SERUM DNA; MICROSATELLITE ALTERATIONS; NUCLEIC-ACIDS; EXPRESSION; APOPTOSIS AB Human urine has been shown to possess submicrogram per milliliter amounts of DNA. We show here that DNA isolated from human urine resolves into two size categories: the large species, greater than I kb, being predominantly cell associated and heterogeneous in size, and the smaller, between 150 to 250 bp, being mostly non-cell associated. We showed that the low molecular weight class of urine DNA is derived from the circulation, by comparing the mutated K-ras sequences present in DNA isolated from tumor, blood, and urine derived from an individual with a colorectal carcinoma (CRC) containing a mutation in codon 12 of the K-ras proto-oncogene. in the urine, mutated K-ras sequences were abundant in the low molecular weight species, but far less abundant in the large molecular weight-derived DNA. Finally, the possibility that detection of mutant K-ras sequences in DNA derived from the urine correlates with the occurrence of a diagnosis of CRC and polyps that contain mutant K-ras was explored in a blinded study. There was an 83% concurrence of mutated DNA detected in urine and its corresponding disease tissue from the same individuals, when paired urine and tissue sections from 20 subjects with either CRC or adenomatous polyps were analyzed for K-ras mutation. The possibility that the source of the trans renal DNA is apoptotic cells, and the potential use of this finding for cancer detection and monitoring is discussed. C1 Thomas Jefferson Univ, Jefferson Ctr Biomed Res, Dept Mol Pharmacol & Biochem, Doylestown, PA 18901 USA. Univ Michigan, Med Ctr, Canc & Geriat Ctr, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Med Ctr, Canc & Geriat Ctr, Dept Pharmacol, Ann Arbor, MI USA. Xenom Inc, Richmond, CA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Gastroenterol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Su, YH (reprint author), Thomas Jefferson Univ, Jefferson Ctr Biomed Res, Dept Mol Pharmacol & Biochem, 700 E Butler Ave, Doylestown, PA 18901 USA. EM Yinghsiu.Su@Jefferson.edu FU NCI NIH HHS [CA86400, U01 CA086400] NR 27 TC 68 Z9 73 U1 2 U2 11 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2004 VL 6 IS 2 BP 101 EP 107 DI 10.1016/S1525-1578(10)60497-7 PG 7 WC Pathology SC Pathology GA 814VP UT WOS:000221002500005 PM 15096565 ER PT J AU Zaidi, NF Thomson, EE Choi, EK Buxbaum, JD Wasco, W AF Zaidi, NF Thomson, EE Choi, EK Buxbaum, JD Wasco, W TI Intracellular calcium modulates the nuclear translocation of calsenilin SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calcium; calsenilin; nuclear translocation; presenilin interactor ID LOCALIZATION SIGNAL; IMPORTIN-BETA; TRANSCRIPTIONAL REPRESSOR; POTASSIUM CHANNELS; PROTEIN IMPORT; EXPORT SIGNAL; BINDING; CELLS; CRM1; SUBSTRATE AB Calsenilin, which was originally identified as a presenilin interacting protein, has since been shown to be involved in the processing of presenilin(s), the modulation of amyloid beta-peptide (Abeta) levels and apoptosis. Subsequent to its original identification, calsenilin was shown to act as a downstream regulatory element antagonist modulator (and termed DREAM), as well as to interact with and modulate A-type potassium channels (and termed KChIP3). Calsenilin is primarily a cytoplasmic protein that must translocate to the nucleus to perform its function as a transcriptional repressor. This study was designed to determine the cellular events that modulate the translocation of calsenilin from the cytoplasm to the nucleus. The nuclear translocation of calsenilin was found to be enhanced following serum deprivation. A similar effect was observed when cells were treated with pharmacological agents that directly manipulate the levels of intracellular calcium (caffeine and the calcium ionophore A23187), suggesting that the increased levels of calsenilin in the nucleus are mediated by changes in intracellular calcium. A calsenilin mutant that was incapable of binding calcium retained the ability to translocate to the nucleus. Taken together, these findings indicate that the level of intracellular calcium can modulate the nuclear translocation of calsenilin and that this process does not involve the direct binding of calcium to calsenilin. C1 Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Genet & Aging Res Unit, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Mt Sinai Sch Med, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY USA. Mt Sinai Sch Med, Dept Neurobiol, Lab Mol Neuropsychiat, New York, NY USA. RP Wasco, W (reprint author), Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Genet & Aging Res Unit, Dept Neurol, Bldg 114,16th St, Charlestown, MA 02129 USA. EM wasco@helix.mgh.harvard.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIA NIH HHS [AG 05138, AG 15801, AG 16361] NR 44 TC 23 Z9 27 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2004 VL 89 IS 3 BP 593 EP 601 DI 10.1046/j.1471-4159.2004.02362.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 812QV UT WOS:000220854900007 PM 15086516 ER PT J AU Venihaki, M Sakihara, S Subramanian, S Dikkes, P Weninger, SC Liapakis, G Graf, T Majzoub, JA AF Venihaki, M Sakihara, S Subramanian, S Dikkes, P Weninger, SC Liapakis, G Graf, T Majzoub, JA TI Urocortin III, a brain neuropeptide of the corticotropin-releasing hormone family: Modulation by stress and attenuation of some anxiety-like behaviours SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE urocortin III; Crh; behaviour; HPA axis ID FACTOR-RECEPTOR; ADRENAL INSUFFICIENCY; TRANSGENIC MICE; CRF RECEPTORS; EXPRESSION; GENE; PITUITARY; RAT; CLONING; PEPTIDE AB Following its discovery 20 years ago, corticotropin-releasing hormone (CRH) has been postulated to mediate both hormonal and behavioural responses to stressors. Here, we characterize and describe a behavioural role for the murine gene, UcnIII, which encodes a recently discovered CRH-related neuropeptide, urocortin III. We found that mouse UcnIII is expressed predominantly in regions of the brain known to be involved in stress-related behaviours, and its expression in the hypothalamus increases following restraint. In addition, we found that intracerebroventricular administration of mUcnIII stimulates behaviours that are associated with reduced anxiety, including exploration of an open field and decreased latency to enter the lit compartment of a dark-light chamber, but has no effect on the elevated-plus maze. Finally, we found that mUcnIII does not exert any effects on the hormonal stress response. Based upon our findings, UcnIII may be an endogenous brain neuropeptide that is modulated by stress and stimulates behaviours associated with reduced anxiety. In this capacity, UcnIII may attenuate stress-related behaviours, which may be useful both to help cope with stressful situations as well as to avoid pathology associated with excessive reaction to stressors. C1 Harvard Univ, Childrens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Crete, Dept Pharmacol, Sch Med, Iraklion, Greece. Dana Farber Canc Inst, Informat Core Serv, Boston, MA 02115 USA. RP Venihaki, M (reprint author), Acad Athens, Fdn Biomed Res, Soranou Ephessiou 4, Athens, Greece. EM maria.venychaki@tch.harvard.edu; joseph.majzoub@tch.harvard.edu FU NIDDK NIH HHS [R01DK50511] NR 47 TC 73 Z9 74 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 2004 VL 16 IS 5 BP 411 EP 422 DI 10.1111/j.1365-2826.2004.01170.x PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 822LX UT WOS:000221542600001 PM 15117334 ER PT J AU Ligon, KL Alberta, JA Kho, AT Weiss, J Kwaan, MR Nutt, CL Louis, DN Stiles, CD Rowitch, DH AF Ligon, KL Alberta, JA Kho, AT Weiss, J Kwaan, MR Nutt, CL Louis, DN Stiles, CD Rowitch, DH TI The oligodendroglial lineage marker OLIG2 is universally expressed in diffuse gliomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE antibody; astrocytoma; glioma; lineage; Olig2; progenitor ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; HUMAN BRAIN-TUMORS; TRANSCRIPTION FACTORS; PROGENITOR CELLS; GENE-EXPRESSION; GLIAL TUMORS; MOTOR-NEURON; IDENTIFICATION; DIFFERENTIATION AB Astrocytomas, oligodendrogliomas, and oligoastrocytomas, collectively referred to as diffuse gliomas, are the most common primary brain tumors. These tumors are classified by histologic similarity to differentiated astrocytes and oligodendrocytes, but this approach has major limitations in guiding modern treatment and research. Lineage markers represent a potentially useful adjunct to morphologic classification. The murine bHLH transcription factors Olig1 and Olig2 are expressed in neural progenitors and oligodendroglia and are essential for oligodendrocyte development. High OLIG expression alone has been proposed to distinguish oligodendrogliomas from astrocytomas, so we critically evaluated OLIG2 as a marker by immunohistochemical and oligonucleotide microarray analysis. OLIG2 protein is faithfully restricted to normal oligodendroglia and their progenitors in human brain. Immumohistochemical analysis of 180 primary, metastatic, and non-neural human tumors shows OLIG2 is highly expressed in all diffuse gliomas. Immunohistochemistry and microarray analyses demonstrate higher OLIG2 in anaplastic oligodendrogliomas versus glioblastomas, which are heterogeneous with respect to OLIG2 levels. OLIG2 protein expression is present but inconsistent and generally lower in most other brain tumors and is absent in non-neuroectodermal tumors. Overall, OLIG2 is a useful marker of diffuse gliomas as a class. However, expression heterogeneity of OLIG2 in astrocytomas precludes immunohistochemical classification of individual gliomas by OLIG2 alone. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Neuropathol, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Childrens Hosp, Informat Program, Boston, MA USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, D640D,44 Binney St, Boston, MA 02115 USA. EM david_rowitch@dfci.harvard.edu RI Nutt, Catherine/K-8794-2012 FU NCI NIH HHS [CA57683, CA95616]; NICHD NIH HHS [HD007466]; NINDS NIH HHS [NS4051, R01 NS047527] NR 48 TC 220 Z9 223 U1 0 U2 5 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 BP 499 EP 509 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400009 PM 15198128 ER PT J AU Camelo, S Iglesias, AH Hwang, D Due, B Gray, SG Imitola, J Duran, G Langley, B Frosch, MP Khoury, SJ Stephanopoulos, G Ratan, RR DeGirolami, U Ferrante, RJ Dangond, F AF Camelo, S Iglesias, AH Hwang, D Due, B Gray, SG Imitola, J Duran, G Langley, B Frosch, MP Khoury, SJ Stephanopoulos, G Ratan, RR DeGirolami, U Ferrante, RJ Dangond, F TI The histone deacetylase inhibitor trichostatin A ameliorates murine experimental autoimmune encephalomyelitis, a mode of multiple sclerosis. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. MIT, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 MA 1 BP 510 EP 510 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400011 ER PT J AU Frosch, MP Robbins, EM Domnitz, S Rebeck, GW Greenberg, SM Bacskai, BJ AF Frosch, MP Robbins, EM Domnitz, S Rebeck, GW Greenberg, SM Bacskai, BJ TI Progression of cerebral amyloid angiopathy in superficial vessels demonstrated by whole brain multiphoton imaging. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Massachusetts Gen Hosp, MassGen Inst Neurodegeneret Dis, Charlestown, MA USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA USA. Georgetown Univ, Dept Neurosci, Washington, DC USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 MA 6 BP 511 EP 511 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400016 ER PT J AU Tian, D Dickerson, B Walsh, RJ Hochberg, F Hedley-Whyte, ET Kubik, CS AF Tian, D Dickerson, B Walsh, RJ Hochberg, F Hedley-Whyte, ET Kubik, CS TI Late onset MELAS due to a rare mitochondrial DNA mutation. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 MA 93 BP 533 EP 533 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400102 ER PT J AU Pierson, C Darras, B Xin, W De Girolami, U AF Pierson, C Darras, B Xin, W De Girolami, U TI Late infantile neuronal ceroid lipofuscinosis due to heterozygous CLN2 mutations including a novel T3915G point mutation in one allele. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neuregenet DNA Diagnost Lab, Boston, MA 02114 USA. RI Pierson, Christopher/E-3869-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 MA 95 BP 534 EP 534 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400105 ER PT J AU Dong, S Nutt, C Stemmer-Rachamimov, AO Louis, DN AF Dong, S Nutt, C Stemmer-Rachamimov, AO Louis, DN TI Gene expression profiling of pseudopalisading perinecrotic cells in glioblastoma. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 MA 101 BP 535 EP 535 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400110 ER PT J AU Kiehl, T Kalkanis, SN Louis, DN AF Kiehl, T Kalkanis, SN Louis, DN TI Pigmented central neurocytoma. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 MA 130 BP 542 EP 542 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400140 ER PT J AU SantaCruz, KS Lewis, J Paulson, J Ingelsson, M Kotilinek, L Forster, C Guimaraes, A Mariash, A Hyman, BT Hutton, M Ashe, KH AF SantaCruz, KS Lewis, J Paulson, J Ingelsson, M Kotilinek, L Forster, C Guimaraes, A Mariash, A Hyman, BT Hutton, M Ashe, KH TI Cognitive impairment in transgenic mice with abnormal intraneuronal tau phosphorylation, but little silver positive neurofibrillary pathology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 80th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 24-27, 2004 CL Cleveland, OH SP Amer Assoc Neuropathologists C1 Univ Minnesota, Minneapolis, MN USA. Mayo Clin, Jacksonville, FL 32224 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2004 VL 63 IS 5 MA 177 BP 554 EP 554 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 822SC UT WOS:000221559400186 ER PT J AU Halpern, LR Kaban, LB Dodson, TB AF Halpern, LR Kaban, LB Dodson, TB TI Perioperative neurosensory changes associated with treatment of mandibular fractures SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INFERIOR ALVEOLAR; TRIGEMINAL NERVE; FIXATION; DISTURBANCES; INJURY AB Purpose: The purpose of this study was to document perioperative neurosensory changes in the inferior alveolar nerve (IAN) after mandibular fracture treatment and to identify risk factors associated with these changes. Materials and Methods: This was a prospective cohort study composed of patients treated for mandibular fractures. The primary study variable was the change between the postinjury/pretreatment IAN neurosensory examination score and the score after fracture reduction. Risk factors were categorized as demographic, anatomic, and treatment. Appropriate descriptive, bivariate, and multivariate statistics were computed. Results: The cohort was composed of 61 patients with 97 fractured sides. Forty-seven fractures (49%) were located between the lingula and mental foramen, and 50 fractures (51%) were located distal to the mental foramen. Thirty-nine fractures (41%) were displaced by 5 nun or more. Abnormal preoperative UN neurosensory examinations were documented in 81% of the fractured sides. Fifty-three fractures (54%) were treated by closed reduction and 44 (46%) by open reduction and internal fixation. In 82 fractures (85%), the IAN neurosensory score was unchanged or improved after treatment. In a multivariate model, preoperative neurosensory score, displacement, and treatment were associated with a statistically significant risk (P less than or equal to .05) for postoperative deterioration of IAN sensation. Conclusion: Open reduction and internal fixation, fracture displacement of 5 mm or more, and a normal preoperative IAN neurosensory examination were associated with an increased risk for deterioration of the UN neurosensory score after treatment of mandibular fractures. Additional studies are indicated to determine long-term IAN neurosensory function after mandibular fracture treatment and the factors that affect prognosis. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Halpern, LR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM lhalpern1@partners.org NR 19 TC 13 Z9 13 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2004 VL 62 IS 5 BP 576 EP 581 DI 10.1016/j.joms.2003.12.006 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 816WG UT WOS:000221139400011 PM 15122563 ER PT J AU Abukawa, H Shin, M Williams, WB Vacanti, JP Kaban, LB Troulis, MJ AF Abukawa, H Shin, M Williams, WB Vacanti, JP Kaban, LB Troulis, MJ TI Reconstruction of mandibular defects with autologous tissue-engineered bone SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MESENCHYMAL STEM-CELLS; GREEN-FLUORESCENT PROTEIN; ENDOTHELIAL GROWTH-FACTOR; IN-VITRO; OSTEOBLASTS; EXPRESSION; SCAFFOLDS; CULTURE AB Purpose: Maxillofacial reconstructive procedures often require bone graft harvesting, which results in donor site morbidity; the use of tissue-engineered bone would eliminate this problem. in this study, a novel scaffold design and new fabrication protocol were used to produce autologous tissue-engineered constructs (scaffolds seeded with cells) to reconstruct segmental mandibular defects in a minipig model. Materials and Methods: Porcine mesenchymal stem cells were isolated from the ilium. They were expanded in culture and seeded onto poly-DL-lactic-coglycolic acid scaffolds. The constructs were placed in a bioreactor and incubated for 10 days in medium and osteogenic supplements. Four full-thickness bony defects (2 X 2 cm) were created in the same pig's mandible. The constructs (n = 2) were placed into 2 of the defects as autologous grafts. One unseeded scaffold and 1 empty defect served as controls. At 6 weeks postimplantation, the pig was sacrificed, the mandible was harvested, and the grafted sites were evaluated by clinical, radiographic, and histologic methods. Results: The construct-implanted defects appeared to be filled with hard tissue resembling bone, whereas controls were filled with fibrous tissue. Radiographically, the tissue-engineered constructs were uniformly radiodense with bone distributed throughout. The interface between native bone and constructs was indistinct. Complete bone ingrowth was not observed in control defects. Osteoblasts, osteocytes, bone trabeculae, and blood vessels were identified throughout the defects implanted with constructs. Conclusion: This "proof-of-principle" study indicates that porcine mandibular defects can be successfully reconstructed by in vitro cultured autologous porcine mesenchymal stem cells on a biodegradable polymer scaffold with penetration of bone and blood vessels. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Minimally Invas Oral Maxillofacial Surg Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Minimally Invas Oral Maxillofacial Surg Program, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM mtroulis@partners.org FU NIDCR NIH HHS [K23-DE14070-01] NR 19 TC 80 Z9 92 U1 1 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2004 VL 62 IS 5 BP 601 EP 606 DI 10.1016/j.joms.2003.11.010 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 816WG UT WOS:000221139400015 PM 15122567 ER PT J AU Bragdon, CR Estok, DM Malchau, H Karrholm, J Yuan, XH Bourne, R Veldhoven, J Harris, WH AF Bragdon, CR Estok, DM Malchau, H Karrholm, J Yuan, XH Bourne, R Veldhoven, J Harris, WH TI Comparison of two digital radio stereometric analysis methods in the determination of femoral head penetration in a total hip replacement phantom SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE radiostereometric analysis; polyethylene wear; total hip arthroplasty; accuracy ID POLYETHYLENE WEAR; CUPS; ARTHROPLASTY; PROSTHESES; PRECISION; MIGRATION AB Radiostereometric analysis (RSA) has been used extensively to evaluate the magnitude and direction of penetration of the femoral head into the acetabular component of a total hip replacement as a result of polyethylene wear and creep. The accuracy and precision of an RSA study depends on several factors, including the radiographic technique, the analytical software, and the positioning of the tantalum markers. This study had three sequential purposes. First, an in vitro phantom model was used to quantify the accuracy and precision of digital images versus conventional radiography in RSA measurements of penetration of the femoral head into the acetabular shell in a total hip replacement. The Umea RSA software package was used for analysis of both the conventional films, which were digitized at a resolution of 300 DPI, and digital radiographs, which were converted from a DICOM format at a resolution of 218 DPI. Digital radiography was found to be superior. Next, two methods of RSA analysis currently in use for determining femoral head penetration into polyethylene of total joint replacements were compared. Using the phantom model, we compared the Umea RSA system (Biomedical Innovations AB) to the RSA-CMS (RSA Clinical Measurement Solution) and in both cases used the digital radiographs. The Umea RSA system was found to be superior. Finally, two methods of marking the position of the acetabular component with tantalum beads were compared: one in which beads were inserted into previously described towers protruding from the back of the acetabular shell and another in which beads were placed into the peripheral flange of the polyethylene liner using the Umea RSA analysis system of the digital radiographs. The results using the two marker configurations were similar. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Adult Reconstruct Unit, Dept Orthopaed Surg,Orthopaed Biomech & Biomat La, Boston, MA 02114 USA. Univ Western Ontario, London, ON N6K 1C7, Canada. Univ Gothenburg, Inst Surg Sci, Dept Orthopaed, Gothenburg, Sweden. RP Bragdon, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Adult Reconstruct Unit, Dept Orthopaed Surg,Orthopaed Biomech & Biomat La, 1126 Fruit St,Jackson Bldg, Boston, MA 02114 USA. EM cbragclon@partners.org NR 14 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 2004 VL 22 IS 3 BP 659 EP 664 DI 10.1016/j.orthres.2003.09.004 PG 6 WC Orthopedics SC Orthopedics GA 817TW UT WOS:000221200800029 PM 15099649 ER PT J AU Yuan, Q Walker, WA AF Yuan, Q Walker, WA TI Innate immunity of the gut: Mucosal defense in health and disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review DE innate immunity; gut immune system; toll-like receptors; caspase recruitment domain/nucleotide oligomerizatin domain; defensins; scavenger receptor deleted in malignant brain tumor 1; DMBT1; pathogen-associated molecular patterns ID TOLL-LIKE RECEPTORS; SURFACTANT PROTEIN-D; INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; PANETH CELL; SCAVENGER RECEPTOR; HOST-DEFENSE; NOD2 GENE; ANTIMICROBIAL PEPTIDES AB The intestine is an important immune organ consisting of a complex cellular network, secreted peptides and proteins and other host defenses. Innate immunity plays a central role in intestinal immune defense against invading pathogens. It also serves as a bridge to the activation of the adaptive immune system. Pattern recognition molecules of microorganisms are an essential component for identifying invading pathogens. Toll-like receptors (TLRs), CARD15/NOD2 and scavenger receptors all serve as the pattern recognition receptors in the innate immune defense system. Secreted bactericidal peptides or defensins produced by the intestinal epithelia represent another crucial element of innate mucosal immune defense. Mutations in pattern recognition receptors and dysfunction of secretory bactericidal peptides may impair host immune defenses leading to an invasion of pathogens resulting in chronic inflammation of the gut. This review updates our current understanding of innate immunity of the gastrointestinal tract. (C) 2004 Lippincott Williams Wilkins. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 114 16th St,114-3503, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NICHD NIH HHS [R01-HD31852, R37-HD12437]; NIDDK NIH HHS [P01-DK33506, P30-DK40561] NR 98 TC 46 Z9 49 U1 1 U2 9 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 MAY PY 2004 VL 38 IS 5 BP 463 EP 473 DI 10.1097/00005176-200405000-00001 PG 11 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 814XU UT WOS:000221008200001 PM 15097431 ER PT J AU Royzman, D Recio, L Badovinac, RL Fiorellini, J Goodson, M Howell, H Karimbux, N AF Royzman, D Recio, L Badovinac, RL Fiorellini, J Goodson, M Howell, H Karimbux, N TI The effect of aspirin intake on bleeding on probing in patients with gingivitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE aspirin/adverse effects; bleeding/prevention and control; clinical trials; dental probes; gingivitis/diagnosis ID DISEASE AB Background: Bleeding indices are used as a screen for periodontal disease activity, a measure of disease prevalence, and a measure of effectiveness in clinical trials. Bleeding on probing (BOP) is widely interpreted as a sign of disease activity whereas its absence is interpreted as both a sign and predictor of health. Aspirin use has become increasingly common in the prevention of cerebrovascular and cardiovascular diseases. Because of its anti-platelet activity, aspirin is a non-disease factor that has the potential to affect the appearance of BOP. The hypothesis being tested is that short-term aspirin use in doses of 81 mg and 325 mg will increase the number of bleeding sites in a population with gingivitis. Methods: Fifty-four subjects were screened initially, those subjects with 20% to 30% whole mouth BOP were randomly assigned to one of three arms: placebo group, 81 mg aspirin group, or 325 mg aspirin group. Before and after exposure to the respective regimens, clinical parameters were measured on all the teeth: the plaque index was recorded at four sites per tooth, and probing depth and BOP were evaluated at six sites per tooth using an automated pressure-sensitive probe. Results: The data obtained in this clinical trial were analyzed utilizing a linear regression analysis to control for confounding variables. The primary measure of interest was BOP in patients clinically demonstrating naturally occurring gingivitis. The results of this study indicate that while controlling for age, gender, and plaque, "low dose" 81 mg and "regular dose" 325 mg of aspirin demonstrated a statistically significant 5.30 (P = 0.001) and 4.13 (P= 0.010) increase from baseline, respectively, in percent BOP. Conclusion: Failure to consider the effects of aspirin on BOP could impair proper diagnosis and treatment planning for clinicians and introduce a significant confounding variable in research situations. C1 Harvard Univ, Sch Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA. Forsyth Inst, Boston, MA USA. RP Karimbux, N (reprint author), Harvard Univ, Sch Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. NR 11 TC 21 Z9 23 U1 0 U2 0 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 MAY PY 2004 VL 75 IS 5 BP 679 EP 684 DI 10.1902/jop.2004.75.5.679 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 822SJ UT WOS:000221560100008 PM 15212350 ER PT J AU Lopez, NJ Socransky, SS Da Silva, I Japlit, MR Haffajee, AD AF Lopez, NJ Socransky, SS Da Silva, I Japlit, MR Haffajee, AD TI Subgingival microbiota of Chilean patients with chronic periodontitis SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Americans (United States); Chileans; comparison studies; dental plaque/microbiology; DNA probes; ethnicity; periodontal diseases/microbiology; periodontitis/microbiology ID RISK INDICATORS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ATTACHMENT LOSS; MICROFLORA; PREVALENCE; PATHOGENS; DISEASES; PLAQUE; POPULATION; HEALTHY AB Background: An association between race/ethnicity and the composition of the subgingival microbiota has been found in chronic periodontitis. A study was undertaken to determine the characteristics of the subgingival microbiota of chronic periodontitis in Chileans residing in Santiago. Methods: Twenty-six subjects (mean age 45 7 years) with chronic periodontitis, mean probing depth (PD) 2.63 +/- 0.5 mm, mean attachment level (AL) 3.70 +/- 0.77 mm, and without a history of periodontal therapy were selected. Measurements of PD, AL, bleeding on probing, and plaque accumulation were recorded at six sites per tooth. Subgingival plaque samples were taken from the mesial aspect of every tooth and evaluated for the presence, levels, and proportions of 40 bacterial taxa using whole genomic DNA probes and checkerboard DNA-DNA hybridization. The microbial data of the Chileans were compared with data from 115 chronic periodontitis patients from Boston, Massachusetts. Since several clinical and demographic parameters differed between the two populations, significance of differences for each species was determined using analysis of covariance, adjusting for age, plaque level, mean PD, gender, and smoking status. Results: Each of the individual test species was present in at least 25 of the 26 subjects, and 12 subjects (46.1%) harbored all 40 test species. With the exception of Prevotella intermedia, all test species colonized more than 75% of sites, and 25 species colonized greater than or equal to90% of sites including the co-colonizing species of advanced periodontal lesions, termed the red complex, composed of the three species Porphyromonas gingivalis, Tannerella forsythensis (formerly Bacteroides forsythus), and Treponema denticola as well as Fusobacterium nucleatum subspecies, Campylobacter rectus, Peptostreptococcus micros, and Treponema socranskii. Sixteen of the 40 species differed significantly between Chilean and U.S. subjects. Red, yellow, and other complexes were significantly higher in the Chileans, while the Actinomyces were higher in the U.S. subjects. Conclusions: The composition of the subgingival plaque differs among different subject populations. Thus, care should be taken when extrapolating the findings of one study to different ethnic groups. C1 Chiba Univ, Fac Dent, Dept Conservat Dent, Sect Periodont, Santiago, Chile. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Lopez, NJ (reprint author), Casilla 89, Santiago, Chile. EM nlopez@interactiva.cl FU NIDCR NIH HHS [DE 12861] NR 29 TC 28 Z9 36 U1 0 U2 3 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 MAY PY 2004 VL 75 IS 5 BP 717 EP 725 DI 10.1902/jop.2004.75.5.717 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 822SJ UT WOS:000221560100013 PM 15212354 ER PT J AU Thomas, TT Kohane, DS Wang, A Langer, R AF Thomas, TT Kohane, DS Wang, A Langer, R TI Mircoparticlulate formulations for the controlled release of interleukin-2 SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE biodegradable polymers; macromolecular drug delivery; microspheres; microparticles; protein delivery; stabilization ID TUMOR-INFILTRATING LYMPHOCYTES; GLYCOL-MODIFIED INTERLEUKIN-2; ACID) PLGA MICROSPHERES; PROTEIN-SUGAR PARTICLES; ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; POLYETHYLENE-GLYCOL; ADOPTIVE IMMUNOTHERAPY; INTRATUMORAL INJECTION; CONTROLLED DELIVERY AB Interleukin 2 (IL-2) is a pleotropic growth factor essential to immune system function. Current methods of administration are limited by the necessity of hospitalization as well as dose-limiting toxicities and side effects. There is also the issue of low therapeutic concentrations at the desired site of action; for instance, in the case of solid tumor treatment. Here we describe the design of controlled-release vehicles for the local administration of IL-2 based on single (SE) and double emulsion (DE) poly(lactic-co-glycolic acid) (PLGA) systems and a newly developed class of spray-dried lipid-protein-sugar systems composed of L-alpha-dipalmitoylphosphatidylcholine (DPPC) and 0.2% Eudragit E 100. All three systems demonstrated the release of therapeutic drug quantities. Totals of 2.0, 0.5, and 2.8 mug of IL-2 (per mg of solid) were encapsulated in the SE, DE, and spray-dried formulations, respectively. The SE and DE released of 30 and 15% of the encapsulated protein, respectively, with delivery of biologically active IL-2 during the first 5 to 10 days. The lipid-protein-sugar-based system demonstrated extended sustained release of biologically active IL-2 for a period of 4 months. These systems provide a potential framework for long-term loco-regional immunotherapeutic treatment regimens. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Alabama, Dept Biomed Engn, Birmingham, AL 35294 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, Bldg E25-342,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rlanger@mit.edu FU NCI NIH HHS [CA-52857-12]; NIBIB NIH HHS [EB-000244-24] NR 59 TC 19 Z9 19 U1 4 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAY PY 2004 VL 93 IS 5 BP 1100 EP 1109 DI 10.1002/jps.20009 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 815JY UT WOS:000221039800002 PM 15067687 ER PT J AU Gong, H McGinty, D Guzman-Marin, R Chew, KT Stewart, D Szymusiak, R AF Gong, H McGinty, D Guzman-Marin, R Chew, KT Stewart, D Szymusiak, R TI Activation of c-fos in GABAergic neurones in the preoptic area during sleep and in response to sleep deprivation SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID WAKING DISCHARGE PATTERNS; POSTERIOR LATERAL HYPOTHALAMUS; MONOAMINERGIC CELL GROUPS; DORSAL RAPHE NEURONS; EYE-MOVEMENT SLEEP; BASAL FOREBRAIN; GALANINERGIC NEURONS; RATS; NUCLEUS; PROJECTIONS AB Neurones in the median preoptic nucleus (MnPN) and the ventrolateral preoptic area (vlPOA) express immunoreactivity for c-Fos protein following sustained sleep, and display elevated discharge rates during both non-REM and REM sleep compared to waking. We evaluated the hypothesis that MnPN and vlPOA sleep-active neurones are GABAergic by combining staining for c-Fos protein with staining for glutamic acid decarboxylase (GAD). In a group of six rats exhibiting spontaneous total sleep times averaging 82.2 +/- 5.1% of the 2 h immediately prior to death, >75% of MnPN neurones that were Fos-immunoreactive (IR) were also GAD-IR. Similar results were obtained in the vlPOA. In a group of 11 rats exhibiting spontaneous sleep times ranging from 20 to 92%, the number of Fos + GAD-IR neurones in MnPN and vlPOA was positively correlated with total sleep time. Compared to control animals, Fos + GAD-IR cell counts in the MnPN were significantly elevated in rats that were sleep deprived for 24 h and permitted 2 h of recovery sleep. These findings demonstrate that a majority of MnPN and vlPOA neurones that express Fos-IR during sustained spontaneous sleep are GABAergic. They also demonstrate that sleep deprivation is associated with increased activation of GABAergic neurones in the MnPN and vlPOA. C1 VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM rszym@ucla.edu FU NHLBI NIH HHS [HL60296, P50 HL060296]; NIMH NIH HHS [MH63323, MH47480, R01 MH047480, R01 MH063323] NR 41 TC 92 Z9 96 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY 1 PY 2004 VL 556 IS 3 BP 935 EP 946 DI 10.1113/jphysiol.2003.056622 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 818TE UT WOS:000221266600020 PM 14966298 ER PT J AU Zang, L Toy, DP Hancock, WS Sgroi, DC Karger, BL AF Zang, L Toy, DP Hancock, WS Sgroi, DC Karger, BL TI Proteomic analysis of ductal carcinoma of the breast using laser capture microdissection, LC-MS, and O-16/O-18 isotopic labeling SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE laser capture microdissection (LCM); O-16/O-18 labeling; breast ductal carcinoma ID CATALYZED O-16-TO-O-18 EXCHANGE; PROTEIN EXPRESSION PROFILES; MASS-SPECTROMETRY; GENE-EXPRESSION; CARBOXYLIC ACIDS; CANCER; TISSUE; IDENTIFICATION; PHOSPHORYLATION; PREDICTION AB The goal of this study was the development of a method for quantitative expression proteomics on the limited sample amounts obtained through laser capture microdissection (LCM) of tissues, e.g., similar to10 000 cells, which typically contain roughly 1-4 mug protein. The O-15/O-18 labeling method was selected as an approach to measure differential expression. A sample preparation protocol including lysis, digestion and O-16/O-18 labeling was first developed for LCM cell samples. The selected protocol was examined using two LCM caps of 10 000 cells from invasive ductal carcinoma of the breast and shown to be repeatable. A further test of LC-IT-MS/MS in combination with the O-16/O-18 post-digestion labeling method for studying low level samples was conducted first on a single protein (BSA) and then on a 5-standard protein mixture digest of different protein amounts, each with a total content approximately 1 mug. Next, protein expression was compared between 10 000 Cells, each of microdissected normal ductal epithelium and metastatic ductal carcinoma, using the developed method. The proteins from the microdissected cells were extracted, precipitated, digested with trypsin and then O-16/O-18 labeled. The normal and metastatic cell samples were analyzed using reversed phase LC-ESI-MS/MS on the ion trap mass spectrometer. A total of 76 proteins were identified. Some, such as mitochondrial isocitrate clehydrogenase, actin and 14-3-3 protein zeta/delta were found to be significantly up-regulated in the breast tumor cells. C1 Northeastern Univ, Dept Chem, Barnett Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. RP Karger, BL (reprint author), Northeastern Univ, Dept Chem, Barnett Inst, 341 Mugar Bldg,300 Huntington Ave, Boston, MA 02115 USA. EM b.karger@neu.edu FU NIGMS NIH HHS [GM 15847] NR 41 TC 119 Z9 131 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAY-JUN PY 2004 VL 3 IS 3 BP 604 EP 612 DI 10.1021/pr034131l PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 829UK UT WOS:000222075500030 PM 15253443 ER PT J AU New, AS Trestman, RF Mitropoulou, V Goodman, M Koenigsberg, HH Silverman, J Siever, LJ AF New, AS Trestman, RF Mitropoulou, V Goodman, M Koenigsberg, HH Silverman, J Siever, LJ TI Low prolactin response to fenfluramine in impulsive aggression SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE serotonin; fenfluramine; personality disorder; impulsive aggression ID POSITRON-EMISSION-TOMOGRAPHY; FLUID AMINE METABOLITES; CEREBROSPINAL-FLUID; PERSONALITY-DISORDER; SEROTONERGIC FUNCTION; VIOLENT OFFENDERS; SUICIDAL-BEHAVIOR; FIRE SETTERS; INDEXES; 5-HIAA AB To examine the prolactin (prl) response to d,l-fenfluramine in a large sample of personality disorder patients with impulsive aggression. Patients were screened from clinics at the Bronx VAMC and the Mount Sinai Medical Center and from press releases. One hundred and forty-six personality disorder patients (90M;56F) and 23 normal controls (15M;8F) underwent oral d,l-fenfluramine challenge. The peak change in prolactin(deltapkprl) was calculated by subtracting baseline prolactin from peak response following fenfluramine administration (3 h). Analysis of variance and regression analysis were used to detect group differences in deltapkprl. Deltapkprl in impulsive aggressive men, but not women, with personality disorders was blunted compared with controls. Men with suicide histories also had a blunted deltapkprl compared with those without, which was not accounted for by depression. This study represents a replication of previous studies, in a much larger sample, showing a blunted PRL response to fenfluramine of male patients with personality disorder in relation to impulsive aggression and to suicide attempts. (C) 2003 Elsevier Ltd. All rights reserved. C1 Bronx Vet Adm Med Ctr, Psychiat Serv 116A, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Gen Clin Res Ctr, New York, NY USA. Univ Connecticut, Dept Psychiat, Storrs, CT 06269 USA. RP New, AS (reprint author), Bronx Vet Adm Med Ctr, Psychiat Serv 116A, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM antonia.new@med.va.gov OI Trestman, Robert/0000-0002-3306-4380 FU NCRR NIH HHS [5-M01-RR00071]; NIMH NIH HHS [5-R01-MH566606] NR 36 TC 31 Z9 32 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAY-JUN PY 2004 VL 38 IS 3 BP 223 EP 230 DI 10.1016/j.jpsychires.2003.09.001 PG 8 WC Psychiatry SC Psychiatry GA 804YU UT WOS:000220334800001 PM 15003426 ER PT J AU Krahl, SE Senanayake, SS Pekary, AE Sattin, A AF Krahl, SE Senanayake, SS Pekary, AE Sattin, A TI Vagus nerve stimulation (VNS) is effective in a rat model of antidepressant action SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE vagus nerve stimulation (VNS); forced-swim test (FST); depression; antidepressant; desipramine; electroconvulsant shock (ECS) ID FORCED SWIMMING TEST; SEIZURES AB Depression is a common but debilitating illness that afflicts a large population and costs the US economy a staggering $40 billion dollars per year. Clinical studies have demonstrated that vagus nerve stimulation (VNS) is an effective treatment for medication-resistant depression. Understanding VNS's antidepressant mechanisms is key to improving the therapy and selecting the best surgical candidates, and demonstration that VNS is effective in a validated test of antidepressant activity allows us to elucidate these mechanisms in a cost-effective manner. In the present study, Wistar Kyoto rats were implanted with a cuff electrode on the left cervical vagus nerve. The next day, they were placed into a water-filled Plexiglas cylinder for 15 min. After this forced-swim session, one of three treatment conditions were administered over 4 consecutive days: 30 min per day of continuous VNS, 10 mg/kg of desipramine twice per day, or three daily electroconvulsive shocks (ECS). Yoked controls underwent sham procedures, but received no treatment. On the fourth day, the rats were given a 5-min, videotaped swim test. A blinded observer used the videotape to calculate the percentage of time that the rats were immobile (an index of depression) during the swim test. VNS significantly reduced immobility time as compared to unstimulated controls, indicating good antidepressant efficacy. This reduction did not differ statistically from that obtained from rats treated with either desipramine or ECS, two standard antidepressant treatments. These results indicate that VNS is an effective antidepressant in the forced-swim test, allowing us to now investigate possible therapeutic mechanisms. Published by Elsevier Ltd. C1 VA Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Neurosurg, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Krahl, SE (reprint author), VA Greater Los Angeles Healthcare Syst, Neurol Serv, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM scott.krahl@med.va.gov NR 18 TC 59 Z9 59 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAY-JUN PY 2004 VL 38 IS 3 BP 237 EP 240 DI 10.1016/j.jpsychires.2003.11.005 PG 4 WC Psychiatry SC Psychiatry GA 804YU UT WOS:000220334800003 PM 15003428 ER PT J AU Wisniewski, SR Stegman, D Trivedi, M Husain, MM Eng, H Shores-Wilson, K Luther, J Biggs, MM Burroughs, D Ritz, AL Fava, M Quitkin, F Rush, AJ AF Wisniewski, SR Stegman, D Trivedi, M Husain, MM Eng, H Shores-Wilson, K Luther, J Biggs, MM Burroughs, D Ritz, AL Fava, M Quitkin, F Rush, AJ CA STAR D Investigators TI Methods of testing feasibility for sequenced treatment alternatives to relieve depression (STAR*D) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE depression; treatment; trials; feasibility; procedures; functionality ID RATING-SCALE; SYMPTOMATOLOGY IDS; PATIENT; QUESTIONNAIRE; INVENTORY; CLAIMS; HEALTH; WORK; CARE AB In large multi-site trials, a feasibility or pilot study can be crucial to test the functionality of all aspects of conducting the study prior to the initiation of the formal study. A feasibility trial was conducted for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Project, a multi-site, prospective, sequentially randomized, clinical trial of outpatients with nonpsychotic major depressive disorder. From 14 December 2000 to 8 June 2001, 42 patients were screened for enrollment into the STAR*D Feasibility Trial. Twenty-four patients who were eligible and consented to participate were treated with citalopram for up to 12 weeks. During the course of this trial, issues were raised that resulted in modifications to the study procedures. Modifications made as a result of this trial affected four domains: (1) communication, (2) patient and provider burden, (3) data collection forms, and (4) recruitment and retention of subjects. This paper describes what was learned during the STAR*D Feasibility Trial so researchers planning to conduct similar trials can learn the practical issues related to conducting such a research project. While the information gathered was useful, it did delay the initiation of the formal trial. We view this cost as an investment in the development of overall study procedures that should lead to a stronger study. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. NIMH, Bethesda, MD 20892 USA. Healthcare Technol Syst, Madison, WI 53717 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. RP Wisniewski, SR (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM wisniew@edc.pitt.edu RI Biggs, Dr. Melanie/C-1468-2010; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 28 TC 6 Z9 6 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAY-JUN PY 2004 VL 38 IS 3 BP 241 EP 248 DI 10.1016/j.jpsychires.2003.06.001 PG 8 WC Psychiatry SC Psychiatry GA 804YU UT WOS:000220334800004 PM 15003429 ER PT J AU Jupiter, JB AF Jupiter, JB TI Corrective valgus osteotomy after free vascularized fibula transfer for the treatment of osteomyelitis at the neck of the femur: Case report - Invited discussion SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Editorial Material ID RECONSTRUCTION; BONE C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Weston, MA 02493 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, 15 Nonesuch Way, Weston, MA 02493 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD MAY PY 2004 VL 20 IS 4 BP 310 EP 310 PG 1 WC Surgery SC Surgery GA 817KZ UT WOS:000221177700006 ER PT J AU Lum, PS Taub, E Schwandt, D Postman, M Hardin, P Uswatte, G AF Lum, PS Taub, E Schwandt, D Postman, M Hardin, P Uswatte, G TI Automated Constraint-Induced Therapy Extension (AutoCITE) for movement deficits after stroke SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE automated rehabilitation; cerebrovascular accident; CI therapy; Constraint-Induced Movement therapy; movement; upper limb ID REHABILITATION AB We report progress in the development of AutoCITE, a workstation that delivers the task practice component of upper-limb Constraint-Induced Movement therapy and that can potentially be used in the clinic or the home without the need for one-on-one supervision from a therapist. AutoCITE incorporates a computer and eight task devices arranged on a modified cabinet. Task performance is automatically recorded, and several types of feedback are provided. In preliminary testing, nine chronic stroke subjects with mild to moderate motor deficits practiced with AutoCITE for 3 h each weekday for 2 weeks. Subjects wore a padded mitt on the less-affected hand for a target of 90% of their waking hours. In terms of effect sizes, gains were large and significant on the Motor Activity Log, and moderate to large on the Wolf Motor Function Test. These gains were comparable to the gains of a matched group of 12 subjects who received standard Constraint-Induced Movement therapy. C1 Virginia Commonwealth Univ, Richmond, VA 23298 USA. Hunter Holmes McGuire Dept Vet Affairs, Ctr Med, Richmond, VA USA. VA Palo Alto Healthcare Syst, Rehabil Res & Dev Ctr, Palo Alto, CA USA. Birmingham VA Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. RP Lum, PS (reprint author), Virginia Commonwealth Univ, MCV Campus,1112 E Clay St,Room 220,POB 980694, Richmond, VA 23298 USA. EM plum@vcu.edu RI Uswatte, Gitendra/C-4913-2009 NR 15 TC 41 Z9 43 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2004 VL 41 IS 3A BP 249 EP 257 DI 10.1682/JRRD.2003.06.0092 PG 9 WC Rehabilitation SC Rehabilitation GA 859ES UT WOS:000224246800014 PM 15543442 ER PT J AU Robinson-Whelen, S Bodenheimer, C AF Robinson-Whelen, S Bodenheimer, C TI Health practices of veterans with unilateral lower-limb loss: Identifying correlates SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputees; foot-care practices; health behavior; health beliefs; psychological adjustment ID DEPRESSIVE SYMPTOMS; LIFE SCALE; AMPUTEES; SATISFACTION; AMPUTATIONS; VALIDATION; BEHAVIORS; SMOKING AB Persons with a nontraumatic lower-limb amputation are at high risk of losing their contralateral limb in the years postamputation. In this study, veterans with a unilateral lower-limb amputation participated in a survey about health beliefs and health practices known to affect risk of amputation (foot care and smoking). Most participants reported good footcare practices (93% checked the top of their foot, 73% checked the bottom of their foot, 75% checked between their toes, and 72% washed their foot-daily); however, a small percentage engaged in important foot-care practices less than once a week (2% checked the top of their foot, 7% checked the bottom of their foot, and 7% checked between their toes less than once a week). In addition, nearly a third still smoked. The belief in one's ability to engage in good foot care and the belief that good foot care reduces the risk of future foot problems were significantly correlated with foot-care practices. In addition, psychological well-being (life satisfaction) was significantly related to foot care and smoking status. Longitudinal research is needed to identify determinants of health behaviors to better direct intervention efforts. C1 Baylor Coll Med, Ctr Res Women Disabil, Houston, TX 77046 USA. Baylor Coll Med, VA Med Ctr, Dept Vet Affairs, Res & Dev Serv, Houston, TX 77046 USA. RP Robinson-Whelen, S (reprint author), Baylor Coll Med, Ctr Res Women Disabil, 3440 Richmond Ave,Suite B, Houston, TX 77046 USA. EM susanrw@bcm.tmc.edu NR 26 TC 8 Z9 8 U1 1 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2004 VL 41 IS 3B BP 453 EP 460 DI 10.1682/JRRD.2004.03.0453 PG 8 WC Rehabilitation SC Rehabilitation GA 859ET UT WOS:000224246900010 PM 15543463 ER PT J AU Deshmukh, AV Perlmutter, GS Zilberfarb, JL Wilson, DR AF Deshmukh, AV Perlmutter, GS Zilberfarb, JL Wilson, DR TI Effect of subacromial decompression on laxity of the acromioclavicular joint: Biomechanical testing in a cadaveric model SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID IMPINGEMENT SYNDROME; ARTHROSCOPIC ACROMIOPLASTY; ANTERIOR ACROMIOPLASTY; TRANSLATION; LIGAMENTS; CLAVICLE; SHOULDER AB Subacromial decompression is a well-accepted treatment for impingement syndrome when nonoperative therapies have failed. However, recent clinical data have raised concern that arthroscopic subacromial decompression may lead to laxity of the acromioclavicu-lar joint and, potentially, predispose patients to late postoperative acromioclavicular joint pain. Our goal was to determine whether subacromial decompression with co-planing of the distal clavicle alters the laxity, or compliance, of the acromioclavicular joint in a cad-averic model. Eighteen cadaveric shoulders were dissected and tested in a specially designed rig, driven by a hydraulic materials testing machine. One hundred-Newton loads were applied to the distal clavicle in the superior, posterior, and anterior directions, while acromioclavicular joint motion was recorded with a 3-dimensional infrared optical measurement system. Acromioplasty was performed with a posterior-referenced cutting block technique and included co-planing of the distal clavicle in all specimens. Joint compliance before and after subacromial decompression was compared with the paired t test. Subacromial decompression increased anteroposterior compliance by 13%, from 8.8 +/- 2.9 mm (mean +/- SD) in the intact joint to 9.9 +/- 3.1 mm (P = 001). Subacromial decompression increased superior compliance by 32%, from 3.1 +/- 1.5 mm in the native specimen to 4.1 +/- 1.8 mm (P = .03). These observations may have implications for the technique of acromioplasty. Although the immediate result of acromioplasty with co-planing appears to be on increase in the compli-ance of the acromioclavicular joint, the clinical significance of these findings has yet to be determined. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. Kaiser W Los Angeles Med Ctr, Dept Orthopaed, Los Angeles, CA USA. Queens Univ, Dept Engn Mech, Kingston, ON K7L 3N6, Canada. RP Perlmutter, GS (reprint author), Massachusetts Gen Hosp, 1 Hawthorne Pl,Suite 105, Boston, MA 02114 USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAY-JUN PY 2004 VL 13 IS 3 BP 338 EP 343 DI 10.1016/j.jse.2004.01.004 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 818TL UT WOS:000221267300014 PM 15111906 ER PT J AU Lehtinen, JT Tingart, MJ Apreleva, M Warner, JJP AF Lehtinen, JT Tingart, MJ Apreleva, M Warner, JJP TI Total, trabecular, and cortical bone mineral density in different regions of the glenoid SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID SUTURE ANCHORS; GLENOHUMERAL JOINT; SHOULDER; ARTHROPLASTY; STRENGTH; STAPLES AB The purpose of this study was to analyze total, trabec-ular, and cortical bone mineral density (BMD) of different regions of the glenoid. Soft tissue was dissected from 20 cadaveric shoulders, and the glenoids were isolated. Axial peripheral quantitative computed tomography (pQCT) scans perpendicular to the articular surface were performed at the middle level of each (superior, middle, and inferior) horizontal third of the glenoid, and the total, trabecular, and cortical BMDs of the anterior and posterior half of each region were determined by use of pQCT software. The total BMDs of the posterior and superior glenoid were significantly higher than those of the anterior and inferior glenoid (P < .01). Trabecular BMD of the posterior glenoid was significantly higher than that of the anterior glenoid, and cortical BMD of the superior glenoid was significantly higher than that of the inferior glenoid (P <. 0 1). These significant differences in distribution of the BMD explain previous findings of the mechanical properties of the glenoid. Future glenoid component design should provide maximal surface area for posterior and superior bone ingrowth to the component. Posteriorly and superiorly, the glenoid bone stock also provides stronger support for any kind of fixation on the bony surface. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA USA. RP Lehtinen, JT (reprint author), Kanta Hame Cent Hosp, Dept Surg, Hameenlinna 13530, Finland. EM janne.lehtinen@khshp.fi NR 22 TC 21 Z9 22 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAY-JUN PY 2004 VL 13 IS 3 BP 344 EP 348 DI 10.1016/j.jse.2004.01.012 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 818TL UT WOS:000221267300015 PM 15111907 ER PT J AU Geisse, J Caro, I Lindholm, J Golitz, L Stampone, P Owens, M AF Geisse, J Caro, I Lindholm, J Golitz, L Stampone, P Owens, M TI Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from two phase III, randomized, vehicle-controlled studies SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Annual Conference of the European-Academy-of-Dermatology-and Venerology CY NOV 19, 2003 CL Barcelona, SPAIN SP European Acad Dermatol & Venerol AB Background: Imiquimod is an immune response modifier that is a Toll-like receptor 7 agonist that induces interferon and other cytokines through the innate immune system and stimulates cell-mediated immunity through T cells. Imiquimod has been shown to be efficacious as a topical treatment for basal cell carcinoma (BCC). Objective. We sought to evaluate the efficacy and safety of imiquimod 5% cream compared with vehicle for treating superficial BCC (sBCC). Methods: Two identical studies were conducted. Subjects with one sBCC were dosed with imiquimod or vehicle cream once daily 5 or 7x/week for 6 weeks in these 2 randomized, double-blind, vehicle-controlled Phase III studies. The lesion site was clinically examined 12 weeks posttreatment and then excised for histological evaluation. Results: Data from both studies were pooled. Composite clearance rates (combined clinical and histological assessments) for the 5 and 7x/week imiquimod groups were 75% and 73%, respectively. Histological clearance rates for the 5 and 7x/week imiquimod groups were 82% and 79%, respectively. Increasing severity of erythema, erosion, and scabbing/crusting was associated with higher clearance rates. Conclusion: Imiquimod appears to be safe and effective for the treatment of sBCC when compared with vehicle cream. The difference in clearance rates between the two imiquimod dosing groups was not significant. The 5x/week regimen is recommended. C1 Solano Dermatol Associates, Vallejo, CA 94589 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Clin Invest Unit, Boston, MA USA. Dermatopathol Serv LLC, Fridley, MA USA. Dermapathol Associates, Denver, CO USA. 3M Pharmaceut, St Paul, MN USA. RP Geisse, J (reprint author), Solano Dermatol Associates, 127 Hosp Dr,Suite 204, Vallejo, CA 94589 USA. EM jgeisse@solderm.com NR 10 TC 239 Z9 246 U1 1 U2 11 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2004 VL 50 IS 5 BP 722 EP 733 DI 10.1016/j.jaad.2003.11.066 PG 12 WC Dermatology SC Dermatology GA 816WE UT WOS:000221139200009 PM 15097956 ER PT J AU El-Gamal, HM Robinson-Bostom, L Saddler, KD Pan, T Mihm, MC AF El-Gamal, HM Robinson-Bostom, L Saddler, KD Pan, T Mihm, MC TI Compound melanocytic nevi with granular cell changes SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID EXPRESSION AB Two cases of compound melanocytic nevi with granular cell changes were studied. Histological examination revealed compound melanocytic nevi with a portion of the dermal component exhibiting a sheet like proliferation of nevoid cells with granular cytoplasm. Immunohistochemically, both populations of cells stained positive for S-100 and Melan-A. However, HMB-45 was positive only for the nevus cells with granular cytoplasm. We believe this represents granular cytoplasmic changes of nevus cells and does not denote malignant transformation. C1 Brown Univ, Sch Med, Dept Dermatol, Providence, RI 02903 USA. Indiana Univ, Sch Med, Dept Dermatol, Indianapolis, IN USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Robinson-Bostom, L (reprint author), Brown Univ, Sch Med, Dept Dermatol, 593 Eddy St,APC-10, Providence, RI 02903 USA. EM LRobinson-Bostom@Lifespan.org NR 4 TC 18 Z9 18 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2004 VL 50 IS 5 BP 765 EP 766 DI 10.1016/j.jaad.2003.11.068 PG 2 WC Dermatology SC Dermatology GA 816WE UT WOS:000221139200017 PM 15097962 ER PT J AU Streams, BN Lio, PA Mihm, MC Sober, AJ AF Streams, BN Lio, PA Mihm, MC Sober, AJ TI A nonepidermal, primary malignant melanoma arising in a giant congenital melanocytic nevus 40 years after partial surgical removal SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID RISK C1 Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Sober, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Bartlett Hall 622, Boston, MA 02114 USA. EM asober@partners.org NR 10 TC 12 Z9 12 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 MAY PY 2004 VL 50 IS 5 BP 789 EP 792 DI 10.1016/j.jaad.2003.09.023 PG 4 WC Dermatology SC Dermatology GA 816WE UT WOS:000221139200023 PM 15097968 ER PT J AU Hynes, DM Weaver, F Morrow, M Folk, F Winchester, DJ Mallard, M Ippolito, D Thakkar, B Henderson, W Khuri, S Daley, J AF Hynes, DM Weaver, F Morrow, M Folk, F Winchester, DJ Mallard, M Ippolito, D Thakkar, B Henderson, W Khuri, S Daley, J TI Breast cancer surgery trends and outcomes: Results from a National Department of Veterans Affairs study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID MODIFIED RADICAL-MASTECTOMY; CARDIAC-SURGERY; SURGICAL CARE; WOUND COMPLICATIONS; RISK ADJUSTMENT; DATA-BASE; ADMINISTRATIVE DATABASES; CONSERVING SURGERY; VIETNAM VETERANS; HEALTH-STATUS AB BACKGROUND: This study examined trends and outcomes for breast cancer surgery performed at Department of Veterans Affairs (VA) hospitals. STUDY DESIGN: We examined breast cancer operations performed in VA hospitals from October 1991 to September 1997. Data from the VA National Surgical Quality Improvement Program, surgical pathology reports, discharge data, and outpatient data were used. Surgical outcomes included postoperative length of stay, 30-day morbidity rates, 1-year surgery-related readmission rates, and mortality. An expert panel of breast cancer clinicians identified surgery-related hospital readmissions. Hierarchical regression analysis was used to identify patient, provider, and hospital characteristics associated with postoperative length of stay, and 30-day morbidity. RESULTS: From October 1991 to September 1997 1,333 breast operations were performed, ranging from I to 38 on average per hospital; 478 operations were for breast cancer. Among breast cancer surgery patients, 25% were men. Thirty-day morbidity rates, 1-year hospital readmission rates, and mortality were very low for both men and women. Postoperative length of stay averaged 6.8 days. Lower income, longer operation times, and older age increased the likelihood of 30-day morbidity. Lower functional status, older age, longer operation time, and lower average annual volume of procedures increased postoperative length of stay, Documentation of the extent of disease and surgical margin in pathology reports was poor in medical records. CONCLUSIONS: Hospital stays were longer, and morbidity and readmission rates for patients having breast cancer operations at VA hospitals were comparable to those reported for private sector hospitals. (J Am Coll Surg 2004;198:707-716. (C) 2004 by the American College of Surgeons) C1 Edward Hines Jr Vet Adm Hosp, VA Informat Resource Ctr, Hines, IL 60141 USA. Edward Hines Jr Vet Adm Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Edward Hines Jr Vet Adm Hosp, Cooperat Studies Program, Coordinating Ctr, Hines, IL 60141 USA. Loyola Univ, Maywood, IL 60153 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL USA. Evanston NW Healthcare, Evanston, IL USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Durham VA Med Ctr, Durham, NC USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston VA Healthcare Syst, Boston, MA USA. Tenet Hlth Syst, Dallas, TX USA. Dartmouth Coll Sch Med, Hanover, NH USA. RP Hynes, DM (reprint author), Edward Hines Jr Vet Adm Hosp, VA Informat Resource Ctr, POB 5000 151V,5th & Roosevelt Rds,Bldg 1,Room C30, Hines, IL 60141 USA. NR 46 TC 20 Z9 20 U1 1 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 MAY PY 2004 VL 198 IS 5 BP 707 EP 716 DI 10.1016/j.jamcollsurg.2004.01.027 PG 10 WC Surgery SC Surgery GA 816XK UT WOS:000221142400003 PM 15110803 ER PT J AU Holroyd-Leduc, JM Mehta, KM Covinsky, KE AF Holroyd-Leduc, JM Mehta, KM Covinsky, KE TI Urinary incontinence and its association with death, nursing home admission, and functional decline SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE urinary incontinence; mortality; nursing homes; activities of daily living ID ELDERLY-PEOPLE; HEALTH DYNAMICS; OLDER-PEOPLE; RISK-FACTORS; PREVALENCE; COMMUNITY; WOMEN; FRAILTY; IMPACT; LIFE AB OBJECTIVES: To determine whether urinary incontinence (UI) is an independent predictor of death, nursing home admission, decline in activities of daily living (ADLs), or decline in instrumental activities of daily living (IADLs). DESIGN: A population-based prospective cohort study from 1993 to 1995. SETTING: Community-dwelling within the United States. PARTICIPANTS: Six thousand five hundred six of the 7,447 subjects aged 70 and older in the Asset and Health Dynamics Among the Oldest Old study who had complete information on continence status and did not require a proxy interview at baseline. MEASUREMENTS: The predictor was UI, and the outcomes were death, nursing home admission, ADL decline, and IADL decline. Potential confounders considered were comorbid conditions, baseline function, sensory impairment, cognition, depressive symptoms, body mass index, smoking and alcohol, demographics, and socioeconomic status. RESULTS: The prevalence of UI was 14.8% (18.5% in women; 8.5% in men). At 2-year follow-up, subjects incontinent at baseline were more likely to have died (10.9% vs 8.7%; unadjusted odds ratio (OR)=1.29, 95% confidence interval (CI)=1.02-1.64), be admitted to a nursing home (4.4% vs 2.6%, OR=1.77; 95% CI=1.18-2.63), and to have declined in ADL function (13.6% vs 8.1%; OR=1.78, 95% CI=1.36-2.33) and IADL function (21.2% vs 13.8%; OR 1.69, 95% CI 1.39-2.05). However, after adjusting for confounders, UI was not an independent predictor of death (adjusted OR (AOR)= 0.90, 95% CI=0.67-1.21), nursing home admission (AOR=1.33, 95% CI=0.86-2.04), or ADL decline (AOR=1.24, 95% CI=0.92-1.68). Incontinence remained a predictor of IADL decline (AOR=1.31; 95% CI=1.05-1.63), although adjustment markedly reduced the strength of this association. CONCLUSION: Higher levels of baseline illness severity and functional impairment appear to mediate the relationship between UI and adverse outcomes. The results suggest that, although UI appears to be a marker of frailty in community-dwelling elderly, it is not a strong independent risk factor for death, nursing home admission, or functional decline. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. RP Holroyd-Leduc, JM (reprint author), San Francisco VA Med Ctr, 181G,4150 Clement St,Bldg 1, San Francisco, CA 94121 USA. EM Jayna.Holroyd-Leduc@med.va.gov FU AHRQ HHS [K02 HS00006-01]; NIA NIH HHS [R01AG19827, T32-AG00212-08] NR 35 TC 73 Z9 73 U1 1 U2 11 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2004 VL 52 IS 5 BP 712 EP 718 DI 10.1111/j.1532-5415.2004.52207.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812QZ UT WOS:000220855300008 PM 15086650 ER PT J AU Lorenz, KA Asch, SM Rosenfeld, KE Liu, H Ettner, SL AF Lorenz, KA Asch, SM Rosenfeld, KE Liu, H Ettner, SL TI Hospice admission practices: Where does hospice fit in the continuum of care? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE hospice; terminal care; geriatrics ID TREATMENT PREFERENCES; MEDICAL-CARE; ILL PATIENTS; DEATH; LIFE; PLACE; RULES; END AB OBJECTIVES: To evaluate selected hospice admission practices that could represent barriers to hospice use and the association between these admission practices and organizational characteristics. DESIGN: From December 1999 to March 2000, hospices were surveyed about selected admission practices, and their responses were linked to the 1999 California Office of Statewide Health Planning and Development's Home and Hospice Care Survey that describes organizational characteristics of California hospices. SETTING: California statewide. PARTICIPANTS: One hundred of 149 (67%) operational licensed hospices. MEASUREMENTS: Whether hospices admit patients who lack a caregiver; would not forgo hospital admissions; or are receiving total parenteral nutrition (TPN), tube feedings, radiotherapy, chemotherapy, or transfusions. RESULTS: Sixty-three percent of hospices restricted admission on at least one criterion. A significant minority of hospices would not admit patients lacking a caregiver (26%). Patients unwilling to forgo hospitalization could not be admitted to 29% of hospices. Receipt of complex medical care, including TPN (38%), tube feedings (3%), transfusions (25%), radiotherapy (36%), and chemotherapy (48%), precluded admission. Larger program size was significantly associated with a lower likelihood of all admission practices except restricting the admission of patients receiving TPN or tube feedings. Hospice programs that were part of a hospice chain were less likely to restrict the admission of patients using TPN, radiotherapy, or chemotherapy than were freestanding programs. CONCLUSION: Patients who are receiving complex palliative treatments could face barriers to hospice enrollment. Policy makers should consider the clinical capacity of hospice providers in efforts to improve access to palliative care and more closely incorporate palliation with other healthcare services. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Vet Integrated Palliat Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RAND Corp, Los Angeles, CA USA. RP Lorenz, KA (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Vet Integrated Palliat Program, 11303 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM karl.lorenz@med.va.gov NR 27 TC 40 Z9 40 U1 1 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2004 VL 52 IS 5 BP 725 EP 730 DI 10.1111/j.1532-5415.2004.52209.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812QZ UT WOS:000220855300010 PM 15086652 ER PT J AU Chodosh, J Solomon, DH Roth, CP Chang, JT MacLean, CH Ferrell, BA Shekelle, PG Wenger, NS AF Chodosh, J Solomon, DH Roth, CP Chang, JT MacLean, CH Ferrell, BA Shekelle, PG Wenger, NS TI The quality of medical care provided to vulnerable older patients with chronic pain 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, IL SP Amer Geriatr Soc DE quality of care; chronic pain; managed care; quality indicators ID NURSING-HOME; MANAGEMENT; INDICATORS; PREVALENCE; ELDERS/; POPULATION; COMMUNITY; SYMPTOMS; PEOPLE; HEALTH AB OBJECTIVES: To assess the quality of chronic pain care provided to vulnerable older persons. DESIGN: Observational study evaluating 11 process-of-care quality indicators using medical records and interviews with patients or proxies covering care received from July 1998 through July 1999. SETTING: Two senior managed care plans. PARTICIPANTS: A total of 372 older patients at increased risk of functional decline or death identified by interview of a random sample of community dwellers aged 65 and older enrolled in these managed-care plans. MEASUREMENTS: Percentage of quality indicators satisfied for patients with chronic pain. RESULTS: Fewer than 40% of vulnerable patients reported having been screened for pain over a 2-year period. One hundred twenty-three patients (33%) had medical record documentation of a new episode of chronic pain during a 13-month period, including 18 presentations for headache, 66 for back pain, and 68 for joint pain. Two or more history elements relevant to the presenting pain complaint were documented for 39% of patients, and at least one relevant physical examination element was documented for 68% of patients. Treatment was offered to 86% of patients, but follow-up occurred in only 66%. Eleven of 18 patients prescribed opioids reported being offered a bowel regimen, and 10% of patients prescribed noncyclooxygenase-selective nonsteroidal antiinflammatory medications received appropriate attention to potential gastrointestinal toxicity. CONCLUSION: Chronic pain management in older vulnerable patients is inadequate. Improvement is needed in screening, clinical evaluation, follow-up, and attention to potential toxicities of therapy. C1 Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Rheumatol, Los Angeles, CA USA. RAND Corp, Hlth, Santa Monica, CA USA. RP Chodosh, J (reprint author), UCLA Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM jchodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 NR 29 TC 51 Z9 52 U1 1 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2004 VL 52 IS 5 BP 756 EP 761 DI 10.1111/j.1532-5415.2004.52214.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812QZ UT WOS:000220855300015 PM 15086657 ER PT J AU Weintraub, D Moberg, PJ Duda, JE Katz, IR Stern, MB AF Weintraub, D Moberg, PJ Duda, JE Katz, IR Stern, MB TI Effect of psychiatric and other nonmotor symptoms on disability in Parkinson's disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Parkinson's disease; disability; psychiatric; depression; cognition ID DAYTIME SLEEPINESS; RISK-FACTORS; DEPRESSION; SCALE; COMORBIDITY; DEMENTIA; VALIDITY AB OBJECTIVES: To examine the effect of depression and other nonmotor symptoms on functional ability in Parkinson's disease (PD). DESIGN: A cross-sectional study of a convenience sample of PD patients receiving specialty care. SETTING: The Parkinson's Disease Research, Education and Clinical Center at the Philadelphia Veterans Affairs Medical Center. PARTICIPANTS: One hundred fourteen community-dwelling patients with idiopathic PD. MEASUREMENTS: The Unified Parkinson's Disease Rating Scale (UPDRS); Hoehn and Yahr Stage; Mini-Mental State Examination; Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depression module; probes for psychotic symptoms; Hamilton Depression Rating Scale; Geriatric Depression Scale-Short Form; Apathy Scale; and Epworth Sleepiness Scale. Disability was rated using the UPDRS activity of daily living (ADL) score and the Schwab and England ADL score. Multivariate analysis determined effect of depression and other nonmotor symptoms on disability. RESULTS: The presence of psychosis, depressive disorder, increasing depression severity, age, duration of PD, cognitive impairment, apathy, sleepiness, motor impairment, and percentage of time with dyskinesias were related to greater disability in bivariate analyses. Entering these factors into two multiple regression analyses, only the increasing severity of depression and worsening cognition were associated with greater disability using the UPDRS ADL score, accounting for 37% of the variance in disability (P<.001). These two factors plus increasing severity of PD accounted for 54% of the variance in disability using the Schwab and England ADL score (P<.001). CONCLUSION: Results support and extend previous findings that psychiatric and other nonmotor symptoms contribute significantly to disability in PD. Screening for nonmotor symptoms in PD is necessary to more fully explain functional limitations. Further study is required to determine whether identifying and treating these symptoms will improve function and quality of life. C1 Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu NR 28 TC 191 Z9 198 U1 2 U2 20 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2004 VL 52 IS 5 BP 784 EP 788 DI 10.1111/j.1532-5415.2004.52219.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 812QZ UT WOS:000220855300020 PM 15086662 ER PT J AU Wolf, M Shah, A Jimenez-Kimble, R Sauk, J Ecker, JL Thadhani, R AF Wolf, M Shah, A Jimenez-Kimble, R Sauk, J Ecker, JL Thadhani, R TI Differential risk of hypertensive disorders of pregnancy among Hispanic women SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MILD GESTATIONAL HYPERTENSION; NUTRITION-EXAMINATION-SURVEY; AUSTRALIAN-BORN WOMEN; BLOOD-PRESSURE; INSULIN-RESISTANCE; UNITED-STATES; MEXICAN-AMERICANS; DIABETES-MELLITUS; NULLIPAROUS WOMEN; ETHNIC-GROUPS AB Preeclampsia and gestational hypertension are leading complications of pregnancy that also portend increased risk of future chronic hypertension. Although rates of chronic hypertension differ between non-Hispanic Caucasian and Hispanic women, few studies examined their relative rates of hypertensive disorders of pregnancy. The purpose of this study was to compare the risk of preeclampsia and gestational hypertension in a prospective cohort of normotensive, nulliparous Hispanic (n = 863) and non-Hispanic Caucasian women (n = 2,381). Compared with non-Hispanic Caucasian women, Hispanic women demonstrated a significantly decreased incidence of gestational hypertension (1.6% versus 8.5%; P < 0.01), but a similar incidence of preeclampsia (3.8% versus 3.7%; P = 0.9). Adjusting for age, smoking, diabetes, BP, body mass index (BMI), and multiple gestation uncovered an increased relative risk (RR) for preeclampsia among Hispanic women (RR 1.9; 95% CI, 1.1 to 3.3; P = 0.01), while their relative risk for gestational hypertension remained significantly decreased (RR 0.39; 95% CI, 0.22 to 0.72; P < 0.01). Among women who initially presented with hypertension during pregnancy, Hispanic women were over threefold (hazard ratio 3.3; 95% Cl, 1.9 to 6.0; P < 0.01) more likely to develop preeclampsia than non-Hispanic Caucasian women. Besides Hispanic ethnicity, baseline BP, BMI, diabetes, and multiple gestation were independent risk factors for preeclampsia, whereas only baseline BP and BMI were associated with gestational hypertension. Socioeconomic status and access to prenatal care were not associated with either disorder. Hispanic ethnicity is independently associated with increased risk for preeclampsia and decreased risk for gestational hypertension. The initial presentation of hypertension during pregnancy in Hispanic women most likely represents early preeclampsia. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Univ Toronto, Ctr Int Hlth, Fac Med, Toronto, ON, Canada. RP Wolf, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, 55 Fruit St,Bartlett 904, Boston, MA 02114 USA. EM mswolf@partners.org FU NCRR NIH HHS [RR17376]; NICHD NIH HHS [HD39232] NR 46 TC 34 Z9 35 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2004 VL 15 IS 5 BP 1330 EP 1338 DI 10.1097/01.ASN.0000125615.35046.59 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 815LE UT WOS:000221043000028 PM 15100374 ER PT J AU Heckenkamp, J Nigri, GR Waterman, PR Overhaus, M Kossodo, SC LaMuraglia, GM AF Heckenkamp, J Nigri, GR Waterman, PR Overhaus, M Kossodo, SC LaMuraglia, GM TI gamma-irradiation modulates vascular smooth muscle cell and extracellular matrix function: Implications for neointimal development SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PORCINE CORONARY-ARTERIES; IN-STENT RESTENOSIS; RADIATION-THERAPY; PHOTODYNAMIC THERAPY; ENDOTHELIAL-CELLS; INJURY; PROLIFERATION; HYPERPLASIA; PREVENTION; INHIBITION AB Objective: Migration of vascular smooth muscle cells (SMCs) into the subintimal space, and their proliferation and resultant deposition of extracellular matrix are key processes in the development of intimal hyperplasia, leading to vascular recurrent stenosis. The purpose of this study was to investigate the effects of clinically administered doses of gamma-radiation on SMCs and extracellular matrix proteins in vitro, to better understand how it impinges on cellular and extracellular components of recurrent stenosis. Methods. The effects of gamma-irradiation (10, 20 Gy) on SMC migration into three-dimensional collagen matrix gels was quantitated by calibrated light microscopy, and the release of metalloproteinases into conditioned media was investigated with an enzyme-linked immunosorbent assay and zymography. Collagen production was assayed with [H-3]-proline incorporation, and SMC phenotype changes with confocal microscopy with a fluorescent alpha-actin antibody. The effect of gamma-irradiation on extracellular matrix was investigated by quantitating untreated SMC proliferation (3 H-thymidine incorporation) on irradiated endothelial cell-derived matrix and by assessing structural collagen matrix changes with sodium dodecylsulfate polyacrylamide gel electrophoresis. All groups were compared with nonirradiated control groups. Results. SMC vertical migration was significantly decreased by gamma-irradiation (48% and 55%, respectively; P < .0001). Irradiation did not generate measurable matrix protein crosslinks, nor did it alter the production of metalloproteinases or collagen synthesis. However, gamma-irradiation decreased the ability of extracellular matrix to induce nonirradiated SMC proliferation (15% reduction; P = .0028). Moreover, gamma-irradiation reversed the secretory phenotype of cultured SMCs to a contractile type. Conclusions: The gamma-irradiation-induced reduction of cellular migration, changes in SMC phenotype, and functional activity of matrix-bound factors, and no measurable effects on the production of extracellular matrix proteins, may in part explain the diverse effects of gamma-irradiation on the restenonotic response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg,Gen Surg Serv, WAC 464,55 Fruit St, Boston, MA 02114 USA. NR 33 TC 5 Z9 5 U1 0 U2 0 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 MAY PY 2004 VL 39 IS 5 BP 1097 EP 1103 DI 10.1016/j.jvs.2003.12.021 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 826VV UT WOS:000221858500036 PM 15111867 ER PT J AU Kaufmann, DE Bailey, PM Sidney, J Wagner, B Norris, PJ Johnston, MN Cosimi, LA Addo, MM Lichterfeld, M Altfeld, M Frahm, N Brander, C Sette, A Walker, BD Rosenberg, ES AF Kaufmann, DE Bailey, PM Sidney, J Wagner, B Norris, PJ Johnston, MN Cosimi, LA Addo, MM Lichterfeld, M Altfeld, M Frahm, N Brander, C Sette, A Walker, BD Rosenberg, ES TI Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of gag and nef and the presence of broadly recognized peptides SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; COMBINATION ANTIRETROVIRAL THERAPY; ANTIGEN-SPECIFIC CD4(+); HIV-1 CAPSID PROTEIN; CLASS-II MOLECULES; IMMUNE-RESPONSES; PROLIFERATIVE RESPONSES; CD8-T-CELL MEMORY; CD4-T-CELL HELP; ACUTE INFECTION AB Increasing evidence suggests that human immunodeficiency virus type 1 (HIV-1) -specific CD4 T-cell responses contribute to effective immune control of HIV-1 infection. However, the breadths and specificities of these responses have not been defined. We screened fresh CD8-depleted peripheral blood mononuclear cells (PBMC) from 36 subjects at different stages of HIV-1 infection for virus-specific CD4 responses by gamma interferon enzyme-linked immunospot assay, using 410 overlapping peptides spanning all HIV-1 proteins (based on the clade B consensus sequence). HIV-1-specific CD4 responses were identified in 30 of the 36 individuals studied, with the strongest and broadest responses detected in persons treated in acute infection who underwent treatment interruption. In individuals with identified responses, the total number of recognized HIV-1 peptides ranged from 1 to 36 (median, 7) and the total magnitude of responses ranged from 80 to >14,600 (median, 990) spot-forming cells/10(6) CD8-depleted PBMC. Neither the total magnitude nor the number of responses correlated with viremia. The most frequent and robust responses were directed against epitopes within the Gag and Nef proteins. Peptides targeted by greater than or equal to25% of individuals were then tested for binding to a panel of common HLA-DR molecules. All bound broadly to at least four of the eight alleles tested, and two bound to all of the HLA-DR molecules studied. Fine mapping and HLA restriction of the responses against four of these peptides showed a combination of clustering of epitopes and promiscuous presentation of the same epitopes by different HLA class II alleles. These findings have implications for the design of immunotherapeutic strategies and for testing candidate HIV vaccines. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92121 USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Div Infect Dis, Gray J-504,55 Fruit St, Boston, MA 02114 USA. EM erosenberg1@partners.org OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [AI040873, AI01698, K08 AI001698, K08 AI001698-04, N01-AI-95362, N01AI95362, R01 AI040873, R21 AI040873]; PHS HHS [N01-A1-15422] NR 70 TC 128 Z9 131 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 9 BP 4463 EP 4477 DI 10.1128/JVI.78.9.4463-4477.2004 PG 15 WC Virology SC Virology GA 813AO UT WOS:000220880200009 PM 15078927 ER PT J AU Chen, B Cheng, YF Calder, L Harrison, SC Reinherz, EL Skehel, JJ Wiley, DC AF Chen, B Cheng, YF Calder, L Harrison, SC Reinherz, EL Skehel, JJ Wiley, DC TI A chimeric protein of simian immunodeficiency virus envelope glycoprotein gp140 and Escherichia coli aspartate transcarbamoylase SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; RECEPTOR-BINDING; TYPE-1; GP120; GP41; CD4; EPITOPE; HIV-1; NEUTRALIZATION AB The envelope glycoproteins of the human immunodeficiency virus and the related simian immunodeficiency virus (SIV) mediate viral entry into host cells by fusing viral and target cell membranes. We have reported expression, purification, and characterization of gp140 (also called gp160e), the soluble, trimeric ectodomain of the SIV envelope glycoprotein, gp160 (B. Chen et al., J. Biol. Chem. 275:34946-34953, 2000). We have now expressed and purified chimeric proteins of SIV gp140 and its variants with the catalytic subunit (C) of Escherichia coli aspartate transcarbamoylase (ATCase). The fusion proteins (SIV gp140-ATC) bind viral receptor CD4 and a number of monoclonal antibodies specific for SIV gp140. The chimeric molecule also has ATCase activity, which requires trimerization of the ATCase C chains. Thus, the fusion protein is trimeric. When ATCase regulatory subunit dimers (R-2) are added, the fusion protein assembles into dimers of trimers as expected from the structure of C,R, ATCase. Negative-stain electron microscopy reveals spikey features of both SIV gp140 and SIV gp140-ATC. The production of the fusion proteins may enhance the possibilities for structure determination of the envelope glycoprotein either by electron cryomicroscopy or X-ray crystallography. C1 Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Inst Med Res, London NW7 1AA, England. RP Harrison, SC (reprint author), Childrens Hosp, Mol Med Lab, 320 Longwood Ave, Boston, MA 02115 USA. EM harrison@crystal.harvard.edu FU NIAID NIH HHS [AI43649, P01 AI043649] NR 44 TC 14 Z9 14 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 9 BP 4508 EP 4516 DI 10.1128/JVI.79.9.4508-4516.2004 PG 9 WC Virology SC Virology GA 813AO UT WOS:000220880200013 PM 15078931 ER PT J AU Holm, GH Zhang, CS Gorry, PR Peden, K Schols, D De Clercq, E Gabuzda, D AF Holm, GH Zhang, CS Gorry, PR Peden, K Schols, D De Clercq, E Gabuzda, D TI Apoptosis of bystander T cells induced by human immunodeficiency virus type 1 with increased envelope/receptor affinity and coreceptor binding site exposure SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; HUMAN LYMPHOID-TISSUE; EXPRESS FAS LIGAND; CD4 CROSS-LINKING; IN-VIVO; ENVELOPE GLYCOPROTEINS; MEMBRANE-FUSION; INFECTED INDIVIDUALS; CLINICAL PROGRESSION; DEPENDENT APOPTOSIS AB Apoptosis of uninfected bystander CD4(+) T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1) pathogenesis. The viral and host mechanisms that lead to bystander apoptosis are not well understood. To investigate properties of the viral envelope glycoproteins (Env proteins) that influence the ability of HIV-1 to induce bystander apoptosis, we used molecularly cloned viruses that differ only in specific amino acids in Env. The ability of these strains to induce bystander apoptosis was tested in herpesvirus saimiri-immortalized primary CD4(+) T cells (CD4/HVS), which resemble activated primary T cells. Changes in Env that increase affinity for CD4 or CCR5 or increase coreceptor binding site exposure enhanced the capacity of HIV-1 to induce bystander apoptosis following viral infection or exposure to nonreplicating virions. Apoptosis induced by HIV-1 virions was inhibited by CD4, CXCR4, and CCR5 antibodies or by the CXCR4 inhibitor AMD3100, but not the fusion inhibitor T20. HIV-1 virions with mutant Envs that bind CXCR4 but are defective for CD4 binding or membrane fusion induced apoptosis, whereas CXCR4 binding-defective mutants did not. These results demonstrate that HIV-1 virions induce apoptosis through a CXCR4- or CCR5-dependent pathway that does not require Env/CD4 signaling or membrane fusion and suggest that HIV-1 variants with increased envelope/receptor affinity or coreceptor binding site exposure may promote T-cell depletion in vivo by accelerating bystander cell death. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Rega Inst Med Res, Lab Expt Chemotherapy, Louvain, Belgium. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Holm, Geoffrey/C-3188-2009 FU NIAID NIH HHS [P30 AI028691, AI28691]; NINDS NIH HHS [NS35734, R01 NS035734] NR 82 TC 48 Z9 49 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 9 BP 4541 EP 4551 DI 10.1128/JVI.78.9.4541-4551.2004 PG 11 WC Virology SC Virology GA 813AO UT WOS:000220880200017 PM 15078935 ER PT J AU Bower, JF Yang, XZ Sodroski, J Ross, TM AF Bower, JF Yang, XZ Sodroski, J Ross, TM TI Elicitation of neutralizing antibodies with DNA vaccines expressing soluble stabilized human immunodeficiency virus type 1 envelope glycoprotein trimers conjugated to C3d SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEIC-ACID IMMUNIZATION; HIV-1 ENV GLYCOPROTEINS; CODON USAGE; MOLECULAR ADJUVANT; ACQUIRED-IMMUNITY; ANTIGEN RECEPTOR; ATOMIC-STRUCTURE; FUSION PROTEINS; CO-LIGATION; B-CELLS AB DNA vaccines expressing the envelope (Env) of human immunodeficiency virus type I (HIV-1) have been relatively ineffective at generating high-titer, long-lasting immune responses. Oligomeric or trimeric (gp140) forms of Env that more closely mimic the native proteins on the virion are often more effective immunogens than monomeric (gp120) envelopes. In this study, several forms of Env constructed from the HIV-1 isolate YU-2 (HIV-1(YU-2)) were tested for their immunogenic potential: a trimeric form of uncleaved (-) Env stabilized with a synthetic trimer motif isolated from the fibritin (IT) protein of the T4 bacteriophage, sgp140(YU-2)(-/FT), was compared to sgp140(YU)-2(-) without a synthetic trimerization domain, as well as to monomeric gp120(YU)-2. DNA plasmids were constructed to express Env alone or fused to various copies of murine C3d (mCM). BALB/c mice were vaccinated (day 1 and week 4) with DNA expressing a codon-optimized envelope gene insert, alone or fused to mC3d. Mice were subsequently boosted (week 8) with the DNA or recombinant Env protein. All mice had high anti-Env antibody titers regardless of the use of mC3d. Sera from mice vaccinated with DNA expressing non-C3d-fused trimers elicited neutralizing antibodies against homologous HIV-1(YU-2) virus infection in vitro. In contrast, sera from mice inoculated with DNA expressing Env-C3d protein trimers elicited antibody that neutralized both homologous HIV-1(YU-2) and heterologous RIV-1(ADA), albeit at low titers. Therefore, DNA vaccines expressing trimeric envelopes coupled to mC3d, expressed in vivo from codon-optimized sequences, elicit low titers of neutralizing antibodies against primary isolates of HIV-1. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. RP Ross, TM (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Scaife Hall,Suite 871,3550 Terrace St, Pittsburgh, PA 15261 USA. EM RossT@msx.dept-med.pitt.edu FU NIAID NIH HHS [R21 AI044325-02, AI44328, AI44325, AI57630, AI31783, R01 AI031783] NR 69 TC 62 Z9 64 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 9 BP 4710 EP 4719 DI 10.1128/JVI.78.9.4710-4719.2004 PG 10 WC Virology SC Virology GA 813AO UT WOS:000220880200035 PM 15078953 ER PT J AU Brainard, DM Tharp, WG Granado, E Miller, N Trocha, AK Ren, XH Conrad, B Terwilliger, EF Wyatt, R Walker, BD Poznansky, MC AF Brainard, DM Tharp, WG Granado, E Miller, N Trocha, AK Ren, XH Conrad, B Terwilliger, EF Wyatt, R Walker, BD Poznansky, MC TI Migration of antigen-specific T cells away from CXCR4-binding human immunodeficiency virus type 1 gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTED RHESUS-MONKEYS; V3 LOOP; ENVELOPE GLYCOPROTEIN; PERFORIN EXPRESSION; CD8(+) LYMPHOCYTES; IMMUNE-RESPONSES; CORECEPTOR USAGE; ACTIVE MOVEMENT; HIV-INFECTION; LARGE NUMBERS AB Cell-mediated immunity depends in part on appropriate migration and localization of cytotoxic T lymphocytes (CTL), a process regulated by chemokines and adhesion molecules. Many viruses, including human immunodeficiency virus type 1 (HIV-1), encode chemotactically active proteins, suggesting that dysregulation of immune cell trafficking may be a strategy for immune evasion. HIV-1 gp120, a retroviral envelope protein, has been shown to act as a T-cell chemoattractant via binding to the chemokine receptor and HIV-1 coreceptor CXCR4. We have previously shown that T cells move away from the chemokine stromal cell-derived factor 1 (SDF-1) in a concentration-dependent and CXCR4 receptor-mediated manner. Here, we demonstrate that CXCR4-binding HIV-1 X4 gp120 causes the movement of T cells, including HIV-specific CTL, away from high concentrations of the viral protein. This migratory response is CD4 independent and inhibited by anti-CXCR4 antibodies and pertussis toxin. Additionally, the expression of X4 gp120 by target cells reduces CTL efficacy in an in vitro system designed to account for the effect of cell migration on the ability of CTL to kill their target cells. Recombinant X4 gp120 also significantly reduced antigen-specific T-cell infiltration at a site of antigen challenge in vivo. The repellant activity of HIV-1 gp120 on immune cells in vitro and in vivo was shown to be dependent on the V2 and V3 loops of HIV-1 gp120. These data suggest that the active movement of T cells away from CXCR4-binding HIV-1 gp120, which we previously termed fugetaxis, may provide a novel mechanism by which HIV-1 evades challenge by immune effector cells in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Cambridge, MA 02114 USA. Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Inst Med, Boston, MA 02115 USA. RP Poznansky, MC (reprint author), Partners AIDS Res Ctr, 149 13th St,5th Floor, Cambridge, MA 02139 USA. EM mpoznansky@partners.org FU NIAID NIH HHS [T32 AI 07387, R01 AI 49757, R01 AI049757, T32 AI007387] NR 76 TC 22 Z9 23 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 10 BP 5184 EP 5193 DI 10.1128/JVI.78.10.5184-5193.2004 PG 10 WC Virology SC Virology GA 817YF UT WOS:000221212100026 PM 15113900 ER PT J AU Owens, CM Song, BW Perron, MJ Yang, PC Stremlau, M Sodroski, J AF Owens, CM Song, BW Perron, MJ Yang, PC Stremlau, M Sodroski, J TI Binding and susceptibility to postentry restriction factors in monkey cells are specified by distinct regions of the human immunodeficiency virus type I capsid SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE TRANSCRIPTION COMPLEXES; HUMAN CYCLOPHILIN-A; HIV-1 VIRIONS; SIMIAN CELLS; RETROVIRUS RESTRICTION; ENVELOPE GLYCOPROTEINS; CYCLOSPORINE-A; LIFE-CYCLE; REPLICATION; INFECTION AB In cells of Old World and some New World monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after virus entry. The simian immunodeficiency virus SIVmac is less susceptible to these restrictions, a property that is determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on the surface of the HIV-1 capsid, changing them to the corresponding residues found on the SIVmac capsid. We identified two distinct pathways of escape from early, postentry restriction in monkey cells. One set of mutants that were altered near the base of the cyclophilin A-binding loop of the N-terminal capsid domain or in the interdomain linker exhibited a decreased ability to bind the restricting factor(s). Consistent with the location of this putative factor-binding site, cyclophilin A and the restricting factor(s) cooperated to achieve the postentry block. A second set of mutants that were altered in the ridge formed by helices 3 and 6 of the N-terminal capsid domain efficiently bound the restricting factor(s) but were resistant to the consequences of factor binding. These results imply that binding of the simian restricting factor(s) is not sufficient to mediate the postentry block to HIV-1 and that SIVmax capsids escape the block by decreases in both factor binding and susceptibility to the effects of the factor(s). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div AIDS,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div AIDS,Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NHLBI NIH HHS [P50 HL054785, HL 57485]; NIAID NIH HHS [P30 AI 28691, P30 AI028691] NR 48 TC 103 Z9 104 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 10 BP 5423 EP 5437 DI 10.1128/JCI.78.10.5423-5437.2004 PG 15 WC Virology SC Virology GA 817YF UT WOS:000221212100048 PM 15113921 ER PT J AU Yuan, W Craig, S Si, ZH Farzan, M Sodroski, J AF Yuan, W Craig, S Si, ZH Farzan, M Sodroski, J TI CD4-induced T-20 binding to human immunodeficiency virus type 1 gp120 blocks interaction with the CXCR4 coreceptor SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 TRANSMEMBRANE GLYCOPROTEIN; FUSION-ACTIVE CONFORMATION; ENVELOPE V3 LOOP; CHEMOKINE RECEPTOR; MONOCLONAL-ANTIBODIES; PEPTIDE INHIBITOR; ENTRY INHIBITORS; ATOMIC-STRUCTURE; SOLUBLE CD4; GP41 AB The synthetic peptide T-20, which corresponds to a sequence within the C-terminal heptad repeat region (HR2) of the human immunodeficiency virus type 1 (HIV-1) gp41 envelope glycoprotein, potently inhibits viral membrane fusion and entry. Although T-20 is thought to bind the N-terminal heptad repeat region (HR1) of gp41 and interfere with gp41 conformational changes required for membrane fusion, coreceptor specificity determined by the V3 loop of gp120 strongly influences the sensitivity of HIV-1 variants to T-20. Here, we show that T-20 binds to the gp120 glycoproteins of HIV-1 isolates that utilize CXCR4 as a coreceptor in a manner determined by the sequences of the gp120 V3 loop. T-20 binding to gp120 was enhanced in the presence of soluble CD4. Analysis of T-20 binding to gp120 mutants with variable loop deletions and the reciprocal competition of T-20 and particular anti-gp120 antibodies suggested that T-20 interacts with a gp120 region near the base of the V3 loop. Consistent with the involvement of this region in coreceptor binding, T-20 was able to block the interaction of gp120-CD4 complexes with the CXCR4 coreceptor. These results help to explain the increased sensitivity of CXCR4-specific HIV-1 isolates to the T-20 peptide. Interactions between the gp41 HR2 region and coreceptor-binding regions of gp120 may also play a role in the function of the HIV-1 envelope glycoproteins. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aids,Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aids,Dept Med & Microbiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aids,Dept Mol Genet, Cambridge, MA 02138 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, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [R01 AI039420, AI 24755, AI 39420, R37 AI024755, AI 41581, P30 AI028691, P30 AI 28691] NR 69 TC 41 Z9 42 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 10 BP 5448 EP 5457 DI 10.1128/JVI.78.10.5448-5457.2004 PG 10 WC Virology SC Virology GA 817YF UT WOS:000221212100050 PM 15113923 ER PT J AU Richardson-Burns, SM Tyler, KL AF Richardson-Burns, SM Tyler, KL TI Regional differences in viral growth and central nervous system injury correlate with apoptosis SO JOURNAL OF VIROLOGY LA English DT Article ID REOVIRUS-INDUCED APOPTOSIS; ATTACHMENT PROTEIN SIGMA-1; NF-KAPPA-B; SIALIC-ACID; TYPE-3; INFECTION; PATHOGENESIS; ACTIVATION; REQUIRES; MUTATIONS AB Infection of neonatal mice with reovirus T3 Dearing (T3D)), the prototypic neurotropic reovirus, causes fatal encephalitis associated with neuronal injury and virus-induced apoptosis throughout the brain. T3D variant K (VarK) is an antigenic variant that has a nearly 1 million-fold reduction in neurovirulence following intracerebral (i.c.) inoculation compared to T3D) and a restricted pattern of central nervous system injury with damage limited to the hippocampus, sparing other brain regions. We wished to determine whether the restricted pattern of VarK-induced injury was due to a reduced capacity to replicate in or injure cortical, as opposed to hippocampal, tissue. We found that following i.c. inoculation, VarK grew to similar titers as T3D in the hippocampus but had significantly lower titers in the cortex. Both viruses grew to identical titers and infected the same percentage of cells in mouse primary hippocampal cultures (MHC. In mouse primary cortical cultures (MCC) both the number of infected cells and the viral yield per infected cell were significantly lower for VarK than T3D. VarK-induced apoptosis was limited to the hippocampus in vivo, and in vitro both viruses induced apoptosis equally in MHC but VarK induced significantly less apoptosis than T3D in MCC. Growth of T3D in MCC was reduced to levels comparable to those of VarK following treatment of MCC with caspase inhibitors. Conversely, induction of apoptosis in VarK-infected MCC with fatty acid synthase-activating antibody significantly enhanced viral yield. These results suggest that the decreased neurovirulence of VarK may be due to its failure to efficiently induce apoptosis in cortical neurons. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, B-182,4200 E 9th Ave, Denver, CO 80262 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 NR 27 TC 30 Z9 30 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2004 VL 78 IS 10 BP 5466 EP 5475 DI 10.1128/JVI.78.10.5466-5475.2004 PG 10 WC Virology SC Virology GA 817YF UT WOS:000221212100052 PM 15113925 ER PT J AU Asthana, S Bhasin, S Butler, RN Fillit, H Finkelstein, J Harman, SM Holstein, L Korenman, SG Matsumoto, AM Morley, JE Tsitouras, P Urban, R AF Asthana, S Bhasin, S Butler, RN Fillit, H Finkelstein, J Harman, SM Holstein, L Korenman, SG Matsumoto, AM Morley, JE Tsitouras, P Urban, R TI Masculine vitality: Pros and cons of testosterone in treating the andropause SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BONE-MINERAL DENSITY; OLDER MEN; SERUM TESTOSTERONE; BODY-COMPOSITION; MUSCLE STRENGTH; YOUNG MEN; HEALTHY; CANCER; AGE; SUPPLEMENTATION C1 USA, Int Longev Ctr, New York, NY 10028 USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Kronos Longev Res Inst, Phoenix, AZ USA. Miraval Life Balance Resort, Tucson, AZ USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Butler, RN (reprint author), USA, Int Longev Ctr, 60 E 86th St, New York, NY 10028 USA. EM robertb@ilcusa.org; robertb@ilcusa.org RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 NR 47 TC 22 Z9 23 U1 3 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2004 VL 59 IS 5 BP 461 EP 465 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 820TB UT WOS:000221411100010 PM 15123756 ER PT J AU Rubenstein, LZ AF Rubenstein, LZ TI Joseph T. Freeman award lecture - Comprehensive geriatric assessment: From miracle to reality SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Biographical-Item C1 GRECC, VA Med Ctr, Sepulveda, CA 91343 USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Rubenstein, LZ (reprint author), GRECC, VA Med Ctr, 11E,16111 Plummer St, Sepulveda, CA 91343 USA. EM lzrubens@ucla.edu NR 0 TC 36 Z9 37 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2004 VL 59 IS 5 BP 473 EP 477 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 820TB UT WOS:000221411100012 PM 15123758 ER PT J AU Carroll, MC AF Carroll, MC TI The lupus paradox: Natural immunity is protective against disease SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Immunology in Renal Disease CY JUN 02-05, 2003 CL Berlin, GERMANY SP Int Soc Nephrol ID COMPLEMENT C1 CBR Inst Biomed Res Inc, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carroll, MC (reprint author), CBR Inst Biomed Res Inc, Boston, MA USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2004 VL 65 IS 5 BP 1540 EP 1540 DI 10.1111/j.1523-1755.2004.05403.x PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 815CR UT WOS:000221020900004 ER PT J AU Lum, G D'Amarino, M AF Lum, G D'Amarino, M TI Suspected transfusion reactions: Can they be computerized? SO LABORATORY MEDICINE LA English DT Article C1 VA Boston Healthcare Syst, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD MAY PY 2004 VL 35 IS 5 BP 307 EP 310 DI 10.1309/XQF0LWEQCL4FY5WB PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 815CU UT WOS:000221021200019 ER PT J AU Albert, C AF Albert, C TI Fish oil - an appetising alternative to anti-arrhythmic drugs? SO LANCET LA English DT Editorial Material ID POLYUNSATURATED FATTY-ACIDS; SUDDEN CARDIAC DEATH; MYOCARDIAL-INFARCTION; CONSUMPTION; PREVENTION; RISK; DISEASE; TRIAL C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02215 USA. RP Albert, C (reprint author), Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. EM calbert@partners.org NR 14 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 1 PY 2004 VL 363 IS 9419 BP 1412 EP 1413 DI 10.1016/S0140-6736(04)16135-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 816ST UT WOS:000221130300004 PM 15121400 ER PT J AU Butt, AA Aldridge, KE Sanders, CV AF Butt, AA Aldridge, KE Sanders, CV TI Infections related to the ingestion of seafood. Part II: parasitic infections and food safety SO LANCET INFECTIOUS DISEASES LA English DT Review ID ANISAKIS-SIMPLEX; CRYPTOSPORIDIUM-PARVUM; NANOPHYETUS-SALMINCOLA; ALLERGIC REACTIONS; ACUTE URTICARIA; FISH; SHELLFISH; DISEASES; ANAPHYLAXIS; OUTBREAK AB Parasites are responsible for a substantial number of seafood-associated infections. The factor most commonly associated with infection is consumption of raw or undercooked seafood. People with underlying disorders, particularly liver disease, are more susceptible to infection. In the first part of this review, published last month, we discussed the viral and bacterial agents associated with consumption of seafood. In part II, we discuss the parasites commonly associated with seafood consumption. Parasites readily identifiable from both consumable seafood and infected human beings include nematodes, trematodes, cestodes, and protozoa. The salient features associated with seafood-related parasite infestations are discussed. To provide a safe product for consumers, the seafood industry and the government in the USA have undertaken specific measures, which include good manufacturing practices and hazards analysis and critical control points implemented by the government and regulatory agencies. Consumers should take common precautions including obtaining seafood from reputable sources especially if the seafood is to be consumed uncooked. Adequate cooking of seafood is the safest way of preventing related infections. C1 Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Louisiana State Univ, Ctr Hlth Sci, Dept Med, Infect Dis Sect, New Orleans, LA USA. RP Butt, AA (reprint author), Univ Pittsburgh, Div Infect Dis, 3601 5th Ave,Suite 3A,Falk Bldg, Pittsburgh, PA 15213 USA. EM butta@msx.dept-med.pitt.edu NR 61 TC 37 Z9 38 U1 1 U2 18 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD MAY PY 2004 VL 4 IS 5 BP 294 EP 300 DI 10.1016/S1473-3099(04)01005-9 PG 7 WC Infectious Diseases SC Infectious Diseases GA 817ER UT WOS:000221161300020 PM 15120346 ER PT J AU Ghersi, D Campbell, EG Pentz, R Macpherson, CC AF Ghersi, D Campbell, EG Pentz, R Macpherson, CC TI The future of institutional review boards SO LANCET ONCOLOGY LA English DT Editorial Material ID RESEARCH ETHICS COMMITTEES; OF-INTEREST; TRIALS; SALE C1 Univ Sydney, Clin Trials Ctr, Natl Hlth & Med Res Ctr, Sydney, NSW 2006, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. St Georges Univ, Sch Med, St Georges, Grenada. RP Ghersi, D (reprint author), Univ Sydney, Clin Trials Ctr, Natl Hlth & Med Res Ctr, Sydney, NSW 2006, Australia. EM Davina@ctc.usyd.edu.au; ecampbell@partners.org; rebecca_pentz@emoryhealthcare.org; ccox@sgu.edu NR 27 TC 7 Z9 7 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2004 VL 5 IS 5 BP 325 EP 329 DI 10.1016/S1470-2045(04)01473-1 PG 5 WC Oncology SC Oncology GA 819CS UT WOS:000221291400023 PM 15120672 ER PT J AU Kamil, SH Vacanti, MP Aminuddin, BS Jackson, MJ Vacanti, CA Eavey, RD AF Kamil, SH Vacanti, MP Aminuddin, BS Jackson, MJ Vacanti, CA Eavey, RD TI Tissue engineering of a human sized and shaped auricle using a mold SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 04-05, 2003 CL NASHVILLE, TN SP Amer Soc Pediat Otolaryngol ID CARTILAGE AB Objectives: The creation of a tissue-engineered auricle was initially successful in an immunocompromised nude mouse model. Subsequently, an immunocompetent porcine model successfully generated a helical construct. We wished to evaluate the novel technique of using a mold to create a complete, anatomically refined auricle in a large animal model. Methods: Mixtures of autogenous chondrocytes and biodegradable polymers were used inside a perforated, auricle shaped hollow gold mold. Three biodegradable polymers (calcium alginate, pluronic F-127, and polyglycolic acid) were used to retain the seeded chondrocytes inside the mold. These molds, along with a control, were implanted subcutaneously in the abdominal area of 10 animals (pigs and sheep). The constructs were removed after 8 to 20 weeks and were assessed by gross morphology and histology. Results: All the gold implants were well tolerated by the animals. The implants using calcium alginate (n = 3) generated constructs of the exact shape and size of a normal human ear; the histology demonstrated mostly normal cartilage with some persistent alginate. The implants with pluronic F-127 (n = 3) resulted in cartilage with essentially normal histology, although leakage outside the molds and external cartilage generation was noted. Polyglycolic acid implants (n = 3) produced no useful cartilage because of an inflammatory reaction with fibrosis. The empty control mold (n = 1) demonstrated only a very small amount of fibrous tissue inside. Conclusion: A tissue-engineered human sized auricle of normal anatomic definition can be generated in an immunocompetent large-animal model using a mold technique. Although further refinements will be necessary, the technique appears promising for potential use in patients with microtia. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM roland_eavey@meei.harvard.edu NR 10 TC 44 Z9 48 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2004 VL 114 IS 5 BP 867 EP 870 DI 10.1097/00005537-200405000-00015 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 822KJ UT WOS:000221537900015 PM 15126746 ER PT J AU Dailey, SH Kobler, JB Zeitels, SM AF Dailey, SH Kobler, JB Zeitels, SM TI A laryngeal dissection station: Educational paradigms in phonosurgery SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT World Congress of Bronchology CY JUN 15, 2002 CL BOSTON, MA ID SURGICAL RESIDENTS; LEARNING-CURVE; VOCAL PITCH; EAR SURGERY; SKILLS; MYRINGOTOMY; EXPERIENCE; INSERTION; MODEL AB Objectives: To introduce a new tool for phonosurgical training and education. A multitude of innovations in complex laryngeal surgery has catalyzed new educational initiatives. Establishing dexterity in phonomicrosurgery is often difficult to achieve while working on patients because of the narrow margin for success. Furthermore, laryngoplastic phonosurgery and open partial laryngectomy require sophisticated knowledge of precise anatomic relationships, which can be difficult to express in images. Finally, many teaching programs do not have a high volume of these procedures, and there is a significant need to transmit this information in continuing education courses. Study Design: Prototype design. Methods: A laryngeal dissection station (LDS) was designed to facilitate the acquisition of high-level procedural skill sets for both transoral and transcervical techniques. Results: This LDS can be used in existing temporal-bone laboratories by using cadaveric larynges. A rectangular frame supports two adjustable holders, one for the larynx and one for the examining speculum of a laryngoscope. Procedures are performed with the larynx fixed in space by a novel fixator. Variation in position and orientation of the components affords simulation of both microlaryngoscopy and open surgery. The dissection station can accommodate virtually any laryngoscope, regardless of size or shape. Conclusions: This training apparatus should facilitate laryngeal surgical instruction in residency training and continuing medical education. This device and others like it can help establish clinical competency in laryngology, should this become necessary in future educational models of residency training and recertification. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Div Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Sch Med,Div Laryngol & Voice & Speech Lab, Boston, MA 02115 USA. RP Dailey, SH (reprint author), 333 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM shdailey@partners.org NR 30 TC 22 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2004 VL 114 IS 5 BP 878 EP 882 DI 10.1097/00005537-200405000-00017 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 822KJ UT WOS:000221537900017 PM 15126748 ER PT J AU Letestu, R Ugo, V Valensi, F Radford-Weiss, I Nataf, J Levy, V Gribben, JG Troussard, X Ajchenbaum-Cymbalista, F AF Letestu, R Ugo, V Valensi, F Radford-Weiss, I Nataf, J Levy, V Gribben, JG Troussard, X Ajchenbaum-Cymbalista, F TI Prognostic impact of p27KIP1 expression in cyclin D1 positive lymphoproliferative disorders SO LEUKEMIA LA English DT Article DE p27KIP1; cyclin D1; lymphoproliferative disorder; mantle cell lymphoma; prognosis ID MANTLE-CELL LYMPHOMA; CHRONIC-LYMPHOCYTIC-LEUKEMIA; DEPENDENT KINASE INHIBITOR; V-H GENES; NON-HODGKINS-LYMPHOMAS; CDK INHIBITOR; AGGRESSIVE VARIANTS; PROTEIN EXPRESSION; SOMATIC MUTATIONS; P27(KIP1) AB Nodal mantle cell lymphoma (MCL) is a well-defined entity, but non-nodal leukemic cyclin D1 positive lymphoproliferative disorders have been reported and their relationship with MCL remains controversial and their prognosis heterogeneous. We prospectively studied the expression of cyclin D1 in CD5 positive leukemic B lymphoproliferative disorders at diagnosis and identified 65 cases overexpressing cyclin D1. We did not distinguish any clinical or biological criteria allowing one to identify a non-MCL group. Multivariate analysis identified age, anemia and p27kip1 expression as independent prognostic factors of survival. By univariate analysis, p27kip1 high expression proved to be the strongest predictor of prolonged survival. The median survival of p27 low expressors was 30 months, while it was not reached for p27 high expressors. A high level of p27 expression was often found associated with the absence of nodal involvement and the presence of somatic mutations, but neither of them was restricted to the p27 high expression group. In conclusion, we hypothesize that MCL and these cyclin D1 positive leukemic lymphoproliferative disorders represent a continuous spectrum of diseases. Determination of p27 expression level appears as a routine applicable test allowing identification of a subset of patients who could be considered for different therapeutic approaches. C1 Hop Avicenne, Serv Hematol Biol, F-93000 Bobigny, France. Hop Necker Enfants Malad, Paris, France. Hop Hotel Dieu, F-75181 Paris, France. Hop St Louis, Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop Cote Nacre, Caen, France. RP Ajchenbaum-Cymbalista, F (reprint author), Hop Avicenne, Serv Hematol Biol, F-93000 Bobigny, France. EM florence.cymbalista@avc.ap-hop-paris.fr NR 63 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2004 VL 18 IS 5 BP 953 EP 961 DI 10.1038/sj.leu.2403337 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 815FB UT WOS:000221027100009 PM 15029207 ER PT J AU Ballen, KK Colvin, G Porter, D Quesenberry, PJ AF Ballen, KK Colvin, G Porter, D Quesenberry, PJ TI Low dose total body irradiation followed by allogeneic lymphocyte infusion for refractory hematologic malignancy - an updated review SO LEUKEMIA & LYMPHOMA LA English DT Article DE transplantation; cellular immune therapy; leukemia ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; DONOR LEUKOCYTE INFUSIONS; VERSUS-HOST-DISEASE; UMBILICAL-CORD BLOOD; ADOPTIVE IMMUNOTHERAPY; MIXED CHIMERISM; TUMOR INDUCTION; THERAPY; RECIPIENTS AB Allogeneic stem cell transplantation is curative for certain cancers, but the high doses of chemotherapy and radiotherapy used in conventional myeloablative conditioning regimens may lead to severe toxicity. In our initial study, we treated 25 patients with refractory cancers with 100 cGy total body irradiation (TBI) followed by allogeneic, non mobilized peripheral blood cells. Eighteen patients received sibling and 7 patients received unrelated cord blood stem cells. None of the 13 patients with solid tumors achieved donor chimerism or had a sustained response. Twelve patients with hematologic malignancies were treated, 1 received a cord blood transplant and 11 received sibling donor cells. Nine of these 11 patients achieved donor chimerism, ranging from 5% to 100%. Four patients had sustained complete remission of their cancers, and 2 are long-term survivors. The development of chimerism correlated with total previous myelotoxic chemotherapy (p<0.001). This technique is now being extended into the haploidentical setting. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Roger Williams Med Ctr, Providence, RI USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM kballen@partners.org FU NCI NIH HHS [L30 CA104092-02, L30 CA104092-01] NR 39 TC 5 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAY PY 2004 VL 45 IS 5 BP 905 EP 910 DI 10.1080/10428190310001628167 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 800YP UT WOS:000220063900005 PM 15291347 ER PT J AU Sattler, M Salgia, R AF Sattler, M Salgia, R TI Targeting c-Kit mutations: basic science to novel therapies SO LEUKEMIA RESEARCH LA English DT Review DE receptor tyrosine kinase; Kit; signal transduction; mutation; c-Kit inhibition ID STEM-CELL FACTOR; GASTROINTESTINAL STROMAL TUMORS; PROTEIN-KINASE-C; RECEPTOR TYROSINE KINASE; GROWTH-FACTOR RECEPTORS; SRC FAMILY KINASES; SPOTTING W LOCUS; LUNG-CANCER; SIGNAL-TRANSDUCTION; IN-VITRO AB The Kit receptor tyrosine kinase is a transmembrane receptor that is expressed in a variety of different tissues and mediates pleiotropic biological effects through its ligand stein cell factor (SCF). Sporadic mutations of Kit as well as autocrine/paracrine activation mechanisms of the SCF/Kit pathway have been implicated in a variety of malignancies, where its primary contribution to metastases is in enhancing tumor growth and reducing apoptosis. For example, Kit is frequently Mutated and activated in gastrointestinal stromal tumors (GISTs) and there is ligand-mediated activation of Kit in some lung cancers. Kit is a convenient target in Kit-induced tumors and inhibition of this receptor with the small molecule drug Gleevec (imatinib mesylate, STI571) in GIST has shown dramatic efficacy. Unfortunately, past experience has demonstrated that chemotherapy of cancers with a single drug often leads to resistance of the cancer. Further understanding of the molecular mechanisms underlying Kit-rnediated transformation is therefore important and may lead to the identification of further novel drug targets. These Kit-specific signaling pathways may then be targeted to overcome potential drug resistance. This review will focus on our understanding of the molecular mechanisms involved in transformation by Kit. The potential mechanisms by which Kit induces cellular transformation are described. We will also discuss the role and expression of Kit in various malignancies. Ultimately, the understanding of c-Kit biology. biochemistry, and mutational analysis will lead to better therapeutics. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Medford, MA 02155 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Salgia, R (reprint author), Univ Chicago, Dept Med, Hematol Oncol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu NR 139 TC 47 Z9 49 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2004 VL 28 SU 1 BP S11 EP S20 DI 10.1016/j.leukres.2003.10.004 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 831QS UT WOS:000222210700003 PM 15036937 ER PT J AU Wittman, B Horan, J Baxter, J Goldberg, J Felgar, R Baylor, E Cromwell, B Cross, N Bennett, JM AF Wittman, B Horan, J Baxter, J Goldberg, J Felgar, R Baylor, E Cromwell, B Cross, N Bennett, JM TI A 2-year-old with atypical CML with a t(5;12)(q33;p13) treated successfully with imatinib mesylate SO LEUKEMIA RESEARCH LA English DT Article DE atypical CML; imatinib mesylate; ETV6-PDGFRB fusion gene; t(5;12) ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; FACTOR RECEPTOR-BETA; ABL TYROSINE KINASE; CHROMOSOME; INHIBITOR; FUSION; MICE; GENE; TEL AB Atypical chronic myelogenous leukemia (aCML) is a myelodysplastic/myeloproliferative disorder that usually occurs in older adults, Here we report a pediatric patient with aCML and a t(5;12)(q33;p13) with a corresponding fusion gene ETV6-PDGFRB. Because the PDGFRB tyrosine kinase is one of the known targets of tyrosine kinase inhibitors, this patient achieved cytogenetic and molecular remission with treatment with imatinib mesylate (formerly STI571; now Gleevec in the United States and Glivec in Europe). This case illustrates one of many myelodysplastic/myeloproliferative disorders that can be treated with this particular tyrosine kinase inhibitor. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Rochester, Golisano Childrens Hosp Strong, Med Ctr, Dept Pediat Hematol Oncol, New Rochelle, NY 14642 USA. Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury SP2 8BJ, Wilts, England. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Horan, J (reprint author), Univ Rochester, Golisano Childrens Hosp Strong, Med Ctr, Dept Pediat Hematol Oncol, B ox 777,601 Elmwood Ave, New Rochelle, NY 14642 USA. NR 18 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2004 VL 28 SU 1 BP S65 EP S69 DI 10.1016/j.leukres.2003.10.011 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 831QS UT WOS:000222210700010 PM 15036944 ER PT J AU Wirth, LJ Carter, MR Janne, PA Johnson, BE AF Wirth, LJ Carter, MR Janne, PA Johnson, BE TI Outcome of patients with pulmonary carcinoid tumors receiving chemotherapy or chemoradiotherapy SO LUNG CANCER LA English DT Article DE carcinoid tumor; neuroendocrine carcinoma; lung neoplasms; chemotherapy; radiotherapy ID CELL LUNG-CANCER; SOUTHWEST-ONCOLOGY-GROUP; NEUROENDOCRINE TUMORS; PHASE-III; ETOPOSIDE; CISPLATIN; SURVIVAL; CLASSIFICATION; COMBINATION; MULTICENTER AB Study objectives: To determine the outcome of patients with pulmonary typical and atypical carcinoid tumors treated with chemotherapy with or without radiotherapy. Methods: Patients with pulmonary neuroendocrine tumors treated at our institution from 1990 to 2001 were identified. The medical records of patients with diagnoses of typical or atypical pulmonary carcinoids were reviewed for the presence of evaluable disease, treatment with chemotherapy with or without radiotherapy, response to these treatments, survival and cause of death. Results: Eighteen patients with typical (n = 8) or atypical (n = 10) pulmonary carcinoid tumors who were treated with chemotherapy with or without radiotherapy were identified. Of these, four received chemotherapy plus chest radiotherapy. Three of these had stable disease and one had a partial response. One of the patients with stable disease to chemoradiotherapy subsequently received chemotherapy atone, to which he had a complete response. Fourteen additional patients were treated with 18 chemotherapy regimens. There were two partial, responses, eight stable disease, seven progressive disease and one allergic reaction precluding further treatment. The overall response rate to any chemotherapy was 3/15 (20%, 95% Cl 0.07-0.45), and the best overall response rate to chemotherapy with or without chest radiotherapy was 4/18 (22%, 95% Cl 0.09-0.45). Median overall survival was 20 months (95% Cl 0-51 months). Conclusions: Patients with typical and atypical pulmonary carcinoid tumors can respond to chemotherapy with or without chest radiotherapy, though with response rates that appear less than those of small cell lung cancers. Further characterization of pulmonary carcinoid tumors and study of treatment alternatives for unresectabte disease is warranted. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wilford Hall USAF Med Ctr, Lackland Air Force Base, Dept Pathol, San Antonio, TX USA. RP Wirth, LJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM lwirth@partners.org NR 35 TC 41 Z9 43 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAY PY 2004 VL 44 IS 2 BP 213 EP 220 DI 10.1016/j.lungcan.2003.11.016 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 817CW UT WOS:000221156600009 PM 15084386 ER PT J AU Janne, PA Gurubhagavatula, S Yeap, BY Lucca, J Ostler, P Skarin, AT Fidias, P Lynch, TJ Johnson, BE AF Janne, PA Gurubhagavatula, S Yeap, BY Lucca, J Ostler, P Skarin, AT Fidias, P Lynch, TJ Johnson, BE TI Outcomes of patients with advanced non-small cell tung cancer treated with gefitinib (ZD1839, 'Iressa') on an expanded access study SO LUNG CANCER LA English DT Article DE lung carcinoma; non-small cell; receptor tyrosine kinase; epidermal growth factor receptor; clinical trial ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; PHASE-III TRIAL; LUNG-CANCER; CHEMOTHERAPY REGIMENS; SURVIVAL; STAGE; VINORELBINE; EXPERIENCE; EXPRESSION AB Purpose: To investigate the anti-tumor activity and toxicity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839 or Iressa(TM); AstraZeneca Pharmaceuticals, Wilmington, DE), in patients with advanced non-small cell lung cancer (NSCLC). Methods: This was an open Label., expanded access program (EAP) of oral gefitinib administered at 250 mg per day continuously until evidence of undue toxicity or disease progression. Results: Two hundred consecutive patients with advanced NSCLC were enrolled in this study. The median number of prior chemotherapy regimens was 2 (range 0-6). One hundred seventy-two patients were treated with gefitinib; 23 expired from disease progression prior to treatment and 5 withdrew their consent. One hundred fifty-four patients are evaluable for toxicity; 8 (5.2%) experienced grade 3/4 toxicity; 2 patients discontinued therapy for grade 3 rash and one for grade 3 nausea. Of 172 patients evaluable for efficacy, 7 (4.1%; 95% Cl; 1.7-8.2%) experienced a partial response (PR); 60 patients (34.9%) had stable disease (SD) as their best response. Median survival for all patients was 4.5 months (95% Cl; 4.1-4.9 months). One-year survival was 29%. Significant independent prognostic factors associated with improved survival were female gender, good performance status (0/1), and adenocarcinoma histology. Conclusion: Gefitinib has anti-tumor activity, in a heterogeneous population of NSCLC patients treated on the EAP study. Treatment with gefitinib in this population is associated with a Longer survival in women, those with good performance status and in patients with adenocarcinomas. These findings need to be further validated in additional clinical studies. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, 44 Binney St,D1234, Boston, MA 02115 USA. EM pjanne@partners.org NR 28 TC 150 Z9 156 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAY PY 2004 VL 44 IS 2 BP 221 EP 230 DI 10.1016/j.lungcan.2003.12.014 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 817CW UT WOS:000221156600010 PM 15084387 ER PT J AU Sun, YP Schmidt, NO Schmidt, K Doshi, S Rubin, JB Mulkern, RV Carroll, R Ziu, M Erkmen, K Poussaint, TY Black, P Albert, M Burstein, D Kieran, MW AF Sun, YP Schmidt, NO Schmidt, K Doshi, S Rubin, JB Mulkern, RV Carroll, R Ziu, M Erkmen, K Poussaint, TY Black, P Albert, M Burstein, D Kieran, MW TI Perfusion MRI of U87 brain tumors in a mouse model SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE arterial spin labeling; perfusion MRI; brain tumor in mouse model; antiangiogenesis ID CEREBRAL-BLOOD-FLOW; GLIOBLASTOMA-MULTIFORME; ARTERIAL WATER; GENE-THERAPY; NMR; SPECTROSCOPY; INVERSION; DISEASE; GROWTH; VOLUME AB Continuous arterial spin labeling (CASL) was used to obtain an index of cerebral blood flow (ICBF) in the normal mouse brain and in an orthotopic mouse model of human U87 high-grade glioma at 8.5 T. Under the assumption of a constant tissue: blood partition coefficient for water in different tissues, the mean ICBF (n = 14) was found to be 50 +/- 9 mL/100g/min for tumor core and 209 +/- 11 mL/100g/min for normal tissue. The apparent T-1 (T-1app) was 2.01 +/- 0.06 sec for tumor core and 1.66 +/- 0.03 sec for normal tissue. The ICBF and the T-1app values were significantly different (P < 0.001) between these two regions. The detailed changes of ICBF and T-1app in the transition from the tumor core through the tumor periphery to surrounding tissue were studied. Immunohistochemistry indicated that tumor vascularity was not uniform, with microvessel density highest in normal brain and the tissue surrounding the tumor and lowest in the tumor core. The large difference in ICBF between the tumor core and normal tissue suggests that this index might be useful for the assessment of the efficacy of antiangiogenic therapy. Magn Reson Med 51:893-899, 2004. (C) 2004 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Sun, YP (reprint author), Brigham & Womens Hosp, Dept Radiol, 221 Longwood Ave, Boston, MA 02115 USA. EM ysun@bwh.harvard.edu RI Schmidt, Nils Ole/D-5696-2014; OI Ziu, Mateo/0000-0002-3671-2638; Kieran, Mark/0000-0003-2184-7692 FU NCRR NIH HHS [RR14792] NR 38 TC 40 Z9 44 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAY PY 2004 VL 51 IS 5 BP 893 EP 899 DI 10.1002/mrm.20029 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 818IO UT WOS:000221239000004 PM 15122670 ER PT J AU Meterko, M Mohr, DC Young, GJ AF Meterko, M Mohr, DC Young, GJ TI Teamwork culture and patient satisfaction in hospitals SO MEDICAL CARE LA English DT Article DE organizational culture; patient satisfaction; teamwork ID CUSTOMER SATISFACTION; MANAGEMENT; ATTITUDES; QUALITY AB Background: A growing line of research indicates a positive relationship between a healthcare organization's culture and various performance measures. In these studies, a key cultural characteristic is the emphasis placed on teamwork. None of the studies, however, have examined teamwork culture relative to patient satisfaction, which is now 1 of the most widely used performance measures for healthcare organizations. Objectives: This study investigated the relationship between teamwork culture of hospitals and patient reports of their satisfaction with the care they received. Methods: The study setting was the Veterans Health Administration (VHA), Department of Veterans Affairs. The study sample consisted of 125 VHA hospitals for which independent and valid sources of data for culture and patient satisfaction were obtained. Each hospital's culture was assessed relative to 4 dimensions: teamwork, entrepreneurial, bureaucratic, and rational. Patient satisfaction data were available for both inpatient and outpatient settings. Results: Results from multivariate regression analyses indicated a significant and positive relation between teamwork culture and patient satisfaction for inpatient care, and a significant and negative relation between bureaucratic culture and patient satisfaction for inpatient care. Additional analyses revealed an almost 1 standard deviation difference in patient satisfaction scores between hospitals in the top third and bottom third of the distribution for the teamwork culture measure. Conclusion: Study results suggest that hospitals and possibly other healthcare organizations should strive to develop a culture emphasizing teamwork and deemphasizing those aspects of bureaucracy that are not essential to assuring efficiency and quality care. C1 VA Boston Healthcare Syst, Management Decis & Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Program Hlth Policy & Management, Boston, MA 02215 USA. RP Young, GJ (reprint author), VA Boston Healthcare Syst, Management Decis & Res Ctr, 152M,150 S Huntington Ave, Boston, MA 02130 USA. EM health@bu.edu NR 19 TC 126 Z9 128 U1 3 U2 38 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2004 VL 42 IS 5 BP 492 EP 498 DI 10.1097/01.mlr.0000124389.58422.b2 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 816KL UT WOS:000221108700014 PM 15083111 ER PT J AU Hirshkowitz, M AF Hirshkowitz, M TI Normal human sleep: an overview SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID CYCLE; BRAIN; AGE AB This article discusses normal human sleep. Landmarks leading up to the understanding of human sleep, electroencephalographic definitions, and general characteristics of normal human sleep are presented. Actuarial laboratory data, for both night 1 and night 2, are provided with an explanation of how they are compiled. Finally, the mechanisms governing sleep and wakefulness are reviewed. This information is critical to understanding abnormal sleep associated with sleep disorders. C1 Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sleep Ctr, Houston, TX 77030 USA. Methodist Hosp, Sleep Diagnost Lab, Houston, TX USA. RP Hirshkowitz, M (reprint author), Baylor Coll Med, Dept Psychiat, 1 Baylor Plaza, Houston, TX 77030 USA. EM maxh@bcm.tmc.edu NR 24 TC 39 Z9 42 U1 5 U2 14 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2004 VL 88 IS 3 BP 551 EP + DI 10.1016/j.mcn.2004.01.001 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 815NS UT WOS:000221049600002 PM 15087204 ER PT J AU Brown, EB Boucher, Y Nasser, S Jain, RK AF Brown, EB Boucher, Y Nasser, S Jain, RK TI Measurement of macromolecular diffusion coefficients in human tumors SO MICROVASCULAR RESEARCH LA English DT Article DE extracellular matrix; FRAP; drug transport; photobleaching ID HUMAN CERVICAL-MUCUS; TRANSPORT; CONVECTION; ANTIBODY; FLUID; PRESSURE; COLLAGEN; MICE; GELS AB The diffusive transport of macromolecules in tumors is an important determinant of the delivery of many anticancer therapeutics. However, measurements of diffusive transport to date have only been performed in animal models. In this work, diffusion coefficients of BSA and IgM were measured in human tumor biopsies (cooled to 4-7degreesC to prevent degradation) using fluorescence recovery after photobleaching. To quantify the effects of excision and cooling, the diffusion coefficient of BSA and IgM was measured in human tumor xenografts in situ and after cooling and excision. The change in diffusion coefficients before and after excision of xenografts was used to calculate in vivo diffusion coefficients in human tumors from ex vivo measurements. Using this approach, we obtained the first quantitative determinations of macromolecular diffusion coefficients in human tumors and find that the diffusion coefficients of BSA and IgM in human colon were adenocarcinomas higher than those in xenografts. This difference is consistent with lower collagen content in the accessible regions of these human tumors. These measurements allow the quantitative prediction of the diffusive transport of like-sized macromolecular therapeutics in human tumors. These measurements should help in modeling the transport of novel large MW therapeutics, and hence in estimating their distribution and efficacy in tumors. (C) 2004 Elsevier Inc. All rights reserved. C1 Edwin L Steele Lab Tumor Biol, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brown, EB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 734, Boston, MA 02114 USA. EM edbrown@steele.mgh.harvard.edu FU NCI NIH HHS [P01CA80134] NR 20 TC 45 Z9 47 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAY PY 2004 VL 67 IS 3 BP 231 EP 236 DI 10.1016/j.mvr.2004.02.001 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 821ER UT WOS:000221443700005 PM 15121448 ER PT J AU Scharschmidt, E Wegener, E Heissmeyer, V Rao, A Krappmann, D AF Scharschmidt, E Wegener, E Heissmeyer, V Rao, A Krappmann, D TI Degradation of Bcl10 induced by T-cell activation negatively regulates NF-kappa B signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CASPASE RECRUITMENT DOMAIN; KINASE-C-THETA; UBIQUITIN-PROTEIN LIGASES; LIPID RAFT RECRUITMENT; CBL-B; LYMPHOCYTE-ACTIVATION; MALT LYMPHOMA; IMMUNE-RESPONSES; IL-2 PROMOTER; PKC-THETA AB Bcl10 is a critical regulator of NF-kappaB activity in T and B cells, coupling antigen receptor signaling to NF-kappaB activation via protein kinase C (PKC). Here we show that PKC or T-cell receptor (TCR)/CD28 signaling results in downregulation of Bcl10 protein levels, thereby attenuating NF-kappaB transcriptional activity. Bcl10 degradation requires an intact caspase recruitment domain and is not observed after stimulation with tumor necrosis factor alpha or lipopolysaccharides. Bcl10 downregulation is not affected by proteasome inhibitors but is accompanied by transient localization to lysosomal vesicles, suggesting involvement of the lysosomal pathway rather than the proteasome. The HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and degradation of Bcl10, thus downmodulating NF-kappaB activation. Since CD3/CD28-induced activation of JNK is not affected by the decline of Bcl10, degradation of Bcl10 selectively terminates IKK/NF-kappaB signaling in response to TCR stimulation. Together, these results suggest a new mechanism of negative signaling in which TCR/PKC signaling initially activates Bcl10 but later promotes its degradation. C1 Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Krappmann, D (reprint author), Max Delbruck Ctr Mol Med, Robert Rossle Str 10, D-13125 Berlin, Germany. EM dkrapp@mdc-berlin.de NR 73 TC 82 Z9 86 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2004 VL 24 IS 9 BP 3860 EP 3873 DI 10.1128/MCB.24.9.3860-3878.2004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 813HL UT WOS:000220898100026 PM 15082780 ER PT J AU Okamura, H Garcia-Rodriguez, C Martinson, H Qin, J Virshup, DM Rao, A AF Okamura, H Garcia-Rodriguez, C Martinson, H Qin, J Virshup, DM Rao, A TI A conserved docking motif for CK1 binding controls the nuclear localization of NFAT1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CASEIN KINASE-I; GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR NFAT1; BETA-CATENIN; PROTEIN-KINASE; NF-AT; PHOSPHORYLATION SITES; SIGNAL-TRANSDUCTION; CUBITUS INTERRUPTUS; GENE-EXPRESSION AB In resting cells, the NFAT1 transcription factor is kept inactive in the cytoplasm by phosphorylation on multiple serine residues. These phosphorylated residues are primarily contained within two types of serine-rich motifs, the SRR-1 and SP motifs, which are conserved within the NFAT family. Several different kinases have been proposed to regulate NFAT, but no single candidate displays the specificity required to fully phosphorylate both types of motifs; thus, the identity of the kinase that regulates NFAT activity remains unclear. Here we show that the NFAT1 serine motifs are regulated by distinct kinases that must coordinate to control NFAT1 activation. CK1 phosphorylates only the SRR-1 motif, the primary region required for NFAT1 nuclear import. CK1 exists with NFAT1 in a high-molecular-weight complex in resting T cells but dissociates upon activation. GSK3 does not phosphorylate the SRR-1 region but can target the NFAT1 SP-2 motif, and it synergizes with CK1 to regulate NFAT1 nuclear export. We identify a conserved docking site for CK1 in NFAT proteins and show that mutation of this site disrupts NFAT1-CK1 interaction and causes constitutive nuclear localization of NFAT1. The CK1 docking motif is present in proteins of the Wnt, Hedgehog, and circadian-rhythm pathways, which also integrate the activities of CK1 and GSK3. C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Baylor Coll Med, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Cellular & Mol Biol, Houston, TX 77030 USA. Univ Utah, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, CBR, Inst Biomed Res, 200 Longwood Ave,Rm 144, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu RI Virshup, David/C-1449-2009 OI Virshup, David/0000-0001-6976-850X FU NCI NIH HHS [T32 CA72320, T32 CA072320]; NIAID NIH HHS [AI 40127, R01 AI040127]; NIGMS NIH HHS [GM 60387, R01 GM060387] NR 58 TC 117 Z9 120 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2004 VL 24 IS 10 BP 4184 EP 4195 DI 10.1128/MCB.24.10.4184-4195.2004 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900010 PM 15121840 ER PT J AU Taubert, S Gorrini, C Frank, SR Parisi, T Fuchs, M Chan, HM Livingston, DM Amati, B AF Taubert, S Gorrini, C Frank, SR Parisi, T Fuchs, M Chan, HM Livingston, DM Amati, B TI E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G(1) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DIHYDROFOLATE-REDUCTASE PROMOTER; CELL-CYCLE; RETINOBLASTOMA PROTEIN; IN-VIVO; C-MYC; TRANSCRIPTION FACTORS; S-PHASE; ONCOGENIC TRANSFORMATION; ESSENTIAL COFACTOR; FAMILY-MEMBERS AB E2F proteins can either activate or repress transcription. Following mitogenic stimulation, repressive E2F4-p130-histone deacetylase complexes dissociate from, while activating species (E2F1, -2, and -3) associate with, target promoters. Histones H3 and H4 simultaneously become hyperacetylated, but it remains unclear whether this is a prerequisite or a consequence of E2F binding. Here, we show that activating E2F species are required for hyperacetylation of target chromatin in human cells. Overexpression of a dominant-negative (DN) E2F1 mutant in serum-stimulated T98G cells blocked all E2F binding, H4 acetylation, and, albeit partially, H3 acetylation. Target gene activation and S-phase entry were also blocked by DN E2F1. Conversely, ectopic activation of E2F1 rapidly induced H3 and H4 acetylation, demonstrating a direct role for E2F in these events. E2F1 was previously shown to bind the histone acetyltransferases (HATs) p300/CBP and PCAF/GCN5. In our hands, ectopically expressed E2F1 also bound the unrelated HAT Tip60 and induced recruitment of five subunits of the Tip60 complex (Tip60, TRRAP, p400, Tip48, and Tip49) to target promoters in vivo. Moreover, E2F-dependent recruitment of Tip60 to chromatin occurred in late G, following serum stimulation. We speculate that the activities of multiple HAT complexes account for E2F-dependent acetylation, transcription, and S-phase entry. C1 European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy. DNAX Res Inst Molec & Cellular Biol Inc, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Amati, B (reprint author), European Inst Oncol, Dept Expt Oncol, Via Ripmonti 435, I-20141 Milan, Italy. EM bruno.amati@ieo-research.it RI Taubert, Stefan/A-8104-2015 OI Taubert, Stefan/0000-0002-2432-7257 NR 56 TC 133 Z9 137 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2004 VL 24 IS 10 BP 4546 EP 4556 DI 10.1128/MCB.24.10.4546-4556.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821DT UT WOS:000221440900041 PM 15121871 ER PT J AU Little, KD Hemler, ME Stipp, CS AF Little, KD Hemler, ME Stipp, CS TI Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: Central role of CD81 in facilitating GPR56-G alpha(q/11) association SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PHOSPHATIDYLINOSITOL 4 KINASE; DIPHTHERIA-TOXIN RECEPTOR; COUPLED RECEPTORS; GROWTH-FACTOR; INTEGRIN ALPHA-3-BETA-1; MONOCLONAL-ANTIBODIES; DRUG DISCOVERY; EGF RECEPTOR; MAJOR CD9; T-CELLS AB By means of a variety of intracellular scaffolding proteins, a vast number of heterotrimeric G protein-coupled receptors (GPCRs) may achieve specificity in signaling through a much smaller number of heterotrimeric G proteins. Members of the tetraspanin family organize extensive complexes of cell surface proteins and thus have the potential to act as GPCR scaffolds; however, tetraspanin-GPCR complexes had not previously been described. We now show that a GPCR, GPR56/TM7XN1, and heterotrimeric G protein subunits, Galpha(q), Galpha(q), and Gbeta, associate specifically with tetraspanins CD9 and CD81, but not with other tetraspanins. Complexes of GPR56 with CD9 and CD81 remained intact when fully solubilized and were resistant to cholesterol depletion. Hence they do not depend on detergent-insoluble, raft-like membrane microdomains for stability. A central role for CD81 in promoting or stabilizing a GPR56-CD81-Galpha(q/11) complex was revealed by CD81 immunodepletion and reexpression experiments. Finally, antibody engagement of cell surface CD81 or cell activation with phorbol ester revealed two distinct mechanisms by which GPR56-CD81-Galpha(q/11) complexes can be dynamically regulated. These data reveal a potential role for tetraspanins CD9 and CD81 as GPCR scaffolding proteins. C1 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), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM martin-hemler@dfci.harvard.edu FU NCI NIH HHS [CA 86712, R01 CA086712] NR 62 TC 116 Z9 119 U1 1 U2 9 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2004 VL 15 IS 5 BP 2375 EP 2387 DI 10.1091/mbc.E03-12-0886 PG 13 WC Cell Biology SC Cell Biology GA 817PL UT WOS:000221189300028 PM 15004227 ER PT J AU Nilsen, T Ghosh, AS Goldberg, MB Young, KD AF Nilsen, T Ghosh, AS Goldberg, MB Young, KD TI Branching sites and morphological abnormalities behave as ectopic poles in shape-defective Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID PENICILLIN-BINDING PROTEINS; CELL-DIVISION; BACILLUS-SUBTILIS; UNIPOLAR LOCALIZATION; SHIGELLA-FLEXNERI; POLAR LOCALIZATION; MUTANTS LACKING; O-ANTIGEN; ICSA; SECRETION AB Certain mutants in Escherichia coli lacking multiple penicillin-binding proteins (PBPs) produce misshapen cells containing kinks, bends and branches. These deformed regions exhibit two structural characteristics of normal cell poles: the peptidoglycan is inert to dilution by new synthesis or turnover, and a similarly stable patch of outer membrane caps the sites. To test the premise that these aberrant sites represent biochemically functional but misplaced cell poles, we assessed the intracellular distribution of proteins that localize specifically to bacterial poles. Green fluorescent protein (GFP) hybrids containing polar localization sequences from the Shigella flexneri IcsA protein or from the Vibrio cholerae EpsM protein formed foci at the poles of wild-type E. coli and at the poles and morphological abnormalities in PBP mutants. In addition, secreted wild-type IcsA localized to the outer membrane overlying these aberrant domains. We conclude that the morphologically deformed sites in these mutants represent fully functional poles or pole fragments. The results suggest that prokaryotic morphology is driven, at least in part, by the controlled placement of polar material, and that one or more of the low-molecular-weight PBPs participate in this process. Such mutants may help to unravel how particular proteins are targeted to bacterial poles, thereby creating important biochemical and functional asymmetries. C1 Univ N Dakota, Sch Med & Hlth Sci, Dept Microbiol & Immunol, Grand Forks, ND 58202 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Young, KD (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Microbiol & Immunol, Grand Forks, ND 58202 USA. EM kyoung@medicine.nodak.edu RI Young, Kevin/A-7954-2013 OI Young, Kevin/0000-0003-1760-281X FU NIAID NIH HHS [AI35817, R01 AI035817]; NIGMS NIH HHS [R01 GM061019, GM61019, R01 GM061019-05, R01 GM061019-06] NR 42 TC 46 Z9 47 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2004 VL 52 IS 4 BP 1045 EP 1054 DI 10.1111/j.1365-2958.2004.04050.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 818FQ UT WOS:000221231400010 PM 15130123 ER PT J AU Chattopadhyay, M Wolfe, DP Goins, WC Huang, SH Glorioso, JC Mata, M Fink, DJ AF Chattopadhyay, M Wolfe, DP Goins, WC Huang, SH Glorioso, JC Mata, M Fink, DJ TI Prolonged bioactive transgene expression driven by the HSV latency active promoter 2 (LAP2) in the peripheral nervous system SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 219 BP S85 EP S85 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600220 ER PT J AU Cole, C Diaz, RM Forshaw, M Kottke, T Thompson, J Gough, M Breakefield, X Sena-Esteves, M Qiao, JA Vile, RG AF Cole, C Diaz, RM Forshaw, M Kottke, T Thompson, J Gough, M Breakefield, X Sena-Esteves, M Qiao, JA Vile, RG TI T cell carriers for gene delivery to tumors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Mayo Clin, Coll Med, Program Mol Med, Rochester, MN USA. Mayo Clin, Coll Med, Dept Immunol, Rochester, MN USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 23 BP S9 EP S10 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600024 ER PT J AU Goss, JR Fetterolf, C Goins, W Wolfe, D Huang, SH Krisky, D Glorioso, JC Mata, M Fink, DJ AF Goss, JR Fetterolf, C Goins, W Wolfe, D Huang, SH Krisky, D Glorioso, JC Mata, M Fink, DJ TI Additive effects of HSV vectors expressing proenkephalin, interleukin-4, and tumor necrosis factor alpha soluble receptor to treat bone cancer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 214 BP S82 EP S82 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600215 ER PT J AU Ino, Y Saeki, Y Chiocca, EA Todo, T AF Ino, Y Saeki, Y Chiocca, EA Todo, T TI Expression of green fluorescent protein modifies the antitumor effect of oncolytic HSV-1 vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Tokyo Univ Hosp, Dept Neurosurg, Tokyo 113, Japan. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 804 BP S305 EP S305 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600805 ER PT J AU Kambara, H Okano, H Chiocca, EA Saeki, Y AF Kambara, H Okano, H Chiocca, EA Saeki, Y TI Effect of an oncolytic HSV mutant expressing ICP34.5 under control of a nestin promoter for brain tumor therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Keio Univ, Sch Med, Dept Physiol, Tokyo 160, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 624 BP S236 EP S237 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600625 ER PT J AU Lawler, SE Senior, S Ingelsson, M Saeki, Y Hyman, BT Monaco, AP Chiocca, EA Wade-Martins, R AF Lawler, SE Senior, S Ingelsson, M Saeki, Y Hyman, BT Monaco, AP Chiocca, EA Wade-Martins, R TI The HSV-1 iBAC amplicon vector for functional genomics studies into the genetic mechanisms of neurodegenerative disease SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 796 BP S301 EP S302 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600797 ER PT J AU Lin, CR Wu, CM Lin, MW Cheng, JT AF Lin, CR Wu, CM Lin, MW Cheng, JT TI Intrathecal electroporation of doxycycline regulated proopiomelanocortin gene for the neuropathic pain therapy in CCI rats SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Chang Gung Mem Hosp, Kaohsiung, Taiwan. Natl Sun Yat Sen Univ, Kaohsiung 80424, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 637 BP S241 EP S241 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600638 ER PT J AU Liu, RB Martuza, RL Rabkin, SD AF Liu, RB Martuza, RL Rabkin, SD TI Intracarotid delivery of oncolytic herpes simplex virus-1 G47 Delta to metastatic breast cancer in the brain SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Charlestown, MA USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 798 BP S302 EP S303 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600799 ER PT J AU Pergolizzi, RG Dragos, R Nakayama, K Wagner, D Crystal, RG AF Pergolizzi, RG Dragos, R Nakayama, K Wagner, D Crystal, RG TI Overcoming the size limitations of gene transfer vectors: Using segmental trans-splicing to deliver the coding sequence of von Willebrand factor SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Cornell Univ, Weill Med Coll, New York, NY USA. CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 160 BP S61 EP S61 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600161 ER PT J AU Puskovic, V Wolfe, D Goss, JR Hang, SH Glorioso, JC Mata, M Finnk, DJ AF Puskovic, V Wolfe, D Goss, JR Hang, SH Glorioso, JC Mata, M Finnk, DJ TI Prolonged biologically active transgene expression driven by HSV latency active promoter 2 (LAP2) in brain in vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 220 BP S85 EP S85 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600221 ER PT J AU Varghese, S Rabkin, SD Wang, WZ Martuza, RL AF Varghese, S Rabkin, SD Wang, WZ Martuza, RL TI Enhanced therapeutic efficacy of a cytokine expressing oncolytic herpes simplex virus against prostate cancer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 351 BP S134 EP S134 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600352 ER PT J AU Wang, S Petravicz, J Breakefield, XO AF Wang, S Petravicz, J Breakefield, XO TI Bioluminescence imaging of regulated gene expression using HSV-1 amplicon vectors in rodent brain SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 7th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 02-06, 2004 CL Minneapolis, MN SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2004 VL 9 SU 1 MA 64 BP S27 EP S27 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 833DM UT WOS:000222316600065 ER PT J AU Peterson, RT Shaw, SY Peterson, TA Milan, DJ Zhong, TP Schreiber, SL MacRae, CA Fishman, MC AF Peterson, RT Shaw, SY Peterson, TA Milan, DJ Zhong, TP Schreiber, SL MacRae, CA Fishman, MC TI Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation SO NATURE BIOTECHNOLOGY LA English DT Article ID ANGIOBLAST MIGRATION; DORSAL AORTA; VEGF; GRIDLOCK; TARGET; NOTCH; CARDIOMYOPATHY; INACTIVATION; LETHALITY; THERAPY AB Conventional drug discovery approaches require a priori selection of an appropriate molecular target, but it is often not obvious which biological pathways must be targeted to reverse a disease phenotype(1,2). Phenotype-based screens offer the potential to identify pathways and potential therapies that influence disease processes. The zebrafish mutation gridlock (grl, affecting the gene hey2) disrupts aortic blood flow in a region and physiological manner akin to aortic coarctation in humans(3-5). Here we use a whole-organism, phenotype-based, small-molecule screen to discover a class of compounds that suppress the coarctation phenotype and permit survival to adulthood. These compounds function during the specification and migration of angioblasts. They act to upregulate expression of vascular endothelial growth factor (VEGF), and the activation of the VEGF pathway is sufficient to suppress the gridlock phenotype. Thus, organism-based screens allow the discovery of small molecules that ameliorate complex dysmorphic syndromes even without targeting the affected gene directly. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu FU NHLBI NIH HHS [K08 HL076361] NR 30 TC 248 Z9 261 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2004 VL 22 IS 5 BP 595 EP 599 DI 10.1038/nbt963 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 817EB UT WOS:000221159700029 PM 15097998 ER PT J AU Zhang, H Smolen, GA Palmer, R Christoforou, A van den Heuvel, S Haber, DA AF Zhang, H Smolen, GA Palmer, R Christoforou, A van den Heuvel, S Haber, DA TI SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2 SO NATURE GENETICS LA English DT Article ID SAM DOMAIN; NUCLEAR-BODIES/; HOMOLOG; TEL AB Post-translational modification of proteins by the ubiquitin-like molecule SUMO (sumoylation) regulates their subcellular localization and affects their functional properties in vitro 1,2, but the physiological function of sumoylation in multicellular organisms is largely unknown. Here, we show that the C. elegans Polycomb group (PcG) protein SOP-2 interacts with the SUMO-conjugating enzyme UBC-9 through its evolutionarily conserved SAM domain. Sumoylation of SOP-2 is required for its localization to nuclear bodies in vivo and for its physiological repression of Hox genes. Global disruption of sumoylation phenocopies a sop-2 mutation by causing ectopic Hox gene expression and homeotic transformations. Chimeric constructs in which the SOP-2 SAM domain is replaced with that derived from fruit fly or mammalian PcG proteins, but not those in which the SOP-2 SAM domain is replaced with the SAM domains of non-PcG proteins, confer appropriate in vivo nuclear localization and Hox gene repression. These observations indicate that sumoylation of PcG proteins, modulated by their evolutionarily conserved SAM domain, is essential to their physiological repression of Hox genes. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu RI van den Heuvel, Sander/B-8892-2011 NR 20 TC 54 Z9 67 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAY PY 2004 VL 36 IS 5 BP 507 EP 511 DI 10.1038/ng1336 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 817NA UT WOS:000221183000025 PM 15107848 ER PT J AU Hu, D Ikizawa, K Lu, LR Sanchirico, ME Shinohara, ML Cantor, H AF Hu, D Ikizawa, K Lu, LR Sanchirico, ME Shinohara, ML Cantor, H TI Analysis of regulatory CD8 T cells in Qa-1-deficient mice SO NATURE IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CLASS IB MOLECULES; NEGATIVE SELECTION; IMMUNE-RESPONSES; VIRAL-INFECTION; IN-VIVO; RECEPTOR; ANTIGEN; PEPTIDE AB The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell-dependent suppression, the physiological relevance of this observation is unclear. We generated mice deficient in Qa-1 to develop an understanding of this process. Qa-1-deficient mice develop exaggerated secondary CD4 responses to foreign and self peptides. Enhanced responses to proteolipid protein self peptide were associated with resistance of Qa-1-deficient CD4 T cells to Qa-1-restricted CD8 T suppressor activity and increased susceptibility to experimental autoimmune encephalomyelitis. These findings delineate a Qa-1-dependent T cell-T cell inhibitory interaction that prevents the pathogenic expansion of autoreactive CD4 T cell populations and consequent autoimmune disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu RI Lu, Linrong/A-1429-2013; Hu, Dan/D-9642-2015; OI Lu, Linrong/0000-0002-0171-4115 FU NIAID NIH HHS [AI 07386, AI 13600, AI 48125, AI37562] NR 41 TC 212 Z9 221 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2004 VL 5 IS 5 BP 516 EP 523 DI 10.1038/ni1063 PG 8 WC Immunology SC Immunology GA 816HN UT WOS:000221101100016 PM 15098030 ER PT J AU Koo, SH Satoh, H Herzig, S Lee, CH Hedrick, S Kulkarni, R Evans, RM Olefsky, J Montminy, M AF Koo, SH Satoh, H Herzig, S Lee, CH Hedrick, S Kulkarni, R Evans, RM Olefsky, J Montminy, M TI PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3 SO NATURE MEDICINE LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTORS; COACTIVATOR PGC-1; HEPATIC GLUCONEOGENESIS; FASTING RESPONSE; GENE-EXPRESSION; NULL MICE; MOUSE; PROTEIN; GLUCOSE; HEPATOCYTES AB Insulin resistance is a major hallmark in the development of type 2 diabetes, which is characterized by an impaired ability of insulin to inhibit glucose output from the liver and to promote glucose uptake in muscle(1,2). The nuclear hormone receptor coactivator PGC-1 (peroxisome proliferator-activated (PPAR)-gamma coactivator-1) has been implicated in the onset of type 2 diabetes. Hepatic PGC-1 expression is elevated in mouse models of this disease, where it promotes constitutive activation of gluconeogenesis and fatty acid oxidation through its association with the nuclear hormone receptors HNF-4 and PPAR-alpha, respectively(3-5). Here we show that PGC-1-deficient mice, generated by adenoviral delivery of PGC-1 RNA interference (RNAi) to the liver, experience fasting hypoglycemia. Hepatic insulin sensitivity was enhanced in PGC-1-deficient mice, reflecting in part the reduced expression of the mammalian tribbles homolog TRB-3, a fasting-inducible inhibitor of the serine-threonine kinase Akt/PKB (ref. 6). We show here that, in the liver, TRB-3 is a target for PPAR-alpha. Knockdown of hepatic TRB-3 expression improved glucose tolerance, whereas hepatic overexpression of TRB-3 reversed the insulin-sensitive phenotype of PGC-1-deficient mice. These results indicate a link between nuclear hormone receptor and insulin signaling pathways, and suggest a potential role for TRB-3 inhibitors in the treatment of type 2 diabetes. C1 Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92037 USA. Salk Inst Biol Studies, Gene Express Labs, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Montminy, M (reprint author), Salk Inst Biol Studies, Peptide Biol Labs, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM montminy@salk.edu RI Koo, Seung-Hoi/E-2763-2015; Satoh, Hiroaki/E-9096-2017 OI Koo, Seung-Hoi/0000-0001-8769-2879; Satoh, Hiroaki/0000-0002-0353-5807 FU NIGMS NIH HHS [GM R01 37828] NR 28 TC 349 Z9 370 U1 6 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2004 VL 10 IS 5 BP 530 EP 534 DI 10.1038/nm1044 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 818JW UT WOS:000221242400032 PM 15107844 ER PT J AU Brown, EN Kass, RE Mitra, PP AF Brown, EN Kass, RE Mitra, PP TI Multiple neural spike train data analysis: state-of-the-art and future challenges SO NATURE NEUROSCIENCE LA English DT Article ID HIPPOCAMPAL PLACE CELLS; RETINAL GANGLION-CELLS; ACTION-POTENTIALS; CORTICAL-NEURONS; FIRING PATTERNS; INFORMATION; MODEL; POPULATION; RECONSTRUCTION; QUANTIFICATION AB Multiple electrodes are now a standard tool in neuroscience research that make it possible to study the simultaneous activity of several neurons in a given brain region or across different regions. The data from multi-electrode studies present important analysis challenges that must be resolved for optimal use of these neurophysiological measurements to answer questions about how the brain works. Here we review statistical methods for the analysis of multiple neural spike-train data and discuss future challenges for methodology research. C1 Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Boston, MA 02114 USA. Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15208 USA. Ctr Neural Basis Cognit, Dept Stat, Pittsburgh, PA 15208 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM brown@neurostat.mgh.harvard.edu FU NIDA NIH HHS [DA015664]; NIMH NIH HHS [MH61637, MH59733, MH62528, MH64537, MH66410] NR 65 TC 434 Z9 445 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2004 VL 7 IS 5 BP 456 EP 461 DI 10.1038/nn1228 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 816HP UT WOS:000221101300013 PM 15114358 ER PT J AU Cheng, LP Arata, A Mizuguchi, R Qian, Y Karunaratne, A Gray, PA Arata, S Shirasawa, S Bouchard, M Luo, P Chen, CL Busslinger, M Goulding, M Onimaru, H Ma, QF AF Cheng, LP Arata, A Mizuguchi, R Qian, Y Karunaratne, A Gray, PA Arata, S Shirasawa, S Bouchard, M Luo, P Chen, CL Busslinger, M Goulding, M Onimaru, H Ma, QF TI Tlx3 and Tlx1 are post-mitotic selector genes determining glutamatergic over GABAergic cell fates SO NATURE NEUROSCIENCE LA English DT Article ID DORSAL SPINAL-CORD; RESPIRATORY RHYTHM GENERATION; PRESYNAPTIC REGULATION; DEVELOPMENTAL SWITCH; SENSORY NEURONS; HOMEOBOX GENES; RAT; EXPRESSION; BRAIN; INTERNEURONS AB Glutamatergic and GABAergic neurons mediate much of the excitatory and inhibitory neurotransmission, respectively, in the vertebrate nervous system. The process by which developing neurons select between these two cell fates is poorly understood. Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord. First, we found that Tlx3 was required for specification of, and expressed in, glutamatergic neurons. Both generic and region-specific glutamatergic markers, including VGLUT2 and the AMPA receptor Gria2, were absent in Tlx mutant dorsal horn. Second, spinal GABAergic markers were derepressed in Tlx mutants, including Pax2 that is necessary for GABAergic differentiation, Gad1/2 and Viaat that regulate GABA synthesis and transport, and the kainate receptors Grik2/3. Third, ectopic expression of Tlx3 was sufficient to suppress GABAergic differentiation and induce formation of glutamatergic neurons. Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RIKEN, Brain Sci Inst, Lab Memory & Learning, Wako, Saitama 3510198, Japan. Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA. Showa Univ, Ctr Biotechnol, Tokyo 1428555, Japan. Int Med Ctr Japan, Dept Pathol, Shinjuku Ku, Tokyo 1628655, Japan. Res Inst Mol Pathol, A-1030 Vienna, Austria. Showa Univ, Sch Med, Dept Physiol, Tokyo 1428555, Japan. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM Qiufu_Ma@dfci.harvard.edu RI Karunaratne, Asanka/B-5808-2008; Busslinger, Meinrad/J-1249-2016 OI Busslinger, Meinrad/0000-0002-9111-9351 NR 49 TC 205 Z9 205 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2004 VL 7 IS 5 BP 510 EP 517 DI 10.1038/nn1221 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 816HP UT WOS:000221101300028 PM 15064766 ER PT J AU Rowitch, DH AF Rowitch, DH TI Glial specification in the vertebrate neural tube SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID OLIGODENDROCYTE PRECURSOR CELLS; CENTRAL-NERVOUS-SYSTEM; DEVELOPING SPINAL-CORD; HOMEODOMAIN TRANSCRIPTION FACTOR; RAT CEREBRAL-CORTEX; SONIC HEDGEHOG; STEM-CELLS; MOTOR-NEURON; SUBVENTRICULAR ZONE; PROGENITOR CELLS AB Vertebrate macroglial cells have diverse roles in the maintenance of neurological function. This review highlights progress in our understanding of the mechanisms that underlie the specification of precursors for two key macroglial subtypes - oligodendrocytes and astrocytes - in the embryo. These mechanisms are strikingly similar to those that underlie the development of neuronal subtypes, including emergence from localized regions of the neural tube, and involvement of common signalling pathways and downstream transcription factors. The switch from neuronal to glial precursor production can be modelled as a complex interplay between regionally-restricted components and generalized temporal regulators. C1 Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Div Newborn Med, 44 Binney St,D640D, Boston, MA 02115 USA. EM david_rowitch@dfci.harvard.edu NR 115 TC 249 Z9 249 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAY PY 2004 VL 5 IS 5 BP 409 EP 419 DI 10.1038/nrn1389 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 817DQ UT WOS:000221158600016 PM 15100723 ER PT J AU Eden, UT Frank, LM Barbieri, R Solo, V Brown, EN AF Eden, UT Frank, LM Barbieri, R Solo, V Brown, EN TI Dynamic analysis of neural encoding by point process adaptive filtering SO NEURAL COMPUTATION LA English DT Article ID RECEPTIVE-FIELD PLASTICITY; ENTORHINAL CORTEX; HIPPOCAMPUS; MONKEYS; ADULT; REPRESENTATIONS; PATTERNS; RAT; MAP AB Neural receptive fields are dynamic in that with experience, neurons change their spiking responses to relevant stimuli. To understand how neural systems adapt their representations of biological information, analyses of receptive field plasticity from experimental measurements are crucial. Adaptive signal processing, the well-established engineering discipline for characterizing the temporal evolution of system parameters, suggests a framework for studying the plasticity of receptive fields. We use the Bayes' rule Chapman-Kolmogorov paradigm with a linear state equation and point process observation models to derive adaptive filters appropriate for estimation from neural spike trains. We derive point process filter analogues of the Kalman filter, recursive least squares, and steepest-descent algorithms and describe the properties of these new filters. We illustrate our algorithms in two simulated data examples. The first is a study of slow and rapid evolution of spatial receptive fields in hippocampal neurons. The second is an adaptive decoding study in which a signal is decoded from ensemble neural spiking activity as the receptive fields of the neurons in the ensemble evolve. Our results provide a paradigm for adaptive estimation for point process observations and suggest a practical approach for constructing filtering algorithms to track neural receptive field dynamics on a millisecond timescale. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ New S Wales, Sch Elect Engn & Telecommun, Sydney, NSW, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Eden, UT (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM tzvi@neurostat.mgh.harvard.edu; loren@neurostat.mgh.harvard.edu; barbieri@neurostat.mgh.harvard.edu; vsolo@nmr.mgh.harvard.edu; brown@neurostat.harvard.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Frank, Loren/0000-0002-1752-5677 FU NIDA NIH HHS [DA015644]; NIMH NIH HHS [MH59733, MH61637, MH65108] NR 32 TC 173 Z9 174 U1 1 U2 8 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD MAY PY 2004 VL 16 IS 5 BP 971 EP 998 DI 10.1162/089976604773135069 PG 28 WC Computer Science, Artificial Intelligence SC Computer Science GA 806OK UT WOS:000220443000003 PM 15070506 ER PT J AU Butterfield, DA Bush, AI AF Butterfield, DA Bush, AI TI Alzheimer's amyloid beta-peptide (1-42): involvement of methionine residue 35 in the oxidative stress and neurotoxicity properties of this peptide SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT Conference on Challenging Views of Alzheimers Disease CY 2003 CL Cincinnati, OH DE amyloid; beta-peptide methionine; oxidative stress; neurotoxicity ID BETA-PEPTIDE; DISEASE BRAIN; LIPID-PEROXIDATION; PROTEOMIC IDENTIFICATION; PROTEIN OXIDATION; NEURONAL DEATH; IN-VIVO; MEMBRANE; REDUCTION; PRODUCT AB In the interesting debate entitled "Challenging Views of Alzheimer's Disease II," we defended the position that factors such as oxygen, the single methionine residue of amyloid beta-peptide(1-42) [Abeta(1-42)], and redox metal ions were important for the oxidative stress and neurotoxic properties of this peptide that is critically involved in the pathogenesis of Alzheimer's disease. This brief review summarizes some of our findings relevant to the role of the single methionine residue of Abeta(1-42) in the oxidative stress and neurotoxic properties of this peptide. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Kentucky, Ctr Membrane Sci, Dept Chem, Lexington, KY 40506 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40506 USA. Harvard Univ, Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Charlestown, MA USA. Univ Melbourne, Dept Pathol, Mental Hlth Res Inst, Parkville, Vic 3052, Australia. RP Butterfield, DA (reprint author), Univ Kentucky, Ctr Membrane Sci, Dept Chem, Lexington, KY 40506 USA. EM dabens@uky.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [AG-05119, AG-10836, R01AG12686] NR 50 TC 93 Z9 97 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 2004 VL 25 IS 5 BP 563 EP 568 DI 10.1016/j.neurobiolaging.2003.12.027 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 832FZ UT WOS:000222254000002 PM 15172731 ER PT J AU D'Andrea, MR Cole, GM Ard, MD AF D'Andrea, MR Cole, GM Ard, MD TI The microglial phagocytic role with specific plaque types in the Alzheimer disease brain SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT Conference on Challenging Views of Alzheimers Disease CY 2003 CL Cincinnati, OH DE Alzheimer's disease; amyloid plaques; beta-amyloid; microglia; astrocytes; transgenic mice; neuropathology; inflammation; plaque formation; phagocytosis; dense-core plaques; diffuse plaques; cerebellum; entorhinal cortex ID AMYLOID-BETA-PEPTIDE; TRANSGENIC MICE; SENILE PLAQUES; A-BETA; MOUSE MODEL; SCAVENGER RECEPTOR; PROTEIN; DIFFUSE; CELLS; ACTIVATION AB Alzheimer disease (AD) involves glial inflammation associated with amyloid plaques. The role of the microglial cells in the AD brain is controversial, as it remains unclear if the microglia form the amyloid fibrils of plaques or react to them in a macrophage-phagocytic role. Also, it is not known why microglia are preferentially associated with some amyloid plaque types. This review will provide substantial evidence to support the phagocytic role of microglia in the brain as well as explain why microglia are generally associated with specific plaque types that may be explained through their unique mechanisms of formation. In summary, the data presented suggests that plaque associated microglial activation is typically subsequent to specific amyloid plaque formations in the AD brain. (C) 2004 Elsevier Inc. All rights reserved. C1 Johnson & Johnson Pharmaceut Res & Dev, Drug Discovery, Spring House, PA 19477 USA. Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, GRECC Res, Dept Med,Alzheimers Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, GRECC Res, Dept Neurol,Alzheimers Dis Res Ctr, Los Angeles, CA USA. Univ Mississippi, Med Ctr, Dept Anat, Jackson, MS 39216 USA. RP D'Andrea, MR (reprint author), Johnson & Johnson Pharmaceut Res & Dev, Drug Discovery, D404, Spring House, PA 19477 USA. EM mdandrea@prdus.jnj.com NR 73 TC 111 Z9 112 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 2004 VL 25 IS 5 BP 675 EP 683 DI 10.1016/j.neurobiolaging.2003.12.026 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 832FZ UT WOS:000222254000018 PM 15172747 ER PT J AU Naeser, MA Martin, PI Baker, EH Hodge, SM Sczerzenie, SE Nicholas, M Palumbo, CL Goodglass, H Wingfield, A Samaraweera, R Harris, G Baird, A Renshaw, P Yurgelun-Todd, D AF Naeser, MA Martin, PI Baker, EH Hodge, SM Sczerzenie, SE Nicholas, M Palumbo, CL Goodglass, H Wingfield, A Samaraweera, R Harris, G Baird, A Renshaw, P Yurgelun-Todd, D TI Overt propositional speech in chronic nonfluent aphasia studied with the dynamic susceptibility contrast fMRI method SO NEUROIMAGE LA English DT Article DE fMRI; DSC fMRI; stroke; aphasia recovery; nonfluent speech; echo planar imaging; cerebral blood volume; contrast agents ID CEREBRAL BLOOD-VOLUME; PREFRONTAL CORTEX; FUNCTIONAL MRI; HUMAN BRAIN; RECOVERY; STROKE; HEMISPHERE; ACTIVATION; PET; PLASTICITY AB This study examined activation levels in the left (L) supplementary motor area (SMA) and the right (R) SMA (separately), and activation in nine R perisylvian language homologues during overt, propositional speech in chronic nonfluent aphasia patients. Previous functional imaging studies with a variety of chronic aphasia patients have reported activation in these regions during different language tasks, however, overt propositional speech has not been examined. In the present research, four nonfluent aphasia patients were studied during overt elicited propositional speech at 4-9 years post-single L hemisphere stroke, which spared the SMA. The dynamic susceptibility contrast (DSC) method of functional MRI was used to calculate relative cerebral blood volume (relCBV) for cortical regions of interest (ROIs) during the first-pass bolus of gadolinium during two conditions: (1) pattern (silent viewing of checkerboard patterns) and (2) story (overt, elicited propositional speech describing sequential pictures, which formed a story). During the story condition, controls had significantly higher relCBV in L SMA than in R SMA; aphasics, however, had significantly higher relCBV in R SMA than in L SMA. During the pattern condition, no significant differences were observed between the L SMA and the R SMA for either controls or aphasics. In addition, aphasics had significantly higher relCBV in the R sensorimotor mouth during story than pattern. This R sensorimotor mouth relCBV was also significantly higher in aphasics than controls during story, and the two groups did not differ during pattern. The overall mean relCBV for the nine R perisylvian ROIs was significantly higher for aphasics than controls during both story and pattern. These results suggest that poor modulation, including possible over-activation of R sensorimotor mouth and other R perisylvian language homologues may underlie in part, the hesitant, poorly articulated, agrammatic speech associated with nonfluent aphasia. Published bv Elsevier Inc. C1 VA Boston Healthcare Syst, Serv Radiol, Boston, MA 02130 USA. Boston Univ, Sch Med, Harold Goodglass Aphasia Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02130 USA. Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, RAD, CADx,LAB, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. RP Naeser, MA (reprint author), VA Boston Healthcare Syst, Serv Radiol, 12-A,150 S Huntington Ave, Boston, MA 02130 USA. EM mnaeser@bu.edu OI Pikula, Aleksandra/0000-0002-8378-5522 FU NIDCD NIH HHS [P30 DC 05207, R01 DC 05672] NR 51 TC 87 Z9 98 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2004 VL 22 IS 1 BP 29 EP 41 DI 10.1016/j.neuroimage.2003.11.016 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 817PU UT WOS:000221190200004 PM 15109995 ER PT J AU Ahlfors, SP Simpson, GV AF Ahlfors, SP Simpson, GV TI Geometrical interpretation of fMRI-guided MEG/EEG inverse estimates SO NEUROIMAGE LA English DT Article DE magnetoencephalography; electroencephalography; functional magnetic resonance imaging; subspace regularization ID EEG SOURCE LOCALIZATION; FUNCTIONAL MRI; BRAIN-FUNCTION; ELECTRICAL-ACTIVITY; BAYESIAN-INFERENCE; EVOKED-POTENTIALS; CORTICAL ACTIVITY; MOTOR CORTEX; MAGNETOENCEPHALOGRAPHY; MEG AB Magneto- and electroencephalography (MEG/EEG) and functional magnetic resonance imaging (fMRI) provide complementary information about the functional organization of the human brain. An important advantage of MEG/EEG is the millisecond time resolution in detecting electrical activity in the cerebral cortex. The interpretation of MEG/EEG signals, however, is limited by the difficulty of determining the spatial distribution of the neural activity. Functional MRI can help in the MEG/EEG source analysis by suggesting likely locations of activity. We present a geometric interpretation of fMRI- guided inverse solutions in which the MEG/EEG source estimate minimizes a distance to a subspace defined by the fMRI data. In this subspace regularization (SSR) approach, the fMRI bias does not assume preferred amplitudes for MEG/EEG sources, only locations. Characteristic dependence of the source estimates on the regularization parameters is illustrated with simulations. When the fMRI locations match the true MEG/EEG source locations, they serve to bias the underdetermined MEG/EEG inverse solution toward the fMRI loci. Importantly, when the fMRI loci do not match the true MEG/EEG loci, the solution is insensitive to those fMRI loci. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH MIT HMS Athinoula A Martios Ctr Biomed Imagin, Charlestown, MA 02129 USA. Univ Calif San Francisco, Dept Radiol, Dynam Neuroimaging Lab, San Francisco, CA 94143 USA. RP Ahlfors, SP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH MIT HMS Athinoula A Martios Ctr Biomed Imagin, Charlestown, MA 02129 USA. EM seppo@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU NCRR NIH HHS [P41 RR 14075]; NIDA NIH HHS [DA 09972]; NIMH NIH HHS [MH/DA 52176]; NINDS NIH HHS [NS 27900] NR 59 TC 48 Z9 48 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2004 VL 22 IS 1 BP 323 EP 332 DI 10.1016/j.neuroimage.2003.12.044 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 817PU UT WOS:000221190200031 PM 15110022 ER PT J AU Schellingerhout, D Josephson, L AF Schellingerhout, D Josephson, L TI Molecular imaging of cell-based therapies SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; CYTOTOXIC ANTITUMOR ANTIBODY; IN-VIVO; GENE-EXPRESSION; REPORTER GENE; TAT PEPTIDE; OPTICAL BIOLUMINESCENCE; MAGNETIC NANOPARTICLES; SOMATOSTATIN RECEPTOR; TRANSGENE EXPRESSION AB This article focuses on molecular imaging of novel cell-based therapies, particularly stem cell therapies and the adoptive transfer of imuunocytes. The animal models, potential clinical applications, and likely future prospects of these therapies are discussed in the context of imaging. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Schellingerhout, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Room 5403,Bldg 149,13th St,Charlestown Navy Yard, Charlestown, MA 02129 USA. EM Dawid@helix.mgh.harvard.edu FU NCI NIH HHS [2P01CA6924605, 1-R24-CA92782-01] NR 104 TC 5 Z9 5 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2004 VL 14 IS 2 BP 331 EP + DI 10.1016/j.nic.2004.03.009 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 828HA UT WOS:000221963200012 PM 15182822 ER PT J AU Nierenberg, AA Quitkin, FM Kremer, C Keller, MB Thase, ME AF Nierenberg, AA Quitkin, FM Kremer, C Keller, MB Thase, ME TI Placebo-controlled continuation treatment with mirtazapine: Acute pattern of response predicts relapse SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE true-drug responders; placebo responders on drug; maintenance treatment; loss of drug effect; predictors of relapse; pattern analysis ID RECURRENT DEPRESSION; MAINTENANCE THERAPIES; PROPHYLACTIC EFFICACY; LITHIUM-CARBONATE; PREVENTION; FLUOXETINE; PHENELZINE; IMIPRAMINE; TOLERANCE; UNIPOLAR AB Pattern of response to antidepressants has been proposed as a method to identify patients whose improvement is more likely due to drug vs those whose improvement on drug is more likely to be a placebo effect. It is hypothesized that those with 'true-drug initial response pattern' are most likely to benefit from continuation treatment. The relationship between acute patterns of response and subsequent placebo-controlled continuation treatment with the antidepressant mirtazapine is examined. A total of 410 outpatients were treated openly with mirtazapine for 8-12 weeks. Patients who remitted in the acute phase were randomized to continue the same dose of mirtazapine or switched to placebo. Acute phase responders were classified as 'placebo initial response pattern' (early responders and nonpersistent responders) and 'true-drug initial response pattern' (delayed and persistent responders). Of those with a 'true-drug initial response pattern,' 10/40 (25.0%) relapsed with continuation mirtazapine, and 23/41 (56.1%) relapsed when switched to placebo. The difference (31.1%) is significant. Of those with a 'placebo initial response pattern,' 5/36 (13.9%) relapsed with continuation mirtazapine, and 12/39 (30.8%) relapsed with placebo substitution. This difference (16.9%) is not statistically significant. Moreover, the relapse rate for 'true-drug initial response pattern' patients switched to placebo (56.1%) was also significantly greater than for 'placebo initial response pattern' patients switched to placebo (30.8%). It has been suggested that patients with late onset and persistence are more likely to have improved because of drug. This hypothesis gains support from this study because of the different relapse rates of 'true-drug' responders on drug and placebo. The low relapse rate for patients with an acute placebo pattern switched to placebo suggests specific drug effect played a smaller role in their initial improvement. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Columbia Univ, Sch Med, New York State Psychiat Inst, New York, NY USA. Brown Univ, Dept Psychiat, Providence, RI 02912 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Pittsburgh, PA 15260 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, ACC 812,15 Parkman St, Boston, MA 02114 USA. EM anierenberg@partners.org FU NIMH NIH HHS [U01 MH061590] NR 27 TC 32 Z9 33 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2004 VL 29 IS 5 BP 1012 EP 1018 DI 10.1038/sj.npp.1300405 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 813PS UT WOS:000220919600018 PM 14997172 ER PT J AU Paez, JG Lin, M Beroukhim, R Lee, JC Zhao, XJ Richter, DJ Gabriel, S Herman, P Sasaki, H Altshuler, D Li, C Meyerson, M Sellers, WR AF Paez, JG Lin, M Beroukhim, R Lee, JC Zhao, XJ Richter, DJ Gabriel, S Herman, P Sasaki, H Altshuler, D Li, C Meyerson, M Sellers, WR TI Genome coverage and sequence fidelity of phi 29 polymerase-based multiple strand displacement whole genome amplification SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ROLLING CIRCLE AMPLIFICATION; NUCLEOTIDE POLYMORPHISM ARRAYS; DNA-POLYMERASE; HETEROZYGOSITY ANALYSIS; LUNG-CANCER; SNP MAP; SAMPLES AB Major efforts are underway to systematically define the somatic and germline genetic variations causally associated with disease. Genome-wide genetic analysis of actual clinical samples is, however, limited by the paucity of genomic DNA available. Here we have tested the fidelity and genome representation of phi29 polymerase-based genome amplification (phi29MDA) using direct sequencing and high density oligonucleotide arrays probing >10 000 SNP alleles. Genome representation was comprehensive and estimated to be 99.82% complete, although six regions encompassing a maximum of 5.62 Mb failed to amplify. There was no degradation in the accuracy of SNP genotyping and, in direct sequencing experiments sampling 500 000 bp, the estimated error rate (9.5 x 10(-6)) was the same as in paired unamplified samples. The detection of cancer-associated loss of heterozygosity and copy number changes, including homozygous deletion and gene amplification, were similarly robust. These results suggest that phi29MDA yields high fidelity, near-complete genome representation suitable for high resolution genetic analysis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. Nagoya City Univ, Sch Med, Nagoya, Aichi 467, Japan. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D720C,44 Binney St, Boston, MA 02115 USA. EM william_sellers@dfci.harvard.edu RI Altshuler, David/A-4476-2009; Meyerson, Matthew/E-7123-2012 OI Altshuler, David/0000-0002-7250-4107; FU NCI NIH HHS [T32 CA009172] NR 23 TC 164 Z9 172 U1 2 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2004 VL 32 IS 9 AR e71 DI 10.1093/nar/gnh069 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 825HM UT WOS:000221746900003 PM 15150323 ER PT J AU Wang, G Brennan, C Rook, M Wolfe, JL Leo, C Chin, L Pan, H Liu, WH Price, B Makrigiorgos, GM AF Wang, G Brennan, C Rook, M Wolfe, JL Leo, C Chin, L Pan, H Liu, WH Price, B Makrigiorgos, GM TI Balanced-PCR amplification allows unbiased identification of genomic copy changes in minute cell and tissue samples SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; BREAST-CANCER; DISPLACEMENT AMPLIFICATION; GENETIC-ANALYSIS; PROSTATE-CANCER; AMPLIFIED DNA; SINGLE CELLS; ARRAY-CGH; HYBRIDIZATION; MICROARRAYS AB Analysis of genomic DNA derived from cells and fresh or fixed tissues often requires whole genome amplification prior to microarray screening. Technical hurdles to this process are the introduction of amplification bias and/or the inhibitory effects of formalin fixation on DNA amplification. Here we demonstrate a balanced-PCR procedure that allows unbiased amplification of genomic DNA from fresh or modestly degraded paraffin-embedded DNA samples. Following digestion and ligation of a target and a control genome with distinct linkers, the two are mixed and amplified in a single PCR, thereby avoiding biases associated with PCR saturation and impurities. We demonstrate genome-wide retention of allelic differences following balanced-PCR amplification of DNA from breast cancer and normal human cells and genomic profiling by array-CGH (cDNA arrays, 100 kb resolution) and by real-time PCR (single gene resolution). Comparison of balanced-PCR with multiple displacement amplification (MDA) demonstrates equivalent performance between the two when intact genomic DNA is used. When DNA from paraffin-embedded samples is used, balanced PCR overcomes problems associated with modest DNA degradation and produces unbiased amplification whereas MDA does not. Balanced-PCR allows amplification and recovery of modestly degraded genomic DNA for subsequent retrospective analysis of human tumors with known outcomes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Arthur & Rochelle Belfer Canc Genom Ctr, Boston, MA 02115 USA. Variagenics Inc, Cambridge, MA USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [T32 CA009078, 5 T32 CA09078, P50 CA 93683, P50 CA093683] NR 32 TC 39 Z9 40 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2004 VL 32 IS 9 AR e76 DI 10.1093/nar/gnh070 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 825HM UT WOS:000221746900008 PM 15155823 ER PT J AU Gibson, WT Pissios, P Trombly, DJ Luan, J Keogh, J Wareham, NJ Maratos-Flier, E O'Rahilly, S Farooqi, LS AF Gibson, WT Pissios, P Trombly, DJ Luan, J Keogh, J Wareham, NJ Maratos-Flier, E O'Rahilly, S Farooqi, LS TI Melanin-concentrating hormone receptor mutations and human obesity: Functional analysis SO OBESITY RESEARCH LA English DT Article DE MCHR1; MCHR2; association study; ERK phosphorylation; G-protein-coupled receptors ID EARLY-ONSET OBESITY; MICE; IDENTIFICATION; DEFICIENCY; RESISTANCE; GENE AB Melanin-concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus, has an important role in the regulation of energy balance and body weight in rodents. We examined whether mutations in the two known MCH receptors might be associated with obesity-related phenotypes in humans. Among 106 subjects with severe early onset obesity and a history of hyperphagia, we found two missense variants in MCHR1: Y181H and R248Q. Neither of these was found in 192 normal weight controls. R248Q cosegregated with obesity across two generations; family data were unavailable for Y181H. When expressed in HEK293 cells, R248Q showed no evidence of constitutive activation or ligand hypersensitivity for extracellular signal-regulated kinase phosphorylation. In addition, R248Q showed no enhanced suppression of CAMP generation. Two common sing] e-nucleotide polymorphisms were found to be in linkage disequilibrium: g.-114A>G,and c.39C>T. No association between either of these single- nucleotide polymorphisms and obesity-related phenotypes was found among a population cohort of 541 whites. Only two rare noncoding variants were found in MCHR2. In conclusion, mutations in the MCH receptors are not commonly found in humans with severe early onset obesity. Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice. C1 Univ Cambridge, Dept Clin Biochem, Cambridge Inst Med Res, Cambridge CB2 1TN, England. Joslin Diabet Ctr, Sect Obes, Div Res, Boston, MA 02215 USA. Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. RP O'Rahilly, S (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge CB2 2QQ, England. EM sorahill@hgmp.mrc.ac.uk OI Gibson, William/0000-0002-6552-402X FU Wellcome Trust [068086] NR 17 TC 38 Z9 41 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAY PY 2004 VL 12 IS 5 BP 743 EP 749 DI 10.1038/oby.2004.89 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 826EY UT WOS:000221813300002 PM 15166293 ER PT J AU Goodman, A AF Goodman, A TI Surgical cytoreduction in ovarian cancer - The McCreath/Chi article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID DEBULKING SURGERY; CARCINOMA; SURVIVAL; TUMORS C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2004 VL 18 IS 5 BP 656 EP + PG 2 WC Oncology SC Oncology GA 052DJ UT WOS:000238211000018 ER PT J AU Kelly, AE Sullivan, P Fawcett, J Samarel, N AF Kelly, AE Sullivan, P Fawcett, J Samarel, N TI Therapeutic touch, quiet time, and dialogue: Perceptions of women with breast cancer SO ONCOLOGY NURSING FORUM LA English DT Article ID NURSING INTERACTION; PAIN; ADMISSION; ANXIETY; MUSIC AB Purpose/Objectives: To compare the perceptions of women with breast cancer to an experimental therapeutic touch (TT) plus dialogue nursing intervention with perceptions of a control quiet time plus dialogue nursing intervention. Design: Qualitative study based on the Science of Unitary Human Beings. Setting: Data collected as part of a larger experimental study of the effects of TT on pre- and postoperative anxiety and mood and postoperative pain in women with breast cancer. Sample: 18 women with early-stage breast cancer. Methods: Telephone interviews at the completion of an experimental or control nursing intervention administered in the women's homes before and after breast cancer surgery. Main Research Variables: Women's perceptions of participation in a study of the effects of dialogue and TT or quiet time. Findings: Content analysis of transcribed telephone interviews revealed few differences in participants' perceptions of experimental and control interventions. Only participants who received the experimental intervention reported body sensations, and only participants in the control group inquired about the study and its purpose. Regardless of experimental or control intervention participation, women expressed feelings of calmness, relaxation, security, and comfort and a sense of awareness. The few women who commented about the nurse who administered the experimental or control intervention indicated that the nurse was empathetic, concerned, supportive, or helpful. Conclusions: The women regarded either nursing intervention as a positive experience. Some also expressed positive regard for the research nurse. Implications for Nursing: Nurses who are not trained in the administration of TT may use quiet time and dialogue to enhance feelings of calmness and relaxation in patients with breast cancer. C1 Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. Dana Farber Canc Inst, Womens Canc Program, Boston, MA 02115 USA. William Paterson Univ, Wayne, NJ USA. RP Fawcett, J (reprint author), Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. EM jacqueline.fawcett@umb.edu NR 40 TC 8 Z9 8 U1 1 U2 8 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAY PY 2004 VL 31 IS 3 BP 625 EP 631 DI 10.1188/04.ONF.625-631 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 875RD UT WOS:000225438500020 PM 15146228 ER PT J AU Durrani, K Papaliodis, GN Foster, CS AF Durrani, K Papaliodis, GN Foster, CS TI Pulse IV cyclophosphamide in ocular inflammatory disease - Efficacy and short-term safety SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Joint Meeting of the American-Academy-of-Ophthalmology/Pan-American-Association-of-Ophthalmol ogy CY OCT, 2002 CL ORLANDO, FL SP Amer Acad Ophthalmol, Pan Amer Assoc Ophthalmol ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTRAVENOUS CYCLOPHOSPHAMIDE; WEGENERS-GRANULOMATOSIS; RHEUMATOID-ARTHRITIS; IMMUNOSUPPRESSIVE THERAPY; VASCULITIS; UVEITIS AB Purpose: To assess the efficacy and short-term safety of appropriately monitored pulse IV cyclophosphamide therapy in the treatment of patients with severe or treatment-resistant autoimmune ocular inflammatory disease. Design: Retrospective noncomparative interventional case series. Participants: Thirty-eight patients with severe or recalcitrant ocular inflammation of diverse etiologies. Methods: Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Thirty-eight consecutive patients treated with pulse IV cyclophosphamide between January 1995 and March 2002 were analyzed. Main Outcome Measures: The control of inflammation, steroid-sparing effect, visual acuity, and adverse reactions. Results: A positive response to treatment occurred in 68% of patients during the study period, with 55% achieving complete quiescence. A steroid-sparing effect was achieved in all patients previously on systemic steroid, allowing successful discontinuation of the drug in 41%. Visual acuity was maintained in 66% and improved in 21% of involved eyes. The most common side effects observed were fatigue (63%), nausea (32%), and headache (22%). None required a permanent discontinuation of therapy. Conclusions: Pulse IV cyclophosphamide is an effective therapeutic modality in patients with severe or treatment-resistant ocular inflammatory disease. (C) 2004 by the American Academy of Ophthalmology. C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Dept Ophthalmol, Boston, MA 02114 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 37 TC 26 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2004 VL 111 IS 5 BP 960 EP 965 DI 10.1016/j.ophtha.2003.08.034 PG 6 WC Ophthalmology SC Ophthalmology GA 818FR UT WOS:000221231500019 PM 15121375 ER PT J AU Nadol, JB Eddington, DK AF Nadol, JB Eddington, DK TI Histologic evaluation of the tissue seal and biologic response around cochlear implant electrodes in the human SO OTOLOGY & NEUROTOLOGY LA English DT Article ID CEREBROSPINAL-FLUID SHUNTS; FOREIGN-BODY INFECTION; TEMPORAL BONE; STAPHYLOCOCCUS-AUREUS; FATAL MENINGITIS; HISTOPATHOLOGY; PATHOGENESIS; STAPEDECTOMY; EPIDERMIDIS; NEUTROPHILS AB Hypothesis: Histopathologic study of the tissue seal and biologic response around cochlear implant electrodes in patients who had received a cochlear implant during life could provide clues concerning the pathogenesis of meningitis after cochlear implantation. Background: Bacterial meningitis has been reported as an infrequent complication of cochlear implantation using a variety of electrode designs. The cause of meningitis in cochlear implant recipients has not been firmly established. In an analo-gous Surgical situation, namely stapedectomy, delayed meningitis could occur as a complication of ipsilateral acute suppurative otitis media in which there was open communica-tion between the middle ear and perilymph. Methods: Twenty-one temporal bones from 20 individuals who had undergone cochlear implantation during life were studied by light microscopy. All sections passing through the cochleostomy site and electrode track were examined to evaluate the tissue seal at the cochleostomy, the presence or absence of an extracochlear electrode sheath, and finally, to seek evidence of a cellular inflammatory response near the electrode. These data were compared with clinical data, including electrode system used, the number of years between implantation and death, type of tissue used at Surgery, and the age and sex of the patients. Results: The 21 specimens included cases implanted with the Symbion Ineraid, Cochlear Corporation Nucleus 22-channel, Cochlear Corporation Nucleus 24-channel, a Cochlear Corporation Nucleus single channel, and Advanced Bionics Clarion C I devices. At the cochleostomy site, and just within the cochlea, there was a robust fibrous and bony tissue response in all 21 ears and in most cases, there was a fibrous sheath surround-ing the electrode in the middle ear. No recognizable open communication or potential communication between the middle ear and the inner ear was seen in any of the 21 ears. An inflam-matory cellular response, including mononuclear leukocytes, histiocytes, and foreign body giant cells, were present in 12 of the 21 temporal bones (57%) and was most intense at the cochleostomy site. No statistically significant relationship was found between the presence or absence of inflammatory cells and the type of tissue graft used at surgery. Conclusions: The histologic evidence presented in this study does not support open communication between the middle and the inner ear as part of the pathogenesis of bacterial meningitis as a late complication after cochlear implantation. Rather, the finding of a cellular inflammatory response in 12 of 21 temporal bones suggests that late hematogenous contamination and colonization of the implant is a much more likely pathogenic mechanism. This putative mechanism has implications for possible strategies to prevent meningitis after cochlear implantation. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meci.harvard.edu FU NIDCD NIH HHS [R01-DC00152-21] NR 50 TC 46 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2004 VL 25 IS 3 BP 257 EP 262 DI 10.1097/00129492-200405000-00010 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 818SV UT WOS:000221265700010 PM 15129102 ER PT J AU Rosowski, JJ Songer, JE Nakajima, HH Brinsko, KM Merchant, SN AF Rosowski, JJ Songer, JE Nakajima, HH Brinsko, KM Merchant, SN TI Clinical, experimental, and theoretical investigations of the effect of superior semicircular canal dehiscence on hearing mechanisms SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 136th Annual Meeting of the American-Otological-Society CY MAY 03-04, 2003 CL Nashville, TN SP Amer Otol Soc DE bone conduction; cochlear potential; conductive hearing loss; laser-doppler; superior semicircular canal dehiscence; third window ID PRESSURE-INDUCED VERTIGO; TYMPANIC MEMBRANE; BONE DEHISCENCE; MIDDLE-EAR; HUMANS; MODEL AB Hypothesis: A superior semicircular canal dehiscence affects hearing by introducing a third window into the inner ear that 1) lowers cochlear input impedance, 2) shunts air-conducted sound away from the cochlea resulting in conductive hearing loss, and 3) improves bone-conduction thresholds by increasing the difference in impedance between the vestibule and the round window. Background: Superior semicircular canal dehiscence has been linked to a "conductive" hearing loss characterized by a decrease in the sensitivity to air-conducted sound and hypersensitivity to bone-conducted sound. Methods: Four investigations were performed: 1) laser-Doppler vibrometer measurements of sound-induced umbo velocity in patients with computed tomographic scan-confirmed superior semicircular canal dehiscence; 2) laser-Doppler vibrometry of sound-induced motions of the vestibular lymph (either perilymph or endolymph) exposed in a chinchilla model of superior semicircular canal dehiscence; 3) studies in chinchillas of the effect of superior semicircular canal dehiscence on the cochlea's sensitivity to bone-conducted sounds; and 4) ana-tomically based theoretical analyses of sound flow through the human cochlea and semicircular canals. Results: The low-frequency umbo velocity in Superior semicircular canal dehiscence patients without previous middle ear surgery ranged from normal through high normal. This tendency toward hypermobility suggests a decrease in cochlear impedance. Measurements of sound-induced velocity of the lymph within a superior semicircular canal dehiscence in chinchillas demonstrated sound flow through the dehiscence. Measurements of the cochlear potential demonstrated a superior semicircular canal dehiscence-induced increase in response to bone-conducted sound in eight of nine chinchillas. An anatomically based model of the human ear predicts changes in auditory sensitivity similar to audiometric changes in superior semicircular canal dehiscence. Conclusion: The results suggest that superior semicircular canal dehiscence can affect hearing function by introducing a third window into the inner ear. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM jjr@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC 00194, R01 DC 04798, R01 DC000194] NR 24 TC 120 Z9 129 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2004 VL 25 IS 3 BP 323 EP 332 DI 10.1097/00129492-200405000-00021 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 818SV UT WOS:000221265700021 PM 15129113 ER PT J AU Rauch, SD Zhou, GW Kujawa, SG Guinan, JJ Herrmann, BS AF Rauch, SD Zhou, GW Kujawa, SG Guinan, JJ Herrmann, BS TI Vestibular evoked myogenic potentials show altered tuning in patients with Meniere's disease SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Meniere's; vestibular evoked myogenic potential; vestibular evoked potentials ID ENDOLYMPHATIC HYDROPS; TONE BURSTS; REFLEX; TIME; CAT AB Objective: Acoustic stimulation of the saccule gives rise to a vestibulocollic reflex, the output of which can be measured in the neck as inhibition of activity in the ipsilateral sternocleidomastoid muscle. This vestibular evoked myogenic potential has been promoted as a means of assessing integrity of saccular function. In this study, we test the hypothesis that the cochleo-saccular hydrops of Meniere's syndrome leads to alterations in saccular motion that change the dynamics of the vestibular evoked myogenic potential. Study Design: Prospective cohort study. Setting: Large specialty hospital, department of otolaryngology. Subjects: Fourteen normal adult volunteers and 34 consecutive consenting adult patients with unilateral Meniere's disease by American Academy of Otolaryngology-Head and Neck Surgery diagnostic criteria. Interventions: All subjects underwent vestibular evoked myogenic potential testing using ipsilateral broadband click and short tone-burst stimuli at 250, 500, 1,000, 2,000, and 4,000 Hz. Main Outcome Measures: Threshold, amplitude, and latency of vestibular evoked myogenic potential responses in normal and Meniere's affected and unaffected ears. Results: Vestibular evoked myogenic potential was present in all ears tested. Normal subjects show a frequency-dependent vestibular evoked myogenic potential threshold, with best response ("frequency tuning") at 500 Hz. Compared with normal subjects and unaffected ears of Meniere's subjects, affected Meniere's ears had significantly increased vestibular evoked myogenic potential thresholds. Affected Meniere's ears showed threshold shifts at all frequencies and there was less tuning apparent at 500 Hz. Unaffected ears of Meniere's subjects also showed significantly elevated vestibular evoked myogenic po-tential thresholds compared with normal Subjects. Analyses of vestibular evoked myogenic potential thresholds for effects of age, hearing loss, and audiometric configuration showed no significant differences. Conclusions: Meniere's ears display alterations in vestibular evoked myogenic potential threshold and tuning, supporting our hypothesis of altered saccular motion mechanics arising from hydropic distention. Unaffected ears of unilateral Meniere's subjects show similar changes, though to a lesser degree. This finding may be because of occult saccular hydrops in the asymptomatic ear or binaural interactions in the vestibular evoked myogenic potential otolith-cervical reflex arc. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM sdr@epl.meei.harverd.edu FU NIDCD NIH HHS [R01-DC04425] NR 25 TC 100 Z9 107 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2004 VL 25 IS 3 BP 333 EP 338 DI 10.1097/00129492-200405000-00022 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 818SV UT WOS:000221265700022 PM 15129114 ER PT J AU Kirsch, DG Tarbell, NJ AF Kirsch, DG Tarbell, NJ TI Part of proceedings - New technologies in radiation therapy for pediatric brain tumors: The rationale for proton radiation therapy SO PEDIATRIC BLOOD & CANCER LA English DT Article; Proceedings Paper CT International Conference on Pediatric Radiation Oncology CY JUN 18-20, 2003 CL Lyon, FRANCE DE childhood brain tumors; late effects; proton irradiation; radiation therapy; second malignancies ID CONFORMAL RADIOTHERAPY; CANCER INCIDENCE; MEDULLOBLASTOMA; ONCOLOGY; RISK AB Background. Pediatric brain tumors are frequently treated with radiation therapy and often cured. The long-term side effects of treatment with high-energy X-rays (photons) can be substantial. Proton radiation therapy may limit these late effects. Procedure. The physical difference between photon and proton irradiation is compared. The clinical benefits of the superior physical properties of proton beam radiation therapy are explained for children with brain tumors. Results. At biologically equivalent doses, proton radiation therapy offers tumor control similar to photon radiation therapy. The superior physical properties of proton beams make this mode of radiation therapy less likely to cause late effects. Conclusions. For many children with brain tumors, proton beam radiation therapy may limit the late effects of radiation therapy and therefore offer an advantage over techniques using photons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Tarbell, NJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St,Bulfinch 360, Boston, MA 02114 USA. EM ntarbell@partners.org NR 13 TC 25 Z9 25 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2004 VL 42 IS 5 BP 461 EP 464 DI 10.1002/pbc.10471 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 812WH UT WOS:000220869100016 PM 15049021 ER PT J AU Yang, F Agulian, T Sudati, JE Rhoads, DB Levitsky, LL AF Yang, F Agulian, T Sudati, JE Rhoads, DB Levitsky, LL TI Developmental regulation of galactokinase in suckling mouse liver by the Egr-1 transcription factor SO PEDIATRIC RESEARCH LA English DT Article ID EARLY GROWTH-RESPONSE; ENZYME GENE-TRANSCRIPTION; IMMEDIATE-EARLY GENES; NGFI-A; 3T3 CELLS; C-FOS; BETA-CELLS; EXPRESSION; PROTEIN; PROMOTER AB The numerous changes in metabolic pathways that accompany liver development entail associated changes in gene expression. Egr-1 is a zinc-finger transcription factor that regulates genes involved in cellular growth, differentiation, stress response, and apoptosis in many cell types. Egr-1 is induced in liver regeneration in rodents, but its role in normal hepatocyte function has not been characterized. We examined the developmental expression of Egr-1 in mouse liver and found that its expression increased during the suckling period. In screening the sequences of the genes involved in lactose assimilation, we found that the galactokinase gene Glk contains four potential Egr-1 binding sites in its proximal promoter. A minimal promoter of 155 nucleotides encompassing the four Egr-1 sites exhibited activity in hepatoma cell lines by transient transfection assays. Moreover, co-transfection of an Egr-1 expression plasmid increased promoter activity. Finally, mutations introduced into three of the four Egr-1 binding sites decreased activity, whereas mutation of the remaining site increased promoter activity. These data tie Egr-1 and galactokinase together in a developmentally regulated chain to prepare the neonate for suckling. C1 Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rhoads, DB (reprint author), Harvard Univ, Sch Med, MassGen Hosp Children, Pediat Endocrine Unit, 55 Fruit St,BHX410, Boston, MA 02114 USA. EM drhoads@partners.org FU NICHD NIH HHS [HD31215]; NIDDK NIH HHS [DK54399] NR 43 TC 5 Z9 5 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 MAY PY 2004 VL 55 IS 5 BP 822 EP 829 DI 10.1203/01.PDR.0000120682.05408.79 PG 8 WC Pediatrics SC Pediatrics GA 813VK UT WOS:000220934400015 PM 14973178 ER PT J AU Einwohner, R Bernardini, J Fried, L Piraino, B AF Einwohner, R Bernardini, J Fried, L Piraino, B TI The effect of depressive symptoms on survival in peritoneal dialysis patients SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article DE depression; comorbidity; mortality ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; HEMODIALYSIS-PATIENTS; MAJOR DEPRESSION; PSYCHOSOCIAL PREDICTORS; UNITED-STATES; MORTALITY; HOSPITALIZATION; ASSOCIATION; OUTPATIENTS AB Objective:There is little information on the relationship between depressive symptoms and survival in peritoneal dialysis (PD) patients. We examined whether a single measurement of depressive symptoms using a simple self-administered tool predicts survival. Design: Screening test of depressive symptoms as a predictor of outcome. Setting: Three dialysis centers in Southwestern Pennsylvania. Participants: 66 adult PD subjects were screened in 1997-1998 for depression using the Zung scale. Main Outcome Measures: Baseline data collection included assessments of comorbidity, residual renal function, total Kt/V, nPNA, previous renal transplant, and serum albumin. Outcomes were collected prospectively after completion of the depression survey to 12/01. Cox regression analysis of patient survival was performed using all cofactors with p < 0.05 on univariate analysis. Results: One third of patients had depressive symptoms. Compared to nondepressed patients, depressive symptom patients were older (62.5 vs 52.5 years, p = 0.012), had borderline lower serum albumin levels (3.47 vs 3.70 g/dL, p = 0.058), and were more disabled (Karnofsky score 70 vs 90, p < 0.001), but had similar Kt/V, residual renal function, and previous time on PD at the point of the testing. Using multivariate analysis and controlling for comorbidity (using a measurement that includes diabetes mellitus and age) and serum albumin, the survival of patients with depressive symptoms was significantly reduced compared to nondepressed patients. Conclusion: A single measurement of depressive symptoms using a simple self-administered test was an independent predictor of death in a cohort of PD patients, which extends observations in hemodialysis patients. Screening for depressive symptoms should be routine for dialysis patients, and those depressed should have thorough assessment and treatment. Whether treating depression will have an impact on survival is unclear and needs to be studied. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Piraino, B (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Suite 200,3504 5th Ave, Pittsburgh, PA 15213 USA. EM piraino@pitt.edu OI Piraino, Beth/0000-0001-5061-0841 NR 30 TC 48 Z9 49 U1 2 U2 2 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD MAY-JUN PY 2004 VL 24 IS 3 BP 256 EP 263 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 825KS UT WOS:000221756700007 PM 15185774 ER PT J AU Hallett, PJ Standaert, DG AF Hallett, PJ Standaert, DG TI Rationale for and use of NMDA receptor antagonists in Parkinson's disease SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE NMDA receptors; Parkinson's disease; basal ganglia; levodopa; striatum; glutamate ID METHYL-D-ASPARTATE; EXCITATORY AMINO-ACID; METABOTROPIC GLUTAMATE RECEPTORS; DEPENDENT PROTEIN-KINASE; STRIATAL SYNAPTIC PLASTICITY; LEVODOPA-INDUCED DYSKINESIAS; SUBUNIT MESSENGER-RNA; DOPAMINE D1 RECEPTOR; NEUROCHEMICALLY IDENTIFIED PROJECTION; ENHANCED TYROSINE PHOSPHORYLATION AB N-Methyl-D-aspartate (NMDA) glutamate receptors are a class of excitatory amino acid receptors, which have several important functions in the motor circuits of the basal ganglia, and are viewed as important targets for the development of new drugs to prevent or treat Parkinson's disease (PD). NMDA receptors are ligand-gated ion channels composed of multiple subunits, each of which has distinct cellular and regional patterns of expression. They have complex regulatory properties, with both agonist and co-agonist binding sites and regulation by phosphorylation and protein-protein interactions. They are found in all of the structures of the basal ganglia, although the subunit composition in the various structures is different. NMDA receptors present in the striatum are crucial for dopamine-glutamate interactions. The abundance, structure, and function of striatal receptors are altered by the dopamine depletion and further modified by the pharmacological treatments used in PD. In animal models, NMDA receptor antagonists are effective antiparkinsonian agents and can reduce the complications of chronic dopaminergic therapy (wearing off and dyskinesias). Use of these agents in humans has been limited because of the adverse effects associated with nonselective blockade of NMDA receptor function, but the development of more potent and selective pharmaceuticals holds the promise of an important new therapeutic approach for PD. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Standaert, DG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM standaert@helix.mgh.harvard.edu OI Hallett, Penelope/0000-0002-8858-9096; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS34361] NR 258 TC 133 Z9 145 U1 1 U2 10 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 MAY PY 2004 VL 102 IS 2 BP 155 EP 174 DI 10.1016/j.pharmthera.2004.04.001 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 828OU UT WOS:000221983400006 PM 15163596 ER PT J AU Hamblin, MR Hasan, T AF Hamblin, MR Hasan, T TI Photodynamic therapy: a new antimicrobial approach to infectious disease? SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Review ID GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI-B; HERPES-SIMPLEX VIRUS; RESISTANT STAPHYLOCOCCUS-AUREUS; YEAST SACCHAROMYCES-CEREVISIAE; LIPID-SOLUBLE PHTHALOCYANINES; TOPICAL 5-AMINOLEVULINIC ACID; ANTIBODY-TARGETED PHOTOLYSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; 500-NM MONOCHROMATIC LIGHT AB Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(-) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(+) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(-) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naive strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [P01-CA84203, P01 CA084203, R01-CA/AI838801]; NIAID NIH HHS [R01 AI050875, R01 AI050875-01A2, R01-AI050875]; NIAMS NIH HHS [R01 AR040352, R01-AR40352] NR 169 TC 782 Z9 810 U1 29 U2 240 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PD MAY PY 2004 VL 3 IS 5 BP 436 EP 450 DI 10.1039/b311900a PG 15 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 828YA UT WOS:000222008500007 PM 15122361 ER PT J AU Gad, F Zahra, T Francis, KP Hasan, T Hamblin, MR AF Gad, F Zahra, T Francis, KP Hasan, T Hamblin, MR TI Targeted photodynamic therapy of established soft-tissue infections in mice SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; IN-VIVO; WOUND INFECTIONS; BACTERIA; VIRULENCE; MODEL AB The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-(-) bacteria in living mice. However, these infected wound models involved a short timespan between infection (30 min) and treatment by PDT. We now report on the use of PDT to treat an established soft-tissue infection in mice. We used Staphylococcus aureus stably transformed with a Photorhabdus luminescens lux operon (luxABCDE) that was genetically modified to be functional in Gram-(+) bacteria. These engineered bacteria emitted bioluminescence, allowing the progress of the infection to be monitored in both space and time with a low light imaging charge-coupled device (CCD) camera. One million cells were injected into one or both thigh muscles of mice that had previously been rendered neutropenic by cyclophosphamide administration, Twenty-four hours later, the bacteria had multiplied more than one hundredfold; poly-L-lysine chlorin e6 conjugate or free chlorin e6 was injected into one area of infected muscle and imaged with the CCD camera. Thirty minutes later, red light from a diode laser was delivered as a surface spot or by interstitial fiber into the infection. There was a light dose dependent loss of bioluminescence (to <5% of that seen in control infections) not seen in untreated infections or those treated with light alone, but in some cases, the infection recurred. Treatment with conjugate alone led to a lesser reduction in bioluminescence. Infections treated with free chlorin e6 responded less well and the infection subsequently increased over the succeeding days, probably due to PDT-mediated tissue damage. PDT-treated infected legs healed better than legs with untreated infections. This data shows that PDT may have applications in drug-resistant soft-tissue infections. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Newton Wellesley Hosp, Newton, MA 02462 USA. Xenogen Corp, Alameda, CA 94501 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875-01A2, R01 AI050875-02, R01AI050879, R01 AI050875] NR 23 TC 104 Z9 111 U1 1 U2 9 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PD MAY PY 2004 VL 3 IS 5 BP 451 EP 458 DI 10.1039/b311901g PG 8 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 828YA UT WOS:000222008500008 PM 15122362 ER PT J AU Fujii, N Aschenbach, WG Musi, N Hirshman, MF Goodyear, LJ AF Fujii, N Aschenbach, WG Musi, N Hirshman, MF Goodyear, LJ TI Regulation of glucose transport by the AMP-activated protein kinase SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Article; Proceedings Paper CT 12th Conference of the International-Research-Group-on-the-Biochemistry-of-Exercise CY JUL, 2003 CL Maastrict, NETHERLANDS SP Nat Sci & Engn Res Council Canada, Int Res Grp Biochem Exercise DE exercise; glucose uptake; AMP-activated protein kinase ID RAT SKELETAL-MUSCLE; ACETYL-COA CARBOXYLASE; EXERCISE INTENSITY; NO SYNTHASE; CONTRACTION; STIMULATION; ISOFORM; INSULIN; PHOSPHORYLATION; TRANSLOCATION AB The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated during exercise and muscle contraction as a result of acute decreases in ATP: AMP and phosphocreatine:creatine. Physical exercise increases muscle glucose uptake, enhances insulin sensitivity and leads to fatty acid oxidation in muscle. An important issue in muscle biology is to understand whether AMPK plays a role in mediating these metabolic processes. AMPK has also been implicated in regulating gene transcription and, therefore, may function in some of the cellular adaptations to training exercise. Recent studies have shown that the magnitude of AMPK activation and associated metabolic responses are affected by factors such as glycogen content, exercise training and fibre type. There have also been conflicting reports as to whether AMPK activity is necessary for contraction-stimulated glucose transport. Thus, during the next several years considerably more research will be necessary in order to fully understand the role of AMPK in regulating glucose transport in skeletal muscle. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Laurie.Goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR42338, R01 AR45670] NR 53 TC 24 Z9 25 U1 1 U2 2 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PD MAY PY 2004 VL 63 IS 2 BP 205 EP 210 DI 10.1079/PNS2004340 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 840ZO UT WOS:000222899300003 PM 15294031 ER PT J AU Wang, HH AF Wang, HH TI Molecular mechanisms of cell-cell recognition SO PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS LA Chinese DT Review DE protein-protein recognition; cell adhesion; three-dimensional structure; immunological synapse; cellular immunity ID MHC CLASS-II; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; HUMAN CD4; INTEGRIN ALPHA-V-BETA-3; EXTRACELLULAR SEGMENT; RECEPTOR INTERFACE; PROTEIN INTERFACES; ATOMIC-STRUCTURE; HOT-SPOT AB Cell-cell recognition is the key for multicellular organisms to survive. This recognition critically depends on protein-protein interactions from opposing cell surfaces. Recent structural investigations reveal unique features of these cell surface receptors and how they interact. These interactions are specific, but usually relatively weak, with more hydrophilic forces involved in binding. The receptors appear to have specialized ways to present their key interacting elements for ligand-binding from the cell surface. Cell-cell contacts are multivalent. A large group of cell surface molecules are engaged in interactions. Characteristic weak interactions make possible for each individual molecule pair within the group to constantly associate:dissociate-reassociate, such that the cell-cell recognition becomes a dynamic process. The immunological synapse is a good example for immune receptors to be orchestrated in performing immunological function in a collective fashion. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wang, HH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu NR 44 TC 0 Z9 0 U1 1 U2 2 PU CHINESE ACAD SCIENCES, INST BIOPHYSICS PI BEIJING PA 15 DATUN RD, CHAOYAND DISTRICT, BEIJING, 100101, PEOPLES R CHINA SN 1000-3282 J9 PROG BIOCHEM BIOPHYS JI Prog. Biochem. Biophys. PD MAY PY 2004 VL 31 IS 5 BP 385 EP 392 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 841FI UT WOS:000222914300001 ER PT J AU Niznikiewicz, MA Friedman, M Shenton, ME Voglmaier, M Nestor, PG Frumin, M Seidman, L Sutton, J McCarley, RW AF Niznikiewicz, MA Friedman, M Shenton, ME Voglmaier, M Nestor, PG Frumin, M Seidman, L Sutton, J McCarley, RW TI Processing sentence context in women with schizotypal personality disorder: An ERP study SO PSYCHOPHYSIOLOGY LA English DT Article DE sentence processing; schizotypal personality disorder women; context; event-related potentials; language; N400 ID AUTOMATIC SPREADING ACTIVATION; EVENT-RELATED POTENTIALS; SCHIZOPHRENIC-PATIENTS; DEFICITS; GENDER AB Accumulating evidence suggests that schizophrenic patients do not use context efficiently. Also, studies suggest similarities in clinical and cognitive profiles between schizophrenic and schizotypal personality disorder (SPD) individuals, and epidemiological studies point to a genetic link between the two disorders. This Study examined electrophysiological correlates of processing sentence context in a group of SPD women in a classical N400 sentence paradigm. The study assessed if the dysfunction in context use found previously in schizophrenia and male SPD also exists in female SPD. We tested 17 SPD and 16 matched normal control women. The results suggest the presence of abnormality in context use in female SPD similar to that previously reported for male schizophrenic and SPD individuals, but of lesser degree of severity. In SPD women, relative to their comparison group, a more negative N400 was found only to auditory congruent sentences. C1 Harvard Univ, Sch Med, Dept Psychiat,VAMC, Neurosci Lab, Brockton, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Niznikiewicz, MA (reprint author), VA Boston Healthcare Syst, Brockton Div, Psychiat 116A,940 Belmont St, Brockton, MA 02301 USA. EM margaret_niznikiewicz@hms.harvard.edu; robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [K05 MH070047, K05 MH070047-01, KO2-MH00746, MH40799, MH52807, R01 MH040799, R01 MH040799-14, R01 MH052807, R01 MH052807-06] NR 29 TC 18 Z9 19 U1 2 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAY PY 2004 VL 41 IS 3 BP 367 EP 371 DI 10.1111/1469-8986.2004.00173.x PG 5 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 821TP UT WOS:000221485900004 PM 15102121 ER PT J AU Kinder, LS Carnethon, MR Palaniappan, LP King, AC Fortmann, SP AF Kinder, LS Carnethon, MR Palaniappan, LP King, AC Fortmann, SP TI Depression and the metabolic syndrome in young adults: Findings from the third national health and nutrition examination survey SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; the metabolic syndrome; the third national health and nutrition examination survey ID HEART-RATE-VARIABILITY; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PSYCHOLOGICAL-FACTORS; MORTALITY; PREVALENCE; ASSOCIATION; RISK; SYMPTOMATOLOGY AB Objective: Previous reports have suggested that depression may lead to the development of cardiovascular disease through its association with the metabolic syndrome; however, little is known about the relationship between depression and the metabolic syndrome. The aim of this study was to establish an association between depression and the metabolic syndrome in a nationally representative sample. Methods: The Third National Health and Nutrition Examination Survey is a population-based health survey of noninstitutionalized US citizens completed between 1988 and 1994. Three thousand one hundred eighty-six men and 3003 women, age 17 to 39, free of coronary heart disease and diabetes, completed the depression module from the Diagnostic Interview Schedule and a medical examination that provided clinical data needed to establish the presence of the metabolic syndrome, as defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults. Results: Women with a history of a major depressive episode were twice as likely to have the metabolic syndrome compared with those with no history of depression. The relationship between depression and metabolic syndrome remained after controlling for age, race, education, smoking, physical inactivity, carbohydrate consumption, and alcohol use. Men with a history of depression were not significantly more likely to have the metabolic syndrome. Conclusions: The prevalence of the metabolic syndrome is elevated among women with a history of depression. It is important to better understand the role depression may play in the effort to reduce the prevalence of the metabolic syndrome and its health consequences. C1 Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, Stanford, CA USA. RP Kinder, LS (reprint author), VA Puget Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM lskinder@stanfordalumni.org FU NHLBI NIH HHS [F32 HL 10338, 5 T32 HL 07034] NR 41 TC 199 Z9 215 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 2004 VL 66 IS 3 BP 316 EP 322 DI 10.1097/01.psy.0000124755.91880.f4 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 822OA UT WOS:000221548300005 PM 15184689 ER PT J AU Naliboff, BD Mayer, M Fass, R Fitzgerald, LZ Chang, L Bolus, R Mayer, EA AF Naliboff, BD Mayer, M Fass, R Fitzgerald, LZ Chang, L Bolus, R Mayer, EA TI The effect of life stress on symptoms of heartburn SO PSYCHOSOMATIC MEDICINE LA English DT Article DE vital exhaustion; visceral sensitivity; gastroesophageal reflux disease ID IRRITABLE-BOWEL-SYNDROME; GASTROESOPHAGEAL-REFLUX DISEASE; VITAL EXHAUSTION; GASTROINTESTINAL-TRACT; MYOCARDIAL-INFARCTION; EVENTS; DYSFUNCTION; PERCEPTION; POPULATION; DISORDER AB Objective: Psycbosocial stressors have been associated with exacerbations of symptoms in functional and inflammatory disorders of the gastrointestinal tract. The present longitudinal study tests the general hypothesis that life stressors can exacerbate symptoms in patients with chronic heartburn. Methods: Sixty subjects with current heartburn symptoms were recruited by community advertisement and assessed for presence of stressful life events retrospectively over the preceding 6 months and prospectively for 4 months. Symptom severity by daily diary, quality of life, and psychological symptoms of anxiety, depression, and vital exhaustion were also measured. Results: The presence of a severe, sustained life stress during the previous 6 months significantly predicted increased heartburn symptoms during the following 4 months. In addition, symptoms showed a strong, independent correlation with vital exhaustion. Affective and subjective stress ratings were not strongly related to heartburn severity; however, anxiety showed the strongest relationship to impaired quality of life and depression to heartburn medication use. Conclusions: As with other chronic conditions such as irritable bowel syndrome (IBS), heartburn severity appears to be most responsive to major life events and not an accumulation of more minor stressors or fluctuations in mood. In addition, vital exhaustion, which may in part result from sustained stress, may represent the psychophysiological symptom complex most closely associated with heartburn exacerbation. Potential mechanisms for these results include increased level and frequency of esophageal acid exposure, inhibition of gastric emptying of acid, or stress-induced hypersensitivity. C1 Univ Calif Los Angeles, Dept Med, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Med Ctr, Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Arizona, VA Med Ctr, GI Div, Tucson, AZ USA. RP Naliboff, BD (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Neuroenter Dis Program, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu FU NIDDK NIH HHS [P50 DK64539]; NINR NIH HHS [NR007768] NR 43 TC 64 Z9 70 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 2004 VL 66 IS 3 BP 426 EP 434 DI 10.1097/01.psy.0000124756.37520.84 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 822OA UT WOS:000221548300023 PM 15184707 ER PT J AU Beresford, TP Martin, B Alfers, J AF Beresford, TP Martin, B Alfers, J TI Developing a brief monitoring procedure for alcohol dependent liver graft recipients SO PSYCHOSOMATICS LA English DT Article ID BRIEF INTERVENTIONS; TRANSPLANT RECIPIENTS; DRINKERS; TRIAL AB To address the occurrence of deaths in later Postoperative years among alcohol-dependent liver graft recipients, the authors developed the Brief Active Focused Follow-Up protocol as an instrument for monitoring alcohol use following liver transplant. In this preliminary study, patient receptiveness to its use was tested and its ability, to identify patient drinking was noted. Alcohol dependent liver transplant recipients (N = 24) and alcohol-dependent nontransplant patients (N = 25) were asked to rate their receptiveness to the Brief Active Focused Follow-Up in three areas. Subjects used a five-point scale for which 5 indicated the highest positive response. Liver transplant recipients responded positively to the Brief Active Focused Follow-Up, with mean responses of 4.92, 4.08, and 4.63 with regard to clarity, usefulness, and ease of completion, respectively. Nontransplant subjects responded similarly, with mean responses of 4.88, 4.12, and 4.52. The two groups were not significantly different in their receptiveness to the Brief Active Focused Follow-Up interview The Brief Active Focused Follow-Up identified alcohol use within the last 30 days: 8% (N = 2 of 24) in the transplant group, and 56% (N = 14 of 25) in the nontransplant group. These results suggest that 1) this manualized, brief monitoring technique is well received by alcohol-dependent liver transplant patients, and 2) the Brief Active Focused Follow-Up's, I user friendliness" makes it a potentially appropriate instrument for long-term monitoring of alcohol use among alcohol-dependent liver graft recipients. C1 Denver VA Med Ctr 151, Denver, CO 80220 USA. Dept Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Beresford, TP (reprint author), Denver VA Med Ctr 151, 1055 Clermont St, Denver, CO 80220 USA. EM thomas.beresford@uchsc.edu FU NIAAA NIH HHS [AA-12095] NR 15 TC 5 Z9 5 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2004 VL 45 IS 3 BP 220 EP 223 DI 10.1176/appi.psy.45.3.220 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 816JZ UT WOS:000221107500006 PM 15123847 ER PT J AU Perlis, RH Iosifescu, DV Alpert, J Nierenberg, AA Rosenbaum, JF Fava, M AF Perlis, RH Iosifescu, DV Alpert, J Nierenberg, AA Rosenbaum, JF Fava, M TI Effect of medical comorbidity on response to fluoxetine augmentation or dose increase in outpatients with treatment-resistant depression SO PSYCHOSOMATICS LA English DT Article ID MAJOR DEPRESSION; ANTIDEPRESSANT RESPONSE; LITHIUM AUGMENTATION; PHYSICAL ILLNESS; CONTROLLED-TRIAL; RATING-SCALE; PREDICTORS; CANCER; WOMEN; NONRESPONDERS AB This study assessed the effect of general medical comorbidity on response to next-step antidepressant treatments among subjects with major depressive disorder whose depression failed to respond to an 8-week open trial of 20 mg/day of fluoxetine. Of the 386 outpatients in the open trial, 101 who remained depressed were randomly assigned to double-blind treatment with either an increased dose of fluoxetine or lithium or desipramine augmentation,for 4 weeks. The Cumulative Illness Rating Scale (CIRS) was used to assess baseline general medical comorbidity and the Hamilton Depression Rating Scale was used to assess depressive symptoms. Logistic regression analysis showed that CIRS score was not associated with likelihood of remission or premature study discontinuation. Medical comorbidity) thus does not appear to be associated with significantly poorer outcome among patients whose major depressive disorder failed initially to respond to an initial trial of 20 mg/day of fluoxetine. C1 Massachusetts Gen Hosp, Dept Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM rperlis@partners.org OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [MH48483-05] NR 33 TC 15 Z9 17 U1 2 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2004 VL 45 IS 3 BP 224 EP 229 DI 10.1176/appi.psy.45.3.224 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 816JZ UT WOS:000221107500007 PM 15123848 ER PT J AU Maher, MM Gervais, DA Kalra, MK Lucey, B Sahani, DV Arellano, R Hahn, PF Mueller, PR AF Maher, MM Gervais, DA Kalra, MK Lucey, B Sahani, DV Arellano, R Hahn, PF Mueller, PR TI The inaccessible or undrainable abscess: How to drain it SO RADIOGRAPHICS LA English DT Article DE abdomen, abscess; abscess, CT; abscess, percutancous drainage; abscess, US; catheters and catheterization; computed tomography (CT) guidance; ultrasound (US) catheter identification; ultrasound (US) guidance; ultrasound (US) transvaginal ID GUIDED TRANSGLUTEAL DRAINAGE; DEEP PELVIC ABSCESSES; CATHETER DRAINAGE AB Percutaneous abscess drainage is a safe, effective, and widely used technique for the treatment of patients with abdominal or pelvic sepsis. The majority of abdominal and pelvic abscesses afford reasonably straightforward access and are amenable to percutaneous drainage. However, requests are occasionally received for drainage of abscesses or fluid collections that initially appear unsuitable for percutaneous drainage. Factors that render collections seemingly unsuitable for imaging-guided drainage include inaccessibility due to surrounding organs, difficult location, and thickened contents (eg, clotted blood, thick pus). Well-established alternative approaches (eg, transgluteal, transvaginal, transrectal) can be used to facilitate drainage of deep-seated collections that are inaccessible via more traditional routes. Other factors that may improve the accessibility of collections include modifications in patient positioning or in the use of imaging hardware (eg, angling of the computed tomography scanner gantry). Use of these techniques and modifications can allow percutaneous drainage of less accessible intraabdominal abscesses, thus eliminating the need for laparotomy. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM pmueller@apartners.org NR 10 TC 48 Z9 51 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2004 VL 24 IS 3 BP 717 EP 735 DI 10.1148/rg.24035100 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 819CB UT WOS:000221289700006 PM 15143224 ER PT J AU Gervais, DA Brown, SD Connolly, SA Brec, SL Harisinghani, MG Mueller, PR AF Gervais, DA Brown, SD Connolly, SA Brec, SL Harisinghani, MG Mueller, PR TI Percutaneous imaging-guided abdominal and pelvic abscess drainage in children SO RADIOGRAPHICS LA English DT Article DE abdomen, abscess; abscess, percutancous drainage; children, infections; Intervention procedures, in infants and children; pelvic organs abscess ID INTERVENTIONAL RADIOLOGIC PROCEDURES; FLUID COLLECTIONS; TRANSRECTAL DRAINAGE; RENAL ABSCESS; FLUOROSCOPIC GUIDANCE; ACUTE-PANCREATITIS; PEDIATRIC-PATIENTS; SEDATION; MANAGEMENT; GUIDELINES AB Percutaneous imaging-guided drainage is the first-line treatment for infected or symptomatic fluid collections in the abdomen and pelvis, in the absence of indications for immediate surgery. The technology and expertise needed to perform percutaneous abscess drainage are widely available and readily adapted for use in the pediatric population. Catheter insertion procedures include the trocar and Seldinger techniques. Imaging guidance for drainage is most commonly performed with ultrasonography (US), computed tomography, or US and fluoroscopy combined. Abscesses in locations that are difficult to access, such as those deep in the pelvis, subphrenic regions, or epigastric region, can be drained by using the appropriate approach-transrectal, transgluteal, intercostal, or transhepatic. Although the causes of abscesses in children differ slightly from those of abscesses in the adult population, the frequency of successful treatment with percutaneous abscess drainage in children is 85%-90%, similar to that in adults. With expertise in imaging-guided drainage techniques and the ability to adjust to the special needs of children, interventional radiologists can successfully drain most abscesses and obviate surgery. Successful adaptation of abscess drainage techniques for pediatric use requires attention to the specific needs of children with respect to sedation, dedicated resuscitation and monitoring equipment, avoidance of body heat loss, minimization of radiation doses, and greater involvement of family compared with that in adult practice. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 34 Fruit St,White 270, Boston, MA 02115 USA. EM dgervais@partners.org NR 34 TC 33 Z9 35 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2004 VL 24 IS 3 BP 737 EP 754 DI 10.1148/rg.243035107 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 819CB UT WOS:000221289700007 PM 15143225 ER PT J AU Harisinghani, MG Dixon, WT Saksena, MA Brachtel, E Blezek, DJ Dhawale, PJ Torabi, M Hahn, PF AF Harisinghani, MG Dixon, WT Saksena, MA Brachtel, E Blezek, DJ Dhawale, PJ Torabi, M Hahn, PF TI MR lymphangiography: Imaging strategies to optimize the imaging of lymph nodes with ferumoxtran-10 SO RADIOGRAPHICS LA English DT Article DE contrast media; lymphatic system, MR; lymphatic system, neoplasms; magnetic resonance (MR), contrast media ID SUPERPARAMAGNETIC IRON-OXIDE; MULTICENTER CLINICAL-TRIAL; CONTRAST AGENT; COMPUTED-TOMOGRAPHY; BREAST-CANCER; METASTASES; NECK; CARCINOMA; SIZE; HEAD AB Detection of local or regional metastases to lymph nodes is clinically important in virtually any type of primary tumor. Current imaging techniques rely heavily on the size criterion for characterization of nodal disease. However, size can be an ineffective parameter for diagnosis of tumor spread to lymph nodes. Magnetic resonance (MR) imaging performed before and after administration of ferumoxtran-10 is a promising technique for characterization of lymph nodes in patients with various primary tumors. Normal homogeneous uptake of ferumoxtran-10 in nonmetastatic nodes shortens the T2 and T2*, turning these nodes dark, whereas malignant nodes lack uptake and remain hyperintense. To optimize acquisition strategies, the following factors should be considered: the timing of contrast material-enhanced imaging, the section thickness, the imaging plane, and the imaging parameters for T2*-weighted sequences. In addition, MR imaging with ferumoxtran-10 allows presurgical mapping of lymph nodes and quantitative estimation of T2*. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Gen Elect Global Res, Niskayuna, NY USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mharisinghani@partners.org NR 33 TC 61 Z9 63 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2004 VL 24 IS 3 BP 867 EP 878 DI 10.1148/rg.243035190 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 819CB UT WOS:000221289700019 PM 15143236 ER PT J AU Landis, D Schultz, D Cormack, R Tempany, C Beard, C Hurwitz, M Valentine, K D'Amico, A AF Landis, D Schultz, D Cormack, R Tempany, C Beard, C Hurwitz, M Valentine, K D'Amico, A TI Acute urinary retention following magnetic-resonance-image-guided prostate brachytherapy SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT GEC/ESTRO/GLAC/ABS Joint Brachytherapy Meeting CY MAY 13-15, 2004 CL Barcelona, SPAIN SP GEC, ESTRO, GLAC, ABS C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAY PY 2004 VL 71 SU 2 MA 87 BP S43 EP S44 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 835GB UT WOS:000222468200088 ER PT J AU Lerman-Garber, I Villa, AR Caballero, E AF Lerman-Garber, I Villa, AR Caballero, E TI Diabetes and cardiovascular disease. Is there a true Hispanic paradox? SO REVISTA DE INVESTIGACION CLINICA LA English DT Review DE Hispanic paradox; diabetes and cardiovascular disease ID NUTRITION EXAMINATION SURVEY; IMPAIRED GLUCOSE-TOLERANCE; CORONARY-HEART-DISEASE; 3RD NATIONAL-HEALTH; INSULIN-RESISTANCE ATHEROSCLEROSIS; BODY-MASS INDEX; NONDIABETIC AFRICAN-AMERICANS; ACUTE MYOCARDIAL-INFARCTION; LOWER-EXTREMITY AMPUTATIONS; MEXICAN-AMERICANS AB The observation that Hispanics have power all-cause and cardiovascular mortality despite increased prevalence of diabetes and obesity, lower socioeconomic status and barriers to health care, has been termed the "Hispanic Paradox". There are problems of data reliability and confounding bias in the analysis of this paradox. Material and methods. An electronic search in the MEDLINE was performed for information published during the last 30 years: National cohort studies, population based and case-control studies, vital statistics and major review articles were included using the following key words: Cardiovascular disease and overall mortality by ethnicity, in diabetic patients from the US and Latin America. Results. A total of 140 articles were included, classified and analyzed separately according to the following thematic: The U.S. Hispanic population, cardiovascular (CV) and overall mortality rates in Hispanics, type 2 diabetes in Hispanics, diabetes and coronary heart disease, CV disease in Hispanic diabetic patients, CV risk profile in Hispanics, ethnicity and CV risk factors, diabetes and CV disease in Latin America and a search for the protective or causative factors for CV disease. Conclusions. Much controversy and diverse confounding factors surround the Hispanic paradox. The present data suggest that the lower mortality in Hispanics is not "genuine", but is rather caused by migratory factors and probably mild distortions due to selection combined with mild reporting errors that may produce the appearance of a paradox when there is none at all. Even more, recent studies do not confirm the lower mortality rates in US Hispanics compared to the Non Hispanic White population, or that Hispanics from Latin America have lower mortality rates from CV disease than the US population. In the current era of globalization, major changes in the socio-economic and cultural status of people in developing countries and disadvantaged and minority groups in developed nations has lead to the current diabetic and atherosclerotic heart disease epidemic. C1 Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metabiol Lipidos, Mexico City 14000, DF, Mexico. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Unidad Epidemiol Clin, Mexico City 14000, DF, Mexico. Joslin Diabet Ctr, HMS, Dept Clin Invest, Boston, MA USA. RP Lerman-Garber, I (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metabiol Lipidos, Vasco Quiroga 15,Tlalpan, Mexico City 14000, DF, Mexico. EM lerman@netservice.com.mx NR 134 TC 25 Z9 26 U1 1 U2 7 PU INST NACIONAL NUTRICION PI TLALPAN PA VASCO DE QUIROZA #15, TLALPAN 14000 D F, MEXICO SN 0034-8376 J9 REV INVEST CLIN JI Rev. Invest. Clin. PD MAY-JUN PY 2004 VL 56 IS 3 BP 282 EP 296 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 850QY UT WOS:000223628700001 PM 15612509 ER PT J AU Young, RH AF Young, RH TI Howard Atwood Kelly, Elizabeth Hurdon, and their great work: "The vermiform appendix and its diseases" SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Warren 215, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD MAY PY 2004 VL 21 IS 2 BP 77 EP 85 DI 10.1053/j.semdp.2004.11.002 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 904LF UT WOS:000227498800002 PM 15807468 ER PT J AU Misdraji, J Young, RH AF Misdraji, J Young, RH TI Primary epithelial neoplasms and other epithelial lesions of the appendix (excluding carcinoid tumors) SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE appendix; mucocele; cystadenoma; adenocarcinoma; hyperplasia; serrated adenoma ID HYPERPLASTIC ADENOMATOUS POLYPS; SYNCHRONOUS MUCINOUS TUMORS; SPORADIC COLORECTAL-CANCER; DNA-REPLICATION ERRORS; PSEUDOMYXOMA-PERITONEI; VERMIFORM APPENDIX; PRIMARY ADENOCARCINOMA; CLINICOPATHOLOGICAL ANALYSIS; MICROSATELLITE INSTABILITY; SERRATED ADENOMAS AB Epithelial tumors of the appendix range from low-grade mucosal-based tumors which, when confined to the appendix, have an excellent prognosis but, once outside the appendix, have a fair prognosis and often a prolonged disease course, to high grade invasive carcinomas that are rapidly fatal. Low grade mucinous neoplasms may rupture and spread to the peritoneum as pseudomyxoma peritonei, and the nomenclature of these tumors has been the subject of considerable disagreement among pathologists; the designation "low grade appendiceal mucinous neoplasm" has recently been proposed for reasons discussed herein. Demonstrating rupture of these neoplasms may require particularly diligent gross and microscopic evaluation as the rupture site often heals over leaving only subtle evidence of its presence. Invasive adenocarcinomas are often mucinous and may also spread to the peritoneum. Against this backdrop, the clinical and pathologic features of low grade appendiceal mucinous neoplasms and mucinous adenocarcinomas, as well as other types such as typical colorectal type and signet-ring cell type, are reviewed. In addition, emerging entities, serrated polyps and serrated adenomas, whose significance is only beginning to be understood, are considered. Retention cysts, hyperplastic polyps, and diffuse mucosal hyperplasia, although not necessarily neoplastic, are reviewed here as they may enter into the differential diagnosis of appendiceal mucinous neoplasms. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Warren Bldg 105F,55 Fruit St, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 104 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD MAY PY 2004 VL 21 IS 2 BP 120 EP 133 DI 10.1053/j.semdp.2004.11.005 PG 14 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 904LF UT WOS:000227498800006 PM 15807472 ER PT J AU Young, RH AF Young, RH TI Pseudomyxoma peritonei and selected other aspects of the spread of appendiceal neoplasms SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE appendix; ovary; pseudomyxoma peritonei ID MUCINOUS TUMORS; CLINICOPATHOLOGICAL ANALYSIS; VERMIFORM APPENDIX; PROGNOSTIC FACTORS; PRIMARY OVARIAN; SCROTAL MASS; ORIGIN; EMPHASIS; WOMEN; SITE AB The varied aspects of spread of appendiceal neoplasms are reviewed with emphasis on the often clinically dramatic phenomenon known as pseudomyxoma peritonei, a term mostly used to describe grossly evident mucin within the peritoneal cavity. The majority of cases of pseudomyxoma peritonei result from tumors primary in the appendix, which are usually low-grade. On microscopic examination pseudomyxoma peritonei is typically characterized by large aggregates of mucin which may be relatively acellular or cellular containing strips of mucincous epithelium, mucincous epithelium encircling glands and cysts, or aggregates of mucinous epithelium lying within mucin pools. High-grade adenocarcinoma of the appendix may spread to the omentum and peritoneal surfaces without grossly striking mucin deposition and resemble spread of other high-grade gastrointestinal adenocarcinomas. In many cases of pseudomyxoma peritonei in females there is involvement of one, or more often, both ovaries. The size of the ovarian neoplasms characteristically dwarfs the often relatively unremarkable appearing appendix in these cases. The ovaries are typically multilocular, although one locule may dominate, and in cases in which the primary is a low-grade appendiceal mucinous neoplasm often have a "jelly-like" consistency. In cases of spread of frank adenocarcinomas the ovarian metastases typically have a more solid, albeit still somewhat gelatinous consistency. Microscopic examination of the ovaries typically shows surface involvement, a characteristic of spread to the ovaries in general, and the glands and cysts that replace most or all of the parenchyma are typically lined by tall mucin-rich cells with, in many cases, relatively bland microscopic features. In cases of frank adenocarcinoma, the tumors may mimic closely a primary mucinous adenocarcinoma of the ovary. Spread to the ovaries may also be seen in cases of frank intestinal-type adenocarcinoma primary in the appendix and the uncommon signet ring cell carcinoma of the appendix, the latter being one cause of the Krukenberg tumor. Occasional cases are reported in the literature of ovarian spread of goblet cell carcinoid tumor of the appendix, but in our opinion most of the primary tumors in those cases are better classified as adenocarcinomas, usually dominantly of signet-ring cell type, albeit sometimes with focal neuroendocrine differentiation. Other interesting aspects of spread of appendiceal neoplasms include to the lining of the uterus and the fallopian tube. In yet other cases the tumors may present clinically as incidentally discovered mucinous aggregates within hernia sac specimens or as a scrotal mass. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Warren 215, Boston, MA 02114 USA. NR 51 TC 38 Z9 39 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 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD MAY PY 2004 VL 21 IS 2 BP 134 EP 150 DI 10.1053/j.semdp.2004.12.002 PG 17 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 904LF UT WOS:000227498800007 PM 15807473 ER PT J AU Misdraji, J Graeme-Cook, FM AF Misdraji, J Graeme-Cook, FM TI Miscellaneous conditions of the appendix SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE appendix; duplication; agenesis; diverticulosis; endometriosis; vasculitis; neuroma; leiomyoma; granular cell tumor; lymphoma; secondary tumor ID PRIMARY MALIGNANT-LYMPHOMA; SYSTEMIC LUPUS-ERYTHEMATOSUS; NON-HODGKINS-LYMPHOMA; GRANULAR-CELL TUMORS; INSIDE-OUT APPENDIX; LOWER QUADRANT PAIN; OF-THE-LITERATURE; VERMIFORM APPENDIX; GASTROINTESTINAL-TRACT; KAPOSIS-SARCOMA AB A variety of miscellaneous conditions affect the appendix, both as incidental findings and as causes of clinical signs and symptoms that often mimic appendicitis. Congenital abnormalities of the appendix are rare; the two most commonly reported are congenital absence and appendiceal duplication. Diverticular disease may be an incidental finding, but when inflamed, can be clinically confused with appendicitis. Endometriosis of the appendix, which usually occurs in the setting of generalized gastrointestinal endometriosis, often presents as acute appendicitis, but may present as intussusception, lower intestinal bleeding, and, particularly during pregnancy, perforation. Peritoneal endosalpingiosis often involves the appendiceal serosa and occasionally the wall but has no clinical manifestations in contrast to endometriosis. Vasculitis may be either isolated to the appendix or part of a systemic vasculitis, most often polyarteritis nodosa. Neural proliferations of the appendix include lesions associated with von Recklinghausen's disease, as well as mucosal and axial neuromas that are theorized to progress to fibrous obliteration of the appendix. Mesenchymal tumors of the appendix are most often of smooth muscle type, usually leiomyoma but rarely leiomyosarcoma; nonmyogenic neoplasms such as gastrointestinal stromal tumor, granular cell tumor, Kaposi's sarcoma, and miscellaneous other curiosities occur rarely. Lymphoma affects the appendix exceptionally; in children, Burkitt lymphoma is most common whereas in adults, large cell lymphomas and low grade B-cell lymphomas predominate. Secondary involvement of the appendix by leukemia has been reported. Secondary involvement of the appendix by carcinomas of the female genital tract, particularly ovary, and diverse other sites are in aggregate common but only rarely a clinical or pathological difficulty. Occasionally, however, appendiceal neoplasia that is secondary from another site may dominate the clinical picture and lead to potential pathologic misdiagnosis as primary appendiceal disease. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Home Wright Pathol Labs, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Home Wright Pathol Labs, Warren Bldg 105F,55 Fruit St, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 164 TC 23 Z9 27 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 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD MAY PY 2004 VL 21 IS 2 BP 151 EP 163 DI 10.1053/j.semdp.2004.11.006 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 904LF UT WOS:000227498800008 PM 15807474 ER PT J AU Johansen, KL AF Johansen, KL TI Testosterone metabolism and replacement therapy in patients with end-stage renal disease SO SEMINARS IN DIALYSIS LA English DT Review ID CLINICAL-RESEARCH-CENTER; CORONARY-ARTERY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PITUITARY-TESTICULAR AXIS; BONE-MINERAL DENSITY; HYPOGONADAL MEN; TRANSDERMAL TESTOSTERONE; OLDER MEN; AGING MALE; ERECTILE DYSFUNCTION AB Hypogonadism is common among men with end-stage renal disease (ESRD), beginning before the need for dialysis and not improved with the initiation of dialysis. Many of the manifestations of hypogonadism, such as bone disease and muscle wasting, are also frequently seen among dialysis patients. There have been few studies of testosterone replacement therapy in this patient population, but available data suggest that testosterone can be administered without adjustment of the doses used in hypogonadal men with normal renal function. Extrapolation from results of treatment of hypogonadal older men with normal renal function suggests that testosterone replacement could improve libido and could have salutary effects on muscle mass and bone mineral density in patients with kidney disease. However, caution is warranted because of the potential side effects of testosterone therapy, and further research is needed to more precisely define the balance of risk and benefit in patients with chronic kidney disease. Specifically it will be important to determine the prevalence and clinical significance of hypogonadism in ESRD patients in the modern era and to measure the effects of replacement therapy on various symptoms of hypogonadism as well as on overall quality of life, physical functioning, and survival. C1 San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM johanse@itsa.ucsf.edu NR 73 TC 29 Z9 32 U1 1 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2004 VL 17 IS 3 BP 202 EP 208 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 821HS UT WOS:000221451600010 PM 15144546 ER PT J AU Wang, PL Watnick, SG AF Wang, PL Watnick, SG TI Depression: A common but underrecognized condition associated with end-stage renal disease SO SEMINARS IN DIALYSIS LA English DT Article ID QUALITY-OF-LIFE; DIALYSIS PATIENTS; HEMODIALYSIS-PATIENTS; MAJOR DEPRESSION; SYMPTOMS; VALIDATION; MORTALITY; INVENTORY; ANXIETY; SCALE AB We describe a patient with end-stage renal disease (ESRD) who developed depression over the period of dialysis initiation. Depression is an extremely common but underrecognized disorder in the dialysis population, which is one of the rationales for this case report. Here we present the epidemiology, mechanisms for diagnosis, associations with medical morbidity, and treatment modalities specifically for patients on dialysis. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Watnick, SG (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM watnicks@ohsu.edu NR 33 TC 14 Z9 15 U1 2 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2004 VL 17 IS 3 BP 237 EP 240 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 821HS UT WOS:000221451600016 PM 15144552 ER PT J AU Rabinov, JD Barker, FG McKenna, MJ Curtin, HD AF Rabinov, JD Barker, FG McKenna, MJ Curtin, HD TI Virtual cisternoscopy: 3D MRI models of the cerebellopontine angle for lesions related to the cranial nerves SO SKULL BASE-AN INTERDISCIPLINARY APPROACH LA English DT Article DE 3D MRI model; acoustic neuroma; CISS ID INNER-EAR; CONSTRUCTIVE INTERFERENCE; SPIN-ECHO; ENDOSCOPY AB This study was conducted to show that high-resolution magnetic resonance imaging (MRI) can aid in the neurosurgical approach to lesions affecting the cranial nerves (CNs) in the cerebellopontine angle (CPA). Three patients with symptomatology related to CNs VII and VIII underwent MRI examinations performed on a 1.5-Tesla Siemens MR scanner. As part of these routine examinations, the imaging technique of constructive interference in the steady state (CISS) was used to collect a volume of data through the brainstem and internal auditory canals. This high-resolution technique acquires a three-dimensional (3D) volume of data at 0.7-mm intervals. Parameters included TR 12.3/TE 5.9, number of acquisitions of 2, a matrix of 230 x 512, bandwidth of 130 Hz per pixel, and time of 8:40. Data were transferred to a commercially available GE workstation and reconstructed into a 3D surface-rendered model. This interactive method allows the model to be visualized from any angle, including that of a standard skull base approach of suboccipital craniotomy for access to the CPA cistern. The images shown include the CPA cistern as seen from the suboccipital surgical approach. CNs V, VII, and VIII can easily be seen in relation to the pons and petrous face. The relationship between the CNs and acoustic neuromas and skull base tumors can be evaluated. Vascular structures, which are often seen in relation to CNs VII and VIII, can be viewed in a 3D format to determine the need for microvascular decompression. Direct intraoperative photographs taken through the operating microscope confirmed the anatomic accuracy of the 3D models. Imaging used for interactive neurosurgical planning must demonstrate a high degree of anatomic detail. Virtual cisternoscopy using CISS MRI technique can achieve the required resolution. Reconstruction algorithms to create surface rendering can generate images with similar 3D anatomic detail to that seen during neurosurgical approaches to the CPA cistern. C1 Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. EM jrabinov@partners.org NR 9 TC 12 Z9 15 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1531-5010 J9 SKULL BASE-INTERD AP JI Skull Base-Interdiscip. Appr. PD MAY PY 2004 VL 14 IS 2 BP 93 EP 99 DI 10.1055/s-2004-828701 PG 7 WC Clinical Neurology; Otorhinolaryngology; Surgery SC Neurosciences & Neurology; Otorhinolaryngology; Surgery GA 825RW UT WOS:000221777000004 PM 16145590 ER PT J AU Patel, SR Ayas, NT Malhotra, MR White, DP Schernhammer, ES Speizer, FE Stampfer, MJ Hu, FB AF Patel, SR Ayas, NT Malhotra, MR White, DP Schernhammer, ES Speizer, FE Stampfer, MJ Hu, FB TI A prospective study of sleep duration and mortality risk in women SO SLEEP LA English DT Article DE sleep; sleep deprivation; proportional hazards models; women; survival rate ID CORONARY-HEART-DISEASE; BREAST-CANCER; NURSES HEALTH; SHIFT WORK; NIGHT; IMPACT; LIGHT AB Study Objectives: It is commonly believed that 8 hours of sleep per night is optimal for good health. However, recent studies suggest the risk of death is lower in those sleeping 7 hours. We prospectively examined the association between sleep duration and mortality in women to better understand the effect of sleep duration on health. Design: Prospective observational study. Setting: Community-based. Participants: Women in the Nurses Health Study who answered a mailed questionnaire asking about sleep duration in 1986. Interventions: None. Measurements and Results: Vital status was ascertained through questionnaires, contact with next of kin, and the National Death Index. During the 14 years of this study (1986-2000), 5409 deaths occurred in the 82,969 women who responded to the initial questionnaire. Mortality risk was lowest among nurses reporting 7 hours of sleep per night. After adjusting for age, smoking, alcohol, exercise, depression, snoring, obesity, and history of cancer and cardiovascular disease, sleeping less than 6 hours or more than 7 hours remained associated with an increased risk of death. The relative mortality risk for sleeping 5 hours or less was 1.15 (95% confidence interval [CI], 1.02-1.29) for 6 hours, 1.01 (95% CI, 0.941.08), for 7 hours, 1.00 (reference group), for 8 hours, 1.12 (95% CI, 1.051.20), and for 9 or more hours 1.42 (95% CI, 1.27-1.58). Conclusions: These results confirm previous findings that mortality risk in women is lowest among those sleeping 6 to 7 hours. Further research is needed to understand the mechanisms by which short and long sleep times can affect health. C1 Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Div Sleep Med,Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. Vancouver Gen Hosp, Ctr Clin Epidemiol & Evaluat, Vancouver, BC, Canada. RP Patel, SR (reprint author), Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Div Sleep Med,Dept Med, 75 Francis St, Boston, MA 02115 USA. EM spatel@partners.org FU NCI NIH HHS [CA87969]; NHLBI NIH HHS [HL48531, P50-HL60292, T32-HL07633] NR 15 TC 333 Z9 338 U1 3 U2 21 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2004 VL 27 IS 3 BP 440 EP 444 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OU UT WOS:000223169000013 PM 15164896 ER PT J AU Littner, MR Kushida, C Anderson, WM Bailey, D Berry, RB Hirshkowitz, M Kapen, S Kramer, M Lee-Chiong, T Li, KK Loube, DL Morgenthaler, T Wise, M AF Littner, MR Kushida, C Anderson, WM Bailey, D Berry, RB Hirshkowitz, M Kapen, S Kramer, M Lee-Chiong, T Li, KK Loube, DL Morgenthaler, T Wise, M TI Practice parameters for the dopaminergic treatment of restless legs syndrome and periodic limb movement disorder SO SLEEP LA English DT Article DE dopaminergic agents; dopamine agonists; restless legs syndrome; periodic limb movement disorder AB Dopaminergic agents, particularly dopamine agonists, have been used with increasing frequency in the treatment of restless legs syndrome and periodic limb movement disorder. These evidence-based practice parameters are complementary to the Practice Parameters for the Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder, published in 1999.1 These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Recommendations are based on the accompanying comprehensive review of the medical literature regarding the dopaminergic treatment of restless legs syndrome (RLS) and periodic limb movement disorder (PLMD), which was developed by a task force commissioned by the American Academy of Sleep Medicine. The following recommendations serve as a guide to the appropriate use of dopaminergic agents in the treatment of RLS and PLMD. Levodopa with decarboxylase inhibitor, and the dopaminergic agonists pergolide, pramipexole, and ropinirole are effective in the treatment of RLS and PLMD. Other dopamine agonists (talipexole, cabergoline, piribidel, and alpha-dihydroergocryptine) and the dopaminergic agents amantadine and selegiline may be effective in the treatment of RLS and PLMD, but the level of effectiveness of these medications is not currently established. Lastly, no specific recommendations can be made regarding dopaminergic treatment of children or pregnant women with RLS or PLMD. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Sepulveda, CA USA. Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. Univ S Florida, Coll Med, Tampa, FL USA. Univ Florida, Malcom Randall VAMC, Gainesville, FL USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Wayne State Univ, Detroit, MI USA. SUNY Hlth Sci Ctr, Dept Psychiat, Maimonides Med Ctr, Brooklyn, NY 11203 USA. NYU, Sch Med, New York, NY USA. Nalt Jewish Med & Res Ctr, Sleep Clin, Denver, CO USA. Stanford Sleep Disorders Clin & Res Ctr, Stanford, CA USA. Swedish Med Ctr, Sleep Med Inst, Seattle, WA USA. Mayo Clin & Mayo Fdn, Mayo Sleep Disorders Ctr, Rochester, MN 55905 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Littner, MR (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. OI Morgenthaler, Timothy/0000-0002-2614-3793 NR 4 TC 93 Z9 93 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2004 VL 27 IS 3 BP 557 EP 559 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OU UT WOS:000223169000031 PM 15164914 ER PT J AU Zhao, JB Bauman, WA Huang, RJ Caplan, AJ Cardozo, C AF Zhao, JB Bauman, WA Huang, RJ Caplan, AJ Cardozo, C TI Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner SO STEROIDS LA English DT Article DE glucocorticoids; anabolic steroids; androgen receptor antagonists; polychlorobiphenyl xenobiotics; steroid hormone receptors; crosstalk ID ANABOLIC-STEROIDS; TRANSCRIPTIONAL ACTIVITY; SEVERE BURN; WEIGHT-LOSS; CROSS-TALK; RAT MUSCLE; INHIBITION; TERMINUS; PATHWAY; BINDING AB The anabolic steroid oxandrolone is increasingly used to preserve or restore muscle mass in those with HIV infection or serious bums. These effects are mediated, in part, by the androgen receptor (AR). Anti-glucocorticoid effects have also been reported for some anabolic steroids, and the goal of our studies was to determine whether oxandrolone had a similar mechanism of action. Studies with in vitro translated glucocorticoid receptor (GR), however, showed no inhibition of cortisol binding by oxandrolone. Conversely, experiments in cell culture systems demonstrated significant antagonism of corti sol-induced transcriptional activation by oxandrolone in cells expressing both the AR and GR. Inhibition was not overcome by increased cortisol concentration, and no inhibition by oxandrolone was observed in cells expressing GR alone, confirming that non-competitive mechanisms were involved. AR-dependent repression of transcriptional activation by oxandrolone was also observed with the synthetic glucocorticoids dexamethasone and methylprednisolone. Furthermore, the AR antagonists 2-hydroxyflutamide and DDE also repressed GR transactivation in an AR-dependent manner. A mutant AR lacking a functional nuclear localization signal (AR(4RKM)) was active in oxandrolone-mediated repression of GR even though oxandrolone-bound AR(4RKM) failed to enter the nucleus and did not affect nuclear import of GR. These data indicate a novel action of oxandrolone to suppress glucocorticoid action via crosstalk between AR and GR. (C) 2004 Elsevier Inc. All rights reserved. C1 Bronx Vet Adm Med Ctr, Spinal Cord Damage Res Ctr, Rehabil & Res Dev Ctr Excellence Med Consequences, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. RP Cardozo, C (reprint author), Bronx Vet Adm Med Ctr, Spinal Cord Damage Res Ctr, Rehabil & Res Dev Ctr Excellence Med Consequences, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM chris.cardozo@mssm.edu FU NCI NIH HHS [R24 CA095823-01]; NIDDK NIH HHS [DK60598]; PHS HHS [P4207384] NR 34 TC 24 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD MAY PY 2004 VL 69 IS 5 BP 357 EP 366 DI 10.1016/j.steroids.2004.01.006 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 838FO UT WOS:000222699100007 PM 15219414 ER PT J AU Arnaout, MA AF Arnaout, MA TI The structural basis of elasticity in fibrillin-based microfibrils SO STRUCTURE LA English DT Editorial Material ID INTEGRINS AB The resiliency of vertebrate tissues such as skin and blood vessels is generated by the elastic fiber network. A recent article by Lee and colleagues (Lee et al., 2004) provides intriguing new cues into the organization and structure of this network. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Struct Biol Program, Boston, MA 02114 USA. RP Arnaout, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2004 VL 12 IS 5 BP 734 EP 736 DI 10.1016/S0969-2126(04)00133-9 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 821VD UT WOS:000221490200003 PM 15130465 ER PT J AU Mezrich, J Yamada, K Sachs, DH Madsen, JC AF Mezrich, J Yamada, K Sachs, DH Madsen, JC TI Regulatory T cells generated by the kidney may mediate the beneficial immune effects of combining kidney with heart transplantation SO SURGERY LA English DT Article ID CARDIAC ALLOGRAFT VASCULOPATHY; MINIATURE SWINE; RENAL-ALLOGRAFTS; CLASS-I; TOLERANCE INDUCTION; GRAFT TOLERANCE; COTRANSPLANTATION; RECIPIENTS; MECHANISMS; SURVIVAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01 HL18646, R01 HL54211, R01 HL67110]; NIAID NIH HHS [P01 AI50157] NR 25 TC 17 Z9 17 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2004 VL 135 IS 5 BP 473 EP 478 DI 10.1016/j.surg.2004.02.009 PG 6 WC Surgery SC Surgery GA 818GK UT WOS:000221233400004 PM 15118583 ER PT J AU Takabayashi, T Shimizu, S Clark, BD Beinborn, M Burke, JF Gelfand, JA AF Takabayashi, T Shimizu, S Clark, BD Beinborn, M Burke, JF Gelfand, JA TI Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells SO SURGERY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HEPATIC ISCHEMIA-REPERFUSION; COLONY-STIMULATING FACTOR; C5A RECEPTOR; U937 CELLS; CARDIOPULMONARY BYPASS; RHEUMATOID-ARTHRITIS; EXPRESSION CLONING; RESPIRATORY BURST; HUMAN EOSINOPHILS AB Background. The anaphylatoxins, C3a and C5a,that are generated during trauma, major surgery, or infection are Potent proinflaminatory mediators that increase interleukin (IL-1) cytokine synthesis. We investigated the effects of IL-1 on anaphylatoxin receptor expression in monocytes. Methods. A human monocytic cell line, MONO-MAC-6, was used. C3a and C5a binding sites were assayed by competitive binding. Levels of messenger RNA for the C3a and C5a receptors were ana zed by 2, reverse transcriptase-polymerase chain reaction. Changes of free cytosolic Ca2+ concentration ([Ca2+]i) in response to C3a and C5a were measured. Results. Basal MONO-MAC-6 cell sites for C3a and C5a binding were 10,900 C3aR/cell (K-d = 2.0 nmol/L), 8700 C5aR/cell (K-d = 0. 9 nmol/L). IL-1alpha increased sites for both C3a (61% increase; P <.01) and C5a (71% increase; P <.001). Levels of C3aR and C5aR messenger RNA also increased in IL-1alpha-stimulated cells. Receptors were coupled to functional responses, which were demonstrated by C3a- or C5a-induced [Ca2+]i increases. IL-1 receptor antagonist blocked the effects of IL-1alpha upregulation of anaphylatoxin receptors. Conclusion. These results suggest that there is an additional link between IL-1 and anaphylatoxins to amplify proinflammatory effects through monocytes and macrophages. Although C3a and C5a can increase the monocyte production of IL-1, IL-1 increases monocyte expression of receptors for these anaphylatoxins, which further amplifies inflammation. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Div Gastroenterol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Div Geog Med & Infect Dis, Boston, MA 02111 USA. RP Gelfand, JA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Mail Stop S50-801, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM-50766, GM-21700] NR 39 TC 14 Z9 17 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2004 VL 135 IS 5 BP 544 EP 554 DI 10.1016/j.surg.2003.09.010 PG 11 WC Surgery SC Surgery GA 818GK UT WOS:000221233400013 PM 15118592 ER PT J AU Stylopoulos, N Cotin, S Maithel, SK Ottensmeyer, M Jackson, PG Bardsley, RS Neumann, PF Rattner, DW Dawson, SL AF Stylopoulos, N Cotin, S Maithel, SK Ottensmeyer, M Jackson, PG Bardsley, RS Neumann, PF Rattner, DW Dawson, SL TI Computer-enhanced laparoscopic training system (CELTS) - Bridging the gap SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE simulation; laparoscopic skills training; education; virtual reality; laparoscopic surgery ID SKILLS AB Background: There is a large and growing gap between the need for better surgical training methodologies and the systems currently available for such training. In an effort to bridge this gap and overcome the disadvantages of the training simulators now in use, we developed the Computer-Enhanced Laparoscopic Training System (CELTS). Methods: CELTS is a computer-based system capable of tracking the motion of laparoscopic instruments and providing feedback about performance in real time. CELTS consists of a mechanical interface, a customizable set of tasks, and an Internet-based software interface. The special cognitive and psychornotor skills a laparoscopic surgeon should master were explicitly defined and transformed into quantitative metrics based on kinematics analysis theory. A single global standardized and task-independent scoring system utilizing a z-score statistic was developed. Validation exercises were performed. Results: The scoring system clearly revealed a gap between experts and trainees, irrespective of the task performed; none of the trainees obtained a score above the threshold that distinguishes the two groups. Moreover, CELTS provided educational feedback by identifying the key factors that contributed to the overall score. Among the defined metrics, depth perception, smoothness of motion, instrument orientation, and the outcome of the task are major indicators of performance and key parameters that distinguish experts from trainees. Time and path length alone, which are the most commonly used metrics in currently available systems, are not considered good indicators of performance. Conclusion: CELTS is a novel and standardized skills trainer that combines the advantages of computer simulation with the features of the traditional and popular training boxes. CELTS can easily be used with a wide array of tasks and ensures comparability across different training conditions. This report further shows that a set of appropriate and clinically relevant performance metrics can be defined and a standardized scoring system can be designed. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. CIMIT, Simulat Grp, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Stylopoulos, N (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. RI Cotin, Stephane/A-2105-2017 OI Cotin, Stephane/0000-0002-2661-505X NR 10 TC 43 Z9 43 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAY PY 2004 VL 18 IS 5 BP 782 EP 789 DI 10.1007/s00464-003-8932-0 PG 8 WC Surgery SC Surgery GA 839ZL UT WOS:000222826700016 PM 15216861 ER PT J AU Deutsch, H Rodriguez, JC Titton, RL AF Deutsch, H Rodriguez, JC Titton, RL TI Lower dose intraventricular T-PA fibrinolysis: Case report SO SURGICAL NEUROLOGY LA English DT Article DE intraventricular hemorrhage; recombinant tissue plasminogen activator; ventriculostomy ID TISSUE-PLASMINOGEN ACTIVATOR; HEMORRHAGE; UROKINASE; HEMATOMA; THERAPY; CLOT AB BACKGROUND Recombinant tissue plasminogen activator (rtPA) intraventricular fibrinolysis has been demonstrated to be efficacious in clearing blood from the ventricular system. Preliminary studies indicate it may improve survival. There have also been reports of adverse affects from intraventricular fibrinolysis. Optimal dosing of rtPA has not been established. METHODS A 40-year-old patient with intraventricular hemorrhage extension secondary to a ruptured aneurysm was treated with a one-time infusion of 1 mg of rtPA through a right ventriculostomy. RESULTS Computed tomography scans demonstrated excellent resolution of intraventricular blood and improvement in cerebral spinal fluid flow after fibrinolysis. Fibrinolysis was most marked in the third and fourth ventricles. There were no adverse effects noted. CONCLUSIONS Intraventricular fibrinolysis is effective at a lower dose than previously used. Lower doses may have fewer adverse affects. (C) 2004 Elsevier Inc. All rights reserved. C1 Chicago Inst Neurosurg & Neurores, Dept Neurosurg, Chicago, IL 60614 USA. Univ Miami, Sch Med, Dept Radiol, Miami, FL 33152 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Deutsch, H (reprint author), Dept Neurosurg, 1365B Clifton Rd,Suite 6400, Atlanta, GA 30322 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD MAY PY 2004 VL 61 IS 5 BP 460 EP 463 DI 10.1016/S0090-3019(03)00538-X PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 818GO UT WOS:000221233800011 PM 15120223 ER PT J AU Chang, MA Jain, S Azar, DT AF Chang, MA Jain, S Azar, DT TI Infections following laser in situ keratomileusis: An integration of the published literature SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE bacterial; complications; infection; keratitis; LASIK ID MYCOBACTERIUM-CHELONAE KERATITIS; ULCERATIVE KERATITIS; REFRACTIVE SURGERY; FUNGAL KERATITIS; POLYMICROBIAL KERATITIS; PNEUMOCOCCAL KERATITIS; INTERFACE KERATITIS; BACTERIAL KERATITIS; LASIK; COMPLICATIONS AB Infections occurring after laser in situ keratomileusis (LASIK) surgery are uncommon, but the number of reports have steadily increased in recent years. This systematic, comprehensive review and analysis of the published literature has been performed in order to develop an integrative perspective on these infections. We have stratified the data by potential associations, microbiology, treatment, and the degree of visual loss, using Fisher's exact tests and Student's t-tests for analysis. In this review, we found that Gram-positive bacteria and mycobacterium were the most common causative organisms. Type of postoperative antibiotic and steroid use was not associated with particular infecting organisms or severity of visual loss. Gram-positive infections were more likely to present less than 7 days after LASIK, and they were associated with pain, discharge, epithelial defects, and anterior chamber reactions. Fungal infections were associated with redness and tearing on presentation. Mycobacterial infections were more likely to present 10 or more days after LASIK surgery. Moderate or severe visual reductions in visual acuity occurred in 49.4% of eyes. Severe reductions in visual acuity were significantly more associated with fungal infections. Flap lift and repositioning peformed within 3 days of symptom onset may be associated with better visual outcome. C1 Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Schepens Eye Res Inst, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10101] NR 66 TC 77 Z9 89 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2004 VL 49 IS 3 BP 269 EP 280 DI 10.1016/j.survophthal.2004.02.007 PG 12 WC Ophthalmology SC Ophthalmology GA 820ZJ UT WOS:000221428400001 PM 15110665 ER PT J AU DeMeo, DL Carey, VJ Chapman, HA Reilly, JJ Ginns, LC Speizer, FE Weiss, ST Silverman, EK AF DeMeo, DL Carey, VJ Chapman, HA Reilly, JJ Ginns, LC Speizer, FE Weiss, ST Silverman, EK TI Familial aggregation of FEF25-75 and FEF25-75/FVC in families with severe, early onset COPD SO THORAX LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; EXCISED HUMAN LUNGS; ENVIRONMENTAL DETERMINANTS; CHRONIC-BRONCHITIS; IDENTICAL-TWINS; VITAL CAPACITY; RISK; FLOW; AIR; DYSANAPSIS AB Background: The Boston Early-Onset COPD study showed that current or ex-smoking first degree relatives of severe early onset COPD probands have significantly lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) values than current or ex-smoking control subjects, which suggests the existence of genetic risk factors for the development of COPD in response to cigarette smoking. We hypothesised that first degree relatives of early onset COPD probands may also have lower values of spirometric parameters such as forced expiratory flow at the mid-portion of forced vital capacity (FEF25-75) and FEF25-75/ FVC. Methods: Using generalised estimating equations, FEF25-75 and FEF25-75/FVC were analysed in 333 first degree relatives of probands with severe early onset COPD and 83 population based controls; analyses were also performed on data stratified by smoking status. Narrow sense heritability estimates were calculated using a variance component approach. Results: Significantly lower FEF25-75 and FEF25-75/ FVC were observed in smoking (FEF25-75: beta - 0.788 l/s (95% CI -1.118 to -0.457), FEF25-75/ FVC: beta - 20.4% (95% CI -29.3 to -11.6, p< 0.0001 for both phenotypes) and non-smoking (FEF25-75: β - 0.357 l/s (95% CI - 0.673 to - 0.041, p = 0.0271), FEF25-75/ FVC: β - 9.5% (95% CI -17.1 to -1.9, p = 0.0145)) first degree relatives of early onset COPD probands. Narrow sense heritability estimates for FEF25-75 (h(2)= 0.38) and FEF25-75/FVC (h(2) = 0.45) were similar to those for FEV1 and FEV1/FVC. Conclusion: Lower values of FEF25-75 and FEF25-75/ FVC in non- smoking first degree relatives of early onset COPD probands than in controls suggest a genetic susceptibility to develop obstructive lung disease, independent of smoking, which is magnified by exposure to deleterious environments as suggested by the further decrements in FEF25-75 and FEF25-75/ FVC seen in smoking first degree relatives. FEF25-75 and FEF25-75/ FVC have high heritability and are important intermediate phenotypes for inclusion in genetic epidemiological studies of COPD. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Pulm & Crit Care Div, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. RP DeMeo, DL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Pulm & Crit Care Div, 181 Longwood Ave, Boston, MA 02115 USA. EM redld@channing.harvard.edu FU NHLBI NIH HHS [R01 HL61575, T32 HL0742722] NR 27 TC 37 Z9 42 U1 2 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD MAY 1 PY 2004 VL 59 IS 5 BP 396 EP 400 DI 10.1136/thx.2003.012856 PG 5 WC Respiratory System SC Respiratory System GA 815WQ UT WOS:000221072800009 PM 15115866 ER PT J AU Bergmeier, W Rabie, T Strehl, A Piffath, CL Prostredna, M Wagner, DD Nieswandt, B AF Bergmeier, W Rabie, T Strehl, A Piffath, CL Prostredna, M Wagner, DD Nieswandt, B TI GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE collagen; glycoprotein; metalloproteinase; platelet; shedding ID RECEPTOR GLYCOPROTEIN-VI; VON-WILLEBRAND-FACTOR; GAMMA-CHAIN; COLLAGEN RECEPTOR; IN-VIVO; THROMBUS FORMATION; INDUCED DECREASE; MOUSE PLATELETS; LIPID RAFTS; ADHESION AB Platelet interaction with subendothelial collagen is crucial for hemostasis and thrombosis. Under conditions of elevated shear, platelet adhesion and activation on collagen requires the coordinated action of glycoprotein (GP) Ib and GPVI,which may be physically and functionally linked in the platelet membrane. While the surface expression of GPIb can be down-regulated by internalization and/or proteolytic cleavage of a 130 kDa fragment of GPIbalpha (glycocalicin, GC), very little is known about the cellular regulation of GPVI. We have recently shown that GPIb on platelets is cleaved by metalloproteinase-dependent mechanisms in response to mitochondrial injury. In the current study, we examined a possible role of platelet metalloproteinases in the regulation of GPVI. Mitochondrial injury induced by incubation of mouse platelets with carbonyl cyanide m-chlorophenyl-hydrazone (CCCP) severely affected the cells' responses to collagen or the GPVI-specific agonist, collagen related peptide (CRP), but not to thrombin or the stable thromboxane A(2) analog U46619. This defect was due to a rapid proteolytic cleavage of GPVI, as shown by the release of the 55 kDa extracellular domain into the supernatant. Both the proteolysis of GPVI and the loss of its activity were inhibited in the presence of the broad range metalloproteinase inhibitor, GM6001. Platelet stimulation with thrombin or CRP, however, resulted in marked metalloproteinase-dependent shedding of GPIbalpha, but not GPVI suggesting that different metalloproteinases are involved in the regulation of the two receptors or, alternatively, an additional signal is required to render GPVI susceptible to cleavage. C1 Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, D-97078 Wurzburg, Germany. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. RP Nieswandt, B (reprint author), Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, Versbacher Str 9, D-97078 Wurzburg, Germany. EM bernhard.nieswandt@virchow.uni-wuerzburg.de RI Rabie, Tamer/C-7886-2013; OI Rabie, Tamer/0000-0001-9060-8797 FU NHLBI NIH HHS [P01 HL056949, P01 HL56949, R37 HL041002, R37 HL41002] NR 37 TC 64 Z9 64 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAY PY 2004 VL 91 IS 5 BP 951 EP 958 DI 10.1160/TH03-12-0795 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 821OR UT WOS:000221471700014 PM 15116256 ER PT J AU Habra, MA Hijazi, R Verstovsek, G Marcelli, M AF Habra, MA Hijazi, R Verstovsek, G Marcelli, M TI Medullary thyroid carcinoma associated with hyperthyroidism: A case report and review of the literature SO THYROID LA English DT Review ID ELEVATED SERUM CALCITONIN; GRAVES-DISEASE; ROUTINE MEASUREMENT; IMMUNOREACTIVE CALCITONIN; HASHIMOTOS THYROIDITIS; PROGNOSTIC FACTORS; ACUTE-PANCREATITIS; CELL-CARCINOMA; CANCER; SOMATOSTATIN AB Thyroid cancer is occasionally associated with hyperthyroidism. Papillary thyroid carcinoma is the most frequently reported histologic type followed by follicular thyroid carcinoma. Medullary thyroid carcinoma (MTC) has been rarely described in association with Graves' disease or other forms of hyperthyroidism. To our knowledge, only 14 cases have been described in which MTC was associated with hyperthyroidism. We report a 70-year-old male who had a clinically significant MTC discovered in the course of diagnostic work-up for hyperthyroidism. We also summarize the clinical features of the other 14 reported cases. C1 Joint Baylor Coll Med & MD Anderson Canc Ctr Fell, Houston, TX USA. Baylor Coll Med, Dept Pathol & Lab Med, VA Med Ctr, Houston, TX USA. Baylor Coll Med, Div Endocrinol, VA Med Ctr, Houston, TX USA. RP Marcelli, M (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM marcelli@bcm.tmc.edu NR 45 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2004 VL 14 IS 5 BP 391 EP 396 DI 10.1089/105072504774193249 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 825RE UT WOS:000221775100011 PM 15186618 ER PT J AU Fujita, Y Terashima, M Kakuta, T Itoh, J Tokimasa, T Brown, D Saito, A AF Fujita, Y Terashima, M Kakuta, T Itoh, J Tokimasa, T Brown, D Saito, A TI Transcellular water transport and stability of expression in aquaporin 1-transfected LLC-PK1 cells in the development of a portable bioartificial renal tubule device SO TISSUE ENGINEERING LA English DT Article ID DARBY CANINE KIDNEY; EPITHELIAL-CELLS; FUNCTIONAL-ANALYSIS; PIG-KIDNEY; RAT-KIDNEY; LLC-PK; LOCALIZATION; CHANNEL; CHIP28; ORIGIN AB We investigated a portable bioartificial renal tubule device (BRTD) consisting of renal tubule cells and hollow fibers, to improve the quality of life of patients. It is necessary for a BRTD system to be compact. A compact portable BRTB requires transfection of an appropriate water channel or electrical pump genes in tubular epithelial cells, which should be based on physiological similarities to human kidney function. LLC-PK1 cells, into which rat kidney aquaporin 1 (AQP1) cDNA was stably transfected, were evaluated for water transport ability. The expression and localization of water AQP1 were examined by Western blotting, RT-PCR, and immunofluorescence. To measure trans-cellular water permeation, a simple method was applied, using phenol red as a cell-impermeant marker of concentration. In contrast to wild-type LLC-PK1 cells, rat AQP1-transfected cells had high transcellular osmotic water permeability. The expression of rat AQP1 mRNA (ratio of AQP1 to beta-actin mRNA) and protein bands (a 28-kDa band and a broad, 35- to 45-kDa band) was confirmed to be stably maintained until a population doubling level of 24. In AQP1-transfected LLC-PK1 cells, the protein was localized mainly to the basolateral side, but also the apical side, of the plasma membrane. Wild-type LLC-PK1 cells were not stained at the plasma membrane. It is possible that enough AQP1-transfected tubule epithelial cells were supplied for a bioartificial renal tubule device. C1 Tokai Univ, Inst Med Sci, Dept Med, Div Nephrol & Metab, Kanagawa 2591100, Japan. Tokai Univ, Inst Med Sci, Labs Struct & Funct Res, Kanagawa 2591100, Japan. Tokai Univ, Inst Med Sci, Dept Physiol, Kanagawa 2591100, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Saito, A (reprint author), Tokai Univ, Inst Med Sci, Div Mol & Cellular Nephrol, Kanagawa 2591193, Japan. EM asait@is.icc.u-tokai.ac.jp NR 34 TC 8 Z9 8 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 MAY PY 2004 VL 10 IS 5-6 BP 711 EP 722 DI 10.1089/1076327041348383 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 836DC UT WOS:000222534500006 PM 15265288 ER PT J AU Casolari, JM Silver, PA AF Casolari, JM Silver, PA TI Guardian at the gate: preventing unspliced pre-mRNA export SO TRENDS IN CELL BIOLOGY LA English DT Article ID MYOSIN-LIKE PROTEIN-1; NUCLEAR EXPORT; QUALITY-CONTROL; TRANSCRIPTION; YEAST; SITE; IDENTIFICATION; RETENTION; PATHWAY AB The production of a mature mRNA requires the assembly and cooperation of numerous complexes before nuclear export. The deleterious effects of intron-containing pre-mRNA leakage into the cytoplasm necessitate mechanisms to prevent premature export of partially processed or unprocessed messages. A new study demonstrates that the Saccharomyces cerevisiae protein MIp1 specifically retains intron-containing pre-mRNAs in the nucleus. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM pamela_silver@dfci.harvard.edu NR 22 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAY PY 2004 VL 14 IS 5 BP 222 EP 225 DI 10.1016/j.tcb.2004.03.007 PG 4 WC Cell Biology SC Cell Biology GA 824ZA UT WOS:000221724600003 PM 15130577 ER PT J AU Emsley, JG Arlotta, P Macklis, JD AF Emsley, JG Arlotta, P Macklis, JD TI Star-cross'd neurons: astroglial effects on neural repair in the adult mammalian CNS SO TRENDS IN NEUROSCIENCES LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; CENTRAL-NERVOUS-SYSTEM; STEM-CELLS; RETINAL TRANSPLANTS; ASTROCYTES; VIMENTIN; BRAIN; REGENERATION; MICE; GFAP AB Astroglia have long been thought to play merely a supporting role in the life of the neuron. However, these star-shaped cells have recently been the focus of intense study that has begun to emphasize remarkable and novel roles for these amazing cells. While astroglia play positive roles in the life of the neuron, they can simultaneously exert negative influences. Kinouchi et al convincingly demonstrate and characterize an inhibitory role played by astroglia after neuronal transplantation. These findings remind us that astroglia exert positive and negative influences on neuronal survival, migration, neurite outgrowth and functional integration. Here, we review the complementary and often contradictory roles of astroglia during neuronal integration. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Neurosci, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu NR 25 TC 26 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 2004 VL 27 IS 5 BP 238 EP 240 DI 10.1016/j.tins.2004.02.008 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 822JK UT WOS:000221535100004 PM 15111002 ER PT J AU Endres, M Laufs, U Liao, JK Moskowitz, MA AF Endres, M Laufs, U Liao, JK Moskowitz, MA TI Targeting eNOS for stroke protection SO TRENDS IN NEUROSCIENCES LA English DT Review ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL PROGENITOR CELLS; FOCAL CEREBRAL-ISCHEMIA; COA REDUCTASE INHIBITOR; PROTEIN-KINASE AKT; ESTROGEN-RECEPTOR; VASCULAR-DISEASE; STATIN TREATMENT; SMOOTH-MUSCLE; MICE LACKING AB Nitric oxide (NO) generated by endothelial NO synthase (eNOS) plays a crucial role in vascular function and homeostasis. NO possesses vasodilatory, anti-inflammatory, antithrombotic and antiproliferative properties. Augmentation of NO production increases cerebral blood flow, which can lead to neuroprotection during brain ischaemia. Several modalities that upregulate eNOS expression and/or activity have recently been identified, including HMG-CoA reductase inhibitors (statins), steroid hormones, nutrients and physical activity. They all increase NO bioavailability, leading to enhanced cerebral blood flow and protection from ischaemic stroke. Thus, therapeutic modalities that target eNOS not only serve as preventive measures to reduce stroke incidence but also could represent novel treatment strategies for reducing brain injury during cerebral ischaemia. C1 Humboldt Univ, Charite Hosp, Dept Neurol, D-10117 Berlin, Germany. Saarland Univ Hosp, Dept Med 3, D-66421 Homburg, Germany. Brigham & Womens Hosp, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Endres, M (reprint author), Humboldt Univ, Charite Hosp, Dept Neurol, Schumanstr 20-21, D-10117 Berlin, Germany. EM matthias.endres@charite.de RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [P01 HL048743-120008, R01 HL052233-05, R01 HL052233-06, R01 HL052233-07, R01 HL070274-01, R01 HL070274-02]; NIDDK NIH HHS [R01 DK062729-01A1, R01 DK062729-02]; NINDS NIH HHS [P01 NS010828-330036, P50 NS010828-290036, P50 NS010828-300036] NR 55 TC 162 Z9 173 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 2004 VL 27 IS 5 BP 283 EP 289 DI 10.1016/j.tins.2004.03.009 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 822JK UT WOS:000221535100013 PM 15111011 ER PT J AU Sanghani, MV Ching, J Schultz, D Cormack, R Loffredo, M McMahon, E Beard, C D'Amico, AV AF Sanghani, MV Ching, J Schultz, D Cormack, R Loffredo, M McMahon, E Beard, C D'Amico, AV TI Impact on rectal dose from the use of a prostate immobilization and rectal localization device for patients receiving dose escalated 3D conformal radiation therapy SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE prostate cancer; intrarectal balloon; dose escalation; rectal toxicity ID GLAND IMMOBILIZATION; CANCER; RADIOTHERAPY; TOXICITY AB Purpose: When >25% of the rectum is irradiated to greater than or equal to70 Gy, the risk of developing Grade 2 or higher rectal complications is significantly increased. This study evaluates the impact on dose to the rectum from the use of an intrarectal (IR) balloon device, previously shown to immobilize the prostate gland and localize the rectum, in patients receiving dose escalated 3-dimentional (3D) conformal radiation therapy. Materials and Methods: From July 2001 through February 2003, 28 consecutive patients with prostate cancer underwent computerized tomography-based simulation with and without the IR balloon in place. Treatment planning was performed for three clinical paradigms in which the IR balloon was not used at all (0 Gy), used during the cone-down for 15 treatments (28.35 Gy), or used for the entire course of 40 treatments (75.6 Gy). The three plans were compared for differences in the percent of rectum receiving >70 Gy. Results: Dose volume histogram (DVH) analysis revealed that the median(range) of percent rectal volume exceeding 70 Gy was 25% (12.7-41.5%), 7.5% (0.9-19.5%), and 3.6% (0-8.7%) for patients in whom the IR balloon was used for 0, 15, and 40 treatments, respectively. The percent of rectum exceeding 70 Gy was significantly different for all treatment plan comparisons (P < 0.0001). Conclusions: Grade 2 or higher rectal toxicity may be minimized during dose escalated 3D conformal radiation therapy through the use of an IR balloon during the 3-week cone down portion of an 8-week treatment course. (C) 2004 Elsevier Inc All rights reserved. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. RP Sanghani, MV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM adamico@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 11 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAY-JUN PY 2004 VL 22 IS 3 BP 165 EP 168 DI 10.1016/j.urolonc.2004.02.002 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 844XY UT WOS:000223195600001 PM 15271308 ER PT J AU Tanrikut, C Sahani, D Dretler, SP AF Tanrikut, C Sahani, D Dretler, SP TI Distinguishing stent from stone: Use of bone windows SO UROLOGY LA English DT Article ID ACUTE FLANK PAIN; HELICAL COMPUTED-TOMOGRAPHY; CT; LITHOTRIPSY; UROGRAPHY; CALCULI AB Objectives. To present a simple method to assist in distinguishing stents or nephrostomy tubes from urinary tract stones. Non-contrast computed tomography (CT) is now routinely used for the diagnosis and follow-up of urinary tract stones. When stents or nephrostomy tubes are in place, it may be difficult to differentiate the stent from the stone. Methods. Three representative patients with ureteral stents or nephrostomy drainage catheters (stents/ tubes) who were suspected of having residual urinary tract stones were studied by visualizing the suspicious density on CT. Abdominal windows were used for initial viewing, then bone windows were used, and the two techniques were compared. The Hounsfield units (HU) of the various stents/tubes were measured in vitro to establish reference points. The pixel densities of stones have a known range and, in our experience, may be as high as 1600 HU. Results. Using the abdominal window, no difference was observed in the radiographic appearance of the stents/tubes compared with urinary calculi. However, when viewed in the bone window, the stone appeared less dense than the stent/tube. The in vitro pixel densities of the stents/tubes measured 1600 to 2600 HU compared with the calculi, which do not exceed 1600 HU. Conclusions. Using the abdominal window, stents and stones may have the same CT appearance. However, the bone window allows a visual distinction between a stent/tube and a stone. This distinction is accounted for by differences in pixel density. This observation allows one to distinguish a stent/tube from a stone on CT in patients in whom a nephrostomy tube or ureteral stent is present. (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Tanrikut, C (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,GRB 1102, Boston, MA 02114 USA. NR 12 TC 11 Z9 11 U1 0 U2 0 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 MAY PY 2004 VL 63 IS 5 BP 823 EP 826 DI 10.1016/j.urology.2003.12.041 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 824ET UT WOS:000221669400004 PM 15134954 ER PT J AU Tiffany, NM Wersinger, EM Garzotto, M Beer, TM AF Tiffany, NM Wersinger, EM Garzotto, M Beer, TM TI Imatinib mesylate and zoledronic acid in an drogen-in dependent prostate cancer SO UROLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; BONE METASTASES; SIGNAL-TRANSDUCTION; RANDOMIZED-TRIAL; CLINICAL-TRIALS; PHASE-II; GROWTH; INHIBITOR; CARCINOMA AB Objectives. To determine the safety and efficacy of zoledronic acid (Zometa) combined with imatinib mesylate (Gleevec) in patients with bone pain due to androgen-independent prostate cancer. Methods. Fifteen patients were treated with zoledronic acid 4 mg intravenously every 28 days and imatinib mesylate 400 mg/day. The pain response, defined as a 2-point reduction in the Present Pain Intensity Scale or normalization if the initial score was 1, was the primary endpoint. Secondary endpoints included palliative response, prostate-specific antigen response, measurable disease response, time to progression, impact on quality of life, decrease in markers of bone turnover, and tolerability of the drug combination. Results. The study was stopped early because of a lack of activity. No palliative or clinical activity was detected for the combination, and no prostate-specific antigen responses were observed. The median time to progression was 4 weeks (95% confidence interval 3 to 5), and the median duration of treatment was 8 weeks (range 1.6 to 16.7). The median overall survival was 54 weeks (95% confidence interval 18 to 90). Therapy was associated with a reduction in urine N-telopeptides and a trend toward a reduction in serum osteocalcin, but no change occurred in bone-specific alkaline phosphatase. Conclusions. In this patient population, imatinib mesylate and zoledronic acid produced no prostate-specific antigen responses and had no palliative or clinical activity. (C) 2004 Elsevier Inc. C1 Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Urol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code CR-145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. FU NCRR NIH HHS [3M01RR00334-33S2] NR 31 TC 30 Z9 32 U1 0 U2 2 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 MAY PY 2004 VL 63 IS 5 BP 934 EP 939 DI 10.1016/j.urology.2003.12.022 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 824ET UT WOS:000221669400034 PM 15134984 ER PT J AU Roberts, TG Goulart, BHL Stallings, SC Squitieri, L Chabner, BA Finkelstein, SN Clark, JW AF Roberts, TG Goulart, BHL Stallings, SC Squitieri, L Chabner, BA Finkelstein, SN Clark, JW TI Analysis of over 2400 modern phase I cancer trials: Composition, outcomes, and use of surrogate endpoints SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 247 EP 247 DI 10.1016/S1098-3015(10)62147-X PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600086 ER PT J AU Goulart, BHL Roberts, TG Liu, Y Clark, JW AF Goulart, BHL Roberts, TG Liu, Y Clark, JW TI Outcomes and costs of Surrogate End-points (SES) and biomarkers in phase I oncology clinical trials SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 248 EP 248 DI 10.1016/S1098-3015(10)62150-X PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600089 ER PT J AU Sadetsky, N Kneier, A Latini, DM Knight, S Loi, J Carroll, PR AF Sadetsky, N Kneier, A Latini, DM Knight, S Loi, J Carroll, PR TI Short-term psychosocial counseling for patients with newly-diagnosed prostate cancer SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 252 EP 252 DI 10.1016/S1098-3015(10)62163-8 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600102 ER PT J AU Wen, L Parchman, M Linn, W Lee, S AF Wen, L Parchman, M Linn, W Lee, S TI Self-monitoring of blood glucose among veterans with diabetes managed on oral therapy SO VALUE IN HEALTH LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 338 EP 338 DI 10.1016/S1098-3015(10)62431-X PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600370 ER PT J AU Wen, L Parchman, M Linn, W AF Wen, L Parchman, M Linn, W TI Hospitalizations within the VA among veterans with diabetes SO VALUE IN HEALTH LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2004 VL 7 IS 3 BP 345 EP 345 DI 10.1016/S1098-3015(10)62453-9 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 819ZW UT WOS:000221356600392 ER PT J AU Sykes, M Sandrin, M Cozzi, E Rees, MA AF Sykes, M Sandrin, M Cozzi, E Rees, MA TI World Health Organization resolution on xenotransplantation SO XENOTRANSPLANTATION LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Austin Repatriat Med Ctr, Austin Res Inst, Heidelberg, Vic, Australia. Univ Padua, Clin Chirurg 4, Dept Surg & Med Sci, Padua, Italy. Med Coll Ohio, Dept Urol, Toledo, OH 43699 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM megan.sykes@tbrc.mgh.harvard.edu; m.sandrin@ari.unimelb.edu.au; emanuele.cozzi@unipd.it NR 5 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2004 VL 11 IS 3 BP 224 EP 225 DI 10.1111/j.1399-3089.2004.00129.x PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 813DV UT WOS:000220888700001 PM 15099198 ER PT J AU Kondo, T Hafezi-Moghadam, A Thomas, K Wagner, DD Kahn, CR AF Kondo, T Hafezi-Moghadam, A Thomas, K Wagner, DD Kahn, CR TI Mice lacking insulin or insulin-like growth factor 1 receptors in vascular endothelial cells maintain normal blood-brain barrier SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE SYNTHASES; TIGHT JUNCTION; ZONULA OCCLUDENS; KNOCKOUT MICE; BREAKDOWN; INJURY; DISRUPTION; EDEMA; ENCEPHALITIS; ANGIOGENESIS AB The blood-brain barrier (BBB) is created by a combination of endothelial cells with tight junctions and astrocytes. One of the key tight junction proteins, zona occludens-1 (ZO-1), has been reported to be stimulated in its expression by insulin and IGF-1. To assess the role of insulin and IGF-1 in endothelial cells in the BBB we have utilized mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) and IGF-1 receptor (VENIFARKO). Both of these mice show a normal BBB based on no increase in leakage of Evans blue dye in the brain of these mice basally or after cold injury. Furthermore, the structural integrity of the BBB and blood-retinal barrier (BRB) was intact using the vascular markers lectin B-4 and ZO-1, and both proteins were properly co-localized in both brain and retinal vascular tissue of these mice. These observations indicate that neither insulin nor IGF-1 signaling in vascular endothelial cells is required for development and maintenance of BBB or BRB. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Dev, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA USA. Childrens Hosp, Dept Pediat, Boston, MA USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Dev, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NHLBI NIH HHS [R01 HL053756, R01HL53756]; NIDDK NIH HHS [DK31036] NR 32 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 30 PY 2004 VL 317 IS 2 BP 315 EP 320 DI 10.1016/j.bbrc.2004.03.043 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 813QS UT WOS:000220922200003 PM 15063759 ER PT J AU Sokolov, M Strissel, KJ Leskov, IB Michaud, NA Govardovskii, VI Arshavsky, VY AF Sokolov, M Strissel, KJ Leskov, IB Michaud, NA Govardovskii, VI Arshavsky, VY TI Phosducin facilitates light-driven transducin translocation in rod photoreceptors - Evidence from the phosducin knockout mouse SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OUTER SEGMENTS; BETA-GAMMA; RAT RETINA; VERTEBRATE PHOTORECEPTORS; ALPHA-SUBUNIT; CGMP CASCADE; PROTEIN; CELLS; BINDING; PHOSPHORYLATION AB Phosducin is a photoreceptor-specific protein known to interact with the betagamma subunits of G proteins. In pursuit of the function of phosducin, we tested the hypothesis that it regulates the light-driven translocation of G protein transducin from the outer segments of rod photoreceptors to other compartments of the rod cell. Transducin translocation has been previously shown to contribute to rod adaptation to bright illumination, yet the molecular mechanisms underlying the translocation phenomenon remain unknown. In this study we provide two major lines of evidence in support of the role of phosducin in transducin translocation. First, we have demonstrated that transducin betagamma subunits interact with phosducin along their entire intracellular translocation route, as evident from their co-precipitation in serial tangential sections from light-adapted but not dark-adapted retinas. Second, we generated a phosducin knockout mouse and found that the degree of light-driven transducin translocation in the rods of these mice was significantly reduced as compared with that observed in the rods of wild type animals. In knockout animals the translocation of transducin betagamma subunits was affected to a larger degree than the translocation of the alpha subunit. We also found that the amount of phosducin in rods is sufficient to interact with practically all of the transducin present in these cells and that the subcellular distribution of phosducin is consistent with that of a soluble protein evenly distributed throughout the entire rod cytoplasm. Together, these data indicate that phosducin binding to transducin betagamma subunits facilitates transducin translocation. We suggest that the mechanism of phosducin action is based on the reduction of transducin affinity to the membranes of rod outer segments, achieved by keeping the transducin betagamma subunits apart from the alpha subunit. This increased solubility of transducin would make it more susceptible to translocation from the outer segments. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Howe Labs MEEI, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Howe Labs MEEI, 243 Charles St, Boston, MA 02114 USA. EM vadim_arshavsky@meei.harvard.edu FU NEI NIH HHS [EY-10336] NR 45 TC 80 Z9 81 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 30 PY 2004 VL 279 IS 18 BP 19149 EP 19156 DI 10.1074/jbc.M311058200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 815KP UT WOS:000221041500128 PM 14973130 ER PT J AU Turney, MK Nicholson, WE Kovacs, WJ AF Turney, MK Nicholson, WE Kovacs, WJ TI Gene expression phenotyping of an ACTH-producing small cell lung cancer line SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE proopiomelanocortin; small cell lung cancer; ectopic ACTH; microarray (human) ID TRANSCRIPTION FACTOR-I; ULNAR-MAMMARY SYNDROME; PROOPIOMELANOCORTIN GENE; GLUCOCORTICOID-RECEPTOR; NEUROENDOCRINE TUMORS; METASTATIC PULMONARY; NONPITUITARY TISSUES; PRECURSOR PEPTIDES; HUMAN-PLASMA; PITUITARY AB DNA microarray techniques were used to compare gene expression in an adrenocorticotropin (ACTH)-producing human small cell lung carcinoma line (DMS-79) with six other small cell lung cancer (SCLC) lines that do not produce ACTH. Twelve genes were expressed at more than five-fold higher levels in DMS-79 cells. Two transcription factors were the genes that exhibited the most remarkable over-expression: T-box 3 mRNA was detected at levels 19.31 +/- 3.78 times those observed in the SCLCs. Thyroid transcription factor (TTF-1, T/ebp, Nkx2.1) was expressed at 14.24 +/- 3.41-fold higher in DMS-79 cells. Seven genes were identified whose expression levels were at least five-fold lower in the ACTH-producing cell line. Variation in culture medium formulation did not significantly affect the gene expression profile of DMS-79 cells and expression data observed in microarray experiments were corroborated by northern blot analysis of RNA from the same cell lines. These experiments reveal new candidate genes that could be involved in the dysregulation of POMC gene expression manifested by ACTH-producing nonpituitary tumors. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Vanderbilt Univ, Sch Med, Div Endocrinol Diabet & Metab, Nashville, TN 37232 USA. US Dept Vet Affairs, Tennessee Valley Hlth Care Syst, Nashville, TN USA. RP Kovacs, WJ (reprint author), Vanderbilt Univ, Sch Med, Div Endocrinol Diabet & Metab, Nashville, TN 37232 USA. EM wiilliam.kovacs@vanderbilt.edu OI Kovacs, William/0000-0002-3940-2109 FU NIDDK NIH HHS [P60 DK020593] NR 51 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD APR 30 PY 2004 VL 219 IS 1-2 BP 105 EP 113 DI 10.1016/j.mce.2004.01.005 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 826NJ UT WOS:000221835500012 PM 15149732 ER PT J AU Biederman, J Petty, C Faraone, SV Hirshfeld-Becker, D Pollack, MH Henin, A Gilbert, J Rosenbaum, JF AF Biederman, J Petty, C Faraone, SV Hirshfeld-Becker, D Pollack, MH Henin, A Gilbert, J Rosenbaum, JF TI Moderating effects of major depression on patterns of comorbidity in patients with panic disorder SO PSYCHIATRY RESEARCH LA English DT Article DE panic disorder; depression; adult; comorbidity ID SUBSTANCE USE DISORDERS; EARLY-ONSET; SEPARATION ANXIETY; RISK-FACTORS; PSYCHOPATHOLOGY; CHILDREN; PARENTS; SYMPTOMS; FAMILY; ATTACK AB Given the high rate of co-occurring major depression in patients with panic disorder, it is unclear whether patterns of comorbidity in individuals with panic disorder reported in the literature are associated with panic disorder or with the presence of major depression. Subjects were 231 adult subjects with panic disorder and major depression (n=102), panic disorder without comorbid major depression (n=29), major depression without comorbid panic disorder (n=39). and neither panic disorder nor major depression (n=61). Subjects were comprehensively assessed with structured diagnostic interviews that examined psychopathology across the life cycle. Panic disorder, independently of comorbidity with major depression, was significantly associated with comorbid separation anxiety disorder, simple phobia. obsessive-compulsive disorder, generalized anxiety. disorder, and agoraphobia. Major depression, independently of comorbidity with panic disorder, was significantly associated with comorbidity with psychoactive substance use disorders and childhood disruptive behavior disorders. Overanxious disorder was associated with both panic disorder and major depression. Major depression has important moderating effects on patterns of comorbidity of panic disorder in referred adults. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [2 R01 MH47077-11] NR 27 TC 11 Z9 12 U1 2 U2 5 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 APR 30 PY 2004 VL 126 IS 2 BP 143 EP 149 DI 10.1016/j.psychres.2004.02.001 PG 7 WC Psychiatry SC Psychiatry GA 823QV UT WOS:000221629000006 PM 15123393 ER PT J AU Brody, AL Mandelkern, MA Lee, G Smith, E Sadeghi, M Saxena, S Jarvik, ME London, ED AF Brody, AL Mandelkern, MA Lee, G Smith, E Sadeghi, M Saxena, S Jarvik, ME London, ED TI Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the Society-for-Research-on-Nicotine-and-Tobacco CY FEB 19-22, 2003 CL NEW ORLEANS, LA SP Soc Res Nicotine & Tobacco DE positron emission tomography; nicotine dependence; brain metabolism; anterior cingulate cortex; orbitofrontal cortex; bupropion hydrochloride ID SUSTAINED-RELEASE BUPROPION; SMOKING-CESSATION; DOPAMINE TRANSPORTER; ORBITOFRONTAL CORTEX; HUMAN BRAIN; NOREPINEPHRINE OUTPUT; COGNITIVE-PROCESSES; RAT; STRESS; WITHDRAWAL AB In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirty-seven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two F-18-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order-one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Positron Emiss Tomog Ctr, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU NIDA NIH HHS [R01 DA15059, R01 DA14093, R01 DA015059-04, R01 DA014093, R01 DA015059]; NIMH NIH HHS [K23 MH001694] NR 75 TC 106 Z9 108 U1 3 U2 5 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 APR 30 PY 2004 VL 130 IS 3 BP 269 EP 281 DI 10.1016/j.psychresns.2003.12.006 PG 13 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 824GB UT WOS:000221673200005 PM 15135160 ER PT J AU Ke, Y Streeter, CC Nassar, LE Sarid-Segal, F Hennen, J Yurgelun-Todd, DA Awad, LA Rendall, MJ Gruber, SA Nason, A Mudrick, MJ Blank, SR Meyer, AA Knapp, C Ciraulo, DA Renshaw, PF AF Ke, Y Streeter, CC Nassar, LE Sarid-Segal, F Hennen, J Yurgelun-Todd, DA Awad, LA Rendall, MJ Gruber, SA Nason, A Mudrick, MJ Blank, SR Meyer, AA Knapp, C Ciraulo, DA Renshaw, PF TI Frontal lobe GABA levels in cocaine dependence: a two-dimensional, J-resolved magnetic resonance spectroscopy study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE brain gamma-aminobutyric acid; cocaine treatment; alcoholism; magnetic resonance spectroscopy; two-dimensional MRS ID GAMMA-AMINOBUTYRIC-ACID; ENDOGENOUS OPIOID SYSTEMS; DOUBLE-QUANTUM FILTER; HUMAN BRAIN; IN-VIVO; MR SPECTROSCOPY; VINYL-GABA; H-1 MRS; ADDICTION; SPECTRA AB Non-invasive measures of brain gamma-aminobutyric acid (GABA) concentrations may be especially useful in the identification of cocaine-related changes in brain chemistry that can be used to guide the development of future treatments for cocaine-dependent persons. This study assessed whether brain GABA levels in cocaine-dependent subjects with and without an alcohol disorder differ from GABA levels in healthy comparison subjects. Two-dimensional, proton magnetic resonance spectroscopy was used to determine GABA levels in the left prefrontal lobe of cocaine-dependent subjects (N = 35) recruited from a National Institute on Drug Abuse (NIDA)-sponsored treatment trial of cocaine dependence and a comparison group (N = 20). At treatment baseline, mean GABA concentrations were 0.93 +/- 0.27 mM/kg in cocaine-dependent subjects and 4.32 +/- 0.44 mM/kg in the comparison sample (t [d.f. = 53] = 3.65, P < 0.001). Cocaine-dependent subjects with a history of a co-morbid alcohol disorder (N = 23) had significantly lower baseline GABA levels (0.87 mM/kg) (t [d.f. = 41] = 4.31, P < 0.001) than the comparison group. However, cocaine-dependent subjects without an alcohol disorder (N = 12) also had lower GABA levels (1.04 mM/kg) than the comparison subjects (t [d.f. = 30] = 2.09, P = 0.045), suggesting that cocaine dependence alone can decrease GABA levels. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. Boston Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02118 USA. RP Ke, Y (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM yke@mclean.harvard.edu OI Knapp, Clifford/0000-0003-4482-7678; Ciraulo, Domenic/0000-0001-7706-8765 FU NIAAA NIH HHS [K23AA13149]; NIDA NIH HHS [DA09448, DA15116, DA50038] NR 49 TC 45 Z9 49 U1 1 U2 5 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 APR 30 PY 2004 VL 130 IS 3 BP 283 EP 293 DI 10.1016/j.pscychresns.2003.12.001 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 824GB UT WOS:000221673200006 PM 15135161 ER PT J AU Ramaswamy, S AF Ramaswamy, S TI Translating cancer genomics into clinical oncology SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Broad Inst, Program Canc Gen, Cambridge, MA USA. RP Ramaswamy, S (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. NR 0 TC 52 Z9 53 U1 0 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 APR 29 PY 2004 VL 350 IS 18 BP 1814 EP 1816 DI 10.1056/NEJMp048059 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 815ZN UT WOS:000221080300003 PM 15115827 ER PT J AU Koralnik, IJ Schellingerhout, D Frosch, MP Harris, NL Buonanno, F Black-Schaffer, RM AF Koralnik, IJ Schellingerhout, D Frosch, MP Harris, NL Buonanno, F Black-Schaffer, RM TI Case 14-2004: A 66-year-old man with progressive neurologic deficits - Progressive multifocal leukoencephalopathy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; HUMORAL IMMUNE-RESPONSE; JC VIRUS EPITOPE; CEREBROSPINAL-FLUID; PROLONGED SURVIVAL; AIDS; BRAIN; DNA; TRANSPLANTATION; AMPLIFICATION C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Koralnik, IJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. FU NCI NIH HHS [1-R24-CA92782-01, 2PO1CA6924605]; NIAID NIH HHS [P30-AI 28691]; NINDS NIH HHS [R01NS/AI 41198, R21 NS 046243, R01 NS 047029] NR 34 TC 40 Z9 40 U1 0 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 APR 29 PY 2004 VL 350 IS 18 BP 1882 EP 1893 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 815ZN UT WOS:000221080300013 PM 15115835 ER PT J AU Chauhan, D Li, GL Hideshima, T Podar, K Shringarpure, R Mitsiades, C Munshi, N Yew, PR Anderson, KC AF Chauhan, D Li, GL Hideshima, T Podar, K Shringarpure, R Mitsiades, C Munshi, N Yew, PR Anderson, KC TI Blockade of ubiquitin-conjugating enzyme CDC34 enhances anti-myeloma activity of Bortezomib/Proteasome inhibitor PS-341 SO ONCOGENE LA English DT Article DE Bortezomib/PS-341; multiple myeloma; apoptosis; 2-Methoxyestradiol; dexamethasone ID MULTIPLE-MYELOMA; INDUCED APOPTOSIS; POLY(ADP-RIBOSE) POLYMERASE; OLIGONUCLEOTIDE ARRAYS; MITOCHONDRIAL PROTEIN; DRUG-RESISTANCE; CELL-CYCLE; MM CELLS; INTERLEUKIN-6; DEXAMETHASONE AB The ubiquitin-conjugating enzyme CDC34 (UBC3) is linked to cell cycle progression in diverse cell types; however, its role in multiple myeloma ( MM) pathogenesis is unclear. Here, we show that CDC34 is highly expressed in patient MM cells and MM cell lines versus normal cells. Blocking CDC34 using a dominant-negative strategy enhances the anti-MM activity of Bortezomib/ Proteasome inhibitor PS-341, dexamethasone (Dex) and 2-Methoxyestradiol (2ME2). The expression of wild-type CDC34 reduces Dex-induced cytotoxicity in MM cells. Moreover, inhibition of CDC34 enzymatic activity abrogates interleukin-6-induced protection against Dex-induced apoptosis. Together, these findings provide evidence that ( 1) CDC34 expression is associated with growth and survival of MM cells and ( 2) blocking CDC34 activity not only enhances anti-MM activity of Bortezomib and 2ME2 but also overcomes IL-6-triggered Dex-resistance. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78245 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [P01 CA 78373, IP50 CA 10070, R01 CA50947] NR 25 TC 34 Z9 34 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 29 PY 2004 VL 23 IS 20 BP 3597 EP 3602 DI 10.1038/sj.onc.1207458 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 816HT UT WOS:000221101700011 PM 15094775 ER PT J AU Chen, ZH Ge, YL Kang, JX AF Chen, ZH Ge, YL Kang, JX TI Down-regulation of the M6P/IGF-II receptor increases cell proliferation and reduces apoptosis in neonatal rat cardiac myocytes SO BMC CELL BIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; MANNOSE 6-PHOSPHATE RECEPTOR; GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR GENE; II RECEPTOR; CATHEPSIN-D; EXPRESSION; RIBOZYMES; CANDIDATE; MICE AB Background: The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) is a multi-functional protein that has been implicated in regulation of cell growth and apoptosis. Cardiac myocytes express relatively high levels of M6P/IGF2R, and cardiomyocyte apoptosis has been identified in a variety of cardiovascular disorders, such as myocardial infarction and heart failure. However, involvement of M6P/IGF2R in the pathogenesis of these conditions has not been determined. Thus, the objective of this study was to determine the role of M6P/IGF2R in regulation of cardiac myocyte growth and apoptosis. Results: We down-regulated the expression of M6P/IGF2R in neonatal rat cardiac myocytes and examined the effect on cell proliferation and apoptosis. Infection of neonatal cardiomyocytes with an adenovirus expressing a ribozyme targeted against the M6P/IGF2R significantly reduced the level of M6P/IGF2R mRNA, as determined by RT-PCR and Ribonuclease Protection Assay (RPA). M6P-containing protein binding and endocytosis as well as the M6P/IGF2R-mediated internalization of I-125-IGF-II were lower in the ribozyme-treated cells than the control myocytes, indicating that the number of functional M6P/IGF2R in the ribozyme treated cells was reduced. Accordingly, a marked increase in cell proliferation and a reduced cell susceptibility to hypoxia- and TNF-induced apoptosis were observed in the ribozyme-treated cells. Conclusions: These findings suggest that M6P/IGF2R may play a role in regulation of cardiac myocyte growth and apoptosis. Down regulation of this gene in cardiac tissues might be a new approach to prevention of cell death or promotion of mitogenesis for certain heart diseases. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM zchen4@partners.org; geyinlin@yahoo.com; jxkang@partners.org FU NCI NIH HHS [CA79553] NR 36 TC 25 Z9 26 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD APR 28 PY 2004 VL 5 AR 15 DI 10.1186/1471-2121-5-15 PG 12 WC Cell Biology SC Cell Biology GA 820SY UT WOS:000221410800001 PM 15115542 ER PT J AU Meigs, JB Hu, FB Rifai, N Manson, JE AF Meigs, JB Hu, FB Rifai, N Manson, JE TI Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID C-REACTIVE PROTEIN; INTERCELLULAR-ADHESION MOLECULE-1; INSULIN-RESISTANCE; DEPENDENT VASODILATION; ATHEROSCLEROSIS RISK; LIFE-STYLE; E-SELECTIN; CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; BLOOD-FLOW AB Context Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus but may also precede development of diabetes. Objective To determine whether elevated plasma levels of biomarkers reflecting endothelial dysfunction (E-selectin; intercellular adhesion molecule 1 [ICAM-1]; and vascular cell adhesion molecule 1 [VCAM-1]) predict development of type 2 diabetes in initially nondiabetic women. Design and Setting Prospective, nested case-control study within the Nurses' Health Study, an ongoing US study initiated in 1976. Participants Of 121700 women initially enrolled, 32826 provided blood samples in 1989-1990; of those free of diabetes, cardiovascular disease, or cancer at baseline, 737 developed incident diabetes by 2000. Controls (n = 785) were selected according to matched age, fasting status, and race. Main Outcome Measure Risk of confirmed clinically diagnosed type 2 diabetes by baseline levels of E-selectin, ICAM-1, and VCAM-1. Results Baseline median levels of the biomarkers were significantly higher among cases than among controls (E-selectin, 61.2 vs 45.4 ng/mL; ICAM-1, 264.9 vs 247.0 ng/mL; VCAM-1, 545.4 vs 526.0 ng/mL [all P values less than or equal to .004]). Elevated E-selectin and ICAM-1 levels predicted incident diabetes in logistic regression models conditioned on matching criteria and adjusted for body mass index (BMI), family history of diabetes, smoking, diet score, alcohol intake, activity index, and postmenopausal hormone use. The adjusted relative risks for incident diabetes in the top quintile vs the bottom quintiles were 5.43 for E-selectin (95% confidence interval [CI], 3.47-8.50), 3.56 for ICAM-1 (95% Cl, 2.28-5.58), and 1.12 for VCAM-1 (95% Cl, 0.76-1.66). Adjustment for waist circumference instead of BMI or further adjustment for baseline levels of C-reactive protein, fasting insulin, and hemoglobin A(1c) or exclusion of cases diagnosed during the first 4 years of follow-up did not alter these associations. Conclusion Endothelial dysfunction predicts type 2 diabetes in women independent of other known risk factors, including obesity and subclinical inflammation. C1 Massachusetts Gen Hosp, Gen Internal Med Unit, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845, DK36798, DK46519] NR 56 TC 320 Z9 339 U1 0 U2 7 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 APR 28 PY 2004 VL 291 IS 16 BP 1978 EP 1986 DI 10.1001/jama.291.16.1978 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 815SM UT WOS:000221062000029 PM 15113816 ER PT J AU Carothers, JM Oestreich, SC Davis, JH Szostak, JW AF Carothers, JM Oestreich, SC Davis, JH Szostak, JW TI Informational complexity and functional activity of RNA structures SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID IN-VITRO EVOLUTION; SECONDARY STRUCTURE; LIGASE RIBOZYME; SEQUENCES; LANDSCAPE; SELECTION; LIBRARIES; EFFICIENT; TEMPLATE; MUTATION AB Very little is known about the distribution of functional DNA, RNA, and protein molecules in sequence space. The question of how the number and complexity of distinct solutions to a particular biochemical problem varies with activity is an important aspect of this general problem. Here we present a comparison of the structures and activities of eleven distinct GTP-binding RNAs (aptamers). By experimentally measuring the amount of information required to specify each optimal binding structure, we show that defining a structure capable of 10-fold tighter binding requires approximately 10 additional bits of information. This increase in information content is equivalent to specifying the identity of five additional nucleotide positions and corresponds to an similar to1000-fold decrease in abundance in a sample of random sequences. We observe a similar relationship between structural complexity and activity in a comparison of two catalytic RNAs (ribozyme ligases), raising the possibility of a general relationship between the complexity of RNA structures and their functional activity. Describing how information varies with activity in other heteropolymers, both biological and synthetic, may lead to an objective means of comparing their functional properties. This approach could be useful in predicting the functional utility of novel heteropolymers. C1 Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molblo.mgh.harvard.edu FU NIGMS NIH HHS [GM53936, R01 GM053936] NR 39 TC 120 Z9 124 U1 2 U2 13 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 APR 28 PY 2004 VL 126 IS 16 BP 5130 EP 5137 DI 10.1021/ja031504a PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 814EL UT WOS:000220957900041 PM 15099096 ER PT J AU Feng, HP Zeng, Y Graner, MW Whitesell, L Katsanis, E AF Feng, HP Zeng, Y Graner, MW Whitesell, L Katsanis, E TI Evidence for a novel, caspase-8-independent, fas death domain-mediated apoptotic pathway SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID CYTOCHROME-C RELEASE; CELL-DEATH; PERMEABILITY TRANSITION; SIGNALING COMPLEX; PROTEIN DAXX; RECEPTOR; MITOCHONDRIA; CASPASES; ACTIVATION; INITIATION AB Certain caspase-8 null cell lines demonstrate resistance to Fas-induced apoptosis, indicating that the Fas/FasL apoptotic pathway may be caspase-8-dependent. Some reports, however, have shown that Fas induces cell death independent of caspase-8. Here we provide evidence for an alternative, caspase-8-independent, Fas death domain-mediated apoptotic pathway. Murine 12B1-D1 cells express procaspase-3, -8, and -9, which were activated upon the dimerization of Fas death domain. Bid was cleaved and mitochondrial transmembrane potential was disrupted in this apoptotic process. All apoptotic events were completely blocked by the broad-spectrum caspase inhibitor Z-VAD-FMK, but not by other peptide caspase inhibitors. Cyclosporin A (CsA), which inhibits mitochondrial transition pore permeability, blocked neither pore permeability disruption nor caspase activation. However, CsA plus caspase-8 inhibitor blocked all apoptotic events of 12B1-D1 induced by Fas death domain dimerization. Our data therefore suggest that there is a novel, caspase-8-independent, Z-VAD-FMK-inhibitable, apoptotic pathway in 12B1-D1 cells that targets mitochondria directly. C1 Univ Arizona, Steele Mem Childrens Res Ctr, Dept Pediat, Tucson, AZ 85724 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Katsanis, E (reprint author), Univ Arizona, Steele Mem Childrens Res Ctr, Dept Pediat, Tucson, AZ 85724 USA. EM katsanis@peds.arizona.edu NR 36 TC 10 Z9 10 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI SYLVANIA PA PO BOX 1210, SYLVANIA, OH 43560 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PD APR 27 PY 2004 IS 1 BP 41 EP 51 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 823HT UT WOS:000221602100008 ER PT J AU Nix, WA Berger, MM Oberste, MS Brooks, BR Mckenna-Yasek, DM Brown, RH Roos, RP Pallansch, MA AF Nix, WA Berger, MM Oberste, MS Brooks, BR Mckenna-Yasek, DM Brown, RH Roos, RP Pallansch, MA TI Failure to detect enterovirus in the spinal cord of ALS patients using a sensitive RT-PCR method SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; NUCLEIC-ACID HYBRIDIZATION; POLYMERASE CHAIN-REACTION; BORRELIA-BURGDORFERI; POLIOVIRUS; SEQUENCES; INFECTION; RNA; AMPLIFICATION AB Objective: To assess the association of enteroviruses (EV) with ALS by applying a sensitive seminested reverse transcription (RT) PCR protocol to the detection of enteroviral RNA in a blinded set of archived tissues from ALS and control cases. Methods: The specimen set consisted of 24 frozen spinal cord samples from ALS cases, 17 frozen spinal cord samples from negative control (non-ALS) cases, and 5 frozen spinal cord positive control samples. The positive controls were two human spinal cord samples spiked with poliovirus (PV) and three spinal cords from PV-infected transgenic mice. A sensitive, EV-specific, seminested RT-PCR assay was used to detect EV genome in RNA extracted from the specimens and controls. Results: The assay detected EV RNA in a 10(-5) dilution of infected mouse tissue. EV RNA was not detected in the ALS specimens or in specimens from control cases, despite the presence of amplifiable RNA as assessed by amplification with control primers, whereas all of the positive control specimens yielded the expected PV amplification product. Conclusion: The reported association between EV infection and ALS was not confirmed by testing this set of specimens with these sensitive methods. C1 Ctr Dis Control & Prevent, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Univ Calif Irvine, Dept Med, Orange, CA 92668 USA. Univ Wisconsin, Sch Med, Dept Neurol, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Serv Neurol, Madison, WI 53705 USA. Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Charlestown, MA USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. RP Pallansch, MA (reprint author), Ctr Dis Control & Prevent, Resp & Enter Viruses Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Mailstop G-17, Atlanta, GA 30333 USA. EM mpallansch@cdc.gov FU NCRR NIH HHS [M01 RR03186]; NIA NIH HHS [AG12992]; NINDS NIH HHS [NS31248, NS37912, 5 PO1 NS21442-18] NR 34 TC 25 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 27 PY 2004 VL 62 IS 8 BP 1372 EP 1377 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 815UM UT WOS:000221067200021 PM 15111676 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI Plasmapheresis improves outcome in postinfectious cerebellitis induced by Epstein-Barr virus SO NEUROLOGY LA English DT Editorial Material ID ATAXIA C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org NR 7 TC 10 Z9 10 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 APR 27 PY 2004 VL 62 IS 8 BP 1443 EP 1443 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 815UM UT WOS:000221067200044 PM 15111700 ER PT J AU Coletta, RD Christensen, K Reichenberger, KJ Lamb, J Micomonaco, D Huang, LL Wolf, DM Muller-Tidow, C Golub, TR Kawakami, K Ford, HL AF Coletta, RD Christensen, K Reichenberger, KJ Lamb, J Micomonaco, D Huang, LL Wolf, DM Muller-Tidow, C Golub, TR Kawakami, K Ford, HL TI The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-CYCLE; GENE-EXPRESSION; DNA-DAMAGE; GERM-CELLS; CANCER; TRANSCRIPTION; MOUSE; MICE; OVEREXPRESSION; ACTIVATION AB Homeobox genes constitute a large family of transcription factors that are essential during normal development and are often dysregulated in cancer. However, the molecular mechanisms by which homeobox genes influence cancer remain largely unknown. Here we show that the tissue-restricted cyclin A1 is a transcriptional target of the Six1 homeoprotein. Both genes are expressed in the embryonic but not the terminally differentiated mammary gland, and Six1-knockout mice show a dramatic reduction of cyclin A1 in the embryonic mammary gland. In addition, both genes are reexpressed in breast cancers. Six1 overexpression increases cyclin Al mRNA levels and activity, cell proliferation, and tumor volume, whereas Six1 down-regulation decreases cyclin A1 mRNA levels and proliferation. Overexpression of Six1 in wild-type mouse embryonic fibroblasts, but not in knockout variants lacking the cyclin A1 gene, induces cell proliferation. Furthermore, inhibition of cyclin A1 in Six1-overexpressing mammary carcinoma cells decreases proliferation. Together these results demonstrate that cyclin A1 is required for the proliferative effect of Six1. We conclude that Six1 overexpression reinstates an embryonic pathway of proliferation in breast cancer by up-regulating cyclin A1. C1 Univ Colorado, Hlth Sci Ctr, Dept Mol Genet & Biochem, Denver, CO 80262 USA. Univ Campinas, Sch Dent, Discipline Pathol, BR-13414018 Piracicaba, SP, Brazil. MIT, Howard Hughes Med Inst, Ctr Genome Res, Cambridge, MA 02139 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Munster, Dept Med A Hematol & Oncol, D-48129 Munster, Germany. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Denver, CO 80262 USA. RP Ford, HL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Denver, CO 80262 USA. EM heide.ford@uchsc.edu RI Muller-Tidow, Carsten/B-5257-2014; Coletta, Ricardo/B-4909-2015; Muller-Tidow, Carsten/L-4062-2015 OI Coletta, Ricardo/0000-0001-5285-3046; FU NCI NIH HHS [1R01CA095277-01, R01 CA095277] NR 45 TC 139 Z9 148 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6478 EP 6483 DI 10.1073/pnas.0401139101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900029 PM 15123840 ER PT J AU Akiyama, H Chaboissier, MC Behringer, RR Rowitch, DH Schedl, A Epstein, JA de Crombrugghe, B AF Akiyama, H Chaboissier, MC Behringer, RR Rowitch, DH Schedl, A Epstein, JA de Crombrugghe, B TI Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXTRACELLULAR-MATRIX PROTEIN; AUTOSOMAL SEX REVERSAL; SRY-RELATED GENE; CAMPOMELIC DYSPLASIA; TRANSCRIPTION FACTOR; NEURAL CREST; CELL-TRANSFORMATION; ENDOCARDIAL CUSHION; CARTILAGE FORMATION; NF-ATC AB Epithelial-mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia of valves and septa, is a classic example of epithelial-mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation. Sox9 is activated when endocardial endothelial cells undergo mesenchymal transformation and migrate into an extracellular matrix, called cardiac jelly, to form endocardial cushions. In Sox9-null mutants, endocardial cushions are markedly hypoplastic. In these mutants, Nfatc1 is ectopically expressed and no longer restricted to endothelial cells. Further, Sox9-deficient endocardial mesenchymal cells fail to express ErbB3, which is required for endocardial cushion cell differentiation and proliferation. Our results reveal a succession of molecular steps in the pathway of endocardial cushion development. We propose that loss of Sox9 inhibits epithelial-mesenchymal transformation after delamination and initial migration, but before definitive mesenchymal transformation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. INSERM U470, Ctr Biochim, F-06108 Nice 2, France. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. RP Epstein, JA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM epsteinj@mail.med.upenn.edu; bdecromb@mail.mdanderson.org RI Schedl, Andreas/F-8823-2015 FU NCI NIH HHS [CA16672, P30 CA016672] NR 40 TC 132 Z9 136 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6502 EP 6507 DI 10.1073/pnas.0401711101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900033 PM 15096597 ER PT J AU Mootha, VK Handschin, C Arlow, D Xie, XH St Pierre, J Sihag, S Yang, WL Altshuler, D Puigserver, P Patterson, N Willy, PJ Schulman, IG Heyman, RA Lander, ES Spiegelman, BM AF Mootha, VK Handschin, C Arlow, D Xie, XH St Pierre, J Sihag, S Yang, WL Altshuler, D Puigserver, P Patterson, N Willy, PJ Schulman, IG Heyman, RA Lander, ES Spiegelman, BM TI Err alpha and Gabpa/b specify PGC-1 alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1; RECEPTOR-GAMMA; SKELETAL-MUSCLE; REGULATORY NETWORK; INSULIN-RESISTANCE; NUCLEAR; CELLS; MITOCHONDRIA; DYSFUNCTION; HETERODIMER AB Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be mediated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). By combining PGC-1alpha-induced genome-wide transcriptional profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related receptor alpha (Erralpha) and GA repeat-binding protein a as key transcription factors regulating the OXPHOS pathway. Interestingly, the genes encoding these two transcription factors are themselves PGC-1alpha-inducible and contain variants of both motifs near their promoters. Cellular assays confirmed that Erra and GA-binding protein a partner with PGC-1alpha a in muscle to form a double-positive-feedback loop that drives the expression of many OXPHOS genes. By using a synthetic inhibitor of Erra, we demonstrated its key role in PGC-1alpha-mediated effects on gene regulation and cellular respiration. These results illustrate the dissection of gene regulatory networks in a complex mammalian system, elucidate the mechanism of PGC-1alpha action in the OXPHOS pathway, and suggest that Erra agonists may ameliorate insulin-resistance in individuals with type 2 diabetes mellitus. C1 MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. X Ceptor Therapeut Inc, San Diego, CA 92121 USA. Harvard Univ, Cambridge, MA 02139 USA. RP Mootha, VK (reprint author), MIT, Eli & Edythe L Broad Inst, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. EM vmootha@broad.mit.edu;; bruce_spiegelman@dfci.harvard.edu RI Altshuler, David/A-4476-2009; Handschin, Christoph/E-6886-2015 OI Altshuler, David/0000-0002-7250-4107; Handschin, Christoph/0000-0003-0603-1097 NR 35 TC 412 Z9 423 U1 0 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6570 EP 6575 DI 10.1073/pnas.0401401101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900045 PM 15100410 ER PT J AU Mandal, AK Skoch, J Bacskai, BJ Hyman, BT Christmas, P Miller, D Yamin, TD Xu, SH Wisniewski, D Evans, JF Soberman, RJ AF Mandal, AK Skoch, J Bacskai, BJ Hyman, BT Christmas, P Miller, D Yamin, TD Xu, SH Wisniewski, D Evans, JF Soberman, RJ TI The membrane organization of leukotriene synthesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MICROSOMAL GLUTATHIONE TRANSFERASE; 5-LIPOXYGENASE-ACTIVATING PROTEIN; HUMAN-LEUKOCYTES; C-4 SYNTHASE; CELLS; EXPRESSION; BINDING; TRANSLOCATION; PURIFICATION; PATHWAY AB Cell signaling leading to the formation of leukotriene (LT)C-4 requires the localization of the four key biosynthetic enzymes on the outer nuclear membrane and endoplasmic reticulum. Whether any macromolecular organization of these proteins exists is unknown. By using fluorescence lifetime imaging microscopy and biochemical analysis, we demonstrate the presence of two distinct multimeric complexes that regulate the formation of LTs in RBL-2H3 cells. One complex consists of multimers of LTC4 synthase and the 5-lipoxy-genase activating protein (FLAP). The second complex consists of multimers of FLAP. Surprisingly, all LTC4 synthase was found to be in association with FLAP. The results indicate that the formation of LTC4 and LTB4 may be determined by the compartmentalization of biosynthetic enzymes in discrete molecular complexes. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Merck Res Labs, Rahway, NJ 07065 USA. RP Soberman, RJ (reprint author), Massachusetts Gen Hosp, Dept Med, 149 Navy Yard,13th St, Charlestown, MA 02129 USA. EM soberman@helix.mgh.harvard.edu RI ID, IMCACAT/D-5867-2014 FU NIA NIH HHS [R37 AG012406, R37AG12406]; NIBIB NIH HHS [R01 EB000786, R01 EB00786]; NIDDK NIH HHS [T32 DK-54740, K01 DK-59992, R01 DK054740]; NIGMS NIH HHS [R01 GM061823, R01 GM61823] NR 32 TC 58 Z9 58 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6587 EP 6592 DI 10.1073/pnas.0308523101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900048 PM 15084748 ER PT J AU Liberati, NT Fitzgerald, KA Kim, DH Feinbaum, R Golenbock, DT Ausubel, FM AF Liberati, NT Fitzgerald, KA Kim, DH Feinbaum, R Golenbock, DT Ausubel, FM TI Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NF-KAPPA-B; DROSOPHILA INNATE IMMUNITY; TOLL-LIKE RECEPTORS; SIGNALING PATHWAY; MODEL HOST; SALMONELLA-TYPHIMURIUM; ADAPTER MOLECULE; GENE; RNAI; PATHOGENESIS AB The p38 mitogen-activated protein kinase pathway regulates innate immune responses in evolutionarily diverse species. We have previously shown that the Caenorhabditis elegans p38 mitogen-activated protein kinase, PMK-1, functions in an innate immune response pathway that mediates resistance to a variety of microbial pathogens. Here, we show that tir-1, a gene encoding a highly conserved Toll/lL-1 resistance (TIR) domain protein, is also required for C elegans resistance to microbial pathogens. RNA interference inactivation of tir-1 resulted in enhanced susceptibility to killing by pathogens and correspondingly diminished PMK-1 phosphorylation. Unlike all known TIR-domain adapter proteins, overexpression of the human TIR-1 homologue, SARM, in mammalian cells was not sufficient to induce expression of NF-kappaB or IRF3-dependent reporter genes that are activated by Toll-like receptor signaling. These data reveal the involvement of a previously uncharacterized, evolutionarily conserved TIR domain protein in innate immunity that is functionally distinct from other known TIR domain signaling adapters. C1 Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. EM ausubel@molbio.mgh.harvard.edu FU NIAID NIH HHS [R01 AI052455, AI52455, R56 AI052455]; NIGMS NIH HHS [GM48707, R01 GM048707, R37 GM048707] NR 55 TC 119 Z9 133 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6593 EP 6598 DI 10.1073/pnas.0308625101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900049 PM 15123841 ER PT J AU Gagne, JM Smalle, J Gingerich, DJ Walker, JM Yoo, SD Yanagisawa, S Vierstra, RD AF Gagne, JM Smalle, J Gingerich, DJ Walker, JM Yoo, SD Yanagisawa, S Vierstra, RD TI Arabidopsis EIN3-binding F-box 1 and 2 form ubiquitin-protein ligases that repress ethylene action and promote growth by directing EIN3 degradation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SCF; RESPONSES; GENE; PROTEOLYSIS; SUBUNIT; PATHWAY; GLUCOSE; FAMILY; PLANTS; GRR1 AB Ubiquitination of various intracellular proteins by ubiquitin-protein ligases (or E3s) plays an essential role in eukaryotic cell regulation primarily through its ability to selectively target proteins for degradation by the 26S proteasome. Skp1, Cullin, F-box (SCF) complexes are one influential E3 class that use F-box proteins to deliver targets to a core ligase activity provided by the Skp1, Cullin, and Rbx1 subunits. Almost 700 F-box proteins can be found in Arabidopsis, indicating that SCF E3s likely play a pervasive role in plant physiology and development. Here, we describe the reverse genetic analysis of two F-box proteins, EBF1 and -2, that work coordinately in SCF complexes to repress ethylene action. Mutations in either gene cause hypersensitivity to exogenous ethylene and its precursor 1-aminocyclopropane-l-carboxylic acid. EBF1 and -2 interact directly with ethylene insensitive 3 (EIN3), a transcriptional regulator important for ethylene signaling. Levels of EIN3 are increased in mutants affecting either EBF1 or -2, suggesting that the corresponding SCF complexes work together in EIN3 breakdown. Surprisingly, double ebf1 ebf2 mutants display a substantial arrest of seedling growth and have elevated EIN3 levels, even in the absence of exogenous ethylene. Collectively, our results show that the SCFEBF1/EBF2-dependent ubiquitination and subsequent removal of EIN3 is critical not only for proper ethylene signaling but also for growth in plants. C1 Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Okayama Univ, Res Inst Bioresources, Kurashiki, Okayama 7100046, Japan. RP Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. EM vierstra@wisc.edu RI Gagne, Jennifer/B-2866-2009 OI Gagne, Jennifer/0000-0003-2563-087X NR 25 TC 204 Z9 227 U1 3 U2 28 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6803 EP 6808 DI 10.1073/pnas.0401698101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900085 PM 15090654 ER PT J AU Jaaskelainen, IP Ahveninen, J Bonmassar, G Dale, AM Ilmoniemi, RJ Levanen, S Lin, FH May, P Melcher, J Stufflebeam, S Tiitinen, H Belliveau, JW AF Jaaskelainen, IP Ahveninen, J Bonmassar, G Dale, AM Ilmoniemi, RJ Levanen, S Lin, FH May, P Melcher, J Stufflebeam, S Tiitinen, H Belliveau, JW TI Human posterior auditory cortex gates novel sounds to consciousness SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SENSORY-MEMORY; NEUROMAGNETIC EVIDENCE; MISMATCH NEGATIVITY; HUMAN BRAIN; MEG; MAGNETOENCEPHALOGRAPHY; INTEGRATION; GENERATION; RESPONSES; STIMULI AB Life or death in hostile environments depends crucially on one's ability to detect and gate novel sounds to awareness, such as that of a twig cracking under the paw of a stalking predator in a noisy jungle. Two distinct auditory cortex processes have been thought to underlie this phenomenon: (i) attenuation of the so-called N1 response with repeated stimulation and (ii) elicitation of a mismatch negativity response (MMN) by changes in repetitive aspects of auditory stimulation. This division has been based on previous studies suggesting that, unlike for the N1, repetitive "standard" stimuli preceding a physically different "novel" stimulus constitute a prerequisite to MMN elicitation, and that the source loci of MMN and NI are different. Contradicting these findings, our combined electromagnetic, hemodynamic, and psychophysical data indicate that the MMN is generated as a result of differential adaptation of anterior and posterior auditory cortex N1 sources by preceding auditory stimulation. Early (approximate to85 ms) neural activity within posterior auditory cortex is adapted as sound novelty decreases. This alters the center of gravity of electromagnetic N1 source activity, creating an illusory difference between N1 and MMN source loci when estimated by using equivalent current dipole fits. Further, our electroencephalography data show a robust MMN after a single standard event when the interval between two consecutive novel sounds is kept invariant. Our converging findings suggest that transient adaptation of feature-specific neurons within human posterior auditory cortex filters superfluous sounds from entering one's awareness. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Univ Helsinki, Dept Psychol, Dept Radiol, FIN-00014 Helsinki, Finland. Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Biomag Lab, Ctr Engn, FIN-00029 Helsinki, Finland. Univ Helsinki, Lab Computat Engn, FIN-02015 Helsinki, Finland. Univ Helsinki, Dept Neurol, FIN-00029 Helsinki, Finland. Helsinki Brain Res Ctr, FIN-00014 Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Jaaskelainen, IP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM iiro@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Jaaskelainen, Iiro/C-7392-2012; Lin, Fa-Hsuan/G-6988-2012; Ilmoniemi, Risto/E-9704-2012; May, Patrick/E-1786-2015 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Lin, Fa-Hsuan/0000-0002-9539-1731; Ilmoniemi, Risto/0000-0002-3340-2618; May, Patrick/0000-0002-3954-0421 FU NCRR NIH HHS [P41 RR014075, P41 RR14075]; NICHD NIH HHS [R01 HD040712]; NINDS NIH HHS [R01 NS037462] NR 30 TC 240 Z9 246 U1 0 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 27 PY 2004 VL 101 IS 17 BP 6809 EP 6814 DI 10.1073/pnas.0303760101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 816KD UT WOS:000221107900086 PM 15096618 ER PT J AU Paty, BW Bonner-Weir, S Laughlin, MR McEwan, J Shapiro, AMJ AF Paty, BW Bonner-Weir, S Laughlin, MR McEwan, J Shapiro, AMJ TI Toward development of imaging modalities for islets after transplantation: Insights from the national institutes of health workshop on beta cell imaging SO TRANSPLANTATION LA English DT Review AB Background. Pancreatic islet transplantation can provide insulin independence and near normal glucose control in selected patients with type 1 diabetes mellitus. However, in most cases, achieving insulin independence necessitates the use of at least two do nor pancreases per recipient and the rate of insulin independence may decline after transplantation. To better understand the fate of transplanted islets am the relationship between transplanted islet mass, graft function, and overall glucose homeostasis, an accurate and reproducible method of imaging islets in vivo is needed. Methods. Recent advances in noninvasive imaging techniques such as magnetic resonance imaging positron emission tomography, and other imaging modalities show great promise as potential tools to monitor islet number, mass, and function in the clinical setting. A recent international workshop, "Imaging the Pancreatic Beta Cell," sponsored by the National Institute of Biomedical Imaging and Bioengineering the National Institute of Diabetes and Digestive an Kidney Diseases, and the Juvenile Diabetes Research Foundation International focused on these emerging efforts to develop novel ways of imaging pancreatic beta cells in vivo. Results. Potential clinically applicable techniques in elude the use of directed magnetic resonance contrast agents such as lanthanides (Ln(3+)) and manganese (Mn2+) or magnetic resonance imaging probes such a superparamagnetic iron oxide nanoparticles. Potentia techniques for positron emission tomography imaging include the use of beta cell-specific antibodies, or pharmacologic agents such as glyburide analogs, or D-mannoheptulose. Optical imaging techniques are also being used to evaluate various aspects of beta cell metabolism including intracellular Ca2+ flux, glucokinase activity, and insulin granular exocytosis. Conclusions. The consensus among investigators at the imaging workshop was that an accurate and reproducible in vivo measure of functional islet mass is critically needed to further the strides that have been made in both islet transplantation and diabetes research as a whole. Such measures would potentially allow the assessment of islet engraftment and the early recognition of graft loss, leading to greater improvements in islet graft survival and function. C1 Univ Alberta, Clin Islet Transplant Program, Dept Med, Edmonton, AB, Canada. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. NIDDK, Bethesda, MD USA. Univ Alberta, Dept Oncol, Edmonton, AB, Canada. Univ Alberta, Dept Surg, Edmonton, AB, Canada. RP Paty, BW (reprint author), Univ Alberta, Clin Islet Transplant Program, Dept Med, 2000 Coll Plaza,8215 112th St, Edmonton, AB, Canada. EM bpaty@ualberta.ca NR 25 TC 49 Z9 52 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2004 VL 77 IS 8 BP 1133 EP 1137 DI 10.1097/01.TP.0000113231.90613.0E PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 816SZ UT WOS:000221130900001 PM 15114073 ER PT J AU Duxbury, MS Grikscheit, TC Gardner-Thorpe, J Rocha, FG Ito, H Perez, A Ashley, SW Vacanti, JP Whang, EE AF Duxbury, MS Grikscheit, TC Gardner-Thorpe, J Rocha, FG Ito, H Perez, A Ashley, SW Vacanti, JP Whang, EE TI Lymphangiogenesis in tissue-engineered small intestine SO TRANSPLANTATION LA English DT Article ID LYMPHATIC ENDOTHELIAL-CELLS; IN-VITRO; SYSTEM; EXPRESSION; ARTERIES; ORIGIN; COLON; GENE AB Background. Lymphangiogenesis, the formation of lymphatic vessels, has not been reported in engineered tissue. The purpose of this study was to characterize lymphangiogenesis in tissue-engineered small intestine. Methods. Biodegradable polymer scaffolds seeded with intestinal organoid units were implanted into syngenic recipient rats. Twenty-three neointestinal grafts were harvested from adult rat recipients I to 8 weeks postimplantation. Cells expressing the lymphatic endothelial marker vascular endothelial growth factor receptor (VEGFR)-3 were detected immunohistochemically. The lymphangiogenic growth factor VEGF-C was quantified by enzyme-linked immunoadsorbent assay. Results. Between the first and eighth weeks, neointestinal cysts increased in volume and mass. Muscular and mucosal layers increased in thickness and developed to resemble normal intestine histologically. The proportion of neointestinal VEGFR-3-positive cells increased and ultimately, tubular structures developed that resembled lymphatics architecturally, were distinct from CD34-positive blood vessels, and lacked luminal erythrocytes. Conclusion. Lymphangiogenesis occurs in tissue-engineered small intestine. This is the first demonstration of lymphatic vessels in an engineered tissue. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Whang, EE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM ewhang1@partners.org NR 26 TC 19 Z9 20 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2004 VL 77 IS 8 BP 1162 EP 1166 DI 10.1097/01.TP.0000121506.34924.3C PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 816SZ UT WOS:000221130900006 PM 15114078 ER PT J AU Baid-Agrawal, S Delmonico, FL Tolkoff-Rubin, NE Farrell, M Williams, WW Shih, V Auchincloss, H Cosimi, AB Pascual, M AF Baid-Agrawal, S Delmonico, FL Tolkoff-Rubin, NE Farrell, M Williams, WW Shih, V Auchincloss, H Cosimi, AB Pascual, M TI Cardiovascular risk profile after conversion from cyclosporine A to tacrolimus in stable renal transplant recipients SO TRANSPLANTATION LA English DT Article ID HYPERHOMOCYSTEINEMIA; IMMUNOSUPPRESSION; MULTICENTER; FIBRINOGEN; DISEASE; FK506 AB Background. Cardiovascular disease is a major cause of morbidity and mortality in renal recipients. In addition to steroids, cyclosporine A (CsA) has been implicated in contributing to increased cardiovascular risk. Conversion from CsA to tacrolimus (TAC) has been shown to improve hyperlipidemia and hypertension, but little is known about the differential effects of CsA versus TAC on other cardiovascular risk factors. We investigated overall cardiovascular risk profile after conversion from CsA to TAC. Methods. This was an open-label, single-arm prospective study; 22 adult renal recipients who were receiving CsA-based immunosuppression with serum total cholesterol greater than 200 mg/dL more than 1 year after transplantation were enrolled. CsA was replaced by TAC. Blood pressure, fasting lipid profile, homocysteine, fibrinogen, C-reactive protein, hemoglobin A1c, and creatinine were measured at baseline and at 3 and 6 months after conversion. Results. There was a significant improvement in fibrinogen (366+/-81-316+/-65 mg/dL, P<0.001), total cholesterol (250+/-50-207+/-29 mg/dL, P<0.001), and low-density lipoprotein cholesterol (155+/-43-121+/-24 mg/dL, P<0.001) after conversion. No new onset or worsening of diabetes mellitus was observed after conversion. There were no significant differences in HDL cholesterol, triglycerides, homocysteine, C-reactive protein, hemoglobin A1c levels, serum creatinine, mean blood pressure, and mean number of antihypertensive medications required before and after conversion. Conclusions. Our results indicate that conversion to low-dose TAC may be preferable over CsA for chronic maintenance immunosuppression because it improves the overall cardiovascular risk profile without any apparent adverse effects. C1 Charite Univ Med Berlin, Med Klin MS Nephrol & Intern Intens Med, Nephrol & Intens Care Med Unit, Internal Med Clin, D-13353 Berlin, Germany. Massachusetts Gen Hosp, Dept Med, Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Neurol Unit, Boston, MA 02114 USA. Charite Univ, Nephrol & Intens Care Med Unit, Internal Med Clin, Berlin, Germany. CHU Vaudois, Transplantat Ctr, CH-1011 Lausanne, Switzerland. RP Baid-Agrawal, S (reprint author), Charite Univ Med Berlin, Med Klin MS Nephrol & Intern Intens Med, Nephrol & Intens Care Med Unit, Internal Med Clin, Campus Virchow Klinikum,Augustenburger Pl 1, D-13353 Berlin, Germany. EM seema.baid-agrawal@charite.de NR 18 TC 40 Z9 42 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 APR 27 PY 2004 VL 77 IS 8 BP 1199 EP 1202 DI 10.1097/01.TP.0000119349.70491.F9 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 816SZ UT WOS:000221130900013 PM 15114085 ER PT J AU Crosby, K Yatko, C Dersimoman, H Pan, LY Edge, ASB AF Crosby, K Yatko, C Dersimoman, H Pan, LY Edge, ASB TI A novel monoclonal antibody inhibits the immune response of human cells against porcine cells: Identification of a porcine antigen homologous to CD58 SO TRANSPLANTATION LA English DT Article ID HUMAN NK CELLS; HUMAN T-CELLS; ENDOTHELIAL-CELLS; HUMAN CD2; LIGANDS; COSTIMULATION; RECOGNITION; INDUCTION; TOLERANCE; ADHESION AB Background. Human CD58 is an adhesion molecule that interacts with CD2 on lymphocytes. We describe here an antibody that blocks responses of human peripheral blood mononuclear cells (PBMCs) to porcine cells and reacts with a porcine protein with homology to CD58. Methods. Antibodies were isolated with a screen for inhibition of the human antiporcine response. One of these antibodies was used for immunoaffinity purification of a protein that was identified by molecular weight determination, endoglycosidase sensitivity, and microsequencing analysis as a porcine homologue of CD58. Results. The antigen recognized by this antibody was a cell surface protein of relative molecular mass (M-r) = 45,000 containing N-linked carbohydrate chains. Immunoaffinity purification of this protein and microsequencing revealed homology to sheep CD58 as well as sequences that were common to this protein and both sheep and human CD58. The protein was widely distributed on porcine cells, including lymphocytes, endothelial cells, muscle cells, and neuronal cells. This antibody efficiently inhibited lysis of porcine targets by human PBMCs in addition to preventing proliferation of the human PBMCs in response to the porcine cells. Conclusions. The CD2 interaction with porcine cells is important for the efficient recognition of porcine tissue, and inhibition of the human antiporcine immune response with the antibody is likely to be caused by the disruption of the human CD2 interaction with this porcine homologue of CD58. The antibody may prove to be useful for the blocking of this interaction without interfering with other functions of T cells. C1 Diacrin Inc, Charlestown, MA USA. RP Edge, ASB (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM albert_edge@MEEI.harvard.edu NR 20 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2004 VL 77 IS 8 BP 1288 EP 1294 DI 10.1097/01.TP.0000120377.57543.D8 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 816SZ UT WOS:000221130900028 PM 15114100 ER PT J AU Rosand, J Eckman, MH Knudsen, KA Singer, DE Greenberg, SM AF Rosand, J Eckman, MH Knudsen, KA Singer, DE Greenberg, SM TI The effect of warfarin and intensity of anticoagulation on outcome of intracerebral Hemorrhage SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; IN-HOSPITAL MORTALITY; ACUTE ISCHEMIC-STROKE; NATIONAL DEATH INDEX; ATRIAL-FIBRILLATION; PONTINE HEMORRHAGE; RISK-FACTORS; INTRACRANIAL HEMORRHAGE; DOSE WARFARIN; HYPERGLYCEMIA AB Background: Warfarin sodium is highly effective for prevention of embolic stroke, particularly in nonvalvular atrial fibrillation, but its expected benefit can be offset by risk of intracerebral hemorrhage (ICH). We studied the determinants of ICH outcome to quantify the independent effect of warfarin. Methods: Consecutive patients with supratentorial ICH treated in a tertiary care hospital with a neurointensive care unit were prospectively identified during a 7-year period, and data on hemorrhage location, clinical characteristics, and warfarin use were collected. Independent predictors of 3-month mortality were determined using multiple logistic regression analysis. Results: Of 435 consecutive patients aged 55 years or older, 102 (23.4%) were taking warfarin at the time of ICH. Three-month mortality was 25.8% for those not taking warfarin and 52.0% for those taking warfarin. Independent predictors of death were warfarin use (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3-3.8), age 70 years or older (OR, 2.4; 95% Cl, 1.4-4.0), and presence of diabetes mellitus (OR, 1.8; 95% Cl, 1.0-3.3). Although 68.0% of all warfarin-related hemorrhages occurred at an international normalized ratio (INR) of 3.0 or less, increasing degrees of anticoagulation were strongly associated with increasing risk of death compared with no warfarin use. Conclusions: Patients taking warfarin had a doubling in the rate of intracerebral hemorrhage mortality in a dose-dependent manner. The data suggest that careful control of the INR, already known to limit the risk of warfarin-related ICH, may also limit its severity. C1 Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trials Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol Clin Trials Unit, ACC 836,15 Parkman St, Boston, MA 02114 USA. EM sgreenberg@partners.org FU NINDS NIH HHS [5K23 NS 042695-02] NR 45 TC 338 Z9 345 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 26 PY 2004 VL 164 IS 8 BP 880 EP 884 DI 10.1001/archinte.164.8.880 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 815LI UT WOS:000221043400008 PM 15111374 ER PT J AU Dolan, S Wilkie, S Aliabadi, N Sullivan, MP Basgoz, N Davis, B Grinspoon, S AF Dolan, S Wilkie, S Aliabadi, N Sullivan, MP Basgoz, N Davis, B Grinspoon, S TI Effects of testosterone administration in human immunodeficiency virus-infected women with low weight - A randomized placebo-controlled study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HUMAN GROWTH-HORMONE; CONTROLLED TRIAL; FUNCTIONAL STATUS; WASTING SYNDROME; UNITED-STATES; DOUBLE-BLIND; HIV; AIDS; MEN; OXANDROLONE AB Background: The prevalence of human immunodeficiency virus (HIV) disease is increasing among women, many of whom remain symptomatic with low weight and poor functional status. Although androgen levels may often be reduced in such patients, the safety, tolerability, and efficacy of testosterone administration in this population remains unknown. Methods: A total of 57 HIV-infected women with free testosterone levels less than the median of the reference range and weight less than 90% of ideal body weight or weight loss greater than 10% were randomly assigned to receive transdermal testosterone (4 mg/patch) twice weekly or placebo for 6 months. Muscle mass was assessed by urinary creatinine excretion. Muscle function was assessed by the Tufts Quantitative Muscle Function Test. Treatment effect at 6 months was determined by analysis of covariance. Results are mean +/-SEM unless otherwise specified. Results: At baseline, subjects were low weight (body mass index [calculated as weight in kilograms divided by the square of height in meters] 20.6 +/- 0.4), with significant weight loss from preillness maximum weight (18.7% +/- 1.2%), and demonstrated reduced muscle function (upper and lower extremity muscle strength, 83% and 67%, respectively, of predicted range). Testosterone treatment resulted in significant increases in testosterone levels vs placebo (total testosterone: 37 +/- 5 vs -2 +/- 2 ng/dL [1.3 +/- 0.2 vs -0.1 +/- 0.1 nmol/L] [P<.001]; free testosterone: 3.7 +/- 0.5 vs -0.4 +/- 0.3 pg/mL [ 12.8 +/- 1.7 vs - 1.4 vs 1.0 pmol/L] [P<.001]) and was well tolerated, without adverse effects on immune function, lipid and glucose levels, liver function, or body composition or the adverse effect of hirsutism. Muscle mass tended to increase (1.4 +/- 0.6 vs 0.3 +/- 0.8 kg; P=.08), and shoulder flexion (0.4 +/- 0.3 vs -0.5 +/- 0.3 kg; P=.02), elbow flexion (0.3 +/- 0.4 vs-0.7 +/- 0.4kg;P=.04), knee extension (0.2 +/- 1.0 vs -1.7 +/- 1.3 kg; P=.02), and knee flexion (0.7 +/- 0.5 vs 0.3 +/- 0.7 kg; P=.04) increased in the testosterone-treated compared with the placebo-treated subjects. Conclusions: Testosterone administration is well-tolerated and increases muscle strength in low-weight HIV-infected women. Testosterone administration may be a useful adjunctive therapy to maintain muscle function in symptomatic HIV-infected women. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NIDDK NIH HHS [DK 54167] NR 36 TC 36 Z9 38 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 26 PY 2004 VL 164 IS 8 BP 897 EP 904 DI 10.1001/archinte.164.8.897 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 815LI UT WOS:000221043400011 PM 15111377 ER PT J AU Song, B Cayabyab, M Phan, N Wang, LP Axthelm, MK Letvin, NL Sodroski, JG AF Song, B Cayabyab, M Phan, N Wang, LP Axthelm, MK Letvin, NL Sodroski, JG TI Neutralization sensitivity of a simian-human immunodeficiency virus (SHIV-HXBc2P 3.2N) isolated from an infected rhesus macaque with neurological disease SO VIROLOGY LA English DT Article DE simian-human immunodeficiency virus; rhesus macaque; AIDS ID HUMAN MONOCLONAL-ANTIBODY; HIV-1 ENVELOPE GLYCOPROTEINS; CHEMOKINE RECEPTORS CCR3; RECOMBINANT SOLUBLE CD4; AIDS DEMENTIA COMPLEX; PIG-TAILED MACAQUES; MACROPHAGE TROPISM; VIRAL REPLICATION; TYPE-1 INFECTION; ATOMIC-STRUCTURE AB Simian-human immunodeficiency virus (SHIV) chimerae, after in vivo passage in monkeys, can induce acquired immunodeficiency syndrome (AIDS)-like illness and death. A monkey infected with the molecularly cloned, pathogenic SHIV-HXBc2P 3.2 exhibited multifocal granulomatous pneumonia as well as progressive neurological impairment characterized by tremors and pelvic limb weakness. SHIV-HXBc2P 3.2N was isolated from brain tissue explants and characterized. Viruses with the envelope glycoproteins of SHIV-HXBc2P 3.2N exhibited increased sensitivity to soluble CD4 and several neutralizing antibodies compared with viruses with the parental SHIV-HXBc2P 3.2 envelope glycoproteins. By contrast, viruses with SHIV-HXBc2P 3.2 and SHIV-HXBc2P 3.2N envelope glycoproteins were neutralized equivalently by 2G12 and 2F5 antibodies, which are rarely elicited in HIV-1-infected humans. A constellation of changes involving both gp120 and gp4l envelope glycoproteins was responsible for the difference in susceptibility to neutralization by most antibodies. Surprisingly, the gain of an N-linked glycosylation site in the gp4l ectodomain contributed greatly to neutralization sensitivity. Thus, the environment of the central nervous system, particularly in the context of immunodeficiency, allows the evolution of immunodeficiency viruses with greater susceptibility to neutralization by antibodies. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Oregon natl Primate Res Ctr, Beaverton, OR 97006 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div Human Retrovirol, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NCRR NIH HHS [RR00163]; NIAID NIH HHS [AI33832, AI42848] NR 85 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2004 VL 322 IS 1 BP 168 EP 181 DI 10.1016/j.virol.2004.02.001 PG 14 WC Virology SC Virology GA 812TF UT WOS:000220861100016 PM 15063126 ER PT J AU Alcazar, O Ho, RC Fujii, N Goodyear, LJ AF Alcazar, O Ho, RC Fujii, N Goodyear, LJ TI cDNA cloning and functional characterization of a novel splice variant of c-Cbl-associated protein from mouse skeletal muscle SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE CAP; c-Cbl; insulin; hypoxia; DNP; L6 cells ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVATION; STIMULATED GLUCOSE-TRANSPORT; GLUT4 TRANSLOCATION; 3T3-L1 ADIPOCYTES; SIGNALING PATHWAYS; KINASE ACTIVATION; EXPRESSION; DNA; SUFFICIENT; GLYCOGEN AB c-Cbl-associated protein (CAP) is an SH3-containing adapter protein that binds to the proto-oncogene c-Cbl. Recent work suggests that signaling through these molecules is involved in the regulation of insulin-stimulated glucose uptake in 3T3-L1 adipo-cytes. Skeletal muscle is the major site of insulin-stimulated glucose disposal but there have been no reports of CAP function in this tissue. Using RT-PCR of mouse skeletal muscle RNA, we discovered a novel splice variant of CAP (CAP(SM); GenBank Accession No. AF521593) that is different from the adipocyte form by inclusion of a novel 168 bp fragment. This fragment encodes a peptide sequence that shows very high similarity with exon 25 of the human homologue of CAP (SORBS1). To understand the function of CAP(SM) in glucose uptake regulation, L6 myotubes were transfected with either CAP(SM) or a truncated CAP(SM) devoid of all three SH3-binding domains (CAPDeltaSH3), which prevents CAP association with c-Cbl. Transfection with CAPDeltaSH3 decreased insulin-stimulated 2-deoxyglucose (2-DG) uptake and reduced c-Cbl phosphorylation. In contrast, transfection of L6 myotubes with CAPDeltaSH3 had no effect on dinitrophenol (DNP)- or hypoxia-stimulated glucose uptake, stimuli that work through insulin-independent mechanisms for the regulation of glucose uptake. These data demonstrate the existence of a novel CAP isoform expressed in skeletal muscle, and suggest the involvement of the CAP/Cbl pathway in the regulation of insulin-stimulated glucose uptake in L6 myotubes. (C) 2004 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Div Res, Joslin Diabetes Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Div Res, Joslin Diabetes Ctr, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 30 TC 14 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 23 PY 2004 VL 317 IS 1 BP 285 EP 293 DI 10.1016/j.bbrc.2004.03.038 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 810TD UT WOS:000220725700041 PM 15047181 ER PT J AU Turner, JH Gelasco, AK Raymond, JR AF Turner, JH Gelasco, AK Raymond, JR TI Calmodulin interacts with the third intracellular loop of the serotonin 5-hydroxytryptamine(1A) receptor at two distinct sites - Putative role in receptor phosphorylation by protein kinase C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN 5-HT1A RECEPTOR; GROWTH-FACTOR RECEPTOR; MEDIATED ERK ACTIVATION; MEMBRANE CA2+ PUMP; RAT HIPPOCAMPUS; NA+/H+ EXCHANGE; COUPLING DOMAIN; BINDING DOMAINS; CHO-K1 CELLS; NEURONS AB The serotonin 5-HT1A receptor couples to heterotrimeric G proteins and intracellular second messengers, yet no studies have investigated the possible role of additional receptor-interacting proteins in 5-HT1A receptor signaling. We have found that the ubiquitous Ca2+-sensor calmodulin (CaM) co-immunoprecipitates with the 5-HT1A receptor in Chinese hamster ovary fibroblasts. The human 5-HT1A receptor contains two putative CaM binding motifs, located in the N- and C-terminal juxtamembrane regions of the third intracellular loop of the receptor. Peptides encompassing both the N- terminal (i3N) and C-terminal (i3C) CaM-binding domains were tested for CaM binding. Using in vitro binding assays in combination with gel shift analysis, we demonstrated Ca2+-dependent formation of complexes between CaM and both peptides. We determined kinetic data using a combination of BIAcore surface plasmon resonance (SPR) and dansyl-CaM fluorescence. SPR analysis gave an apparent K-D of similar to110 nM for the i3N peptide and similar to700 nM for the i3C peptide. Both peptides also caused characteristic shifts in the fluorescence emission spectrum of dansyl-CaM, with apparent affinities of 87 +/- 23 nM and 1.70 +/- 0.16 muM. We used bioluminescence resonance energy transfer to show that CaM interacts with the 5-HT1A receptor in living cells, representing the first in vivo evidence of a G protein-coupled receptor interacting with CaM. Finally, we showed that CaM binding and phosphorylation of the 5-HT1A receptor i3 loop peptides by protein kinase C are antagonistic in vitro, suggesting a possible role for CaM in the regulation of 5-HT1A receptor phosphorylation and desensitization. These data suggest that the 5-HT1A receptor contains high and moderate affinity CaM binding regions that may play important roles in receptor signaling and function. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Raymond, JR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,Rm 829 CSB,POB 250623, Charleston, SC 29425 USA. EM raymondj@musc.edu FU NIDDK NIH HHS [DK59950, DK52448]; NIGMS NIH HHS [GM63909]; NIMH NIH HHS [MH64795] NR 57 TC 49 Z9 52 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 APR 23 PY 2004 VL 279 IS 17 BP 17027 EP 17037 DI 10.1074/jbc.M313919200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WU UT WOS:000220870400019 PM 14752100 ER PT J AU Ziebell, MR Nirthanan, S Husain, SS Miller, KW Cohen, JB AF Ziebell, MR Nirthanan, S Husain, SS Miller, KW Cohen, JB TI Identification of binding sites in the nicotinic acetylcholine receptor for [H-3]azietomidate, a photoactivatable general anesthetic SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SODIUM DODECYL-SULFATE; GATED ION CHANNELS; AMINO-ACIDS; NONCOMPETITIVE ANTAGONIST; H-3 CHLORPROMAZINE; GEL-ELECTROPHORESIS; DELTA-SUBUNIT; GAMMA; ETOMIDATE; BLOCKERS AB To identify binding domains in a ligand-gated ion channel for etomidate, an intravenous general anesthetic, we photolabeled nicotinic acetylcholine receptor (nAChR)-rich membranes from Torpedo electric organ with a photoactivatable analog, [H-3]azietomidate. Based upon the inhibition of binding of the noncompetitive antagonist [H-3]phencyclidine, azietomidate and etomidate bind with 10-fold higher affinity to nAChRs in the desensitized state (IC50 = 70 muM) than in the closed channel state. In addition, both drugs between 0.1 and 1 mM produced a concentration-dependent enhancement of [H-3]ACh equilibrium binding affinity, but they inhibited binding at higher concentrations. UV irradiation resulted in preferential [H-3]azietomidate photoincorporation into the nAChR alpha and delta subunits. Photolabeled amino acids in both subunits were identified in the ion channel domain and in the ACh binding sites by Edman degradation. Within the nAChR ion channel in the desensitized state, there was labeling of alphaGlu-262 and deltaGln-276 at the extracellular end and deltaSer-258 and deltaSer-262 toward the cytoplasmic end. Within the acetylcholine binding sites, [H-3]azietomidate photolabeled alphaTyr-93, alphaTyr-190, and alphaTyr-198 in the site at the alpha-gamma interface and deltaAsp-59 (but not the homologous position, gammaGlu-57). Increasing [H-3]azietomidate concentration from 1.8 to 150 muM increased the efficiency of incorporation into amino acids within the ion channel by 10-fold and in the ACh sites by 100-fold, consistent with higher affinity binding within the ion channel. The state dependence and subunit selectivity of [H-3]azietomidate photolabeling are discussed in terms of the structures of the nAChR transmembrane and extracellular domains. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Cohen, JB (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM jonathan_cohen@hms.harvard.edu FU NIGMS NIH HHS [GM58448] NR 42 TC 61 Z9 62 U1 1 U2 7 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 APR 23 PY 2004 VL 279 IS 17 BP 17640 EP 17649 DI 10.1074/jbc.M313886200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 812WU UT WOS:000220870400093 PM 14761946 ER PT J AU Shelkovnikov, S Merlic, CA Gonick, HC AF Shelkovnikov, S Merlic, CA Gonick, HC TI Influence of nitric oxide donors and peroxynitrite on the contractile effect and concentration of norepinephrine SO LIFE SCIENCES LA English DT Article DE norepinephrine; nitric oxide; peroxynitrite; rat; aorta; contraction ID VASCULAR SMOOTH-MUSCLE; PULMONARY-ARTERY; NITROGEN-OXIDES; RAT AORTA; CHANNELS; VASODILATION; NITRATION; NO; CATECHOLAMINES; HYPERTENSION AB Nitric oxide (NO) and peroxynitrite (ONOO) are said to destroy norepinephrine (NE). We studied the role of NE decomposition by NO donors and ONOO as they affect the contractile activity of NE in rat denuded thoracic aorta. First, we determined the relaxing effect of NO donors (SNAP, PROLI/NO, Sodium nitrite, SIN-1) and ONOO after precontraction by NE (1 muM). SNAP and SIN-1 (EC50 50-110 nM) were more active than PROLI/ NO, Sodium nitrite or ONOO (EC50 19-30 muM). The relaxing effect of NO donors and ONOO were decreased by ODQ (10 muM), a guanylate cyclase inhibitor. Second, we compared the contractile activity of NE before and after preincubation with NO donors or ONOO in presence of ODQ. NE (1 muM) was incubated with NO donors or ONOO at the concentrations of 0.1 mM in both Krebs solution or phosphate buffer (PH 7.4; 0.1 M) for 10 minutes at 37degreesC. NE evoked the aorta contraction in the same concentrations before and after preincubation with NO donors. In contrast, ONOO decreased effect of NE, EC50 was measured at 4.3 +/- 0.3 nM and 13.4 +/- 1.6 nM, before and after preincubation of NE with ONOO respectively. Third, we measured the NE concentration using the HPLC method. We revealed that the concentration of NE after preincubation with NO donors was unaltered. However HPLC measurement revealed that NE concentration after preincubation with ONOO was reduced 2-3-fold. Therefore, under these experimental conditions ONOO, but not NO donors, was capable of destroying NE. (C) 2004 Elsevier Inc. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Med & Res Serv, Nephrol Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. RP Shelkovnikov, S (reprint author), W Los Angeles Vet Affairs Med Ctr, Med & Res Serv, Nephrol Sect, Room 304,Bld 114,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM shelkovnikov@pcmagic.net NR 33 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 23 PY 2004 VL 74 IS 23 BP 2919 EP 2928 DI 10.1016/j.lfs.2003.11.006 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 809HX UT WOS:000220628900011 PM 15050429 ER PT J AU Settleman, J AF Settleman, J TI Tension precedes commitment - Even for a stem cell SO MOLECULAR CELL LA English DT Editorial Material ID TENSEGRITY; MODULATION AB The differentiation potential of stem cells is influenced by cell density. An article in the April issue of Developmental Cell (McBeath et al., 2004) demonstrates that lineage commitment by mesenchymal stem cells is regulated by shape-induced changes in Rho GTPase activity and cytoskeletal tension. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. NR 9 TC 28 Z9 31 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 23 PY 2004 VL 14 IS 2 BP 148 EP 150 DI 10.1016/S1097-2765(04)00207-2 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 815OK UT WOS:000221051400002 PM 15099513 ER PT J AU Yang, YT Jun, CD Liu, JH Zhang, RG Joachimiak, A Springer, TA Wang, JH AF Yang, YT Jun, CD Liu, JH Zhang, RG Joachimiak, A Springer, TA Wang, JH TI Structural basis for dimerization of ICAM-1 on the cell surface SO MOLECULAR CELL LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; IMMUNOLOGICAL SYNAPSE; CRYSTAL-STRUCTURE; LFA-1; DOMAINS; INTEGRINS; RECEPTOR; CLONING; BINDING; RECOGNITION AB We have determined the 3.0 Angstrom crystal structure of the three C-terminal domains 3-5 (D3-D5) of ICAM-1. Combined with the previously known N-terminal two-domain structure (D1D2), a model of an entire ICAM-1 extracellular fragment has been constructed. This model should represent a general architecture of other ICAM family members, particularly ICAM-3 and ICAM-5. The observed intimate dimerization interaction at D4 and a stiff D4-D5 stem-like architecture provide a good structural explanation for the existence of preformed ICAM-1 cis dimers on the cell membrane. Together with another dimerization interface at D1, a band-like one-dimensional linear cluster of ICAM-1 on an antigen-presenting cell (APC) surface can be envisioned, which might explain the formation of an immunological synapse between an activated T cell and APC which is critical for T cell receptor signaling. C1 Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Springer, TA (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM springer@cbr.med.harvard.edu; jwang@red.dfci.harvard.edu FU NHLBI NIH HHS [HL48675] NR 28 TC 64 Z9 68 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 23 PY 2004 VL 14 IS 2 BP 269 EP 276 DI 10.1016/S1097-2765(04)00204-7 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 815OK UT WOS:000221051400014 PM 15099525 ER PT J AU Mulliken, JB Anupindi, S Ezekowitz, RAB Mihm, MC Harris, NL Kerzner, LS Avram, MM AF Mulliken, JB Anupindi, S Ezekowitz, RAB Mihm, MC Harris, NL Kerzner, LS Avram, MM TI A newborn girl with a large cutaneous lesion, thrombocytopenia, and anemia - Kaposiform hemangioendothelioma with the Kasabach-Merritt phenomenon. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CONGENITAL HEMANGIOMA; RADIATION-THERAPY; SUCCESSFUL MANAGEMENT; JUVENILE HEMANGIOMAS; INTERFERON ALPHA-2A; VASCULAR TUMORS; TUFTED ANGIOMA; INFANT; MALFORMATIONS; RETROPERITONEUM C1 Childrens Hosp, Div Plast Surg, Craniofacial Ctr, Boston, MA 02115 USA. Childrens Hosp, Vasc Anomalies Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Mulliken, JB (reprint author), Childrens Hosp, Div Plast Surg, Craniofacial Ctr, Boston, MA 02115 USA. NR 40 TC 40 Z9 42 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 APR 22 PY 2004 VL 350 IS 17 BP 1764 EP 1775 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 814AJ UT WOS:000220947300013 PM 15103004 ER PT J AU Scheijen, B Ngo, HT Kang, H Griffin, JD AF Scheijen, B Ngo, HT Kang, H Griffin, JD TI FLT3 receptors with internal tandem duplications promote cell viability and proliferation by signaling through Foxo proteins SO ONCOGENE LA English DT Article DE Akt; Bim; FLT3; forkhead transcription factors; p27(Kip1) ID FORKHEAD TRANSCRIPTION FACTOR; ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; BCL-2 FAMILY; FACTOR FKHR; GENE-EXPRESSION; FACTOR AFX; IN-VIVO; PHOSPHATIDYLINOSITOL 3-KINASE; CAENORHABDITIS-ELEGANS AB In about 30% of the patients with acute myeloid leukemia, activating FLT3 receptor mutations have been identified, often as in-frame internal tandem duplications (ITD) at the juxtamembrane domain of the receptor. FLT3-ITD receptors exhibit constitutive tyrosine kinase activity in the absence of FLT3 ligand (FL) binding, and when expressed in cytokine-dependent cell lines and primary hematopoietic cells suppress programmed cell death and increase cell division. However, the signaling pathways important for transformation, in particular the nuclear targets, are unknown. Here we demonstrate that FLT3-ITD expression in Ba/F3 cells results in activation of Akt and concomitant phosphorylation of the Forkhead family member Foxo3a. Phosphorylation of Foxo proteins through FLT3-ITD signaling promotes their translocation from the nucleus into the cytoplasm, which requires the presence of conserved Akt phosphorylation sites in Forkhead transcription factors and PI3K activity. Induction of Foxo3a phosphorylation by FLT3-ITD receptors in Ba/F3 cells correlates with the suppression of Foxo-target genes p27(Kip1) and the proapoptotic Bcl-2 family member Bim. Specifically, FLT3-ITD expression prevents Foxo3a-mediated apoptosis and upregulation of p27(Kip1) and Bim gene expression. These data indicate that the oncogenic tyrosine kinase FLT3 can negatively regulate Foxo transcription factors, thereby promoting cell survival and proliferation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 540,44 Binney St, Boston, MA 02115 USA. EM James_Griffin@dfci.harvard.edu RI Scheijen, Blanca/E-3523-2016 OI Scheijen, Blanca/0000-0001-8029-9230 FU NCI NIH HHS [R01 CA66996] NR 81 TC 62 Z9 63 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 22 PY 2004 VL 23 IS 19 BP 3338 EP 3349 DI 10.1038/sj.onc.1207456 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 814LA UT WOS:000220975000008 PM 14981546 ER PT J AU Aoyama, Y Avruch, J Zhang, XF AF Aoyama, Y Avruch, J Zhang, XF TI Norel inhibits tumor cell growth independent of Ras or the MST1/2 kinases SO ONCOGENE LA English DT Article DE Nore1; RASSF1A; growth suppression; Ras; MST ID EPIGENETIC INACTIVATION; SUPPRESSOR GENE; PROMOTES APOPTOSIS; FAMILY PROTEIN; HUMAN CANCER; RASSF1A; LUNG; IDENTIFICATION; BINDING; PROLIFERATION AB Nore1, a noncatalytic protein identified by its ability to bind selectively to active Ras, is most closely related in amino-acid sequence to the tumor suppressor RASSF1. Both are expressed predominantly as a longer (Nore1A/RASSF1A) and/or shorter (Nore1B/RASSF1C) polypeptide; all four polypeptides contain a Ras-association domain and bind, through their conserved carboxytermini, the proapoptotic protein kinases MST1 and MST2. Moreover, the expression of the longer polypeptide is downregulated in human tumor cell lines through promoter methylation (frequently for RASSF1A, less regularly for Nore1A). Forced expression of RASSF1A in several such lines (including the NSCLC line A549) has been shown to suppress tumorigenicity; herein we inquire whether Nore has growth inhibitory activity. Four tumor cell lines were tested, selected for their low expression of both Nore1A and Nore1B; the two NSCLC lines, A549 and NCI-H460, each have a mutant active Ras oncogene, whereas the two melanoma lines G361 and M14 each contain the constitutively active BRaf(V599E) oncogene and wild-type Ras. The expression of Nore1A or Nore1B suppresses colony formation by the A549 and G361 lines, as effectively in A549 as does RASSF1A; colony formation in the NCI-H460 and M14 lines is unaffected. Nore1A inhibits anchorage-independent growth by A549 cells and delays A549 progression through G1 without evidence of increased apoptosis. The growth suppressive action of Nore1A is largely unaffected by deletion of both the MST- and Ras-binding domains, as well as by mutation of the Nore1A zinc finger. Thus, Nore1 suppresses the growth of some tumor cell lines through as yet unidentified effectors, independent of Ras-like proteins or MST1/2. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM avruch@helix.mgh.harvard.edu; zhang@mmolbio.mgh.harvard.edu FU NCI NIH HHS [CA073818]; NIDDK NIH HHS [DK17776] NR 27 TC 57 Z9 66 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 22 PY 2004 VL 23 IS 19 BP 3426 EP 3433 DI 10.1038/sj.onc.1207486 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 814LA UT WOS:000220975000017 PM 15007383 ER PT J AU Partridge, AH Hackett, N Blood, E Gelman, R Joffe, S Bauer-Wu, S Knudsen, K Emmons, K Collyar, D Schilsky, RL Winer, EP AF Partridge, AH Hackett, N Blood, E Gelman, R Joffe, S Bauer-Wu, S Knudsen, K Emmons, K Collyar, D Schilsky, RL Winer, EP TI Oncology physician and nurse practices and attitudes regarding offering clinical trial results to study participants SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NEEDS AB Despite recent interest on the part of advocates and researchers of oncology clinical trials in sharing study results, participants in these trials are not routinely informed about the results. We identified oncology physicians and nurses through the Cancer and Leukemia Group B database and surveyed them about sharing clinical trial results with participants. Of 1977 eligible members, 796 (40.3%) responded to the mailed survey, 497 (62.4%) of whom reported that they offer trial results to participants less than one-fifth of the time. A total of 576 (72.4%) of responders believed that most patients want to know the results of studies, and 634 (79.7%) of responders expressed willingness to offer results to most study participants in the future, believing that most patients want to know trial results and that routinely offering results would not have a negative effect on patients. Concerns of some responders about routinely offering trial results included negative emotional effect on patients, patient difficulty understanding the information, and resources required to offer the results. Of concern, 16.2% (129/796) of responders believed an obligation to offer results to study participants would make them less likely to enroll patients on studies. Future studies should consider sharing trial results with patients and evaluating the process and its effect on both patients and clinicians. [J Natl Cancer Inst 2004; 96:629-32] C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. Patient Advocates Res, Danville, CA USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [CA32291, CA31946] NR 8 TC 37 Z9 37 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 21 PY 2004 VL 96 IS 8 BP 629 EP 632 DI 10.1093/jnci/djh096 PG 4 WC Oncology SC Oncology GA 813DD UT WOS:000220886900013 PM 15100341 ER PT J AU Lorberbaum, JP Williams, WR AF Lorberbaum, JP Williams, WR TI Are there really no evolutionarily stable strategies in the iterated prisoner's dilemma? (vol 214, pg 155) SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Correction C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. RP Lorberbaum, JP (reprint author), Med Univ S Carolina, Dept Psychiat, POB 250861,67 President St, Charleston, SC 29425 USA. EM lorberjp@musc.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD APR 21 PY 2004 VL 227 IS 4 BP 593 EP 593 DI 10.1016/j.jtbi.2004.01.005 PG 1 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 809ZH UT WOS:000220674100012 ER PT J AU Schaumberg, DA Glynn, RJ Jenkins, AJ Lyons, TJ Rifai, N Ridker, PM Manson, JE Nathan, DM AF Schaumberg, DA Glynn, RJ Jenkins, AJ Lyons, TJ Rifai, N Ridker, PM Manson, JE Nathan, DM TI Effect of intensive glycemic control on levels of markers of inflammation in the Diabetes Control and Complications Trial SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Childrens Hosp, Boston, MA 02115 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 0009-7322 J9 CIRCULATION JI Circulation PD APR 20 PY 2004 VL 109 IS 15 MA LB6 BP E188 EP E188 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 813KO UT WOS:000220906200026 ER PT J AU Hernandez, SE Settleman, J Koleske, AJ AF Hernandez, SE Settleman, J Koleske, AJ TI Adhesion-dependent regulation of p190RhoGAP in the developing brain by the Abl-related gene tyrosine kinase SO CURRENT BIOLOGY LA English DT Article ID ACTIN CYTOSKELETON; FAMILY KINASES; GROWTH-FACTOR; P190 RHOGAP; F-ACTIN; C-ABL; MECHANISM; INHIBITION; RHOA AB Abl family kinases, which include the mammalian Abl and Arg (Abl-related gene) kinases, regulate neuronal morphogenesis in developing metazoa (for review, see [1]). Activation of Abl kinase activity directs changes in actin-dependent processes such as membrane ruffling, filopodial protrusion, and cell motility [2-6]. However, the mechanisms by which increased Abl or Arg kinase activity promote cytoskeletal rearrangements are unclear. We provide evidence that the Rho inhibitor p190RhoGAP (GTPase-activating protein) is an Arg substrate in the postnatal mouse brain. We show that p190RhoGAP has reduced phosphotyrosine content in postnatal arg(-/-) mouse brain extracts relative to wild-type extracts. In addition, the adhesion-dependent stimulation of p190RhoGAP phosphorylation observed in wild-type cells is not observed in arg(-/-) fibroblasts and neurons. Arg can phosphorylate p190RhoGAP in vitro and in vivo on tyrosine (Y) 1105. We find that Arg can stimulate p190RhoGAP to inhibit Rho and that Arg-mediated phosphorylation is required for this stimulation. Phosphorylation by Arg also promotes p190RhoGAP's association with p120RasGAP and stimulates p190RhoGAP's ability to induce neurito-genesis in neuroblastoma cells. Our results demonstrate that p190RhoGAP is an Arg substrate in the developing brain and suggest that Arg mediates the adhesion-dependent regulation of neuronal morphogenesis in the postnatal brain by phosphorylating p190RhoGAP. C1 Yale Univ, Interdept Neurosci Program, New Haven, CT 06520 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Charlestown, MA 02139 USA. RP Koleske, AJ (reprint author), Yale Univ, Interdept Neurosci Program, New Haven, CT 06520 USA. EM anthony.koleske@yale.edu FU NINDS NIH HHS [NS 39475, NS 42365, R01 NS039475] NR 18 TC 64 Z9 64 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 20 PY 2004 VL 14 IS 8 BP 691 EP 696 DI 10.1016/j.cub.2004.03.062 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 814QR UT WOS:000220989700021 PM 15084284 ER PT J AU Rita, M Young, I AF Rita, M Young, I TI Tumor skewing of CD34(+) progenitor cell differentiation into endothelial cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE angiogenesis; angiopoietin-1; CD34(+); endothelial cells; progenitor cells; vasculogenesis; VEGF ID COLONY-STIMULATING FACTOR; LEWIS LUNG-CARCINOMA; HEMATOPOIETIC STEM-CELLS; IMMUNE SUPPRESSOR CELLS; GROWTH-FACTOR-BETA; BONE-MARROW; NECK-CANCER; PERIPHERAL-BLOOD; MICE BEARING; ANGIOGENIC FACTORS AB Tumor production of granulocyte-macrophage colony-stimulating factor (GM-CSF) results in the mobilization of CD34(+) progenitor cells into the peripheral blood and tumor tissue. Using the Lewis lung carcinoma (LLC) model, in vitro studies showed that LLC cells could chemoattract CD34(+) cells predominantly through tumor production of VEGF. Addition of LLC-conditioned medium to CD34(+) cells that were cultured under conditions that support myeloid lineage cells skewed the differentiation of these precursor cells toward endothelial cells expressing CD31 and CD144. This differentiation of CD34(+) cells toward endothelial cells was attributed predominantly to angiopoietin-1 in the tumor-conditioned medium. The CD34(+) cells expressed the angiopoietin receptor Tie-2 and their differentiation into endothelial cells was blocked with neutralizing angiopoietin-1 antibodies. In vivo studies showed that infusion of lacZ(+) CD34(+) cells from the bone marrow of transgenic mice into wild-type mice bearing LLC tumors resulted in the accumulation of lacZ(+) cells within the tumor mass, particularly at the tumor's periphery. That these infused CD34(+) progenitor cells could develop into endothelial cells of the tumor vasculature was supported by their acquisition of the endothelial cell markers CD31 or CD144 within the tumor tissue. These studies demonstrate the capacity of tumor to attract CD34(+) cells to the tumor site and to direct the differentiation of these CD34(+) cells into endothelial cells that can become a component of the tumor vasculature. (C) 2004 Wiley-Liss, Inc. C1 Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Otolaryngol, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. RP Young, I (reprint author), Ralph H Johnson Vet Affairs Hosp, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM rita.young@med.va.gov NR 58 TC 16 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 20 PY 2004 VL 109 IS 4 BP 516 EP 524 DI 10.1002/ijc.2003 PG 9 WC Oncology SC Oncology GA 803UY UT WOS:000220257200005 ER PT J AU Mercier, GT Campbell, JA Chappell, JD Stehle, T Dermody, TS Barry, MA AF Mercier, GT Campbell, JA Chappell, JD Stehle, T Dermody, TS Barry, MA TI Chimeric adenovirus vector encoding reovirus attachment protein sigma 1 targets cells expressing junctional adhesion molecule 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTESTINAL M-CELLS; GUT EPITHELIAL MONOLAYERS; DENDRITIC CELLS; SIALIC-ACID; TIGHT JUNCTION; CELLULAR RECEPTOR; GENE DELIVERY; FIBER; BINDING; MECHANISM AB The utility of adenovirus (Ad) vectors for gene transduction can be limited by receptor specificity. We developed a gene-delivery vehicle in which the potent Ad5 vector was genetically reengineered to display the mucosal-targeting sigma1 protein of reovirus type 3 Dearing (T3D). A sigma1 construct containing all but a small virion-anchoring domain was fused to the N-terminal 44 aa of Ad5 fiber. This chimeric attachment protein Fibtail-T3Dsigma1 forms trimers and assembles onto Ad virions. Fibtail-T3Dsigma1 was recombined into the Ad5 genome, replacing sequences encoding wild-type fiber. The resulting vector, Ad5-T3Dsigma1, expresses Fibtail-T3Dsigma1 and infects Chinese hamster ovary cells transfected with human or mouse homologs of the reovirus receptor, junctional adhesion molecule 1 (JAM1), but not the coxsackievirus and Ad receptor. Treatment of Caco-2 intestinal epithelial cells with either JAM1-specific antibody or neuraminidase reduced transduction by Ad5T3Dsigma1, and their combined effect decreased transduction by 95%. Ad5-T3Dsigma1 transduces primary cultures of human dendritic cells substantially more efficiently than does Ad5, and this transduction depends on expression of JAM1. These data provide strong evidence that Ad5-T3Dsigma1 can be redirected to cells expressing JAM1 and sialic acid for application as a vaccine vector. C1 Rice Univ, Dept Bioengn, Houston, TX 77005 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. RP Dermody, TS (reprint author), Rice Univ, Dept Bioengn, Houston, TX 77005 USA. EM terry.dermody@vanderbilt.edu; mab@bcm.tmc.edu FU NCI NIH HHS [CA68485, T32 CA009385, P30 CA068485, T32 CA09385]; NHLBI NIH HHS [T32 HL007751, T32 HL07751]; NIAID NIH HHS [R01 AI43588, R01 AI038296, P30 AI036211, AI36211, R01 AI042588]; NIDDK NIH HHS [P60 DK020593, P30 DK020593, DK20593, P30 DK056338, DK056338]; NIGMS NIH HHS [R01 GM67853, R01 GM067853]; PHS HHS [R01 38296] NR 51 TC 58 Z9 61 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 20 PY 2004 VL 101 IS 16 BP 6188 EP 6193 DI 10.1073/pnas.0400542101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 814ME UT WOS:000220978000091 PM 15079060 ER PT J AU MacNeil, MA Heussy, JK Dacheux, RF Raviola, E Masland, RH AF MacNeil, MA Heussy, JK Dacheux, RF Raviola, E Masland, RH TI The population of bipolar cells in the rabbit retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE fluorescence; morphology; classification; axons ID MACAQUE MONKEY RETINA; INNER PLEXIFORM LAYER; CAT RETINA; GANGLION-CELLS; MAMMALIAN RETINA; AMACRINE CELLS; FUNCTIONAL ARCHITECTURE; CONE PHOTORECEPTORS; PRIMATE RETINA; ON-CENTER AB The population of bipolar cells in the rabbit retina was studied using Golgi impregnation and photocatalyzed filling of single cells with dihydrorhodamine, a quantitative sampling technique. The Golgi method revealed the morphology and stratification of cells in detail. The photofilling method allowed us to estimate the frequency of the cell types. From a sample of 243 Golgi-impregnated bipolar cells and 107 photofilled cells, we identified 1 type of rod bipolar cell and 12 types of cone bipolar cells. An analysis based on retinal coverage indicates that this number of types could be contained within the number of bipolar cells known to exist. The dendrites of most cone bipolars contacted all the cones within the individual cone bipolar cell's dendritic field. Types of bipolar cell were encountered at roughly similar frequency, without any one type predominating. The rabbit retina thus contains about a dozen parallel and roughly equipotent through-pathways. (C) 2004 Wiley-Liss, Inc. C1 York Coll Penn, Dept Nat Sci, Jamaica, NY 11451 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Alabama, Dept Ophthalmol, Eye Fdn Hosp, Birmingham, AL 35233 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP MacNeil, MA (reprint author), York Coll Penn, Dept Nat Sci, 94-20 Guy R Brewer Blvd, Jamaica, NY 11451 USA. EM macneil@york.cuny.edu FU NEI NIH HHS [EY-01344, EY-03011]; NIGMS NIH HHS [GM-08153] NR 52 TC 55 Z9 57 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 APR 19 PY 2004 VL 472 IS 1 BP 73 EP 86 DI 10.1002/cne.20063 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 806WG UT WOS:000220463400006 PM 15024753 ER PT J AU Scimone, ML Felbinger, TW Mazo, IB Stein, JV von Andrian, UH Weninger, W AF Scimone, ML Felbinger, TW Mazo, IB Stein, JV von Andrian, UH Weninger, W TI CXCL12 mediates CCR7-independent homing of central memory cells, but not naive T cells, in peripheral lymph nodes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE lymphocytes; chemokines; migration; secondary lymphoid organs; recirculation ID MICE LACKING EXPRESSION; MOLECULAR-MECHANISMS; ORGAN CHEMOKINE; IN-VIVO; EFFECTOR; DIFFERENTIATION; MOUSE; LYMPHOCYTES; DELETION; GENE AB Central memory CD8(+) T cells (T-CM) confer superior protective immunity against infectious compared with other T cell subsets. T-CM recirculate mainly through secondary lymphoid organs, including peripheral lymph nodes (PLNs). Here, we report that T-CM, unlike naive T cells, can home to PLNs in both a CCR7-dependent and -independent manner. Homing experiments in paucity of lymph node T cells (plt/plt) mice, which do riot express CCR7 ligands in secondary lymphoid organs, revealed that T-CM migrate to PLNs at similar to20% of wild-type (WT) levels, Whereas homing of naive T cells was reduced by 95%. Accordingly, a large fraction of endogenous CD8(+) T cells in plt/plt PLNs displayed a T-CM phenotype. Intravital microscopy of plt/plt subiliac lymph nodes showed that T-CM rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking. Sticking of T-CM in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1alpha). Anti-CXCL12 also reduced homing of T-CM to PLNs in WT animals by 20%, indicating, a nonredundant role for this chemokine in the presence of physiologic CCR7 agonists. Together, these data distinguish naive T cells from T-CM, whereby only the hatter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL048675, HL48675, HL54936, HL56949, P01 HL056949, R01 HL054936] NR 30 TC 64 Z9 66 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 19 PY 2004 VL 199 IS 8 BP 1113 EP 1120 DI 10.1084/jem.20031645 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 815JR UT WOS:000221039100008 PM 15096537 ER PT J AU Zorn, E Miklos, DB Floyd, BH Mattes-Ritz, A Guo, LX Soiffer, RJ Antin, JH Ritz, J AF Zorn, E Miklos, DB Floyd, BH Mattes-Ritz, A Guo, LX Soiffer, RJ Antin, JH Ritz, J TI Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE minor histocompatibility antigen; chronic graft-versus-host disease; hematopoietic stem cell transplantation; H-Y antigen; class II epitope ID VERSUS-HOST-DISEASE; MHC CLASS-I; H-Y-ANTIGEN; GRAFT-REJECTION; DENDRITIC CELLS; BONE-MARROW; GENE CODES; IDENTIFICATION; PEPTIDES; IMMUNOGENICITY AB We examined the immune response to DBY, a model H-Y minor histocompatibility antigen (mHA) in a male patient with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stein cell transplant from a human histocompatibility leukocyte antigen (HLA)-identical female sibling. Patient peripheral blood mononuclear cells were screened for reactivity against a panel of 93 peptides representing the entire amino acid sequence of DBY. This epitope screen revealed a high frequency CD4(+) T cell response to a single DBY peptide that persisted from 8 to 21 mo after transplant. A CD4(+) T cell clone displaying the same reactivity was,as established from posttransplant patient cells and used to characterize the T cell epitope as a 19-mer peptide starting at position 30 in the DBY sequence and restricted by HLA-DRB 1*1501. Remarkably, the corresponding X homologue peptide was also recognized by donor T cells. Moreover, the T cell clone responded equally to mature HLA-DRB1*1501 male and female dendritic cells, indicating that both DBY and DBX peptides were endogenously processed. After transplant, the patient also developed antibodies that were specific for recombinant DBY protein and did not react with DBX. This antibody response was mapped to two DBY peptides beginning it positions 118 and 536. Corresponding DBX peptides were not recognized. These studies provide the first demonstration of a coordinated B and T cell immune response to an H-Y antigen after allogeneic transplant. The specificity for recipient male cells was mediated by the B cell response and not by donor T cells. This dual DBX/DBY antigen is the first mHA to be identified in the context of chronic GVHD. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M530, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NHLBI NIH HHS [HL70149, P01 HL070149]; NIAID NIH HHS [AI29530, P01 AI029530, U19 AI029530] NR 27 TC 115 Z9 119 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 19 PY 2004 VL 199 IS 8 BP 1133 EP 1142 DI 10.1084/jcm.20031560 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 815JR UT WOS:000221039100010 PM 15096539 ER PT J AU Schmidt, EV AF Schmidt, EV TI The role of c-myc in regulation of translation initiation SO ONCOGENE LA English DT Article DE translational; control; eIF4E; ribosomal synthesis; rDNA transcription ID HUMAN TUMOR-CELLS; ORNITHINE-DECARBOXYLASE; MESSENGER-RNA; CYCLIN D1; FACTOR 4E; TRANSCRIPTION FACTOR; PROTEIN-SYNTHESIS; SACCHAROMYCES-CEREVISIAE; INCREASED EXPRESSION; RIBOSOME BIOGENESIS AB Translation initiation is important for the regulation of both cell growth and cell division. It is uniquely poised to coordinate overall cell proliferation by its effects on both growth and division. A number of translation initiation factors are transcriptional targets of c-myc in a variety of assays. In particular, the mRNA cap-binding protein eIF4E has a myc-binding sequence in its promoter that is myc responsive in reporter assays and contains a high-affinity myc-binding site in chromosome immunoprecipitation experiments. Several differential expression screens have demonstrated altered levels of eIF4E, along with several other translation initiation factors, in response to alterations of c-myc levels. The potential for eIF4E and other translational control elements to mediate myc's transforming functions is particularly important because eIF4E is itself a known oncogenic factor. The ability of translation initiation factors to affect both cell division control and cell growth control coincides with myc's remarkable effects on both cell growth and cell division. C1 Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. MassGen Hosp Children, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, 55 Fruit St, Boston, MA 02114 USA. EM schmidt@helix.mgh.harvard.edu FU NCI NIH HHS [R01-CA63117] NR 66 TC 91 Z9 100 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 19 PY 2004 VL 23 IS 18 BP 3217 EP 3221 DI 10.1038/sj.onc.1207548 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 813AJ UT WOS:000220879700010 PM 15094771 ER PT J AU Choi, HK Atkinson, K Karlson, EW Willett, W Curhan, G AF Choi, HK Atkinson, K Karlson, EW Willett, W Curhan, G TI Alcohol intake and risk of incident gout in men: a prospective study SO LANCET LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; ADENINE-NUCLEOTIDE TURNOVER; CORONARY-HEART-DISEASE; URIC-ACID; CONSUMPTION; WOMEN; REPRODUCIBILITY; HYPERURICEMIA; ACTIVATION; METABOLISM C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Rheumatol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Choi, HK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Rheumatol Unit, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464]; NIAAA NIH HHS [AA11181]; NIDDK NIH HHS [DK58573] NR 30 TC 284 Z9 313 U1 2 U2 31 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 17 PY 2004 VL 363 IS 9417 BP 1277 EP 1281 DI 10.1016/S0140-6736(04)16000-5 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 813KB UT WOS:000220904900009 PM 15094272 ER PT J AU Shiraishi, I Melendez, J Ahn, Y Skavdahl, M Murphy, E Welch, S Schaefer, E Walsh, K Rosenzweig, A Torella, D Nurzynska, D Kajstura, J Leri, A Anversa, P Sussman, MA AF Shiraishi, I Melendez, J Ahn, Y Skavdahl, M Murphy, E Welch, S Schaefer, E Walsh, K Rosenzweig, A Torella, D Nurzynska, D Kajstura, J Leri, A Anversa, P Sussman, MA TI Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes SO CIRCULATION RESEARCH LA English DT Article DE Akt; apoptosis; nuclear; cardiomyocytes; transgenic ID PROTEIN-TYROSINE-PHOSPHATASE; FORKHEAD TRANSCRIPTION FACTOR; GROWTH-FACTOR-I; NF-KAPPA-B; ISCHEMIA-REPERFUSION INJURY; PROMOTES CELL-SURVIVAL; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSGENIC MICE; FACTOR AFX; CARDIAC MYOCYTES AB Heart failure is associated with death of cardiomyocytes leading to loss of contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition of cell death and prevention of pathogenesis induced by cardiomyopathic stimuli. However, recent studies by our group have found accumulation of activated Akt in the nucleus, suggesting that biologically relevant target(s) of Akt activity may be located there. To test this hypothesis, a targeted Akt construct was created to determine the antiapoptotic action of nuclear Akt accumulation. Nuclear localization of the adenovirally encoded Akt construct was confirmed by confocal microscopy. Cardiomyocytes expressing nuclear-targeted Akt showed no evidence of morphological remodeling such as altered myofibril density or hypertrophy. Nuclear-targeted Akt significantly elevated levels of phospho-Akt and kinase activity and inhibited apoptosis as effectively as myristolated-Akt in hypoxia-induced cell death. Transgenic overexpression of nuclear-targeted Akt did not result in hypertrophic remodeling, altered cardiomyocyte DNA content or nucleation, or enhanced phosphorylation of typical cytoplasmic Akt substrates, yet transgenic hearts were protected from ischemia-reperfusion injury. Gene array analyses demonstrated changes in the transcriptional profile of Akt/nuc hearts compared with nontransgenic controls distinct from prior characterizations of Akt expression in transgenic hearts. Collectively, these experiments show that targeting of Akt to the nucleus mediates inhibition of apoptosis without hypertrophic remodeling, opening new possibilities for therapeutic applications of nuclear-targeted Akt to inhibit cell death associated with heart disease. C1 San Diego State Univ, SDSU Heart Inst, San Diego, CA 92182 USA. San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. New York Med Coll, Cardiovasc Res Inst, Valhalla, NY USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Biosource Int, Hopkinton, MA USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp Res Fdn, Div Mol Cardiovasc Biol, Cincinnati, OH USA. RP Sussman, MA (reprint author), San Diego State Univ, SDSU Heart Inst, 5500 Campanile Dr, San Diego, CA 92182 USA. EM sussman@sciences.sdsu.edu RI Nurzynska, Daria/A-2161-2010; OI TORELLA, Daniele/0000-0002-4915-5084 FU NHLBI NIH HHS [HL66035, HL58224, HL67245] NR 57 TC 148 Z9 155 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 16 PY 2004 VL 94 IS 7 BP 884 EP 891 DI 10.1161/01.RES.0000124394.01180.BE PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 816MG UT WOS:000221113400007 PM 14988230 ER PT J AU Carven, GJ Chitta, S Hilgert, I Rushe, MM Baggio, RF Palmer, M Arenas, JE Strominger, JL Horejsi, V Santambrogio, L Stern, LJ AF Carven, GJ Chitta, S Hilgert, I Rushe, MM Baggio, RF Palmer, M Arenas, JE Strominger, JL Horejsi, V Santambrogio, L Stern, LJ TI Monoclonal antibodies specific for the empty conformation of HLA-DR1 reveal aspects of the conformational change associated with peptide binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MHC; MYELIN BASIC-PROTEIN; HLA-DM; ANTIGENIC PEPTIDE; ESCHERICHIA-COLI; STRUCTURAL BASIS; DENDRITIC CELLS; ALPHA-CHAIN; ACIDIC PH AB Class II major histocompatibility complex (MHC) proteins bind peptides and present them at the cell surface for interaction with CD4(+) T cells as part of the system by which the immune system surveys the body for signs of infection. Peptide binding is known to induce conformational changes in class II MHC proteins on the basis of a variety of hydrodynamic and spectroscopic approaches, but the changes have not been clearly localized within the overall class II MHC structure. To map the peptide-induced conformational change for HLA-DR1, a common human class II MHC variant, we generated a series of monoclonal antibodies recognizing the beta subunit that are specific for the empty conformation. Each antibody reacted with the empty but not the peptide-loaded form, for both soluble recombinant protein and native protein expressed at the cell surface. Antibody binding epitopes were characterized using overlapping peptides and alanine scanning substitutions and were localized to two distinct regions of the protein. The pattern of key residues within the epitopes suggested that the two epitope regions undergo substantial conformational alteration during peptide binding. These results illuminate aspects of the structure of the empty forms and the nature of the peptide-induced conformational change. C1 Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Acad Sci Czech Republ, Inst Genet Mol, CZ-16637 Prague, Czech Republic. Appl Biosyst Cell Biol & Funct Proteom, Bedford, MA 01730 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. RP Stern, LJ (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, Rm S2-127, Worcester, MA 01655 USA. EM lawrence.stern@umassmed.edu RI Horejsi, Vaclav/G-3113-2014 FU NIAID NIH HHS [AI-49524, AI-48832, AI-48833] NR 62 TC 35 Z9 35 U1 0 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 APR 16 PY 2004 VL 279 IS 16 BP 16561 EP 16570 DI 10.1074/jbc.M314315200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 811BR UT WOS:000220747900106 PM 14757758 ER PT J AU Dokholyan, RS Albert, CM Appel, LJ Cook, NR Whelton, PK Hennekens, CH AF Dokholyan, RS Albert, CM Appel, LJ Cook, NR Whelton, PK Hennekens, CH TI Trial of omega-3 fatty acids for prevention of hypertension SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-PRESSURE; FISH-OIL; FATTY-ACIDS; PHASE-I; LIPIDS; SUPPLEMENTATION; METAANALYSIS AB Although w-3 polyunsaturated fatty acid supplements reduce blood pressure (BP), the typical doses cause untoward side effects. A novel fatty acid supplement was tested in a randomized trial of patients with high normal diastolic BP. The novel fatty acid supplement did not significantly reduce BP in patients with high normal diastolic blood pressure. (C) 2004 by Excerpta Medica, Inc. C1 Duke Clin Res Inst, Durham, NC 27715 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. RP Dokholyan, RS (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM Rachel.dokholyan@duke.edu NR 15 TC 16 Z9 18 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2004 VL 93 IS 8 BP 1041 EP 1043 DI 10.1016/j.amjcard.2004.01.013 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 812ZH UT WOS:000220876900020 PM 15081453 ER PT J AU Ottowitz, W Derro, D Dougherty, DD Fischman, AJ Hall, J AF Ottowitz, W Derro, D Dougherty, DD Fischman, AJ Hall, J TI Use of PET in the evaluation of hypothalamic function: An endocrine paradigm SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Psychiat Neurosci Program, Charlestown, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 40 BP 12S EP 12S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300042 ER PT J AU Goff, DC AF Goff, DC TI Folate, homocysteine, and negative symptoms in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR 15 PY 2004 VL 55 SU 8 MA 80 BP 23S EP 24S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300082 ER PT J AU Martin, LF Hall, MH Leonard, S Olincy, A Freedman, R AF Martin, LF Hall, MH Leonard, S Olincy, A Freedman, R TI Diminished P50 suppression is associated with alpha-7 nicotinic receptor gene promoter region single nucleotide polymorphisms in schizoaffective disorder, bipolar type SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 78 BP 23S EP 23S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300080 ER PT J AU Reddy, R Keshavan, MS Yao, JK AF Reddy, R Keshavan, MS Yao, JK TI Blunted serotonergic responsivity in platelets from neuroleptic-naive patients at first episode of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 81 BP 24S EP 24S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300083 ER PT J AU Brambilla, P Stanley, JA Nicoletti, MA Sassi, RB Mallinger, AG Kupfer, DJ Frank, E Keshavan, MS Soares, JC AF Brambilla, P Stanley, JA Nicoletti, MA Sassi, RB Mallinger, AG Kupfer, DJ Frank, E Keshavan, MS Soares, JC TI H-1 magneticresonance spectroscopy investigation of dorso-lateral prefrontal cortex in adult bipolar disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Verona, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Texas, Dept Psychiat, San Antonio, TX 78285 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 103 BP 30S EP 30S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300105 ER PT J AU Chen, HH Monkul, ES Nicoletti, MA Hatch, JP Sassi, RB Axelson, D Brambilla, P Keshavan, MS Ryan, ND Birmaher, B Soares, JC AF Chen, HH Monkul, ES Nicoletti, MA Hatch, JP Sassi, RB Axelson, D Brambilla, P Keshavan, MS Ryan, ND Birmaher, B Soares, JC TI Abnormal left superior temporal gyrus volumes in children and adolescents with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Psychiat, San Antonio, TX 78284 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Verona, Sch Med, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 104 BP 30S EP 30S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300106 ER PT J AU Glahn, DC Kaur, S Bearden, CE Monkul, ES Sanches, M Najt, P Villarreal, V Bowden, CL Soares, JC AF Glahn, DC Kaur, S Bearden, CE Monkul, ES Sanches, M Najt, P Villarreal, V Bowden, CL Soares, JC TI Declarative memory dysfunction in patients with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Dept Psychiat, San Antonio, TX USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 108 BP 32S EP 32S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300110 ER PT J AU Petersen, T Papakostas, GI Posternak, MA Kant, A Iosifescu, DV Yeung, AS Nierenberg, AA Fava, M AF Petersen, T Papakostas, GI Posternak, MA Kant, A Iosifescu, DV Yeung, AS Nierenberg, AA Fava, M TI Empirical testing of two models for staging antidepressant treatment resistance SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Rhode Isl Hosp, Providence, RI 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 122 BP 35S EP 35S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300124 ER PT J AU Yao, JK Magan, S Sonel, AF Gurklis, JA Sanders, R Reddy, RD AF Yao, JK Magan, S Sonel, AF Gurklis, JA Sanders, R Reddy, RD TI Effects of omega-3 fatty acids on platelet serotonin responsivity in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Nursing Serv, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Med Serv, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Psychiat Serv, Pittsburgh, PA USA. Dayton VA Med Ctr, Psychiat Serv, Dayton, OH USA. Univ Pittsburgh, Med Ctr Hlth Syst, Dept Psychiat, Pittsburgh, PA 15260 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 147 BP 42S EP 43S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300149 ER PT J AU Spencer, TJ AF Spencer, TJ TI Atomoxetine treatment in children with Attention-Deficit/Hyperactivity Disorder and comorbid tic disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 185 BP 53S EP 53S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300187 ER PT J AU Olincy, A Ross, RG Rieger, KP Zerbe, GO Johnson, LL Freedman, R AF Olincy, A Ross, RG Rieger, KP Zerbe, GO Johnson, LL Freedman, R TI Admixture analysis of an antisaccade eye movement task in probands with schizophrenia and their relatives SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Colorado, Hlth Sci Ctr, Dept Biostat & Prevent Med, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 215 BP 62S EP 62S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300217 ER PT J AU Henderson, DC Louie, P Borba, C Daley, TB Goff, DC AF Henderson, DC Louie, P Borba, C Daley, TB Goff, DC TI Glucose metabolism in schizophrenia patients treated with atypical antipsychotics: A frequent sampled intravenous glucose tolerance test and minimal model analysis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 229 BP 65S EP 66S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300231 ER PT J AU Henderson, DC Louie, P Nguyen, D Daley, TB Salib, E Koul, P Kunkel, L AF Henderson, DC Louie, P Nguyen, D Daley, TB Salib, E Koul, P Kunkel, L TI Clozapine and cardiovascular risks: 10 year estimates SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Northeastern Univ, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 238 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300239 ER PT J AU Weiss, AP Ditman, T Goff, DC Schacter, D Heckers, S AF Weiss, AP Ditman, T Goff, DC Schacter, D Heckers, S TI Aberrant anterior hippocampal activity during contextual memory decision in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 250 BP 71S EP 71S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300250 ER PT J AU Kennedy, A Rosengren, K Kilzieh, N Wood, AE Tapp, A AF Kennedy, A Rosengren, K Kilzieh, N Wood, AE Tapp, A TI Does depression predict quality of life in outpatients with schizophrenia spectrum disorders? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Washington, Dept Psychiat & Behav Sci, Tacoma, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Tacoma, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 15 PY 2004 VL 55 SU 8 MA 259 BP 73S EP 74S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300259 ER PT J AU McCarley, RW Shenton, ME Kasai, K Kuroki, N AF McCarley, RW Shenton, ME Kasai, K Kuroki, N TI Progression of STG gray matter volume decrease in first-episode schizophrenia but not in first episode mania SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 VA Boston Healthcare, Brockton, MA USA. Harvard Univ, Sch Med, Brockton, MA 02401 USA. Univ Tokyo, Sch Med, Tokyo 113, Japan. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 257 BP 73S EP 73S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300257 ER PT J AU Rassovsky, Y Green, MF Nuechterlein, KH Breitmeyer, BG Mintz, J AF Rassovsky, Y Green, MF Nuechterlein, KH Breitmeyer, BG Mintz, J TI Visual masking and attentional processing in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Houston, Houston, TX 77004 USA. RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 272 BP 77S EP 77S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300272 ER PT J AU Deckersbach, T Dougherty, DD Savage, C Sachs, GS Rauch, SL AF Deckersbach, T Dougherty, DD Savage, C Sachs, GS Rauch, SL TI Impaired recruitment of prefrontal cortex and hippocampus during episodic memory encoding in euthymic bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 289 BP 81S EP 82S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300288 ER PT J AU Kaur, S de Macedo-Soares, CMS Brambilla, P Nicoletti, MA Sassi, RB Axelson, D Hatch, JP Keshavan, MS Ryan, ND Birmaher, B Soares, JC AF Kaur, S de Macedo-Soares, CMS Brambilla, P Nicoletti, MA Sassi, RB Axelson, D Hatch, JP Keshavan, MS Ryan, ND Birmaher, B Soares, JC TI Corpus callosum signal intensity in young bipolar disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. ABC Med Sch, Sao Paulo, Brazil. Univ Verona, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. Univ Sao Paulo, Sch Med, Inst Psychiat, BR-05508 Sao Paulo, Brazil. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 15 PY 2004 VL 55 SU 8 MA 290 BP 82S EP 82S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300289 ER PT J AU Soares, JC Kochunov, P Monkul, ES Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Lancaster, J Fox, PT AF Soares, JC Kochunov, P Monkul, ES Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Lancaster, J Fox, PT TI Gender specific structural abnormalities in bipolar disorder by deformation field morphometry SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Verona, Sch Med, Dept Med & Publ Hlth, I-37100 Verona, Italy. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 291 BP 82S EP 82S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300290 ER PT J AU Monkul, ES Fawthrop, SC Brambilla, P Nicoletti, MA Sassi, RB Lacerda, ALT Mallinger, AG Kupfer, DJ Keshavan, MS Frank, E Soares, JC AF Monkul, ES Fawthrop, SC Brambilla, P Nicoletti, MA Sassi, RB Lacerda, ALT Mallinger, AG Kupfer, DJ Keshavan, MS Frank, E Soares, JC TI Fronto-limbic brain structures in suicidal and nonsuicidal patients with unipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Div, San Antonio, TX 78284 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Verona, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. Univ Sao Paulo, Sch Med, Inst Psychiat, BR-05508 Sao Paulo, Brazil. State Univ Campinas, Sch Med Sci, Dept Med Psychol & Psychiat, Campinas, SP, Brazil. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Lacerda, Acioly/A-7052-2010; brambilla, paolo/B-4184-2010 OI Lacerda, Acioly/0000-0002-9370-0449; brambilla, paolo/0000-0002-4021-8456 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 305 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300303 ER PT J AU Walder, DJ Walker, EF Bollini, AM Kestler, LP AF Walder, DJ Walker, EF Bollini, AM Kestler, LP TI Cortisol release, memory dysfunction and depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Emory Univ, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 310 BP 87S EP 88S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300308 ER PT J AU Koenigsberg, HW Siever, LJ Gu, XD New, AS Goodman, M Prohovnik, I AF Koenigsberg, HW Siever, LJ Gu, XD New, AS Goodman, M Prohovnik, I TI An fMRI study of emotion processing in borderline personality disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Affairs Med Ctr, Mirecc, Bronx, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 APR 15 PY 2004 VL 55 SU 8 MA 317 BP 89S EP 90S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300315 ER PT J AU Soares, CN Arsenio, HC Cassano, P Cohen, LS AF Soares, CN Arsenio, HC Cassano, P Cohen, LS TI Impact of escitalopram versus norethindrone acetate and ethinyl estradiol on depression, vasomotor symptoms, and quality of life in peri and postmenopausal women: An eight-week, randomized trial. SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 330 BP 93S EP 93S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300327 ER PT J AU Sachs, GS AF Sachs, GS TI Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Bipolar Treatment Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Bipolar Mood Disorder Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 338 BP 95S EP 95S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300334 ER PT J AU Dougherty, DD Rauch, SL Deckersbach, T Marci, C Loh, R Shin, LM Alpert, NM Fischman, AJ Fava, M AF Dougherty, DD Rauch, SL Deckersbach, T Marci, C Loh, R Shin, LM Alpert, NM Fischman, AJ Fava, M TI Orbitofrontal cortex-amygdala interactions during anger induction in patients with major depression with and without anger attacks SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 363 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300353 ER PT J AU Shin, LM Pitman, RK Orr, SP Rauch, SL AF Shin, LM Pitman, RK Orr, SP Rauch, SL TI Amygdalo-frontal interactions in posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Tufts Univ, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. VAMC, Res Serv, Manchester, NH USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 361 BP 100S EP 100S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300351 ER PT J AU Caetano, SC Nicoletti, MA Hatch, JP Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Caetano, SC Nicoletti, MA Hatch, JP Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI Associations of age and length of illness with hippocampus and amygdala volumes in mood disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Verona, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI brambilla, paolo/B-4184-2010; Caetano, Sheila/H-5010-2012 OI brambilla, paolo/0000-0002-4021-8456; Caetano, Sheila/0000-0001-8403-7078 NR 0 TC 2 Z9 2 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 394 BP 109S EP 110S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300384 ER PT J AU Caetano, SC Olvera, R Hunter, K Nicoletti, MA Dalwani, M Ortiz, O Hatch, JP Bazan, C Bowden, CL Pliszka, SR Soares, JC AF Caetano, SC Olvera, R Hunter, K Nicoletti, MA Dalwani, M Ortiz, O Hatch, JP Bazan, C Bowden, CL Pliszka, SR Soares, JC TI Abnormal amygdala volumes in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Psychiat, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR 15 PY 2004 VL 55 SU 8 MA 398 BP 111S EP 111S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300388 ER PT J AU Dracheva, S Elhakem, SL Marcus, SM Siever, LJ McGurk, SR Haroutunian, V AF Dracheva, S Elhakem, SL Marcus, SM Siever, LJ McGurk, SR Haroutunian, V TI RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 419 BP 117S EP 117S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300409 ER PT J AU Levitt, JJ Ersner-Hershfield, H Kubicki, M Westin, CF Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Levitt, JJ Ersner-Hershfield, H Kubicki, M Westin, CF Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI An MR-DTI study of thalamo-cortical connections in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RI Hershfield, Hal/J-2919-2016 OI Hershfield, Hal/0000-0002-1507-7022 NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 453 BP 126S EP 126S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300442 ER PT J AU Hudziak, JJ Wilens, TE Connor, DF Haight, BR Horrigan, JP Hampton, KD Richard, NE Modell, JG AF Hudziak, JJ Wilens, TE Connor, DF Haight, BR Horrigan, JP Hampton, KD Richard, NE Modell, JG TI A controlled trial of extended-release bupropion in adult ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Vermont, Coll Med, Dept Psychiat, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. Univ Massachusetts, Mem Med Ctr, Dept Psychiat, Worcester, MA 01605 USA. GlaxoSmithKline, Psychiat, Res Triangle Pk, NC USA. GlaxoSmithKline, Biomed Data Sci, Res Triangle Pk, NC 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 485 BP 135S EP 135S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300473 ER PT J AU Sassi, RB Stanley, JA Axelson, D Brambilla, P Nicoletti, MA Keshavan, MS Ramos, RT Ryan, ND Birmaher, B Soares, JC AF Sassi, RB Stanley, JA Axelson, D Brambilla, P Nicoletti, MA Keshavan, MS Ramos, RT Ryan, ND Birmaher, B Soares, JC TI Reduced N-acetyl-aspartate levels in the dorsolateral prefrontal cortex of adolescent bipolar patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Sao Paulo, Sch Med, BR-05508 Sao Paulo, Brazil. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Verona, I-37100 Verona, Italy. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RI brambilla, paolo/B-4184-2010; Ramos, Renato/G-1566-2013 OI brambilla, paolo/0000-0002-4021-8456; NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 487 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300475 ER PT J AU Caetano, SC Olvera, R Hunter, K Najt, P Hatch, JP Bowden, CL Pliszka, SR Soares, JC AF Caetano, SC Olvera, R Hunter, K Najt, P Hatch, JP Bowden, CL Pliszka, SR Soares, JC TI Association of psychotic symptoms and suicidal plans in pediatric bipolar patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Dept Psychiat, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 494 BP 138S EP 138S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300482 ER PT J AU Brambilla, P Stanley, JA Sassi, RB Mallinger, AG Kupfer, DJ Frank, E Keshavan, MS Soares, JC AF Brambilla, P Stanley, JA Sassi, RB Mallinger, AG Kupfer, DJ Frank, E Keshavan, MS Soares, JC TI Investigation of dorso-lateral prefrontal cortex in unipolar disorder patients with H-1 magnetic resonance spectroscopy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Verona, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Texas, Dept Psychiat, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78285 USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 500 BP 139S EP 140S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300488 ER PT J AU Dougherty, DD Deckersbach, T Rauch, SL Marci, C Loh, R Alpert, NM Fischman, AJ Fava, M AF Dougherty, DD Deckersbach, T Rauch, SL Marci, C Loh, R Alpert, NM Fischman, AJ Fava, M TI Reciprocity of dorsal and ventral limbic and paralimbic brain regions during mood induction in healthy volunteers and patients with major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 499 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300487 ER PT J AU Papakostas, GI Iosifescu, DV Renshaw, PF Alpert, JE Fava, M AF Papakostas, GI Iosifescu, DV Renshaw, PF Alpert, JE Fava, M TI Brain MRI white matter hyperintensities, cardiovascular risk factors, one-carbon cycle metabolism as predictors of outcome in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 502 BP 140S EP 140S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300490 ER PT J AU Henderson, DC Daley, TB Nguyen, D Kunkel, L Louie, P Goff, DC AF Henderson, DC Daley, TB Nguyen, D Kunkel, L Louie, P Goff, DC TI Aripiprazole as an adjunct to clozapine therapy in chronic schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 530 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300517 ER PT J AU Cannistraro, PA Wright, CI Wedig, MM Martis, B Shin, LM Rauch, SL AF Cannistraro, PA Wright, CI Wedig, MM Martis, B Shin, LM Rauch, SL TI Amygdala and cortical responses to emotionally valenced human faces in obsessive-compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Charlestown, MA USA. Brigham & Womens Hosp, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Univ Illinois, Chicago, IL 60680 USA. Tufts Univ, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 555 BP 155S EP 156S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300542 ER PT J AU Kuperberg, GR Caplan, D Sitnikova, T Goff, DC Holcomb, P AF Kuperberg, GR Caplan, D Sitnikova, T Goff, DC Holcomb, P TI Making sense of sentences: Towards an understanding of language disorders in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Medford, MA 02155 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 557 BP 156S EP 156S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300544 ER PT J AU Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Arana, GW George, MS AF Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Arana, GW George, MS TI An fMRI study of healthy fathers hearing infant cries SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Clin, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. NICHHD, NIH, Poolesville, MD 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 582 BP 163S EP 163S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300569 ER PT J AU Henderson, DC Mollica, RF Tor, S Lavelle, J Hayden, D AF Henderson, DC Mollica, RF Tor, S Lavelle, J Hayden, D TI Building primary care practioners' confidence in mental health skills in a post-conflict society: A Cambodian example SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Program Refugee Trauma, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 584 BP 164S EP 164S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300571 ER PT J AU Holt, DJ Weiss, AP Ditman, T Wright, CI Rauch, SL Goff, DC Heckers, S AF Holt, DJ Weiss, AP Ditman, T Wright, CI Rauch, SL Goff, DC Heckers, S TI Decreased habituation of hippocampal activation to fearful faces in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 594 BP 166S EP 166S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300580 ER PT J AU Harte, CB Matthysse, S Holzman, PS Gusella, JF Levy, DL Jorgensen, A Moller, L Parnas, J AF Harte, CB Matthysse, S Holzman, PS Gusella, JF Levy, DL Jorgensen, A Moller, L Parnas, J TI Linkage of eye movement dysfunction to chromosome 6p in schizophrenia: Additional evidence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 McLean Hosp, Psychol Res Lab, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA USA. Univ Copenhagen, Hvidovre Hosp, Dept Psychiat, Copenhagen, Denmark. Kommune Hosp Copenhagen, Dept Psychiat, Copenhagen, Denmark. Univ Copenhagen, Danish Natl Res Fdn, Ctr Subject Res, DK-1168 Copenhagen, Denmark. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 610 BP 171S EP 171S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300596 ER PT J AU Holt, DJ Titone, D Long, LS Cather, C Judge, A Rauch, SL Goff, DC Kuperberg, GR AF Holt, DJ Titone, D Long, LS Cather, C Judge, A Rauch, SL Goff, DC Kuperberg, GR TI The evaluation of emotional salience in delusional patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. McGill Univ, Montreal, PQ H3A 2T5, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 616 BP 172S EP 173S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300602 ER PT J AU Mullen, JA Suppes, T Chengappa, KNR Sachs, GS AF Mullen, JA Suppes, T Chengappa, KNR Sachs, GS TI Quetiapine adjunctive therapy for mania associated with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 AstraZeneca, Clin Res & Dev, Wilmington, DE USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Massachusetts Gen Hosp, Harvard Bipolar Res Program, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 645 BP 180S EP 181S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300631 ER PT J AU Fraguas, R Papakostas, GI Mischoulon, D Alpert, JE Fava, M AF Fraguas, R Papakostas, GI Mischoulon, D Alpert, JE Fava, M TI Serum homocysteine, anger attacks and hostility in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Conselho Nacl Desenvolvimento Cientif & Tecnol, Programas Tematicos & Setorias Pesquisa Saude Med, Brasilia, DF, Brazil. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 652 BP 182S EP 183S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300638 ER PT J AU Bush, G Spencer, TJ Surman, C Holmes, J Seidman, LJ Valera, EM Biederman, J AF Bush, G Spencer, TJ Surman, C Holmes, J Seidman, LJ Valera, EM Biederman, J TI Functional MRI of two classes of ADHD therapy (methylphenidate and galantamine) versus placebo SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Funct Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 698 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300683 ER PT J AU Seidman, LJ Faraone, SV Biederman, J Valera, EM Rauch, SL Makris, N Schlerf, J AF Seidman, LJ Faraone, SV Biederman, J Valera, EM Rauch, SL Makris, N Schlerf, J TI Investigation of structural brain abnormalities in adult ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 15 PY 2004 VL 55 SU 8 MA 696 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300681 ER PT J AU Spencer, TJ Dougherty, DD Fischman, AJ Bonab, A Rauch, SL Madras, B AF Spencer, TJ Dougherty, DD Fischman, AJ Bonab, A Rauch, SL Madras, B TI Dopamine transporter density in patients with attention deficit hyperactivity disorder using PET SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, New England Primate Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 699 BP 195S EP 196S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300684 ER PT J AU Valera, EM Seidman, LJ Biederman, J Faraone, SV AF Valera, EM Seidman, LJ Biederman, J Faraone, SV TI Functional neuroanatomy of working memory in adults with ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 697 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300682 ER PT J AU Rauch, SL Dougherty, DD Greenberg, BD AF Rauch, SL Dougherty, DD Greenberg, BD TI Imaging effects of deep brain stimulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Butler Hosp, Providence, RI 02906 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 706 BP 197S EP 198S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300691 ER PT J AU Lorberbaum, JP Kose, S Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Bohning, DE Arana, GW George, MS AF Lorberbaum, JP Kose, S Dubno, JR Horwitz, AR Newman, JD Kose, R Hamner, MB Bohning, DE Arana, GW George, MS TI A third fMRI study of healthy mothers hearing infant cries SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. NICHHD, NIH, Bethesda, MD 20892 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 728 BP 204S EP 204S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300713 ER PT J AU Spencer, KM Perlmutter, R Klump, M Niznikiewicz, MA Nestor, PG Frumin, M Shenton, ME McCarley, RW AF Spencer, KM Perlmutter, R Klump, M Niznikiewicz, MA Nestor, PG Frumin, M Shenton, ME McCarley, RW TI Gamma-band EEG synchrony and hallucinations in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 APR 15 PY 2004 VL 55 SU 8 MA 740 BP 207S EP 207S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300723 ER PT J AU Jakary, A Davis, KA Deicken, RF AF Jakary, A Davis, KA Deicken, RF TI Bilateral N-acetylaspartate deficits in the mediodorsal and anterior thalamus in schizophrenia verified by tissue segmentation and thalamic volume mask techniques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 778 BP 218S EP 218S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300761 ER PT J AU Steinhauer, SR Siegle, GJ Condray, R Carter, KN Yanuzo, AD AF Steinhauer, SR Siegle, GJ Condray, R Carter, KN Yanuzo, AD TI Disruption of the temporal course of central inhibition in schizophrenia as reflected by the pupillomotor system SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 801 BP 225S EP 225S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300784 ER PT J AU Evins, AE Cather, C Culhane, M Freudenreich, O Rigotti, NA Goff, DC AF Evins, AE Cather, C Culhane, M Freudenreich, O Rigotti, NA Goff, DC TI Smoking cessation in schizophrenia: A double blind placebo controlled trial of bupropion SR added to cognitive behavioral therapy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 806 BP 226S EP 226S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300789 ER PT J AU Kasai, K Gilbertson, MW Shenton, ME Yamasue, H Lasko, NB Orr, SP Pitman, RK AF Kasai, K Gilbertson, MW Shenton, ME Yamasue, H Lasko, NB Orr, SP Pitman, RK TI Determining structural brain abnormalities predicting vulnerability to psychological trauma SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Tokyo, Dept Neuropsychiat, Tokyo, Japan. Harvard Univ, Sch Med, Neurosci Lab,Dept Psychiat, Clin Neurosci Div,VA Boston Healthcare Syst, Brockton, MA 02401 USA. VA Med Ctr, Res Serv, Manchester, NH USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Surg Planning Lab,Dept Radiol, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 813 BP 228S EP 228S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300796 ER PT J AU Truesdell, KC Glahn, DC Kaur, S Monkul, ES Sanches, M Najt, P Villarreal, V Bowden, CL Soares, JC AF Truesdell, KC Glahn, DC Kaur, S Monkul, ES Sanches, M Najt, P Villarreal, V Bowden, CL Soares, JC TI Attention deficits in bipolar disorder: A comparison of performance on the continuous performance task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 823 BP 231S EP 231S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300806 ER PT J AU Moran, EK Satlin, A Becker, JA Johnson, KA AF Moran, EK Satlin, A Becker, JA Johnson, KA TI Psychotic symptoms in Alzheimer's disease associated with gender-specific abnormal cerebral perfusion SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut Corp, Psychiat, E Hanover, NJ USA. Brigham & Womens Hosp, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 828 BP 232S EP 232S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300811 ER PT J AU Kaur, S Brambilla, P Sassi, RB Nicoletti, MA Caetano, SC Hatch, JP Keshavan, MS Mallinger, AG Kupfer, DJ Frank, E Soares, JC AF Kaur, S Brambilla, P Sassi, RB Nicoletti, MA Caetano, SC Hatch, JP Keshavan, MS Mallinger, AG Kupfer, DJ Frank, E Soares, JC TI Smaller Cingulate gray matter volumes in unipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Psychiat, San Antonio, TX USA. Univ Verona, Dept Med & Publ Hlth, Sect Psychiat, I-37100 Verona, Italy. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI brambilla, paolo/B-4184-2010; Caetano, Sheila/H-5010-2012 OI brambilla, paolo/0000-0002-4021-8456; Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 832 BP 233S EP 234S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300815 ER PT J AU Henderson, DC Daley, TB Louie, P Nguyen, D Copeland, P Hayden, D Borba, C Goff, DC AF Henderson, DC Daley, TB Louie, P Nguyen, D Copeland, P Hayden, D Borba, C Goff, DC TI A placebo-controlled trial of sibutramine added to patients with olanzapine-induced weight gain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2004 VL 55 SU 8 MA 853 BP 239S EP 239S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EN UT WOS:000220755300835 ER PT J AU Mu, QW Bohning, DE Nahas, Z Walker, J Anderson, B Johnson, KA Denslow, S Lomarev, M Moghadam, P Chae, JH George, MS AF Mu, QW Bohning, DE Nahas, Z Walker, J Anderson, B Johnson, KA Denslow, S Lomarev, M Moghadam, P Chae, JH George, MS TI Acute vagus nerve stimulation using different pulse widths produces varying brain effects SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Convention of the Society-of-Biological-Psychiatry CY MAY 17, 2003 CL San Francisco, CA SP Soc Biolog Psychiatry DE vagus nerve stimulation; pulse width; depression; functional magnetic resonance imaging ID BLOOD-FLOW; ELECTRICAL-STIMULATION; REFRACTORY EPILEPSY; VAGAL-STIMULATION; RESISTANT DEPRESSION; PARTIAL SEIZURES; CELL-BODIES; FMRI; THERAPY; VNS AB Background: Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and has been investigated in clinical trials of depression. Little is known about the relationship of VNS parameters to brain function. Using the interleaved VATS functional magnetic. resonance imaging (fMPI) technique, we tested whether variations of VNS pulse width (PW) would produce different immediate brain activation in a manner consistent with single neuron PWstudies. Methods: Twelve adult patients with major depression, treated with VNS. underwent three consecutive VNS/fMRI scans, each randomly using one of three PWs (130 mus, 250 mus, or 500 mus). The data were analyzed with SPM2. Results: Global activations induced by PWs 250 and 500 were both significantly greater than that induced by PW 130 but not significantly different from each other. For global deactivation, PWs 130 and 250 were both signifcantly greater than PW 500 but not significantly different from each other. Regional similarities and differences were also seen with the various PWs. Conclusions: The data confirm our hypothesis that VNS at PW500 globally produces no more activation than does PW 250. and PW 130 is insufficient for activation of some regions. These data suggest that PW is an important variable in producing VNS brain effects. C1 Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, Ctr Adv Imaging, Charleston, SC 29425 USA. Med Univ S Carolina, Inst Psychiat, Dept Radiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Mu, QW (reprint author), Med Univ S Carolina, Inst Psychiat, Brain Stimulat Lab, Ctr Adv Imaging, 502 N,67 President St, Charleston, SC 29425 USA. FU NIA NIH HHS [R01 AG 40956] NR 51 TC 42 Z9 43 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 APR 15 PY 2004 VL 55 IS 8 BP 816 EP 825 DI 10.1016/j.biopsych.2003.12.004 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 811EL UT WOS:000220755100007 PM 15050863 ER PT J AU Bono, P Krause, A von Mehren, M Heinrich, MC Blanke, CD Dimitrijevic, S Demetri, GD Joensuu, H AF Bono, P Krause, A von Mehren, M Heinrich, MC Blanke, CD Dimitrijevic, S Demetri, GD Joensuu, H TI Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib SO BLOOD LA English DT Article ID STEM-CELL FACTOR; ENDOTHELIAL GROWTH-FACTOR; C-KIT; TYROSINE KINASE; SOLUBLE KIT; MYELOID-LEUKEMIA; CANCER-PATIENTS; MESYLATE; RECEPTOR; EXPRESSION AB Imatinib mesylate is a selective inhibitor of a few tyrosine kinases including KIT, and it is the first effective treatment for gastrointestinal stromal tumors (GISTs). We monitored the serum levels of KIT, KIT ligand (stem cell factor, SCIF), and the vascular endothelial growth factor (VEGF) in patients with advanced GISTs treated with imatinib in a prospective randomized trial. Patients with GISTs (n = 66) had elevated pretreatment serum KIT and VEGF levels as compared with controls (median, 292 AU/mL [409 ng/mL] vs 238 AU/mL [333 ng/mL], P = .037; and median, 303 pg/mL vs 190 pg/mL, P = .013, respectively), but lower levels of SCIF (median, 645 pg/mL vs 950 pg/mL; P less than or equal to .0001). After 1 and 6 months of imatinib treatment the average serum KIT levels decreased 31% and 52% from pretreatment levels, whereas SCIF levels increased 11% and 33%, respectively. Serum VEGF levels decreased during treatment in responding patients. The median serum SCF/KIT ratio increased with treatment duration, and was 7.7-fold higher after 12 months of treatment than at baseline (range, 3.1-259-fold). A high serum SCF/KIT ratio may increase SCF-induced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors. (C) 2004 by The American Society of Hematology. C1 Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00029 Helsinki, Finland. Novartis Oncol, Basel, Switzerland. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Boston, MA 02115 USA. RP Joensuu, H (reprint author), Univ Helsinki, Cent Hosp, Dept Oncol, POB 180, FIN-00029 Helsinki, Finland. EM heikki.joensuu@hus.fi NR 42 TC 44 Z9 45 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 APR 15 PY 2004 VL 103 IS 8 BP 2929 EP 2935 DI 10.1182/blood-2003-10-3443 PG 7 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500020 PM 15070666 ER PT J AU Kolesnikova, TV Stipp, CS Rao, RM Lane, WS Luscinskas, FW Hemler, ME AF Kolesnikova, TV Stipp, CS Rao, RM Lane, WS Luscinskas, FW Hemler, ME TI EWI-2 modulates lymphocyte integrin alpha 4 beta 1 functions SO BLOOD LA English DT Article ID ALPHA(4) INTEGRINS; LIGAND-BINDING; CELL-SURFACE; MAJOR CD9; PROTEINS; CD81; IDENTIFICATION; COMPLEXES; VLA-4; CD63 AB The most prominent cell-surface integrin alpha4beta1 partner, a 70-kDa protein, was isolated from MOLT-4 T leukemia cells, using anti-alpha4beta1 integrin antibody-coated beads. By mass spectrometry, this protein was identified as EWI-2, a previously described cell-surface partner for tetraspanin proteins CD9 and CD81. Wildtype EWI-2 overexpression had no effect on MOLT-4 cell tethering and adhesion strengthening on the alpha4beta1 ligand, vascular cell adhesion molecule-1 (VCAM-1), in shear flow assays. However, EWI-2 markedly impaired spreading and ruffling on VCAM-1. In contrast, a mutant EWI-2 molecule, with a different cytoplasmic tall, neither impaired cell spreading nor associated with alpha4beta1 and CD81. The endogenous wild-type EWI-2-CD81-alpha4beta1 complex was fully soluble, and highly specific as seen by the absence of other MOLT-4 cell-surface proteins. Also, it was relatively small in size (0.5 x 10(6) Da to 4 x 10(6) Da), as estimated by size exclusion chromatography. Overexpression of EWI-2 in MOLT-4 cells caused reorganization of cell-surface CD81, increased the extent of CD81-CD81, CD81-alpha4beta1, and alpha4beta1-alpha4beta1 associations, and increased the apparent size of CD81-alpha4beta1 complexes. We suggest that EWI-2-dependent reorganization of alpha4beta1-CD81 complexes on the cell surface is responsible for EWI-2 effects on integrin-dependent morphology and motility functions. (C) 2004 by The American Society of Hematology. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Microchem Facil, Cambridge, MA 02138 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430, Boston, MA 02115 USA. EM martin_hemler@dfci.harvard.edu FU NIGMS NIH HHS [GM38903] NR 33 TC 36 Z9 38 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 APR 15 PY 2004 VL 103 IS 8 BP 3013 EP 3019 DI 10.1182/blood-2003-07-2201 PG 7 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500032 PM 15070678 ER PT J AU Chauhan, D Li, G Podar, K Hideshima, T Shringarpure, R Catley, L Mitsiades, C Munshi, N Tai, YT Suh, N Gribble, GW Honda, T Schlossman, R Richardson, P Sporn, MB Anderson, KC AF Chauhan, D Li, G Podar, K Hideshima, T Shringarpure, R Catley, L Mitsiades, C Munshi, N Tai, YT Suh, N Gribble, GW Honda, T Schlossman, R Richardson, P Sporn, MB Anderson, KC TI The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance SO BLOOD LA English DT Article ID NF-KAPPA-B; 2-CYANO-3,12-DIOXOOLEANA-1,9-DIEN-28-OIC ACID CDDO; HUMAN LEUKEMIA-CELLS; CYTOCHROME-C; DRUG-RESISTANCE; THERAPEUTIC IMPLICATIONS; MITOCHONDRIAL PROTEIN; MULTIDRUG-RESISTANCE; REFRACTORY MYELOMA; LYMPHOMA-CELLS AB The synthetic triterpenoid 2-cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid (CDDO) induces apoptosis in leukemic cells. Here we show that CDDO and its new derivative CDDO-imidazolide (CDDO-Im) trigger apoptosis in multiple myeloma (MM) cells resistant to conventional therapies including melphalan (LR-5), doxorubicin (Dox-40), and dexamethasone (MMAR, U266, RPMI 8226) without affecting the viability of normal cells. CDDO-IM also triggers apoptosis in bone marrow stromal cells (BMSCs) and decreases interieukin-6 (IL-6) secretion induced by MM cell adhesion to BMSCs. Moreover, CDDO-im-induced apoptosis in MM cells is not blocked by IL-6 or insulin growth factor-1 (IGF-1). Importantly, CDDO-Im and bortezomib/proteasome inhibitor PS-341 trigger synergistic apoptosis in MM cells associated with loss of mitochondrial membrane potential, superoxide generation, release of mitochondrial proteins cytochrome c/second mitochondria-derived activator of caspases (cyctochrome c/Smac), and activation of caspase-8, -9, and -3. Conversely, the pancaspase inhibitor Z-VAD-fmk abrogates the CDDO-Im + bortezomib-induced apoptosis. Low doses of CDDO-Im and bortezomib overcome the proteins Bcl2 and heat shock protein-27 (Hsp27) as well as nuclear factor-kappa B (NF-kappaB)-mediated growth/survival and drug resistance. Finally, combining CDDO-Im and bortezomib induces apoptosis even in bortezomib-resistant MM patient cells. Together, these findings provide the framework for clinical evaluation of CDDO-Im, either alone or in combination with bortezomib, to overcome drug resistance and improve patient outcome in MM. cytoprotective effects of antiapoptotic. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Pharmacol, Hanover, NH USA. RP Anderson, KC (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU NCI NIH HHS [CA 78373, CA 78814, P01 CA078378-06, P50 CA100707-01]; PHS HHS [50947] NR 54 TC 82 Z9 85 U1 1 U2 4 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 APR 15 PY 2004 VL 103 IS 8 BP 3158 EP 3166 DI 10.1182/blood-2003-08-2873 PG 9 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500052 PM 15070698 ER PT J AU Matsunaga, T Inaba, T Matsui, H Okuya, M Miyajima, A Inukai, T Funabiki, T Endo, M Look, AT Kurosawa, H AF Matsunaga, T Inaba, T Matsui, H Okuya, M Miyajima, A Inukai, T Funabiki, T Endo, M Look, AT Kurosawa, H TI Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; B-LINEAGE LEUKEMIA; TRANSCRIPTION FACTOR; DNA-BINDING; ANTIAPOPTOTIC ACTIVITY; PLASMIN GENERATION; DOWNSTREAM TARGET; FUSION PROTEINS; CELL-SURFACE AB In pro-B cell acute lymphoblastic leukemia (ALL), expression of the E2A-HLF fusion gene as a result of t(17;19)(q22; p13) is associated with poor prognosis, hypercalcemia, and hemorrhagic complications. We previously reported that the E2A-HLF fusion protein protects interleukin-3 (1L-3)-dependent lymphoid cells from apoptosis caused by cytokine starvation. Here, we report that annexin II, a surface phospholipid-binding protein and one of the proposed causes of the hemorrhagic complications of acute promyelocytic leukemia (APL), is also implicated in t(17;19)(+) ALL. Annexin 11 was expressed at high levels in APL cells and in each of 4 t(17;19)(+) leukemia cell lines, and annexin II expression was induced by enforced expression of E2A-HLF in leukemia cells. In IL-3-dependent cells, we found that annexin II expression was regulated by IL-3 mainly by Ras pathways, including Ras/phosphatidylinositol 3-kinase pathways. Moreover, E2A-HLF increased annexin II expression in IL-3-dependent cells in the absence of the cytokine. These findings indicate that E2A-HLF induces annexin II by substituting for cytokines that activate downstream pathways of Ras. (C) 2004 by The American Society of Hematology. C1 Dokkyo Univ, Sch Med, Dept Pediat, Div Hematol, Mibu, Tochigi 3210293, Japan. Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Mol Oncol, Hiroshima 730, Japan. Univ Tokyo, Dept Mol Oncol, Tokyo, Japan. Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan. Univ Yamanashi, Sch Med, Dept Pediat, Yamanashi, Japan. Iwate Med Univ, Dept Pediat, Morioka, Iwate, Japan. Yokohama City Univ, Dept Pediat, Yokohama, Kanagawa 232, Japan. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kurosawa, H (reprint author), Dokkyo Univ, Sch Med, Dept Pediat, Div Hematol, Mibu, Tochigi 3210293, Japan. EM hidekuro@dokkyomed.ac.jp NR 39 TC 16 Z9 22 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 APR 15 PY 2004 VL 103 IS 8 BP 3185 EP 3191 DI 10.1182/blood-2003-09-3022 PG 7 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500055 PM 15070701 ER PT J AU Peters, LL Swearingen, RA Andersen, SG Gwynn, B Lambert, AJ Li, RH Lux, SE Churchill, GA AF Peters, LL Swearingen, RA Andersen, SG Gwynn, B Lambert, AJ Li, RH Lux, SE Churchill, GA TI Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency SO BLOOD LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FL SP Amer Soc Hematol ID BLOOD-CELL MEMBRANE; ERYTHROCYTE-MEMBRANE; BETA-SPECTRIN; PROTEIN 4.1; ANKYRIN DEFICIENCY; BINDING INTERFACE; HEMOLYTIC-ANEMIA; ANION-EXCHANGER; FUNCTIONAL-ROLE; GLYCOPHORIN-C AB Defects in red blood cell (RBC) membrane skeleton components cause hereditary spherocytosis (HS). Clinically, HS varies significantly even among individuals with identical gene defects, illustrating the profound effects of genetic background on disease severity. We exploited a new spontaneous mouse model, wan, which arose on the inbred C3H/HeJ strain, to identify quantitative trait loci (QTL) that modify the HS phenotype. Homozygous wan mice have severe HS due to a complete deficiency of erythroid band 3. A QTL analysis of RBC count, hemoglobin, hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin content (MCHC) was performed in wan/wan mice from an F2 intercross between C3H/HeJ(+/wan) and CAST/Ei(+/+) F1 hybrids. Hematologic and survival data from C3H, CAST/Ei F2 wan homozygotes support the hypothesis that genetic modifiers significantly influence the band-3 null HS phenotype. Significant QTL were identified for the MCV trait only, suggesting that RBC membrane characteristics are a target for modifier gene action. The most significant quantitative trait locus, Hsm1 ((h) under bar ereditary (s) under bar pherocytosis (m) under bar odifier 1), localizes to mouse Chromosome 12 and is dominant. The peak LOD score was obtained with a marker for Spnb1 encoding erythroid beta-spectrin, an obvious candidate gene. (C) 2004 by The American Society of Hematology. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peters, LL (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM luanne@jax.org FU NCI NIH HHS [CA34196]; NCRR NIH HHS [RR01183]; NHLBI NIH HHS [HL32262, HL64885, R01 HL064885]; NIDDK NIH HHS [DK34083] NR 52 TC 20 Z9 21 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 APR 15 PY 2004 VL 103 IS 8 BP 3233 EP 3240 DI 10.1182/blood-2003-08-2813 PG 8 WC Hematology SC Hematology GA 830ZU UT WOS:000222163500063 PM 15070709 ER PT J AU Lao, CD Simmons, M Syngal, S Bresalier, RS Fortlage, L Normolle, D Griffith, KA Appelman, HD Brenner, DE AF Lao, CD Simmons, M Syngal, S Bresalier, RS Fortlage, L Normolle, D Griffith, KA Appelman, HD Brenner, DE TI Dysplasia in Barrett esophagus - Implications for chemoprevention SO CANCER LA English DT Article DE dysplasia; Barrett esophagus; chemoprevention; esophageal adenocarcinoma ID HIGH-GRADE DYSPLASIA; ESOPHAGOGASTRIC JUNCTION; ENDOSCOPIC SURVEILLANCE; ADENOCARCINOMA; PROGRESSION; CANCER; DIAGNOSIS; METAPLASIA; RISK; ESOPHAGECTOMY AB BACKGROUND. Dysplasia in Barrett esophagus is a premalignant condition that is associated with an increased risk of developing esophageal adenocarcinoma. Unfortunately, clinical investigation aimed at prevention of progression to malignant disease has been hampered by the variable prevalence of dysplasia reported in the literature. The objective of the current study was to more accurately determine the prevalence of dysplasia among individuals with Barrett esophagus who would be available for enrollment in a chemoprevention trial. METHODS. The pathology archives of 3 institutions were reviewed over a 5-year period for all reports of diagnoses of Barrett esophagus. Surgical cases, malignancies, and duplicate or referral cases were excluded from the analysis. RESULTS. A total of 790 cases of Barrett esophagus were identified. Of these, 37 (4.7%) were cases of low-grade dysplasia (LGD), and 20 (2.5%) were cases of 2 high-grade dysplasia. The University of Michigan Medical Center (Ann Arbor, MI) diagnosed 18 cases of LGD, Henry Ford Hospital (Detroit, MI) diagnosed 15 cases 3 of LGD, and Brigham and Women's Hospital (Boston, MA) diagnosed 4 cases of LGD in patients with Barrett. esophagus over the 5-year study period. CONCLUSIONS. The confirmed low prevalence of cases of LGD will affect the design of future clinical trials of chemopreventive interventions for Barrett esophagus. (C) 2004 American Cancer Society. C1 Univ Michigan, Med Ctr, Ctr Canc 2150, Dept Internal Med, Ann Arbor, MI 48109 USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Henry Ford Med Ctr, Div Gastroenterol, Detroit, MI USA. Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP Brenner, DE (reprint author), Univ Michigan, Med Ctr, Ctr Canc 2150, Dept Internal Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM dbrenner@umich.edu OI Normolle, Daniel/0000-0001-8675-5014 FU NCI NIH HHS [CN-65000]; NCRR NIH HHS [MO1-RR000042] NR 34 TC 14 Z9 14 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 APR 15 PY 2004 VL 100 IS 8 BP 1622 EP 1627 DI 10.1002/cncr.20149 PG 6 WC Oncology SC Oncology GA 810TA UT WOS:000220725400009 PM 15073848 ER PT J AU Freedland, SJ Aronson, WJ Presti, JC Amling, CL Terris, MK Trock, B Kane, CJ AF Freedland, SJ Aronson, WJ Presti, JC Amling, CL Terris, MK Trock, B Kane, CJ TI Predictors of prostate-specific antigen progression among men with seminal vesicle invasion at the time of radical prostatectomy SO CANCER LA English DT Article DE prostate carcinoma; radical prostatectomy; prostate-specific antigen recurrence; seminal vesicle invasion; Gleason score ID SEXTANT BIOPSIES; PROGNOSTIC-SIGNIFICANCE; CANCER; RECURRENCE; INVOLVEMENT; ADENOCARCINOMA; RADIOTHERAPY; FAILURE; RACE; RISK AB BACKGROUND. Seminal vesicle (SV) invasion at the time of radical prostatectomy (RP) generally is considered to be indicative of poor outcome. The authors examined whether there was a subset of men with SV invasion who had long-term prostate-specific antigen (PSA) progression-free survival. METHODS. Data were examined from 1687 men who underwent RP between 1988 and 2002 at 5 equal-access medical centers. Patients were grouped based on the presence or absence of SV invasion at the time of RP. Clinical and pathologic variables as well as biochemical outcome data were compared across the groups using rank-sum, chi-square, and log-rank tests. Multivariate Cox proportional hazards analysis was used to determine the significant predictors of time to PSA failure among men with SV invasion. RESULTS. Men with SV invasion had significantly higher PSA values, higher clinical stage, higher grade tumors, and were more likely to have concomitant extracapsular extension or a positive surgical margin. The 5-year PSA progression-free rates for men who had SV invasion was 36%, compared with 70% among men who had no SV invasion. Among men who had SV invasion, using multivariate analysis, only age (P = 0.023), pathologic Gleason score (P = 0.041), and surgical margin status (P = 0.019) were found to be independent predictors of PSA failure. By combining significant prognostic variables, the authors identified a subset of men with SV invasion, low-grade tumors (Gleason score 2-6), and negative surgical margins who had a 5-year PSA progression-free rate of 69%. Men with SV invasion, Gleason scores 2-6 tumors, negative surgical margins, and age greater than or equal to 60 years (n = 11; 8%) had a 5-year PSA progression-free rate of 100%. CONCLUSIONS. Although the majority of men with SV invasion have high-grade disease and a short time to biochemical failure, the authors identified a subset of men with low-grade disease, negative surgical margins, and older age who, despite SV invasion, had an extremely favorable clinical course. Thus, SV invasion does not uniformly suggest an unfavorable prognosis. (C) 2004 American Cancer Society. C1 Johns Hopkins Sch Med, Dept Urol, Baltimore, MD 21287 USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90024 USA. Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. San Francisco Vet Adm Med Ctr, Dept Surg, Urol Sect, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. RP Freedland, SJ (reprint author), Johns Hopkins Sch Med, Dept Urol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM sfreedl1@jhmi.edu OI Terris, Martha/0000-0002-3843-7270 NR 21 TC 22 Z9 22 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 APR 15 PY 2004 VL 100 IS 8 BP 1633 EP 1638 DI 10.1002/cncr.20122 PG 6 WC Oncology SC Oncology GA 810TA UT WOS:000220725400011 PM 15073850 ER PT J AU Dreicer, R Manola, J Roth, BJ See, WA Kuross, S Edelman, MJ Hudes, GR Wilding, G AF Dreicer, R Manola, J Roth, BJ See, WA Kuross, S Edelman, MJ Hudes, GR Wilding, G TI Phase III trial of methotrexate, vinblastine, doxorubicin, and cisplatin versus carboplatin and paclitaxel in patients with advanced carcinoma of the urothelium - A trial of the eastern cooperative oncology group SO CANCER LA English DT Article DE methotrexate; vinblastine; doxorubicin; and cisplatin (M-VAC) regimen; carboplatin and paclitaxel (CP) regimen; urothelial carcinoma; survival; quality of life ID TRANSITIONAL-CELL-CARCINOMA; METASTATIC BLADDER-CANCER; COMBINATION; SURVIVAL; REGIMEN AB BACKGROUND. The regimens of carboplatin plus paclitaxel (CP) and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) were compared in patients with advanced urothelial carcinoma. METHODS. Patients with metastatic urothelial carcinoma were randomized to receive either CP (paclitaxel at a dose of 225 mg/m(2) and carboplatin [targeted area under the concentration-time curve (AUC) of 6] given every 21 days) or the standard M-VAC dosage. RESULTS. Eighty-five patients were randomized to the respective treatment regimens (41 to CP and 44 to M-VAC). Response rates and overall survival were similar for both treatment arms. Patients treated with CP had an overall response rate of 28.2% (95% binomial confidence interval, 15.0-44.9%) compared with an overall response rate of 35.9% for the M-VAC arm (95% binomial confidence interval, 21.2-52.8%) (P = 0.63, Fisher exact test). The median progression-free survival among patients who were treated with M-VAC was 8.7 months and was 5.2 months for patients receiving CP (P = 0.24, log-rank test). At a median follow-up of 32.5 months, the median survival for patients treated with M-VAC was 15.4 months versus 13.8 months for patients treated with CP (P = 0.65, log-rank test). Patients treated with M-VAC were found to have more severe worst-degree toxicities compared with patients treated with CP (P = 0.0001). There were no significant differences with regard to duality of life as assessed by the Functional Assessment of Cancer Therapy-Bladder (FACT-BL) instrument (P = 0.33). CONCLUSIONS. interpretation of the results of this study must be made with caution because the study failed to reach its accrual goal. Patients treated with CP had a median survival of 13.8 months compared with 15.4 months for patients treated with M-VAC. Patients treated with CP appeared in general to better tolerate their treatment; however, there were no significant differences noted with regard to measured quality of life parameters. (C) 2004 American Cancer Society. C1 Cleveland Clin Fdn, Dept Hematol Oncol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Inst Urol, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA. Med Coll Wisconsin, Dept Urol, Milwaukee, WI 53226 USA. Duluth Clin, Duluth, MN USA. Univ Maryland, Ctr Canc, Div Hematol Oncol, Baltimore, MD 21201 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Wisconsin, Ctr Clin Canc, Madison, WI 53706 USA. RP Dreicer, R (reprint author), Cleveland Clin Fdn, Dept Hematol Oncol, R35,9500 Euclid Ave, Cleveland, OH 44195 USA. EM dreicer@cc.ccf.org FU NCI NIH HHS [CA13650, CA21076, CA21115, CA23318, CA27525, CA31946-17, CA49957, CA66636] NR 17 TC 101 Z9 103 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2004 VL 100 IS 8 BP 1639 EP 1645 DI 10.1002/cncr.20123 PG 7 WC Oncology SC Oncology GA 810TA UT WOS:000220725400012 PM 15073851 ER PT J AU Agarwala, SS Neuberg, D Park, Y Kirkwood, JM AF Agarwala, SS Neuberg, D Park, Y Kirkwood, JM TI Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673) - A trial of the eastern cooperative oncology group SO CANCER LA English DT Article DE melanoma; adjuvant therapy; Phase III clinical trials; bacillus Calmette-Guerin (BCG) ID MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; IMMUNOTHERAPY; CHEMOTHERAPY; SKIN AB BACKGROUND. The local and systemic effects of bacillus Calmette-Guerin (BCG) have been known for decades. To investigate the adjuvant effect of BCG on resected American Joint Committee on Cancer (AJCC) Stage I-III melanoma, the Eastern Cooperative Oncology Group conducted a large trial to study the use of BCG alone or a combination of BCG and dacarbazine between 1974 and 1978. METHODS. A total of 734 patients were randomized to 4 clinical groups consolidated into 2 cohorts. Cohort I compared BCG with observation and Cohort 11 compared BCG with a combination of BCG and dacarbazine. The primary end points were survival time and time to disease progression. RESULTS. Within Cohort 1, no statistically significant difference in disease-free survival (DFS) (P = 0.84) or overall survival (OS) (5-year survival 67% vs. 62%; P 0.40) was observed between BCG treatment and observation. Within Cohort 11 the addition of dacarbazine to BCG did not improve DFS (P = 0.74) or OS (P = 0.81) compared with BCG alone. Toxicity was mild to moderate in both cohorts. Although toxicity with this agent is mild, the use of BCG is associated with the development of punctate abscesses in greater than two-thirds of patients treated. CONCLUSIONS. in what to our knowledge is the largest ever trial to test the role of BCG as adjuvant therapy for melanoma, no benefit for BCG was observed for patients with AJCC Stage I-III disease. The mature results of the current trial projected to 30 years confirmed the negative results of previous smaller studies utilizing this agent. (C) 2004 American Cancer Society. C1 Univ Pittsburgh, Med Ctr, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15232 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Agarwala, SS (reprint author), Univ Pittsburgh, Med Ctr, Dept Med, Div Hematol Oncol, 5150 Ctr Ave,5th Floor, Pittsburgh, PA 15232 USA. EM agarwalass@msx.upmc.edu FU NCI NIH HHS [CA21115, CA66636, CA23318, CA39229] NR 16 TC 37 Z9 39 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 APR 15 PY 2004 VL 100 IS 8 BP 1692 EP 1698 DI 10.1002/cncr.20166 PG 7 WC Oncology SC Oncology GA 810TA UT WOS:000220725400019 PM 15073858 ER PT J AU Tai, YT Catley, LP Mitsiades, CS Burger, R Podar, K Shringpaure, R Hideshima, T Chauhan, D Hamasaki, M Ishitsuka, K Richardson, P Treon, SP Munshi, NC Anderson, KC AF Tai, YT Catley, LP Mitsiades, CS Burger, R Podar, K Shringpaure, R Hideshima, T Chauhan, D Hamasaki, M Ishitsuka, K Richardson, P Treon, SP Munshi, NC Anderson, KC TI Mechanisms by which SGN-40, a humanized anti-CD40 antibody, induces cytotoxicity in human multiple myeloma cells: Clinical implications SO CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCLONAL-ANTIBODIES; THERAPEUTIC APPLICATIONS; INTERLEUKIN-6 RECEPTOR; CD40 STIMULATION; IN-VITRO; ACTIVATION; LIGAND; APOPTOSIS; EXPRESSION AB CD40 is expressed on B-cell malignancies, including human multiple myeloma (MM) and a variety of carcinomas. We examined the potential therapeutic utility of SGN-40, the humanized anti-CD40 monoclonal antibody, for treating human MM using MM cell lines and patient MM cells (CD138(++), CD40(+)). SGN-40 (0.01-100 mug/ml) induces modest cytotoxicity in MM cell lines and patient MM cells. In the presence of de novo protein synthesis inhibitor cycloheximide, SGN-40 significantly induced apoptosis in Dexamethasone (Dex)-sensitive MM.1S and Dex-resistant MM.1R cells and in patient MM cells. SGN-40-mediated cytotoxicity is associated with up-regulation of cytotoxic ligands of the tumor necrosis factor family (Fas/FasL, tumor necrosis factor-related apoptosis-inducing ligand, and tumor necrosis factor a). SGN-40 treatment also induces a down-regulation of CD40 dependent on an endocytic pathway. Consequently, pretreatment of MM cells with SGN-40 blocked sCD40L-mediated phosphatidylinositol 3'-kinase/AKT and nuclear factor kappaB activation. Importantly, pretreatment of MM.1S and MM.1R cells with SGN-40 inhibited proliferation triggered by interleukin 6 (IL-6) but not by insulin-like growth factor-I. In addition, SGN-40 pretreatment of MM.1S cells blocked the ability of IL-6 to protect against Dex-induced inhibition of DNA synthesis. This was associated with a 2-4-fold reduction of IL-6 receptor at protein and mRNA levels in SGN-40-treated MM.1S cells and patient MM cells. Taken together, these results provide the preclinical rationale for the evaluation of SGN-40 as a potential new therapy to improve patient outcome in MM. C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, M557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU PHS HHS [R01-50947, P01-78378] NR 44 TC 92 Z9 96 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2004 VL 64 IS 8 BP 2846 EP 2852 DI 10.1158/0008-5472.CAN-03-3630 PG 7 WC Oncology SC Oncology GA 811ZS UT WOS:000220810400032 PM 15087402 ER PT J AU Zippelius, A Batard, P Rubio-Godoy, V Bioley, G Lienard, D Lejeune, F Rimoldi, D Guillaume, P Meidenbauer, N Mackensen, A Rufer, N Lubenow, N Speiser, D Cerottini, JC Romero, P Pittet, MJ AF Zippelius, A Batard, P Rubio-Godoy, V Bioley, G Lienard, D Lejeune, F Rimoldi, D Guillaume, P Meidenbauer, N Mackensen, A Rufer, N Lubenow, N Speiser, D Cerottini, JC Romero, P Pittet, MJ TI Effector function of human tumor-specific CD8 T cells in melanoma lesions: A state of local functional tolerance SO CANCER RESEARCH LA English DT Article ID INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; IMMUNE-RESPONSE; REACTIVE CTL; ANTIGEN; PEPTIDE; DIFFERENTIATION; SELF; POPULATION; GENERATION AB Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result in tumor eradication. We aimed at studying directly the functional efficacy of tumor-specific CD8 T cells at the site of immune attack. Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1. Comparative analysis was conducted with peripheral blood T cells. We provide evidence that in vivo-priming selects, within the available naive Melan-A/MART-1-specific CD8 T-cell repertoire, cells with high T-cell receptor avidity that can efficiently kill melanoma cells in vitro. In vivo, primed Melan-A/MART-1-specific CD8 T cells accumulate at high frequency in both lymphoid and nonlymphoid tumor lesions. Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant. We show that both the lymph node and the tumor environments blunt T-cell effector functions and offer a rationale for the failure of tumor-specific responses to effectively counter tumor progression. C1 CHU Vaudois, Div Clin Onco Immunol, Ludwig Inst Canc Res, CH-1011 Lausanne, Switzerland. CHU Vaudois, Multidisciplinary Oncol Ctr, CH-1011 Lausanne, Switzerland. Univ Lausanne, Lausanne Branch, Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland. Univ Regensburg, Dept Hematol Oncol, D-8400 Regensburg, Germany. Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. Natl Ctr Competence Res, Program Mol Oncol, Epalinges, Switzerland. Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany. RP Pittet, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5029, Charlestown, MA 02129 USA. EM mpittet@hms.harvard.edu NR 43 TC 249 Z9 251 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2004 VL 64 IS 8 BP 2865 EP 2873 DI 10.1158/0008-5472.CAN-03-3066 PG 9 WC Oncology SC Oncology GA 811ZS UT WOS:000220810400035 PM 15087405 ER PT J AU Nouriani, M Bahador, A Berek, JS Cheng, JP Chi, DS Cliby, WA Del Priore, G Dodson, MK Duggan, BD Gershenson, DM Lentz, SE Penson, RT Robinson, WR Rodriguez, M Roman, LD Yu, MC Zempolich, K Dubeau, L AF Nouriani, M Bahador, A Berek, JS Cheng, JP Chi, DS Cliby, WA Del Priore, G Dodson, MK Duggan, BD Gershenson, DM Lentz, SE Penson, RT Robinson, WR Rodriguez, M Roman, LD Yu, MC Zempolich, K Dubeau, L TI Detection of residual subclinical ovarian carcinoma after completion of adjuvant chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID NEGATIVE 2ND-LOOK LAPAROTOMY; SECONDARY CYTOREDUCTIVE SURGERY; CANCER PATIENTS; STAGE-III; COMPUTED-TOMOGRAPHY; TELOMERASE ACTIVITY; HUMAN FIBROBLASTS; SURVIVAL; DISEASE; RECURRENCE AB Purpose: We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma. Experimental Design: Peritoneal washings were obtained from 100 consecutive patients undergoing a secondlook procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls). The washings were assayed for telomerase activity using the telomerase repeat amplification protocol. The results were compared to the histological and cytological findings. Results: Among our 100 cases, 82 (82%) had either positive second-look procedures or expressed telomerase in their peritoneal washings. Fifty-three (53%) had positive second-look procedures, whereas 66 (66%) tested positive for telomerase. Twenty-nine of the 47 patients (62%) with negative second-look procedures tested positive for telomerase. Of the 53 patients with positive second-look procedures, 37 (70%) tested positive for telomerase. None of the 100 controls (0%) expressed telomerase in their peritoneal washings. Conclusions: Telomerase activity in peritoneal washings of patients treated for ovarian carcinoma and undergoing a second-look procedure may provide a means of increasing the sensitivity of such procedures for the detection of residual disease while maintaining a high level of specificity. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Div Gynecol Oncol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Sch Med, Div Gynecol Oncol, Los Angeles, CA USA. Tulane Med Sch, Div Gynecol Oncol, New Orleans, LA USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Mayo Clin, Sect Gynecol Surg, Rochester, MN USA. NYU, Sch Med, New York, NY USA. Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. Gynecol Oncol Associates, La Jolla, CA USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol, Boston, MA USA. RP Dubeau, L (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Pathol, 1441 Eastlake Ave, Los Angeles, CA 90033 USA. EM ldubeau@usc.edu FU NCI NIH HHS [R01CA79750] NR 36 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2004 VL 10 IS 8 BP 2681 EP 2686 DI 10.1158/1078-0432.CCR-0523-03 PG 6 WC Oncology SC Oncology GA 813VE UT WOS:000220933800015 PM 15102671 ER PT J AU Michaelson, MD Marujo, RM Smith, MR AF Michaelson, MD Marujo, RM Smith, MR TI Contribution of androgen deprivation therapy to elevated osteoclast activity in men with metastatic prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol ID PREVENT BONE LOSS; ZOLEDRONIC ACID; CONTROLLED-TRIAL; CROSS-LINKS; MARKERS; FRACTURE; RESORPTION AB Purpose: Biochemical markers of both osteoblast and osteoclast activity are elevated in men with osteoblastic metastases from prostate cancer. Androgen deprivation therapy (ADT), the mainstay of therapy for advanced prostate cancer, increases markers of osteoblast and osteoclast activity, even in the absence of bone metastases. Little is known about the relative contributions of ADT and skeletal metastases to elevated bone turnover in men with prostate cancer. Experimental Design: To evaluate the relative contributions of ADT and skeletal metastases to osteoblast and osteoclast activity, we performed a cross-sectional study in three groups of men with advanced prostate cancer: (a) hormone-naive men without bone metastases; (b) castrate men without bone metastases; and (c) castrate men with bone metastases. The primary study end points were serum levels of bone-specific alkaline phosphatase (BSAP), a marker of osteoblast activity, and N-telopeptide (NTX), a marker of osteoclast activity. Results: Serum levels of both BSAP and NTX were significantly higher in groups of castrate men (groups 2 and 3) than in hormone-naive men (group 1; P < 0.01 for all comparisons). Among castrate men, serum BSAP was significantly higher in men with bone metastases than in men without bone metastases (P = 0.01). In contrast, serum levels of NTX were similar in groups 2 and 3 (P = 0.33). Conclusions: The unintended effects of ADT on the skeleton are sufficient to explain increased osteoclast activity in castrate men with bone metastases. These results may have important implications for the optimal timing and schedule of osteoclast-targeted therapy in men with advanced prostate cancer. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Div Hematol Oncol, Boston, MA 02114 USA. RP Michaelson, MD (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM dmichaelson1@partners.org FU NCI NIH HHS [1K12CA87723-01] NR 16 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2004 VL 10 IS 8 BP 2705 EP 2708 DI 10.1158/1078-0432.CCR-03-0735 PG 4 WC Oncology SC Oncology GA 813VE UT WOS:000220933800018 PM 15102674 ER PT J AU Yang, SC Hillinger, S Riedl, K Zhang, L Zhu, L Huang, M Atianzar, K Kuo, BY Gardner, B Batra, RK Strieter, RM Dubinett, SM Sharma, S AF Yang, SC Hillinger, S Riedl, K Zhang, L Zhu, L Huang, M Atianzar, K Kuo, BY Gardner, B Batra, RK Strieter, RM Dubinett, SM Sharma, S TI Intratumoral administration of dendritic cells overexpressing CCL21 generates systemic antitumor responses and confers tumor immunity SO CLINICAL CANCER RESEARCH LA English DT Article ID LYMPHOID-TISSUE CHEMOKINE; COLONY-STIMULATING FACTOR; GROWTH-FACTOR-BETA; ANGIOGENESIS IN-VIVO; X-C-CHEMOKINE; MHC CLASS-I; LUNG-CANCER; MURINE TUMORS; GENE-THERAPY; T-CELLS AB To achieve in situ tumor antigen uptake and presentation, intratumoral administration of ex vivo-generated, gene-modified murine bone marrow-derived dendritic cells (DC) was used in a murine lung cancer model. To attract mature host DC and activated T cells at the tumor site, the DC were transduced with an adenoviral vector expressing secondary lymphoid tissue chemokine (CCL21/SLC). Sixty percent of the mice treated with 106 DC-AdCCL21 intratumorally (7-10 ng/ml/10(6) cells/24 h of CCL21) at weekly intervals for 3 weeks showed complete tumor eradication, whereas only 25% of mice had complete resolution of tumors when mice were treated with fibroblasts expressing CCL21. In contrast only 12% of the mice treated with unmodified or control vector modified DC (DC-AdCV) showed complete tumor eradication. DC-AdCCL21 administration led to increases in the CD4(+), CD8(+), and CD3(+)CXCR3(+) T cells, as well as DC expressing CD11c(+) DEC205(+). CD4(+)CD25(+) T-regulatory cells infiltrating the tumors were markedly reduced after DC-AdCCL21 therapy. The tumor site cellular infiltrates were accompanied by the enhanced elaboration of granulocyte macrophage colony-stimulating factor, IFN-gamma, MIG/CXCL9, IP-10/CXCL10, and interleukin 12, but decreases in the immunosuppressive mediators transforming growth factor beta and prostaglandin E-2. DC-AdCCL21-treated tumor-bearing mice showed enhanced frequency of tumor-specific T lymphocytes secreting IFN-gamma, and tumor protective immunity was induced after DC-AdCCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9, or IFN-gamma significantly reduced the antitumor efficacy of DC-AdCCL21. These findings provide a strong rationale for the evaluation of DC-AdCCL21 in cancer immunotherapy. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Lung Canc Res Program, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Jonsson Comprehens Canc Ctr, 37-131 Ctr Hlth Sci,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM sharmasp@ucla.edu FU NCI NIH HHS [CA71818, R01 CA078654-03, R01 CA78654, 1P50 CA90388, CA78654] NR 82 TC 74 Z9 84 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2004 VL 10 IS 8 BP 2891 EP 2901 DI 10.1158/1078-0432.CCR-03-0380 PG 11 WC Oncology SC Oncology GA 813VE UT WOS:000220933800042 PM 15102698 ER PT J AU Rodriguez, M Sifri, CD Fishman, JA AF Rodriguez, M Sifri, CD Fishman, JA TI Failure of low-dose atovaquone prophylaxis against Pneumocystis jiroveci infection in transplant recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CARINII-PNEUMONIA PROPHYLAXIS; AEROSOLIZED PENTAMIDINE; PREVENTION; TRIMETHOPRIM; SULFONAMIDES; INTOLERANT; DAPSONE AB Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against Pneumocystis jiroveci pneumonia. Alternative agents are used in treating patients who do not tolerate this medication. We report 2 cases of prophylaxis failure in patients receiving low-dose atovaquone. We discuss the use of atovaquone as an alternative agent for prophylaxis in transplant recipients. C1 Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant Infect Dis & Compromised Host Program, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org NR 13 TC 14 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2004 VL 38 IS 8 BP E76 EP E78 DI 10.1086/383150 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 810WU UT WOS:000220735200033 PM 15095235 ER PT J AU Schmitt-Ney, M Habener, JF AF Schmitt-Ney, M Habener, JF TI Cell-density-dependent regulation of actin gene expression due to changes in actin treadmilling SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE treadmilling; G-actin; F-actin ID SERUM RESPONSE FACTOR; EMBRYONIC STEM-CELLS; BETA-ACTIN; MESSENGER-RNA; CYTOSKELETAL ACTIN; CYTOCHALASIN-D; SRF ACTIVITY; F-ACTIN; DYNAMICS; MOTILITY AB The actins are essential cytoskeletal proteins required for the survival and growth of cells. The transitions between soluble (G-actin) and filamentous (F-actin) forms of actin (actin treadmilling) are complexly regulated. Here we show that the expression of the cytoplasmic beta-actin and gamma-actin genes is down-regulated in mouse fibroblasts when the cell density of the culture increases. Conversely, a dense culture replated at lower density results in increases in actin mRNA levels within a few hours. Concomitant with these changes in mRNA levels, we observe increased depolymerization of actin microfilaments at higher densities resulting in an elevated G-actin to F-actin ratio. By using actin polymerization inhibitors, we show that the density-dependent change in actin gene expression is dependent on changes in the ratio of G-actin vs. F-actin levels. Therefore, actin treadmilling and actin gene regulation are not coregulated by cell density, but represent a linear signal transduction pathway in which actin treadmilling regulates actin gene transcription. The physiological transition represented by the growth of a sparse fibroblast population into a confluent and growth-arrested population represents a useful model for the study of how the actin treadmill exerts its action on the gene expression program of cells. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Boston, MA 02115 USA. RP Schmitt-Ney, M (reprint author), Univ Turin, Dept Anat Pharmacol & Forens Med, Corso Massimo dAzeglio 52, I-10126 Turin, Italy. EM michel.schmitt-ney@unito.it NR 50 TC 5 Z9 5 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 15 PY 2004 VL 295 IS 1 BP 236 EP 244 DI 10.1016/j.yexcr.2003.12.022 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 810SR UT WOS:000220724500022 PM 15051506 ER PT J AU Volberding, PA AF Volberding, PA TI Meeting challenges - Overcoming limitations: Advances of the protease inhibitor class - Proceedings of an expert roundtable SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Editorial Material C1 San Francisco Vet Affairs Med Ctr, Med Serv, San Francisco, CA 94121 USA. RP Volberding, PA (reprint author), San Francisco Vet Affairs Med Ctr, Med Serv, 4150 Clement St,VAMC 111V, San Francisco, CA 94121 USA. EM Paul.Volberding@med.va.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 15 PY 2004 VL 35 SU 1 BP S1 EP S2 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 811TK UT WOS:000220794000001 ER PT J AU Ghosh, PM Bedolla, R Thomas, CA Kreisberg, JI AF Ghosh, PM Bedolla, R Thomas, CA Kreisberg, JI TI Role of protein kinase C in arginine vasopressin-stimulated ERK and p70S6 kinase phosphorylation SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE proliferation; EGF-R; PI3K ID GLOMERULAR MESANGIAL CELLS; GROWTH-FACTOR RECEPTOR; FREE CALCIUM-CONCENTRATION; SMOOTH-MUSCLE CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; HIGH GLUCOSE; S6 KINASE; PHOSPHOINOSITIDE 3-KINASE; ANGIOTENSIN-II; PI 3-KINASE AB We previously showed in rat renal glomerular mesangial cells, that arginine vasopressin (AVP)-stimulated cell proliferation was mediated by epidermal growth factor receptor (EGF-R) transactivation, and activation (phosphorylation) of ERK1/2 and p70S6 kinase (Ghosh et al. [2001]: Am J Physiol Renal Physiol 280:F972-F979]. In this paper, we extend these observations and show that different protein kinase C (PKC) isoforms play different roles in mediating AVP-stimulated ERK1/2 and p70S6 kinase phosphorylation and cell proliferation. AVP treatment for 0-60 min stimulated the serine/threonine phosphorylation of PKC isoforms alpha, delta, epsilon, and zeta. The activation of PKC was dependent on EGF-R and phosphatidylinositol 3-kinase (PI3K) activation. In addition, inhibition of conventional and novel PKC isoforms by chronic (24 h) exposure to phorbol 12-myristate 13-acetate (PMA) inhibited AVP-induced activation of ERK and p70S6 kinase as well as EGF-R phosphorylation. Rottlerin, a specific inhibitor of PKCdelta, inhibited both ERK and p70S6 kinase phosphorylation and cell proliferation. In contrast, a PKCepsilon translocation inhibitor decreased ERK1/2 activation without affecting p70S6 kinase or cell proliferation, while a dominant negative PKCzeta (K281W) cDNA delayed p70S6 kinase activation without affecting ERK1/2. On the other hand, Go6976, an inhibitor of conventional PKC isoforms, did not affect p70S6 kinase, but stimulated ERK1/2 phosphorylation without affecting cell proliferation. Our results indicate that PKCdelta plays an important role in AVP-stimulated ERK and p70S6 kinase activation and cell proliferation. (C) 2004 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kreisberg, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Kreisberg@uthscsa.edu NR 67 TC 17 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 15 PY 2004 VL 91 IS 6 BP 1109 EP 1129 DI 10.1002/jcb.10789 PG 21 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810JQ UT WOS:000220701000003 PM 15048868 ER PT J AU Meyerhardt, JA Kwok, A Ratain, MJ McGovren, JP Fuchs, CS AF Meyerhardt, JA Kwok, A Ratain, MJ McGovren, JP Fuchs, CS TI Relationship of baseline serum bilirubin to efficacy and toxicity of single-agent irinotecan in patients with metastatic colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVE METABOLITE; CPT-11; SN-38; GLUCURONIDATION; SURVIVAL AB Purpose To examine the predictive value of baseline serum bilirubin measurement for chemotherapy-related toxicity or efficacy among patients receiving irinotecan for metastatic colorectal cancer. Methods We performed a secondary analysis of a cohort of 287 patients treated in a multicenter, phase III study with single-agent irinotecan administered either weekly or once every 3 weeks. Patients were grouped into three categories of baseline bilirubin measurements (0 to 0.4, 0.5 to 0.9, and 1.0 to 1.5 mg/dL). We performed analyses of overall survival, time to progression, and treatment-related toxicity based on bilirubin category, as well as using bilirubin as a continuous variable. Results With a median follow-up of 15.8 months, baseline serum bilirubin was not predictive of 1-year survival (42.4%, bilirubin 0 to 0.4; 42.3%, bilirubin 0.5 to 0.9; 48.1%, bilirubin 1.0 to 1.5 mg/dL), median overall survival (10.1, 9.7, and 15.6 months, respectively; P = .5), or median time to progression (2.8, 3.0, and 4.1 months, respectively; P = .5). Patients with elevated bilirubin had a significantly greater risk grade 3 to 4 neutropenia; however, this was limited to patients treated on a weekly schedule (P trend = .03) and not once every 3 weeks (P trend = .8). Other toxicities were not significantly different by initial bilirubin measurement. Conclusion Although modest elevations of bilirubin (1.0 to 1.5 mg/dL) are associated with increased grade 3 to 4 neutropenia in patients treated with weekly irinotecan, baseline serum bilirubin does not reliably predict overall irinotecan-related toxicity or efficacy. Additional methods, including potential application of pharmacogenetic information, are needed to optimize irinotecan dosing and tailor therapy to individual patients. (C) 2004 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Pfizer Oncol, New York, NY USA. Univ Chicago, Comm Clin Pharmacol & Pharmacogenom, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Res Ctr, Chicago, IL 60637 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org FU NCI NIH HHS [1K07 CA 097992-01A1] NR 23 TC 41 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 APR 15 PY 2004 VL 22 IS 8 BP 1439 EP 1446 DI 10.1200/JCO.2004.10.043 PG 8 WC Oncology SC Oncology GA 813MW UT WOS:000220912200014 PM 15084617 ER PT J AU Garcia-Carbonero, R Supko, JG Manola, J Seiden, MV Harmon, D Ryan, DP Quigley, MT Merriam, P Canniff, J Goss, G Matulonis, U Maki, RG Lopez, T Puchalski, TA Sancho, MA Gomez, J Guzman, C Jimeno, J Demetri, GD AF Garcia-Carbonero, R Supko, JG Manola, J Seiden, MV Harmon, D Ryan, DP Quigley, MT Merriam, P Canniff, J Goss, G Matulonis, U Maki, RG Lopez, T Puchalski, TA Sancho, MA Gomez, J Guzman, C Jimeno, J Demetri, GD TI Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CA SP Amer Soc Clin Oncol ID DOXORUBICIN PLUS IFOSFAMIDE; EUROPEAN-ORGANIZATION; ANTITUMOR-ACTIVITY; 2ND-LINE CHEMOTHERAPY; SOLID MALIGNANCIES; CLINICAL-TRIALS; MINOR-GROOVE; CANCER; TURBINATA; INFUSION AB Purpose To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. Patients and Methods Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 mug/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. Results Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. Conclusion ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. PharmaMar, Clin Res & Dev, Madrid, Spain. RP Demetri, GD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Shields Warren Bldg,Room G530,44 Binney St, Boston, MA 02115 USA. EM gdemetri@partners.org RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 52 TC 183 Z9 189 U1 0 U2 2 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 APR 15 PY 2004 VL 22 IS 8 BP 1480 EP 1490 DI 10.1200/JCO.2004.02.098 PG 11 WC Oncology SC Oncology GA 813MW UT WOS:000220912200019 PM 15084621 ER PT J AU Sparano, JA Lee, S Chen, MG Nazeer, T Einzig, A Ambinder, RF Henry, DH Manalo, J Li, TH Von Roenn, JH AF Sparano, JA Lee, S Chen, MG Nazeer, T Einzig, A Ambinder, RF Henry, DH Manalo, J Li, TH Von Roenn, JH TI Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV associated non-Hodgkin's lymphoma: An eastern cooperative oncology group trial (E1494) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; B-CELL LYMPHOMA; DOSE-ADJUSTED EPOCH; PROGNOSTIC-FACTORS; ELDERLY-PATIENTS; CHEMOTHERAPY; AIDS; INFECTION; RITUXIMAB AB Purpose To determine the effectiveness of an infusional chemotherapy regimen in patients with HIV-associated lymphoma treated before and after the use of highly active antiretroviral therapy (HAART) in routine clinical practice. Patients and Methods Ninety-eight assessable patients with HIV-associated intermediate- or high-grade non-Hodgkin's lymphoma received cyclophosphamide 200 mg/m(2)/d, doxorubicin 12.5 mg/m(2)/d, and etoposide 60 mg/m(2)/d (CDE) given by continuous intravenous infusion for 4 days (96 hours) every 4 weeks plus filgrastim. Concurrent antiretroviral treatment consisted of the nucleoside analog didanosine in the first 43 patients enrolled before December 1996 (pre-HAART group), or HAART in the remaining 55 patients enrolled after that time (HAART group). Results Complete response occurred in 44 patients (45%; 95% Cl, 35% to 55%). Failure-free survival and overall survival (CS) at 2 years was 36% (95% Cl, 26% to 46%) and 43% (95% Cl, 33% to 53%), respectively. At the time of the analysis, 30% in the pre-HAART group were alive compared with 47% in the HAART group; when adjusted for varying length of follow-up, patients in the HAART group had improved CS (P=.039). Patients in the HAABT group experienced less grade 4 nonhematologic toxicity (22% v 42%; P=.037), thrombocytopenia (31% v 52%; P=.033), and anemia (9% v 27%; P=.021), and had fewer treatment-associated deaths (0% v 10%; P=.013). Conclusion Infusional CDE is an effective and potentially curative regimen for patients with HIV-associated lymphoma. Patients treated in the HAART era have less chemotherapy-associated toxicity and improved survival. C1 Montefiore Med Ctr, Albert Einstein Canc Ctr, Weiler Div, Bronx, NY 10461 USA. Albany Med Coll, Albany, NY 12208 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Eastern Cooperat Oncol Grp, Brookline, MA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Northwestern Univ, Ctr Med, Chicago, IL 60611 USA. RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Canc Ctr, Weiler Div, 1825 Eastchester Rd,2 South,Rm 47-48, Bronx, NY 10461 USA. EM jsparano@montefiore.org FU NCI NIH HHS [CA 17145, CA 13650, CA 21115, CA 23318, CA 15488, CA 14958, CA 16116, CA 66636] NR 54 TC 63 Z9 66 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 APR 15 PY 2004 VL 22 IS 8 BP 1491 EP 1500 DI 10.1200/JCO.2004.08.195 PG 10 WC Oncology SC Oncology GA 813MW UT WOS:000220912200020 PM 15084622 ER PT J AU Blackard, JT Yang, YJ Bordoni, P Sherman, KE Chung, RT AF Blackard, JT Yang, YJ Bordoni, P Sherman, KE Chung, RT CA AIDS Clin Trials Grp 383 Study Tea TI Hepatitis C virus (HCV) diversity in HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; HYPERVARIABLE REGION 1; LIVER-DISEASE; PROTEASE INHIBITORS; INFECTED PATIENTS; EVOLUTION; VIREMIA; IMPACT; RNA AB Because of increased mortality and reduced treatment response rates in subjects coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), understanding the selection pressures underlying the evolution of HCV is important for the development of strategies to control both viruses. We therefore investigated diversity of HCV in 11 HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy ( HAART). Distinct categories of HCV virologic response to suppression of HIV were identified. The diversity of quasi species at several genomic regions was characterized over the course of a 48-week period. Consensus data suggested a shift in the virus population at all loci except the 5' untranslated region (UTR) after initiation of HAART. Intrasubject genetic distance and entropy were highest in hypervariable region (HVR)-1. In contrast, variation in the 5' UTR was limited. Positive immune selection pressure directed against HVR-1, but not other protein-coding regions, was also detected. These data suggest that there are several mechanisms by which suppression of HIV replication and a reconstituted immune system influence diversity of HCV in HIV-HCV coinfected subjects. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Dept Med, Cincinnati, OH USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID NIH HHS [P30-AI42851] NR 51 TC 29 Z9 29 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2004 VL 189 IS 8 BP 1472 EP 1481 DI 10.1086/382959 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 810WW UT WOS:000220735400018 PM 15073685 ER PT J AU Snyder, EY Daley, GQ Goodell, M AF Snyder, EY Daley, GQ Goodell, M TI Taking stock and planning for the next decade: Realistic prospects for stem cell therapies for the nervous system SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article; Proceedings Paper CT Satellite Symposium on Neural Stem Cells and Brain Repair CY JUL 07-10, 2003 CL Prague, CZECH REPUBLIC DE neural transplantation; gene therapy; neuroregeneration; neurodegeneration; endogenous stem cells; neuroprotection; injury; vascular; clinical trials; transdifferentiation ID SPINAL-CORD-INJURY; NEURAL PROGENITOR CELLS; ADULT HUMAN HIPPOCAMPUS; NEUROTROPHIC FACTOR; MAMMALIAN BRAIN; IN-VITRO; MOUSE-BRAIN; GROWTH-FACTOR; HUMAN CNS; NEURONS AB In thinking about the practical application of stem cell biology to clinical situations-particularly for the central nervous system (CNS)-it is instructive to remember that the neural stem cell (NSC) field-as a prototype for somatic stem cells in general-emerged as the unanticipated byproduct of investigations by developmental neurobiologists into fundamental aspects of neural determination, commitment, and plasticity. Stem cell behavior is ultimately an expression of developmental principles, an alluring vestige from the more plastic and generative stages of organogenesis. In attempting to apply stem cell biology therapeutically, it is instructive always to bear in mind what role the stem cell plays in development and to what cues it was "designed" to respond in trying to understand the "logic" behind its behavior (both what investigators want to see and what investigators do not want to see). Furthermore, in transplantation paradigms, the interaction between engrafted NSCs and recipient host is a dynamic, complex, ongoing reciprocal interaction where both entities are constantly in flux. In this review, we propose a "roadmap" to the clinic, with a particular emphasis on flagging the "potholes" and "speed bumps" through which we must navigate. Despite the admonitions to be circumspect, we also suggest disease processes that may be within the grasp of proven stem cell properties and might be approachable in the relatively near future. (C) 2004 Wiley-Liss, Inc. C1 Burnham Inst, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. RP Snyder, EY (reprint author), Burnham Inst, 10901 N Torrey Pines Rd,Rm 7261, La Jolla, CA 92037 USA. EM esnyder@burnham.org OI Goodell, Margaret/0000-0003-1111-2932 NR 60 TC 60 Z9 66 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD APR 15 PY 2004 VL 76 IS 2 BP 157 EP 168 DI 10.1002/jnr.20033 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 809MK UT WOS:000220640600002 PM 15048913 ER PT J AU O'Gara, PT Greenfield, AJ Afridi, NA Houser, SL Harris, NL Januzzi, JL Evans-Molina, C AF O'Gara, PT Greenfield, AJ Afridi, NA Houser, SL Harris, NL Januzzi, JL Evans-Molina, C TI A 38-year-old woman with acute onset of pain in the chest - Proximal aortic dissection, associated with pregnancy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INTRAMURAL HEMATOMA; COMPUTED-TOMOGRAPHY; INTERNATIONAL REGISTRY; THORACIC AORTA; ULCER; PROGRESSION; MANAGEMENT; DIAGNOSIS; CRITERIA; ANEURYSM C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP O'Gara, PT (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 35 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 APR 15 PY 2004 VL 350 IS 16 BP 1666 EP 1674 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 812DI UT WOS:000220819800013 PM 15084700 ER PT J AU Netscher, DT Spira, M AF Netscher, David T. Spira, Melvin TI Basal Cell Carcinoma: An Overview of Tumor Biology and Treatment SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Learning Objectives: After studying this article, the participant should be able to: 1. Describe the epidemiology and etiology of basal cell carcinomas. 2. Understand the biology, histogenesis, predisposing conditions, and syndromes associated with basal cell carcinomas. 3. Have a clear understanding of tumor types and their clinical behavior. 4. Discuss the importance of diagnostic tumor biopsy and treatment options as they pertain to anatomic site, tumor type, and patient age. 5. Understand the basis for surgical management of basal cell carcinomas, the margins of excision, indications for frozen section, and Mohs micrographic surgery. 6. Discuss the value of patient follow-up after treatment of a primary basal cell carcinoma. 7. Review the most recently published literature on this topic and understand new concepts in tumor biology as they relate to diagnosis and treatment options. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Plast Surg Serv, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. EM netscher@bcm.tmc.edu NR 99 TC 29 Z9 31 U1 0 U2 1 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 APR 15 PY 2004 VL 113 IS 5 BP 74E EP 94E DI 10.1097/01.PRS.0000113025.69154.D1 PG 21 WC Surgery SC Surgery GA V13NG UT WOS:000207672900001 ER PT J AU Xu, JW Zaporojan, V Peretti, GM Roses, RE Morse, KB Roy, AK Mesa, JM Randolph, MA Bonassar, LJ Yaremchuk, MJ AF Xu, JW Zaporojan, V Peretti, GM Roses, RE Morse, KB Roy, AK Mesa, JM Randolph, MA Bonassar, LJ Yaremchuk, MJ TI Injectable tissue-engineered cartilage with different chondrocyte sources SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Plastic-Surgery-Research-Council CY APR 17-20, 2002 CL BOSTON, MA SP Plastic Surg Res Council ID SCAFFOLD; POLYMER; REPAIR; SHAPE AB Injectable engineered cartilage that maintains a predictable shape and volume would allow recontouring of craniomaxillofacial irregularities with minimally invasive techniques. This study investigated how chondrocytes from different cartilage sources, encapsulated in fibrin polymer, affected construct mass and volume with time. Swine auricular, costal, and articular chondrocytes were isolated and mixed with fibrin polymer (cell concentration of 40 x 10(6) cells/ml for all groups). Eight samples (1 cm x 1 cm x 0.3 cm) per group were implanted into nude mice for each time period (4, 8, and 12 weeks). The dimensions and mass of each specimen were recorded before implantation and after explantation. Ratios comparing final measurements and original measurements were calculated. Histological, biochemical, and biomechanical analyses were performed. Histological evaluations (n = 3) indicated that new cartilaginous matrix was synthesized by the transplanted chondrocytes in all experimental groups. At 12 weeks, the ratios of dimension and mass (n = 8) for auricular chondrocyte constructs increased by 20 to 30 percent, the ratios for costal chondrocyte constructs were equal to the initial values, and the ratios for articular chondrocyte constructs decreased by 40 to 50 percent. Constructs made with auricular chondrocytcs had the highest modulus (n = 3 to 5) and glycosaminoglycan content (n = 4 or 5) and the lowest permeability value (n = 3 to 5) and water content (n = 4 or 5). Constructs made with articular chondrocytes had the lowest modulus and glycosaminoglycan content and the highest permeability value and water content (p < 0.05). The amounts of hydroxyproline (n = 5) and DNA (n = 5) were not significantly different among the experimental groups (p > 0.05). It was possible to engineer injectable cartilage with chondrocytes from different sources, resulting in neocartilage with different properties. Although cartilage made with articular chondrocytcs shrank and cartilage made with auricular chondrocytes overgrew, the injectable tissue-engineered cartilage made with costal chondrocytes was stable during the time periods studied. Further-more, the biomechanical properties of the engineered cartilage made with auricular or costal chondrocytes were superior to those of cartilage made with articular chondrocytes, in this model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Ctr Tissue Engn, Boston, MA 02125 USA. Zhongshan Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China. Fudan Univ, Shanghai 200433, Peoples R China. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. EM marandolph@partners.org RI Bonassar, Lawrence/C-2103-2016; Peretti, Giuseppe/K-6358-2016 OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 NR 21 TC 88 Z9 91 U1 0 U2 10 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 APR 15 PY 2004 VL 113 IS 5 BP 1361 EP 1371 DI 10.1097/01.PRS.000011594.52661.29 PG 11 WC Surgery SC Surgery GA 809DZ UT WOS:000220618700007 PM 15060348 ER PT J AU Vagefi, PA Ierino, FL Gianello, PR Shimizu, A Kamano, C Sachs, DH Yamada, K AF Vagefi, PA Ierino, FL Gianello, PR Shimizu, A Kamano, C Sachs, DH Yamada, K TI Role of the thymus in transplantation tolerance in miniature swine: IV. The thymus is required during the induction phase, but not the maintenance phase, of renal allograft tolerance SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELLS; INDIRECT ALLORECOGNITION; PERIPHERAL TOLERANCE; INFECTIOUS TOLERANCE; CARDIAC ALLOGRAFTS; STABLE INDUCTION; DENDRITIC CELLS; MECHANISMS; ANTIGEN AB Background. The authors' laboratory previously demonstrated that long-term tolerance to class I-disparate renal allografts in miniature swine can be induced by a short course of cyclosporine A (CsA), and that this stable tolerance is dependent on the presence of an intact thymus. In the present study, the authors have examined the requirement for a thymus during the pretransplant, induction, and maintenance phases of tolerance. Methods. Twenty-two miniature swine underwent class I major histocompatibility complex-mismatched renal transplantation, with a 12-day course of CsA. Thymectomies were performed on days -21, 0, +8, +21, and greater than or equal to +42, in relation to the day of transplantation. Historical controls consisted of euthymic and sham-thymectomized recipients. Results. Euthymic, sham-thymectomized, and day-greater than or equal to +42 thymectomized recipients demonstrated stable renal function and minimal anti-donor cytotoxic T-lymphocyte (CTL) responses. In contrast, day -21 and day 0 thymectomized recipients demonstrated allograft dysfunction, marked cellular infiltrates, with severe vasculitis and glomerular changes, and strong anti-donor CTL responses. Animals thymectomized on days +8 and +21 did not undergo severe rejection, but likewise did not demonstrate a stable clinical course. Conclusions. These data indicate that the requirement for thymic function in the induction of rapid and stable tolerance is greatest during the first 8 days and then diminishes over the next 2 weeks posttransplant. Failure of thymectomy to affect the course of tolerance after day +21 suggests that thymic function is not required for the maintenance of tolerance. Understanding the role of the thymus in establishing tolerance may permit the development of tolerance induction strategies, especially for pediatric transplant recipients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM kaz.yamada@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [2P01HL18646]; NIAID NIH HHS [5R01AI31046, 5P01 AI5897] NR 30 TC 20 Z9 23 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 APR 15 PY 2004 VL 77 IS 7 BP 979 EP 985 DI 10.1097/01.TP.0000116416.10799.C6 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 813FN UT WOS:000220893100004 PM 15087757 ER PT J AU Makhlouf, L Grey, ST Dong, V Csizmadia, E Arvelo, MB Auchincloss, H Ferran, C Sayegh, MH AF Makhlouf, L Grey, ST Dong, V Csizmadia, E Arvelo, MB Auchincloss, H Ferran, C Sayegh, MH TI Depleting anti-CD4 monoclonal antibody cures new-onset diabetes, prevents recurrent autoimmune diabetes, and delays allograft rejection in nonobese diabetic mice SO TRANSPLANTATION LA English DT Article ID NONDEPLETING ANTI-CD4; NOD MICE; ISLET ALLOGRAFTS; BETA-CELLS; T-CELLS; DESTRUCTION; MOUSE; INSULITIS; SURVIVAL; CD40 AB Background. The prevention of recurrent autoimmunity is a prerequisite for successful islet transplantation in patients with type I diabetes. Therapies effective in preserving pancreatic beta-cell mass in patients with newly diagnosed diabetes are good candidates for achieving this goal. Anti-CD3 monoclonal antibody (mAb) and antilymphocyte antisera are the only therapies to date that have cured early diabetic disease in the nonobese diabetic (NOD) mouse. We investigated whether other immunosuppressive therapies, including short-term depleting anti-CD4 mAb or costimulation blockade, would affect the disease progression in recently diabetic NOD mice. We also evaluated the effect of the anti-CD4 mAb on syngeneic and allogeneic graft survival in diabetic NOD recipients. Methods and Results. We demonstrate that a short course of anti-CD4 mAb early after hyperglycemia onset cured diabetes. Normal islets and islets with CD4+ and CD8+ T-cell peri-insulitic infiltrate were found in the pancreata of cured NOD mice. A similar regimen prevented the recurrence of autoimmune diabetes in NOD/severe combined immunodeficient disease (SCID) islet isografts and delayed the rejection of allogeneic C57BL/6 islet allografts in diabetic female NOD mice. The co-transfer of diabetogenic splenocytes with splenocytes from anti-CD4 mAb-treated and cured NOD mice into 7-week-old, irradiated, NOD male mice was not able to protect from diabetes occurrence. This indicates that an anti-CD4-mediated cure of diabetes is independent of the induction of immunoregulatory T cells. Anti-CD154 mAb and cytotoxic T-lymphocyte antigen 4 immunoglobulin were ineffective in early-onset diabetes. Conclusion. Our results provide the first evidence that newly established autoimmune islet destruction in NOD mice responds to a short course of anti-CD4 mAb. In contrast, costimulation blockade is ineffective in this clinically relevant model. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg & Med,Immunobiol Res Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Immunogenet & Transplantat,Renal Div, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Ferran, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg & Med,Immunobiol Res Ctr, 99 Brookline Ave, Boston, MA 02215 USA. EM cferran@caregroup.harvard.edu RI Grey, Shane/B-3020-2008 OI Grey, Shane/0000-0003-2160-1625 FU NIAID NIH HHS [P01 AI4152]; NIDDK NIH HHS [R21 DK062601] NR 30 TC 44 Z9 47 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2004 VL 77 IS 7 BP 990 EP 997 DI 10.1097/01.TP.0000118410.61419.59 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 813FN UT WOS:000220893100006 PM 15087759 ER PT J AU Orosz, GM Magaziner, J Hannan, EL Morrison, RS Koval, K Gilbert, M McLaughlin, M Halm, EA Wang, JJ Litke, A Silberzweig, SB Siu, AL AF Orosz, GM Magaziner, J Hannan, EL Morrison, RS Koval, K Gilbert, M McLaughlin, M Halm, EA Wang, JJ Litke, A Silberzweig, SB Siu, AL TI Association of timing of surgery for hip fracture and patient outcomes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FEMORAL FRACTURE; ELDERLY PATIENTS; OPERATIVE DELAY; MORTALITY; TIME; COMPLICATIONS; MORBIDITY; ADMISSION; RECOVERY; IMPACT AB Context. Previous studies of surgical timing in patients with hip fracture have yielded conflicting findings on mortality and have not focused on functional outcomes. Objective To examine the association of timing of surgical repair of hip fracture with function and other outcomes, Design Prospective cohort study including analyses matching cases of early (:524 hours) and late (>24 hours) surgery with propensity scores and excluding patients who might not. be candidates for early surgery. Setting Four hospitals in the New York City metropolitan area. Participants A total of 1206 patients aged 50 years or older admitted with hip fracture over 29 months, ending December 1999. Main Outcome Measures Function (using the Functional Independence Measure), survival, pain, and length of stay (LOS). Results Of the patients treated with surgery (n=1178), 33.8% had surgery within 24 hours. Earlier surgery was not associated with improved mortality (hazard ratio, 0.75; 95% confidence interval [CI], 0.52-1.08) or improved locomotion (difference of -0.04 points; 95% Cl, -0.49 to 0.39). Earlier surgery was associated with fewer days of severe and very severe pain (difference of -0.22 days; 95% Cl, -0.41 to -0.03) and shorter LOS by 1.94 days (P<.001), but postoperative pain and LOS after surgery did not differ: Analyses with propensity scores yielded similar results. When the cohort included only patients who were medically stable at admission and therefore eligible for early surgery, the results were unchanged except that early surgery was associated with fewer major complications (odds ratio, 0.26; 95% Cl, 0.07-0.95). Conclusions Early surgery was not associated with improved function or mortality, but it was associated with reduced pain and LOS and probably major complications among patients medically stable at admission. Additional research is needed on whether functional outcomes may be improved. In the meantime, patients with hip fracture who are medically stable should receive early surgery when possible. C1 Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. Mt Sinai Sch Med, Dept Orthoped, New York, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. SUNY Albany, Sch Publ Hlth, Dept Hlth Policy & Management, Albany, NY 12222 USA. Hosp Joint Dis & Med Ctr, Dept Orthoped, New York, NY USA. Bronx Vet Adm Med Ctr, GRECC, Bronx, NY USA. RP Siu, AL (reprint author), Mt Sinai Med Ctr, Box 1070,1 Gustave L Levy Pl, New York, NY 10029 USA. EM albert.siu@mssm.edu FU AHRQ HHS [R01HS09973, R01 HS009973, U18 HS009459, U18HS09459-0]; NIA NIH HHS [K08AG00833-01, K24 AG000918, R01 AG021992] NR 28 TC 215 Z9 230 U1 1 U2 8 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 APR 14 PY 2004 VL 291 IS 14 BP 1738 EP 1743 DI 10.1001/jama.291.14.1738 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 811RJ UT WOS:000220788700031 PM 15082701 ER PT J AU O'Connell, JJ AF O'Connell, JJ TI Dying in the shadows: the challenge of providing health care for homeless people SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material ID MEN; ADULTS C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP O'Connell, JJ (reprint author), Boston Hlth Care Homeless Program, 729 Massachusetts Ave, Boston, MA 02118 USA. NR 7 TC 19 Z9 19 U1 0 U2 4 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD APR 13 PY 2004 VL 170 IS 8 BP 1251 EP 1252 DI 10.1503/cmaj.1040008 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 814JE UT WOS:000220970200032 PM 15078847 ER PT J AU Revzin, A Rajagopalan, P Tilles, AW Berthiaume, FO Yarmush, ML Toner, M AF Revzin, A Rajagopalan, P Tilles, AW Berthiaume, FO Yarmush, ML Toner, M TI Designing a hepatocellular microenvironment with protein microarraying and poly(ethylene glycol) photolithography SO LANGMUIR LA English DT Article ID CELL-INTERACTIONS; SANDWICH CONFIGURATION; HEPATOCYTE FUNCTION; COCULTURES; DIFFERENTIATION; PEPTIDE; CULTURE; ARRAYS AB In this study, robotic protein printing was employed as a method for designing a cellular microenvironment. Protein printing proved to be an effective strategy for creating micropatterned co-cultures of primary rat hepatocytes and 3T3 fibroblasts. Collagen spots (ca. 170 mum in diameter) were printed onto amino-silane-and glutaraldehyde-modified glass slides. Groups of 15-20 hepatocytes attached to collagen regions in a highly selective manner forming cell clusters corresponding in size to the printed collagen domains. Fibroblasts, seeded onto the same surface, adhered and spread around arrays of hepatocyte islands creating a heterotypic environment. The co-cultured hepatocytes produced and maintained high levels of liver-specific biomarkers, albumin and urea, over the course of 2 weeks. In addition, protein printing was combined with poly(ethylene glycol) photolithography to define intercellular contacts within the clusters of hepatocytes residing on individual collagen islands. Glass slides, treated with 3-acryloxypropyl trichlorosilane and imprinted with 170 mum diameter collagen spots, were micropatterned with a highdensity array of 30 mum x 30 mum poly(ethylene glycol) (PEG) wells. As a result, discrete groups of ca. 9 PEG microwells became functionalized with the cell-adhesive ligand. When exposed to micropatterned surfaces, hepatocytes interacted exclusively with collagen-modified regions, attaching and becoming confined at a single-cell level within the hydrogel wells. Micropatterning strategies proposed here will lead to greater insights into hepatocellular behavior and will benefit the fields of hepatic tissue engineering and liver biology. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med & Surg Sci, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org RI Yu, weiting/I-7417-2013 FU NIBIB NIH HHS [P41 EB002503]; NIDDK NIH HHS [DK 43371]; NIGMS NIH HHS [T32GM07035] NR 32 TC 82 Z9 84 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD APR 13 PY 2004 VL 20 IS 8 BP 2999 EP 3005 DI 10.1021/la035827w PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 811CP UT WOS:000220750300002 PM 15875819 ER PT J AU Tschanz, JT Corcoran, C Skoog, I Khachaturian, AS Herrick, J Hayden, KM Welsh-Bohmer, KA Calvert, T Norton, MC Zandi, P Breitner, JCS AF Tschanz, JT Corcoran, C Skoog, I Khachaturian, AS Herrick, J Hayden, KM Welsh-Bohmer, KA Calvert, T Norton, MC Zandi, P Breitner, JCS CA Cache Cty Study Grp TI Dementia: The leading predictor of death in a defined elderly population - The Cache County Study SO NEUROLOGY LA English DT Article ID 5-YEAR FOLLOW-UP; ALZHEIMERS-DISEASE; VASCULAR-DEMENTIA; SURVIVAL; MORTALITY; AGE; QUESTIONNAIRE; DIAGNOSIS; DECLINE; SAMPLE AB Objective: To examine the relative risk and population attributable risk ( PAR) of death with dementia of varying type and severity and other risk factors in a population of exceptional longevity. Methods: Deaths were monitored over 5 years using vital statistics records and newspaper obituaries in 355 individuals with prevalent dementia and 4,328 without in Cache County, UT. Mean age was 83.3 (SD 7.0) years with dementia and 73.7 (SD 6.8) years without. History of coronary artery disease, hypertension, diabetes, and other life-shortening illness was ascertained from interviews. Results: Death certificates implicated dementia as an important cause of death, but other data suggested a stronger association. Adjusted Cox relative hazard and PAR of death were higher with dementia than with any other illness studied. Relative hazard of death with dementia was highest at ages 65 to 74, but the high prevalence of dementia after age 85 resulted in 27% PAR among the oldest old. Mortality increased substantially with severity of dementia. Alzheimer disease shortened survival time most dramatically in younger participants, but vascular dementia posed a greater mortality risk among the oldest old. Conclusion: In this population, dementia was the strongest predictor of mortality, with a risk two to three times those of other life-shortening illnesses. C1 Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Khachaturian Radebaugh & Associates Inc, Potomac, MD USA. Johns Hopkins Univ, Dept Mental Hyg, Baltimore, MD USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Gothenburg, Inst Clin Neurosci, Neuropsychiat Epidemiol Unit, Gothenburg, Sweden. RP Tschanz, JT (reprint author), Utah State Univ, Ctr Epidemiol Studies, 4440 Old Main Hill, Logan, UT 84322 USA. EM joannt@cc.usu.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [AG11380, AG21136] NR 37 TC 95 Z9 102 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 13 PY 2004 VL 62 IS 7 BP 1156 EP 1162 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 811JX UT WOS:000220769300021 PM 15079016 ER PT J AU del Monte, F Lebeche, D Guerrero, JL Tsuji, T Doye, AA Gwathmey, JK Hajjar, RJ AF del Monte, F Lebeche, D Guerrero, JL Tsuji, T Doye, AA Gwathmey, JK Hajjar, RJ TI Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEART-FAILURE; GENE-TRANSFER; INOTROPIC THERAPY; LOOKING BACKWARD; CLINICAL-USE; RAT; CONTRACTION; MYOCYTES AB Abnormal intracellular Ca2+ cycling plays an important role in cardiac dysfunction and ventricular arrhythmias in the setting of heart failure and transient cardiac ischemia followed by reperfusion (I/R). We hypothesized that overexpression of the sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) may improve both contractile dysfunction and ventricular arrhythmias. Continuous ECG recordings were obtained in 46 conscious rats after adenoviral gene transfer of either SERCA2a or the reporter gene beta-galactosidase (betagal) or parvalbumin (PV), as early as 48 h before and 48 h after 30 min ligation of the left anterior descending artery by using an implantable telemetry system. Sham-operated animals were used for comparison for hemodynamic measurements, whereas within-animal baseline was used for electrocardiographic and echocardiographic parameters. All episodes of nonsustained ventricular tachycardia (VT) and ventricular fibrillation (VF) were counted, and their durations were summed by telemetry. I/R decreased regional cardiac wall thickening as well as the maximal rate of left ventricular pressure rise (+dP/dt) and ventricular pressure fall (-dP/dt). SERCA2a restored regional wall thickening and +dP/dt and -dP/dt to levels seen preoperatively. Regional-wall motion and anterior-wall thickening were improved in the SERCA2a animals, as assessed by echocardiography and piezoelectric crystals. To assess whether these effects are SERCA2a specific, we overexpressed a skeletal-muscle protein, PV, to examine whether Ca2+ buffering alone can mitigate ventricular arrhythmias. During the first hour after I/R, the rate of nonsustained VT plus VF was 16 +/- 5 episodes per h (n = 6) in the Ad.betagal group, 22 +/- 6 in the Ad.PV group, and 4 +/- 2 (n = 6, P < 0.01) in the Ad.SERCA2a group. The decrease in VT plus VF in the Ad.SERCA2a group was consistent throughout the 48 h of monitoring. These results show that improving intracellular Ca2+ handling by overexpression of SERCA2a restores contractile function and reduces ventricular arrhythmias during I/R. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Gwathmey Inc, Cambridge, MA 02138 USA. RP del Monte, F (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Charlestown, MA 02129 USA. EM fdelmonte@partners.org FU NHLBI NIH HHS [HL-057623, HL-06982, HL-071763, K08 HL069842, R01 HL071763] NR 15 TC 132 Z9 132 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2004 VL 101 IS 15 BP 5622 EP 5627 DI 10.1073/pnas.0305778101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 812TJ UT WOS:000220861500059 PM 15044708 ER PT J AU Halpern, SD Karlawish, JHT Casarett, D Berlin, JA Asch, DA AF Halpern, SD Karlawish, JHT Casarett, D Berlin, JA Asch, DA TI Empirical assessment of whether moderate payments are undue or unjust inducements for participation in clinical trials SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 19-23, 2002 CL BALTIMORE, MD SP Soc Med Decis Making ID SUBJECT AB Background: Paying patients to participate in clinical trials is ethically controversial. However, there has been no empirical documentation regarding whether payment represents an undue or unjust inducement. Methods: To evaluate these questions, we described hypothetical placebo-controlled trials of a new antihypertensive drug to 126 patients with mild-to-moderate hypertension recruited from hypertension and general medicine clinics at a university hospital. Using a 3x3, within-subjects design, we altered a risk to participation (either adverse effect rate or rate of randomization to placebo) and the payment participants would receive ($100, $1000, and $2000) and asked patients to indicate their willingness to participate (WTP) in each trial using a 6-point scale. Results: Clustered ordinal logistic regression models revealed that patients' WTP decreased with higher risk of adverse effects (P<.001), higher risk of being assigned to placebo (P=.02), and lower payment level (P<.001). There were no significant interactions between payment level and either risk variable, suggesting that increasing payments do not alter peoples' perceptions of risk. There was a trend toward a positive interaction between income and the influence of payment on WTP (P=.09), suggesting that payment more strongly influences WTP among wealthier people. Wealthier patients were more likely to state that payment was important in their participation decision (37% vs 20%, P=.05). Conclusion: Although higher payment motivates research participation, we found no evidence that commonly used payment levels represent undue or unjust inducements. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Halpern, SD (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 115 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM shalpern@cceb.med.upenn.edu NR 10 TC 82 Z9 84 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 12 PY 2004 VL 164 IS 7 BP 801 EP 803 DI 10.1001/archinte.164.7.801 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 812GR UT WOS:000220828500013 PM 15078651 ER PT J AU Lee, K Hwang, D Stephanopoulos, G Stephanopoulos, GN Yarmush, ML AF Lee, K Hwang, D Stephanopoulos, G Stephanopoulos, GN Yarmush, ML TI Identification of optimal classification functions for biological sample and state discrimination from metabolic profiling data SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION PROFILES; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; TUMOR CLASSIFICATION; CANCER PROTEOMICS; HEPATIC-FAILURE; AMINO-ACIDS; DISCOVERY; GLUCOSE; GALACTOSAMINE AB Motivations: Classification of biological samples for diagnostic purposes is a difficult task because of the many decisions involved on the number, type and functional manipulations of the input variables. This study presents a generally applicable strategy for systematic formulation of optimal diagnostic indexes. To this end, we develop a novel set of computational tools by integrating regression optimization, stepwise variable selection and cross-validation algorithms. Results: The proposed discrimination methodology was applied to plasma and tissue (liver) metabolic profiling data describing the time progression of liver dysfunction in a rat model of acute hepatic failure generated by d-galactosamine (GalN) injection. From the plasma data, our methodology identified seven (out of a total of 23) metabolites, and the corresponding transform functions, as the best inputs to the optimal diagnostic index. This index showed better time resolution and increased noise robustness compared with an existing metabolic index, Fischer's BCAA/AAA molar ratio, as well as indexes generated using other commonly used discriminant analysis tools. Comparison of plasma and liver indexes found two consensus metabolites, lactate and glucose, which implicate glycolysis and/or gluconeogenesis in mediating the metabolic effects of GalN. C1 Shriners Burn Hosp, Boston, MA 02114 USA. Tufts Univ, Medford, MA 02155 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Shriners Burn Hosp, GRB 1402, Boston, MA 02114 USA. EM ireis@sbi.org RI Lee, Kyongbum/D-9230-2013 FU NIGMS NIH HHS [GM58125] NR 40 TC 12 Z9 12 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 12 PY 2004 VL 20 IS 6 BP 959 EP 969 DI 10.1093/bioinformatics/bth015 PG 11 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 813GH UT WOS:000220895100020 PM 14751977 ER PT J AU Draenert, R Brander, C Yu, XG Altfeld, M Verrill, CL Feeney, ME Walker, BD Goulder, PJR AF Draenert, R Brander, C Yu, XG Altfeld, M Verrill, CL Feeney, ME Walker, BD Goulder, PJR TI Impact of intrapeptide epitope location on CD8 T cell recognition: implications for design of overlapping peptide panels SO AIDS LA English DT Article DE cytotoxic T cells; CD8; CTL epitopes; overlapping peptides; C terminal anchor position; MHC class I molecules ID BARR-VIRUS INFECTION; VIRAL LOAD; CTL RESPONSES; HIV-1; PROGRESSION; LYMPHOCYTES; PROTEIN; VIREMIA; PLASMA; ESCAPE AB Background: Antigen-specific CD8 T cells following infection or immunization are typically assessed by measuring interferon-gamma production after stimulation with overlapping peptides spanning the region of interest. The effect of epitope location within such peptides is not known but may influence recognition. Objective: To examine if peptides containing the appropriate C-terminal anchor amino acid residue would provide more sensitive detection of T cell responses. The impact was examined of epitope location within overlapping peptides on recognition of epitope-specific CD8 T cell responses. Methods: C-terminal amino acid residues were analyzed in well-defined optimal epitopes for HIV, Epstein-Barr virus, cytomegalovirus and influenza and in peptide-binding motifs. Recognition of known epitopes within longer synthesized peptides by peripheral blood mononuclear cells or CD8 T cell lines was tested using interferongamma Elispot at various peptide concentrations. Results: Only 9 of 20 amino acids served as the C-terminal anchor position in 96% of described optimal epitopes and in 95% of peptide-binding motifs. A CD8 T cell response to an epitope within a longer peptide is best detected when the epitope is situated at the C-terminal end of the longer peptide, both when using peptides designed to include the optimal epitope at every possible position and when comparing responses towards optimal epitopes and corresponding overlapping peptides in a larger group of subjects. Conclusion: When using overlapping peptides to screen for CD8 T cell responses, more sensitive detection will be achieved using known C-terminal anchor amino acid residues at the C-terminus. (C) 2004 Lippincott Williams Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Div Aids, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Div Aids, Boston, MA USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. RP Goulder, PJR (reprint author), Univ Oxford, S Parks Rd,Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. FU NIAID NIH HHS [R01 AI 46995, R01 AI 28568, N01 AI 15442, R01 AI 050429] NR 19 TC 31 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 9 PY 2004 VL 18 IS 6 BP 871 EP 876 DI 10.1097/01.aids.0000111400.02002.db PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 818DJ UT WOS:000221225500004 PM 15060434 ER PT J AU Nagano, S Huang, XD Moir, RD Payton, SM Tanzi, RE Bush, AI AF Nagano, S Huang, XD Moir, RD Payton, SM Tanzi, RE Bush, AI TI Peroxidase activity of cyclooxygenase-2 (COX-2) cross-links beta-amyloid (A beta) and generates A beta-COX-2 hetero-oligomers that are increased in Alzheimer's disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MOUSE MODEL; HIPPOCAMPAL-FORMATION; HYDROGEN-PEROXIDE; CLINICAL-TRIAL; METAL-BINDING; PLAQUE CORES; HUMAN BRAIN; PROTEIN; OXIDATION AB Oxidative stress is associated with the neuropathology of Alzheimer's disease. We have previously shown that human Abeta has the ability to reduce Fe(III) and Cu(II) and produce hydrogen peroxide coupled with these metals, which is correlated with toxicity against primary neuronal cells. Cyclooxygenase (COX)-2 expression is linked to the progression and severity of pathology in AD. COX is a heme-containing enzyme that produces prostaglandins, and the enzyme also possesses peroxidase activity. Here we investigated the possibility of direct interaction between human Abeta and COX-2 being mediated by the peroxidase activity. Human Abeta formed dimers when it was reacted with COX-2 and hydrogen peroxide. Moreover, the peptide formed a cross-linked complex directly with COX-2. Such cross-linking was not observed with rat Abeta, and the sole tyrosine residue specific for human Abeta might therefore be the site of cross-linking. Similar complexes of Abeta and COX-2 were detected in post-mortem brain samples in greater amounts in AD tissue than in age-matched controls. COX-2-mediated cross-linking may inhibit Abeta catabolism and possibly generate toxic intracellular forms of oligomeric Abeta. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Lab Oxidat Biol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Lab Oxidat Biol, Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. EM bush@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU PHS HHS [R01-1912686] NR 53 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 2004 VL 279 IS 15 BP 14673 EP 14678 DI 10.1074/jbc.M313003200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 808UT UT WOS:000220594700026 PM 14724276 ER PT J AU Zou, JH Barahmand-pour, F Blackburn, ML Matsui, Y Chansky, HA Yang, L AF Zou, JH Barahmand-pour, F Blackburn, ML Matsui, Y Chansky, HA Yang, L TI Survival motor neuron (SMN) protein interacts with transcription corepressor mSin3A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINAL MUSCULAR-ATROPHY; DISEASE GENE-PRODUCT; HISTONE DEACETYLASES; SINGLE NUCLEOTIDE; BINDING-PROTEIN; COMPLEX; REPRESSION; SIN3; METHYLTRANSFERASE; IDENTIFICATION AB Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. SMA results from loss of survival motor neuron (SMN) expression and subsequent death of motor neuron cells. To study SMN-associated proteins that may be involved in transcriptional regulation, we carried out immunoprecipitation experiments and found that the transcription corepressor mSin3A associates with SMN protein. Deletional analysis localized the mSin3A-interacting domain to the exon 6 region of SMN. When targeted to a promoter, wild-type SMN was able to repress transcription of a downstream luciferase reporter gene. This repression was relieved by treatment with the histone deacetylase inhibitor trichostatin A in a dose-dependent manner, and deletion of exon 6 abolished the ability of SMN to repress the reporter gene. Analysis of SMN missense mutations within the exon 6 region implicated the SMA-associated mutation Y272C with impairment of the mSin3A-interaction. Gel filtration experiments revealed that wild-type SMN, via the exon 6 region, forms protein supra-complexes exceeding 40,000 kDa in size, whereas the Y272C mutation may affect higher order protein assembly, as the mutant SMN was more abundant in smaller complexes. Together, these findings provide a potential mechanism by which lack of fully functional SMN protein is detrimental to motor neuron survival. C1 Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98108 USA. Univ Washington, Dept Med Hematol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. RP Yang, L (reprint author), Univ Washington, Dept Orthoped & Sports Med, 1660 S Columbian Way,GMR-151, Seattle, WA 98108 USA. EM lyang@u.washington.edu FU NCI NIH HHS [1R01CA90941] NR 35 TC 14 Z9 14 U1 0 U2 4 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 APR 9 PY 2004 VL 279 IS 15 BP 14922 EP 14928 DI 10.1074/jbc.M309218200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 808UT UT WOS:000220594700054 PM 14749338 ER PT J AU Mahimainathan, L Choudhury, GG AF Mahimainathan, L Choudhury, GG TI Inactivation of platelet-derived growth factor receptor by the tumor suppressor PTEN provides a novel mechanism of action of the phosphatase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTORS; MESANGIAL CELL-PROLIFERATION; INDUCED DNA-SYNTHESIS; PDGF-BETA-RECEPTOR; NEGATIVE REGULATION; PROTEIN-KINASE; C-FOS; MICE; AKT; ACTIVATION AB PTEN, mutated in a variety of human cancers, is a dual specificity protein phosphatase and also possesses D3-phosphoinositide phosphatase activity on phosphatidylinositol 3,4,5-tris-phosphate (PIP3), a product of phosphatidylinositol 3-kinase. This PIP3 phosphatase activity of PTEN contributes to its tumor suppressor function by inhibition of Akt kinase, a direct target of PIP3. We have recently shown that Akt regulates PDGF-induced DNA synthesis in mesangial cells. In this study, we demonstrate that expression of PTEN in mesangial cells inhibits PDGF-induced Akt activation leading to reduction in PDGF-induced DNA synthesis. As a potential mechanism, we show that PTEN inhibits PDGF-induced protein tyrosine phosphorylation with concomitant dephosphorylation and inactivation of tyrosine phosphorylated and activated PDGF receptor. Recombinant as well as immunopurified PTEN dephosphorylates autophosphorylated PDGF receptor in vitro. Expression of phosphatase deficient mutant of PTEN does not dephosphorylate PDGF-induced tyrosine phosphorylated PDGF receptor. Rather its expression increases tyrosine phosphorylation of PDGF receptor. Furthermore, expression of PTEN attenuated PDGF-induced signal transduction including phosphatidylinositol 3-kinase and Erk1/2 MAPK activities. Our data provide the first evidence that PTEN is physically associated with platelet-derived growth factor (PDGF) receptor and that PDGF causes its dissociation from the receptor. Finally, we show that both the C2 and tail domains of PTEN contribute to binding to the PDGF receptor. These data demonstrate a novel aspect of PTEN function where it acts as an effector for the PDGF receptor function and negatively regulates PDGF receptor activation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu OI /0000-0001-5077-3552 FU NIDDK NIH HHS [P50 DK 61597, R01 DK 55815] NR 64 TC 80 Z9 83 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 APR 9 PY 2004 VL 279 IS 15 BP 15258 EP 15268 DI 10.1074/jbc.M314328200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 808UT UT WOS:000220594700093 PM 14718524 ER PT J AU Walker, AK Shi, Y Blackwell, TK AF Walker, AK Shi, Y Blackwell, TK TI An extensive requirement for transcription factor IID-specific TAF-1 in Caenorhabditis elegans embryonic transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; TBP-LIKE FACTOR; CELL-CYCLE PROGRESSION; C-TERMINAL DOMAIN; IN-VIVO; GENE-EXPRESSION; P-TEFB; SINGLE BLASTOMERE; SAGA COMPLEXES; YEAST AB The general transcription factor TFIID sets the mRNA start site and consists of TATA-binding protein and associated factors (TAF(II)s), some of which are also present in SPT-ADA-GCN5 (SAGA)-related complexes. In yeast, results of multiple studies indicate that TFIID-specific TAFIIs are not required for the transcription of most genes, implying that intact TFIID may have a surprisingly specialized role in transcription. Relatively little is known about how TAFIIs contribute to metazoan transcription in vivo, especially at developmental and tissue-specific genes. Previously, we investigated functions of four shared TFIID/SAGA TAF(II)s in Caenorhabditis elegans. Whereas TAF-4 was required for essentially all embryonic transcription, TAF-5, TAF-9, and TAF-10 were dispensable at multiple developmental and other metazoan-specific promoters. Here we show evidence that in C. elegans embryos transcription of most genes requires TFIID-specific TAF-1. TAF-1 is not as universally required as TAF-4, but it is essential for a greater proportion of transcription than TAF-5, -9, or -10 and is important for transcription of many developmental and other metazoan-specific genes. TAF-2, which binds core promoters with TAF-1, appears to be required for a similarly substantial proportion of transcription. C. elegans TAF-1 overlaps functionally with the coactivator p300/CBP (CBP-1), and at some genes it is required along with the TBP-like protein TLF(TRF2). We conclude that during C. elegans embryogenesis TAF-1 and TFIID have broad roles in transcription and development and that TFIID and TLF may act together at certain promoters. Our findings imply that in metazoans TFIID may be of widespread importance for transcription and for expression of tissue-specific genes. C1 Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02115 USA. EM keith.blackwell@joslin.harvard.edu FU NIGMS NIH HHS [R01 GM062891] NR 71 TC 9 Z9 55 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 2004 VL 279 IS 15 BP 15339 EP 15347 DI 10.1074/jbc.M310731200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 808UT UT WOS:000220594700103 PM 14726532 ER PT J AU Woolf, CJ AF Woolf, CJ TI Dissecting out mechanisms responsible for peripheral neuropathic pain: Implications for diagnosis and therapy SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 1st Pfizer Science and Research Symposium CY JUN 24, 2003 CL Nagoya, JAPAN DE peripheral neuropathic pain; primary sensory neurons; ectopic excitability; phenotypic switch; sensory neuron loss; central sensitization; disinhibition ID DORSAL-ROOT GANGLION; SPINAL NERVE LIGATION; SENSORY NEURONS; UP-REGULATION; HYPERSENSITIVITY; ALLODYNIA; INJURY; CORD; RAT; CONTRIBUTES AB Peripheral neuropathic pain, that clinical pain syndrome associated with lesions to the peripheral nervous system, is characterized by positive and negative symptoms. Positive symptoms include spontaneous pain, paresthesia and dysthesia, as well as a pain evoked by normally innocuous stimuli (allodynia) and an exaggerated or prolonged pain to noxious stimuli (hyperalgesia/hyperpathia). The negative symptoms essentially reflect loss of sensation due to axon/neuron loss, the positive symptoms reflect abnormal excitability of the nervous system. Diverse disease conditions can result in neuropathic pain but the disease diagnosis by itself is not helpful in selecting the optimal pain therapy. Identification of the neurobiological mechanisms responsible for neuropathic pain is leading to a mechanism-based approach to this condition, which offers the possibility of greater diagnostic sensitivity and a more rational basis for therapy. We are beginning to move from an empirical symptom control approach to the treatment of pain to one targeting the specific mechanisms responsible. This review highlights some of the mechanisms underlying neuropathic pain and the novel targets they reveal for future putative analgesics. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St, Boston, MA 02129 USA. EM cwoolf@partners.org NR 33 TC 175 Z9 187 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 9 PY 2004 VL 74 IS 21 BP 2605 EP 2610 DI 10.1016/j.lfs.2004.01.003 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 807XW UT WOS:000220535200003 PM 15041442 ER PT J AU Cannon, CP Braunwald, E McCabe, CH Rader, DJ Rouleau, JL Belder, R Joyal, SV Hill, KA Pfeffer, MA Skene, AM AF Cannon, CP Braunwald, E McCabe, CH Rader, DJ Rouleau, JL Belder, R Joyal, SV Hill, KA Pfeffer, MA Skene, AM CA Pravastatin Atorvastatin Evaluatio TI Intensive versus moderate lipid lowering with statins after acute coronary syndromes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DENSITY-LIPOPROTEIN CHOLESTEROL; ACUTE MYOCARDIAL-INFARCTION; HEART-DISEASE; TASK-FORCE; AMERICAN-COLLEGE; PRAVASTATIN; ATHEROSCLEROSIS; PREVENTION; ATORVASTATIN AB BACKGROUND: Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. METHODS: We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). RESULTS: The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. CONCLUSIONS: Among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Montreal, Montreal, PQ, Canada. Bristol Myers Squibb Co, Princeton, NJ USA. Nottingham Clin Res Grp, Nottingham, England. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 27 TC 2564 Z9 2763 U1 6 U2 58 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 APR 8 PY 2004 VL 350 IS 15 BP 1495 EP 1504 DI 10.1056/NEJMoa040583 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 810CI UT WOS:000220682000005 PM 15007110 ER PT J AU Somers, MJ Daouk, GH McCluskey, RT AF Somers, MJ Daouk, GH McCluskey, RT TI Case 11-2004: A boy with rash, edema, and hypertension - Severe lupus nephritis with mixed proliferative and membranous features (World Health Organization class IV or V), with high activity and moderate chronicity indexes. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MYCOPHENOLATE-MOFETIL; RENAL-DISEASE; ERYTHEMATOSUS; CHILDHOOD; GLOMERULONEPHRITIS; ONSET; METAANALYSIS; PROGRESSION; CHILDREN C1 Childrens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat Nephrol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Somers, MJ (reprint author), Childrens Hosp, Dept Med, Div Nephrol, Boston, MA 02115 USA. NR 35 TC 1 Z9 1 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 APR 8 PY 2004 VL 350 IS 15 BP 1550 EP 1559 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 810CI UT WOS:000220682000012 PM 15071130 ER PT J AU Janne, PA Li, C Zhao, XJ Girard, L Chen, TH Minna, J Christiani, DC Johnson, BE Meyerson, M AF Janne, PA Li, C Zhao, XJ Girard, L Chen, TH Minna, J Christiani, DC Johnson, BE Meyerson, M TI High-resolution single-nucleotide polymorphism array and clustering analysis of loss of heterozygosity in human lung cancer cell lines SO ONCOGENE LA English DT Article DE lung neoplasm; non-small cell; small-cell carcinoma; loss of heterozygosity; single-nucleotide polymorphism ID GENOME-WIDE DETECTION; GENE-EXPRESSION; TUMOR PROGRESSION; BLADDER-CANCER; ADENOCARCINOMA; CARCINOMAS; CLASSIFICATION; PATTERNS; SURVIVAL; DNA AB Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. Hybridization to single-nucleotide polymorphism (SNP) arrays is an efficient method to detect genome-wide cancer LOH. Here, we survey LOH patterns in a panel of 33 human lung cancer cell lines using SNP array hybridization containing 1500 SNPs. We compared the LOH patterns generated by SNP array hybridization to those previously obtained by 399 microsatellite markers and find a high degree of concordance between the two methods. A novel informatics platform, dChipSNP, was used to perform hierarchical tumor clustering based on genome-wide LOH patterns. We demonstrate that this method can separate non-small-cell and small-cell lung cancer samples based on their shared LOH. Furthermore, we analysed seven human lung cancer cell lines using a novel 10000 SNP array and demonstrate that this is an efficient and reliable method of high-density allelotyping. Using this array, we identified small regions of LOH that were not detected by lower density SNP arrays or by standard microsatellite marker panels. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 446,44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [1K12CA87723-01, 2P30 CA06516-39, P50CA70907, R01CA92824] NR 30 TC 76 Z9 81 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 8 PY 2004 VL 23 IS 15 BP 2716 EP 2726 DI 10.1038/sj.onc.1207329 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 810OZ UT WOS:000220714900013 PM 15048096 ER PT J AU Tian, XJ Gotoh, T Tsuji, K Lo, EH Huang, S Feig, LA AF Tian, XJ Gotoh, T Tsuji, K Lo, EH Huang, S Feig, LA TI Developmentally regulated role for Ras-GRFs in coupling NMDA glutamate receptors to Ras, Erk and CREB SO EMBO JOURNAL LA English DT Article DE calcium signaling; NMDA glutamate receptors; Ras; Ras-GRF; Sos ID NUCLEOTIDE-RELEASING FACTOR; ELEMENT-BINDING PROTEIN; HIPPOCAMPAL-NEURONS; EXCHANGE FACTORS; CALCIUM INFLUX; IN-VIVO; ACTIVATION; KINASE; PHOSPHORYLATION; EXPRESSION AB p140 Ras-GRF1 and p130 Ras-GRF2 constitute a family of calcium/calmodulin-regulated guanine-nucleotide exchange factors that activate the Ras GTPases. Studies on mice lacking these exchange factors revealed that both p140 Ras-GRF1 and p130 Ras-GRF2 couple NMDA glutamate receptors (NMDARs) to the activation of the Ras/Erk signaling cascade and to the maintenance of CREB transcription factor activity in cortical neurons of adult mice. Consistent with this function for Ras-GRFs and the known neuroprotective effect of CREB activity, ischemia-induced CREB activation is reduced in the brains of adult Ras-GRF knockout mice and neuronal damage is enhanced. Interestingly, in cortical neurons of neonatal animals NMDARs signal through Sos rather than Ras-GRF exchange factors, implying that Ras-GRFs endow NMDARs with functions unique to mature neurons. C1 Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Feig, LA (reprint author), Tufts Univ, Sch Med, Dept Biochem, 136 Harrison Ave, Boston, MA 02111 USA. EM larry.feig@tufts.edu FU NIDDK NIH HHS [P30 DK034928, P30-DK34928] NR 42 TC 80 Z9 85 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 7 PY 2004 VL 23 IS 7 BP 1567 EP 1575 DI 10.1038/sj.emboj.7600151 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 819QC UT WOS:000221328700016 PM 15029245 ER PT J AU Gibson, CM Karha, J Murphy, SA de Lemos, JA Morrow, DA Giugliano, RP Roe, MT Harrington, RA Cannon, CP Antman, EM Califf, RM Braunwald, E AF Gibson, CM Karha, J Murphy, SA de Lemos, JA Morrow, DA Giugliano, RP Roe, MT Harrington, RA Cannon, CP Antman, EM Califf, RM Braunwald, E CA TIMI Study Grp TI Association of a pulsatile blood flow pattern on coronary arteriography and short-term clinical outcomes in acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; COMBINATION REPERFUSION THERAPY; TIMI FRAME COUNT; THROMBOLYTIC THERAPY; VELOCITY PATTERN; ARTERY PATENCY; TRIAL; ABCIXIMAB; PREDICTORS AB OBJECTIVES We hypothesized that recognition of systolic flow reversal (pulsatile flow) after thrombolytic administration on coronary angiography is associated with angiographic and electrocardiogram findings reflecting impaired myocardial perfusion, as well as poorer clinical outcomes. BACKGROUND Reversal of systolic flow on Doppler velocity wire recordings has been associated with impaired tissue perfusion on myocardial contrast echocardiography in the setting of myocardial infarction (MI). METHODS Patients (n = 1,062) with a patent infarct-related artery were drawn from the Thrombolysis In Myocardial Infarction (TIMI) 10, TIMI 14, and Integrillin and Tenecteplase acute MI. trials. RESULTS Pulsatile flow (systolic flow reversal with cessation of antegrade contrast-dye motion or frank reversal of contrast-dye motion during systole) at 60 min after fibrinolytic administration was present in 11.0% of patients. Pulsatile flow was associated with higher corrected TIMI frame counts (slower epicardial flow) (median 40.1 frames, IQ 30 of 63 vs. 30 frames, interquartile 22 of 42, p < 0.0001), a closed microvasculature (TIMI myocardial perfusion grades 0 of 1, 57.1% vs. 37.8%, p = 0.03) and less complete (greater than or equal to70%) ST-segment resolution (23.5% vs. 58.9%, p = 0.008). Patients with pulsatile flow had a higher risk of death or reinfarction at 30 days (10.3% vs. 5.0%, p = 0.019). After controlling for age, pulse, blood pressure, anterior MI location, epicardial flow, and creatine kinase, pulsatile flow remained associated with an increased risk of death/MI (odds ratio 3.1, p = 0.006). CONCLUSIONS A pulsatile pattern of flow is associated with impaired myocardial perfusion and poorer clinical outcomes independent of the velocity of antegrade flow in the epicardial artery. This simple and easily identifiable angiographic flow pattern may be useful in clinical risk stratification. (C) 2004 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX 75230 USA. Duke Clin Res Inst, Durham, NC USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org RI bashzar, salman/R-5748-2016 NR 19 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 7 PY 2004 VL 43 IS 7 BP 1170 EP 1176 DI 10.1016/j.jacc.2003.11.035 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809MI UT WOS:000220640400007 PM 15063425 ER PT J AU Olshansky, B Rosenfeld, LE Warner, AL Solomon, AJ O'Neill, G Sharma, A Platia, E Feld, GK Akiyama, T Brodsky, MA Greene, HL AF Olshansky, B Rosenfeld, LE Warner, AL Solomon, AJ O'Neill, G Sharma, A Platia, E Feld, GK Akiyama, T Brodsky, MA Greene, HL CA AFFIRM Investigators TI The atrial fibrillation follow-up investigation of rhythm management (AFFIRM) study - Approaches to control rate in atrial fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VENTRICULAR RATE CONTROL; HEART-RATE CONTROL; LOW-DOSE DILTIAZEM; EXERCISE CAPACITY; INTRAVENOUS DILTIAZEM; CALCIUM-ANTAGONISTS; ORAL VERAPAMIL; SINUS RHYTHM; DIGOXIN; EFFICACY AB OBJECTIVES We sought to evaluate approaches used to control rate, the effectiveness of rate control, and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. BACKGROUND The AFFIRM study showed that atrial fibrillation (AF) can be treated effectively with rate control and anticoagulation, but drug efficacy to control rate remains uncertain. METHODS Patients (n = 2,027) randomized to rate control in the AFFIRM study were given rate-controlling drugs by their treating physicians. Standardized rate-control efficacy criteria developed a priori included resting heart rate and 6-min walk tests and/or ambulatory electrocardiographic results. RESULTS Average follow-up was 3.5 +/- 1.3 years. Initial treatment included a beta-adrenergic blocker (beta-blocker) alone in 24%, a calcium channel blocker alone in 17%, digoxin alone in 16%, a beta-blocker and digoxin in 14%, or a calcium channel blocker and digoxin in 14% of patients. Overall rate control was achieved in 70% of patients given beta-blockers as the first drug (with or without digoxin), 54% with calcium channel blockers (with or without digoxin), and 58% with digoxin alone. Adequate overall rate control was achieved in 58% of patients with the first drug or combination. Multivariate analysis revealed an association between first drug class and several clinical variables. There were more changes to beta-blockers than to the other two-drug classes (p < 0.0001). CONCLUSIONS Rate control in AF is possible in the majority of patients with AF. Beta-blockers were the most effective drugs. To achieve the goal of adequate rate control in all patients, frequent medication changes and drug combinations were needed. (C) 2004 by the American College of Cardiology Foundation. C1 Univ Iowa, Iowa City, IA 52242 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Georgetown Univ, Med Ctr, Washington, DC 20057 USA. Sutter Inst Med Res, Sacramento, CA USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Rochester, Rochester, NY 14627 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Univ Washington, Seattle, WA 98195 USA. Axio Res Corp, Seattle, WA USA. RP Olshansky, B (reprint author), Univ Iowa Hosp & Clin, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM brian-olshansky@uiowa.edu FU NHLBI NIH HHS [N01-HC-55139] NR 40 TC 156 Z9 166 U1 1 U2 2 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 APR 7 PY 2004 VL 43 IS 7 BP 1201 EP 1208 DI 10.1016/j.jacc.2003.11.032 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809MI UT WOS:000220640400012 PM 15063430 ER PT J AU D'Amico, AV Moul, JW Carroll, PR Cote, K Sun, L Lubeck, D Renshaw, AA Loffredo, M Chen, MH AF D'Amico, AV Moul, JW Carroll, PR Cote, K Sun, L Lubeck, D Renshaw, AA Loffredo, M Chen, MH TI Intermediate end point for prostate cancer-specific mortality following salvage hormonal therapy for prostate-specific antigen failure SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; CAPSURE DATABASE; PROGRESSION; RECURRENCE; TRIAL AB Background: Whether the prostate-specific antigen (PSA) response to salvage hormonal therapy can act as an intermediate end point for prostate cancer-specific mortality (PCSM) remains unclear. Therefore, we evaluated whether PSA response, defined as the absolute value of the ratio of the rate of PSA change after salvage hormonal therapy to the rate of PSA change before salvage therapy, is associated with the time to PCSM following salvage hormonal therapy. Methods: A single-institution and two pooled multi-institution databases containing baseline, treatment, and follow-up information on men who received salvage hormonal therapy for PSA failure following surgery or radiation therapy from January 1, 1988, to January 1, 2002, formed the study (n = 199) and validation cohorts (n = 1255), respectively. The ability of PSA response and its constituents (i.e., pre-salvage hormonal therapy PSA slope and post-salvage hormonal therapy PSA slope) to predict time to PCSM following salvage hormonal therapy was assessed using Cox regression analysis. For illustrative purposes, PSA response was analyzed as a dichotomous variable with a breakpoint for the ratio of PSA response of 1. All statistical tests were two-sided. Results: PSA response was statistically significantly associated with time to PCSM following salvage hormonal therapy in both the study (P-Cox = .0014) and validation (P-Cox < .001) cohorts; however, its constituents were not (pre-salvage hormonal therapy PSA Slope: PCox-study = .97, PCox-validation = .57; post-salvage hormonal therapy PSA slope: PCox-study = .27, PCox-validation = .31). Patients with a PSA response that was less than or equal to 1 had a statistically significantly shorter time to PCSM than patients with a PSA response of greater than 1 in both the study (hazard ratio [HR] = 3.6, 95% confidence interval [CI] = 1.3 to 10.3; P-Cox = .01) and validation (HR = 12.8, 95% CI = 6.2 to 26.3; P-Cox < .001) cohorts. Conclusion: The PSA response to salvage hormonal therapy can serve as an intermediate end point for PCSM in patients with a rising PSA level following surgery or radiation therapy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, ASBI, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Urol Serv, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, ASBI, 75 Francis St,L2, Boston, MA 02115 USA. EM adamico@lroc.harvard.edu NR 24 TC 28 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 2004 VL 96 IS 7 BP 509 EP 515 DI 10.1093/jnci/djh086 PG 7 WC Oncology SC Oncology GA 810LF UT WOS:000220705100006 PM 15069112 ER PT J AU Barton, MB Morley, DS Moore, S Allen, JD Kleinman, KP Emmons, KM Fletcher, SW AF Barton, MB Morley, DS Moore, S Allen, JD Kleinman, KP Emmons, KM Fletcher, SW TI Decreasing women's anxieties after abnormal mammograms: A controlled trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POSITIVE SCREENING MAMMOGRAMS; BREAST-CANCER; FOLLOW-UP; PSYCHOLOGICAL CONSEQUENCES; PREDICTIVE-VALUE; OUTCOMES; DISTRESS; IMPACT; RECALL; STRESS AB Background: Few studies have evaluated interventions to decrease a woman's anxiety after she receives an abnormal mammogram (i.e., one with a recommendation for follow-up). We performed a controlled trial to compare the effects of both an immediate reading of mammograms (i.e., a radiology intervention) and of an educational intervention that taught skills to cope with anxiety on the psychological status of women whose mammograms were normal or abnormal. Methods: Eligible women (n = 8543) aged 39 years or older were recruited from seven mammography sites at the time of their scheduled mammography screening and assigned to receive no intervention, either the radiology or the educational intervention, or both interventions. We used the Impact of Events Scale (IES) and the Hopkins Symptom Checklist subscales for Anxiety (HSC-A) and Depression (HSC-D) in structured telephone interviews of 2844 women to assess the psychological status of all women with abnormal mammograms (excluding women diagnosed with breast cancer) and of a random sample of women with normal mammograms at 3 weeks and 3 months after their mammograms. All statistical tests were two-sided. Results: We obtained usable 3-week interviews for 2390 (84%) women. By the 3-week interview, 1037 (72.1%) of the 1439 interviewed women with abnormal mammograms had completed the recommended work-up and knew that their abnormal mammograms were false positives. Women with abnormal mammograms had higher IES and HSC-A scores (i.e., more anxiety) than women with normal mammograms (mean IES scores: 4.97 [95% confidence interval {CI} = 4.47 to 5.50] and 1.82 [95% CI = 1.51 to 2.14], respectively; P < .001; mean HSC-A scores: 1.14 [95% CI = 1.12 to 1.15] and 1.11 [95% CI = 1.09 to 1.13], respectively, P = .002). Among women with false-positive mammograms, those who had received the radiology intervention reported less anxiety than those who had not (mean IES scores: 4.42 [95% CI = 3.73 to 5.07] and 5.53 [95% CI = 4.82 to 6.28], respectively, P = .026). The educational intervention was not associated with any difference in psychological outcomes. Three months after the mammogram, by which time more than 80% of the women with abnormal results knew their mammograms to be false positives, anxiety levels of women with false-positive mammograms remained higher than those of women with normal mammograms (mean IES scores: 2.34 [95% CI = 1.99 to 2.69] and 1.15 [95% CI = 0.87 to 1.47], respectively, P < .001). Conclusion: Immediate reading of screening mammograms, but not an educational intervention targeting coping skills, was associated with less anxiety among women with false-positive mammograms 3 weeks after mammography. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Barton, MB (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Fl, Boston, MA 02215 USA. EM mary_barton@hms.harvard.edu RI Allen, Jennifer/M-2113-2015 FU NCI NIH HHS [1 R01 CA72570] NR 39 TC 85 Z9 85 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 2004 VL 96 IS 7 BP 529 EP 538 DI 10.1093/jnci/djh083 PG 10 WC Oncology SC Oncology GA 810LF UT WOS:000220705100009 PM 15069115 ER PT J AU Ma, J Giovannucci, E Pollak, M Leavitt, A Tao, YZ Gaziano, JM Stampfer, MJ AF Ma, J Giovannucci, E Pollak, M Leavitt, A Tao, YZ Gaziano, JM Stampfer, MJ TI A prospective study of plasma C-peptide and colorectal cancer risk in men SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR-I; ABERRANT CRYPT FOCI; COLON-CANCER; INSULIN-RESISTANCE; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; CALORIC RESTRICTION; GLUCOSE-TOLERANCE; DIETARY PATTERNS; FACTOR (IGF)-I AB Background: Colorectal cancer and type 2 diabetes share many risk factors, and hyperinsulinemia appears to be associated with an increased risk of colorectal cancer. We used the concentration of plasma C-peptide (an indicator of insulin production) to determine whether insulin and insulin resistance are associated with the risk of developing colorectal cancer. Methods: We conducted a nested case-control study in the Physicians' Health Study. Plasma samples were collected from 14 916 cancer-free men from August 1982 through December 1984. Plasma C-peptide concentration, measured with an enzyme-linked immunosorbent assay, was available for 176 case patients who developed incident colorectal cancer through December 31, 1995, and 294 age- and smoking status-matched control subjects. Information on four other insulin resistance-related factors at baseline was obtained. We used conditional logistic regression models to investigate associations. All statistical tests were two-sided. Results: Plasma C-peptide concentration was positively associated with age, body mass index (BMI), and number of insulin resistance-related factors, and it was inversely associated with fasting time before the blood draw, alcohol consumption, and vigorous exercise. An increased concentration of plasma C-peptide was statistically significantly associated with an increased risk of colorectal cancer (relative risk [RR] for the highest versus lowest quintile of plasma C-peptide = 2.7, 95% confidence interval [CI] = 1.2 to 6.2; P-trend = .047), after adjusting for age, smoking status, fasting, BMI, alcohol consumption, vigorous exercise, and aspirin assignment in the Physicians' Health Study. The association became even stronger when the analysis was further adjusted for factors related to insulin resistance other than insulin levels (RR for the highest versus lowest quintile = 3.4, 95% CI = 1.4 to 8.3; P-trend = .02) or when data from case patients who were diagnosed during the first 5 years of follow-up were excluded (RR for the highest versus the lowest quintile = 3.4, 95% CI = 1.3 to 8.8; P-trend = .03). Adjusting for plasma levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) did not materially change the results. There was apparent modification of risk by BMI, insulin resistance-related factors, or vigorous exercise. Conclusion: Elevated insulin production, as reflected by elevated concentrations of plasma C-peptide, may predict the risk of developing colorectal cancer, independently of BMI, factors related to insulin resistance, or levels of IGF-I and IGFBP-3. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Jewish Gen Hosp, Lady Davis Res Inst, Dept Med, Canc Prevent Res Unit, Montreal, PQ, Canada. Jewish Gen Hosp, Lady Davis Res Inst, Dept Oncol, Canc Prevent Res Unit, Montreal, PQ, Canada. McGill Univ, Montreal, PQ, Canada. VA Boston Healthcare Syst, Moss Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Ma, J (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU NCI NIH HHS [CA78293, CA42182, CA58684, CA70817, CA90598, R01 CA097193] NR 51 TC 190 Z9 200 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 2004 VL 96 IS 7 BP 546 EP 553 DI 10.1093/jnci/djh082 PG 8 WC Oncology SC Oncology GA 810LF UT WOS:000220705100011 PM 15069117 ER PT J AU Le, A Dasgupta, S Planque, S Paul, S Thiagarajan, P AF Le, A Dasgupta, S Planque, S Paul, S Thiagarajan, P TI Lupus-derived antiprothrombin autoantibodies from a V gene phage display library are specific for the kringle 2 domain of prothrombin SO BIOCHEMISTRY LA English DT Article ID MIDDLE-AGED MEN; ANTIPHOSPHOLIPID ANTIBODIES; PROTEIN-C; MYOCARDIAL-INFARCTION; ALPHA-THROMBIN; ACTIVATION; MEIZOTHROMBIN; BINDING; ANTICOAGULANTS; COAGULATION AB Autoantibodies to prothrombin are common in patients with systemic lupus erythematosus. Although their presence is a risk factor for thrombosis, neither their origin nor their precise role in inducing the procoagulant state is known. We have developed a phage-display antibody library from patients with systemic lupus erythematosus with antiprothrombin antibodies, and we have selected two single-chain Fv antibody fragments (ScFvs) by panning on a prothrombin-coated surface. In prothrombin activation assays using purified components, these antibodies promoted prothrombin activation. These ScFvs, termed AN78 and AN129, bound to immobilized prothrombin in a concentration-dependent specific manner but not to other anionic phospholipid binding proteins such as beta2-glycoprotein I or annexin V. Phosphatidylserine-bound prothrombin, but not soluble prothrombin, inhibited the binding suggesting that the epitope is available only on immobilized prothrombin. To localize the epitope, prothrombin was treated with thrombin or factor Xa and various prothrombin activation fragments were subsequently isolated and tested in ELISA with the ScFvs. Both AN78 and AN129 bound to prethrombin I (the fragment lacking the Gla domain and the first kringle domain), to fragment 1.2 (containing Gla and the two kringle domains only) and to fragment 2 but not to thrombin, thus localizing the cognate epitope to the kringle 2 domain in prothrombin. Analysis of the cDNA sequences of these antibodies show clustered mutational patterns in the complementarity determining region, suggesting that variable domains are the products of antigen-driven B cell clonal maturation. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Houston, TX USA. RP Thiagarajan, P (reprint author), VA Med Ctr, Mail 113,2002 Holcombe Blvd, Houston, TX 77030 USA. EM perumalt@bcm.tmc.edu FU NHLBI NIH HHS [HL 65096] NR 40 TC 4 Z9 4 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 6 PY 2004 VL 43 IS 13 BP 4047 EP 4054 DI 10.1021/bi030167f PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 808PC UT WOS:000220580000031 PM 15049712 ER PT J AU Vahanian, A Palacios, IF AF Vahanian, A Palacios, IF TI Percutaneous approaches to valvular disease SO CIRCULATION LA English DT Review DE valves; valvuloplasty; balloon; mitral valve ID MITRAL BALLOON VALVULOPLASTY; AORTIC-VALVE REPLACEMENT; FOLLOW-UP; INOUE BALLOON; HEART-DISEASE; TRANSCATHETER IMPLANTATION; METALLIC VALVULOTOME; COMMISSUROTOMY; STENOSIS; ECHOCARDIOGRAPHY C1 Hop Xavier Bichat, APHP, Dept Cardiol, F-75018 Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA USA. RP Vahanian, A (reprint author), Hop Xavier Bichat, APHP, Dept Cardiol, 46 Henri Huchard, F-75018 Paris, France. EM alec.vahanian@bch.ap-hop-paris.fr NR 59 TC 63 Z9 66 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 6 PY 2004 VL 109 IS 13 BP 1572 EP 1579 DI 10.1161/01.CIR.0000124794.1680.E3 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 809PI UT WOS:000220648200001 PM 15066960 ER PT J AU Williams, ML Hata, JA Schroder, J Rampersaud, E Petrofski, J Jakoi, A Milano, CA Koch, WJ AF Williams, ML Hata, JA Schroder, J Rampersaud, E Petrofski, J Jakoi, A Milano, CA Koch, WJ TI Targeted beta-adrenergic receptor kinase (beta ARK1) inhibition by gene transfer in failing human hearts SO CIRCULATION LA English DT Article DE myocytes; heart failure; gene therapy ID TRANSGENIC MICE; FAILURE; EXPRESSION; RESPONSIVENESS; STIMULATION; MYOCYTES AB Background - Failing human myocardium is characterized by an attenuated contractile response to beta-adrenergic receptor (betaAR) stimulation due to changes in this signaling cascade, including increased expression and activity of the beta-adrenergic receptor kinase (betaARK1). This leads to desensitization and downregulation of betaARs. Previously, expression of a peptide inhibitor of betaARK1 (betaARKct) has proven beneficial in several animal models of heart failure (HF). Methods and Results - To test the hypothesis that inhibition of betaARK1 could improve beta-adrenergic signaling and contractile function in failing human myocytes, the betaARKct was expressed via adenovirus-mediated (AdbetaARKct) gene transfer in ventricular myocytes isolated from hearts explanted from 10 patients with end-stage HF undergoing cardiac transplantation. AdbetaARKct also contained the marker gene, green fluorescent protein, and successful gene transfer was confirmed via fluorescence and immunoblotting. Compared with uninfected failing myocytes ( control), the velocities of both contraction and relaxation in the AdbetaARKct-treated cells were increased in response to the beta-agonist isoproterenol ( contraction: 57.5 +/- 6.6% versus 37.0 +/- 4.2% shortening per second, P < 0.05; relaxation: 43.8 &PLUSMN; 5.5% versus 27.5 &PLUSMN; 3.9% lengthening per second, P < 0.05). Fractional shortening was similarly enhanced (12.2 +/- 1.2% versus 8.0 +/- 0.9%, P < 0.05). Finally, adenylyl cyclase activity in response to isoproterenol was also increased in AdβARKct-treated myocytes. Conclusions - These results demonstrate that as in animal models of HF, expression of the βARKct can improve contractile function and β-adrenergic responsiveness in failing human myocytes. Thus, βARK1 inhibition may represent a therapeutic strategy for human HF. C1 Thomas Jefferson Univ, Jefferson Med Coll, Ctr Translat Med, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Koch, WJ (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Ctr Translat Med, 1025 Walnut St,Room 410, Philadelphia, PA 19107 USA. EM walter.koch@jefferson.edu FU NHLBI NIH HHS [R01 HL56205, R01 HL072183, HL59533] NR 18 TC 63 Z9 69 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 APR 6 PY 2004 VL 109 IS 13 BP 1590 EP 1593 DI 10.1161/01.CIR.0000125521.40985.28 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 809PI UT WOS:000220648200003 PM 15051637 ER PT J AU Si, ZH Madani, N Cox, JM Chruma, JJ Klein, JC Schon, A Phan, N Wang, L Biorn, AC Cocklin, S Chaiken, I Freire, E Smith, AB Sodroski, JG AF Si, ZH Madani, N Cox, JM Chruma, JJ Klein, JC Schon, A Phan, N Wang, L Biorn, AC Cocklin, S Chaiken, I Freire, E Smith, AB Sodroski, JG TI Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS TYPE-1 GP120; ATOMIC-STRUCTURE; GP41; CD4; BINDING; FUSION; CORECEPTOR; RETROVIRUS; PEPTIDE; NEUTRALIZATION AB When interacting with the CD4 receptor, the HIV gp120 envelope glycoprotein undergoes conformational changes that allow binding to the chemokine receptor. Receptor binding is proposed to lead to conformational changes in the gp41 transmembrane envelope glycoprotein involving the creation and/or exposure of a coiled coil consisting of three heptad repeat (HR) sequences. The subsequent interaction of the HR2 region of gp41 with this coiled coil results in the assembly of a six-helix bundle that promotes the fusion of the viral and target cell membranes. Here we show that CD4 binding to gp120 induces the formation and/or exposure of the gp41 HR1 coiled coil in a process that does not involve gp120 shedding and that depends on the proteolytic maturation of the gp160 envelope glycoprotein precursor. Importantly, BMS-806 and related HIV-1 entry inhibitors bind gp120 and block the CD4 induction of Hill exposure without significantly affecting CD4 binding. Moreover, these compounds do not disrupt gp120-chemokine receptor binding or the HR1-HR2 interaction within gp41. These studies thus define a receptor-induced conformational rearrangement of gp120-gp41 that is important for both CD4-dependent and CD4-independent HIV-1 entry and is susceptible to inhibition by low-molecular-weight compounds. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, DIV AIDS, Boston, MA 02115 USA. Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Drexel Univ, Coll Med, Dept Biochem, Philadelphia, PA 19102 USA. Drexel Univ, Coll Med, AJ Drexel Inst Basic & Appl Prot Sci, Philadelphia, PA 19102 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, JG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy FUnd Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [AI24755, AI28691, AI39420, P30 AI028691, R01 AI039420, R37 AI024755]; NIGMS NIH HHS [P01 GM056550, P01-GM56550]; NINDS NIH HHS [F32 NS043260, F32 NS43260M] NR 40 TC 164 Z9 172 U1 2 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 6 PY 2004 VL 101 IS 14 BP 5036 EP 5041 DI 10.1073/pnas.0307953101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 811GU UT WOS:000220761200057 PM 15051887 ER PT J AU Forsch, RA Queener, SF Rosowsky, A AF Forsch, RA Queener, SF Rosowsky, A TI Preliminary in vitro studies on two potent, water-soluble trimethoprim analogues with exceptional species selectivity against dihydrofolate reductase from Pneumocystis carinii and Mycobacterium avium SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TOXOPLASMA-GONDII; PNEUMONIA; AGENTS; SULFAMETHOXAZOLE; TRANSPLANTATION; PROPHYLAXIS; INHIBITORS; PIRITREXIM; AIDS AB 2,4-Diamino-5-[3',4'-dimethoxy-5'-(5-carboxy-1-pentynyl)]benzylpyrimidine (6) and 2,4-diamino-5-[3',4'-dimethoxy-5'(4-carboxyphenylethynyl)benzylpyrimidine (7) were synthesized from 2,4-diamino-5-(5'-iodo-3',4'-dimethoxybenzyl)pyrimidine (9) via a Sonogashira reaction with appropriate acetylenic esters followed by saponification, and were tested as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), Mycobacterium avium (Ma), and rat in comparison with the widely used antibacterial agent 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine (trimethoprim, TMP). The selectivity index (SI) for each compound was calculated by dividing its 50% inhibitory concentration (IC50) against rat DHFR by its IC50 against Pc, Tg, or Ma DHFR. The IC50 of 6 against Pc DHFR was 1.0 nM, with an SI of 5000. Compound 7 had an IC50 Of 8.2 nM against Ma DHFR, with an SI of 11000. By comparison, the IC50 of TMP was 12000 nM against Pc, 300 nM against Ma, and 180000 against rat DHFR. The potency and selectivity values of 6 and 7 were not as high against Tg as they were against Pc or Ma DHFR, but nonetheless exceeded those of TMP. Because of the outstanding selectivity of 6 against Pc and of 7 against Ma DHFR, these novel analogues may be viewed as promising leads for further structure-activity optimization. (C) 2004 Elsevier 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. EM andre_rosowsky@dfci.harvard.edu FU NIAID NIH HHS [R01-AI29904] NR 32 TC 54 Z9 55 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 5 PY 2004 VL 14 IS 7 BP 1811 EP 1815 DI 10.1016/j.bmcl.2003.12.103 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 806CE UT WOS:000220411200044 PM 15026078 ER PT J AU Willers, H Dahm-Daphi, J Powell, SN AF Willers, H Dahm-Daphi, J Powell, SN TI Repair of radiation damage to DNA SO BRITISH JOURNAL OF CANCER LA English DT Review DE ionising radiation; DNA double-strand breaks; repair; recombination; replication ID DOUBLE-STRAND BREAKS; HOMOLOGOUS RECOMBINATION; CELL-CYCLE; FANCONI-ANEMIA; CANCER; BRCA2; P53; RADIOSENSITIVITY; REPLICATION; FIDELITY AB DNA double-strand breaks constitute the most dangerous type of DNA damage induced by ionising radiation (IR). Accordingly, the resistance of cells to IR is modulated by three intimately related cellular processes: DNA repair, recombination, and replication. Significant discoveries in this field of research have been made over the last few years. A picture seems to be emerging in which perturbations of recombination in cancer cells are a more widespread cause of genomic instability than previously appreciated. Conversely, such cells may also be more sensitive to certain chemotherapeutic drugs and to IR. Thus, the alterations in recombination that promote carcinogenesis by causing genomic instability may also be the weakness of the tumours that arise in this setting, a concept which could hold great promise for the advancement of cancer treatment in the not too distant future. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Hamburg, Hosp Eppendorf, Dept Radiotherapy & Radiooncol, D-20246 Hamburg, Germany. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM snpowell@partners.org NR 33 TC 61 Z9 67 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 APR 5 PY 2004 VL 90 IS 7 BP 1297 EP 1301 DI 10.1038/sj.bjc.6601729 PG 5 WC Oncology SC Oncology GA 816QQ UT WOS:000221124800001 PM 15054444 ER PT J AU Draenert, R Le Gall, S Pfafferott, KJ Leslie, AJ Chetty, P Brander, C Holmes, EC Chang, SC Feeney, ME Addo, MM Ruiz, LD Ramduth, D Jeena, P Altfeld, M Thomas, S Tang, TH Verrill, CL Dixon, C Prado, JG Kiepiela, P Martinez-Picado, J Walker, BD Goulder, PJR AF Draenert, R Le Gall, S Pfafferott, KJ Leslie, AJ Chetty, P Brander, C Holmes, EC Chang, SC Feeney, ME Addo, MM Ruiz, LD Ramduth, D Jeena, P Altfeld, M Thomas, S Tang, TH Verrill, CL Dixon, C Prado, JG Kiepiela, P Martinez-Picado, J Walker, BD Goulder, PJR TI Immune selection for altered antigen processing leads to cytotoxic T lymphocyte escape in chronic HIV-1 infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE CD8 T cell responses; viral evolution; immune evasion; antigen presentation ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-I MOLECULES; FLANKING RESIDUES; CELL RESPONSES; ENDOPLASMIC-RETICULUM; THIMET OLIGOPEPTIDASE; PRESENTED PEPTIDES; MAXIMUM-LIKELIHOOD; FINE SPECIFICITY; INFLUENZA-VIRUS AB Mutations within cytotoxic T lymphocyte (CTL) epitopes impair T cell recognition, but escape mutations arising in flanking regions that alter antigen processing have not been defined in natural human infections. In human histocompatibility leukocyte antigen (HLA)-B57(+) HIV-infected persons, immune selection pressure leads to a mutation from alanine to proline at Gag residue 146 immediately preceding the NH2 terminus of a dominant HLA-B57-restricted epitope, ISPRTLNAW. Although N-extended wild-type or mutant peptides remained well-recognized, mutant virus-infected CD4 T cells failed to be recognized by the same CTL clones. The A146P mutation prevented NH2-ternnnal trimming of the optimal epitope by the endoplasmic reticulum aminopeptidase I. These results demonstrate that allele-associated sequence variation within the flanking region of CTL epitopes can alter antigen processing. Identifying such mutations is of major relevance in the construction of vaccine sequences. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. John Radcliffe Hosp, Dept Paediat, Nuffield Dept Med, Oxford OX1 3SY, England. Univ Natal, HIV Pathogenesis Program, Doris Duke Med Res Inst, ZA-4015 Durban, South Africa. Univ Natal, Dept Pediat, ZA-4015 Durban, South Africa. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Hosp Germans Trias I Pujol, irsiCaixa Fdn, Retrovirus Lab, Badalona 08916, Spain. Univ Oxford, Dept Zool, Oxford OX1 3PS, England. RP Goulder, PJR (reprint author), Univ Oxford, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM philip.goulder@clinical-medicine.oxford.ac.uk RI Martinez-Picado, Javier/G-5507-2012; OI Martinez-Picado, Javier/0000-0002-4916-2129; Brander, Christian/0000-0002-0548-5778; CHANG, SHIH-CHUNG/0000-0002-5015-8178; Holmes, Edward/0000-0001-9596-3552 FU NIAID NIH HHS [R01 AI028568, R01 AI046995, R01 AI28568, R01 AI46995-01A1]; PHS HHS [N01-A1-15442] NR 63 TC 213 Z9 217 U1 5 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 5 PY 2004 VL 199 IS 7 BP 905 EP 915 DI 10.1084/jem.20031982 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 811GS UT WOS:000220761000003 PM 15067030 ER PT J AU Qiu, JH Takagi, Y Harada, J Rodrigues, N Moskowitz, MA Scadden, DT Cheng, T AF Qiu, JH Takagi, Y Harada, J Rodrigues, N Moskowitz, MA Scadden, DT Cheng, T TI Regenerative response in ischemic brain restricted by p21(cip1/waf1) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE neural stem cells; cell cycle; p21; neural regeneration; brain ischemia ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; FOCAL CEREBRAL-ISCHEMIA; ADULT-RAT; SUBVENTRICULAR ZONE; DENTATE GYRUS; PROGENITOR PROLIFERATION; GROWTH-FACTOR; IN-VIVO; NEUROGENESIS AB Neural precursor cells from adults have exceptional proliferative and differentiative capability in vitro yet respond minimally to in vivo brain injury due to constraining mechanisms that are poorly defined. We assessed whether cell cycle inhibitors that restrict stem cell populations in other tissues may participate in limiting neural stem cell reactivity in vivo. The cyclin-dependent kinase inhibitor, p21(cip1/waf1) (p21), maintains hematopoietic stem cell quiescence, and we evaluated its role in the regenerative response of neural tissue after ischemic injury using the mice deficient in p21. Although steady-state conditions revealed no increase in primitive cell proliferation in p21-null mice, a significantly larger fraction of quiescent neural precursors was activated in the hippocampus and subventricular zone after brain ischemia. The hippocampal precursors migrated and differentiated into a higher number of neurons after injury. Therefore, p21 is an intrinsic suppressor to neural regeneration after brain injury and may serve as a common molecular regulator restricting proliferation among stem cell pools from distinct tissue types. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02129 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Radiat Oncol, Sch Med, Pittsburgh, PA 15213 USA. RP Cheng, T (reprint author), Hillman Canc Ctr, Off Ste 2 42E, Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM chengtao@pitt.edu RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [HL65909, HL70561, R01 HL065909, R01 HL070561]; NIDDK NIH HHS [DK02761, DK50234, K08 DK002761, R01 DK050234]; NINDS NIH HHS [P50 NS10828, P50 NS010828] NR 49 TC 34 Z9 38 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 5 PY 2004 VL 199 IS 7 BP 937 EP 945 DI 10.1084/jem.20031385 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 811GS UT WOS:000220761000006 PM 15067031 ER PT J AU Akiyama, M Yamada, O Hideshima, T Yanagisawa, T Yokoi, K Fujisawa, K Eto, Y Yamada, H Anderson, KC AF Akiyama, M Yamada, O Hideshima, T Yanagisawa, T Yokoi, K Fujisawa, K Eto, Y Yamada, H Anderson, KC TI TNF alpha induces rapid activation and nuclear translocation of telomerase in human lymphocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE telomerase; hTERT; nuclear translocation; TNF alpha; NF-kappa B; Akt ID FACTOR-KAPPA-B; MULTIPLE-MYELOMA; PROTEIN; PHOSPHORYLATION; APOPTOSIS; TARGET; CELLS AB Maintenance of telomeres regulates chromosomal stability and cellular mitosis through a checkpoint mechanism. Continuous cell proliferation requires telomerase to maintain chromosomal stability and to counteract the cellular mitotic clock. Importantly, nuclear expression of telomerase activity is required for elongation of telomere sequences. In this study, we show that tumor necrosis factor alpha (TNFalpha) induces telomerase activity in the cytoplasm of peripheral blood lymphocytes (PBL) at 60 min, followed by translocation of activated telomerase to the nucleus at 120 min. Conversely, the phosphoinositol 3-kinase (PI3K) inhibitor wortmannin blocks TNFalpha-induced activation of telomerase, whereas the specific NF-kappaB translocation inhibitor SN-50 blocks TNFalpha-induced nuclear translocation of activated telomerase. These studies suggest that activation and nuclear translocation of telomerase are regulated by PI3K/Akt/NF-kappaB signaling pathways in PBL. (C) 2004 Elsevier Inc. All rights reserved. C1 Jikei Univ, Sch Med, Dept Pediat, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Mol Genet, Inst DNA Med, Tokyo 1058461, Japan. Tokyo Womens Med Univ, Dept Hematol, Tokyo 1628666, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Akiyama, M (reprint author), Jikei Univ, Sch Med, Dept Pediat, Tokyo 1058461, Japan. EM makiyama@jikei.ac.jp FU PHS HHS [P0-1 78378, R0-1 50947] NR 14 TC 36 Z9 39 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 2 PY 2004 VL 316 IS 2 BP 528 EP 532 DI 10.1016/j.bbrc.2004.02.080 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 804YE UT WOS:000220333200034 PM 15020249 ER PT J AU Carlson, CJ White, MF Rondinone, CM AF Carlson, CJ White, MF Rondinone, CM TI Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE signal transduction; c-Jun NH2 terminal kinase; 3T3-L1 adipocytes; insulin; cellular localization; PP2A; okadaic acid ID INSULIN-RECEPTOR SUBSTRATE-1; PROTEIN-KINASE-B; SERINE/THREONINE PHOSPHORYLATION; TYROSINE PHOSPHORYLATION; MEDIATE INSULIN; RAT ADIPOCYTES; PHOSPHATASE 2A; S6 KINASE; DEGRADATION; RESISTANCE AB Insulin signaling can be negatively regulated by phosphorylation of serine 307 of the insulin receptor substrate (IRS)-1. Rapamycin, an inhibitor of the kinase mTOR, can prevent serine 307 phosphorylation and the development of insulin resistance. We further investigated the role of mTOR in regulating serine 307 phosphorylation, demonstrating that serine 307 phosphorylation in response to insulin. anisomycin, or tumor necrosis factor was quantitatively and temporally associated with activation of mTOR and could be inhibited by rapamycin. Amino acid stimulation activated mTOR and resulted in IRS-1 serine 307 phosphorylation without activating PKB or JNK. Okadaic acid, an inhibitor of the phosphatase PP2A, activated mTOR and stimulated the phosphorylation of serine 307 in a rapamycin-sensitive manner, indicating serine 307 phosphorylation requires mTOR activity but not PP2A, suggesting that mTOR itself may be responsible for phosphorylating serine 307. Finally, we demonstrated that serine 307 phosphorylated IRS-1 is detected primarily in the cytosolic fraction. (C) 2004 Elsevier Inc. All rights reserved. C1 Abbott Labs, Global Pharmaceut Res Div, Insulin Signaling, Metab Dis Div, Abbott Pk, IL 60064 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. RP Rondinone, CM (reprint author), Abbott Labs, Global Pharmaceut Res Div, Insulin Signaling, Metab Dis Div, Abbott Pk, IL 60064 USA. EM Cristina.Rondinone@abbott.com NR 33 TC 91 Z9 93 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 2 PY 2004 VL 316 IS 2 BP 533 EP 539 DI 10.1016/j.bbrc.2004.02.082 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 804YE UT WOS:000220333200035 PM 15020250 ER PT J AU Jiang, YF Minet, E Zhang, ZX Silver, PA Bai, M AF Jiang, YF Minet, E Zhang, ZX Silver, PA Bai, M TI Modulation of interprotomer relationships is important for activation of dimeric calcium-sensing receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METABOTROPIC GLUTAMATE-RECEPTOR; INTERMOLECULAR INTERACTIONS; BRAIN-FUNCTION; SWISS-MODEL; DIMERIZATION; DOMAIN; MUTAGENESIS; INTERFACE; CELLS; SITE AB The extracellular calcium-sensing receptor (CaR) forms a disulfide-linked dimer through cysteine residues within its N-terminal extracellular domain (ECD). However, these disulfide linkages are dispensable for the formation of the dimeric CaR and for the functional reconstitution of two inactive CaRs. In this study, using molecular modeling, mutagenesis, and biochemical and biophysical analyses, we examined the importance of two leucine residues, Leu-112 and Leu-156, in the ECD of the CaR for the non-covalent dimerization and functional reconstitution. We found that the mutant receptor carrying L112S and L156S still exists mostly as a covalently linked dimer and has a significantly higher apparent affinity for calcium than the wild-type receptor. However, a combination of four mutations, L112S, L156S, C129S, and C131S, significantly reduces receptor dimerization and markedly inactivates the CaR. We also found that L112S and L156S mediate the non-covalent intermolecular interactions important for functional reconstitution. Because mutating either the two cysteines or the two leucines enhances the apparent ligand affinity of the CaR, it is likely that the changes in intermolecular relationships between two receptor protomers linked by these leucines and cysteines are essential for receptor activation. Moreover, these mutations are unlikely to have negative effects on the secondary structure of each protomer of the dimeric receptor. Thus, the detrimental effects of the combined mutations on the function of the CaR further suggest that CaR dimerization through its ECD is essential for the formation of a functional tertiary structure of the CaR. C1 Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Bai, M (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, 221 Longwood Ave, Boston, MA 02115 USA. EM mbai@rics.bwh.harvard.edu FU NIDDK NIH HHS [DK54934] NR 23 TC 21 Z9 21 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 APR 2 PY 2004 VL 279 IS 14 BP 14147 EP 14156 DI 10.1074/jbc.M307422200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 807CB UT WOS:000220478500105 PM 14729680 ER PT J AU Williams, ME AF Williams, ME TI Promise or peril? Impact of the Medicare drug benefit on the ESRD population SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article ID CHRONIC-HEMODIALYSIS PATIENTS; PRESCRIPTION DRUGS; DIALYSIS PATIENTS; HYPERTENSION; DISEASE; PATHOPHYSIOLOGY; EXPENDITURES; HEALTH C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Williams, ME (reprint author), Harvard Univ, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 27 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2004 VL 11 IS 2 BP 228 EP 233 DI 10.1053/j.arrt.2004.02.002 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 863NU UT WOS:000224569500015 PM 15216496 ER PT J AU Hasty, P Vijg, J AF Hasty, P Vijg, J TI Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity SO AGING CELL LA English DT Editorial Material DE accelerated aging; genome maintenance; mouse models; progeroid syndromes ID TRANSCRIPTION FACTOR FOXO3A; WERNER-SYNDROME HELICASE; OXIDATIVE STRESS; DNA-REPAIR; LIFE-SPAN; SOMATIC MUTATIONS; NATURAL-SELECTION; MUTANT MICE; CHROMOSOME-ABERRATIONS; TELOMERE DYSFUNCTION AB Investigating the molecular basis of aging has been difficult, primarily owing to the pleiotropic and segmental nature of the aging phenotype. There are many often interacting symptoms of aging, some of which are obvious and appear to be common to every aged individual, whereas others affect only a subset of the elderly population. Although at first sight this would suggest multiple molecular mechanisms of aging, there now appears to be almost universal consensus that aging is ultimately the result of the accumulation of somatic damage in cellular macromolecules, with reactive oxygen species likely to be the main damage-inducing agent. What remains significant is unravelling how such damage can give rise to the large variety of aging symptoms and how these can be controlled. Although humans, with over a century of clinical observations, remain the obvious target of study, the mouse, with a relatively short lifespan, easy genetic accessibility and close relatedness to humans, is the tool par excellence to model aging-related phenotypes and test strategies of intervention. Here we present the argument that mouse models with engineered defects in genome maintenance systems are especially important because they often exhibit a premature appearance of aging symptoms. Confirming studies on human segmental progeroid syndromes, most of which are based on heritable mutations in genes involved in genome maintenance, the results thus far obtained with mouse models strongly suggest that lifespan and onset of aging are directly related to the quality of DNA metabolism. This may be in keeping with the recent discovery of a possible 'universal survival' pathway that improves antioxidant defence and genome maintenance and simultaneously extends lifespan in the mouse and several invertebrate species. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Hasty, P (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. EM hastye@uthscsa.edu; vijg@uthscsa.edu FU NCI NIH HHS [R01 CA76317-05A1]; NIA NIH HHS [AG20438, AG 17242]; NIEHS NIH HHS [ES11044] NR 79 TC 46 Z9 52 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2004 VL 3 IS 2 BP 55 EP 65 DI 10.1111/j.1474-9728.2004.00082.x PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 812GN UT WOS:000220828100004 PM 15038819 ER PT J AU Hasty, P Vijg, J AF Hasty, P Vijg, J TI Rebuttal to Miller: "Accelerated aging": a primrose path to insight?' SO AGING CELL LA English DT Editorial Material ID MOUSE; GENES C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Hasty, P (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. EM vijg@uthscsa.edu NR 9 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2004 VL 3 IS 2 BP 67 EP 69 DI 10.1111/j.1474-9728.2004.00087.x PG 3 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 812GN UT WOS:000220828100005 PM 15038820 ER PT J AU Cavacini, L Posner, M AF Cavacini, L Posner, M TI Native HIV type 1 virion surface structures: Relationships between antibody binding and neutralization or lessons from the viral capture assay SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; RECEPTOR-BINDING; ADHESION RECEPTORS; MEMBRANE-PROTEINS; EPITOPE EXPOSURE; EPITHELIAL-CELLS; IMMUNOGLOBULIN-A; IN-VITRO AB Despite a vigorous antibody response following HIV-1 infection, antibodies which neutralize primary isolates tend to be of low titer or sporadic. Similarly, antibodies produced in response to HIV-1 vaccines in human and animals react with HIV but, only on occasion, do these antibodies neutralize primary isolates. The failure of the immune system to respond in an effective manner is related to the inherent structural properties of the HIV-1 envelope expressed on the native virion and the pathogenesis of HIV infection. Identification of effective antibody interactions with HIV, as judged by inhibition of virus, is crucial for the development of broadly effective HIV vaccines and immune therapeutics. It has been proposed that antibodies must bind and neutralize virus to be effective at controlling HIV infection. We propose that this hypothesis may limit the identification of effective antibodies that are desperately needed given the difficulty in preventing and treating HIV. We provide evidence that the viral capture assay (VCA) is an important adjunct to the study of antibody interactions with primary isolate virus. Further, we propose that antibodies that are ineffective in traditional neutralization assays may also be effective at limiting viral spread and preventing viral infection. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Cavacini, L (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,BL556, Boston, MA 02215 USA. EM lcavacin@bidmc.harvard.edu FU NIAID NIH HHS [AI26826, AI45320] NR 63 TC 17 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2004 VL 20 IS 4 BP 435 EP 441 DI 10.1089/088922204323048186 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 818KI UT WOS:000221243600011 PM 15157362 ER PT J AU Samet, JH Horton, NJ Meli, S Freedberg, KA Palepu, A AF Samet, JH Horton, NJ Meli, S Freedberg, KA Palepu, A TI Alcohol consumption and antiretroviral adherence among HIV-infected persons with alcohol problems SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE HIV; adherence; alcohol; highly active antiretroviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONGITUDINAL DATA-ANALYSIS; SELF-REPORTED ADHERENCE; DRUG-USERS; CAGE QUESTIONNAIRE; THERAPY ADHERENCE; VIRAL SUPPRESSION; BRIEF PHYSICIAN; PRIMARY-CARE; OUTCOMES AB Background: Alcohol abuse has been associated with poor adherence to highly active antiretroviral therapy (HAART). We examined the relative importance of varying levels of alcohol consumption on adherence in HIV-infected patients with a history of alcohol problems. Methods: We surveyed 349 HIV-infected persons with a history of alcohol problems at 6-month intervals. Of these subjects, 267 were taking HAART at one or more time periods during the 30-month follow-up period. Interviews assessed recent adherence to HAART and past month alcohol consumption, defined as "none", "moderate", and "at risk". We investigated the relationship between adherence to HAART and alcohol consumption at baseline and at each subsequent 6-month follow-up interval using multivariable longitudinal regression models, while controlling for potential confounders. Results: Among the 267 HIV-infected persons with a history of alcohol problems who were receiving HAART, alcohol consumption was the most significant predictor of adherence (p < 0.0001), with better adherence being associated with recent abstinence from alcohol, compared with at-risk level usage (odds ratio = 3.6, 95% confidence interval = 2.1-6.2) or compared with moderate usage (odds ratio = 3.0, 95% confidence interval = 2.0-4.5). Conclusions: Any alcohol use among HIV-infected persons with a history of alcohol problems is associated with worse HAART adherence. Addressing alcohol use in HIV-infected persons may improve antiretroviral adherence and ultimately clinical outcomes. C1 Boston Univ, Sch Med, CARE Unit, Gen Internal Med Sect,Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. Smith Coll, Dept Math, Northampton, MA 01063 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Univ British Columbia, Ctr Hlth Evaluat & Outcome Sci, St Pauls Hosp, Dept Med, Vancouver, BC V5Z 1M9, Canada. RP Samet, JH (reprint author), Boston Med Ctr, 91 E Concord St,Suite 200, Boston, MA 02118 USA. EM jsamet@bu.edu RI Horton, Nicholas/A-2493-2008; OI Samet, Jeffrey/0000-0002-0897-3400; Palepu, Anita/0000-0002-7881-4800; Horton, Nicholas/0000-0003-3332-4311 FU NCRR NIH HHS [M01 RR000533, M01 RR00533]; NIAAA NIH HHS [R01-AA10870, R01 AA010870, R01 AA011785, R01-AA11785, R01-AA13766] NR 43 TC 136 Z9 137 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2004 VL 28 IS 4 BP 572 EP 577 DI 10.1097/01.ALC.0000122103.74491.78 PG 6 WC Substance Abuse SC Substance Abuse GA 815UX UT WOS:000221068300008 PM 15100608 ER PT J AU Masoudi, FA Plomondon, ME Magid, DJ Sales, A Rumsfeld, JS AF Masoudi, FA Plomondon, ME Magid, DJ Sales, A Rumsfeld, JS TI Renal insufficiency and mortality from acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; NATIONAL REGISTRY; FAILURE; DISEASE; DYSFUNCTION; OUTCOMES; SURVIVAL; SURGERY; MILD AB Background Although there is accumulating evidence that renal insufficiency is an independent risk factor for mortality after acute myocardial infarction (AMI), it is not known whether renal dysfunction is associated with an increased mortality rate after a broad range of acute coronary syndromes, including unstable angina. Methods We examined consecutive patients from 24 Veterans Affairs hospitals with confirmed AMI or unstable angina between March 1998 and February 1999, who were categorized into groups according to estimated glomerular filtration rate (GFR). Multivariable regression was used to assess the independent association between GFR and the 7-month mortality rate, adjusting for differences in patient characteristics and treatment. Results Of the 2706 patients, 436 (16%) had normal renal function (GFR >90 mL/min/1.73 m(2)), 1169 (43%) had mild renal insufficiency (GFR 60-89 mL/min/1.73 m(2)), 864 (32%) had moderate renal insufficiency (GFR 30-59 mL/ min/1.73 m(2)), and 237 (9%) had severe renal insufficiency (GFR <30 mL/min/1.73 m(2)). Patients with renal insufficiency were less likely to undergo coronary angiography or to receive aspirin or beta-blockers of discharge. In multivariable models, renal insufficiency was associated with a higher odds of death (mild renal insufficiency: odds ratio [OR] = 1.76; 95% Cl, 0.93-3.33; moderate renal insufficiency: OR = 272; 95% Cl, 1.43-5.15; and severe renal insufficiency: OR = 6.18; 95% Cl, 3.09-12.36; all compared with normal renal function). The associations between renal insufficiency and mortality rate were similar in both the AMI and unstable angina subgroups (P value for interaction =.45). Conclusions Renal insufficiency is common and is associated with higher risks for death in patients with a broad range of ACS at presentation. Future efforts should be dedicated to determining whether more aggressive treatment will optimize outcomes in this patient population. C1 Denver Hlth Med Ctr, Div Cardiol, Dept Med, Denver, CO 80204 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO USA. Denver VA Med Ctr, Dept Med, Denver, CO USA. Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA USA. RP Masoudi, FA (reprint author), Denver Hlth Med Ctr, Div Cardiol, Dept Med, MC0960,777 Bannock St, Denver, CO 80204 USA. EM fred.mosoudi@uchsc.edu OI Sales, Anne/0000-0001-9360-3334 FU NIA NIH HHS [K08-AG01011] NR 29 TC 71 Z9 81 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2004 VL 147 IS 4 BP 623 EP 629 DI 10.1016/j.ahj.2003.12.010 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 895XG UT WOS:000226896900010 PM 15077076 ER PT J AU Servoss, SJ Wan, Y Snapinn, SM DiBattiste, PM Zhao, XQ Theroux, P Jang, IK Januzzi, JL AF Servoss, SJ Wan, Y Snapinn, SM DiBattiste, PM Zhao, XQ Theroux, P Jang, IK Januzzi, JL TI Tirofiban therapy for patients with acute coronary syndromes and prior coronary artery bypass grafting in the PRISM-PLUS trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PLATELET GLYCOPROTEIN IIB/IIIA; ELEVATION MYOCARDIAL-INFARCTION; ISCHEMIC SYNDROME MANAGEMENT; UNSTABLE ANGINA; RECEPTOR INHIBITION; RISK SCORE; OUTCOMES; BENEFIT; THROMBOLYSIS; SYMPTOMS AB The role of glycoprotein IIb/IIIa platelet receptor antagonist therapy for patients with an acute coronary syndrome (ACS) and a history of coronary artery bypass grafting (CABG) remains incompletely defined. We examined the outcomes of patients with an ACS and prior CABG who were treated with tirofiban versus placebo among subjects with prior CABG in the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial. Of 1,570 patients treated with tirofiban plus heparin (n = 773) or heparin alone (n = 797), 231 had prior CABG. Compared with patients without prior CABG, those with prior CABG were more likely to have risk factors for a complicated ACS course, including severe coronary artery disease and heart failure (all p < 0.0001), typically had clinical predictors of benefit from tirofiban, such as ST-segment depression (p = 0.01) or a TIMI risk score; greater than or equal to 4 (p < 0.001), and were more likely to die or have a myocardial infarction or refractory ischemia at all time points examined (p < 0.0001). Among patients with prior CABG, decreases in the incidence of death, myocardial infarction, or refractory ischemia with tirofiban and heparin versus heparin alone were noted at 7 and 30 days (7 days: 16.9% vs 29.0%, p = 0.035; 30 days: 25.0% vs 40.2%, p = 0.015). Trends toward a decrease in death, myocardial infarction, and refractory ischemia with tirofiban and heparin versus heparin alone in the prior CABG subgroup were noted at 48 hours and 180 days (48 hours: 6.5% vs 14.0%, p = 0.09; 180 days: 37.1% vs 48.6%, p = 0.057). Bleeding rates were similar in patients with and without prior CABG. Tirofiban was well tolerated and tended to decrease the considerable risk for ischemic ACS complications in patients with prior CABG. (C) 2004 by Excerpta Medica, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Merck Res Labs, W Point, PA USA. Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Montreal Heart Inst, Div Cardiol, Montreal, PQ H1T 1C8, Canada. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Bulfinch 019,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 14 TC 15 Z9 18 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2004 VL 93 IS 7 BP 843 EP 847 DI 10.1016/j.amjcard.2003.12.021 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 807HW UT WOS:000220493600007 PM 15050486 ER PT J AU Ferencik, M Abbara, S Hoffmann, U Cury, RC Brady, TJ Achenbach, S AF Ferencik, M Abbara, S Hoffmann, U Cury, RC Brady, TJ Achenbach, S TI Left ventricular thin-point detection using multidetector spiral computed tomography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEART; CT AB We systematically studied the thickness of the myocardium in the left ventricular apical region in patients without a history of myocardial infarction and with no hemodynamically significant coronary artery disease, using contrast-enhanced multidetector spiral computed tomography with submillimeter collimation. We confirmed previous pathology data and reliably detected a small confined region of the normal apical myocardium with a thickness of less than or equal to3 mm, i.e., the left ventricular thin point. (C) 2004 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Ctr Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Internal Med 2, Erlangen, Germany. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM maros_ferencik@hms.harvard.edu NR 10 TC 4 Z9 5 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 APR 1 PY 2004 VL 93 IS 7 BP 949 EP 951 DI 10.1016/j.amjcard.2003.12.033 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 807HW UT WOS:000220493600030 PM 15050509 ER PT J AU Mozaffarian, D Pischon, T Hankinson, SE Rifai, N Joshipura, K Willett, WC Rimm, EB AF Mozaffarian, D Pischon, T Hankinson, SE Rifai, N Joshipura, K Willett, WC Rimm, EB TI Dietary intake of trans fatty acids and systemic inflammation in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE trans Fatty acids; diet; inflammation; tumor necrosis factor receptors; women ID TUMOR-NECROSIS-FACTOR; CORONARY-HEART-DISEASE; INTERLEUKIN-6 GENE POLYMORPHISM; FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; INSULIN-RESISTANCE; FACTOR-ALPHA; ENDOTHELIAL-CELLS; SOLUBLE RECEPTORS; UNITED-STATES AB Background: trans Fatty acid (TFA) intake predicts risks of coronary artery disease and diabetes. Systemic inflammation may be involved in the pathogenesis of such conditions; however, relations between TFA intake and systemic inflammation are not well established. Objective: We investigated the relations between TFA intake and inflammatory markers. Design: In 823 generally healthy women in the Nurses' Health Study I and II, concentrations of soluble tumor necrosis factor a receptors 1 and 2 (sTNF-R1, sTNF-R2), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured. Usual dietary intakes assessed from 2 semiquantitative food-frequency questionnaires were averaged for each subject. Results: In age-adjusted analyses, TFA intake was positively associated with sTNF-R1 and sTNF-R2 (P for trend < 0.001 for each): sTNF-R1 and sTNF-R2 concentrations were 10% (+ 108 pg/mL; 95% CI: 50,167 pg/mL) and 12% (+258 pg/mL; 138,377 pg/mL) higher, respectively, in the highest intake quintile than m the lowest. These associations were not appreciably altered by adjustment for body mass index, smoking, physical activity, aspirin and nonsteroidal antiinflammatory drug use, alcohol consumption, and intakes of saturated fat, protein, n-6 and n-3 fatty acids, fiber, and total energy. Adjustment for serum lipid concentrations partly attenuated these associations, which suggests that they may be partly mediated by effects of TFAs on serum lipids. TFA intake was not associated with IL-6 or CRP concentrations overall but was positively associated with IL-6 and CRP in women with higher body mass index (P for interaction = 0.03 for each). Conclusions: TFA intake is positively associated with markers of systemic inflammation in women. Further investigation of the influences of TFAs on inflammation and of implications for coronary disease, diabetes, and other conditions is warranted. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Humboldt Univ, Franz Volhard Clin, Charite, D-1086 Berlin, Germany. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. RP Mozaffarian, D (reprint author), 665 Huntington Ave,Bldg 2,Room 315, Boston, MA 02115 USA. EM darymd@hotmail.com RI Mozaffarian, Dariush/B-2276-2008 FU NCI NIH HHS [CA40356, CA50385, R01 CA040356, R01 CA050385]; NHLBI NIH HHS [K08 HL075628, HL24074, HL34594, R01 HL034594]; NIDCR NIH HHS [DE12102, R01 DE012102]; NIDDK NIH HHS [DK07703, DK46200, P30 DK046200, T32 DK007703, T32DK07703] NR 53 TC 209 Z9 231 U1 3 U2 15 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2004 VL 79 IS 4 BP 606 EP 612 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 807IZ UT WOS:000220496500013 PM 15051604 ER PT J AU Isomoto, H Saenko, VA Kanazawa, Y Nishi, Y Ohtsuru, A Inoue, K Akazawa, Y Takeshima, F Omagari, K Miyazaki, M Mizuta, Y Murata, I Yamashita, S Kohno, S AF Isomoto, H Saenko, VA Kanazawa, Y Nishi, Y Ohtsuru, A Inoue, K Akazawa, Y Takeshima, F Omagari, K Miyazaki, M Mizuta, Y Murata, I Yamashita, S Kohno, S TI Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BARRETTS-ESOPHAGUS; ACID; METAPLASIA; CHEMOKINES; PREVALENCE; APOPTOSIS; DIAGNOSIS; JUNCTION; RECEPTOR; TUMORS AB OBJECTIVE: Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression. METHODS: We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1. RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells. CONCLUSIONS: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD. C1 Nagasaki Univ, Sch Med, Shunkaikai Inoue Hosp, Dept Internal Med 2, Nagasaki 852, Japan. Nagasaki Univ, Sch Med, Shunkaikai Inoue Hosp, Dept Int Hlth & Radiat Res, Nagasaki 852, Japan. Nagasaki Univ, Sch Med, Shunkaikai Inoue Hosp, Dept Mol Med, Nagasaki 852, Japan. RP Massachusetts Gen Hosp, Gastrointestinal Unit, Jackson 706,55 Fruit St, Boston, MA 02114 USA. OI Yamashita, Shunichi/0000-0001-6399-6261 NR 33 TC 52 Z9 55 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2004 VL 99 IS 4 BP 589 EP 597 DI 10.1111/j.1572-0241.2004.04110.x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 816KF UT WOS:000221108100005 PM 15089887 ER PT J AU Shi, CW Gralnek, IM Dulai, GS Towfigh, A Asch, S AF Shi, CW Gralnek, IM Dulai, GS Towfigh, A Asch, S TI Consumer usage patterns of nonprescription histamine2-receptor antagonists SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SELF-MEDICATION; THERAPY; WOMEN; DRUGS AB OBJECTIVE: Prescription to over-the-counter (OTC) drug switches are increasingly common. Yet little is known about how the public uses these reclassified products. Histamine2-receptor antagonists (H2RAs) are popular examples, although they may be supplanted by OTC proton pump inhibitors (PPIs). We examined the extent to which consumers substitute OTC H2RAs for physician care and/or engage in off-label use of these medications. METHODS: Self-administered anonymous survey of 1,116 adult OTC H2RA consumers in a random sample of 20 Los Angeles pharmacies from a major retail chain. Off-label use was defined by FDA warning label (e.g., bloody stools, dysphagia). Substitution was defined by intent to use H2RA instead of going to a physician. RESULTS: Forty-six percent engaged in off-label use of OTC H2RAs. Off-label use was independently associated with lower income, substitution for physician care, prior gastrointestinal disease, and past prescription H2RA use. Thirty-four percent substituted OTC H2RA use for physician care, and 54% of these met the criteria for off-label use. Substitution was associated with lack of health insurance, lack of time to see a physician, the belief that OTC H2RA was cheaper than clinic visits, and nonwhite race. CONCLUSION: Almost one-half of adult consumers reported using OTC H2RAs in a manner inconsistent with FDA labeling, and this off-label use was associated with substitution for physician care. Traditionally vulnerable populations were more prone to off-label use and to substituting H2RAs for physician care. Further studies are needed to assess patient outcomes, identify remedies, and explore implications for the reclassification of PPIs. C1 Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst,Ctr Study, Div Gastroenterol & Hepatol,CURE Digest Dis Res C, David Geffen Sch Med,Ctr Hlth Sci,Div Digest Dis, Los Angeles, CA 90024 USA. Va Greater Los Angeles Healthcare Syst, Dept Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Shi, CW (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, 9500 Gilman Dr,Mailcode 0807, La Jolla, CA 92093 USA. NR 23 TC 12 Z9 12 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 APR PY 2004 VL 99 IS 4 BP 606 EP 610 DI 10.1111/j.1572-0241.2004.04130.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 816KF UT WOS:000221108100007 PM 15089889 ER PT J AU Barbeau, E Roelofs, C Youngstrom, R Sorensen, G Stoddard, A LaMontagne, AD AF Barbeau, E Roelofs, C Youngstrom, R Sorensen, G Stoddard, A LaMontagne, AD TI Assessment of occupational safety and health programs in small businesses SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupational safety and health programs; occupational safety and health management systems; assessment methods; qualitative-quantitative; occupational safety and health policy; intervention research ID PERFORMANCE-MEASUREMENT TOOL; MANAGEMENT-SYSTEM; RATES AB Background Occupational safety and health (OSH) programs are a strategy for protecting workers' health, yet there are few peer-reviewed reports oil methods for assessing them, or on the prevalent characteristics of OSH programs, especially in small businesses. Methods We adapted an occupational safety and health administration (OSHA) survey instrument to assess: management commitment and employee participation, workplace analysis, hazard prevention and control, and education and training. This was supplemented by a series of open-ended questions. We administered the survey in 25 small worksites. Results Scores for each element ranged widely, with distribution of most scores being positively skewed. Barriers to addressing OSH included lack of time and in-house expertise, and production pressures. External agents, including corporate parents, liability insurers, and OSHA, played an important role in motivating OSH programs. Conclusions Small businesses were able to mount comprehensive programs, however, they may rely on outside resources for this task. Being small may not be a barrier to meeting the requirements of an OSHA program management rule. (C) 2004 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Dept Biostat, Amherst, MA 01003 USA. Univ Melbourne, Ctr Study Hlth & Soc, Melbourne, Vic 3010, Australia. RP Barbeau, E (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM elizabeth.barbeau@dfci.harvard.edu FU NCI NIH HHS [5 P01 CA75308-02]; NIOSH CDC HHS [1 R01OH04012-01] NR 25 TC 33 Z9 33 U1 0 U2 15 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD APR PY 2004 VL 45 IS 4 BP 371 EP 379 DI 10.1002/ajim.10336 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 809TB UT WOS:000220657900008 PM 15029570 ER PT J AU Chen, YM Polci, R Litchfield, P Gaczynska, M Riley, DJ AF Chen, YM Polci, R Litchfield, P Gaczynska, M Riley, DJ TI Nek1 regulates renal epithelial cell apoptosis through phosphorylation of the mitochondrial transition pore channel VDAC SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 28-MAY 02, 2004 CL Chicago, IL SP Natl Kidney Fdn C1 Univ Texas, Hlth Sci Ctr, Inst Biotechnol, San Antonio, TX USA. Univ Roma La Sapienza, Policlin Umberto I, Div Nephrol, Rome, Italy. S Texas Vet Hlth Care Syst, Div Res, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2004 VL 43 IS 4 MA 17 BP A19 EP A19 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 811RR UT WOS:000220789500043 ER PT J AU Dean, B Dylan, M Gano, A Knight, K Chan, W Ofman, JJ Levine, B AF Dean, B Dylan, M Gano, A Knight, K Chan, W Ofman, JJ Levine, B TI Erythropoiesis-stimulating protein therapy and decline of renal function SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 28-MAY 02, 2004 CL Chicago, IL SP Natl Kidney Fdn C1 Zynx Hlth, Beverly Hills, CA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2004 VL 43 IS 4 MA 26 BP A21 EP A21 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 811RR UT WOS:000220789500052 ER PT J AU Wagner, B Gorin, Y Ghosh-Choudhury, G Ricono, JM Abboud, HE AF Wagner, B Gorin, Y Ghosh-Choudhury, G Ricono, JM Abboud, HE TI NAD(P)H oxidase signaling in platelet-derived growth factor-BB stimulated metanephric mesenchymal cells SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 28-MAY 02, 2004 CL Chicago, IL SP Natl Kidney Fdn C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. UTHSCSA, Div Nephrol, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2004 VL 43 IS 4 MA 122 BP A45 EP A45 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 811RR UT WOS:000220789500148 ER PT J AU Goldzweig, CL Parkerton, PH Washington, DL Lanto, AB Yano, EM AF Goldzweig, CL Parkerton, PH Washington, DL Lanto, AB Yano, EM TI Primary care practice and facility quality orientation: Influence on breast and cervical cancer screening rates SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH-CARE; PHYSICIAN GENDER; AMBULATORY CARE; SERVICES; WOMEN; INTERVENTIONS; IMPROVEMENT; PREDICTORS; BIAS AB Background: Despite the importance of early cancer detection, variation in screening rates among physicians is high. Insights into factors influencing variation can guide efforts to decrease variation and increase screening rates. Objectives: To explore the association of primary care practice features and a facility's quality orientation with breast and cervical cancer screening rates. Study Design: Cross-sectional study of screening rates among 144 Department of Veterans Affairs (VA) medical centers and for a national sample of women. Methods: We linked practice structure and quality improvement characteristics of individual VA medical centers from 2 national surveys (I to primary care directors and I to a stratified random sample of employees) to breast and cervical cancer screening rates determined from a review of random medical records. We conducted bivariate analyses and multivariate logistic regression of primary care practice and facility features on cancer screening rates, above and below the median. Results: While the national screening rates were high for breast (87%) and cervical cancer (90%), higher screening rates were more likely when primary care providers were consistently notified of specialty visits and when staff perceived a greater organizational commitment to quality and anticipated rewards and recognition for better performance. Conclusions: Organization and quality orientation of the primary care practice and its facility can enhance breast and cervical cancer screening rates. Internal recognition of quality performance and an overall commitment to quality improvement may foster improved prevention performance, with impact varying by clinical service. C1 VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, DAvid Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. RP Goldzweig, CL (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gen Internal Med, 11301 Wilshire Blvd 111-G, Los Angeles, CA 90073 USA. EM caroline.goldzweig@med.va.gov NR 30 TC 23 Z9 24 U1 2 U2 6 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2004 VL 10 IS 4 BP 265 EP 272 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 811SO UT WOS:000220791800004 PM 15124503 ER PT J AU Devlin, B Bennett, P Dawson, G Figlewicz, DA Grigorenko, EL McMahon, W Minshew, N Pauls, D Smith, M Spence, MA Rodier, PM Stodgell, C Schellenberg, GD AF Devlin, B Bennett, P Dawson, G Figlewicz, DA Grigorenko, EL McMahon, W Minshew, N Pauls, D Smith, M Spence, MA Rodier, PM Stodgell, C Schellenberg, GD CA CPEA Genetics Network TI Alleles of a Reelin CGG repeat do not convey liability to autism in a sample from the CPEA network SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE autism; Reelin; language development; genetic association; autistic disorder ID FAMILY-BASED ASSOCIATION; GENOMEWIDE SCREEN; SUSCEPTIBILITY LOCUS; VULNERABILITY FACTOR; SPECTRUM DISORDERS; GENOMIC SCREEN; CHROMOSOME 7Q; GENERAL-CLASS; LINKAGE; SCHIZOPHRENIA AB A recent study by Persico et al. [2001: Mol Psychiatry 6:150-159] suggests alleles of a CGG polymorphism, just 5' of the reelin gene (RELN) initiator codon, confer liability for autism, especially alleles bearing 11 or more CGG repeats (long alleles). The association is consistent across both a case-control and family-based sample. We attempted to replicate their finding using a larger, independent family-based sample from the NIH Collaborative Programs of Excellence in Autism (CPEA) Network. In our data, allele transmissions to individuals with autism versus unaffected individuals are unbiased, both when alleles are classified by repeat length and when they are classified into long/short categories. Because of the apparent linkage of autism to chromosome 7q, particularly related to the development of language, we also evaluate the relationship between Reelin alleles and the age at which autism subjects use their first word or first phrase. Neither is significantly associated with Reelin alleles. Our results are not consistent with a major role for Reelin alleles in liability to autism. C1 Vet Affairs Med Ctr, Seattle, WA 98108 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Utah, Dept Psychiat, Div Child & Adolescent Psychiat, Salt Lake City, UT 84112 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Michigan, Dept Neurol Neurobiol & Anat, Ann Arbor, MI 48109 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Unit Psychiat & Neurodev Genet, Boston, MA USA. Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. Univ Rochester, Med Ctr, Dept Obstet Gynecol, Rochester, NY 14627 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Chicago, Chicago, IL 60637 USA. RP Schellenberg, GD (reprint author), Vet Affairs Med Ctr, 182B,1660 S Columbian Rd, Seattle, WA 98108 USA. EM zachdad@u.washington.edu RI Stodgell, Christopher/A-1161-2007; OI Stodgell, Christopher/0000-0002-1666-5299 FU NCRR NIH HHS [M01 RR 00064]; NICHD NIH HHS [P01 HD 34565, P01 HD 35476]; NIMH NIH HHS [MH 57881, R01 MH057881] NR 42 TC 51 Z9 56 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 1 PY 2004 VL 126B IS 1 BP 46 EP 50 DI 10.1002/ajmg.b.20125 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 808ZP UT WOS:000220607300009 PM 15048647 ER PT J AU Mullins, ME Lev, MH Bove, P O'Reilly, CE Saini, S Rhea, JT Thrall, JH Hunter, GJ Hamberg, LM Gonzalez, G AF Mullins, ME Lev, MH Bove, P O'Reilly, CE Saini, S Rhea, JT Thrall, JH Hunter, GJ Hamberg, LM Gonzalez, G TI Comparison of image quality between conventional and low-dose nonenhanced head CT SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID UNENHANCED MULTIDETECTOR CT; SINGLE-DETECTOR; ROW CT AB BACKGROUND AND PURPOSE: Increasing use of CT for evaluating neurologic disease may expose patients to considerable levels of ionizing radiation. We compared the image quality of low-mAs head CT scans with that of conventional nonenhanced scans. METHODS: Conventional head CT scans were obtained in 20 patients (all > 65 years with history of non-CNS malignancy) by using a multidetector technique: 170 mA and 1-second scanning time (ie, 170 mAs), 140 kVp, table speed of 7.5 mm per rotation, pitch of 0.75, section thickness of 5 mm, and field of view of 25 rum. A limited volume helical data acquisition covering four 5-mm-thick images was obtained by using 90 mAs but otherwise the same parameters. Three neuroradiologists visually rated the resulting images for quality in a blinded comparison. Representative 1- to 4-mm(2) regions of interest were chosen in gray matter and white matter locations. Conspicuity and the contrast-to-noise ratio were analyzed. Statistical comparisons were done by using the Student t test. RESULTS: Mean gray matter conspicuity was not significantly different between the 170- and 90-mAs groups (0.39 +/- 0.19 vs 0.41 +/- 0.03, P =.32). Mean gray matter contrast-to-noise ratio was approximately 22% higher with 170 mAs than with 90 mAs (1.77 +/- 0.52 vs 1.39 +/- 0.38, P = .005). All 90-mAs images were rated as having slightly greater image noise than the 170-mAs scans but with sufficient perceived resolution. CONCLUSION. Although 90-mAs head CT images were moderately noisier than 170-mAs images, they were rated as having acceptable diagnostic quality. C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Abdominal Imaging Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Emergency Radiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Off Chairman, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Diagnost Imaging, Orlando, FL USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB285,55 Fruit St, Boston, MA 02114 USA. NR 17 TC 53 Z9 58 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2004 VL 25 IS 4 BP 533 EP 538 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 815LD UT WOS:000221042900004 PM 15090337 ER PT J AU Choulika, S Grabowski, E Holmes, LB AF Choulika, S Grabowski, E Holmes, LB TI Is antenatal vitamin K prophylaxis needed for pregnant women taking anticonvulsants? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE anticonvulsant drugs; pregnancy; vitamin K ID EPILEPSY AB The objective of this cohort study of a consecutive sample of infants exposed during pregnancy to anticonvulsant drugs was to determine if the mother received late pregnancy prophylaxis with vitamin K, and if any infants had signs of hemorrhagic disease. The medical records of 204 neonates exposed to anticonvulsant drugs in utero and 77 unexposed control neonates were retrospectively reviewed. No hemorrhagic disease was observed, and the incidence of bleeding tendencies was not higher in infants exposed to these drugs compared with control infants, despite no prenatal vitamin K supplementation in all but I epileptic woman. (C) 2004 Elsevier Inc. All rights reserved. C1 MassGen Hosp Children, Genet & Teratol Unit, Boston, MA USA. RP Choulika, S (reprint author), MassGen Hosp Children, Genet & Teratol Unit, Boston, MA USA. FU NINDS NIH HHS [NS2412] NR 3 TC 22 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2004 VL 190 IS 4 BP 882 EP 883 DI 10.1016/j.ajog.2004.01.041 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 817XG UT WOS:000221209600006 PM 15118607 ER PT J AU Poulaki, V Mitsiades, N Kruse, FE Radetzky, S Iliaki, E Kirchhof, B Joussen, AM AF Poulaki, V Mitsiades, N Kruse, FE Radetzky, S Iliaki, E Kirchhof, B Joussen, AM TI Activin A in the regulation of corneal neovascularization and vascular endothelial growth factor expression SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; DIFFERENTIATION FACTOR EDF; BETA SIGNAL-TRANSDUCTION; TGF-BETA; ERYTHROID-DIFFERENTIATION; CELL-GROWTH; IN-VIVO; SERINE-THREONINE; ANGIOGENESIS; INHIBITION AB Activin A, a dimeric glycoprotein that belongs to the transforming growth factor-beta superfamily, governs cellular differentiation in a wide variety of models and has been implicated in the regulation of angiogenesis. We examined the role of activin A and its downstream signaling pathway in a murine model of inflammatory corneal neovascularization induced by mechanical injury (debridement), and in vitro in corneal epithelial cells. Activin A expression increased steadily from day 2 until day 8 after mechanical debridement in vivo, paralleling vascular endothelial growth factor (VEGF) expression. Administration of recombinant activin A in mice increased the area of neovascularization, VEGF expression, and the kinase activities of p38 and p42/44 MAPKs after mechanical debridement. Systemic inhibition of activin A in vivo with a neutralizing antibody reduced the area of neovascularization, VEGF expression, and p38 and p42/44 MAPK activity, whereas administration of an isotype-matched control antibody had no effect. In vitro treatment with activin A increased VEGF secretion, as well as p38 and p42/44 MAPK activity in corneal epithelial cells, whereas concurrent administration of specific inhibitors of p38 or p42/44 MAPK abolished the stimulatory effect of activin A on VEGF production. We conclude that activin A stimulates inflammatory corneal angiogenesis by increasing VEGF levels through a p38 and p42/44 MAPK-dependent mechanism. C1 Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50931 Cologne, Germany. Univ Cologne, Ctr Mol Medd, D-50931 Cologne, Germany. Univ Heidelberg, Dept Ophthalmol, Heidelberg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Joussen, AM (reprint author), Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50931 Cologne, Germany. EM joussena@aol.com NR 58 TC 28 Z9 34 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2004 VL 164 IS 4 BP 1293 EP 1302 DI 10.1016/S0002-9440(10)63216-6 PG 10 WC Pathology SC Pathology GA 806CB UT WOS:000220410900018 PM 15039217 ER PT J AU Farris, W Mansourian, S Leissring, MA Eckman, EA Bertram, L Eckman, CB Tanzi, RE Selkoe, DJ AF Farris, W Mansourian, S Leissring, MA Eckman, EA Bertram, L Eckman, CB Tanzi, RE Selkoe, DJ TI Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ONSET ALZHEIMERS-DISEASE; C-TERMINAL FRAGMENTS; PRECURSOR PROTEIN; A-BETA; SUSCEPTIBILITY LOCUS; EXTRACELLULAR LEVELS; CONVERTING ENZYME; BRAIN; PEPTIDE; ASSOCIATION AB The causes of cerebral accumulation of amyloid beta-protein (Abeta) in most cases of Alzheimer's disease (AD) remain unknown. We recently found that homozygous deletion of the insulin-degrading enzyme (IDE) gene in mice results in an early and marked elevation of cerebral Abeta. Both genetic linkage and allelic association in the DDE region of chromosome 10 have been reported in families with late-onset AD. For IDE to remain a valid candidate gene for late-onset AD on functional grounds, it must be shown that partial loss of function of IDE can still alter Abeta degradation, but without causing early, severe elevation of brain Abeta. Here, we show that naturally occurring IDE missense mutations in a well-characterized rat model of type 2 diabetes mellitus (DM2) result in decreased catalytic efficiency and a significant similar to15 to 30% deficit in the degradation of both insulin and Abeta. Endogenously secreted Abeta(40) and Abeta(42) are significantly elevated in primary neuronal cultures from animals with the IDE mutations, but there is no increase in steady-state levels of rodent Abeta in the brain up to age 14 months. We conclude that naturally occurring, partial loss-of-function mutations in IDE sufficient to cause DM2 also impair neuronal regulation of Abeta levels, but the brain can apparently compensate for the partial deficit during the life span of the rat. Our findings have relevance for the emerging genetic evidence suggesting that IDE may be a late-onset AD-risk gene, and for the epidemiological relationships among hyperinsulinemia, DM2, and AD. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit,Ctr Aging Gene, Boston, MA 02115 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. RP Selkoe, DJ (reprint author), Ctr Neurol Dis, HIM 730,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dselkoe@rics.bwh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NIA NIH HHS [AG12479] NR 64 TC 149 Z9 155 U1 2 U2 7 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 APR PY 2004 VL 164 IS 4 BP 1425 EP 1434 DI 10.1016/S0002-9440(10)63229-4 PG 10 WC Pathology SC Pathology GA 806CB UT WOS:000220410900031 PM 15039230 ER PT J AU El Annan, J Brown, D Breton, S Bourgoin, S Ausiello, DA Marshansky, V AF El Annan, J Brown, D Breton, S Bourgoin, S Ausiello, DA Marshansky, V TI Differential expression and targeting of endogenous Arf1 and Arf6 small GTPases in kidney epithelial cells in situ SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE protein trafficking; immunofluorescence microscopy; Western blotting; endocytosis ID ADP-RIBOSYLATION FACTOR; NUCLEOTIDE EXCHANGE FACTOR; RECEPTOR-MEDIATED ENDOCYTOSIS; MALE REPRODUCTIVE-TRACT; PHOSPHOLIPASE-D; ORGANELLE STRUCTURE; PROXIMAL TUBULES; MAMMALIAN-CELLS; PLASMA-MEMBRANE; COAT PROTEINS AB ADP-ribosylation factors (Arfs) are small GTPases that regulate vesicular trafficking in exo- and endocytotic pathways. As a first step in understanding the role of Arfs in renal physiology, immunocytochemistry and Western blotting were performed to characterize the expression and targeting of Arf1 and Arf6 in epithelial cells in situ. Arf1 and Arf6 were associated with apical membranes and subapical vesicles in proximal tubules, where they colocalized with megalin. Arf1 was also apically expressed in the distal tubule, connecting segment, and collecting duct ( CD). Arf1 was abundant in intercalated cells (IC) and colocalized with V-ATPase in A-IC ( apical) and B-IC ( apical and/or basolateral). In contrast, Arf6 was associated exclusively with basolateral membranes and vesicles in the CD. In the medulla, basolateral Arf6 was detectable mainly in A-IC. Expression in principal cells became weaker throughout the outer medulla, and Arf6 was not detectable in principal cells in the inner medulla. In some kidney epithelial cells Arf1 but not Arf6 was also targeted to a perinuclear patch, where it colocalized with TGN38, a marker of the trans-Golgi network. Quantitative Western blotting showed that expression of endogenous Arf1 was 26 - 180 times higher than Arf6. These data indicate that Arf GTPases are expressed and targeted in a cell- and membrane-specific pattern in kidney epithelial cells in situ. The results provide a framework on which to base and interpret future studies on the role of Arf GTPases in the multitude of cellular trafficking events that occur in renal tubular epithelial cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. Univ Laval, CHUQ, Ctr Rech, Ctr Rech Rhumatol & Immunol, Ste Foy, PQ G1V 4G2, Canada. RP Marshansky, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, 149 13th St,CNY-8,Suite 8203, Boston, MA 02129 USA. EM vladimir_marshansky@hms.harvard.edu NR 54 TC 21 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR 1 PY 2004 VL 286 IS 4 BP C768 EP C778 DI 10.1152/ajpcell.00250.2003 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 800MR UT WOS:000220032900005 PM 14684384 ER PT J AU Hafezi-Moghadam, A Thomas, KL Cornelssen, C AF Hafezi-Moghadam, A Thomas, KL Cornelssen, C TI A novel mouse-driven ex vivo flow chamber for the study of leukocyte and platelet function SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE autoperfused flow chamber; intravital microscopy; inflammation; thrombus formation ID INTERCELLULAR-ADHESION MOLECULE-1; HIGH-ENDOTHELIAL VENULES; NITRIC-OXIDE SYNTHASE; L-SELECTIN; IN-VIVO; THROMBUS FORMATION; P-SELECTIN; CREMASTER MUSCLE; BLOOD-PLATELETS; CELL-ADHESION AB Various in vitro and in vivo techniques exist for study of the microcirculation. Whereas in vivo systems impress with their physiological fidelity, in vitro systems excel in the amount of reduction that can be achieved. Here we introduce the autoperfused ex vivo flow chamber designed to study murine leukocytes and platelets under well-defined hemodynamic conditions. In our model, the murine heart continuously drives the blood flow through the chamber, providing a wide range of physiological shear rates. We used a balance of force approach to quantify the prevailing forces at the chamber walls. Numerical simulations show the flow characteristics in the chamber based on a shear-thinning fluid model. We demonstrate specific rolling of wild-type leukocytes on immobilized P-selectin, abolished by a blocking MAb. When uncoated, the surfaces having a constant shear rate supported individual platelet rolling, whereas on areas showing a rapid drop in shear platelets interacted in previously unreported grapelike conglomerates, suggesting an influence of shear rate on the type of platelet interaction. In summary, the ex vivo chamber amounts to an external vessel connecting the arterial and venous systems of a live mouse. This method combines the strengths of existing in vivo and in vitro systems in the study of leukocyte and platelet function. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Tech Univ Berlin, Fac 5, Inst Mech, D-10623 Berlin, Germany. RP Hafezi-Moghadam, A (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 325 Cambridge St, Boston, MA 02114 USA. EM Ali_Hafezi-Moghadam@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NIAID NIH HHS [K08-AI-50775] NR 65 TC 21 Z9 21 U1 0 U2 3 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 APR 1 PY 2004 VL 286 IS 4 BP C876 EP C892 DI 10.1152/ajpcell.00500.2003 PG 17 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 800MR UT WOS:000220032900018 PM 14668262 ER PT J AU Otte, JM Podolsky, DK AF Otte, JM Podolsky, DK TI Functional modulation of enterocytes by gram-positive and gram-negative microorganisms SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE probiotics; Escherichia coli Nissle 1917; probiotic mixture VSL# 3; intestinal epithelial cell lines; interleukin-8; transepithelial resistance; zonula occludens-1; mucins ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; PLACEBO-CONTROLLED TRIAL; GENE-DEFICIENT MICE; TOLL-LIKE RECEPTORS; ULCERATIVE-COLITIS; ESCHERICHIA-COLI; CROHNS-DISEASE; DOUBLE-BLIND; INTERLEUKIN-10-DEFICIENT MICE AB Clinical studies have suggested that so-called probiotic bacteria may be effective as therapy in inflammatory bowel disease. However, the molecular mechanisms of their interaction with the intestinal surface remain undefined. The influence of whole probiotic bacteria [Escherichia coli Nissle 1917 (EcN); probiotic mixture VSL#3 (PM)], bacterial cell lysates, and conditioned media on transepithelial resistance (TER), IL-8 secretion, mucin gene expression, and tight junction proteins were determined in T84 and HT-29 intestinal epithelial cells (IEC). In addition, effects on pathogen (Salmonella dublin)-induced alterations were analyzed. EcN as well as debris and cell extracts induced IL-8 secretion from IEC, whereas no such effect was observed following incubation with the PM. The PM and soluble protein(s) released from the PM increased TER, prevented pathogen-induced decrease in TER, and were shown to stabilize tight junctions. The PM induced expression of mucins in IEC, and these organisms as well as EcN diminished S. dublin-induced cell death. Inhibition of MAPKs with PD-98059 or SB-203580 significantly decreased alterations in IL-8 synthesis and mucin expression and affected the regulation of TER. Probiotics and protein(s) released by these organisms may functionally modulate the intestinal epithelium of the host by different mechanisms, including the competition of whole organisms for contact with the epithelial surface as well as stabilization of the cytoskeleton and barrier function and the induction of mucin expression. Gram-negative and gram-positive organisms differ in the mechanisms activated, and a combination of organisms might be more effective than the application of a single strain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit GRJ719, 32 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [DK-43351, DK-60049] NR 51 TC 215 Z9 224 U1 1 U2 11 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 APR PY 2004 VL 286 IS 4 BP G613 EP G626 DI 10.1152/ajpgi.00341.2003 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 801HE UT WOS:000220086200013 PM 15010363 ER PT J AU Schwetz, I Bradesi, S McRoberts, JA Sablad, M Miller, JC Zhou, HP Ohning, G Mayer, EA AF Schwetz, I Bradesi, S McRoberts, JA Sablad, M Miller, JC Zhou, HP Ohning, G Mayer, EA TI Delayed stress-induced colonic hypersensitivity in male Wistar rats: role of neurokinin-1 and corticotropin-releasing factor-1 receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE visceral pain; stress ID IRRITABLE-BOWEL-SYNDROME; INDUCED VISCERAL HYPERSENSITIVITY; MESSENGER-RIBONUCLEIC-ACID; PARAVENTRICULAR NUCLEUS; GASTROINTESTINAL-TRACT; RECTAL DISTENSION; MAST-CELLS; HYPERALGESIA; CRF; HYPOTHALAMUS AB The mechanism(s) underlying stress-induced colonic hypersensitivity (SICH) are incompletely understood. Our aims were to assess the acute and delayed (24 h) effect of water avoidance (WA) stress on visceral nociception in awake male Wistar rats and to evaluate the role of two stress-related modulation systems: the substance P/neurokinin-1 receptor (SP/NK(1)R)and the corticotropin-releasing factor (CRF)/CRF(1) receptor (CRF/CRF(1)R) systems, as well as the possible involvement of the sympathetic nervous system. Visceral pain responses were measured as the visceromotor response to colorectal distension (CRD) at baseline, immediately after WA and again 24 h later. The NK(1)R antagonists RP-67580 and SR-140333 and the CRF(1)R antagonist CP-154526 were injected 15 min before WA or 1 h before the CRD on day 2. Chemical sympathectomy was performed by repeated injection of 6-hydroxydopamine. WA stress resulted in a significant increase in the visceromotor response on day 2, but no change immediately after WA. Injection of CP-154526 abolished delayed SICH when applied either before WA stress or before the CRD on day 2. Both NK(1)R antagonists only decreased SICH when injected before the CRD on day 2. Chemical sympathectomy did not affect delayed SICH. Our results indicate that in male Wistar rats, both NK(1)R and CRF(1)R activation, but not sympathetic nervous system activation, play a role in the development of SICH. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Mayer, EA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, W Los Angeles Healthcare Ctr, Bldg 115 Ctr Ulcer Res & Educ,Rm 223,11301 Wilshi, Los Angeles, CA 90073 USA. EM emayer@ucla.edu FU NIDDK NIH HHS [1P50-DK64539-01, P30-DK-41301] NR 44 TC 54 Z9 54 U1 0 U2 4 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 APR PY 2004 VL 286 IS 4 BP G683 EP G691 DI 10.1152/ajpgi.00358.2003 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 801HE UT WOS:000220086200020 PM 14615283 ER PT J AU Meck, JV Waters, WW Ziegler, MG deBlock, HF Mills, PJ Robertson, D Huang, PL AF Meck, JV Waters, WW Ziegler, MG deBlock, HF Mills, PJ Robertson, D Huang, PL TI Mechanisms of postspaceflight orthostatic hypotension: low alpha(1)-adrenergic receptor responses before flight and central autonomic dysregulation postflight SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE tyramine; phenylephrine; dihydroxyphenylglycol; tilt tests; arginine vasopressin ID SHORT-DURATION SPACEFLIGHT; HEAD-UP TILT; BAROREFLEX CONTROL; NERVOUS-SYSTEM; VASOPRESSIN; HUMANS; NOREPINEPHRINE; ADRENOCEPTORS; INHIBITION; ASTRONAUTS AB Although all astronauts experience symptoms of orthostatic intolerance after short-duration spaceflight, only similar to 20% actually experience presyncope during upright posture on landing day. The presyncopal group is characterized by low vascular resistance before and after flight and low norepinephrine release during orthostatic stress on landing day. Our purpose was to determine the mechanisms of the differences between presyncopal and nonpresyncopal groups. We studied 23 astronauts 10 days before launch, on landing day, and 3 days after landing. We measured pressor responses to phenylephrine injections; norepinephrine release with tyramine injections; plasma volumes; resting plasma levels of chromogranin A ( a marker of sympathetic nerve terminal release), endothelin, dihydroxyphenylglycol ( DHPG, an intracellular metabolite of norepinephrine); and lymphocyte beta(2)-adrenergic receptors. We then measured hemodynamic and neurohumoral responses to upright tilt. Astronauts were separated into two groups according to their ability to complete 10 min of upright tilt on landing day. Compared with astronauts who were not presyncopal on landing day, presyncopal astronauts had 1) significantly smaller pressor responses to phenylephrine both before and after flight; 2) significantly smaller baseline norepinephrine, but significantly greater DHPG levels, on landing day; 3) significantly greater norepinephrine release with tyramine on landing day; and 4) significantly smaller norepinephrine release, but significantly greater epinephrine and arginine vasopressin release, with upright tilt on landing day. These data suggest that the etiology of orthostatic hypotension and presyncope after spaceflight includes low alpha(1)-adrenergic receptor responsiveness before flight and a remodeling of the central nervous system during spaceflight such that sympathetic responses to baroreceptor input become impaired. C1 NASA, Lyndon B Johnson Space Ctr, Human Adaptat & Countermeasures Off, Space & Life Sci Directorate,SK, Houston, TX 77058 USA. Baylor Coll Med, Natl Space Biomed Res Inst, Houston, TX 77030 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Albany Med Coll, Dept Surg, Albany, NY 12208 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02129 USA. RP Meck, JV (reprint author), NASA, Lyndon B Johnson Space Ctr, Human Adaptat & Countermeasures Off, Space & Life Sci Directorate,SK, Houston, TX 77058 USA. EM jmeck@ems.jsc.nasa.gov FU NCRR NIH HHS [M01RR-00827] NR 34 TC 73 Z9 74 U1 3 U2 6 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 APR 1 PY 2004 VL 286 IS 4 BP H1486 EP H1495 DI 10.1152/ajpheart.00740.2003 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 802ZL UT WOS:000220201300033 PM 14670816 ER PT J AU Yonkers, KA Wisner, KL Stowe, Z Leibenluft, E Cohen, L Miller, L Manber, R Viguera, A Suppes, T Altshuler, L AF Yonkers, KA Wisner, KL Stowe, Z Leibenluft, E Cohen, L Miller, L Manber, R Viguera, A Suppes, T Altshuler, L TI Management of bipolar disorder during pregnancy and the postpartum period SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID VALPROIC ACID; ANTIEPILEPTIC DRUGS; SPINA-BIFIDA; DOUBLE-BLIND; IN-UTERO; NEONATAL PHARMACOKINETICS; CALCIUM-ANTAGONISTS; MAJOR MALFORMATIONS; BENZODIAZEPINE USE; PLACENTAL-TRANSFER AB Objective: Bipolar disorder affects 0.5%-1.5% of individuals in the United States. The typical age at onset is late adolescence or early adulthood, placing women at risk for episodes throughout their reproductive years. General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when these guidelines are applied in the treatment of peripartum women. The authors summarize knowledge regarding the management of bipolar disorder during pregnancy and the postpartum period, with a focus on managing mania, hypomania, and the psychotic components of the illness. Method: An expert panel reviewed articles that address the management of bipolar disorder and the consequences of the use of mood stabilizers during pregnancy, and a consensus document was generated. Results: The treatment of bipolar disorder in pregnant women involves significant challenges. Some mood stabilizers, e.g., sodium valproate and carbamazepine, are human teratogens. On the other hand, the teratogenicity associated with lithium may have been overestimated in the past. Conclusions: Since treatment can be managed most effectively if pregnancy is planned, clinicians should discuss the issue of pregnancy and its management with every bipolar disorder patient who has childbearing potential, regardless of future reproductive plans. Additional research should address the risks of disturbed sleep to pregnant and postpartum women with bipolar disorder, as well as structural and behavioral consequences to offspring when mood stabilizers are used during pregnancy. Longitudinal and cohort studies can promote these efforts. Given the rate of bipolar disorder in the general population, research efforts will need to be broad based and include multiple collaborating centers. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. NIMH, Pediat & Dev Neuropsychiat Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. RP Yonkers, KA (reprint author), Yale Univ, Sch Med, Dept Psychiat, 142 Temple St,Suite 301, New Haven, CT 06510 USA. EM kimberly.yonkers@yale.edu NR 103 TC 171 Z9 179 U1 1 U2 11 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2004 VL 161 IS 4 BP 608 EP 620 DI 10.1176/appi.ajp.161.4.608 PG 13 WC Psychiatry SC Psychiatry GA 818WW UT WOS:000221276200003 PM 15056503 ER PT J AU Faraone, SV Glatt, SJ Su, J Tsuang, MT AF Faraone, SV Glatt, SJ Su, J Tsuang, MT TI Three potential susceptibility loci shown by a genome-wide scan for regions influencing the age at onset of mania SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID INITIATIVE BIPOLAR PEDIGREES; DEFICIT HYPERACTIVITY DISORDER; FAMILIAL TRANSMISSION; DIAGNOSTIC INTERVIEW; LINKAGE ANALYSIS; GENETICS; ILLNESS; RELATIVES; SYMPTOMS; PROBANDS AB Objective: The age at onset of bipolar disorder is associated with clinical features of the illness, including duration, severity, and pattern of comorbidity with other disorders. Age at onset is familial and heritable, and it correlates inversely with the prevalence of bipolar disorder among relatives. Because age at onset may have utility in resolving the complexity and heterogeneity of the disorder, the authors sought to identify chromosomal loci that harbor the genes influencing this trait. Method: A genome scan of 539 genotyped people in 97 families ascertained for the NIMH Bipolar Disorder Genetics Initiative was performed by using multipoint variance-components linkage analysis. Results: The age at onset of mania was significantly heritable in these families. Three chromosomal regions yielded nonsignificant but suggestive multipoint lod scores greater than 2.5, with the strongest evidence observed at markers D12S1292, GATA31B, and GATA50C, on chromosomes 12p, 14q, and 15q, respectively. Conclusions: Although firm conclusions await an independent replication, these results suggest that three regions of the genome may contain genes influencing the age at onset of mania in bipolar disorder. To the authors' knowledge, these regions have not been implicated previously in risk for the disorder, suggesting that separate sets of genes influence disease susceptibility and the age which it appears. C1 Massachusetts Gen Hosp, Stanley Ctr Pediat Mania, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Johnson & Johnson Consumer Prod Inc, Stanley Ctr Pediat Mania, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Stanley Ctr Pediat Mania, WRN 705,55 Fruit St, Boston, MA 02114 USA. EM sfaraone@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [HD-37694]; NIMH NIH HHS [MH-43518, MH-57934, MH-59126, MH-59624, MH-60485] NR 54 TC 53 Z9 54 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2004 VL 161 IS 4 BP 625 EP 630 DI 10.1176/appi.ajp.161.4.625 PG 6 WC Psychiatry SC Psychiatry GA 818WW UT WOS:000221276200007 PM 15056507 ER PT J AU Heckers, S Weiss, AP Deckersbach, T Goff, DC Morecraft, RJ Bush, G AF Heckers, S Weiss, AP Deckersbach, T Goff, DC Morecraft, RJ Bush, G TI Anterior cingulate cortex activation during cognitive interference in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID STROOP TASK-PERFORMANCE; SELECTIVE ATTENTION; RHESUS-MONKEY; PET; DEFICITS; BRAIN; VARIABILITY; MODULATION; MEDICATION; REGIONS AB Background: Previous studies have reported evidence of structural and functional abnormalities in the anterior cingulate cortex of patients with schizophrenia. Method: The authors studied 19 male patients with chronic schizophrenia and 15 healthy male comparison subjects with functional magnetic resonance imaging and the novel Multi-Source Interference Task, a task designed to elicit robust dorsal anterior cingulate cortex activation in individual subjects. Group averaged and individual (region-of-interest-based) brain activation patterns were compared during the performance of control and interference trials. Results: Performance (reaction times and accuracy) did not differ between healthy subjects and patients with schizophrenia. Comparison of interference and neutral blocks revealed activation in the medial wall of the prefrontal cortex in 93% (N = 14) of the healthy subjects and 84% (N = 16) of the subjects with schizophrenia. Sixty-seven percent (N = 10) of the healthy subjects but only 16% (N = 3) of the subjects with schizophrenia displayed maximum medial wall activation within the dorsal anterior cingulate cortex. jConclusions: The Multi-Source Interference Task produced robust activation in the medial wall of the prefrontal cortex during cognitive interference. Analysis of individual activation patterns revealed medial wall abnormalities in schizophrenia patients. C1 Univ S Dakota, Sch Med, Div Basic Biomed Sci, Vermillion, SD 57069 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Funct & Struct Biomed Im, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, CNY-9112,Bldg 149,13th St, Charlestown, MA 02129 USA. EM heckers@psych.mgh.harvard.edu RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIMH NIH HHS [MH-01763] NR 35 TC 58 Z9 60 U1 4 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2004 VL 161 IS 4 BP 707 EP 715 DI 10.1176/appi.ajp.161.4.707 PG 9 WC Psychiatry SC Psychiatry GA 818WW UT WOS:000221276200018 PM 15056518 ER PT J AU Barr, RG Wentowski, CC Curhan, GC Somers, SC Stampfer, MJ Schwartz, J Speizer, FE Camargo, CA AF Barr, RG Wentowski, CC Curhan, GC Somers, SC Stampfer, MJ Schwartz, J Speizer, FE Camargo, CA TI Prospective study of acetaminophen use and newly diagnosed asthma among women SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE analgesics; paracetamol; aspirin; analgesic drugs, nonsteriodal ID ANTI-INFLAMMATORY DRUGS; S-TRANSFERASE M1; CHILDHOOD ASTHMA; PARACETAMOL USE; LUNG INJURY; ASPIRIN; GLUTATHIONE; CHILDREN; PREVALENCE; CHALLENGE AB Acetaminophen decreases glutathione levels in the lung, which may predispose to oxidative injury and bronchospasm. Acetaminophen use has been associated with asthma in cross-sectional studies and a birth cohort. We hypothesized that acetaminophen use would be associated with newly diagnosed adult-onset asthma in the Nurses' Health Study, a prospective cohort study of 121,700 women. Participants were first asked about frequency of acetaminophen use in 1990. Cases with asthma were defined as those with a new physician diagnosis of asthma between 1990 and 1996 plus reiteration of the diagnosis and controller medication use. Proportional hazard models included age, race, socioeconomic status, body mass index, smoking, other analgesic use, and postmenopausal hormone use. During 352,719 person-years of follow-up, 346 participants reported a new physician diagnosis of asthma meeting diagnostic criteria. Increasing frequency of acetaminophen use was positively associated with newly diagnosed asthma (p for trend = 0.006). The multivariate rate ratio for asthma for participants who received acetaminophen for more than 14 days per month was 1.63 (95% confidence interval, 1.11-2.39) compared with nonusers. It would be premature to recommend acetaminophen avoidance for patients with asthma, but further research on pulmonary responses to acetaminophen is necessary to confirm or refute these findings and to identify subgroups whose asthma may be modified by acetaminophen. C1 Columbia Univ, Coll Phys & Surg, Dept Med, Div Gen Med, New York, NY 10027 USA. Columbia Univ, Mailman Sch Publ Hlth, Div Epidemiol, New York, NY 10027 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Barr, RG (reprint author), Columbia Presbyterian Med Ctr, Div Gen Med, PH-9E 105,622 W 168th St, New York, NY 10032 USA. EM rgb9@columbia.edu FU NCI NIH HHS [CA87969]; NHLBI NIH HHS [HL-63841, HL-07427] NR 39 TC 82 Z9 82 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2004 VL 169 IS 7 BP 836 EP 841 DI 10.1164/rccm.200304-596OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 807IB UT WOS:000220494100015 PM 14711794 ER PT J AU Asad, S Aquino, SL Piyavisetpa, N Fischman, AJ AF Asad, S Aquino, SL Piyavisetpa, N Fischman, AJ TI False-positive FDG positron emission tomography uptake in nonmalignant chest abnormalities SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CANCER; PET C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Emory Univ Hosp, Dept Neurol, Atlanta, GA 30322 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM saquino@partners.org NR 9 TC 40 Z9 44 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2004 VL 182 IS 4 BP 983 EP 989 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 805RG UT WOS:000220382800034 PM 15039176 ER PT J AU Eichhorn, JH Young, RH AF Eichhorn, JH Young, RH TI Transitional cell carcinoma of the ovary - A morphologic study of 100 cases with emphasis on differential diagnosis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; malignant neoplasm; transitional cell carcinoma; mixed epithelial carcinomas ID BRENNER TUMORS; UROTHELIAL DIFFERENTIATION; URINARY-BLADDER; PATTERN; CHEMOTHERAPY; NEOPLASMS; MARKERS AB Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer, and studies of its morphology are few. As a result, the criteria for its diagnosis and spectrum of its morphology are not clearly established. One hundred consecutive consultation cases of ovarian carcinoma with a pure or partial transitional cell pattern (excluding malignant Brenner tumor) diagnosed between 1989 and 2001 were evaluated for the frequency of various pathologic features and the relation of TCC to other surface epithelial-stromal carcinomas. The women were 33 to 94 years of age (mean, 56 years). A total of 47 tumors were stage I, 21 stage II, 31 stage III, and I stage IV; 13% of the stage I tumors and 41% of tumors of all stages were bilateral. The tumors ranged from 3.0 to 30 cm in greatest dimension (mean, 10 cm); 60% of them were solid and cystic, 24% solid, and 16% cystic. TCC was the exclusive or predominant component in 93% of the tumors and showed undulating (93%), diffuse (57%), insular (55%), and trabecular (43%) patterns. In four tumors with an insular growth, the pattern focally mimicked a Brenner tumor. Necrosis was present in 57% of the cases. Features that were seen in the tumors that in aggregate produced a relatively consistent appearance were "punched out" micro-spaces (87%), often the size of Call-Exner bodies, large cystic spaces (73%), and large blunt papillae (63%). Features that were sometimes seen, usually as a focal finding, included slit-like fenestrations (49%), bizarre giant cells (35%), small filiforin papillae (18%), gland-like tubules (17%), squamous differentiation (13%), and psammoma bodies (4%). In 23 cases, TCC was a component of a mixed epithelial carcinoma, the additional components being serous adenocarcinoma in 16, endometrioid in 5, mucinous in 1, and clear cell carcinoma in 1. The tumor cells of the TCC component often were relatively monomorphic; 6% of the tumors were grade 1, 43% grade 2, and 51% grade 3. The nuclei were oblong or round and often had large single nucleoli (69%) or longitudinal grooves (48%). The cytoplasm was typically pale and granular but was rarely strikingly clear or oxyphilic. TCC of the ovary usually occurs in pure form but is also common as a component of a surface epithelial carcinoma of mixed cell type. In either situation, TCC has a constellation of architectural and cytologic features that readily distinguish it in most cases from other types of ovarian cancer. Recognition of these features will lead to a more consistent diagnosis of this tumor and aid in determining whether it has distinctive clinical features, particularly with regard to its behavior. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Eichhorn, JH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Warren 105C,32 Fruit St, Boston, MA 02114 USA. EM jeichhorn@partners.org NR 31 TC 62 Z9 68 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2004 VL 28 IS 4 BP 453 EP 463 DI 10.1097/00000478-200404000-00004 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 808CZ UT WOS:000220548500004 PM 15087664 ER PT J AU Misdraji, J Thiim, M Graeme-Cook, FM AF Misdraji, J Thiim, M Graeme-Cook, FM TI Autoimmune hepatitis with centrilobular necrosis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol DE autoimmune hepatitis; centrilobular necrosis; zone 3 hepatitis; zonal necrosis; confluent necrosis ID CHOLESTATIC HEPATITIS; LIVER-TRANSPLANTATION; ATORVASTATIN; DISEASE AB Autoimmune hepatitis (AIH) is usually a chronic portalbased hepatitis with prominent plasma cells. Although necroinflammatory activity throughout the lobule is described, centrilobular necrosis (CN) is only rarely the predominant pattern of injury. Recognition of the possibility of AIH in zone 3 hepatitis will lead to prompt steroid therapy and may avert cirrhosis. We report the clinicopathologic features of 6 cases of AIH with CN. The 3 females and 3 males averaged 48 years of age (range 32-66 years). Four patients had a history of autoimmune disorders. All had elevated transaminases and negative serology for viral hepatitis B and C. One had a history of ethanol use. One patient was taking interferon-beta and 1 patient was taking atorvastatin, but none of the patients was taking medication with a temporal relationship to suggest a drug hypersensitivity hepatitis. All patients had positive antinuclear antibody, anti-smooth muscle antibody, or both, although 1 patient was negative for autoantibodies at initial laboratory testing. Four biopsies showed confluent zone 3 necrosis, whereas two biopsies showed spotty CN. Portal inflammation was relatively mild in all cases. Plasma cells were few to numerous in both zone 3 and portal tracts in four biopsies; they were absent in 2 cases. All patients responded to steroid therapy. Two patients relapsed, and rebiopsy in 1 of them showed CN, bridging necrosis, and an increase in the degree of portal-based hepatitis. Another patient was not treated initially; a second biopsy 35 months after presenting revealed periportal hepatitis as well as CN. The histologic spectrum of AM should be expanded to include zone 3 hepatitis. As with classic AIH, most patients with CN demonstrate serologic and clinical evidence of autoimmunity. Subsequent biopsies in patients with a centrilobular pattern may show evolution to portal-based hepatitis characteristic of AIH but may also show persistence of the zone 3 hepatitis. Unlike other causes of zone 3 hepatitis, AIH is steroid responsive; therefore, timely diagnosis is important. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 24 TC 43 Z9 46 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 APR PY 2004 VL 28 IS 4 BP 471 EP 478 DI 10.1097/00000478-200404000-00006 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 808CZ UT WOS:000220548500006 PM 15087666 ER PT J AU Lachenbruch, PA Rosenberg, AS Bonvini, E Cavaille-Coll, MW Colvin, RB AF Lachenbruch, PA Rosenberg, AS Bonvini, E Cavaille-Coll, MW Colvin, RB TI Biomarkers and surrogate endpoints in renal transplantation: Present status and considerations for clinical trial design SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE allograft rejection; predictive variables; surrogate endpoints ID CHRONIC ALLOGRAFT-REJECTION; KIDNEY-TRANSPLANTATION; QUANTITATIVE DETECTION; HUMORAL REJECTION; MESSENGER-RNA; EXPRESSION; CLASSIFICATION; BIOPSIES; REPRODUCIBILITY; CAPILLARIES AB Of major importance in clinical trials is the ability to predict individual patient outcome or endpoints using biomarkers, also known as variables or predictors, in as safe, efficient, and accurate a manner as possible. This review addresses the concepts and possible strategies for use of predictor and surrogate biomarkers in the design of clinical trials in renal transplantation. The statistical concepts apply equally well to other organ grafts. C1 US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Biostat, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Special Pathogen & Immunol Drug Prod, Rockville, MD USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rosenberg, AS (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Therapeut Prot, Bethesda, MD 20892 USA. EM rosenberg@cber.fda.gov NR 31 TC 49 Z9 50 U1 0 U2 2 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 APR PY 2004 VL 4 IS 4 BP 451 EP 457 DI 10.1111/j.1600-6143.2004.00386.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 810YZ UT WOS:000220740900001 PM 15023136 ER PT J AU Rojas, J Ichinose, F MacGillivray, T Walker, J Agnihotri, A Hess, D Melo, MV AF Rojas, J Ichinose, F MacGillivray, T Walker, J Agnihotri, A Hess, D Melo, MV TI Exhaled nitric oxide is reduced after coronary artery bypass surgery in patients with chronic obstructive pulmonary disease SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-Cardiovascular-Anesthesiologists CY APR 24-28, 2004 CL Honolulu, HI SP Soc Cardiovasc Anesthesiologists C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2004 VL 98 IS 4 SU S BP 48 EP 48 PG 1 WC Anesthesiology SC Anesthesiology GA 808SG UT WOS:000220588200048 ER EF